FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Spellberg, B
Walsh, TJ
Kontoyiannis, DP
Edwards, J
Ibrahim, AS
AF Spellberg, Brad
Walsh, Thomas J.
Kontoyiannis, Dimitrios P.
Edwards, John, Jr.
Ibrahim, Ashraf S.
TI Recent Advances in the Management of Mucormycosis: From Bench to Bedside
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID LIPOSOMAL AMPHOTERICIN-B; STEM-CELL TRANSPLANT; INVASIVE
FUNGAL-INFECTIONS; IN-VITRO SUSCEPTIBILITIES; COLONY-STIMULATING FACTOR;
CARE CANCER CENTER; REAL-TIME PCR; DISSEMINATED ZYGOMYCOSIS; FILAMENTOUS
FUNGI; RHIZOPUS-ORYZAE
AB Recent therapeutic advances have the potential to improve outcomes of mucormycosis. Lipid formulations of amphotericin B (LFAB) have evolved as the cornerstone of primary therapy for mucormycosis. Posaconazole may be useful as salvage therapy, but it cannot be recommended as primary therapy for mucormycosis on the basis of available data. Preclinical and limited retrospective clinical data suggest that combination LFAB-echinocandin therapy may improve survival during mucormycosis. A definitive trial is needed to confirm these results. Combination therapy with LFAB and the iron chelator, deferasirox, also improved outcomes in animal models of mucormycosis. In contrast, combination polyene-posaconazole therapy was of no benefit in preclinical studies. Adjunctive therapy with recombinant cytokines, hyperbaric oxygen, and/or granulocyte transfusions can be considered for selected patients. Early initiation of therapy is critical to maximizing outcomes; recent developments in polymerase chain reaction technology are advancing early diagnostic strategies. Prospective, randomized clinical trials are needed to define optimal management strategies for mucormycosis.
C1 [Spellberg, Brad; Edwards, John, Jr.; Ibrahim, Ashraf S.] Harbor UCLA Med Ctr, Div Infect Dis, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA.
[Spellberg, Brad; Edwards, John, Jr.; Ibrahim, Ashraf S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Walsh, Thomas J.] NCI, Bethesda, MD 20892 USA.
[Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Spellberg, B (reprint author), Harbor UCLA Med Ctr, Div Infect Dis, Los Angeles Biomed Res Inst, 1124 W Carson St RB2, Torrance, CA 90502 USA.
EM bspellberg@labiomed.org
RI a, a/M-9467-2013
FU Public Health Service [R01 AI063503, R21 AI064716]; National Cancer
Institute
FX Public Health Service (K08 to B.J.S. and R01 AI063503 and R21 AI064716
to A. S. I.) and the intramural research program of the National Cancer
Institute ( to T.J.W.).
NR 96
TC 158
Z9 168
U1 1
U2 7
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 15
PY 2009
VL 48
IS 12
BP 1743
EP 1751
DI 10.1086/599105
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 450YY
UT WOS:000266439100019
PM 19435437
ER
PT J
AU Yamamoto, N
Okano, T
Ma, XF
Adelstein, RS
Kelley, MW
AF Yamamoto, Norio
Okano, Takayuki
Ma, Xuefei
Adelstein, Robert S.
Kelley, Matthew W.
TI Myosin II regulates extension, growth and patterning in the mammalian
cochlear duct
SO DEVELOPMENT
LA English
DT Article
DE Hair cell; Organ of Corti; Inner ear; Pillar cell; Mouse
ID PLANAR CELL POLARITY; KINASE RHO-KINASE; INNER-EAR; HEARING IMPAIRMENT;
SMOOTH-MUSCLE; PCP PATHWAY; DROSOPHILA; HEAVY; GENE; IDENTIFICATION
AB The sensory epithelium of the mammalian cochlea comprises mechanosensory hair cells that are arranged into four ordered rows extending along the length of the cochlear spiral. The factors that regulate the alignment of these rows are unknown. Results presented here demonstrate that cellular patterning within the cochlea, including the formation of ordered rows of hair cells, arises through morphological remodeling that is consistent with the mediolateral component of convergent extension. Non-muscle myosin II is shown to be expressed in a pattern that is consistent with an active role in cellular remodeling within the cochlea, and genetic or pharmacological inhibition of myosin II results in defects in cellular patterning that are consistent with a disruption in convergence and extension. These results identify the first molecule, myosin II, which directly regulates cellular patterning and alignment within the cochlear sensory epithelium. Our results also provide insights into the cellular mechanisms that are required for the formation of highly ordered cellular patterns.
C1 [Yamamoto, Norio; Okano, Takayuki; Kelley, Matthew W.] NHLBI, Sect Dev Neurosci, Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
[Ma, Xuefei; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Kelley, MW (reprint author), NHLBI, Sect Dev Neurosci, Natl Inst Deafness & Other Commun Disorders, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM kelleymt@nidcd.nih.gov
OI , Norio/0000-0001-8924-0710; Adelstein, Robert/0000-0002-8683-2144
FU NIH; JSPS
FX The authors wish to acknowledge the excellent technical assistance of
Weise Chang. This project was supported by funds from the NIH Intramural
program to R. S. A. and M. W. K. and by grants from the JSPS Research
Fellowship for Japanese Biomedical and Behavioral Researchers at NIH to
N.Y. and T.O. Deposited in PMC for release after 12 months.
NR 59
TC 52
Z9 54
U1 0
U2 1
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD JUN 15
PY 2009
VL 136
IS 12
BP 1977
EP 1986
DI 10.1242/dev.030718
PG 10
WC Developmental Biology
SC Developmental Biology
GA 448XX
UT WOS:000266296400002
PM 19439495
ER
PT J
AU Nagy, N
Mwizerwa, O
Yaniv, K
Carmel, L
Pieretti-Vanmarcke, R
Weinstein, BM
Goldstein, AM
AF Nagy, Nandor
Mwizerwa, Olive
Yaniv, Karina
Carmel, Liran
Pieretti-Vanmarcke, Rafael
Weinstein, Brant M.
Goldstein, Allan M.
TI Endothelial cells promote migration and proliferation of enteric neural
crest cells via beta 1 integrin signaling
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Enteric nervous system; Endothelial cells; Blood vessels; Hirschsprung's
disease; Integrins; Avian; Zebrafish
ID EXTRACELLULAR-MATRIX; MONOCLONAL-ANTIBODY; NERVOUS-SYSTEM; TRANSGENIC
ZEBRAFISH; AGANGLIONIC BOWEL; AVIAN EMBRYO; LAMININ; FIBRONECTIN;
RECEPTOR; NEURONS
AB Enteric neural crest-derived cells (ENCCs) migrate along the intestine to form a highly organized network of ganglia that comprises the enteric nervous system (ENS). The signals driving the migration and patterning of these cells are largely unknown. Examining the spatiotemporal development of the intestinal neurovasculature in avian embryos, we find endothelial cells (ECs) present in the gut prior to the arrival of migrating ENCCs. These ECs are patterned in concentric rings that are predictive of the positioning of later arriving crest-derived cells, leading us to hypothesize that blood vessels may serve as a substrate to guide ENCC migration. Immunohistochemistry at multiple stages during ENS development reveals that ENCCs are positioned adjacent to vessels as they colonize the gut. A similar close anatomic relationship between vessels and enteric neurons was observed in zebrafish larvae. When EC development is inhibited in Cultured avian intestine, ENCC migration is arrested and distal aganglionosis results, suggesting that ENCCs require the presence of vessels to colonize the gut. Neural tube and avian midgut were explanted onto a variety of substrates, including components of the extracellular matrix and various cell types, such as fibroblasts, smooth muscle cells, and endothelial cells. We find that crest-derived cells from both the neural tube and the midgut migrate avidly onto Cultured endothelial cells. This EC-induced migration is inhibited by the presence of CSAT antibody, which blocks binding to beta 1 integrins expressed on the surface of crest-derived cells. These results demonstrate that ECs provide a Substrate for the migration of ENCCs via an interaction between beta 1 integrins on the ENCC surface and extracellular matrix proteins expressed by the intestinal vasculature. These interactions may play an important role in guiding migration and patterning in the developing ENS. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Nagy, Nandor; Mwizerwa, Olive; Pieretti-Vanmarcke, Rafael; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02115 USA.
[Nagy, Nandor] Semmelweis Univ, Fac Med, Dept Human Morphol & Dev Biol, H-1094 Budapest, Hungary.
[Yaniv, Karina; Weinstein, Brant M.] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
[Carmel, Liran] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02115 USA.
EM agoldstein@partners.org
FU NIH [K08HD46655]; Hungarian Scientific Research Fund [K-69061];
Semmelweis University; NICHD; EMBO fellowship
FX We thank Drucilla Roberts and Joanne Chan for helpful discussions, Csaba
Bodor for Huvec cells, and Ajay Chitnis for the HuC:GFP transgenic
zebrafish line. Several antibodies in Table 1 were obtained from the
Developmental Studies Hybridoma Bank developed under the auspices of the
NICHD and maintained by University of Iowa, Dept. of Biological
Sciences, Iowa City, IA 52242. AMG is supported by NIH K08HD46655, NN by
a grant from the Hungarian Scientific Research Fund (K-69061) and a
Young Investigator Award from Semmelweis University, BMW by the
intramural program of the NICHD, and KY by an EMBO fellowship.
NR 54
TC 38
Z9 41
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUN 15
PY 2009
VL 330
IS 2
BP 263
EP 272
DI 10.1016/j.ydbio.2009.03.025
PG 10
WC Developmental Biology
SC Developmental Biology
GA 452XN
UT WOS:000266574600005
PM 19345201
ER
PT J
AU Buchmann-Moller, S
Miescher, I
John, N
Krishnan, J
Deng, CX
Sommer, L
AF Buechmann-Moller, Stine
Miescher, Iris
John, Nessy
Krishnan, Jaya
Deng, Chu-Xia
Sommer, Lukas
TI Multiple lineage-specific roles of Smad4 during neural crest development
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Neural crest; Smooth muscle formation; Autonomic neurogenesis; Sensory
neurogenesis; Smad4; TGF beta; BMP; Cell survival; Proliferation; Fate
decision
ID SMOOTH-MUSCLE DIFFERENTIATION; BONE MORPHOGENETIC PROTEIN-4; MAMMALIAN
ACHAETE-SCUTE; CARDIAC OUTFLOW TRACT; STEM-CELL FUNCTION; TGF-BETA;
AUTONOMIC NEUROGENESIS; SYMPATHETIC NEURONS; DIGEORGE-SYNDROME; KNOCKOUT
MICE
AB During vertebrate development, neural crest cells are exposed to multiple extracellular cues that drive their differentiation into neural and non-neural cell lineages. Insights into the signals potentially involved in neural crest cell fate decisions in vivo have been gained by cell culture experiments that have allowed the identification of instructive growth factors promoting either proliferation of multipotent neural crest cells or acquisition of specific fates. For instance, members of the TGF factor family induce neurogenesis and smooth muscle cell formation at the expense of other fates in culture. In vivo, conditional ablation of various TGF signaling components resulted in malformations of non-neural derivatives of the neural crest, but it is unclear whether these phenotypes involved aberrant fate decisions. Moreover, it remains to be shown whether neuronal determination indeed requires TGF factor activity in vivo. To address these issues, we conditionally deleted Smad4 in the neural crest, thus inactivating all canonical TGF beta factor signaling. Surprisingly, neural crest cell fates were not affected in these mutants, with the exception of sensory neurogenesis in trigeminal ganglia. Rather, Smad4 regulates survival of smooth muscle and proliferation of autonomic and ENS neuronal progenitor cells. Thus, Smad signaling plays multiple, lineage-specific roles in vivo, many of which are elicited only after neural crest cell fate decision. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Buechmann-Moller, Stine; Miescher, Iris; John, Nessy; Sommer, Lukas] Univ Zurich, Inst Anat, Div Cell & Dev Biol, CH-8057 Zurich, Switzerland.
[Buechmann-Moller, Stine; John, Nessy; Krishnan, Jaya] ETH, Inst Cell Biol, CH-8093 Zurich, Switzerland.
[Deng, Chu-Xia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Sommer, L (reprint author), Univ Zurich, Inst Anat, Div Cell & Dev Biol, CH-8057 Zurich, Switzerland.
EM lukas.sommer@anatom.uzh.ch
RI deng, chuxia/N-6713-2016
FU Swiss National Science Foundation; National Center of Competence in
Research "Neural Plasticity and Repair"; Vontobel Foundation;
Oncosuisse/Swiss Cancer League; ETH Zurich; University of Zurich
FX We are grateful to S. Karlsson, A. McMahon and P. Soriano for providing
transgenic animals. This work was supported by the Swiss National
Science Foundation, the National Center of Competence in Research
"Neural Plasticity and Repair", the Vontobel Foundation,
Oncosuisse/Swiss Cancer League, ETH Zurich and the University of Zurich.
NR 61
TC 17
Z9 17
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUN 15
PY 2009
VL 330
IS 2
BP 329
EP 338
DI 10.1016/j.ydbio.2009.04.001
PG 10
WC Developmental Biology
SC Developmental Biology
GA 452XN
UT WOS:000266574600010
PM 19361496
ER
PT J
AU Song, HL
Ramus, SJ
Kjaer, SK
DiCioccio, RA
Chenevix-Trench, G
Pearce, CL
Hogdall, E
Whittemore, AS
McGuire, V
Hogdall, C
Blaakaer, J
Wu, AH
Van Den Berg, DJ
Stram, DO
Menon, U
Gentry-Maharaj, A
Jacobs, IJ
Webb, PM
Beesley, J
Chen, XQ
Rossing, MA
Doherty, JA
Chang-Claude, J
Wang-Gohrke, S
Goodman, MT
Lurie, G
Thompson, PJ
Carney, ME
Ness, RB
Moysich, K
Goode, EL
Vierkant, RA
Cunningham, JM
Anderson, S
Schildkraut, JM
Berchuck, A
Iversen, ES
Moorman, PG
Garcia-Closas, M
Chanock, S
Lissowska, J
Brinton, L
Anton-Culver, H
Ziogas, A
Brewster, WR
Ponder, BAJ
Easton, DF
Gayther, SA
Pharoah, PDP
AF Song, Honglin
Ramus, Susan J.
Kjaer, Susanne Kruger
DiCioccio, Richard A.
Chenevix-Trench, Georgia
Pearce, Celeste Leigh
Hogdall, Estrid
Whittemore, Alice S.
McGuire, Valerie
Hogdall, Claus
Blaakaer, Jan
Wu, Anna H.
Van Den Berg, David J.
Stram, Daniel O.
Menon, Usha
Gentry-Maharaj, Aleksandra
Jacobs, Ian J.
Webb, Penny M.
Beesley, Jonathan
Chen, Xiaoqing
Rossing, Mary Anne
Doherty, Jennifer A.
Chang-Claude, Jenny
Wang-Gohrke, Shan
Goodman, Marc T.
Lurie, Galina
Thompson, Pamela J.
Carney, Michael E.
Ness, Roberta B.
Moysich, Kirsten
Goode, Ellen L.
Vierkant, Robert A.
Cunningham, Julie M.
Anderson, Stephanie
Schildkraut, Joellen M.
Berchuck, Andrew
Iversen, Edwin S.
Moorman, Patricia G.
Garcia-Closas, Montserrat
Chanock, Stephen
Lissowska, Jolanta
Brinton, Louise
Anton-Culver, Hoda
Ziogas, Argyrios
Brewster, Wendy R.
Ponder, Bruce A. J.
Easton, Douglas F.
Gayther, Simon A.
Pharoah, Paul D. P.
CA Australian Canc Ovarian Study
Australian Ovarian Canc Study Grp
OCAC
TI Association between invasive ovarian cancer susceptibility and 11 best
candidate SNPs from breast cancer genome-wide association study
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENETIC ASSOCIATION; LOCI; VARIANTS; RISK
AB Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.
C1 [Song, Honglin; Ponder, Bruce A. J.; Pharoah, Paul D. P.] Univ Cambridge, Strangeways Res Lab, CR UK Dept Oncol, Cambridge, England.
[Ramus, Susan J.; Menon, Usha; Gentry-Maharaj, Aleksandra; Jacobs, Ian J.; Gayther, Simon A.] UCL, UCL EGA Inst Womens Hlth, Gynaecol Oncol Unit, London WC1E 6BT, England.
[Kjaer, Susanne Kruger; Hogdall, Estrid] Danish Canc Soc, Inst Canc Epidemiol, Dept Viruses Hormones & Canc, Copenhagen, Denmark.
[DiCioccio, Richard A.] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA.
[Chenevix-Trench, Georgia; Webb, Penny M.; Beesley, Jonathan; Chen, Xiaoqing] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Pearce, Celeste Leigh; Wu, Anna H.; Van Den Berg, David J.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Whittemore, Alice S.; McGuire, Valerie] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Hogdall, Claus] Univ Copenhagen, Rigshosp, Juliane Marie Ctr, Gynaecol Clin, DK-2100 Copenhagen, Denmark.
[Blaakaer, Jan] Skejby Univ Hosp, Dept Obstet & Gynaecol, Aarhus, Denmark.
[Rossing, Mary Anne; Doherty, Jennifer A.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany.
[Goodman, Marc T.; Lurie, Galina; Thompson, Pamela J.; Carney, Michael E.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96822 USA.
[Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Moysich, Kirsten] Roswell Pk Canc Ctr, Buffalo, NY USA.
[Goode, Ellen L.; Vierkant, Robert A.; Cunningham, Julie M.; Anderson, Stephanie] Mayo Clin, Coll Med, Rochester, MN USA.
[Schildkraut, Joellen M.; Berchuck, Andrew; Iversen, Edwin S.] Duke Univ, Med Ctr, Ctr Comprehens Canc, Durham, NC 27710 USA.
[Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC 27710 USA.
[Garcia-Closas, Montserrat; Chanock, Stephen; Brinton, Louise] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Lissowska, Jolanta] M Sklodowska Curie Inst Oncol & Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Brewster, Wendy R.] Univ N Carolina, Sch Med, Dept OB GYN, Chapel Hill, NC 27599 USA.
[Easton, Douglas F.] Univ Cambridge, Strangeways Res Lab, CR UK Genet Epidemiol Unit, Cambridge, England.
RP Song, HL (reprint author), Univ Cambridge, Strangeways Res Lab, CR UK Dept Oncol, Cambridge, England.
EM honglin@srl.cam.ac.uk
RI Menon, Usha/C-4716-2008; Webb, Penelope/D-5736-2013; Jacobs,
Ian/F-1743-2013; Garcia-Closas, Montserrat /F-3871-2015; Brinton,
Louise/G-7486-2015; Bowtell, David/H-1007-2016;
OI Lissowska, Jolanta/0000-0003-2695-5799; Webb,
Penelope/0000-0003-0733-5930; Jacobs, Ian/0000-0002-8112-4624;
Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; Bowtell, David/0000-0001-9089-7525;
Vierkant, Robert/0000-0001-6242-5221; Kjaer,
Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798
FU Cancer Research UK; Roswell Park Alliance; Danish Cancer Society;
National Cancer Institute [CA71766, CA16056, RO1 CA61107, RO1 CA122443];
Ovarian Cancer Research Fund.; US Army Medical Research and Materiel
Command [DAMD17-01-1-0729]; Cancer Council Tasmania and Cancer
Foundation of Western Australia (AOCS study),; National Health and
Medical Research Council of Australia [199600]; US national Cancer
Institute [R01 CA87538, R01 CA112523]; German Federal Ministry of
Education and Research of Germany, [01 GB 9401]; state of
Baden-Wurttemberg through Medical Faculty of the University of Ulm
[P.685]; US Public Health Service [R01-CA-58598]; National Cancer
Institute, NIH, Department of Health and Human Services [N01-CN-55424,
N01-PC-35137, CA-58860, CA-92044]; OAK Foundation; Department of
Health's NIHR Biomedical Research Centre
FX This work was supported by Cancer Research UK, The Roswell Park
Alliance, The Danish Cancer Society and The National Cancer Institute
(CA71766, CA16056, RO1 CA61107 and RO1 CA122443). We are grateful to the
family and friends of Kathryn Sladek Smith for their generous support of
OCAC through their donations to the Ovarian Cancer Research Fund. US
Army Medical Research and Materiel Command under DAMD17-01-1-0729, the
Cancer Council Tasmania and Cancer Foundation of Western Australia (AOCS
study), The National Health and Medical Research Council of Australia
(199600) (ACS study). DOV study was supported by the US national Cancer
Institute grants R01 CA87538 and R01 CA112523. The German Ovarian Cancer
Study was supported by the German Federal Ministry of Education and
Research of Germany, Programme of Clinical Biomedical Research grant 01
GB 9401 and the genotyping in part by the state of Baden-Wurttemberg
through Medical Faculty of the University of Ulm (P.685). HAW study was
supported by US Public Health Service grant R01-CA-58598, and contracts
N01-CN-55424 and N01-PC-35137 from the National Cancer Institute, NIH,
Department of Health and Human Services. UCI study was supported by the
National Institutes of Health, National Cancer Institute grants
CA-58860, CA-92044 and the Lon V Smith Foundation grant LVS-39420. The
UKOPS study is funded by the OAK Foundation. Some of this work was
undertaken at UCLH/UCL who received a proportion of funding from the
Department of Health's NIHR Biomedical Research Centre funding scheme.
NR 16
TC 19
Z9 20
U1 3
U2 8
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 JUN 15
PY 2009
VL 18
IS 12
BP 2297
EP 2304
DI 10.1093/hmg/ddp138
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 449SD
UT WOS:000266349400017
PM 19304784
ER
PT J
AU Pathare, S
Schaffer, AA
Beerenwinkel, N
Mahimkar, M
AF Pathare, Swapnali
Schaeffer, Alejandro A.
Beerenwinkel, Niko
Mahimkar, Manoj
TI Construction of oncogenetic tree models reveals multiple pathways of
oral cancer progression
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE oral cancer; CGH; comparative genomic hybridization; oncogenetic tree;
progression pathways; genetic progression score
ID COMPARATIVE GENOMIC HYBRIDIZATION; SQUAMOUS-CELL CARCINOMAS;
PHYLOGENETIC TREES; MUTAGENETIC TREES; TUMOR PROGRESSION; POOR SURVIVAL;
SOLID TUMORS; NECK-CANCER; HEAD; IMBALANCES
AB Oral cancer develops and progresses by accumulation of genetic alterations. The interrelationship between these alterations and their sequence of occurrence in oral cancers has not been thoroughly understood. In the present study, we applied oncogenetic tree models to comparative genomic hybridization (CGH) data of 97 primary oral cancers to identify pathways of progression. CGH revealed the most frequent gains on chromosomes 8q (72.4%) and 9q (41.2%) and frequent losses on 3p (49.5%) and 8p (47.5%). Both mixture and distance-based tree models suggested multiple progression pathways and identified +8q as an early event. The mixture model suggested two independent pathways namely a major pathway with -8p and a less frequent pathway with +9q. The distance-based tree identified three progression pathways, one characterized by -8p, another by -3p and the third by alterations +11q and +7p. Differences were observed in cytogenetic pathways of node-positive and node-negative oral cancers. Node-positive cancers were characterized by more non-random aberrations (n = 11) and progressed via -8p or -3p. On the other hand, node-negative cancers involved fewer non-random alterations (n = 6) and progressed along -3p. In summary, the tree models for oral cancers provided novel information about the interactions between genetic alterations and predicted their probable order of occurrence. (C) 2009 UICC
C1 [Pathare, Swapnali; Mahimkar, Manoj] Tata Mem Hosp, Canc Res Inst, Adv Ctr Treatment Res & Educ Canc, Kharghar 410210, Navi Mumbai, India.
[Schaeffer, Alejandro A.] NIH, Computat Biol Branch, Natl Biotechnol Ctr, DHHS, Bethesda, MD 20892 USA.
[Beerenwinkel, Niko] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.
RP Mahimkar, M (reprint author), Tata Mem Hosp, Canc Res Inst, Adv Ctr Treatment Res & Educ Canc, Kharghar 410210, Navi Mumbai, India.
EM mmahimkar@actrec.gov.in
RI Schaffer, Alejandro/F-2902-2012
FU Indian Council of Medical Research (ICMR) [5/13/2/TF/2001-NCD-III];
National Institutes of Health
FX Grant sponsor: Indian Council of Medical Research (ICMR); Grant number:
5/13/2/TF/2001-NCD-III; Grant sponsor: Intramural Research program of
the National Institutes of Health.
NR 46
TC 14
Z9 14
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUN 15
PY 2009
VL 124
IS 12
BP 2864
EP 2871
DI 10.1002/ijc.24267
PG 8
WC Oncology
SC Oncology
GA 444RG
UT WOS:000265997500013
PM 19267402
ER
PT J
AU Guo, XC
Johnson, RC
Deng, H
Liao, J
Guan, L
Nelson, GW
Tang, MZ
Zheng, YM
de The, G
O'Brien, SJ
Winkler, CA
Zeng, Y
AF Guo, Xiuchan
Johnson, Randall C.
Deng, Hong
Liao, Jian
Guan, Li
Nelson, George W.
Tang, Mingzhong
Zheng, Yuming
de The, Guy
O'Brien, Stephen J.
Winkler, Cheryl A.
Zeng, Yi
TI Evaluation of nonviral risk factors for nasopharyngeal carcinoma in a
high-risk population of Southern China
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE nasopharyngeal carcinoma; risk factor; epidemiology; Southern China;
Epstein Barr Virus
ID EPSTEIN-BARR-VIRUS; SALTED FISH; MALAYSIAN CHINESE; PRESERVED FOODS;
OCCUPATIONAL-EXPOSURE; SINGAPORE CHINESE; CIGARETTE-SMOKING;
WUZHOU-CITY; HONG-KONG; FORMALDEHYDE
AB To understand the role of environmental and genetic influences on nasopharyngeal carcinoma (NPC) in populations at high risk of NPC, we have performed a case-control study in Guangxi Province of Southern China in 2004-2005. NPC cases (n = 1,049) were compared with 785 NPC-free matched controls who were seropositive for IgA antibodies (IgA) to Epstein-Barr virus (EBV) capsid antigen (VCA)-a predictive marker for NPC in Chinese populations. A questionnaire was used to capture exposure and NPC family history data. Risk factors associated with NPC in a multi-variant analysis model were the following: (i) a first, second or third degree relative with NPC [attributable risk (AR) = 6%, odds ratio (OR) = 3.1, 95% confidence interval (CI) = 2.0-4.9, p < 0.001]; (ii) consumption of salted fish 3 or more than 3 times per month (AR = 3%, OR = 1.9, 95% CI = 1.1-3.5, p = 0.035); (iii) exposure to domestic wood cooking fires for more than 10 years (AR = 69%, OR = 5.8,95% CI = 2.5-13.6, p < 0.001); and (iv) exposure to occupational solvents for 10 or less years (AR = 4%, OR = 2.6, 95% CI = 1.4-4.8, p = 0.002). Consumption of preserved meats or a history of tobacco smoking were not associated with NPC (p > 0.05). We also assessed the contribution of EBV/IgA/VCA antibody serostatus to NPC risk-32.2% of NPC can be explained by IgA+ status. However, family history and environmental risk factors cumulatively explained only 2.7% of NPC development in NPC high risk population. These findings should have important public health implications for NPC risk reduction in endemic regions. (C) 2009 UICC
C1 [Guo, Xiuchan; Johnson, Randall C.; Guan, Li; Nelson, George W.; Winkler, Cheryl A.] NCI, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD USA.
[Guo, Xiuchan; Zeng, Yi] Chinese CDC, Inst Viral Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Beijing, Peoples R China.
[Deng, Hong; Tang, Mingzhong; Zheng, Yuming] Wuzhou Red Cross Hosp, Ctr Canc, Wuzhou, Guangxi, Peoples R China.
[Liao, Jian] Cangwu Inst Nasopharyngeal Carcinoma Control & Pr, Wuzhou, Guangxi, Peoples R China.
[de The, Guy] Inst Pasteur, Paris, France.
[Winkler, Cheryl A.] NCI, Lab Genom Divers, SAIC Frederick, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Winkler, CA (reprint author), NCI, Lab Genom Divers, SAIC Frederick, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
EM winkler@ncifcrf.gov; zengy@public.bta.net.cn
RI Johnson, Randall/B-1517-2014
OI Johnson, Randall/0000-0001-7754-0847
FU National Natural Science Foundation of China [30672377]; National Cancer
Institute, National Institutes of Health [N01-CO-12400]; NIH, National
Cancer Institute, Center for Cancer Research
FX Grant sponsors: National Natural Science Foundation of China; Grant
number: 30672377; Grant sponsor: National Cancer Institute. National
Institutes of Health; Grant number: N01-CO-12400; Grant sponsor:
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 50
TC 57
Z9 62
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUN 15
PY 2009
VL 124
IS 12
BP 2942
EP 2947
DI 10.1002/ijc.24293
PG 6
WC Oncology
SC Oncology
GA 444RG
UT WOS:000265997500025
PM 19296536
ER
PT J
AU Golden, A
Liu, J
Cohen-Fix, O
AF Golden, Andy
Liu, Jun
Cohen-Fix, Orna
TI Inactivation of the C-elegans lipin homolog leads to ER disorganization
and to defects in the breakdown and reassembly of the nuclear envelope
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Peripheral ER; Lamin; Nuclear shape; Nuclear architecture; Lipid
droplets; Diabetes; Insulin resistance; Majeed syndrome
ID ENDOPLASMIC-RETICULUM; CAENORHABDITIS-ELEGANS; PHOSPHOLIPID
BIOSYNTHESIS; PROTEIN; DYNAMICS; GENE; RNAI; LIPODYSTROPHY; ROLES; CELLS
AB The nuclear envelope (NE) is a dynamic structure, undergoing periods of growth, breakdown and reassembly during the cell cycle. In yeast, altering lipid synthesis by inactivating the yeast homolog of lipin, a phosphatidic acid phosphohydrolase, leads to disorganization of the peripheral ER and abnormal nuclear shape. These results suggest that lipid metabolism contributes to NE dynamics; however, since yeast undergo closed mitosis, the relevance of these observations to higher eukaryotes is unclear. In mammals, lipin has been implicated in adipose tissue differentiation, insulin resistance, lipid storage and obesity, but the underlying cellular defects caused by altering lipin levels are not known. Here, we identify the Caenorhabditis elegans lipin homolog (LPIN-1) and examine its affect on NE dynamics. We find that downregulating LPIN-1 by RNAi results in the appearance of membrane sheets and other abnormal structures in the peripheral ER. Moreover, lpin-1 RNAi causes defects in NE breakdown, abnormal chromosome segregation and irregular nuclear morphology. These results uncover cellular processes affected by lipin in metazoa, and suggest that lipid synthesis has a role in NE dynamics.
C1 [Cohen-Fix, Orna] NIH, Mol & Cellular Biol Lab, Bethesda, MD 20892 USA.
[Golden, Andy] Lab Biochem & Genet, Bethesda, MD 20892 USA.
[Golden, Andy] NIDDK, Bethesda, MD 20892 USA.
[Liu, Jun] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.
RP Cohen-Fix, O (reprint author), NIH, Mol & Cellular Biol Lab, 8 Ctr Dr, Bethesda, MD 20892 USA.
EM ornacf@helix.nih.gov
FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM066953]
NR 37
TC 66
Z9 69
U1 0
U2 5
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD JUN 15
PY 2009
VL 122
IS 12
BP 1970
EP 1978
DI 10.1242/jcs.044743
PG 9
WC Cell Biology
SC Cell Biology
GA 453TE
UT WOS:000266634800007
PM 19494126
ER
PT J
AU You, YY
Zhao, H
Wang, Y
Carter, RH
AF You, Yuying
Zhao, Hong
Wang, Yue
Carter, Robert H.
TI Cutting Edge: Primary and Secondary Effects of CD19 Deficiency on Cells
of the Marginal Zone
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID B-CELLS; POSITIVE SELECTION; CD19-DEFICIENT MICE; SPLEEN; LYMPHOCYTES;
SUBSETS
AB Marginal zone (MZ) B cells are absent in CD19(-/-) mice. Possible causes include an intrinsic defect in B cells and/or a secondary defect in the extrinsic MZ microenvironment as a result of changes in B cell differentiation in mice lacking CD19. Cells in the MZ also include MZ macrophages (MZM) and MZ dendritic cells (DC). Although CD19 is only expressed on B cells, SIGN-R1(+) MZM are absent and CD11c(+) MZ DC distribution is abnormal in CD19(-/-) mice. Adoptively transferred B cells from normal mice are able to reconstitute MZ B cells in CD19(-/-) mice. In contrast, CD19(-/-) B cells could not enter the MZ of the normal mice. Furthermore, MZM distribution and MZ DC distribution are restored following MZ B cell reconstitution in CD19(-/-) mice. Thus, MZ B cells are required for MZM differentiation and MZ DC localization, but the deficiency of MZ B cells in CD19(-/-) mice is caused by a defect of intrinsic B cell signaling. The Journal of Immunology, 2009, 182: 7343-7347.
C1 [You, Yuying] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Zhao, Hong; Wang, Yue] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Carter, Robert H.] NIAMSD, Bethesda, MD 20892 USA.
RP Carter, RH (reprint author), Bldg 31,Room 4C32,31 Ctr Dr,Mail Stop Code 2350, Bethesda, MD 20892 USA.
EM carterrob@mail.nih.gov
FU National Institute of Arthritis, Musculoskeletal, and Skin Diseases,
National Institutes of Health [RO1 AI 46225]; Office of Research and
Development, Medical Research Service, Department of Veterans Affairs
FX This work was supported by the National Institute of Arthritis,
Musculoskeletal, and Skin Diseases, National Institutes of Health Grant
RO1 AI 46225 (to R.H.C.) and the Office of Research and Development,
Medical Research Service, Department of Veterans Affairs (to R.H.C.).
NR 19
TC 17
Z9 17
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 JUN 15
PY 2009
VL 182
IS 12
BP 7343
EP 7347
DI 10.4049/jimmunol.0804295
PG 5
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900002
PM 19494255
ER
PT J
AU Sa-Nunes, A
Bafica, A
Antonelli, LR
Choi, EY
Francischetti, IMB
Andersen, JF
Shi, GP
Chavakis, T
Ribeiro, JM
Kotsyfakis, M
AF Sa-Nunes, Anderson
Bafica, Andre
Antonelli, Lis R.
Choi, Eun Young
Francischetti, Ivo M. B.
Andersen, John F.
Shi, Guo-Ping
Chavakis, Triantafyllos
Ribeiro, Jose M.
Kotsyfakis, Michalis
TI The Immunomodulatory Action of Sialostatin L on Dendritic Cells Reveals
Its Potential to Interfere with Autoimmunity
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MHC CLASS-II; COLLAGEN-INDUCED ARTHRITIS; SALIVARY-GLAND EXTRACTS; TICK
IXODES-SCAPULARIS; CATHEPSIN-S INHIBITOR; LYME-DISEASE VECTOR; ANTIGEN
PRESENTATION; IMMUNE-RESPONSE; BALB/C MICE; DERMACENTOR-ANDERSONI
AB Sialostatin L (SialoL) is a secreted cysteine protease inhibitor identified in the salivary glands of the Lyme disease vector Ixodes scapularis. In this study, we reveal the mechanisms of SialoL immunomodulatory actions on the vertebrate host. LPS-induced maturation of dendritic cells from C57BL/6 mice was significantly reduced in the presence of SialoL. Although OVA degradation was not affected by the presence of SialoL in dendritic cell cultures, cathepsin S activity was partially inhibited, leading to an accumulation of a 10-kDa invariant chain intermediate in these cells. As a consequence, in vitro Ag-specific CD4(+) T cell proliferation was inhibited in a time-dependent manner by SialoL, and further studies engaging cathepsin S(-/-) or cathepsin L(-/-) dendritic cells confirmed that the immunomodulatory actions of SialoL are mediated by inhibition of cathepsin S. Moreover, mice treated with SialoL displayed decreased early T cell expansion and recall response upon antigenic stimulation. Finally, SialoL administration during the immunization phase of experimental autoimmune encephalomyelitis in mice significantly prevented disease symptoms, which was associated with impaired IFN-gamma and IL-17 production and specific T cell proliferation. These results illuminate the dual mechanism by which a human disease vector protein modulates vertebrate host immunity and reveals its potential in prevention of an autoimmune disease. The Journal of Immunology, 2009, 182: 7422-7429.
C1 [Sa-Nunes, Anderson] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Expt Immunol Lab, Sao Paulo, Brazil.
[Sa-Nunes, Anderson; Francischetti, Ivo M. B.; Andersen, John F.; Ribeiro, Jose M.; Kotsyfakis, Michalis] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Bafica, Andre] Univ Fed Santa Catarina, Div Immunol, Dept Microbiol & Parasitol, Florianopolis, SC, Brazil.
[Antonelli, Lis R.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Choi, Eun Young; Chavakis, Triantafyllos] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Shi, Guo-Ping] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Shi, Guo-Ping] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Sa-Nunes, A (reprint author), Inst Ciencias Biomed IV, Dept Imunol, Lab Imunol Expt, Cidade Univ,Ave Prof Lineu Preste 1730, BR-05590890 Sao Paulo, Brazil.
EM sanunes@usp.br; mkotsyfakis@mail.nih.gov
RI Sa-Nunes, Anderson/D-8667-2012; Antonelli, Lis/G-2907-2012; Vacinas,
Inct/J-9431-2013; Kotsyfakis, Michail/G-9525-2014;
OI Sa-Nunes, Anderson/0000-0002-1859-4973; Kotsyfakis,
Michail/0000-0002-7526-1876; Ribeiro, Jose/0000-0002-9107-0818
FU Intramural Research Program of the Division of Intramural Research;
National Institute of Allergy and Infectious Diseases; National
Institutes of Health; Conselho Nacional de Pesquisas [472477/2007-2,
565496/2008-5]; Fundacao de Apoio a Pesquisa Cientifica e Tecnologica do
Estado de Santa Catarina [04524/2008-1]; World Health Organization/TDR
[2008-8734-0]
FX This work was supported by funding from the Intramural Research Program
of the Division of Intramural Research, National Institute of Allergy
and Infectious Diseases, National Institutes of Health. A.B. received
funding front Conselho Nacional de Pesquisas Grants 472477/2007-2 and
565496/2008-5, Fundacao de Apoio a Pesquisa Cientifica e Tecnologica do
Estado de Santa Catarina Grant 04524/2008-1, and World Health
Organization/TDR Grant 2008-8734-0.
NR 46
TC 38
Z9 39
U1 1
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2009
VL 182
IS 12
BP 7422
EP 7429
DI 10.4049/jimmunol.0900075
PG 8
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900012
PM 19494265
ER
PT J
AU Cyphert, JM
Kovarova, M
Allen, IC
Hartney, JM
Murphy, DL
Wess, J
Koller, BH
AF Cyphert, Jaime M.
Kovarova, Martina
Allen, Irving C.
Hartney, John M.
Murphy, Dennis L.
Wess, Juergen
Koller, Beverly H.
TI Cooperation between Mast Cells and Neurons Is Essential for
Antigen-Mediated Bronchoconstriction
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID AIRWAY SMOOTH-MUSCLE; MUSCARINIC ACETYLCHOLINE-RECEPTOR; HISTAMINE H-1
RECEPTORS; SEROTONIN TRANSPORTER; RESPIRATORY RESPONSES; NERVE
INTERACTIONS; PROSTAGLANDIN D-2; ALLERGIC RESPONSE; GANGLION NEURONS;
TISSUE MECHANICS
AB Mast cells are important sentinels guarding the interface between the environment and the body: a breach in the integrity of this interface can lead to the release of a plethora of mediators that engage the foreign agent, recruit leukocytes, and initiate adaptive physiological changes in the organism. While these capabilities make mast cells critical players in immune defense, it also makes them important contributors to the pathogenesis of diseases such as asthma. Mast cell mediators induce dramatic changes in smooth muscle physiology, and the expression of receptors for these factors by smooth muscle suggests that they act directly to initiate constriction. Contrary to this view, we show herein that mast cell-mediated bronchoconstriction is observed only in animals with intact innervation of the lung and that serotonin release alone is required for this action. While ablation of sensory neurons does not limit bronchoconstriction, constriction after Ag challenge is absent in mice in which the cholinergic pathways are compromised. Linking mast cell function to the cholinergic system likely provides an important means of modulating the function of these resident immune cells to physiology of the lung, but may also provide a safeguard against life-threatening anaphylaxis during mast cell degranulation. The Journal of Immunology, 2009, 182: 7430-7439.
C1 [Kovarova, Martina; Koller, Beverly H.] Univ N Carolina, Div Pulm & Crit Care Med, Dept Med, Chapel Hill, NC 27599 USA.
[Cyphert, Jaime M.; Allen, Irving C.; Hartney, John M.; Koller, Beverly H.] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA.
[Murphy, Dennis L.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA.
[Wess, Juergen] NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
RP Koller, BH (reprint author), Univ N Carolina, Div Pulm & Crit Care Med, Dept Med, 5067 Genet Med Bldg,CB 7264,120 Mason Farm Rd, Chapel Hill, NC 27599 USA.
EM treawouns@aol.com
FU National Institutes of Health [NIH/NHLBI R01 HL080697, HL068141]
FX This work was supported by National Institutes of Health Grants
NIH/NHLBI R01 HL080697 and HL068141 (to B.H.K.).
NR 56
TC 29
Z9 29
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2009
VL 182
IS 12
BP 7430
EP 7439
DI 10.4049/jimmunol.0900039
PG 10
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900013
PM 19494266
ER
PT J
AU Nagata, S
Ise, T
Pastan, I
AF Nagata, Satoshi
Ise, Tomoko
Pastan, Ira
TI Fc Receptor-Like 3 Protein Expressed on IL-2 Nonresponsive Subset of
Human Regulatory T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TGF-BETA; MONOCLONAL-ANTIBODIES;
INTERLEUKIN (IL)-2; AUTOIMMUNE-DISEASE; FOXP3 EXPRESSION;
FLOW-CYTOMETRY; TARGET GENES; STIMULATION; INDUCTION
AB Fc receptor-like 3 (FCRL3) is a cell surface protein homologous to Fe receptors. The FCRL3 gene is present in humans but not in mice. We found that FCRL3 protein is expressed on 40% of human naturally occurring CD4(+) regulatory T (nTreg) cells (CD4(+)CD25(+)CD127(low)). Sorted nTreg cells with the surface phenotype FCRL3(+) and FCRL3(-) were both hypoproliferative to TCR stimulation and both suppressive on proliferation of conventional T cells (CD4(+)CD25(-)) in vitro. They both expressed forkhead box p3 (Foxp3) protein, the intracellular regulatory T cell marker. However, in contrast to FCRL3(-) nTreg cells, FCRL3(+) nTreg cells were not stimulated to proliferate by the addition of exogenous IL-2. In addition, Foxp3(+) cells induced from conventional T cells by TGF-beta treatment did not exhibit FCRL3 expression. These results suggest that the FCRL3(+) subset of human nTreg cells identified in this study arise in vivo and Foxp3 expression alone is not sufficient to induce FCRL3 expression. FCRL3 may be involved in human-specific mechanisms to control the generation of nTreg cells. The Journal of Immunology,2009,182: 7518-7526.
C1 [Nagata, Satoshi; Ise, Tomoko] Sanford Res USD, Canc Biol Res Ctr, Sioux Falls, SD 57105 USA.
[Nagata, Satoshi; Ise, Tomoko; Pastan, Ira] NCI, Ctr Canc Res, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Nagata, S (reprint author), Sanford Res USD, Canc Biol Res Ctr, 1400 W 22nd St,Room L08, Sioux Falls, SD 57105 USA.
EM nagatas@sanfordhealth.org
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 51
TC 26
Z9 27
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2009
VL 182
IS 12
BP 7518
EP 7526
DI 10.4049/jimmunol.0802230
PG 9
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900022
PM 19494275
ER
PT J
AU Yoshimi, R
Chang, TH
Wang, HS
Atsumi, T
Morse, HC
Ozato, K
AF Yoshimi, Ryusuke
Chang, Tsung-Hsien
Wang, Hongsheng
Atsumi, Toru
Morse, Herbert C., III
Ozato, Keiko
TI Gene Disruption Study Reveals a Nonredundant Role for TRIM21/Ro52 in
NF-kappa B-Dependent Cytokine Expression in Fibroblasts
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRIM FAMILY PROTEINS; E3 UBIQUITIN LIGASE;
AUTOANTIGEN RO52; INTERFERON-ALPHA; SEQUESTOSOME 1/P62; FINGER PROTEIN;
IMMUNE CELLS; HEAVY-CHAIN; MOTIF
AB The tripartite motif (TRIM) family member, TRIM21, is an E3 ubiquitin ligase for IFN regulatory factor (IRF)3 and IRF8 that functions in both innate and acquired immunity. It is also an autoantigen known as Ro52/SS-A. The function of TRIM21 in vivo, however, has remained elusive. We generated Trim21(-/-) mice with the Trim21 gene replaced by an enhanced GFP (EGFP) reporter. EGFP expression analyses showed that Trim21 was widely expressed in many tissues, with the highest levels in immune cells. Studies of Trim21(-/-) embryonic fibroblasts demonstrated that TLR-mediated induction of proinflammatory cytokines, including IL-1 beta, IL-6, TNF-alpha, and CXCL 10, was consistently tip-regulated relative to wild-type cells. Reporter analyses demonstrated that TLR-mediated NF-kappa B activation was higher in Trim21(-/-) cells than in wild-type cells, most likely accounting for their enhanced cytokine expression. In contrast, functional analyses of immune cells from Trim21(-/-) mice revealed no abnormalities in their composition or function, even though ubiquitylation of IRF3 and IRF8 was impaired. These results suggested possible redundancies in activities mediated by TRIM21. In keeping with this concept, we found that a number of TRIM family members were up-regulated in Trim21(-/-) cells. Taken together, these findings demonstrate that TRIM21 plays a previously unrecognized role in the negative regulation of NF-kappa B-dependent proinflammatory cytokine responses, and suggest that multiple TRIM proteins contribute to the maintenance of functional equilibrium in inflammatory responses, in part through functional redundancy. The Journal of Immunology, 2009, 182: 7527-7538.
C1 [Yoshimi, Ryusuke; Chang, Tsung-Hsien; Atsumi, Toru; Ozato, Keiko] NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA.
[Wang, Hongsheng; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA.
RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6,Room 2A01,6 Ctr Dr, Bethesda, MD 20892 USA.
EM hmorse@niaid.nih.gov; ozatok@nih.gov
OI Morse, Herbert/0000-0002-9331-3705; Yoshimi, Ryusuke/0000-0002-3945-307X
FU National Institutes of Health; National Institute of Child Health and
Human Development; National Institute of Allergy and Infectious
Diseases; Japan Society for the Promotion of Science Research
FX This work Was Supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Child Health and
Human Development, and National Institute of Allergy and Infectious
Diseases. R.Y. and T.A. were supported in part by the Japan Society for
the Promotion of Science Research Fellowship for Japanese Biomedical and
Behavioral Researchers at the National Institutes of Health.
NR 50
TC 68
Z9 69
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 JUN 15
PY 2009
VL 182
IS 12
BP 7527
EP 7538
DI 10.4049/jimmunol.0804121
PG 12
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900023
PM 19494276
ER
PT J
AU Castro, I
Wright, JA
Damdinsuren, B
Hoek, KL
Carlesso, G
Shinners, NP
Gerstein, RM
Woodland, RT
Sen, R
Khan, WN
AF Castro, Iris
Wright, Jacqueline A.
Damdinsuren, Bazarragchaa
Hoek, Kristen L.
Carlesso, Gianluca
Shinners, Nicholas P.
Gerstein, Rachel M.
Woodland, Robert T.
Sen, Ranjan
Khan, Wasif N.
TI B Cell Receptor-Mediated Sustained c-Rel Activation Facilitates Late
Transitional B Cell Survival through Control of B Cell Activating Factor
Receptor and NF-kappa B2
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID KAPPA-B; MARGINAL ZONE; LYMPHOCYTE-PROLIFERATION; POSITIVE SELECTION;
SIGNALING PATHWAY; TYROSINE KINASE; MICE LACKING; BAFF; EXPRESSION;
IMMATURE
AB Signaling from the BCR anti B cell activating factor receptor (BAFF-R or BR3) differentially regulates apoptosis within early transitional (T1) and late transitional (T2; CD21(int)-T2) B cells during selection processes to generate mature B lymphocytes. However, molecular mechanisms underlying the differential sensitivity of transitional B cells to apoptosis remain unclear. In this study, we demonstrate that BC R signaling induced more long-term c-Rel activation in T2 anti mature than in T1 B cells leading to increased expression of anti-apoptotic genes as well as prosurvival BAFF-R and its downstream substrate p100 (NF-kappa B2). Sustained c-Rel activation required de novo c-Rel gene transcription and translation via Btk-dependent mechanisms. Like T1 cells, mature B cells from Btk- and c-Rel-deficient mice also failed to activate these genes. These findings suggest that the gain of survival potential within transitional 13 cells is dependent on the ability to produce a long-term c-Rel response, which plays a critical role in T2 B cell survival and differentiation in vivo by inducing anti-apoptotic genes, BAFF-R and NF-kappa B2, an essential component for BAFF-R survival signaling. Thus, acquisition of resistance to apoptosis during transitional B cell maturation is achieved by integration of BCR and BAFF-R signals. The Journal of Immunology, 2009, 182: 7729-7737.
C1 [Castro, Iris; Wright, Jacqueline A.; Hoek, Kristen L.; Carlesso, Gianluca; Shinners, Nicholas P.; Khan, Wasif N.] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA.
[Castro, Iris; Wright, Jacqueline A.; Khan, Wasif N.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA.
[Damdinsuren, Bazarragchaa] NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA.
[Gerstein, Rachel M.; Woodland, Robert T.] Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA.
RP Khan, WN (reprint author), Univ Miami, Leonard Miller Sch Med, Dept Microbiol & Immunol, 1600 NW 10th Ave, Miami, FL 33136 USA.
EM wnkhan@med.miami.edu
FU National Institutes of Health [AI060729, AI041054, AI057463, AI043534,
P30DK32520, DK32520, T32 HL69715-0, T32 CA09385-20, 5 T32 HL069765]
FX This study is supported in part by National Institutes of Health
AI060729 (to W.N.K.), AI041054 and AI057463 (to R.T.W), AI043534 (to
R.M.G), P30DK32520 (to University of Massachusetts Medical Flow
Cytometry Core) and DK32520 (to the University of Miami Miller School of
Medicine Diabetes and Endocrinology Center). K.L.H and N.P.S. are
supported by NIH T32 HL69715-0. I.C. by NIH T32 CA09385-20 and J.A.W. by
NIH 5 T32 HL069765. B.D. and R.S. are supposed by intramural research
program of the National Institute of Health on Aging, Baltimore, MD.
NR 49
TC 25
Z9 26
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2009
VL 182
IS 12
BP 7729
EP 7737
DI 10.4049/jimmunol.0803281
PG 9
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900044
PM 19494297
ER
PT J
AU Barlic, J
Zhu, WJ
Murphy, PM
AF Barlic, Jana
Zhu, Wenjia
Murphy, Philip M.
TI Atherogenic Lipids Induce High-Density Lipoprotein Uptake and
Cholesterol Efflux in Human Macrophages by Up-Regulating Transmembrane
Chemokine CXCL16 without Engaging CXCL16-Dependent Cell Adhesion
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; ATHEROSCLEROTIC LESION DEVELOPMENT; ACTIVATED
RECEPTOR-GAMMA; CORONARY-ARTERY-DISEASE; SCAVENGER RECEPTOR; SR-PSOX;
ACCELERATES ATHEROSCLEROSIS; INTERFERON-GAMMA; HUMAN ATHEROMA; OXIDIZED
LDL
AB Atherosclerosis is a complex pathologic process in which chemokine-mediated leukocyte accumulation in arterial walls is thought to be an important mechanism of pathogenesis. An interesting exception to this paradigm is the chemokine CXCL16, also known as the scavenger receptor for phosphatidylserine and oxidized low density lipoprotein, which is highly expressed in mouse and human atherosclerotic lesions, yet appears to be atheroprotective. In this study, we address potential mechanisms responsible for this activity. Consistent with its presence in atherosclerotic plaque, we found that atherogenic lipids up-regulated CXCL16 in primary human monocyte-derived macrophages. However, the same lipids down-regulated the CXCL16-targeted protease ADAM10, resulting in preferential expression of CXCL16 as the transmembrane form, not the shed form. Although transmembrane CXCL16 is known to mediate cell-cell adhesion by binding its receptor CXCR6, and atherogenic lipids are known to stimulate macrophage adhesion to coronary artery smooth muscle cells, we found that heterotypic adhesion of these cell types occurred in a CXCL16-independent manner. Instead we found that in macrophages, CXCL16 promoted internalization of both oxidized low density lipoprotein and high density lipoprotein, as well as release of cholesterol. Moreover, CXCL16 deficiency in macrophages interfered with oxidized low density lipoprotein-induced up-regulation of atheroprotective genes: adenosine triphosphate-binding cassette transporter A1 and G1 as well as apolipoprotein E. Thus, our findings support the hypothesis that CXCL16 mediates atheroprotection through its scavenger role in macrophages and not by cell-cell adhesion. The Journal of Immunology, 2009, 182: 7928-7936.
C1 [Barlic, Jana; Zhu, Wenjia; Murphy, Philip M.] NIAID, Mol Signalling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Barlic, Jana] Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA.
RP Murphy, PM (reprint author), NIAID, Mol Signalling Sect, Lab Mol Immunol, NIH, Bldg 10,Room 11N113,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pmm@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Wellcome Trust Career Development Award in Basic
Biomedical Sciences Reference [081169]
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, and in part by Wellcome Trust Career Development
Award in Basic Biomedical Sciences Reference 081169 (to J.B.).
NR 58
TC 19
Z9 20
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 JUN 15
PY 2009
VL 182
IS 12
BP 7928
EP 7936
DI 10.4049/jimmunol.0804112
PG 9
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900064
PM 19494317
ER
PT J
AU Lindenstrom, T
Agger, EM
Korsholm, KS
Darrah, PA
Aagaard, C
Seder, RA
Rosenkrands, I
Andersen, P
AF Lindenstrom, Thomas
Agger, Else Marie
Korsholm, Karen S.
Darrah, Patricia A.
Aagaard, Claus
Seder, Robert A.
Rosenkrands, Ida
Andersen, Peter
TI Tuberculosis Subunit Vaccination Provides Long-Term Protective Immunity
Characterized by Multifunctional CD4 Memory T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MYCOBACTERIUM-TUBERCULOSIS; CATIONIC LIPOSOMES; INTERFERON-GAMMA;
LEISHMANIA-MAJOR; RESPONSES; IMMUNIZATION; OPTIMIZATION; PERSISTENCE;
LYMPHOCYTES; GENERATION
AB Improved vaccines capable of promoting long-term cellular immunity are urgently required for a number of diseases that remain global health problems. In the present study, we demonstrate that a tuberculosis subunit vaccine, Ag85B-ESAT-6/CAF01 (where ESAT-6 is early secreted antigenic target of 6 kDa and CAF01 is cationic adjuvant formulation 0l), induces very robust memory CD4 T cell responses that are maintained at high levels for >1 year postvaccination. This long-term, vaccine-induced memory response protects against a challenge with Mycobacterium tuberculosis at levels that are comparable to or better than those of bacillus Calmette-Guerin. Characterization of the CD4 memory T cells by multicolor flow cytometry demonstrated that the long-lived memory population consisted almost exclusively of TNF-alpha(+)IL-2(+) and IFN-gamma(+)TNF-alpha(+)IL-2(+) multifunctional T cells. In addition, memory cells isolated >1 year postvaccination maintained a strong, vaccine-specific proliferative potential. Long-term memory induced by the BCG vaccine contained fewer multifunctional T cells and was biased toward effector cells mainly of the TNF-alpha(+)IFN-gamma(+)-coexpressing subset. Ag85B-ESAT-6/CAF01 vaccination very efficiently sustained multifunctional CD4 T cells that accumulated at the site of infection after M. tuberculosis challenge, whereas the response in unvaccinated animals was characterized by CD4 effector T cells. Our data demonstrate that adjuvanted subunit vaccines can promote long-term protective immune responses characterized by high levels of persisting multifunctional T cells and that the quality and profile of this response is sustained postinfection. The Journal of Immunology, 2009, 182: 8047-8055.
C1 [Lindenstrom, Thomas; Agger, Else Marie; Korsholm, Karen S.; Aagaard, Claus; Rosenkrands, Ida; Andersen, Peter] Statens Serum Inst, Dept Infect Dis Immunol, DK-2300 Copenhagen S, Denmark.
[Darrah, Patricia A.; Seder, Robert A.] NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Andersen, P (reprint author), Statens Serum Inst, Dept Infect Dis Immunol, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
EM THI@ssi.dk; PA@ssi.dk
FU European Commission [LSHP-CT-2003-503367]; Danish Agency for Science
Technology and Innovation (Medical Sciences) [271-05-0440]
FX This study was funded by the European Commission's TB Vaccine Cluster
(TB-VAC) project, contract no. LSHP-CT-2003-503367. Additional funding
was provided by Danish Agency for Science Technology and Innovation
(Medical Sciences) Grant 271-05-0440.
NR 32
TC 186
Z9 192
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2009
VL 182
IS 12
BP 8047
EP 8055
PG 9
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900077
PM 19494330
ER
PT J
AU Kari, L
Whitmire, WM
Crane, DD
Reveneau, N
Carlson, JH
Goheen, MM
Peterson, EM
Pal, S
de la Maza, LM
Caldwell, HD
AF Kari, Laszlo
Whitmire, William M.
Crane, Deborah D.
Reveneau, Nathalie
Carlson, John H.
Goheen, Morgan M.
Peterson, Ellena M.
Pal, Sukumar
de la Maza, Luis M.
Caldwell, Harlan D.
TI Chlamydia trachomatis Native Major Outer Membrane Protein Induces
Partial Protection in Nonhuman Primates: Implication for a Trachoma
Transmission-Blocking Vaccine
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID INCLUSION CONJUNCTIVITIS; MONOCLONAL-ANTIBODIES; GENITAL CHALLENGE;
IMMUNE-RESPONSE; CELL EPITOPES; ANIMAL-MODEL; FIELD TRIAL; T-HELPER;
NEUTRALIZATION; IMMUNIZATION
AB A vaccine is likely the most effective strategy for controlling human chlamydial infections. Recent studies have shown immunization with Chlamydia muridarum major outer membrane protein (MOMP) can induce significant protection against infection and disease in mice if its native trimeric structure is preserved (nMOMP). The objective of this study was to investigate the immunogenicity and vaccine efficacy of Chlamydia trachomatis nMOMP in a nonhuman primate trachoma model. Cynomolgus monkeys (Macaca fascicularis) were immunized systemically with nMOMP, and monkeys were challenged ocularly. Immunization induced high serum IgG and IgA ELISA Ab titers, with Abs displaying high strain-specific neutralizing activity. The PBMCs of immunized monkeys produced a broadly cross-reactive, Ag-specific IFN-gamma response equivalent to that induced by experimental infection. Immunized monkeys exhibited a significant decrease in infectious burden during the early peak shedding periods (days 3-14). However, at later time points, they exhibited no difference from control animals in either burden or duration of infection. Immunization had no effect on the progression of ocular disease. These results show that systemically administered nMOMP is highly immunogenic in nonhuman primates and elicits partially protective immunity against ocular chlamydial challenge. This is the first time a subunit vaccine has shown a significant reduction in ocular shedding in nonhuman primates. A partially protective vaccine, particularly one that reduces infectious burden after primary infection of children, could interrupt the natural trachoma reinfection cycle. This would have a beneficial effect on the transmission between children and sensitized adults which drives blinding inflammatory disease. The Journal of Immunology, 2009, 182: 8063-8070.
C1 [Kari, Laszlo; Whitmire, William M.; Crane, Deborah D.; Reveneau, Nathalie; Carlson, John H.; Goheen, Morgan M.; Caldwell, Harlan D.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Peterson, Ellena M.; Pal, Sukumar; de la Maza, Luis M.] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA.
RP Caldwell, HD (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM hcaldwell@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health; National Institute of Allergy and Infectious
Diseases [AI-32248]
FX This work was supported in part by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health, and by Public Health Service Grant AI-32248 (to
L.M.de la M.) from the National Institute of Allergy and Infectious
Diseases, National Institutes of Health.
NR 48
TC 52
Z9 57
U1 1
U2 10
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2009
VL 182
IS 12
BP 8063
EP 8070
PG 8
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900079
PM 19494332
ER
PT J
AU Yoshinobu, K
Baudino, L
Santiago-Raber, ML
Morito, N
Dunand-Sauthier, I
Morley, BJ
Evans, LH
Izui, S
AF Yoshinobu, Kumiko
Baudino, Lucie
Santiago-Raber, Marie-Laure
Morito, Naoki
Dunand-Sauthier, Isabelle
Morley, Bernard J.
Evans, Leonard H.
Izui, Shozo
TI Selective Up-Regulation of Intact, but Not Defective env RNAs of
Endogenous Modified Polytropic Retrovirus by the Sgp3 Locus of
Lupus-Prone Mice
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MURINE LEUKEMIA-VIRUS; GP70 IMMUNE-COMPLEXES; CELL-SURFACE RECEPTOR;
NEW-ZEALAND MICE; SYSTEMIC-LUPUS; DNA METHYLATION; BXSB MICE;
AUTOANTIBODY PRODUCTION; ENVELOPE GLYCOPROTEIN; ANTIBODY REACTIVITY
AB Endogenous retroviruses are implicated in the pathogenesis of systemic lupus erythematosus (SLE). Because four different classes of endogenous retroviruses, i.e., ecotropic, xenotropic, polytropic, or modified polytropic (mPT), are expressed in mice, we investigated the possibility that a particular class of endogenous retroviruses is associated with the development of murine SLE. We observed >15-fold increased expression of mPT env (envelope) RNA in livers of all four lupus-prone mice, as compared with those of nine nonautoimmune strains of mice. This was not the case for the three other classes of retroviruses. Furthermore, we found that in addition to intact mPT transcripts, many strains of mice expressed two defective mPT env transcripts which carry a deletion in the env sequence of the 3' portion of the gp70 surface protein and the 5' portion of the p15E transmembrane protein, respectively. Remarkably, in contrast to nonautoimmune strains of mice, all four lupus-prone mice expressed abundant levels of intact mPT env transcripts, but only low or nondetectable levels of the mutant env transcripts. The Sgp3 (serum gp70 production 3) locus derived from lupus-prone mice was responsible for the selective up-regulation of the intact mPT env RNA. Finally, we observed that single-stranded RNA-specific TLR7 played a critical role in the production of anti-gp70 autoantibodies. These data suggest that lupus-prone mice may possess a unique genetic mechanism responsible for the expression of mPT retroviruses, which could act as a triggering factor through activating TLR7 for the development of autoimmune responses in mice predisposed to SLE. The Journal of Immunology, 2009, 182: 8094-8103.
C1 [Yoshinobu, Kumiko; Baudino, Lucie; Santiago-Raber, Marie-Laure; Morito, Naoki; Dunand-Sauthier, Isabelle; Izui, Shozo] Univ Geneva, Dept Pathol & Immunol, Ctr Med Univ, CH-1211 Geneva 4, Switzerland.
[Morley, Bernard J.] Univ London Imperial Coll Sci Technol & Med, Mol Genet & Rheumatol Sect, London, England.
[Evans, Leonard H.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Izui, S (reprint author), Univ Geneva, Dept Pathol & Immunol, Ctr Med Univ, CH-1211 Geneva 4, Switzerland.
EM Shozo.Izui@unige.ch
FU Swiss National Foundation for Scientific Research; National Institute of
Allergy and Infectious Diseases; National Institutes of Health
FX This work was supported by a grant from the Swiss National Foundation
for Scientific Research. L.H.E. was supported by the intramural research
program of the National Institute of Allergy and Infectious Diseases,
National Institutes of Health.
NR 58
TC 23
Z9 23
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2009
VL 182
IS 12
BP 8094
EP 8103
PG 10
WC Immunology
SC Immunology
GA 456HD
UT WOS:000266833900082
PM 19494335
ER
PT J
AU Zhou, L
Liao, QH
Dong, LB
Huai, Y
Bai, T
Xiang, NJ
Shu, YL
Liu, W
Wang, SW
Qin, PZ
Wang, M
Xing, XS
Lv, J
Chen, RY
Feng, ZJ
Yang, WZ
Uyeki, TM
Yu, HJ
AF Zhou, Lei
Liao, Qiaohong
Dong, Libo
Huai, Yang
Bai, Tian
Xiang, Nijuan
Shu, Yuelong
Liu, Wei
Wang, Shiwen
Qin, Pengzhe
Wang, Min
Xing, Xuesen
Lv, Jun
Chen, Ray Y.
Feng, Zijian
Yang, Weizhong
Uyeki, Timothy M.
Yu, Hongjie
TI Risk Factors for Human Illness with Avian Influenza A (H5N1) Virus
Infection in China
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID TO-PERSON TRANSMISSION; HONG-KONG; POULTRY; DUCKS; ASIA; MARKETS;
VACCINATION; EVOLUTION; CHICKENS; BIRDS
AB Background. In China, 30 human cases of avian influenza A (H5N1) virus infection were identified through July 2008. We conducted a retrospective case-control study to identify risk factors for influenza H5N1 disease in China.
Methods. A questionnaire about potential influenza H5N1 exposures was administered to 28 patients with influenza H5N1 and to 134 randomly selected control subjects matched by age, sex, and location or to proxies. Conditional logistic regression analyses were performed.
Results. Before their illness, patients living in urban areas had visited wet poultry markets, and patients living in rural areas had exposure to sick or dead backyard poultry. In multivariable analyses, independent risk factors for influenza H5N1 were direct contact with sick or dead poultry (odds ratio [OR], 506.6 [95% confidence interval {CI}, 15.7-16319.6]; P < .001), indirect exposure to sick or dead poultry (OR, 56.9 [95% CI, 4.3-745.6]; P = .002), and visiting a wet poultry market (OR, 15.4 [95% CI, 3.0-80.2]; P = .001).
Conclusions. To prevent human influenza H5N1 in China, the level of education about avoiding direct or close exposures to sick or dead poultry should be increased, and interventions to prevent the spread of influenza H5N1 at live poultry markets should be implemented.
C1 [Zhou, Lei; Liao, Qiaohong; Huai, Yang; Xiang, Nijuan; Feng, Zijian; Yang, Weizhong; Yu, Hongjie] Peking Univ, Sch Publ Hlth, Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent,Off Dis Con, Beijing 100871, Peoples R China.
[Dong, Libo; Bai, Tian; Shu, Yuelong; Wang, Shiwen; Wang, Min] Peking Univ, Sch Publ Hlth, Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent,State Key L, Beijing 100871, Peoples R China.
[Lv, Jun] Peking Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Beijing 100871, Peoples R China.
[Liu, Wei] Wuhan Ctr Dis Control & Prevent, Wuhan, Peoples R China.
[Liu, Wei] Hubei Prov Ctr Dis Control & Prevent, Wuhan, Peoples R China.
[Qin, Pengzhe] Guangzhou Ctr Dis Control & Prevent, Guangzhou, Guangdong, Peoples R China.
[Chen, Ray Y.] NIAID, NIH, Bethesda, MD 20892 USA.
[Uyeki, Timothy M.] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
RP Yu, HJ (reprint author), China CDC, Off Dis Control & Emergency Response, 27 Nanwei Rd, Beijing 100050, Peoples R China.
EM yuhj@chinacdc.cn
OI Chen, Ray/0000-0001-6344-1442
FU US National Institutes of Health [U19 AI51915]; Ministry of Science and
Technology of the People's Republic of China [2004BA519A17,
2004BA519A71, 2006BAD06A02]
FX US National Institutes of Health (Comprehensive International Program
for Research on AIDS grant U19 AI51915); Ministry of Science and
Technology of the People's Republic of China (2004BA519A17, 2004BA519A71
and 2006BAD06A02).
NR 44
TC 63
Z9 71
U1 3
U2 17
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 15
PY 2009
VL 199
IS 12
BP 1726
EP 1734
DI 10.1086/599206
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 448BM
UT WOS:000266236500004
PM 19416076
ER
PT J
AU Babu, S
Kumaraswami, V
Nutman, TB
AF Babu, Subash
Kumaraswami, V.
Nutman, Thomas B.
TI Alternatively Activated and Immunoregulatory Monocytes in Human Filarial
Infections
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID ANTIGEN-PRESENTING CELLS; NITRIC-OXIDE; LYMPHATIC FILARIASIS;
BRUGIA-MALAYI; HELMINTH INFECTION; DIVERGENT ROLES; ARGINASE-I;
MACROPHAGES; EXPRESSION; MICROFILARIAE
AB Background. Monocytes/macrophages from filaria-infected animals exhibit an alternatively activated phenotype; however, very little is known about the alternative activation phenotype of monocytes in human filarial infection.
Methods. To elucidate the activation and cytokine profile of monocytes in human filarial infection, we examined the expression patterns of genes encoding arginase, nitric oxide synthase 2, alternative activation markers, and cytokines in monocytes from individuals with asymptomatic filarial infection and individuals without filarial infection, ex vivo and in response to filarial antigen (Brugia malayi antigen [BmA]).
Results. Monocytes from patients with asymptomatic filarial infection exhibited significantly diminished expression of NOS2 and significantly enhanced expression of ARG1. These changes were associated with significantly increased expression of the genes encoding resistin, mannose receptor C type 1 (MRC1), macrophage galactose type C lectin (MGL), and chemokine ligand 18 (CCL18). In response to BmA, purified monocytes from infected individuals also expressed significantly lower levels of interleukin (IL)-12 and IL-18 but, in contrast, expressed significantly higher levels of transforming growth factor beta, IL-10, and suppressor of cytokine signaling 1 mRNA. Inhibition of arginase-1 resulted in significantly diminished expression of the genes encoding resistin, MRC1, MGL, and CCL18, as well as significantly enhanced expression of NOS2 and the genes encoding IL-12 and IL-18.
Conclusion. Patent human filarial infection is associated with the presence of monocytes characterized by an alternatively activated immunoregulatory phenotype.
C1 [Babu, Subash] NIH ICER, TB Res Ctr, Madras 600031, Tamil Nadu, India.
[Babu, Subash] SAIC Frederick, Frederick, MD USA.
[Babu, Subash] NCI, Frederick, MD 21701 USA.
[Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Babu, S (reprint author), NIH ICER, TB Res Ctr, Mayor Ramanathan Rd, Madras 600031, Tamil Nadu, India.
EM sbabu@mail.nih.gov
FU Intramural Research Program, Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX Intramural Research Program, Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 35
TC 49
Z9 51
U1 0
U2 5
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 15
PY 2009
VL 199
IS 12
BP 1827
EP 1837
DI 10.1086/599090
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 448BM
UT WOS:000266236500016
PM 19456233
ER
PT J
AU Guadalupe, I
Mitre, E
Benitez, S
Chico, ME
Nutman, TB
Cooper, PJ
AF Guadalupe, Irene
Mitre, Edward
Benitez, Susana
Chico, Martha E.
Nutman, Thomas B.
Cooper, Philip J.
TI Evidence for In Utero Sensitization to Ascaris lumbricoides in Newborns
of Mothers with Ascariasis
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID INDUCED INTERLEUKIN-10; INFECTED MOTHERS; SKIN-TEST; HELMINTH;
REACTIVITY; SCHISTOSOMIASIS; CHILDHOOD; IMMUNITY; MANSONI; ATOPY
AB Ascaris lumbricoides infections in humans may have important effects on the development of allergy and on susceptibility to infectious diseases that start during early life. To investigate whether sensitization to A. lumbricoides occurs in utero, we measured interferon (IFN)-gamma and interleukin (IL)-4 responses in A. lumbricoides antigen-stimulated cord blood from newborns of infected and noninfected mothers by flow cytometry. There was evidence of higher frequencies of IFN-gamma-expressing and IL-4-expressing CD4(+) T cells in newborns of infected mothers than in newborns of noninfected mothers. Our data provide evidence of in utero sensitization to A. lumbricoides and raise the possibility that the immunological effects of infection start in the fetus.
C1 [Guadalupe, Irene; Benitez, Susana; Chico, Martha E.; Cooper, Philip J.] Lab Invest FEPIS, Quininde, Esmeraldas Prov, Ecuador.
[Cooper, Philip J.] Univ San Francisco, Inst Microbiol, Quito, Ecuador.
[Mitre, Edward] Uniformed Serv Univ Hlth Sci, Dept Microbiol, Bethesda, MD 20814 USA.
[Nutman, Thomas B.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Cooper, Philip J.] St Georges Univ London, Ctr Infect, London, England.
RP Cooper, PJ (reprint author), Hosp Pedro Vicente Maldonado, Casilla 17-14-39, Quito, Ecuador.
EM pcooper@ecnet.ec
FU Wellcome Trust [074679/Z/04/Z]; Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX Wellcome Trust (grant 074679/Z/04/Z); Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 15
TC 18
Z9 20
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 15
PY 2009
VL 199
IS 12
BP 1846
EP 1850
DI 10.1086/599214
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 448BM
UT WOS:000266236500018
PM 19426111
ER
PT J
AU Singh, DK
Anastos, K
Hoover, DR
Burk, RD
Shi, QH
Ngendahayo, L
Mutimura, E
Cajigas, A
Bigirimani, V
Cai, XT
Rwamwejo, J
Vuolo, M
Cohen, M
Castle, PE
AF Singh, Diljeet K.
Anastos, Kathryn
Hoover, Donald R.
Burk, Robert D.
Shi, Qiuhu
Ngendahayo, Louis
Mutimura, Eugene
Cajigas, Antonio
Bigirimani, Venerand
Cai, Xiaotao
Rwamwejo, Janvier
Vuolo, Magalis
Cohen, Mardge
Castle, Philip E.
TI Human Papillomavirus Infection and Cervical Cytology in HIV-Infected and
HIV-Uninfected Rwandan Women
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 37th Annual Meeting of the Society-of-Gynecologic-Oncologists
CY MAR 22-26, 2006
CL Palm Springs, CA
SP Soc Gynecol Oncol
ID RANDOMIZED CONTROLLED-TRIAL; PARTICLE VACCINE; YOUNG-WOMEN; SUSTAINED
EFFICACY; DOUBLE-BLIND; FOLLOW-UP; TYPE-18; CANCER; LESIONS;
METAANALYSIS
AB Background. Data on human papillomavirus (HPV) prevalence are essential for developing cost-effective cervical cancer prevention programs.
Methods. In 2005, 710 human immunodeficiency virus (HIV)-positive and 226 HIV-negative Rwandan women enrolled in an observational prospective cohort study. Sociodemographic data, CD4(+) cell counts, and cervical specimens were obtained. Cervicovaginal lavage specimens were collected from each woman and tested for >40 HPV types by a polymerase chain reaction assay; HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 were considered primary carcinogenic HPV types.
Results. The prevalence of HPV was higher in HIV-positive women than in HIV-negative women in all age groups. Among HIV-infected women, 69% were positive for >= 1 HPV type, 46% for a carcinogenic HPV type, and 10% for HPV-16. HPV prevalence peaked at 75% in the HIV-positive women aged 25-34 years and then declined with age to 37.5% in those >= 55 years old (P(trend) < .001). A significant trend of higher prevalence of HPV and carcinogenic HPV with lower CD4(+) cell counts and increasing cytologic severity was seen among HIV-positive women.
Conclusions. We found a higher prevalence of HPV infection in HIV-positive than in HIV-negative Rwandan women, and the prevalence of HPV and carcinogenic HPV infection decreased with age.
C1 [Singh, Diljeet K.] Northwestern Univ, Div Gynecol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Cohen, Mardge] Cook Cty Hosp, Chicago, IL 60612 USA.
[Anastos, Kathryn; Cajigas, Antonio; Vuolo, Magalis] Montefiore Med Ctr, Bronx, NY 10467 USA.
[Anastos, Kathryn; Burk, Robert D.; Cajigas, Antonio; Vuolo, Magalis] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Cai, Xiaotao] Data Solut, Bronx, NY USA.
[Shi, Qiuhu] New York Med Coll, Valhalla, NY 10595 USA.
[Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA.
[Hoover, Donald R.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA.
[Castle, Philip E.] NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Ngendahayo, Louis] Natl Univ Rwanda, Butare, Rwanda.
[Mutimura, Eugene] Womens Equ Access Care & Treatment, Kigali, Rwanda.
[Bigirimani, Venerand; Rwamwejo, Janvier] King Faisal Hosp, Kigali, Rwanda.
RP Singh, DK (reprint author), 250 E Super St 5-2168, Chicago, IL 60611 USA.
EM dsingh2@nmff.org
FU Intramural NIH HHS; NIAID NIH HHS [U01 AI035004, AI-51519, U01
AI035004-15, U01-AI-35004, P30 AI051519]; NIDDK NIH HHS [DK54615, R01
DK054615]
NR 26
TC 40
Z9 41
U1 1
U2 4
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 15
PY 2009
VL 199
IS 12
BP 1851
EP 1861
DI 10.1086/599123
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 448BM
UT WOS:000266236500019
PM 19435429
ER
PT J
AU De Bruyne, S
Boos, TL
Wyffels, L
Goeman, JL
Rice, KC
De Vos, F
AF De Bruyne, S.
Boos, T. L.
Wyffels, L.
Goeman, J. L.
Rice, K. C.
De Vos, F.
TI Synthesis, radiosynthesis and in vivo evaluation of
[I-123]-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidi
ne as a selective tracer for imaging the dopamine transporter
SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
LA English
DT Article
DE dopamine transporter; SPECT;
[I-123]-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidi
ne; brain
ID HIGH-AFFINITY; PARKINSONS-DISEASE; UPTAKE SITES; HUMAN BRAIN; BETA-CIT;
BINDING; SYSTEM; AUTORADIOGRAPHY; RECEPTORS; MONKEY
AB Dopamine transporter (DAT) neuroimaging is a useful tool in Parkinson's disease diagnosis, staging and follow-up providing information on the integrity of the dopaminergic neurotransmitter system in vivo. 4-(2-(Bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine (7) has nanomolar affinity for DAT and better selectivity over the other monoamine transporters compared with the existing SPECT radioligands for DAT. The aim of this study was to synthesize and evaluate [I-123]-7 as an in vivo tracer for DAT.
The tributylstannyl precursor was synthesized with an overall yield of 25%. [I-123]-7 was synthesized by electrophilic destannylation with a yield of 40 +/- 10%. Radiochemical purity appeared to be >98%, whereas specific activity was at least 667GBq/mu mol. Biodistribution studies in mice showed brain uptake of 0.96 +/- 0.53%ID/g at 30 s post injection (p.i.) and 0.26 +/- 0.02%ID/g at 3 h p.i. High blood activity was observed at all time points. Pretreatment with Cyclosporin A raised brain uptake indicating that [I-123]-7 is transported by P-glycoprotein (P-gp) pumps. In rats, regional brain distribution of [I-123]-7 was not in agreement with DAT distribution. These results indicate that [I-123]-7 is not suitable for mapping DAT in vivo but could be a useful tracer for the P-gp transporter.
C1 [De Bruyne, S.; Wyffels, L.; De Vos, F.] Univ Ghent, Lab Radiopharm, B-9000 Ghent, Belgium.
[Boos, T. L.; Rice, K. C.] Natl Inst Drug Abuse, Chem Biol Res Branch, NIH, Bethesda, MD USA.
[Boos, T. L.; Rice, K. C.] NIAAA, NIH, Bethesda, MD USA.
[Goeman, J. L.] Univ Ghent, Dept Organ Chem, B-9000 Ghent, Belgium.
RP De Vos, F (reprint author), Univ Ghent, Lab Radiopharm, Harelbekestr 72, B-9000 Ghent, Belgium.
EM filipxdevos@ugent.be
OI wyffels, Leonie/0000-0002-5618-8191
FU National Institute on Drug Abuse; National Institute on Alcohol Abuse
and Alcoholism; National Institutes of Health
FX The authors thank the PhD student Liesbet Vervoort (Laboratory for
Radiopharmacy, Ghent University, Belgium) for her assistance in the mice
studies. This work was supported in part by the Intramural Research
Programs of the National Institute on Drug Abuse, the National Institute
on Alcohol Abuse and Alcoholism and the National Institute on Diabetes,
Digestive and Kidney Diseases of the National Institutes of Health.
NR 31
TC 1
Z9 1
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0362-4803
J9 J LABELLED COMPD RAD
JI J. Label. Compd. Radiopharm.
PD JUN 15
PY 2009
VL 52
IS 7-8
BP 304
EP 311
DI 10.1002/jlcr.1603
PG 8
WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry,
Analytical
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 479VS
UT WOS:000268690300033
PM 19746191
ER
PT J
AU Wurtz, RH
AF Wurtz, Robert H.
TI Recounting the impact of Hubel and Wiesel
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Review
ID STRIATE CORTEX NEURONS; SINGLE UNIT ACTIVITY; RECEPTIVE FIELDS;
VISUAL-CORTEX; EYE MOVEMENTS; FUNCTIONAL ARCHITECTURE; UNRESTRAINED
CATS; RHESUS-MONKEY; OPTIC TRACT; ATTENTION
AB David Hubel and Torsten Wiesel provided a quantum step in our understanding of the visual system. In this commemoration of the 50th year of their initial publication, I would like to examine two aspects of the impact of their work. First, from the viewpoint of those interested in the relation of brain to behaviour, I recount why their initial experiments produced such an immediate impact. Hubel and Wiesel's work appeared against a background of substantial behavioural knowledge about visual perception, a growing desire to know the underlying brain mechanisms for this perception, and an abysmal lack of physiological information about the neurons in visual cortex that might underlie these mechanisms. Their initial results showed both the transformations that occur from one level of processing to the next and how a sequence of these transformations might lead to at least the elements of pattern perception. Their experiments immediately provided a structure for conceptualizing how cortical neurons could be organized to produce perception. A second impact of Hubel and Wiesel's work has been the multiple paths of research they blazed. I comment here on just one of these paths, the analysis of visual cortex in the monkey, particularly in the awake monkey. This direction has led to an explosion in the number of investigations of cortical areas beyond striate cortex and has addressed more complex behavioural questions, but it has evolved from the approach to neuronal processing pioneered by Hubel and Wiesel.
C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Rm 2A50, Bethesda, MD 20892 USA.
EM bob@lsr.nei.nih.gov
FU NIH
FX This research was supported by the Intramural Research Program of the
National Eye Institute, NIH.
NR 43
TC 7
Z9 7
U1 0
U2 12
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD JUN 15
PY 2009
VL 587
IS 12
BP 2817
EP 2823
DI 10.1113/jphysiol.2009.170209
PG 7
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 458AJ
UT WOS:000266981400016
PM 19525566
ER
PT J
AU Portis, JL
Askovich, P
Austin, J
Gutierrez-Cotto, Y
McAtee, FJ
AF Portis, J. L.
Askovich, P.
Austin, J.
Gutierrez-Cotto, Y.
McAtee, F. J.
TI The Degree of Folding Instability of the Envelope Protein of a
Neurovirulent Murine Retrovirus Correlates with the Severity of the
Neurological Disease
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; INDUCED SPONGIFORM NEURODEGENERATION;
LEUKEMIA-VIRUS-TB; MOTOR NEURON DISEASE; PARALYTOGENIC MUTANT; OXIDATIVE
STRESS; INFECTED-CELLS; FRIEND; MICE; RECEPTOR
AB A small group of ecotropic murine retroviruses cause a spongiform neurodegenerative disease manifested by tremor, paralysis, and wasting. The neurovirulence of these viruses has long been known to be determined by the sequence of the viral envelope protein, although the nature of the neurotoxicity remains to be clarified. Studies on the neurovirulent viruses FrCas(NC) and Moloney murine leukemia virus ts1 indicate that the nascent envelope protein misfolds, is retained in the endoplasmic reticulum (ER), and induces an unfolded protein response. In the present study we constructed a series of viruses with chimeric envelope genes containing segments from virulent and avirulent retroviruses. Each of the viruses studied was highly neuroinvasive but differed in the severity of the neurological disease they induced. Only viruses that contained the receptor-binding domain (RBD) of the neurovirulent virus induced neurological disease. Likewise, only viruses containing the RBD of the neurovirulent virus exhibited increased binding of the ER chaperone BiP to the envelope precursor protein and induced the unfolded protein response. Thus, the RBD determined both neurovirulence and folding instability. Among viruses carrying the neurovirulent RBD, the severity of the disease was increased when envelope sequences from the neurovirulent virus outside the RBD were also present. Interestingly, these sequences appeared to further increase the degree of folding instability (BiP binding) of the viral envelope protein. These results provide strong support for the hypothesis that this spongiform neurodegenerative disease represents a virus-induced protein folding disorder.
C1 [Portis, J. L.; Askovich, P.; Austin, J.; Gutierrez-Cotto, Y.; McAtee, F. J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Portis, JL (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM jportis@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health
FX We thank Cynthia Martellero of the Laboratory of Persistent Viral
Diseases (LPVD), RML, for technical assistance and Gary Hettrick of the
Visual Medical Arts Department, RML, for assembling the figures. We also
are grateful to Bruce Chesebro and Kim Hasenkrug of LPVD, RML, and Sonja
Best of Laboratory of Virology, RML, for reading and critiquing the
manuscript.
NR 55
TC 7
Z9 7
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN 15
PY 2009
VL 83
IS 12
BP 6079
EP 6086
DI 10.1128/JVI.02647-08
PG 8
WC Virology
SC Virology
GA 448BV
UT WOS:000266237900012
PM 19339354
ER
PT J
AU McDonald, SM
Aguayo, D
Gonzalez-Nilo, FD
Patton, JT
AF McDonald, Sarah M.
Aguayo, Daniel
Gonzalez-Nilo, Fernando D.
Patton, John T.
TI Shared and Group-Specific Features of the Rotavirus RNA Polymerase
Reveal Potential Determinants of Gene Reassortment Restriction
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID GROUP-C ROTAVIRUS; GROUP-B ROTAVIRUSES; GROUP-A; MOLECULAR
CHARACTERIZATION; GENOMIC REASSORTMENT; REPLICATION; PROTEIN; SEQUENCE;
STRAINS; EXPRESSION
AB Rotaviruses (RVs) are nonenveloped, 11-segmented, double-stranded RNA viruses that are major pathogens associated with acute gastroenteritis. Group A, B, and C RVs have been isolated from humans; however, intergroup gene reassortment does not occur for reasons that remain unclear. This restriction might reflect the failure of the viral RNA-dependent RNA polymerase (RdRp; VP1) to recognize and replicate the RNA of a different group. To address this possibility, we contrasted the sequences, structures, and functions of RdRps belonging to RV groups A, B, and C (A-VP1, B-VP1, and C-VP1, respectively). We found that conserved amino acid residues are located within the hollow center of VP1 near the active site, whereas variable, group-specific residues are mostly surface exposed. By creating a three-dimensional homology model of C-VP1 with the A-VP1 crystallographic data, we provide evidence that these RV RdRps are nearly identical in their tertiary folds and that they have the same RNA template recognition mechanism that differs from that of B-VP1. Consistent with the structural data, recombinant A-VP1 and C-VP1 are capable of replicating one another's RNA templates in vitro. Nonetheless, the activity of both RdRps is strictly dependent upon the presence of cognate RV core shell protein A-VP2 or C-VP2, respectively. Together, the results of this study provide unprecedented insight into the structure and function of RV RdRps and support the notion that VP1 interactions may influence the emergence of reassortant viral strains.
C1 [McDonald, Sarah M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20826 USA.
[Aguayo, Daniel; Gonzalez-Nilo, Fernando D.] Univ Talca, Ctr Bioinformat & Mol Simulat, Talca 721, Chile.
RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20826 USA.
EM jpatton@niaid.nih.gov
RI Patton, John/P-1390-2014; Gonzalez-Nilo, Fernando/M-5671-2016
OI Gonzalez-Nilo, Fernando/0000-0001-6857-3575
FU PBCT-Conicyt, Chile [ACT/24]; NIH National Institute of Allergy and
Infectious Diseases
FX We express our appreciation to Tamara Bar-Magen and Hongyan Yang for
technical assistance and to Kristen Guglielmi, Harish Ramanathan, and Al
Kapikian for insightful comments and critical reading of the manuscript.
F. D. G.- N. and D. A. are supported by grant ACT/24 of PBCT-Conicyt,
Chile. J. T. P. and S. M. M. are supported by the Intramural Research
Program of the NIH National Institute of Allergy and Infectious
Diseases.
NR 46
TC 26
Z9 26
U1 1
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 JUN 15
PY 2009
VL 83
IS 12
BP 6135
EP 6148
DI 10.1128/JVI.00409-09
PG 14
WC Virology
SC Virology
GA 448BV
UT WOS:000266237900018
PM 19357162
ER
PT J
AU Keck, ZY
Li, SH
Xia, J
von Hahn, T
Balfe, P
McKeating, JA
Witteveldt, J
Patel, AH
Alter, H
Rice, CM
Foung, SKH
AF Keck, Zhen-yong
Li, Sophia H.
Xia, Jinming
von Hahn, Thomas
Balfe, Peter
McKeating, Jane A.
Witteveldt, Jeroen
Patel, Arvind H.
Alter, Harvey
Rice, Charles M.
Foung, Steven K. H.
TI Mutations in Hepatitis C Virus E2 Located outside the CD81 Binding Sites
Lead to Escape from Broadly Neutralizing Antibodies but Compromise Virus
Infectivity
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN MONOCLONAL-ANTIBODIES; POST-TRANSFUSION HEPATITIS; T-CELL
RESPONSES; ENVELOPE GLYCOPROTEIN; IN-VITRO; CONFORMATIONAL EPITOPES;
HEPATOMA-CELLS; HYPERVARIABLE REGION; IMMUNE GLOBULIN; LOW-DENSITY
AB Broadly neutralizing antibodies are commonly present in the sera of patients with chronic hepatitis C virus (HCV) infection. To elucidate possible mechanisms of virus escape from these antibodies, retrovirus particles pseudotyped with HCV glycoproteins (HCVpp) isolated from sequential samples collected over a 26-year period from a chronically infected patient, H, were used to characterize the neutralization potential and binding affinity of a panel of anti-HCV E2 human monoclonal antibodies (HMAbs). Moreover, AP33, a neutralizing murine monoclonal antibody (MAb) to a linear epitope in E2, was also tested against selected variants. The HMAbs used were previously shown to broadly neutralize HCV and to recognize a cluster of highly immunogenic overlapping epitopes, designated domain B, containing residues that are also critical for binding of viral E2 glycoprotein to CD81, a receptor essential for virus entry. Escape variants were observed at different time points with some of the HMAbs. Other HMAbs neutralized all variants except for the isolate 02.E10, obtained in 2002, which was also resistant to MAb AP33. The 02.E10 HCVpp that have reduced binding affinities for all antibodies and for CD81 also showed reduced infectivity. Comparison of the 02.E10 nucleotide sequence with that of the strain H-derived consensus variant, H77c, revealed the former to have two mutations in E2, S501N and V506A, located outside the known CD81 binding sites. Substitution A506V in 02.E10 HCVpp restored binding to CD81, but its antibody neutralization sensitivity was only partially restored. Double substitutions comprising N501S and A506V synergistically restored 02.E10 HCVpp infectivity. Other mutations that are not part of the antibody binding epitope in the context of N501S and A506V were able to completely restore neutralization sensitivity. These findings showed that some nonlinear overlapping epitopes are more essential than others for viral fitness and consequently are more invariant during earlier years of chronic infection. Further, the ability of the 02.E10 consensus variant to escape neutralization by the tested antibodies could be a new mechanism of virus escape from immune containment. Mutations that are outside receptor binding sites resulted in structural changes leading to complete escape from domain B neutralizing antibodies, while simultaneously compromising viral fitness by reducing binding to CD81.
C1 [Keck, Zhen-yong; Li, Sophia H.; Xia, Jinming; Foung, Steven K. H.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
[von Hahn, Thomas; Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10065 USA.
[Balfe, Peter; McKeating, Jane A.] Univ Birmingham, Inst Biomed Res, Birmingham, W Midlands, England.
[Witteveldt, Jeroen; Patel, Arvind H.] Univ Glasgow, Inst Virol, MRC Virol Unit, Glasgow G11 5JR, Lanark, Scotland.
[Alter, Harvey] NIH, Dept Transfus Med, Infect Dis Sect, Bethesda, MD 20892 USA.
RP Foung, SKH (reprint author), Stanford Med Sch, Ctr Blood, 3373 Hillview Ave, Palo Alto, CA 94304 USA.
EM sfoung@stanford.edu
OI McKeating, Jane/0000-0002-7229-5886
FU PHS [HL079381, AI072613, AI40034]; Greenberg Medical Research Institute;
Starr Foundation; Medical Research Council, United Kingdom
FX This work was supported in part by PHS grant HL079381 to S. K. H. F.,
PHS grants AI072613 and AI40034, support from the Greenberg Medical
Research Institute and the Starr Foundation to C. M. R., and a grant
from the Medical Research Council, United Kingdom, to A. H. P.
NR 56
TC 43
Z9 44
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 JUN 15
PY 2009
VL 83
IS 12
BP 6149
EP 6160
DI 10.1128/JVI.00248-09
PG 12
WC Virology
SC Virology
GA 448BV
UT WOS:000266237900019
PM 19321602
ER
PT J
AU Koup, RA
Lamoreaux, L
Zarkowsky, D
Bailer, RT
King, CR
Gall, JGD
Brough, DE
Graham, BS
Roederer, M
AF Koup, Richard A.
Lamoreaux, Laurie
Zarkowsky, David
Bailer, Robert T.
King, C. Richter
Gall, Jason G. D.
Brough, Douglas E.
Graham, Barney S.
Roederer, Mario
TI Replication-Defective Adenovirus Vectors with Multiple Deletions Do Not
Induce Measurable Vector-Specific T Cells in Human Trials
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID DNA-BINDING PROTEIN; HIV-1 VACCINE; GENE-THERAPY; IMMUNOGENICITY
EVALUATION; CANDIDATE VACCINE; PHASE-1 SAFETY; VIRAL-ANTIGENS; IMMUNITY;
CHALLENGES; STEP
AB The magnitude and character of adenovirus serotype 5 (Ad5)-specific T cells were determined in volunteers with and without preexisting neutralizing antibodies (NAs) to Ad5 who received replication-defective Ad5 (rAd5)-based human immunodeficiency virus vaccines. There was no correlation between T-cell responses and NAs to Ad5. There was no increase in magnitude or activation state of Ad5-specific CD4(+) T cells at time points where antibodies to Ad5 and T-cell responses to the recombinant gene products could be measured. These data indicate that rAd5-based vaccines containing deletions in the E1, E3, and E4 regions do not induce appreciable expansion of vector-specific CD4(+) T cells.
C1 [Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Koup, Richard A.; Lamoreaux, Laurie; Zarkowsky, David; Bailer, Robert T.] NIAID, Immunol Core Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[King, C. Richter; Gall, Jason G. D.; Brough, Douglas E.] GenVec Inc, Gaithersburg, MD USA.
RP Koup, RA (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3022,Bldg 40,Room 3502, Bethesda, MD 20892 USA.
EM rkoup@mail.nih.gov
FU NIAID; Bill and Melinda Gates Foundation [38650]
FX These studies were funded by NIAID intramural funds and award 38650 from
the Bill and Melinda Gates Foundation.
NR 21
TC 26
Z9 26
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 JUN 15
PY 2009
VL 83
IS 12
BP 6318
EP 6322
DI 10.1128/JVI.00384-09
PG 5
WC Virology
SC Virology
GA 448BV
UT WOS:000266237900036
PM 19339347
ER
PT J
AU Muthusamy, BP
Raychaudhuri, S
Natarajan, P
Abe, F
Liu, K
Prinz, WA
Graham, TR
AF Muthusamy, Baby-Periyanayaki
Raychaudhuri, Sumana
Natarajan, Paramasivam
Abe, Fumiyoshi
Liu, Ke
Prinz, William A.
Graham, Todd R.
TI Control of Protein and Sterol Trafficking by Antagonistic Activities of
a Type IV P-type ATPase and Oxysterol Binding Protein Homologue
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID YEAST GOLGI MEMBRANES; PLASMA-MEMBRANE; SACCHAROMYCES-CEREVISIAE;
AMINOPHOSPHOLIPID TRANSLOCASE; PHOSPHOLIPID TRANSLOCATION;
ENDOPLASMIC-RETICULUM; CANALICULAR MEMBRANE; ATP8B1 DEFICIENCY; IN-VIVO;
TRANSPORT
AB The oxysterol binding protein homologue Kes1p has been implicated in nonvesicular sterol transport in Saccharomyces cerevisiae. Kes1p also represses formation of protein transport vesicles from the trans-Golgi network (TGN) through an unknown mechanism. Here, we show that potential phospholipid translocases in the Drs2/Dnf family (type IV P-type ATPases [P4-ATPases]) are downstream targets of Kes1p repression. Disruption of KES1 suppresses the cold-sensitive (cs) growth defect of drs2 Delta, which correlates with an enhanced ability of Dnf P4-ATPases to functionally substitute for Drs2p. Loss of Kes1p also suppresses a drs2-ts allele in a strain deficient for Dnf P4-ATPases, suggesting that Kes1p antagonizes Drs2p activity in vivo. Indeed, Drs2-dependent phosphatidylserine translocase (flippase) activity is hyperactive in TGN membranes from kes1 Delta cells and is potently attenuated by addition of recombinant Kes1p. Surprisingly, Drs2p also antagonizes Kes1p activity in vivo. Drs2p deficiency causes a markedly increased rate of cholesterol transport from the plasma membrane to the endoplasmic reticulum (ER) and redistribution of endogenous ergosterol to intracellular membranes, phenotypes that are Kes1p dependent. These data suggest a homeostatic feedback mechanism in which appropriately regulated flippase activity in the Golgi complex helps establish a plasma membrane phospholipid organization that resists sterol extraction by a sterol binding protein.
C1 [Muthusamy, Baby-Periyanayaki; Natarajan, Paramasivam; Liu, Ke; Graham, Todd R.] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA.
[Raychaudhuri, Sumana; Prinz, William A.] NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
[Abe, Fumiyoshi] Japan Agcy Marine Earth Sci & Technol, Extremobiosphere Res Ctr, Yokosuka, Kanagawa 2370061, Japan.
RP Graham, TR (reprint author), Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA.
EM tr.graham@vanderbilt.edu
OI Raychaudhuri, Sumana/0000-0002-3164-0057
FU National Institutes of Health [GM-62367]; Japan Society for the
Promotion of Science [18658039]; NIDDK
FX We thank Vytas Bankaitis (University of North Carolina, Chapel Hill),
Chris Beh (Simon Fraser University), and Susan Wente (Vanderbilt
University) for providing plasmids, yeast strains, and antibodies; Larry
Swift and Carla Harris for assistance with ergosterol quantitation; and
Denny Kerns for assistance with electron microscopy. We also thank
Rohini Khatri, Sophie Chen, and the other members of the Graham
laboratory for support during these experiments. This work was supported
by National Institutes of Health grant GM-62367 (to T. R. G.). This work
was partly supported by the Japan Society for the Promotion of Science
(No. 18658039 to F. A.). S. R. and W. A. P. were supported by the
Intramural Research Program of the NIDDK.
NR 62
TC 25
Z9 25
U1 1
U2 2
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD JUN 15
PY 2009
VL 20
IS 12
BP 2920
EP 2931
DI 10.1091/mbc.E08-10-1036
PG 12
WC Cell Biology
SC Cell Biology
GA 457RR
UT WOS:000266951000011
PM 19403696
ER
PT J
AU Perkins, NJ
Schisterman, EF
Vexler, A
AF Perkins, Neil J.
Schisterman, Enrique F.
Vexler, Albert
TI Generalized ROC curve inference for a biomarker subject to a limit of
detection and measurement error
SO STATISTICS IN MEDICINE
LA English
DT Article
DE ROC curve; limit of detection; measurement error; area under the curve;
replicates
ID OPERATING CHARACTERISTIC CURVE
AB The receiver operating characteristic (ROC) Curve is it tool commonly used to evaluate biomarker utility in clinical diagnosis of disease. especially during biomarker development research. Emerging biomarkers are often measured with random measured error and subject to limits of detection that hinder their potential utility or mask an ability to discriminate by negatively biasing the estimates of ROC curves and subsequent area Under the curve. Methods have been developed to correct the ROC curve for each Of these types of Sources of bias but here we develop a method by which the ROC curve is corrected for both simultaneously through replicate measures and maximum likelihood. Our Method is evaluated via simulation Study and applied to two potential discriminators of women with and without preeclampsia. Published in 2009 by John Wiley & Sons, Ltd.
C1 [Perkins, Neil J.; Schisterman, Enrique F.; Vexler, Albert] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bethesda, MD 20852 USA.
[Vexler, Albert] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA.
RP Perkins, NJ (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, 6100 Execut BLVD,Rm 7B03, Bethesda, MD 20852 USA.
EM perkinsn@mail.nih.gov
OI Perkins, Neil/0000-0002-6802-4733; Schisterman,
Enrique/0000-0003-3757-641X
FU Intramural Research Program
FX Contract/grant sponsor: Intramural Research Program
NR 19
TC 10
Z9 11
U1 0
U2 6
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD JUN 15
PY 2009
VL 28
IS 13
BP 1841
EP 1860
DI 10.1002/sim.3575
PG 20
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 452BN
UT WOS:000266514700006
PM 19340817
ER
PT J
AU Nabel, EG
Stevens, S
Smith, R
AF Nabel, Elizabeth G.
Stevens, Simon
Smith, Richard
TI Combating chronic disease in developing countries
SO LANCET
LA English
DT Editorial Material
C1 [Nabel, Elizabeth G.] NHLBI, Bethesda, MD 20892 USA.
[Stevens, Simon; Smith, Richard] UnitedHlth Grp, Minneapolis, MN 55440 USA.
RP Nabel, EG (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
EM nhlbiiod@nhlbi.nih.gov
OI Smith, Richard/0000-0003-3837-6559
NR 12
TC 24
Z9 24
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD JUN 13
PY 2009
VL 373
IS 9680
BP 2004
EP 2006
DI 10.1016/S0140-6736(09)61074-6
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 459DJ
UT WOS:000267080100007
PM 19523681
ER
PT J
AU Friedman, JS
Ray, JW
Waseem, N
Johnson, K
Brooks, MJ
Hugosson, T
Breuer, D
Branham, KE
Krauth, DS
Bowne, SJ
Sullivan, LS
Ponjavic, V
Granse, L
Khanna, R
Trager, EH
Gieser, LM
Hughbanks-Wheaton, D
Cojocaru, RI
Ghiasvand, NM
Chakarova, CF
Abrahamson, M
Goring, HHH
Webster, AR
Birch, DG
Abecasis, GR
Fann, Y
Bhattacharya, SS
Daiger, SP
Heckenlively, JR
Andreasson, S
Swaroop, A
AF Friedman, James S.
Ray, Joseph W.
Waseem, Naushin
Johnson, Kory
Brooks, Matthew J.
Hugosson, Therese
Breuer, Debra
Branham, Kari E.
Krauth, Daniel S.
Bowne, Sara J.
Sullivan, Lori S.
Ponjavic, Vesna
Granse, Lotta
Khanna, Ritu
Trager, Edward H.
Gieser, Linn M.
Hughbanks-Wheaton, Dianna
Cojocaru, Radu I.
Ghiasvand, Noor M.
Chakarova, Christina F.
Abrahamson, Magnus
Goering, Harald H. H.
Webster, Andrew R.
Birch, David G.
Abecasis, Goncalo R.
Fann, Yang
Bhattacharya, Shomi S.
Daiger, Stephen P.
Heckenlively, John R.
Andreasson, Sten
Swaroop, Anand
TI Mutations in a BTB-Kelch Protein, KLHL7, Cause Autosomal-Dominant
Retinitis Pigmentosa
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GIANT AXONAL NEUROPATHY; SWISS-MODEL; RETINAL DEGENERATION; RHODOPSIN
GENE; CHROMOSOME 7P; PHOTORECEPTOR; HOMOLOGY; UBIQUITIN; FAMILIES;
LOCALIZATION
AB Retinitis pigmentosa (RP) refers to a genetically heterogeneous group of progressive neurodegenerative diseases that result in dysfunction and/or death of rod and cone photoreceptors in the retina. So far, 18 genes have been identified for autosomal-dominant (ad) RP. Here, we describe an adRP locus (RP42) at chromosome 7p15 through linkage analysis in a six-generation Scandinavian family and identify a disease-causing mutation, c.449G -> A (p.S150N), in exon 6 of the KLHL7 gene. Mutation screening of KLHL7 in 502 retinopathy probands has revealed three different missense mutations in six independent families. KLHL7 is widely expressed, including expression in rod photoreceptors, and encodes a 75 kDa protein of the BTB-Kelch Subfamily within the BTB superfamily. BTB-Kelch proteins have been implicated in ubiquitination through Cullin E3 ligases. Notably, all three putative disease-causing KLHL7 mutations are within a conserved BACK domain; homology modeling suggests that mutant amino acid side chains can potentially fill the cleft between two helices, thereby affecting the ubiquitination complexes. Mutations in an identical region of another BTB-Kelch protein, gigaxonin, have previously been associated with giant axonal neuropathy. Our studies suggest an additional role of the ubiquitin-proteasome protein-degradation pathway in maintaining neuronal health and in disease.
C1 [Friedman, James S.; Brooks, Matthew J.; Krauth, Daniel S.; Gieser, Linn M.; Cojocaru, Radu I.; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Ray, Joseph W.; Bowne, Sara J.; Sullivan, Lori S.; Daiger, Stephen P.] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX 77030 USA.
[Waseem, Naushin; Chakarova, Christina F.; Webster, Andrew R.; Bhattacharya, Shomi S.] Inst Ophthalmol, Dept Mol Genet, London EC1 9EL, England.
[Johnson, Kory; Fann, Yang] Natl Inst Neurol Disorders & Stroke, Bioinformat Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Hugosson, Therese; Ponjavic, Vesna; Granse, Lotta; Andreasson, Sten] Univ Lund Hosp, Dept Ophthalmol, S-22185 Lund, Sweden.
[Breuer, Debra; Branham, Kari E.; Khanna, Ritu; Trager, Edward H.; Ghiasvand, Noor M.; Heckenlively, John R.; Swaroop, Anand] Univ Michigan, Dept Ophthalmol, Ann Arbor, MI 48105 USA.
[Hughbanks-Wheaton, Dianna; Birch, David G.] Retina Fdn SW, Dallas, TX 75231 USA.
[Abrahamson, Magnus] Lund Univ, Dept Lab Med, S-22185 Lund, Sweden.
[Goering, Harald H. H.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78227 USA.
[Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48105 USA.
[Swaroop, Anand] Univ Michigan, Dept Human Genet, Sch Med, Ann Arbor, MI 48109 USA.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
EM swaroopa@mail.nih.gov
RI Abecasis, Goncalo/B-7840-2010; Chakarova, Christina/C-9479-2013; Waseem,
Naushin/C-9573-2013;
OI Swaroop, Anand/0000-0002-1975-1141; Birch, David/0000-0002-6594-2897;
Abecasis, Goncalo/0000-0003-1509-1825
FU NEI; NIH; Foundation Fighting Blindness; Harold F. Falls and Paul R.
Lichter Professorships; Research to Prevent Blindness; Elmer and Sylvia
Sramek Foundation; European Union (GENORET); British Retinitis
Pigmentosa Society (UK); NIHR Biomedical Research Centre for
Ophthalmology (UK); Swedish Medical Research Council
FX We sincerely acknowledge Abby Woodroffe for discussions; Rivka Rachel
and Tiziana Cogliati for comments on the manuscript; and Mohammad
Othman, Jessica Chang, Bob Fariss, Manessa Shaw, Ashley Garibaldi, Hema
Karamchandani, and George Thomas for technical assistance. We thank
Lucia Lawrence and Sharyn Ferrara for administrative support. This work
was supported by NEI intramural funds and grants from the NIH, The
Foundation Fighting Blindness, Harold F. Falls and Paul R. Lichter
Professorships, Research to Prevent Blindness, the Elmer and Sylvia
Sramek Foundation, the European Union (GENORET), The British Retinitis
Pigmentosa Society (UK), The NIHR Biomedical Research Centre for
Ophthalmology (UK), and the Swedish Medical Research Council.
NR 45
TC 45
Z9 46
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUN 12
PY 2009
VL 84
IS 6
BP 792
EP 800
DI 10.1016/j.ajhg.2009.05.007
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 458SC
UT WOS:000267042800009
PM 19520207
ER
PT J
AU Lee, SB
Park, JH
Kaevel, J
Sramkova, M
Weigert, R
Park, MH
AF Lee, Seung Bum
Park, Jong Hwan
Kaevel, Joern
Sramkova, Monika
Weigert, Roberto
Park, Myung Hee
TI The effect of hypusine modification on the intracellular localization of
eIF5A
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Hypusine; eIF5A; Acetylation; Deoxyhypusine synthase; Deoxyhypusine
hydroxylase; Polyamine; Nuclear export
ID INITIATION-FACTOR 5A; AMINO-ACID; TRANSLATION; PROTEIN; PURIFICATION;
APOPTOSIS; CELLS; YEAST; COMPLEX; CANCER
AB Eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein essential for eukaryotic cell proliferation and is the only protein containing hypusine, [N(epsilon)-(4-amino-2-hydroxybutyl)lysine]. eIF5A is activated by the post-translational synthesis of hypusine. eIF5A also undergoes an acetylation at specific Lys residue(s). in this study, we have investigated the effect of hypusine modification and acetylation on the subcellular localization of eIF5A. immunocytochemical analyses showed differences in the distribution of non-hypusinated eIF5A precursor and the hypusine-containing mature eIF5A. While the precursor is found in both cytoplasm and nucleus, the hypusinated eIF5A is primarily localized in cytoplasm. eIF5A mutant proteins, defective in hypusine modification (K50A, K50R) were localized in a similar manner to the eIF5A precursor, whereas hypusine-modified mutant proteins (K47A, K47R, K68A) were localized mainly in the cytoplasm. These findings provide strong evidence that the hypusine modification of eIF5A dictates its localization in the cytoplasmic compartment where it is required for protein synthesis. Published by Elsevier Inc.
C1 [Lee, Seung Bum; Park, Jong Hwan; Kaevel, Joern; Sramkova, Monika; Weigert, Roberto; Park, Myung Hee] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Park, MH (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bldg 30 Rm 211,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mhpark@nih.gov
FU NIDCR, NIH
FX This research was supported by the Intramural Research Program of the
NIDCR, NIH. We thank J. Silvio Gutkind (NIDCR/NIH) for the pCEFL/GFP
vector and Edith C. Wolff (NIDCR, NIH) for critical reading of the
manuscript.
NR 22
TC 32
Z9 36
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUN 12
PY 2009
VL 383
IS 4
BP 497
EP 502
DI 10.1016/j.bbrc.2009.04.049
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 447YC
UT WOS:000266227000023
PM 19379712
ER
PT J
AU Mane, SP
Evans, C
Cooper, KL
Crasta, OR
Folkerts, O
Hutchison, SK
Harkins, TT
Thierry-Mieg, D
Thierry-Mieg, J
Jensen, RV
AF Mane, Shrinivasrao P.
Evans, Clive
Cooper, Kristal L.
Crasta, Oswald R.
Folkerts, Otto
Hutchison, Stephen K.
Harkins, Timothy T.
Thierry-Mieg, Danielle
Thierry-Mieg, Jean
Jensen, Roderick V.
TI Transcriptome sequencing of the Microarray Quality Control (MAQC) RNA
reference samples using next generation sequencing
SO BMC GENOMICS
LA English
DT Article
ID GENE-EXPRESSION; CELL TRANSCRIPTOME; GENOME; DISCOVERY
AB Background: Transcriptome sequencing using next-generation sequencing platforms will soon be competing with DNA microarray technologies for global gene expression analysis. As a preliminary evaluation of these promising technologies, we performed deep sequencing of cDNA synthesized from the Microarray Quality Control (MAQC) reference RNA samples using Roche's 454 Genome Sequencer FLX.
Results: We generated more that 3.6 million sequence reads of average length 250 bp for the MAQC A and B samples and introduced a data analysis pipeline for translating cDNA read counts into gene expression levels. Using BLAST, 90% of the reads mapped to the human genome and 64% of the reads mapped to the RefSeq database of well annotated genes with e-values <= 10(-20). We measured gene expression levels in the A and B samples by counting the numbers of reads that mapped to individual RefSeq genes in multiple sequencing runs to evaluate the MAQC quality metrics for reproducibility, sensitivity, specificity, and accuracy and compared the results with DNA microarrays and Quantitative RT-PCR (QRTPCR) from the MAQC studies. In addition, 88% of the reads were successfully aligned directly to the human genome using the AceView alignment programs with an average 90% sequence similarity to identify 137,899 unique exon junctions, including 22,193 new exon junctions not yet contained in the RefSeq database.
Conclusion: Using the MAQC metrics for evaluating the performance of gene expression platforms, the ExpressSeq results for gene expression levels showed excellent reproducibility, sensitivity, and specificity that improved systematically with increasing shotgun sequencing depth, and quantitative accuracy that was comparable to DNA microarrays and QRTPCR. In addition, a careful mapping of the reads to the genome using the AceView alignment programs shed new light on the complexity of the human transcriptome including the discovery of thousands of new splice variants.
C1 [Jensen, Roderick V.] Virginia Tech, Dept Biol Sci, Blacksburg, VA 24061 USA.
[Mane, Shrinivasrao P.; Evans, Clive; Cooper, Kristal L.; Crasta, Oswald R.; Folkerts, Otto] Virginia Tech, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA.
[Hutchison, Stephen K.] 454 Life Sci Inc, Branford, CT 06405 USA.
[Harkins, Timothy T.] Roche Appl Sci, Indianapolis, IN 46250 USA.
[Thierry-Mieg, Danielle; Thierry-Mieg, Jean] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Jensen, RV (reprint author), Virginia Tech, Dept Biol Sci, Blacksburg, VA 24061 USA.
EM smane@vbi.vt.edu; cevans@vbi.vt.edu; krcooper@vbi.vt.edu;
ocrasta@vbi.vt.edu; folkerts@vbi.vt.edu; shutchison@454.com;
tim.harkins@roche.com; mieg@ncbi.nlm.nih.gov; mieg@ncbi.nlm.nih.gov;
rvjensen@vt.edu
RI THIERRY-MIEG, Jean/F-1975-2017
OI THIERRY-MIEG, Jean/0000-0002-0396-6789
FU Virginia Bioinformatics Institute by the Commonwealth Research
Initiative of the Commonwealth of Virginia
FX The authors thank Jessica Krasjewski, and Adam Jerauld for technical
assistance in processing RNA samples, performing the GS-FLX sequencing
and running the Affymetrix Exon Arrays. RVJ also thanks Lingsheng Dong
for valuable discussions of transcriptome sequencing data. The work in
this publication was supported in part by funding provided to the
Virginia Bioinformatics Institute by the Commonwealth Research
Initiative of the Commonwealth of Virginia.
NR 29
TC 51
Z9 53
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUN 12
PY 2009
VL 10
AR 264
DI 10.1186/1471-2164-10-264
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 480RB
UT WOS:000268753400001
PM 19523228
ER
PT J
AU Xu, XLL
Fang, YQ
Lee, TC
Forrest, D
Gregory-Evans, C
Almeida, D
Liu, AH
Jhanwar, SC
Abramson, DH
Cobrinik, D
AF Xu, Xiaoliang L.
Fang, Yuqiang
Lee, Thomas C.
Forrest, Douglas
Gregory-Evans, Cheryl
Almeida, Dena
Liu, Aihong
Jhanwar, Suresh C.
Abramson, David H.
Cobrinik, David
TI Retinoblastoma Has Properties of a Cone Precursor Tumor and Depends Upon
Cone-Specific MDM2 Signaling
SO CELL
LA English
DT Article
ID THYROID-HORMONE RECEPTOR; DEVELOPING MOUSE RETINA; CELL-CYCLE CONTROL;
GENOMIC INSTABILITY; DEFICIENT MICE; EXPRESSION; P53; RB;
PHOTORECEPTORS; GENE
AB Retinoblastomas result from the inactivation of the RB1 gene and the loss of Rb protein, yet the cell type in which Rb suppresses retinoblastoma and the circuitry that underlies the need for Rb are undefined. Here, we show that retinoblastoma cells express markers of postmitotic cone precursors but not markers of other retinal cell types. We also demonstrate that human cone precursors prominently express MDM2 and N-Myc, that retinoblastoma cells require both of these proteins for proliferation and survival, and that MDM2 is needed to suppress ARF-induced apoptosis in cultured retinoblastoma cells. Interestingly, retinoblastoma cell MDM2 expression was regulated by the cone-specific RXR gamma transcription factor and a human-specific RXR gamma consensus binding site, and proliferation required RXR gamma, as well as the cone-specific thyroid hormone receptor-beta 2. These findings provide support for a cone precursor origin of retinoblastoma and suggest that human cone-specific signaling circuitry sensitizes to the oncogenic effects of RB1 mutations.
C1 [Xu, Xiaoliang L.; Almeida, Dena; Liu, Aihong; Cobrinik, David] Weill Cornell Med Coll, Dyson Vis Res Inst, New York, NY 10021 USA.
[Xu, Xiaoliang L.; Almeida, Dena; Liu, Aihong; Abramson, David H.; Cobrinik, David] Weill Cornell Med Coll, Dept Ophthalmol, New York, NY 10021 USA.
[Xu, Xiaoliang L.; Fang, Yuqiang; Jhanwar, Suresh C.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Jhanwar, Suresh C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Lee, Thomas C.] Childrens Hosp Los Angeles, Vis Ctr, Los Angeles, CA 90027 USA.
[Forrest, Douglas] NIDDK, NIH, Bethesda, MD 20892 USA.
[Gregory-Evans, Cheryl] Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, London SW7 2AZ, England.
[Abramson, David H.] Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10021 USA.
RP Cobrinik, D (reprint author), Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, 1275 York Ave, New York, NY 10021 USA.
EM cobrinid@mskcc.org
RI Gregory-Evans, Cheryl/G-9550-2011
FU Starr Foundation Tri-Institutional Stem Cell Initiative; Research to
Prevent Blindness; Fund for Ophthalmic Knowledge
FX We thank J. Nathans and A. Swaroop for antibodies, H. te Riele for mou
tumors, J. Blaydes for plasmids, M. Pappas for compiling Table S1, and
A. Koff for facilitating the completion of this study. This work was
supported by the Starr Foundation Tri-Institutional Stem Cell
Initiative, Research to Prevent Blindness, and the Fund for Ophthalmic
Knowledge.
NR 56
TC 92
Z9 96
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUN 12
PY 2009
VL 137
IS 6
BP 1018
EP 1031
DI 10.1016/j.cell.2009.03.051
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 457GL
UT WOS:000266916400015
PM 19524506
ER
PT J
AU Chakrabarti, O
Hegde, RS
AF Chakrabarti, Oishee
Hegde, Ramanujan S.
TI Functional Depletion of Mahogunin by Cytosolically Exposed Prion Protein
Contributes to Neurodegeneration
SO CELL
LA English
DT Article
ID ENDOPLASMIC-RETICULUM; DISEASE; SCRAPIE; PRP; NEUROTOXICITY;
TRANSLOCATION; DEGRADATION; PATHWAY; TRANSMISSION; PURIFICATION
AB The pathways leading from aberrant Prion protein (PrP) metabolism to neurodegeneration are poorly understood. Some familial PrP mutants generate increased (Ctm)PrP, a transmembrane isoform associated with disease. In other disease situations, a potentially toxic cytosolic form (termed cyPrP) might be produced. However, the mechanisms by which (Ctm)PrP or cyPrP cause selective neuronal dysfunction are unknown. Here, we show that both (Ctm)PrP and cyPrP can interact with and disrupt the function of Mahogunin (Mgrn), a cytosolic ubiquitin ligase whose loss causes spongiform neurodegeneration. Cultured cells and transgenic mice expressing either (Ctm)PrP-producing mutants or cyPrP partially phenocopy Mgrn depletion, displaying aberrant lysosomal morphology and loss of Mgrn in selected brain regions. These effects were rescued by either Mgrn overexpression, competition for PrP-binding sites, or prevention of cytosolic PrP exposure. Thus, transient or partial exposure of PrP to the cytosol leads to inappropriate Mgrn sequestration that contributes to neuronal dysfunction and disease.
C1 [Chakrabarti, Oishee; Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Hegde, RS (reprint author), NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM hegder@mail.nih.gov
OI Hegde, Ramanujan/0000-0001-8338-852X
FU NICHD at the National Institutes of Health
FX We are grateful to N. Rane for providing transgenic mouse tissues and
constructs, E. Whiteman for making the initial Mgrn constructs, Y. Abebe
for expert animal care, L. Greene and H. Lorenz for constructs and
sharing unpublished results, G. Patterson for help with microscopy, and
L. DaSilva, G. Mardones, and P. Burgos for advice and reagents. This
work was supported by the Intramural Research Program of the NICHD at
the National Institutes of Health.
NR 35
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U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUN 12
PY 2009
VL 137
IS 6
BP 1136
EP 1147
DI 10.1016/j.cell.2009.03.042
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 457GL
UT WOS:000266916400024
PM 19524515
ER
PT J
AU Strech, D
Danis, M
Lob, M
Marckmann, G
AF Strech, D.
Danis, M.
Loeb, M.
Marckmann, G.
TI Extent and impact of bedside rationing in German hospitals: results of a
representative survey among physicians
SO DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT
LA German
DT Article
DE rationing; prioritizing; cardiology; critical care medicine; national
survey; ethics
AB Background: Healthcare rationing is increasingly discussed among German physicians. However, in contrast to the relatively intense debates on how to prioritize and ration on the macro level of the health system, there is hardly any discussion on how doctors can make the unavoidable rationing decisions on the micro level in a medically and ethically appropriate manner. The development of both accountable and feasible guidance requires empirical evidence about the prevalence of bedside rationing and a more in-depth understanding of the practical challenges.
Methods: Based on the official German hospital registry a national survey was performed nationwide among 1,137 randomly selected physicians working in cardiology or critical care medicine.
Results: 68% of the respondents stated that they had already withheld from patients medical services with a potentiol benefit for the patient because of cost considerations. However, only few of them indicated that this happens often. The frequency of bedside rationing differed, in some cases significantly, in relation to specialty, professional status and hospital funding. The majority of clinicians describes a negative impact of cost pressure on their work satisfaction and on the patient-doctor relationship. German clinicians have become aware of only a few opportunities that would allow them to increase their efficiency with a view to avoiding healthcare rationing. Instead, more then 50% of the doctors considered additional funding for the health care system, through higher contributions to the statutory health insurance or higher out-of-pocket spending by patients, to be an acceptable approach to dealing with scarce resources.
Conclusion: There is a need to develop explicit methods that support physicians in making inevitable rationing decisions at the bedside. Such methods must be accompanied by consultation procedures so that a rational and fair use of scarce health care resources is achieved.
C1 [Strech, D.] Hannover Med Sch, Inst Geschichte Eth Philosophie Med, D-30625 Hannover, Germany.
[Danis, M.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[Loeb, M.] Helios Klinikum Berlin Buch, Klin Kinder & Jugendpsychiat & Psychotherapie, Berlin, Germany.
[Marckmann, G.] Univ Tubingen, Inst Eth & Geschichte Med, D-72074 Tubingen, Germany.
RP Strech, D (reprint author), Hannover Med Sch, Inst Geschichte Eth Philosophie Med, Carl Neuberg Str 1, D-30625 Hannover, Germany.
EM strech.daniel@mh-hannover.de
OI Strech, Daniel/0000-0002-9153-079X
NR 16
TC 29
Z9 29
U1 0
U2 5
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0012-0472
J9 DEUT MED WOCHENSCHR
JI Dtsch. Med. Wochenschr.
PD JUN 12
PY 2009
VL 134
IS 24
BP 1261
EP 1266
DI 10.1055/s-0029-1225273
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 464GN
UT WOS:000267493500005
PM 19499496
ER
PT J
AU Kang, ZG
Marketon, JIW
Johnson, A
Sternberg, EM
AF Kang, Zhigang
Marketon, Jeanette I. Webster
Johnson, Antoinette
Sternberg, Esther M.
TI Bacillus anthracis Lethal Toxin Represses MMTV Promoter Activity through
Transcription Factors
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE anthrax lethal toxin (LeTx); MMTV promoter; transcription factors;
overexpression; repression
ID MAMMARY-TUMOR VIRUS; RECEPTOR-DEPENDENT TRANSCRIPTION; CARBOXYKINASE
GENE PROMOTER; PITUITARY-ADRENAL AXIS; LONG TERMINAL REPEAT;
GLUCOCORTICOID-RECEPTOR; IN-VIVO; CHROMATIN-STRUCTURE; PROTEIN-KINASE;
MURINE MACROPHAGES
AB We have recently shown that the anthrax lethal toxin (LeTx) selectively represses nuclear hormone receptors. In this study, we found that LeTx repressed the activation of the mouse mammary tumor virus promoter related to overexpression of the transcription factors hepatocyte nuclear factor 3, octamer-binding protein I. and c-Jun. LeTx transcriptional repression was associated with a decrease in the protein levels of these transcription factors in a lethal factor protease activity-dependent manner. Early administration of LeTx antagonists partially or completely abolished the repressive effects of LeTx. In contrast to the rapid cleavage of mitogen-activated protein kinase kinases by LeTx, the degradation of these transcription factors occurred at a relatively late stage after LeTx treatment. In addition, LeTx repressed phorbol-12-myristate-13-acetate-induced mouse mammary tumor virus promoter activity and phorbol 12-myristate 13-acetate induction of endogenous c-Jun protein. Collectively, these findings suggest that transcription factors are intracellular targets of LeTx and expand our understanding of the molecular action of LeTx at a later stage of low-dose exposure. Published by Elsevier Ltd.
C1 [Kang, Zhigang; Johnson, Antoinette; Sternberg, Esther M.] NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Marketon, Jeanette I. Webster] Ohio State Univ, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med, Columbus, OH 43210 USA.
[Marketon, Jeanette I. Webster] Ohio State Univ, Inst Behav Med Res, Columbus, OH 43210 USA.
RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Dept Hlth & Human Serv, 5625 Fishers Lane,Room 4N13 MSC 9401, Bethesda, MD 20892 USA.
EM sternbee@mail.nih.gov
RI Webster Marketon, Jeanette/H-5613-2011
OI Webster Marketon, Jeanette/0000-0002-3627-1094
FU National Institute of Mental Health/National Institutes of Health
Intramural Research Program; National Institute of Allergy and
Infectious Diseases/National Institutes of Health Intramural Biodefense
Research Program
FX This work was supported by the National Institute of Mental
Health/National Institutes of Health Intramural Research Program and the
National Institute of Allergy and Infectious Diseases/National
Institutes of Health Intramural Biodefense Research Program through a
research grant.
NR 83
TC 2
Z9 2
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD JUN 12
PY 2009
VL 389
IS 3
BP 595
EP 605
DI 10.1016/j.jmb.2009.04.030
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 465BX
UT WOS:000267556700011
PM 19389405
ER
PT J
AU Guynet, C
Achard, A
Hoang, BT
Barabas, O
Hickman, AB
Dyda, F
Chandler, M
AF Guynet, Catherine
Achard, Adeline
Hoang, Bao Ton
Barabas, Orsolya
Hickman, Alison Burgess
Dyda, Frederick
Chandler, Michael
TI Resetting the Site: Redirecting Integration of an Insertion Sequence in
a Predictable Way
SO MOLECULAR CELL
LA English
DT Article
ID TARGET SITE; ESCHERICHIA-COLI; TRANSPOSITION; SPECIFICITY; SELECTION;
MECHANISM; ELEMENTS
AB Target site choice is a complex and poorly understood aspect of DNA transposition despite its importance in rational transposon-mediated gene delivery. Though most transposons choose target sites essentially randomly or with some slight sequence or structural preferences, insertion sequence IS608 from Helicobacter pylori, which transposes using single-stranded DNA, always inserts just 3' of a TTAC tetranucleotide. Our results from studies on the IS608 transposition mechanism demonstrated that the transposase recognizes its target site by co-opting an internal segment of transposon DNA and utilizes it for specific recognition of the target sites through base-pairing. This suggested a way to redirect IS608 transposition to novel target sites. As we demonstrate here, we can now direct insertions in a predictable way into a variety of different chosen target sequences, both in vitro and in vivo.
C1 [Guynet, Catherine; Achard, Adeline; Hoang, Bao Ton; Chandler, Michael] CNRS, Lab Microbiol & Genet Mol, UMR5100, F-31062 Toulouse, France.
[Barabas, Orsolya; Hickman, Alison Burgess; Dyda, Frederick] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hoang, BT (reprint author), CNRS, Lab Microbiol & Genet Mol, UMR5100, 118 Rte Narbonne, F-31062 Toulouse, France.
EM bao.tonhoang@ibcg.biotoul.fr; michael.chandler@ibcg.biotoul.fr
RI Guynet, Catherine/A-4815-2011; Barabas, Orsolya/F-3961-2012;
OI Barabas, Orsolya/0000-0002-2873-5872; Chandler,
Michael/0000-0002-0292-6662
FU CNRS (France); ANR; French MENRT; NIH NIDDK; [LSHM-CT-2005-019023]
FX We would like to thank members of the Chandler lab (G. Duval-Valentin,
P. Kichenaradia, B. Marty, P. Rousseau, P. Siguier, O. Walisko, and E.
Simmonot). The Chandler lab was supported by continuous intramural
funding from the CNRS (France), by European contract
LSHM-CT-2005-019023, and partially by ANR grant MOBIGEN. C.G. received a
training grant from the French MENRT and A.A. was supported by European
contract LSHM-CT-2005-019023. The Dyda lab was supported by the NIH
NIDDK intramural program.
NR 22
TC 17
Z9 17
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD JUN 12
PY 2009
VL 34
IS 5
BP 612
EP 619
DI 10.1016/j.molcel.2009.05.017
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 459PX
UT WOS:000267117000010
PM 19524540
ER
PT J
AU Dunleavy, K
Pittaluga, S
Czuczman, MS
Dave, SS
Wright, G
Grant, N
Shovlin, M
Jaffe, ES
Janik, JE
Staudt, LM
Wilson, WH
AF Dunleavy, Kieron
Pittaluga, Stefania
Czuczman, Myron S.
Dave, Sandeep S.
Wright, George
Grant, Nicole
Shovlin, Margaret
Jaffe, Elaine S.
Janik, John E.
Staudt, Louis M.
Wilson, Wyndham H.
TI Differential efficacy of bortezomib plus chemotherapy within molecular
subtypes of diffuse large B-cell lymphoma
SO BLOOD
LA English
DT Article
ID NON-HODGKINS-LYMPHOMAS; DOSE-ADJUSTED EPOCH; NF-KAPPA-B; PROTEASOME
INHIBITORS; TISSUE MICROARRAY; BURKITTS-LYMPHOMA; CANCER-THERAPY;
RESISTANCE; SUBGROUPS; RITUXIMAB
AB Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed distinct molecular subtypes that include germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL. ABC DLBCL has a worse survival after upfront chemotherapy and is characterized by constitutive activation of the antiapoptotic nuclear factor-kappa B (NF-kappa B) pathway, which can inhibit chemotherapy. We hypothesized that inhibition of NF-kappa B might sensitize ABC but not GCB DLBCL to chemotherapy and improve outcome. As the proteasome inhibitor bortezomib can inhibit NF-kappa B through blocking I kappa B alpha degradation, we investigated bortezomib alone followed by bortezomib and doxorubicin-based chemotherapy in recurrent DLBCL. Tumor tissue was analyzed by gene expression profiling and/or immunohistochemistry to identify molecular DLBCL subtypes. As a control, we showed that relapsed/refractory ABC and GCB DLBCL have equally poor survivals after upfront chemotherapy. Bortezomib alone had no activity in DLBCL, but when combined with chemotherapy, it demonstrated a significantly higher response (83% vs 13%; P < .001) and median overall survival (10.8 vs 3.4 months; P = .003) in ABC compared with GCB DLBCL, respectively. These results suggest bortezomib enhances the activity of chemotherapy in ABC but not GCB DLBCL, and provide a rational therapeutic approach based on genetically distinct DLBCL subtypes. This trial is registered with http://www.ClinicalTrials.gov under identifier NCT00057902. (Blood. 2009; 113: 6069-6076)
C1 [Dunleavy, Kieron; Pittaluga, Stefania; Dave, Sandeep S.; Wright, George; Grant, Nicole; Shovlin, Margaret; Jaffe, Elaine S.; Janik, John E.; Staudt, Louis M.; Wilson, Wyndham H.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
RP Wilson, WH (reprint author), NCI, Metab Branch, Ctr Canc Res, Bldg 10,Rm 4N115,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM wilsonw@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health
National Cancer Institute Center for Cancer Research; Millennium
Pharmaceuticals; Roswell Park Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health National Cancer Institute Center for
Cancer Research and financed by Millennium Pharmaceuticals for its
conduct at Roswell Park Cancer Institute.
NR 27
TC 278
Z9 288
U1 0
U2 8
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 11
PY 2009
VL 113
IS 24
BP 6069
EP 6076
DI 10.1182/blood-2009-01-199679
PG 8
WC Hematology
SC Hematology
GA 459XS
UT WOS:000267147100010
PM 19380866
ER
PT J
AU Lundqvist, A
Yokoyama, H
Smith, A
Berg, M
Childs, R
AF Lundqvist, Andreas
Yokoyama, Hisayuki
Smith, Aleah
Berg, Maria
Childs, Richard
TI Bortezomib treatment and regulatory T-cell depletion enhance the
antitumor effects of adoptively infused NK cells
SO BLOOD
LA English
DT Article
ID APOPTOSIS-INDUCING LIGAND; TRAIL-INDUCED APOPTOSIS; TUMOR-CELLS; IMMUNE
ESCAPE; GRANZYME-B; IN-VIVO; C-FLIP; EXPRESSION; TRANSPLANTATION;
CYTOTOXICITY
AB Ligation of inhibitory receptors renders natural killer (NK) cells inactive against autologous tumors. Recently, the proteasome inhibitor bortezomib was shown to sensitize tumors to autologous NK-cell cytotoxicity in vitro. Here, we show bortezomib augments the antitumor effects of syngeneic NK-cell infusions in tumor-bearing animals; this effect is further enhanced in regulatory T cell (Treg cell)depleted hosts. In vitro, bortezomib-treated tumors had higher tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and perforin/granzyme-mediated caspase-8 activity, which enhanced their susceptibility to NK-cell lysis. Bioluminescence imaging of mice with established tumors showed treatment with bortezomib and syngeneic NK cells reduced tumor growth and prolonged survival compared with controls receiving bortezomib or NK cells alone. In contrast, tumor progression was not delayed when animals received bortezomib and perforin-deficient NK cells, showing drug-induced augmentation in NK-cell cytotoxicity was mediated through perforin/granzyme. Furthermore, tumor growth was slower in bortezomib-treated recipients when host Treg cells were eradicated with anti-CD25 antibody before infusing NK cells compared with mice without Treg-cell ablation (tumor doubling time, 16.7 vs 4.9 days, respectively; P = .02). These findings suggest that depletion of Treg cells followed by bortezomib-induced tumor sensitization to autologous NK cells could be used as a novel strategy to treat cancer. (Blood. 2009; 113: 6120-6127)
C1 [Lundqvist, Andreas; Yokoyama, Hisayuki; Smith, Aleah; Berg, Maria; Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Lundqvist, Andreas] Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, Stockholm, Sweden.
RP Childs, R (reprint author), NHLBI, Hematol Branch, NIH, Rm 3-5140,Bldg 10-CRC,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA.
EM childsr@nih.gov
OI Lundqvist, Andreas/0000-0002-9709-2970
FU NIH; NHLBI, Hematology Branch; Action to Cure Kidney Cancer (ACKC); Dean
R. O'Neill Memorial Fellowship
FX This research was supported by the intramural research program of NIH,
NHLBI, Hematology Branch. We also wish to acknowledge Action to Cure
Kidney Cancer (ACKC) and The Dean R. O'Neill Memorial Fellowship for
generous contributions supporting this research.
NR 34
TC 54
Z9 56
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 11
PY 2009
VL 113
IS 24
BP 6120
EP 6127
DI 10.1182/blood-2008-11-190421
PG 8
WC Hematology
SC Hematology
GA 459XS
UT WOS:000267147100016
PM 19202127
ER
PT J
AU van Cruijsen, H
Ruiz, MG
van der Valk, P
de Gruijl, TD
Giaccone, G
AF van Cruijsen, Hester
Ruiz, Marielle Gallegos
van der Valk, Paul
de Gruijl, Tanja D.
Giaccone, Giuseppe
TI Tissue micro array analysis of ganglioside N-glycolyl GM3 expression and
signal transducer and activator of transcription (STAT)-3 activation in
relation to dendritic cell infiltration and microvessel density in
non-small cell lung cancer
SO BMC CANCER
LA English
DT Article
ID 1E10 ANTIIDIOTYPE VACCINE; GROWTH-FACTOR EXPRESSION; TUMOR ANGIOGENESIS;
BREAST-CARCINOMA; PROGNOSTIC VALUE; MELANOMA TUMORS; SURVIVAL;
DIFFERENTIATION; IMMUNOTHERAPY; NEUROBLASTOMA
AB Background: Tumor immune escape and angiogenesis contribute to tumor progression, and gangliosides and activation of signal transducer and activator of transcription (STAT)-3 are implicated in these processes. As both are considered as novel therapeutic targets, we assessed the possible association of ganglioside GM3 expression and STAT3 activation with suppression of dendritic cell (DC) activation and angiogenesis in non-small cell lung cancer (NSCLC).
Methods: Immunohistochemistry was performed on a tissue array to determine N-glycolyl GM3 (GM3) and phosphorylated STAT3 (pSTAT3) expression in 176 primary NSCLC resections. Median values of GM3 and pSTAT3 expression were used as cut off. Microvessel density (MVD) was determined by CD34 staining and morphology. CD1a and CD83 were used to determine infiltrating immature and mature dendritic cells, respectively.
Results: 94% and 71% of the NSCLC samples expressed GM3 and nuclear pSTAT3, respectively. Median overall survival was 40.0 months. Both low GM3 expression and high pSTAT3 expression were associated with a worse survival, which reached near significance for GM3 (P = 0.08). Microvessel density (MVD), determined by CD34 staining and morphology, was lower in NSCLC samples with high GM3 expression. CD1a(+) cells (immature DCs) were more frequent in NSCLC tissues as compared to peritumoral lung tissue, while CD83(+) cells (mature DCs) were more frequent in peritumoral lung tissue. CD83(+) DCs were less frequent in NSCLC tissues with high GM3 expression.
Conclusion: GM3 and pSTAT3 are widely expressed in NSCLC. Based on CD83 expression, GM3, but not pSTAT3, appeared to be involved in tumor-induced DC suppression. pSTAT3 expression was not associated with MVD, while GM3 might play an anti-angiogenic role.
C1 [van Cruijsen, Hester; Ruiz, Marielle Gallegos; de Gruijl, Tanja D.; Giaccone, Giuseppe] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands.
[van der Valk, Paul] Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1081 HV Amsterdam, Netherlands.
[Giaccone, Giuseppe] NCI, Med Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.
EM h.vancruijsen@vumc.nl; mgallegosruiz@vumc.nl; pvandervalk@vumc.nl;
td.degruijl@vumc.nl; giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
NR 39
TC 37
Z9 37
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD JUN 11
PY 2009
VL 9
AR 180
DI 10.1186/1471-2407-9-180
PG 9
WC Oncology
SC Oncology
GA 477CK
UT WOS:000268495000001
PM 19519895
ER
PT J
AU Kulkarni, SS
Zou, MF
Cao, JJ
Deschamps, JR
Rodriguez, AL
Conn, PJ
Newman, AH
AF Kulkarni, Santosh S.
Zou, Mu-Fa
Cao, Jianjing
Deschamps, Jeffrey R.
Rodriguez, Alice L.
Conn, P. Jeffrey
Newman, Amy Hauck
TI Structure-Activity Relationships Comparing
N-(6-Methylpyridin-yl)-Substituted Aryl Amides to
2-Methyl-6-(substituted-arylethynyl)pyridines or
2-Methyl-4-(substituted-arylethynyl)thiazoles as Novel Metabotropic
Glutamate Receptor Subtype 5 Antagonists
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; MGLUR5 ANTAGONIST; ALLOSTERIC MODULATORS;
ANXIOLYTIC ACTIVITY; SQUIRREL-MONKEYS; COCAINE SEEKING; POTENT;
PHARMACOLOGY; DESIGN; MPEP
AB The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in anxiety, depression, pain, mental retardation, and addiction. The potent and selective noncompetitive mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP, 1) has been a critically important tool used to further elucidate the role of mGluR5 in these CNS disorders. In an effort to provide novel and structurally diverse selective mGluR5 antagonists, we previously described a set of analogues with moderate activity wherein the alkyne bond was replaced with an amide group. In the present report, extended series of both amide and alkyne-based ligands were synthesized. MGluR5 binding and functional data were obtained that identified (1) several novel alkynes with comparable affinities to 1 at mGluR5 (e.g., 10 and 20-23), but (2) most structural variations to the amide template were not well tolerated, although a few potent amides were discovered (e.g., 55 and 56). Several of these novel analogues show drug-like physical properties (e.g., cLogP range = 2-5) that support their use for in vivo investigation into the role of mGluR5 in CNS disorders.
C1 [Kulkarni, Santosh S.; Zou, Mu-Fa; Cao, Jianjing; Newman, Amy Hauck] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Deschamps, Jeffrey R.] USN, Res Lab, Washington, DC 20375 USA.
[Rodriguez, Alice L.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Vanderbilt Program Drug Discovery, Dept Pharmacol, Nashville, TN 37232 USA.
RP Newman, AH (reprint author), Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
RI Conn, Peter/D-7848-2012
FU NIDA-IRP; NINDS [F32 NS049865]; National Institutes of Health (NIH);
NIDA Addiction Treatment Discovery P [N01DA-1-8816]
FX This work was funded by the NIDA-IRP and an NRSA Fellowship F32 NS049865
awarded by NINDS to A.L.R. S.S.K. was supported by a National Institutes
of Health (NIH) Visiting Fellowship. In vitro data as indicated in
Tables I and 2 were provided by the National Institute of Mental
Health's Psychoactive Drug Screening Program, Contract no. NOIMH32004
(NIMH PDSP). The NIMH PDSP is directed by Bryan L. Roth M.D., Ph.D., at
the University of North Carolina at Chapel Hill and Project Officer
Jamie Driscol at NIMH, Bethesda MD. The NIDA Addiction Treatment
Discovery Program contract with SRI (N01DA-1-8816) is acknowledged for
providing DAT, NET, and SERT data and for further supporting our
(A.H.N.) research program.
NR 38
TC 29
Z9 29
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD JUN 11
PY 2009
VL 52
IS 11
BP 3563
EP 3575
DI 10.1021/jm900172f
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 454XX
UT WOS:000266718600016
PM 19445453
ER
PT J
AU Sharma, KK
Razskazovskiy, Y
Purkayastha, S
Bernhard, WA
AF Sharma, Kiran K.
Razskazovskiy, Yuriy
Purkayastha, Shubhadeep
Bernhard, William A.
TI Mechanisms of Strand Break Formation in DNA due to the Direct Effect of
Ionizing Radiation: The Dependency of Free Base Release on the Length of
Alternating CG Oligodeoxynucleotides
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID IRRADIATED CRYSTALLINE DNA; SINGLE-STRAND; PLASMID DNA;
ROOM-TEMPERATURE; 4 K; DAMAGE; HYDRATION; RADICALS; LESIONS; YIELDS
AB The question of how NA base sequence influences the yield of DNA strand breaks produced by the direct effect of ionizing radiation was investigated in a series of oligodeoxynucleotides of the form (d(CG)(n))(2) and (d(GC)(n))(2). The yields of free base release from X-irradiated DNA films containing 2.5 waters/nucleotide were measured by HPLC as a function of oligomer length. For (d(CG)(n))(2), the ratio of the Gua yield to Cyt yield, R, was relatively constant at 2.4-2.5 for n = 2-4 and it decreased to 1.2 as n increased from 5 to 10. When Gua was moved to the 5' end, for example going from d(CG)(5) to d(GC)(5), R dropped from 1.9 +/- 0.1 to 1.1 +/- 0.1. These effects are poorly described if the chemistry at the oligomer ends is assumed to be independent of the remainder of the oligomer. A mathematical model incorporating charge transfer through the base stack was derived to explain these effects. In addition, EPR was used to measure the yield of trapped-deoxyribose radicals at 4 K following X-irradiation at 4 K. The yield of free base release was substantially greater, by 50-100 nmol/J, than the yield of trapped-deoxyribose radicals. Therefore, a large fraction of free base release stems from a nonradical intermediate. For this intermediate, a deoxyribose carbocation formed by two one-electron oxidations is proposed. This reaction pathway requires that the hole (electron loss site) transfers through the base stack and, upon encountering a deoxyribose hole, oxidizes that site to form a deoxyribose carbocation. This reaction mechanism provides a consistent way of explaining both the absence of trapped radical intermediates and the unusual dependence of free base release on oligomer length.
C1 [Sharma, Kiran K.; Bernhard, William A.] Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA.
[Razskazovskiy, Yuriy] E Tennessee State Univ, Dept Phys, Johnson City, TN 37614 USA.
[Purkayastha, Shubhadeep] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Bernhard, WA (reprint author), Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA.
EM William_Bernhard@urmc.rochester.edu
RI SHARMA, KIRAN KUMAR/G-9565-2013;
OI Sharma, Kiran Kumar/0000-0003-1823-1934
FU National Cancer Institute [R01CA032546]
FX The authors thank Ken-nit R. Mercer for his excellent technical support.
The project described was supported by Award Number R01CA032546 from the
National Cancer Institute. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Cancer Institute or the National Institutes of Health.
NR 31
TC 10
Z9 10
U1 1
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD JUN 11
PY 2009
VL 113
IS 23
BP 8183
EP 8191
DI 10.1021/jp900803b
PG 9
WC Chemistry, Physical
SC Chemistry
GA 454JW
UT WOS:000266679200031
PM 19492855
ER
PT J
AU Matsumoto, M
Hikosaka, O
AF Matsumoto, Masayuki
Hikosaka, Okihide
TI Two types of dopamine neuron distinctly convey positive and negative
motivational signals
SO NATURE
LA English
DT Article
ID SACCADIC EYE-MOVEMENTS; VENTRAL TEGMENTAL AREA; MIDBRAIN DOPAMINE;
NUCLEUS-ACCUMBENS; LATERAL HABENULA; AVERSIVE STIMULI; DISCHARGE RATE;
REWARD; STRIATUM; PRIMATE
AB Midbrain dopamine neurons are activated by reward or sensory stimuli predicting reward(1-4). These excitatory responses increase as the reward value increases(5). This response property has led to a hypothesis that dopamine neurons encode value-related signals and are inhibited by aversive events. Here we show that this is true only for a subset of dopamine neurons. We recorded the activity of dopamine neurons in monkeys (Macaca mulatta) during a Pavlovian procedure with appetitive and aversive outcomes (liquid rewards and airpuffs directed at the face, respectively). We found that some dopamine neurons were excited by reward-predicting stimuli and inhibited by airpuff-predicting stimuli, as the value hypothesis predicts. However, a greater number of dopamine neurons were excited by both of these stimuli, inconsistent with the hypothesis. Some dopamine neurons were also excited by both rewards and airpuffs themselves, especially when they were unpredictable. Neurons excited by the airpuff-predicting stimuli were located more dorsolaterally in the substantia nigra pars compacta, whereas neurons inhibited by the stimuli were located more ventromedially, some in the ventral tegmental area. A similar anatomical difference was observed for their responses to actual airpuffs. These findings suggest that different groups of dopamine neurons convey motivational signals in distinct manners.
C1 [Matsumoto, Masayuki; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Matsumoto, M (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM matsumotom@nei.nih.gov
FU Intramural Research Program at the National Institutes of Health,
National Eye Institute
FX We thank S. Hong, E. Bromberg-Martin, M. Yasuda, S. Yamamoto and Y.
Tachibana for discussion, M. K. Smith for his histological expertise, J.
W. McClurkin, A. M. Nichols, T. W. Ruffner, A. V. Hays and L. P. Jensen
for technical assistance, and G. Tansey, D. Parker and B. Nagy for
animal care. This research was supported by the Intramural Research
Program at the National Institutes of Health, National Eye Institute.
NR 29
TC 492
Z9 495
U1 6
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 11
PY 2009
VL 459
IS 7248
BP 837
EP U4
DI 10.1038/nature08028
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 459EV
UT WOS:000267084500038
PM 19448610
ER
PT J
AU Landgren, O
Ghia, P
Caporaso, NE
AF Landgren, Ola
Ghia, Paolo
Caporaso, Neil E.
TI The Precursor of Chronic Lymphocytic Leukemia REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Landgren, Ola; Caporaso, Neil E.] NCI, Bethesda, MD 20892 USA.
[Ghia, Paolo] Univ Vita Salute San Raffaele, I-20132 Milan, Italy.
RP Landgren, O (reprint author), NCI, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
RI Ghia, Paolo/K-7138-2016
OI Ghia, Paolo/0000-0003-3750-7342
NR 1
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 11
PY 2009
VL 360
IS 24
BP 2575
EP 2576
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 456BS
UT WOS:000266813800017
ER
PT J
AU Betz, JM
Wise, SA
AF Betz, Joseph M.
Wise, Stephen A.
TI More on Iodine Content of Prenatal Vitamins
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Betz, Joseph M.] NIH, Bethesda, MD 20892 USA.
[Wise, Stephen A.] NIST, Gaithersburg, MD 20899 USA.
RP Betz, JM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM betzj@od.nih.gov
NR 5
TC 2
Z9 2
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 11
PY 2009
VL 360
IS 24
BP 2582
EP 2582
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 456BS
UT WOS:000266813800032
PM 19516043
ER
PT J
AU Masur, H
Kaplan, JE
AF Masur, Henry
Kaplan, Jonathan E.
TI New Guidelines for the Management of HIV-Related Opportunistic
Infections
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID RECOMMENDATIONS
C1 [Masur, Henry] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Kaplan, Jonathan E.] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Masur, H (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 2C145, Bethesda, MD 20892 USA.
EM hmasur@nih.gov
NR 15
TC 2
Z9 2
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 10
PY 2009
VL 301
IS 22
BP 2378
EP 2380
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 455OT
UT WOS:000266773400031
PM 19509385
ER
PT J
AU Dieffenbach, CW
Fauci, AS
AF Dieffenbach, Carl W.
Fauci, Anthony S.
TI Universal Voluntary Testing and Treatment for Prevention of HIV
Transmission
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID ANTIRETROVIRAL THERAPY; HETEROSEXUAL TRANSMISSION; VIRAL LOAD
C1 [Dieffenbach, Carl W.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Dieffenbach, CW (reprint author), NIAID, NIH, 6700-B Rockledge Dr, Bethesda, MD 20892 USA.
EM cdieffenba@niaid.nih.gov
NR 13
TC 149
Z9 153
U1 0
U2 9
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 10
PY 2009
VL 301
IS 22
BP 2380
EP 2382
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 455OT
UT WOS:000266773400032
PM 19509386
ER
PT J
AU Thanassoulis, G
O'Donnell, CJ
AF Thanassoulis, George
O'Donnell, Christopher J.
TI Mendelian Randomization Nature's Randomized Trial in the Post-Genome Era
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID CORONARY-HEART-DISEASE; APOLIPOPROTEIN(A) GENE; PLASMA LIPOPROTEIN(A);
ARTERY-DISEASE; POLYMORPHISM; ASSOCIATION; PREVENTION; VARIANTS; RISK;
MEN
C1 [Thanassoulis, George; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Thanassoulis, George] Boston Univ, Sch Med, Boston, MA 02118 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA.
EM codonnell@nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 17
TC 32
Z9 32
U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 10
PY 2009
VL 301
IS 22
BP 2386
EP 2388
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 455OT
UT WOS:000266773400034
PM 19509388
ER
PT J
AU Hoe, HS
Lee, KJ
Carney, RSE
Lee, J
Markova, A
Lee, JY
Howell, BW
Hyman, BT
Pak, DTS
Bu, GJ
Rebeck, GW
AF Hoe, Hyang-Sook
Lee, Kea Joo
Carney, Rosalind S. E.
Lee, Jiyeon
Markova, Alexandra
Lee, Ji-Yun
Howell, Brian W.
Hyman, Bradley T.
Pak, Daniel T. S.
Bu, Guojun
Rebeck, G. William
TI Interaction of Reelin with Amyloid Precursor Protein Promotes Neurite
Outgrowth
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ALZHEIMERS-DISEASE; HIPPOCAMPAL-NEURONS; F-SPONDIN; SYNAPTIC PLASTICITY;
TAU PHOSPHORYLATION; ACTIN CYTOSKELETON; SIGNALING PATHWAY; RNA
INTERFERENCE; RECEPTOR APOER2; TRANSGENIC MICE
AB The processing of amyloid precursor protein (APP) to A beta is an important event in the pathogenesis of Alzheimer's disease, but the physiological function of APP is not well understood. Our previous work has shown that APP processing and A beta production are regulated by the extracellular matrix protein Reelin. In the present study, we examined whether Reelin interacts with APP, and the functional consequences of that interaction in vitro. Using coimmunoprecipitation, we found that Reelin interacted with APP through the central domain of Reelin (repeats 3-6) and the E1 extracellular domain of APP. Reelin increased cell surface levels of APP and decreased endocytosis of APP in hippocampal neurons in vitro. In vivo, Reelin levels were increased in brains of APP knock-out mice and decreased in APP-overexpressing mice. RNA interference knockdown of APP decreased neurite outgrowth in vitro and prevented Reelin from increasing neurite outgrowth. Knock-out of APP or Reelin decreased dendritic arborization in cortical neurons in vivo, and APP overexpression increased dendritic arborization. APP and Reelin have previously been shown to promote neurite outgrowth through interactions with integrins. We confirmed that APP interacted with alpha 3 beta 1 integrin, and alpha 3 beta 1 integrin altered APP trafficking and processing. Addition of an alpha 3 beta 1 integrin antibody prevented APP and Reelin-induced neurite outgrowth. These findings demonstrate that Reelin interacts with APP, potentially having important effects on neurite development.
C1 [Hoe, Hyang-Sook; Rebeck, G. William] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA.
[Lee, Kea Joo; Lee, Ji-Yun; Pak, Daniel T. S.] Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20057 USA.
[Carney, Rosalind S. E.] Childrens Natl Med Ctr, Ctr Res Neurosci, Washington, DC 20010 USA.
[Lee, Jiyeon; Bu, Guojun] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Markova, Alexandra; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Disorders, Charlestown, MA 02129 USA.
[Howell, Brian W.] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Rebeck, GW (reprint author), Georgetown Univ, Med Ctr, Dept Neurosci, 3970 Reservoir Rd NW, Washington, DC 20057 USA.
EM gwr2@georgetown.edu
RI Lee, Ji-Yun/F-8127-2013;
OI Howell, Brian/0000-0002-0204-0773
FU National Institutes of Health [AG014473, R01 AG027924, R37 AG012406,
AG032330]; Alzheimer's Research Fund
FX This work was supported by National Institutes of Health Grants AG014473
( G. W. R.), R01 AG027924 ( G. B.), R37 AG012406 ( B. T. H.), and
AG032330 (H.-S.H.), and the Alzheimer's Research Fund in memory of Bill
and Marie Drach. We thank Drs. Andre Goffinet and Tom Curren for
providing Reelin constructs and Drs. Mary Ann Stepp and Susette Mueller
for integrin antibodies. We thank Drs. Sam Gandy and Paul Mathews for
APP antibodies, and Drs. Yasuji Matsuoka and Baoji Xu for helpful
suggestions. We also thank Ulrike Muller for the APP/APLP1 DKO tissue.
NR 55
TC 110
Z9 111
U1 1
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 10
PY 2009
VL 29
IS 23
BP 7459
EP 7473
DI 10.1523/JNEUROSCI.4872-08.2009
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 459SV
UT WOS:000267130800010
PM 19515914
ER
PT J
AU Bennett, MJ
Chik, JK
Slysz, GW
Luchko, T
Tuszynski, J
Sackett, DL
Schriemer, DC
AF Bennett, Melissa J.
Chik, John. K.
Slysz, Gordon W.
Luchko, Tyler
Tuszynski, Jack
Sackett, Dan L.
Schriemer, David C.
TI Structural Mass Spectrometry of the alpha beta-Tubulin Dimer Supports a
Revised Model of Microtubule Assembly
SO BIOCHEMISTRY
LA English
DT Article
ID STATE HYDROGEN-EXCHANGE; MOLECULAR-DYNAMICS; GUANINE-NUCLEOTIDE;
PROTEIN; STABILIZATION; BINDING; GTP; POLYMERIZATION; RESOLUTION;
IDENTIFICATION
AB The molecular basis of microtubule lattice instability derives from the hydrolysis of GTP to GDP in the lattice-bound state of alpha beta-tubulin. While this has been appreciated for many years, there is ongoing debate over the molecular basis of this instability and the possible role of altered nucleotide occupancy in the induction of a conformational change in tubulin. The debate has organized around seemingly contradictory models. The allosteric model invokes nucleotide-dependent states of curvature in the free tubulin dimer, such that hydrolysis leads to pronounced bending and thus disruption of the lattice. The more recent lattice model describes a predominant role for the lattice in straightening free dimers that are curved regardless of their nucleotide state. In this model, lattice-bound GTP-tubulin provides the necessary force to straighten an incoming dimer. Interestingly, there is evidence for both models. The enduring nature of this debate stems from a lack of high-resolution data on the free dimer. In this study, we have prepared alpha beta-tubulin samples at high dilution and characterized the nature of nucleotide-Induced conformational stability using bottom-up hydrogen/deuterium exchange mass spectrometry (H/DX-MS) coupled with isothermal urea denaturation experiments. These experiments were accompanied by molecular dynamics simulations of the free dimer. We demonstrate an intermediate state unique to GDP-tubulin, suggestive of the curved colchicine-stabilized structure at the intradimer interface but show that intradimer flexibility is an important property of the free dimer regardless of nucleotide occupancy. Our results indicate that the assembly properties of the free dimer may be better described on the basis of this flexibility. A blended model of assembly emerges in which free-dimer allosteric effects retain importance, in an assembly process dominated by lattice-induced effects.
C1 [Bennett, Melissa J.; Chik, John. K.; Slysz, Gordon W.; Schriemer, David C.] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada.
[Luchko, Tyler; Tuszynski, Jack] Cross Canc Inst, Div Expt Oncol, Edmonton, AB T6G 1Z2, Canada.
[Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA.
RP Schriemer, DC (reprint author), Univ Calgary, Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
EM dschriem@ucalgary.ca
FU Alberta Cancer Board; Canadian Institutes of Health Research; National
Institute of Child Health and Human Development, NIH; Canada Research
Chair program; Alberta Heritage Foundation for Medical Research (AHFMR);
Ailard Foundation; Alberta Advanced Education and Technology
FX This research was supported by grants from the Alberta Cancer Board, the
Canadian Institutes of Health Research, and intramural funds from the
National Institute of Child Health and Human Development, NIH. D.C.S.
gratefully acknowledges the support of the Canada Research Chair program
and the Alberta Heritage Foundation for Medical Research (AHFMR). J.T.
gratefully acknowledges generous support of the Ailard Foundation and
Alberta Advanced Education and Technology.
NR 48
TC 28
Z9 28
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUN 9
PY 2009
VL 48
IS 22
BP 4858
EP 4870
DI 10.1021/bi900200q
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 453HM
UT WOS:000266601500023
PM 19388626
ER
PT J
AU Ullah, Z
Lee, CY
DePamphilis, ML
AF Ullah, Zakir
Lee, Chrissie Y.
DePamphilis, Melvin L.
TI Cip/Kip cyclin-dependent protein kinase inhibitors and the road to
polyploidy
SO CELL DIVISION
LA English
DT Review
ID TROPHOBLAST GIANT-CELLS; CDK INHIBITORS; S-PHASE; MEGAKARYOCYTIC
DIFFERENTIATION; DROSOPHILA ENDOCYCLE; P57(KIP2) EXPRESSION; GENOMIC
INSTABILITY; REPLICATION ORIGINS; DNA-CONTENT; DEGRADATION
AB Cyclin-dependent kinases (CDKs) play a central role in the orderly transition from one phase of the eukaryotic mitotic cell division cycle to the next. In this context, p27(Kip1) (one of the CIP/KIP family of CDK specific inhibitors in mammals) or its functional analogue in other eukarya prevents a premature transition from G1 to S-phase. Recent studies have revealed that expression of a second member of this family, p57(Kip2), is induced as trophoblast stem (TS) cells differentiate into trophoblast giant (TG) cells. p57 then inhibits CDK1 activity, an enzyme essential for initiating mitosis, thereby triggering genome endoreduplication (multiple S-phases without an intervening mitosis). Expression of p21(Cip1), the third member of this family, is also induced in during differentiation of TS cells into TG cells where it appears to play a role in suppressing the DNA damage response pathway. Given the fact that p21 and p57 are unique to mammals, the question arises as to whether one or both of these proteins are responsible for the induction and maintenance of polyploidy during mammalian development.
C1 [Ullah, Zakir; Lee, Chrissie Y.; DePamphilis, Melvin L.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP DePamphilis, ML (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ullahzak@mail.nih.gov; leecy3@mail.nih.gov; depamphm@mail.nih.gov
FU National Institute of Child Health and Human Development
FX This work was supported by the intramural program of the National
Institute of Child Health and Human Development.
NR 83
TC 40
Z9 45
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1747-1028
J9 CELL DIV
JI Cell Div.
PD JUN 9
PY 2009
VL 4
AR 10
DI 10.1186/1747-1028-4-10
PG 15
WC Cell Biology
SC Cell Biology
GA 674WL
UT WOS:000283781000001
PM 19490616
ER
PT J
AU Walker, CS
Jensen, S
Ellison, M
Matta, JA
Lee, WY
Imperial, JS
Duclos, N
Brockie, PJ
Madsen, DM
Isaac, JTR
Olivera, B
Maricq, AV
AF Walker, Craig S.
Jensen, Stori
Ellison, Michael
Matta, Jose A.
Lee, Won Yong
Imperial, Julita S.
Duclos, Nick
Brockie, Penelope J.
Madsen, David M.
Isaac, John T. R.
Olivera, Baldomero
Maricq, Andres V.
TI A Novel Conus Snail Polypeptide Causes Excitotoxicity by Blocking
Desensitization of AMPA Receptors
SO CURRENT BIOLOGY
LA English
DT Article
ID GLUTAMATE RECEPTORS; ION CHANNELS; CAENORHABDITIS-ELEGANS;
SYNAPTIC-TRANSMISSION; HIPPOCAMPAL-NEURONS; AUXILIARY SUBUNITS;
CYCLOTHIAZIDE; PROTEINS; KAINATE; DOMAIN
AB Background: Ionotropic glutamate receptors (iGluRs) are glutamate-gated ion channels that mediate excitatory neurotransmission in the central nervous system. Based on both molecular and pharmacological criteria, iGluRs have been divided into two major classes, the non-NMDA class, which includes both AMPA and kainate subtypes of receptors, and the NMDA class. One evolutionarily conserved feature of iGluRs is their desensitization in the continued presence of glutamate. Thus, when in a desensitized state, iGluRs can be bound to glutamate, yet the channel remains closed. However, the relevance of desensitization to nervous system function has remained enigmatic.
Results: Here, we report the identification and characterization of a novel polypeptide (con-ikot-ikot) from the venom of a predatory marine snail Conus striatus that specifically disrupts the desensitization of AMPA receptors (AMPARs). The stoichiometry of con-ikot-ikot appears reminiscent of the proposed subunit organization of AMPARs, i.e., a dimer of dimers, suggesting that it acts as a molecular four-legged clamp that holds the AMPAR channel open. Application of con-ikot-ikot to hippocampal slices caused a large and rapid increase in resting AMPAR-mediated current leading to neuronal death.
Conclusions: Our findings provide insight into the mechanisms that regulate receptor desensitization and demonstrate that in the arms race between prey and predators, evolution has selected for a toxin that blocks AMPAR desensitization, thus revealing the fundamental importance of desensitization for regulating neural function.
C1 [Walker, Craig S.; Jensen, Stori; Ellison, Michael; Lee, Won Yong; Imperial, Julita S.; Duclos, Nick; Brockie, Penelope J.; Madsen, David M.; Olivera, Baldomero; Maricq, Andres V.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
[Matta, Jose A.; Isaac, John T. R.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Maricq, AV (reprint author), Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
EM maricq@biology.utah.edu
FU NIH [MH067747, GM48677]; NINDS; PRAT Fellowship
FX We thank R. Shackman and C. Nielsen of the University of Utah Pepticle
Synthesis and Mass Spectrometry Facilities. This research was made
possible by support from NIH Grants MH067747 (A.V.M) and GM48677 (B.O.),
the NINDS Intramural program (J.A.M., J.T.R.I.), and a PRAT Fellowship
(J.A.M.).
NR 40
TC 34
Z9 36
U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD JUN 9
PY 2009
VL 19
IS 11
BP 900
EP 908
DI 10.1016/j.cub.2009.05.017
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 456YX
UT WOS:000266891900022
PM 19481459
ER
PT J
AU Yaffe, K
Fiocco, AJ
Lindquist, K
Vittinghoff, E
Simonsick, EM
Newman, AB
Satterfield, S
Rosano, C
Rubin, SM
Ayonayon, HN
Harris, TB
AF Yaffe, K.
Fiocco, A. J.
Lindquist, K.
Vittinghoff, E.
Simonsick, E. M.
Newman, A. B.
Satterfield, S.
Rosano, C.
Rubin, S. M.
Ayonayon, H. N.
Harris, T. B.
CA Hlth ABC Study
TI Predictors of maintaining cognitive function in older adults The Health
ABC Study
SO NEUROLOGY
LA English
DT Article
ID ATTENTIONAL CONTROL; ALZHEIMERS-DISEASE; GLUCOSE-TOLERANCE; LIFE-STYLE;
WOMEN; PLASTICITY; EXERCISE; DECLINE; BRAIN; AGE
AB Background: Although several risk factors for cognitive decline have been identified, much less is known about factors that predict maintenance of cognitive function in advanced age.
Methods: We studied 2,509 well-functioning black and white elders enrolled in a prospective study. Cognitive function was measured using the Modified Mini-Mental State Examination at baseline and years 3, 5, and 8. Random effects models were used to classify participants as cognitive maintainers (cognitive change slope >= 0), minor decliners (slope <0 and >1 SD below mean), or major decliners (slope <= 1 SD below mean). Logistic regression was used to identify domain-specific factors associated with being a maintainer vs a minor decliner.
Results: Over 8 years, 30% of the participants maintained cognitive function, 53% showed minor decline, and 16% had major cognitive decline. In the multivariate model, baseline variables significantly associated with being a maintainer vs a minor decliner were age (odds ratio [OR] = 0.65, 95% confidence interval [CI] 0.55-0.77 per 5 years), white race (OR = 1.72, 95% CI 1.30-2.28), high school education level or greater (OR = 2.75, 95% CI 1.78-4.26), ninth grade literacy level or greater (OR = 4.85, 95% CI 3.00-7.87), weekly moderate/vigorous exercise (OR = 1.31, 95% CI 1.06-1.62), and not smoking (OR = 1.84, 95% CI 1.14-2.97). Variables associated with major cognitive decline compared to minor cognitive decline are reported.
Conclusion: Elders who maintain cognitive function have a unique profile that differentiates them from those with minor decline. Importantly, some of these factors are modifiable and thus may be implemented in prevention programs to promote successful cognitive aging. Further, factors associated with maintenance may differ from factors associated with major cognitive decline, which may impact prevention vs treatment strategies. Neurology (R) 2009; 72: 2029-2035
C1 [Yaffe, K.; Fiocco, A. J.] Univ San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94117 USA.
[Yaffe, K.; Vittinghoff, E.; Rubin, S. M.; Ayonayon, H. N.] Univ San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94117 USA.
[Yaffe, K.] Univ San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94117 USA.
[Lindquist, K.] Univ San Francisco, Sch Med, Dept Med, San Francisco, CA 94117 USA.
[Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Simonsick, E. M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Baltimore, MD 21224 USA.
[Newman, A. B.; Rosano, C.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Satterfield, S.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
RP Fiocco, AJ (reprint author), Univ San Francisco, Sch Med, Dept Psychiat, 4150 Clement St, San Francisco, CA 94117 USA.
EM jazzfiocco@hotmail.com
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506;
Rosano, Caterina/0000-0002-4271-6010
FU Intramural NIH HHS; NIA NIH HHS [AG 031155, AG021918, N01-AG-6-2101,
N01-AG-6-2103, N01-AG-6-2106]
NR 36
TC 112
Z9 118
U1 0
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN 9
PY 2009
VL 72
IS 23
BP 2029
EP 2035
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 455QI
UT WOS:000266777500012
PM 19506226
ER
PT J
AU Hindorff, LA
Sethupathy, P
Junkins, HA
Ramos, EM
Mehta, JP
Collins, FS
Manolio, TA
AF Hindorff, Lucia A.
Sethupathy, Praveen
Junkins, Heather A.
Ramos, Erin M.
Mehta, Jayashri P.
Collins, Francis S.
Manolio, Teri A.
TI Potential etiologic and functional implications of genome-wide
association loci for human diseases and traits
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE catalog; evolution; GWAS; polymorphism; disorders
ID PROSTATE-CANCER SUSCEPTIBILITY; POSITIVE SELECTION; SKIN PIGMENTATION;
POLYMORPHISMS; GENETICS
AB We have developed an online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs (TASs). Reported TASs were common [ median risk allele frequency 36%, interquartile range (IQR) 21% - 53%] and were associated with modest effect sizes [ median odds ratio ( OR) 1.33, IQR 1.20 - 1.61]. Among 20 genomic annotation sets, reported TASs were significantly overrepresented only in nonsynonymous sites [ OR = 3.9 (2.2 - 7.0), p = 3.5 x 10(-7)] and 5kb-promoter regions [ OR = 2.3 (1.5 - 3.6), p = 3 x 10(-4)] compared to SNPs randomly selected from genotyping arrays. Although 88% of TASs were intronic (45%) or intergenic (43%), TASs were not overrepresented in introns and were significantly depleted in intergenic regions [ OR = 0.44 (0.34 = 0.58), p = 2.0 x 10(-9)]. Only slightly more TASs than expected by chance were predicted to be in regions under positive selection [OR = 1.3 (0.8 x 2.1), p = 0.2]. This new online resource, together with bioinformatic predictions of the underlying functionality at trait/disease-associated loci, is well-suited to guide future investigations of the role of common variants in complex disease etiology.
C1 [Sethupathy, Praveen; Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Hindorff, Lucia A.; Junkins, Heather A.; Ramos, Erin M.; Manolio, Teri A.] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA.
[Mehta, Jayashri P.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
RP Collins, FS (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
EM francis_collins2@nih.gov; manolio@nih.gov
FU National Human Genome Research Institute; National Library of Medicine
FX We thank Judy Wyatt and Kent Klemm (NHGRI) for their work in developing
the catalog into an online resource and Narisu Narisu, Lori Bonnycastle,
and Samir Kelada ( NHGRI) for several helpful discussions and insightful
suggestions for the manuscript. We also would like to thank Praveen
Cherukuri in the J. Mullikin Lab ( NHGRI) for kindly sharing the program
CDPred and the 3 reviewers for their expertise and insightful
suggestions that greatly improved the manuscript. This work was
supported in part by the intramural programs of the National Human
Genome Research Institute and the National Library of Medicine.
NR 18
TC 2021
Z9 2077
U1 16
U2 151
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 JUN 9
PY 2009
VL 106
IS 23
BP 9362
EP 9367
DI 10.1073/pnas.0903103106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 456CN
UT WOS:000266817500047
PM 19474294
ER
PT J
AU Haruta, M
Bush, RA
Kjellstrom, S
Vijayasarathy, C
Zeng, Y
Le, YZ
Sieving, PA
AF Haruta, Masatoshi
Bush, Ronald A.
Kjellstrom, Sten
Vijayasarathy, Camasamudram
Zeng, Yong
Le, Yun-Zheng
Sieving, Paul A.
TI Depleting Rac1 in mouse rod photoreceptors protects them from
photo-oxidative stress without affecting their structure or function
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE apoptosis; retinal degeneration; Rho GTPases; retinal light damage;
superoxide anions
ID RETINAL DEGENERATION; NADPH-OXIDASE; RHO-GTPASES; IN-VIVO; TRANSGENIC
MICE; OUTER SEGMENTS; LIGHT DAMAGE; CELL-DEATH; A-WAVE; RHODOPSIN
AB In nonphagocytic cells, Rac1 is a component of NADPH oxidase that produces reactive oxygen species [Ushio-Fukai M (2006) Sci STKE 2006:re8]. Rac1 is expressed abundantly in mammalian retinal photoreceptors, where it is activated in response to light stimuli [Balasubramanian N, Slepak VZ (2003) Curr Biol 13:1306-1310]. We used Cre-LoxP conditional gene targeting to knock down Rac1 expression in mouse rod photoreceptors and found protection against light-induced photoreceptor death compared with WT litter-mates. We also found a similar protective effect on rods using apocynin, which inhibits NADPH oxidase activity. These results implicate both neuronal Rac1 and NADPH oxidase in cell death in this model of CNS degeneration. Studies in which dominant-mutants of Rac1 were expressed in transgenic Drosophila species demonstrated that Rac1 is a key regulator of photoreceptor morphogenesis and polarity [Chang HY, Ready DF (2000) Science 290:1978-1980]. However, we found that diminished Rac1 expression in mouse rods had no effect on retinal structure or function examined by light microscopy, electron microscopy, rhodopsin measurement, electroretinogram activity, and visual acuity, indicating rod outer segment morphogenesis proceeded normally in Rac1 conditional knockout mice. The lack of structural or functional effect of Rac1 depletion on photoreceptors, but protection under conditions of stress, indicate that the Rac1 pathway warrants exploration as a target for therapy in retinal neurodegenerative diseases.
C1 [Haruta, Masatoshi; Bush, Ronald A.; Kjellstrom, Sten; Vijayasarathy, Camasamudram; Zeng, Yong; Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
[Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
[Le, Yun-Zheng] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA.
[Le, Yun-Zheng] Univ Oklahoma, Hlth Sci Ctr, Harold Hamm Oklahoma Diabet Ctr, Oklahoma City, OK 73104 USA.
RP Sieving, PA (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
EM paulsieving@nei.nih.gov
NR 52
TC 32
Z9 33
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 9
PY 2009
VL 106
IS 23
BP 9397
EP 9402
DI 10.1073/pnas.0808940106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 456CN
UT WOS:000266817500053
PM 19470639
ER
PT J
AU Dinoso, JB
Kim, SY
Wiegand, AM
Palmer, SE
Gange, SJ
Cranmer, L
O'Shea, A
Callender, M
Spivak, A
Brennan, T
Kearney, MF
Proschan, MA
Mican, JM
Rehm, CA
Coffin, JM
Mellors, JW
Siliciano, RF
Maldarelli, F
AF Dinoso, J. B.
Kim, S. Y.
Wiegand, A. M.
Palmer, S. E.
Gange, S. J.
Cranmer, L.
O'Shea, A.
Callender, M.
Spivak, A.
Brennan, T.
Kearney, M. F.
Proschan, M. A.
Mican, J. M.
Rehm, C. A.
Coffin, J. M.
Mellors, J. W.
Siliciano, R. F.
Maldarelli, F.
TI Treatment intensification does not reduce residual HIV-1 viremia in
patients on highly active antiretroviral therapy
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE antiretroviral drug intensification; HIV-1 persistance; viral reservoir
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; CD4(+) T-CELLS;
RECEIVING COMBINATION THERAPY; CEREBROSPINAL-FLUID; LATENT RESERVOIR;
HIV-1-INFECTED PATIENTS; DRUG CONCENTRATIONS; LIFELONG PERSISTENCE;
VIROLOGICAL OUTCOMES
AB In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.
C1 [Wiegand, A. M.; Palmer, S. E.; Kearney, M. F.; Coffin, J. M.; Maldarelli, F.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA.
[Dinoso, J. B.; Kim, S. Y.; Cranmer, L.; Callender, M.; Spivak, A.; Brennan, T.; Siliciano, R. F.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Dinoso, J. B.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
[Gange, S. J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[O'Shea, A.] NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Proschan, M. A.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Mican, J. M.; Rehm, C. A.] NIAID, Div Clin Res, Bethesda, MD 20892 USA.
[Coffin, J. M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
[Mellors, J. W.] Univ Pittsburgh, Sch Med, Dept Infect Dis, Pittsburgh, PA 15261 USA.
[Siliciano, R. F.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
RP Coffin, JM (reprint author), NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA.
EM john.coffin@tufts.edu; fmalli@mail.nih.gov
OI Gange, Stephen/0000-0001-7842-512X; Spivak, Adam/0000-0003-1815-7893
FU Science Applications International Corporation [25XS119]
FX We are grateful to the participants who volunteered for this study. We
thank the laboratory of C. Flexner for performing drug level monitoring.
We thank R. Burke and S. Stallings for assistance and thank J. Kovacs,
R. Davey, M. Polis, H. Masur, V. Boltz, and H. C. Lane for helpful
discussions. J. M. C. was a Research Professor of the American Cancer
Society, with support from the George Kirby Foundation. J. W. M.
received support through Science Applications International Corporation
Subcontract 25XS119.
NR 54
TC 257
Z9 262
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 9
PY 2009
VL 106
IS 23
BP 9403
EP 9408
DI 10.1073/pnas.0903107106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 456CN
UT WOS:000266817500054
PM 19470482
ER
PT J
AU Mullighan, CG
Zhang, JH
Harvey, RC
Collins-Underwood, JR
Schulman, BA
Phillips, LA
Tasian, SK
Loh, ML
Su, XP
Liu, W
Devidas, M
Atlas, SR
Chen, IM
Clifford, RJ
Gerhard, DS
Carroll, WL
Reaman, GH
Smith, M
Downing, JR
Hunger, SP
Willman, CL
AF Mullighan, Charles G.
Zhang, Jinghui
Harvey, Richard C.
Collins-Underwood, J. Racquel
Schulman, Brenda A.
Phillips, Letha A.
Tasian, Sarah K.
Loh, Mignon L.
Su, Xiaoping
Liu, Wei
Devidas, Meenakshi
Atlas, Susan R.
Chen, I-Ming
Clifford, Robert J.
Gerhard, Daniela S.
Carroll, William L.
Reaman, Gregory H.
Smith, Malcolm
Downing, James R.
Hunger, Stephen P.
Willman, Cheryl L.
TI JAK mutations in high-risk childhood acute lymphoblastic leukemia
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE IKAROS; kinase; mutation
ID DEPENDENT KINASE CDK6; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA-VERA;
CRYSTAL-STRUCTURE; STRUCTURAL BASIS; COMPETING RISK; ACTIVATION;
INHIBITOR; CLASSIFICATION; JANUS-KINASE-2
AB Pediatric acute lymphoblastic leukemia (ALL) is a heterogeneous disease consisting of distinct clinical and biological subtypes that are characterized by specific chromosomal abnormalities or gene mutations. Mutation of genes encoding tyrosine kinases is uncommon in ALL, with the exception of Philadelphia chromosome-positive ALL, where the t(9,22)(q34;q11) translocation encodes the constitutively active BCR-ABL1 tyrosine kinase. We recently identified a poor prognostic subgroup of pediatric BCR-ABL1-negative ALL patients characterized by deletion of IKZF1 (encoding the lymphoid transcription factor IKAROS) and a gene expression signature similar to BCR-ABL1-positive ALL, raising the possibility of activated tyrosine kinase signaling within this leukemia subtype. Here, we report activating mutations in the Janus kinases JAK1 (n = 3), JAK2 (n = 16), and JAK3 (n = 1) in 20 (10.7%) of 187 BCR-ABL1-negative, high-risk pediatric ALL cases. The JAK1 and JAK2 mutations involved highly conserved residues in the kinase and pseudokinase domains and resulted in constitutive JAK-STAT activation and growth factor independence of Ba/F3-EpoR cells. The presence of JAK mutations was significantly associated with alteration of IKZF1 (70% of all JAK-mutated cases and 87.5% of cases with JAK2 mutations; P = 0.001) and deletion of CDKN2A/B (70% of all JAK-mutated cases and 68.9% of JAK2-mutated cases). The JAK-mutated cases had a gene expression signature similar to BCR-ABL1 pediatric ALL, and they had a poor outcome. These results suggest that inhibition of JAK signaling is a logical target for therapeutic intervention in JAK mutated ALL.
C1 [Mullighan, Charles G.; Collins-Underwood, J. Racquel; Phillips, Letha A.; Su, Xiaoping; Downing, James R.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Liu, Wei] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA.
[Zhang, Jinghui] NCI, Ctr Biomed Informat & Informat Technol, NIH, Rockville, MD 20852 USA.
[Harvey, Richard C.; Atlas, Susan R.; Chen, I-Ming; Willman, Cheryl L.] Univ New Mexico, Canc Res & Treatment Ctr, Canc Res Facil, Albuquerque, NM 87131 USA.
[Schulman, Brenda A.] St Jude Childrens Hosp, Dept Biol Struct, Memphis, TN 38105 USA.
[Schulman, Brenda A.] St Jude Childrens Hosp, Howard Hughes Med Inst, Memphis, TN 38105 USA.
[Tasian, Sarah K.; Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Devidas, Meenakshi] Univ Florida, Coll Med, Dept Epidemiol & Hlth Policy Res, Childrens Oncol Grp, Gainesville, FL 32601 USA.
[Atlas, Susan R.] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA.
[Clifford, Robert J.] NCI, Lab Populat Genet, NIH, Bethesda, MD 20852 USA.
[Gerhard, Daniela S.] NCI, Off Canc Genom, NIH, Bethesda, MD 20852 USA.
[Carroll, William L.] NYU, Inst Canc, New York, NY 10016 USA.
[Reaman, Gregory H.] George Washington Univ, Sch Med & Hlth Sci, Bethesda, MD 20814 USA.
[Smith, Malcolm] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20852 USA.
[Hunger, Stephen P.] Univ Colorado Denver, Sch Med, Sect Pediat Hematol Oncol Bone Marrow Transplanta, Aurora, CO 80045 USA.
[Hunger, Stephen P.] Univ Colorado Denver, Sch Med, Ctr Canc & Blood Disorders, Aurora, CO 80045 USA.
RP Downing, JR (reprint author), St Jude Childrens Hosp, Dept Pathol, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM james.downing@stjude.org; hunger.stephen@tchden.org;
cwillman@salud.unm.edu
OI Tasian, Sarah/0000-0003-1327-1662; Harvey, Richard/0000-0002-4904-9767;
Mullighan, Charles/0000-0002-1871-1850
FU Howard Hughes Medical Institute; NCI NIH HHS [CA098543, CA114762, L40
CA142226, P30 CA118100, T32 CA128583, U01 CA114762, U10 CA098413, U10
CA098543, U10 CA98413, U10 CA98543]; NICHD NIH HHS [T32 HD044331]; PHS
HHS [N01-C0-12400]
NR 33
TC 262
Z9 269
U1 2
U2 10
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 9
PY 2009
VL 106
IS 23
BP 9414
EP 9418
DI 10.1073/pnas.0811761106
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 456CN
UT WOS:000266817500056
PM 19470474
ER
PT J
AU Goldstein, RZ
Alia-Klein, N
Tomasi, D
Carrillo, JH
Maloney, T
Woicik, PA
Wang, RL
Telang, F
Volkow, ND
AF Goldstein, Rita Z.
Alia-Klein, Nelly
Tomasi, Dardo
Carrillo, Jean Honorio
Maloney, Thomas
Woicik, Patricia A.
Wang, Ruiliang
Telang, Frank
Volkow, Nora D.
TI Anterior cingulate cortex hypoactivations to an emotionally salient task
in cocaine addiction
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE blood-oxygen-level-dependent fMRI; salience; brain-behavior
dissociation; craving; cocaine use
ID POSTTRAUMATIC-STRESS-DISORDER; BRAIN ACTIVATION; COUNTING STROOP;
FRONTAL-CORTEX; FMRI; DYSFUNCTION; DEPRESSION; CONFLICT; ABUSERS;
IMPULSIVITY
AB Anterior cingulate cortex (ACC) hypoactivations during cognitive processing characterize drug addicted individuals as compared with healthy controls. However, impaired behavioral performance or task disengagement may be crucial factors. We hypothesized that ACC hypoactivations would be documented in groups matched for performance on an emotionally salient task. Seventeen individuals with current cocaine use disorders ( CUD) and 17 demographically matched healthy controls underwent functional magnetic resonance imaging during performance of a rewarded drug cue-reactivity task previously shown to engage the ACC. Despite lack of group differences in objective or subjective task-related performance, CUD showed more ACC hypoactivations throughout this emotionally salient task. Nevertheless, intensity of emotional salience contributed to results: (i) CUD with the largest rostroventral ACC [Brodmann Area (BA) 10, 11, implicated in default brain functionl hypoactivations to the most salient task condition (drug words during the highest available monetary reward), had the least task-induced cocaine craving; (ii) CUD with the largest caudal-dorsal ACC (BA 32) hypoactivations especially to the least salient task condition (neutral words with no reward) had the most frequent current cocaine use; and (iii) responses to the most salient task condition in both these ACC major subdivisions were positively intercorrelated in the controls only. In conclusion, ACC hypoactivations in drug users cannot be attributed to task difficulty or disengagement. Nevertheless, emotional salience modulates ACC responses in proportion to drug use severity. Interventions to strengthen ACC reactivity or interconnectivity may be beneficial in enhancing top-down monitoring and emotion regulation as a strategy to reduce impulsive and compulsive behavior in addiction.
C1 [Goldstein, Rita Z.; Alia-Klein, Nelly; Tomasi, Dardo; Carrillo, Jean Honorio; Maloney, Thomas; Woicik, Patricia A.; Wang, Ruiliang; Telang, Frank] Brookhaven Natl Lab, Dept Med Res, Ctr Translat Neuroimaging, Upton, NY 11973 USA.
[Carrillo, Jean Honorio] SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11794 USA.
[Telang, Frank] NIAAA, Rockville, MD 20857 USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, Rockville, MD 20892 USA.
RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, Dept Med Res, Ctr Translat Neuroimaging, Upton, NY 11973 USA.
EM rgoldstein@bnl.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institute on Drug Abuse [1R01DA023579, R21DA02062]; General
Clinical Research Center [5-MO1-RR-10710]
FX We thank Muhammad A. Parvaz for help with task administration, Alex
Panagopoulos and Dimitris Samaras for help with early data analyses, and
Gene- Jack Wang for help with medical screens. This study was supported
by National Institute on Drug Abuse Grants 1R01DA023579 and R21DA02062
(to R.Z.G.) and General Clinical Research Center Grant 5-MO1-RR-10710.
NR 51
TC 89
Z9 92
U1 5
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 JUN 9
PY 2009
VL 106
IS 23
BP 9453
EP 9458
DI 10.1073/pnas.0900491106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 456CN
UT WOS:000266817500063
PM 19478067
ER
PT J
AU Wilke, M
Mueller, KM
Leopold, DA
AF Wilke, Melanie
Mueller, Kai-Markus
Leopold, David A.
TI Neural activity in the visual thalamus reflects perceptual suppression
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE vision; LGN; awareness; pulvinar; attention
ID LATERAL GENICULATE-NUCLEUS; MOTION-INDUCED BLINDNESS; BINOCULAR-RIVALRY;
PATTERN-DISCRIMINATION; HUMAN PULVINAR; RHESUS-MONKEY; AWAKE MONKEY;
CORTEX; ATTENTION; LESIONS
AB To examine the role of the visual thalamus in perception, we recorded neural activity in the lateral geniculate nucleus (LGN) and pulvinar of 2 macaque monkeys during a visual illusion that induced the intermittent perceptual suppression of a bright luminance patch. Neural responses were sorted on the basis of the trial-to-trial visibility of the stimulus, as reported by the animals. We found that neurons in the dorsal and ventral pulvinar, but not the LGN, showed changes in spiking rate according to stimulus visibility. Passive viewing control sessions showed such modulation to be independent of the monkeys' active report. Perceptual suppression was also accompanied by a marked drop in low-frequency power (9-30 Hz) of the local field potential (LFP) throughout the visual thalamus, but this modulation was not observed during passive viewing. Our findings demonstrate that visual responses of pulvinar neurons reflect the perceptual awareness of a stimulus, while those of LGN neurons do not.
C1 [Wilke, Melanie; Mueller, Kai-Markus; Leopold, David A.] NIMH, Unit Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Mueller, Kai-Markus] Univ Tubingen, Int Max Planck Res Sch, D-72074 Tubingen, Germany.
[Leopold, David A.] NIMH, Neurophysiol Imaging Facil, NINDS, NEI,NIH, Bethesda, MD 20892 USA.
RP Wilke, M (reprint author), CALTECH, Div Biol, Pasadena, CA 91125 USA.
EM melanie@vis.caltech.edu
OI Leopold, David/0000-0002-1345-6360
FU Intramural NIH HHS [Z01 MH002838-04, Z01 MH002898-02]
NR 53
TC 53
Z9 53
U1 2
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 9
PY 2009
VL 106
IS 23
BP 9465
EP 9470
DI 10.1073/pnas.0900714106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 456CN
UT WOS:000266817500065
PM 19458249
ER
PT J
AU Balla, T
AF Balla, Tamas
TI Finding Partners for PI3K gamma: When 84 Is Better Than 101
SO SCIENCE SIGNALING
LA English
DT Article
ID MYELOID-DERIVED CELLS; PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL
3-KINASE; REGULATORY SUBUNIT; KINASE; GAMMA; INHIBITION; P110-GAMMA;
WORTMANNIN; P110-ALPHA
AB Phosphatidylinositol 3-kinase (PI3K) enzymes phosphorylate phosphatidylinositol 4,5-bisphosphate [ PtdIns( 4,5) P(2), also known as PIP(2)], a minor but critically important phospholipid of the inner leaflet of the plasma membrane. The resulting PtdIns( 3,4,5) P(3) (PIP(3)) acts as a membrane-bound attractant that recruits and activates a set of proteins to execute specific downstream signaling events to achieve the desired biological outcomes. Several genes that encode different PI3Ks exist in mammalian cells, and in the case of each PI3K, a partner protein that is tightly associated with the kinase ensures that the enzyme is localized to and activated at the correct membrane compartment. Excess PtdIns( 3,4,5) P3 is a major contributor to many forms of cancer, and dysregulation of PI3Ks leads to severe immunological and metabolic abnormalities. Given the multitude of proteins that are regulated by PtdIns( 3,4,5) P3, it is puzzling that not all of these targets are activated as soon as the lipid is produced in the plasma membrane. Reports have begun to shed light on the mechanism by which cells can discriminate between PtdIns( 3,4,5) P3 depending on the distinct PI3K protein that produced it. A study shows that PtdIns( 3,4,5) P3 regulates the degranulation of mast cells, but only if it is made by a PI3K that is associated with a specific adaptor protein. This remarkable specificity challenges our views of how phosphoinositides regulate their downstream effectors.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, NIH, Bethesda, MD 20892 USA.
RP Balla, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
EM ballat@mail.nih.gov
OI Balla, Tamas/0000-0002-9077-3335
FU Intramural NIH HHS
NR 29
TC 2
Z9 2
U1 3
U2 4
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD JUN 9
PY 2009
VL 2
IS 74
AR pe35
DI 10.1126/scisignal.274pe35
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 567VP
UT WOS:000275475300002
PM 19509404
ER
PT J
AU Kai, K
D'Costa, S
Sills, RC
Kim, Y
AF Kai, Kiyonori
D'Costa, Susan
Sills, Robert C.
Kim, Yongbaek
TI Inhibition of the insulin-like growth factor 1 receptor pathway enhances
the antitumor effect of cisplatin in human malignant mesothelioma cell
lines
SO CANCER LETTERS
LA English
DT Article
DE Malignant mesothelioma; Insulin-like growth factor 1 receptor; AG1024;
Cisplatin; Chemoresistance
ID LUNG-CANCER CELLS; OVARIAN-CANCER; PLEURAL MESOTHELIOMA; FACTOR-I;
INDUCED APOPTOSIS; HUMAN-BREAST; RESISTANCE; PTEN; ACTIVATION;
EXPRESSION
AB Human malignant mesothelioma (HMM) is a fatal tumor and is poorly responsive to current therapeutic regimens. The insulin-like growth factor 1 receptor (IGF-1R) pathway is activated in HMM cell lines and tissues. Treatment with AG1024, an inhibitor of the IGF-1R pathway, significantly decreased cell proliferation and attenuated the phosphorylation of Akt and p44/42. In addition, it significantly enhanced the cytotoxic effects of cisplatin in HMM cell lines. This study supports the conjecture that inhibition of the IGF-1R pathway may be a useful target for reducing toxicity and alleviating chemoresistance to traditional anticancer drugs in HMM patients. (c) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Kai, Kiyonori; D'Costa, Susan; Kim, Yongbaek] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC 27606 USA.
[Sills, Robert C.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
[Kai, Kiyonori] Daiichi Sankyo Co Ltd, Med Safety Res Labs, Shinagawa Ku, Tokyo 1408710, Japan.
RP Kim, Y (reprint author), N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, 4700 Hillsborough St, Raleigh, NC 27606 USA.
EM yongbaek_kim@ncsu.edu
FU CVM; North Carolina State University
FX We would like to thank all of the researchers who provided cell lines
and reagents. This study was supported by a CVM grant funded by North
Carolina State University.
NR 33
TC 22
Z9 22
U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD JUN 8
PY 2009
VL 278
IS 1
BP 49
EP 55
DI 10.1016/j.canlet.2008.12.023
PG 7
WC Oncology
SC Oncology
GA 440PS
UT WOS:000265712800008
PM 19178995
ER
PT J
AU Kawakami, Y
Tomimori, Y
Yumoto, K
Hasegawa, S
Ando, T
Tagaya, Y
Crotty, S
Kawakami, T
AF Kawakami, Yuko
Tomimori, Yoshiaki
Yumoto, Kenji
Hasegawa, Shunji
Ando, Tomoaki
Tagaya, Yutaka
Crotty, Shane
Kawakami, Toshiaki
TI Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce
severe skin lesions in a mouse model of eczema vaccinatum
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID ATOPIC-DERMATITIS; SMALLPOX VACCINATION; T-CELLS; IL-21; INSIGHTS;
INVIVO
AB Threats of bioterrorism have renewed efforts to better understand poxvirus pathogenesis and to develop a safer vaccine against smallpox. Individuals with atopic dermatitis are excluded from smallpox vaccination because of their propensity to develop eczema vaccinatum, a disseminated vaccinia virus (VACV) infection. To study the underlying mechanism of the vulnerability of atopic dermatitis patients to VACV infection, we developed a mouse model of eczema vaccinatum. Virus infection of eczematous skin induced severe primary erosive skin lesions, but not in the skin of healthy mice. Eczematous mice exhibited lower natural killer (NK) cell activity but similar cytotoxic T lymphocyte activity and humoral immune responses. The role of NK cells in controlling VACV-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. The proinflammatory cytokine interleukin (IL)-17 reduced NK cell activity in mice with preexisting dermatitis. Given low NK cell activities and increased IL-17 expression in atopic dermatitis patients, these results can explain the increased susceptibility of atopic dermatitis patients to eczema vaccinatum.
C1 [Kawakami, Yuko; Tomimori, Yoshiaki; Yumoto, Kenji; Hasegawa, Shunji; Ando, Tomoaki; Kawakami, Toshiaki] La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA.
[Crotty, Shane] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA.
[Crotty, Shane; Kawakami, Toshiaki] La Jolla Inst Allergy & Immunol, Ctr Infect Dis, La Jolla, CA 92037 USA.
[Tagaya, Yutaka] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Kawakami, T (reprint author), La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA.
EM yuko@liai.org; toshi@liai.org
RI Kawakami, Toshiaki/O-1616-2015
FU NIAID NIH HHS [AI77953, AI63107, N01AI40030, R01 AI063107, U01 AI077953]
NR 27
TC 53
Z9 57
U1 0
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUN 8
PY 2009
VL 206
IS 6
BP 1219
EP 1225
DI 10.1084/jem.20082835
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 459TS
UT WOS:000267133700003
PM 19468065
ER
PT J
AU la Sala, A
He, JP
Laricchia-Robbio, L
Gorini, S
Iwasaki, A
Braun, M
Yap, GS
Sher, A
Ozato, K
Kelsall, B
AF la Sala, Andrea
He, Jianping
Laricchia-Robbio, Leopoldo
Gorini, Stefania
Iwasaki, Akiko
Braun, Michael
Yap, George S.
Sher, Alan
Ozato, Keiko
Kelsall, Brian
TI Cholera toxin inhibits IL-12 production and CD8 alpha(+) dendritic cell
differentiation by cAMP-mediated inhibition of IRF8 function
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID SEQUENCE-BINDING-PROTEIN; REGULATORY FACTOR-I; TOXOPLASMA-GONDII;
INTERLEUKIN-12; MACROPHAGES; ACTIVATION; ICSBP; EXPRESSION; INFECTION;
PROMOTER
AB Prior studies have demonstrated that cholera toxin (CT) and other cAMP-inducing factors inhibit interleukin (IL)-12 production from monocytes and dendritic cells (DCs). We show that CT inhibits Th1 responses in vivo in mice infected with Toxoplasma gondii. This correlated with low serum IL-12 levels and a selective reduction in the numbers of CD8 alpha(+) conventional DCs (cDCs) in lymphoid organs. CT inhibited the function of interferon (IFN) regulatory factor (IRF) 8, a transcription factor known to positively regulate IL-12p35 and p40 gene expression, and the differentiation of CD8 alpha(+) and plasmacytoid DCs (pDCs). Fluorescence recovery after photobleaching analysis showed that exposure to CT, forskolin, or dibutyryl (db) cAMP blocked LPS and IFN-gamma-induced IRF8 binding to chromatin. Moreover, CT and dbcAMP inhibited the binding of IRF8 to the IFN-stimulated response element (ISRE)-like element in the mouse IL-12p40 promoter, likely by blocking the formation of ISRE-binding IRF1-IRF8 heterocomplexes. Furthermore, CT inhibited the differentiation of pDCs from fms-like tyrosine kinase 3 ligand-treated bone marrow cells in vitro. Therefore, because IRF8 is essential for IL-12 production and the differentiation of CD8 alpha(+) cDCs and pDCs, these data suggest that CT and other Gs-protein agonists can affect IL-12 production and DC differentiation via a common mechanism involving IRF8.
C1 [He, Jianping; Kelsall, Brian] NICHHD, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Sher, Alan] NICHHD, Immunobiol Sect, Parasit Dis Lab, NIAID,NIH, Bethesda, MD 20892 USA.
[Laricchia-Robbio, Leopoldo; Ozato, Keiko] NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA.
[la Sala, Andrea; Gorini, Stefania] Ist Ricovero & Cura Carattere Sci San Raffaele, Lab Mol & Cellular Immunol, I-00163 Rome, Italy.
[Iwasaki, Akiko] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
[Braun, Michael] Univ Texas Hlth Sci Ctr Houston, Dept Pediat, Div Pediat Nephrol & Hypertens, Houston, TX 77030 USA.
[Yap, George S.] Univ Med & Dent New Jersey, Sch Med, Ctr Immun & Inflammat, Newark, NJ 07101 USA.
RP Kelsall, B (reprint author), NICHHD, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
EM kelsall@nih.gov
RI la Sala, Andrea/A-3228-2009
OI la Sala, Andrea/0000-0003-1268-6516
FU Division of Intramural Research; National Institutes of Allergy and
Infectious Diseases; National Institutes of Health
FX This work was supported by research funds from the Division of
Intramural Research, National Institutes of Allergy and Infectious
Diseases, National Institutes of Health.
NR 32
TC 31
Z9 32
U1 0
U2 4
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUN 8
PY 2009
VL 206
IS 6
BP 1227
EP 1235
DI 10.1084/jem.20080912
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 459TS
UT WOS:000267133700004
PM 19487420
ER
PT J
AU Rajagopal, D
Maul, RW
Ghosh, A
Chakraborty, T
Khamlichi, AA
Sen, R
Gearhart, PJ
AF Rajagopal, Deepa
Maul, Robert W.
Ghosh, Amalendu
Chakraborty, Tirtha
Khamlichi, Ahmed Amine
Sen, Ranjan
Gearhart, Patricia J.
TI Immunoglobulin switch mu sequence causes RNA polymerase II accumulation
and reduces dA hypermutation
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID ACTIVATION-INDUCED DEAMINASE; SOMATIC HYPERMUTATION; R-LOOPS; IN-VIVO;
DNA; RECOMBINATION; TRANSCRIPTION; MUTATIONS; REGIONS; STRAND
AB Repetitive DNA sequences in the immunoglobulin switch. region form RNA-containing secondary structures and undergo hypermutation by activation-induced deaminase ( AID). To examine how DNA structure affects transcription and hypermutation, we mapped the position of RNA polymerase II molecules and mutations across a 5-kb region spanning the intronic enhancer to the constant. gene. For RNA polymerase II, the distribution was determined by nuclear run-on and chromatin immunoprecipitation assays in B cells from uracil-DNA glycosylase (UNG)-deficient mice stimulated ex vivo. RNA polymerases were found at a high density in DNA flanking both sides of a 1-kb repetitive sequence that forms the core of the switch region. The pileup of polymerases was similar in unstimulated and stimulated cells from Ung(-/-) and Aid(-/-)Ung(-/-) mice but was absent in cells from mice with a deletion of the switch region. For mutations, DNA was sequenced from Ung(-/-) B cells stimulated in vivo. Surprisingly, mutations of A nucleotides, which are incorporated by DNA polymerase., decreased 10-fold before the repetitive sequence, suggesting that the polymerase was less active in this region. We propose that altered DNA structure in the switch region pauses RNA polymerase II and limits access of DNA polymerase. during hypermutation.
C1 [Rajagopal, Deepa; Maul, Robert W.; Gearhart, Patricia J.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Ghosh, Amalendu; Chakraborty, Tirtha; Sen, Ranjan] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA.
[Rajagopal, Deepa] Univ Maryland, Sch Med, Grad Program Mol Microbiol & Immunol, Baltimore, MD 21201 USA.
[Khamlichi, Ahmed Amine] Univ Toulouse, CNRS, UMR IPBS 5089, F-31077 Toulouse, France.
RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
EM gearhartp@grc.nia.nih.gov
OI Maul, Robert/0000-0002-6958-8514
FU National Institutes of Health National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the National Institutes of Health National Institute on Aging.
NR 30
TC 63
Z9 63
U1 0
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUN 8
PY 2009
VL 206
IS 6
BP 1237
EP 1244
DI 10.1084/jem.20082514
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 459TS
UT WOS:000267133700005
PM 19433618
ER
PT J
AU Strowig, T
Gurer, C
Ploss, A
Liu, YF
Arrey, F
Sashihara, J
Koo, G
Rice, CM
Young, JW
Chadburn, A
Cohen, JI
Munz, C
AF Strowig, Till
Gurer, Cagan
Ploss, Alexander
Liu, Yi-Fang
Arrey, Frida
Sashihara, Junji
Koo, Gloria
Rice, Charles M.
Young, James W.
Chadburn, Amy
Cohen, Jeffrey I.
Muenz, Christian
TI Priming of protective T cell responses against virus-induced tumors in
mice with human immune system components
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID EPSTEIN-BARR-VIRUS; HEMATOPOIETIC STEM-CELLS; HUMAN CD34(+) CELLS;
B-CELLS; LYMPHOPROLIFERATIVE DISORDERS; RHESUS MACAQUES; DENDRITIC
CELLS; MOUSE MODEL; IN-VIVO; INFECTION
AB Many pathogens that cause human disease infect only humans. To identify the mechanisms of immune protection against these pathogens and also to evaluate promising vaccine candidates, a small animal model would be desirable. We demonstrate that primary T cell responses in mice with reconstituted human immune system components control infection with the oncogenic and persistent Epstein-Barr virus (EBV). These cytotoxic and interferon. gamma-producing T cell responses were human leukocyte antigen (HLA) restricted and specific for EBV-derived peptides. In HLA-A2 transgenic animals and similar to human EBV carriers, T cell responses against lytic EBV antigens dominated over recognition of latent EBV antigens. T cell depletion resulted in elevated viral loads and emergence of EBV-associated lymphoproliferative disease. Both loss of CD4(+) and CD8(+) T cells abolished immune control. Therefore, this mouse model recapitulates features of symptomatic primary EBV infection and generates T cell-mediated immune control that resists oncogenic transformation.
C1 [Strowig, Till; Gurer, Cagan; Arrey, Frida; Muenz, Christian] Rockefeller Univ, Lab Viral Immunobiol, New York, NY 10065 USA.
[Strowig, Till; Gurer, Cagan; Arrey, Frida; Muenz, Christian] Rockefeller Univ, Christopher H Browne Ctr Immunol & Immune Dis, New York, NY 10065 USA.
[Ploss, Alexander; Rice, Charles M.] Rockefeller Univ, Lab Virol & Infect Dis, New York, NY 10065 USA.
[Ploss, Alexander; Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10065 USA.
[Liu, Yi-Fang; Chadburn, Amy] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Pathol, New York, NY 10065 USA.
[Sashihara, Junji; Cohen, Jeffrey I.] NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Koo, Gloria] Mem Sloan Kettering Canc Ctr, Dept Med, Div Hematol Oncol, Dept Pediat, New York, NY 10065 USA.
[Young, James W.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Hematol Oncol, Lab Cellular Immunobiol, New York, NY 10065 USA.
[Young, James W.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Hematol Oncol, Adult Allogene Bone Marrow Transplantat Serv, New York, NY 10065 USA.
[Koo, Gloria] Hosp Special Surg, Inflammatory Effector Mech Lab, New York, NY 10021 USA.
[Muenz, Christian] Univ Zurich Hosp, Inst Expt Immunol, CH-8091 Zurich, Switzerland.
RP Munz, C (reprint author), Rockefeller Univ, Lab Viral Immunobiol, New York, NY 10065 USA.
EM christian.muenz@usz.ch
OI Strowig, Till/0000-0003-0185-1459
FU Intramural NIH HHS; NCI NIH HHS [P01 CA023766, P01CA23766, R01 CA083070,
R01 CA101741, R01 CA108609, R01CA083070, R01CA101741, R01CA108609]; PHS
HHS [BAA-06-19]
NR 47
TC 134
Z9 136
U1 0
U2 4
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUN 8
PY 2009
VL 206
IS 6
BP 1423
EP 1434
DI 10.1084/jem.20081720
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 459TS
UT WOS:000267133700019
PM 19487422
ER
PT J
AU Beckstead, WA
Ebbert, MTW
Rowe, MJ
McClellan, DA
AF Beckstead, Wesley A.
Ebbert, Mark T. W.
Rowe, Mark J.
McClellan, David A.
TI Evolutionary Pressure on Mitochondrial Cytochrome b Is Consistent with a
Role of CytbI7T Affecting Longevity during Caloric Restriction
SO PLOS ONE
LA English
DT Article
AB Background: Metabolism of energy nutrients by the mitochondrial electron transport chain (ETC) is implicated in the aging process. Polymorphisms in core ETC proteins may have an effect on longevity. Here we investigate the cytochrome b (cytb) polymorphism at amino acid 7 (cytbI7T) that distinguishes human mitochondrial haplogroup H from haplogroup U.
Principal Findings: We compared longevity of individuals in these two haplogroups during historical extremes of caloric intake. Haplogroup H exhibits significantly increased longevity during historical caloric restriction compared to haplogroup U (p = 0.02) while during caloric abundance they are not different. The historical effects of natural selection on the cytb protein were estimated with the software TreeSAAP using a phylogenetic reconstruction for 107 mammal taxa from all major mammalian lineages using 13 complete protein-coding mitochondrial gene sequences. With this framework, we compared the biochemical shifts produced by cytbI7T with historical evolutionary pressure on and near this polymorphic site throughout mammalian evolution to characterize the role cytbI7T had on the ETC during times of restricted caloric intake.
Significance: Our results suggest the relationship between caloric restriction and increased longevity in human mitochondrial haplogroup H is determined by cytbI7T which likely enhances the ability of water to replenish the Q(i) binding site and decreases the time ubisemiquinone is at the Q(o) site, resulting in a decrease in the average production rate of radical oxygen species (ROS).
RP Beckstead, WA (reprint author), Natl Canc Inst, Oncogenom Sect, Pediat Oncol Branch, Adv Technol Ctr, Gaithersburg, MD USA.
EM dmcclellan@bigelow.org
NR 45
TC 16
Z9 16
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 8
PY 2009
VL 4
IS 6
AR e5836
DI 10.1371/journal.pone.0005836
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 454XN
UT WOS:000266717400015
PM 19503808
ER
PT J
AU Tokumasu, F
Nardone, GA
Ostera, GR
Fairhurst, RM
Beaudry, SD
Hayakawa, E
Dvorak, JA
AF Tokumasu, Fuyuki
Nardone, Glenn A.
Ostera, Graciela R.
Fairhurst, Rick M.
Beaudry, Steven D.
Hayakawa, Eri
Dvorak, James A.
TI Altered Membrane Structure and Surface Potential in Homozygous
Hemoglobin C Erythrocytes
SO PLOS ONE
LA English
DT Article
AB Background: Hemoglobin C differs from normal hemoglobin A by a glutamate-to-lysine substitution at position 6 of beta globin and is oxidatively unstable. Compared to homozygous AA erythrocytes, homozygous CC erythrocytes contain higher levels of membrane-associated hemichromes and more extensively clustered band 3 proteins. These findings suggest that CC erythrocytes have a different membrane matrix than AA erythrocytes.
Methodology and Findings: We found that AA and CC erythrocytes differ in their membrane lipid composition, and that a subset of CC erythrocytes expresses increased levels of externalized phosphatidylserine. Detergent membrane analyses for raft marker proteins indicated that CC erythrocyte membranes are more resistant to detergent solubilization. These data suggest that membrane raft organization is modified in CC erythrocytes. In addition, the average zeta potential (a measure of surface electrochemical potential) of CC erythrocytes was approximate to 2 mV lower than that of AA erythrocytes, indicating that substantial rearrangements occur in the membrane matrix of CC erythrocytes. We were able to recapitulate this low zeta potential phenotype in AA erythrocytes by treating them with NaNO(2) to oxidize hemoglobin A molecules and increase levels of membrane-associated hemichromes.
Conclusion: Our data support the possibility that increased hemichrome deposition and altered lipid composition induce molecular rearrangements in CC erythrocyte membranes, resulting in a unique membrane structure.
RP Tokumasu, F (reprint author), NIAID, Biophys & Biochem Parasitol Sect, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ftokumasu@niaid.nih.gov
OI Tokumasu, Fuyuki/0000-0003-2790-1071
NR 64
TC 11
Z9 11
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 8
PY 2009
VL 4
IS 6
AR e5828
DI 10.1371/journal.pone.0005828
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 454XN
UT WOS:000266717400008
PM 19503809
ER
PT J
AU Talaat, KR
Karron, RA
Callahan, KA
Luke, CJ
DiLorenzo, SC
Chen, GL
Lamirande, EW
Jin, H
Coelingh, KL
Murphy, BR
Kemble, G
Subbarao, K
AF Talaat, Kawsar R.
Karron, Ruth A.
Callahan, Karen A.
Luke, Catherine J.
DiLorenzo, Susan C.
Chen, Grace L.
Lamirande, Elaine W.
Jin, Hong
Coelingh, Kathy L.
Murphy, Brian R.
Kemble, George
Subbarao, Kanta
TI A live attenuated H7N3 influenza virus vaccine is well tolerated and
immunogenic in a Phase I trial in healthy adults
SO VACCINE
LA English
DT Article
DE Avian; Influenza; H7N3 vaccine
ID FOWL PLAGUE VIRUS; AVIAN INFLUENZA; A VIRUS; PANDEMIC INFLUENZA;
ANTIBODY-RESPONSES; H5N1 VIRUS; RECEPTOR SPECIFICITY; RESPIRATORY-TRACT;
YOUNG-CHILDREN; HUMAN-BEINGS
AB Background: Live attenuated influenza vaccines (LAIVs) are being developed and tested against a variety of influenza viruses with pandemic potential. We describe the results of an open-label Phase I trial of a live attenuated H7N3 virus vaccine.
Methods and findings: The H7N3 BC 2004/AA ca virus is a live attenuated, cold-adapted, temperature-sensitive influenza virus derived by reverse genetics from the wild-type low pathogenicity avian influenza virus A/chicken/British Columbia/CN-6/2004 (H7N3) and the A/AA/6/60 ca (H2N2) virus that is the Master Donor Virus of the live, intranasal seasonal influenza vaccine. We evaluated the safety, infectivity, and immunogenicity of two doses of 10(7.5) TCID(50) of the vaccine administered by nasal spray 5 weeks apart to normal healthy seronegative adult volunteers in an inpatient isolation unit. The subjects were followed for 2 months after one dose of vaccine or for 4 weeks after the second dose.
Twenty-one subjects received the first dose of the vaccine, and 17 subjects received two doses. The vaccine was generally well tolerated. No serious adverse events occurred during the trial. The vaccine was highly restricted in replication: 6 (29%) subjects had virus recoverable by culture or by real-time reverse transcription polymerase chain reaction (rRT-PCR) after the first dose. Replication of vaccine virus was not detected following the second dose. Despite the restricted replication of the vaccine, 90% of the subjects developed an antibody response as measured by any assay: 62% by hemagglutination inhibition assay, 48% by microneutralization assay, 48% by ELISA for H7 HA-specific serum IgG or 71% by ELISA for H7 HA-specific serum IgA, after either one or two doses. Following the first dose, vaccine-specific IgG secreting cells as measured by ELISPOT increased from a mean of 0.1 to 41.6/10(6) PBMCs; vaccine-specific IgA secreting cells increased from 2 to 16.4/10(7) PBMCs. The antibody secreting cell response after the second dose was less vigorous, which is consistent with the observed low replication of vaccine virus after the second dose and consequent lower antigenic stimulation.
Conclusion: The live attenuated H7N3 vaccine was generally well tolerated but was highly restricted in replication in healthy seronegative adults. Despite the restricted replication, the vaccine was immunogenic, with serum IgA being the most sensitive measure Of immunogenicity. Further development of this vaccine is warranted (ClinicalTrials.gov Identifier: NCT00516035). (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Talaat, Kawsar R.; Karron, Ruth A.; Callahan, Karen A.; DiLorenzo, Susan C.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA.
[Luke, Catherine J.; Chen, Grace L.; Lamirande, Elaine W.; Murphy, Brian R.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Jin, Hong; Coelingh, Kathy L.; Kemble, George] MedImmune, Mountain View, CA 94043 USA.
RP Talaat, KR (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA.
EM ktalaat@jhsph.edu
FU Intramural Research Program of the NIAID; NIH
FX We wish to thank Julie McArthur, Philana Liang, Bridget McMahonjasmine
Jennings, Ruval Cornenclador and Paula Williams-Soro for expert clinical
and administrative assistance, Bhagvanji Thumar for expert technical
assistance, Wilbert van Panhuis for statistical analysis and Romeo
Paredes for expert data management. We would also like to thank Edith
Matsuyama, Silas Nwagwu, Steve Thompson, Weidong Cui, Chin-Fen Yang, Bin
Lu, Lynne Fitch, Alfred Pan, and Meredith Uebersax of Medimmune for
vaccine manufacture and testing. This research was supported by the
Intramural Research Program of the NIAID, NIH. This research was
performed as a Cooperative Research and Development Agreement (CRADA No:
Al-0155) between the Laboratory of Infectious Diseases, NIAID and
Medimmune.
NR 63
TC 64
Z9 66
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUN 8
PY 2009
VL 27
IS 28
BP 3744
EP 3753
DI 10.1016/j.vaccine.2009.03.082
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 465JZ
UT WOS:000267581200013
PM 19464558
ER
PT J
AU Miller, DC
Saigal, CS
Warren, JL
Leventhal, M
Deapen, D
Banerjee, M
Lai, J
Hanley, J
Litwin, MS
AF Miller, David C.
Saigal, Christopher S.
Warren, Joan L.
Leventhal, Meryl
Deapen, Dennis
Banerjee, Mousumi
Lai, Julie
Hanley, Jan
Litwin, Mark S.
TI External validation of a claims-based algorithm for classifying
kidney-cancer surgeries
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
ID RENAL-CELL CARCINOMA; SEER-MEDICARE DATA; NEPHRECTOMY; DIFFUSION
AB Background: Unlike other malignancies, there is no literature supporting the accuracy of medical claims data for identifying surgical treatments among patients with kidney cancer. We sought to validate externally a previously published Medicare-claims-based algorithm for classifying surgical treatments among patients with early-stage kidney cancer. To achieve this aim, we compared procedure assignments based on Medicare claims with the type of surgery specified in SEER registry data and clinical operative reports.
Methods: Using linked SEER-Medicare data, we calculated the agreement between Medicare claims and SEER data for identification of cancer-directed surgery among 6,515 patients diagnosed with early-stage kidney cancer. Next, for a subset of 120 cases, we determined the agreement between the claims algorithm and the medical record. Finally, using the medical record as the reference-standard, we calculated the sensitivity, specificity, and positive and negative predictive values of the claims algorithm.
Results: Among 6,515 cases, Medicare claims and SEER data identified 5,483 (84.1%) and 5,774 (88.6%) patients, respectively, who underwent cancer-directed surgery (observed agreement = 93%, kappa = 0.69, 95% CI 0.66-0.71). The two data sources demonstrated 97% agreement for classification of partial versus radical nephrectomy (kappa = 0.83, 95% CI 0.81-0.86). We observed 97% agreement between the claims algorithm and clinical operative reports; the positive predictive value of the claims algorithm exceeded 90% for identification of both partial nephrectomy and laparoscopic surgery.
Conclusion: Medicare claims represent an accurate data source for ascertainment of population-based patterns of surgical care among patients with early-stage kidney cancer.
C1 [Miller, David C.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
[Miller, David C.] VA Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA.
[Saigal, Christopher S.; Litwin, Mark S.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA.
[Saigal, Christopher S.; Litwin, Mark S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Saigal, Christopher S.; Lai, Julie; Hanley, Jan; Litwin, Mark S.] RAND Corp, RAND Hlth, Santa Monica, CA USA.
[Warren, Joan L.] NCI, Appl Res Program, Bethesda, MD 20892 USA.
[Leventhal, Meryl; Deapen, Dennis] Univ So Calif, Canc Surveillance Program, Los Angeles, CA USA.
[Banerjee, Mousumi] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Banerjee, Mousumi] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Litwin, Mark S.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA.
RP Miller, DC (reprint author), Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
EM dcmiller@umich.edu; csaigal@mednet.ucla.edu; warrenj@mail.nih.gov;
leventha@usc.edu; ddeapen@usc.edu; mousumib@umich.edu; jlai@rand.org;
janh@rand.org; mlitwin@mednet.ucla.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[N01-DK-1-2460]; National Cancer Institute [NIH-1-F32 CA123819-01];
American Cancer Society [PF CPHPS-112124]; American Urological
Association Foundation Research Scholar Program; California Department
of Health Services as part of the statewide cancer reporting program
mandated by California Health and Safety Code Section [103885]; National
Cancer Institute's Surveillance, Epidemiology and End Results Program
[00261200306D261035139]; NCI [N01-PC-35139]; University of Southern
California; Public Health Institute [N02-PC- 15105]; Centers for Disease
Control and Prevention's National Program of Cancer Registries
[U55/CCR921930]
FX The collection of cancer data by the Los Angeles Cancer Surveillance
Program is supported by the California Department of Health Services as
part of the statewide cancer reporting program mandated by California
Health and Safety Code Section 103885; the National Cancer Institute's
Surveillance, Epidemiology and End Results Program under contract
00261200306D261035139 and NCI Control N01-PC-35139 awarded to the
University of Southern California, and contract N02-PC- 15105 awarded to
the Public Health Institute; and the Centers for Disease Control and
Prevention's National Program of Cancer Registries, under agreement
U55/CCR921930 awarded to the Public Health Institute. The ideas and
opinions expressed herein are those of the author(s) and endorsement by
the State of California, Department of Health Services, the National
Cancer Institute, and the Centers for Disease Control and Prevention or
their contractors and subcontractors is not intended nor should be
inferred.
NR 13
TC 38
Z9 38
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD JUN 6
PY 2009
VL 9
AR 92
DI 10.1186/1472-6963-9-92
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 467MI
UT WOS:000267742600002
PM 19500395
ER
PT J
AU Asthagiri, AR
Parry, DM
Butman, JA
Kim, HJ
Tsilou, ET
Zhuang, ZP
Lonser, RR
AF Asthagiri, Ashok R.
Parry, Dilys M.
Butman, John A.
Kim, H. Jeffrey
Tsilou, Ekaterini T.
Zhuang, Zhengping
Lonser, Russell R.
TI Neurofibromatosis type 2
SO LANCET
LA English
DT Review
ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; SPINAL-CORD EPENDYMOMAS; NF2
TUMOR-SUPPRESSOR; GENOTYPE-PHENOTYPE CORRELATIONS; VESTIBULAR SCHWANNOMA
GROWTH; NERVOUS-SYSTEM TUMORS; OF-THE-LITERATURE; TERM-FOLLOW-UP;
NATURAL-HISTORY; STEREOTACTIC RADIOSURGERY
AB Neurofibromatosis type 2 is an autosomal-dominant multiple neoplasia syndrome that results from mutations in the NF2 tumour suppressor gene located on chromosome 22q. It has a frequency of one in 25 000 livebirths and nearly 100% penetrance by 60 years of age. Half of patients inherit a germline mutation from an affected parent and the remainder acquire a de novo mutation for neurofibromatosis type 2. Patients develop nervous system tumours (schwannomas, meningiomas, ependymomas, astrocytomas, and neurofibromas), peripheral neuropathy, ophthalmological lesions (cataracts, epiretinal membranes, and retinal hamartomas), and cutaneous lesions (skin tumours). Optimum treatment is multidisciplinary because of the complexities associated with management of the multiple, progressive, and protean lesions associated with the disorder. We review the molecular pathogenesis, genetics, clinical findings, and management strategies for neurofibromatosis type 2.
C1 [Asthagiri, Ashok R.; Zhuang, Zhengping; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Parry, Dilys M.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Butman, John A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Kim, H. Jeffrey] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Bethesda, MD USA.
[Tsilou, Ekaterini T.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Asthagiri, AR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM asthagiria@ninds.nih.gov
RI Butman, John/A-2694-2008; Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU Intramural Research Program of the National Institute of Neurological
Disorders; Stroke at the National Institutes of Health
FX We thank the Intramural Research Program of the National Institute of
Neurological Disorders and Stroke at the National Institutes of Health
for their support of this Seminar.
NR 139
TC 134
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U1 2
U2 35
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD JUN 6
PY 2009
VL 373
IS 9679
BP 1974
EP 1986
DI 10.1016/S0140-6736(09)60259-2
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 456GT
UT WOS:000266832500033
PM 19476995
ER
PT J
AU Tavakoli, T
Xu, XR
Derby, E
Serebryakova, Y
Reid, Y
Rao, MS
Mattson, MP
Ma, W
AF Tavakoli, Tahereh
Xu, Xiangru
Derby, Eric
Serebryakova, Yevgeniya
Reid, Yvonne
Rao, Mahendra S.
Mattson, Mark P.
Ma, Wu
TI Self-renewal and differentiation capabilities are variable between human
embryonic stem cell lines 13, 16 and BG01V
SO BMC CELL BIOLOGY
LA English
DT Article
ID GENE-EXPRESSION SIGNATURES; CULTURE; BODIES
AB Background: A unique and essential property of embryonic stem cells is the ability to self-renew and differentiate into multiple cell lineages. However, the possible differences in proliferation and differentiation capabilities among independently-derived human embryonic stem cells (hESCs) are not well known because of insufficient characterization. To address this question, a side-by-side comparison of 1) the ability to maintain an undifferentiated state and to self-renew under standard conditions; 2) the ability to spontaneously differentiate into three primary embryonic germ lineages in differentiating embryoid bodies; and 3) the responses to directed neural differentiation was made between three NIH registered hES cell lines 13 (TE03), 16 (TE06) and BG01V. Lines 13 and 16 possess normal XX and a normal XY karyotype while BG01V is a variant cell line with an abnormal karyotype derived from the karyotypically normal cell line BG01.
Results: Using immunocytochemistry, flow cytometry, qRT-PCR and MPSS, we found that all three cell lines actively proliferated and expressed similar "stemness" markers including transcription factors POU5F1/Oct3/4 and NANOG, glycolipids SSEA4 and TRA-1-81, and alkaline phosphatase activity. All cell lines differentiated into three embryonic germ lineages in embryoid bodies and into neural cell lineages when cultured in neural differentiation medium. However, a profound variation in colony morphology, growth rate, BrdU incorporation, and relative abundance of gene expression in undifferentiated and differentiated states of the cell lines was observed. Undifferentiated 13 cells grew significantly slower but their differentiation potential was greater than 16 and BG01V. Under the same neural differentiation-promoting conditions, the ability of each cell line to differentiate into neural progenitors varied.
Conclusion: Our comparative analysis provides further evidence for similarities and differences between three hESC lines in self-renewal, and spontaneous and directed differentiation. These differences may be associated with inherited variation in the sex, stage, quality and genetic background of embryos used for hESC line derivation, and/or changes acquired during passaging in culture.
C1 [Tavakoli, Tahereh; Derby, Eric; Serebryakova, Yevgeniya; Reid, Yvonne; Ma, Wu] ATCC, Stem Cell Ctr Dev Biol, Manassas, VA USA.
[Xu, Xiangru; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Rao, Mahendra S.] Stem Cells & Regenerat Med Res, Carlsbad, CA USA.
RP Ma, W (reprint author), Izumi Bio Inc, 951 Gateway Blvd, San Francisco, CA 94080 USA.
EM ttavakoli@atcc.org; xiangru.xu@yale.edu; ederby@atcc.org;
jserebryakova@atcc.org; yreid@atcc.org; mahendra.rao@invitrogen.com;
mattsonm@grc.nia.nih.gov; wu.ma@izumibio.com
RI Mattson, Mark/F-6038-2012
FU NIH/National Institute on Aging, [N01AG40002]; intramural research
program of the National Institute on Aging
FX This work was supported by contract grant N01AG40002 from NIH/National
Institute on Aging, and by the intramural research program of the
National Institute on Aging. We thank Dr. Dezhong Yin for assistance
with the qRT-PCR analysis and Tina Zadeh for performing
immunocytochemistry.
NR 29
TC 34
Z9 35
U1 0
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2121
J9 BMC CELL BIOL
JI BMC Cell Biol.
PD JUN 5
PY 2009
VL 10
AR 44
DI 10.1186/1471-2121-10-44
PG 15
WC Cell Biology
SC Cell Biology
GA 476ZW
UT WOS:000268486700001
PM 19500347
ER
PT J
AU Woolard, K
Fine, HA
AF Woolard, Kevin
Fine, Howard A.
TI Glioma Stem Cells: Better Flat Than Round
SO CELL STEM CELL
LA English
DT Editorial Material
ID TUMORS; NEUROSPHERE; EXPRESSION
AB Glioma-initiating cells/glioma stem cells (GIC/GSCs) are grown in vitro using a cumbersome and inefficient spheroid assay. In this issue of Cell Stern Cell, Pollard and coworkers present a protocol for the efficient derivation of GIC/GSC lines that may greatly improve the isolation and the potential clinical application of these cells.
C1 [Woolard, Kevin; Fine, Howard A.] Natl Inst Neurol Disorders & Stroke, Neurooncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Fine, HA (reprint author), Natl Inst Neurol Disorders & Stroke, Neurooncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM hfine@mail.nih.gov
NR 10
TC 20
Z9 23
U1 2
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD JUN 5
PY 2009
VL 4
IS 6
BP 466
EP 467
DI 10.1016/j.stem.2009.05.013
PG 2
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 455UY
UT WOS:000266793600002
PM 19497271
ER
PT J
AU Bulterys, M
Vermund, SH
Chen, RY
Ou, CY
AF Bulterys, Marc
Vermund, Sten H.
Chen, Ray Y.
Ou, Chin-Yih
TI A public health approach to rapid scale-up of free antiretroviral
treatment in China: an ounce of prevention is worth a pound of cure
SO CHINESE MEDICAL JOURNAL
LA English
DT Article
DE antiretroviral therapy; China; human immunodeficiency virus; drug
resistance; universal access
ID FORMER PLASMA DONORS; SOUTH-AFRICA; CARE-SYSTEM; HIV; THERAPY;
MORTALITY; HIV/AIDS; CHALLENGES; ADHERENCE; RISK
C1 [Bulterys, Marc; Ou, Chin-Yih] US Ctr Dis Control & Prevent, Global AIDS Program China Off, Beijing 100600, Peoples R China.
[Bulterys, Marc; Ou, Chin-Yih] Ctr Dis Control & Prevent, Div Global AIDS, Natl Ctr HIV Viral Hepatitis STD & TB Prevent, Atlanta, GA USA.
[Vermund, Sten H.] Vanderbilt Univ, Sch Med, Inst Global Hlth, Nashville, TN 37212 USA.
[Vermund, Sten H.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA.
[Chen, Ray Y.] NIAID, US Embassy Beijing, Natl Inst Hlth, Beijing 100600, Peoples R China.
RP Bulterys, M (reprint author), US Ctr Dis Control & Prevent, Global AIDS Program China Off, Beijing 100600, Peoples R China.
EM bulterys@cn.cdc.gov
OI Chen, Ray/0000-0001-6344-1442; Vermund, Sten/0000-0001-7289-8698
FU NIAID NIH HHS [P30 AI054999]
NR 42
TC 12
Z9 13
U1 1
U2 2
PU CHINESE MEDICAL ASSOC
PI BEIJING
PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA
SN 0366-6999
J9 CHINESE MED J-PEKING
JI Chin. Med. J.
PD JUN 5
PY 2009
VL 122
IS 11
BP 1352
EP 1355
DI 10.3760/cma.j.issn.0366-6999.2009.11.021
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 459JC
UT WOS:000267097000021
PM 19567150
ER
PT J
AU Juhaszova, M
Zorov, DB
Yaniv, Y
Nuss, HB
Wang, S
Sollott, SJ
AF Juhaszova, Magdalena
Zorov, Dmitry B.
Yaniv, Yael
Nuss, H. Bradley
Wang, Su
Sollott, Steven J.
TI Role of Glycogen Synthase Kinase-3 beta in Cardioprotection
SO CIRCULATION RESEARCH
LA English
DT Review
DE mitochondria; ROS-induced ROS release; permeability transition pore
ID PERMEABILITY TRANSITION PORE; ISCHEMIA-REPERFUSION INJURY; DEPENDENT
ANION CHANNEL; PROTEIN-KINASE-C; OPIOID-INDUCED CARDIOPROTECTION;
SENSITIVE POTASSIUM CHANNELS; MITOCHONDRIAL INNER MEMBRANE;
PKB/SGK-RESISTANT GSK3; K-ATP CHANNELS; CELL-DEATH
AB Limitation of infarct size by ischemic/pharmacological pre- and postconditioning involves activation of a complex set of cell-signaling pathways. Multiple lines of evidence implicate the mitochondrial permeability transition pore (mPTP) as a key end effector of ischemic/pharmacological pre- and postconditioning. Increasing the ROS threshold for mPTP induction enhances the resistance of cardiomyocytes to oxidant stress and results in infarct size reduction. Here, we survey and synthesize the present knowledge about the role of glycogen synthase kinase (GSK)-3 beta in cardioprotection, including pre- and postconditioning. Activation of a wide spectrum of cardioprotective signaling pathways is associated with phosphorylation and inhibition of a discrete pool of GSK-3 beta relevant to mitochondrial signaling. Therefore, GSK-3 beta has emerged as the integration point of many of these pathways and plays a central role in transferring protective signals downstream to target(s) that act at or in proximity to the mPTP. Bcl-2 family proteins and mPTP-regulatory elements, such as adenine nucleotide translocator and cyclophilin D (possibly voltage-dependent anion channel), may be the functional downstream target(s) of GSK-3 beta. Gaining a better understanding of these interactions to control and prevent mPTP induction when appropriate will enable us to decrease the negative impact of the reperfusion-induced ROS burst on the fate of mitochondria and perhaps allow us to limit propagation of damage throughout and between cells and consequently, to better limit infarct size. (Circ Res. 2009; 104: 1240-1252.)
C1 [Juhaszova, Magdalena; Zorov, Dmitry B.; Yaniv, Yael; Nuss, H. Bradley; Wang, Su; Sollott, Steven J.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
RP Sollott, SJ (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Box 13,5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM sollotts@mail.nih.gov
RI Yaniv, Yael/B-3311-2015
OI Yaniv, Yael/0000-0002-5183-6284
FU NIH, National Institute on Aging
FX This research was entirely supported by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 134
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Z9 192
U1 3
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD JUN 5
PY 2009
VL 104
IS 11
BP 1240
EP 1252
DI 10.1161/CIRCRESAHA.109.197996
PG 13
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 454BZ
UT WOS:000266657900003
PM 19498210
ER
PT J
AU Tanigaki, K
Mineo, C
Yuhanna, IS
Chambliss, KL
Quon, MJ
Bonvini, E
Shaul, PW
AF Tanigaki, Keiji
Mineo, Chieko
Yuhanna, Ivan S.
Chambliss, Ken L.
Quon, Michael J.
Bonvini, Ezio
Shaul, Philip W.
TI C-Reactive Protein Inhibits Insulin Activation of Endothelial Nitric
Oxide Synthase via the Immunoreceptor Tyrosine-Based Inhibition Motif of
Fc gamma RIIB and SHIP-1
SO CIRCULATION RESEARCH
LA English
DT Article
DE C-reactive protein; insulin; eNOS; Fc gamma RIIB; SHIP1
ID INOSITOL PHOSPHATASE; RECEPTOR SUBSTRATE-1; HOMOLOGY DOMAIN; NO
SYNTHASE; CELLS; PHOSPHORYLATION; DYSFUNCTION; RESISTANCE; IGG; AKT
AB Insulin promotes the cardiovascular protective functions of the endothelium including NO production by endothelial NO synthase (eNOS), which it stimulates via Akt kinase which phosphorylates eNOS Ser1179. C-reactive protein (CRP) is an acute-phase reactant that is positively correlated with cardiovascular disease risk in patients with type 2 diabetes. We previously showed that CRP inhibits eNOS activation by insulin by blunting Ser1179 phosphorylation. We now elucidate the underlying molecular mechanisms. We first show in mice that CRP inhibits insulin-induced eNOS phosphorylation, indicating that these processes are operative in vivo. In endothelial cells we find that CRP attenuates insulin-induced Akt phosphorylation, and CRP antagonism of eNOS is negated by expression of constitutively active Akt; the inhibitory effect of CRP on Akt is also observed in vivo. A requirement for the IgG receptor Fc gamma RIIB was demonstrated in vitro using blocking antibody, and reconstitution experiments with wild-type and mutant Fc gamma RIIB in NIH3T3(IR) cells revealed that these processes require the ITIM (immunoreceptor tyrosine-based inhibition motif) of the receptor. Furthermore, we find that endothelium express SHIP-1 (Src homology 2 domain-containing inositol 5'-phosphatase 1), that CRP induces SHIP-1 stimulatory phosphorylation in endothelium in culture and in vivo, and that SHIP-1 knockdown by small interfering RNA prevents CRP antagonism of insulin-induced eNOS activation. Thus, CRP inhibits eNOS stimulation by insulin via Fc gamma RIIB and its ITIM, SHIP-1 activation, and resulting blunted activation of Akt. These findings provide mechanistic linkage among CRP, impaired insulin signaling in endothelium, and greater cardiovascular disease risk in type 2 diabetes. (Circ Res. 2009; 104: 1275-1282.)
C1 [Tanigaki, Keiji; Mineo, Chieko; Yuhanna, Ivan S.; Chambliss, Ken L.; Shaul, Philip W.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Div Pulm & Vasc Biol, Dallas, TX 75390 USA.
[Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
[Bonvini, Ezio] MacroGenics Inc, Res Dept, Rockville, MD USA.
RP Mineo, C (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pediat, Div Pulm & Vasc Biol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Chieko.Mineo@utsouthwestern.edu
OI Quon, Michael/0000-0002-9601-9915
FU NIH [HL75473]; Crystal Charity Ball Center for Pediatric Critical Care
Research; Lowe Foundation
FX This work was supported by NIH grants HL75473 (to P. W. S.). Additional
support was provided by the Crystal Charity Ball Center for Pediatric
Critical Care Research and the Lowe Foundation (to P. W. S.).
NR 43
TC 27
Z9 28
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD JUN 5
PY 2009
VL 104
IS 11
BP 1275
EP 1282
DI 10.1161/CIRCRESAHA.108.192906
PG 8
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 454BZ
UT WOS:000266657900007
PM 19423845
ER
PT J
AU Mittelstadt, PR
Yamaguchi, H
Appella, E
Ashwell, JD
AF Mittelstadt, Paul R.
Yamaguchi, Hiroshi
Appella, Ettore
Ashwell, Jonathan D.
TI T Cell Receptor-mediated Activation of p38 alpha by Mono-phosphorylation
of the Activation Loop Results in Altered Substrate Specificity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID STAT4 SERINE PHOSPHORYLATION; ATF2 TRANSCRIPTION FACTOR; IFN-GAMMA
PRODUCTION; MAP KINASE PATHWAYS; PROTEIN-KINASE; DUAL PHOSPHORYLATION;
BCL-2 PHOSPHORYLATION; ACTIVE MUTANTS; P38 MAPK; IN-VIVO
AB p38 MAPKs are typically activated by upstream MAPK kinases that phosphorylate a Thr-X-Tyr motif in the activation loop. An exception is the T cell antigen receptor signaling pathway, which bypasses the MAPK cascade and activates p38 alpha and p38 beta by phosphorylation of Tyr-323 and subsequent autophosphorylation of the activation loop. Here we show that, unlike the classic MAPK cascade, the alternative pathway results primarily in mono-phosphorylation of the activation loop residue Thr180. Recombinant mono-phosphorylated and dual phosphorylated p38 alpha differed widely with regard to activity and substrate preference. Altered substrate specificity was reproduced in T cells in which p38 was activated by the alternative or classical MAPK pathways. These findings suggest that T cells have evolved a mechanism to utilize p38 in a specialized manner independent of and distinct from the classical p38 MAPK signaling cascade.
C1 [Mittelstadt, Paul R.; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
[Yamaguchi, Hiroshi; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Rm 3002,37 Convent Dr, Bethesda, MD 20892 USA.
EM jda@mail.nih.gov
FU National Institutes of Health
FX This work was supported, in whole or in part, by the National Institutes
of Health NCI Intramural Research Program, Center for Cancer Research.
NR 44
TC 26
Z9 26
U1 2
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 5
PY 2009
VL 284
IS 23
BP 15469
EP 15474
DI 10.1074/jbc.M901004200
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 451WG
UT WOS:000266501000015
PM 19324872
ER
PT J
AU Nelson, MI
Simonsen, L
Viboud, C
Miller, MA
Holmes, EC
AF Nelson, Martha I.
Simonsen, Lone
Viboud, Cecile
Miller, Mark A.
Holmes, Edward C.
TI The origin and global emergence of adamantane resistant A/H3N2 influenza
viruses
SO VIROLOGY
LA English
DT Article
DE Human influenza A virus; Evolution; Adamantane resistance; Reassortment;
Global migration
ID A H3N2 VIRUSES; HONG-KONG; ISOLATED WORLDWIDE; SURVEILLANCE; A(H3N2);
REASSORTMENT; AUSTRALIA; EVOLUTION; REVEALS
AB Resistance to the adamantane class of antiviral drugs by human A/H3N2 influenza viruses currently exceeds 90% in the United States and multiple Asian countries. Adamantane resistance is associated with a single amino acid change (S31N) in the M2 protein, which was shown to rapidly disseminate globally in 2005 in association with a genome reassortment event. However, the exact origin of influenza A/H3N2 viruses carrying the S31N mutation has not been characterized, particularly in South-East Asia. We therefore conducted a phylogenetic analysis of the HA, NA, and M1/2 segments of viral isolates collected between 1997 and 2007 from temperate localities in the Northern hemisphere (New York State, United States, 492 isolates) and Southern hemisphere (New Zealand and Australia, 629 isolates) and a subtropical locality in South-East Asia (Hong Kong, 281 isolates). We find that although the S31N mutation was independently introduced at least 11 times, the vast majority of resistant viruses now circulating globally descend from a single introduction that was first detected in the summer of 2003 in Hong Kong. These resistant viruses were continually detected in Hong Kong throughout 2003-2005, acquired a novel HA through reassortment during the first part of 2005, and thereafter spread globally. The emergence and persistence of adamantane resistant viruses in Hong Kong further supports a source-sink model of global influenza virus ecology, in which South-East Asia experiences continuous viral activity and repeatedly seeds epidemics in temperate areas. (c) 2009 Elsevier Inc. All rights reserved.
C1 [Nelson, Martha I.; Viboud, Cecile; Miller, Mark A.; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, Lone] George Washington Univ, Dept Global Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC 20037 USA.
[Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
RP Nelson, MI (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM nelsonma@mail.nih.gov
OI Simonsen, Lone/0000-0003-1535-8526; Holmes, Edward/0000-0001-9596-3552
FU Infectious Disease Dynamics (RAPIDD)
FX Funding support for Lone Simonsen came from the Research and Policy for
Infectious Disease Dynamics (RAPIDD) joint program of the Science and
Technology Directorate, Department of Homeland Security, and Fogarty
International Center, National Institutes of Health.
NR 39
TC 50
Z9 53
U1 1
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JUN 5
PY 2009
VL 388
IS 2
BP 270
EP 278
DI 10.1016/j.virol.2009.03.026
PG 9
WC Virology
SC Virology
GA 453OV
UT WOS:000266621400005
PM 19394063
ER
PT J
AU de Souza-Pinto, NC
Mason, PA
Hashiguchi, K
Weissman, L
Tian, JY
Guay, D
Lebel, M
Stevnsner, TV
Rasmussen, LJ
Bohr, VA
AF de Souza-Pinto, Nadja C.
Mason, Penelope A.
Hashiguchi, Kazunari
Weissman, Lior
Tian, Jingyan
Guay, David
Lebel, Michel
Stevnsner, Tinna V.
Rasmussen, Lene Juel
Bohr, Vilhelm A.
TI Novel DNA mismatch-repair activity involving YB-1 in human mitochondria
SO DNA REPAIR
LA English
DT Article
DE Base mismatches; Microsatellite instability; Mismatch repair;
Mitochondria; Mitochondrial DNA; YB-1
ID NITRO-N-NITROSOGUANIDINE; RAT-LIVER MITOCHONDRIA; BASE EXCISION-REPAIR;
BOX-BINDING-PROTEIN; CANCER CELL-LINES; MICROSATELLITE INSTABILITY;
MAMMALIAN MITOCHONDRIA; SOMATIC MUTATIONS; NUCLEAR-DNA; COLORECTAL
CARCINOMAS
AB Maintenance of the mitochondrial genome (mtDNA) is essential for proper cellular function. The accumulation of damage and mutations in the mtDNA leads to diseases, cancer, and aging. Mammalian mitochondria have proficient base excision repair, but the existence of other DNA repair pathways is still unclear. Deficiencies in DNA mismatch repair (MMR), which corrects base mismatches and small loops, are associated with DNA microsatellite instability, accumulation of mutations, and cancer. MMR proteins have been identified in yeast and coral mitochondria; however, MMR proteins and function have not yet been detected in human mitochondria. Here we show that human mitochondria have a robust mismatch-repair activity, which is distinct from nuclear MMR. Key nuclear MMR factors were not detected in mitochondria, and similar mismatch-binding activity was observed in mitochondrial extracts from cells lacking MSH2, suggesting distinctive pathways for nuclear and mitochondrial MMR We identified the repair factor YB-1 as a key candidate fora mitochondrial mismatch-binding protein. This protein localizes to mitochondria in human cells, and contributes significantly to the mismatch-binding and mismatch-repair activity detected in HeLa mitochondrial extracts, which are significantly decreased when the intracellular levels of YB-1 are diminished. Moreover, YB-1 depletion in cells increases mitochondrial DNA mutagenesis. Our results show that human mitochondria contain a functional MMR repair pathway in which YB-1 participates, likely in the mismatch-binding and recognition steps. Published by Elsevier B.V.
C1 [de Souza-Pinto, Nadja C.; Mason, Penelope A.; Hashiguchi, Kazunari; Weissman, Lior; Tian, Jingyan; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, IRP, NIH, Baltimore, MD 21224 USA.
[Guay, David; Lebel, Michel] Dept Hop Hotel Dieu Quebec, Ctr Rech Cancerol, Quebec City, PQ, Canada.
[Stevnsner, Tinna V.] Aarhus Univ, Dept Mol Biol, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark.
[Rasmussen, Lene Juel] Roskilde Univ Ctr, Dept Sci Syst & Models, Roskilde, Denmark.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, IRP, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
RI Souza-Pinto, Nadja/C-3462-2013; 3, INCT/H-4497-2013; Redoxoma,
Inct/H-9962-2013
OI Souza-Pinto, Nadja/0000-0003-4206-964X;
FU National Institutes of Health, National Institute on Aging, USA; Danish
Cancer Society [DP05118]; Cancer Research Society Inc; CIHR; NSERC of
Canada
FX Funding: This work (PM, KH, LW, JT, NSP, and VB) was funded by the
Intramural Research Program of the National Institutes of Health,
National Institute on Aging, USA. TS and LJR are supported by the Danish
Cancer Society (grant DP05118). ML was supported partly by a grant from
the Cancer Research Society Inc. and is a CIHR scholar, and DG is an
NSERC of Canada scholar.
NR 83
TC 78
Z9 81
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD JUN 4
PY 2009
VL 8
IS 6
BP 704
EP 719
DI 10.1016/j.dnarep.2009.01.021
PG 16
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 460BF
UT WOS:000267159000004
PM 19272840
ER
PT J
AU Zanuy, D
Flores-Ortega, A
Jimenez, AI
Calaza, MI
Cativiela, C
Nussinov, R
Ruoslahti, E
Aleman, C
AF Zanuy, David
Flores-Ortega, Alejandra
Jimenez, Ana I.
Calaza, M. Isabel
Cativiela, Carlos
Nussinov, Ruth
Ruoslahti, Erkki
Aleman, Carlos
TI In Silico Molecular Engineering for a Targeted Replacement in a
Tumor-Homing Peptide
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID AMINO ACID RESIDUES; CONFORMATIONAL PREFERENCES; PROTEASE-RESISTANT;
FORCE-FIELD; ENERGY; PROTEINS; PROLINE; DYNAMICS; MODELS; STABILITY
AB A new amino acid has been designed as a replacement for arginine (Arg, R) to protect the tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) from proteases. This amino acid, denoted (Pro)hArg, is characterized by a proline skeleton bearing a specifically oriented guanidinium side chain. This residue combines the ability of Pro to induce turn-like conformations with the Arg side-chain functionality. The conformational profile of the CREKA analogue incorporating this Arg Substitute has been investigated by a combination of simulated annealing and molecular dynamics. Comparison of the results with those previously obtained for the natural CREKA shows that (Pro)hArg significantly reduces the conformational flexibility of the peptide. Although some changes are observed in the backbone center dot center dot center dot backbone and side-chain center dot center dot center dot side-chain interactions, the modified peptide exhibits a strong tendency to accommodate turn conformations centered at the (Pro)hArg residue and the overall shape of the molecule in the lowest energy conformations characterized for the natural and the modified peptides exhibit a high degree of similarity. In particular, the turn orients the backbone such that the Arg, Glu, and Lys side chains face the same side of the molecule, which is considered important for bioactivity. These results suggest that replacement of Arg by (Pro)hArg in CREKA may be useful in providing resistance against proteolytic enzymes while retaining conformational features which are essential for tumor-homing activity.
C1 [Jimenez, Ana I.; Calaza, M. Isabel; Cativiela, Carlos] Univ Zaragoza, Dept Quim Organ, Inst Ciencia Mat Aragon, CSIC, E-50009 Zaragoza, Spain.
[Zanuy, David; Flores-Ortega, Alejandra; Aleman, Carlos] Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain.
[Nussinov, Ruth] NCI, Basic Res Program, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Dept Human Genet Sackler, Sch Med, IL-69978 Tel Aviv, Israel.
[Ruoslahti, Erkki] UCSB, Vasc Mapping Ctr, Burnham Inst Med Res, Santa Barbara, CA 93106 USA.
[Ruoslahti, Erkki] Burnham Inst Med Res, Canc Res Ctr, La Jolla, CA 92037 USA.
[Aleman, Carlos] Univ Politecn Cataluna, Ctr Res Nanoengn, E-08028 Barcelona, Spain.
RP Jimenez, AI (reprint author), Univ Zaragoza, Dept Quim Organ, Inst Ciencia Mat Aragon, CSIC, E-50009 Zaragoza, Spain.
EM anisjim@unizar.es; aleman@upc.edu
RI Zanuy, David/G-3930-2014
OI Zanuy, David/0000-0001-7704-2178
FU Ministerio de Educacion y Ciencia [CTQ2007-62245]; Ramon y Cajal
contract; Gobierno de Aragon; U.S. National Cancer Institute [CA124427,
CA 119335]; Generalitat de Catalunya; National Cancer Institute;
National Institutes of Health [N01-CO-12400]; Center for Cancer Research
FX Gratitude is expressed to the Centre de Supercomputacio de Catalunya
(CESCA) and to the Barcelona Supercomputer Center (BSC) for
computational resources. We also acknowledge the National Cancer
Institute for partial allocation of computing time and staff support at
the Advanced Biomedical Computing Center of the Frederick Cancer
Research and Development Center. Classic calculations were partially
formed by utilizing the high-performance computational capabilities of
the Biowulf PC/Linux cluster at the National Institutes of Health,
Bethesda, MID (http://biowulf.nih.gov). Financial support from the
Ministerio de Educacion y Ciencia (project CTQ2007-62245, Ramon y Cajal
contract for D.Z.), Gobierno de Aragon (research group E40), and from
the U.S. National Cancer Institute (Grants CA124427 and CA 119335 to
E.R.) is gratefully acknowledged. Support for the research of C.A. was
received through the prize "ICREA Academia" for excellence in research
funded by the Generalitat de Catalunya. This project has been funded in
whole or in part with Federal funds from the National Cancer Institute,
National Institutes of Health, under contract number N01-CO-12400. The
content of this publication does not necessarily reflect the view of the
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products. or organization imply
endorsement by the U.S. Government. This research was supported [in
part] by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 54
TC 12
Z9 12
U1 7
U2 47
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD JUN 4
PY 2009
VL 113
IS 22
BP 7879
EP 7889
DI 10.1021/jp9006119
PG 11
WC Chemistry, Physical
SC Chemistry
GA 452MX
UT WOS:000266545500021
PM 19432404
ER
PT J
AU Slezak, S
Jin, P
Caruccio, L
Ren, JQ
Bennett, M
Zia, N
Adams, S
Wang, E
Ascensao, J
Schechter, G
Stroncek, D
AF Slezak, Stefanie
Jin, Ping
Caruccio, Lorraine
Ren, Jiaqiang
Bennett, Michael
Zia, Nausheen
Adams, Sharon
Wang, Ena
Ascensao, Joao
Schechter, Geraldine
Stroncek, David
TI Gene and microRNA analysis of neutrophils from patients with
polycythemia vera and essential thrombocytosis: down-regulation of micro
RNA-1 and-133a
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; PANCREATIC DUCTAL ADENOCARCINOMA; TYROSINE
KINASE JAK2; ZINC-FINGER PROTEIN; NF-KAPPA-B; MYELOPROLIFERATIVE
DISORDERS; EXPRESSION PATTERNS; MYELOID METAPLASIA; PERIPHERAL-BLOOD;
CD34(+) CELLS
AB Background: Since the V617F mutation in JAK2 may not be the initiating event in myeloprofilerative disorders (MPDs) we compared molecular changes in neutrophils from patients with polycythemia vera (PV) and essential thrombocythosis (ET), to neutrophils stimulated by GCSF administration and to normal unstimulated neutrophils
Methods: A gene expression oligonucleotide microarray with more than 35,000 probes and a microRNA (miR) expression array with 827 probes were used to assess neutrophils from 6 MPD patients; 4 with PV and 2 with ET, 5 healthy subjects and 6 healthy subjects given G-CSF. In addition, neutrophil antigen expression was analyzed by flow cytometry and 64 serum protein levels were analyzed by ELISA.
Results: Gene expression profiles of neutrophils from the MPD patients were similar but distinct from those of healthy subjects, either unstimulated or G-CSF-mobilized. The differentially expressed genes in MPD neutrophils were more likely to be in pathways involved with inflammation while those of G-CSF-mobilized neutrophils were more likely to belong to metabolic pathways. In MPD neutrophils the expression of CCR1 was increased and that of several NF-kappa B pathway genes were decreased. MicroRNA miR-133a and miR-1 in MPD neutrophils were down-regulated the most. Levels of 11 serum proteins were increased in MPD patients including MMP-10, MMP-13, VCAM, P-selectin, PDGF-BB and a CCR1 ligand, MIP-1a.
Conclusion: These studies showed differential expression of genes particularly involved in inflammatory pathways including the NF-.B pathway and down-regulation of miR-133a and miR-1. These two microRNAs have been previous associated with certain cancers as well as the regulation of hyperthrophy of cardiac and skeletal muscle cells. These changes may contribute to the clinical manifestations of the MPDs.
C1 [Slezak, Stefanie; Jin, Ping; Caruccio, Lorraine; Ren, Jiaqiang; Zia, Nausheen; Adams, Sharon; Wang, Ena; Stroncek, David] Natl Inst Hlth, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
[Bennett, Michael] Emek Hosp, Dept Hematol, Afula, Israel.
[Ascensao, Joao; Schechter, Geraldine] Vet Affairs Med Ctr, Hematol Sect, Washington, DC 20422 USA.
RP Stroncek, D (reprint author), Natl Inst Hlth, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
EM stefanie.slezak@gmail.com; pjin@cc.nih.gov; lcaruccio@cc.nih.gov;
renj@cc.nih.gov; benet_m@clalit.org.il; zianau@sgu.edu;
sadams1@cc.nih.gov; EWang@cc.nih.gov; joao.ascensao@va.gov;
g.p.schechter@va.gov; dstroncek@cc.nih.gov
NR 54
TC 27
Z9 29
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUN 4
PY 2009
VL 7
AR 39
DI 10.1186/1479-5876-7-39
PG 17
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 473JU
UT WOS:000268203100001
PM 19497108
ER
PT J
AU Aksentijevich, I
Masters, SL
Ferguson, PJ
Dancey, P
Frenkel, J
van Royen-Kerkhoff, A
Laxer, R
Tedgard, U
Cowen, EW
Pham, TH
Booty, M
Estes, JD
Sandler, NG
Plass, N
Stone, DL
Turner, ML
Hill, S
Butman, JA
Schneider, R
Babyn, P
El-Shanti, HI
Pope, E
Barron, K
Bing, XY
Laurence, A
Lee, CCR
Chapelle, D
Clarke, GI
Ohson, K
Nicholson, M
Gadina, M
Yang, B
Korman, BD
Gregersen, PK
van Hagen, PM
Hak, AE
Huizing, M
Rahman, P
Douek, DC
Remmers, EF
Kastner, DL
Goldbach-Mansky, R
AF Aksentijevich, Ivona
Masters, Seth L.
Ferguson, Polly J.
Dancey, Paul
Frenkel, Joost
van Royen-Kerkhoff, Annet
Laxer, Ron
Tedgard, Ulf
Cowen, Edward W.
Pham, Tuyet-Hang
Booty, Matthew
Estes, Jacob D.
Sandler, Netanya G.
Plass, Nicole
Stone, Deborah L.
Turner, Maria L.
Hill, Suvimol
Butman, John A.
Schneider, Rayfel
Babyn, Paul
El-Shanti, Hatem I.
Pope, Elena
Barron, Karyl
Bing, Xinyu
Laurence, Arian
Lee, Chyi-Chia R.
Chapelle, Dawn
Clarke, Gillian I.
Ohson, Kamal
Nicholson, Marc
Gadina, Massimo
Yang, Barbara
Korman, Benjamin D.
Gregersen, Peter K.
van Hagen, P. Martin
Hak, A. Elisabeth
Huizing, Marjan
Rahman, Proton
Douek, Daniel C.
Remmers, Elaine F.
Kastner, Daniel L.
Goldbach-Mansky, Raphaela
TI An Autoinflammatory Disease with Deficiency of the
Interleukin-1-Receptor Antagonist
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID INFANTILE CORTICAL HYPEROSTOSIS; GENE-CLUSTER; MULTIFOCAL OSTEOMYELITIS;
CIAS1 MUTATIONS; INNATE IMMUNITY; ASSOCIATION; FAMILY; ARTHRITIS;
MEMBER; MICE
AB BACKGROUND
Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T cells. We report a disorder caused by mutations of IL1RN, which encodes the interleukin-1-receptor antagonist, with prominent involvement of skin and bone.
METHODS
We studied nine children from six families who had neonatal onset of sterile multifocal osteomyelitis, periostitis, and pustulosis. Response to empirical treatment with the recombinant interleukin-1-receptor antagonist anakinra in the first patient prompted us to test for the presence of mutations and changes in proteins and their function in interleukin-1-pathway genes including IL1RN.
RESULTS
We identified homozygous mutations of IL1RN in nine affected children, from one family from Newfoundland, Canada, three families from the Netherlands, and one consanguineous family from Lebanon. A nonconsanguineous patient from Puerto Rico was homozygous for a genomic deletion that includes IL1RN and five other interleukin-1-family members. At least three of the mutations are founder mutations; heterozygous carriers were asymptomatic, with no cytokine abnormalities in vitro. The IL1RN mutations resulted in a truncated protein that is not secreted, thereby rendering cells hyperresponsive to interleukin-1 beta stimulation. Patients treated with anakinra responded rapidly.
CONCLUSIONS
We propose the term deficiency of the interleukin-1-receptor antagonist, or DIRA, to denote this autosomal recessive autoinflammatory disease caused by mutations affecting IL1RN. The absence of interleukin-1-receptor antagonist allows unopposed action of interleukin-1, resulting in life-threatening systemic inflammation with skin and bone involvement. (ClinicalTrials.gov number, NCT00059748.)
C1 [Aksentijevich, Ivona; Masters, Seth L.; Pham, Tuyet-Hang; Booty, Matthew; Plass, Nicole; Stone, Deborah L.; Laurence, Arian; Chapelle, Dawn; Gadina, Massimo; Yang, Barbara; Korman, Benjamin D.; Remmers, Elaine F.; Kastner, Daniel L.; Goldbach-Mansky, Raphaela] NIAMSD, Bethesda, MD 20892 USA.
[Cowen, Edward W.; Estes, Jacob D.; Turner, Maria L.; Lee, Chyi-Chia R.] NCI, Bethesda, MD 20892 USA.
[Sandler, Netanya G.; Douek, Daniel C.] Vaccine Res Ctr, Bethesda, MD USA.
[Barron, Karyl] NIAID, Bethesda, MD 20892 USA.
[Hill, Suvimol; Butman, John A.] Ctr Clin, Bethesda, MD USA.
[Huizing, Marjan] NHGRI, Bethesda, MD 20892 USA.
[Ferguson, Polly J.; Bing, Xinyu] Univ Iowa, Iowa City, IA USA.
[Dancey, Paul; Clarke, Gillian I.; Ohson, Kamal; Nicholson, Marc; Rahman, Proton] Mem Univ Newfoundland, St John, NF, Canada.
[Frenkel, Joost; van Royen-Kerkhoff, Annet] Univ Utrecht, Utrecht, Netherlands.
[Laxer, Ron; Schneider, Rayfel; Babyn, Paul; Pope, Elena] Univ Toronto, Toronto, ON, Canada.
[Tedgard, Ulf] Lund Univ, Malmo, Sweden.
[El-Shanti, Hatem I.] Shafallah Med Genet Ctr, Doha, Qatar.
[Gregersen, Peter K.] Feinstein Inst, Manhasset, NY USA.
[van Hagen, P. Martin; Hak, A. Elisabeth] Erasmus Univ, Med Ctr, Rotterdam, Netherlands.
RP Goldbach-Mansky, R (reprint author), Bldg 10,Rm 6D-47B,10 Ctr Dr, Bethesda, MD 20892 USA.
EM goldbacr@mail.nih.gov
RI Laurence, Arian/A-8770-2009; Butman, John/A-2694-2008; Butman,
John/J-2780-2013; Lee, Chyi-Chia/I-1938-2013; EL-SHANTI,
HATEM/Q-4932-2016;
OI Laurence, Arian/0000-0003-0942-8292; Butman, John/0000-0002-1547-9195;
Lee, Chyi-Chia/0000-0002-5306-7781; EL-SHANTI,
HATEM/0000-0001-6230-8316; Utay, Netanya/0000-0002-6407-8670; Booty,
Matthew/0000-0002-0835-3439; masters, seth/0000-0003-4763-576X
FU Intramural Research Programs of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS); National Human Genome
Research Institute (NHGRI); National Institutes of Health (NIH); NIAMS;
Children's Miracle Network; Peregrine Charities; Hoffmann-La Roche;
Amgen; NIH Clinical Research Training Program; Foundation for the NIH;
Pfizer; Roche Pharmaceuticals
FX Dr. Ferguson reports receiving grant support from the National
Institutes of Health (NIH) and NIAMS, the Children's Miracle Network,
and the Peregrine Charities; Dr. Schneider, consulting and lecture fees
and a grant support from Hoffmann-La Roche and grant support from Amgen,
the company that makes anakinra; and Dr. Korman, grant support from the
NIH Clinical Research Training Program, a public - private partnership
between the Foundation for the NIH and Pfizer. Dr. Gregersen reports
receiving consulting fees from Roche Pharmaceuticals and holding stock
options in Amgen, Illumina, and Genentech. No other potential conflict
of interest relevant to this article was reported.
NR 34
TC 378
Z9 391
U1 0
U2 14
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 4
PY 2009
VL 360
IS 23
BP 2426
EP 2437
DI 10.1056/NEJMoa0807865
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 453DN
UT WOS:000266590500008
PM 19494218
ER
PT J
AU Barry, CE
AF Barry, Clifton E., III
TI Unorthodox Approach to the Development of a New Antituberculosis Therapy
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID TUBERCULOSIS; DRUGS
C1 NIAID, TB Res Sect, Bethesda, MD 20892 USA.
RP Barry, CE (reprint author), NIAID, TB Res Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RI Barry, III, Clifton/H-3839-2012
FU Intramural NIH HHS [ZIA AI000693-17, Z01 AI000734-12]
NR 6
TC 17
Z9 18
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 4
PY 2009
VL 360
IS 23
BP 2466
EP 2467
DI 10.1056/NEJMe0903012
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 453DN
UT WOS:000266590500014
PM 19494223
ER
PT J
AU Friew, YN
Boyko, V
Hu, WS
Pathak, VK
AF Friew, Yeshitila N.
Boyko, Vitaly
Hu, Wei-Shau
Pathak, Vinay K.
TI Intracellular interactions between APOBEC3G, RNA, and HIV-1 Gag:
APOBEC3G multimerization is dependent on its association with RNA
SO RETROVIROLOGY
LA English
DT Article
ID VIRUS-LIKE PARTICLES; EDITING ENZYME APOBEC3G; ANTIVIRAL ACTIVITY;
NUCLEOCAPSID PROTEIN; ZINC-FINGER; VIF PROTEIN; TYPE-1 VIF; FLUORESCENCE
COMPLEMENTATION; CYTIDINE DEAMINASES; VIRAL-RNA
AB Background: Host restriction factor APOBEC3G (A3G) blocks human immunodeficiency virus type 1 (HIV-1) replication by G-to-A hypermutation, and by inhibiting DNA synthesis and provirus formation. Previous reports have suggested that A3G is a dimer and its virion incorporation is mediated through interactions with viral or nonviral RNAs and/or HIV-1 Gag. We have now employed a bimolecular fluorescence complementation assay (BiFC) to analyze the intracellular A3G-A3G, A3G-RNA, and A3G-Gag interactions in living cells by reconstitution of yellow fluorescent protein (YFP) from its N- or C-terminal fragments.
Results: The results obtained with catalytic domain 1 and 2 (CD1 and CD2) mutants indicate that A3G-A3G and A3G-Gag multimerization is dependent on an intact CD1 domain, which is required for RNA binding. A mutant HIV-1 Gag that exhibits reduced RNA binding also failed to reconstitute BiFC with wild-type A3G, indicating a requirement for both HIV-1 Gag and A3G to bind to RNA for their multimerization. Addition of a non-specific RNA binding peptide (P22) to the N-terminus of a CD1 mutant of A3G restored BiFC and virion incorporation, but failed to inhibit viral replication, indicating that the mutations in CD1 resulted in additional defects that interfere with A3G's antiviral activity.
Conclusion: These studies establish a robust BiFC assay for analysis of intracellular interactions of A3G with other macromolecules. The results indicate that in vivo A3G is a monomer that forms multimers upon binding to RNA. In addition, we observed weak interactions between wild-type A3G molecules and RNA binding-defective mutants of A3G, which could explain previously described protein-protein interactions between purified A3G molecules.
C1 [Friew, Yeshitila N.; Boyko, Vitaly; Hu, Wei-Shau; Pathak, Vinay K.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM yfriew@ncifcrf.gov; vb@ncifcrf.gov; whu@ncifcrf.gov; vpathak@ncifcrf.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We especially thank Eric Freed and David Derse, Wei Bu, Jean Mbisa, and
Rebecca Russell for critical readings of the manuscript and for valuable
discussions. The ApoC17 rabbit anti-human A3G antiserum and
HIV-1HXB2Vif antiserum reagents were obtained through the NIH
AIDS Research and Reference Reagent Program, Division of AIDS, NIAID,
NIH: the anti-ApoC17 antiserum from Dr. Klaus Strebel and anti-Vif
antiserum from Dr. Dana Gabuzda. This research was supported by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U. S. Government.
NR 65
TC 39
Z9 39
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD JUN 4
PY 2009
VL 6
AR 56
DI 10.1186/1742-4690-6-56
PG 20
WC Virology
SC Virology
GA 463KN
UT WOS:000267430900002
PM 19497112
ER
PT J
AU Makarova, KS
Wolf, YI
Koonin, EV
AF Makarova, Kira S.
Wolf, Yuri I.
Koonin, Eugene V.
TI Comprehensive comparative-genomic analysis of Type 2 toxin-antitoxin
systems and related mobile stress response systems in prokaryotes
SO BIOLOGY DIRECT
LA English
DT Review
ID MESSENGER-RNA INTERFERASES; PHAGE ABORTIVE INFECTION; PROGRAMMED
CELL-DEATH; ESCHERICHIA-COLI; DEINOCOCCUS-RADIODURANS; MULTIDRUG
TOLERANCE; NUCLEOTIDE-SEQUENCE; BACILLUS-SUBTILIS; CRYSTAL-STRUCTURE;
DNA-BINDING
AB Background: The prokaryotic toxin-antitoxin systems (TAS, also referred to as TA loci) are widespread, mobile two-gene modules that can be viewed as selfish genetic elements because they evolved mechanisms to become addictive for replicons and cells in which they reside, but also possess "normal" cellular functions in various forms of stress response and management of prokaryotic population. Several distinct TAS of type 1, where the toxin is a protein and the antitoxin is an antisense RNA, and numerous, unrelated TAS of type 2, in which both the toxin and the antitoxin are proteins, have been experimentally characterized, and it is suspected that many more remain to be identified.
Results: We report a comprehensive comparative-genomic analysis of Type 2 toxin-antitoxin systems in prokaryotes. Using sensitive methods for distant sequence similarity search, genome context analysis and a new approach for the identification of mobile two-component systems, we identified numerous, previously unnoticed protein families that are homologous to toxins and antitoxins of known type 2 TAS. In addition, we predict 12 new families of toxins and 13 families of antitoxins, and also, predict a TAS or TAS-like activity for several gene modules that were not previously suspected to function in that capacity. In particular, we present indications that the two-gene module that encodes a minimal nucleotidyl transferase and the accompanying HEPN protein, and is extremely abundant in many archaea and bacteria, especially, thermophiles might comprise a novel TAS. We present a survey of previously known and newly predicted TAS in 750 complete genomes of archaea and bacteria, quantitatively demonstrate the exceptional mobility of the TAS, and explore the network of toxin-antitoxin pairings that combines plasticity with selectivity.
Conclusion: The defining properties of the TAS, namely, the typically small size of the toxin and antitoxin genes, fast evolution, and extensive horizontal mobility, make the task of comprehensive identification of these systems particularly challenging. However, these same properties can be exploited to develop context-based computational approaches which, combined with exhaustive analysis of subtle sequence similarities were employed in this work to substantially expand the current collection of TAS by predicting both previously unnoticed, derived versions of known toxins and antitoxins, and putative novel TAS-like systems. In a broader context, the TAS belong to the resistome domain of the prokaryotic mobilome which includes partially selfish, addictive gene cassettes involved in various aspects of stress response and organized under the same general principles as the TAS. The "selfish altruism", or "responsible selfishness", of TAS-like systems appears to be a defining feature of the resistome and an important characteristic of the entire prokaryotic pan-genome given that in the prokaryotic world the mobilome and the "stable" chromosomes form a dynamic continuum.
Reviewers: This paper was reviewed by Kenn Gerdes (nominated by Arcady Mushegian), Daniel Haft, Arcady Mushegian, and Andrei Osterman. For full reviews, go to the Reviewers' Reports section.
C1 [Makarova, Kira S.; Wolf, Yuri I.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM makarova@ncbi.nlm.nih.gov; wolf@ncbi.nlm.nih.gov;
koonin@ncbi.nlm.nih.gov
FU DHHS (NIH, National Library of Medicine)
FX The authors' research is supported by intramural funds of the DHHS (NIH,
National Library of Medicine)
NR 107
TC 171
Z9 176
U1 3
U2 36
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD JUN 3
PY 2009
VL 4
AR 19
DI 10.1186/1745-6150-4-19
PG 38
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 464QP
UT WOS:000267521000001
PM 19493340
ER
PT J
AU Chen, M
Wang, J
Dickerson, KE
Kelleher, J
Xie, T
Gupta, D
Lai, EW
Pacak, K
Gavrilova, O
Weinstein, LS
AF Chen, Min
Wang, Jie
Dickerson, Kathryn E.
Kelleher, James
Xie, Tao
Gupta, Divakar
Lai, Edwin W.
Pacak, Karel
Gavrilova, Oksana
Weinstein, Lee S.
TI Central Nervous System Imprinting of the G Protein G(s)alpha and Its
Role in Metabolic Regulation
SO CELL METABOLISM
LA English
DT Article
ID CENTRAL MELANOCORTIN SYSTEM; RECEPTOR MESSENGER-RNA; ADIPOSE-TISSUE;
FOOD-INTAKE; TARGETED DISRUPTION; LIPID-METABOLISM; GNAS GENE; ALPHA-S;
OBESITY; MICE
AB In Albright hereditary osteodystrophy, a monogenic obesity disorder linked to heterozygous mutations of G(s)alpha, the G protein that mediates receptor-stimulated cAMP generation, obesity develops only when the mutation is on the maternal allele. Likewise, mice with maternal (but not paternal) germline G(s)alpha mutation develop obesity, insulin resistance, and diabetes. These parent-of-origin effects are due to G(s)alpha imprinting, with preferential expression from the maternal allele in some tissues. As G(s)alpha is ubiquitously expressed, the tissue involved in this metabolic imprinting effect is unknown. Using brain-specific G(s)alpha knockout mice, we show that G,m imprinting within the central nervous system underlies these effects and that G(s)alpha is imprinted in the paraventricular nucleus of the hypothalamus. Maternal G,m mutation impaired melanocortin stimulation of energy expenditure but did not affect melanocortin's effect on food intake, suggesting that melanocortins may regulate energy balance in the central nervous system through both G(s)alpha-dependent and -independent pathways.
C1 [Chen, Min; Wang, Jie; Dickerson, Kathryn E.; Kelleher, James; Xie, Tao; Gupta, Divakar; Weinstein, Lee S.] NIDDK, Signal Transduct Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
[Gavrilova, Oksana] NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA.
[Lai, Edwin W.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endorcrinol, NIH, Bethesda, MD 20892 USA.
RP Chen, M (reprint author), NIDDK, Signal Transduct Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
EM minc@intra.niddk.nih.gov; leew@amb.niddk.nih.gov
FU NIDDK and NICHD Intramural Research Programs
FX We thank R. Vinitsky for technical support. This work was supported by
the NIDDK and NICHD Intramural Research Programs.
NR 36
TC 59
Z9 62
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD JUN 3
PY 2009
VL 9
IS 6
BP 548
EP 555
DI 10.1016/j.cmet.2009.05.004
PG 8
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 453ZU
UT WOS:000266652200009
PM 19490909
ER
PT J
AU Tondera, D
Grandemange, S
Jourdain, A
Karbowski, M
Mattenberger, Y
Herzig, S
Da Cruz, S
Clerc, P
Raschke, I
Merkwirth, C
Ehses, S
Krause, F
Chan, DC
Alexander, C
Bauer, C
Youle, R
Langer, T
Martinou, JC
AF Tondera, Daniel
Grandemange, Stephanie
Jourdain, Alexis
Karbowski, Mariusz
Mattenberger, Yves
Herzig, Sebastien
Da Cruz, Sandrine
Clerc, Pascaline
Raschke, Ines
Merkwirth, Carsten
Ehses, Sarah
Krause, Frank
Chan, David C.
Alexander, Christiane
Bauer, Christoph
Youle, Richard
Langer, Thomas
Martinou, Jean-Claude
TI SLP-2 is required for stress-induced mitochondrial hyperfusion
SO EMBO JOURNAL
LA English
DT Article
DE ATP; fusion; mitochondria; stress; survival
ID DYNAMIN-RELATED PROTEIN; DOMINANT OPTIC ATROPHY; PROTEOLYTIC CLEAVAGE;
MAMMALIAN-CELLS; OUTER-MEMBRANE; INNER MEMBRANE; ACTINOMYCIN-D; OPA1;
FUSION; APOPTOSIS
AB Mitochondria are dynamic organelles, the morphology of which results from an equilibrium between two opposing processes, fusion and fission. Mitochondrial fusion relies on dynamin-related GTPases, the mitofusins (MFN1 and 2) in the outer mitochondrial membrane and OPA1 (optic atrophy 1) in the inner mitochondrial membrane. Apart from a role in the maintenance of mitochondrial DNA, little is known about the physiological role of mitochondrial fusion. Here we report that mitochondria hyperfuse and form a highly interconnected network in cells exposed to selective stresses. This process precedes mitochondrial fission when it is triggered by apoptotic stimuli such as UV irradiation or actinomycin D. Stress-induced mitochondrial hyperfusion (SIMH) is independent of MFN2, BAX/BAK, and prohibitins, but requires L-OPA1, MFN1, and the mitochondrial inner membrane protein SLP-2. In the absence of SLP-2, L-OPA1 is lost and SIMH is prevented. SIMH is accompanied by increased mitochondrial ATP production and represents a novel adaptive pro-survival response against stress. The EMBO Journal (2009) 28, 1589-1600. doi:10.1038/emboj.2009.89; Published online 9 April 2009
C1 [Tondera, Daniel; Grandemange, Stephanie; Jourdain, Alexis; Mattenberger, Yves; Herzig, Sebastien; Da Cruz, Sandrine; Martinou, Jean-Claude] Univ Geneva, Dept Cell Biol, CH-1211 Geneva 4, Switzerland.
[Karbowski, Mariusz] Univ Maryland, Ctr Med Biotechnol, Inst Biotechnol, Baltimore, MD 21201 USA.
[Clerc, Pascaline; Youle, Richard] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Raschke, Ines; Merkwirth, Carsten; Ehses, Sarah; Langer, Thomas] Univ Cologne, Inst Genet, D-5000 Cologne, Germany.
[Raschke, Ines; Merkwirth, Carsten; Ehses, Sarah; Langer, Thomas] Univ Cologne, Ctr Mol Med CMMC, D-5000 Cologne, Germany.
[Krause, Frank] Tech Univ Darmstadt, Dept Chem, Darmstadt, Germany.
[Chan, David C.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
[Alexander, Christiane] Max Delbruck Ctr Mol Med, Dept Neurosci, Berlin, Germany.
[Bauer, Christoph] Univ Geneva, NCCR Frontiers Genet, CH-1211 Geneva 4, Switzerland.
RP Martinou, JC (reprint author), Univ Geneva, Dept Cell Biol, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland.
EM Jean-Claude.Martinou@unige.ch
RI Merkwirth, Carsten/H-5992-2012;
OI Merkwirth, Carsten/0000-0001-8895-3495; Lauria,
Ines/0000-0001-5813-3103; Langer, Thomas/0000-0003-1250-1462
FU Deutsche Forschungsgemeinschaft (DFG) [TO540/1-1]; NIH; Swiss National
Science Foundation [3100A0-109419/1]; Oncosuisse Trust; Roche Reasearch
Foundation; Geneva Department of Education; European Union
[LSHM-CT-2004-512020]
FX We thank Dr Mihara and Dr Ishihara for rat OPA1-V1, OPA1-V1DS1, OPA1-V7,
and AIF-OPA1-V7 230 -997 cDNAs, Dr Scorrano for OPA1 cDNA, Dr Rojo for
human Mfn1 cDNA, Professor Wiesner for 143B rho0 cells, Professor Picard
for pdtTomato-C1, Dr Dencher and Dr Madrenas for support, Dr Rossignol
for his advices and all members of the lab for fruitful discussions.
This work was funded by the Deutsche Forschungsgemeinschaft (DFG)
(TO540/1-1), the NIH intramural program, the Swiss National Science
Foundation (subsidy 3100A0-109419/1), Oncosuisse Trust, Roche Reasearch
Foundation and the Geneva Department of Education. FK is funded in part
by the European Union (MiMage, EC FP6 Contract No. LSHM-CT-2004-512020).
NR 52
TC 244
Z9 253
U1 2
U2 30
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD JUN 3
PY 2009
VL 28
IS 11
BP 1589
EP 1600
DI 10.1038/emboj.2009.89
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 453KG
UT WOS:000266608700007
PM 19360003
ER
PT J
AU Abbas, AI
Yadav, PN
Yao, WD
Arbuckle, MI
Grant, SGN
Caron, MG
Roth, BL
AF Abbas, Atheir I.
Yadav, Prem N.
Yao, Wei-Dong
Arbuckle, Margaret I.
Grant, Seth G. N.
Caron, Marc G.
Roth, Bryan L.
TI PSD-95 Is Essential for Hallucinogen and Atypical Antipsychotic Drug
Actions at Serotonin Receptors
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID EXTRACELLULAR-REGULATED KINASE; PREPULSE INHIBITION DEFICITS; ACTIVATED
PROTEIN-KINASE; LONG-TERM POTENTIATION; 2C RECEPTOR; SELECTIVE AGONIST;
5-HT2A RECEPTORS; IN-VIVO; 5-HYDROXYTRYPTAMINE(2C) RECEPTOR; MESANGIAL
CELLS
AB Here, we report that postsynaptic density protein of 95 kDa (PSD-95), a postsynaptic density scaffolding protein, classically conceptualized as being essential for the regulation of ionotropic glutamatergic signaling at the postsynaptic membrane, plays an unanticipated and essential role in mediating the actions of hallucinogens and atypical antipsychotic drugs at 5-HT(2A) and 5-HT(2C) serotonergic G-protein-coupled receptors. We show that PSD-95 is crucial for normal 5-HT(2A) and 5-HT(2C) expression in vivo and that PSD-95 maintains normal receptor expression by promoting apical dendritic targeting and stabilizing receptor turnover in vivo. Significantly, 5-HT(2A)- and 5-HT(2C)-mediated downstream signaling is impaired in PSD-95(null) mice, and the 5-HT(2A)-mediated head-twitch response is abnormal. Furthermore, the ability of 5-HT(2A) inverse agonists to normalize behavioral changes induced by glutamate receptor antagonists is abolished in the absence of PSD-95 in vivo. These results demonstrate that PSD-95, in addition to the well known role it plays in scaffolding macromolecular glutamatergic signaling complexes, profoundly modulates metabotropic 5-HT(2A) and 5-HT(2C) receptor function.
C1 [Yadav, Prem N.; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Abbas, Atheir I.; Roth, Bryan L.] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA.
[Roth, Bryan L.] Univ N Carolina, Dept Med Chem, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC 27599 USA.
[Yao, Wei-Dong; Caron, Marc G.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
[Yao, Wei-Dong; Caron, Marc G.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Yao, Wei-Dong; Caron, Marc G.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
[Yao, Wei-Dong] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Psychiat,Div Neurosci, Boston, MA 02115 USA.
[Arbuckle, Margaret I.; Grant, Seth G. N.] Univ Edinburgh, Div Neurosci, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Grant, Seth G. N.] Wellcome Trust Sanger Inst, Genes Cognit Programme, Cambridge CB10 1SA, England.
RP Roth, BL (reprint author), Univ N Carolina, Dept Pharmacol, 4009 Genet Med Bldg,CB 7365, Chapel Hill, NC 27599 USA.
EM bryan_roth@med.unc.edu
RI Roth, Bryan/F-3928-2010
FU National Institute of Mental Health-National Institutes of Health (NIH)
[NIMH61887, U19MH82441, T32 GM007250, NS-19576, MH-73853]; Case Western
Reserve University (CWRU) Medical Scientist Training Program; National
Institute on Drug Abuse [DA021420]; National Institute of Neurological
Disorders and Stroke [NS057311]; New England Primate Research Center
[RR00168]
FX A. I. A., P. N.Y., and B. L. R. were supported by Grants NIMH61887 and
U19MH82441 from the National Institute of Mental Health-National
Institutes of Health (NIH), and the National Institute of Mental Health
Psychoactive Drug Screening Program; B. L. R. received additional
support as a National Alliance for Research on Schizophrenia and
Depression (NARSAD) Distinguished Investigator. A. I. A. was also
supported by the Case Western Reserve University (CWRU) Medical
Scientist Training Program and NIH Grant T32 GM007250. W.-D.Y. received
funding support from the following: DA021420 (National Institute on Drug
Abuse), NS057311 (National Institute of Neurological Disorders and
Stroke), RR00168 (New England Primate Research Center). M. G. C. was
funded by NIH Grants NS-19576 and MH-73853. M. G. C. is the NARSAD
Lattner Foundation Distinguished Investigator. S.G.N.G. is funded by the
Wellcome Trust Genes to Cognition Programme. We thank the Gene
Expression and Genotyping Core Facility at the Case Comprehensive Cancer
Center at CWRU and the Mouse Behavioral Phenotyping Laboratory Core
Facility in the Neurodevelopmental Disorders Research Center at
University of North Carolina, Chapel Hill. We also thank Dr. Blaine
Armbruster for his technical help.
NR 81
TC 57
Z9 58
U1 1
U2 7
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 3
PY 2009
VL 29
IS 22
BP 7124
EP 7136
DI 10.1523/JNEUROSCI.1090-09.2009
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 453SP
UT WOS:000266632400004
PM 19494135
ER
PT J
AU Weiss, NS
Doria-Rose, VP
AF Weiss, Noel S.
Doria-Rose, V. Paul
TI The Effectiveness of Colonoscopy in Reducing Mortality From Colorectal
Cancer
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
ID EFFICACY
C1 [Weiss, Noel S.] Univ Washington, Seattle, WA 98195 USA.
[Doria-Rose, V. Paul] NCI, NIH, Bethesda, MD 20892 USA.
RP Weiss, NS (reprint author), Univ Washington, Seattle, WA 98195 USA.
NR 4
TC 1
Z9 1
U1 0
U2 1
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUN 2
PY 2009
VL 150
IS 11
BP 817
EP 818
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 452HC
UT WOS:000266530000014
PM 19487720
ER
PT J
AU Arias, HR
Gumilar, F
Rosenberg, A
Targowska-Duda, KM
Feuerbach, D
Jozwiak, K
Moaddel, R
Wainer, IW
Bouzat, C
AF Arias, Hugo R.
Gumilar, Fernanda
Rosenberg, Avraham
Targowska-Duda, Katarzyna M.
Feuerbach, Dominik
Jozwiak, Krzysztof
Moaddel, Ruin
Wainer, Irving W.
Bouzat, Cecilia
TI Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine
Receptors in Different Conformational States
SO BIOCHEMISTRY
LA English
DT Article
ID ANTAGONIST BINDING-SITES; CYS-LOOP RECEPTORS; NONCOMPETITIVE INHIBITORS;
AFFINITY-CHROMATOGRAPHY; MOLECULAR-MECHANISMS; ION-CHANNEL; TRICYCLIC
ANTIDEPRESSANTS; GATING KINETICS; ALPHA-3-BETA-4; ALPHA-4-BETA-2
AB To characterize the binding sites and the mechanisms of inhibition of bupropion on muscle-type nicotinic acetylcholine receptors (AChRs), structural and functional approaches were used. The results established that bupropion (a) inhibits epibatidine-induced Ca(2+) influx in embryonic muscle AChRs, (b) inhibits adult muscle AChR macroscopic currents in the resting/activatable state with similar to 100-fold higher potency compared to that in the open state, (c) increases the desensitization rate of adult muscle AChRs from the open state and impairs channel opening from the resting state, (d) inhibits binding of [(3)H]TCP and [(3)H]imipramine to the desensitized/carbamylcholine-bound Torpedo AChR with higher affinity compared to the resting/alpha-bungarotoxin-bound AChR, (e) binds to the Torpedo AChR in either state mainly by an entropy-driven process, and (f) interacts with a binding domain located between the serine (position 6') and valine (position 13') rings, by a network of van der Waals, hydrogen bond, and polar interactions. Collectively, our data indicate that bupropion first binds to the resting AChR, decreasing the probability of ion channel opening. The remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process. Bupropion interacts with a luminal binding domain shared with PCP that is located between the serine and valine rings, and this interaction is mediated mainly by an entropy-driven process.
C1 [Arias, Hugo R.] Midwestern Univ, Coll Pharm, Dept Pharmaceut Sci, Glendale, AZ 85308 USA.
[Gumilar, Fernanda; Bouzat, Cecilia] Univ Nacl Sur, CONICET, Inst Invest Bioquim Bahia Blanca, RA-8000 Bahia Blanca, Buenos Aires, Argentina.
[Rosenberg, Avraham; Moaddel, Ruin; Wainer, Irving W.] NIA, Gerontol Res Ctr, NIH, Bethesda, MD 20892 USA.
[Targowska-Duda, Katarzyna M.; Jozwiak, Krzysztof] Med Univ Lublin, Dept Chem, Lublin, Poland.
[Feuerbach, Dominik] Novartis Inst Biomed Res, Neurosci Res, Basel, Switzerland.
RP Arias, HR (reprint author), Midwestern Univ, Coll Pharm, Dept Pharmaceut Sci, 19555 N 59th Ave, Glendale, AZ 85308 USA.
EM harias@midwestern.edu
RI Targowska-Duda, Katarzyna/I-3434-2016;
OI Gumilar, Fernanda/0000-0002-7789-2647
FU Science Foundation Arizona; Stardust Foundation; Office of Research;
ANPCyT; CONICET; UNS; Loreal-UNESCO; Fundacion F. Fiorini; National
Institute on Aging
FX This research was supported by grants from the Science Foundation
Arizona and Stardust Foundation and the Office of Research and Sponsored
Programs, Midwestern University (to H.R.A.), by grants from ANPCyT,
CONICET, UNS, Loreal-UNESCO, and Fundacion F. Fiorini (to C.B.), and by
the FOCUS research subsidy from the Foundation for Polish Science (to
K.J.). This research was also supported in part by the Intramural
Research Program of the National Institute on Aging.
NR 46
TC 24
Z9 24
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUN 2
PY 2009
VL 48
IS 21
BP 4506
EP 4518
DI 10.1021/bi802206k
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 450PC
UT WOS:000266412300009
PM 19334677
ER
PT J
AU Jagu, S
Karanam, B
Gambhira, R
Chivukula, SV
Chaganti, RJ
Lowy, DR
Schiller, JT
Roden, RBS
AF Jagu, Subhashini
Karanam, Balasubramanyam
Gambhira, Ratish
Chivukula, Sudha V.
Chaganti, Revathi J.
Lowy, Douglas R.
Schiller, John T.
Roden, Richard B. S.
TI Concatenated Multitype L2 Fusion Proteins as Candidate Prophylactic
Pan-Human Papillomavirus Vaccines
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID MINOR CAPSID PROTEIN; VIRUS-LIKE PARTICLES; IMMUNOSTIMULATORY
PHOSPHOROTHIOATE OLIGONUCLEOTIDE; COTTONTAIL RABBIT PAPILLOMAVIRUS;
CROSS-NEUTRALIZATION EPITOPE; RANDOMIZED CONTROLLED-TRIAL; BOVINE
PAPILLOMAVIRUS; MUCOSAL PAPILLOMAVIRUS; SUSTAINED EFFICACY;
HEALTHY-VOLUNTEERS
AB Vaccination with minor capsid protein L2 induces antibodies that cross-neutralize diverse papillomavirus types. However, neutralizing antibody titers against the papillomavirus type from which the L2 vaccine was derived are generally higher than the titers against heterologous types, which could limit effectiveness against heterologous types. We hypothesized that vaccination with concatenated multitype L2 fusion proteins derived from known cross-protective epitopes of several divergent human papillomavirus (HPV) types might enhance immunity across clinically relevant HPV genotypes.
Antibody responses of mice (n = 120) and rabbits (n = 23) to vaccination with HPV-16 amino-terminal L2 polypeptides or multitype L2 fusion proteins, namely, 11-200 x 3 (HPV types 6, 16, 18), 11-88 x 5 (HPV types 1, 5, 6, 16, 18), or 17-36 x 22 (five cutaneous, two mucosal low-risk, and 15 oncogenic types), that were formulated alone or in GPI-0100, alum, or 1018 ISS adjuvants were compared with vaccination with L1 virus-like particles (VLPs), including Gardasil, a licensed quadrivalent HPV L1 vaccine, and a negative control. Mice were challenged with HPV-16 pseudovirions 4 months after vaccination. Statistical tests were two-sided.
The HPV-16 L2 polypeptides generated robust HPV-16-neutralizing antibody responses, albeit lower than those to HPV-16 L1 VLPs, and lower responses against other HPVs. In contrast, vaccination with the multitype L2 fusion proteins 11-200 x 3 and 11-88 x 5 induced high serum neutralizing antibody titers against all heterologous HPVs tested. 11-200 x 3 formulated in GPI-0100 adjuvant or alum with 1018 ISS protected mice against HPV-16 challenge (reduction in HPV-16 infection vs phosphate-buffered saline control, P < .001) 4 months after vaccination as well as HPV-16 L1 VLPs, but 11-200 x 3 alone or formulated with either alum or 1018 ISS was less effective (reduction in HPV-16 infection, P < .001).
Concatenated multitype L2 proteins in adjuvant have potential as pan-oncogenic HPV vaccines.
C1 [Jagu, Subhashini; Karanam, Balasubramanyam; Gambhira, Ratish; Roden, Richard B. S.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA.
[Roden, Richard B. S.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21231 USA.
[Roden, Richard B. S.] Johns Hopkins Univ, Dept Obstet & Gynecol, Baltimore, MD 21231 USA.
[Chivukula, Sudha V.; Chaganti, Revathi J.] Shantha Biotech Ltd, Hyderabad, Andhra Pradesh, India.
[Lowy, Douglas R.; Schiller, John T.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
RP Roden, RBS (reprint author), Johns Hopkins Univ, Dept Pathol, Rm 308,Canc Res Bldg 2,1550 Orleans St, Baltimore, MD 21231 USA.
EM roden@jhmi.edu
FU GlaxoSmithKline
FX R. B. S. Roden is a paid consultant of Merck & Co, Inc., and Knobbe
Martens Olson & Bear LLC. S. Jagu and R. B. S. Roden have received
unrestricted educational grant funding from GlaxoSmithKline. R. B. S.
Roden, R. Gambhira, D. R. Lowy, and J. T. Schiller are coinventors on L2
patents licensed to Shantha Biotechnics Ltd, PaxVax, Inc., and Acambis,
Inc. The terms of these arrangements are being managed by Johns Hopkins
University in accordance with its conflict of interest policies. D. R.
Lowy and J. T. Schiller are inventors on US government-owned HPV VLP
patents that are licensed to Merck & Co, Inc., and GlaxoSmithKline. S.
V. Chivukula and R. J. Chaganti are employees of Shantha Biotechnics
Ltd, which is a collaborator in the CRADA for the development of a
pan-HPV vaccine with an interest in commercialization, and they hold
stock in the company.The sponsors had no role in the study design, the
collection and analysis of the data, the interpretation of the results,
the preparation of the manuscript, or the decision to submit the
manuscript for publication. SVC and RJC of Shantha Biotechnics Ltd
cloned and expressed the HPV-16 L2 proteins and performed all rabbit
immunizations.
NR 59
TC 96
Z9 102
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 JUN 2
PY 2009
VL 101
IS 11
BP 782
EP 792
DI 10.1093/jnci/djp106
PG 11
WC Oncology
SC Oncology
GA 454QL
UT WOS:000266697300006
PM 19470949
ER
PT J
AU Jackson, SL
Taplin, SH
Sickles, EA
Abraham, L
Barlow, WE
Carney, PA
Geller, B
Berns, EA
Cutter, GR
Elmore, JG
AF Jackson, Sara L.
Taplin, Stephen H.
Sickles, Edward A.
Abraham, Linn
Barlow, William E.
Carney, Patricia A.
Geller, Berta
Berns, Eric A.
Cutter, Gary R.
Elmore, Joann G.
TI Variability of Interpretive Accuracy Among Diagnostic Mammography
Facilities
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SCREENING MAMMOGRAPHY; BREAST-CANCER; PERFORMANCE BENCHMARKS;
RADIOLOGISTS; WOMEN; STATES
AB Interpretive performance of screening mammography varies substantially by facility, but performance of diagnostic interpretation has not been studied.
Facilities performing diagnostic mammography within three registries of the Breast Cancer Surveillance Consortium were surveyed about their structure, organization, and interpretive processes. Performance measurements (false-positive rate, sensitivity, and likelihood of cancer among women referred for biopsy [positive predictive value of biopsy recommendation {PPV2}]) from January 1, 1998, through December 31, 2005, were prospectively measured. Logistic regression and receiver operating characteristic (ROC) curve analyses, adjusted for patient and radiologist characteristics, were used to assess the association between facility characteristics and interpretive performance. All statistical tests were two-sided.
Forty-five of the 53 facilities completed a facility survey (85% response rate), and 32 of the 45 facilities performed diagnostic mammography. The analyses included 28 100 diagnostic mammograms performed as an evaluation of a breast problem, and data were available for 118 radiologists who interpreted diagnostic mammograms at the facilities. Performance measurements demonstrated statistically significant interpretive variability among facilities (sensitivity, P = .006; false-positive rate, P < .001; and PPV2, P < .001) in unadjusted analyses. However, after adjustment for patient and radiologist characteristics, only false-positive rate variation remained statistically significant and facility traits associated with performance measures changed (false-positive rate = 6.5%, 95% confidence interval [CI] = 5.5% to 7.4%; sensitivity = 73.5%, 95% CI = 67.1% to 79.9%; and PPV2 = 33.8%, 95% CI = 29.1% to 38.5%). Facilities reporting that concern about malpractice had moderately or greatly increased diagnostic examination recommendations at the facility had a higher false-positive rate (odds ratio [OR] = 1.48, 95% CI = 1.09 to 2.01) and a non-statistically significantly higher sensitivity (OR = 1.74, 95% CI = 0.94 to 3.23). Facilities offering specialized interventional services had a non-statistically significantly higher false-positive rate (OR = 1.97, 95% CI = 0.94 to 4.1). No characteristics were associated with overall accuracy by ROC curve analyses.
Variation in diagnostic mammography interpretation exists across facilities. Failure to adjust for patient characteristics when comparing facility performance could lead to erroneous conclusions. Malpractice concerns are associated with interpretive performance.
C1 [Jackson, Sara L.; Elmore, Joann G.] Univ Washington, Sch Med, Dept Internal Med, Seattle, WA 98104 USA.
[Taplin, Stephen H.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA.
[Sickles, Edward A.] Univ Calif San Francisco, Med Ctr, Dept Radiol, San Francisco, CA 94143 USA.
[Abraham, Linn] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA.
[Barlow, William E.] Canc Res & Biostat, Seattle, WA USA.
[Carney, Patricia A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA.
[Geller, Berta] Univ Vermont, Coll Med, Burlington, VT USA.
[Berns, Eric A.] Univ Colorado Hosp, Dept Radiol, Denver, CO USA.
[Cutter, Gary R.] Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA.
RP Jackson, SL (reprint author), Univ Washington, Sch Med, Dept Internal Med, Box 359854, Seattle, WA 98104 USA.
EM sljack@u.washington.edu
FU Agency for Healthcare Research and Quality [R01 HS-010591]; National
Cancer Institute (NCI) [R01 CA-107623, K05 CA-104699]; NCI-funded Breast
Cancer Surveillance Consortium cooperative agreement [U01CA63740,
U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731,
U01CA70040]
FX Agency for Healthcare Research and Quality (public health service grant
R01 HS-010591 to J.G.E.) and National Cancer Institute (NCI) (grants R01
CA-107623 and K05 CA-104699 to J.G.E.). NCI-funded Breast Cancer
Surveillance Consortium cooperative agreement (grants U01CA63740,
U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731,
and U01CA70040 for data collection). Dr Jackson is supported by Dr
Elmore's R01 grant. The collection of cancer incidence data used in this
study was supported in part by several state public health departments
and cancer
NR 24
TC 15
Z9 15
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JUN 2
PY 2009
VL 101
IS 11
BP 814
EP 827
DI 10.1093/jnci/djp105
PG 14
WC Oncology
SC Oncology
GA 454QL
UT WOS:000266697300009
PM 19470953
ER
PT J
AU Driscoll, I
Davatzikos, C
An, Y
Wu, X
Shen, D
Kraut, M
Resnick, SM
AF Driscoll, I.
Davatzikos, C.
An, Y.
Wu, X.
Shen, D.
Kraut, M.
Resnick, S. M.
TI Longitudinal pattern of regional brain volume change differentiates
normal aging from MCI
SO NEUROLOGY
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; VOXEL-BASED MORPHOMETRY; ALZHEIMERS-DISEASE;
OLDER-ADULTS; MRI; TRAJECTORIES; DIAGNOSIS; DECLINE; PREDICT; LOBE
AB Background: Neuroimaging measures have potential as surrogate markers of disease through identification of consistent features that occur prior to clinical symptoms. Despite numerous investigations, especially in relation to the transition to clinical impairment, the regional pattern of brain changes in clinically normal older adults has not been established. We predict that the regions that show early pathologic changes in association with Alzheimer disease will show accelerated volume loss in mild cognitive impairment (MCI) compared to normal aging.
Methods: Through the Baltimore Longitudinal Study of Aging, we prospectively evaluated 138 nondemented individuals (age 64-86 years) annually for up to 10 consecutive years. Eighteen participants were diagnosed with MCI over the course of the study. Mixed-effects regression was used to compare regional brain volume trajectories of clinically normal individuals to those with MCI based on a total of 1,017 observations.
Results: All investigated volumes declined with normal aging (p < 0.05). Accelerated change with age was observed for ventricular CSF (vCSF), frontal gray matter, superior, middle, and medial frontal, and superior parietal regions (p <= 0.04). The MCI group showed accelerated changes compared to normal controls in whole brain volume, vCSF, temporal gray matter, and orbitofrontal and temporal association cortices, including the hippocampus (p <= 0.04).
Conclusion: Although age-related regional volume loss is apparent and widespread in nondemented individuals, mild cognitive impairment is associated with a unique pattern of structural vulnerability reflected in differential volume loss in specific regions. Early identification of patterns of abnormality is of fundamental importance for detecting disease onset and tracking progression. Neurology (R) 2009; 72: 1906-1913
C1 [Resnick, S. M.] NIA, GRC, LPC, Baltimore, MD 21224 USA.
[Davatzikos, C.; Wu, X.; Shen, D.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Kraut, M.] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21205 USA.
RP Resnick, SM (reprint author), NIA, GRC, LPC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM resnicks@mail.nih.gov
FU Intramural NIH HHS [Z01 AG000191-11]; NIA NIH HHS [N01-AG-3-2124,
R01-AG14971]
NR 33
TC 170
Z9 172
U1 1
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN 2
PY 2009
VL 72
IS 22
BP 1906
EP 1913
DI 10.1212/WNL.0b013e3181a82634
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 452FD
UT WOS:000266524600006
PM 19487648
ER
PT J
AU Kireeva, ML
Kashlev, M
AF Kireeva, Maria L.
Kashlev, Mikhail
TI Mechanism of sequence-specific pausing of bacterial RNA polymerase
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE backtracking; elongation; transcription; translocation
ID PAUSED TRANSCRIPTION COMPLEX; RIBONUCLEIC-ACID POLYMERASE; II ELONGATION
COMPLEX; OPERON LEADER REGION; STRUCTURAL BASIS; DNA HYBRID; TRIGGER
LOOP; SUBSTRATE-SPECIFICITY; SITE; TERMINATION
AB Sequence-specific pausing of multisubunit RNA polymerases (RNAPs) represents a rate-limiting step during transcription elongation. Pausing occurs on average every 100 bases of DNA. Several models have been proposed to explain pausing, including backtracking of the ternary elongation complex, delay of translocation of the enzyme along DNA, or a conformational change in the active site preventing formation of the phosphodiester bond. Here, we performed biochemical characterization of previously-reported pauses of Escherichia coli RNAP and found that they are not associated with backtracking or a translocation delay. Instead, the paused complex contains the 3' end of the transcript in the active center and is capable of binding the next cognate NTP. However, bond formation occurs much slower in the paused complex compared with its fully-active counterpart. The pausing is dramatically decreased by a substitution of the base encoding the next incoming NTP and the base encoding the 3' end of the nascent RNA, suggesting that (mis)-alignment of the 3' end of the RNA and the incoming NTP in the active site is crucial for pausing. These pause sites are conserved between E. coli and Thermus thermophilus RNAPs, but are not recognized by Saccharomyces cerevisiae RNAP II, indicating that prokaryotic RNAPs might be more sensitive to the changes in the alignment of the nascent transcript and the substrate NTP in the active site.
C1 [Kireeva, Maria L.; Kashlev, Mikhail] NCI, Ctr Canc Res, Frederick, MD 21702 USA.
RP Kashlev, M (reprint author), NCI, Ctr Canc Res, Frederick, MD 21702 USA.
EM mkashlev@mail.ncifcrf.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX We thank Irina Artsimovitch, Sergey Borukhov, and Robert Landick for
helpful comments; Zachary Burton and Dwight Nissley for critical reading
of the manuscript; Irina Artsimovitch (Ohio State University, Columbus,
OH) for a generous gift of T. thermophilus RNAP holoenzyme; and Lucyna
Lubkowska for protein purification. This work was supported by the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research. The content of
this publication does not necessarily reflect the views and policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the U.
S. Government.
NR 47
TC 63
Z9 63
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 2
PY 2009
VL 106
IS 22
BP 8900
EP 8905
DI 10.1073/pnas.0900407106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 452ZU
UT WOS:000266580500024
PM 19416863
ER
PT J
AU Fischer, T
Cui, BW
Dhakshnamoorthy, J
Zhou, M
Rubin, C
Zofall, M
Veenstra, TD
Grewal, SIS
AF Fischer, Tamas
Cui, Bowen
Dhakshnamoorthy, Jothy
Zhou, Ming
Rubin, Chanan
Zofall, Martin
Veenstra, Timothy D.
Grewal, Shiv I. S.
TI Diverse roles of HP1 proteins in heterochromatin assembly and functions
in fission yeast
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE chromosome segregation; histone deacetylase; silencing; centromere; RNAi
ID CHROMATIN-REMODELING COMPLEX; SCHIZOSACCHAROMYCES-POMBE; HISTONE H3;
GENE-EXPRESSION; CHROMOSOME SEGREGATION; LYSINE-9 METHYLATION;
EPIGENETIC CONTROL; FAMILY PROTEINS; DOMAIN; RNAI
AB Conserved chromosomal HP1 proteins capable of binding to histone H3 methylated at lysine 9 are believed to provide a dynamic platform for the recruitment and/or spreading of various regulatory proteins involved in diverse chromosomal processes. The fission yeast Schizosaccharomyces pombe HP1 family members Chp2 and Swi6 are important for heterochromatin assembly and transcriptional silencing, but their precise roles are not fully understood. Here, we show that Swi6 and Chp2 associate with histone deacetylase ( HDAC) protein complexes containing class I HDAC Clr6 and class II HDAC Clr3 ( a component of Snf2/HDAC repressor complex), which are critical for transcriptional silencing of centromeric repeats targeted by the heterochromatin machinery. Mapping of RNA polymerase (Pol) II distribution in single and double mutant backgrounds revealed that Swi6 and Chp2 proteins and their associated HDAC complexes have overlapping functions in limiting Pol II occupancy across pericentromeric heterochromatin domains. The purified Swi6 fraction also contains factors involved in various chromosomal processes such as chromatin remodeling and DNA replication. Also, Swi6 copurifies with Mis4 protein, a cohesin loading factor essential for sister chromatid cohesion, and with centromere-specific histone H3 variant CENP-A, which is incorporated into chromatin in a heterochromatin-dependent manner. These analyses suggest that among other functions, HP1 proteins associate with chromatin-modifying factors that in turn cooperate to assemble repressive chromatin; thus, precluding accessibility of underlying DNA sequences to transcriptional machinery.
C1 [Fischer, Tamas; Cui, Bowen; Dhakshnamoorthy, Jothy; Rubin, Chanan; Zofall, Martin; Grewal, Shiv I. S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Zhou, Ming; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
RP Grewal, SIS (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM grewals@mail.nih.gov
RI Cui, Bowen/F-1038-2011; Fischer, Tamas/A-7729-2016
OI Fischer, Tamas/0000-0002-7996-4042
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Center for Cancer Research
FX We thank S. Jia, T. Yamada, and T. Sugiyama for strain constructions; S.
Jia for generating anti-Chp2 antibody; K. Takahashi and M. Yanagida
(Kyoto University, Kyoto, Japan) for providing a strain expressing
Cnp1-HA; and I. Hall and H. Cam for comments on the manuscript. This
work was supported by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, and Center for Cancer
Research.
NR 59
TC 64
Z9 65
U1 1
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 2
PY 2009
VL 106
IS 22
BP 8998
EP 9003
DI 10.1073/pnas.0813063106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 452ZU
UT WOS:000266580500041
PM 19443688
ER
PT J
AU Zhou, HH
Thompson, KG
AF Zhou, Hui-Hui
Thompson, Kirk G.
TI Cognitively directed spatial selection in the frontal eye field in
anticipation of visual stimuli to be discriminated
SO VISION RESEARCH
LA English
DT Article; Proceedings Paper
CT Buenos Aires Workshop on Visual Attention
CY MAR 11-15, 2007
CL San Telmo, ARGENTINA
DE Vision; Saccade; Attention; Luminance; Monkey; Physiology
ID CORTICAL MAGNIFICATION FACTOR; TOP-DOWN CONTROL; NEURONAL-ACTIVITY;
CONTRAST SENSITIVITY; NEURAL MECHANISMS; SINGLE NEURONS; ATTENTION;
CORTEX; MACAQUE; MODULATION
AB Single neuron activity was recorded in the frontal eye field (FEF) of monkeys trained to perform a difficult luminance discrimination task. The appearance of a cue stimulus informed the monkeys of the locations of two gray luminance stimuli that would appear within 500-1500 ms. The monkeys were rewarded for making a saccade to the brighter of the two luminance stimuli, or if they were the same luminance, for making a saccade to the cue stimulus. Sixty percent (51/85) of FEF neurons exhibited elevated activity when the cue informed the monkeys that one of the luminance stimuli would appear in their response field (RF). This spatially selective anticipatory activity occurred without any visual stimulus appearing in their RF and was not related to saccade choice or latency. The responses of 27 of the anticipatory neurons (32% of the total sample) were also incompatible with the hypothesis that the activity represents saccade probability because they did not exhibit elevated activity for the cue stimulus which was the most probable saccade target. Behaviorally, monkeys exhibited improved perception at locations informed by cue than at unpredictable locations. These results provide physiological evidence that FEF serves an important role in endogenous spatial attention in addition to its well-known role in saccade production. Published by Elsevier Ltd.
C1 [Zhou, Hui-Hui; Thompson, Kirk G.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Thompson, KG (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA.
EM kgt@nei.nih.gov
FU Intramural NIH HHS [Z01 EY000389-06]
NR 52
TC 15
Z9 15
U1 2
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD JUN 2
PY 2009
VL 49
IS 10
BP 1205
EP 1215
DI 10.1016/j.visres.2008.03.024
PG 11
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 460DS
UT WOS:000267168800016
PM 18501402
ER
PT J
AU Berman, R
Colby, C
AF Berman, Rebecca
Colby, Carol
TI Attention and active vision
SO VISION RESEARCH
LA English
DT Article; Proceedings Paper
CT Buenos Aires Workshop on Visual Attention
CY MAR 11-15, 2007
CL San Telmo, ARGENTINA
DE Updating; Parietal; Neuron; Macaque; Imaging
ID LATERAL INTRAPARIETAL AREA; SACCADIC EYE-MOVEMENTS; POSTERIOR PARIETAL
CORTEX; HUMAN VISUAL-CORTEX; UPDATING SPATIAL REPRESENTATIONS;
MEMORY-GUIDED SACCADES; DOUBLE-STEP SACCADES; SPLIT-BRAIN MACAQUE;
CORTICAL AREAS; SELECTIVE ATTENTION
AB Visual perception results from the interaction of incoming sensory signals and top down cognitive and motor signals. Here we focus on the representation of attended locations in parietal cortex and in earlier visual cortical areas. We review evidence that these spatial representations are modulated not only by selective attention but also by the intention to move the eyes. We describe recent experiments in monkey and human that elucidate the mechanisms and circuitry involved in updating, or remapping, the representations of salient stimuli. Two central ideas emerge. First, selective attention and remapping are closely intertwined, and together contribute to the percept of spatial stability. Second, remapping is accomplished not by a single area but by the participation of parietal, frontal and extrastriate cortex as well as subcortical structures. This neural circuitry is distinguished by significant redundancy and plasticity, suggesting that the updating of salient stimuli is fundamental for spatial stability and visuospatial behavior. We conclude that multiple processes and pathways contribute to active vision in the primate brain. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Berman, Rebecca] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Colby, Carol] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15213 USA.
[Colby, Carol] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA.
RP Berman, R (reprint author), NEI, Sensorimotor Res Lab, NIH, Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA.
EM bermanr@nei.nih.gov; ccolby@cnbc.cmu.edu
FU NCRR NIH HHS [P41 RR003631-120005, P41 RR003631-130005, P41
RR003631-140005, P41 RR003631-150005, P41RR-03631]; NEI NIH HHS
[EY-08908, EY-12032, R01 EY012032, R01 EY012032-02, R01 EY012032-03, R01
EY012032-04, R01 EY012032-05, R01 EY012032-06, R01 EY012032-07, R01
EY012032-08]; NIMH NIH HHS [MH-45156, P50 MH045156]
NR 143
TC 32
Z9 32
U1 2
U2 16
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD JUN 2
PY 2009
VL 49
IS 10
BP 1233
EP 1248
DI 10.1016/j.visres.2008.06.017
PG 16
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 460DS
UT WOS:000267168800019
PM 18627774
ER
PT J
AU Shen, JX
Yakel, JL
AF Shen, Jian-xin
Yakel, Jerrel L.
TI Nicotinic acetylcholine receptor-mediated calcium signaling in the
nervous system
SO ACTA PHARMACOLOGICA SINICA
LA English
DT Review
DE nicotinic acetylcholine receptors; calcium; cellular signaling; nervous
system
ID ADRENAL CHROMAFFIN CELLS; PROTEIN-KINASE-C; CHOLINERGIC ANTIINFLAMMATORY
PATHWAY; HIPPOCAMPAL SYNAPTIC PLASTICITY; RAT STRIATAL SYNAPTOSOMES;
INTRACELLULAR CALCIUM; TYROSINE-HYDROXYLASE; GENE-EXPRESSION; ACH
RECEPTORS; ENDOPLASMIC-RETICULUM
AB Based on the composition of the five sub-units forming functional neuronal nicotinic acetylcholine receptors (nAChRs), they are grouped into either heteromeric (comprising both alpha and beta subunits) or homomeric (comprising only a subunits) receptors. The nAChRs are known to be differentially permeable to calcium ions, with the alpha 7 nAChR subtype having one of the highest permeabilities to calcium. Calcium influx through nAChRs, particularly through the alpha-bungarotoxin-sensitive alpha 7-containing nAChRs, is a very efficient way to raise cytoplasmic calcium levels. The activation of nAChRs can mediate three types of cytoplasmic calcium signals: (1) direct calcium influx through the nAChRs, (2) indirect calcium influx through voltage-dependent calcium channels (VDCCs) which are activated by the nAChR-mediated depolarization, and (3) calcium-induced calcium release (CICR) (triggered by the first two sources) from the endoplasmic reticulum (ER) through the ryanodine receptors and inositol (1,4,5)-triphosphate receptors (IP(3)Rs). Downstream signaling events mediated by nAChR-mediated calcium responses can be grouped into instantaneous effects (such as neurotransmitter release, which can occur in milliseconds after nAChR activation), short-term effects (such as the recovery of nAChR desensitization through cellular signaling cascades), and long-term effects (such as neuroprotection via gene expression). In addition, nAChR activity can be regulated by cytoplasmic calcium levels, suggesting a complex reciprocal relationship. Further advances in imaging techniques, animal models, and more potent and subtype-selective ligands for neuronal nAChRs would help in understanding the neuronal nAChR-mediated calcium signaling, and lead to the development of improved therapeutic treatments.
C1 [Shen, Jian-xin; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Shen, Jian-xin] Shantou Univ, Coll Med, Shantou 515041, Peoples R China.
RP Shen, JX (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM shenj2@niehs.nih.gov; yakel@niehs.nih.gov
FU NIH; National Institute of Environmental Health Sciences; National
Natural Science Foundation of China [30470900]; Natural Science
Foundation of Guangdong Province [04020253]
FX We would like to thank S DUDEK and S B SIMONS for advice in preparing
the manuscript. Research was supported by the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences;
the National Natural Science Foundation of China (No 30470900), Natural
Science Foundation of Guangdong Province (No 04020253) and SRF for ROCS,
SEM.
NR 95
TC 65
Z9 67
U1 2
U2 23
PU ACTA PHARMACOLOGICA SINICA
PI SHANGHAI
PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1671-4083
EI 1745-7254
J9 ACTA PHARMACOL SIN
JI Acta Pharmacol. Sin.
PD JUN
PY 2009
VL 30
IS 6
BP 673
EP 680
DI 10.1038/aps.2009.64
PG 8
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 457GQ
UT WOS:000266916900004
PM 19448647
ER
PT J
AU Xi, ZX
Spiller, K
Gardner, EL
AF Xi, Zheng-xiong
Spiller, Krista
Gardner, Eliot L.
TI Mechanism-based medication development for the treatment of nicotine
dependence
SO ACTA PHARMACOLOGICA SINICA
LA English
DT Review
DE nicotine; reward; addiction; smoking cessation
ID DOPAMINE D-3 RECEPTOR; VENTRAL TEGMENTAL AREA; BRAIN REWARD FUNCTION;
CANNABINOID CB1 RECEPTORS; CONDITIONED PLACE PREFERENCES;
PROGRESSIVE-RATIO SCHEDULES; TREATING TOBACCO DEPENDENCE; RANDOMIZED
CONTROLLED-TRIAL; MPEP DECREASED NICOTINE; SMOKING-CESSATION
AB Tobacco use is a global problem with serious health consequences. Though some treatment options exist, there remains a great need for new effective pharmacotherapies to aid smokers in maintaining long-term abstinence. In the present article, we first discuss the neural mechanisms underlying nicotine reward, and then review various mechanism-based pharmacological agents for the treatment of nicotine dependence. An oversimplified hypothesis of addiction to tobacco is that nicotine is the major addictive component of tobacco. Nicotine binds to alpha 4 beta 2 and alpha 7 nicotinic acetylcholine receptors (nAChRs) located on dopaminergic, glutamatergic and GABAergic neurons in the mesolimbic dopamine (DA) system, which causes an increase in extracellular DA in the nucleus accumbens (NAc). That increase in DA reinforces tobacco use, particularly during the acquisition phase. Enhanced glutamate transmission to DA neurons in the ventral tegmental area appears to play an important role in this process. In addition, chronic nicotine treatment increases endocannabinoid levels in the mesolimbic DA system, which indirectly modulates NAc DA release and nicotine reward. Accordingly, pharmacological agents that target brain acetylcholine, DA, glutamate, GABA, or endocannabonoid signaling systems have been proposed to interrupt nicotine action. Furthermore, pharmacokinetic strategies that alter plasma nicotine availability, metabolism and clearance also significantly alter nicotine's action in the brain. Progress using these pharmacodynamic and pharmacokinetic agents is reviewed. For drugs in each category, we discuss the mechanistic rationale for their potential anti-nicotine efficacy, major findings in preclinical and clinical studies, and future research directions.
C1 [Xi, Zheng-xiong; Spiller, Krista; Gardner, Eliot L.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Xi, ZX (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM zxi@mail.nih.gov
FU National Institute on Drug Abuse; National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, National Institutes of Health.
NR 199
TC 16
Z9 18
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1671-4083
J9 ACTA PHARMACOL SIN
JI Acta Pharmacol. Sin.
PD JUN
PY 2009
VL 30
IS 6
BP 723
EP 739
DI 10.1038/aps.2009.46
PG 17
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 457GQ
UT WOS:000266916900009
PM 19434058
ER
PT J
AU Walter, BL
Armitage, AE
Graham, SC
de Oliveira, T
Skinhoj, P
Jones, EY
Stuart, DI
McMichael, AJ
Chesebro, B
Iversen, AKN
AF Walter, Brandon L.
Armitage, Andrew E.
Graham, Stephen C.
de Oliveira, Tulio
Skinhoj, Peter
Jones, E. Yvonne
Stuart, David I.
McMichael, Andrew J.
Chesebro, Bruce
Iversen, Astrid K. N.
TI Functional characteristics of HIV-1 subtype C compatible with increased
heterosexual transmissibility
SO AIDS
LA English
DT Article
DE CCR5; cervix; evolution; HIV-1; phylogeny; subtype A; subtype C;
transmission
ID IMMUNODEFICIENCY-VIRUS TYPE-1; SUB-SAHARAN AFRICA/; GENETIC SUBTYPES;
CCR5 EXPRESSION; VIRAL ENTRY; V2 REGIONS; 4 CITIES; INFECTION;
SEQUENCES; ANTIBODY
AB Background: Despite the existence of over 50 subtypes and circulating recombinant forms of HIV-1, Subtype C dominates the heterosexual pandemic causing approximately 56% of all infections.
Objective: To evaluate whether viral genetic factors may contribute to the observed subtype-C predominance.
Methods: Chimeric viruses were generated using V1-V3 envelope fragments from a subtype-A/C dually infected woman with preferential genital replication of subtype C. Viral adaptation, spread and cell fusion ability were evaluated in vitro using peripheral blood mononuclear cells and HeLa-CD4-CCR5 cell lines, sequencing and cloning. Structural modeling was performed using a crystal structure of gp120-CD4-X5. Phylogenetic analysis was done using subtype-A, subtype-B and subtype-C sequences from blood and cervix of 37 infected women and database sequences.
Results: We identified two envelope motifs, compact V1-V2 loops and V3-316T, which are found at high frequency throughout subtype-C evolution and affect gp120 interactions with CD4 and CCR5, respectively. When a V1-Delta 5 deletion or V3-A316T was incorporated into subtype A, each increased viral fusion and spread several fold in peripheral blood mononuclear cell and cell lines with low CCR5 expression. Structural modeling suggested the formation of an additional hydrogen bond between V3 and CCR5. Moreover, we found preferential selection of HIV with 316T and/or extremely short V1-V2 loops in cervices of three women infected with subtypes A/C, B or C.
Conclusion: As CD(4+)-CCR(5+)-T cells are key targets for genital HIV infection and cervical selection can favor compact V1-V2 loops and 316T, which increase viral infectivity, we propose that these conserved subtype-C motifs may contribute to transmission and spread of this subtype. (C) 2009 Wolters Kluwer Health vertical bar Lippincotl Williams & Wilkins
C1 [Armitage, Andrew E.; McMichael, Andrew J.; Iversen, Astrid K. N.] Univ Oxford, John Radcliffe Hosp, MRC HIU, WIMM, Oxford OX3 9DS, England.
[Walter, Brandon L.; Chesebro, Bruce] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Natl Inst Hlth, Hamilton, MT USA.
[Graham, Stephen C.; Jones, E. Yvonne; Stuart, David I.] Ctr Human Genet, Wellcome Trust, Div Struct Biol, Oxford, England.
[de Oliveira, Tulio] Univ Western Cape, S African Natl Bioinformat Inst, HRC Pathogen Bioinformat Unit, Cape Town, South Africa.
[Skinhoj, Peter] Rigshosp, Dept Infect Dis, DK-2100 Copenhagen, Denmark.
RP Iversen, AKN (reprint author), Univ Oxford, John Radcliffe Hosp, MRC HIU, WIMM, Oxford OX3 9DS, England.
EM astrid.iversen@imm.ox.ac.uk
RI Graham, Stephen/B-5173-2010; Jones, Yvonne/J-2293-2016
OI Graham, Stephen/0000-0003-4547-4034; Jones, Yvonne/0000-0002-3834-1893
FU Danish AIDS Foundation; Nuffield Dominions Trust; Cancer Research UK,;
EU [LSHG-CT-2006-031220]; MRC, UK
FX Funding was provided by the Danish AIDS Foundation, the Nuffield
Dominions Trust, Cancer Research UK, the EU (LSHG-CT-2006-031220) and
MRC, UK. The authors have no competing financial interests.
Supplementary documentation can be obtained on request.
NR 55
TC 13
Z9 13
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUN 1
PY 2009
VL 23
IS 9
BP 1047
EP 1057
DI 10.1097/QAD.0b013e32832a1806
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 452VN
UT WOS:000266569400002
PM 19390419
ER
PT J
AU Haubrich, RH
Riddler, SA
DiRienzo, AG
Komarow, L
Powderly, WG
Klingman, K
Garren, KW
Butcher, DL
Rooney, JF
Haas, DW
Mellors, JW
Havliri, DV
AF Haubrich, Richard H.
Riddler, Sharon A.
DiRienzo, A. Gregory
Komarow, Lauren
Powderly, William G.
Klingman, Karin
Garren, Kevin W.
Butcher, David L.
Rooney, James F.
Haas, David W.
Mellors, John W.
Havliri, Diane V.
CA AIDS Clinical Trials Grp ACTG
TI Metabolic outcomes in a randomized trial of nucleoside, nonnucleoside
and protease inhibitor-sparing regimens for initial HIV treatment
SO AIDS
LA English
DT Article
DE antiretroviral therapy; lipoatrophy; metabolic complication;
nonnucleoside reverse-transcriptase inhibitor; protease inhibitor;
treatment naive
ID REVERSE-TRANSCRIPTASE INHIBITORS; COMBINATION ANTIRETROVIRAL THERAPY;
PLUS DUAL NUCLEOSIDES; MYOCARDIAL-INFARCTION; MORPHOLOGIC CHANGES;
MITOCHONDRIAL-DNA; INFECTED ADULTS; NAIVE PATIENTS; LIPODYSTROPHY; RISK
AB Background: The metabolic effects of initial therapy for HIV-1 infection are important determinants of regimen selection.
Methods: Open-label study in 753 subjects randomized equally toefavirenz or lopinavir/ritonavir(r) plus two nucleoside reverse-transcriptase inhibitor (NRTI) vs. the NRTI-sparing regimen of lopinavir/rplus efavirenz. Zidovudine, stavudine, or tenofovir with lamivudine was selected prior to randomization. Metabolic outcomes through 96 weeks were lipoatrophy, defined as at least 20% loss in extremity fat, and fasting serum lipids.
Results: Lipoatrophy by dual-energy X-ray absorptiometry at week 96 occurred in 32% [95% confidence interval (CI) 25-39%] of subjects in the efavirenz plus two NRTIs arm, 17% (95% CI 12-24) in the lopinavir/r plus two NRTIs arm, and 9% (95% CI 5-14) in the NRTI-sparing arm (P <= 0.023 for all comparisons). Varying the definition of lipoatrophy (>= 10 to >= 40% fat loss) and correction for baseline risk factors did not affect the significant difference in lipoatrophy between the NRTI-containing regimens. Lipoatrophy was most frequent with stavudine-containing regimens and least frequent with tenofovir-containing regimens (P<0.001), which were not significantly different from the NRTI-sparing regimen. Total cholesterol increases at week 96 were greatest in the NRTI-sparing arm (median +57 mg/dl) compared with the other two arms (+32-33 mg/dl; P < 0.001). Use of lipid-lowering agents was more common (25 vs. 11-13%) in the NRTI-sparing arm.
Conclusion: Lipoatrophy was more frequent with efavirenz than lopinavir/r when combined with stavudine or zidovudine, and less frequent when either drug was combined with tenofovir. Lipoatrophy was least frequent with the NRTI-sparing regimen, but this benefit was offset by greater cholesterol elevations and the need for lipid-lowering agents. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Haubrich, Richard H.] Univ Calif San Diego, Antiviral Res Ctr, San Diego, CA 92103 USA.
[Riddler, Sharon A.; Mellors, John W.] Univ Pittsburgh, Pittsburgh, PA USA.
[DiRienzo, A. Gregory; Komarow, Lauren] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA.
[Powderly, William G.] Univ Coll Dublin, Dublin 2, Ireland.
[Klingman, Karin] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Garren, Kevin W.] Abbott Labs, Abbott Pk, IL 60064 USA.
[Butcher, David L.] Bristol Myers Squibb, Virol Med Affairs, Plainsboro, NJ USA.
[Rooney, James F.] Gilead Sci, Foster City, CA USA.
[Haas, David W.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Havliri, Diane V.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Haubrich, RH (reprint author), Univ Calif San Diego, Antiviral Res Ctr, 150 W Washington St,Suite 100, San Diego, CA 92103 USA.
EM rhaubrich@ucsd.edu
FU National Institute of Allergy and Infectious Disease [AI 068634, AI
069471, AI 27661, AI 069439, AI 25859, AI 069477, AI 069513, AI 069452,
AI 27673, AI 069470, AI 069474, AI 069411, AI 069423, AI 069494, AI
069484, AI 069472]; National Institutes of Health
FX This work was supported by grants AI 068636 (AIDS Clinical Trials Group
Central Grant), AI 068634, AI 069471, AI 27661, AI 069439, AI 25859, At
069477, AI 069513, AI 069452, AI 27673, AI 069470, AI 069474, AI 069411,
AI 069423, AI 069494, AI 069484, AI 069472, AI 38858, AI 069501, AI
32783, AI 069450, AI 32782, AI 069465, AI 069424, AI 38858, AI 069447,
AI 069495, AI 069502, AI 069556, AI 069432, AI 46370, AI 069532, AI
46381, AI 46376, AI 34853, AI 069434, AI 060354, AI 064086, AI 36214, AI
069419, AI 069418, AI 50410, AI 45008, RR 00075, RR 00032, RR 00044, RR
00046, RR 02635, RR 00051, RR 00052, RR 00096, RR 00047, RR 00039, and
DA 12121 from the National Institute of Allergy and Infectious Disease,
National Institutes of Health. The collaborating pharmaceutical
companies provided Lopinavir-ritonavir (Abbott), efavirenz and stavudine
XR (Bristol-Myers Squibb), and tenofovir DF (Gilead).
NR 33
TC 151
Z9 157
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUN 1
PY 2009
VL 23
IS 9
BP 1109
EP 1118
DI 10.1097/QAD.0b013e32832b4377
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 452VN
UT WOS:000266569400008
PM 19417580
ER
PT J
AU Carrico, AW
Chesney, MA
Johnson, MO
Morin, SF
Neilands, TB
Remien, RH
Rotheram-Borus, MJ
Wong, FL
AF Carrico, Adam W.
Chesney, Margaret A.
Johnson, Mallory O.
Morin, Stephen F.
Neilands, Torsten B.
Remien, Robert H.
Rotheram-Borus, Mary Jane
Wong, F. Lennie
CA NIMH Healthy Living Project Team
TI Randomized Controlled Trial of a Cognitive-Behavioral Intervention for
HIV-Positive Persons: An Investigation of Treatment Effects on
Psychosocial Adjustment
SO AIDS AND BEHAVIOR
LA English
DT Article
DE AIDS; Anxiety; Depression; HIV; Intervention; Positive affect
ID STRESS-MANAGEMENT INTERVENTIONS; ACTIVE ANTIRETROVIRAL THERAPY; HEALTHY
LIVING PROJECT; DEPRESSIVE SYMPTOMS; INFECTED PERSONS; CLINICAL-TRIAL;
UNITED-STATES; VIRAL LOAD; DRUG-USE; MEN
AB Questions remain regarding the clinical utility of psychological interventions for HIV-positive persons because randomized controlled trials have utilized stringent inclusion criteria and focused extensively on gay men. The present randomized controlled trial examined the efficacy of a 15-session, individually delivered cognitive-behavioral intervention (n = 467) compared to a wait-list control (n = 469) in a diverse sample of HIV-positive persons who reported HIV transmission risk behavior. Five intervention sessions that dealt with executing effective coping responses were delivered between baseline and the 5 months post-randomization. Additional assessments were completed through 25 months post-randomization. Despite previously documented reductions in HIV transmission risk, no intervention-related changes in psychosocial adjustment were observed across the 25-month investigation period. In addition, there were no intervention effects on psychosocial adjustment among individuals who presented with mild to moderate depressive symptoms. More intensive mental health interventions may be necessary to improve psychosocial adjustment among HIV-positive individuals.
C1 [Carrico, Adam W.] Univ Calif San Francisco, Dept Psychiat, Hlth Psychol Program, San Francisco, CA 94143 USA.
[Chesney, Margaret A.; Johnson, Mallory O.; Morin, Stephen F.; Neilands, Torsten B.] Univ Calif San Francisco, NIMH Healthy Living Project Team, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA.
[Remien, Robert H.] Columbia Univ, New York State Psychiat Inst, NIMH Healthy Living Project Team, New York, NY USA.
[Rotheram-Borus, Mary Jane; Wong, F. Lennie] Univ Calif Los Angeles, NIMH Healthy Living Project Team, Los Angeles, CA USA.
Med Coll Wisconsin, NIMH Healthy Living Project Team, Milwaukee, WI USA.
RP Carrico, AW (reprint author), Univ Calif San Francisco, Dept Psychiat, Hlth Psychol Program, 3333 Calif St,Suite 465,Box 0848, San Francisco, CA 94143 USA.
EM adam.carrico@ucsf.edu
FU NIMH NIH HHS [U10 MH057616-05S1, P30-MH062246, P30-MH43520, U10-MH57636,
U10-MH57631, U10-MH57615, U10 MH057616-07, U10 MH057616-05, U10
MH057616, T32-MH019391, P30-MH058107, P30 MH043520, U10-MH57616, U10
MH057616-06, P30-MH57226]
NR 38
TC 14
Z9 16
U1 1
U2 7
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS behav.
PD JUN
PY 2009
VL 13
IS 3
BP 555
EP 563
DI 10.1007/s10461-008-9429-6
PG 9
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 449NI
UT WOS:000266336900018
PM 18626764
ER
PT J
AU Osinusi, A
Kleiner, D
Wood, B
Polis, M
Masur, H
Kottilil, S
AF Osinusi, Anu
Kleiner, David
Wood, Brad
Polis, Michael
Masur, Henry
Kottilil, Shyam
TI Rapid Development of Advanced Liver Fibrosis after Acquisition of
Hepatitis C Infection during Primary HIV Infection
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; COINFECTED PATIENTS; PROGRESSION;
ACTIVATION
AB We report the first reported case of a 61-year-old MSM who was diagnosed with syphilis, primary HIV infection, and acute hepatitis C (HCV) within the same time period who rapidly developed significant liver fibrosis within 6 months of acquisition of both infections. It has been well described that individuals with primary HIV infection have an increase in activated CD8(+) T cells, which causes a state of immune activation as was evident in this patient. Acquisition of HCV during this time could have further skewed this response resulting in massive hepatocyte destruction, inflammation, and subsequent liver fibrosis. Recent literature suggest that MSM with primary HIV infection have higher rates of acquisition of HCV than other HIV-positive cohorts and HCV acquisition can occur very soon after acquiring HIV. This case of rapid hepatic fibrosis progression coupled with the increasing incidence of HCV in individuals with primary HIV infection demonstrates a need for this phenomenon to be studied more extensively.
C1 [Polis, Michael; Kottilil, Shyam] NIAID, Immunoregulat Lab, Bethesda, MD 20814 USA.
[Kleiner, David] NCI, Dept Pathol, Bethesda, MD 20892 USA.
[Osinusi, Anu] Univ Maryland, Dept Infect Dis, Baltimore, MD 21201 USA.
[Masur, Henry] NIH, Dept Crit Care Med, Clin Res Ctr, Bethesda, MD 20892 USA.
[Wood, Brad] NIH, Div Radiol Radiol & Imaging Sci, Bethesda, MD 20892 USA.
RP Kottilil, S (reprint author), NIAID, Immunoregulat Lab, 9000 Rockville Pike,Bldg 10-11N204, Bethesda, MD 20814 USA.
EM skottilil@mail.nih.gov
OI Polis, Michael/0000-0002-9151-2268; Kleiner, David/0000-0003-3442-4453
FU National Institutes of Health; National Institute of Allergy and
Infectious Diseases; National Cancer Institute
FX This research was supported in whole by the Intramural Research Program
of the National Institutes of Health, National Institute of Allergy and
Infectious Diseases, and the National Cancer Institute.
NR 13
TC 5
Z9 5
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD JUN
PY 2009
VL 23
IS 6
BP 403
EP 406
DI 10.1089/apc.2008.0238
PG 4
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 457GB
UT WOS:000266915400001
PM 19519227
ER
PT J
AU Rudy, BJ
Sleasman, J
Kapogiannis, B
Wilson, CM
Bethel, J
Serchuck, L
Ahmad, S
Cunningham, CK
AF Rudy, Bret J.
Sleasman, John
Kapogiannis, Bill
Wilson, Craig M.
Bethel, James
Serchuck, Leslie
Ahmad, Sushma
Cunningham, Coleen K.
CA Adolescent Trials Network HIV AIDS
TI Short-Cycle Therapy in Adolescents after Continuous Therapy with
Established Viral Suppression: The Impact on Viral Load Suppression
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID STRUCTURED TREATMENT INTERRUPTION; ACTIVE ANTIRETROVIRAL THERAPY;
CHRONIC HIV-INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; DRUG-RESISTANCE;
RANDOMIZED-TRIAL; HAART; STRATEGY; RISK
AB This was a proof-of-principle study to evaluate the impact of short cycle therapy (SCT; 4 days on/3 days off) in adolescents and young adults with good viral suppression on a protease inhibitor-based antiretroviral regimen. Subjects were recruited by the Adolescent Trials Network for HIV/AIDS Interventions and the Pediatric AIDS Clinical Trials Group. Subjects were infected either through perinatal/early childhood transmission or later via risk behaviors. All subjects were required to have at least 6 months of documented viral suppression below 400 copies/ml plus a preentry value below 200 copies/ml and an entry CD4(+) T cell count above 350 cells/mm(3). Of the 32 subjects enrolled, 12 (37.5%) had confirmed viral load rebound >400 copies, with 18 subjects (56%) coming off for any reason. The majority of subjects resuppressed when placed back onto continuous therapy using the same agents. Although no difference was found in virologic rebound rates between the early and later transmission groups, those infected early in life had higher rates of coming off SCT for any reason. There was no impact of SCT on the CD4(+) T cell counts in those who remained on study or those who came off SCT for any reason. Subjects demonstrated good adherence to the SCT regimen. This study suggests that further evaluation of SCT may be warranted in some groups of adolescents and young adults infected with HIV.
C1 [Rudy, Bret J.] Childrens Hosp Philadelphia, Craig Dalsimer Div Adolescent Med, Philadelphia, PA 19104 USA.
[Rudy, Bret J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Sleasman, John] Univ S Florida, Coll Med, St Petersburg, FL 33701 USA.
[Kapogiannis, Bill; Serchuck, Leslie] NICHHD, Bethesda, MD 20892 USA.
[Wilson, Craig M.] Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Ahmad, Sushma] Westat Corp, Rockville, MD USA.
[Cunningham, Coleen K.] Duke Univ, Sch Med, Durham, NC USA.
RP Rudy, BJ (reprint author), Childrens Hosp Philadelphia, Craig Dalsimer Div Adolescent Med, 3535 Market St,Suite 1517, Philadelphia, PA 19104 USA.
EM rudy@email.chop.edu
FU National Institutes of Health [U01 HD 040533, U01 HD 040474]; National
Institutes on Drug Abuse and Mental Health; Pediatric AIDS Clinical
Trials Group [U01-A141089]; Children's National Medical Center
[5-MO1-RR-020359-04]; Children's Hospital of Philadelphia
[UL1-RR-024134]
FX This work was supported by the Adolescent Trials Network for HIV/AIDS
Interventions (ATN) from the National Institutes of Health (U01 HD
040533 and U01 HD 040474) through the National Institute of Child Health
and Human Development (B. Kapogiannis, L. Serchuck), with supplemental
funding from the National Institutes on Drug Abuse (N. Borek) and Mental
Health (P. Brouwers, S. Allison). The study was scientifically reviewed
by the ATN's Therapeutic Leadership Group. Network, scientific, and
logistical support was provided by the ATN Coordinating Center (C.
Wilson, C. Partlow) at the University of Alabama at Birmingham. Network
operations and analytic support were provided by the ATN Data and
Operations Center at Westat, Inc. (J. Korelitz, B. Driver). Additional
support was provided by the Pediatric AIDS Clinical Trials Group funded
by grant no. U01-A141089. The following GCRC/CTRC grants provided
support: Children's National Medical Center (5-MO1-RR-020359-04) and the
Children's Hospital of Philadelphia (UL1-RR-024134). The team would like
to thank Kelly Lannutti for assistance with manuscript preparation.
NR 26
TC 5
Z9 5
U1 1
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD JUN
PY 2009
VL 25
IS 6
BP 555
EP 561
DI 10.1089/aid.2008.0203
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 459GP
UT WOS:000267089800002
PM 19534628
ER
PT J
AU Moykkynen, TP
Coleman, SK
Keinanen, K
Lovinger, DA
Korpi, ER
AF Moykkynen, Tommi P.
Coleman, Sarah K.
Keinanen, Kari
Lovinger, David A.
Korpi, Esa R.
TI Ethanol increases desensitization of recombinant GluR-D AMPA receptor
and TARP combinations
SO ALCOHOL
LA English
DT Article
DE GluA4 receptors; Alcohol; Protein interactions; Recombinant receptors;
Patch-clamp; Desensitization
ID CENTRAL-NERVOUS-SYSTEM; 2 DISTINCT MECHANISMS; LIGAND-BINDING CORE;
GLUTAMATE RECEPTORS; SYNAPTIC PLASTICITY; AUXILIARY SUBUNITS; MOUSE
STARGAZER; TERMINAL DOMAIN; CELLS; ACID
AB Glutamate receptors are important target molecules of the acute effect of ethanol. We studied ethanol sensitivity of homomeric GluR-D receptors expressed in human embryonic kidney 293 cells and examined whether recently discovered transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor regulatory proteins (TARPs) affect ethanol sensitivity. Coexpression of the TARPs, stargazin, and gamma 4 increased the time constant (tau-value) of current decay in the presence of agonist, thus slowing the onset of desensitization and increasing the steady-state current. Ethanol produced less inhibition of the peak current than the steady-state current for all types of the GluR-D receptors. In addition, ethanol concentration-dependently accelerated the rate of desensitization, measured as the tau-value of fast decay of peak current. This effect was enhanced with coexpression of TARPs. The recovery from desensitization was slowed down by coexpression of gamma 4 but ethanol did not affect this process in any GluR-D combination. The results support the idea that increased desensitization is an important mechanism in the ethanol inhibition of AMPA receptors and indicate that coexpression of TARPs can alter this effect of ethanol. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Moykkynen, Tommi P.; Korpi, Esa R.] Univ Helsinki, Inst Biomed, Biomedicum Helsinki, FI-00014 Helsinki, Finland.
[Coleman, Sarah K.; Keinanen, Kari] Univ Helsinki, Viikki Bioctr, Dept Biol & Environm Sci, Div Biochem, Helsinki, Finland.
[Lovinger, David A.] NIAAA, Lab Integrat Neurosci, US Natl Inst Hlth, Rockville, MD 20852 USA.
RP Korpi, ER (reprint author), Univ Helsinki, Inst Biomed, Biomedicum Helsinki, POB 63,Haartmaninkatu 8, FI-00014 Helsinki, Finland.
EM esa.korpi@helsinki.fi
RI Keinanen, Kari/E-9122-2010;
OI Coleman, Sarah/0000-0002-1066-8296; Korpi, Esa R./0000-0003-0683-4009
FU Finnish Cultural Foundation; Finnish Foundation for Alcohol Studies;
Sigrid Juselius Foundation; National Institute on Alcohol Abuse and
Alcoholism, USA
FX This study was supported by the Finnish Cultural Foundation, the Finnish
Foundation for Alcohol Studies, the Sigrid Juselius Foundation, as well
as the Division of Intramural Clinical and Basic Research of the
National Institute on Alcohol Abuse and Alcoholism, USA.
NR 46
TC 7
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U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
J9 ALCOHOL
JI Alcohol
PD JUN
PY 2009
VL 43
IS 4
BP 277
EP 284
DI 10.1016/j.alcohol.2009.04.005
PG 8
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 470HI
UT WOS:000267965400004
PM 19560629
ER
PT J
AU Srivastava, V
Buzas, B
Momenan, R
Oroszi, G
Enoch, MA
Hommer, D
Goldman, D
AF Srivastava, Vibhuti
Buzas, Beata
Momenan, Reza
Oroszi, Gabor
Enoch, Mary-Anne
Hommer, Daniel
Goldman, David
TI VARIATIONS IN SOD2, A GENE IMPLICATED IN OXIDATIVE STRESS, PREDICTS
BRAIN GRAY MATTER SHRINKAGE IN CHRONIC ALCOHOLICS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Srivastava, Vibhuti; Oroszi, Gabor; Enoch, Mary-Anne; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Buzas, Beata] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Momenan, Reza; Hommer, Daniel] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
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PI MALDEN
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SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 11A
EP 11A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100005
ER
PT J
AU Bevilacqua, L
Zhou, Z
Yuan, Q
Yamini, G
Moore, E
Virkkunen, M
Goldman, D
AF Bevilacqua, L.
Zhou, Z.
Yuan, Q.
Yamini, G.
Moore, E.
Virkkunen, M.
Goldman, D.
TI RE-SEQUENCING FOR RARE AND UNCOMMON GENETIC VARIANTS THAT MAY INFLUENCE
IMPULSIVE BEHAVIOR IN ALCOHOLICS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Bevilacqua, L.; Zhou, Z.; Yuan, Q.; Yamini, G.; Moore, E.; Virkkunen, M.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 13A
EP 13A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100012
ER
PT J
AU Morton, RA
Luo, GX
Davis, MI
Hales, TG
Lovinger, DM
AF Morton, Russell A.
Luo, Guoxiang
Davis, Margaret I.
Hales, Tim G.
Lovinger, David M.
TI ETHANOL AND TRAFFICKING OF 5-HT3A RECEPTORS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Morton, Russell A.; Luo, Guoxiang; Davis, Margaret I.; Hales, Tim G.; Lovinger, David M.] George Washington Univ, NIAAA, NIH, Dept Pharmacol & Physiol, Washington, DC 20052 USA.
RI Davis, Margaret/F-4165-2010
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PI MALDEN
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
SI S1
BP 19A
EP 19A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100035
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PT J
AU Xiong, W
Lovinger, DM
Zhang, L
AF Xiong, Wei
Lovinger, David M.
Zhang, Li
TI GLYCINE RECEPTORS CONTRIBUTE TO CANNABINOID ENHANCEMENT OF LOW DOSE
ETHANOL-INDUCED INCOORDINATION IN MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
RI Xiong, Wei/F-8251-2011
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
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PY 2009
VL 33
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BP 22A
EP 22A
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SC Substance Abuse
GA 449MQ
UT WOS:000266335100047
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PT J
AU Chesney, M
Donnell, D
Seage, G
Bryant, K
AF Chesney, Margaret
Donnell, Deborah
Seage, George
Bryant, Kendall
TI PROJECT EXPLORE: IMPACT OF ALCOHOL USE ON HIV SERO-INCIDENCE AMONG
HIGH-RISK MSM IN A LARGE-SCALE PROSPECTIVE PREVENTIVE INTERVENTION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Chesney, Margaret] Univ Maryland, Ctr Integrat Med, College Pk, MD 20742 USA.
[Seage, George] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Bryant, Kendall] NIAAA, NIH, Bethesda, MD USA.
NR 0
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U1 1
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PI MALDEN
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SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 41A
EP 41A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100122
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PT J
AU Lee, HK
AF Lee, H. K.
TI THE PREVALENCE OF HARZADOUS DRINKING AND RELATED FACTOR IN KOREAN
POPULATION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Lee, H. K.] Catholic Univ Korea, Seoul, South Korea.
[Lee, H. K.] NIAAA, NIH, Dept Epidemiol & Prevent Res, Bethesda, MD 20892 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 58A
EP 58A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100193
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PT J
AU Goldstein, RB
Dawson, DA
Grant, BF
AF Goldstein, R. B.
Dawson, D. A.
Grant, B. F.
TI ANTISOCIAL BEHAVIORAL SYNDROMES IN ADULTHOOD AND ALCOHOL USE DISORDER
TREATMENT UTILIZATION OVER THREE-YEAR FOLLOW-UP
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Goldstein, R. B.; Dawson, D. A.; Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA.
NR 0
TC 0
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U1 0
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PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 67A
EP 67A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100228
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PT J
AU Chou, SP
Stinson, FS
Dawson, DA
Goldstein, RB
Grant, BF
AF Chou, S. P.
Stinson, F. S.
Dawson, D. A.
Goldstein, R. B.
Grant, B. F.
TI THE ROLE OF TOBACCO USE IN THE FIRST INCIDENCE OF DSM-IV ALCOHOL USE
DISORDERS: A PROSPECTIVE STUDY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Chou, S. P.; Stinson, F. S.; Dawson, D. A.; Goldstein, R. B.; Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
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PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 68A
EP 68A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100232
ER
PT J
AU Hingson, RW
Edwards, E
Heeren, T
Rosenbloom, D
AF Hingson, R. W.
Edwards, E.
Heeren, T.
Rosenbloom, D.
TI EARLY AGE OF DRINKING ONSET, PARENTAL PROVISION OF ALCOHOL TO YOUTH, AND
THE DEVELOPMENT OF ALCOHOL DEPENDENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 NIAAA, Bethesda, MD 20892 USA.
Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 68A
EP 68A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100233
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PT J
AU Ruan, WJ
Dawson, DA
Pickering, RP
Grant, BF
AF Ruan, W. J.
Dawson, D. A.
Pickering, R. P.
Grant, B. F.
TI ASSOCIATION OF RELIGIOSITY AND 12-MONTH INCIDENCE OF ALCOHOL USE
DISORDERS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Ruan, W. J.; Dawson, D. A.; Pickering, R. P.; Grant, B. F.] NIAAA, NIH, Rockville, MD 20852 USA.
NR 0
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PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 68A
EP 68A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100231
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PT J
AU Smith, SM
Dawson, DA
Grant, BF
AF Smith, S. M.
Dawson, D. A.
Grant, B. F.
TI THE ASSOCIATION BETWEEN PERCEIVED DISCRIMINATION AND INCIDENT ALCOHOL
DEPENDENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Smith, S. M.; Dawson, D. A.; Grant, B. F.] NIAAA, NIH, Bethesda, MD 20892 USA.
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PU WILEY-BLACKWELL PUBLISHING, INC
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 68A
EP 68A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100230
ER
PT J
AU Thorsell, A
Singley, E
Hunt, SP
Heilig, M
AF Thorsell, A.
Singley, E.
Hunt, S. P.
Heilig, M.
TI THE NEUROKININ-1 RECEPTOR IN ALCOHOL REWARD AND INTAKE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Thorsell, A.; Singley, E.; Hunt, S. P.; Heilig, M.] NIAAA, LCTS, NIH, Bethesda, MD 20892 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 75A
EP 75A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100259
ER
PT J
AU Rice, OV
Schonhar, D
Rubel, K
Piyis, YK
Volkow, ND
Thanos, PK
AF Rice, O. V.
Schonhar, D.
Rubel, K.
Piyis, Y. K.
Volkow, N. D.
Thanos, P. K.
TI THE EFFECTS OF ACUTE VERSUS CHRONIC ETHANOL BINGE DRINKING ON BRAIN
GLUCOSE UTILIZATION IN MICE LACKING THE CANNABINOID 1 RECEPTOR (CB1)
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Rice, O. V.; Schonhar, D.; Rubel, K.] Furman Univ, Dept Psychol & Neurosci, Greenville, SC 29613 USA.
[Piyis, Y. K.; Thanos, P. K.] Brookhaven Natl Lab, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
[Volkow, N. D.; Thanos, P. K.] NIH, Intramural NIAAA Program, Bethesda, MD 20892 USA.
NR 0
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 76A
EP 76A
PG 1
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GA 449MQ
UT WOS:000266335100264
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PT J
AU Talani, G
Lovinger, DM
AF Talani, G.
Lovinger, D. M.
TI ETHANOL-ENDOCANNABINOID INTERACTIONS AT GABAERGIC SYNAPSES IN THE
BASOLATERAL AMYGDALA
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
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C1 [Talani, G.; Lovinger, D. M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
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VL 33
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UT WOS:000266335100289
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PT J
AU Jun, S
Talani, G
Lovinger, DM
AF Jun, S.
Talani, G.
Lovinger, D. M.
TI GABA(B)R-DEPENDENT ETHANOL POTENTIATION OF GABAERGIC SYNAPTIC
TRANSMISSION MODULATED BY 5-HT RECEPTORS IN HIPPOCAMPAL CA1 NEURONS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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C1 [Jun, S.; Talani, G.; Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
SI S1
BP 84A
EP 84A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100294
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PT J
AU Delis, F
Xenos, M
Grandy, DK
Wang, GJ
Volkow, ND
Thanos, PK
AF Delis, F.
Xenos, M.
Grandy, D. K.
Wang, G. J.
Volkow, N. D.
Thanos, P. K.
TI EFFECTS OF CHRONIC ALCOHOL INTAKE AND DOPAMINE D2 GENE EXPRESSION ON
BRAIN ANATOMY: AN IN-VIVO MRI SHAPE AND VOLUMETRIC ANALYSIS OF THE MOUSE
BRAIN
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Delis, F.; Wang, G. J.; Thanos, P. K.] BNL, Behav Neuropharm & Neuroimaging Lab, Upton, NY USA.
[Xenos, M.] Stony Brook U, Dept Biomed Engn, Stony Brook, NY USA.
[Grandy, D. K.] Oregon Hlth & Sci Univ, Dept Phys & Pharm, Portland, OR 97201 USA.
[Volkow, N. D.; Thanos, P. K.] NIAAA, Lab Neuroimaging, NIH, Bethesda, MD USA.
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VL 33
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UT WOS:000266335100303
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PT J
AU Camp, MC
Ihne, JL
Holmes, A
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Ihne, Jessica L.
Holmes, Andrew
TI INTERMITTENT VAPOR EXPOSURE AS A MODEL FOR EXAMINING WITHDRAWAL-INDUCED
ANXIETY, TOLERANCE AND INCREASED ETHANOL SELF-ADMINISTRATION IN MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
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CL San Diego, CA
SP Res Soc Alcoholism
C1 [Camp, Marguerite C.; Ihne, Jessica L.; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
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VL 33
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UT WOS:000266335100329
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PT J
AU Falk, D
Mattson, M
Fertig, J
Ryan, M
Litten, R
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Mattson, M.
Fertig, J.
Ryan, M.
Litten, R.
TI EFFICACY OF NALTREXONE IN COMBINE TRIAL USING PERCENTAGE OF SUBJECTS
WITH NO HEAVY DRINKING DAYS AS TREATMENT OUTCOME MEASURE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 CSR Inc, Arlington, VA 22201 USA.
NIAAA, Bethesda, MD 20892 USA.
NR 0
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 114A
EP 114A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100416
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PT J
AU George, DT
Phillips, MJ
Lifshitz, M
Lionetti, TA
Spero, DE
Ghassemzedeh, N
Doty, L
Umhau, JC
Rawlings, RR
AF George, D. T.
Phillips, M. J.
Lifshitz, M.
Lionetti, T. A.
Spero, D. E.
Ghassemzedeh, N.
Doty, L.
Umhau, J. C.
Rawlings, R. R.
TI FLUOXETINE DECREASES ANGER AND AGGRESSION IN ALCOHOL DEPENDENT
PERPETRATORS OF DOMESTIC VIOLENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [George, D. T.; Phillips, M. J.; Lifshitz, M.; Lionetti, T. A.; Spero, D. E.; Ghassemzedeh, N.; Doty, L.; Umhau, J. C.; Rawlings, R. R.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 117A
EP 117A
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WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100428
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PT J
AU Huang, B
Dawson, DA
Grant, BF
Stinson, FS
Chou, SP
Smith, S
Pulay, AJ
Ruan, WJ
AF Huang, B.
Dawson, D. A.
Grant, B. F.
Stinson, F. S.
Chou, S. P.
Smith, S.
Pulay, A. J.
Ruan, W. J.
TI PROTECTIVE EFFECTS OF MODERATE ALCOHOL CONSUMPTION TO CORONARY HEART
DISEASES AMONG INDIVIDUALS WITH VARIOUS HEALTH CONDITIONS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Huang, B.; Dawson, D. A.; Grant, B. F.; Stinson, F. S.; Chou, S. P.; Smith, S.; Pulay, A. J.; Ruan, W. J.] NIAAA, NIH, Bethesda, MD 20892 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 120A
EP 120A
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SC Substance Abuse
GA 449MQ
UT WOS:000266335100440
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PT J
AU Pulay, AJ
Grant, BF
AF Pulay, Attila J.
Grant, Bridget F.
TI RELATIONSHIP OF DSM-IV PERSONALITY DISORDERS TO ALCOHOL CONSUMPTION:
RESULTS FROM THE WAVE 2 NESARC
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Pulay, Attila J.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 120A
EP 120A
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WC Substance Abuse
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GA 449MQ
UT WOS:000266335100441
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PT J
AU Pickering, RP
Chou, P
Grant, BF
AF Pickering, R. P.
Chou, P.
Grant, B. F.
TI ALCOHOL AND DRUG ABUSE AND DEPENDENCE AMOUNG THE US ADULT HOMOSEXUAL AND
BISEXUAL POPULATION BY SEX
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Pickering, R. P.; Chou, P.; Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20892 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 124A
EP 124A
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WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100457
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PT J
AU Chen, A
Schwandt, ML
Lindell, SG
Sun, H
Heilig, M
Barr, CS
AF Chen, A.
Schwandt, M. L.
Lindell, S. G.
Sun, H.
Heilig, M.
Barr, C. S.
TI NALTREXONE REDUCES ALCOHOL CONSUMPTION AS A FUNCTION OF OPRM1 C77G
GENOTYPE IN RHESUS MACAQUES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Chen, A.; Schwandt, M. L.; Lindell, S. G.; Sun, H.; Heilig, M.; Barr, C. S.] NIAAA, NIH, Bethesda, MD 20892 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 138A
EP 138A
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SC Substance Abuse
GA 449MQ
UT WOS:000266335100513
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PT J
AU Schwandt, ML
Newman, TK
Suomi, SJ
Higley, JD
Heilig, M
Barr, CS
AF Schwandt, M. L.
Newman, T. K.
Suomi, S. J.
Higley, J. D.
Heilig, M.
Barr, C. S.
TI LOW MAOA ACTIVITY IS ASSOCIATED WITH HIGH RISK AGGRESSION AND ALCOHOL
CONSUMPTION IN RHESUS MACAQUES EXPOSED TO EARLY LIFE STRESS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Schwandt, M. L.; Newman, T. K.; Suomi, S. J.; Higley, J. D.; Heilig, M.; Barr, C. S.] NIAAA LCTS, NIH, Poolesville, MD 20837 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 138A
EP 138A
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WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335100512
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PT J
AU Umhau, JC
George, DT
Usala, JM
Geyer, CL
Heilig, M
AF Umhau, J. C.
George, D. T.
Usala, J. M.
Geyer, C. L.
Heilig, M.
TI MODULATION OF PHARMACOLOGICALLY INDUCED ALCOHOL CRAVING IN RECENTLY
DETOXIFIED ALCOHOLICS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Umhau, J. C.; George, D. T.; Usala, J. M.; Geyer, C. L.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 145A
EP 145A
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SC Substance Abuse
GA 449MQ
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PT J
AU Miller, AM
Park, O
Wang, H
Moh, A
Fu, XY
Gao, B
AF Miller, Andrew M.
Park, Ogyi
Wang, Hua
Moh, Akira
Fu, Xin Yuan
Gao, Bin
TI ANTI-INFLAMMATORY AND ANTI-APOPTOTIC EFFECTS OF ENDOTHELIAL CELL STAT3
IN ALCOHOLIC LIVER INJURY IN MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Miller, Andrew M.; Park, Ogyi; Wang, Hua; Gao, Bin] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Moh, Akira; Fu, Xin Yuan] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 160A
EP 160A
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SC Substance Abuse
GA 449MQ
UT WOS:000266335100599
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PT J
AU Gremel, CM
Costa, RM
AF Gremel, Christina M.
Costa, Rui M.
TI THE ROLE OF THE ANTERIOR CINGULATE AND ORBITAL FRONTAL CORTEX IN
GOAL-DIRECTED BEHAVIOR AND HABIT FORMATION IN MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Gremel, Christina M.; Costa, Rui M.] NIAAA, NIH, Bethesda, MD 20852 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 219A
EP 219A
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SC Substance Abuse
GA 449MQ
UT WOS:000266335100836
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PT J
AU Abdelmegeed, MA
Song, BJ
AF Abdelmegeed, M. A.
Song, B. J.
TI ROLE OF ETHANOL-INDUCIBLE CYTOCHROME P450 2E1 (CYP2E1) IN CAUSING
NITROSATIVE STRESS DURING ACETAMINOPHEN-MEDIATED ACUTE LIVER DAMAGE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Abdelmegeed, M. A.; Song, B. J.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 227A
EP 227A
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SC Substance Abuse
GA 449MQ
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PT J
AU Kim, BJ
Moon, KH
Abdelmegeed, MA
Song, BJ
AF Kim, B. J.
Moon, K. H.
Abdelmegeed, M. A.
Song, B. J.
TI INCREASED SECRETION OF CELLULAR PROTEINS VIA CLASSICAL AND NONCLASSICAL
PATHWAYS IN ETHANOL-EXPOSED HUMAN E47 HEPATOMA CELLS AND RATS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Kim, B. J.; Moon, K. H.; Abdelmegeed, M. A.; Song, B. J.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 227A
EP 227A
PG 1
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GA 449MQ
UT WOS:000266335100867
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PT J
AU Stinson, FS
Grant, BF
Dawson, DA
Chou, SP
Goldstein, RB
AF Stinson, F. S.
Grant, B. F.
Dawson, D. A.
Chou, S. P.
Goldstein, R. B.
TI THE ROLE OF ALCOHOL CONSUMPTION, SUBSTANCE USE DISORDERS AND OTHER
PSYCHIATRIC DISORDERS IN THE ONSET OF MEDICAL CONDITIONS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Stinson, F. S.; Grant, B. F.; Dawson, D. A.; Chou, S. P.; Goldstein, R. B.] NIAAA, Rockville, MD 20852 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 244A
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SC Substance Abuse
GA 449MQ
UT WOS:000266335100933
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PT J
AU Saha, TD
Grant, BF
Dawson, D
AF Saha, Tulshi D.
Grant, Bridget F.
Dawson, Deborah
TI DIMENSIONS OF HARM AND THEIR ASSOCIATIONS WITH ALCOHOL USE DISORDER
(AUD): A MIMIC MODEL
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Saha, Tulshi D.; Grant, Bridget F.; Dawson, Deborah] NIAAA, Lab Epidemiol & Bimetry, NIH, Bethesda, MD 20892 USA.
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JI Alcoholism (NY)
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PY 2009
VL 33
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PT J
AU White, AM
Hingson, RW
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Hingson, R. W.
TI EPIDEMIOLOGY OF ALCOHOL-INDUCED MEMORY BLACKOUTS: GENDER DIFFERENCES AND
CHANGES OVER TIME
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [White, A. M.; Hingson, R. W.] NIAAA, Div Epidemiol & Prevent Res, NIH, Bethesda, MD 20892 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 255A
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PT J
AU Mattson, ME
Stout, R
Fertig, J
Litten, R
Ryan, M
Falk, D
AF Mattson, M. E.
Stout, R.
Fertig, J.
Litten, R.
Ryan, M.
Falk, D.
TI FREQUENCY OF VERY HEAVY DRINKING IN THE COMBINE SAMPLE: A POTENTIAL
PHENOTYPIC MARKER FOR DIFFERENTIAL OUTCOME
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 NIAAA, Bethesda, MD 20892 USA.
CSR Inc, Arlington, VA 22201 USA.
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 258A
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GA 449MQ
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PT J
AU Blaine, SK
Brar, S
Jones, C
Kim, HY
Venitz, J
George, DT
Heilig, M
Ramchandani, VA
AF Blaine, S. K.
Brar, S.
Jones, C.
Kim, H-Y.
Venitz, J.
George, D. T.
Heilig, M.
Ramchandani, V. A.
TI SALSOLINOL AND BETA-CARBOLINE LEVELS IN ALCOHOLIC INPATIENTS AND
RELATIONSHIP TO SOBRIETY DURING FOLLOW-UP OUTPATIENT TREATMENT
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA 23284 USA.
NIAAA, LCTS, NIH, Bethesda, MD 20892 USA.
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JI Alcoholism (NY)
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PT J
AU Grant, BF
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TI ALCOHOL CONSUMPTION AS A DIAGNOSTIC RESEARCH CRITERION FOR DSM-V
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Grant, B. F.; Saha, T. D.; Stinson, F. S.] NIAAA, Rockville, MD 20852 USA.
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JI Alcoholism (NY)
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PY 2009
VL 33
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AU Murray, P
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TI INFUSING ALCOHOL RESEARCH INTO MEDICAL EDUCATION: A PERSPECTIVE FROM
NIAAA
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Murray, Peggy] NIAAA, Bethesda, MD USA.
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JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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GA 449MQ
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PT J
AU Ramchandani, VA
Umhau, J
Jones, C
Issa, J
Kerich, M
Hommer, DW
Heilig, M
AF Ramchandani, V. A.
Umhau, J.
Jones, C.
Issa, J.
Kerich, M.
Hommer, D. W.
Heilig, M.
TI OPRM1 A118G POLYMORPHISM AND ALCOHOL-INDUCED STRIATAL DOPAMINE RELEASE:
AN ALCOHOL CLAMP/PET STUDY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Ramchandani, V. A.; Umhau, J.; Jones, C.; Issa, J.; Kerich, M.; Hommer, D. W.; Heilig, M.] NIAAA, Bethesda, MD 20892 USA.
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JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 288A
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GA 449MQ
UT WOS:000266335101103
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PT J
AU Holmes, A
AF Holmes, A.
CA NIAAA
TI GLUTAMATERGIC MEDIATION OF ACUTE INTOXICATING EFFECTS OF ETHANOL IN MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Holmes, A.; NIAAA] NIAAA, Rockville, MD 20852 USA.
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JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
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BP 290A
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GA 449MQ
UT WOS:000266335101109
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PT J
AU Krystal, JH
Petrakis, IL
D'Souza, DC
Watson, T
Mathalon, D
AF Krystal, J. H.
Petrakis, I. L.
D'Souza, D. C.
Watson, T.
Mathalon, D.
TI NMDA RECPTORS AND THE ALCOHOL CUE: INSIGHTS INTO INTOXICATION,
DEPENDENCE, AND VULNERABILITY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 Yale Univ, Sch Med, NIAAA, Ctr Translat Neurosci Alcoholism, New Haven, CT USA.
VA Connecticut Healthcare Syst, VA Alcohol Res Ctr, West Haven, CT 06516 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 290A
EP 290A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101110
ER
PT J
AU Dawson, DA
Moss, HB
Goldstein, RB
Grant, BF
AF Dawson, D. A.
Moss, H. B.
Goldstein, R. B.
Grant, B. F.
TI GENDER DIFFERENCES IN THE PREVALENCE AND EXPRESSION OF ALCOHOLIC
PHENOTYPES BASED ON INTERNALIZING AND EXTERNALIZING DISORDERS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Dawson, D. A.; Moss, H. B.; Goldstein, R. B.; Grant, B. F.] NIAAA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 294A
EP 294A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101127
ER
PT J
AU Enoch, MA
Yuan, Q
Hodgkinson, CA
Ducci, F
Shen, PH
Virkkunen, M
Roy, A
Goldman, D
AF Enoch, M. -A.
Yuan, Q.
Hodgkinson, C. A.
Ducci, F.
Shen, P. -H.
Virkkunen, M.
Roy, A.
Goldman, D.
TI VARIATION IN GENES ENCODING 5-HT3 RECEPTORS INFLUENCES ALCOHOLISM
VULNERABILITY IN DIVERSE POPULATIONS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Enoch, M. -A.; Yuan, Q.; Hodgkinson, C. A.; Ducci, F.; Shen, P. -H.; Virkkunen, M.; Roy, A.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 295A
EP 295A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101130
ER
PT J
AU Heilig, M
Momenan, R
Umhau, J
George, T
AF Heilig, M.
Momenan, R.
Umhau, J.
George, T.
TI MODULATION OF CENTRAL GLUTAMATE BY ACAMPROSATE IN ALCOHOL DEPENDENT
SUBJECTS ENTERING ABSTINENCE: A MAGNETIC RESONANCE SPECTROSCOPY (MRS)
STUDY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Heilig, M.; Momenan, R.; Umhau, J.; George, T.] NIAAA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 296A
EP 296A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101136
ER
PT J
AU Tabakoff, B
Snell, L
Pridzun, L
Herion, D
Heilig, M
AF Tabakoff, Boris
Snell, Lawrence
Pridzun, Lutz
Herion, David
Heilig, Markus
TI PLATELETS PROTEINS AS MARKERS FOR HAZARDOUS/HARMFUL ALCOHOL CONSUMPTION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 Lohocla Res Corp, Denver, CO USA.
Univ Colorado, Denver, CO 80202 USA.
Mediagnost Inc, Reutlingen, Germany.
NIAAA, Rockville, MD 20852 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 304A
EP 304A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101166
ER
PT J
AU Gilman, JM
Ramchandani, VA
Crouss, TM
Hommer, DW
AF Gilman, Jodi M.
Ramchandani, Vijay A.
Crouss, Tess M.
Hommer, Daniel W.
TI USING THE ALCOHOL CLAMP TO EVALUATE NEURAL CORRELATES OF TOLERANCE TO
THE REWARDING AND ANXIOYTIC EFFECTS OF ALCOHOL IN HEAVY DRINKERS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Gilman, Jodi M.; Ramchandani, Vijay A.; Crouss, Tess M.; Hommer, Daniel W.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 313A
EP 313A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101201
ER
PT J
AU Lovinger, DM
Talani, G
AF Lovinger, David M.
Talani, Giuseppe
TI ETHANOL INTERACTIONS WITH GI/O-COUPLED G-PROTEINS IN GABAERGIC TERMINALS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Lovinger, David M.; Talani, Giuseppe] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 314A
EP 314A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101207
ER
PT J
AU Cippitelli, A
Damadzic, R
Hansson, AC
Singley, E
Sommer, WH
Thorsell, A
Heilig, M
AF Cippitelli, A.
Damadzic, R.
Hansson, A. C.
Singley, E.
Sommer, W. H.
Thorsell, A.
Heilig, M.
TI NEUROPEPTIDEY (NPY) SYSTEM ON RELAPSE-LIKE BEHAVIOR IN RATS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Cippitelli, A.; Damadzic, R.; Hansson, A. C.; Singley, E.; Sommer, W. H.; Thorsell, A.; Heilig, M.] NIAAA, LCTS, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 317A
EP 317A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101219
ER
PT J
AU Jerlhag, E
Egecioglu, E
Landgren, S
Salome, N
Heilig, M
Moechars, D
Datta, R
Perissoud, D
Dickson, SL
Engel, JA
AF Jerlhag, Elisabet
Egecioglu, Emil
Landgren, Sara
Salome, Nicolas
Heilig, Markus
Moechars, Diederik
Datta, Rakesh
Perissoud, Daniel
Dickson, Suzanne L.
Engel, Jorgen A.
TI REQUIREMENT OF CENTRAL GHRELIN SIGNALING FOR ALCOHOL REWARD
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 20-24, 2009
CL San Diego, CA
SP Res Soc Alcoholism
C1 [Jerlhag, Elisabet; Landgren, Sara; Engel, Jorgen A.] Univ Gothenburg, Pharmacol Sect, Gothenburg, Sweden.
[Egecioglu, Emil; Salome, Nicolas; Dickson, Suzanne L.] Univ Gothenburg, Physiol Sect, Gothenburg, Sweden.
[Moechars, Diederik] Johnson & Johnson Pharmaceut, Beerse, Belgium.
[Heilig, Markus] NIAAA, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2009
VL 33
IS 6
BP 317A
EP 317A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 449MQ
UT WOS:000266335101220
ER
PT J
AU Shea, MK
O'Donnell, CJ
Hoffmann, U
Dallal, GE
Dawson-Hughes, B
Ordovas, JM
Price, PA
Williamson, MK
Booth, SL
AF Shea, M. Kyla
O'Donnell, Christopher J.
Hoffmann, Udo
Dallal, Gerard E.
Dawson-Hughes, Bess
Ordovas, Jose M.
Price, Paul A.
Williamson, Matthew K.
Booth, Sarah L.
TI Vitamin K supplementation and progression of coronary artery calcium in
older men and women
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID MATRIX GLA PROTEIN; GAMMA-CARBOXYGLUTAMIC ACID; VASCULAR CALCIFICATION;
ASYMPTOMATIC SUBJECTS; POSTMENOPAUSAL WOMEN; ATHEROSCLEROSIS MESA;
COMPUTED-TOMOGRAPHY; RISK-FACTORS; WARFARIN; ATORVASTATIN
AB Background: Coronary artery calcification (CAC) is an independent predictor of cardiovascular disease. A preventive role for vitamin K in CAC progression has been proposed on the basis of the properties of matrix Gla protein (MGP) as a vitamin K-dependent calcification inhibitor.
Objective: The objective was to determine the effect of phylloquinone (vitamin K1) supplementation on CAC progression in older men and women.
Design: CAC was measured at baseline and after 3 y of follow-up in 388 healthy men and postmenopausal women; 200 received a multivitamin with 500 mu g phylloquinone/d (treatment), and 188 received a multivitamin alone (control).
Results: In an intention-to-treat analysis, there was no difference in CAC progression between the phylloquinone group and the control group; the mean (+/- SEM) changes in Agatston scores were 27 +/- 6 and 37 +/- 7, respectively. In a subgroup analysis of participants who were >= 85% adherent to supplementation (n = 367), there was less CAC progression in the phylloquinone group than in the control group (P = 0.03). Of those with preexisting CAC (Agatston score > 10), those who received phylloquinone supplements had 6% less progression than did those who received the multivitamin alone (P = 0.04). Phylloquinone-associated decreases in CAC progression were independent of changes in serum MGP. MGP carboxylation status was not determined.
Conclusions: Phylloquinone supplementation slows the progression of CAC in healthy older adults with preexisting CAC, independent of its effect on total MGP concentrations. Because our data are hypothesis-generating, further studies are warranted to clarify this mechanism. This trial was registered at clinicaltrials. gov as NCT00183001. Am J Clin Nutr 2009; 89: 1799-807.
C1 [Shea, M. Kyla; Dawson-Hughes, Bess; Ordovas, Jose M.; Booth, Sarah L.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Bethesda, MD USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, CIMIT, Boston, MA 02114 USA.
[Price, Paul A.; Williamson, Matthew K.] Univ Calif San Diego, Div Biol Sci, San Diego, CA 92103 USA.
RP Booth, SL (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM sarah.booth@tufts.edu
OI Ordovas, Jose/0000-0002-7581-5680
FU US Department of Agriculture, Agricultural Research Service
[58-1950-7-707]; National Institutes of Health [AG14759, HL69272,
T32HL69772]; American Heart Association [0515605T]
FX Supported by the US Department of Agriculture, Agricultural Research
Service, under Cooperative Agreement no. 58-1950-7-707; National
Institutes of Health (AG14759, HL69272, and T32HL69772); and the
American Heart Association (0515605T).
NR 37
TC 65
Z9 67
U1 0
U2 1
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN 1
PY 2009
VL 89
IS 6
BP 1799
EP 1807
DI 10.3945/ajcn.2008.27338
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 448EI
UT WOS:000266245500014
PM 19386744
ER
PT J
AU Combs, GF
Midthune, DN
Patterson, KY
Canfield, WK
Hill, AD
Levander, OA
Taylor, PR
Moler, JE
Patterson, BH
AF Combs, Gerald F., Jr.
Midthune, Douglas N.
Patterson, Kristine Y.
Canfield, Wesley K.
Hill, A. David
Levander, Orville A.
Taylor, Philip R.
Moler, James E.
Patterson, Blossom H.
TI Effects of selenomethionine supplementation on selenium status and
thyroid hormone concentrations in healthy adults
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; AUTOIMMUNE-THYROIDITIS; IODOTHYRONINE
DEIODINASE; GLUTATHIONE-PEROXIDASE; METABOLISM; IODINE; DEFICIENT;
POPULATION; CHILDREN; BLOOD
AB Background: Selenium, a potential cancer prevention agent currently being tested against prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), plays an integral role in thyroid metabolism. The effects of long-term selenium supplementation on thyroid hormone concentrations are unknown.
Objective: The objective was to investigate the effects of long-term selenium supplementation on thyroid hormone concentrations.
Design: Twenty-eight healthy adults took 200 mu g selenomethionine/d for 28 mo. The thyroid hormones triiodothyronine (T(3)), thyroxine (T(4)), and thyrotropin (TSH) were measured in plasma for 4 mo before supplementation and quarterly during supplementation. The assay methods were changed midstudy; the results of the 2 methods were not comparable. Therefore, one analysis was conducted based on the results of the first method, and a second analysis was based on all of the data, adjusted for the change. Serial data collection permitted a test for trends rather than simply a difference between initial and final values.
Results: By 9 mo, mean (+/- SEM) plasma selenium concentrations had increased from 1.78 +/- 0.07 mu mol/L at baseline to 2.85 +/- 0.11 mu mol/L for men and from 1.64 +/- 0.04 to 3.32 +/- 0.1.2 mu mol/L for women. T(3) concentrations in men increased 5% per year (P = 0.01). T(4) and TSH concentrations were unchanged.
Conclusions: Selenium supplementation produced no clinically significant changes in thyroid hormone concentrations. A small but statistically significant increase in T(3) concentrations was noted in men, with no corresponding decreases in TSH. A subset of SELECT subjects might be monitored periodically for changes during long-term selenium supplementation. Am J Clin Nutr 2009; 89: 1808-14.
C1 [Combs, Gerald F., Jr.; Canfield, Wesley K.] USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA.
[Combs, Gerald F., Jr.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
[Midthune, Douglas N.; Taylor, Philip R.; Patterson, Blossom H.] NCI, Canc Prevent Div, Rockville, MD USA.
[Patterson, Kristine Y.; Hill, A. David; Levander, Orville A.] USDA ARS, Beltsville Human Nutr Res Ctr, Beltsville, MD USA.
[Moler, James E.] Informat Management Serv Inc, Rockville, MD USA.
RP Combs, GF (reprint author), USDA ARS, Grand Forks Human Nutr Res Ctr, 2420 2nd Ave N, Grand Forks, ND 58202 USA.
EM gerald.combs@ars.usda.gov
OI Moler, James/0000-0001-8738-6898
FU NIH, the National Cancer Institute; Division of Cancer Epidemiology and
Genetics
FX Supported by the Intramural Research Program of the NIH, the National
Cancer Institute, and the Division of Cancer Epidemiology and Genetics
through an interagency agreement with the Agricultural Research Service
and a specific cooperative agreement with Cornell University.
NR 43
TC 33
Z9 35
U1 0
U2 1
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN 1
PY 2009
VL 89
IS 6
BP 1808
EP 1814
DI 10.3945/ajcn.2008.27356
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 448EI
UT WOS:000266245500015
PM 19403637
ER
PT J
AU Xu, Q
Parks, CG
Deroo, LA
Cawthon, RM
Sandler, DP
Chen, HL
AF Xu, Qun
Parks, Christine G.
DeRoo, Lisa A.
Cawthon, Richard M.
Sandler, Dale P.
Chen, Honglei
TI Multivitamin use and telomere length in women
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID INTRACELLULAR OXIDATIVE-STRESS; PREDISPOSITION FACTOR;
CIGARETTE-SMOKING; CHRONIC DISEASE; CANCER RISK; VITAMIN-C; HEALTH;
MORTALITY; QUESTIONNAIRE; HOMOCYSTEINE
AB Background: Telomere length may be a marker of biological aging. Multivitamin supplements represent a major source of micronutrients, which may affect telomere length by modulating oxidative stress and chronic inflammation.
Objective: The objective was to examine whether multivitamin use is associated with longer telomeres in women.
Design: We performed a cross-sectional analysis of data from 586 early participants (age 35-74 y) in the Sister Study. Multivitamin use and nutrient intakes were assessed with a 146-item food-frequency questionnaire, and relative telomere length of leukocyte DNA was measured by quantitative polymerase chain reaction.
Results: After age and other potential confounders were adjusted for, multivitamin use was associated with longer telomeres. Compared with nonusers, the relative telomere length of leukocyte DNA was on average 5.1% longer among daily multivitamin users (P for trend = 0.002). In the analysis of micronutrients, higher intakes of vitamins C and E from foods were each associated with longer telomeres, even after adjustment for multivitamin use. Furthermore, intakes of both nutrients were associated with telomere length among women who did not take multivitamins.
Conclusion: This study provides the first epidemiologic evidence that multivitamin use is associated with longer telomere length among women. Am J Clin Nutr 2009; 89: 1857-63.
C1 [Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Cawthon, Richard M.] Univ Utah, Dept Human Genet, Salt Lake City, UT USA.
RP Chen, HL (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM chenh2@niehs.nih.gov
OI Parks, Christine/0000-0002-5734-3456; Sandler, Dale/0000-0002-6776-0018;
Chen, Honglei/0000-0003-3446-7779
FU NIH, National Institute of Environmental Health Sciences [Z01ES044005,
Z01ES101986]; Department of Defense Breast Cancer Research Concept Award
[BC045286]
FX Supported by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences (Z01ES044005 AND
Z01ES101986), and the Department of Defense Breast Cancer Research
Concept Award (BC045286).
NR 38
TC 69
Z9 69
U1 1
U2 21
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN 1
PY 2009
VL 89
IS 6
BP 1857
EP 1863
DI 10.3945/ajcn.2008.26986
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 448EI
UT WOS:000266245500021
PM 19279081
ER
PT J
AU Tasevska, N
Sinha, R
Kipnis, V
Subar, AF
Leitzmann, MF
Hollenbeck, AR
Caporaso, NE
Schatzkin, A
Cross, AJ
AF Tasevska, Natasa
Sinha, Rashmi
Kipnis, Victor
Subar, Amy F.
Leitzmann, Michael F.
Hollenbeck, Albert R.
Caporaso, Neil E.
Schatzkin, Arthur
Cross, Amanda J.
TI A prospective study of meat, cooking methods, meat mutagens, heme iron,
and lung cancer risks
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID POLYCYCLIC AROMATIC-HYDROCARBONS; FOOD FREQUENCY QUESTIONNAIRE;
HETEROCYCLIC AMINE CONTENT; LOW-ENERGY REPORTERS; RED MEAT;
NITROSO-COMPOUNDS; NONSMOKING WOMEN; DIETARY FACTORS; VARYING DEGREES;
N-NITROSATION
AB Background: Red and processed meat consumption may play a role in lung cancer pathogenesis because of these meats' fat and carcinogen content.
Objective: We prospectively investigated whether meat type, cooking method, doneness level, and intake of specific meat mutagens and heme iron are associated with lung carcinoma.
Design: Men (n = 278,380) and women (n = 189,596) from the National Institutes of Health-AARP Diet and Health Study with no history of cancer at baseline were monitored for 8 y. Diet was assessed with a 124-item food-frequency questionnaire. A meat-cooking module was used to estimate the intake of individual heterocyclic amines, benzo(a) pyrene, and heme iron. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs.
Results: In a comparison of quintiles 5 with 1 (Q5vsQ1), a high intake of red meat was associated with an increased risk of lung carcinoma in both men (HR(Q5vsQ1): 1.22; 95% CI: 1.09, 1.38; P for trend = 0.005) and women (HR(Q5vsQ1): 1.13; 95% CI: 0.97, 1.32; P for trend = 0.05). A high intake of processed meat increased the risk only in men (HR(Q5vsQ1): 1.23; 95% CI: 1.10, 1.37; P for trend = 0.003). In an analysis stratified by smoking status, we observed a tendency for an increased risk with red meat intake in never smoking men and women; however, the risks were not statistically significant. In a comparison of tertiles 3 and 1 (T3vsT1), the risk of lung carcinoma was associated with intake of well-/very-well-done meat (HR(T3vsT1): 1.20; 95% CI: 1.07, 1.35; P for trend = 0.002) and the intake of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (HR(Q5vsQ1): 1.20; 95% CI: 1.04, 1.38; P for trend = 0.04) in men. Heme iron intake increased the risk of lung carcinoma in both men (HR(Q5vsQ1): 1.25; 95% CI: 1.07, 1.45; P for trend = 0.02) and women (HR(Q5vsQ1): 1.18; 95% CI: 0.99, 1.42; P for trend = 0.002).
Conclusion: We observed a moderate association between meat consumption and lung carcinoma, which might be explained by heme iron intake, high-temperature cooking, and associated mutagens. Am J Clin Nutr 2009; 89: 1884-94.
C1 [Tasevska, Natasa] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Kipnis, Victor] NCI, Biometry Res Grp, Canc Prevent Div, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Subar, Amy F.] NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH,Dept Hlth & Hu, Bethesda, MD 20892 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Tasevska, N (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Executive Blvd,EPS-3032, Bethesda, MD 20892 USA.
EM tasevskan@mail.nih.gov
RI Sinha, Rashmi/G-7446-2015
OI Sinha, Rashmi/0000-0002-2466-7462
FU National Cancer Institute; National Institutes of Health; Department of
Health and Human Services
FX Supported by the Intramural Research Program of the National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services.
NR 52
TC 42
Z9 43
U1 1
U2 10
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN 1
PY 2009
VL 89
IS 6
BP 1884
EP 1894
DI 10.3945/ajcn.2008.27272
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 448EI
UT WOS:000266245500024
PM 19369370
ER
PT J
AU Lee, SA
Shu, XO
Li, HL
Yang, G
Cai, H
Wen, WQ
Ji, BT
Gao, J
Gao, YT
Zheng, W
AF Lee, Sang-Ah
Shu, Xiao-Ou
Li, Honglan
Yang, Gong
Cai, Hui
Wen, Wanqing
Ji, Bu-Tian
Gao, Jing
Gao, Yu-Tang
Zheng, Wei
TI Adolescent and adult soy food intake and breast cancer risk: results
from the Shanghai Women's Health Study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID CORONARY-HEART-DISEASE; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN;
STEROID-HORMONES; FAT DISTRIBUTION; SUBSEQUENT RISK; JAPANESE WOMEN;
CHINESE WOMEN; CONSUMPTION; COHORT
AB Background: Soy food is a rich source of isoflavones-a class of phytoestrogens that has both antiestrogenic and anticarcinogenic properties.
Objective: The objective was to evaluate the association of adolescent and adult soy food intake with breast cancer risk in a cohort of 73,223 Chinese women who participated in the Shanghai Women's Health Study.
Design: A validated food-frequency questionnaire was used to assess usual dietary intake during adulthood and adolescence. After a mean follow-up of 7.4 y, 592 incident cases of breast cancer were identified for longitudinal analyses by using Cox regressions.
Results: Adult soy food consumption, measured either by soy protein or isoflavone intake, was inversely associated with the risk of premenopausal breast cancer, and the association was highly statistically significant (P for trend < 0.001). The multivariate-adjusted relative risks (RRs) for the upper intake quintile compared with the lowest quintile were 0.41 (95% CI: 0.25, 0.70) for soy protein intake and 0.44 (95% CI: 0.26, 0.73) for isoflavone intake. High intake of soy foods during adolescence was also associated with a reduced risk of premenopausal breast cancer (RR: 0.57; 95% CI: 0.34, 0.97). Women who consumed a high amount of soy foods consistently during adolescence and adulthood had a substantially reduced risk of breast cancer. No significant association with soy food consumption was found for postmenopausal breast cancer.
Conclusion: This large, population-based, prospective cohort study provides strong evidence of a protective effect of soy food intake against premenopausal breast cancer. Am J Clin Nutr 2009; 89: 1920-6.
C1 [Zheng, Wei] Vanderbilt Univ, Sch Med, Inst Med & Publ Hlth,Div Epidemiol,Dept Med, Vanderbilt Epidemiol Ctr,Vanderbilt Ingram Canc C, Nashville, TN 37203 USA.
[Li, Honglan; Gao, Jing; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Lee, Sang-Ah] Kangwon Natl Univ, Dept Preventat Med, Gangwon Do, South Korea.
RP Zheng, W (reprint author), Vanderbilt Univ, Sch Med, Inst Med & Publ Hlth,Div Epidemiol,Dept Med, Vanderbilt Epidemiol Ctr,Vanderbilt Ingram Canc C, 2525 W End Ave,8th Floor, Nashville, TN 37203 USA.
EM wei.zheng@vanderbilt.edu
FU National Institutes of Health [R01 CA070867]
FX Supported by US Public Health Service grant number R01 CA070867 from the
National Institutes of Health.
NR 34
TC 104
Z9 110
U1 0
U2 13
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 JUN 1
PY 2009
VL 89
IS 6
BP 1920
EP 1926
DI 10.3945/ajcn.2008.27361
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 448EI
UT WOS:000266245500029
PM 19403632
ER
PT J
AU Solomon, D
Papillo, JL
Davey, DD
AF Solomon, Diane
Papillo, Jacalyn L.
Davey, Diane D.
CA CETC
TI Statement on HPV DNA Test Utilization
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Molecular diagnostics; Cytology; Human papillomavirus DNA
ID CANCER
C1 [Solomon, Diane] NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Papillo, Jacalyn L.] Fletcher Allen Hlth Care, Dept Anat Pathol, Burlington, VT USA.
[Davey, Diane D.] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA.
RP Solomon, D (reprint author), NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Execut Plaza N,Room 2130,6130 Execut Blvd, Rockville, MD 20852 USA.
NR 3
TC 10
Z9 10
U1 1
U2 1
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD JUN
PY 2009
VL 131
IS 6
BP 768
EP 769
DI 10.1309/AJCPQCIBCZ22ZIMG
PG 2
WC Pathology
SC Pathology
GA 448CB
UT WOS:000266238600002
PM 19461079
ER
PT J
AU Cox, JT
Moriarty, AT
Castle, PE
AF Cox, J. Thomas
Moriarty, Ann T.
Castle, Philip E.
TI Commentary on Statement on HPV DNA Test Utilization
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Editorial Material
DE Molecular diagnostics; Cytology; Human papillomavirus
ID CANCER-SOCIETY GUIDELINE; HUMAN-PAPILLOMAVIRUS; CERVICAL-CANCER;
SCREENING-TESTS; NEOPLASIA; COHORT; WOMEN; MANAGEMENT; AMERICAN; RISK
AB Michaela had a Papanicolaou (Pap) test at age 17 years, less than 3 months from her first intercourse. The Pap was interpreted as atypical squamous cells of undetermined significance (ASC-US) and the laboratory automatically "reflexed" this to human papillomavirus (HPV) testing. Michaela tested positive for high-risk (carcinogenic) HPV underwent colposcopy and biopsy, and had cryotherapy for cervical intraepithelial neoplasia (CIN), grade 1. Her 4-month postcryotherapy Pap was ASC-US HPV+.
C1 [Cox, J. Thomas] Univ Calif Santa Barbara, Gynecol & Colposcopy Clin Student Hlth Serv, Santa Barbara, CA 93106 USA.
[Moriarty, Ann T.] AmeriPath Indiana, Indianapolis, IN USA.
[Castle, Philip E.] NCI, Div Canc Epidemiol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Castle, Philip E.] NCI, Div Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Cox, JT (reprint author), Univ Calif Santa Barbara, Gynecol & Colposcopy Clin Student Hlth Serv, Santa Barbara, CA 93106 USA.
NR 19
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U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD JUN
PY 2009
VL 131
IS 6
BP 770
EP 773
DI 10.1309/AJCPGBTXGMQMNV12
PG 4
WC Pathology
SC Pathology
GA 448CB
UT WOS:000266238600003
ER
PT J
AU Koster, A
Harris, TB
Moore, SC
Schatzkin, A
Hollenbeck, AR
van Eijk, JTM
Leitzmann, MF
AF Koster, Annemarie
Harris, Tamara B.
Moore, Steven C.
Schatzkin, Arthur
Hollenbeck, Albert R.
van Eijk, Jacques Th. M.
Leitzmann, Michael F.
TI Joint Associations of Adiposity and Physical Activity With Mortality The
National Institutes of Health-AARP Diet and Health Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE abdominal fat; adiposity; body fat distribution; body mass index;
exercise; mortality; motor activity
ID BODY-MASS INDEX; ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE MORTALITY;
LIFE-STYLE INTERVENTION; CARDIORESPIRATORY FITNESS; WAIST CIRCUMFERENCE;
OLDER-ADULTS; RISK-FACTORS; WEIGHT-LOSS; WOMEN
AB The authors examined the joint associations of adiposity (assessed by body mass index (BMI; weight (kg)/height (m)(2)) and waist circumference) and physical activity with mortality to evaluate whether physical activity protects against the adverse effects of high adiposity. Using data on 185,412 men and women aged 51-72 years participating in the National Institutes of Health-AARP Diet and Health Study, the authors assessed all-cause mortality over 10 years (1996-2006). Overweight (BMI 25-<30), obesity (BMI >= 30), a large waist circumference (men: >= 102 cm; women: >= 88 cm), and low physical activity were each independent predictors of mortality. Compared with normal-weight persons (BMI 18.5-<25) who were physically active (>7 hours/week of moderate physical activity), mortality risks were 1.62 (95% confidence interval (CI): 1.50, 1.75) for inactive normal-weight persons, 1.79 (95% CI: 1.37, 2.33) for active morbidly obese (BMI >= 35) persons, and 3.45 (95% CI: 2.79, 4.00) for inactive morbidly obese persons. Similar results were found for the combined relation of BMI and vigorous physical activity. Inactive persons with a large waist circumference had 2 times' greater mortality risk than active persons with a normal waist circumference. High physical activity attenuated but did not eliminate the increased mortality risk associated with obesity. Preventing weight gain and promoting physical activity in older persons may lower mortality risk.
C1 [Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Koster, Annemarie; van Eijk, Jacques Th. M.] Univ Maastricht, Fac Hlth Med & Life Sci, Maastricht, Netherlands.
[Moore, Steven C.; Schatzkin, Arthur; Leitzmann, Michael F.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Leitzmann, Michael F.] Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Koster, A (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA.
EM kostera@mail.nih.gov
RI Koster, Annemarie/E-7438-2010; Moore, Steven/D-8760-2016
OI Moore, Steven/0000-0002-8169-1661
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute; Intramural Research Program of the National
Institutes of Health; National Institute on Aging; Georgia Center for
Cancer Statistics; California Department of Health Services, Cancer
Surveillance Section; Louisiana Tumor Registry
FX 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. (The Pennsylvania Department of Health specifically disclaims
responsibility for any analyses, interpretations, or conclusions.)
NR 33
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U1 0
U2 2
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 JUN 1
PY 2009
VL 169
IS 11
BP 1344
EP 1351
DI 10.1093/aje/kwp053
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 446GF
UT WOS:000266109400010
PM 19372216
ER
PT J
AU Basso, O
Wilcox, AJ
AF Basso, O.
Wilcox, A. J.
TI DECONSTRUCTING THE MORTALITY OF PRETERM BABIES: HOW MUCH IS REALLY DUE
TO IMMATURITY?
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Basso, O.; Wilcox, A. J.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S20
EP S20
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300078
ER
PT J
AU Beydoun, MA
Kuczmarski, MF
Wang, Y
Mason, M
Evans, MK
Zonderman, AB
AF Beydoun, M. A.
Kuczmarski, M. F.
Wang, Y.
Mason, M.
Evans, M. K.
Zonderman, A. B.
TI RECEIVER-OPERATING CHARACTERISTIC OF ADIPOSITY FOR METABOLIC SYNDROME:
HANDLS STUDY.
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Beydoun, M. A.; Kuczmarski, M. F.; Wang, Y.; Mason, M.; Evans, M. K.; Zonderman, A. B.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 JUN 1
PY 2009
VL 169
BP S114
EP S114
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300453
ER
PT J
AU Beydoun, MA
Boueiz, A
Abougergi, M
Kitner-Triolo, MH
Beydoun, HA
Resnick, SM
O'Brien, R
Zonderman, AB
AF Beydoun, M. A.
Boueiz, A.
Abougergi, M.
Kitner-Triolo, M. H.
Beydoun, H. A.
Resnick, S. M.
O'Brien, R.
Zonderman, A. B.
TI THE ROLE OF SEX IN THE ASSOCIATION OF THE APOLIPOPROTEIN E EPSILON 4
ALLELE WITH INCIDENCE OF DEMENTIA, COGNITIVE IMPAIRMENT AND DECLINE
AMONG OLDER US ADULTS
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Beydoun, M. A.; Boueiz, A.; Abougergi, M.; Kitner-Triolo, M. H.; Beydoun, H. A.; Resnick, S. M.; O'Brien, R.; Zonderman, A. B.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
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U1 0
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S89
EP S89
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300352
ER
PT J
AU Boyles, AL
Deroo, LA
Wilcox, AJ
Taylor, JA
Jugessur, A
Christensen, K
Murray, JC
Lie, RT
AF Boyles, A. L.
DeRoo, L. A.
Wilcox, A. J.
Taylor, J. A.
Jugessur, A.
Christensen, K.
Murray, J. C.
Lie, R. T.
TI MATERNAL ALCOHOL CONSUMPTION AND INFANT CLEFTS: THE ROLE OF ALCOHOL
METABOLISM GENE VARIANTS
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Boyles, A. L.; DeRoo, L. A.; Wilcox, A. J.; Taylor, J. A.; Jugessur, A.; Christensen, K.; Murray, J. C.; Lie, R. T.] NIEHS, Durham, NC USA.
RI Christensen, Kaare/C-2360-2009
OI Christensen, Kaare/0000-0002-5429-5292
NR 0
TC 0
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U1 0
U2 1
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 JUN 1
PY 2009
VL 169
BP S1
EP S1
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300002
ER
PT J
AU Brinton, L
Carreon, JD
Gierach, G
McGlynn, K
Gridley, G
AF Brinton, L.
Carreon, J. D.
Gierach, G.
McGlynn, K.
Gridley, G.
TI MALE BREAST CANCER IN THE VETERAN'S ADMINISTRATION HOSPITALIZATION
DATABASE.
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Brinton, L.; Carreon, J. D.; Gierach, G.; McGlynn, K.; Gridley, G.] NCI, Rockville, MD 20852 USA.
RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016
OI Brinton, Louise/0000-0003-3853-8562; Gierach,
Gretchen/0000-0002-0165-5522
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S51
EP S51
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300203
ER
PT J
AU Cao, Y
Blount, BC
Valentin-Blasini, L
Bernbaum, JC
Phillips, TM
Rogan, WJ
AF Cao, Y.
Blount, B. C.
Valentin-Blasini, L.
Bernbaum, J. C.
Phillips, T. M.
Rogan, W. J.
TI PERCHLORATE, THYROTROPIN, AND THYROID HORMONE IN INFANTS
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Cao, Y.; Blount, B. C.; Valentin-Blasini, L.; Bernbaum, J. C.; Phillips, T. M.; Rogan, W. J.] NIEHS, Epidemiol Branch, Durham, NC 27713 USA.
RI Rogan, Walter/I-6034-2012
OI Rogan, Walter/0000-0002-9302-0160
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S103
EP S103
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300410
ER
PT J
AU Cook, MB
Akre, O
Forman, D
Madigan, MP
Richiardi, L
McGlynn, KA
AF Cook, M. B.
Akre, O.
Forman, D.
Madigan, M. P.
Richiardi, L.
McGlynn, K. A.
TI A SYSTEMATIC REVIEW AND META-ANALYSIS OF PERINATAL VARIABLES IN RELATION
TO THE RISK OF TESTICULAR CANCER - EXPERIENCES OF THE SON.
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Cook, M. B.; Akre, O.; Forman, D.; Madigan, M. P.; Richiardi, L.; McGlynn, K. A.] NCI, Rockville, MD 20852 USA.
NR 0
TC 0
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U1 0
U2 1
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 JUN 1
PY 2009
VL 169
SU 11
BP S53
EP S53
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300208
ER
PT J
AU Cook, MB
Akre, O
Forman, D
Madigan, MP
Richiardi, L
McGlynn, KA
AF Cook, M. B.
Akre, O.
Forman, D.
Madigan, M. P.
Richiardi, L.
McGlynn, K. A.
TI A SYSTEMATIC REVIEW AND META-ANALYSIS OF PERINATAL VARIABLES IN RELATION
TO THE RISK OF TESTICULAR CANCER - EXPERIENCES OF THE MOTHER.
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Cook, M. B.; Akre, O.; Forman, D.; Madigan, M. P.; Richiardi, L.; McGlynn, K. A.] NCI, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
SU 11
BP S53
EP S53
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300210
ER
PT J
AU Cupul-Uicab, LA
Hernandez-Avila, M
Longnecker, MP
AF Cupul-Uicab, L. A.
Hernandez-Avila, M.
Longnecker, M. P.
TI PRENATAL EXPOSURE TO THE MAJOR DDT METABOLITE
1,1-DICHLORO-2,2-BIS(P-CHLOROPHENYL)ETHYLENE (DDE) AND LONGITUDINAL
GROWTH IN BOYS FROM MEXICO
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Cupul-Uicab, L. A.; Hernandez-Avila, M.; Longnecker, M. P.] NIEHS, Epidemiol Branch, NIH, DHHS,USA, Bethesda, MD 20892 USA.
NR 0
TC 0
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S44
EP S44
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300175
ER
PT J
AU Deroo, LA
Parks, CG
Kim, S
Cawthon, RM
Weinberg, C
Sandler, DP
AF DeRoo, L. A.
Parks, C. G.
Kim, S.
Cawthon, R. M.
Weinberg, C.
Sandler, D. P.
TI CHILDHOOD SOCIOECONOMIC FACTORS AND TELOMERE LENGTH
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [DeRoo, L. A.; Parks, C. G.; Kim, S.; Cawthon, R. M.; Weinberg, C.; Sandler, D. P.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
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U2 2
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 JUN 1
PY 2009
VL 169
BP S88
EP S88
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300350
ER
PT J
AU Freedman, DM
Rajaraman, P
Fuhrman, B
Hoffbeck, R
Alexander, B
AF Freedman, D. M.
Rajaraman, P.
Fuhrman, B.
Hoffbeck, R.
Alexander, B.
TI SUNLIGHT, HORMONE REPLACMENT STATUS AND COLORECTAL CANCER RISK IN
POST-MENOPAUSAL WOMEN
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Freedman, D. M.; Rajaraman, P.; Fuhrman, B.; Hoffbeck, R.; Alexander, B.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S81
EP S81
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300322
ER
PT J
AU Kim, S
DeRoo, LA
Sandler, DP
AF Kim, S.
DeRoo, L. A.
Sandler, D. P.
TI EATING PATTERNS AND NUTRITIONAL CHARACTERISTICS ASSOCIATED WITH SLEEP
DURATION
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Kim, S.; DeRoo, L. A.; Sandler, D. P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S120
EP S120
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300478
ER
PT J
AU Klebanoff, M
AF Klebanoff, M.
CA Vaginal Flora Study Grp
TI PERSONAL HYGIENIC BEHAVIORS AND BACTERIAL VAGINOSIS (BV)
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Klebanoff, M.; Vaginal Flora Study Grp] NICHD, NIH, Bethesda, MD 20892 USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S30
EP S30
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300120
ER
PT J
AU Landgren, O
Kyle, RA
Hoppin, JA
Freeman, LEB
Cerhan, JR
Katzmann, JA
Rajkumar, SV
Alavanja, M
AF Landgren, O.
Kyle, R. A.
Hoppin, J. A.
Freeman, L. E. B.
Cerhan, J. R.
Katzmann, J. A.
Rajkumar, S. V.
Alavanja, M.
TI PESTICIDE EXPOSURE AND RISK OF MONOCLONAL GAMMOPATHY OF UNDETERMINED
SIGNIFICANCE (MGUS) IN THE AGRICULTURAL HEALTH STUDY
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Landgren, O.; Kyle, R. A.; Hoppin, J. A.; Freeman, L. E. B.; Cerhan, J. R.; Katzmann, J. A.; Rajkumar, S. V.; Alavanja, M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S47
EP S47
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300187
ER
PT J
AU Laughlin, SK
Baird, DD
AF Laughlin, S. K.
Baird, D. D.
TI THE ASSOCIATION OF FIBROIDS WITH REPRODUCTIVE TRACT INFECTIONS
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Laughlin, S. K.; Baird, D. D.] NIEHS, Durham, NC 27707 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 JUN 1
PY 2009
VL 169
BP S80
EP S80
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300318
ER
PT J
AU Launer, LJ
AF Launer, L. J.
TI MEASURING COGNITIVE FUNCTION IN OLDER POPULATIONS
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Launer, L. J.] NIA, Bethesda, MD 20892 USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S126
EP S126
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300501
ER
PT J
AU Lum, KJ
Louis, GM
Sundaram, R
AF Lum, K. J.
Louis, G. M.
Sundaram, R.
TI DO WOMEN CHANGE BEHAVIOR WHILE ATTEMPTING PREGNANCY?
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Lum, K. J.; Louis, G. M.; Sundaram, R.] NICHD, NIH, DHHS, Bethesda, MD 20892 USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S22
EP S22
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300086
ER
PT J
AU Neta, G
von Ehrenstein, O
Lum, K
Sundaram, R
Andrews, W
Zhang, J
AF Neta, G.
von Ehrenstein, O.
Lum, K.
Sundaram, R.
Andrews, W.
Zhang, J.
TI CYTOKINE LEVELS IN UMBILICAL CORD BLOOD AND RISKS OF PRETERM DELIVERY
AND SMALL-FOR-GESTATIONAL-AGE BIRTH
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Neta, G.; von Ehrenstein, O.; Lum, K.; Sundaram, R.; Andrews, W.; Zhang, J.] NIH, Bethesda, MD 20852 USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S133
EP S133
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300527
ER
PT J
AU Perkins, NJ
Schisterman, EF
Vexler, A
AF Perkins, N. J.
Schisterman, E. F.
Vexler, A.
TI GENERALIZED ROC CRITERION FOR MULTIPLE BIOMARKERS WITH LIMITS OF
DETECTION
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Perkins, N. J.; Schisterman, E. F.; Vexler, A.] NICHD, NIH, DESPR, Rockville, MD 20852 USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S112
EP S112
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300446
ER
PT J
AU Schisterman, EF
Perkins, NJ
Mumford, SL
Roy, A
Ye, A
AF Schisterman, E. F.
Perkins, N. J.
Mumford, S. L.
Roy, A.
Ye, A.
TI WHAT TO DO ABOUT COLLINEARITY
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Schisterman, E. F.; Perkins, N. J.; Mumford, S. L.; Roy, A.; Ye, A.] NICHD, NIH, Bethesda, MD USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S113
EP S113
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300450
ER
PT J
AU Simard, EP
Pfeiffer, RM
Engels, EA
AF Simard, E. P.
Pfeiffer, R. M.
Engels, E. A.
TI SPECTRUM OF CANCER RISK LATE AFTER AIDS IN THE UNITED STATES
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Simard, E. P.; Pfeiffer, R. M.; Engels, E. A.] Natl Canc Inst, Rockville, MD 20892 USA.
RI Simard, Edgar/G-4552-2010
OI Simard, Edgar/0000-0001-8093-2067
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S136
EP S136
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300539
ER
PT J
AU van Bemmel, DM
Li, Y
Graubard, B
Rajaraman, P
AF van Bemmel, D. M.
Li, Y.
Graubard, B.
Rajaraman, P.
CA CDC NCI NHANES III Genomics Workin
TI ALAD G177C POLYMORPHISM ASSOCIATED WITH DEATH FROM ALL CAUSES,
CARDIOVASCULAR DISEASE, AND CANCER
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [van Bemmel, D. M.; Li, Y.; Graubard, B.; Rajaraman, P.; CDC NCI NHANES III Genomics Workin] NCI, Bethesda, MD 20892 USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S6
EP S6
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300025
ER
PT J
AU Waggoner, JK
Blair, A
Kullman, GJ
Henneberger, PK
Alavanja, M
Kamel, F
Lynch, CF
Knott, C
London, SJ
Umbach, DM
Hines, CJ
Sandler, DP
Lubin, JH
Freeman, LEB
Hoppin, JA
AF Waggoner, J. K.
Blair, A.
Kullman, G. J.
Henneberger, P. K.
Alavanja, M.
Kamel, F.
Lynch, C. F.
Knott, C.
London, S. J.
Umbach, D. M.
Hines, C. J.
Sandler, D. P.
Lubin, J. H.
Freeman, L. E. Beane
Hoppin, J. A.
TI ELEVATED INJURY MORTALITY IN THE AGRICULTURAL HEALTH STUDY
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Waggoner, J. K.; Blair, A.; Kullman, G. J.; Henneberger, P. K.; Alavanja, M.; Kamel, F.; Lynch, C. F.; Knott, C.; London, S. J.; Umbach, D. M.; Hines, C. J.; Sandler, D. P.; Lubin, J. H.; Freeman, L. E. Beane; Hoppin, J. A.] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S106
EP S106
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300423
ER
PT J
AU Xu, Q
Song, Y
Park, Y
Hollenbeck, A
Blair, A
Schatzkin, A
Chen, H
AF Xu, Q.
Song, Y.
Park, Y.
Hollenbeck, A.
Blair, A.
Schatzkin, A.
Chen, H.
TI DAYTIME NAPPING AND NIGHT SLEEP DURATION AND DIABETES MELLITUS IN THE
NIH-AARP DIET AND HEALTH STUDY
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2009
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Xu, Q.; Song, Y.; Park, Y.; Hollenbeck, A.; Blair, A.; Schatzkin, A.; Chen, H.] NIEHS, Epi Branch, Res Triangle Pk, NC 27709 USA.
NR 0
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2009
VL 169
BP S1
EP S1
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 456SK
UT WOS:000266868300003
ER
PT J
AU Wong, RKH
Altekruse, SF
AF Wong, Roy K. H.
Altekruse, Sean F.
TI Where Are You and How Do We Find You? The Dilemma of Identifying
Barrett's Epithelium Before Adenocarcinoma of the Esophagus
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Editorial Material
ID GASTROESOPHAGEAL-REFLUX DISEASE; SPECIALIZED INTESTINAL METAPLASIA;
ESOPHAGOGASTRIC JUNCTION; CLINICAL-DATA; LYMPH-NODES; CANCER; DYSPLASIA;
OBESITY; RISK; MANIFESTATION
AB The incidence of esophageal adenocarcinoma in white males has been increasing steadily over the past decade. However, attempts to identify the precursor lesion, intestinal metaplasia of the esophagus, or early in-situ cancers have been dismal, with no increase in the diagnosis of early cancers over 9 years of follow-up, as noted in the study by Cooper et al. Important predictors of such as a previous diagnosis of gastroesophageal reflux disease, endoscopy, and the diagnosis of intestinal metaplasia, continue to represent a minority of patients who present with esophageal adenocarcinoma. A discussion on the possible pathophysiology, and reasons for the poor diagnostic yields in spite of performing more endoscopies, are presented. It may be that most patients are relatively asymptomatic, or have very distal, endoscopically imperceptible intestinal metaplasia. Over time, that encourage localized, distal esophageal reflux may be the insidious culprit that leads to intestinal metaplasia.
C1 [Wong, Roy K. H.] Walter Reed Army Med Ctr, Gastroenterol Serv, Washington, DC 20307 USA.
[Altekruse, Sean F.] NCI, Div Canc Control & Populat Sci, Canc Stat Branch, Rockville, MD USA.
RP Wong, RKH (reprint author), Walter Reed Army Med Ctr, Gastroenterol Serv, 6900 Georgia Ave NW, Washington, DC 20307 USA.
EM roy.wong@amedd.army.mil
NR 25
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 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD JUN
PY 2009
VL 104
IS 6
BP 1363
EP 1365
DI 10.1038/ajg.2009.167
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 457DR
UT WOS:000266906900011
PM 19436281
ER
PT J
AU Nichols, WL
Rick, ME
Ortel, TL
Montgomery, RR
Sadler, JE
Yawn, BP
James, AH
Hultin, MB
Manco-Johnson, MJ
Weinstein, M
AF Nichols, William L.
Rick, Margaret E.
Ortel, Thomas L.
Montgomery, Robert R.
Sadler, J. Evan
Yawn, Barbara P.
James, Andra H.
Hultin, Mae B.
Manco-Johnson, Marilyn J.
Weinstein, Mark
TI Clinical and laboratory diagnosis of von Willebrand disease: A synopsis
of the 2008 NHLBI/NIH guidelines
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID CARDIOMYOPATHY
AB Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/ vwd). Am. J. Hematol. 84:366-370, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Nichols, William L.] Mayo Clin, Special Coagulat Lab, Coll Med, Dept Lab Med & Pathol,Div Hematopathol, Rochester, MN 55905 USA.
[Nichols, William L.] Mayo Clin, Coll Med, Div Hematol & Internal Med, Coagulat Clin, Rochester, MN 55905 USA.
[Nichols, William L.] Mayo Clin, Coll Med, Div Hematol & Internal Med, Comprehens Hemophilia Ctr, Rochester, MN 55905 USA.
[Rick, Margaret E.] NIH, Hematol Serv, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Ortel, Thomas L.] Duke Univ, Med Ctr, Dept Med, Div Hematol, Durham, NC 27710 USA.
[Ortel, Thomas L.] Duke Univ, Med Ctr, Dept Pathol, Clin Coagulat Lab, Durham, NC 27710 USA.
[Montgomery, Robert R.] Med Coll Wisconsin, Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI 53226 USA.
[Montgomery, Robert R.] Med Coll Wisconsin, Dept Pediat, Sect Pediat Hematol, Milwaukee, WI 53226 USA.
[Sadler, J. Evan] Washington Univ, Dept Med, St Louis, MO USA.
[Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA.
[Yawn, Barbara P.] Univ Minnesota, Dept Family & Community Med, Minneapolis, MN USA.
[James, Andra H.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Hultin, Mae B.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA.
[Manco-Johnson, Marilyn J.] Univ Colorado Denver, Dept Pediat, Aurora, CO USA.
[Manco-Johnson, Marilyn J.] Childrens Hosp, Ctr Canc & Blood Disorders, Denver, CO 80218 USA.
[Weinstein, Mark] US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20857 USA.
RP Nichols, WL (reprint author), Mayo Clin, Special Coagulat Lab, Coll Med, Dept Lab Med & Pathol,Div Hematopathol, Hilton 200,200 1st St SW, Rochester, MN 55905 USA.
EM nichols.william@mayo.edu
RI Sadler, Evan/D-8556-2011
NR 11
TC 34
Z9 34
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2009
VL 84
IS 6
BP 366
EP 370
DI 10.1002/ajh.21405
PG 5
WC Hematology
SC Hematology
GA 452VW
UT WOS:000266570300011
PM 19415721
ER
PT J
AU Vupputuri, S
Fox, CS
Coresh, J
Woodward, M
Muntner, P
AF Vupputuri, Suma
Fox, Caroline S.
Coresh, Josef
Woodward, Mark
Muntner, Paul
TI Differential Estimation of CKD Using Creatinine-Versus Cystatin C-Based
Estimating Equations by Category of Body Mass Index
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Chronic kidney insufficiency; cystatin C; creatinine; glomerular
filtration rate; body mass index
ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; SERUM CREATININE;
EDUCATION-PROGRAM; RENAL-DISEASE; UNITED-STATES; CATHEPSIN-S; MARKER;
HEALTH; RISK
AB Backgound: Adiposity is associated with cystatin C. Cystatin C-based glomerular filtration rate (GFR) equations may result in overestimation of chronic kidney disease (CKD) prevalence at greater body mass index (BMI) levels.
Study Design: Cross-sectional.
Setting & Participants: 6,709 US adult Third National Health and Nutrition Examination Survey participants.
Factor: BMI.
Outcome: Absolute percentage of difference in prevalence of stage 3 or 4 CKD between creatinine and cystatin C-based estimating equations by level of BMI.
Measurements: Normal weight, overweight, and obesity were defined as BMI of 18.5 to less than 25.0, 25 to less than 30.0, and 30 kg/m(2) or greater, respectively. Stage 3 or 4 CKD (estimated glomerular filtration rate [eGFR], 15 to 59 mL/min/1.73 m(2)) was defined using the 4-variable creatinine-based Modification of Diet in Renal Disease Study equation (eGFR(MDRD)); cystatin C level, age, sex, and race equation (eGFR(Cysc,age,sex,race)); cystatin C-only equation (eGFR(Cysc)); cystatin C level of 1.12 mg/L or greater (increased cystatin C); and an equation incorporating serum creatinine level, cystatin C level, age, sex, and race (eGFR(Cr,CysC,age,sex,race)).
Results: Differences in stage 3 or 4 CKD prevalence estimates between eGFR(CysC,age,sex, race), eGFR(Cysc), and increased cystatin C, separately, and eGFR(MDRD) were greater at higher BMI levels. Specifically, compared with estimates derived using eGFR(MDRD) for normal-weight, overweight, and obese participants, estimated prevalences of stage 3 or 4 CKD were 2.1%, 3.0%, and 6.5% greater when estimated by using eGFR(Cysc,age,sex,race) (P trend = 0.005); 0.1 %, 0.6%, and 2.2% greater for eGFR(Cysc) (P trend = 0.03); 2.9%, 5.2%, and 9.5% greater for increased cystatin C (P trend < 0.001); and -0.1 %, -0.4%, and 0.0% greater for eGFR(Cr,CysC,age,sex,race), respectively (P trend = 0.7).
Limitations: No gold-standard measure of GFR was available.
Conclusions: BMI may influence the estimated prevalence of stage 3 or 4 CKD when cystatin C-based equations are used. Am J Kidney Dis 53:993-1001. (C) 2009 by the National Kidney Foundation, Inc.Inc
C1 [Vupputuri, Suma] Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA 30305 USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol & Metab, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Coresh, Josef] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Bethesda, MD USA.
[Woodward, Mark] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Muntner, Paul] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA.
RP Vupputuri, S (reprint author), Kaiser Permanente Georgia, Ctr Hlth Res, 3495 Piedmont Rd,Bdg 10,Ste 205, Atlanta, GA 30305 USA.
EM suma.vupputuri@kp.org
RI Woodward, Mark/D-8492-2015
FU NIDDK NIH HHS [U01 DK067651-02, U01 DK035073, U01 DK035073-14, U01
DK053869, U01 DK067651, UO1 DK 053869, UO1 DK 067651, UO1 DK 35073]
NR 31
TC 34
Z9 40
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JUN
PY 2009
VL 53
IS 6
BP 993
EP 1001
DI 10.1053/j.ajkd.2008.12.043
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 456RY
UT WOS:000266866600014
PM 19394726
ER
PT J
AU Parisi, MA
Zayed, H
Slavotinek, AM
Rutledge, JC
AF Parisi, Melissa A.
Zayed, Hatem
Slavotinek, Anne M.
Rutledge, Joe C.
TI Congenital Diaphragmatic Hernia and Microtia in a Newborn With
Mycophenolate Mofetil (MMF) Exposure: Phenocopy for Fryns Syndrome or
Broad Spectrum of Teratogenic Effects?
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE mycophenolate mofetil; teratogen; Fryns syndrome; congenital
diaphragmatic hernia; microtia; embryopathy
ID IN-UTERO EXPOSURE; ORGAN TRANSPLANT; PREGNANCY; DEFECTS;
IMMUNOSUPPRESSION; MALFORMATIONS; PHENOTYPE
AB A newborn female infant born to a woman on immunosuppressive medications including mycophenolate mofetil (MMF) for a renal graft secondary to lupus nephritis presented with congenital diaphragmatic hernia (CDH) and additional findings of microtia, esophageal atresia with tracheoesophageal fistula, cleft palate, congenital heart defect, digital anomalies, and dysmorphic facial features. Pulmonary hypoplasia resulted in death at day 2 of life. She was presumed to have Fryns syndrome based on diagnostic criteria established for this recessive disorder with prominent features including CDH, facial anomalies, and nail hypoplasia. In retrospect, this infant's findings are more likely the result of teratogenic exposure to MMF, as more recent data have emerged linking aural atresia, digital anomalies, and dysmorphic features to this drug. To date, this is the only human report of CDH in an infant with prenatal exposure to MMF, although the manufacturer's package insert alludes to animal studies with a broad spectrum of malformations, including CDH. Thus, a teratogenic exposure can mimic a known Mendelian genetic syndrome, and caution is urged in presuming a genetic etiology for infants with potential teratogenic exposure to relatively new drugs with limited published animal data. (C) 2009 Wiley-Liss, Inc.
C1 [Rutledge, Joe C.] Seattle Childrens Hosp, Dept Labs, Seattle, WA 98105 USA.
[Parisi, Melissa A.] Seattle Childrens Hosp, Dept Pediat, Seattle, WA 98105 USA.
[Parisi, Melissa A.; Rutledge, Joe C.] Univ Washington, Seattle, WA 98195 USA.
[Zayed, Hatem; Slavotinek, Anne M.] Univ Calif San Francisco, Dept Pediat, Div Genet, San Francisco, CA 94143 USA.
[Parisi, Melissa A.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Rutledge, JC (reprint author), Seattle Childrens Hosp, Dept Labs, 4800 Sand Point Way NE, Seattle, WA 98105 USA.
EM joe.rutledge@seattlechildrens.org
OI Zayed, Hatem/0000-0001-8838-6638
FU National Institute of Child Health and Human Development (NICHD)
[5R03HD049411-02, K08HD053476-01A1]
FX Grant sponsor: National Institute of Child Health and Human Development
(NICHD); Grant numbers: 5R03HD049411-02, K08HD053476-01A1.
NR 21
TC 16
Z9 17
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUN
PY 2009
VL 149A
IS 6
BP 1237
EP 1240
DI 10.1002/ajmg.a.32684
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 454LT
UT WOS:000266684200018
PM 19449404
ER
PT J
AU Jiang, YH
Fang, P
Adesina, AM
Furman, P
Johnston, JJ
Biesecker, LG
Brown, CW
AF Jiang, Yong-hui
Fang, Ping
Adesina, Adekunle M.
Furman, Patricia
Johnston, Jennifer J.
Biesecker, Leslie G.
Brown, Chester W.
TI Molecular Characterization of Co-Occurring Duchenne Muscular Dystrophy
and X-Linked Oculo-Facio-Cardio-Dental Syndrome in a Girl
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE Duchenne muscular dystrophy; oculo-facio-cardio-dental syndrome;
X-inactivation
ID OFCD SYNDROME; CHROMOSOME INACTIVATION; MALES; DISORDERS; DAUGHTER;
CHILDREN; MOTHER; GENE
AB Duchenne muscular dystrophy is an X-linked condition at the severe end of the spectrum of dystrophinopathies. Females with dystrophin mutations are at risk for cardiomyopathy, but are usually asymptomatic during childhood. However, some girls can exhibit features of Duchenne muscular dystrophy because of skewed X-inactivation, aneuploidy, or chromosomal rearrangement. Oculo-facio-cardio-dental syndrome is a rare X-linked disorder, lethal in males, that comprises microphthalmia, congenital cataracts, congenital heart defect, canine radiculomegaly, and digital anomalies. We report on a 7-year-old girl who was referred for muscular hypotonia, with clinical features of Duchenne muscular dystrophy, including elevated serum creatine phosphokinase, pseudohypertrophy of calf muscles, and muscle weakness, which became evident at 3 years of age. In addition, she had multiple congenital anomalies including atrial septal defect, cataracts, dental and digital anomalies, a constellation that suggested the diagnosis of oculo-facio-cardio-dental syndrome, a condition caused by mutations in BCOR. Immunohistochemistry and Western blot analysis of muscle, and mutation analysis of DMD showed a maternally inherited deletion of exons 30-43, confirming the diagnosis of Duchenne muscular dystrophy. Studies of lymphocytes showed essentially complete skewing of X-inactivation. Mutation analysis of BCOR revealed a de novo frameshift mutation (c.1005delC). Thus, we report for the first time on an individual with the co-occurrence of Duchenne muscular dystrophy and oculo-facio-cardio-dental syndrome. (C) 2009 Wiley-Liss, Inc.
C1 [Fang, Ping; Furman, Patricia; Brown, Chester W.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Jiang, Yong-hui] Duke Univ, Sch Med, Dept Pediat & Neurobiol, Durham, NC USA.
[Adesina, Adekunle M.] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
[Adesina, Adekunle M.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Johnston, Jennifer J.; Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Brown, Chester W.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
RP Brown, CW (reprint author), Baylor Coll Med, Dept Mol & Human Genet, BCM 225,Room R717,1 Baylor Plaza, Houston, TX 77030 USA.
EM cbrown@bcm.edu
FU Baylor College of Medicine Molecular Medicine Program; NIH
FX Grant sponsor: Baylor College of Medicine Molecular Medicine Program;
Grant sponsor: NIH.
NR 17
TC 1
Z9 1
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUN
PY 2009
VL 149A
IS 6
BP 1249
EP 1252
DI 10.1002/ajmg.a.32863
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 454LT
UT WOS:000266684200020
PM 19449433
ER
PT J
AU Conde-Agudelo, A
Romero, R
AF Conde-Agudelo, Agustin
Romero, Roberto
TI Antenatal magnesium sulfate for the prevention of cerebral palsy in
preterm infants less than 34 weeks' gestation: a systematic review and
metaanalysis
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Review
DE cerebral palsy; infant development; magnesium sulfate; metaanalysis;
neurologic handicap; pediatric mortality; prematurity; preterm birth;
systematic review
ID BIRTH-WEIGHT CHILDREN; CONTROLLED-TRIAL; NMDA RECEPTORS; RISK;
PREVALENCE; EXPOSURE; BRAIN; MECHANISMS; MORTALITY; PREGNANCY
AB We conducted a systematic review and metaanalysis of randomized controlled trials to determine whether magnesium sulfate administered to women at risk of preterm delivery before 34 weeks of gestation may reduce the risk of cerebral palsy in their children. Six trials involving 4796 women and 5357 infants were included. Antenatal magnesium sulfate was associated with a significant reduction in the risk of cerebral palsy (relative risk [RR], 0.69; 95% confidence interval [CI], 0.55-0.88), moderate or severe cerebral palsy (RR, 0.64; 95% CI, 0.44-0.92), and substantial gross motor dysfunction (RR, 0.60; 95% CI, 0.43-0.83). There was no overall difference in the risk of total pediatric mortality (RR, 1.01; 95% CI, 0.89-1.14). Minor side effects were more frequent among women receiving magnesium sulfate. In conclusion, magnesium sulfate administered to women at risk of delivery before 34 weeks of gestation reduces the risk of cerebral palsy.
C1 [Conde-Agudelo, Agustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
RP Conde-Agudelo, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institutes of
Health; Department of Health and Human Services
FX Supported was provided by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services.
NR 48
TC 82
Z9 91
U1 0
U2 1
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 JUN
PY 2009
VL 200
IS 6
BP 595
EP 609
DI 10.1016/j.ajog.2009.04.005
PG 15
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 451XX
UT WOS:000266505300003
PM 19482113
ER
PT J
AU Havrilesky, LJ
Maxwell, GL
Myers, ER
AF Havrilesky, Laura J.
Maxwell, G. Larry
Myers, Evan R.
TI Cost-effectiveness analysis of annual screening strategies for
endometrial cancer
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE cost-effectiveness; endometrial cancer; serum screening
ID BREAST-CANCER; RISK; TAMOXIFEN; WOMEN; THICKNESS; MORTALITY; OBESITY;
BIOPSY; ADULTS; STATES
AB OBJECTIVE: The objective of the study was to determine the cost-effectiveness of annual screening tests for endometrial cancer.
STUDY DESIGN: Markov state transition model of the natural history of endometrial cancer used as the design for the study. Incidence was modeled for the general population and high risk groups (obese, body mass index [BMI] of > 30 kg/m(2); tamoxifen users). Strategies evaluated were no screening, annual endometrial biopsy, annual endovaginal ultrasound, and annual serum screening. Serum screening was based on a recently described biomarker panel (sensitivity of 0.98, specificity of 0.98).
RESULTS: In the general population model, no screening was least expensive, whereas annual serum screening age at 50-75 years had incremental cost-effectiveness ratio (ICER) of $60,363 per year of life saved (YLS) compared with no screening. In a high-risk population (obesity, BMI of >= 30 kg/m(2)), annual serum screening at age 45-80 years had ICER of $41,226 per YLS compared with no screening. Annual endometrial biopsy and annual transvaginal ultrasound were dominated.
CONCLUSION: Annual serum screening for endometrial cancer has the potential to be cost effective when applied to high-risk populations.
C1 [Havrilesky, Laura J.] Duke Univ, Med Ctr, Div Gynecol Oncol, Durham, NC 27710 USA.
[Myers, Evan R.] Duke Univ, Med Ctr, Div Clin & Epidemiol Res, Durham, NC 27710 USA.
[Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Maxwell, G. Larry] NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA.
[Maxwell, G. Larry] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Maxwell, G. Larry] US Mil Canc Inst, Washington, DC USA.
RP Havrilesky, LJ (reprint author), Duke Univ, Med Ctr, Div Gynecol Oncol, Box 3079, Durham, NC 27710 USA.
EM havri001@mc.duke.edu
FU American Board of Obstetrics; Gynecology/American Association of
Obstetricians and Gynecologists Foundation
FX Supported by a Grant from the American Board of Obstetrics and
Gynecology/American Association of Obstetricians and Gynecologists
Foundation.
NR 19
TC 1
Z9 1
U1 0
U2 1
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 JUN
PY 2009
VL 200
IS 6
AR 640.e1
DI 10.1016/j.ajog.2009.02.022
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 451XX
UT WOS:000266505300017
PM 19380121
ER
PT J
AU Nosov, V
Su, F
Amneus, M
Birrer, M
Robins, T
Kotlerman, J
Reddy, S
Farias-Eisner, R
AF Nosov, Vladimir
Su, Feng
Amneus, Malaika
Birrer, Michael
Robins, Terry
Kotlerman, Jenny
Reddy, Srinivasa
Farias-Eisner, Robin
TI Validation of serum biomarkers for detection of early-stage ovarian
cancer
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE biomarker; early stage; ovarian cancer
ID CA 125; CA-125
AB OBJECTIVE: Ovarian cancer has the highest mortality of all the gynecologic malignancies with most patients diagnosed at late stages. Serum CA-125 is elevated in only half of patients with stages I-II. We identified 3 serum proteins (apolipoprotein A-1, transthyretin, and transferrin) for the detection of ovarian cancer and reported them combined with CA-125 to effectively detect early-stage mucinous tumors. The objectives of this study were to assess the effectiveness of the panel in detection of early-stage serous and endometrioid ovarian cancers.
STUDY DESIGN: In all, 358 serum samples (control, benign adnexal masses, and early-stage and late-stage ovarian cancer) were obtained from the National Cancer Institute. The level of each marker was measured. Multiple logistic regression models were built to calculate sensitivity and specificity.
RESULTS: When combined with CA-125, the panel detected early-stage cancer with a sensitivity of 96%. The highest sensitivity was seen for detection of endometrioid subtype of early-stage carcinomas (98%).
CONCLUSION: A panel of 4 serum biomarkers effectively detected early-stage ovarian cancers with the highest reported overall sensitivity of 96%. Endometrioid tumors were detected at early stages with a sensitivity of 98%. Prospective clinical analysis of the panel is needed to validate it as an effective screening tool for early-stage ovarian cancer.
C1 [Farias-Eisner, Robin] Univ Calif Los Angeles, Sch Med, Dept Obstet & Gynecol, Med Ctr, Los Angeles, CA 90095 USA.
[Birrer, Michael] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Rockville, MD USA.
[Robins, Terry] Pathway Diagnost Corp, Malibu, CA USA.
[Kotlerman, Jenny] Univ Calif Los Angeles, Sch Med, Dept Med Cardiol, Atherosclerosis Res Unit, Los Angeles, CA 90095 USA.
[Reddy, Srinivasa] Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
RP Farias-Eisner, R (reprint author), Univ Calif Los Angeles, Sch Med, Dept Obstet & Gynecol, Med Ctr, 10833 LeConte Ave,Room 24-137 CHS, Los Angeles, CA 90095 USA.
EM rfeisner@mednet.ucla.edu
NR 15
TC 17
Z9 18
U1 0
U2 1
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 JUN
PY 2009
VL 200
IS 6
AR 639.e1
DI 10.1016/j.ajog.2008.12.042
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 451XX
UT WOS:000266505300016
PM 19285648
ER
PT J
AU Sibai, B
Romero, R
Klebanoff, MA
Rice, MM
Caritis, S
Lindheimer, MD
Van Dorsten, JP
Landon, M
Miodovnik, M
Dombrowski, M
Meis, P
AF Sibai, Baha
Romero, Roberto
Klebanoff, Mark A.
Rice, Madeline Murguia
Caritis, Steve
Lindheimer, Marshall D.
Van Dorsten, J. Peter
Landon, Mark
Miodovnik, Menachem
Dombrowski, Mitchell
Meis, Paul
CA Eunice Kennedy Shriver Natl Inst
TI Maternal plasma concentrations of the soluble tumor necrosis factor
receptor 2 are increased prior to the diagnosis of preeclampsia
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE prediction; preeclampsia; tumor necrosis factor
ID FACTOR-ALPHA; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; NORMAL-PREGNANCY;
TISSUE FACTOR; P55 STNFP55; HIGH-RISK; WOMEN; INTERLEUKIN-6; CYTOKINES
AB OBJECTIVE: Soluble receptor levels of tumor necrosis factor (sTNF-R)-1 and -2 are increased during preeclampsia. We postulated the increase preceded overt disease.
STUDY DESIGN: Archived plasma from the Eunice Kennedy Shriver National Institute of Child Health and Human Development aspirin to prevent preeclampsia in high risk women trial were used to measure serial sTNF-R1 and sTNF-R2 (enrollment, 24-28 week's gestation) in 986 women (577 also sampled at 34- 38 weeks).
RESULTS: Preeclampsia incidence was 21.2%. sTNF-R2 levels were higher at enrollment (P = .02) and weeks 24-28 (P = .01) in women who eventually developed preeclampsia. The magnitude of increase from baseline of both receptors was significantly greater in women who developed preeclampsia in the future. Women with week 24-28 sTNF-R2 levels in the highest quartile had significantly increased odds to develop preeclampsia (P = .03 vs quartile 1). This association was observed in the placebo but not the aspirin arm (P <= .002). Sensitivities and positive predictive values were low.
CONCLUSION: sTNF-R2 levels are elevated prior to overt preeclampsia, suggesting a pathogenetic role for these proinflammatory cytokines.
C1 [Sibai, Baha] Univ Cincinnati, Coll Med, Dept Obstet & Gynecol, Cincinnati, OH 45267 USA.
[Sibai, Baha] Univ Tennessee, Dept Obstet, Memphis, TN USA.
[Sibai, Baha] Univ Tennessee, Dept Gynecol, Memphis, TN USA.
[Romero, Roberto; Klebanoff, Mark A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Rice, Madeline Murguia] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Caritis, Steve] Univ Pittsburgh, Pittsburgh, PA USA.
[Lindheimer, Marshall D.] Univ Chicago, Chicago, IL 60637 USA.
[Van Dorsten, J. Peter] Med Univ S Carolina, Charleston, SC 29425 USA.
[Landon, Mark] Ohio State Univ, Columbus, OH 43210 USA.
[Dombrowski, Mitchell] Wayne State Univ, Detroit, MI USA.
[Meis, Paul] Wake Forest Univ, Winston Salem, NC 27109 USA.
RP Sibai, B (reprint author), Univ Cincinnati, Coll Med, Dept Obstet & Gynecol, 231 Albert Sabin Way, Cincinnati, OH 45267 USA.
OI caritis, steve/0000-0002-2169-0712
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development [HD19897, HD36801, HD21410,
HD21414, HD21434, HD27860, HD27861, HD27869, HD27883, HD27889, HD27905,
HD27915, HD27917]
FX This study was supported in part by the Division of Intramural Research
of the National Institutes of Health and Grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(HD19897, HD36801, HD21410, HD21414, HD21434, HD27860, HD27861, HD27869,
HD27883, HD27889, HD27905, HD27915, and HD27917).
NR 31
TC 5
Z9 5
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUN
PY 2009
VL 200
IS 6
AR 630.e1
DI 10.1016/j.ajog.2009.01.033
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 451XX
UT WOS:000266505300012
PM 19306961
ER
PT J
AU Szabo, R
Kosa, P
List, K
Bugge, TH
AF Szabo, Roman
Kosa, Peter
List, Karin
Bugge, Thomas H.
TI Loss of Matriptase Suppression Underlies Spint1 Mutation-Associated
Ichthyosis and Postnatal Lethality
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; FACTOR ACTIVATOR INHIBITOR; SERINE-PROTEASE
INHIBITOR; AUTOSOMAL RECESSIVE ICHTHYOSIS; KUNITZ DOMAINS;
FUNCTIONAL-CHARACTERIZATION; FOLLICULAR ATROPHODERMA; HYPOTRICHOSIS
SYNDROME; CONGENITAL ICHTHYOSIS; TRANSMEMBRANE DOMAIN
AB Hepatocyte growth factor activator inhibitor-1 (HAI)-1 is an epithelial Kunitz-type transmembrane serine protease inhibitor that is encoded by the SPINT1 gene. HAI-1 displays potent inhibitory activity toward a large number of trypsin-like serine proteases. HAI-1 was recently shown to play an essential role in postnatal epithelial homeostasis. Thus, Spint1-deficient mice were found to display severe growth retardation and are unable to survive beyond postnatal day 16. The mice present histologically with overt hyperkeratosis of die forestomach, hyperkeratosis and acanthosis of the epidermis, and hypotrichosis associated with abnormal cuticle development. in this study, we show that loss of inhibition of a proteolytic pathway that is dependent on the type H transmembrane serine protease, matriptase, underlies die detrimental effects of postnatal Spint1 deficiency. Matriptase and HAI-1 precisely co-localize in all tissues that are affected by the Spint1 disruption. Spint1-deficient mice that have low matriptase levels, caused by a hypomorphic mutation in the St14 gene that encodes matriptase, not only survived the neonatal period but were healthy and displayed normal long-term survival. Furthermore, a detailed histological analysis of neonatal, young adult, as well as aged mice did not reveal any abnormalities in Spint1-deficent mice that have low matriptase levels. This study identifies matriptase suppression as an essential function of HAI-1 in postnatal tissue homeostasis. (Am J Pathol 2009, 174:2015-2022; DOI:10.2353/ajpath.2009.090053)
C1 [Bugge, Thomas H.] NIH, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, Natl Inst Dent & Carniofacial Res, Bethesda, MD 20892 USA.
[List, Karin] Wayne State Univ, Sch Med, Dept Pharmacol, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA.
RP Bugge, TH (reprint author), NIH, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, Natl Inst Dent & Carniofacial Res, 30 Convent Dr,Room 211, Bethesda, MD 20892 USA.
EM thomas.bugge@nih.gov
FU NIDCR Intramural Research Program; Wayne State University
FX Supported by the NIDCR Intramural Research Program (T.H.B.) and by
startup funds from Wayne State University (K.L.)
NR 46
TC 38
Z9 38
U1 0
U2 1
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2009
VL 174
IS 6
BP 2015
EP 2022
DI 10.2353/ajpath.2009.090053
PG 8
WC Pathology
SC Pathology
GA 449ZT
UT WOS:000266370600006
PM 19389929
ER
PT J
AU Rodriguez, OC
Lai, EW
Vissapragada, S
Cromelin, C
Avetian, M
Salinas, P
Ramos, H
Kallakury, B
Casimiro, M
Lisanti, MP
Tanowitz, HB
Pacak, K
Glazer, RI
Avantaggiati, M
Albanese, C
AF Rodriguez, Olga C.
Lai, Edwin W.
Vissapragada, Sarada
Cromelin, Caroline
Avetian, Maral
Salinas, Patricia
Ramos, Hida
Kallakury, Bhaskar
Casimiro, Mathew
Lisanti, Michael P.
Tanowitz, Herbert B.
Pacak, Karel
Glazer, Robert I.
Avantaggiati, Maria
Albanese, Chris
TI A Reduction in Pten Tumor Suppressor Activity Promotes ErbB-2-Induced
Mouse Prostate Adenocarcinoma Formation through the Activation of
Signaling Cascades Downstream of PDK1
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID CANCER CELLS; CYCLIN D1; IN-VIVO; 4E-BINDING PROTEIN-1; MAMMALIAN
TARGET; HUMAN BREAST; EXPRESSION; PATHWAY; GROWTH; TUMORIGENESIS
AB Loss of function at the Pten tumor-suppressor locus is a common genetic modification found in human prostate cancer. While recent in vivo and in vitro data support an important role of aberrant ErbB-2 signaling to clinically relevant prostate target genes, such as cyclin D1, the role of Pten in ErbB-2-induced prostate epithelial proliferation is not well understood. in the Pten-deficient prostate cancer cell line, LNCaP, restoration of Pten was able to inhibit ErbB-2- and heregulin-induced cell cycle progression, as well as cyclin D1 protein levels and promoter activity. Previously, we established that probasin-driven ErbB-2 transgenic mice presented with high-grade prostate intraepithelial neoplasia and increased nuclear cyclin D1 levels. We show that monoallelic loss of pten in the probasin-driven-ErbB-2 model resulted in increased nuclear cyclin D1 and proliferating cell nuclear antigen levels and decreased disease latency compared to either individual genetic model and, unlike the probasin-driven-ErbB-2 mice, progression to adenocarcinoma. Activated 3-phosphoinositide-dependent protein kinase-1 was observed during cancer initiation combined with die activation of p70S6K (phospho-T389) and inactivation of die 4E-binding protein-1 (phosphorylated on T37/46) and was primarily restricted to those cases of prostate cancer that had progressed to adenocarcinoma. Activation of mTOR was not seen. Our data demonstrates that Pten functions downstream of ErbB-2 to restrict prostate epithelial transformation by blocking full activation of the PDK1 signaling cascade. (Am J Pathol, 2009, 174:2051-2060; DOI:10.2353/ajpath.2009.080859)
C1 [Rodriguez, Olga C.; Lai, Edwin W.; Vissapragada, Sarada; Cromelin, Caroline; Avetian, Maral; Salinas, Patricia; Ramos, Hida; Kallakury, Bhaskar; Glazer, Robert I.; Avantaggiati, Maria; Albanese, Chris] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
[Kallakury, Bhaskar; Albanese, Chris] Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC 20057 USA.
[Lai, Edwin W.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Program, Bethesda, MD USA.
[Casimiro, Mathew; Lisanti, Michael P.] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
[Tanowitz, Herbert B.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.
RP Albanese, C (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
EM albanese@georgetown.edu
RI Lisanti, Michael/C-6866-2013
FU National Institutes of Health (NIH) [R01CA129003, U54CA100970-02,
R01CA111482]; American Institute for Cancer Research [AICR05B131];
Intramural Research Program of the NIH; National Institute for Child
Health and Human Development
FX Supported by grants from the National Institutes of Health (NIH)
R01CA129003, U54CA100970-02, and the American Institute for Cancer
Research (AICR05B131), (to C.A.) NIH R01CA111482 (R.I.G) and in part by
grants from the Intramural Research Program of the NIH and the National
Institute for Child Health and Human Development (to E.W.L. and K.P.).
NR 36
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Z9 15
U1 0
U2 3
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2009
VL 174
IS 6
BP 2051
EP 2060
DI 10.2353/ajpath.2009.080859
PG 10
WC Pathology
SC Pathology
GA 449ZT
UT WOS:000266370600010
PM 19443706
ER
PT J
AU Ju, WJ
Eichinger, F
Bitzer, M
Oh, J
McWeeney, S
Berthier, CC
Shedden, K
Cohen, CD
Henger, A
Krick, S
Kopp, JB
Stoeckert, CJ
Dikman, S
Schroppel, B
Thomas, DB
Schlondorff, D
Kretzler, M
Bottinger, EP
AF Ju, Wenjun
Eichinger, Felix
Bitzer, Markus
Oh, Jun
McWeeney, Shannon
Berthier, Celine C.
Shedden, Kerby
Cohen, Clemens D.
Henger, Anna
Krick, Stefanie
Kopp, Jeffrey B.
Stoeckert, Christian J., Jr.
Dikman, Steven
Schroeppel, Bernd
Thomas, David B.
Schlondorff, Detlef
Kretzler, Matthias
Boettinger, Erwin P.
TI Renal Gene and Protein Expression Signatures for Prediction of Kidney
Disease Progression
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID GROWTH-FACTOR-BETA; TGF-BETA; DIABETIC-NEPHROPATHY; TRANSGENIC MICE;
MICROARRAY DATA; RISK SCORES; APOPTOSIS; ACTIVATION; FIBROSIS; SURVIVAL
AB Although chronic kidney disease (CKD) is common, only a fraction of CKD patients progress to end-stage renal disease. Molecular predictors to stratify CKD populations according to their risk of progression remain undiscovered. Here we applied transcriptional profiling of kidneys from transforming growth factor-beta 1 transgenic (Tg) mice, characterized by heterogeneity of kidney disease progression, to identify 43 genes that discriminate kidneys by severity of glomerular apoptosis before the onset of tubulointerstitial fibrosis in 2-week-old animals. Among the genes examined, 19 showed significant correlation between mRNA expression in uninephrectomized left kidneys at 2 weeks of age and renal disease severity in right kidneys of Tg mice at 4 weeks of age. Gene expression profiles of human orthologs of the 43 genes in kidney biopsies were highly significantly related (R(2) = 0.53; P < 0.001) to the estimated glomerular filtration rates in patients with CKD stages I to V, and discriminated groups of CKD stages I/II and III/IV/V with positive and negative predictive values of 0.8 and 0.83, respectively. Protein expression patterns for selected genes were successfully validated by immunohistochemistry in kidneys of Tg mice and kidney biopsies of patients with IgA nephropathy and CKD stages I to V, respectively. In conclusion, we developed novel mRNA and protein expression signatures that predict progressive renal fibrosis in mice and may be useful molecular predictors of CKD progression in humans. (Am J Pathol 2009, 174:2073-2085; DOI:10.2353/ajpath.2009.080888)
C1 [Boettinger, Erwin P.] Mt Sinai Med Ctr, Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA.
[Dikman, Steven] Mt Sinai Med Ctr, Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA.
[Eichinger, Felix; Berthier, Celine C.; Henger, Anna; Kretzler, Matthias] Univ Michigan, Dept Internal Med Nephrol, Ann Arbor, MI 48109 USA.
[Shedden, Kerby] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA.
[Bitzer, Markus] Albert Einstein Coll Med, Dept Med, Div Nephrol, Bronx, NY 10467 USA.
[Oh, Jun] Univ Heidelberg, Dept Pediat Nephrol, Heidelberg, Germany.
[McWeeney, Shannon] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97201 USA.
[Cohen, Clemens D.] Univ Zurich, Nephrol Clin, Zurich, Switzerland.
[Cohen, Clemens D.] Univ Zurich, Inst Physiol, Zurich, Switzerland.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD USA.
[Stoeckert, Christian J., Jr.] Univ Penn, Sch Med, Dept Genet, Ctr Bioinformat, Philadelphia, PA 19104 USA.
[Thomas, David B.] Nephrocor, New York Lab, Uniondale, NY USA.
RP Bottinger, EP (reprint author), Mt Sinai Med Ctr, Mt Sinai Sch Med, Dept Med, Div Nephrol, 1 Gustave L Levy Pl,Box 1118, New York, NY 10029 USA.
EM kretzler@med.umich.edu
OI McWeeney, Shannon/0000-0001-8333-6607; Kopp, Jeffrey/0000-0001-9052-186X
FU National Institutes of Health [5R01DK056077-09, 5R01DK060043-07,
5R01DK073960-02, 5U01DK060995-08, R01 DK079912-01]; Else-Kroener
Fresenius Foundation; American Heart Association; National Kidney
Foundation
FX Supported by the National Institutes of Health (grants 5R01DK056077-09
to E.P.B., 5R01DK060043-07 to E.P.B., 5R01DK073960-02 to E.P.B.,
5U01DK060995-08 to E.P.B., R01 DK079912-01 to M.K. and R21 DK079441-01
M.K.), the Else-Kroener Fresenius Foundation (to C.D.C., D.S., and
M.K.), the American Heart Association (research fellowship to W.J.), and
the National Kidney Foundation (to M.B. and C.B).
NR 55
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U1 0
U2 1
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2009
VL 174
IS 6
BP 2073
EP 2085
DI 10.2353/ajpath.2009.080888
PG 13
WC Pathology
SC Pathology
GA 449ZT
UT WOS:000266370600012
PM 19465643
ER
PT J
AU Auerbach, MB
Shimoda, N
Amano, H
Rosenblum, JM
Kish, DD
Farber, JM
Fairchild, RL
AF Auerbach, Michael B.
Shimoda, Naohiko
Amano, Hiroyuki
Rosenblum, Joshua M.
Kish, Danielle D.
Farber, Joshua M.
Fairchild, Robert L.
TI Monokine Induced by Interferon-gamma (MIG/CXCL9) Is Derived from Both
Donor and Recipient Sources during Rejection of Class II Major
Histocompatibility Complex Disparate Skin Allografts
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID CHEMOKINE RECEPTOR CXCR3; IFN-GAMMA; CARDIAC ALLOGRAFTS;
GRAFT-REJECTION; GENE-EXPRESSION; IMMUNE-RESPONSE; CRITICAL TARGET;
VASCULAR BED; T-CELLS; IN-VIVO
AB Chemokines, including monokine induced by interferon-gamma (Mig/CXCL9), are produced both in allografts and during the direct T-cell infiltration that mediates graft rejection. Neither the specific production nor contribution of allograft donor versus recipient Mig in allograft rejection is currently known. C57BL/6 mice with a targeted deletion in the Mig gene were used as both skin allograft donors and recipients in a class II major histocompatibility complex-mismatched graft model to test the requirement for donor- versus recipient-derived Mig for acute rejection. B6.Mig(-/-) allografts had a 10-day prolonged survival in B6.H-2(bm12) recipients when compared with wildtype C57BL/6 allograft donors, and B6.H-2(bm12) skin allografts had a 5-day prolonged survival in B6.Mig(-/-) versus wild-type recipients. Transplantation of B6.Mig(-/-) skin grafts onto B6.H-2(bm12).Mig(-/-) recipients resulted in further prolonged allograft survival with more than 30% of the grafts surviving longer than 60 days. Prolonged allograft survival was also associated with delayed cellular infiltration into grafts but not with altered T-cell proliferative responses to donor stimulators. Immunohistochemical staining of allograft sections indicated that Mig is produced by both donor- and recipient-derived sources, but Mig from each of these sources appeared in different areas of the allograft tissue. These results therefore demonstrate the synergy of donor- and recipient-derived Mig in promoting T-cell infiltration into allografts. (Am J Pathol 2009, 174:2172-2181; DOI:10.2353/ajpath.2009.080516)
C1 [Auerbach, Michael B.; Shimoda, Naohiko; Amano, Hiroyuki; Rosenblum, Joshua M.; Kish, Danielle D.; Fairchild, Robert L.] Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA.
[Shimoda, Naohiko; Amano, Hiroyuki; Fairchild, Robert L.] Cleveland Clin Fdn, Glickman Urol Inst, Cleveland, OH 44195 USA.
[Rosenblum, Joshua M.; Fairchild, Robert L.] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA.
[Farber, Joshua M.] NIAID, Inflammat Biol Sect, Lab Mol Immunol, Bethesda, MD 20892 USA.
RP Fairchild, RL (reprint author), Cleveland Clin Fdn, Dept Immunol, NB3-59,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM fairchr@ccf.org
FU National Institute of Allergy and Infectious Diseases [RO1-40459,
RO1-51620]
FX Supported by the National Institute of Allergy and Infectious Diseases
(grants RO1-40459 and RO1-51620 to R.L.F).
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U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2009
VL 174
IS 6
BP 2172
EP 2181
DI 10.2353/ajpath.2009.080516
PG 10
WC Pathology
SC Pathology
GA 449ZT
UT WOS:000266370600021
PM 19389928
ER
PT J
AU Madson, JG
Lynch, DT
Svoboda, J
Ophardt, R
Yanagida, J
Putta, SK
Bowles, A
Trempus, CS
Tennant, RW
Hansen, LA
AF Madson, Justin G.
Lynch, David T.
Svoboda, Jessica
Ophardt, Rebecca
Yanagida, Jodi
Putta, Sumanth K.
Bowles, Andrew
Trempus, Carol S.
Tennant, Raymond W.
Hansen, Laura A.
TI Erbb2 Suppresses DNA Damage-Induced Checkpoint Activation and UV-Induced
Mouse Skin Tumorigenesis
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID GROWTH-FACTOR-RECEPTOR; ULTRAVIOLET-IRRADIATION; HUMAN KERATINOCYTES;
HUMAN CDC25A; CELL-CYCLE; PATHWAY; CHK1; PHOSPHORYLATION; PROLIFERATION;
INHIBITION
AB The Erbb2 receptor is activated by UV irradiation, the primary cause of non-melanoma skin cancer. We hypothesized that Erbb2 activation contributes to UV-induced skin tumorigenesis by suppressing cell cycle arrest. Consistent with this hypothesis, inhibition of Erbb2 in v-ras(Ha) transgenic mice before UV exposure resulted in both 56% fewer skin tumors and tumors that were 70% smaller. Inhibition of the UV-induced activation of Erbb2 also resulted in milder epidermal hyperplasia, S-phase accumulation, and decreased levels of the cell cycle regulator Cdc25a, suggesting altered cell cycle regulation on inhibition of Erbb2. Further investigation using inhibition or genetic deletion of Erbb2 in vitro revealed reduced Cdc25a levels and increased S-phase arrest in UV-irradiated cells lacking Erbb2 activity. Ectopic expression of Cdc25a prevented UV-induced S-phase arrest in keratinocytes lacking Erbb2 activity, demonstrating that maintenance of Cdc25a by Erbb2 suppresses cell cycle arrest. Examination of checkpoint pathway activation upstream of Cdc25a revealed Erbb2 activation did not alter Ataxia Telangiectasia and Rad3-related/Ataxia Telangiectasia Mutated activity but increased inhibitory phosphorylation of Chk1-Ser(280). Since Akt phosphorylates; Chk1-Ser(280), the effect of Erbb2 on phosphatidyl inositol-3-kinase (PI3K)/Akt signaling during UV-induced cell cycle arrest was determined. Erbb2 ablation reduced the UV-induced activation of PI3K while inhibition of PI3K/Akt increased UV-induced S-phase arrest. Thus, UV-induced Erbb2 activation increases skin tumorigenesis through inhibitory phosphorylation of Chk1, Cdc25a maintenance, and suppression of S-phase arrest via a PI3K/Akt-dependent mechanism. (Am J Pathol 2009, 174:2357-4306; DOI: 10.2353/ajpath.2009.080638)
C1 [Hansen, Laura A.] Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA.
[Trempus, Carol S.; Tennant, Raymond W.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
RP Hansen, LA (reprint author), Creighton Univ, Sch Med, Dept Biomed Sci, 2500 Calif Plaza, Omaha, NE 68178 USA.
EM lhanqen@creighton.edu
RI putta, sumanth/E-3933-2010
FU National Institutes of Health (NIH) [P20 RR018759, 1RO1ES015585];
National Institute for Environmental, Health Sciences, NIH; State of
Nebraska [LB595]; National Center for Research Resources, NIH [1 CO6
RR17417-01]
FX Supported in part by the Intramural Research Program of the National
Institutes of Health (NIH). National Institute for Environmental and
Health Sciences, NIH (grants P20 RR018759 and 1RO1ES015585) and by the
State of Nebraska LB595 This investigation was conducted in a facility
constructed with support from Research Facilities Improvement Program
Grant Number 1 CO6 RR17417-01 from the National Center for Research
Resources, NIH.
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U1 1
U2 2
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2009
VL 174
IS 6
BP 2357
EP 2366
DI 10.2353/ajpath.2009.080638
PG 10
WC Pathology
SC Pathology
GA 449ZT
UT WOS:000266370600038
PM 19406993
ER
PT J
AU Sonies, BC
Cintas, HL
Parks, R
Miller, J
Caggiano, C
Gottshall, SG
Gerber, L
AF Sonies, Barbara C.
Cintas, Holly Lea
Parks, Rebecca
Miller, Jeri
Caggiano, Collette
Gottshall, Shawna Gearhart
Gerber, Lynn
TI Brief Assessment of Motor Function Content Validity and Reliability of
the Oral Motor Scales
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article; Proceedings Paper
CT 15th International Congress of the
World-Confederation-for-Physical-Therapy
CY JUN 02-06, 2007
CL Vancouver, CANADA
SP World Confederat Phys Therapy
DE Rehabilitation; Articulation; Deglutition; Oral Motor Assessment
AB Objective: The Brief Assessment of Motor Function consists of five 0- to 10-point hierarchical scales designed for rapid assessment of gross, fine, and oral motor skills. We describe the development and evaluation of the two Brief Assessment of Motor Function Oral Motor Scales: Oral Motor Articulation and Oral Motor Deglutition.
Design: This validation study employed an expert panel of 28 speech-language pathologists, who rated the Brief Assessment of Motor Function Oral Motor Scales items on a scale from 1 to 4 (disagree to agree) to establish content validity. For reliability, oral motor performances of 18 participants (6 mos-20 yrs) were videotaped to represent a wide range of articulation and deglutition capabilities. Four speech-language pathologists, and I undergraduate and 10 graduate speech-language pathology students rated the participants' taped samples using the Brief Assessment of Motor Function Oral Motor Scales.
Results: All items on the content validity questionnaire had average agreement scores that exceeded criteria, except two, which were not clearly worded; these were clarified. Interrater and intrarater reliability values were 0.997 and 0.986 for the Oral Motor Articulation Scale and 0.977 and 0.997 for the Oral Motor Deglutition Scale.
Conclusions: Expert feedback and reliability procedures suggest that the Brief Assessment of Motor Function Oral Motor Articulation and Deglutition Scales represent the content that they are designed to assess and are reliable for rapid assessment of oral motor skills.
C1 [Cintas, Holly Lea; Caggiano, Collette; Gottshall, Shawna Gearhart] NIH, Summer Res Student Program, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Sonies, Barbara C.] Univ Maryland, Dept Speech & Hearing Sci, College Pk, MD 20742 USA.
[Gottshall, Shawna Gearhart] Horizon High Sch Cerebral Palsy N Jersey, Livingston, NJ USA.
[Gerber, Lynn] George Mason Univ, Ctr Chron Illness & Disabil, Fairfax, VA 22030 USA.
RP Cintas, HL (reprint author), NIH, Summer Res Student Program, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bldg 10,Room 1-146 9NE, Bethesda, MD 20892 USA.
NR 20
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U1 0
U2 3
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 JUN
PY 2009
VL 88
IS 6
BP 464
EP 472
DI 10.1097/PHM.0b013e3181a5abad
PG 9
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 451DM
UT WOS:000266450900004
PM 19454854
ER
PT J
AU Wansapura, AN
Lasko, V
Xie, ZJ
Fedorova, OV
Bagrov, AY
Lingrel, JB
Lorenz, JN
AF Wansapura, Arshani N.
Lasko, Valerie
Xie, Zijian
Fedorova, Olga V.
Bagrov, Alexei Y.
Lingrel, Jerry B.
Lorenz, John N.
TI Marinobufagenin enhances cardiac contractility in mice with
ouabain-sensitive alpha(1) Na+-K+-ATPase
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE cardiotonic steroids; sodium-potassium-adenosinetriphosphatase isoforms
ID ENDOGENOUS OUABAIN; UREMIC CARDIOMYOPATHY; VOLUME EXPANSION;
SODIUM-PUMP; NA,K-ATPASE; HYPERTENSION; NA+,K+-ATPASE; GLYCOSIDE;
LIGANDS; HEART
AB Wansapura AN, Lasko V, Xie Z, Fedorova OV, Bagrov AY, Lingrel JB, Lorenz JN. Marinobufagenin enhances cardiac contractility in mice with ouabain-sensitive alpha(1) Na+-K+-ATPase. Am J Physiol Heart Circ Physiol 296: H1833-H1839, 2009. First published April 17, 2009; doi:10.1152/ajpheart.00285.2009.-Endogenous Na+ pump inhibitors are thought to play important (patho) physiological roles and occur in two different chemical forms in the mammalian circulation: cardenolides, such as ouabain, and bufadienolides, such as marinobufagenin (MBG). Although all alpha Na+-K+-ATPase isoforms (alpha(1-4))are sensitive to ouabain in most species, in rats and mice the ubiquitously expressed alpha(1) Na+-K+-ATPase is resistant to ouabain. We have previously shown that selective modification of the putative ouabain binding site of either the alpha(1) or alpha(2) Na+-K+-ATPase subunit in mice substantially alters the cardiotonic influence of exogenously applied cardenolides. To determine whether the ouabain binding site also interacts with MBG and if this interaction plays a functional role, we evaluated cardiovascular function in alpha(1)-resistant/alpha(2)-resistant (alpha(R/R)(1)alpha(R/R)(2)), alpha(1)-sensitive/alpha(2)-resistant (alpha(S/S)(1)alpha(R/R)(2)), and alpha(1)-resistant/alpha(2)-sensitive mice (alpha(R/R)(1)alpha(S/S)(2), wild type). Cardiovascular indexes were evaluated in vivo by cardiac catheterization at baseline and during graded infusions of MBG. There were no differences in baseline measurements of targeted mice, indicating normal hemodynamics and cardiac function. MBG at 0.025, 0.05, and 0.1 nmol.min(-1).g body wt(-1) significantly increased cardiac performance to a greater extent in alpha(S/S)(1)alpha(R/R)(2) compared with alpha(R/R)(1)alpha(R/R)(2) and wild-type mice. The increase in LVdP/dt(max) in alpha(S/S)(1)alpha(R/R)(2) mice was greater at higher concentrations of MBG compared with both alpha(R/R)(1)alpha(R/R)(2) and alpha(R/R)(1)alpha(S/S)(2) mice (P < 0.05). These results suggest that MBG interacts with the ouabain binding site of the alpha(1) Na+-K+-ATPase subunit and can thereby influence cardiac inotropy.
C1 [Wansapura, Arshani N.; Lasko, Valerie; Lorenz, John N.] Univ Cincinnati, Coll Med, Dept Mol & Cellular Physiol, Cincinnati, OH 45267 USA.
[Lingrel, Jerry B.] Univ Cincinnati, Coll Med, Dept Mol Genet, Cincinnati, OH 45267 USA.
[Xie, Zijian] Univ Toledo, Coll Med, Dept Physiol & Pharmacol, Toledo, OH 43606 USA.
[Fedorova, Olga V.; Bagrov, Alexei Y.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
RP Lorenz, JN (reprint author), Univ Cincinnati, Coll Med, Dept Mol & Cellular Physiol, 231 Albert Sabin Way,POB 670576, Cincinnati, OH 45267 USA.
EM john.lorenz@uc.edu
FU National Institutes of Health (NIH) [DK-57552, HL-66062, HL-28573];
National Institute of Aging, NIH
FX This work was supported by National Institutes of Health (NIH) Grants
DK-57552 (J. N. Lorenz), HL-66062, and HL-28573 (J. B. Lingrel) and the
by Intramural Research Program, National Institute of Aging, NIH (A. Y.
Bagrov and O. V. Fedorova).
NR 27
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U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JUN
PY 2009
VL 296
IS 6
BP H1833
EP H1839
DI 10.1152/ajpheart.00285.2009
PG 7
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 450JT
UT WOS:000266397500016
PM 19376809
ER
PT J
AU Francis, RJB
Chatterjee, B
Loges, NT
Zentgraf, H
Omran, H
Lo, CW
AF Francis, Richard J. B.
Chatterjee, Bishwanath
Loges, Niki T.
Zentgraf, Hanswalter
Omran, Heymut
Lo, Cecilia W.
TI Initiation and maturation of cilia-generated flow in newborn and
postnatal mouse airway
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE ciliogenesis; development; murine model; primary ciliary dyskinesia;
trachea
ID BEAT FREQUENCY; NASAL CILIARY; DYSKINESIA; MICE; DEFECTS; MUTATIONS;
HYDROCEPHALUS; CILIOPATHIES; CILIOGENESIS; DYSFUNCTION
AB Francis RJ, Chatterjee B, Loges NT, Zentgraf H, Omran H, Lo CW. Initiation and maturation of cilia-generated flow in newborn and postnatal mouse airway. Am J Physiol Lung Cell Mol Physiol 296: L1067-L1075, 2009. First published April 3, 2009; doi: 10.1152/ajplung.00001.2009.-Mucociliary clearance in the adult trachea is well characterized, but there are limited data in newborns. Cilia-generated flow was quantified across longitudinal sections of mouse trachea from birth through postnatal day (PND) 28 by tracking fluorescent microsphere speed and directionality. The percentage of ciliated tracheal epithelial cells, as determined by immunohistochemistry, was shown to increase linearly between PND 0 and PND 21 (R(2) = 0.94). While directionality measurements detected patches of flow starting at PND 3, uniform flow across the epithelia was not observed until PND 7 at a similar to 35% ciliated cell density. Flow became established at a maximal rate at PND 9 and beyond. A linear correlation was observed between the percentage of ciliated cells versus flow speed (R(2) = 0.495) and directionality (R(2) = 0.975) between PND 0 and PND 9. Cilia beat frequency (CBF) was higher at PND 0 than at all subsequent time points, but cilia beat waveform was not noticeably different. Tracheal epithelia from a mouse model of primary ciliary dyskinesia (PCD) harboring a Mdnah5 mutation showed that ciliated cell density was unaffected, but no cilia-generated flow was detected. Cilia in mutant airways were either immotile or with slow dyssynchronous beat and abnormal ciliary waveform. Overall, our studies showed that the initiation of cilia-generated flow is directly correlated with an increase in epithelial ciliation, with the measurement of directionality being more sensitive than speed for detecting flow. The higher CBF observed in newborn epithelia suggests unique physiology in the newborn trachea, indicating possible clinical relevance to the pathophysiology of respiratory distress seen in newborn PCD patients.
C1 [Francis, Richard J. B.; Chatterjee, Bishwanath; Lo, Cecilia W.] NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Loges, Niki T.; Omran, Heymut] Univ Hosp Freiburg, Dept Pediat & Adolescent Med, Freiburg, Germany.
[Zentgraf, Hanswalter] German Canc Res Ctr, Dept Tumor Virol, D-6900 Heidelberg, Germany.
RP Lo, CW (reprint author), 10 Ctr Dr,Bldg 10,Room 6C-103A,MSC-1583, Bethesda, MD 20892 USA.
EM loc@nhlbi.nih.gov
RI Francis, Richard/P-2524-2015
FU National Heart, Lung, and Blood Institute [ZO1-HL-005701]
FX This work was supported by National Heart, Lung, and Blood Institute
Grant ZO1-HL-005701.
NR 34
TC 19
Z9 20
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD JUN
PY 2009
VL 296
IS 6
BP L1067
EP L1075
DI 10.1152/ajplung.00001.2009
PG 9
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 450YQ
UT WOS:000266438300024
PM 19346437
ER
PT J
AU Boini, KM
Graf, D
Hennige, AM
Koka, S
Kempe, DS
Wang, K
Ackermann, TF
Foller, M
Vallon, V
Pfeifer, K
Schleicher, E
Ullrich, S
Haring, HU
Haussinger, D
Lang, F
AF Boini, Krishna M.
Graf, Dirk
Hennige, Anita M.
Koka, Saisudha
Kempe, Daniela S.
Wang, Kan
Ackermann, Teresa F.
Foeller, Michael
Vallon, Volker
Pfeifer, Karl
Schleicher, Erwin
Ullrich, Susanne
Haering, Hans-Ulrich
Haeussinger, Dieter
Lang, Florian
TI Enhanced insulin sensitivity of gene-targeted mice lacking functional
KCNQ1
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Article
DE K(+) channels; blood glucose; kidney; liver; skeletal muscle
ID PERFUSED-RAT-LIVER; K-ATP-CHANNELS; CELL-VOLUME; POTASSIUM CHANNELS;
PARIETAL-CELLS; METABOLIC SENSORS; SECRETION; SHRINKAGE; MEMBRANE;
PROTEIN
AB Boini KM, Graf D, Hennige AM, Koka S, Kempe DS, Wang K, Ackermann TF, Foller M, Vallon V, Pfeifer K, Schleicher E, Ullrich S, Haring HU, Haussinger D, Lang F. Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1. Am J Physiol Regul Integr Comp Physiol 296: R1695-R1701, 2009. First published April 15, 2009; doi:10.1152/ajpregu.90839.2008.-The pore-forming K(+)-channel alpha-subunit KCNQ1 is expressed in a wide variety of tissues including heart, skeletal muscle, liver, and epithelia. Most recent evidence revealed an association of the KCNQ1 gene with the susceptibility to type 2 diabetes. KCNQ1 participates in the regulation of cell volume, which is, in turn, critically important for the regulation of metabolism by insulin. The present study explored the influence of KCNQ1 on insulin-induced cellular K(+) uptake and glucose metabolism. Insulin (100 nM)-induced K(+) uptake was determined in isolated perfused livers from KCNQ1-deficient mice (kcnq1(-/-)) and their wild-type littermates (kcnq1(+/+)). Moreover, plasma glucose and insulin levels, intraperitoneal glucose (3 g/kg) tolerance, insulin (0.15 U/kg)-induced hypoglycemia, and peripheral uptake of radiolabeled (3)H-deoxy-glucose were determined in both genotypes. Insulin-stimulated hepatocellular K(+) uptake was significantly more sustained in isolated perfused livers from kcnq1(-/-) mice than from kcnq1(+/+) mice. The decline of plasma glucose concentration following an intraperitoneal injection of insulin was again significantly more sustained in kcnq1(-/-) than in kcnq1(+/+) mice. Both fasted and nonfasted plasma glucose and insulin concentrations were significantly lower in kcnq1(-/-) than in kcnq1(+/+) mice. Following an intraperitoneal glucose injection, the peak plasma glucose concentration was significantly lower in kcnq1(-/-) than in kcnq1(+/+) mice. Uptake of (3)H-deoxy-glucose into skeletal muscle, liver, kidney and lung tissue was significantly higher in kcnq1(-/-) than in kcnq1(+/+) mice. In conclusion, KCNQ1 counteracts the stimulation of cellular K(+) uptake by insulin and thereby influences K(+)-dependent insulin signaling on glucose metabolism. The observations indicate that KCNQ1 is a novel molecule affecting insulin sensitivity of glucose metabolism.
C1 [Boini, Krishna M.; Koka, Saisudha; Kempe, Daniela S.; Wang, Kan; Ackermann, Teresa F.; Foeller, Michael; Lang, Florian] Univ Tubingen, Dept Physiol 1, D-72076 Tubingen, Germany.
[Hennige, Anita M.; Schleicher, Erwin; Ullrich, Susanne; Haering, Hans-Ulrich] Univ Tubingen, Dept Internal Med, Div Diabetol Endocrinol Angiol Nephrol & Clin Che, D-72076 Tubingen, Germany.
[Graf, Dirk; Haeussinger, Dieter] Univ Dusseldorf, Dept Gastroenterol Hepatol & Infectiol, Dusseldorf, Germany.
[Vallon, Volker] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Vallon, Volker] Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92103 USA.
[Pfeifer, Karl] NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA.
RP Lang, F (reprint author), Univ Tubingen, Dept Physiol, Gmelinstr 5, D-72076 Tubingen, Germany.
EM florian.lang@uni-tuebingen.de
RI Boini, Krishna/H-3548-2011; koka, Saisudha/F-2381-2012;
OI Pfeifer, Karl/0000-0002-0254-682X
FU Deutsche Forschungsgemeinschaft [GK 1302]; Sonderforschungsbereich 575
Experimental Hepatology
FX This study was supported by the Deutsche Forschungsgemeinschaft (GK
1302) and Sonderforschungsbereich 575 Experimental Hepatology.
NR 56
TC 27
Z9 28
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 JUN
PY 2009
VL 296
IS 6
BP R1695
EP R1701
DI 10.1152/ajpregu.90839.2008
PG 7
WC Physiology
SC Physiology
GA 448FE
UT WOS:000266247700003
PM 19369585
ER
PT J
AU Puertollano, R
Kiselyov, K
AF Puertollano, Rosa
Kiselyov, Kirill
TI TRPMLs: in sickness and in health
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Review
DE mucolipin; endocytosis; ion channel; membrane traffic; lysosome
ID MUCOLIPIDOSIS TYPE-IV; FOCAL SEGMENTAL GLOMERULOSCLEROSIS;
VARITINT-WADDLER PHENOTYPE; RECEPTOR POTENTIAL CHANNEL; INTEGRAL
MEMBRANE-PROTEIN; X-RAY-STRUCTURE; CATION CHANNEL; LYSOSOMAL PATHWAY;
PLASMA-MEMBRANE; RELEASE CHANNEL
AB Puertollano R, Kiselyov K. TRPMLs: in sickness and in health. Am J Physiol Renal Physiol 296: F1245-F1254, 2009. First published January 21, 2009; doi: 10.1152/ajprenal.90522.2008.-TRPML1, TRPML2 and TRPML3 belong to the mucolipin family of the TRP superfamily of ion channels. The founding member of this family, TRPML1, was cloned during the search for the genetic determinants of the lysosomal storage disease mucolipidosis type IV (MLIV). Mucolipins are predominantly expressed within the endocytic pathway, where they appear to regulate membrane traffic and/or degradation. The physiology of mucolipins raises some of the most interesting questions of modern cell biology. Their traffic and localization is a multistep process involving a system of adaptor proteins, while their ion channel activity possibly exemplifies the rare cases of regulation of endocytic traffic and hydrolysis by ion channels. Finally, dysregulation of mucolipins results in cell death leading to neurodegenerative phenotypes of MLIV and of the varitint-waddler mouse model of familial deafness. The present review discusses current knowledge and questions regarding this novel family of disease-relevant ion channels with a specific focus on mucolipin regulation and their role in membrane traffic and cell death. Since mucolipins are ubiquitously expressed, this review may be useful for a wide audience of basic biologists and clinicians.
C1 [Puertollano, Rosa] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Kiselyov, Kirill] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
RP Puertollano, R (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM puertolr@mail.nih.gov; kiselyov@pitt.edu
FU National Heart, Lung, and Blood Institute; National Institutes of
Health; Mucolipidosis 4 Foundation
FX R. Puertollano is supported by the Intramural Research Program of the
National Heart, Lung, and Blood Institute, National Institutes of Health
and K. Kiselyov by funding from the Mucolipidosis 4 Foundation.
NR 78
TC 62
Z9 64
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD JUN
PY 2009
VL 296
IS 6
BP F1245
EP F1254
DI 10.1152/ajprenal.90522.2008
PG 10
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 449PO
UT WOS:000266342700002
PM 19158345
ER
PT J
AU Ruggiero, AM
Novak, MFSX
Woodward, RA
Suomi, SJ
AF Ruggiero, Angela M.
Novak, Matthew F. S. X.
Woodward, Ruth A.
Suomi, Stephen J.
TI Successful Behavioral Strategy to Unite Mother and Infant Rhesus Monkeys
(Macaca mulatta) After Cesarean Delivery
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Article
DE mother-infant introduction; cesarean delivery; mother-rearing; Macaca
mulatta
AB Developmental studies of pre- to postnatal continuities in rhesus monkeys sometimes require infants be reared with their mothers. However, complications during pregnancy or experimental designs may require cesarean delivery. Owing to lack of published information on this subject, strategies are needed to introduce mothers to their infants following cesarean delivery. Using positive and negative reinforcement techniques we attempted to unite six infant rhesus macaques, Macaca mulatta, to their mothers following c-sections. For our seventh subject, we attempted to cross-foster an infant onto an unrelated female after she had undergone a cesarean surgery for a late-term spontaneous abortion. The mothers varied in age, parity, previous postnatal mothering experience with infants, housing earlier to delivery, and housing subsequent to introduction. Although there were large individual differences among the mother-infant pairs, all seven introductions were successful. The mothers learned to accept and care for their infants from the continuous application of operant conditioning techniques. These data suggest that mother-rearing following cesarean section is a realistic possibility whether required for clinical reasons or for proper experimental control. Furthermore, the ability to successfully mother-rear infants produced from cesarean delivery lessens the impact this potential confound of not being reared by their mothers exerts on many types of developmental studies. Am. J. Primatol. 71:510-522, 2009. (dagger)Published 2009 Wiley-Liss, Inc.
C1 [Ruggiero, Angela M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Dept Hlth & Human Serv, NIH,Anim Ctr, Poolesville, MD 20837 USA.
[Woodward, Ruth A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, Res Anim Management Branch, NIH, Poolesville, MD 20837 USA.
RP Ruggiero, AM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Dept Hlth & Human Serv, NIH,Anim Ctr, POB 529, Poolesville, MD 20837 USA.
EM ruggiera@mail.nih.gov
FU National Institutes of Health Intramural Research Program
FX The animals used in this report were supported by funding from the
National Institutes of Health Intramural Research Program. The
Laboratory of Comparative Ethology of The Eunice Kennedy Shriver
National Institute of Child Health and Human Development at the National
Institutes of Health is an AAALAC International accredited facility; as
such its policies are in accordance with those from the USDA Animal
Welfare Act, the Public Health Service Policy on Humane Care and Use of
Laboratory Animals and the Guide for the Care and Use of Laboratory
Animals. We thank the animal care and veterinary staff for all their
efforts. We thank the assistance of our nursery personnel. All the help
we received was greatly appreciated.
NR 5
TC 0
Z9 0
U1 1
U2 6
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD JUN
PY 2009
VL 71
IS 6
BP 510
EP 522
DI 10.1002/ajp.20681
PG 13
WC Zoology
SC Zoology
GA 446PR
UT WOS:000266134100008
PM 19373875
ER
PT J
AU Joseph, JG
El-Mohandes, AAE
Kiely, M
El-Khorazaty, MN
Gantz, MG
Johnson, AA
Katz, KS
Blake, SM
Rossi, MW
Subramanian, S
AF Joseph, Jill G.
El-Mohandes, Ayman A. E.
Kiely, Michele
El-Khorazaty, M. Nabil
Gantz, Marie G.
Johnson, Allan A.
Katz, Kathy S.
Blake, Susan M.
Rossi, Maryann W.
Subramanian, Siva
TI Reducing Psychosocial and Behavioral Pregnancy Risk Factors: Results of
a Randomized Clinical Trial Among High-Risk Pregnant African American
Women
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID LOW-BIRTH-WEIGHT; MENTAL-HEALTH-SERVICES; SYMPTOM CHECKLIST HSCL;
PRIMARY-CARE PATIENTS; PRENATAL-CARE; SMOKING-CESSATION; COUNSELING
INTERVENTIONS; PSYCHIATRIC-DISORDERS; DOMESTIC VIOLENCE;
VITAL-STATISTICS
AB Objectives. We evaluated the efficacy of a primary care intervention targeting pregnant African American women and focusing on psychosocial and behavioral risk factors for poor reproductive outcomes (cigarette smoking, second-hand smoke exposure, depression, and intimate partner violence).
Methods. Pregnant African American women (N = 1044) were randomized to an intervention or usual care group. Clinic-based, individually tailored counseling sessions were adapted from evidence-based interventions. Follow-up data were obtained for 850 women. Multiple imputation methodology was used to estimate missing data. Outcome measures were number of risks at baseline, first follow-up, and second follow-up and within-person changes in risk from baseline to the second follow-tip.
Results. Number of risks did not differ between the intervention and usual care groups at baseline, the second trimester, or the third trimester. Women in the intervention group more frequently resolved some or all of their risks than did women in the usual care group (odds ratio = 1.61; 95% confidence interval = 1.08, 2.39; P = .021).
Conclusions. In comparison with usual care, a clinic-based behavioral intervention significantly reduced psychosocial and behavioral pregnancy risk factors among high-risk African American women receiving prenatal care. (Am J Public Health. 2009;99:1053-1061. doi:10.2105/AJPH.2007.131425)
C1 [Kiely, Michele] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Joseph, Jill G.] Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA.
[El-Mohandes, Ayman A. E.; Blake, Susan M.] George Washington Univ, Dept Prevent & Community Hlth, Washington, DC USA.
[El-Khorazaty, M. Nabil; Gantz, Marie G.] Res Triangle Inst Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Johnson, Allan A.] Howard Univ, Dept Nutr Sci, Washington, DC 20059 USA.
[Katz, Kathy S.; Subramanian, Siva] Georgetown Univ, Dept Pediat, Washington, DC 20057 USA.
[Rossi, Maryann W.] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
RP Kiely, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Rm 7B-05, Rockville, MD 20852 USA.
EM kielym@nih.gov
FU National Institute of Child Health and Human Development; National
Center on Minority Health and Health Disparities; National Institutes of
Health [3U18HD030445, 3U18HD030447, 5U18HD31206, 3UI811D031919,
5U18HD0361104]
FX This study was supported by the Eunice Kennedy Shriver, National
Institute of Child Health and Human Development and the National Center
on Minority Health and Health Disparities. National Institutes of Health
(grants 3U18HD030445, 3U18HD030447, 5U18HD31206, 3UI811D031919, and
5U18HD0361104)
NR 67
TC 37
Z9 38
U1 1
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 JUN
PY 2009
VL 99
IS 6
BP 1053
EP 1061
DI 10.2105/AJPH.2007.131425
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 448VE
UT WOS:000266289300021
PM 19372532
ER
PT J
AU Kelloff, GJ
Choyke, P
Coffey, DS
AF Kelloff, Gary J.
Choyke, Peter
Coffey, Donald S.
CA Prostate Canc Imaging Working Grp
TI Challenges in Clinical Prostate Cancer: Role of Imaging
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE diffusion-weighted MRI; dynamic contrast-enhanced MRI; FDG PET imaging;
functional imaging; high-intensity focused ultrasound imaging; MRI;
prostate cancer imaging; SPECT
ID POSITRON-EMISSION-TOMOGRAPHY; PLANAR BONE-SCINTIGRAPHY; EXTERNAL-BEAM
RADIATION; RADICAL PROSTATECTOMY; INITIAL-EXPERIENCE; ANTIGEN
RECURRENCE; TREATMENT RESPONSE; ANDROGEN ABLATION; C-11-ACETATE PET;
LOCAL RECURRENCE
AB OBJECTIVE. This article reviews a recent 2-day workshop on prostate cancer and imaging technology that was conducted by the Cancer Imaging Program of the National Cancer Institute. The workshop dealt with research trends and avenues for improving imaging and applications across the clinical spectrum of the disease.
CONCLUSION. After a summary of prostate cancer incidence and mortality, four main clinical challenges in prostate cancer treatment and management-diagnostic accuracy; risk stratification, initial staging, active surveillance, and focal therapy; prostate-specific antigen relapse after radiation therapy or radical prostatectomy; and assessing response to therapy in advanced disease-were discussed by the 55-member panel. The overarching issue in prostate cancer is distinguishing lethal from nonlethal disease. New technologies and fresh uses for established procedures make imaging effective in both assessing and treating prostate cancer.
C1 [Kelloff, Gary J.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20852 USA.
[Choyke, Peter] NCI, Mol Imaging Program, NIH, Bethesda, MD 20852 USA.
[Coffey, Donald S.] Johns Hopkins Univ, Dept Urol, Baltimore, MD USA.
RP Kelloff, GJ (reprint author), NCI, Div Canc Treatment & Diag, NIH, 6130 Execut Blvd,EPN Rm 6058, Bethesda, MD 20852 USA.
EM kelloffg@mail.nih.gov
FU NCI NIH HHS [K24 CA121990-05, R01 CA111291-03, K24 CA121990-04, R01
CA111291, K24 CA121990]
NR 103
TC 82
Z9 84
U1 1
U2 7
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 JUN
PY 2009
VL 192
IS 6
BP 1455
EP 1470
DI 10.2214/AJR.09.2579
PG 16
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 447FQ
UT WOS:000266177400004
PM 19457806
ER
PT J
AU Turkbey, B
Albert, PS
Kurdziel, K
Choyke, PL
AF Turkbey, Baris
Albert, Paul S.
Kurdziel, Karen
Choyke, Peter L.
TI Imaging Localized Prostate Cancer: Current Approaches and New
Developments
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE MRI; PET; prostate cancer
ID POSITRON-EMISSION-TOMOGRAPHY; IN-111 CAPROMAB PENDETIDE;
CONTRAST-ENHANCED MRI; PELVIC LYMPH-NODES; RADICAL PROSTATECTOMY;
MONOCLONAL-ANTIBODY; C-11-CHOLINE PET/CT; ANTIGEN RELAPSE; ENDORECTAL
MR; TOMOGRAPHY/COMPUTERIZED TOMOGRAPHY
AB OBJECTIVE. Prostate cancer is the most common noncutaneous malignancy among men in the Western world. Imaging has recently become more important in the diagnosis, local staging, and treatment follow-up of prostate cancer. In this article, we review conventional and functional imaging methods as well as targeted imaging approaches with novel tracers used in the diagnosis and staging of prostate cancer.
CONCLUSION. Although prostate cancer is the second leading cause of cancer death in men, imaging of localized prostate cancer remains limited. Recent developments in imaging technologies, particularly MRI and PET, may lead to significant improvements in lesion detection and staging.
C1 [Turkbey, Baris; Kurdziel, Karen; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Rm 1B40, Bethesda, MD 20892 USA.
EM pchoyke@nih.gov
FU Intramural NIH HHS [Z01 BC010655-04]
NR 92
TC 99
Z9 109
U1 0
U2 5
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 JUN
PY 2009
VL 192
IS 6
BP 1471
EP 1480
DI 10.2214/AJR.09.2527
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 447FQ
UT WOS:000266177400005
PM 19457807
ER
PT J
AU Orta, L
Klimstra, DS
Qin, J
Mecca, P
Tang, LH
Busam, KJ
Shia, J
AF Orta, Lurmag
Klimstra, David S.
Qin, Jing
Mecca, Patricia
Tang, Laura H.
Busam, Klaus J.
Shia, Jinru
TI Towards Identification of Hereditary DNA Mismatch Repair Deficiency:
Sebaceous Neoplasm Warrants Routine Immunohistochemical Screening
Regardless of Patient's Age or Other Clinical Characteristics
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article; Proceedings Paper
CT 97th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 01-07, 2008
CL Denver, CO
SP US & Canadian Acad Pathol
DE Muir-Torre syndrome; immunohistochemistry; sebaceous adenoma; sebaceous
carcinoma; microsatellite instability; hereditary nonpolyposis
colorectal cancer
ID MUIR-TORRE-SYNDROME; NONPOLYPOSIS COLORECTAL-CANCER; PREDICTING
MICROSATELLITE INSTABILITY; TUMOR-INFILTRATING LYMPHOCYTES;
LYNCH-SYNDROME; ENDOMETRIAL CANCER; COLON-CANCER; GLAND CARCINOMAS; MSH2
MUTATIONS; SKIN-LESIONS
AB Although the significance of immunohistochemical detection of DNA mismatch repair proteins and/or microsatellite instability testing in identifying patients at risk for germline deficiency in DNA mismatch repair genes is well established in colorectal carcinomas. the proper use of such techniques in sebaceous neoplasms, another tumor type that has been implicated in patients with hereditary DNA mismatch repair deficiency, has not been clearly defined. In this study. we stratified a series of 27 patients with 1 or more sebaceous neoplasms based on the pattern of immunohistochemical expression of MLH1. MSH2. MSH6, and PMS2. and comparatively analyzed their clinical and pathologic characteristics, including tumor-infiltrating lymphocytes and peritumoral lymphocytic response as determined by immunohistochemical staining for CD3. The study tissue samples included 30 sebaceous carcinomas, 14 sebaceous adenomas, and 7 sebaceous hyperplasias, along with 8 concurrent nonsebaceous lesions from 6 patients. Overall, 12 of the 27 (44%) patients showed abnormal IHC staining with mismatch repair proteins in then sebaceous tumors. the most commonly seen abnormality being Concurrent loss of MSH2 and MSH6 (8/12, 67%). sebaceous adenomas and carcinomas occurring in the same patients showed an identical staining pattern, as did hereditary nonpolyposis colorectal cancer-related nonsebaceous tumors in the same patients. When compared with cases that had normal expression of the mismatch repair proteins, cases with abnormal expression tended to be younger (median age, 56.5 y vs. 68 y), more likely to involve sites outside the head and neck (9/12 vs. 0/15), and more likely to have synchronous or metachronous visceral malignancies (8/12 vs. 3/15) and a positive family history. Furthermore, sebaceous tumors with abnormal expression had significantly higher CD3-positive tumor-infiltrating lymphocytes and peritumoral lymphocytic response. Thus, all these factors (age less than 60 y, involvement of nonhead and neck sites. visceral malignancy. family history fulfilling at least Bethesda guidelines, and lymphocytic infiltration) bore informative value in predicting abnormal expression of DNA mismatch repair proteins. However, their sensitivity was only modest. being 58%, 75%, 67%, 78%, and 75%, respectively, on such a premise given that sebaceous neoplasms are only infrequently encountered, and that immunohistochemistry is easily available and reasonably reliable, we recommend that. when there exists a desire to identify hereditary DNA mismatch repair deficiency, routine immunohistochemical detection of DNA mismatch repair proteins be performed in all sebaceous neoplasms regardless of patient's age or other clinical characteristics.
C1 [Orta, Lurmag; Klimstra, David S.; Mecca, Patricia; Tang, Laura H.; Busam, Klaus J.; Shia, Jinru] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Shia, J (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA.
EM Shiaj@mskcc.org
OI Shia, Jinru/0000-0002-4351-2511
NR 33
TC 38
Z9 38
U1 1
U2 3
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 JUN
PY 2009
VL 33
IS 6
BP 934
EP 944
PG 11
WC Pathology; Surgery
SC Pathology; Surgery
GA 451IP
UT WOS:000266464200014
PM 19342947
ER
PT J
AU Sahut-Barnola, I
De Joussineau, C
Val, P
Lambert-Langlais, S
Lefrancois-Martinez, AM
Pointud, JC
Marceau, G
Sapin, V
Ragazzon, B
Bertherat, J
Kirschner, LS
Stratakis, CA
Martinez, A
AF Sahut-Barnola, I.
De Joussineau, C.
Val, P.
Lambert-Langlais, S.
Lefrancois-Martinez, A. -M.
Pointud, J. -C.
Marceau, G.
Sapin, V.
Ragazzon, B.
Bertherat, J.
Kirschner, L. S.
Stratakis, C. A.
Martinez, A.
TI Mouse model for bilateral adrenal hyperplasia
SO ANNALES D ENDOCRINOLOGIE
LA English
DT Article; Proceedings Paper
CT 52nd International Endocrinology Clinic
CY MAY 14-15, 2009
CL Paris, FRANCE
ID REGULATORY SUBUNIT; CARNEY COMPLEX; MUTATIONS; MYXOMAS; GENE
C1 [Sahut-Barnola, I.; De Joussineau, C.; Val, P.; Lambert-Langlais, S.; Lefrancois-Martinez, A. -M.; Pointud, J. -C.; Marceau, G.; Sapin, V.; Martinez, A.] Univ Clermont Ferrand, CNRS, UMR Genet Reprod & Dev GReD 6247, F-63177 Aubiere, France.
[Ragazzon, B.; Bertherat, J.] Univ Paris 05, Dept Endocrinol, INSERM, CNRS,UMR Metab & Canc 8104,Inst Cochin,U567, Paris, France.
[Kirschner, L. S.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH USA.
[Kirschner, L. S.] Ohio State Univ, Div Endocrinol Diabet & Metab, Dept Internal Med, Columbus, OH USA.
[Stratakis, C. A.] NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP Martinez, A (reprint author), Univ Clermont Ferrand, CNRS, UMR Genet Reprod & Dev GReD 6247, 24 Ave Landais, F-63177 Aubiere, France.
EM Antoine.martinez@univ-bpclermont.fr
RI Ragazzon, Bruno/E-6541-2017
OI Ragazzon, Bruno/0000-0001-9476-4973
FU Intramural NIH HHS [ZIA HD000642-13]
NR 6
TC 0
Z9 0
U1 0
U2 0
PU MASSON EDITEUR
PI MOULINEAUX CEDEX 9
PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE
SN 0003-4266
J9 ANN ENDOCRINOL-PARIS
JI Ann Endocrinol.
PD JUN
PY 2009
VL 70
IS 3
BP 194
EP 194
DI 10.1016/j.ando.2009.02.004
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 449KJ
UT WOS:000266329200015
PM 19286161
ER
PT J
AU Karaczyn, AA
Cheng, RYS
Buzard, GS
Hartley, J
Esposito, D
Kasprzak, KS
AF Karaczyn, Aldona A.
Cheng, Robert Y. S.
Buzard, Gregory S.
Hartley, James
Esposito, Dominic
Kasprzak, Kazimierz S.
TI Truncation of Histone H2A's C-terminal Tail, as Is Typical for
Ni(II)-Assisted Specific Peptide Bond Hydrolysis, Has Gene Expression
Altering Effects
SO ANNALS OF CLINICAL AND LABORATORY SCIENCE
LA English
DT Article
DE histone H2A; nickel carcinogenesis; gene expression; cancer-related
genes
ID CENTRAL-NERVOUS-SYSTEM; RENAL-CELL CARCINOMA; GROWTH-FACTOR; PCPH
PROTOONCOGENE; NEUTRAL PROTEASE; GASTRIC-CANCER; OVARIAN-CANCER;
UP-REGULATION; IDENTIFICATION; CHROMATIN
AB Nickel(II), capable of transforming cells and causing tumors in humans and animals, has been previously shown by us to mediate hydrolytic truncation of histone H2A's C-terminal tail by 8 amino acids in both cell-free and cell culture systems. Since H2A's C-tail is involved in maintaining chromatin structure, such truncation might alter this structure and affect gene expression. To test the latter possibility, we transfected cultured T-REx 293 human embryonic kidney cells with plasmids expressing either wild type (wt) or truncated (q) histone H2A proteins, which were either untagged or N-terminally tagged with fluorescent proteins. Each histone variant was found to be incorporated into chromatin at 24 and 48 hr post-transfection. Cells transfected with the untagged plasmids were tested for gene expression by microarray and real-time PCR. Evaluation of the results for over 21,000 genes using the multidimensional scaling and hierarchical clustering methods revealed significant differences in expression of numerous genes between the q-H2A and wt-H2A transfectants. Many of the differentially expressed genes, including BAZ2A, CLDN18, CYP51A1, GFR, GIPC2, HMGB1, IRF7, JAK3, PSIP1, and VEGF, are cancer-related genes. The results thus demonstrate the potential of q-H2A to contribute to the process of carcinogenesis through epigenetic mechanisms.
C1 [Karaczyn, Aldona A.; Kasprzak, Kazimierz S.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
[Cheng, Robert Y. S.] NCI, Lab Metab, Cellular Def & Carcinogenesis Sect, Frederick, MD 21702 USA.
[Buzard, Gregory S.] SAIC Frederick, Intramural Res Support Program, Frederick, MD USA.
[Hartley, James; Esposito, Dominic] SAIC Frederick, Prot Express Lab, Frederick, MD USA.
RP Kasprzak, KS (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538,Room 205E, Frederick, MD 21702 USA.
EM kasprkaz@mail.ncifcrf.gov
OI Cheng, Robert/0000-0003-0287-6439
FU National Cancer Institute, Center for Cancer Research, National
Institutes of Health [N01-CO-12400]
FX The authors are grateful to Dr. William M. Bonner for the generous gift
of human H2A plasmid, and to Drs. Steven Lockett, Yih-Horng Shiao, and
Lucy M. Anderson for technical help and critical discussion of this
study. Skillful technical assistance of Ms. S. Lynn North and Mr. Robert
M. Bare is also gratefully acknowledged. This project was funded in
whole with federal funds from the National Cancer Institute, Center for
Cancer Research, National Institutes of Health, under the Intramural
Research Program and 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 organization imply endorsement by the
United States Government.
NR 87
TC 8
Z9 8
U1 0
U2 1
PU ASSOC CLINICAL SCIENTISTS
PI MIDDLEBURY
PA PO BOX 1287, MIDDLEBURY, VT 05753 USA
SN 0091-7370
J9 ANN CLIN LAB SCI
JI Ann. Clin. Lab. Sci.
PD SUM
PY 2009
VL 39
IS 3
BP 251
EP 262
PG 12
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 481LR
UT WOS:000268813000004
PM 19667409
ER
PT J
AU Johnson, MD
Moots, PL
Zhuang, ZP
Weil, RJ
AF Johnson, Mahlon D.
Moots, Paul L.
Zhuang, Zhengping
Weil, Robert J.
TI Molecular Genetic Analysis of a Primitive Neuroectodermal Tumor Arising
after Intracranial Radiation and Chemotherapy for Leukemia
SO ANNALS OF CLINICAL AND LABORATORY SCIENCE
LA English
DT Article
DE chemotherapy; primitive neuroectodermal tumor; leukemia; loss of
heterozygosity; allelic imbalance; radiation-induced tumors; secondary
neoplasms; microdissection; RET protooncogene
ID CENTRAL-NERVOUS-SYSTEM; ACUTE LYMPHOBLASTIC-LEUKEMIA; CRANIAL
IRRADIATION; BRAIN-TUMORS; CHILDHOOD; MEDULLOBLASTOMA; RADIOTHERAPY;
SUBSEQUENT; NEOPLASMS; THERAPY
AB Primitive neuroectodermal tumors are aggressive tumors of the central nervous system (CNS), yet their etiology remains unclear. We report a case of a primitive neuroectodermal tumor (PNET) arising in the cerebellum and pons 7 yr after intracranial radiation and chemotherapy for leukemia involving the CNS. This case suggests a possible link between radiation, chemotherapy, and the formation of these tumors, with a potential new pathogenetic role for somatic inactivation of the protooncogene RET.
C1 [Weil, Robert J.] Cleveland Clin Fdn, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA.
[Johnson, Mahlon D.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA.
[Weil, Robert J.] Vanderbilt Univ, Med Ctr, Dept Neurosurg, Nashville, TN 37232 USA.
[Moots, Paul L.] Vanderbilt Univ, Med Ctr, Dept Neurol, Nashville, TN 37232 USA.
[Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Johnson, Mahlon D.] Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA.
RP Weil, RJ (reprint author), Cleveland Clin Fdn, Brain Tumor & Neurooncol Ctr, ND4-40 Lerner Res Inst,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM mahlon_johnson@urmc.rochester.edu; weilr@ccf.org
FU Brain Tumor and Neuro-oncology Center at the Cleveland Clinic Foundation
FX We thank 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 for partial
support and funding.
NR 23
TC 2
Z9 2
U1 0
U2 2
PU ASSOC CLINICAL SCIENTISTS
PI MIDDLEBURY
PA PO BOX 1287, MIDDLEBURY, VT 05753 USA
SN 0091-7370
J9 ANN CLIN LAB SCI
JI Ann. Clin. Lab. Sci.
PD SUM
PY 2009
VL 39
IS 3
BP 295
EP 302
PG 8
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 481LR
UT WOS:000268813000010
PM 19667415
ER
PT J
AU Delancey, JOL
Alavanja, MCR
Coble, J
Blair, A
Hoppin, JA
Austin, HD
Freeman, LEB
AF Delancey, John Oliver L.
Alavanja, Michael C. R.
Coble, Joseph
Blair, Aaron
Hoppin, Jane A.
Austin, Harland D.
Freeman, Laura E. Beane
TI Occupational Exposure to Metribuzin and the Incidence of Cancer in the
Agricultural Health Study
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Pesticides; Cancer; Occupation; Metribuzin; Agricultural Health Study
ID PESTICIDES; GENOTOXICITY; ASSAY; METABOLISM; HERBICIDES
AB PURPOSE: Little is known about the potential carcinogenicity of the triazinone herbicide metribuzin. We evaluated the association between metribuzin use and cancer risk in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina.
METHODS: Applicators (N = 23,072) provided information on metribuzin use on a self-administered questionnaire at enrollment (1993-1997). Among metribuzin users (n = 8,504), there were 554 incident cancer cases. We used multivariable Poisson regression to evaluate potential associations between metribuzin use and cancer incidence by using two quantitative exposure metrics, lifetime days and intensity-weighted lifetime days.
RESULTS: Using intensity-weighted lifetime days, the rate ratio (RR) and 95% confidence interval (CI) for the highest exposed tertile for lymphohematopoietic malignancies were 2.09 (95% CI: 0.99-4.29), P trend = 0.02 and 2.42 (95% Cl: 0.82-7.19), p trend = 0.08 for leukemia. For non-Hodgkin lymphoma, the RR was 2.64 (95% Cl: 0.76-9.11), p trend = 0.13 for lifetime days and 2.52 (95% Cl: 0.66-9.59), p trend = 0.13 for intensity-weighted lifetime days. Patterns of association were similar for both exposure metrics, but associations were generally weaker than for intensity-weighted days.
CONCLUSIONS: The results from this Study suggest a potential association between metribuzin use and certain lymphohematopoietic malignancies; however, having not been observed previously, caution should be used in interpretation. Ann Epidemiol 2009;19:388-395. Published by Elsevier Inc.
C1 [Alavanja, Michael C. R.; Coble, Joseph; Blair, Aaron; Freeman, Laura E. Beane] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Austin, Harland D.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Delancey, John Oliver L.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA.
RP Freeman, LEB (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8112, Bethesda, MD 20892 USA.
EM freemala@mail.nih.gov
RI Beane Freeman, Laura/C-4468-2015
OI Beane Freeman, Laura/0000-0003-1294-4124
FU Intramural NIH HHS [Z01 CP010119-12]
NR 20
TC 14
Z9 14
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD JUN
PY 2009
VL 19
IS 6
BP 388
EP 395
DI 10.1016/j.annepidem.2008.12.018
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 453YE
UT WOS:000266648000005
PM 19369095
ER
PT J
AU Mochel, F
Yang, BZ
Barritault, J
Thompson, JN
Engelke, UFH
McNeill, NH
Benko, WS
Kaneski, CR
Adams, DR
Tsokos, M
Abu-Asab, M
Huizing, M
Seguin, F
Wevers, RA
Ding, JH
Verheijen, FW
Schiffmann, R
AF Mochel, Fanny
Yang, Bingzhi
Barritault, Julie
Thompson, Jerry N.
Engelke, Udo F. H.
McNeill, Nathan H.
Benko, William S.
Kaneski, Christine R.
Adams, David R.
Tsokos, Maria
Abu-Asab, Mones
Huizing, Marjan
Seguin, Francois
Wevers, Ron A.
Ding, Jiahuan
Verheijen, Frans W.
Schiffmann, Raphael
TI Free Sialic Acid Storage Disease without Sialuria
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID MAGNETIC-RESONANCE-SPECTROSCOPY; INBORN-ERRORS; SALLA-DISEASE;
METABOLISM; DISORDERS; TRANSPORTER; GENE
AB We performed high-resolution in vitro proton nuclear magnetic resonance spectroscopy on cerebrospinal fluid and Urine samples of 44 patients with leukodystrophies Of Unknown cause. Free sialic acid concentration was increased in cerebrospinal fluid of two siblings with mental retardation and mild hypomyelination. By, contrast, urinary excretion of free sialic acid in urine was normal oil repeated testing by two independent methods. Both patients were homozygous for the K136E mutation in SLC17A5, the gene responsible for the free sialic acid storage diseases. Our findings demonstrate that mutations ill the SLC17A5 gene have to be considered in patients with hypomyelination, even in the absence of sialuria.
C1 [Mochel, Fanny] Baylor Univ, Med Ctr, Baylor Res Inst, Inst Metab Dis, Dallas, TX 75226 USA.
[Mochel, Fanny] Hop La Pitie Salpetriere, INSERM, UMR S679, Paris, France.
[Barritault, Julie; Seguin, Francois] Univ Poitiers, Hop La Miletrie, INSERM, U927, Poitiers, France.
[Thompson, Jerry N.] Univ Alabama, Dept Genet, Birmingham, AL USA.
[Engelke, Udo F. H.; Wevers, Ron A.] Radboud Univ Nijmegen, Med Ctr, Lab Pediat & Neurol, NL-6525 ED Nijmegen, Netherlands.
[Benko, William S.] WellSpan Neurosci, Pediat Neurol, York, PA USA.
[Adams, David R.; Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Tsokos, Maria; Abu-Asab, Mones] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Verheijen, Frans W.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
RP Mochel, F (reprint author), Baylor Univ, Med Ctr, Baylor Res Inst, Inst Metab Dis, 3812 Elm St, Dallas, TX 75226 USA.
EM fanny.mochel@baylorhealth.edu
RI Wevers, Ron/H-8116-2014; Engelke, U.F.H./L-4293-2015;
OI Wevers, Ron/0000-0003-2278-9746; Abu-Asab, Mones/0000-0002-4047-1232;
Kaneski, Christine/0000-0003-1453-2502
FU NIH (Intramural Program of the National Institute of Neurological
Disorders and Stroke); Baylor Research Foundation
FX This work was supported by the NIH (Intramural Program of the National
Institute of Neurological Disorders and Stroke) and Baylor Research
Foundation.
NR 19
TC 6
Z9 6
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD JUN
PY 2009
VL 65
IS 6
BP 753
EP 757
DI 10.1002/ana.21624
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 465FD
UT WOS:000267566800018
PM 19557856
ER
PT J
AU Strasak, AM
Pfeiffer, RM
Brant, LJ
Rapp, K
Hilbe, W
Oberaigner, W
Lang, S
Borena, W
Concin, H
Diem, G
Ruttmann, E
Glodny, B
Pfeiffer, KP
Ulmer, H
AF Strasak, A. M.
Pfeiffer, R. M.
Brant, L. J.
Rapp, K.
Hilbe, W.
Oberaigner, W.
Lang, S.
Borena, W.
Concin, H.
Diem, G.
Ruttmann, E.
Glodny, B.
Pfeiffer, K. P.
Ulmer, H.
CA VHM&PP Study Grp
TI Time-dependent association of total serum cholesterol and cancer
incidence in a cohort of 172 210 men and women: a prospective 19-year
follow-up study
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE cancer incidence; prospective study; reverse causality; time dependency;
total serum cholesterol
ID HIGH-DENSITY-LIPOPROTEIN; PLASMA-CHOLESTEROL; BREAST-CANCER; COLON
CANCER; RISK-FACTORS; MALE SMOKERS; 7 COUNTRIES; URIC-ACID; MORTALITY;
POPULATION
AB Background: The relationship between serum cholesterol and cancer incidence remains controversial.
Patients and methods: We investigated the association of total serum cholesterol (TSC) with subsequent cancer incidence in a population-based cohort of 172 210 Austrian adults prospectively followed up for a median of 13.0 years. Cox regression, allowing for time-dependent effects, was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the association of TSC with cancer.
Results: We observed pronounced short-term associations of TSC and overall cancer incidence in both men and women. For malignancies diagnosed shortly (< 5 months) after baseline TSC measurement, the highest TSC tertile (> 235.0 mg/dl in men and > 229.0 in women) compared with the lowest tertile (< 194.0 mg/dl in men and < 190.0 in women) was associated with a significantly lower overall cancer risk [HR = 0.58 (95% CI 0.43-0.78, P-trend = 0.0001) in men, HR = 0.69 (95% CI 0.49-0.99, P-trend = 0.03) in women]. However, after roughly 5 months from baseline measurement, overall cancer risk was not significantly associated with TSC. The short-term inverse association of TSC with cancer was mainly driven by malignancies of the digestive organs and lymphoid and hematopoietic tissue.
Conclusion: The short-term decrease of cancer risk seen for high levels of TSC may largely capture preclinical effects of cancer on TSC.
C1 [Strasak, A. M.; Borena, W.; Pfeiffer, K. P.; Ulmer, H.] Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, A-6020 Innsbruck, Austria.
[Pfeiffer, R. M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Brant, L. J.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Rapp, K.] Univ Ulm, Inst Epidemiol, Ulm, Germany.
[Hilbe, W.] Innsbruck Med Univ, Dept Haematol & Oncol, A-6020 Innsbruck, Austria.
[Oberaigner, W.] Tyrolean State Hosp Ltd, Dept Clin Epidemiol, Canc Registry Tyrol, Innsbruck, Austria.
[Lang, S.] Univ Innsbruck, Inst Stat, A-6020 Innsbruck, Austria.
[Concin, H.; Diem, G.] Agcy Prevent & Social Med, Bregenz, Austria.
[Glodny, B.] Innsbruck Med Univ, Dept Radiol, A-6020 Innsbruck, Austria.
[Ruttmann, E.] Innsbruck Med Univ, Dept Cardiac Surg, A-6020 Innsbruck, Austria.
RP Strasak, AM (reprint author), Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Schoepfstr 41, A-6020 Innsbruck, Austria.
EM alexander.strasak@i-med.ac.at
RI Glodny, Bernhard/E-7984-2010; Lang, Stefan/E-7500-2010; Ruttmann,
Elfriede/D-6501-2011; Pfeiffer, Ruth /F-4748-2011; vhmpp,
aks/F-9756-2012; Klenk, Jochen/C-2164-2012; Ulmer, Hanno/C-3488-2011;
OI Lang, Stefan/0000-0003-0739-3858; Ulmer, Hanno/0000-0001-5911-1002;
Klenk, Jochen/0000-0002-5987-447X
FU Austrian National Bank [OENB-12737]; National Institute on Aging
Intramural Research Program
FX Supported by Austrian National Bank Grant OENB-12737 (to HU) and
National Institute on Aging Intramural Research Program (to LJB).
NR 46
TC 27
Z9 27
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD JUN
PY 2009
VL 20
IS 6
BP 1113
EP 1120
DI 10.1093/annonc/mdn736
PG 8
WC Oncology
SC Oncology
GA 449QA
UT WOS:000266343900023
PM 19164459
ER
PT J
AU Sarkar, SK
Guo, WG
AF Sarkar, Sanat K.
Guo, Wenge
TI ON A GENERALIZED FALSE DISCOVERY RATE
SO ANNALS OF STATISTICS
LA English
DT Article
DE Average power; gene expression; generalized FDR; generalized FWER;
multiple hypothesis testing; oracle k-FDR procedure; stepup procedures
ID MULTIPLE TESTING PROCEDURES; FAMILYWISE ERROR RATE; STEPUP PROCEDURES;
PROPORTION; NUMBER; NULL; FDR
AB The concept of k-FWER has received much attention lately as an appropriate error rate for multiple testing when one seeks to control at least k false rejections, for some fixed k >= 1. A less conservative notion, the k-FDR, has been introduced very recently by Sarkar [Ann. Statist. 34 (2006) 394-415], generalizing the false discovery rate of Benjamini and Hochberg [J. Roy. Statist. Soc. Ser. B 57 (1995) 289-300]. In this article, we bring newer insight to the k-FDR considering a mixture model involving independent p-values before motivating the developments of some new procedures that control it. We prove the k-FDR control of the proposed methods under a slightly weaker condition than in the mixture model. We provide numerical evidence of the proposed methods' superior power performance over some k-FWER and k-FDR methods. Finally, we apply our methods to a real data set.
C1 [Sarkar, Sanat K.] Temple Univ, Dept Stat, Fox Sch Business & Management, Philadelphia, PA 19122 USA.
[Guo, Wenge] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Sarkar, SK (reprint author), Temple Univ, Dept Stat, Fox Sch Business & Management, Philadelphia, PA 19122 USA.
EM sanat@temple.edu; guow@niehs.nih.gov
OI Guo, Wenge/0000-0003-3777-2058
FU NSF [DMS-06-03868]
FX Supported by NSF Grant DMS-06-03868.
NR 28
TC 6
Z9 6
U1 1
U2 3
PU INST MATHEMATICAL STATISTICS
PI CLEVELAND
PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA
SN 0090-5364
J9 ANN STAT
JI Ann. Stat.
PD JUN
PY 2009
VL 37
IS 3
BP 1545
EP 1565
DI 10.1214/08-AOS617
PG 21
WC Statistics & Probability
SC Mathematics
GA 439IB
UT WOS:000265619700016
ER
PT J
AU Minig, L
Biffi, R
Zanagnolo, V
Attanasio, A
Beltrami, C
Bocciolone, L
Botteri, E
Colombo, N
Iodice, S
Landoni, F
Peiretti, M
Roviglione, G
Maggioni, A
AF Minig, L.
Biffi, R.
Zanagnolo, V.
Attanasio, A.
Beltrami, C.
Bocciolone, L.
Botteri, E.
Colombo, N.
Iodice, S.
Landoni, F.
Peiretti, M.
Roviglione, G.
Maggioni, A.
TI Early Oral Versus "Traditional" Postoperative Feeding in Gynecologic
Oncology Patients Undergoing Intestinal Resection: a Randomized
Controlled Trial
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; MULTIMODAL REHABILITATION PROGRAM; ELECTIVE COLORECTAL
SURGERY; NORTHERN EUROPEAN COUNTRIES; COLONIC RESECTION; OVARIAN-CANCER;
CYTOREDUCTIVE SURGERY; QUESTIONNAIRE MODULE; ENHANCED RECOVERY;
CLINICAL-TRIALS
AB A randomized controlled trial was performed to assess the outcome of early oral postoperative feeding (EOF) compared with traditional oral feeding (TOF) in gynecologic oncology patients undergoing laparotomy with associated intestinal resection.
Patients aged 18-75 years, undergoing elective laparotomy, and with preoperative diagnosis of gynecologic malignancy, were eligible. Exclusion criteria included infectious conditions, intestinal obstruction, severe malnutrition, American Society of Anesthesiologists (ASA) score a parts per thousand yen4, and postoperative stay in the intensive care unit lasting > 24 h. Patients allocated to EOF received liquid diet in the first postoperative day and then regular diet. Patients received traditional feeding scheme until resolution of postoperative ileus to start liquid diet. The primary end-point of the trial was length of hospital stay.
Between January 1st, 2007 and March 15th, 2008, 40 patients were randomized to receive either EOF or TOF. Hospital stay in patients who received EOF (n = 18) was 6.9 days versus 9.1 days in the TOF group (n = 22) (P = 0.022). Requirements for analgesic and antiemetic drugs, intensity of pain, intestinal function recovery, mean levels of postoperative satisfaction, postoperative complications, and quality-of-life scores did not differ between the two groups.
Early resumption of oral intake is feasible and safe in gynecologic oncology patients undergoing intestinal resection as part of a planned surgical procedure. Moreover, significant reduction in length of hospital stay was demonstrated.
C1 [Minig, L.; Zanagnolo, V.; Bocciolone, L.; Colombo, N.; Landoni, F.; Peiretti, M.; Roviglione, G.; Maggioni, A.] European Inst Oncol, Dept Gynecol, Milan, Italy.
[Biffi, R.] European Inst Oncol, Dept Abdominopelv Surg, Milan, Italy.
[Attanasio, A.] European Inst Oncol, Dept Anesthesiol, Milan, Italy.
[Beltrami, C.] European Inst Oncol, Dept Gynecol Nurses, Milan, Italy.
[Botteri, E.; Iodice, S.] European Inst Oncol, Dept Epidemiol & Biostat, Milan, Italy.
[Minig, L.] NCI, NIH, Bethesda, MD 20892 USA.
RP Minig, L (reprint author), European Inst Oncol, Dept Gynecol, Milan, Italy.
EM lucasminig@yahoo.com
NR 41
TC 24
Z9 26
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUN
PY 2009
VL 16
IS 6
BP 1660
EP 1668
DI 10.1245/s10434-009-0444-2
PG 9
WC Oncology; Surgery
SC Oncology; Surgery
GA 441RD
UT WOS:000265787200033
PM 19330379
ER
PT J
AU Petraitis, V
Petraitiene, R
Hope, WW
Meletiadis, J
Mickiene, D
Hughes, JE
Cotton, MP
Stergiopoulou, T
Kasai, M
Francesconi, A
Schaufele, RL
Sein, T
Avila, NA
Bacher, J
Walsh, TJ
AF Petraitis, Vidmantas
Petraitiene, Ruta
Hope, William W.
Meletiadis, Joseph
Mickiene, Diana
Hughes, Johanna E.
Cotton, Margaret P.
Stergiopoulou, Theodouli
Kasai, Miki
Francesconi, Andrea
Schaufele, Robert L.
Sein, Tin
Avila, Nilo A.
Bacher, John
Walsh, Thomas J.
TI Combination Therapy in Treatment of Experimental Pulmonary
Aspergillosis: In Vitro and In Vivo Correlations of the Concentration-
and Dose-Dependent Interactions between Anidulafungin and Voriconazole
by Bliss Independence Drug Interaction Analysis
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID NERVOUS-SYSTEM ASPERGILLOSIS; AMPHOTERICIN-B; INVASIVE ASPERGILLOSIS;
ANTIFUNGAL THERAPY; OPPORTUNISTIC MYCOSES; CASPOFUNGIN; FUMIGATUS;
ITRACONAZOLE; EFFICACY; MODEL
AB We studied the antifungal activity of anidulafungin (AFG) in combination with voriconazole (VRC) against experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits and further explored the in vitro and in vivo correlations by using Bliss independence drug interaction analysis. Treatment groups consisted of those receiving AFG at 5 (AFG5 group) and 10 (AFG10 group) mg/kg of body weight/day, VRC at 10 mg/kg every 8 h (VRC group), AFG5 plus VRC (AFG5+VRC group), and AFG10 plus VRC (AFG10+VRC group) and untreated controls. Survival throughout the study was 60% for the AFG5+VRC group, 50% for the VRC group, 27% for the AFG10+VRC group, 22% for the AFG5 group, 18% for the AFG10 group, and 0% for control rabbits (P < 0.001). There was a significant reduction of organism-mediated pulmonary injury, measured by infarct scores, lung weights, residual fungal burdens, and galactomannan indexes, in AFG5+VRC-treated rabbits versus those treated with AFG5 and VRC alone (P < 0.05). In comparison, AFG10+VRC significantly lowered only infarct scores and lung weights in comparison to those of AFG10-treated animals (P < 0.05). AFG10+VRC showed no significant difference in other outcome variables. Significant Bliss synergy was found in vivo between AFG5 and VRC, with observed effects being 24 to 30% higher than expected levels if the drugs were acting independently. These synergistic interactions were also found between AFG and VRC in vitro. However, for AFG10+VRC, only independence and antagonism were observed among the outcome variables. We concluded that the combination of AFG with VRC in treatment of experimental IPA in persistently neutropenic rabbits was independent to synergistic at a dosage of 5 mg/kg/day but independent to antagonistic at 10 mg/kg/day, as assessed by Bliss independence analysis, suggesting that higher dosages of an echinocandin may be deleterious to the combination.
C1 [Petraitis, Vidmantas; Petraitiene, Ruta; Hope, William W.; Meletiadis, Joseph; Mickiene, Diana; Hughes, Johanna E.; Cotton, Margaret P.; Stergiopoulou, Theodouli; Kasai, Miki; Francesconi, Andrea; Schaufele, Robert L.; Sein, Tin; Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Petraitis, Vidmantas; Petraitiene, Ruta; Mickiene, Diana; Sein, Tin] SAIC Frederick, Lab Anim Sci Program, Frederick, MD USA.
[Bacher, John] NIH, Surg Serv, Vet Resources Program, Off Res Serv, Bethesda, MD 20892 USA.
[Avila, Nilo A.] NIH, Dept Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 1W-5750,10 Ctr Dr, Bethesda, MD 20892 USA.
EM walsht@mail.nih.gov
OI Hope, William/0000-0001-6187-878X
NR 38
TC 52
Z9 53
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JUN
PY 2009
VL 53
IS 6
BP 2382
EP 2391
DI 10.1128/AAC.00329-09
PG 10
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 448DY
UT WOS:000266244500022
PM 19307368
ER
PT J
AU Bailey, CM
Kasiviswanathan, R
Copeland, WC
Anderson, KS
AF Bailey, Christopher M.
Kasiviswanathan, Rajesh
Copeland, William C.
Anderson, Karen S.
TI R964C Mutation of DNA Polymerase gamma Imparts Increased Stavudine
Toxicity by Decreasing Nucleoside Analog Discrimination and Impairing
Polymerase Activity
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID MITOCHONDRIAL TOXICITY; ANTIRETROVIRAL THERAPY; REVERSE-TRANSCRIPTASE;
SUBUNIT; INHIBITORS; DRUGS
AB The R964C mutation of human DNA polymerase gamma was recently linked to stavudine (d4T)-mediated mitochondrial toxicity. We utilized pre-steady-state kinetics to determine the effect of this mutation on incorporation of natural substrate dTTP and the active metabolite of d4T (d4TTP). The R964C polymerase gamma holoenzyme demonstrated a 33% decrease in dTTP incorporation efficiency and a threefold-lower d4TTP discrimination relative to that of the wild-type polymerase gamma, providing a mechanistic basis for genetic predisposition to nucleoside reverse transcriptase inhibitor toxicity.
C1 [Bailey, Christopher M.; Anderson, Karen S.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA.
[Kasiviswanathan, Rajesh; Copeland, William C.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Anderson, KS (reprint author), Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA.
EM karen.anderson@yale.edu
RI Kasiviswanathan, Rajesh/D-2744-2012;
OI Bailey, Chris/0000-0002-5962-9511
FU NIH [GM49551, ES065080]
FX This work was supported by NIH GM49551 to K. S. A. and NIH intramural
research funds (ES065080) to W. C. C.
NR 22
TC 26
Z9 27
U1 0
U2 0
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 JUN
PY 2009
VL 53
IS 6
BP 2610
EP 2612
DI 10.1128/AAC.01659-08
PG 3
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 448DY
UT WOS:000266244500052
PM 19364868
ER
PT J
AU Zarember, KA
Cruz, AR
Huang, CY
Gallin, JI
AF Zarember, Kol A.
Cruz, Anna R.
Huang, Chiung-Yu
Gallin, John I.
TI Antifungal Activities of Natural and Synthetic Iron Chelators Alone and
in Combination with Azole and Polyene Antibiotics against Aspergillus
fumigatus
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; FUNGAL-INFECTIONS; INVASIVE ASPERGILLOSIS;
PRIMARY IMMUNODEFICIENCIES; THERAPY; MUCORMYCOSIS; ITRACONAZOLE;
POSACONAZOLE; FLUCONAZOLE; NEUTROPENIA
AB Antifungal effects of iron chelators (lactoferrin, deferoxamine, deferiprone, and ciclopirox) were tested alone and in combination with antifungal drugs against Aspergillus fumigatus B5233 conidia. Lactoferrin, ciclopirox, and deferiprone inhibited whereas deferoxamine enhanced fungal growth. Antifungal synergy against conidia was observed for combinations of ketoconazole with ciclopirox or deferiprone, lactoferrin with amphotericin B, and fluconazole with deferiprone. Iron chelation alone or combined with antifungal drugs may be useful for prevention and treatment of mycosis.
C1 [Zarember, Kol A.; Cruz, Anna R.; Gallin, John I.] Host Def Lab, Bethesda, MD 20892 USA.
[Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Zarember, KA (reprint author), Host Def Lab, 10 Ctr Dr,RM 5W 3816,MSC 1456, Bethesda, MD 20892 USA.
EM kzarember@niaid.nih.gov
FU NIAID; NIH Clinical Center
FX This work was supported by the Division of Intramural Research of the
NIAID and the NIH Clinical Center.
NR 25
TC 38
Z9 38
U1 0
U2 5
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 JUN
PY 2009
VL 53
IS 6
BP 2654
EP 2656
DI 10.1128/AAC.01547-08
PG 3
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 448DY
UT WOS:000266244500065
PM 19307370
ER
PT J
AU Altekruse, SF
Berrang, ME
Marks, H
Patel, B
Shaw, WK
Saini, P
Bennett, PA
Bailey, JS
AF Altekruse, Sean F.
Berrang, Mark E.
Marks, Harry
Patel, Bharat
Shaw, William K., Jr.
Saini, Parmesh
Bennett, Patricia A.
Bailey, J. Stan
TI Enumeration of Escherichia coli Cells on Chicken Carcasses as a
Potential Measure of Microbial Process Control in a Random Selection of
Slaughter Establishments in the United States
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID CAMPYLOBACTER SPP.; BROILER CARCASSES; SALMONELLA; CONTAMINATION;
POPULATIONS; POSTCHILL; NUMBERS; PLANTS
AB To evaluate whether the number of Escherichia coli bacteria in carcass rinses from chicken slaughter establishments could be monitored for the purpose of microbial process control, we drew a random sample from 20 of 127 large USDA-inspected operations. In 2005, every 3 months, two sets of 10 carcass rinses, 100 ml each, were collected from establishments, netting 80 sample sets from the rehang and postchill stages. E. coli and Campylobacter numbers and Salmonella prevalence were measured. Mixed-effect models were used to estimate variance of mean log(10) E. coli cell numbers of 10-carcass rinse sample sets. Relationships between E. coli and Campylobacter and Salmonella were examined. For 10-carcass rinse sets, at both the rehang and postchill stages the mean log(10) E. coli CFU/ml fit the logistic distribution better than the normal distribution. The rehang overall mean log(10) E. coli was 3.3 CFU/ml, with a within- sample set standard deviation of 0.6 CFU/ml. The overall postchill mean log(10) E. coli was 0.8 CFU/ml, with 13 establishments having mean log(10) E. coli CFU/ml values of less than 1.0 and 7 having mean values of 1.2 or more. At the midpoint separating these establishments, a mean log(10) E. coli CFU/ml of 1.1, the within- sample set standard deviation was 0.5 CFU/ml, with smaller standard deviations as means increased. Postchill sample sets with mean log(10) E. coli counts less than or equal to 1.1 CFU/ml had lower overall prevalence of Salmonella and mean log(10) Campylobacter CFU/ml than sample sets with higher means. These findings regarding reductions in E. coli numbers provide insight relevant to microbial process control.
C1 [Altekruse, Sean F.; Marks, Harry; Patel, Bharat; Shaw, William K., Jr.; Saini, Parmesh; Bennett, Patricia A.] USDA, Food Safety & Inspect Serv, Washington, DC 20250 USA.
[Berrang, Mark E.; Bailey, J. Stan] USDA ARS, Athens, GA 30605 USA.
RP Altekruse, SF (reprint author), NCI, Canc Surveillance Branch, 6116 Execut Blvd,Room 5003, Rockville, MD 20852 USA.
EM altekrusesf@mail.nih.gov
FU USDA; ARS; FSIS
FX Funding was provided by both collaborating USDA agencies, ARS and FSIS.
NR 23
TC 12
Z9 12
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0099-2240
J9 APPL ENVIRON MICROB
JI Appl. Environ. Microbiol.
PD JUN 1
PY 2009
VL 75
IS 11
BP 3522
EP 3527
DI 10.1128/AEM.02685-08
PG 6
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 449QT
UT WOS:000266345800017
PM 19363066
ER
PT J
AU Khrutchinsky, A
Kutsen, S
Minenko, V
Zhukova, O
Luckyanov, N
Bouville, A
Drozdovitch, V
AF Khrutchinsky, A.
Kutsen, S.
Minenko, V.
Zhukova, O.
Luckyanov, N.
Bouville, A.
Drozdovitch, V.
TI Monte Carlo modeling of beta-radiometer device used to measure milk
contaminated as a result of the Chernobyl accident
SO APPLIED RADIATION AND ISOTOPES
LA English
DT Article
DE Geiger-Mueller; Radionuclide; Calibration factor; Chernobyl
AB This paper presents results of Monte Carlo modeling of the beta-radiometer device with Geiger-Mueller detector used in Belarus and Russia to measure the radioactive contamination of milk after the Chernobyl accident. This type of detector, which is not energy selective, measured the total beta-activity of the radionuclide mix. A mathematical model of the beta-radiometer device, namely DP-100, was developed, and the calibration factors for the different radionuclides that might contribute to the milk contamination were calculated. The estimated calibration factors for (131)I, (137)Cs, (134)Cs, (90)Sr, (144)Ce, and (106)Ru reasonably agree with calibration factors determined experimentally. The calculated calibration factors for (132)Te, (132)l, (133)I, (136)Cs, (89)Sr, (103)Ru, (140)Ba, (140)La, and (141)Ce had not been previously determined experimentally. The obtained results allow to derive the activity of specific radionuclides, in particular (131)I, from the results of the total beta-activity measurements in milk. Results of this study are important for the purposes of retrospective dosimetry that uses measurements of radioactivity in environmental samples performed with beta-radiometer devices. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Luckyanov, N.; Bouville, A.; Drozdovitch, V.] NCI, DHHS, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Khrutchinsky, A.; Kutsen, S.] Res Inst Nucl Problems, Minsk 220050, Byelarus.
[Minenko, V.] Belarusian Med Acad Postgrad Educ, Minsk 220714, Byelarus.
[Zhukova, O.] Ctr Radiat Control & Environm Monitoring, Minsk 220023, Byelarus.
RP Drozdovitch, V (reprint author), NCI, DHHS, NIH, Div Canc Epidemiol & Genet, 6120 Executive Blvd,EPS 7100, Bethesda, MD 20892 USA.
EM drozdovv@mail.nih.gov
RI Kuten, Semen/F-6699-2016
OI Kuten, Semen/0000-0003-0827-8421
FU National Cancer Institute (USA) [B-488P]; Intra-Agency Agreement between
the National Institute of Allergy and Infectious Diseases (USA) and the
National Cancer Institute; MAID agreement [Y2-Al-5077]; NCI agreement
[Y3-CO-5117]
FX This work was supported by the National Cancer Institute (USA) within
the framework of the ISTC Project B-488P and by the Intra-Agency
Agreement between the National Institute of Allergy and Infectious
Diseases (USA) and the National Cancer Institute, MAID agreement
#Y2-Al-5077 and NCI agreement #Y3-CO-5117.
NR 9
TC 1
Z9 1
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0969-8043
J9 APPL RADIAT ISOTOPES
JI Appl. Radiat. Isot.
PD JUN
PY 2009
VL 67
IS 6
BP 1089
EP 1093
DI 10.1016/j.apradiso.2009.01.072
PG 5
WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology,
Nuclear Medicine & Medical Imaging
SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 447GX
UT WOS:000266180700019
PM 19233662
ER
PT J
AU King, BH
Hollander, E
Sikich, L
McCracken, JT
Scahill, L
Bregman, JD
Donnelly, CL
Anagnostou, E
Dukes, K
Sullivan, L
Hirtz, D
Wagner, A
Ritz, L
AF King, Bryan H.
Hollander, Eric
Sikich, Linmarie
McCracken, James T.
Scahill, Lawrence
Bregman, Joel D.
Donnelly, Craig L.
Anagnostou, Evdokia
Dukes, Kimberly
Sullivan, Lisa
Hirtz, Deborah
Wagner, Ann
Ritz, Louise
CA STAART Psychopharmacology Network
TI Lack of Efficacy of Citalopram in Children With Autism Spectrum
Disorders and High Levels of Repetitive Behavior Citalopram Ineffective
in Children With Autism
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID PERVASIVE DEVELOPMENTAL DISORDERS; OBSESSIVE-COMPULSIVE DISORDER;
SEROTONIN-REUPTAKE INHIBITORS; DOUBLE-BLIND; ADOLESCENT AUTISM;
CROSSOVER TRIAL; MEDICATION USE; OPEN-LABEL; PLACEBO; FLUVOXAMINE
AB Context: Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders.
Objectives: To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders.
Design: National Institutes of Health-sponsored randomized controlled trial.
Setting: Six academic centers, including Mount Sinai School of Medicine, North Shore-Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School. Participants: One hundred forty-nine volunteers 5 to 17 years old(mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram(n = 73) or placebo(n = 76).
Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders.
Interventions: Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d).
Main Outcome Measures: Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form.
Results: There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P > . 99). There was no difference in score reduction on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], -2.0 [3.4] points for the citalopram-treated group and -1.9[2.5] points for the placebo group; P = . 81). Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus.
Conclusion: Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders.
C1 [King, Bryan H.] Univ Washington, Seattle Childrens Hosp, Dept Psychiat, Seattle, WA 98105 USA.
[Hollander, Eric; Anagnostou, Evdokia] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Bregman, Joel D.] N Shore Long Isl Jewish Hlth Syst, Dept Psychiat, Great Neck, NY USA.
[Sikich, Linmarie] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[McCracken, James T.] Univ Calif Los Angeles, Semel Inst, Dept Psychiat, Los Angeles, CA 90024 USA.
[Scahill, Lawrence] Yale Univ, Sch Nursing, New Haven, CT 06536 USA.
[Scahill, Lawrence] Yale Univ, Ctr Child Study, New Haven, CT 06536 USA.
[Donnelly, Craig L.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03756 USA.
DM STAT Inc, Malden, MA USA.
[Dukes, Kimberly; Sullivan, Lisa] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Hirtz, Deborah] Natl Inst Neurol Disorders & Stroke, Off Clin Res, Bethesda, MD USA.
[Wagner, Ann; Ritz, Louise] NIMH, Div Dev Translat Res, Rockville, MD 20857 USA.
RP King, BH (reprint author), Univ Washington, Seattle Childrens Hosp, Dept Psychiat, 4800 Sand Point Way NE, Seattle, WA 98105 USA.
EM bhking@u.washington.edu
OI Scahill, Lawrence/0000-0001-5073-1707
FU NICHD NIH HHS [U01 HD045023, U01-HD045023]; NIMH NIH HHS [U54 MH066418,
U54 MH066398, U54 MH066494, U54 MH066673, U54 MH068172, U54-MH066398,
U54-MH066494, U54-MH066673, U54-MH068172]
NR 44
TC 189
Z9 191
U1 1
U2 15
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 JUN
PY 2009
VL 66
IS 6
BP 583
EP 590
PG 8
WC Psychiatry
SC Psychiatry
GA 452UN
UT WOS:000266566800003
PM 19487623
ER
PT J
AU Spinelli, S
Chefer, S
Suomi, SJ
Higley, JD
Barr, CS
Stein, E
AF Spinelli, Simona
Chefer, Svetlana
Suomi, Stephen J.
Higley, J. Dee
Barr, Christina S.
Stein, Elliot
TI Early-Life Stress Induces Long-term Morphologic Changes in Primate Brain
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID ANTERIOR CINGULATE CORTEX; MAGNETIC-RESONANCE SPECTROSCOPY;
PITUITARY-ADRENAL AXIS; RHESUS-MONKEY INFANTS; NONHUMAN-PRIMATES;
PLASMA-CORTISOL; CHILDHOOD MALTREATMENT; SEPARATION PARADIGM;
ALCOHOL-CONSUMPTION; REARING CONDITION
AB Context: Traumatic experiences in early childhood are associated with increased risk of developing stress-related disorders, which are linked to structural brain abnormalities. However, it is unclear whether these volumetric brain changes are present before disease onset or reflect the consequences of disease progression.
Objective: To identify structural abnormalities in the nonhuman primate brain that may predict increased risk of stress-related neuropsychiatric disorders in human beings.
Design: Rhesus monkeys were divided into 2 groups at birth: a group raised with their mothers and other juvenile and adult animals (mother reared) and a group raised with 3 age-matched monkeys only (peer reared) for the first 6 months of life. Anatomical brain images were acquired in juvenile male and female rhesus monkeys using magnetic resonance imaging.
Setting: National Institutes of Health Animal Center in Poolesville, Maryland.
Subjects: Twenty-eight rhesus monkeys (Macaca mulatta) aged 24 to 30 months were used for the study.
Main Outcome Measures: Volumetric measures of the anterior cingulate cortex, medial prefrontal cortex, hippocampus, corpus callosum, and cerebellar vermis were compared between mother-reared (n = 15) and peer-reared animals (n = 13).
Results: Compared with mother-reared monkeys, we found an enlarged vermis, dorsomedial prefrontal cortex, and dorsal anterior cingulate cortex in peer-reared monkeys without any apparent differences in the corpus callosum and hippocampus.
Conclusions: Peer-rearing during infancy induces enlargement in stress-sensitive brain regions. These changes may be a structural phenotype for increased risk of stress-related neuropsychiatric disorders in human beings.
C1 [Higley, J. Dee] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA.
[Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA.
[Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, Natl Inst Human Serv, Bethesda, MD 20892 USA.
[Chefer, Svetlana; Stein, Elliot] Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Bethesda, MD USA.
[Spinelli, Simona; Barr, Christina S.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
RP Spinelli, S (reprint author), Johns Hopkins Sch Med, Kennedy Krieger Inst, 707 N Broadway, Baltimore, MD 21205 USA.
EM spinellis@kennedykrieger.org
FU National Institute on Alcohol Abuse and Alcoholism; National Institute
on Drug Abuse; National Institute of Child Health and Human Development
FX This study was supported by the Intramural Research Programs of the
National Institute on Alcohol Abuse and Alcoholism, the National
Institute on Drug Abuse, and the National Institute of Child Health and
Human Development.
NR 44
TC 96
Z9 97
U1 2
U2 15
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 JUN
PY 2009
VL 66
IS 6
BP 658
EP 665
PG 8
WC Psychiatry
SC Psychiatry
GA 452UN
UT WOS:000266566800011
PM 19487631
ER
PT J
AU Kim, C
Taniyama, Y
Paik, S
AF Kim, Chungyeul
Taniyama, Yusuke
Paik, Soonmyung
TI Gene Expression-Based Prognostic and Predictive Markers for Breast
Cancer A Primer for Practicing Pathologists
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID DNA MICROARRAY; ADJUVANT; CHEMOTHERAPY; THERAPY; WOMEN; ASSAY
AB Context.-Gene expression-based prognostic assays for breast cancer are now available as commercial reference laboratory tests covered by insurance.
Objective.-To provide practicing pathologists with information about the nature of these assays, differences among them, and their use by clinical oncologists in the management of patients diagnosed with breast cancer.
Data Sources.-Review of literature and unpublished data from the National Surgical Adjuvant Breast and Bowel Project. This review focused on a general conceptual description of the technology behind these assays and differences among them to aid understanding by pathologists in practice.
Conclusions.-While these assays are clinically useful, they are still evolving. The future development of gene expression-based markers will need to be more clinical-context-specific to be clinically useful. (Arch Pathol Lab Med. 2009; 133: 855-859)
C1 [Paik, Soonmyung] Natl Surg Adjuvant Breast & Bowel Project Fdn, Div Pathol, NSABP, Pittsburgh, PA 15212 USA.
RP Paik, S (reprint author), Natl Surg Adjuvant Breast & Bowel Project Fdn, Div Pathol, NSABP, 4 Allegheny Ctr 5th Floor,E Commons Profess Bldg, Pittsburgh, PA 15212 USA.
EM soon.paik@nsabp.org
FU NCI NIH HHS [U10 CA069651-15, U10CA-69974, U10 CA069974-13, U10
CA069974, U10CA-12027, U10CA-37377, U10CA-69651, U10 CA012027, U10
CA069651, U10 CA037377, U10 CA037377-23, U10 CA012027-38]
NR 19
TC 9
Z9 9
U1 0
U2 2
PU COLLEGE AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD JUN
PY 2009
VL 133
IS 6
BP 855
EP 859
PG 5
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA 457CS
UT WOS:000266903900005
PM 19492877
ER
PT J
AU Colburn, NT
Zaal, KJM
Wang, F
Tuan, RS
AF Colburn, Nona T.
Zaal, Kristien J. M.
Wang, Francis
Tuan, Rocky S.
TI A Role for gamma/delta T Cells in a Mouse Model of Fracture Healing
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID COLLAGEN-INDUCED ARTHRITIS; IMMUNE MICROENVIRONMENT; INFLAMMATORY
RESPONSE; SYSTEMIC IMMUNITY; TISSUE HEMATOMAS; GROWTH-FACTORS;
BONE-FRACTURE; MUTANT MICE; IN-VIVO; GAMMA
AB Objective. Fractures can initiate an immune response that disturbs osteoblastic and osteoclastic cellular homeostasis through cytokine production and release. The aim of our study was to investigate gamma/delta T cells, innate lymphocytes known to be involved in tissue repair, as potential cellular components of the osteoimmune system's response to an in vivo model of bone injury. The absence of such cells or their effector cytokines influences the fate of other responder cells in proliferation, differentiation, matrix production, and ultimate callus formation.
Methods. Tibia fractures were created in 60 gamma/delta T cell-deficient mice (also called 5 T cell receptor [TCR]-knockout mice) and 60 control C57BL/6 mice. Analysis included radiographs, basic histology, mechanical testing, now cytometry, and immunohistochemical localization of gamma/delta TCR-positive subsets from control animals and of CD44 expression from both groups, as well as enzyme-linked immunosorbent assay for the effector cytokines interleukin-2 (IL-2), interferon-gamma (IFN gamma), and IL-6.
Results. Animals deficient in gamma/delta T cells demonstrated more mature histologic elements and quantitative increases in the expression of major bone (bone sialoprotein) and cartilage (type II collagen) matrix proteins and in the expression of bone morphogenetic protein 2 at a critical reparative phase. Moreover, only gamma/delta T cell-deficient animals had a decrease in the osteoprogenitor antiproliferative cytokines IL-6 and IFN gamma at the reparative phase. The result was improved stability at the repair site and an overall superior biomechanical strength in gamma/delta T cell-deficient mice compared with controls.
Conclusion. The evidence for a role of gamma/delta T cells in the context of skeletal injury demonstrates the importance of the immune system's effect on bone biology, which is relevant to the field of osteoimmunology, and offers a potential molecular platform from which to develop essential therapeutic strategies.
C1 [Colburn, Nona T.; Zaal, Kristien J. M.; Tuan, Rocky S.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Wang, Francis] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA.
RP Colburn, NT (reprint author), NIAMSD, NIH, 9000 Rockville Pike,Bldg 10,Room 10C-212, Bethesda, MD 20892 USA.
EM ColburnN@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
[Z01-AR-41131]; National Institute of Standards and Technology
FX Supported by the NIH (grant Z01-AR-41131 from the Intramural Research
Program of the National Institute of Arthritis and Musculoskeletal and
Skin Diseases) and the National Institute of Standards and Technology
(official contribution of the National Institute of Standards and
Technology; not subject to copyright in the United States).
NR 56
TC 33
Z9 33
U1 1
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRITIS RHEUM
JI Arthritis Rheum.
PD JUN
PY 2009
VL 60
IS 6
BP 1694
EP 1703
DI 10.1002/art.24520
PG 10
WC Rheumatology
SC Rheumatology
GA 459PV
UT WOS:000267116800019
PM 19479830
ER
PT J
AU Booty, MG
Chae, JJ
Masters, SL
Remmers, EF
Barham, B
Le, JM
Barron, KS
Holland, SM
Kastner, DL
Aksentijevich, I
AF Booty, Matthew G.
Chae, Jae Jin
Masters, Seth L.
Remmers, Elaine F.
Barham, Beverly
Le, Julie M.
Barron, Karyl S.
Holland, Steve M.
Kastner, Daniel L.
Aksentijevich, Ivona
TI Familial Mediterranean Fever With a Single MEFV Mutation Where Is the
Second Hit?
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID NF-KAPPA-B; DIAGNOSTIC-VALUE; MESSENGER-RNA; GENE ANALYSIS; PYRIN; FMF;
PROTEIN; INFLAMMATION; ENVIRONMENT; RECRUITMENT
AB Objective. Familial Mediterranean fever (IMF) has traditionally been considered an autosomal-recessive disease; however, it has been observed that a substantial number of patients with clinical IMF possess only 1 demonstrable MEFV mutation. The purpose of this study was to perform an extensive search for a second MEFV mutation in 46 patients diagnosed clinically as having FMF and carrying only 1 high-penetrance IMF mutation.
Methods. MEFV and other candidate genes were sequenced by standard capillary electrophoresis. In 10 patients, the entire 15-kb MEFV genomic region was resequenced using hybridization-based chip technology. MEFV gene expression levels were determined by quantitative reverse transcription-polymerase chain reaction. Pyrin protein levels were examined by Western blotting.
Results. A second MEFV mutation was not identified in any of the patients who were screened. Haplotype analysis did not identify a common haplotype that might be associated with the transmission of a second IMF allele. Western blots did not demonstrate a significant difference in pyrin levels between patients with a single mutation and those with a double mutation; however, FMF patients of both types showed higher protein expression as compared with controls and with non-FMF patients with active inflammation. Screening of genes encoding pyrin-interacting proteins identified rare mutations in a small number of patients, suggesting the possibility of digenic inheritance.
Conclusion. Our data underscore the existence of a significant subset of IMF patients who are carriers of only 1 MEFV mutation and demonstrate that complete MEFV sequencing is not likely to yield a second mutation. Screening for the set of the most common mutations and detection of a single mutation appears to be sufficient in the presence of clinical symptoms for the diagnosis of IMF and the initiation of a trial of colchicine.
C1 [Aksentijevich, Ivona] NIAMSD, NIH, Genet & Genom Branch, Bethesda, MD 20892 USA.
[Barron, Karyl S.; Holland, Steve M.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Aksentijevich, I (reprint author), NIAMSD, NIH, Genet & Genom Branch, Bldg 10,Room 10C101A, Bethesda, MD 20892 USA.
EM aksentii@exchange.nih.gov
RI Masters, Seth/N-2886-2013;
OI Masters, Seth/0000-0003-4763-576X; Booty, Matthew/0000-0002-0835-3439
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
FX Supported by the Intramural Research program of the National Institute
of Arthritis and Musculoskeletal and Skin Diseases.
NR 41
TC 93
Z9 93
U1 1
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRITIS RHEUM
JI Arthritis Rheum.
PD JUN
PY 2009
VL 60
IS 6
BP 1851
EP 1861
DI 10.1002/art.24569
PG 11
WC Rheumatology
SC Rheumatology
GA 459PV
UT WOS:000267116800039
PM 19479870
ER
PT J
AU Luangwedchakarn, V
Jirapongsaranuruk, O
Niemela, JE
Thepthai, C
Chokephaibulkit, K
Sukpanichnant, S
Pacharn, P
Visitsunthorn, N
Vichyanond, P
Piboonpocanun, S
Fleisher, TA
AF Luangwedchakarn, Voravich
Jirapongsaranuruk, Orathai
Niemela, Julie E.
Thepthai, Charin
Chokephaibulkit, Kulkanya
Sukpanichnant, Sanya
Pacharn, Punchama
Visitsunthorn, Nualanong
Vichyanond, Pakit
Piboonpocanun, Surapon
Fleisher, Thomas A.
TI A Novel Mutation of the IL12RB1 Gene in a Child with Nocardiosis,
Recurrent Salmonellosis and Neurofibromatosis Type I: First Case Report
from Thailand
SO ASIAN PACIFIC JOURNAL OF ALLERGY AND IMMUNOLOGY
LA English
DT Article
ID IL-12 RECEPTOR; INTERLEUKIN-12; IMMUNITY; DEFICIENCY; MYCOBACTERIAL;
RESISTANCE; EXPRESSION; IL-23
AB Genetic defects of interleukin (IL)-12/23-and interferon (IFN)-gamma-mediated immunity can cause increased susceptibility to intracellular microbes. Among these defects, a mutation of the gene encoding the IL-12 receptor beta 1 (IL-12R beta 1) is the most common worldwide. A 12-year old Thai boy with pre-existing neurofibromatosis type 1 (NF1) was evaluated for primary immunodeficiency after a history of tuberculous lymphadenitis, recurrent Salmonella infections and nocardiosis. Flow cytometry of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) revealed a defect in the IL-12R beta 1 surface expression. A genetic study showed a novel nonsense homozygous mutation of the IL12RB1 gene in exon 4 (402C>A), confirming the diagnosis of IL-12R beta 1 deficiency. This is the first case report of a primary IL-12R beta 1 deficiency in Thailand with the interesting finding of a coexisting NF1.
C1 [Luangwedchakarn, Voravich; Thepthai, Charin] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Immunol, Bangkok 10700, Thailand.
[Jirapongsaranuruk, Orathai; Chokephaibulkit, Kulkanya; Pacharn, Punchama; Visitsunthorn, Nualanong; Vichyanond, Pakit] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Pediat, Bangkok 10700, Thailand.
[Niemela, Julie E.; Fleisher, Thomas A.] Natl Inst Hlth, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Sukpanichnant, Sanya] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Pathol, Bangkok 10700, Thailand.
[Piboonpocanun, Surapon] Mahidol Univ, Inst Mol Biol & Genet, Nakhon Pathom, Thailand.
RP Luangwedchakarn, V (reprint author), Mahidol Univ, Siriraj Hosp, Fac Med, Dept Immunol, Bangkok 10700, Thailand.
EM sivlw@mahidol.ac.th
OI Niemela, Julie/0000-0003-4197-3792
NR 19
TC 7
Z9 7
U1 0
U2 1
PU ALLERGY IMMUNOL SOC THAILAND,
PI BANGKOK
PA MAHIDOL UNIV, DEPT MICROBIOL IMMUNOL, FACULTY TROPICAL MED, BANGKOK
10400, THAILAND
SN 0125-877X
J9 ASIAN PAC J ALLERGY
JI Asian Pac. J. Allergy Immunol.
PD JUN-SEP
PY 2009
VL 27
IS 2-3
BP 161
EP 165
PG 5
WC Allergy; Immunology
SC Allergy; Immunology
GA 506SO
UT WOS:000270796500011
PM 19839503
ER
PT J
AU Glaser, V
Gottesman, MM
AF Glaser, Vicki
Gottesman, Michael M.
TI An Interview with Michael M. Gottesman, MD
SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
LA English
DT Editorial Material
C1 [Glaser, Vicki] NCI, Cell Biol Lab, Bethesda, MD 20892 USA.
[Glaser, Vicki; Gottesman, Michael M.] NIH, Bethesda, MD 20892 USA.
[Gottesman, Michael M.] Harvard Univ, Dept Anat, Cambridge, MA 02138 USA.
RP Glaser, V (reprint author), NCI, Cell Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-658X
J9 ASSAY DRUG DEV TECHN
JI ASSAY DRUG DEV. TECHNOL.
PD JUN
PY 2009
VL 7
IS 3
BP 213
EP 218
DI 10.1089/adt.2009.9991
PG 6
WC Biochemical Research Methods; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 470WM
UT WOS:000268013100001
ER
PT J
AU Brimacombe, KR
Hall, MD
Auld, DS
Inglese, J
Austin, CP
Gottesman, MM
Fung, KL
AF Brimacombe, Kyle R.
Hall, Matthew D.
Auld, Douglas S.
Inglese, James
Austin, Christopher P.
Gottesman, Michael M.
Fung, King-Leung
TI A Dual-Fluorescence High-Throughput Cell Line System for Probing
Multidrug Resistance
SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
LA English
DT Article
ID P-GLYCOPROTEIN; MICROPLATE CYTOMETRY; CANCER; TRANSPORTERS; ATP; ASSAYS;
EXPRESSION; PREDICTION; INHIBITORS; SCREEN
AB The efflux pump P-glycoprotein (ATP-binding cassette B1, multidrug resistance [MDR] 1, P-gp) has long been known to contribute to MDR against cancer chemotherapeutics. We describe the development of a dual-fluorescent cell line system to allow multiplexing of drug-sensitive and P-gp-mediated MDR cell lines. The parental OVCAR-8 human ovarian carcinoma cell line and the isogenic MDR NCI/ADR-RES subline, which stably expresses high levels of endogenous P-gp, were transfected to express the fluorescent proteins Discosoma sp. red fluorescent protein DsRed2 and enhanced green fluorescent protein, respectively. Co-culture conditions were defined, and fluorescent barcoding of each cell line allowed for the direct, simultaneous comparison of resistance to cytotoxic compounds in sensitive and MDR cell lines. We show that this assay system retains the phenotypes of the original lines and is suitable for multiplexing using confocal microscopy, flow cytometry, or laser scanning microplate cytometry in 1,536-well plates, enabling the high-throughput screening of large chemical libraries.
C1 [Brimacombe, Kyle R.; Hall, Matthew D.; Gottesman, Michael M.; Fung, King-Leung] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Auld, Douglas S.; Inglese, James; Austin, Christopher P.] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA.
EM gottesmm@mail.nih.gov
RI Hall, Matthew/B-2132-2010
FU National Institutes of Health; Center for Cancer Research/NCI
FX The authors gratefully acknowledge the assistance of Susan H. Garfield
and Poonam Mannan of the National Cancer Institute Confocal Microscopy
Core Facility, Drs. Natasha Thorne and Noel Southall of the National
Institutes of Health Chemical Genomics Center, and George Leiman for his
editorial assistance. This research was supported by the Intramural
Research Program of the National Institutes of Health. K. R. B. was
supported by a Center for Cancer Research/NCI training fellowship.
NR 40
TC 24
Z9 24
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-658X
J9 ASSAY DRUG DEV TECHN
JI ASSAY DRUG DEV. TECHNOL.
PD JUN
PY 2009
VL 7
IS 3
BP 233
EP 249
DI 10.1089/adt.2008.165
PG 17
WC Biochemical Research Methods; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 470WM
UT WOS:000268013100002
PM 19548831
ER
PT J
AU Sanderson, SC
Kumari, M
Brunner, EJ
Miller, MA
Rumley, A
Lowe, GD
Marmot, MG
Humphries, SE
AF Sanderson, Saskia C.
Kumari, Meena
Brunner, Eric J.
Miller, Michelle A.
Rumley, Ann
Lowe, Gordon D.
Marmot, Michael G.
Humphries, Steve E.
TI Association between IL6 gene variants-174G > C and-572G > C and serum
IL-6 levels: Interactions with social position in the Whitehall II
cohort
SO ATHEROSCLEROSIS
LA English
DT Article
DE Epidemiology; Genes; Genetics; Inflammation; Interleukins
ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; CARDIOVASCULAR RISK-FACTORS;
INTERLEUKIN-6 GENE; MYOCARDIAL-INFARCTION; PROMOTER POLYMORPHISMS;
ENVIRONMENT INTERACTION; INSULIN-RESISTANCE; NO ASSOCIATION; PLASMA
AB Objective: To examine the impact of -174G>C and -572G>C variants in the promoter region of the IL6 gene, and their interactions with social position, on interleukin-6 (IL-6) levels in the Whitehall II cohort.
Methods and results: SNPs were genotyped by TaqMan. IL-6 was measured by ELISA. Employment grade was assessed to indicate social position. ANOVAs were used to examine genotype-phenotype associations. 4165 white men and women provided data on IL-6 levels at two study time points, Phase 3 (1991-1993) and Phase 7 (2002-2004). Distributions were as expected for Hardy-Weinberg equilibrium. At Phase 3, overall IL-6 levels did not differ by either genotype, but -174C was associated with higher IL-6 levels within the lowest employment grades (P(interaction) = 0.046). At Phase 7, IL-6 levels overall were 6% higher in -174C (p=0.002) and 9% lower in -572C (p=0.003) carriers. The lowering effect of -572C was not apparent in the lowest employment grades (P(interaction) = 0.05).
Conclusions: IL-6 levels are determined in part by interaction between common functional IL6 gene variants and yet to be identified components of social position. These results highlight the importance of considering interactions between genes and social environments in future study designs. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Sanderson, Saskia C.; Kumari, Meena; Brunner, Eric J.; Marmot, Michael G.] UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
[Sanderson, Saskia C.; Humphries, Steve E.] Royal Free & Univ Coll Med Sch, Ctr Cardiovasc Genet, Dept Med, British Heart Fdn Labs, London WC1E 6JF, England.
[Sanderson, Saskia C.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Miller, Michelle A.] Warwick Med Sch, Clin Sci Res Inst, Coventry CV2 2DX, W Midlands, England.
[Lowe, Gordon D.] Univ Glasgow, Div Cardiovasc & Med Sci, Royal Infirm, Glasgow G31 2ER, Lanark, Scotland.
RP Kumari, M (reprint author), UCL, Dept Epidemiol & Publ Hlth, Whitehall 2,19 Torrington Pl, London WC1E 6BT, England.
EM m.kumari@ucl.ac.uk
RI Miller, Michelle/D-1840-2009; Brunner, Eric/H-2114-2011;
OI Humphries, Stephen E/0000-0002-8221-6547; Kumari,
Meena/0000-0001-9716-1035; Marmot, Michael/0000-0002-2431-6419
FU British Heart Foundation [RG/07/008/23674, RG/08/008/25291, RG2005/014];
Department of Health; Medical Research Council [G0100222, , G19/35,
G8802774]; NHLBI NIH HHS [HL36310]; NIA NIH HHS [AG13196]
NR 32
TC 11
Z9 12
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JUN
PY 2009
VL 204
IS 2
BP 459
EP 464
DI 10.1016/j.atherosclerosis.2008.09.019
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 460PW
UT WOS:000267200600025
PM 19019369
ER
PT J
AU Koh, KK
Quon, MJ
Han, SH
Lee, Y
Kim, SJ
Park, JB
Shin, EK
AF Koh, Kwang Kon
Quon, Michael J.
Han, Seung Hwan
Lee, Yonghee
Kim, Soo Jin
Park, Jeong Beorn
Shin, Eak Kyun
TI Differential metabolic effects of pravastatin and simvastatin in
hypercholesterolemic patients
SO ATHEROSCLEROSIS
LA English
DT Article
DE Statins; Adipocytokines; Insulin resistance; Endothelial function
ID C-REACTIVE PROTEIN; ASSESSING INSULIN SENSITIVITY; SCOTLAND CORONARY
PREVENTION; DEPENDENT DIABETES-MELLITUS; RANDOMIZED CONTROLLED-TRIAL;
HYPERTENSIVE PATIENTS; THERAPEUTIC INTERVENTIONS; ENDOTHELIAL
DYSFUNCTION; CARDIOVASCULAR-DISEASE; ADIPONECTIN LEVELS
AB Background: Lipophilic and hydrophilic statins have different effects on adiponectin and insulin resistance in experimental studies and different effects on the rate of onset of new diabetes in large scale clinical studies. Therefore, we hypothesized that simvastatin and pravastatin may have differential metabolic effects in hypercholesterolemic patients.
Methods: This was a randomized, single-blind, placebo-controlled, parallel study. Age, gender, and body mass index were matched. Forty-three patients were given placebo, simvastatin 20mg. or pravastatin 40 mg, respectively once daily for 2 months.
Results: Simvastatin and pravastatin therapy significantly changed lipoprotein levels and improved flow-mediated dilation after 2 months when compared with baseline (P<0.001) or placebo treatment (P<0.001 by ANOVA). Simvastatin therapy significantly increased insulin levels (mean % changes; 127%, P=0.014) and decreased plasma adiponectin levels (10%, P=0.012) and insulin sensitivity as assessed by QUICK1 (6%, P=0.007) when compared with baseline. By contrast, pravastatin therapy did not significantly change insulin levels (-3%, P=0.437) but significantly increased plasma adiponectin levels (9%, P=0.011) and insulin sensitivity (6%, P=0.008) when compared with baseline. In addition, these effects of simvastatin were significant when compared with pravastatin (P<0.001 for insulin levels by ANOVA on Ranks, P<0.001 for adiponectin and P= 0.001 for QUICK1 by ANOVA). When compared with baseline, simvastatin significantly increased plasma leptin levels (35%, P=0.028), but pravastatin did not (1%, P=0.822).
Conclusions: Despite causing comparable changes in lipoprotein and endothelium-dependent dilation, simvastatin and pravastatin therapy had differential metabolic effects in hypercholesterolemic patients that may be clinically relevant. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Koh, Kwang Kon] Gachon Univ, Vasc Med & Atherosclerosis Unit, Gil Med Ctr, Inchon 405760, South Korea.
[Quon, Michael J.] NIH, Diabet Unit, NCCAM, Bethesda, MD 20892 USA.
[Lee, Yonghee] Ewha Womans Univ, Dept Stat, Seoul, South Korea.
RP Koh, KK (reprint author), Gachon Univ, Vasc Med & Atherosclerosis Unit, Gil Med Ctr, 1198 Kuwol Dong, Inchon 405760, South Korea.
EM kwangk@gilhospital.com
OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707
FU Gachon UniversityGil Medical Center [2006-1, 2007-1]
FX This study was partly supported by grants from established investigator
award (2006-1,2007-1), Gachon UniversityGil Medical Center.
NR 45
TC 68
Z9 70
U1 1
U2 2
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 JUN
PY 2009
VL 204
IS 2
BP 483
EP 490
DI 10.1016/j.atherosclerosis.2008.09.021
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 460PW
UT WOS:000267200600029
PM 18977478
ER
PT J
AU Schnabel, R
Dupuis, J
Larson, MG
Lunetta, KL
Robins, SJ
Zhu, YY
Rong, J
Yin, XY
Stirnadel, HA
Nelson, JJ
Wilson, PWF
Keaney, JF
Vasan, RS
Benjamin, EJ
AF Schnabel, Renate
Dupuis, Josee
Larson, Martin G.
Lunetta, Kathryn L.
Robins, Sander J.
Zhu, Yanyan
Rong, Jian
Yin, Xiaoyan
Stirnadel, Heide A.
Nelson, Jeanne J.
Wilson, Peter W. F.
Keaney, John F.
Vasan, Ramachandran S.
Benjamin, Emelia J.
TI Clinical and genetic factors associated with lipoprotein-associated
phospholipase A(2) in the Framingham Heart Study
SO ATHEROSCLEROSIS
LA English
DT Article
DE Lipoprotein-associated phospholipase A2; Inflammation; Heritability;
Single nucleotide polymorphism
ID ACTIVATING-FACTOR-ACETYLHYDROLASE; CORONARY-ARTERY-DISEASE; FUTURE
CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; INDEPENDENT PREDICTOR;
RISK-FACTORS; POPULATION; PLASMA; ATHEROSCLEROSIS; INFLAMMATION
AB Objective: To conduct an investigation of clinical and genetic correlates of lipoprotein-associated phospholipase (Lp-PLA(2)) activity and mass in a large community-based cohort. Higher circulating Lp-PLA2 predicts cardiovascular disease risk, but sources of inter-individual variability are incompletely understood.
Methods: We conducted stepwise regression of clinical correlates of Lp-PLA2 in four Framingham Heart Study cohorts (n = 8185; meanage 50 +/- 14 years, 53.8% women, 9.8% ethnic/racial minority cohort). We also conducted heritability and linkage analyses in Offspring and Generation 3 cohorts (n = 6945). In Offspring cohort participants we performed association analyses (it = 1535 unrelated) with 1943 common tagging SNPs in 233 inflammatory candidate genes.
Results: Sixteen clinical variables explained 57% of the variability in Lp-PLA2 activity; covariates associated with Lp-PLA2 mass were similar but only explained 27% of the variability. Multivariable-adjusted heritability estimates for Lp-PLA2 activity and mass were 41% and 25%, respectively. A linkage peak was observed for Lp-PLA2 activity (chromosome 6, LOD score 2.4). None of the SNPs achieved experiment-wide statistical significance, though 12 had q values <0.50, and hence we expect at least 50% of these associations to be true positives. The strongest multivariable-association with Lp-PLA2 activity was found for MEF2A (rs2033547: nominal p = 3.20 x 10(-4)); SNP rs1051931 in PLA2G7 was nominally associated (p = 1.26 x 10(-3)). The most significant association to Lp-PLA2 mass was in VEGFC (rs10520358, p = 9.14 x 10-4).
Conclusions: Cardiovascular risk factors and genetic variation contribute to variability in Lp-PLA(2) activity and mass. Our genetic association analyses need replication, which will be facilitated by web posting of our genetic association results. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Dept Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Robins, Sander J.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA.
[Dupuis, Josee; Lunetta, Kathryn L.; Zhu, Yanyan] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA.
[Wilson, Peter W. F.] Emory Univ, Sch Med, Dept Med, Div Cardiol, Harlow, Essex, England.
[Stirnadel, Heide A.; Nelson, Jeanne J.] GlaxoSmithKIine R&D, Cardiovasc Metab & Genet Support, Harlow, Essex, England.
[Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, NHLBI, Framingham, MA 01702 USA.
RP Benjamin, EJ (reprint author), Boston Univ, Framingham Heart Study, NHLBI, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM emelia@bu.edu
RI Zhu, Yanyan/C-7833-2011; Schnabel, Renate/F-6527-2014;
OI Lunetta, Kathryn/0000-0002-9268-810X; Larson,
Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970;
Dupuis, Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336
FU NCRR NIH HHS [1S10RR163736-01A1]; NHGRI NIH HHS [HG000848, R01 HG000848,
R01 HG000848-12]; NHLBI NIH HHS [R01 HL071039-02, HL04334, HL076784,
HL64753, HL70139, K24 HL004334, K24 HL004334-08, N01 HC025195,
N01-HC-25195, N01HC25195, R01 HL064753, R01 HL064753-04, R01 HL071039,
R01 HL076784, R01 HL076784-05]; NIA NIH HHS [AG028321, R01 AG028321, R01
AG028321-04]
NR 28
TC 13
Z9 14
U1 0
U2 4
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 JUN
PY 2009
VL 204
IS 2
BP 601
EP 607
DI 10.1016/j.atherosclerosis.2008.10.030
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 460PW
UT WOS:000267200600049
PM 19135199
ER
PT J
AU Amar, M
Stonick, J
Remaley, A
AF Amar, M.
Stonick, J.
Remaley, A.
TI TRANSFER OF CHOLESTERYL ESTER FROM HDL TO LDL BY A CETP-INDEPENDENT
PATHWAY IN MICE
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
C1 [Amar, M.; Stonick, J.; Remaley, A.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN
PY 2009
VL 10
IS 2
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA V17SO
UT WOS:000207957101064
ER
PT J
AU Fleg, J
Meta, M
Howard, B
Roman, M
Howard, W
AF Fleg, J.
Meta, M.
Howard, B.
Roman, M.
Howard, W.
TI THE SANDS TRIAL: THE EFFECT OF STATINS WITH VERSUS WITHOUT EZETIMIBE ON
CAROTID ATHEROSCLEROSIS IN TYPE 2 DIABETES
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
C1 [Fleg, J.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Meta, M.; Howard, B.] MedStar Res Inst, Hyatsville, MD USA.
[Roman, M.] Weil Cornell Med Ctr, New York, NY USA.
[Howard, W.] Washington Hosp Ctr, Washington, DC 20010 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN
PY 2009
VL 10
IS 2
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA V17SO
UT WOS:000207957100694
ER
PT J
AU O'Donnell, C
AF O'Donnell, C.
TI FROM RISK FACTORS TO GENETIC AND SERUM MARKERS: NEW DIRECTIONS IN NHLBI
OBSERVATIONAL STUDIES
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
C1 [O'Donnell, C.] NHLBI, Framingham Heart Study, Framingham, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN
PY 2009
VL 10
IS 2
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA V17SO
UT WOS:000207957100651
ER
PT J
AU Rousset, X
Vaisman, B
Stonik, J
Duarte, C
Remaley, A
AF Rousset, X.
Vaisman, B.
Stonik, J.
Duarte, C.
Remaley, A.
TI EFFECT OF RAPID INFUSION OF LCAT ON HDL METABOLISM AND ITS POSSIBLE
UTILITY FOR ENZYME REPLACEMENT THERAPY
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
C1 [Rousset, X.; Vaisman, B.; Stonik, J.; Duarte, C.; Remaley, A.] NHLBI, PVMB, Bethesda, MD 20892 USA.
RI Rousset, Xavier/B-3352-2008; Rousset, Xavier/H-5490-2015
OI Rousset, Xavier/0000-0002-5830-6577; Rousset, Xavier/0000-0002-5830-6577
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN
PY 2009
VL 10
IS 2
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA V17SO
UT WOS:000207957101097
ER
PT J
AU Sethi, A
Stonik, J
Rousset, X
Demosky, S
Voogt, J
Turner, S
Remaley, A
AF Sethi, A.
Stonik, J.
Rousset, X.
Demosky, S.
Voogt, J.
Turner, S.
Remaley, A.
TI PHOSPHOLIPID COMPLEXATION TO THE 37PA APO MIMETIC PEPTIDE INCREASES
CHOLESTEROL EFFLUX BY ABCA1 AND ABCG1 TRANSPORTERS BUT DOES NOT INCREASE
IN VIVO REVERSE CHOLESTEROL TRANSPORT
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
C1 [Sethi, A.; Stonik, J.; Rousset, X.; Demosky, S.; Remaley, A.] NIH, Bethesda, MD 20892 USA.
[Voogt, J.; Turner, S.] KineMed, Emeryville, CA USA.
RI Rousset, Xavier/B-3352-2008; Rousset, Xavier/H-5490-2015
OI Rousset, Xavier/0000-0002-5830-6577; Rousset, Xavier/0000-0002-5830-6577
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN
PY 2009
VL 10
IS 2
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA V17SO
UT WOS:000207957101426
ER
PT J
AU Shurin, S
AF Shurin, S.
TI FUNDING FROM THE NATIONAL HEART, LUNG, AND BLOOD INSTITUTE.
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
C1 [Shurin, S.] NHLBI, Off Director, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN
PY 2009
VL 10
IS 2
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA V17SO
UT WOS:000207957100612
ER
PT J
AU Tabet, F
Remaley, A
Barter, P
Rye, KA
Lambert, G
AF Tabet, F.
Remaley, A.
Barter, P.
Rye, K-a
Lambert, G.
TI THE 5A APOA-I MIMETIC PEPTIDE DISPLAYS ANTI-INFLAMMATORY AND ANTIOXIDANT
PROPERTIES MEDIATED BY ABCA1
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
C1 [Tabet, F.; Barter, P.; Rye, K-a; Lambert, G.] HRI, Sydney, NSW, Australia.
[Remaley, A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN
PY 2009
VL 10
IS 2
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA V17SO
UT WOS:000207957101675
ER
PT J
AU Vickers, K
Castro-Chavez, F
Morrisett, J
AF Vickers, K.
Castro-Chavez, F.
Morrisett, J.
TI LYSO-PHOSPHATIDYLCHOLINE INDUCES OSTEOGENIC GENE EXPRESSION AND
PHENOTYPE IN VASCULAR SMOOTH MUSCLE CELLS
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
C1 [Vickers, K.] NHLBI, Lipoprot Metab Sect, PVMB, NIH, Bethesda, MD 20892 USA.
[Vickers, K.; Castro-Chavez, F.; Morrisett, J.] Baylor Coll Med, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN
PY 2009
VL 10
IS 2
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA V17SO
UT WOS:000207957101220
ER
PT J
AU Vickers, K
Remaley, A
AF Vickers, K.
Remaley, A.
TI SCAVENGER RECEPTOR B1 HOSTS A SELF-REGULATING INTRONIC MICRORNA AT A
POLYMORPHIC LOCUS
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
C1 [Vickers, K.; Remaley, A.] NHLBI, Lipoprot Metab Sect, PVMB, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN
PY 2009
VL 10
IS 2
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA V17SO
UT WOS:000207957101086
ER
PT J
AU Crow, SJ
Mitchell, JE
Crosby, RD
Swanson, SA
Wonderlich, S
Lancanster, K
AF Crow, Scott J.
Mitchell, James E.
Crosby, Ross D.
Swanson, Sonja A.
Wonderlich, Stephen
Lancanster, Kathy
TI The cost effectiveness of cognitive behavioral therapy for bulimia
nervosa delivered via telemedicine versus face-to-face
SO BEHAVIOUR RESEARCH AND THERAPY
LA English
DT Article
DE Bulimia nervosa; Cognitive behavioral therapy; Cost effectiveness
ID EATING-DISORDERS
AB Objective: A number of effective treatments for bulimia nervosa have been developed, but they are infrequently used, in part due to problems with dissemination. The goal of this study was to examine the cost effectiveness of telemedicine delivery of cognitive behavioral therapy for bulimia nervosa.
Method: A randomized controlled trial of face-to-face versus telemedicine cognitive behavioral therapy for bulimia nervosa. One hundred twenty eight women with DSM-IV bulimia nervosa or eating disorder, not otherwise specified subsyndromal variants of bulimia nervosa were randomized to 20 sessions of treatment over 16 weeks. A cost effectiveness analysis from a societal perspective was conducted.
Results: The total cost per recovered (abstinent) subject was $9324.68 for face-to-face CBT, and $7300.40 for telemedicine CBT. The cost differential was accounted for largely by therapist travel costs. Sensitivity analyses examining therapy session costs, gasoline costs and telemedicine connection costs yielded fundamentally similar results.
Discussion: In this study, CBT delivered face-to-face and via telemedicine were similarly effective, and telemedicine delivery Cost Substantially less. These findings underscore the potential applicability of telemedicine approaches to eating disorder treatment and psychiatric treatment in general. (c) 2009 Elsevier Ltd. All rights reserved.
C1 [Crow, Scott J.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55454 USA.
[Mitchell, James E.; Crosby, Ross D.; Wonderlich, Stephen; Lancanster, Kathy] Neuropsychiat Res Inst, Fargo, ND 58103 USA.
[Swanson, Sonja A.] NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20814 USA.
RP Crow, SJ (reprint author), Univ Minnesota, Sch Med, Dept Psychiat, F282-2A W Bldg,2450 Riverside Av, Minneapolis, MN 55454 USA.
EM crowx002@umn.edu; mail@nrifargo.com; mail@nrifargo.com;
swansons@mail.nih.gov; mail@nrifargo.com; mail@nrifargo.com
OI Crosby, Ross/0000-0001-9131-1629
FU NIDDK NIH HHS [P30 DK050456, P30 DK050456-119006, P30 DK 50456]; NIMH
NIH HHS [K02 MH 65919, K02 MH065919, K02 MH065919-01A1, R01 MH 058820,
R01 MH058820, R01 MH058820-04, R01 MH059674, R13 MH081447, R34 MH077571]
NR 14
TC 26
Z9 27
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0005-7967
J9 BEHAV RES THER
JI Behav. Res. Ther.
PD JUN
PY 2009
VL 47
IS 6
BP 451
EP 453
DI 10.1016/j.brat.2009.02.006
PG 3
WC Psychology, Clinical
SC Psychology
GA 455IR
UT WOS:000266752700001
PM 19356743
ER
PT J
AU Yong, ASM
Melo, JV
AF Yong, Agnes S. M.
Melo, Junia V.
TI The impact of gene profiling in chronic myeloid leukaemia
SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
LA English
DT Article
DE chronic myeloid leukaemia; gene expression; microarray; molecular
biology; BCR-ABL; tyrosine kinase
ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ABL TYROSINE
KINASE; CYTOTOXIC T-LYMPHOCYTES; PHASE CML PATIENTS; BLAST-CRISIS CML;
BCR-ABL; CD34(+) CELLS; MOLECULAR SIGNATURE; EXPRESSION PROFILES
AB The use of microarray technology in chronic myeloid leukaemia (CIVIL) has increased Our understanding of the biology of this disease. From early studies of gene expression profiling in BCR-ABL-positive cell lines to samples from patients in different disease phases of CIVIL, using resting cells or cells treated with a variety of therapeutic agents, the field has now moved on to profiling microRNA and single nucleotide polymorphisms of CML cells. With the advent of tyrosine kinase inhibitors, several groups have also attempted to use microarray profiling to ascertain if particular gene expression profiles pre-existing in patients' CML cells, which could reflect intrinsic disease biology, would predict for response to treatment. This could streamline patients for alternative treatments upfront should a poor risk profile be found. In this article, we provide an overview of the progress made so far in this field, and outline the more substantial results of available microarray Studies to date. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.
C1 [Melo, Junia V.] Inst Med & Vet Sci, Div Haematol, Adelaide, SA 5000, Australia.
[Yong, Agnes S. M.] NHLBI, Haematol Branch, NIH, Bethesda, MD 20892 USA.
RP Melo, JV (reprint author), Inst Med & Vet Sci, Div Haematol, Frome Rd, Adelaide, SA 5000, Australia.
EM junia.melo@imvs.sa.gov.au
NR 75
TC 16
Z9 16
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1521-6926
J9 BEST PRACT RES CL HA
JI Best Pract. Res. Clin. Haematol.
PD JUN
PY 2009
VL 22
IS 2
BP 181
EP 190
DI 10.1016/j.beha.2009.04.002
PG 10
WC Hematology
SC Hematology
GA 498AL
UT WOS:000270107200003
PM 19698927
ER
PT J
AU Simon, R
AF Simon, Richard
TI Analysis of DNA microarray expression data
SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
LA English
DT Article
DE bioinformatics; biomarkers; gene expression signatures; microarray data
analysis
ID DIFFERENTIAL GENE-EXPRESSION; CLINICAL-TRIAL DESIGN; B-CELL LYMPHOMA;
BREAST-CANCER; PROGNOSTIC CLASSIFICATION; MOLECULAR CLASSIFICATION;
NORMALIZATION METHODS; CLASS PREDICTION; PROFILES; DISCOVERY
AB DNA microarrays are powerful tools for studying biological mechanisms and for developing prognostic and predictive classifiers for identifying the patients who require treatment and are best candidates for specific treatments. Because microarrays produce so much data from each specimen, they offer great opportunities for discovery and great dangers or producing misleading claims. Microarray based studies require clear objectives for selecting cases and appropriate analysis methods. Effective analysis of microarray data, where the number of measured variables is orders of magnitude greater than the number of cases, requires specialized statistical methods which have recently been developed. Recent literature reviews indicate that serious problems of analysis exist a substantial proportion of publications. This manuscript attempts to provide a non-technical summary of the key principles of statistical design and analysis for studies that utilize microarray expression profiling. Published by Elsevier Ltd.
C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Simon, R (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rsimon@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 63
TC 13
Z9 13
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1521-6926
J9 BEST PRACT RES CL HA
JI Best Pract. Res. Clin. Haematol.
PD JUN
PY 2009
VL 22
IS 2
BP 271
EP 282
DI 10.1016/j.beha.2009.07.001
PG 12
WC Hematology
SC Hematology
GA 498AL
UT WOS:000270107200009
PM 19698933
ER
PT J
AU Gahmberg, CG
Fagerholm, SC
Nurmi, SM
Chavakis, T
Marchesan, S
Gronholm, M
AF Gahmberg, Carl G.
Fagerholm, Susanna C.
Nurmi, Susanna M.
Chavakis, Triantafyllos
Marchesan, Silvia
Gronholm, Mikaela
TI Regulation of integrin activity and signalling
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Review
DE Leukocyte; Signalling; Integrin; LFA-1; Phosphorylation
ID PROTEIN-KINASE-C; INTERCELLULAR-ADHESION MOLECULE; EXTRACELLULAR
ADHERENCE PROTEIN; CD11/CD18 LEUKOCYTE INTEGRINS; INFLAMMATORY CELL
RECRUITMENT; T-CELL; STRUCTURAL BASIS; CYTOPLASMIC DOMAIN; BETA-SUBUNIT;
CRYSTAL-STRUCTURE
AB The ability of cells to attach to each other and to the extracellular matrix is of pivotal significance for the formation of functional organs and for the distribution of cells in the body. Several molecular families of proteins are involved in adhesion, and recent work has substantially improved Our understanding of their structures and functions. Also, these molecules are now being targeted in the fight against disease. However, less is known about how their activity is regulated. It is apparent that among the different classes of adhesion molecules, the integrin family of adhesion receptors is unique in the sense that they constitute a large group of widely distributed receptors, they are unusually complex and most importantly their activities are strictly regulated from the inside of the cell. The activity regulation is achieved by a complex interplay of cytoskeletal proteins, protein kinases, phosphatases, small G proteins and adaptor proteins. Obviously, we are only in the beginning of our understanding of how the integrins function, but already now fascinating details have become apparent. Here, we describe recent progress in the field, concentrating mainly on mechanistical and structural studies of integrin regulation. Due to the large number of articles dealing with integrins, we focus on what we think are the most exciting and rewarding directions of contemporary research on cell adhesion and integrins. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Gahmberg, Carl G.; Nurmi, Susanna M.; Marchesan, Silvia; Gronholm, Mikaela] Univ Helsinki, Fac Biosci, Div Biochem, FIN-00014 Helsinki, Finland.
[Fagerholm, Susanna C.] Univ Dundee, Ninewells Hosp & Med Sch, Div Pathol & Neurosci, Dundee DD1 4HN, Scotland.
[Chavakis, Triantafyllos] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Gahmberg, CG (reprint author), Univ Helsinki, Fac Biosci, Div Biochem, Viikinkaari 5, FIN-00014 Helsinki, Finland.
EM Carl.Gahmberg@helsinki.fi
RI Gronholm, Mikaela/B-4225-2010; Marchesan, Silvia/F-9366-2011;
OI Marchesan, Silvia/0000-0001-6089-3873; Gahmberg,
Carl/0000-0001-9892-9296; Fagerholm, Susanna Carola/0000-0002-0354-8763
FU Academy of Finland; Sigrid Juselius Foundation; Finnish Cancer Society;
Finska lakaresallskapet; Liv och Halsa Foundation; Magnus Ehrnrooth
Foundation.
FX We thank Yvonne Heinila for secretarial assistance and Professor Jari
Ylanne for Fig. 7. The original work was supported by the Academy of
Finland, the Sigrid Juselius Foundation, the Finnish Cancer Society, the
Finska lakaresallskapet, the Liv och Halsa Foundation and the Magnus
Ehrnrooth Foundation.
NR 159
TC 86
Z9 90
U1 3
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4165
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD JUN
PY 2009
VL 1790
IS 6
BP 431
EP 444
DI 10.1016/j.bbagen.2009.03.007
PG 14
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 460ML
UT WOS:000267191700006
PM 19289150
ER
PT J
AU Boeggeman, E
Ramakrishnan, B
Pasek, M
Manzoni, M
Puri, A
Loomis, KH
Waybright, TJ
Qasba, PK
AF Boeggeman, Elizabeth
Ramakrishnan, Boopathy
Pasek, Marta
Manzoni, Maria
Puri, Anu
Loomis, Kristin H.
Waybright, Timothy J.
Qasba, Pradman K.
TI Site Specific Conjugation of Fluoroprobes to the Remodeled Fc N-Glycans
of Monoclonal Antibodies Using Mutant Glycosyltransferases: Application
for Cell Surface Antigen Detection
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID IN-VITRO; CANCER-THERAPY; GLYCOSYLATION; THERAPEUTICS; RESIDUES;
OLIGOSACCHARIDES; IMMUNOGLOBULINS; GLYCOPROTEINS; BIOMOLECULES;
GALACTOSE
AB The Fc N-glycan chains of four therapeutic monoclonal antibodies (mAbs), namely, Avastin, Rituxan, Remicade, and Herceptin, released by PNGase F, show by MALDI analysis that these biantermary N-glycans are a mixture of GO, G 1, and G2 glycoforms. The GO glycoform has no galactose on the terminal GlcNAc residues, and the G I and G2 glycoforms have one or two terminal galactose residues, respectively, while no N-glycan with terminal sialic acid residue is observed. We show here that under native conditions we can convert the N-glycans of these mAbs to a homogeneous population of GO glycoform using beta 1,4 galactosidase from Streptococcus pneumoniae. The GO glycoforms of mAbs can be galactosylated with a modified galactose having a chemical handle at the C2 position, such as ketone or azide, using a mutant beta 1,4-galactosyltransferase (beta 1,4Gal-T1-Y289L). The addition of the modified galactose at a specific glycan residue of a mAb permits the coupling of a biomolecule that carries an orthogonal reactive group. The linking of a biotinylated or a fluorescent dye carrying derivatives selectively occurs with the modified galactose, C2-keto-Gal, at the heavy chain of these mAbs, without altering their antigen binding activities, as shown by indirect enzyme linked immunosorbent assay (ELISA) and fluorescence activated cell sorting (FACS) methods. Our results demonstrate that the linking of cargo molecules to mAbs via glycans could prove to be an invaluable tool for potential drug targeting by immunotherapeutic methods.
C1 [Boeggeman, Elizabeth; Ramakrishnan, Boopathy; Pasek, Marta; Manzoni, Maria; Qasba, Pradman K.] SAIC Frederick Inc, Struct Glycobiol Sect, CCR Nanobiol Program, Frederick, MD USA.
[Boeggeman, Elizabeth; Ramakrishnan, Boopathy; Puri, Anu; Loomis, Kristin H.; Waybright, Timothy J.] SAIC Frederick Inc, Membrane Struct & Funct Sect, CCR Nanobiol Program, Frederick, MD USA.
[Boeggeman, Elizabeth; Ramakrishnan, Boopathy] SAIC Frederick Inc, Basic Res Program, Frederick, MD USA.
[Waybright, Timothy J.] SAIC Frederick Inc, Lab Prote & Analyt Technol, Frederick, MD USA.
RP Qasba, PK (reprint author), NCI Frederick, Struct Glycobiol Sect, CCR Nanobiol Program, Bldg 469,Room 221, Frederick, MD 21702 USA.
EM qasba@helix.nih.gov
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
Intramural Research Program, Center for Cancer Research, National Cancer
Institute, NIH
FX We thank Dr. Natalia Mercer for critical reading of the manuscript and
Dr. Linda Hsieh-Wilson, CalTech, for helping Dr. Maria Manzoni during
the synthesis of UDP-C2-keto-Gal. We also thank Dr. John T. Simpson,
Protein Chemistry laboratory, NCI-Frederick, for helping with mass
spectrometric analysis. This project has been funded in part with
Federal funds from the National Cancer Institute, National Institutes of
Health, under contract no. N01-CO-12400. The content of this publication
does not necessarily reflect the view or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported [in part] by the Intramural Research
Program, Center for Cancer Research, National Cancer Institute, NIH.
NR 30
TC 44
Z9 46
U1 0
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD JUN
PY 2009
VL 20
IS 6
BP 1228
EP 1236
DI 10.1021/bc900103p
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 459QD
UT WOS:000267117600019
PM 19425533
ER
PT J
AU Singh, DK
Ahn, B
Bohr, VA
AF Singh, Dharmendra Kumar
Ahn, Byungchan
Bohr, Vilhelm A.
TI Roles of RECQ helicases in recombination based DNA repair, genomic
stability and aging
SO BIOGERONTOLOGY
LA English
DT Article
CT International Workshop on Cell Semescemce - Future of Ageing
CY JUL 07-08, 2008
CL Oriel Coll, Oxford, ENGLAND
HO Oriel Coll
DE Genome stability; RecQ helicases; Homologous recombination (HR); Double
strand break (DSB); Non-homologous end joining (NHEJ)
ID ROTHMUND-THOMSON-SYNDROME; WERNER-SYNDROME PROTEIN; BLOOMS-SYNDROME
HELICASE; INTERSTRAND CROSS-LINKS; TOPOISOMERASE-III-ALPHA; STRAND BREAK
REPAIR; NUCLEOTIDE EXCISION-REPAIR; REPLICATION FORK PROGRESSION;
SISTER-CHROMATID EXCHANGE; SYNDROME GENE-PRODUCT
AB The maintenance of the stability of genetic material is an essential feature of every living organism. Organisms across all kingdoms have evolved diverse and highly efficient repair mechanisms to protect the genome from deleterious consequences of various genotoxic factors that might tend to destabilize the integrity of the genome in each generation. One such group of proteins that is actively involved in genome surveillance is the RecQ helicase family. These proteins are highly conserved DNA helicases, which have diverse roles in multiple DNA metabolic processes such as DNA replication, recombination and DNA repair. In humans, five RecQ helicases have been identified and three of them namely, WRN, BLM and RecQL4 have been linked to genetic diseases characterized by genome instability, premature aging and cancer predisposition. This helicase family plays important roles in various DNA repair pathways including protecting the genome from illegitimate recombination during chromosome segregation in mitosis and assuring genome stability. This review mainly focuses on various roles of human RecQ helicases in the process of recombination-based DNA repair to maintain genome stability and physiological consequences of their defects in the development of cancer and premature aging.
C1 [Singh, Dharmendra Kumar; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Ahn, Byungchan] Univ Ulsan, Dept Life Sci, Ulsan 680749, South Korea.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
FU Intramural NIH HHS [Z01 AG000726-16]
NR 139
TC 49
Z9 51
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1389-5729
J9 BIOGERONTOLOGY
JI Biogerontology
PD JUN
PY 2009
VL 10
IS 3
BP 235
EP 252
DI 10.1007/s10522-008-9205-z
PG 18
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 441RH
UT WOS:000265787600002
PM 19083132
ER
PT J
AU Richmond, BJ
AF Richmond, Barry J.
TI Stochasticity, spikes and decoding: sufficiency and utility of order
statistics
SO BIOLOGICAL CYBERNETICS
LA English
DT Review
ID SPATIOTEMPORAL FIRING PATTERNS; PRIMARY VISUAL-CORTEX; SINGLE NEURONS;
TEMPORAL PRECISION; CORTICAL-NEURONS; INFORMATION; TRAINS; MONKEY;
RELIABILITY; RESPONSES
AB For over 75 years it has been clear that the number of spikes in a neural response is an important part of the neuronal code. Starting as early as the 1950's with MacKay and McCullough, there has been speculation over whether each spike and its exact time of occurrence carry information. Although it is obvious that the firing rate carries information it has been less clear as to whether there is information in exactly timed patterns, when they arise from the dynamics of the neurons and networks, as opposed to when they represent some strong external drive that entrains them. One strong null hypothesis that can be applied is that spike trains arise from stochastic sampling of an underlying deterministic temporally modulated rate function, that is, there is a time-varying rate function. In this view, order statistics seem to provide a sufficient theoretical construct to both generate simulated spike trains that are indistinguishable from those observed experimentally, and to evaluate (decode) the data recovered from experiments. It remains to learn whether there are physiologically important signals that are not described by such a null hypothesis.
C1 NIMH, Neuropsychol Lab, NIH, DHHS, Bethesda, MD 20892 USA.
RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, DHHS, Bldg 49,Rm 1B80, Bethesda, MD 20892 USA.
EM bjr@ln.nimh.nih.gov
FU National Institute of Mental Health/U.S. National Institutes of Health
FX This work was supported by the Intramural Program of the National
Institute of Mental Health/U.S. National Institutes of Health.
NR 37
TC 9
Z9 10
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-1200
J9 BIOL CYBERN
JI Biol. Cybern.
PD JUN
PY 2009
VL 100
IS 6
BP 447
EP 457
DI 10.1007/s00422-009-0321-x
PG 11
WC Computer Science, Cybernetics; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 459KS
UT WOS:000267101600005
PM 19517130
ER
PT J
AU Meetam, P
Srimaroeng, C
Soodvilai, S
Chatsudthipong, V
AF Meetam, Paranee
Srimaroeng, Chutima
Soodvilai, Sunhapas
Chatsudthipong, Varanuj
TI Regulatory Role of Testosterone in Organic Cation Transport: in Vivo and
in Vitro Studies
SO BIOLOGICAL & PHARMACEUTICAL BULLETIN
LA English
DT Article
DE organic cation transporter; testosterone; renal tubular secretion;
tetraethylammonium
ID FINAL EXCRETION STEP; FUNCTIONAL-CHARACTERIZATION; TISSUE DISTRIBUTION;
RAT-KIDNEY; GENDER-DIFFERENCES; ANION TRANSPORTERS; EXPRESSION LEVELS;
GENE-EXPRESSION; OCT2; MULTIDRUG
AB The renal proximal tubule (RPT) plays a crucial role in organic cation (OC) secretion and has a major impact on pharmacokinetics of OC drugs. Secretory transport is vectorial. Thus, it involves transporters located at both basolateral and apical membranes. Although sex hormones have been shown to regulate OC transport, there is little data on the effect of testosterone on OC secretion in a whole animal. Therefore, we determined the clearance of tetraethylammonium (TEA), a model OC substrate, in intact and castrated male mice. Castration significantly decreased renal TEA secretion by 30%, and testosterone supplementation returned TEA secretion to control levels in castrated mice. The mechanism of this effect was further examined in isolated mouse renal proximal tubules (mRPT). TEA uptake in isolated mRPT from castrated mice was reduced by 36%. This effect was reversed in tubules from castrated mice supplemented with testosterone. Kinetic analysis of [H-3]-TEA uptake in isolated mRPT showed a decreased V-max with no change in K-m, implying that the decrease in transport rate was caused by lowering in the number of transporters in castrated mice rather than a change in transporter affinity. Quantitative real time polymerase chain reaction (real time PCR) revealed that organic cation transporter (OCT)2 is the major TEA transporter in male mice. Moreover, OCT2 mRNA level was significantly reduced after castration. Castrated mice also showed a modest increase in organic cation/carnitine transporter 1 (OCTN1) mRNA level, indicating that testosterone may also regulate apical OCTN1 expression. These data suggest that testosterone regulates transepithelial transport of OC through modulation of OCT2 expression in male mice.
C1 [Meetam, Paranee; Soodvilai, Sunhapas; Chatsudthipong, Varanuj] Mahidol Univ, Fac Sci, Dept Physiol, Bangkok 10400, Thailand.
[Srimaroeng, Chutima] NIEHS, Pharmacol Lab, Res Triangle Pk, NC 27709 USA.
RP Chatsudthipong, V (reprint author), Mahidol Univ, Fac Sci, Dept Physiol, Rama 6 Rd, Bangkok 10400, Thailand.
EM scvcs@mahidol.ac.th
OI Srimaroeng, Chutima/0000-0002-5537-1023
FU Faculty of Graduate Studies, Mahidol University [2548]; National Center
for Genetic Engineering and Biotechnology; National Science and
Technology Development Agency, Thailand [3-2548]; NIH, National
Institute of Environmental Health Sciences
FX We gratefully acknowledge Dr. John B. Pritchard, Prof. Prapon Wilairat,
and Prof. William H. Dantzler for valuable comments and critical reading
of the manuscript. We also thank Kristen K. Evans for assistance in
kinetic data analysis, Dr. G. Kissling for consultation on statistical
analysis and Prof. Stephen H. Wright for providing radiolabeled
tetraethylammonium bromide. This work was supported by grants from the
Faculty of Graduate Studies, Mahidol University (2005 academic year to
PM), National Center for Genetic Engineering and Biotechnology, National
Science and Technology Development Agency, Thailand (grant 3-2548 to
VC), Mahidol University Grant 2548 (to VC) and Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences
(to CS).
NR 46
TC 9
Z9 10
U1 0
U2 0
PU PHARMACEUTICAL SOC JAPAN
PI TOKYO
PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN
SN 0918-6158
J9 BIOL PHARM BULL
JI Biol. Pharm. Bull.
PD JUN
PY 2009
VL 32
IS 6
BP 982
EP 987
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 451QA
UT WOS:000266483500005
PM 19483302
ER
PT J
AU Milaneschi, Y
Corsi, AM
Penninx, BW
Bandinelli, S
Guralnik, JM
Ferrucci, L
AF Milaneschi, Yuri
Corsi, Anna Maria
Penninx, Brenda W.
Bandinelli, Stefania
Guralnik, Jack M.
Ferrucci, Luigi
TI Interleukin-1 Receptor Antagonist and Incident Depressive Symptoms Over
6 Years in Older Persons: The InCHIANTI Study
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Aging; cytokines; depression; inflammation
ID LATE-LIFE DEPRESSION; CORONARY-HEART-DISEASE; MAJOR DEPRESSION;
INFLAMMATORY MARKERS; INTERFERON-GAMMA; CLINICAL-TRIALS; L-TRYPTOPHAN;
IMMUNE; CYTOKINES; COMMUNITY
AB Background: We test the hypothesis that in older persons higher plasma levels of inflammatory markers predict the development of depressive symptoms during a 6-year follow-up.
Method: This study is part of the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study, a prospective population-based study of older persons. The sample consisted of 991 participants, ages 65 years and older. Serum levels of C-reactive protein, interleukin (IL)-1 beta, IL-1 receptor antagonist (ra), tumor necrosis factor-alpha, IL-6, IL-6 receptor, and IL-18 were measured. Depressive symptoms were assessed at baseline and at the 3- and 6-year follow-ups with the Center for Epidemiological Studies-Depression Scale (CES-D). Depressed mood was defined as CES-D > 20. Potential confounders were baseline variables related to sociodemographic, somatic health, and functional status.
Results: At baseline, IL-1ra levels were significantly higher (p = .004) in depressed compared with nondepressed participants. After adjustment for confounders, among subjects free of depression at baseline, those in the third and fourth IL-1 ra quartiles compared with those in the lowest quartile had, respectively, a 2.32-fold (95% confidence interval: 1.21-4.42, p = .01) and 2.78-fold (95% confidence interval: 1.47-5.26, p = .002) higher risk of developing depressed mood during a 6-year follow-up.
Conclusions: In old age, persons with high plasma levels of IL1-ra had a higher risk of developing depressive symptoms over time. These findings suggest a potential causal role for inflammation in the development of depressive symptoms in older persons.
C1 [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Harbor Hosp Ctr, Baltimore, MD 21225 USA.
[Milaneschi, Yuri; Corsi, Anna Maria] ASF, Tuscany Hlth Reg Agcy, Florence, Italy.
[Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy.
[Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, Harbor Hosp Ctr, Room NM540,3001 S Hanover St, Baltimore, MD 21225 USA.
EM ferruccilu@grc.nia.nih.gov
FU NIA NIH HHS [N 01-AG-5-0002, N01 AG5-002]
NR 46
TC 66
Z9 66
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUN 1
PY 2009
VL 65
IS 11
BP 973
EP 978
DI 10.1016/j.biopsych.2008.11.01
PG 6
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 448AA
UT WOS:000266232300009
PM 19111279
ER
PT J
AU Uthus, EO
Ross, S
AF Uthus, Eric O.
Ross, Sharon
TI Dietary Selenium (Se) and Copper (Cu) Interact to Affect Homocysteine
Metabolism in Rats
SO BIOLOGICAL TRACE ELEMENT RESEARCH
LA English
DT Article
DE Selenium; Copper
ID GLUTATHIONE-PEROXIDASE; DEFICIENT RATS; PLASMA HOMOCYSTEINE; DECREASES
PLASMA; FISHER-344 RATS; METHIONINE; LIVER; CYSTEINE; CHICK
AB Previously, we reported that both Se deficiency and Cu deficiency decreased plasma homocysteine (pHcys) and increased plasma glutathione (pGSH) in rats. We also showed that the catalytic subunit of glutamate-cysteine ligase (Gclc), which catalyzes the rate-limiting step in glutathione biosynthesis, was upregulated in Se and Cu deficiencies. We suggested that in both deficiencies, Hcys was being shunted through the trans-sulfuration pathway as a result of this up-regulation. Because both Se and Cu deficiencies have similar effects, we hypothesized that a combined deficiency would exacerbate the decrease in pHcys and the increase in pGSH by further up-regulating Gclc. In a 2 x 2 experiment, male weanling Sprague-Dawley rats (n = 8-20/group) were fed an amino-acid-based diet containing either 0 or 0.2 A mu g Se (as selenite)/g and < 1 or 6 A mu g Cu (as Cu carbonate)/g for 5 weeks. Our findings show that a combined deficiency of both Se and Cu results in lower pHcys and significantly elevated pGSH. However, the up-regulation of liver Gclc alone cannot explain why rats fed with the doubly deficient diet have the lowest pHcys and the highest pGSH.
C1 [Uthus, Eric O.] USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA.
[Ross, Sharon] NCI, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA.
RP Uthus, EO (reprint author), USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA.
EM eric.uthus@ars.usda.gov
NR 23
TC 5
Z9 6
U1 0
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0163-4984
J9 BIOL TRACE ELEM RES
JI Biol. Trace Elem. Res.
PD JUN
PY 2009
VL 129
IS 1-3
BP 213
EP 220
DI 10.1007/s12011-008-8295-4
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 448MJ
UT WOS:000266266400025
PM 19104759
ER
PT J
AU Chen, GS
Cannata, J
Liu, RB
Chang, H
Shung, KK
AF Chen, Gin-Shin
Cannata, Jonathan
Liu, Ruibin
Chang, Hsu
Shung, K. Kirk
TI DESIGN AND FABRICATION OF HIGH-INTENSITY FOCUSED ULTRASOUND PHASED ARRAY
FOR LIVER TUMOR THERAPY
SO BIOMEDICAL ENGINEERING-APPLICATIONS BASIS COMMUNICATIONS
LA English
DT Article
DE HIFU; Moving liver tumor; Dynamic focusing; Field II; Spatial averaged
intensity
ID UTERINE FIBROIDS; SURGERY; MOTION
AB Noninvasive surgery of the liver tumors has been carried out by using the high-intensity focused ultrasound (HIFU). However, the liver tumor can be moved by the human respirations and heartbeats, which may cause the ablation and damage of normal tissues during the sonications of HIFU. The purpose of this study was to design and fabricate a cylindrical HIFU phased array transducer for treating the moving liver tumor efficiently. The total number of the element was 512 but only 256 channels were required since the elements along the elevation direction were connected in pairs with respect to the central line of the array. Field II software was used to simulate the acoustic field, and a formula for predicting the spatial averaged intensity at focus was developed based on the practical factors. The results of the simulations showed that the cylindrical HIFU phased array in water had a dynamic focusing range from 145 to 175 mm in the depth direction and a steering range from -15 to 15 mm in azimuthal direction with respect to the center of the array. After the dissipation of cables and the attenuation of various media, the designed array could still generate the intensity at focus up to 1095W/cm(2) when the input electrical power was approximately 410 W. The prototype of the array was fabricated and the preliminary test was completed. The testing results showed that each element of the array prototype can work well.
C1 [Chen, Gin-Shin; Chang, Hsu] Natl Hlth Res Inst, Div Med Engn Res, Zhunan, Taiwan.
[Cannata, Jonathan; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, NIH, Ultrasound Transducer Resources Ctr, Los Angeles, CA 90089 USA.
[Liu, Ruibin] Blatek Inc, State Coll, PA USA.
RP Chen, GS (reprint author), Natl Hlth Res Inst, Div Med Engn Res, Zhunan, Taiwan.
EM gschen@nhri.org.tw
RI Chen, Gin-Shin /E-3988-2010; Chang, Hsu /E-3971-2010;
OI Chen, Gin-Shin/0000-0003-3368-7470
NR 14
TC 3
Z9 3
U1 0
U2 5
PU WORLD SCIENTIFIC PUBL CO PTE LTD
PI SINGAPORE
PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE
SN 1016-2372
J9 BIOMED ENG-APP BAS C
JI Biomed. Eng.-Appl. Basis Commun.
PD JUN
PY 2009
VL 21
IS 3
BP 187
EP 192
PG 6
WC Engineering, Biomedical
SC Engineering
GA 461KJ
UT WOS:000267265400005
ER
PT J
AU Cosyn, L
Van Calenbergh, S
Joshi, BV
Ko, H
Carter, RL
Harden, TK
Jacobson, KA
AF Cosyn, Liesbet
Van Calenbergh, Serge
Joshi, Bhalchandra V.
Ko, Hyojin
Carter, Rhonda L.
Harden, T. Kendall
Jacobson, Kenneth A.
TI Synthesis and P2Y receptor activity of nucleoside 5 '-phosphonate
derivatives
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Purines; Pyrimidines; G protein-coupled receptors; Phospholipase C;
Agonist; Nucleotide
ID URACIL NUCLEOTIDES; AGONISTS; URIDINE; ANALOGS; THERAPY; POTENCY;
DESIGN; UPDATE; UDP
AB Ribose-based nucleoside 5'-diphosphates and triphosphates and related nucleotides were compared in their potency at the P2Y receptors with the corresponding nucleoside 5'-phosphonate derivatives. Phosphonate derivatives of UTP and ATP activated the P2Y(2) receptor but were inactive or weakly active at P2Y(4) receptor. Uridine 5'-(diphospho) phosphonate was approximately as potent at the P2Y(2) receptor as at the UDP-activated P2Y(6) receptor. These results suggest that removal of the 5'-oxygen atom from nucleotide agonist derivatives reduces but does not prevent interaction with the P2Y(2) receptor. Uridine 5'-(phospho) phosphonate as well as the 5'-methylenephosphonate equivalent of UMP were inactive at the P2Y4 receptor and exhibited maximal effects at the P2Y(2) receptor that were <= 50% of that of UTP suggesting novel action of these analogues. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Joshi, Bhalchandra V.; Ko, Hyojin; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Cosyn, Liesbet; Van Calenbergh, Serge] Univ Ghent, Med Chem Lab, Fac Pharmaceut Sci, FFW, B-9000 Ghent, Belgium.
[Carter, Rhonda L.; Harden, T. Kendall] Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA.
RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Van Calenbergh, Serge/A-3167-2008; Jacobson, Kenneth/A-1530-2009
OI Van Calenbergh, Serge/0000-0002-4201-1264; Jacobson,
Kenneth/0000-0001-8104-1493
FU Intramural Research Program of the NIH; National Institute of Diabetes &
Digestive & Kidney Diseases; NIH [GM38213]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Diabetes & Digestive & Kidney Diseases and by
an NIH Grant GM38213.
NR 21
TC 14
Z9 14
U1 0
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JUN 1
PY 2009
VL 19
IS 11
BP 3002
EP 3005
DI 10.1016/j.bmcl.2009.04.027
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 444LG
UT WOS:000265981900023
PM 19419868
ER
PT J
AU Patnaik, S
Stevens, KL
Gerding, R
Deanda, F
Shotwell, JB
Tang, J
Hamajima, T
Nakamura, H
Leesnitzer, MA
Hassell, AM
Shewchuck, LM
Kumar, R
Lei, HS
Chamberlain, SD
AF Patnaik, Samarjit
Stevens, Kirk L.
Gerding, Roseanne
Deanda, Felix
Shotwell, J. Brad
Tang, Jun
Hamajima, Toshihiro
Nakamura, Hiroko
Leesnitzer, M. Anthony
Hassell, Anne M.
Shewchuck, Lisa M.
Kumar, Rakesh
Lei, Huangshu
Chamberlain, Stanley D.
TI Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent
inhibitors of the insulin-like growth factor-1 receptor (IGF-1R)
tyrosine kinase
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE IGF-1R; IGF-IR; Pyrrolopyridine; Kinase inhibitor
ID SELECTIVE INHIBITOR; CANCER; VIVO
AB Exploration of the SAR around a series of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines led to the discovery of novel pyrrolopyridine inhibitors of the IGF-1R tyrosine kinase. Several compounds demonstrated nanomolar potency in enzyme and cellular mechanistic assays. (C) 2009 Published by Elsevier Ltd.
C1 [Patnaik, Samarjit; Stevens, Kirk L.; Gerding, Roseanne; Shotwell, J. Brad; Tang, Jun; Leesnitzer, M. Anthony; Hassell, Anne M.; Lei, Huangshu; Chamberlain, Stanley D.] GlaxoSmithKline Inc, Oncol R&D, Res Triangle Pk, NC 27709 USA.
[Deanda, Felix; Shewchuck, Lisa M.] GlaxoSmithKline Inc, Computat & Struct Chem, Res Triangle Pk, NC 27709 USA.
[Hamajima, Toshihiro; Nakamura, Hiroko] GlaxoSmithKline Inc, K K Tsukuba Res Labs, Ibaraki 3004247, Japan.
[Kumar, Rakesh] GlaxoSmithKline Inc, Oncol R&D, Collegeville, PA 19426 USA.
RP Patnaik, S (reprint author), NIH, Chem Genom Ctr, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM patnaiks@mail.nih.gov
NR 17
TC 18
Z9 19
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JUN 1
PY 2009
VL 19
IS 11
BP 3136
EP 3140
DI 10.1016/j.bmcl.2008.12.110
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 444LG
UT WOS:000265981900054
PM 19394223
ER
PT J
AU Jahrling, P
Rodak, C
Bray, M
Davey, RT
AF Jahrling, Peter
Rodak, Colleen
Bray, Mike
Davey, Richard T.
TI TRIAGE AND MANAGEMENT OF ACCIDENTAL LABORATORY EXPOSURES TO BIOSAFETY
LEVEL-3 AND-4 AGENTS
SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE
LA English
DT Article
ID FRAMEWORK; CONSENSUS; DISEASES; UNIT; CARE
AB The recent expansion of biocontainment laboratory capacity in the United States has drawn attention to the possibility of occupational exposures to BSL-3 and -4 agents and has prompted a reassessment of medical management procedures and facilities to deal with these contingencies. A workshop hosted by the National Interagency Biodefense Campus was held in October 2007 and was attended by representatives of all existing and planned BSL-4 research facilities in the U. S. and Canada. This report summarizes important points of discussion and recommendations for future coordinated action, including guidelines for the engineering and operational controls appropriate for a hospital care and isolation unit. Recommendations pertained to initial management of exposures (ie, immediate treatment of penetrating injuries, reporting of exposures, initial evaluation, and triage). Isolation and medical care in a referral hospital (including minimum standards for isolation units), staff recruitment and training, and community outreach also were addressed. Workshop participants agreed that any unit designated for the isolation and treatment of laboratory employees accidentally infected with a BSL-3 or -4 pathogen should be designed to maximize the efficacy of patient care while minimizing the risk of transmission of infection. Further, participants concurred that there is no medically based rationale for building care and isolation units to standards approximating a BSL-4 laboratory. Instead, laboratory workers accidentally exposed to pathogens should be cared for in hospital isolation suites staffed by highly trained professionals following strict infection control procedures.
C1 [Jahrling, Peter; Bray, Mike] NIAID, Integrated Res Facil, Frederick, MD 21702 USA.
[Rodak, Colleen; Davey, Richard T.] NIAID, Div Clin Res, Bethesda, MD 20892 USA.
RP Jahrling, P (reprint author), NIAID, Integrated Res Facil, 8200 Res Plaza, Frederick, MD 21702 USA.
EM jahrlingp@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000984-01]
NR 10
TC 4
Z9 4
U1 1
U2 5
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1538-7135
J9 BIOSECUR BIOTERROR
JI Biosecur. Bioterror.
PD JUN
PY 2009
VL 7
IS 2
BP 135
EP 143
DI 10.1089/bsp.2009.0002
PG 9
WC Public, Environmental & Occupational Health; International Relations
SC Public, Environmental & Occupational Health; International Relations
GA 475DC
UT WOS:000268337100008
PM 19634998
ER
PT J
AU Holleley, CE
Geerts, PG
AF Holleley, Clare E.
Geerts, Paul G.
TI Multiplex Manager 1.0: a cross-platform computer program that plans and
optimizes multiplex PCR
SO BIOTECHNIQUES
LA English
DT Article
DE multiplex PCR; polymerase chain reaction; multiplexing
ID DROSOPHILA-MELANOGASTER; PRIMER-DESIGN; LINKAGE MAP; TOOL; POPULATIONS;
AMERICAN; ALLELES
AB Multiplex Manager 1.0 is a user-friendly cross-platform program that designs efficient combinations of existing genetic marker loci into multiplex polymerase chain reactions and optimizes using prior marker information. The program has the flexibility to solve two design problems: combining all markers into the smallest number of reactions, or alternatively, selecting a subset from many available markers to design an efficient and robust multiplex. Our program minimizes the number of reactions, the genetic linkage, and the difference in annealing temperature. At the same time it maximizes the spacing between markers, the heterozygosity, and the number of alleles. The final output provides easily interpreted and informative graphical representations of reactions, as well as the option of manually editing final reactions. Multiplex Manager 1.0 is freely available at www.multiplexmanager.com.
C1 [Holleley, Clare E.; Geerts, Paul G.] Univ New S Wales, Evolut & Ecol Res Ctr, Sch Biol Earth & Environm Sci, Sydney, NSW, Australia.
RP Holleley, CE (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA.
EM holleleyce@mail.nih.gov
RI Holleley, Clare/C-4629-2011
OI Holleley, Clare/0000-0002-5257-0019
FU Australian Research Council [DP0559363]
FX The authors declare no competing interests.
NR 19
TC 141
Z9 143
U1 0
U2 23
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 0736-6205
J9 BIOTECHNIQUES
JI Biotechniques
PD JUN
PY 2009
VL 46
IS 7
BP 511
EP +
DI 10.2144/000113156
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 461DS
UT WOS:000267245400013
PM 19594450
ER
PT J
AU Drevets, WC
AF Drevets, W. C.
TI Cholinergic receptor imaging in bipolar disorder: relationship to
genotype and illness severity
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
C1 [Drevets, W. C.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
BP 4
EP 4
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500012
ER
PT J
AU Insel, T
AF Insel, T.
TI Report from the NIMH
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
C1 [Insel, T.] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
BP 8
EP 8
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500022
ER
PT J
AU Goes, FS
Belmonte, P
Zandi, PP
McMahon, FJ
Kelsoe, JR
Potash, JB
AF Goes, F. S.
Belmonte, P.
Zandi, P. P.
McMahon, F. J.
Kelsoe, J. R.
Potash, J. B.
CA BIGS Consortium
TI Genome-wide association study of the Mood-Incongruent Psychotic Bipolar
Disorder Phenotype provides suggestive evidence for association to the
schizophrenia susceptibility gene ERBB4
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
DE psychotic; schizophrenia; bipolar; genetics
C1 [Goes, F. S.; Belmonte, P.; Potash, J. B.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Zandi, P. P.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[McMahon, F. J.] NIMH, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Kelsoe, J. R.] Univ Calif San Diego, San Diego, CA 92103 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
BP 10
EP 10
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500026
ER
PT J
AU Frye, M
Hellemann, G
Suppes, T
McElroy, S
Grunze, H
Altshuler, L
Keck, P
Kupka, R
Nolen, W
Leverich, G
Post, R
AF Frye, M.
Hellemann, G.
Suppes, T.
McElroy, S.
Grunze, H.
Altshuler, L.
Keck, P.
Kupka, R.
Nolen, W.
Leverich, G.
Post, R.
TI Prevalence rate of mixed depression and its impact on remission: a
controlled evaluation
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
SP NIMH
DE mixed; depression; remission
C1 [Frye, M.] Mayo Clin, Dept Psychiat, Rochester, MN USA.
[Hellemann, G.; Altshuler, L.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
[Suppes, T.] Stanford Univ, Dept Psychiat, Stanford, CA 94305 USA.
[Suppes, T.] Palo Alto VA Med Ctr, Palo Alto, CA USA.
[McElroy, S.; Keck, P.] Lindner Ctr HOPE, Cincinnati, OH USA.
[Grunze, H.] Univ Newcastle, Inst Neurosci, Newcastle, England.
[Kupka, R.] Altrecht Inst Mental Hlth Care, Utrecht, Netherlands.
[Kupka, R.] Univ Med Ctr, Utrecht, Netherlands.
[Nolen, W.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Leverich, G.] NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Post, R.] George Washington Sch Med, Bethesda, MD USA.
[Post, R.] Bipolar Collaborat Network, Bethesda, MD USA.
RI Nolen, Willem/E-9006-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
SU 1
BP 40
EP 40
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500107
ER
PT J
AU Jamain, S
Cichon, S
Etain, B
Muhleisen, TW
Georgi, A
Zidane, N
Herms, S
Mattheisen, M
Priebe, L
Mathieu, F
Henry, C
Boland, A
Zelenika, D
Gut, I
Maier, W
Albus, M
Schulze, T
Bellivier, F
Rietschel, M
Nothen, MM
Leboyer, M
AF Jamain, S.
Cichon, S.
Etain, B.
Muehleisen, T. W.
Georgi, A.
Zidane, N.
Herms, S.
Mattheisen, M.
Priebe, L.
Mathieu, F.
Henry, C.
Boland, A.
Zelenika, D.
Gut, I.
Maier, W.
Albus, M.
Schulze, T.
Bellivier, F.
Rietschel, M.
Noethen, M. M.
Leboyer, M.
TI Genome-wide association study on early-onset bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
DE bipolar disorder; genome-wide association study; early age at onset
C1 [Jamain, S.; Etain, B.; Zidane, N.; Mathieu, F.; Henry, C.; Bellivier, F.; Leboyer, M.] INSERM, U955, IMRB, Dept Genet, F-94010 Creteil, France.
[Etain, B.; Henry, C.; Bellivier, F.; Leboyer, M.] Univ Paris 12, Fac Med, IFR10, F-94010 Creteil, France.
[Henry, C.; Bellivier, F.; Leboyer, M.] AP HP, Henri Mondor Albert Chenevier Grp, Dept Psychiat, F-94010 Creteil, France.
[Cichon, S.; Muehleisen, T. W.; Herms, S.; Mattheisen, M.; Priebe, L.; Noethen, M. M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
[Cichon, S.; Muehleisen, T. W.; Herms, S.; Mattheisen, M.; Priebe, L.; Noethen, M. M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany.
[Georgi, A.; Albus, M.; Schulze, T.; Rietschel, M.] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany.
[Georgi, A.; Maier, W.; Rietschel, M.] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany.
[Etain, B.; Boland, A.; Zelenika, D.; Gut, I.] CEA, Inst Genom, Ctr Natl Genotypage, F-91000 Evry, France.
[Schulze, T.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RI Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; BELLIVIER,
FRANK/H-5197-2012
OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
BP 49
EP 49
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500131
ER
PT J
AU Juruena, MF
Ottoni, GL
Machado-Vieira, R
Carneiro, RM
Weingarthner, N
Marquardt, AR
Fleig, SS
Broilo, L
Busnello, ED
AF Juruena, M. F.
Ottoni, G. L.
Machado-Vieira, R.
Carneiro, R. M.
Weingarthner, N.
Marquardt, A. R.
Fleig, S. S.
Broilo, L.
Busnello, E. D.
TI Residual symptoms in bipolar I and II: oxcarbazepine and carbamazepine
as add-on treatment to lithium in a double-blind, randomized trial
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
DE bipolar disorder; carbamazepine; clinical trial; lithium; oxcarbazepine;
residual symptoms
C1 [Juruena, M. F.] Kings Coll London, Inst Psychiat, Sect Neurobiol Mood Disorders, London WC2R 2LS, England.
[Juruena, M. F.; Ottoni, G. L.; Machado-Vieira, R.; Carneiro, R. M.; Weingarthner, N.; Marquardt, A. R.; Fleig, S. S.; Broilo, L.; Busnello, E. D.] Fed Univ Healthy Sci Porto Alegre UFCSPA, Dept Psychiat, Affect Disorders Unit, Porto Alegre, RS, Brazil.
[Juruena, M. F.] Univ Sao Paulo, Dept Neurosci & Behav Sci, Sch Med Ribeirao Preto, BR-05508 Sao Paulo, Brazil.
[Machado-Vieira, R.] NIMH, Mood & Anxiety Disorders Program, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Juruena, Mario/D-5571-2009
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Juruena,
Mario/0000-0001-8558-3396
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
BP 51
EP 51
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500138
ER
PT J
AU Khairova, RA
Machado-Vieira, R
Wei, Y
Du, J
Manji, HK
AF Khairova, R. A.
Machado-Vieira, R.
Wei, Y.
Du, J.
Manji, H. K.
TI A dual role for TNF-alpha in the regulations of hippocampal
synaptogenesis: potential implications in mood disorders
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
DE mood disorders; synaptic plasticity; cytokines; hippocampus
C1 [Khairova, R. A.; Machado-Vieira, R.; Wei, Y.; Du, J.; Manji, H. K.] NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
RI Du, Jing/A-9023-2012; MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
BP 53
EP 54
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500145
ER
PT J
AU Machado-Vieira, R
Yuan, P
Brutsche, N
DiazGranados, N
Luckenbaugh, D
Manji, HK
Zarate, CA
AF Machado-Vieira, R.
Yuan, P.
Brutsche, N.
DiazGranados, N.
Luckenbaugh, D.
Manji, H. K.
Zarate, C. A., Jr.
TI Brain derived neurotrophic factor and initial antidepressant response to
an NMDA antagonist
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
SP NIMH
DE ketamine; depression; glutamate; biomarker; plasticity; brain-derived
neurotrophic factor
C1 [Machado-Vieira, R.; Yuan, P.; Brutsche, N.; DiazGranados, N.; Luckenbaugh, D.; Manji, H. K.; Zarate, C. A., Jr.] NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Machado-Vieira, R.; Yuan, P.; DiazGranados, N.; Manji, H. K.; Zarate, C. A., Jr.] NIMH, Lab Mol Pathophysiol & Expt Therapeut, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
SU 1
BP 58
EP 59
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500158
ER
PT J
AU Machado-Vieira, R
Pivovarova, N
Stanika, R
Du, J
Khairova, R
Drevets, W
Zarate, CA
Chen, G
Andrews, SB
Manji, HK
AF Machado-Vieira, R.
Pivovarova, N.
Stanika, R.
Du, J.
Khairova, R.
Drevets, W.
Zarate, C. A., Jr.
Chen, G.
Andrews, S. B.
Manji, H. K.
TI Altered endoplasmic reticulum calcium dynamics in bipolar subjects: A
Bcl-2 gene polymorphism (rs956572) as a risk allele for Bipolar Disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
SP NIMH
DE bipolar disorder; calcium; endoplasmic reticulum; Bcl-2; genetics;
lithium
C1 [Machado-Vieira, R.; Du, J.; Khairova, R.; Drevets, W.; Zarate, C. A., Jr.; Chen, G.; Manji, H. K.] NIMH, Lab Mol Pathophysiol & Expt Therapeut, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Pivovarova, N.; Stanika, R.; Andrews, S. B.] Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, NIH, Bethesda, MD USA.
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Chen, Guang/A-2570-2017
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190;
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 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
SU 1
BP 58
EP 58
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500157
ER
PT J
AU Mallinger, AG
Frank, E
Thase, ME
Barwell, MM
DiazGranados, N
Luckenbaugh, DA
Kupfer, DJ
AF Mallinger, A. G.
Frank, E.
Thase, M. E.
Barwell, M. M.
DiazGranados, N.
Luckenbaugh, D. A.
Kupfer, D. J.
TI Monoamine oxidase inhibitors are superior to standard antidepressants in
bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
DE antidepressive agents; bipolar disorder; depressive disorder; clinical
trial; monoamine oxidase inhibitors; treatment outcome
C1 [Mallinger, A. G.; DiazGranados, N.; Luckenbaugh, D. A.] NIMH, Mood & Anxiety Disorders Program, IRP, NIH, Bethesda, MD 20892 USA.
[Frank, E.; Barwell, M. M.; Kupfer, D. J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Thase, M. E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
BP 59
EP 59
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500159
ER
PT J
AU Post, RM
Leverich, GS
Kupka, R
Keck, P
McElroy, S
Altshuler, L
Frye, M
Luckenbaugh, DA
Rowe, M
Grunze, H
Suppes, T
Nolen, WA
AF Post, R. M.
Leverich, G. S.
Kupka, R.
Keck, P., Jr.
McElroy, S.
Altshuler, L.
Frye, M.
Luckenbaugh, D. A.
Rowe, M.
Grunze, H.
Suppes, T.
Nolen, W. A.
TI Delay to first treatment is inversely related to age of onset of bipolar
disorder and an independent contributor to a poor outcome in adulthood
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
DE Mood Stabilizers; atypicals; early intervention; mania; depression
C1 [Post, R. M.] George Washington Univ, Washington, DC USA.
[Leverich, G. S.; Rowe, M.] Bipolar Collaborat Network, Bethesda, MD USA.
[Kupka, R.] Altrecht Inst Mental Hlth Care, Utrecht, Netherlands.
[Keck, P., Jr.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Keck, P., Jr.] HOPE, Lindner Ctr, Mason, OH USA.
[McElroy, S.] Univ Texas SW Med Ctr Dallas, Bipolar Disorder Res Program, Dept Psychiat, Dallas, TX 75390 USA.
[Altshuler, L.] Univ Calif Los Angeles, Mood Disorders Res Program, Los Angeles, CA USA.
[Altshuler, L.] Univ Calif Los Angeles, VA Med Ctr, Los Angeles, CA USA.
[Frye, M.] Mayo Clin, Rochester, MI USA.
[Luckenbaugh, D. A.] NIMH, NIH, Bethesda, MD 20892 USA.
[Grunze, H.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England.
[Suppes, T.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Suppes, T.] Stanford Univ, VA Palo Alto Hlth Care Syst Palo Alto, Stanford, CA 94305 USA.
[Nolen, W. A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
RI Nolen, Willem/E-9006-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
BP 70
EP 70
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500188
ER
PT J
AU Suppes, T
Hellemann, G
Frye, M
McElroy, S
Nolen, W
Kupka, R
Leverich, G
Grunze, H
Altshuler, L
Keck, P
Post, R
AF Suppes, T.
Hellemann, G.
Frye, M.
McElroy, S.
Nolen, W.
Kupka, R.
Leverich, G.
Grunze, H.
Altshuler, L.
Keck, P.
Post, R.
TI Mixed depression in bipolar disorder: prevalence rate and clinical
correlates during naturalistic follow up
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
SP NIMH
DE bipolar disorder; mixed; subsyndromal symptoms
C1 [Suppes, T.] Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA.
[Suppes, T.] Palo Alto VA Med Ctr, Palo Alto, CA USA.
[Hellemann, G.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
[Frye, M.] Mayo Clin, Dept Psychiat, Rochester, MN USA.
[McElroy, S.; Keck, P.] HOPE, Lindner Ctr, Cincinnati, OH USA.
[Nolen, W.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Kupka, R.] Altrecht Inst Mental Hlth Care, Utrecht, Netherlands.
[Kupka, R.] Univ Med Ctr, Utrecht, Netherlands.
[Leverich, G.] NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Grunze, H.; Altshuler, L.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Post, R.] George Washington Sch Med, Bipolar Collaborat Network, Bethesda, MD USA.
RI Nolen, Willem/E-9006-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
SU 1
BP 83
EP 84
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483KH
UT WOS:000268963500228
ER
PT J
AU Machado-Vieira, R
Manji, HK
Zarate, CA
AF Machado-Vieira, Rodrigo
Manji, Husseini K.
Zarate, Carlos A., Jr.
TI The role of lithium in the treatment of bipolar disorder: convergent
evidence for neurotrophic effects as a unifying hypothesis
SO BIPOLAR DISORDERS
LA English
DT Review
DE bipolar disorder; depression; GSK-3; lithium; mania; mitochondria; mood
stabilizer; neurodegenerative; neurotrophic effects; oxidative stress;
PKC; protein kinase C
ID PROTEIN-KINASE-C; MAGNETIC-RESONANCE-SPECTROSCOPY; GLYCOGEN-SYNTHASE
KINASE-3; NERVE GROWTH-FACTOR; N-ACETYL-ASPARTATE; AMYLOID-INDUCED
NEURODEGENERATION; IMMORTALIZED HIPPOCAMPAL CELLS;
AMYOTROPHIC-LATERAL-SCLEROSIS; CEREBELLAR GRANULE NEURONS;
MANIC-DEPRESSIVE ILLNESS
AB Lithium has been and continues to be the mainstay of bipolar disorder (BID) pharmacotherapy for acute mood episodes, switch prevention, prophylactic treatment, and suicide prevention. Lithium is also the definitive proof-of-concept agent in BID, although it has recently been studied in other psychoses as well as diverse neurodegenerative disorders. Its neurotrophic effects can be viewed as a unifying model to explain several integrated aspects of the pathophysiology of mood disorders and putative therapeutics for those disorders. Enhancing neuroprotection (which directly involves neurotrophic effects) is a therapeutic strategy intended to slow or halt the progression of neuronal loss, thus producing long-term benefits by favorably influencing outcome and preventing either the onset of disease or clinical decline. The present article: (i) reviews what has been learned regarding lithium's neurotrophic effects since Cade's original studies with this compound; (ii) presents human data supporting the presence of cellular atrophy and death in BD as well as neurotrophic effects associated with lithium in human studies; (iii) describes key direct targets of lithium involved in these neurotrophic effects, including neurotrophins, glycogen synthase kinase 3 (GSK-3), and mitochondrial/endoplasmic reticulum key proteins; and (iv) discusses lithium's neurotrophic effects in models of apoptosis and excitotoxicity as well as its potential neurotrophic effects in models of neurological disorders. Taken together, the evidence reviewed here suggests that lithium's neurotrophic effects in BID are an example of an old molecule acting as a new proof-of-concept agent. Continued work to decipher lithium's molecular actions will likely lead to the development of not only improved therapeutics for BID, but to neurotrophic enhancers that could prove useful in the treatment of many other illnesses.
C1 [Zarate, Carlos A., Jr.] NIMH, Mood & Anxiety Disorders Res Program, Mark O Hatfield Clin Res Ctr, NIH,Dept Human & Hlth Serv, Bethesda, MD 20892 USA.
[Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
RP Zarate, CA (reprint author), NIMH, Mood & Anxiety Disorders Res Program, Mark O Hatfield Clin Res Ctr, NIH,Dept Human & Hlth Serv, 10 Ctr Dr,CRC Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190
FU National Institute of Mental Health (NIMH); NARSAD
FX Funding for this work was supported by the Intramural Research Program
of the National Institute of Mental Health (NIMH) and a NARSAD Award
(CAZ). Ioline Henter provided outstanding editorial assistance.
NR 179
TC 115
Z9 116
U1 5
U2 34
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 JUN
PY 2009
VL 11
SU 2
BP 92
EP 109
PG 18
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 478OH
UT WOS:000268597100010
PM 19538689
ER
PT J
AU Creson, TK
Hao, YL
Engel, S
Shen, Y
Hamidi, A
Zhuo, M
Manji, HK
Chen, G
AF Creson, Thomas K.
Hao, Yanlei
Engel, Sharon
Shen, Yi
Hamidi, Anahita
Zhuo, Min
Manji, Husseini K.
Chen, Guang
TI The anterior cingulate ERK pathway contributes to regulation of
behavioral excitement and hedonic activity
SO BIPOLAR DISORDERS
LA English
DT Article
DE anterior cingulate cortex; mania; signal transduction cascade
ID TRANSCRANIAL MAGNETIC STIMULATION; MEDIAL PREFRONTAL CORTEX; VOXEL-BASED
MORPHOMETRY; BIPOLAR-DISORDER; FRONTAL-CORTEX; ANIMAL-MODEL; MICE
LACKING; MAP KINASE; DEPRESSION; MANIA
AB Several intracellular signaling cascades, such as the extracellular signal-regulated kinase (ERK), Wnt-signaling/GSK-3, PLC/PKC, and PI3K pathways, have been shown to be affected directly or indirectly by mood stabilizers. Clinical imaging studies reveal that mood disorders are associated with structural and/or metabolic changes in specific brain regions such as the anterior cingulate cortex (ACC). Here we investigated the extent to which perturbation of one of the affected pathways, the ERK pathway, in the ACC influences affective-related behavior.
The regional perturbation was induced by two means: local continuous infusion of PD98059, an ERK pathway inhibitor, and microinjection of a lentiviral-mediated gene delivery system encoding functional negative ERK1. The outcomes were monitored with a battery of affective-related tests similar to those used in several previous studies.
Compared to their respective controls, rats infused with PD98059 or injected with the lentiviral negative ERK1 construct displayed hyperactivities in multiple tests, exhibited preferentially more open-arm activity in the elevated-plus-maze test, consumed more sweetened liquid in a saccharin preference test, and showed heightened response to amphetamine.
These data support a role for the ACC ERK pathway in the regulation of affective-related behaviors. However, the medial prefrontal cortex (mPFC) comprises at least three other regions that will need to be similarly examined before specific roles of the ACC ERK pathway can be definitively attributed to affective behaviors. Additionally, responses of other signaling pathways to mood stabilizers in these mPFC regions, as well as the limbic regions to which they project, will be important to examine.
C1 [Creson, Thomas K.; Hao, Yanlei; Engel, Sharon; Shen, Yi; Hamidi, Anahita; Manji, Husseini K.; Chen, Guang] NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Zhuo, Min] Univ Toronto, Dept Physiol, Toronto, ON, Canada.
RP Chen, G (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, NIH, 35 Convent Dr,Bldg 35,Room 1C-912, Bethesda, MD 20892 USA.
EM guangchen@mail.nih.gov
RI Zhuo, Min/A-2072-2008; Chen, Guang/A-2570-2017
OI Zhuo, Min/0000-0001-9062-3241;
FU U.S. National Institutes of Health; National Institute of Mental Health
(NIMH) Intramural Research Program
FX We are grateful to Dr. J. Silvio Gutkind of the National Institute of
Dental and Craniofacial Research for his generous contribution of the
dominant negative ERK construct used in our study. This work was
supported by the U.S. National Institutes of Health, National Institute
of Mental Health (NIMH) Intramural Research Program. We are grateful to
Dr. Robert Schloesser of the Laboratory of Molecular Pathophysiology and
Experimental Therapeutics, NIMH, for his work on assessing the in vivo
infectivity of the lentiviral-mediated GFP control vector in the
anterior cingulate cortex of the rat as developed in this study.
NR 50
TC 13
Z9 14
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
IS 4
BP 339
EP 350
DI 10.1111/j.1399-5618.2009.00697.x
PG 12
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 443TP
UT WOS:000265934000001
PM 19500087
ER
PT J
AU Luckenbaugh, DA
Findling, RL
Leverich, GS
Pizzarello, SM
Post, RM
AF Luckenbaugh, David A.
Findling, Robert L.
Leverich, Gabriele S.
Pizzarello, Scott M.
Post, Robert M.
TI Earliest symptoms discriminating juvenile-onset bipolar illness from
ADHD
SO BIPOLAR DISORDERS
LA English
DT Article
DE ADHD; bipolar; depression; mania; onset; symptom
ID DISORDER PHENOTYPE; I-DISORDER; DEVELOPMENTAL SUBTYPE; PREPUBERTAL
CHILDREN; CONDUCT DISORDER; PEDIATRIC MANIA; ADOLESCENTS; PHENOMENOLOGY;
CHILDHOOD; AGE
AB Controversy surrounds the diagnosis and earliest symptoms of childhood-onset bipolar illness, emphasizing the importance of prospective longitudinal studies. To acquire a preliminary, more immediate view of symptom evolution, we examined the course of individual symptoms over the first 10 years of life in juvenile-onset bipolar illness (JO-BP) compared with attention-deficit hyperactivity disorder (ADHD).
Parents of formally diagnosed children retrospectively rated 37 symptoms in each year of the child's life based on the degree of dysfunction in their child's usual family, social, or educational roles. A subset of children with onset of bipolar disorder prior to age 9 (JO-BP) compared with those with ADHD was the focus of this analysis.
Brief and extended periods of mood elevation and decreased sleep were strong early differentiators of JO-BP and ADHD children. Depressive and somatic symptoms were later differentiators. Irritability and poor frustration tolerance differentiated the two groups only in their greater incidence and severity in JO-BP compared with a moderate occurrence in ADHD. In contrast, hyperactivity, impulsivity, and decreased attention showed highly similar trajectories in the two groups.
Elevated mood and decreased sleep discriminated JO-BP and ADHD as early as age 3, while classic ADHD symptoms were parallel in the groups. These retrospective results provide preliminary insights into symptom differences and their temporal evolution between bipolar disorder and ADHD in the first 10 years of life.
C1 [Luckenbaugh, David A.] NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Findling, Robert L.] Univ Hosp Case Med Ctr, Dept Psychiat, Cleveland, OH USA.
[Findling, Robert L.] Univ Hosp Case Med Ctr, Dept Pediat, Cleveland, OH USA.
[Findling, Robert L.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Leverich, Gabriele S.; Pizzarello, Scott M.] NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA.
[Post, Robert M.] Penn State Univ, Sch Med, Hershey, PA USA.
[Post, Robert M.] George Washington Univ, Sch Med, Washington, DC USA.
RP Post, RM (reprint author), 5415 W Cedar Lane,Suite 201B, Bethesda, MD 20814 USA.
EM robert.post@speakeasy.net
FU Stanley Medical Research Institute
FX The authors would like to thank Harriet Brightman and Chris Gavin for
help in manuscript preparation. The conception of the study, development
of methods, data analysis, and writing of this manuscript were performed
as part of the NIMH Intramural Research Program. Support of the Stanley
Medical Research Institute is gratefully acknowledged.
NR 54
TC 27
Z9 27
U1 1
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2009
VL 11
IS 4
BP 441
EP 451
DI 10.1111/j.1399-5618.2009.00684.x
PG 11
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 443TP
UT WOS:000265934000012
PM 19500097
ER
PT J
AU Aravind, L
Anantharaman, V
Venancio, TM
AF Aravind, L.
Anantharaman, Vivek
Venancio, Thiago M.
TI Apprehending Multicellularity: Regulatory Networks, Genomics, and
Evolution
SO BIRTH DEFECTS RESEARCH PART C-EMBRYO TODAY-REVIEWS
LA English
DT Review
ID PUTATIVE TRANSCRIPTION FACTOR; PROTEIN-INTERACTION NETWORK; NOTCH
SIGNALING PATHWAY; ESCHERICHIA-COLI K-12; ZINC-FINGER PROTEIN; OF-SPLIT
COMPLEX; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; BTB-DOMAIN;
DROSOPHILA-MELANOGASTER
AB The genomic revolution has provided the first glimpses of the architecture of regulatory networks. Combined with evolutionary information, the "network view" of life processes leads to remarkable insights into how biological systems have been shaped by various forces. This understanding is critical because biological systems, including regulatory networks, are not products of engineering but of historical contingencies. In this light, we attempt a synthetic overview of the natural history of regulatory networks operating in the development and differentiation of multicellular organisms. We first introduce regulatory networks and their organizational principles as can be deduced using ideas from the graph theory. We then discuss findings from comparative genomics to illustrate the effects of lineage-specific expansions, gene-loss, and nonprotein-coding DNA on the architecture of networks. We consider the interaction between expansions of transcription factors, and cis regulatory and more general chromatin state stabilizing elements in the emergence of morphological complexity. Finally, we consider a case study of the Notch subnetwork, which is present throughout Metazoa, to examine how such a regulatory system has been pieced together in evolution from new innovations and pre-existing components that were originally functionally distinct. Birth Defects Research (Part C) 87:143-164, 2009. (c) 2009 Wiley-Liss, Inc.
C1 [Aravind, L.; Anantharaman, Vivek; Venancio, Thiago M.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@ncbi.nlm.nih.gov
RI Venancio, Thiago/B-5003-2011; Entomologiamolecular, Inct/J-8214-2013;
OI Anantharaman, Vivek/0000-0001-8395-0009
FU NIH; National Library of Medicine
FX Intramural Research Program of the NIH; National Library of Medicine
NR 203
TC 10
Z9 10
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-975X
EI 1542-9768
J9 BIRTH DEFECTS RES C
JI Birth Defects Res. Part C-Embryo Today-Rev.
PD JUN
PY 2009
VL 87
IS 2
BP 143
EP 164
DI 10.1002/bdrc.20153
PG 22
WC Developmental Biology; Reproductive Biology
SC Developmental Biology; Reproductive Biology
GA 470AX
UT WOS:000267945100003
PM 19530132
ER
PT J
AU Aragon-Ching, JB
Jain, L
Gulley, JL
Arlen, PM
Wright, JJ
Steinberg, SM
Draper, D
Venitz, J
Jones, E
Chen, CC
Figg, WD
Dahut, WL
AF Aragon-Ching, Jeanny B.
Jain, Lokesh
Gulley, James L.
Arlen, Philip M.
Wright, John J.
Steinberg, Seth M.
Draper, David
Venitz, Juergen
Jones, Elizabeth
Chen, Clara C.
Figg, William D.
Dahut, William L.
TI Final analysis of a phase II trial using sorafenib for metastatic
castration-resistant prostate cancer
SO BJU INTERNATIONAL
LA English
DT Article
DE castration-resistant prostate cancer; angiogenesis; Raf-kinase
inhibitor; sorafenib
ID REFRACTORY SOLID TUMORS; 2ND-LINE CHEMOTHERAPY; CLINICAL-TRIALS; RAF
KINASE; PHARMACOKINETICS; MITOXANTRONE; INHIBITOR; DOCETAXEL; SAFETY;
PREDNISONE
AB To determine if sorafenib is associated with an improved 4-month probability of progression-free survival, using radiographic and clinical criteria alone, in patients with metastatic castration-resistant prostate cancer. Secondary endpoints included pharmacokinetics, toxicity analysis and overall survival.
The study was an open-label, phase II, two-stage design, focusing on the results from the second stage, as criteria for progression were modified after completing the first stage. Sorafenib was given at a dose of 400 mg orally twice daily in 28-day cycles. Clinical and laboratory assessments were done every 4 weeks, and radiographic scans were obtained every 8 weeks.
Twenty-four patients were accrued in the second stage; the median (range) age was 66 (49-85) years, the on-study prostate-specific antigen level was 68.45 (5.8-995) ng/mL, the Gleason score 8 (6-9) and Eastern Cooperative Oncology Group status 1 (in 17 patients). Of the 24 patients, 21 had previous chemotherapy with docetaxel. All patients had bony metastases, either alone (in 11) or with soft-tissue disease (in 13). One patient had a partial response; 10 patients had stable disease (median duration 18 weeks, range 15-48). At a median potential follow-up of 27.2 months, the median progression-free survival was 3.7 months and the median overall survival was 18.0 months. For the whole trial of 46 patients the median survival was 18.3 months. Most frequent toxicities included hand-foot skin reaction (grade 2 in nine patients, grade 3 in three), rash, abnormalities in liver function tests, and fatigue.
Sorafenib has moderate activity as a second-line treatment for metastatic castration-resistant prostate cancer.
C1 [Figg, William D.] NCI, Med Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Jain, Lokesh; Figg, William D.] NCI, Mol Pharmacol Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Wright, John J.] NCI, Canc Therapy Evaluat Program, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Jones, Elizabeth] NCI, Dept Radiol, Bethesda, MD 20892 USA.
[Chen, Clara C.] NCI, Dept Nucl Med, Bethesda, MD 20892 USA.
[Jain, Lokesh; Venitz, Juergen; Figg, William D.] Virginia Commonwealth Univ, Sch Pharm, Dept Pharmaceut, Richmond, VA USA.
RP Figg, WD (reprint author), NCI, Med Oncol Branch, CCR, NIH, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016;
OI Gulley, James/0000-0002-6569-2912; Aragon-Ching,
Jeanny/0000-0002-6714-141X
FU Intramural NIH HHS [Z01 SC006538-15]
NR 20
TC 73
Z9 76
U1 1
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD JUN
PY 2009
VL 103
IS 12
BP 1636
EP 1640
DI 10.1111/j.1464-410X.2008.08327.x
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 451DJ
UT WOS:000266450600008
PM 19154507
ER
PT J
AU Rahimi, Z
Nomani, H
Mozafari, H
Vaisi-Raygani, A
Madani, H
Malek-Khosravi, S
Parsian, A
AF Rahimi, Zohreh
Nomani, Hamid
Mozafari, Hadi
Vaisi-Raygani, Asad
Madani, Hamid
Malek-Khosravi, Shohreh
Parsian, Abbas
TI Factor V G1691A, prothrombin G20210A and methylenetetrahydrofolate
reductase polymorphism C677T are not associated with coronary artery
disease and type 2 diabetes mellitus in western Iran
SO BLOOD COAGULATION & FIBRINOLYSIS
LA English
DT Article
DE coronary artery disease; diabetes; factor V Leiden;
methylentetrahydrofolate reductase; prothrombin G20210A; western Iran
ID ACTIVATED PROTEIN-C; ACUTE MYOCARDIAL-INFARCTION; COAGULATION-FACTOR-V;
VENOUS THROMBOSIS; GENE POLYMORPHISM; LEIDEN MUTATION; YOUNG-PATIENTS;
HEART-DISEASE; RISK-FACTORS; PREVALENCE
AB There are controversial results related to the contribution of factor V Leiden G1691 A, prothrombin gene G20210A and methylentetrahydrofolate reductase (MTHFR) C677T mutations in the development of coronary artery disease (CAD) and their association with diabetes. To assess the distribution of these thrombophilic mutations in CAD patients with and without type 2 diabetes mellitus (T2DM), we studied 117 CAD patients [65 CAD patients with diabetes (CAD/T2DM) and 52 CAD patients without diabetes (CAD/ND)] and 59 age-matched and sex-matched healthy individuals without CAD from population of western Iran. Genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism using MnI 1, Hind III and Hinf I for factor V Leiden, prothrombin G20210A and MTHFR Cl respectively. The prevalence of prothrombin G20210A variant in CAD/T2DM, CAD/ND and control individuals was 3.1, 1.9 and 0%, respectively. Factor V Leiden G1691 A was found in 4.6% of patients with CAD/T2DM, 3.8% of patients with CAD/ND and 3.4% of healthy individuals. The prevalence of MTHFR C677T was found to be 49.2, 32.7 and 44.1% in CAD/T2DM, CAD/ND and control group, respectively. Our results indicate that there is no significant difference between the prevalence of thrombophilic mutations of factor V Leiden, prothrombin G20210A variant and MTHFR C677T in CAD patients with or without diabetes compared with controls. Although a higher prevalence of these thrombophilic mutations was observed in CAD patients, especially in those patients with diabetes, it seems that these variants may not be considered as independent risk factors for CAD or diabetes in our sample. These findings are discussed in relation to available literature. Blood Coagul Fibrinolysis 20:252-256 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Rahimi, Zohreh] Kermanshah Univ Med Sci, Sch Med, Med Biol Res Ctr, Kermanshah, Iran.
[Rahimi, Zohreh; Nomani, Hamid; Vaisi-Raygani, Asad] Kermanshah Univ Med Sci, Sch Med, Dept Biochem, Kermanshah, Iran.
[Rahimi, Zohreh] Kurdistan Univ Med Sci, Dept Biochem, Sch Med, Kurdistan, Iran.
[Madani, Hamid] Kermanshah Univ Med Sci, Dept Pathol, Sch Med, Kermanshah, Iran.
[Malek-Khosravi, Shohreh] Kermanshah Univ Med Sci, Dept Obstet & Gynecol, Sch Med, Kermanshah, Iran.
[Parsian, Abbas] NIH, Div Neurosci & Behav, Rockville, MD USA.
RP Rahimi, Z (reprint author), Kermanshah Univ Med Sci, Sch Med, Med Biol Res Ctr, Daneshgah Ave,POB 671551957, Kermanshah, Iran.
EM zrahimi@kums.ac.ir
OI Rahimi, Zohreh/0000-0001-7589-3307; Vaisi-Raygani,
Asad/0000-0002-3042-2832
NR 34
TC 10
Z9 10
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0957-5235
J9 BLOOD COAGUL FIBRIN
JI Blood Coagul. Fibrinolysis
PD JUN
PY 2009
VL 20
IS 4
BP 252
EP 256
DI 10.1097/MBC.0b013e3283255487
PG 5
WC Hematology
SC Hematology
GA 446VB
UT WOS:000266148400006
PM 19349859
ER
PT J
AU Barnes, AM
Lindahl, K
Whyte, MP
Hefferan, T
Rubin, C
Kindmark, A
McAlister, W
Mumm, S
Ljunggren, O
Marini, JC
AF Barnes, A. M.
Lindahl, K.
Whyte, M. P.
Hefferan, T.
Rubin, C.
Kindmark, A.
McAlister, W.
Mumm, S.
Ljunggren, O.
Marini, J. C.
TI Distinct OI phenotype caused by COL1 C-proteinase site mutations
SO BONE
LA English
DT Meeting Abstract
CT 36th European Symposium on Calcified Tissues
CY MAY 23-27, 2009
CL Vienna, AUSTRIA
SP Int Res Austrian Soc Bone & Mineral Res
C1 [Barnes, A. M.; Marini, J. C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA.
[Lindahl, K.; Rubin, C.; Kindmark, A.; Ljunggren, O.] Uppsala Univ, Dept Endocrinol, Uppsala, Sweden.
[Whyte, M. P.; McAlister, W.; Mumm, S.] Shriners Hosp Children, Ctr Metab Bone Dis & Mol Res, St Louis, MO USA.
[Hefferan, T.] Mayo Clin, Dept Orthoped, Rochester, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD JUN
PY 2009
VL 44
IS 2
BP S344
EP S344
DI 10.1016/j.bone.2009.03.152
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 449RV
UT WOS:000266348600364
ER
PT J
AU Marini, J
Chang, W
Glorieux, FH
Hefferan, TE
Rauch, F
Abukhaled, M
Smith, PA
Eyre, D
AF Marini, J.
Chang, W.
Glorieux, F. H.
Hefferan, T. E.
Rauch, F.
Abukhaled, M.
Smith, P. A.
Eyre, D.
TI Severe non-lethal recessive type viii oi: clinical, histological and
radiographic features
SO BONE
LA English
DT Meeting Abstract
CT 36th European Symposium on Calcified Tissues
CY MAY 23-27, 2009
CL Vienna, AUSTRIA
SP Int Res Austrian Soc Bone & Mineral Res
C1 [Marini, J.; Chang, W.; Abukhaled, M.] NICHD, BEMB, NIH, Bethesda, MD USA.
[Glorieux, F. H.; Rauch, F.] McGill Univ, Shriners Hosp Children, Montreal, PQ, Canada.
[Hefferan, T. E.] Mayo Clin, Rochester, MN USA.
[Smith, P. A.] Shriners Hosp Children, Chicago, IL USA.
[Eyre, D.] Univ Washington, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD JUN
PY 2009
VL 44
IS 2
BP S283
EP S284
DI 10.1016/j.bone.2009.03.506
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 449RV
UT WOS:000266348600205
ER
PT J
AU Roschger, P
Pfeffer, S
Misof, BM
Fratzl-Zelman, N
Rauch, F
Collins, MT
Fratzl, P
Klaushofer, K
AF Roschger, P.
Pfeffer, S.
Misof, B. M.
Fratzl-Zelman, N.
Rauch, F.
Collins, M. T.
Fratzl, P.
Klaushofer, K.
TI Evidence of genetic disorders which affect the primary mineralization
process of bone matrix
SO BONE
LA English
DT Meeting Abstract
CT 36th European Symposium on Calcified Tissues
CY MAY 23-27, 2009
CL Vienna, AUSTRIA
SP Int Res Austrian Soc Bone & Mineral Res
C1 [Roschger, P.; Pfeffer, S.; Misof, B. M.; Fratzl-Zelman, N.; Klaushofer, K.] Hanusch Hosp WGKK, Ludwig Boltzmann Inst Osteol, Vienna, Austria.
[Roschger, P.; Pfeffer, S.; Misof, B. M.; Fratzl-Zelman, N.; Klaushofer, K.] Hanusch Hosp, Dept Med 4, AUVA Trauma Ctr Meidling, Vienna, Austria.
[Rauch, F.] Shriners Hosp Children, Genet Unit, Montreal, PQ, Canada.
[Rauch, F.] McGill Univ, Montreal, PQ, Canada.
[Collins, M. T.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
[Fratzl, P.] Max Planck Inst Colloids & Interfaces, Dept Biomat, Potsdam, Germany.
RI Fratzl, Peter/H-9095-2012
OI Fratzl, Peter/0000-0003-4437-7830
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD JUN
PY 2009
VL 44
IS 2
BP S287
EP S288
DI 10.1016/j.bone.2009.03.517
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 449RV
UT WOS:000266348600216
ER
PT J
AU Dalakas, MC
Rakocevic, G
Schmidt, J
Salajegheh, M
McElroy, B
Harris-Love, MO
Shrader, JA
Levy, EW
Dambrosia, J
Kampen, RL
Bruno, DA
Kirk, AD
AF Dalakas, Marinos C.
Rakocevic, Goran
Schmidt, Jens
Salajegheh, Mohammad
McElroy, Beverly
Harris-Love, Michael O.
Shrader, Joseph A.
Levy, Ellen W.
Dambrosia, James
Kampen, Robert L.
Bruno, David A.
Kirk, Allan D.
TI Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body
myositis
SO BRAIN
LA English
DT Article
DE Alemtuxumab; IBM; muscle inflammation; muscle degeneration; lymphocyte
depletion; endomysial inflammation; stressor molecules
ID T-CELL DEPLETION; MONOCLONAL-ANTIBODY; MULTIPLE-SCLEROSIS; MUSCLE;
DERMATOMYOSITIS; POLYMYOSITIS; DISORDERS; THERAPY; BETA; IBM
AB Sporadic inclusion-body myositis (sIBM) is the most common disabling, adult-onset, inflammatory myopathy histologically characterized by intense inflammation and vacuolar degeneration. In spite of T cell-mediated cytotoxicity and persistent, clonally expanded and antigen-driven endomysial T cells, the disease is resistant to immunotherapies. Alemtuzumab is a humanized monoclonal antibody that causes an immediate depletion or severe reduction of peripheral blood lymphocytes, lasting at least 6 months. We designed a proof-of-principle study to examine if one series of Alemtuzumab infusions in sIBM patients depletes not only peripheral blood lymphocytes but also endomysial T cells and alters the natural course of the disease. Thirteen sIBM patients with established 12-month natural history data received 0.3 mg/kg/day Alemtuzumab for 4 days. The study was powered to capture 10 increase strength 6 months after treatment. The primary end-point was disease stabilization compared to natural history, assessed by bi-monthly Quantitative Muscle Strength Testing and Medical Research Council strength measurements. Lymphocytes and T cell subsets were monitored concurrently in the blood and the repeated muscle biopsies. Alterations in the mRNA expression of inflammatory, stressor and degeneration-associated molecules were examined in the repeated biopsies. During a 12-month observation period, the patients total strength had declined by a mean of 14.9 based on Quantitative Muscle Strength Testing. Six months after therapy, the overall decline was only 1.9 (P 0.002), corresponding to a 13 differential gain. Among those patients, four improved by a mean of 10 and six reported improved performance of daily activities. The benefit was more evident by the Medical Research Council scales, which demonstrated a decline in the total scores by 13.8 during the observation period but an improvement by 11.4 (P 0.001) after 6 months, reaching the level of strength recorded 12 months earlier. Depletion of peripheral blood lymphocytes, including the naive and memory CD8 cells, was noted 2 weeks after treatment and persisted up to 6 months. The effector CD45RACD62L cells, however, started to increase 2 months after therapy and peaked by the 4th month. Repeated muscle biopsies showed reduction of CD3 lymphocytes by a mean of 50 (P 0.008), most prominent in the improved patients, and reduced mRNA expression of stressor molecules Fas, Mip-1a and B-crystallin; the mRNA of desmin, a regeneration-associated molecule, increased. This proof-of-principle study provides insights into the pathogenesis of inclusion-body myositis and concludes that in sIBM one series of Alemtuzumab infusions can slow down disease progression up to 6 months, improve the strength of some patients, and reduce endomysial inflammation and stressor molecules. These encouraging results, the first in sIBM, warrant a future study with repeated infusions (Clinical Trials. Gov NCT00079768).
C1 [Dalakas, Marinos C.; Rakocevic, Goran; Schmidt, Jens; Salajegheh, Mohammad; McElroy, Beverly] NINDS, Neuromuscular Dis Sect, Bethesda, MD 20892 USA.
[Harris-Love, Michael O.; Shrader, Joseph A.; Levy, Ellen W.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Dambrosia, James] NINDS, Biostat Branch, Bethesda, MD 20892 USA.
[Kampen, Robert L.; Bruno, David A.; Kirk, Allan D.] NIDDK, Transplantat Branch, Bethesda, MD USA.
RP Dalakas, MC (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp Campus,Burlington Danes Bldg,Off, London W12 0NN, England.
EM m.dalakas@imperial.ac.uk
RI Harris-Love, Michael/J-1359-2014; Kirk, Allan/B-6905-2012; Schmidt,
Jens/B-5791-2013
OI Harris-Love, Michael/0000-0002-1842-3269;
FU National Institutes of Health
FX Intramural funding from National Institutes of Health.
NR 27
TC 79
Z9 81
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD JUN
PY 2009
VL 132
BP 1536
EP 1544
DI 10.1093/brain/awp104
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 451VG
UT WOS:000266498400020
PM 19454532
ER
PT J
AU Beason-Held, LL
Kraut, MA
Resnick, SM
AF Beason-Held, L. L.
Kraut, M. A.
Resnick, S. M.
TI Stability of Default-Mode Network Activity in the Aging Brain
SO BRAIN IMAGING AND BEHAVIOR
LA English
DT Article
DE Functional imaging; Brain function; Activation; Age; fMRI; Human;
Default activity
ID EARLY ALZHEIMERS-DISEASE; RESTING-STATE NETWORKS; OLDER-ADULTS; AGE;
CORTEX; MEMORY; DEACTIVATION; DEMENTIA; MRI
AB Activity attributed to the default-mode occurs during the resting state and is thought to represent self-referential and other intrinsic processes. Although activity in default-associated regions changes across the lifespan, little is known about the stability of default-mode activity in the healthy aging brain. We investigated changes in rest-specific activity across an 8 year period in older participants in the Baltimore Longitudinal Study of Aging (BLSA) neuroimaging study. Comparison of resting-state and recognition memory PET regional cerebral blood flow conditions from baseline and 8-year follow-up shows relative stability of rest-specific activity over time in medial frontal/anterior cingulate, hippocampal and posterior cingulate regions commonly associated with the default-mode. In contrast, prefrontal, parahippocampal and occipital cortical regions, which are not typically associated with default-mode activity, show changes over time. Overall, activity in the major components of the default-mode network remains stable in healthy older individuals, a finding which may assist in identifying factors that discriminate between normal and pathological aging.
C1 [Beason-Held, L. L.; Resnick, S. M.] NIA, LPC, NIH, Baltimore, MD 21224 USA.
[Beason-Held, L. L.; Kraut, M. A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
RP Beason-Held, LL (reprint author), NIA, LPC, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM heldlo@mail.nih.gov
FU NIH, National Institute on Aging and by 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 and by Research and Development
Contract N01-AG-3-2124. We are grateful to the BLSA participants and
neuroimaging staff for their dedication to these studies and the staff
of the Johns Hopkins PET facility for their assistance.
NR 33
TC 37
Z9 38
U1 2
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1931-7557
J9 BRAIN IMAGING BEHAV
JI Brain Imaging Behav.
PD JUN
PY 2009
VL 3
IS 2
BP 123
EP 131
DI 10.1007/s11682-008-9054-z
PG 9
WC Neuroimaging
SC Neurosciences & Neurology
GA 510LS
UT WOS:000271090600002
PM 19568331
ER
PT J
AU LaKind, JS
Berlin, CM
Mattison, DR
AF LaKind, Judy S.
Berlin, Cheston M., Jr.
Mattison, Donald R.
TI Regarding: The Heart of the Matter on Breastmilk and Environmental
Chemicals: Essential Points for Healthcare Providers and New Parents
Response
SO BREASTFEEDING MEDICINE
LA English
DT Letter
C1 [LaKind, Judy S.] LaKind Associates, Catonsville, MD 21228 USA.
[LaKind, Judy S.; Berlin, Cheston M., Jr.] Penn State Coll Med, Milton S Hershey Med Ctr, Dept Pediat, Hershey, PA USA.
[LaKind, Judy S.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
[Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol Branch, NIH, US Dept HHS, Bethesda, MD USA.
RP LaKind, JS (reprint author), LaKind Associates, 106 Oakdale Ave, Catonsville, MD 21228 USA.
EM lakindassoc@comcast.net
RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013
OI Mattison, Donald/0000-0001-5623-0874
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1556-8253
J9 BREASTFEED MED
JI Breastfeed. Med.
PD JUN
PY 2009
VL 4
IS 2
BP 127
EP 127
DI 10.1089/bfm.2009.0011
PG 1
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 583KN
UT WOS:000276674000014
ER
PT J
AU Ratanatharathorn, V
Logan, B
Wang, D
Horowitz, M
Uberti, JP
Ringden, O
Gale, RP
Khoury, H
Arora, M
Spellman, S
Cutler, C
Antin, J
Bornhauser, M
Hale, G
Verdonck, L
Cairo, M
Gupta, V
Pavletic, S
AF Ratanatharathorn, Voravit
Logan, Brent
Wang, Dan
Horowitz, Mary
Uberti, Joseph P.
Ringden, Olle
Gale, Robert Peter
Khoury, Hanna
Arora, Mukta
Spellman, Stephen
Cutler, Corey
Antin, Joseph
Bornhaeuser, Martin
Hale, Gregory
Verdonck, Leo
Cairo, Mitchell
Gupta, Vikas
Pavletic, Steven
CA CIBMTR
TI Prior rituximab correlates with less acute graft-versus-host disease and
better survival in B-cell lymphoma patients who received allogeneic
peripheral blood stem cell transplantation
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE rituximab; lymphoma; graft-versus-host disease; allogeneic;
transplantation
ID NON-HODGKINS-LYMPHOMA; IDIOPATHIC THROMBOCYTOPENIC PURPURA;
MONOCLONAL-ANTIBODY TREATMENT; MARROW-TRANSPLANTATION; COMPARING
METHOTREXATE; FOLLICULAR LYMPHOMA; DEPLETING THERAPY; LOW-GRADE;
IN-VIVO; CYCLOSPORINE
AB Prior therapy with rituximab might attenuate disparate histocompatibility antigen presentation by B cells, thus decreased the risk of acute graft-versus-host disease (GVHD) and improved survival. We tested this hypothesis by comparing the outcomes of 435 B-cell lymphoma patients who received allogeneic transplantation from 1999 to 2004 in the Center for International Blood and Marrow Transplant Research database: 179 subjects who received rituximab within 6 months prior to transplantation (RTX cohort) and 256 subjects who did not receive RTX within 6 months prior to transplantation (No-RTX cohort). The RTX cohort had a significantly lower incidence of treatment-related mortality (TRM) [relative risk (RR) = 0.68; 95% confidence interval (CI), 0.47-1.0; P = 0.05], lower acute grade II-IV (RR = 0.72; 95% CI, 0.53-0.97; P = 0.03) and III-IV GVHD (RR = 0.55; 95% CI, 0.34-0.91; P = 0.02). There was no difference in the risk of chronic GVHD, disease progression or relapse. Progression-free survival (PFS) (RR = 0.68; 95% CI 0.50-0.92; P = 0.01) and overall survival (OS) (RR = 0.63; 95% CI, 0.46-0.86; P = 0.004) were significantly better in the RTX cohort. Prior RTX therapy correlated with less acute GVHD, similar chronic GVHD, less TRM, better PFS and OS.
C1 [Ratanatharathorn, Voravit] Wayne State Univ, Sch Med, Blood & Marrow Transplantat Program, Karmanos Canc Inst, Detroit, MI 48201 USA.
[Logan, Brent; Horowitz, Mary] CIBMTR, Milwaukee, WI USA.
[Wang, Dan; Spellman, Stephen] CIBMTR, Minneapolis, MN USA.
[Ringden, Olle] Karolinska Univ Hosp, Dept Clin Immunol, Stockholm, Sweden.
[Gale, Robert Peter] Celgene, Summit, NJ USA.
[Khoury, Hanna] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA.
[Arora, Mukta] Univ Minnesota, Minneapolis, MN USA.
[Cutler, Corey; Antin, Joseph] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bornhaeuser, Martin] Tech Univ Dresden, Inst Immunol, Dresden, Germany.
[Hale, Gregory] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Verdonck, Leo] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Cairo, Mitchell] Columbia Univ, Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA.
[Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Pavletic, Steven] NIH, Bethesda, MD 20892 USA.
RP Ratanatharathorn, V (reprint author), Wayne State Univ, Sch Med, Blood & Marrow Transplantat Program, Karmanos Canc Inst, 4100 John R,4th Floor Hudson Webber Bldg, Detroit, MI 48201 USA.
EM ratanath@karmanos.org
FU National Marrow Donor Program; Department of the Navy; Office of Naval
Research [N00014-05-1-0859]; National Cancer Institute [U24-CA76518];
National Institute of Allergy and Infectious Diseases; National Heart,
Lung and Blood Institute; Health Services Research Administration
(DHHS); Abbott Laboratories; Aetna; American International Group, Inc.;
American Red Cross; Amgen, Inc
FX This project has been supported by funding from the National Marrow
Donor Program and the Department of the Navy, Office of Naval Research
Grant #N00014-05-1-0859 to the NMDP. Any opinions, findings and
conclusions or recommendations expressed in this material are those of
the authors and do not necessarily reflect the views of the Office of
Naval Research or the National Marrow Donor Program. The CIBMTR is
supported by Public Health Service Grant U24-CA76518 from the National
Cancer Institute, the National Institute of Allergy and Infectious
Diseases and the National Heart, Lung and Blood Institute; Office of
Naval Research; Health Services Research Administration (DHHS); and
grants from Abbott Laboratories; Aetna; American International Group,
Inc.; American Red Cross; Amgen, Inc.; Anonymous donation to the Medical
College of Wisconsin; AnorMED, Inc.; Astellas Pharma US, Inc.; Baxter
International, Inc.; Berlex Laboratories, Inc.; Biogen IDEC, Inc.; Blood
Center of Wisconsin; Blue Cross and Blue Shield Association;
Bristol-Myers Squibb Company; BRT Laboratories, Inc.; Cangene
Corporation; Celgene Corporation; CellGenix, Inc.; Cell Therapeutics,
Inc.; CelMed Biosciences; Cylex Inc.; Cytonome, Inc.; CytoTherm; DOR
BioPharma, Inc.; Dynal Biotech, an Invitrogen Company; Enzon
Pharmaceuticals, Inc.; Gambro BCT, Inc.; Gamida Cell, Ltd.; Genzyme
Corporation; Gift of Life Bone Marrow Foundation; GlaxoSmithKline, Inc.;
Histogenetics, Inc.; HKS Medical Information Systems; Kirin Brewery Co.,
Ltd.; Merck & Company; The Medical College of Wisconsin; Millennium
Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.;
Miltenyi Biotec, Inc.; MultiPlan, Inc.; National Marrow Donor Program;
Nature Publishing Group; Novartis Pharmaceuticals, Inc.; Osiris
Therapeutics, Inc.; Pall Medical; Pfizer, Inc.; Pharmion Corporation;
PDL BioPharma, Inc; Roche Laboratories; Sanofi-aventis; Schering Plough
Corporation; StemCyte, Inc.; StemSoft Software, Inc.; SuperGen, Inc.;
Sysmex; The Marrow Foundation; THERAKOS, Inc.; University of Colorado
Cord Blood Bank; ViaCell, Inc.; ViraCor Laboratories; Wellpoint, Inc.;
and Zelos Therapeutics, Inc. The views expressed in this article do not
reflect the official policy or position of the National Institute of
Health, the Department of the Navy, the Department of Defense, or any
other agency of the US Government.
NR 34
TC 46
Z9 48
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD JUN
PY 2009
VL 145
IS 6
BP 816
EP 824
DI 10.1111/j.1365-2141.2009.07674.x
PG 9
WC Hematology
SC Hematology
GA 453KJ
UT WOS:000266609000012
PM 19344418
ER
PT J
AU Hitsman, B
Moss, TG
Montoya, ID
George, TP
AF Hitsman, Brian
Moss, Taryn G.
Montoya, Ivan D.
George, Tony P.
TI Treatment of Tobacco Dependence in Mental Health and Addictive Disorders
SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE
LA English
DT Review
DE tobacco dependence; mental health; addiction; smoking cessation; smoking
reduction; pharmacotherapy; cognitive-behavioural treatment; tobacco ban
ID SMOKING-CESSATION TREATMENT; POSTTRAUMATIC-STRESS-DISORDER;
SUSTAINED-RELEASE BUPROPION; RECEPTOR PARTIAL AGONIST; RANDOMIZED
CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; PSYCHIATRIC INPATIENT
SETTINGS; NICOTINE REPLACEMENT THERAPY; CIGARETTE-SMOKING;
FAGERSTROM-TEST
AB People with mental health and addictive (MHA) disorders smoke at high rates and require tobacco treatment as a part of their comprehensive psychiatric care. Psychiatric care providers often do not address tobacco use among people with mental illness, possibly owing to the belief that their patients will not be able to quit successfully or that even short-term abstinence will adversely influence psychiatric status. Progress in the development of treatments has been slow in part because smokers with current MHA disorders have been excluded from most smoking cessation trials. There are several smoking cessation treatment options, including psychological and pharmacological interventions, that should be offered to people with an MHA disorder who smoke. Building motivation and readiness to quit smoking is a major challenge, and therefore motivational interventions are essential. We review the treatment options for people with tobacco dependence and MHA disorders, offer recommendations on tobacco assessment and tailored treatment strategies, and provide suggestions for future research. Treatment efficacy could be enhanced through promoting smoking reduction as an initial treatment goal, extending duration of treatment, and delivering it within an integrated care model that also aims to reduce the availability of tobacco in MHA treatment settings and in the community.
C1 [Hitsman, Brian] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Moss, Taryn G.] Univ Toronto, Dept Psychol, Ctr Addict & Mental Hlth, Toronto, ON M5S 1A1, Canada.
[Montoya, Ivan D.] Natl Inst Drug Abuse, Div Pharmacotherapies & Med Tox, Bethesda, MD USA.
[George, Tony P.] Univ Toronto, Dept Psychiat, Div Addict Psychiat, Toronto, ON, Canada.
[George, Tony P.] Ctr Addict & Mental Hlth, Schizophrenia Program, Toronto, ON, Canada.
RP Hitsman, B (reprint author), Northwestern Univ, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA.
EM b-hitsman@northwestern.edu
FU National Institute on Drug Abuse (NIDA) [K08 DA017145, K02 DA16611, R01
DA13672, R01 DA14039, R01 DA15757]; National Alliance for Research on
Schizophrenia and Depression; Canadian Institutes of Health
Research-Canadian Tobacco Control Research Initiative [19588]; Canada
Foundation for Innovation; Social Sciences and Humanities Research
Council; GlaxoSmithKline [2006]; Pfizer; Sepracor; Targacept;
Sanofi-aventis
FX Funding for this review was provided by a National Institute on Drug
Abuse (NIDA) grant K08 DA017145 to Dr Hitsman, NIDA grants K02 DA16611,
R01 DA13672, R01 DA14039, and R01 DA15757, a National Alliance for
Research on Schizophrenia and Depression Independent Investigator Award,
Canadian Institutes of Health Research-Canadian Tobacco Control Research
Initiative grant #19588, the Canada Foundation for Innovation, and the
Endowed Chair in Addiction Psychiatry at the University of Toronto to Dr
George, and a Social Sciences and Humanities Research Council Master's
Scholarship to Ms Moss.; Dr Hitsman has consulted for Pinney Associates,
subcontracted by GlaxoSmithKline (2006). Dr George has received grant
support from Pfizer, Sepracor, Targacept, and Sanofi-aventis, and is a
consultant to Pfizer, Prempharm, Glaxo-SmithKline, Eli Lilly,
Janssen-Ortho, and Evotec.
NR 97
TC 57
Z9 58
U1 12
U2 20
PU CANADIAN PSYCHIATRIC ASSOC
PI OTTAWA
PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA
SN 0706-7437
J9 CAN J PSYCHIAT
JI Can. J. Psychiat.-Rev. Can. Psychiat.
PD JUN
PY 2009
VL 54
IS 6
BP 368
EP 378
PG 11
WC Psychiatry
SC Psychiatry
GA 554LF
UT WOS:000274435800004
PM 19527557
ER
PT J
AU Nwe, K
Brechbiel, MW
AF Nwe, Kido
Brechbiel, Martin W.
TI Growing Applications of "Click Chemistry" for Bioconjugation in
Contemporary Biomedical Research
SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
LA English
DT Article
DE click chemistry; bioconjugation; bioorthogonal; radiochemistry; imaging;
bifunctional
ID POSITRON-EMISSION-TOMOGRAPHY; IN-SITU; STAUDINGER LIGATION; 1,3-DIPOLAR
CYCLOADDITIONS; PROTEASE INHIBITORS; CHEMICAL LIGATION; TERMINAL
ALKYNES; VERSATILE METHOD; LIVING SYSTEMS; CELL-SURFACES
AB This update summarizes the growing application of "click'' chemistry in diverse areas such as bioconjugation, drug discovery, materials science, and radiochemistry. This update also discusses click chemistry reactions that proceed rapidly with high selectivity, specificity, and yield. Two important characteristics make click chemistry so attractive for assembling compounds, reagents, and biomolecules for preclinical and clinical applications. First, click reactions are bio-orthogonal; neither the reactants nor their product's functional groups interact with functionalized biomolecules. Second, the reactions proceed with ease under mild nontoxic conditions, such as at room temperature and, usually, in water. The copper-catalyzed Huisgen cycloaddition, azide-alkyne [3 + 2] dipolar cycloaddition, Staudinger ligation, and azide-phosphine ligation each possess these unique qualities. These reactions can be used to modify one cellular component while leaving others unharmed or untouched. Click chemistry has found increasing applications in all aspects of drug discovery in medicinal chemistry, such as for generating lead compounds through combinatorial methods. Bioconjugation via click chemistry is rigorously employed in proteomics and nucleic research. In radiochemistry, selective radiolabeling of biomolecules in cells and living organisms for imaging and therapy has been realized by this technology. Bifunctional chelating agents for several radionuclides useful for positron emission tomography and single-photon emission computed tomography imaging have also been prepared by using click chemistry. This review concludes that click chemistry is not the perfect conjugation and assembly technology for all applications, but provides a powerful, attractive alternative to conventional chemistry. This chemistry has proven itself to be superior in satisfying many criteria (e. g., biocompatibility, selectivity, yield, stereospecificity, and so forth); thus, one can expect it will consequently become a more routine strategy in the near future for a wide range of applications.
C1 [Nwe, Kido; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room B3B69,10 Ctr Dr, Bethesda, MD 20892 USA.
EM martinwb@mail.nih.gov
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. The authors would also like to thank Kwamena Baidoo for
his assistance in the preparation and revision of the manuscript for
this article.
NR 87
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Z9 105
U1 4
U2 74
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1084-9785
J9 CANCER BIOTHER RADIO
JI Cancer Biother. Radiopharm.
PD JUN
PY 2009
VL 24
IS 3
BP 289
EP 302
DI 10.1089/cbr.2008.0626
PG 14
WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy;
Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy;
Radiology, Nuclear Medicine & Medical Imaging
GA 460RP
UT WOS:000267205100001
PM 19538051
ER
PT J
AU Zhang, ML
Yao, ZS
Garmestani, K
Yu, S
Goldman, CK
Paik, CH
Brechbiel, MW
Carrasquillo, JA
Waldmann, TA
AF Zhang, Meili
Yao, Zhengsheng
Garmestani, Kayhan
Yu, Sarah
Goldman, Carolyn K.
Paik, Chang H.
Brechbiel, Martin W.
Carrasquillo, Jorge A.
Waldmann, Thomas A.
TI Preclinical Evaluation of an Anti-CD25 Monoclonal Antibody, 7G7/B6,
Armed with the beta-Emitter, Yttrium-90, as a Radioimmunotherapeutic
Agent for Treating Lymphoma
SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
LA English
DT Article
DE radioimmunotherapy; monoclonal antibody; CD25; lymphoma; beta-emitter
ID T-CELL LEUKEMIA; MURINE MODEL; CHEMOTHERAPY PLUS; XENOGRAFTED MICE;
BREAST-CANCER; ALPHA-EMITTER; THERAPY; TAC; INTERLEUKIN-2-RECEPTOR;
IMMUNOTHERAPY
AB Objective: Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. We evaluated an anti-CD25 monoclonal Antibody, 7G7/B6, armed with (90)Y as a potential radioimmunotherapeutic agent for CD25-expressing lymphomas.
Materials and Methods: The lymphoma model was established by subcutaneous injection of 1 x 10(7) SUDHL-1 cells into nude mice. The biodistribution of (111)In-7G7/B6 and therapeutic studies with (90)Y-7G7/B6 were performed in the tumor-bearing mice.
Results: Therapy using (90)Y-7G7/B6 prolonged survival of the SUDHL-1 lymphoma-bearing mice significantly, as compared with either untreated mice or the mice treated with (90)Y-11F11, a radiolabeled isotype-matched control antibody (p < 0.001). All of the mice in the control and the (90)Y-11F11 treatment groups died by days 18 and 24, respectively. In contrast, 30% of the mice in the low-dose group (75 mu Ci of (90)Y-7G7/B6/mouse) and 75% in the high-dose group (150 mu Ci of (90)Y-7G7/B6/mouse) became tumor free and remained healthy for greater than 6 months.
Conclusions: Our findings suggested that (90)Y-7G7/B6 is a potentially useful radioimmunotherapeutic agent for the treatment of patients with CD25-expressing lymphomas.
C1 [Zhang, Meili; Yao, Zhengsheng; Garmestani, Kayhan; Goldman, Carolyn K.; Waldmann, Thomas A.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Brechbiel, Martin W.] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yao, Zhengsheng; Yu, Sarah; Paik, Chang H.; Carrasquillo, Jorge A.] NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA.
[Zhang, Meili] NCI Frederick, Lab Anim Sci Program, Frederick, MD USA.
[Garmestani, Kayhan] NCI Frederick, Appl Dev Res Support Program, SAIC Frederick Inc, Frederick, MD USA.
RP Waldmann, TA (reprint author), NCI, Metab Branch, NIH, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA.
EM tawald@helix.nih.gov
RI Carrasquillo, Jorge/E-7120-2010
FU National Cancer Institute; NIH [N01-CO-12400]
FX The authors thank Nhat Le for the labeling of 90Y-7G7/B6.
This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. This project
has been funded, in whole or in part, with federal funds from the
National Cancer Institute, NIH (under contract N01-CO-12400). The
content of this article 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 U. S. government.
NR 30
TC 3
Z9 3
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1084-9785
J9 CANCER BIOTHER RADIO
JI Cancer Biother. Radiopharm.
PD JUN
PY 2009
VL 24
IS 3
BP 303
EP 309
DI 10.1089/cbr.2008.0577
PG 7
WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy;
Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy;
Radiology, Nuclear Medicine & Medical Imaging
GA 460RP
UT WOS:000267205100002
PM 19538052
ER
PT J
AU Kolesar, J
Huang, W
Eickhoff, J
Hahn, K
Alberti, D
Attia, S
Schelman, W
Holen, K
Traynor, A
Ivy, P
Wilding, G
AF Kolesar, Jill
Huang, Wei
Eickhoff, Jens
Hahn, Kristine
Alberti, Dona
Attia, Steven
Schelman, William
Holen, Kyle
Traynor, Anne
Ivy, Percy
Wilding, George
TI Evaluation of mRNA by Q-RTPCR and protein expression by AQUA of the M2
subunit of ribonucleotide reductase (RRM2) in human tumors
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Triapine (R); 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone;
Ribonucleotide reductase; Automated quantitative immunohistochemistry
(AQUA); Quantitative real time PCR
ID PHASE-II; CELL-PROLIFERATION; R2 COMPONENT; IN-VITRO; CANCER;
OVEREXPRESSION; GEMCITABINE; TRANSFORMATION; RESISTANCE; INCREASES
AB The purpose of this study was to evaluate baseline RRM2 protein and gene expression in tumors of patients receiving 3-AP.
Tumor blocks from patients enrolled in phase I and II clinical studies using 3-AP, were evaluated for RRM2 gene and protein expression by quantitative real time polymerase chain reaction (Q-RTPCR) and automated quantitative analysis (AQUA).
Esophageal and gastric cancers overexpressed RRM2 protein when compared to prostate cancer (Z-score, 0.68 +/- A 0.94 SD, vs 0.41 +/- A 0.84 SD, respectively; p = 0.04). Esophageal and gastric cancers also overexpressed RRM2 mRNA when compared to prostate cancer (relative gene expression 2.56 +/- A 1.49 SD, vs 0.29 +/- A 0.20 SD, respectively; p = 0.02). Protein and gene expression were moderately associated (Spearman's rank correlation = 0.30; p = 0.12).
RRM2 gene and protein expression varies by tumor type.
C1 [Kolesar, Jill; Huang, Wei; Eickhoff, Jens; Hahn, Kristine; Alberti, Dona; Attia, Steven; Schelman, William; Holen, Kyle; Traynor, Anne; Wilding, George] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53792 USA.
[Kolesar, Jill] Univ Wisconsin, Sch Pharm, Madison, WI 53792 USA.
[Huang, Wei] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol, Madison, WI 53792 USA.
[Eickhoff, Jens] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat, Madison, WI 53792 USA.
[Hahn, Kristine; Alberti, Dona; Attia, Steven; Schelman, William; Holen, Kyle; Traynor, Anne; Wilding, George] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA.
[Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Kolesar, J (reprint author), Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, 600 Highland Ave,K4-554, Madison, WI 53792 USA.
EM jmkolesar@pharmacy.wisc.edu
FU Early Clinical Trials of Anti-Cancer Agents with Phase I Emphasis
[U01CA062491]; NCI; CTEP Translational Research Initiative Funding
[24XS090, 1ULRR025011]; National Center for Research Resources; NIH [T32
CA009614]; Physician Scientist Training in Cancer Medicine
FX Supported by: U01CA062491 "Early Clinical Trials of Anti-Cancer Agents
with Phase I Emphasis" NCI; CTEP Translational Research Initiative
Funding 24XS090, and 1ULRR025011. Clinical and Translational Science
Award of the National Center for Research Resources, NIH; and NIH grant
T32 CA009614. Physician Scientist Training in Cancer Medicine (Dr.
Attia).
NR 25
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Z9 14
U1 1
U2 4
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 JUN
PY 2009
VL 64
IS 1
BP 79
EP 86
DI 10.1007/s00280-008-0845-0
PG 8
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 440ER
UT WOS:000265683600009
PM 18941749
ER
PT J
AU Anderson, WF
AF Anderson, William F.
TI Cancer Surveillance Research
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Editorial Material
ID TEMPORAL VARIATION; COHORT MODELS; AGE PERIOD; RATES; EPIDEMIOLOGY;
TRENDS
C1 NCI, Biostat Branch, DHHS, NIH,DCEG,EPS, Bethesda, MD 20892 USA.
RP Anderson, WF (reprint author), NCI, Biostat Branch, DHHS, NIH,DCEG,EPS, Room 8036,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM wanderso@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010183-06]
NR 17
TC 5
Z9 5
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2009
VL 18
IS 6
BP 1669
EP 1671
DI 10.1158/1055-9965.EPI-09-0318
PG 3
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 455JD
UT WOS:000266754100001
PM 19505896
ER
PT J
AU Umar, A
Greenwald, P
AF Umar, Asad
Greenwald, Peter
TI Alarming Colorectal Cancer Incidence Trends: A Case for Early Detection
and Prevention
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Editorial Material
ID RANDOMIZED-TRIAL; ASPIRIN; ADENOMAS
C1 [Umar, Asad; Greenwald, Peter] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Umar, A (reprint author), NCI, EPN 2141, Rockville, MD 20852 USA.
EM umara@mail.nih.gov
NR 12
TC 16
Z9 16
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2009
VL 18
IS 6
BP 1672
EP 1673
DI 10.1158/1055-9965.EPI-09-0320
PG 2
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 455JD
UT WOS:000266754100002
PM 19505897
ER
PT J
AU Cronin, KA
Miglioretti, DL
Krapcho, M
Yu, BB
Geller, BM
Carney, PA
Onega, T
Feuer, EJ
Breen, N
Ballard-Barbash, R
AF Cronin, Kathleen A.
Miglioretti, Diana L.
Krapcho, Martin
Yu, Binbing
Geller, Berta M.
Carney, Patricia A.
Onega, Tracy
Feuer, Eric J.
Breen, Nancy
Ballard-Barbash, Rachel
TI Bias Associated With Self-Report of Prior Screening Mammography
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID MANAGED CARE POPULATION; PAP-SMEAR; CANCER; VALIDITY; WOMEN; ACCURACY;
VALIDATION; RECALL; BREAST
AB Background: Self-reported screening behaviors from national surveys often overestimate screening use, and the amount of overestimation may vary by demographic characteristics. We examine self-report bias in mammography screening rates overall, by age, and by race/ethnicity.
Methods: We use mammography registry data (19992000) from the Breast Cancer Surveillance Consortium to estimate the validity of self-reported mammography screening collected by two national surveys. First, we compare mammography use from 1999 to 2000 for a geographically defined population (Vermont) with self-reported rates in the prior two years from the 2000 Vermont Behavioral Risk Factor Surveillance System. We then use a screening dissemination simulation model to assess estimates of mammography screening from the 2000 National Health Interview Survey.
Results: Self-report estimates of mammography use in the prior 2 years from the Vermont Behavioral Risk Factor Surveillance System are 15 to 25 percentage points higher than actual screening rates across age groups. The differences in National Health Interview Survey screening estimates from models are similar for women 40 to 49 and 50 to 59 years and greater than for those 60 to 69, or 70 to 79 (27 and 26 percentage points versus 14, and 1.4, respectively). Overreporting is highest among African American women (24.4 percentage points) and lowest among Hispanic women (17.9) with non-Hispanic White women in between (19.3). Values of sensitivity and specificity consistent with our results are similar to previous validation studies of mammography.
Conclusion: Overestimation of self-reported mammography usage from national surveys varies by age and race/ethnicity. A more nuanced approach that accounts for demographic differences is needed when adjusting for overestimation or assessing disparities between populations. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1699-705)
C1 [Cronin, Kathleen A.; Feuer, Eric J.] NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Breen, Nancy; Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Miglioretti, Diana L.] Grp Hlth Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA USA.
[Miglioretti, Diana L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Krapcho, Martin; Yu, Binbing] Informat Management Serv Inc, Silver Spring, MD USA.
[Geller, Berta M.] Univ Vermont, Off Hlth Promot Res, Burlington, VT USA.
[Carney, Patricia A.] Oregon Hlth & Sci Univ, Dept Family Med & Publ Hlth & Prevent Med, Portland, OR 97201 USA.
[Onega, Tracy] Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH USA.
[Onega, Tracy] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA.
[Onega, Tracy] Norris Cotton Canc Ctr, Dartmouth Med Sch, Lebanon, NH USA.
RP Cronin, KA (reprint author), NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Suite 504,6116 Execut Blvd, Bethesda, MD 20892 USA.
EM cronink@mail.nih.gov
FU National Cancer Institute [U01CA63740, U01CA86076, U01CA86082,
U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040]
FX Data collection for this work was supported by a National Cancer
Institute-funded Breast Cancer Surveillance Consortium cooperative
agreement (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013,
U01CA69976, U01CA637,31, U01CA70040). The collection of cancer incidence
data used in this study was supported in part by several state public
health departments and cancer registries throughout the United States.
For a full description of these sources, please
see:http//breastscreeing.cancer.gov/work/,acknowledgement.html.
NR 23
TC 55
Z9 55
U1 4
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2009
VL 18
IS 6
BP 1699
EP 1705
DI 10.1158/1055-9965.EPI-09-0020
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 455JD
UT WOS:000266754100008
PM 19505902
ER
PT J
AU Lee, JE
Mannisto, S
Spiegelman, D
Hunter, DJ
Bernstein, L
van den Brandt, PA
Buring, JE
Cho, E
English, DR
Flood, A
Freudenheim, JL
Giles, GG
Giovannucci, E
Hakansson, N
Horn-Ross, PL
Jacobs, EJ
Leitzmann, MF
Marshall, JR
McCullough, ML
Miller, AB
Rohan, TE
Ross, JA
Schatzkin, A
Schouten, LJ
Virtamo, J
Wolk, A
Zhang, SM
Smith-Warner, SA
AF Lee, Jung Eun
Mannisto, Satu
Spiegelman, Donna
Hunter, David J.
Bernstein, Leslie
van den Brandt, Piet A.
Buring, Julie E.
Cho, Eunyoung
English, Dallas R.
Flood, Andrew
Freudenheim, Jo L.
Giles, Graham G.
Giovannucci, Edward
Hakansson, Niclas
Horn-Ross, Pamela L.
Jacobs, Eric J.
Leitzmann, Michael F.
Marshall, James R.
McCullough, Marjorie L.
Miller, Anthony B.
Rohan, Thomas E.
Ross, Julie A.
Schatzkin, Arthur
Schouten, Leo J.
Virtamo, Jarmo
Wolk, Alicja
Zhang, Shumin M.
Smith-Warner, Stephanie A.
TI Intakes of Fruit, Vegetables, and Carotenoids and Renal Cell Cancer
Risk: A Pooled Analysis of 13 Prospective Studies
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID FOOD-FREQUENCY QUESTIONNAIRE; COLORECTAL-CANCER; UNITED-STATES;
CALIFORNIA TEACHERS; DIETARY CAROTENOIDS; PROSPECTIVE COHORT; KIDNEY
CANCER; MALE SMOKERS; FOLLOW-UP; CARCINOMA
AB Fruit and vegetable consumption has been hypothesized to reduce the risk of renal cell cancer. We conducted a pooled analysis of 13 prospective studies, including 1,478 incident cases of renal cell cancer (709 women and 769 men) among 530,469 women and 244,483 men followed for up to 7 to 20 years. Participants completed a validated food-frequency questionnaire at baseline. Using the primary data from each study, the study-specific relative risks (RR) were calculated using the Cox proportional hazards model and then pooled using a random effects model. We found that fruit and vegetable consumption was associated with a reduced risk of renal cell cancer. Compared with <200 g/d of fruit and vegetable intake, the pooled multivariate RR for >= 600 g/d was 0.68 [95% confidence interval (95% CI) = 0.54-0.87; P for between-studies heterogeneity = 0.86; P for trend = 0.001]. Compared with <100 g/d, the pooled multivariate RRs (95% CI) for 400 g/d were 0.79 (0.63-0.99; P for trend = 0.03) for total fruit and 0.72 (0.48-1.08; P for trend = 0.07) for total vegetables. For specific carotenoids, the pooled multivariate RRs (95% CIs) comparing the highest and lowest quintiles were 0.87 (0.73-1.03) for alpha-carotene, 0.82 (0.69-0.98) for beta-carotene, 0.86 (0.73-1.01) for beta-cryptoxanthin, 0.82 (0.64-1.06) for lutein/zeaxanthin, and 1.13 (0.95-1.34) for lycopene. In conclusion, increasing fruit and vegetable consumption is associated with decreasing risk of renal cell cancer; carotenoids present in fruit and vegetables may partly contribute to this protection. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1730-9)
C1 [Lee, Jung Eun; Hunter, David J.; Cho, Eunyoung; Giovannucci, Edward] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Buring, Julie E.; Zhang, Shumin M.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Buring, Julie E.; Zhang, Shumin M.] Harvard Univ, Sch Med, Boston, MA USA.
[Spiegelman, Donna; Hunter, David J.; Buring, Julie E.; Giovannucci, Edward; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Hunter, David J.; Cho, Eunyoung; Giovannucci, Edward; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Mannisto, Satu; Virtamo, Jarmo] Natl Inst Hlth & Welf, Helsinki, Finland.
[Bernstein, Leslie] City Hope Natl Med Ctr, City Hope Comprehens Canc Ctr, Duarte, CA 91010 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[van den Brandt, Piet A.; Schouten, Leo J.] Univ Maastricht, GROW Sch Oncol & Dev Biol, Dept Epidemiol, Maastricht, Netherlands.
[English, Dallas R.; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Flood, Andrew] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Ross, Julie A.] Univ Minnesota, Dept Pediat, Div Epidemiol & Clin Res, Minneapolis, MN 55455 USA.
[Freudenheim, Jo L.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Marshall, James R.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Hakansson, Niclas; Wolk, Alicja] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
[Horn-Ross, Pamela L.] No Calif Canc Ctr, Fremont, CA USA.
[Jacobs, Eric J.; McCullough, Marjorie L.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Leitzmann, Michael F.] Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany.
[Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Hlth Serv, Bethesda, MD USA.
RP Lee, JE (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA.
EM jung.lee@channing.harvard.edu
RI Schouten, Leo/G-3713-2012; Hakansson, Niclas/L-7913-2013;
OI Hakansson, Niclas/0000-0001-7673-5554; Mannisto,
Satu/0000-0002-8668-3046; Lee, Jung Eun/0000-0003-1141-878X; Giles,
Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188
FU National Cancer Institute [CA55075]
FX The Pooling Project is supported by National Cancer Institute grant
CA55075. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National Cancer
Institute or the NIH.
NR 56
TC 48
Z9 48
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2009
VL 18
IS 6
BP 1730
EP 1739
DI 10.1158/1055-9965.EPI-09-0045
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 455JD
UT WOS:000266754100012
PM 19505906
ER
PT J
AU Zhu, KM
Devesa, SS
Wu, HY
Zahm, SH
Jatoi, I
Anderson, WE
Peoples, GE
Maxwell, LG
Granger, E
Potter, JE
McGlynn, KA
AF Zhu, Kangmin
Devesa, Susan S.
Wu, Hongyu
Zahm, Shelia Hoar
Jatoi, Ismail
Anderson, William E.
Peoples, George E.
Maxwell, Larry G.
Granger, Elder
Potter, John E.
McGlynn, Katherine A.
TI Cancer Incidence in the US Military Population: Comparison with Rates
from the SEER Program
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HEALTH INTERVIEW SURVEY; DEPARTMENT-OF-DEFENSE; GERM-CELL TUMORS;
UNITED-STATES; BREAST-CANCER; PROSTATE-CANCER; WHITE WOMEN; AIR-FORCE;
TRENDS; CARCINOMA
AB The U.S. active-duty military population may differ from the U.S. general population in its exposure to cancer risk factors and access to medical care. Yet, it is not known if cancer incidence rates differ between these two populations. We therefore compared the incidence of four cancers common in U.S. adults (lung, colorectal, prostate, and breast cancers) and two cancers more common in U.S. young adults (testicular and cervical cancers) in the military and general populations. Data from the Automated Central Tumor Registry (ACTUR) of the Department of Defense and the nine cancer registries of the Surveillance, Epidemiology and End Results (SEER) of the National Cancer Institute for the years 1990 to 2004 for persons with ages 20 to 59 years were analyzed. Incidence rates were significantly lower in the military population for colorectal cancer in White men, lung cancer in White and Black men and White women, and cervical cancer in Black women. In contrast, incidence rates of breast and prostate cancers were significantly higher in the military among Whites and Blacks. Incidence rates of testicular cancer did not differ between ACTUR and SEER. Although the numbers of diagnoses among military personnel were relatively small for temporal trend analysis, we found a more prominent increase in prostate cancer in ACTUR than in SEER. Overall, these results suggest that cancer patterns may differ between military and nonmilitary populations. Further studies are needed to confirm these findings and explore contributing factors. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1740-5)
C1 [Zhu, Kangmin] US Mil Canc Inst, Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Devesa, Susan S.; Zahm, Shelia Hoar; Anderson, William E.; McGlynn, Katherine A.] NIH, Div Canc Epidemiol & Genet, NCI, Bethesda, MD 20892 USA.
[Zhu, Kangmin; Jatoi, Ismail; Potter, John E.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Jatoi, Ismail] Natl Naval Med Ctr, Bethesda, MD USA.
[Peoples, George E.] Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA.
[Granger, Elder] Tricare Management Act, Falls Church, VA USA.
RP Zhu, KM (reprint author), US Mil Canc Inst, Walter Reed Army Med Ctr, Suite A-109,Bldg 1,6900 Georgia Ave NW, Washington, DC 20307 USA.
EM kangmin.zhu@amedd.army.mil
RI Zahm, Shelia/B-5025-2015
FU U.S. Military Cancer Institute the Uniformed Services; National
Institutes of Health (National Cancer Institute)
FX U.S. Military Cancer Institute the Uniformed Services University of the
Health Sciences tinder the auspices of the Henry M. Jackson Foundation
for the Advancement of Military Medicine and the Intramural Research
program of the National Institutes of Health (National Cancer
Institute).
NR 37
TC 27
Z9 28
U1 2
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2009
VL 18
IS 6
BP 1740
EP 1745
DI 10.1158/1055-9965.EPI-09-0041
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 455JD
UT WOS:000266754100013
PM 19505907
ER
PT J
AU Sun, P
Qiu, YL
Zhang, ZB
Wan, JX
Wang, T
Jin, XP
Lan, Q
Rothman, N
Xia, ZL
AF Sun, Pin
Qiu, Yulan
Zhang, Zhongbin
Wan, Junxiang
Wang, Tong
Jin, Xipeng
Lan, Qing
Rothman, Nathaniel
Xia, Zhao-lin
TI Association of Genetic Polymorphisms, mRNA Expression of p53 and p21
with Chronic Benzene Poisoning in a Chinese Occupational Population
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; FAMILIAL BREAST-CANCER; CODON 72 POLYMORPHISM;
WILD-TYPE P53; LUNG-CANCER; BONE-MARROW; LINKAGE DISEQUILIBRIUM; INDUCED
HEMATOTOXICITY; INHALED BENZENE; INCREASED RISK
AB DNA damage induced by benzene reactive metabolites is thought of as an important mechanism underlying benzene hematotoxicity and genotoxicity, and genetic variation in cell-cycle control genes may contribute to susceptibility to chronic benzene poisoning (CBP). Using a case-control study that included 307 benzene-poisoned patients and 299 workers occupationally exposed to benzene in south China, we aimed to investigate the association between genetic polymorphisms of p53 and p21 and the odds of CBP. To investigate whether benzene exposure may influence mRNA expression of p53 and p21 in benzene-exposed workers, we also chose 39 CBP workers, 38 occupationally benzene-exposure workers, and 37 nonexposure workers in the same region of China. PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53 (rs17878362, rs1042522, and rs1625895) and p21 (rs1801270 and rs1059234), and real-time PCR was applied to detect the quantity of gene mRNA expression. We found that p21 C98A variant genotypes (CA+AA) or C70T variant genotypes (CT+TT) were associated with decreased odds of CBP [odds ratio (OR), 0.51; 95% confidence interval (95% CI), 0.320.83, and OR, 0.53; 95% CI, 0.29-0.95, respectively. Further analysis showed the decreased odds of CBP in the subjects with p21 MAT diplotype (OR, 0.51; 95% CI, 0.30-0.85). In addition, p53 mRNA expression of CBP workers or benzene-exposure workers was significantly lower than that of nonexposure workers. Although these results require confirmation and extension, our results show that polymorphisms in p21 may be protective against the risk of CBP in the Chinese occupational population. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1821-8)
C1 [Sun, Pin; Qiu, Yulan; Zhang, Zhongbin; Wan, Junxiang; Jin, Xipeng; Xia, Zhao-lin] Fudan Univ, Sch Publ Hlth, Dept Occupat Hlth, Shanghai 200433, Peoples R China.
[Sun, Pin; Qiu, Yulan; Zhang, Zhongbin; Wan, Junxiang; Jin, Xipeng; Xia, Zhao-lin] Fudan Univ, Minist Educ, Key Lab Publ Hlth Safety, Shanghai, Peoples R China.
[Qiu, Yulan] Shanxi Med Univ, Sch Publ Hlth, Dept Hlth Toxicol, Taiyuan, Peoples R China.
[Wang, Tong] Shanxi Med Univ, Sch Publ Hlth, Dept Hlth Stat, Taiyuan, Peoples R China.
[Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Xia, ZL (reprint author), Fudan Univ, Sch Publ Hlth, Dept Occupat Hlth, Shanghai 200433, Peoples R China.
EM zlxia@shmu.edu.cn
FU National Natural Science Foundation of China [30271113]; China National
Key Basic Research and Development Program [2002CB512902]; Scientific
and Technical Supporting Programs of China [2006BAK05B01]; Shanghai
Bureau of Public Health [08GWD12, 08GWZX0402]
FX National Natural Science Foundation of China grant (grant number
30271113), China National Key Basic Research and Development Program
grant (grant number 2002CB512902), Scientific and Technical Supporting
Programs of China grant (grant number 2006BAK05B0l), and grants from
Shanghai Bureau of Public Health (grant number 08GWD12 and 08GWZX0402).
NR 49
TC 15
Z9 16
U1 1
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2009
VL 18
IS 6
BP 1821
EP 1828
DI 10.1158/1055-9965.EPI-09-0140
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 455JD
UT WOS:000266754100024
PM 19505915
ER
PT J
AU Bhatti, P
Stewart, PA
Hutchinson, A
Rothman, N
Linet, MS
Inskip, PD
Rajaraman, P
AF Bhatti, Parveen
Stewart, Patricia A.
Hutchinson, Amy
Rothman, Nathaniel
Linet, Martha S.
Inskip, Peter D.
Rajaraman, Preetha
TI Lead Exposure, Polymorphisms in Genes Related to Oxidative Stress, and
Risk of Adult Brain Tumors
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID NERVOUS-SYSTEM; OCCUPATIONAL EXPOSURES; CANCER-MORTALITY;
XANTHINE-OXIDASE; NORTHEAST CHINA; GLIOMAS; WORKERS; WOMEN; RAC2
AB There is some evidence that oxidative stress plays a role in lead-induced toxicity. Mechanisms for dealing with oxidative stress may be of particular relevance in the brain given the high rate of oxygen metabolism. Using a hospital-based case-control study, we investigated the role of oxidative stress in the potential carcinogenicity of lead through examination of effect modification of the association between occupational lead exposure and brain tumors by single nucleotide polymorphisms in genes with functions related to oxidative stress. The study included 362 patients with glioma (176 of which had glioblastoma multiforme), 134 patients with meningioma, and 494 controls. Lead exposure was estimated by expert review of detailed job history data for each participant. We evaluated effect modification with 142 single nucleotide polymorphisms using likelihood ratio tests that compared nested unconditional logistic regression models that did and did not include a cross-product term for cumulative lead exposure and genotype. When the analyses were restricted to cases with glioblastoma multiforme, RAC2 rs2239774 and two highly correlated GPX1 polymorphisms (rs1050450 and rs18006688) were found to significantly modify the association with lead exposure (P <= 0.05) after adjustment for multiple comparisons. Furthermore, the same GPX1 polymorphisms and XDH rs7574920 were found to significantly modify the association between cumulative lead exposure and meningioma. Although the results of this study provide some evidence that lead may cause glioblastoma multiforme and meningioma through mechanisms related to oxidative damage, the results must be confirmed in other populations. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1841-8)
C1 [Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA.
[Bhatti, Parveen; Rothman, Nathaniel; Linet, Martha S.; Inskip, Peter D.; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA.
[Hutchinson, Amy] NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet,Adv Technol Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
RP Bhatti, P (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, POB 19024,M4-B874, Seattle, WA 98109 USA.
EM pbhatti@fhcrc.org
FU Intramural NIH HHS [NIH0011946573, Z01 CP010135-12]; NCI NIH HHS
[N01CO12400, N01-CO-12400]
NR 28
TC 34
Z9 36
U1 2
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2009
VL 18
IS 6
BP 1841
EP 1848
DI 10.1158/1055-9965.EPI-09-0197
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 455JD
UT WOS:000266754100026
PM 19505917
ER
PT J
AU Holt, SK
Kwon, EM
Peters, U
Ostrander, EA
Stanford, JL
AF Holt, Sarah K.
Kwon, Erika M.
Peters, Ulrike
Ostrander, Elaine A.
Stanford, Janet L.
TI Vitamin D Pathway Gene Variants and Prostate Cancer Risk
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID D-RECEPTOR GENE; LINKAGE DISEQUILIBRIUM; POLYMORPHISMS; INHIBITION;
MORTALITY; GROWTH
AB Vitamin D has antiproliferative, antiangiogenic, and apoptotic properties. There is some evidence supporting an association between vitamin D-related gene variants and prostate cancer risk. We report results from this population-based case-control study of genes encoding for the vitamin D receptor (VDR), the vitamin D activating enzyme 1-alpha-hydroxylase (CYP27B1), and deactivating enzyme 24-hydroxylase (CYP24A1). Forty-eight tagging single nucleotide polymorphisms (tagSNP) were analyzed in 827 incident prostate cancer cases diagnosed from 2002 to 2005, and in 787 age-matched controls. Contrary to some earlier studies, we found no strong evidence of altered risk of developing prostate cancer overall or within clinical measures of tumor aggressiveness for any of the tagSNPs when they were assessed individually or in haplotypes. (Cancer Epidemiol Biomarkers Prev 2009;18 (6):1929-33)
C1 [Holt, Sarah K.; Peters, Ulrike; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Peters, Ulrike; Stanford, Janet L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
RP Holt, SK (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Mailstop M4-A402,POB 19024, Seattle, WA 98109 USA.
EM skholt@fhcrc.org
OI Ostrander, Elaine/0000-0001-6075-9738
FU Intramural NIH HHS; NCI NIH HHS [P50 CA097186, P50 CA097186-07,
P50-CA097186, R01 CA092579, R01 CA092579-05, R01-CA092579]
NR 14
TC 29
Z9 30
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2009
VL 18
IS 6
BP 1929
EP 1933
DI 10.1158/1055-9965.EPI-09-0113
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 455JD
UT WOS:000266754100039
PM 19454612
ER
PT J
AU Litzinger, MT
Foon, KA
Sabzevari, H
Tsang, KY
Schlom, J
Palena, C
AF Litzinger, Mary T.
Foon, Kenneth A.
Sabzevari, Helen
Tsang, Kwong-Yok
Schlom, Jeffrey
Palena, Claudia
TI Chronic lymphocytic leukemia (CLL) cells genetically modified to express
B7-1, ICAM-1, and LFA-3 confer APC capacity to T cells from CLL patients
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE CLL; T cells; Acquisition; Costimulation; Immunotherapy
ID ANTIGEN-PRESENTING CELLS; HIV-INFECTED INDIVIDUALS; COSTIMULATORY
MOLECULES; MHC/COSTIMULATORY COMPLEX; SURFACE MOLECULES; PRESENTASOME
APS; ACQUISITION; ACTIVATION; CD80; RECEPTOR
AB In chronic lymphocytic leukemia (CLL), malignant B cells and nonmalignant T cells exhibit dysfunction. We previously demonstrated that infection of CLL cells with modified vaccinia Ankara (MVA) expressing the costimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM) increased expression of these costimulatory molecules on the surface of CLL cells and thus augmented their antigen-presenting capability. Here, we evaluate the effect of MVA-TRICOM-modified CLL cells on T cells. Following incubation with irradiated MVA-TRICOM-modified CLL cells, allogeneic and autologous CD4(+) and CD8(+) T cells expressed significantly higher levels of B7-1, ICAM-1, and LFA-3. We show that this increase was the result of physical acquisition from the antigen-presenting cells (APCs), and that purified T cells that acquired costimulatory molecules from MVA-TRICOM-modified CLL cells were able to stimulate the proliferation of untreated T cells. These results demonstrate for the first time that T cells from CLL patients can acquire multiple costimulatory molecules from autologous CLL cells and can then act as APCs themselves. Given the immunodeficiencies characteristic of CLL, enhancing the antigen-presenting function of CLL cells and T cells simultaneously could be a distinct advantage in the effort to elicit antitumor immune responses.
C1 [Litzinger, Mary T.; Sabzevari, Helen; Tsang, Kwong-Yok; Schlom, Jeffrey; Palena, Claudia] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Foon, Kenneth A.] Univ Pittsburgh, Inst Canc, Div Hematol Oncol, Pittsburgh, PA USA.
RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA.
EM js141c@nih.gov
FU NIH Intramural Research Program, Center for Cancer Research, National
Cancer Institute
FX `We acknowledge the technical assistance of Margie Duberstein and the
editorial assistance of Bonnie L. Casey and Debra Weingarten in the
preparation of this manuscript. This research was supported by the NIH
Intramural Research Program, Center for Cancer Research, National Cancer
Institute.
NR 27
TC 7
Z9 7
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD JUN
PY 2009
VL 58
IS 6
BP 955
EP 965
DI 10.1007/s00262-008-0611-5
PG 11
WC Oncology; Immunology
SC Oncology; Immunology
GA 428FF
UT WOS:000264832700011
PM 19009294
ER
PT J
AU Fu, HJ
He, J
Mei, F
Zhang, Q
Hara, Y
Ryota, S
Lubet, RA
Chen, R
Chen, DR
You, M
AF Fu, Huijing
He, Jun
Mei, Fan
Zhang, Qi
Hara, Yukihiko
Ryota, Seto
Lubet, Ronald A.
Chen, Ruth
Chen, Da-Ren
You, Ming
TI Lung Cancer Inhibitory Effect of Epigallocatechin-3-Gallate Is Dependent
on Its Presence in a Complex Mixture (Polyphenon E)
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID A/J MICE; GREEN TEA; PULMONARY CARCINOGENESIS; AEROSOLIZED BUDESONIDE;
CHEMOPREVENTIVE AGENTS; TUMORIGENESIS; DELIVERY; PROGRESSION;
INHALATION; EFFICACY
AB Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. However, (-)-epigallocatechin-3-gallate (EGCG) alone was shown to be ineffective in preventing lung tumorigenesis in mice by aerosol administration. In this study, Polyphenon E and Polyphenon E without EGCG were administered by aerosol delivery to A/J mice 2 weeks after carcinogen treatment and continuing daily throughout the remainder of the study (20 weeks). An improved aerosol delivery system with a custom-built atomizer, an efficient solvent remove system, and a nose-only exposure chamber was used to provide aerosols with stable size distribution. There were no significant differences in the size distributions of Polyphenon E and Polyphenon E without EGCG. With a relatively low dose level (4.19 mg/kg), Polyphenon E decreased tumor multiplicity by 53%, whereas Polyphenon E without EGCG at the same dose failed to inhibit lung carcinogenesis. These results indicate that aerosol administration can be an effective approach in chemoprevention study, and aerosolized Polyphenon E can significantly inhibit pulmonary adenoma formation and growth in A/J mice. Furthermore, in aerosolized form, EGCG, which is thought to be the most active component of Polyphenon E, has to be present with other tea catechins to show chemopreventive activity on lung tumorigenesis.
C1 [He, Jun; Zhang, Qi; Ryota, Seto; You, Ming] Washington Univ, Dept Surg, Alvin J Siteman Canc Ctr, Sch Med, St Louis, MO 63110 USA.
[Fu, Huijing; Mei, Fan; Chen, Ruth; Chen, Da-Ren] Washington Univ, Dept Energy Environm & Chem Engn, St Louis, MO 63110 USA.
[Hara, Yukihiko; You, Ming] Mitsui Norin Co Ltd, Shizuoka, Japan.
[Lubet, Ronald A.] NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
RP You, M (reprint author), Washington Univ, Dept Surg, Alvin J Siteman Canc Ctr, Sch Med, 660 S Euclid Ave,Campus Box 8109,10130 Wohl Clin, St Louis, MO 63110 USA.
EM youm@wudosis.wustl.edu
RI Mei, Fan/H-2665-2012; Mei, Fan/D-9953-2013
NR 27
TC 24
Z9 25
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JUN
PY 2009
VL 2
IS 6
BP 531
EP 537
DI 10.1158/1940-6207.CAPR-08-0185
PG 7
WC Oncology
SC Oncology
GA 453RW
UT WOS:000266629700005
PM 19470785
ER
PT J
AU D'Agostini, F
Mastracci, L
Izzotti, A
Balansky, R
Pennisi, TM
Steele, VE
De Flora, S
AF D'Agostini, Francesco
Mastracci, Luca
Izzotti, Alberto
Balansky, Roumen
Pennisi, Tanya M.
Steele, Vernon E.
De Flora, Silvio
TI Modulation by Phenethyl Isothiocyanate and Budesonide of Molecular and
Histopathologic Alterations Induced by Environmental Cigarette Smoke in
Mice
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID INDUCED LUNG-TUMORS; CANCER CHEMOPREVENTIVE AGENTS; FEMALE A/J MICE;
TOBACCO-SMOKE; N-ACETYLCYSTEINE; RESPIRATORY-TRACT; PULMONARY
CARCINOGENESIS; CYTOGENETIC ALTERATIONS; AEROSOLIZED BUDESONIDE;
GENE-EXPRESSION
AB Our discovery that the perinatal period involves nucleotide modifications and gene overexpression in mouse lung prompted us to evaluate whether mice may become more susceptible to cigarette smoke when exposure starts immediately after birth. We previously showed that mainstream cigarette smoke is a quite potent carcinogen in neonatal mice. Further on, we showed that exposure of mice to environmental cigarette smoke (ECS), starting at birth, results in alterations of a variety of intermediate biomarkers. However, after 4 months of exposure to ECS followed by 7 months of recovery in filtered air, the lung tumor yield was rather low. In the present study, we evaluated the protective effects of the glucocorticoid budesonide and of the dietary agent phenethyl isothiocyanate in mice exposed to ECS for 9 months followed by 2 months of recovery. After weanling, the mice exposed to ECS since birth underwent a variety of alterations of molecular and cytogenetical end points, and 11 months after birth, they exhibited significant histopathologic changes, such as pulmonary anthracosis, emphysema, hemorrhagic areas, alveolar bronchiolarization, bronchial hyperplasia, and tumors, both benign and malignant. The carcinogenic response was less evident in dams exposed to ECS under identical conditions. Both phenethyl isothiocyanate and budesonide, administered daily with the diet after weanling, attenuated several alterations of ECS-related biomarkers and moderately protected the lungs from histopathologic alterations, including tumors. Thus, although not as efficiently as the bioassay in mainstream cigarette smoke-exposed mice, the model in neonatal mice is suitable to evaluate both ECS carcinogenicity and its modulation by chemopreventive agents.
C1 [D'Agostini, Francesco; Izzotti, Alberto; Balansky, Roumen; Pennisi, Tanya M.; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy.
[Mastracci, Luca] Univ Genoa, Dept Surg & Morphol Sci, I-16132 Genoa, Italy.
[Balansky, Roumen] Natl Oncol Ctr, BU-1157 Sofia, Bulgaria.
[Steele, Vernon E.] NCI, Rockville, MD USA.
RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy.
EM sdf@unige.it
OI izzotti, alberto/0000-0002-8588-0347; Mastracci,
Luca/0000-0003-0193-5281
FU National Cancer Institute [N01-CN53301]
FX Grant support: National Cancer Institute contract N01-CN53301.
NR 55
TC 13
Z9 14
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JUN
PY 2009
VL 2
IS 6
BP 546
EP 556
DI 10.1158/1940-6207.CAPR-08-0235
PG 11
WC Oncology
SC Oncology
GA 453RW
UT WOS:000266629700007
PM 19491290
ER
PT J
AU Zhao, C
Ivanov, I
Dougherty, ER
Hartman, TJ
Lanza, E
Bobe, G
Colburn, NH
Lupton, JR
Davidson, LA
Chapkin, RS
AF Zhao, Chen
Ivanov, Ivan
Dougherty, Edward R.
Hartman, Terryl J.
Lanza, Elaine
Bobe, Gerd
Colburn, Nancy H.
Lupton, Joanne R.
Davidson, Laurie A.
Chapkin, Robert S.
TI Noninvasive Detection of Candidate Molecular Biomarkers in Subjects with
a History of Insulin Resistance and Colorectal Adenomas
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID COLON-CANCER; MESSENGER-RNA; DIETARY FIBER; FECAL DNA; PUTATIVE
BIOMARKERS; GENE-EXPRESSION; OCCULT BLOOD; OB/OB MICE; STOOL; RISK
AB We have developed novel molecular methods using a stool sample, which contains intact sloughed colon cells, to quantify colonic gene expression profiles. In this study, our goal was to identify diagnostic gene sets (combinations) for the noninvasive classification of different phenotypes. For this purpose, the effects of a legume-enriched, low glycemic index, high fermentable fiber diet was evaluated in subjects with four possible combinations of risk factors, including insulin resistance and a history of adenomatous polyps. In a randomized crossover design controlled feeding study, each participant (a total of 23; 5-12 per group) consumed the experimental diet (1.5 cups of cooked dry beans) and a control diet (isocaloric average American diet) for 4 weeks with a 3-week washout period between diets. Using prior biological knowledge, the complexity of feature selection was reduced to perform an exhaustive search on all allowable feature (gene) sets of size 3, and among these, 27 had (unbiased) error estimates of 0.15 or less. Linear discriminant analysis was successfully used to identify the best single genes and two-to three-gene combinations for distinguishing subjects with insulin resistance, a history of polyps, or exposure to a chemoprotective legume-rich diet. These results support our premise that gene products (RNA) isolated from stool have diagnostic value in terms of assessing colon cancer risk.
C1 [Ivanov, Ivan; Lupton, Joanne R.; Davidson, Laurie A.; Chapkin, Robert S.] Texas A&M Univ, Ctr Environm & Rural Hlth, College Stn, TX 77843 USA.
[Zhao, Chen; Dougherty, Edward R.] Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA.
[Ivanov, Ivan] Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA.
[Lupton, Joanne R.; Davidson, Laurie A.; Chapkin, Robert S.] Texas A&M Univ, Intercoll Fac Nutr, College Stn, TX 77843 USA.
[Lupton, Joanne R.; Davidson, Laurie A.; Chapkin, Robert S.] Texas A&M Univ, Program Integrat Nutr & Complex Dis, College Stn, TX 77843 USA.
[Hartman, Terryl J.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Lanza, Elaine; Bobe, Gerd; Colburn, Nancy H.] NCI, Bethesda, MD 20892 USA.
RP Chapkin, RS (reprint author), Texas A&M Univ, Ctr Environm & Rural Hlth, 218 Kleberg Ctr,TAMU 2253, College Stn, TX 77843 USA.
EM r-chapkin@tamu.edu
OI Chapkin, Robert/0000-0002-6515-3898
FU National Cancer Institute and NIH [CA59034, CA129444, DK071707,
P30ES09106]
FX Grant support: National Cancer Institute and NIH grants CA59034,
CA129444, DK071707, and P30ES09106.
NR 49
TC 9
Z9 9
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JUN
PY 2009
VL 2
IS 6
BP 590
EP 597
DI 10.1158/1940-6207.CAPR-08-0233
PG 8
WC Oncology
SC Oncology
GA 453RW
UT WOS:000266629700012
PM 19470793
ER
PT J
AU Costantino, CL
Witkiewicz, AK
Kuwano, Y
Cozzitorto, JA
Kennedy, EP
Dasgupta, A
Keen, JC
Yeo, CJ
Gorospe, M
Brody, JR
AF Costantino, Christina L.
Witkiewicz, Agnieszka K.
Kuwano, Yuki
Cozzitorto, Joseph A.
Kennedy, Eugene P.
Dasgupta, Abhijit
Keen, Judith C.
Yeo, Charles J.
Gorospe, Myriam
Brody, Jonathan R.
TI The Role of HuR in Gemcitabine Efficacy in Pancreatic Cancer: HuR
Up-regulates the Expression of the Gemcitabine Metabolizing Enzyme
Deoxycytidine Kinase
SO CANCER RESEARCH
LA English
DT Article
ID INCREASED CYCLOOXYGENASE-2 EXPRESSION; BINDING PROTEIN HUR; CARCINOMA;
SURVIVAL
AB RNA-binding protein HuR binds U- or AU-rich sequences in the 3'-untranslated regions of target mRNAs, stabilizing them and/or modulating their translation. Given the links of HuR with cancer, we studied the consequences of modulating HuR levels in pancreatic cancer cells. HuR-overexpressing cancer cells, in some instances, are roughly up to 30-fold more sensitive to treatment with gemcitabine, the main chemotherapeutic component of treatment regimens for pancreatic ductal adenocarcinoma (PDA), compared with control cells. In pancreatic cancer cells, HuR associates with deoxycytidine kinase (dCK) mRNA, which encodes the enzyme that metabolizes and thereby activates gemcitabine. Gemcitabine exposure to pancreatic cancer cells enriches the association between HuR and dCK mRNA and increases cytoplasmic HuR levels. Accordingly, HuR overexpression elevates, whereas HuR silencing reduces, dCK protein expression in pancreatic cancer cells. In a clinical correlate study of gemcitabine treatment, we found a 7-fold increase in risk of mortality in PDA patients with low cytoplasmic HuR levels compared with patients with high HuR levels, after adjusting for other treatments and demographic variables. These data support the notion that HuR is a key mediator of gemcitabine efficacy in cancer cells, at least in part through its ability to regulate dCK levels posttranscriptionally. We propose that HuR levels in PDA modulate the therapeutic efficacy of gemcitabine, thus serving as a marker of the clinical utility of this common chemotherapeutic agent and a potential target for intervention in pancreatic cancer. [Cancer Res 2009;69(11):4567-72]
C1 [Costantino, Christina L.; Cozzitorto, Joseph A.; Kennedy, Eugene P.; Yeo, Charles J.; Brody, Jonathan R.] Thomas Jefferson Univ, Dept Surg, Jefferson Ctr Pancreat Biliary & Related Canc, Philadelphia, PA 19107 USA.
[Witkiewicz, Agnieszka K.] Thomas Jefferson Univ, Dept Pathol, Philadelphia, PA 19107 USA.
[Dasgupta, Abhijit] Thomas Jefferson Univ, Dept Pharmacol & Expt Therapeut, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
[Kuwano, Yuki; Gorospe, Myriam] NIA, LCMB, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Keen, Judith C.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA.
RP Brody, JR (reprint author), Thomas Jefferson Univ, Dept Surg, Jefferson Ctr Pancreat Biliary & Related Canc, 1015 Walnut St,Curtis 611A, Philadelphia, PA 19107 USA.
EM Jonathan.Brody@jefferson.edu
FU National Institute on Aging-Intramural Research Program, NIH
FX National Institute on Aging-Intramural Research Program, NIH (Y. Kuwano
and M. Gorospe).
NR 17
TC 81
Z9 85
U1 2
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2009
VL 69
IS 11
BP 4567
EP 4572
DI 10.1158/0008-5472.CAN-09-0371
PG 6
WC Oncology
SC Oncology
GA 455JL
UT WOS:000266755000004
PM 19487279
ER
PT J
AU Calvisi, DF
Donninger, H
Vos, MD
Birrer, MJ
Gordon, L
Leaner, V
Clark, GJ
AF Calvisi, Diego F.
Donninger, Howard
Vos, Michele D.
Birrer, Michael J.
Gordon, Laura
Leaner, Virna
Clark, Geoffrey J.
TI NORE1A Tumor Suppressor Candidate Modulates p21(CIP1) via p53
SO CANCER RESEARCH
LA English
DT Article
ID CELL-CYCLE; ELONGATION-FACTOR-2 KINASE; RAS EFFECTOR; CANCER-CELLS;
DNA-DAMAGE; P21; IDENTIFICATION; PATHWAY; PROTEIN; GENE
AB NORE1A (RASSF5) is a proapoptotic Ras effector that is frequently inactivated by promoter methylation in human tumors. It is structurally related to the RASSF1A tumor suppressor and is itself implicated as a tumor suppressor. In the presence of activated Ras, NORE1A is a potent inducer of apoptosis. However, when expressed at lower levels in the absence of activated Ras, NORE1A seems to promote cell cycle arrest rather than apoptosis. The mechanisms underlying NORE1A action are poorly understood. We have used microarray analysis of an inducible NORE1A system to screen for physiologic signaling targets of NORE1A action. Using this approach, we have identified several potential signaling pathways modulated by NORE1A. In particular, we identify the cyclin-dependent kinase inhibitor p21(CIP1) as a target for NORE1A activation and show that it is a vital component of NORE1A-mediated growth inhibition. In primary human hepatocellular carcinomas (HCC), loss of NORE1A expression is frequent and correlates tightly with loss of p21(CIP1) expression. NORE1A down-regulation in HCC also correlates with poor prognosis, enhanced proliferation, survival, and angiogenic tumor characteristics. Experimental inactivation of NORE1A results in the loss of p21(CIP1) expression and promotes proliferation. The best characterized activator of p21(CIP1) is the p53 master tumor suppressor. Further experiments showed that NORE1A activates p21(CIP1) via promoting p53 nuclear localization. Thus, we define the molecular basis of NORE1A-mediated growth inhibition and implicate NORE1A as a potential component of the ill-defined connection between Ras and p53. [Cancer Res 2009;69(11):4629-37]
C1 [Donninger, Howard; Gordon, Laura; Clark, Geoffrey J.] Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Grp, Louisville, KY 40202 USA.
[Calvisi, Diego F.] Ernst Moritz Arndt Univ Greifswald, Inst Pathol, Greifswald, Germany.
[Vos, Michele D.; Birrer, Michael J.] NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA.
[Leaner, Virna] Univ Cape Town, Inst Infect Dis & Mol Med, Div Med Biochem, ZA-7925 Cape Town, South Africa.
RP Clark, GJ (reprint author), Univ Louisville, James Graham Brown Canc Ctr, Mol Targets Grp, Room 119C,Baxter II Res Bldg,580 S Preston St, Louisville, KY 40202 USA.
EM gjclar01@louisville.edu
FU NIH [RR18733]; National Cancer Institute intramural funds
FX NIH grant RR18733 (G.J. Clark) and National Cancer Institute intramural
funds (G.J. Clark and M.J. Birrer).
NR 43
TC 29
Z9 33
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2009
VL 69
IS 11
BP 4629
EP 4637
DI 10.1158/0008-5472.CAN-08-3672
PG 9
WC Oncology
SC Oncology
GA 455JL
UT WOS:000266755000013
PM 19435914
ER
PT J
AU Schindler, EM
Hindes, A
Gribben, EL
Burns, CJ
Yin, Y
Lin, MH
Owen, RJ
Longmore, GD
Kissling, GE
Arthur, JSC
Efimova, T
AF Schindler, Eva M.
Hindes, Anna
Gribben, Erin L.
Burns, Carole J.
Yin, Yan
Lin, Meei-Hua
Owen, Robert J.
Longmore, Gregory D.
Kissling, Grace E.
Arthur, J. Simon C.
Efimova, Tatiana
TI p38 delta Mitogen-Activated Protein Kinase Is Essential for Skin Tumor
Development in Mice
SO CANCER RESEARCH
LA English
DT Article
ID SIGNAL-TRANSDUCTION PATHWAY; INVOLUCRIN PROMOTER ACTIVITY;
GENE-EXPRESSION; EPIDERMAL-KERATINOCYTES; EPITHELIAL CARCINOGENESIS;
CELL PROLIFERATION; CANCER-CELLS; MAP KINASE; MOUSE SKIN; P38
AB Activating Ras mutations occur in a large portion of human tumors. Yet, the signaling pathways involved in Ras-induced tumor formation remain incompletely understood. The mitogen-activated protein kinase pathways are among the best studied Ras effector pathways. The p38 mitogen-activated protein kinase isoforms are important regulators of key biological processes including cell proliferation, differentiation, survival, inflammation, senescence, and tumorigenesis. However, the specific in vivo contribution of individual p38 isoforms to skin tumor development has not been elucidated. Recent studies have shown that p38 delta, a p38 family member, functions as an important regulator of epidermal keratinocyte differentiation and survival. In the present study, we have assessed the effect of p38 delta deficiency on skin tumor development in vivo by subjecting p38 delta knockout mice to a two-stage 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate chemical skin carcinogenesis protocol. We report that mice lacking p38 delta gene exhibited a marked resistance to development of 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin papillomas, with increased latency and greatly reduced incidence, multiplicity, and size of tumors compared with wild-type mice. Our data suggest that the underlying mechanism for reduced susceptibility to skin carcinogenesis in p38 delta-null mice involves a defect in proliferative response associated with aberrant signaling through the two major transformation-promoting pathways: extracellular signal-regulated kinase 1/2-activator protein 1 and signal transducer and activator of transcription 3. These findings strongly suggest an in vivo role for p38 delta in promoting cell proliferation and tumor development in epidermis and may have therapeutic implication for skin cancer. [Cancer Res 2009;69(11):4648-55]
C1 [Efimova, Tatiana] Washington Univ, Sch Med, Dept Med, Div Dermatol, St Louis, MO 63110 USA.
[Lin, Meei-Hua] Washington Univ, Sch Med, Dept Med, Div Renal, St Louis, MO 63110 USA.
[Owen, Robert J.; Longmore, Gregory D.] Washington Univ, Sch Med, Dept Cell Biol, St Louis, MO 63110 USA.
[Kissling, Grace E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Arthur, J. Simon C.] Univ Dundee, Fac Life Sci, MRC Prot Phosphorylat Unit, Dundee, Scotland.
RP Efimova, T (reprint author), Washington Univ, Sch Med, Dept Med, Div Dermatol, Campus Box 8123,660 S Euclid Ave, St Louis, MO 63110 USA.
EM tefimova@im.wustl.edu
RI Arthur, J. Simon/B-8058-2010; Yin, Yan/D-3881-2012
OI Arthur, J. Simon/0000-0002-8135-1958;
FU Dermatology Foundation Research Career Development; American Cancer
Society Institutional Research; American Skin Association Research;
Division of Dermatology, Department of Internal Medicine, Washington
University School of Medicine
FX Dermatology Foundation Research Career Development Award and Research
Grant, American Cancer Society Institutional Research Grant, American
Skin Association Research Grant, and Division of Dermatology, Department
of Internal Medicine, Washington University School of Medicine (T.
Efimova).
NR 48
TC 38
Z9 38
U1 1
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2009
VL 69
IS 11
BP 4648
EP 4655
DI 10.1158/0008-5472.CAN-08-4455
PG 8
WC Oncology
SC Oncology
GA 455JL
UT WOS:000266755000015
PM 19458068
ER
PT J
AU Beroukhim, R
Brunet, JP
Di Napoli, A
Mertz, KD
Seeley, A
Pires, MM
Linhart, D
Worrell, RA
Moch, H
Rubin, MA
Sellers, WR
Meyerson, M
Linehan, WM
Kaelin, WG
Signoretti, S
AF Beroukhim, Rameen
Brunet, Jean-Philippe
Di Napoli, Arianna
Mertz, Kirsten D.
Seeley, Apryle
Pires, Maira M.
Linhart, David
Worrell, Robert A.
Moch, Holger
Rubin, Mark A.
Sellers, William R.
Meyerson, Matthew
Linehan, W. Marston
Kaelin, William G., Jr.
Signoretti, Sabina
TI Patterns of Gene Expression and Copy-Number Alterations in von-Hippel
Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the
Kidney
SO CANCER RESEARCH
LA English
DT Article
ID COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; TARGETED
THERAPY; GASTRIC-CANCER; VHL GENE; IDENTIFICATION; ABERRATIONS;
DISCOVERY; PROFILES; MUTATION
AB Recent insights into the role of the von-Hippel Lindau (M) tumor suppressor gene in hereditary and sporadic clear-cell renal cell carcinoma (ccRCC) have led to new treatments for patients with metastatic ccRCC, although virtually all patients eventually succumb to the disease. We performed an integrated, genome-wide analysis of copy-number changes and gene expression profiles in 90 tumors, including both sporadic and VHL disease-associated tumors, in hopes of identifying new therapeutic targets in ccRCC. We identified 14 regions of nonrandom copy-number change, including 7 regions of amplification (1q, 2q, 5q, 7q, 8q, 12p, and 20q) and 7 regions of deletion (1p, 3p, 4q, 6q, 8p, 9p, and 14q). An analysis aimed at identifying the relevant genes revealed VHL as one of three genes in the 3p deletion peak, CDKN2A and CDKN2B as the only genes in the 9p deletion peak, and MYC as the only gene in the 8q amplification peak. An integrated analysis to identify genes in amplification peaks that are consistently overexpressed among amplified samples confirmed MYC as a potential target of 8q amplification and identified candidate oncogenes in the other regions. A comparison of genomic profiles revealed that VHL disease-associated tumors are similar to a subgroup of sporadic tumors and thus more homogeneous overall. Sporadic tumors without evidence of biallelic VHL inactivation fell into two groups: one group with genomic profiles highly dissimilar to the majority of ccRCC and a second group with genomic profiles that are much more similar to tumors with biallelic inactivation of VHL. [Cancer Res 2009;69(11):4674-81]
C1 [Di Napoli, Arianna; Mertz, Kirsten D.; Seeley, Apryle; Pires, Maira M.; Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Beroukhim, Rameen; Sellers, William R.; Meyerson, Matthew; Kaelin, William G., Jr.; Signoretti, Sabina] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA.
[Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Sellers, William R.; Kaelin, William G., Jr.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Sellers, William R.] Novartis Inst BioMed Res, Cambridge, MA USA.
[Worrell, Robert A.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Moch, Holger] Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland.
[Rubin, Mark A.] Weill Cornell Med Ctr, Dept Pathol & Lab Med, New York, NY USA.
[Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Signoretti, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM rameen@broad.mit.edu; ssignoretti@partners.org
RI Meyerson, Matthew/E-7123-2012;
OI Rubin, Mark/0000-0002-8321-9950
FU NIH [U54CA112962]; Department of Defense [PC050266, PC040638, PC061642];
Istituto Dermopatico dell'Immacolata award; Swiss National Science
Foundation [3238B0-103145]; Sasella Stiftung; Achilie Lattuca
Foundation, Italy
FX NIH (Dana-Farber/Harvard Cancer Center Kidney Cancer SPORE and
U54CA112962), Department of Defense grant PC050266, and Istituto
Dermopatico dell'Immacolata award (S. Signoretti); NIH
(Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE and
K08CA122833) and Department of Defense grants PC040638 and PC061642 (R.
Beroukhim); Swiss National Science Foundation grant 3238B0-103145,
Sasella Stiftung. Switzerland, and Zurich Cancer League, Switzerland (H.
Moch); and Doris Duke Charitable Foundation. W.G. Kaelin, Jr., is
recipient of a Doris Duke Clinical Scientist Development Award. A. Di
Napoli is recipient of a fellowship award from the Achilie Lattuca
Foundation, Italy.
NR 34
TC 169
Z9 173
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2009
VL 69
IS 11
BP 4674
EP 4681
DI 10.1158/0008-5472.CAN-09-0146
PG 8
WC Oncology
SC Oncology
GA 455JL
UT WOS:000266755000018
PM 19470766
ER
PT J
AU Zhu, WG
DePamphilis, ML
AF Zhu, Wenge
DePamphilis, Melvin L.
TI Selective Killing of Cancer Cells by Suppression of Geminin Activity
SO CANCER RESEARCH
LA English
DT Article
ID ORIGIN DECISION POINT; XENOPUS EGG EXTRACTS; DNA-REPLICATION;
RE-REPLICATION; PREVENTS REREPLICATION; RESTRICTION POINT;
MAMMALIAN-CELLS; S-PHASE; CDT1; CHECKPOINT
AB Eukaryotic cells normally restrict genome duplication to once per cell division. In metazoa, re-replication of DNA during a single S phase seems to be prevented solely by suppressing CDT1 activity, a protein required for loading the replicative MCM DNA helicase. However, siRNA suppression of geminin (a specific inhibitor of CDT1) arrested proliferation only of cells derived from cancers by inducing DNA re-replication and DNA damage that spontaneously triggered apoptosis. None of these effects were detected either in cells derived from normal human tissues or in cells immortalized by a viral oncogene. To induce these effects in noncancer cells required suppression of both geminin and cyclin A, another cell cycle regulator. Therefore, initiating DNA replication in some cancer cells is limited solely by regulating the level of CDT1 activity with geminin, whereas noncancer cells contain additional safeguards that prevent DNA re-replication. These results show that inhibition of geminin activity could be used to selectively kill cancer cells without harming other cells. [Cancer Res 2009;69(11):4870-7]
C1 [Zhu, Wenge; DePamphilis, Melvin L.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP DePamphilis, ML (reprint author), NICHHD, NIH, Bldg 6-3A-02,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM depamphm@mail.nih.gov
FU National Institute of Child Health and Human Development
FX Grant support: Intramural program of the National Institute of Child
Health and Human Development.
NR 46
TC 58
Z9 60
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2009
VL 69
IS 11
BP 4870
EP 4877
DI 10.1158/0008-5472.CAN-08-4559
PG 8
WC Oncology
SC Oncology
GA 455JL
UT WOS:000266755000041
PM 19487297
ER
PT J
AU Pantanelli, SM
Li, ZQ
Fariss, R
Mahesh, SP
Liu, BY
Nussenblatt, RB
AF Pantanelli, Seth M.
Li, Zhuqing
Fariss, Robert
Mahesh, Sankaranarayana P.
Liu, Baoying
Nussenblatt, Robert B.
TI Differentiation of Malignant B-Lymphoma Cells from Normal and Activated
T-Cell Populations by Their Intrinsic Autofluorescence
SO CANCER RESEARCH
LA English
DT Article
ID PRIMARY INTRAOCULAR LYMPHOMA; NERVOUS-SYSTEM LYMPHOMA;
CLINICAL-FEATURES; DIAGNOSIS; FLUORESCENCE; INTERLEUKIN-10; VITRECTOMY;
EPITHELIUM; UVEITIS; BREAST
AB Patients with active posterior and intermediate uveitis have inflammatory cells in their vitreous; those with primary intraocular lymphoma have malignant B-lymphoma cells concomitantly. These cell types cannot be distinguished clinically. The goal of this study was to investigate intrinsic autofluorescence as a noninvasive way of differentiating immune and lymphomatous cell populations. Human primary T cells were stimulated with or without anti-CD3 plus anti-CD28 stimulation. B-lymphoma cells (CA46) were cultured separately. Five experimental groups were prepared: unstimulated T cells, stimulated T cells, CA46 cells, and stimulated T cells mixed with CA46 cells at a ratio of 1:3 or mixed at a ratio of 3:1. Samples were excited with three wavelengths and imaged with a confocal microscope. For each condition, the autofluorescent emissions from the sample were measured. In separate experiments, T cells or CA46 cells were injected into the anterior chamber of a BALB/c mouse eye and autofluorescence was measured. Pure T-cell and lymphoma populations were clearly distinguishable based on autofluorescence intensity spectra. CA46 cells were the least fluorescent when excited,with 351-nm light, but most fluorescent when excited with longer wavelengths like 488 mu. Mixed populations of T cells and CA46 cells had emission intensities that fell predictably in between those of the pure populations. An ex vivo study showed that CA46 cells could be detected based on their intrinsic autofluorescence. Our studies showed that normal activated and malignant lymphocyte populations can be distinguished based on their intrinsic autofluorescent properties. Future work with in vivo models may prove useful in facilitating the diagnosis of uveitis and other ocular diseases. [Cancer Res 2009;69(11):4911-7]
C1 [Pantanelli, Seth M.; Nussenblatt, Robert B.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
[Pantanelli, Seth M.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
RP Nussenblatt, RB (reprint author), NIH, Howard Hughes Med Inst, Res Scholars Program, Bldg 10,Room 10S219,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM DrBob@nei.nih.gov
OI Pantanelli, Seth/0000-0003-4992-9606
FU National Eye Institute; Howard Hughes Medical Institute
FX Grant support: The intramural research program at the National Eye
Institute and the Howard Hughes Medical Institute.
NR 31
TC 9
Z9 9
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2009
VL 69
IS 11
BP 4911
EP 4917
DI 10.1158/0008-5472.CAN-08-2761
PG 7
WC Oncology
SC Oncology
GA 455JL
UT WOS:000266755000046
PM 19458079
ER
PT J
AU Mendelsohn, JB
Li, QZ
Ji, BT
Shu, XO
Yang, G
Li, HL
Lee, KM
Yu, K
Rothman, N
Gao, YT
Zheng, W
Chow, WH
AF Mendelsohn, Julie Bloch
Li, Qi-Zhai
Ji, Bu-Tian
Shu, Xiao-Ou
Yang, Gong
Li, Hong-Lan
Lee, Kyoung-Mu
Yu, Kai
Rothman, Nathaniel
Gao, Yu-Tang
Zheng, Wei
Chow, Wong-Ho
TI Personal use of hair dye and cancer risk in a prospective cohort of
Chinese women
SO CANCER SCIENCE
LA English
DT Article
ID NON-HODGKIN-LYMPHOMA; BLADDER-CANCER; MULTIPLE-MYELOMA; COLORING
PRODUCTS; MYELODYSPLASTIC SYNDROMES; HEMATOPOIETIC NEOPLASMS;
UNITED-STATES; METAANALYSIS; LEUKEMIA; N-ACETYLTRANSFERASE-2
AB Although widely studied over the past 40 years, personal use of hair dye generally has not been associated with overall cancer risk. The association between hair dye use and risk of bladder and hematopoietic cancers has been less conclusive. Most hair dye studies have been case-control studies conducted in Caucasian populations. We examined the relationship between personal hair dye use and cancer risk in a prospective cohort of 70 366 Chinese women. After an average of 7 years of follow up, 2437 women were newly diagnosed with cancer by 31 December 2005. Cox proportional hazard models were used to estimate relative risks (RR) and 95% confidence intervals (CI) of cancer risk associated with hair dye use, adjusting for potential confounding factors. Compared with women who reported no hair dye use, ever users had an overall cancer risk of 0.89 (95% CI 0.82, 0.97). No significant association was observed for several common cancers, including cancers of the breast (RR 0.93, 95% CI 0.78, 1.09), lung (RR 0.81, 95% CI 0.62, 1.09), stomach (RR 0.90, 95% CI 0.66, 1.21), and colorectum (RR 1.04, 95% CI 0.84, 1.28). We also found no significant association with most other cancers, including bladder cancer (RR 1.14, 95% CI 0.56, 2.35) and hematopoietic cancers overall (RR 0.89, 95% CI 0.59, 1.35) or their subtypes, including non-Hodgkin lymphoma, multiple myeloma, and leukemia. We generally found no evidence of an association between personal use of hair dye and cancer risk, although our study is limited by small numbers for certain cancer types. (Cancer Sci 2009; 100: 1088-1091).
C1 [Mendelsohn, Julie Bloch; Li, Qi-Zhai; Ji, Bu-Tian; Lee, Kyoung-Mu; Yu, Kai; Rothman, Nathaniel; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Li, Qi-Zhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China.
[Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Dept Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Li, Hong-Lan; Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China.
RP Mendelsohn, JB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM mendelju@mail.nih.gov
FU National Institutes of Health (NIH) [R01 CA70867]; Intramural Research
Program of NIH
FX This work was supported by National Institutes of Health (NIH) research
grant R01 CA70867 and by the Intramural Research Program of NIH
(Division of Cancer Epidemiology and Genetics, National Cancer
Institute). The authors wish to thank Sheila H. Zahm for her helpful
advice on this manuscript. The authors express their appreciation to the
Shanghai residents who participated in the study and thank the research
staff of the Shanghai Women's Health Study for their dedication and
contributions to the study.
NR 37
TC 13
Z9 14
U1 0
U2 11
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1347-9032
J9 CANCER SCI
JI Cancer Sci.
PD JUN
PY 2009
VL 100
IS 6
BP 1088
EP 1091
DI 10.1111/j.1349-7006.2009.01149.x
PG 4
WC Oncology
SC Oncology
GA 444XU
UT WOS:000266015000016
PM 19385970
ER
PT J
AU Longmire, M
Kosaka, N
Ogawa, M
Choyke, PL
Kobayashi, H
AF Longmire, Michelle
Kosaka, Nobuyuki
Ogawa, Mikako
Choyke, Peter L.
Kobayashi, Hisataka
TI Multicolor in vivo targeted imaging to guide real-time surgery of
HER2-positive micrometastases in a two-tumor coincident model of ovarian
cancer
SO CANCER SCIENCE
LA English
DT Article
ID LABELED MONOCLONAL-ANTIBODIES; TUMORS; EXPRESSION; ANTIGEN; MICE
AB One of the primary goals of oncological molecular imaging is to accurately identify and characterize malignant tissues in vivo. Currently, molecular imaging relies on targeting a single molecule that while overexpressed in malignancy, is often also expressed at lower levels in normal tissue, resulting in reduced tumor to background ratios. One approach to increasing the specificity of molecular imaging in cancer is to use multiple probes each with distinct fluorescence to target several surface antigens simultaneously, in order to identify tissue expression profiles, rather than relying on the expression of a single target. This next step forward in molecular imaging will rely on characterization of tissue based on fluorescence and therefore will require the ability to simultaneously identify several optical probes each attached to different targeting ligands. We created a novel 'coincident' ovarian cancer mouse model by coinjecting each animal with two distinct cell lines, HER2(+)/red fluorescent protein (RFP)(-) SKOV3 and HER2(-)/RFP(+) SHIN3-RFP, in order to establish a model of disease in which animals simultaneously bore tumors with two distinct phenotypes (HER2(+)/RFP(-), HER2(-)/RFP(+)), which could be utilized for multicolor imaging. The HER2 receptor of the SKOV3 cell line was targeted with a trastuzumab-rhodamine green conjugate to create green tumor implants, whereas the RFP plasmid of the SHIN3 cells created red tumor implants. We demonstrate that real-time in vivo multicolor imaging is feasible and that fluorescence characteristics can then serve to guide the surgical removal of disease. (Cancer Sci 2009; 100: 1099-1104).
C1 [Longmire, Michelle; Kosaka, Nobuyuki; Ogawa, Mikako; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Longmire, Michelle] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 21
TC 34
Z9 34
U1 0
U2 10
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1347-9032
J9 CANCER SCI
JI Cancer Sci.
PD JUN
PY 2009
VL 100
IS 6
BP 1099
EP 1104
DI 10.1111/j.1349-7006.2009.01133.x
PG 6
WC Oncology
SC Oncology
GA 444XU
UT WOS:000266015000018
PM 19302283
ER
PT J
AU Balla, T
AF Balla, Tamas
TI Regulation of Ca2+ entry by inositol lipids in mammalian cells by
multiple mechanisms
SO CELL CALCIUM
LA English
DT Review
DE Calcium; Phosphoinositide; Ion channel; Phospholipase C
ID CAPACITATIVE CALCIUM-ENTRY; DOMAIN K+ CHANNELS; PLASMA-MEMBRANE;
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; PHOSPHOLIPASE-C;
ENDOPLASMIC-RETICULUM; ION CHANNELS; TRP CHANNELS; SUBCELLULAR
TRANSLOCATION; POTASSIUM CHANNELS
AB Increased phosphoinositide turnover was first identified as an early signal transduction event initiated by cell surface receptors that were linked to calcium signaling. Subsequently, the generation of inositol 1,4,5-trisphosphate by phosphoinositide-specific phospholipase C enzymes was defined as the major link between inositide turnover and the cytosolic Ca2+ rise in response to external stimulation. However, in the last decades, phosphoinositides have been emerging as major regulatory lipids involved in virtually every membrane-associated signaling process. Phosphoinositides regulate both the activity and the trafficking of almost all ion channels and transporters contributing to the maintenance of the ionic gradients that are essential for the proper functioning of all eukaryotic cells. Here we summarize the various means by which phosphoinositides affect ion channel functions with special emphasis on Ca2+ signaling and outline the principles that govern the highly compartmentalized roles of these regulatory lipids. Published by Elsevier Ltd.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Balla, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bldg 49,Rm 6A35,49 Convent Dr, Bethesda, MD 20892 USA.
EM ballat@mail.nih.gov
OI Balla, Tamas/0000-0002-9077-3335
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health; Human Development of the National Institutes
of Health
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the National Institutes of Health.
NR 112
TC 13
Z9 15
U1 0
U2 4
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0143-4160
J9 CELL CALCIUM
JI Cell Calcium
PD JUN
PY 2009
VL 45
IS 6
SI SI
BP 527
EP 534
DI 10.1016/j.ceca.2009.03.013
PG 8
WC Cell Biology
SC Cell Biology
GA 467HK
UT WOS:000267729100003
PM 19395084
ER
PT J
AU Gerlitz, G
Bustin, M
AF Gerlitz, Gabi
Bustin, Michael
TI Nucleosome binding proteins potentiate ATM activation and DNA damage
response by modifying chromatin
SO CELL CYCLE
LA English
DT Editorial Material
ID HISTONE H1; DYNAMICS; HMGN1
C1 [Gerlitz, Gabi; Bustin, Michael] NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Gerlitz, G (reprint author), NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA.
EM gerlitzg@mail.nih.gov
RI Bustin, Michael/G-6155-2015
FU Intramural NIH HHS [ZIA BC004496-33]
NR 12
TC 4
Z9 4
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUN 1
PY 2009
VL 8
IS 11
BP 1641
EP 1641
DI 10.4161/cc.8.11.8569
PG 1
WC Cell Biology
SC Cell Biology
GA 451GR
UT WOS:000266459200001
PM 19411861
ER
PT J
AU Iyer, LM
Tahiliani, M
Rao, A
Aravind, L
AF Iyer, Lakshminarayan M.
Tahiliani, Mamta
Rao, Anjana
Aravind, L.
TI Prediction of novel families of enzymes involved in oxidative and other
complex modifications of bases in nucleic acids
SO CELL CYCLE
LA English
DT Article
DE DNA methylation; dioxygenases; mom; transposons; bacteriophage; AlkB;
hydroxymethylcytosine; demethylation; algae; RNA modification; CXXC
domain
ID DNA ADENINE METHYLTRANSFERASE; CRYSTAL-STRUCTURE; COMPARATIVE GENOMICS;
DEAMINASE AID; PROTEIN; METHYLATION; EVOLUTION; GENE; CYTOSINE; RNA
AB Modified bases in nucleic acids present a layer of information that directs biological function over and beyond the coding capacity of the conventional bases. While a large number of modified bases have been identified, many of the enzymes generating them still remain to be discovered. Recently, members of the 2-oxoglutarate-and iron(II)-dependent dioxygenase superfamily, which modify diverse substrates from small molecules to biopolymers, were predicted and subsequently confirmed to catalyze oxidative modification of bases in nucleic acids. Of these, two distinct families, namely the AlkB and the kinetoplastid base J binding proteins (JBP) catalyze in situ hydroxylation of bases in nucleic acids. Using sensitive computational analysis of sequences, structures and contextual information from genomic structure and protein domain architectures, we report five distinct families of 2-oxoglutarate-and iron(II)-dependent dioxygenase that we predict to be involved in nucleic acid modifications. Among the DNA-modifying families, we show that the dioxygenase domains of the kinetoplastid base J-binding proteins belong to a larger family that includes the Tet proteins, prototyped by the human oncogene Tet1, and proteins from basidiomycete fungi, chlorophyte algae, heterolobosean amoeboflagellates and bacteriophages. We present evidence that some of these proteins are likely to be involved in oxidative modification of the 5-methyl group of cytosine leading to the formation of 5-hydroxymethyl-cytosine. The Tet/JBP homologs from basidiomycete fungi such as Laccaria and Coprinopsis show large lineage-specific expansions and a tight linkage with genes encoding a novel and distinct family of predicted transposases, and a member of the Maelstrom-like HMG family. We propose that these fungal members are part of a mobile transposon. To the best of our knowledge, this is the first report of a eukaryotic transposable element that encodes its own DNA-modification enzyme with a potential regulatory role. Through a wider analysis of other poorly characterized DNA-modifying enzymes we also show that the phage Mu Mom-like proteins, which catalyze the N6-carbamoylmethylation of adenines, are also linked to diverse families of bacterial transposases, suggesting that DNA modification by transposable elements might have a more general presence than previously appreciated. Among the other families of 2-oxoglutarate-and iron(II)-dependent dioxygenases identified in this study, one which is found in algae, is predicted to mainly comprise of RNA-modifying enzymes and shows a striking diversity in protein domain architectures suggesting the presence of RNA modifications with possibly unique adaptive roles. The results presented here are likely to provide the means for future investigation of unexpected epigenetic modifications, such as hydroxymethyl cytosine, that could profoundly impact our understanding of gene regulation and processes such as DNA demethylation.
C1 [Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Tahiliani, Mamta; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Tahiliani, Mamta; Rao, Anjana] Immune Dis Inst, Boston, MA USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg38A,Rm5n505, Bethesda, MD 20894 USA.
EM aravind@mail.nih.gov
FU National Library of Medicine; National Institutes of Health, USA;
Harvard Stem Cell Institute
FX L. A. and L. M. I. acknowledge the Intramural research program of the
National Library of Medicine, National Institutes of Health, USA for
funding their research. M. T. and A. R. are supported by a pilot grant
from the Harvard Stem Cell Institute.
NR 69
TC 173
Z9 177
U1 3
U2 25
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUN 1
PY 2009
VL 8
IS 11
BP 1698
EP 1710
DI 10.4161/cc.8.11.8580
PG 13
WC Cell Biology
SC Cell Biology
GA 451GR
UT WOS:000266459200017
PM 19411852
ER
PT J
AU Park, SY
Kim, S
Cho, H
Kwon, SH
Chae, S
Kang, D
Seong, YS
Cho, H
AF Park, Sun-Yi
Kim, Sujeong
Cho, Hyeseon
Kwon, Soon-Hwan
Chae, Sunyoung
Kang, Dongmin
Seong, Yeon-Sun
Cho, Hyeseong
TI Depletion of BubR1 promotes premature centrosomal localization of cyclin
B-1 and accelerates mitotic entry
SO CELL CYCLE
LA English
DT Article
DE BubR1; cyclin B-1; centrosomes; G(2)/M transition; CENP-F
ID CELL-CYCLE; CHECKPOINT; MITOSIS; PHOSPHORYLATION; KINASE; INSUFFICIENCY;
PROMETAPHASE; DEGRADATION; INHIBITION; ACTIVATION
AB The role of BubR1 has been established mainly in mitosis as an essential mitotic checkpoint protein although it is expressed throughout the cell cycle. To explore a possible role of BubR1 in regulating the G(2) phase of cell cycle, we have employed siRNA-mediated hBubR1 knockdown in HeLa cells. Here, we demonstrate that reducing BubR1 levels during the G(2) phase causes accelerated mitotic entry. As expected, BubR1 depletion leads to degradation of cyclin B-1 in the G(2) phase. Intriguingly, cyclin B-1 is prematurely targeted to centrosomes appearing at early G(2) phase in BubR1-depleted cells despite its low levels. This is in contrast to control cells where cyclin B-1 appears at the centrosomes in early prophase based on cell cycle-specific localization of CENP-F. Furthermore, cyclin B/Cdk1 kinase activity in early G(2) is aberrantly high in BubR1-depleted cells. Together, our results indicate that hBubR1 depletion triggers premature centrosomal localization of cyclin B-1 probably leading to premature mitotic entry. This study is the first to suggest a role of hBubR1 in controlling centrosome targeting of cyclin B-1 and timing of mitotic entry.
C1 [Park, Sun-Yi; Kim, Sujeong; Kwon, Soon-Hwan; Chae, Sunyoung; Cho, Hyeseong] Ajou Univ, Sch Med, Dept Biochem, Suwon 443721, South Korea.
[Park, Sun-Yi; Kim, Sujeong; Chae, Sunyoung; Cho, Hyeseong] Ajou Univ, Grad Sch, Dept Mol Sci & Technol, Suwon 443721, South Korea.
[Kwon, Soon-Hwan] NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Kang, Dongmin] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul, South Korea.
[Seong, Yeon-Sun] Dan Kook Univ, Coll Med, Dept Biochem, Chunan, South Korea.
RP Cho, H (reprint author), Ajou Univ, Sch Med, Dept Biochem, Suwon 443721, South Korea.
EM hscho@ajou.ac.kr
FU National R&D Program for Cancer Control; Ministry of Health and Welfare
[0820060]; Korea Science and Engineering Foundation through Chronic
Inflammatory Disease Research Center, Republic of Korea [R132003-019]
FX This study was supported by grants from the National R&D Program for
Cancer Control, Ministry of Health and Welfare (0820060) and from Korea
Science and Engineering Foundation through Chronic Inflammatory Disease
Research Center (R132003-019), Republic of Korea.
NR 31
TC 2
Z9 3
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUN 1
PY 2009
VL 8
IS 11
BP 1754
EP 1764
DI 10.4161/cc.8.11.8671
PG 11
WC Cell Biology
SC Cell Biology
GA 451GR
UT WOS:000266459200024
PM 19411850
ER
PT J
AU Sato, Y
Ding, A
Heimeier, RA
Yousef, AF
Mymryk, JS
Walfish, PG
Shi, YB
AF Sato, Yukiyasu
Ding, Andrew
Heimeier, Rachel A.
Yousef, Ahmed F.
Mymryk, Joe S.
Walfish, Paul G.
Shi, Yun-Bo
TI The adenoviral E1A protein displaces corepressors and relieves gene
repression by unliganded thyroid hormone receptors in vivo
SO CELL RESEARCH
LA English
DT Article
DE adenoviral E1A; thyroid hormone receptor; corepressor; coactivator;
chromatin
ID NUCLEAR RECEPTOR; N-COR; XENOPUS-LAEVIS; HISTONE ACETYLTRANSFERASE;
AMPHIBIAN METAMORPHOSIS; COMPLEX; COACTIVATOR; RECRUITMENT;
DIFFERENTIATION; TRANSCRIPTION
AB The human adenovirus type 5 early region 1A (E1A) is one of two oncogenes present in the adenovirus genome and functions by interfering with the activities of cellular regulatory proteins. The E1A gene is alternatively spliced to yield five products. Earlier studies have revealed that E1A can regulate the function of thyroid hormone (T3) receptors (TRs). However, analysis in yeast compared with transfection studies in mammalian cell cultures yields surprisingly different effects. Here, we have examined the effect of E1A on TR function by using the frog oocyte in vivo system, where the effects of E1A can be studied in the context of chromatin. We demonstrate that different isoforms of E1A have distinct effects on TR function. The two longest forms inhibit both the repression by unliganded TR and activation by T3-bound TR. We further show that E1A binds to unliganded TR to displace the endogenous corepressor nuclear receptor corepressor, thus relieving the repression by unliganded TR. On the other hand, in the presence of T3, E1A inhibits gene activation by T3-bound TR indirectly, through a mechanism that requires its binding domain for the general coactivator p300. Taken together, our results thus indicate that E1A affects TR function through distinct mechanisms that are dependent upon the presence or absence of T3.
C1 [Sato, Yukiyasu; Ding, Andrew; Heimeier, Rachel A.; Shi, Yun-Bo] NICHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, PCRM,NIH, Bethesda, MD 20892 USA.
[Walfish, Paul G.] Mt Sinai Hosp, Dept Med, Div Endocrine, Toronto, ON M5G 1X5, Canada.
[Yousef, Ahmed F.; Mymryk, Joe S.] Univ Western Ontario, Dept Oncol, London, ON N6A 4L6, Canada.
[Yousef, Ahmed F.; Mymryk, Joe S.] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 4L6, Canada.
[Sato, Yukiyasu] Kyoto Univ, Grad Sch Med, Dept Gynecol & Obstet, Obstet Div,Sakyo Ku, Kyoto 6068507, Japan.
RP Shi, YB (reprint author), NICHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, PCRM,NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA.
EM walfish@mshri.on.ca; Shi@helix.nih.gov
FU NICHD; NIH, USA; Joseph and Mildred Sonshine Family Centre; Julius Kuhl
Family Foundation, USA
FX This research was supported in part by the Intramural Research Program
of NICHD, NIH, USA, unrestricted educational grants from the Joseph and
Mildred Sonshine Family Centre for Head and Neck Diseases at Mount Sinai
Hospital, and the Julius Kuhl Family Foundation, USA.
NR 63
TC 8
Z9 8
U1 1
U2 1
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 JUN
PY 2009
VL 19
IS 6
BP 783
EP 792
DI 10.1038/cr.2009.55
PG 10
WC Cell Biology
SC Cell Biology
GA 452GJ
UT WOS:000266528000011
PM 19434099
ER
PT J
AU de Vega, S
Iwamoto, T
Yamada, Y
AF de Vega, S.
Iwamoto, T.
Yamada, Y.
TI Fibulins: Multiple roles in matrix structures and tissue functions
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Fibulins; protein interactions; extracellular matrix network; embryonic
development; elastogenesis; angiogenesis; genetic disorders
ID GROWTH-FACTOR-BETA; CONTROLS CELL-MIGRATION; ELASTIC FIBER FORMATION;
RECESSIVE CUTIS LAXA; EXTRACELLULAR-MATRIX; MACULAR DEGENERATION;
BREAST-CANCER; C-ELEGANS; IN-VIVO; CAENORHABDITIS-ELEGANS
AB The fibulins are a family of secreted glycoproteins associated with basement membranes, elastic fibers, and other matrices. They are expressed in a variety of tissues. Association with these matrix structures is mediated by their ability to interact with many extracellular matrix constituents. The seven members of the family are defined by the presence of two structural modules, a tandem repeat of epidermal growth factor-like modules and a unique C-terminal fibulin-type module. They act not only as intermolecular bridges within the extracellular matrix to form supramolecular structures, but also as mediators for cellular processes and tissue remodeling. These important functions of fibulins in a wide range of biological processes have been shown in in vitro systems, gene knockout mice, and human genetic disorders. In this review, we describe the structure and function of these proteins and discuss the implication of fibulins in development and diseases.
C1 [de Vega, S.; Iwamoto, T.; Yamada, Y.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, DHHS, Bethesda, MD 20892 USA.
[Iwamoto, T.] Kyushu Univ, Sch Dent, Dept Pediat Dent, Fukuoka 8128582, Japan.
RP Yamada, Y (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, DHHS, Bldg 30,Rm 407,30 Convent Dr MSC 4370, Bethesda, MD 20892 USA.
EM yoshi.yamada@nih.gov
RI Perez , Claudio Alejandro/F-8310-2010
OI Perez , Claudio Alejandro/0000-0001-9688-184X
FU Intramural Research Program of the National Institutes of Health;
National Institute of Dental and Craniofacial Research, USA
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Dental and
Craniofacial Research, USA.
NR 104
TC 106
Z9 108
U1 0
U2 13
PU BIRKHAUSER VERLAG AG
PI BASEL
PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD JUN
PY 2009
VL 66
IS 11-12
BP 1890
EP 1902
DI 10.1007/s00018-009-8632-6
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 470TT
UT WOS:000268004300010
PM 19189051
ER
PT J
AU Garraffo, HM
AF Garraffo, H. Martin
TI John William Daly, 1933-2008
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Biographical-Item
C1 NIDDK, NIH, Bethesda, MD 20892 USA.
RP Garraffo, HM (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM garraffo@helix.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD JUN
PY 2009
VL 29
IS 4
BP 439
EP 440
DI 10.1007/s10571-008-9280-3
PG 2
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 457IH
UT WOS:000266921200001
PM 18404366
ER
PT J
AU Saavedra, JM
AF Saavedra, Juan M.
TI In Memoriam John William Daly (1933-2008)
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Biographical-Item
C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA.
RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Bethesda, MD 20892 USA.
EM saavedrj@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD JUN
PY 2009
VL 29
IS 4
BP 441
EP 442
DI 10.1007/s10571-008-9334-6
PG 2
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 457IH
UT WOS:000266921200002
PM 19109768
ER
PT J
AU Liu, TT
Shi, J
Epstein, DH
Bao, YP
Lu, L
AF Liu, Ting-ting
Shi, Jie
Epstein, David H.
Bao, Yan-ping
Lu, Lin
TI A Meta-Analysis of Acupuncture Combined with Opioid Receptor Agonists
for Treatment of Opiate-Withdrawal Symptoms
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Acupuncture; Opioid; Detoxification; Meta-analysis
ID RANDOMIZED CONTROLLED-TRIAL; ADDICTION; MORPHINE; RATS;
ELECTROACUPUNCTURE; TOLERANCE; NUCLEUS; HEROIN
AB This review extends a prior meta-analysis of acupuncture's utility for treating opioid detoxification, addressing the efficacy of acupuncture when combined with allopathic therapies. Both English and Chinese databases were searched for randomized trials comparing acupuncture combined with opioid agonist treatment versus opioid agonists alone for treating symptoms of opioid withdrawal. The methodological quality of each study was assessed with Jadad's scale (1-2 = low; 3-5 = high). Meta-analysis was performed with fixed- or random-effect models in RevMan software; the outcome measures assessed were withdrawal-symptoms score, relapse rate, side effects, and medication dosage. Withdrawal-symptom scores were lower in combined treatment trials than in agonist-alone trials on withdrawal days 1, 7, 9, and 10. Combined treatment also produced lower reported rates of side effects and appeared to lower the required dose of opioid agonist. There was no significant difference on relapse rate after 6 months. This meta-analysis suggests that acupuncture combined with opioid agonists can effectively be used to manage the withdrawal symptoms. One limitation of this meta-analysis is the poor quality of the methodology of some included trials. High-quality studies are needed to confirm findings regarding the side effects and medication dosage.
C1 [Liu, Ting-ting; Shi, Jie; Bao, Yan-ping; Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China.
[Epstein, David H.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Shi, J (reprint author), Peking Univ, Natl Inst Drug Dependence, 38 Xue Yuan Rd, Beijing 100083, Peoples R China.
EM shijie@bjmu.edu.cn; linlu@bjmu.edu.cn
FU National Basic Research Program of China [2003CB515400]; National High
Technology Research and Development Program of China [2006AA02Z4D1];
China-Canada Joint Health Research Program [30611120528]
FX This work was supported in part by the National Basic Research Program
of China (973 Program, 2003CB515400), the National High Technology
Research and Development Program of China (863 Program, 2006AA02Z4D1),
and the China-Canada Joint Health Research Program (No: 30611120528).
NR 35
TC 12
Z9 14
U1 0
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD JUN
PY 2009
VL 29
IS 4
BP 449
EP 454
DI 10.1007/s10571-008-9336-4
PG 6
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 457IH
UT WOS:000266921200004
PM 19109766
ER
PT J
AU Li, SJ
Yen, TY
Endo, Y
Klauzinska, M
Baljinnyam, B
Macher, B
Callahan, R
Rubin, JS
AF Li, Sheng-Jian
Yen, Ten-Yang
Endo, Yoshimi
Klauzinska, Malgorzata
Baljinnyam, Bolormaa
Macher, Bruce
Callahan, Robert
Rubin, Jeffrey S.
TI Loss-of-function point mutations and two-furin domain derivatives
provide insights about R-spondin2 structure and function
SO CELLULAR SIGNALLING
LA English
DT Article
DE R-spondin2; Wnt signaling; beta-catenin; LRP6; Furin domain; Disulfide
mapping
ID AUTOSOMAL-RECESSIVE ANONYCHIA; APICAL ECTODERMAL RIDGE; WNT CORECEPTOR
LRP6; R-SPONDIN; INHERITED ANONYCHIA; SEX DETERMINATION; FURIN-LIKE;
GENE; MECHANISM; EXPRESSION
AB R-spondins (Rspos) potentiate Wnt/beta-catenin signaling, an important pathway in embryonic development that is constitutively active in many cancers. To analyze Rspo structure and function, we expressed full-length wild-type Rspo2 and Rspo2 point mutants corresponding to Rspo4 variants that have been linked to developmental defects. The Rspo2 mutants had markedly reduced potency relative to the wild-type protein, demonstrating for the first time specific amino acid residues in Rspos that are critical for beta-catenin signaling. The diminished activity of Rspo2/C78 gamma and Rspo2/C113R was attributable to a defect in their secretion, while Rspo2/Q70R exhibited a decrease in its intrinsic activity. Cysteine assignments in a Rspo2 derivative containing only the two furin-like domains (Rspo2-2F) provided the first information about the disulfide-bonding pattern of this motif, which was characterized by multiple short loops and unpaired cysteine residues, and established that the loss-of-function cysteine mutants disrupted disulfide bond formation. Moreover, Rspo2-2F demonstrated potent activity and synergized strongly with Wnt-3a in a beta-catenin reporter assay. In contrast, an Rspo2-2F derivative containing the Q70R substitution showed significantly reduced activity, although it still synergized with Wnt-3a in the reporter assay. Rspo2-2F derivatives elicited an unusually sustained phosphorylation (20 h) of the Wnt co-receptor. low density lipoprotein receptor-related protein 6 (LRP6), as well as an increase in cell surface LRP6. Co-immunoprecipitation experiments involving LRP6 and Kremens suggested that these associations contribute to Rspo2 activity, although the lack of major differences between wild-type and Q70R derivatives implied that additional interactions may be important. Published by Elsevier Inc.
C1 [Li, Sheng-Jian; Endo, Yoshimi; Baljinnyam, Bolormaa; Rubin, Jeffrey S.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
[Yen, Ten-Yang; Macher, Bruce] San Francisco State Univ, Dept Chem & Biochem, San Francisco, CA 94132 USA.
[Klauzinska, Malgorzata; Callahan, Robert] NCI, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA.
RP Rubin, JS (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37,Room 2042,37 Convent Dr,MSC 4256, Bethesda, MD 20892 USA.
EM rubinj@mail.nih.gov
RI li, shengjian/B-4866-2013
FU National Institutes of Health [P20 MD000262]; National Cancer Institute;
National Science Foundation [CHEM-0619163]
FX The authors thank Drs. Xi He and Christof Niehrs for providing plasmid
constructs, Dr. Jeremy Nathans for providing STF cells, Dr. Eric
Anderson for preliminary analysis of the disulfide bonding pattern of
Rspo2-2F, and the NCI-Frederick Protein Chemistry Lab for performing the
Edman degradation amino-terminal sequence analysis of Rspo2-2F. This
research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute. MS analysis
was supported by grants from the National Institutes of Health, Grant
P20 MD000262 and the National Science Foundation, Grant CHEM-0619163.
NR 44
TC 15
Z9 16
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD JUN
PY 2009
VL 21
IS 6
BP 916
EP 925
DI 10.1016/j.cellsig.2009.02.001
PG 10
WC Cell Biology
SC Cell Biology
GA 437FK
UT WOS:000265471900011
PM 19385064
ER
PT J
AU Bohlhalter, S
Hattori, N
Wheaton, L
Fridman, E
Shamim, EA
Garraux, G
Hallett, M
AF Bohlhalter, S.
Hattori, N.
Wheaton, L.
Fridman, E.
Shamim, E. A.
Garraux, G.
Hallett, M.
TI Gesture Subtype-Dependent Left Lateralization of Praxis Planning: An
Event-Related fMRI Study
SO CEREBRAL CORTEX
LA English
DT Article
DE intransitive; left lateralization; praxis planning; transitive
ID HAND-OBJECT INTERACTIONS; IDEOMOTOR APRAXIA; TOOL-USE; NEURAL
REPRESENTATIONS; HEMISPHERE DAMAGE; PREMOTOR AREAS; LIMB APRAXIA; BODY
PART; STROKE; PANTOMIME
AB Ideomotor apraxia is a disorder mainly of praxis planning, and the deficit is typically more evident in pantomiming transitive (tool related) than intransitive (communicative) gestures. The goal of the present study was to assess differential hemispheric lateralization of praxis production using event-related functional magnetic resonance imaging. Voxel-based analysis demonstrated significant activations in posterior parietal cortex (PPC) and premotor cortex (PMC) association areas, which were predominantly left hemispheric, regardless of whether planning occurred for right or left hand transitive or intransitive pantomimes. Furthermore, region of interest-based calculation of mean laterality index (LI) revealed a significantly stronger left lateralization in PPC/PMC clusters for planning intransitive (LI = -0.49 + 0.10, mean + standard deviation [SD]) than transitive gestures (-0.37 + 0.08, P = 0.02, paired t-tests) irrespective of the hand involved. This differential left lateralization for planning remained significant in PMC (LI = -0.47 + 0.14 and -0.36 + 0.13, mean + SD, P = 0.04), but not in PPC (-0.56 + 0.11 and -0.45 + 0.12, P = 0.11), when both regions were analyzed separately. In conclusion, the findings point to a left-hemispheric specialization for praxis planning, being more pronounced for intransitive gestures in PMC, possibly due to their communicative nature.
C1 [Bohlhalter, S.; Hattori, N.; Wheaton, L.; Fridman, E.; Shamim, E. A.; Garraux, G.; Hallett, M.] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1430, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
RI Wheaton, Lewis /B-4482-2009; Garraux, Gaetan/G-9050-2011;
OI Wheaton, Lewis /0000-0003-0771-0294; Fridman,
Esteban/0000-0001-7879-8874
FU National Institute of Neurological Disorders and Stroke; National
Institutes of Health
FX Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, National Institutes of Health.
NR 44
TC 40
Z9 40
U1 2
U2 5
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 JUN
PY 2009
VL 19
IS 6
BP 1256
EP 1262
DI 10.1093/cercor/bhn168
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 444AC
UT WOS:000265951000002
PM 18796430
ER
PT J
AU Pachiappan, A
Thwin, MM
Keong, LW
Lee, FK
Manikandan, J
Sivakumar, V
Gopalakrishnakone, P
AF Pachiappan, Arjunan
Thwin, Maung Maung
Keong, Loke Weng
Lee, Fook Kay
Manikandan, Jayapal
Sivakumar, Viswanathan
Gopalakrishnakone, Ponnampalam
TI ETS2 Regulating Neurodegenerative Signaling Pathway of Human Neuronal
(SH-SY5Y) Cells Exposed to Single and Repeated Low-Dose Sarin (GB)
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID RAT-BRAIN; GENE; EXPRESSION; NEUROPATHOLOGY; MECHANISMS; MICROARRAY
AB The mechanistic understanding of low-level sarin-induced neurotoxicity after single or repeated doses has yet to be explored at a cellular level. Using the microarray (Affymetrix-GeneChips) transcription profiling approach, the present study examined gene expression in human SH-SY5Y cells exposed to,single Q and 24 h) or repeated (2 x 24 h) doses of sarin (5 mu g/mL) to delineate the possible mechanism. Two hundred twenty-four genes whose expression was significantly (P < 0.01) altered by at least 3-fold were selected by GeneSpringGX analysis. The comparative gene expression data confirmed the transcriptional changes to be related to close and exposure time of sarin. The effect of a single noncytotoxic sarin dose on gene transcription was variable, whereas repeated doses over 48 h persistently down-regulated genes linked to neurodegenerative mechanisms. Thirty persistently altered genes were validated using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Similar qRT-PCR profiles obtained in sarin-treated SH-SY5Y and HCN-1A cells confirmed the cell-independent alterations in expression levels. Genes (ETS2, APOE, PSEN1, DDC, and CD9) implicated mainly in the regulation of sarin-induced neuropathogenesis were further confirmed by Western blot and double-immunofluorescence assays. The regulome pathway suggests a new feasible mechanism by which sarin increases ETS2 expression and takes control over other genes involved in the neurodegenerative pathway. The overall data delineate an in vitro experimental model suitable for studying the neuropathology of cells and may provide novel insights into therapeutic interventions.
C1 [Pachiappan, Arjunan; Thwin, Maung Maung; Sivakumar, Viswanathan; Gopalakrishnakone, Ponnampalam] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, Singapore 117597, Singapore.
[Manikandan, Jayapal] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117597, Singapore.
[Keong, Loke Weng; Lee, Fook Kay] DSO Natl Labs, Singapore 118230, Singapore.
[Pachiappan, Arjunan] NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
RP Gopalakrishnakone, P (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, Singapore 117597, Singapore.
EM antgopal@nus.edu.sg
RI Jayapal, Manikandan/H-9847-2012
FU National University of Singapore; DSO National Laboratories; DSTA,
Singapore [R 181-000-066-123/232]
FX We are thankful to the National University of Singapore and DSO National
Laboratories. This research was supported by research grant #R
181-000-066-123/232 from DSTA, Singapore.
NR 23
TC 13
Z9 13
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD JUN
PY 2009
VL 22
IS 6
BP 990
EP 996
DI 10.1021/tx8003467
PG 7
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA 458KX
UT WOS:000267020500004
PM 19522546
ER
PT J
AU Lardinois, OM
Maltby, DA
Medzihradszky, KF
de Montellano, PRO
Tomer, KB
Mason, RP
Deterding, LJ
AF Lardinois, Olivier M.
Maltby, David A.
Medzihradszky, Katalin F.
de Montellano, Paul R. Ortiz
Tomer, Kenneth B.
Mason, Ronald P.
Deterding, Leesa J.
TI Spin Scavenging Analysis of Myoglobin Protein-Centered Radicals Using
Stable Nitroxide Radicals: Characterization of Oxoammonium
Cation-Induced Modifications
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; SPERM-WHALE MYOGLOBIN; HYDROGEN-PEROXIDE;
LIQUID-CHROMATOGRAPHY; CROSS-LINKING; OXIDATIVE DAMAGE;
AQUEOUS-SOLUTION; HUMAN-DISEASE; COMPOUND-I; METMYOGLOBIN
AB Spin scavenging combined with chromatographic and mass spectrometric procedures can, in principle, be employed to detect and identify protein-based radicals within complex biological matrices. This approach is based on the well-known ability of stable synthetic nitroxide radicals to scavenge carbon-centered radicals, forming stable diamagnetic addition products. Hence, characterization of these addition products would allow for the identification of specific free radicals. In the present work, we have explored the use of the stable nitroxide radical 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) in scavenging protein-based radicals generated in a horse heart metmyoglobin/hydrogen peroxide (metMb/H(2)O(2)) system. Inclusion of a substoichiometric amount of TEMPOL in the metMb/H(2)O(2) system resulted in a complete loss of peroxyl and tyrosyl radical signals and effectively inhibited the formation of oxidatively damaged heme species, as monitored by electron paramagnetic resonance and reversed-phase liquid chromatography. Scavenging of globin radicals by TEMPOL did not lead to the formation of stable diamagnetic addition adducts; in fact, reversed-phase liquid chromatographic studies and oxygen electrode measurements indicated that TEMPOL acts as a catalyst and is recycled in this system. The oxoammonium cation generated in the course of this reaction initiated secondary reactions resulting in the formation of a free carbonyl on the N-terminal Gly-residue of the protein. This oxidative deamination was confirmed through the combined use of reversed-phase liquid chromatographic purification, tandem MS experiments, and chemical analysis (e.g., by use of 2,4-dinitrophenyl hydrazine). The results reveal the pitfalls inherent in using stable nitroxide radicals such as TEMPOL to identify sites of radical formation on hemoproteins.
C1 [Lardinois, Olivier M.; Mason, Ronald P.] NIEHS, Pharmacol Lab, Res Triangle Pk, NC 27709 USA.
[Tomer, Kenneth B.; Deterding, Leesa J.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
[Maltby, David A.; Medzihradszky, Katalin F.] Univ Calif San Francisco, Mass Spectrometry Facil, San Francisco, CA 94158 USA.
[de Montellano, Paul R. Ortiz] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
RP Lardinois, OM (reprint author), NIEHS, Pharmacol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
EM lardinois.olivier@gmail.com
RI Tomer, Kenneth/E-8018-2013
FU National Institutes of Health; National Institute of Environmental
Health Sciences; National Center for Research Resources [RR001614,
RR012961, GM32488]
FX This work has been supported by the Intramural Research Program of the
National Institutes of Health and the National Institute of
Environmental Health Sciences, the National Center for Research
Resources Grants RR001614 and RR012961 (to D.A.M., K.F.M., and director
A. L. Burlingame), and GM32488 (P.R.O.M.). We thank Dr. Arno Siraki and
Dr. Marcelo Bonini for their careful review of the manuscript and Mrs.
Anne Froment, Ms. Jean Corbett, Mrs. Mary J. Mason, and Dr. Ann Motten
for their valuable assistance in the preparation of this manuscript. We
also thank Dr. Jinjie Jiang for advice and for kindly providing us
training and access to the EPR spectrometer (to O.M.L.), and Mr. Robert
Sik for synthesis of the spin trap DBNBS.
NR 65
TC 18
Z9 18
U1 1
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD JUN
PY 2009
VL 22
IS 6
BP 1034
EP 1049
DI 10.1021/tx9000094
PG 16
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA 458KX
UT WOS:000267020500009
PM 19449826
ER
PT J
AU Zhu, X
Gallogly, MM
Mieyal, JJ
Anderson, VE
Sayre, LM
AF Zhu, Xiaochun
Gallogly, Molly M.
Mieyal, John J.
Anderson, Vernon E.
Sayre, Lawrence M.
TI Covalent Cross-Linking of Glutathione and Carnosine to Proteins by
4-Oxo-2-nonenal
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article; Proceedings Paper
CT 234th National Meeting of the American-Chemical-Society
CY AUG 19-23, 2007
CL Boston, MA
SP Amer Chem Soc
ID PAAL-KNORR SYNTHESIS; OXIDATIVE STRESS; LIPID-PEROXIDATION;
MASS-SPECTROMETRY; S-GLUTATHIONYLATION; BETA-LACTOGLOBULIN; EPISULFONIUM
ION; MICHAEL ADDUCTS; SKELETAL-MUSCLE; PRODUCTS
AB The lipid oxidation product 4-oxo-2-nonenal (ONE) derived from peroxidation of polyunsaturated fatty acids is a highly reactive protein cross-linking reagent. The major family of cross-links reflects conjugate addition of side chain nucleophiles such as sulfhydryl or imidazole groups to the C=C of ONE to give either a 2- or 3-substituted 4-ketoaldehyde, which then undergoes Paal-Knorr condensation with the primary amine of protein lysine side chains. If ONE is intercepted in biological fluids by antielectrophiles such as glutathione (GSH) or beta-alanylhistidine (carnosine), this would lead to circulating 4-ketoaldehydes that could then bind covalently to the protein Lys residues. This phenomenon was investigated by SDS-PAGE and mass spectrometry (matrix-assisted laser desorption/ionization time-of-flight and LC-ESI-MS/MS with both tryptic and chymotryptic digestion). Under the reaction conditions of 0.25-2 mM ONE, I mM GSH or carnosine, 0.25 mM bovine beta-lactoglobulin (beta-LG), and 100 mM phosphate buffer (pH 7.4, 10% ethanol) for 24 h at 37 degrees C, virtually every Lys of beta-LG was found to be fractionally cross-linked to GSH. Cross-linking of Lys to carnosine was less efficient. Using cytochrome c and RNase A, we showed that ONE becomes more protein-reactive in the presence of GSH, whereas protein modification by 4-hydroxy-2-nonenal is inhibited by GSH. Stable antielectrophile-ONE-protein cross-links may serve as biomarkers of oxidative stress and may represent a novel mechanism of irreversible protein glutathionylation.
C1 [Zhu, Xiaochun; Sayre, Lawrence M.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
[Gallogly, Molly M.; Mieyal, John J.] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA.
[Anderson, Vernon E.] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA.
RP Anderson, VE (reprint author), NIGMS, Bethesda, MD 20892 USA.
EM andersonve@mail.nih.gov
RI Zhu, Xiaochun/A-5179-2010
FU NHLBI NIH HHS [R01 HL053315, R01 HL053315-04, HL 53315]; NIA NIH HHS [AG
15885, P01 AG015885]; NIGMS NIH HHS [T32 GM007250]
NR 46
TC 21
Z9 22
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
EI 1520-5010
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD JUN
PY 2009
VL 22
IS 6
BP 1050
EP 1059
DI 10.1021/tx9000144
PG 10
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA 458KX
UT WOS:000267020500010
PM 19480392
ER
PT J
AU Barnett, CF
Bonura, EJ
Nathan, SD
Ahmad, S
Shlobin, OA
Osei, K
Zaiman, AL
Hassoun, PM
Moller, DR
Barnett, SD
Girgis, RE
AF Barnett, Christopher F.
Bonura, Eric J.
Nathan, Steven D.
Ahmad, Shahzad
Shlobin, Oksana A.
Osei, Kwabena
Zaiman, Ari L.
Hassoun, Paul M.
Moller, David R.
Barnett, Scott D.
Girgis, Reda E.
TI Treatment of Sarcoidosis-Associated Pulmonary Hypertension A Two-Center
Experience
SO CHEST
LA English
DT Article
DE bosentan; prostacyclin; pulmonary hypertension; sarcoidosis; sildenafil
ID 6-MINUTE WALK TEST; ARTERIAL-HYPERTENSION; SILDENAFIL; HEMODYNAMICS;
STENOSIS; DISEASE
AB Background: Pulmonary hypertension (PH) is a common complication of sarcoidosis that is associated with increased mortality. The pathogenesis of PH in sarcoidosis is uncertain, and the role of pulmonary arterial hypertension (PAH)-specific therapies remains to be determined.
Methods: Nile conducted a retrospective study of patients with sarcoidosis and PH at two referral centers. New York Heart Association (NYHA) functional class, exercise capacity, hemodynamic data, pulmonary function tests, and survival were collected and analyzed.
Results: Twenty-two sarcoidosis patients treated with PAH-specific therapies were identified. After a median of 11 months of follow-up, NYHA class was improved in nine subjects. Mean 6-min walk distance (n = 18) increased by 59 in (p = 0.032). Patients with a higher FVC experienced a greater increment in exercise capacity. Among 12 patients with follow-up hemodynamic data, mean pulmonary artery pressure was reduced from 48.5 +/- 4.3 to 39.4 +/- 2.8 min Hg (p = 0.008). The 1- and 3-year transplant-free survival rates were 90% and 74%, respectively.
Conclusions: PAH-specific therapy may improve functional class, exercise capacity, and hemodynamics in PH associated with sarcoidosis. Prospective, controlled trials of PAH therapies for sarcoidosis are warranted to verify this apparent benefit. Mortality among the study population was high, highlighting the need for urgent evaluation at a lung transplant Center. (CHEST 2009; 135:1455-1461)
C1 [Barnett, Christopher F.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Bonura, Eric J.] Georgetown Univ, Dept Internal Med, Washington, DC USA.
[Nathan, Steven D.; Ahmad, Shahzad; Shlobin, Oksana A.; Barnett, Scott D.] Inova Fairfax Hosp, Falls Church, VA USA.
[Osei, Kwabena; Zaiman, Ari L.; Hassoun, Paul M.; Moller, David R.; Girgis, Reda E.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA.
RP Barnett, CF (reprint author), 200 W Arbor Dr,MPF 360, San Diego, CA 92103 USA.
EM cbarnett@ucsd.edu
FU National Institutes of Health; National Heart, Lung, and Blood
Institute; Clinical Center, Critical Care Medicine Department
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health; the National Heart, Lung, and
Blood Institute; and Clinical Center, Critical Care Medicine Department
NR 29
TC 57
Z9 58
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 JUN
PY 2009
VL 135
IS 6
BP 1455
EP 1461
DI 10.1378/chest.08-1881
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 455UE
UT WOS:000266791100011
PM 19118270
ER
PT J
AU Yuan, LX
Sun, LG
Fortin, D
Wang, YH
Wu, ZJ
Yin, XB
AF Yuan LinXi
Sun LiGuang
Fortin, Danielle
Wang YuHong
Wu ZiJun
Yin XueBin
TI Characterization of Fe-S minerals influenced by buried ancient woods in
the intertidal zone, East China Sea
SO CHINESE SCIENCE BULLETIN
LA English
DT Article
DE Intertidal zone; ancient wood layer; Fe-S minerals; iron-oxidizing
bacteria (FeOB); sulfate-reducing bacteria (SRB); East China Sea
ID SULFATE-REDUCING BACTERIA; IRON-OXIDIZING BACTERIA; 125 DEGREES-C;
PYRITE FORMATION; DISSIMILATORY FE(III); ATMOSPHERIC OXYGEN;
AQUEOUS-SOLUTIONS; MARINE-SEDIMENTS; ORGANIC-MATTER; H2S OXIDATION
AB An ancient wood layer dated at about 5600 cal. a BP by AMS(14)C dating was discovered in the intertidal zone, East China Sea. Samples affected by ancient woods, including fresh coast bedrock, weathering bedrock, seepage water from coast, seepage water from ancient wood layer, intertidal seawater, fresh water, beach mud, ancient wood barks and ancient peat, were collected for geochemical analysis. The beach mud and the bacteriogenic iron oxides (BIOS) in coastal seepage water were analyzed by mineralogical and high-resolution transmission electron microscopy (HRTEM)-selected area electron diffraction (SAED) analysis. Inorganic sulfur compositions and delta (34)S of the ancient peat and the beach mud were determined. The results showed that Fe, Mn, S (SO (4) (2-) ) were enriched in the intertidal area at different levels, very likely caused by fermentation of ancient woods. The presence of abundant ironoxidizing bacteria (FeOB) and sulfate-reducing bacteria (SRB) in this intertidal zone was confirmed by HRTEM-SAED observation, and these bacteria were involved in Fe-S cycle to induce extracellular biomineralization. The negative delta (34)S(V-CDT) (-2.9aEuro degrees) likely indicated the biogenic origin of iron-sulfide minerals in the beach mud at high sulfate reduction rate (SRR). These findings are helpful for understanding the biogeochemical Fe-S cycle and biomineralization process at high organic matter deposition rate and high SRR in the intertidal zone, estuary, or near shoreline.
C1 [Yuan LinXi; Sun LiGuang; Wu ZiJun; Yin XueBin] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Peoples R China.
[Fortin, Danielle] Univ Ottawa, Dept Earth Sci, Ottawa, ON K1N 6N5, Canada.
[Wang YuHong] NIH, Bethesda, MD 20892 USA.
[Yin XueBin] USTC City U Joint Adv Res Ctr, ALERT, Suzhou 215123, Peoples R China.
RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Peoples R China.
EM slg@ustc.edu.cn
FU Chinese Academy of Sciences [KZCX3-SW-151]
FX Supported by the Project of the Knowledge Innovation Program of the
Chinese Academy of Sciences (Grant No. KZCX3-SW-151)
NR 68
TC 1
Z9 1
U1 5
U2 13
PU SCIENCE PRESS
PI BEIJING
PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA
SN 1001-6538
J9 CHINESE SCI BULL
JI Chin. Sci. Bull.
PD JUN
PY 2009
VL 54
IS 11
BP 1931
EP 1940
DI 10.1007/s11434-009-0334-9
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 453AJ
UT WOS:000266582000019
ER
PT J
AU Fujimoto, C
Klinman, DM
Shi, G
Yin, H
Vistica, BP
Lovaas, JD
Wawrousek, EF
Igarashi, T
Chan, CC
Gery, I
AF Fujimoto, C.
Klinman, D. M.
Shi, G.
Yin, H.
Vistica, B. P.
Lovaas, J. D.
Wawrousek, E. F.
Igarashi, T.
Chan, C. -C.
Gery, I.
TI A suppressive oligodeoxynucleotide inhibits ocular inflammation
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Article
DE EAU; immunopathogenic process; immunosuppression; ODN
ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; RETINOID-BINDING PROTEIN;
T-CELLS; CPG MOTIFS; UVEITIS; MICE; DISEASE; INDUCTION; DIFFERENTIATION;
ANTIGEN
AB Synthetic oligodeoxynucleotides (ODN) expressing 'suppressive' TTAGGG motifs down-regulate a variety of proinflammatory and T helper type 1 (Th1)-mediated pathological immune responses. The ability of the archetypal suppressive ODN A151 to inhibit ocular inflammation was examined in two murine models: experimental autoimmune uveitis, induced by immunization with a retinal antigen, interphotoreceptor retinoid-binding protein (IRBP) and adoptively transferred ocular inflammation, induced by transferring Th1 cells specific to hen egg lysozyme (HEL) into recipient mice that express HEL in their eyes. A151 treatment suppressed the inflammation in both models. In addition, A151 inhibited IRBP-specific cytokine production and lymphocyte proliferation in mice immunized with IRBP. These findings suggest that suppressive ODN affects both afferent and efferent limbs of the immunopathogenic process and may be of use in the treatment of autoimmune ocular inflammation.
C1 [Gery, I.] NEI, Expt Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Klinman, D. M.] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA.
RP Gery, I (reprint author), NEI, Expt Immunol Sect, Immunol Lab, NIH, Bldg 10,Room 10N208,10 Ctr Dr, Bethesda, MD 20892 USA.
EM geryi@nei.nih.gov
OI Igarashi, Tsutomu/0000-0002-7467-6746
FU Intramural Research Program of the National Eye Institute, NIH
FX This research was supported by the Intramural Research Program of the
National Eye Institute, NIH. We thank Robert S. Lee for tail DNA
analysis, Ricardo Dreyfuss for digital microphotography and the National
Eye Institute Histology Core Facility for tissue section preparations.
NR 40
TC 16
Z9 18
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9104
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD JUN
PY 2009
VL 156
IS 3
BP 528
EP 534
DI 10.1111/j.1365-2249.2009.03918.x
PG 7
WC Immunology
SC Immunology
GA 443AU
UT WOS:000265883400020
PM 19438607
ER
PT J
AU Goldstein, DS
Orimo, S
AF Goldstein, David S.
Orimo, Satoshi
TI Cardiac sympathetic neuroimaging: summary of the First International
Symposium
SO CLINICAL AUTONOMIC RESEARCH
LA English
DT Review
DE Sympathetic nervous system; Fluorodopamine; MIBG; Positron-emission
tomography
ID VENTRICULAR EJECTION FRACTION; CONGESTIVE-HEART-FAILURE; MULTIPLE SYSTEM
ATROPHY; LEWY BODY DISEASE; PARKINSONS-DISEASE; EMOTIONAL-STRESS;
PROGNOSTIC VALUE; I-123-MIBG; NERVE; CARDIOMYOPATHY
AB The First International Symposium on Cardiac Sympathetic Neuroimaging brought together for the first time clinical and preclinical researchers evaluating autonomic and neurocardiologic disorders by this modality. The invited lectures and posters presented some uses of cardiac sympathetic neuroimaging for diagnosis, prognosis, and monitoring treatments. The Symposium also included a discussion about whether and how to expand the availability of cardiac sympathetic neuroimaging at medical centers in the United States. Here, we review the background for the Symposium, provide an annotated summary of the lectures and posters, discuss some of the take-home points from the roundtable discussion, and propose a plan of action for the future.
C1 [Goldstein, David S.] Natl Inst Neurol Disorders & Stroke, Clin Neurosci Program, Clin Neurocardiol Sect, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[Orimo, Satoshi] Kanto Cent Hosp, Tokyo, Japan.
RP Goldstein, DS (reprint author), Natl Inst Neurol Disorders & Stroke, Clin Neurosci Program, Clin Neurocardiol Sect, Div Intramural Res,NIH, Bldg 10,Room 6N252,10 Ctr Dr,MSC 1620, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU Intramural NIH HHS [Z99 NS999999]
NR 21
TC 6
Z9 6
U1 0
U2 1
PU DR DIETRICH STEINKOPFF VERLAG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY
SN 0959-9851
J9 CLIN AUTON RES
JI Clin. Auton. Res.
PD JUN
PY 2009
VL 19
IS 3
BP 137
EP 148
DI 10.1007/s10286-009-0002-9
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 456BB
UT WOS:000266811900002
PM 19266158
ER
PT J
AU Khanna, C
Gordon, I
AF Khanna, Chand
Gordon, Ira
TI Catching Cancer by the Tail: New Perspectives on the Use of Kinase
Inhibitors
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
ID MAST-CELL TUMORS; C-KIT; TANDEM DUPLICATIONS; THERAPY; SU11654; DOGS;
GIST
AB In this issue of Clinical Cancer Research, London and colleagues evaluate a small molecule multiple-targeted tyrosine kinase inhibitor in dogs with c-kit driven skin cancer. The study represents another example of opportunities to include pet dogs in studies that improve our understanding of human cancer biology and therapy.
C1 [Khanna, Chand] NCI, Ctr Canc Res, Comparat Oncol Program, Bethesda, MD 20892 USA.
[Gordon, Ira] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
RP Khanna, C (reprint author), NCI, Ctr Canc Res, Comparat Oncol Program, 37 Convent Dr,Rm 2144, Bethesda, MD 20892 USA.
EM khannac@mail.nih.gov
NR 11
TC 9
Z9 9
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 1
PY 2009
VL 15
IS 11
BP 3645
EP 3647
DI 10.1158/1078-0432.CCR-09-0132
PG 3
WC Oncology
SC Oncology
GA 454CJ
UT WOS:000266659000001
PM 19470723
ER
PT J
AU Kacinko, SL
Jones, HE
Johnson, RE
Choo, RE
Concheiro-Guisan, M
Huestis, MA
AF Kacinko, Sherri L.
Jones, Hendree E.
Johnson, Rolley E.
Choo, Robin E.
Concheiro-Guisan, Marta
Huestis, Marilyn A.
TI Urinary Excretion of Buprenorphine, Norbuprenorphine,
Buprenorphine-Glucuronide, and Norbuprenorphine-Glucuronide in Pregnant
Women Receiving Buprenorphine Maintenance Treatment
SO CLINICAL CHEMISTRY
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; CLINICAL-RELEVANCE;
HAIR SAMPLES; DRUG-USERS; METABOLITES; PLASMA; PHARMACOKINETICS;
QUANTIFICATION; DISPOSITION
AB BACKGROUND: Buprenorphine (BUP) is under investigation as a medication therapy for opioid-dependent pregnant women. We investigated BUP and metabolite disposition in urine from women maintained on BUP during the second and third trimesters of pregnancy and postpartum.
METHODS: We measured BUP, norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and NBUP-Gluc concentrations in 515 urine specimens collected thrice weekly from 9 women during pregnancy and postpartum. Specimens were analyzed using a fully validated liquid chromatography-in ass spectrometry method with limits of quantification of 5 mu g/L for BUP and BUP-Gluc and 25 mu g/L for NBUP and its conjugated metabolite. We examined ratios of metabolites across trimesters and postpartum to identify possible changes in metabolism during pregnancy.
RESULTS: NBUP-Gluc was the primary metabolite identified in urine and exceeded BUP-Gluc concentrations. in 99% of specimens. Whereas BUP-Gluc was identified in more specimens than NBUP, NBUP exceeded BUP-Gluc concentrations in 77.9% of specimens that contained both analytes. Among all participants, the mean BUP-Gluc:NBUP-Gluc ratio was significantly higher in the second trimester compared to the third trimester, and there were significant intrasubject differences between trimesters in 71% of participants. In 3 women, the percent daily dose excreted was higher during pregnancy than postpregnancy, consistent with other data indicating increased renal elimination of drugs during pregnancy.
CONCLUSIONS: These data are the first to evaluate urinary disposition of BUP and metabolites in a cohort of pregnant women. Variable BUP excretion during pregnancy may indicate metabolic changes requiring dose adjustment during later stages of gestation. (C) 2009 American Association for Clinical Chemistry
C1 [Kacinko, Sherri L.; Concheiro-Guisan, Marta; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Jones, Hendree E.; Johnson, Rolley E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Johnson, Rolley E.] Reckitt Benckiser Pharmaceut Inc, Richmond, VA USA.
[Choo, Robin E.] Univ Pittsburgh, Dept Biol, Titusville, PA USA.
RP Huestis, MA (reprint author), 251 Bayview Blvd,Suite 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program; NIH; National Institute on Drug Abuse
FX Intramural Research Program, NIH, National Institute on Drug Abuse.
NR 37
TC 11
Z9 11
U1 0
U2 2
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 JUN
PY 2009
VL 55
IS 6
BP 1177
EP 1187
DI 10.1373/clinchem.2008.113712
PG 11
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 454MV
UT WOS:000266687200019
PM 19325013
ER
PT J
AU Schwilke, EW
Karschner, EL
Lowe, RH
Gordon, AM
Cadet, JL
Herning, RI
Huestis, MA
AF Schwilke, Eugene W.
Karschner, Erin L.
Lowe, Ross H.
Gordon, Ann M.
Cadet, Jean Lud
Herning, Ronald I.
Huestis, Marilyn A.
TI Intra- and Intersubject Whole Blood/Plasma Cannabinoid Ratios Determined
by 2-Dimensional, Electron Impact GGMS with Cryofocusing
SO CLINICAL CHEMISTRY
LA English
DT Article
ID MASS-SPECTROMETRY; GAS-CHROMATOGRAPHY;
11-NOR-DELTA(9)-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID;
DELTA-9-TETRAHYDROCANNABINOL THC; TETRAHYDROCANNABINOL GLUCURONIDE;
BLOOD CANNABINOIDS; PLASMA-PROTEINS; STABILITY; BINDING; MARIJUANA
AB BACKGROUND: Whole-blood concentrations of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) are approximately half of those in plasma due to high plasma protein binding and poor cannabinoid distribution into erythrocytes. Whole blood is frequently the only specimen available in forensic investigations; controlled cannabinoid administration studies provide scientific data for interpretation of cannabinoid tests but usually report plasma concentrations. Whole-blood/plasma cannabinoid ratios from simultaneously collected authentic specimens are rarely reported.
METHODS: We collected whole blood for 7 days from 32 individuals residing on a closed research unit. Part of the whole blood was processed to obtain plasma, and the whole blood and plasma were stored at -20 degrees C until analysis by validated 2-dimensional GC-MS methods.
RESULTS: We measured whole-blood/plasma cannabinoid ratios in 187 specimen pairs. Median (interquartile range) whole-blood/plasma ratios were 0.39 (0.28-0.48) for THC (n = 75), 0.56 (0.43-0.73) for 11-OH-THC (n = 17), and 0.37 (0.24-0.56) for THCCOOH (n = 187). Intrasubject variability was determined for the first time: 18.1%-56.6% CV (THC) and 10.8%-38.2% CV (THCCOOH). The mean whole-blood/plasma THC ratio was significantly lower than the THCCOOH ratio (P = 0.0001; 4 participants' mean THCCOOH ratios were >0.8).
CONCLUSIONS: Intra- and intersubject whole-blood/plasma THC and THCCOOH ratios will aid interpretation of whole-blood cannabinoid data. (C) 2008 American Association for Clinical Chemistry
C1 [Schwilke, Eugene W.; Karschner, Erin L.; Lowe, Ross H.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Gordon, Ann M.] Washington State Toxicol Lab, Washington State Patrol, Seattle, WA USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse; NIH
FX This research was funded and approved by the Intramural Research Program
of the National Institute on Drug Abuse, NIH.
NR 25
TC 23
Z9 23
U1 1
U2 5
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 JUN
PY 2009
VL 55
IS 6
BP 1188
EP 1195
DI 10.1373/clinchem.2008.114405
PG 8
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 454MV
UT WOS:000266687200020
PM 19264857
ER
PT J
AU Annesley, T
Hsing, A
Majzoub, J
Wu, A
Rockwood, A
Mason, D
AF Annesley, Thomas
Hsing, Ann
Majzoub, Joseph
Wu, Alan
Rockwood, Alan
Mason, Donald
TI Mass Spectrometry in the Clinical Laboratory: How Have We Done, and
Where Do We Need to Be?
SO CLINICAL CHEMISTRY
LA English
DT Editorial Material
C1 [Annesley, Thomas] Univ Michigan, Dept Pathol, Hlth Sci Ctr, Ann Arbor, MI 48109 USA.
[Hsing, Ann] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Majzoub, Joseph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Majzoub, Joseph] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Wu, Alan] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Wu, Alan] San Francisco Gen Hosp, San Francisco, CA USA.
[Rockwood, Alan] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA.
[Rockwood, Alan] ARUP Labs, Salt Lake City, UT USA.
[Mason, Donald] Waters Corp, Milford, MA USA.
RP Annesley, T (reprint author), Univ Michigan, Dept Pathol, Hlth Sci Ctr, Ann Arbor, MI 48109 USA.
NR 0
TC 9
Z9 10
U1 1
U2 1
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 JUN
PY 2009
VL 55
IS 6
BP 1236
EP 1239
DI 10.1373/clinchem.2009.127522
PG 4
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 454MV
UT WOS:000266687200030
PM 19395433
ER
PT J
AU Browne, RW
Bloom, MS
Schisterman, EF
Wactawski-Wende, J
Hovey, K
Trevisan, M
Gross, M
AF Browne, Richard W.
Bloom, Michael S.
Schisterman, Enrique F.
Wactawski-Wende, Jean
Hovey, Kathy
Trevisan, Maurizio
Gross, Myron
TI Analytical and Biological Variation of F(2)-Isoprostanes during the
Menstrual Cycle
SO CLINICAL CHEMISTRY
LA English
DT Letter
ID STRESS
C1 [Browne, Richard W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14214 USA.
[Browne, Richard W.; Wactawski-Wende, Jean; Hovey, Kathy; Trevisan, Maurizio] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA.
[Bloom, Michael S.] SUNY Albany, Dept Environm Hlth Sci, Albany, NY 12222 USA.
[Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Trevisan, Maurizio] Dept Lab Med & Pathol, Las Vegas, NV USA.
[Trevisan, Maurizio] Hlth Sci Syst Nevada Syst Higher Educ, Las Vegas, NV USA.
[Gross, Myron] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
RP Browne, RW (reprint author), SUNY Buffalo, Dept Biotech & Clin Lab Sci, 26 Cary Hall, Buffalo, NY 14214 USA.
EM rwbrowne@buffalo.edu
OI Schisterman, Enrique/0000-0003-3757-641X; Bloom,
Michael/0000-0002-0028-5494
FU Intramural NIH HHS [Z01 HD008762-05]; NICHD NIH HHS [ADB-N01-HD-4-3394]
NR 5
TC 8
Z9 8
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 JUN
PY 2009
VL 55
IS 6
BP 1245
EP 1247
DI 10.1373/clinchem.2008.122101
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 454MV
UT WOS:000266687200035
PM 19359531
ER
PT J
AU Bosworth, TL
Sampson, M
Remaley, AT
AF Bosworth, T. L.
Sampson, M.
Remaley, A. T.
TI Effect of Contamination of Heparinized Blood Collection Tubes with
Oversulfated Chondrotin Sulfate
SO CLINICAL CHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Clinical-Chemistry
CY JUL 19-23, 2009
CL Chicago, IL
SP Amer Assoc Clin Chem
C1 [Bosworth, T. L.; Sampson, M.; Remaley, A. T.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
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 JUN
PY 2009
VL 55
IS 6
BP A22
EP A22
PG 1
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 456ZZ
UT WOS:000266895400067
ER
PT J
AU Mendu, DR
Gu, J
Soldin, SJ
AF Mendu, D. R.
Gu, J.
Soldin, S. J.
TI Measurement of Cyclosporine A on the Siemens Dimension RxL Chemistry
analyzer: Comparison of results with Tandem Mass Spectrometry
SO CLINICAL CHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Clinical-Chemistry
CY JUL 19-23, 2009
CL Chicago, IL
SP Amer Assoc Clin Chem
C1 [Mendu, D. R.] Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC USA.
[Gu, J.] Georgetown Univ, Gen Clin Res Ctr, Washington, DC USA.
[Soldin, S. J.] Georgetown Univ, Dept Med, Dept Oncol, Dept Pharmacol, Washington, DC USA.
NIH, Dept Lab Med, Ctr Clin, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 JUN
PY 2009
VL 55
IS 6
SU S
BP A246
EP A247
PG 2
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 456ZZ
UT WOS:000266895401340
ER
PT J
AU Mendu, DR
Soldin, SJ
AF Mendu, D. R.
Soldin, S. J.
TI The concentration of plasticizers di(2-ethylhexyl)phthalate( DEHP) and
mono(2-ethylhexyl) phthalate (MEHP) in commercial drinking water
bottles.
SO CLINICAL CHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Clinical-Chemistry
CY JUL 19-23, 2009
CL Chicago, IL
SP Amer Assoc Clin Chem
C1 [Mendu, D. R.] Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC USA.
[Soldin, S. J.] Georgetown Univ, Dept Med, Dept Oncol, Dept Physiol & Pharmacol, Washington, DC USA.
[Soldin, S. J.] NIH, Georgetown Clin Res Ctr, Dept Lab Med Prote & Mass Spectrometry, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
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 JUN
PY 2009
VL 55
IS 6
BP A247
EP A247
PG 1
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 456ZZ
UT WOS:000266895401341
ER
PT J
AU Sethi, AA
Sampson, M
Vazquez, E
Pham, C
Remaley, AT
AF Sethi, A. A.
Sampson, M.
Vazquez, E.
Pham, C.
Remaley, A. T.
TI A Modified Oxygen Radical Absorbance Capacity Method for the Assessment
of the Anti-oxidant Capacity of High Density Lipoproteins
SO CLINICAL CHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Clinical-Chemistry
CY JUL 19-23, 2009
CL Chicago, IL
SP Amer Assoc Clin Chem
C1 [Sethi, A. A.; Sampson, M.; Vazquez, E.; Pham, C.; Remaley, A. T.] NIH, Bethesda, MD 20892 USA.
NR 0
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 JUN
PY 2009
VL 55
IS 6
BP A91
EP A91
PG 1
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 456ZZ
UT WOS:000266895400282
ER
PT J
AU Price, LN
Maholmes, V
AF Price, LeShawndra N.
Maholmes, Valerie
TI Understanding the Nature and Consequences of Children's Exposure to
Violence: Research Perspectives
SO CLINICAL CHILD AND FAMILY PSYCHOLOGY REVIEW
LA English
DT Article
DE Community violence; Children and youth; Funding opportunities
ID DATING VIOLENCE; SCHOOL-STUDENTS
AB The National Institutes of Health (NIH) has a long history of supporting research to enhance the scientific understanding of and effective interventions for a range of problems associated with children's exposure to violence. Recently, funded research has improved our understanding of the nature and consequences of children's exposure to violence. This article describes an NIH initiative for research on children's exposure to violence, examples of projects supported by the initiative, and emerging research topics for this important scientific area.
C1 [Price, LeShawndra N.] Natl Inst Drug Abuse, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Maholmes, Valerie] NICHHD, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
RP Price, LN (reprint author), Natl Inst Drug Abuse, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
EM lprice@mail.nih.gov
NR 12
TC 2
Z9 2
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1096-4037
J9 CLIN CHILD FAM PSYCH
JI Clin. Child Fam. Psychol. Rev.
PD JUN
PY 2009
VL 12
IS 2
BP 65
EP 70
DI 10.1007/s10567-009-0057-0
PG 6
WC Psychology, Clinical
SC Psychology
GA 461TF
UT WOS:000267293700001
PM 19533352
ER
PT J
AU Juan, JY
Tracy, K
Zhang, LH
Munasinghe, J
Shapiro, E
Koretsky, A
Kelly, K
AF Juan JuanYin
Tracy, Kirsten
Zhang, Luhua
Munasinghe, Jeeva
Shapiro, Erik
Koretsky, Alan
Kelly, Kathleen
TI Noninvasive imaging of the functional effects of anti-VEGF therapy on
tumor cell extravasation and regional blood volume in an experimental
brain metastasis model
SO CLINICAL & EXPERIMENTAL METASTASIS
LA English
DT Article
DE Animal model; AZD2171/Cediranib; Blood volume; Brain metastasis; MPIO;
MRI; Prostate cancer; USPIO
ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; CANCER METASTASIS;
PROSTATE-CANCER; ANTIANGIOGENIC THERAPY; MRI; PERMEABILITY; VASCULATURE;
EXPRESSION; PARTICLES
AB Brain metastasis has become an increasing cause of morbidity and mortality in cancer patients as the treatment of systemic disease has improved. Brain metastases frequently are highly vascularized, a process driven primarily by VEGF. VEGF mediates numerous changes within the vasculature including endothelial cell retraction and increased permeability, vasodilation, and new vessel formation. Here we describe a xenograft brain metastasis model that mimics the critical steps of metastasis including tumor cell dissemination and vascular adhesion, tumor growth and tumor associated angiogenesis. Magnetic resonance (MR) imaging was used to evaluate two aspects of the functional response of brain metastasis to the anti-VEGF receptor therapeutic, AZD2171 (Cediranib, RECENTIN (TM)). MR tracking of individual cells demonstrated that cediranib did not impede tumor cell extravasation into the brain parenchyma despite evidence that anti-VEGF treatment decreases the permeability of the blood brain barrier. In a second assay, blood volume imaging using ultrasmall superparamagnetic iron oxide revealed that treatment of well-developed brain metastasis with cediranib for 7 days led to a heterogeneous response with respect to individual tumors. Overall, there was a significant average decrease in the tumor vascular bed volume. The majority of large tumors demonstrated substantially reduced central blood volumes relative to normal brain while retaining a rim of elevated blood volume at the tumor brain interface. Small tumors or occasional large tumors displayed a static response. Models and assays such as those described here will be important for designing mechanism-based approaches to the use of anti-angiogenesis therapies for the treatment of brain metastasis.
C1 [Juan JuanYin; Tracy, Kirsten; Zhang, Luhua; Kelly, Kathleen] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Shapiro, Erik; Koretsky, Alan] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Munasinghe, Jeeva] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA.
RP Kelly, K (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, 37 Convent Dr,Room 1068, Bethesda, MD 20892 USA.
EM kellyka@mail.nih.gov
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU Intramural NIH HHS [Z01 NS003047-01]
NR 30
TC 23
Z9 24
U1 1
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0262-0898
J9 CLIN EXP METASTAS
JI Clin. Exp. Metastasis
PD JUN
PY 2009
VL 26
IS 5
BP 403
EP 414
DI 10.1007/s10585-009-9238-y
PG 12
WC Oncology
SC Oncology
GA 448CF
UT WOS:000266239100002
PM 19277878
ER
PT J
AU Klarmann, GJ
Hurt, EM
Mathews, LA
Zhang, XH
Duhagon, MA
Mistree, T
Thomas, SB
Farrar, WL
AF Klarmann, George J.
Hurt, Elaine M.
Mathews, Lesley A.
Zhang, Xiaohu
Duhagon, Maria A.
Mistree, Tashan
Thomas, Suneetha B.
Farrar, William L.
TI Invasive prostate cancer cells are tumor initiating cells that have a
stem cell-like genomic signature
SO CLINICAL & EXPERIMENTAL METASTASIS
LA English
DT Article
DE Cancer stem cells; Metastasis; Invasion; EMT; Prostate cancer; Hedgehog
ID EPITHELIAL-MESENCHYMAL TRANSITION; E-CADHERIN EXPRESSION; BREAST-CANCER;
PANCREATIC-CANCER; BONE-MARROW; METASTASIS; CD44; PROGRESSION;
DISSEMINATION; TRANSCRIPTION
AB Development of metastasis is a leading cause of cancer-induced death. Acquisition of an invasive tumor cell phenotype suggests loss of cell adhesion and basement membrane breakdown during a process termed epithelial-to-mesenchymal transition (EMT). Recently, cancer stem cells (CSC) were discovered to mediate solid tumor initiation and progression. Prostate CSCs are a subpopulation of CD44(+) cells within the tumor that give rise to differentiated tumor cells and also self-renew. Using both primary and established prostate cancer cell lines, we tested the assumption that CSCs are more invasive. The ability of unsorted cells and CD44-positve and -negative subpopulations to undergo Matrigel invasion and EMT was evaluated, and the gene expression profiles of these cells were analyzed by microarray and a subset confirmed using QRT-PCR. Our data reveal that a subpopulation of CD44(+) CSC-like cells invade Matrigel through an EMT, while in contrast, CD44(-) cells are non-invasive. Furthermore, the genomic profile of the invasive cells closely resembles that of CD44(+)CD24(-) prostate CSCs and shows evidence for increased Hedgehog signaling. Finally, invasive cells from DU145 and primary prostate cancer cells are more tumorigenic in NOD/SCID mice compared with non-invasive cells. Our data strongly suggest that basement membrane invasion, an early and necessary step in metastasis development, is mediated by these potential cancer stem cells.
C1 [Hurt, Elaine M.; Mathews, Lesley A.; Duhagon, Maria A.; Mistree, Tashan; Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
[Klarmann, George J.; Zhang, Xiaohu; Thomas, Suneetha B.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Duhagon, Maria A.] Univ Republica, LIM F Ciencias, Montevideo 11800, Uruguay.
RP Farrar, WL (reprint author), NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, 1050 Boyles St,Bldg 560,Room 21-81, Frederick, MD 21702 USA.
EM farrar@mail.ncifcrf.gov
FU National Cancer Institute; National Institutes of Health [N01-CO-12400];
Center for Cancer Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract N01-CO-12400, and supported (in part) by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the US Government.
NR 55
TC 121
Z9 129
U1 0
U2 17
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0262-0898
J9 CLIN EXP METASTAS
JI Clin. Exp. Metastasis
PD JUN
PY 2009
VL 26
IS 5
BP 433
EP 446
DI 10.1007/s10585-009-9242-2
PG 14
WC Oncology
SC Oncology
GA 448CF
UT WOS:000266239100005
PM 19221883
ER
PT J
AU Kluijt, I
de Jong, D
Teertstra, HJ
Axwijk, PH
Gille, JJP
Bell, K
van Rens, A
van der Velden, AWG
Middelton, L
Horenblas, S
AF Kluijt, I.
de Jong, D.
Teertstra, H. J.
Axwijk, P. H.
Gille, J. J. P.
Bell, K.
van Rens, A.
van der Velden, A. W. G.
Middelton, L.
Horenblas, S.
TI Early onset of renal cancer in a family with Birt-Hogg-DubE syndrome
SO CLINICAL GENETICS
LA English
DT Article
DE Birt-Hogg-DubE syndrome; congenital anomalies; connective tissue;
fibrofolliculomas; FLCN gene; renal cancer
ID BHD GENE; SPONTANEOUS PNEUMOTHORAX; CELL CARCINOMA; MTOR PATHWAY;
TUMORS; MUTATIONS; RADIATION; RISKS; CT; FIBROFOLLICULOMAS
AB Kluijt I, de Jong D, Teertstra HJ, Axwijk PH, Gille JJP, Bell K, van Rens A, van der Velden AWG, Middelton L, Horenblas S. Early onset of renal cancer in a family with Birt-Hogg-DubE syndrome.Clin Genet 2009: 75: 537-543. (C) John Wiley & Sons A/S, 2009
Birt-Hogg-DubE syndrome is a hereditary syndrome characterized by benign disease of skin and lungs and a risk of malignant renal tumors. We describe a clinical and genetic study of a large Dutch family with a novel mutation in the FLCN gene. Renal cancer at very young age occurred in one branch of this family, while in other branches, cutaneous and pulmonary symptoms predominated. A variety of congenital anomalies and connective tissue abnormalities were observed, possibly associated with the gene mutation.
C1 [Kluijt, I.; Axwijk, P. H.; van Rens, A.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, NL-1006 BE Amsterdam, Netherlands.
[de Jong, D.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Pathol, NL-1006 BE Amsterdam, Netherlands.
[Teertstra, H. J.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Radiol, NL-1006 BE Amsterdam, Netherlands.
[Gille, J. J. P.] VU Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[Bell, K.] McMaster Univ, Med Ctr, Genet Serv, Hamilton, ON, Canada.
[van der Velden, A. W. G.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Internal Med, NL-1006 BE Amsterdam, Netherlands.
[Middelton, L.] NCI, NIH, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Horenblas, S.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Urol, NL-1006 BE Amsterdam, Netherlands.
RP Kluijt, I (reprint author), Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, POB 90203, NL-1006 BE Amsterdam, Netherlands.
EM i.kluijt@nki.nl
NR 29
TC 12
Z9 12
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD JUN
PY 2009
VL 75
IS 6
BP 537
EP 543
DI 10.1111/j.1399-0004.2009.01159.x
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 451RR
UT WOS:000266488100007
PM 19320655
ER
PT J
AU Greenberg, DE
Goldberg, JB
Stock, F
Murray, PR
Holland, SM
LiPuma, JJ
AF Greenberg, David E.
Goldberg, Joanna B.
Stock, Frida
Murray, Patrick R.
Holland, Steven M.
LiPuma, John J.
TI Recurrent Burkholderia Infection in Patients with Chronic Granulomatous
Disease: 11-Year Experience at a Large Referral Center
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID CYSTIC-FIBROSIS; CEPACIA COMPLEX
AB The epidemiology of Burkholderia infection in persons with chronic granulomatous disease is poorly understood. We used species-specific polymerase chain reaction-based assays and genotyping analyses to identify 32 strains representing 9 Burkholderia species among 50 isolates recovered from 18 patients with chronic granulomatous disease. We found that recurrent pulmonary infection with distinct Burkholderia strains is common in chronic granulomatous disease.
C1 [Greenberg, David E.; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Stock, Frida; Murray, Patrick R.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Goldberg, Joanna B.] Univ Virginia, Hlth Sci Ctr, Dept Microbiol, Charlottesville, VA 22908 USA.
[LiPuma, John J.] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Ann Arbor, MI USA.
RP LiPuma, JJ (reprint author), 1150 W Med Ctr Dr,8323 MSRB 3,SPC 5646, Ann Arbor, MI 48109 USA.
EM jlipuma@umich.edu
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases; Clinical Center of the National Institutes of
Health; Cystic Fibrosis Foundation
FX Financial support. Division of Intramural Research, National Institute
of Allergy and Infectious Diseases; Clinical Center of the National
Institutes of Health; and Cystic Fibrosis Foundation. J.J.L. is
supported by the Cystic Fibrosis Foundation.
NR 14
TC 16
Z9 19
U1 1
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 1
PY 2009
VL 48
IS 11
BP 1577
EP 1579
DI 10.1086/598937
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 441DL
UT WOS:000265749400012
PM 19400745
ER
PT J
AU Muehlbauer, PM
Thorpe, D
Davis, A
Drabot, R
Rawlings, BL
Kiker, E
AF Muehlbauer, Paula M.
Thorpe, Deborah
Davis, Arlene
Drabot, Rachael
Rawlings, Barbara L.
Kiker, Elizabeth
TI Putting Evidence Into Practice: Evidence-Based Interventions to Prevent,
Manage, and Treat Chemotherapy- and Radiotherapy-Induced Diarrhea
SO CLINICAL JOURNAL OF ONCOLOGY NURSING
LA English
DT Article
ID RADIATION-INDUCED DIARRHEA; CANCER-PATIENTS; OCTREOTIDE; PROBIOTICS;
EFFICACY
AB Diarrhea is a common side effect of chemotherapy regimens, particularly fluorouracil- and irinotecan-based therapies and abdominal and pelvic radiation regimens. Diarrhea can cause depletion of fluids and electrolytes, malnutrition, dehydration, and hospitalization, all of which can lead to cardiovascular compromise and death. Therefore, diarrhea can interfere with and detract from cancer treatment by causing dosing delays or reductions. Evidence supports pharmacologic interventions such as loperamide and octreotide as recommendations for practice. Emerging evidence suggests that probiotics are likely to be effective, but more extensive research is warranted as the field evolves. Soluble fiber supplements are likely to be effective for treating chemotherapy- or radiotherapy-induced diarrhea; however, additional research is needed because the type and dose of soluble fiber most effective in treating and preventing these types of diarrhea are unknown. This article is limited to recommendations for chemotherapy- and radiotherapy-induced diarrhea. The chemotherapy regimens included in most of the studies reviewed were the commonly used regimens containing drugs such as fluorouracil, cisplatin, adriamycin, and irinotecan.
C1 [Muehlbauer, Paula M.] San Diego VA Healthcare Syst, San Diego, CA USA.
[Thorpe, Deborah] Univ Utah, Pain Med & Palliat Care Program, Huntsman Canc Inst, Salt Lake City, UT USA.
[Davis, Arlene; Kiker, Elizabeth] N Florida S Georgia Vet Hlth Syst, Gainesville, FL USA.
[Drabot, Rachael; Rawlings, Barbara L.] NIH, Bethesda, MD 20892 USA.
RP Muehlbauer, PM (reprint author), San Diego VA Healthcare Syst, San Diego, CA USA.
EM paula.muehlbauer@gmail.com
NR 26
TC 13
Z9 16
U1 0
U2 8
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 1092-1095
J9 CLIN J ONCOL NURS
JI Clin. J. Oncol. Nurs.
PD JUN
PY 2009
VL 13
IS 3
BP 336
EP 341
DI 10.1188/09.CJON.336-341
PG 6
WC Oncology; Nursing
SC Oncology; Nursing
GA 456MB
UT WOS:000266849500020
PM 19502193
ER
PT J
AU Young, JM
Terrin, N
Wang, XL
Greene, T
Beck, GJ
Kusek, JW
Collins, AJ
Sarnak, MJ
Menon, V
AF Young, Jill Melendez
Terrin, Norma
Wang, Xuelei
Greene, Tom
Beck, Gerald J.
Kusek, John W.
Collins, Allan J.
Sarnak, Mark J.
Menon, Vandana
TI Asymmetric Dimethylarginine and Mortality in Stages 3 to 4 Chronic
Kidney Disease
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
CT 40th Annual Meeting of the American-Society-of-Nephrology/Annual Renal
Week
CY OCT 31-NOV 05, 2007
CL San Francisco, CA
SP Amer Soc Nephrol
ID INTIMA-MEDIA THICKNESS; RENAL-DISEASE; ENDOTHELIAL DYSFUNCTION;
CARDIOVASCULAR MORBIDITY; MYOCARDIAL-INFARCTION; DIABETIC-NEPHROPATHY;
PLASMA-CONCENTRATION; INSULIN-RESISTANCE; ADMA; PROGRESSION
AB Background and objectives: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, reduces bioavailability of nitric oxide and induces endothelial dysfunction. This dimethylated amino acid accumulates in chronic kidney disease and may be involved in the pathophysiology of cardiovascular disease (CVD) in this population.
Design, settings, participants, & methods: The Modification of Diet in Renal Disease Study was a randomized, controlled trial conducted between 1989 and 1993. We measured ADMA in frozen samples collected at baseline (n = 820) and obtained survival status, up to December 31, 2000, from the National Death Index. We examined the relationship of ADMA with prevalent CVD and performed multivariable Cox models to examine the relationship of ADMA with all-cause and CVD mortality.
Results: Mean (SD) age was 52 (12) yr, GFR was 32 +/- 12 ml/min per 1.73 m(2), and ADMA was 0.70 +/- 0.25 mu mol/L. A 1-SD increase in ADMA was associated with a 31% increased odds of prevalent CVD in an adjusted logistic regression model. During the 10-yr follow-up period, 202 (25%) participants died of any cause, 122 (15%) from CVD, and 545 (66%) reached kidney failure. In multivariable Cox models, a 1-SD increase in ADMA was associated with a 9% increased risk for all-cause and 19% increased risk for CVD mortality.
Conclusions: In this cohort of patients with predominantly nondiabetic, stages 3 to 4 chronic kidney disease, there was a strong association of ADMA with prevalent CVD and a modest association with all-cause and CVD mortality. Clin J Am Soc Nephrol 4: 1115-1120, 2009. doi: 10.2215/CJN.06671208
C1 [Young, Jill Melendez; Sarnak, Mark J.; Menon, Vandana] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA 02111 USA.
[Terrin, Norma] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA.
[Wang, Xuelei; Beck, Gerald J.] Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA.
[Greene, Tom] Univ Utah, Div Clin Epidemiol, Salt Lake City, UT USA.
[Kusek, John W.] NIH, Bethesda, MD 20892 USA.
[Collins, Allan J.] Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA.
RP Menon, V (reprint author), Tufts Med Ctr, Dept Med, Div Nephrol, 750 Washington St 391, Boston, MA 02111 USA.
EM vmenon@tufts-nemc.org
FU NIDDK NIH HHS [K23 DK002904, K23 DK02904, K23 DK067303, K24 DK078204]
NR 31
TC 48
Z9 49
U1 0
U2 1
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 JUN
PY 2009
VL 4
IS 6
BP 1115
EP 1120
DI 10.2215/CJN.06671208
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 451OD
UT WOS:000266478600015
PM 19389824
ER
PT J
AU Montello, M
Mooney, M
Denicoff, A
Adler, J
Goldberg, J
Abrams, J
AF Montello, Mike
Mooney, Margaret
Denicoff, Andrea
Adler, Jeanne
Goldberg, Jacquelyn
Abrams, Jeffrey
TI National Cancer Institute-Sponsored Cooperative Groups: Changing Process
to Speed Progress
SO CLINICAL LYMPHOMA & MYELOMA
LA English
DT Editorial Material
ID CLINICAL-TRIALS
C1 [Montello, Mike; Mooney, Margaret; Denicoff, Andrea; Adler, Jeanne; Goldberg, Jacquelyn; Abrams, Jeffrey] NIH, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Montello, M (reprint author), NIH, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bldg 10, Bethesda, MD 20892 USA.
NR 6
TC 0
Z9 0
U1 0
U2 0
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1557-9190
J9 CLIN LYMPHOMA MYELOM
JI Clin. Lymphoma Myeloma
PD JUN
PY 2009
VL 9
IS 3
BP 194
EP 196
DI 10.3816/CLM.2009.n.040
PG 3
WC Oncology
SC Oncology
GA 456OW
UT WOS:000266857500001
PM 19525187
ER
PT J
AU Mani, H
Jaffe, ES
AF Mani, Haresh
Jaffe, Elaine S.
TI Hodgkin Lymphoma: An Update on its Biology with New Insights into
Classification
SO CLINICAL LYMPHOMA & MYELOMA
LA English
DT Review
DE Classical Hodgkin's lymphoma; Epstein-Barr virus; HIV; Immunophenotype;
Nodular lymphocyte-predominant disease; Primary mediastinal large B-cell
lymphoma
ID REED-STERNBERG CELLS; EPSTEIN-BARR-VIRUS; CENTER B-CELL; EUROPEAN
TASK-FORCE; REGULATORY T-CELLS; TRANSCRIPTION FACTORS; IMMUNOGLOBULIN
TRANSCRIPTION; TISSUE MICROARRAY; PROGNOSTIC-SIGNIFICANCE;
DIFFERENTIAL-DIAGNOSIS
AB In the past few years, there has been a greater understanding of the spectrum and biology of Hodgkin lymphoma (HL). In standard texts, HL is classified as 2 distinct entities, namely nodular lymphocyte-predominant HL and classical HL (CHL). However, recent evidence suggests that CHL is not a single disease. Although the mixed cellularity and lymphocyte-depleted subtypes might be part of a biologic continuum, the nodular sclerosis subtype has a distinct epidemiology, clinical presentation, and histology. Nodular sclerosis HL might also be related to primary mediastinal B-cell lymphoma and mediastinal gray-zone lymphomas. We present an update on the pathobiology of HL and discuss these biologic and clinical differences in this review.
C1 [Mani, Haresh; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Jaffe, ES (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM ejaffe@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute
FX This work was prepared with the support of the Center for Cancer
Research, National Cancer Institute.
NR 204
TC 48
Z9 53
U1 0
U2 5
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1557-9190
J9 CLIN LYMPHOMA MYELOM
JI Clin. Lymphoma Myeloma
PD JUN
PY 2009
VL 9
IS 3
BP 206
EP 216
DI 10.3816/CLM.2009.n.042
PG 11
WC Oncology
SC Oncology
GA 456OW
UT WOS:000266857500008
PM 19525189
ER
PT J
AU Miranda, PC
Faria, P
Hallett, M
AF Miranda, Pedro Cavaleiro
Faria, Paula
Hallett, Mark
TI What does the ratio of injected current to electrode area tell us about
current density in the brain during tDCS?
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Stimulation; Electric; Current density; Direct current; Polarization;
Transcranial; tDCS
ID DIRECT-CURRENT STIMULATION; HUMAN MOTOR CORTEX; EXCITABILITY;
POLARIZATION; SAFETY
AB Objective: To examine the relationship between the ratio of injected current to electrode area (I/A) and the current density at a fixed target point in the brain under the electrode during transcranial direct current stimulation (tDCS).
Methods: Numerical methods were used to calculate the current density distribution in a standard spherical head model as well as in a homogeneous cylindrical conductor.
Results: The calculations using the cylindrical model showed that, for the same I/A ratio, the current density at a fixed depth under the electrode was lower for the smaller of the two electrodes. Using the spherical model, the current density at a fixed target point in the brain under the electrode was found to be a non-linear function of the I/A ratio. For smaller electrodes, more current than predicted by the I/A ratio was required to achieve a predetermined current density in the brain.
Conclusions: A non-linear relationship exists between the injected current, the electrode area and the current density at a fixed target point in the brain, which can be described in terms of a montage-specific I-A curve.
Significance: I-A curves calculated using realistic head models or obtained experimentally should be used when adjusting the current for different electrode sizes or when comparing the effect of different current-electrode area combinations. (C) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Miranda, Pedro Cavaleiro; Faria, Paula] Univ Lisbon, Fac Ciencias, Inst Biofis & Engn Biomed, P-1749016 Lisbon, Portugal.
[Faria, Paula] Polytech Inst Leiria, Sch Technol & Management, Leiria, Portugal.
[Hallett, Mark] NINDS, Human Motor Control Sect, MNB, NIH, Bethesda, MD 20892 USA.
RP Miranda, PC (reprint author), Univ Lisbon, Fac Ciencias, Inst Biofis & Engn Biomed, Campo Grande, P-1749016 Lisbon, Portugal.
EM pcmiranda@fc.ul.pt
RI Miranda, Pedro/A-5643-2013;
OI Miranda, Pedro/0000-0002-6793-8111; Faria, Paula/0000-0003-1474-9496
FU NIH; Foundation for Science and Technology (FCT), Portugal
[SFRH/BD/29020/2006]
FX This work was supported in part by the NIH Intramural Program, USA and
by the Foundation for Science and Technology (FCT), Portugal. Paula
Faria gratefully acknowledges the support of FCT under Grant
SFRH/BD/29020/2006.
NR 12
TC 77
Z9 78
U1 0
U2 10
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 JUN
PY 2009
VL 120
IS 6
BP 1183
EP 1187
DI 10.1016/j.clinph.2009.03.023
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 463WT
UT WOS:000267464800024
PM 19423386
ER
PT J
AU Russmann, H
Lamy, JC
Shamim, EA
Meunier, S
Hallett, M
AF Russmann, Heike
Lamy, Jean-Charles
Shamim, Ejaz A.
Meunier, Sabine
Hallett, Mark
TI Associative plasticity in intracortical inhibitory circuits in human
motor cortex
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Plasticity; Transcranial magnetic stimulation; GABAergic inhibitory
interneurones; Motor cortex; Sensorimotor coupling
ID TRANSCRANIAL MAGNETIC STIMULATION; SILENT PERIOD; CORTICAL EXCITABILITY;
WRITERS CRAMP; FACILITATION; MODULATION; THRESHOLD; DYSTONIA;
CONTRACTION; MECHANISMS
AB Objective: Paired associative stimulation (PAS) is a transcranial magnetic stimulation technique inducing Hebbian-like synaptic plasticity in the human motor cortex (M 1). PAS is produced by repetitive pairing of a peripheral nerve shock and a transcranial magnetic stimulus (TMS). Its effect is assessed by a change in size of a motor evoked response (MEP). MEP size results from excitatory and inhibitory influences exerted on cortical pyramidal cells, but no robust effects on inhibitory networks have been demonstrated so far.
Method: In 38 healthy volunteers, we assessed whether a PAS intervention influences three intracortical inhibitory circuits: short (SICI) and long (LICI) intracortical inhibitions reflecting activity of GABA(A) and GABA(B) interneurons, respectively, and long afferent inhibition (LAI) reflecting activity of somatosensory inputs.
Results: After PAS, MEP sizes, LICI and LAI levels were significantly changed while changes of SICI were inconsistent. The changes in LICI and LAI lasted 45 min after PAS. Their direction depended on the delay between the arrival time of the afferent volley at the cortex and the TMS-induced cortical activation during the PAS.
Conclusions: PAS influences inhibitory circuits in M1.
Significance: PAS Paradigms can demonstrate Hebbian-like plasticity at selected inhibitory networks as well as excitatory networks. (C) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Russmann, Heike] CHU Vaudois, Dept Neurol, CH-1011 Lausanne, Switzerland.
[Russmann, Heike; Lamy, Jean-Charles; Shamim, Ejaz A.; Meunier, Sabine; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Meunier, Sabine] Univ Paris 06, ER6, F-75005 Paris, France.
RP Russmann, H (reprint author), CHU Vaudois, Dept Neurol, BH 07,11 Route Bugnon, CH-1011 Lausanne, Switzerland.
EM Heike.Russmann@chuv.ch
RI meunier, sabine/G-7622-2014
OI meunier, sabine/0000-0002-6167-4602
FU Intramural NIH HHS [Z01 NS003031-01]
NR 52
TC 41
Z9 41
U1 0
U2 6
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 JUN
PY 2009
VL 120
IS 6
BP 1204
EP 1212
DI 10.1016/j.clinph.2009.04.005
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 463WT
UT WOS:000267464800027
PM 19435676
ER
PT J
AU Zeuner, KE
Peller, M
Knutzen, A
Groppa, S
Holler, I
Kopper, F
Raethjen, J
Dressler, D
Hallett, M
Deuschl, G
Siebner, HR
AF Zeuner, K. E.
Peller, M.
Knutzen, A.
Groppa, S.
Holler, I.
Kopper, F.
Raethjen, J.
Dressler, D.
Hallett, M.
Deuschl, G.
Siebner, H. R.
TI Slow pre-movement cortical potentials do not reflect individual response
to therapy in writer's cramp
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Movement-related cortical potentials MRCP; Bereitschaftspotential;
Writer's cramp; Task-specific dystonia; Immobilization; Motor training
ID FOCAL HAND DYSTONIA; VOLUNTARY MUSCLE-RELAXATION; SUPPLEMENTARY MOTOR
AREA; FORCE PRODUCTION; BOTULINUM TOXIN; BASAL GANGLIA; HUMAN BRAIN;
ACTIVATION; IMMOBILIZATION; REORGANIZATION
AB Objective: To investigate whether movement-related cortical potentials (MRCP) provide a physiological correlate that indicates the response to treatment in patients with writer's cramp,
Methods: In 21 patients with writer's cramp, who underwent 4 weeks of limb immobilization followed by re-training for 8 weeks, we recorded MRCPs preceding a self-initiated brisk finger abduction movement. MRCP measurements of pre-movement activity were performed at baseline, after the end of immobilization and four and 8 weeks of re-training. We examined 12 controls, who received no intervention, twice 4 weeks apart.
Results: Patients benefited from the therapeutical intervention (Zeuner et al., 2008). They showed no abnormalities of the MRCPs at baseline. In controls, MRCPs did not significantly change after 4 weeks. In patients, immobilization and re-training had no effect on MRCPs. There was no correlation between the severity of dystonic symptoms or the individual treatment response and MRCPs.
Conclusion: MRCPs are stable measures for interventional studies. However, they do not reflect clinical severity of dystonic symptoms or improvement after therapeutic interventions.
Significance: This is the first study to investigate MRCPs in a large cohort of patients with writer's cramp compared to a control group at different time points. These potentials do not reflect the motor control disorder in patients with writer's cramp. (C) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Zeuner, K. E.; Peller, M.; Knutzen, A.; Groppa, S.; Holler, I.; Kopper, F.; Raethjen, J.; Deuschl, G.; Siebner, H. R.] Univ Kiel, Dept Neurol, D-24105 Kiel, Germany.
[Siebner, H. R.] Hvidovre Univ Hosp, Danish Res Ctr Magnet Resonance, Copenhagen, Denmark.
[Dressler, D.] Hannover Med Sch, Dept Neurol, D-3000 Hannover, Germany.
[Hallett, M.] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Zeuner, KE (reprint author), Univ Kiel, Dept Neurol, Arnold Heller Str 3,Haus 41, D-24105 Kiel, Germany.
EM k.zeuner@neurologie.uni-kiel.de
RI Deuschl, Gunther/A-7986-2010; Groppa, Sergiu/G-4606-2014; Siebner,
Hartwig/G-4052-2016
NR 49
TC 2
Z9 2
U1 0
U2 0
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 JUN
PY 2009
VL 120
IS 6
BP 1213
EP 1219
DI 10.1016/j.clinph.2009.04.010
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 463WT
UT WOS:000267464800028
PM 19447675
ER
PT J
AU Hebert, MF
Ma, X
Naraharisetti, SB
Krudys, KM
Umans, JG
Hankins, GDV
Caritis, SN
Miodovnik, M
Mattison, DR
Unadkat, JD
Kelly, EJ
Blough, D
Cobelli, C
Ahmed, MS
Snodgrass, WR
Carr, DB
Easterling, TR
Vicini, P
AF Hebert, M. F.
Ma, X.
Naraharisetti, S. B.
Krudys, K. M.
Umans, J. G.
Hankins, G. D. V.
Caritis, S. N.
Miodovnik, M.
Mattison, D. R.
Unadkat, J. D.
Kelly, E. J.
Blough, D.
Cobelli, C.
Ahmed, M. S.
Snodgrass, W. R.
Carr, D. B.
Easterling, T. R.
Vicini, P.
CA Obstet Fetal Pharmacol Res Unit Ne
TI Are We Optimizing Gestational Diabetes Treatment With Glyburide? The
Pharmacologic Basis for Better Clinical Practice
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID NORMAL GLUCOSE-TOLERANCE; INSULIN SENSITIVITY; MINIMAL MODEL;
LONGITUDINAL CHANGES; PREGNANCY OUTCOMES; OBESE WOMEN; IN-VITRO;
PHARMACOKINETICS; MELLITUS; GLIBENCLAMIDE
AB Glyburide's pharmacokinetics (PK) and pharmacodynamics have not been studied in women with gestational diabetes mellitus (GDM). The objective of this study was to assess steady-state PK of glyburide, as well as insulin sensitivity, beta-cell responsivity, and overall disposition indices after a mixed-meal tolerance test (MMTT) in women with GDM (n = 40), nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 26), and healthy pregnant women (n = 40, MMTT only). At equivalent doses, glyburide plasma concentrations were similar to 50% lower in pregnant women than in nonpregnant subjects. The average umbilical cord/maternal plasma glyburide concentration ratio at the time of delivery was 0.7 +/- 0.4. Insulin sensitivity was approximately fivefold lower in women with GDM as compared with healthy pregnant women. Despite comparable beta-cell responsivity indices, the average beta-cell function corrected for insulin resistance was more than 3.5-fold lower in women with glyburide-treated GDM than in healthy pregnant women. Women with GDM in whom glyburide treatment has failed may benefit from alternative medication or dosage escalation; however, fetal safety should be kept in mind.
C1 [Hebert, M. F.; Blough, D.] Univ Washington, Dept Pharm, Seattle, WA 98195 USA.
[Ma, X.; Krudys, K. M.; Vicini, P.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA.
[Hebert, M. F.; Carr, D. B.; Easterling, T. R.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
[Naraharisetti, S. B.; Unadkat, J. D.; Kelly, E. J.] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA.
[Umans, J. G.; Miodovnik, M.] Washington Hosp Ctr, MedStar Res Inst, Washington, DC 20010 USA.
[Umans, J. G.; Miodovnik, M.] Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA.
[Caritis, S. N.] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA.
[Hankins, G. D. V.; Ahmed, M. S.; Snodgrass, W. R.] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX USA.
[Cobelli, C.] Univ Padua, Dipartimento Elettron & Informat, I-35131 Padua, Italy.
[Mattison, D. R.] NICHHD, NIH, Rockville, MD USA.
RP Hebert, MF (reprint author), Univ Washington, Dept Pharm, Seattle, WA 98195 USA.
EM mhebert@u.washington.edu
RI Mattison, Donald/L-4661-2013;
OI Mattison, Donald/0000-0001-5623-0874; caritis, steve/0000-0002-2169-0712
FU National Institutes of Health (NIH)/National Institute of Child Health
and Human [U10HD047892, U10HD047905, U10HD047890, U10HD047891];
NIH/National Center for Research Resources [UL1RR025014, M01RR00037,
M01RR023942, P41EB001975]
FX This work was supported by National Institutes of Health (NIH)/National
Institute of Child Health and Human Development grants U10HD047892,
U10HD047905, U10HD047890, and U10HD047891, as well as NIH/National
Center for Research Resources grants UL1RR025014, M01RR00037,
M01RR023942, and P41EB001975.
NR 49
TC 88
Z9 93
U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD JUN
PY 2009
VL 85
IS 6
BP 607
EP 614
DI 10.1038/clpt.2009.5
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 448VL
UT WOS:000266290000015
PM 19295505
ER
PT J
AU Merikangas, KR
Pato, M
AF Merikangas, Kathleen R.
Pato, Michael
TI Recent Developments in the Epidemiology of Bipolar Disorder in Adults
and Children: Magnitude, Correlates, and Future Directions
SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE
LA English
DT Article
DE bipolar disorder; future directions; prevalence; risk factors
ID DSM-IV DISORDERS; DEFICIT HYPERACTIVITY DISORDER; COMORBIDITY SURVEY
REPLICATION; COMMON MENTAL-DISORDERS; 12-MONTH PREVALENCE;
PSYCHIATRIC-DISORDERS; LIFETIME PREVALENCE; MOOD DISORDERS;
YOUNG-ADULTS; II DISORDER
AB During the past decade, there has been increasing recognition of the dramatic personal and societal impact of bipolar disorder I and II (DSM-IV). The estimated disability-adjusted life years of bipolar disorder outrank all cancers and primary neurologic disorders, such as epilepsy and Alzheimer's disease, primarily because of its early onset and chronicity across the lifespan (World Health Report, 2002). The results of numerous international epidemiologic surveys using contemporary diagnostic criteria have strengthened the evidence base on the magnitude, correlates, and consequences of bipolar disorder in representative samples of the general population. Epidemiologic research has also demonstrated the differences between clinical and community samples in terms of demographic factors, comorbidity, patterns of onset, severity, treatment utilization, and response. The aims of this article are (a) to summarize the magnitude of the prevalence of bipolar disorder in adults and children through a comprehensive review of DSM-IV bipolar disorder in the general population; (b) to describe the risk factors and correlates of bipolar disorder in community surveys; and (c) to describe the future directions for the field of epidemiology of bipolar disorder.
C1 [Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, Mood & Anxiety Disorders Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, Mood & Anxiety Disorders Program, Intramural Res Program,NIH, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM kathleen.merikangas@nih.gov
NR 93
TC 28
Z9 28
U1 2
U2 9
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0969-5893
J9 CLIN PSYCHOL-SCI PR
JI Clin. Psychol.-Sci. Pract.
PD JUN
PY 2009
VL 16
IS 2
BP 121
EP 133
PG 13
WC Psychology, Clinical
SC Psychology
GA 457IT
UT WOS:000266922400004
ER
PT J
AU Meister, M
Choyke, P
Anderson, C
Patel, U
AF Meister, M.
Choyke, P.
Anderson, C.
Patel, U.
TI Radiological evaluation, management, and surveillance of renal masses in
Von Hippel-Lindau disease
SO CLINICAL RADIOLOGY
LA English
DT Review
ID PARENCHYMAL SPARING SURGERY; BOSNIAK CATEGORY-III; CELL CARCINOMA; VHL
GENE; RADIOFREQUENCY ABLATION; PROGNOSTIC-SIGNIFICANCE; IMAGING
FEATURES; TUMOR SIZE; CANCER; CT
AB Von Hippel-Lindau disease (VHL) is a rare, autosomal-dominant condition that predisposes patients to developing renal cysts and tumours. VHL is the most common of the hereditary renal cancer syndromes, and is exclusively associated with the clear cell histological subtype of renal cell carcinoma. This review focuses on the genetics, surveillance, and management of complex renal masses in VHL. The current status of renal cyst analysis in general. and in the context of VHL is also reviewed. (C) 2008 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
C1 [Meister, M.; Patel, U.] St George Hosp, Dept Radiol, London SW17 0QT, England.
[Choyke, P.] St George Hosp, Dept Urol, London SW17 0QT, England.
[Anderson, C.] NIH, Dept Radiol, Bethesda, MD 20892 USA.
RP Patel, U (reprint author), St George Hosp, Dept Radiol, Blackshaw Rd, London SW17 0QT, England.
EM uday.patel@stgeorges.nhs.uk
NR 53
TC 19
Z9 20
U1 1
U2 4
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0009-9260
J9 CLIN RADIOL
JI Clin. Radiol.
PD JUN
PY 2009
VL 64
IS 6
BP 589
EP 600
DI 10.1016/j.crad.2008.10.010
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 455UK
UT WOS:000266791700003
PM 19414081
ER
PT J
AU Korrchoubey, B
Kaiser, J
Bostanov, V
Lutzenberger, W
Birbaumer, N
AF Korrchoubey, Boris
Kaiser, Jochen
Bostanov, Vladimir
Lutzenberger, Werner
Birbaumer, Niels
TI Recognition of affective prosody in brain-damaged patients and healthy
controls: A neurophysiological study using EEG and whole-head MEG
SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE
LA English
DT Review
ID AMYOTROPHIC-LATERAL-SCLEROSIS; EVENT-RELATED POTENTIALS; MINIMALLY
CONSCIOUS STATE; HUMAN AUDITORY-CORTEX; MISMATCH NEGATIVITY; EMOTIONAL
PROSODY; SENTENCE COMPREHENSION; SYNTACTIC VIOLATIONS; VEGETATIVE STATE;
RIGHT-HEMISPHERE
AB A passive oddball experiment was used in which stimuli were emotional exclamations differing in their affective tone. In both electroencephalography (EEG) and magnetoencephalography (MEG), deviants elicited an N300 component, sometimes accompanied by a slow wave. Both components had a symmetrical distribution, but the former was more posterior than the latter. The same responses to prosodic stimuli were significant in 6 of 27 patients with severe disorders of consciousness (persistent vegetative state and minimally conscious state) and in all 3 of the examined locked-in patients, indicating that the procedure can be applied for testing neurological patients. The occurrence of significant responses depended on the presence or absence of a lesion to the right temporal lobe. Obviously, the N300 depends on the activity of the right temporal cortex but does not originate there. We suggest that the component is related not to the recognition of affective prosody as such, but to the following detection of affective mismatch due to violations of emotional context of stimulation.
C1 [Korrchoubey, Boris] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany.
[Kaiser, Jochen] Univ Frankfurt, Frankfurt, Germany.
[Birbaumer, Niels] NIH, Washington, DC USA.
RP Korrchoubey, B (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72074 Tubingen, Germany.
EM boris.kotchoubey@uni-tuebingen.de
FU German Research Society (DFG)
FX We regret to note that Professor Lutzenberger died 2 days after the
manuscript was accepted. The study was supported by the German Research
Society (DFG). The authors thank Christoph Braun (University of
Tubingen), Manfred Schneck (Munster Clinics Zwiefalten), Dieter
Schmalohr (Youth Rehabilitation Center at Gailingen), Gerhard Mezger
(Hospital for Neurorehabilitation, Wangen Allgau), and Simone Lang
(University of Heidelberg), as well as all our patients. Correspondence
concerning this article should be addressed to B. Kotchoubey, Institute
of Medical Psychology and Behavioral Neurobiology, University of
Tubingen, Gartenstr. 29, 72074 Tubingen, Germany (e-mail:
boris.kotchoubey@uni-tuebingen.de).
NR 129
TC 0
Z9 0
U1 2
U2 8
PU PSYCHONOMIC SOC INC
PI AUSTIN
PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA
SN 1530-7026
J9 COGN AFFECT BEHAV NE
JI Cogn. Affect. Behav. Neurosci.
PD JUN
PY 2009
VL 9
IS 2
BP 153
EP 167
DI 10.3758/CABN.9.2.153
PG 15
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 439ZE
UT WOS:000265666100003
ER
PT J
AU Hansen, L
Lee, EA
Hestir, K
Williams, LT
Farrelly, D
AF Hansen, Loren
Lee, Ernestine A.
Hestir, Kevin
Williams, Lewis T.
Farrelly, David
TI Controlling Feature Selection in Random Forests of Decision Trees Using
a Genetic Algorithm: Classification of Class I MHC Peptides
SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
LA English
DT Article
DE Decision trees; random forests; feature selection; genetic algorithms;
evolutionary computation
ID T-CELL EPITOPES; BINDING-AFFINITY; PREDICTION
AB Feature selection is an important challenge in many classification problems, especially if the number of features greatly exceeds the number of examples available. We have developed a procedure - GenForest - which controls feature selection in random forests of decision trees by using a genetic algorithm. This approach was tested through our entry into the Comparative Evaluation of Prediction Algorithms 2006 (CoEPrA) competition (accessible online at: http://www.coepra.org). CoEPrA was a modeling competition organized to provide an objective testing for various classification and regression algorithms via the process of blind prediction. In the competition GenForest ranked 10/23, 5/16 and 9/16 on CoEPrA classification problems 1, 3 and 4, respectively, which involved the classification of type I MHC nonapeptides i.e. peptides containing nine amino acids. These problems each involved the classification of different sets of nonapeptides. Associated with each amino acid was a set of 643 features for a total of 5787 features per peptide. The method, its application to the CoEPrA datasets, and its performance in the competition are described.
C1 [Hansen, Loren] Boston Univ, Program Bioinformat, Boston, MA 02215 USA.
[Lee, Ernestine A.; Hestir, Kevin; Williams, Lewis T.] FivePrime Therapeut, San Francisco, CA 94158 USA.
[Farrelly, David] Utah State Univ, Dept Chem & Biochem, Logan, UT 84322 USA.
[Farrelly, David] Univ Autonoma Madrid, Dept Quim, E-28049 Madrid, Spain.
RP Hansen, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM hansenlo@ncbi.nlm.nih.gov
FU National Science Foundation [0202185, 0718547]; MEC-Spain [SAB
2006-0086]
FX The work was supported, in part, by the National Science Foundation
though grants 0202185 and 0718547 to Utah State University and by
MEC-Spain, under contract - SAB 2006-0086.
NR 20
TC 7
Z9 7
U1 0
U2 5
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1386-2073
J9 COMB CHEM HIGH T SCR
JI Comb. Chem. High Throughput Screen
PD JUN
PY 2009
VL 12
IS 5
BP 514
EP 519
PG 6
WC Biochemical Research Methods; Chemistry, Applied; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
GA 452FS
UT WOS:000266526200008
PM 19519331
ER
PT J
AU Sturm, A
George, SS
Dean, M
Cunningham, P
Treuner-Freeman, A
AF Sturm, Armin
George, Stephen S.
Dean, Michael
Cunningham, Phil
Treuner-Freeman, Anke
TI ABC transporters in the Daphnia pulex genome: implications for
ecotoxicology and drug resistance in crustacean parasites
SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE
PHYSIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Experimental-Biology
CY JUN 28-JUL 01, 2009
CL Glasgow, SCOTLAND
SP Soc Expt Biol
C1 [Sturm, Armin; George, Stephen S.; Treuner-Freeman, Anke] Univ Stirling, Inst Aquaculture, Stirling FK9 4LA, Scotland.
[Dean, Michael] NCI, Frederick, MD 21701 USA.
[Cunningham, Phil] Kings Coll London, London, England.
EM armin.sturm@stir.ac.uk
NR 0
TC 3
Z9 3
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1095-6433
J9 COMP BIOCHEM PHYS A
JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol.
PD JUN
PY 2009
VL 153A
IS 2
BP S109
EP S109
DI 10.1016/j.cbpa.2009.04.154
PG 1
WC Biochemistry & Molecular Biology; Physiology; Zoology
SC Biochemistry & Molecular Biology; Physiology; Zoology
GA 464QM
UT WOS:000267520700199
ER
PT J
AU Cohen, JI
AF Cohen, Jeffrey I.
TI Cytomegalovirus in the intensive care unit: Pathogen or passenger?
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE cytomegalovirus; reactivation; intensive care unit; herpesvirus;
prophylaxis
ID CRITICALLY-ILL PATIENTS; TRANSPLANT RECIPIENTS; INFECTION; REACTIVATION;
DISEASE
C1 NIH, Med Virol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
RP Cohen, JI (reprint author), NIH, Med Virol Sect, Lab Clin Infect Dis, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA AI000058-35]
NR 17
TC 8
Z9 8
U1 0
U2 0
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 JUN
PY 2009
VL 37
IS 6
BP 2095
EP 2096
DI 10.1097/CCM.0b013e3181a5e725
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 448ZK
UT WOS:000266300300038
PM 19448451
ER
PT J
AU Compton, CC
AF Compton, Carolyn C.
TI Making Economic Sense of Cancer Biospecimen Banks
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Editorial Material
C1 NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA.
RP Compton, CC (reprint author), NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA.
EM comptcar@mail.nih.gov
NR 3
TC 1
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1752-8054
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD JUN
PY 2009
VL 2
IS 3
BP 172
EP 174
DI 10.1111/j.1752-8062.2008.00108.x
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 533RW
UT WOS:000272843300006
PM 20443887
ER
PT J
AU McBain, CJ
Kauer, JA
AF McBain, Chris J.
Kauer, Julie A.
TI Presynaptic plasticity: targeted control of inhibitory networks
SO CURRENT OPINION IN NEUROBIOLOGY
LA English
DT Review
ID LONG-TERM POTENTIATION; CELL-DEPENDENT PLASTICITY; SYNAPTIC PLASTICITY;
HIPPOCAMPAL INTERNEURONS; FEEDFORWARD INHIBITION; CANNABINOID RECEPTORS;
GABAERGIC SYNAPSES; RAT HIPPOCAMPUS; RELEASE SITES; DEPRESSION
AB GABAergic inhibitory interneurons are embedded in almost all central neuronal networks, where they act to influence cell excitability, spike timing, synchrony, and oscillatory activity, that is, almost every physiologically relevant process in the mammalian central nervous system. Consequently, presynaptic plasticity of the synaptic input onto, or the outputs from, a single inhibitory interneuron can have major ramifications for the activity of the often thousands of downstream target neurons. Here we discuss several recently described forms of presynaptic long-term potentiation (LTP) and long-term depression (LTD) occurring at synapses either made onto inhibitory interneurons, or at inhibitory synapses onto downstream targets in a number of central structures. As we will illustrate, the induction mechanisms underlying these disparate examples of presynaptic plasticity share few common features, however, their expression mechanisms converge on the presynaptic release machinery. We hypothesize that these varied forms of presynaptic plasticity can operate in a manner fundamentally distinct from most postsynaptic 'point to point' forms of plasticity, to achieve powerful modification of the integration and output of large-scale networks.
C1 [McBain, Chris J.] NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA.
[Kauer, Julie A.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
[Kauer, Julie A.] Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA.
RP McBain, CJ (reprint author), NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bldg 35, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA HD001205-18]; NIDA NIH HHS [R01 DA011289-13, R01
DA011289-08, R01 DA011289-11S1, R01 DA011289-09A1, R01 DA011289, R01
DA011289-12, R01 DA011289-10, R01 DA011289-11]; NINDS NIH HHS [R01
NS050570-01A1, R01 NS050570-02, R01 NS050570, R01 NS050570-04, R01
NS050570-03]
NR 50
TC 40
Z9 40
U1 0
U2 7
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-4388
J9 CURR OPIN NEUROBIOL
JI Curr. Opin. Neurobiol.
PD JUN
PY 2009
VL 19
IS 3
BP 254
EP 262
DI 10.1016/j.conb.2009.05.008
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 493VC
UT WOS:000269765400004
PM 19581079
ER
PT J
AU Ruder, EH
Hartman, TJ
Goldman, MB
AF Ruder, Elizabeth H.
Hartman, Terryl J.
Goldman, Marlene B.
TI Impact of oxidative stress on female fertility
SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY
LA English
DT Article
DE antioxidants; female infertility; oxidative stress
ID POLYCYSTIC-OVARY-SYNDROME; PREOVULATORY FOLLICULAR-FLUID; VITAMIN-E;
REACTIVE OXYGEN; ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; WOMEN;
MELATONIN; INFERTILITY; RISK
AB Purpose of review
To review the role of oxidative stress in the context of female fertility.
Recent findings
Oxidative stress is associated with decreased female fertility in animal and in-vitro models, but no studies to date have directly assessed the relationship in women. Exposures associated with oxidative stress and with evidence to influence the timing and maintenance of a viable pregnancy include pregnancy complications (e.g. preeclampsia) extremes of body weight, alcohol, tobacco, and caffeine intake. Intake of antioxidant nutrients, including use of multivitamins, impacts the generation of reactive oxygen species and may play a beneficial role in female fertility.
Summary
Infertility is a significant public health problem and diagnosis and treatment are stressful, invasive, and costly. The role of oxidative stress in female fertility is an understudied and compelling area for investigation. Identifying modifiable factors to decrease oxidative stress in the gynecologic environment may be an inexpensive and noninvasive therapy for increasing fertility.
C1 [Ruder, Elizabeth H.] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA.
[Hartman, Terryl J.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Goldman, Marlene B.] Dartmouth Med Sch, Dept Obstet & Gynecol & Community & Family Med, Lebanon, NH USA.
[Goldman, Marlene B.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
RP Ruder, EH (reprint author), NCI, Canc Prevent Fellowship Program, NIH, 6120 Execut Blvd,Room 150E,MSC 7105, Bethesda, MD 20892 USA.
EM eruder@jhsph.edu
FU National Institute of Child Health and Human Development [R01 HD049762]
FX The work described was supported by Grant Number R01 HD049762 from the
National Institute of Child Health and Human Development. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institute of Child Health
and Human Development or the National Institutes of Health.
NR 44
TC 51
Z9 55
U1 1
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-872X
J9 CURR OPIN OBSTET GYN
JI Curr. Opin. Obstet. Gynecol.
PD JUN
PY 2009
VL 21
IS 3
BP 219
EP 222
DI 10.1097/GCO.0b013e32832924ba
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 452YF
UT WOS:000266576400003
PM 19469044
ER
PT J
AU Schisterman, EF
Gaskins, AJ
Whitcomb, BW
AF Schisterman, Enrique F.
Gaskins, Audrey J.
Whitcomb, Brian W.
TI Effects of low-dose aspirin in in-vitro fertilization
SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY
LA English
DT Article
DE aspirin; implantation; in-vitro fertilization; pregnancy
ID OVARIAN RESPONSIVENESS; METAANALYSIS; PREGNANCY; IMPLANTATION;
CONSUMPTION; OUTCOMES; RATES; TIME; IVF
AB Purpose of review
In theory, use of aspirin in IVF is based on its anti-inflammatory, vasodilatory, and platelet aggregation inhibition properties, which improve blood flow to a woman's implantation site. It is hypothesized that this effect on blood flow will improve success rates.
Recent findings
Clinical studies investigating the use of low-dose aspirin (LDA) as an adjuvant therapy to IVF have produced conflicting results. The conflicting results have come as a consequence of the heterogeneous mixture of clinical trials with lack of adequate power. Even after multiple meta-analyses, differing estimates of effect were calculated as to whether aspirin should be used in conjunction with IVF.
Summary
Conflicting results leave the question of the effects of LIDA in IVF unanswered. More trials are required for analysis to have adequate statistical power and until then the data remain unclear. At this point, there are not enough data to show that aspirin has a beneficial effect on the outcomes of IVF, but absence of effect is not adequate grounds to overturn the current clinical practice for those using LDA in efforts aimed at achieving success with IVF
C1 [Schisterman, Enrique F.; Gaskins, Audrey J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Whitcomb, Brian W.] Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA.
RP Schisterman, EF (reprint author), 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM schistee@mail.nih.gov
OI Schisterman, Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This work was supported in part by an intramural contract with the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 16
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-872X
J9 CURR OPIN OBSTET GYN
JI Curr. Opin. Obstet. Gynecol.
PD JUN
PY 2009
VL 21
IS 3
BP 275
EP 278
DI 10.1097/GCO.0b013e32832a0673
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 452YF
UT WOS:000266576400013
PM 19300253
ER
PT J
AU Ludlow, CL
AF Ludlow, Christy L.
TI Treatment for spasmodic dysphonia: limitations of current approaches
SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY
LA English
DT Article
DE botulinum toxin injection; denervation; myectomy; reinnervation;
thyroplasty
ID BOTULINUM TOXIN INJECTIONS; ADDUCTOR SPASTIC DYSPHONIA; ESSENTIAL VOICE
TREMOR; TECHNOLOGY-ASSESSMENT SUBCOMMITTEE; LARYNGEAL NERVE RESECTION;
ACADEMY-OF-NEUROLOGY; NEUROTOXIN TYPE-A; TERM-FOLLOW-UP; LIFE V-RQOL;
MUSCLE-ACTIVITY
AB Purpose of review
Although botulinum toxin injection is the gold standard for treatment of spasmodic dysphonia, surgical approaches aimed at providing long-term symptom control have been advancing over recent years.
Recent findings
When surgical approaches provide greater long-term benefits to symptom control, they also increase the initial period of side effects of breathiness and swallowing difficulties. Recent analyses of quality-of-life questionnaires in patients undergoing regular injections of botulinum toxin demonstrate that a large proportion of patients have limited relief for relatively short periods due to early breathiness and loss-of-benefit before reinjection.
Summary
Most medical and surgical approaches to the treatment of spasmodic dysphonia have been aimed at denervation of the laryngeal muscles to block symptom expression in the voice, and have both adverse effects as well as treatment benefits. Research is needed to identify the central neuropathophysiology responsible for the laryngeal muscle spasms in order target treatment towards the central neurological abnormality responsible for producing symptoms.
C1 NINDS, Laryngeal & Speech Sect, Clin Neurosci Program, NIH, Bethesda, MD 20892 USA.
RP Ludlow, CL (reprint author), NINDS, Laryngeal & Speech Sect, Clin Neurosci Program, NIH, 10 Ctr Dr,MSC 1416, Bethesda, MD 20892 USA.
EM ludlowc@ninds.nih.gov
OI Ludlow, Christy/0000-0002-2015-6171
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke; NIH
FX Preparation of this review was supported by the Intramural Research
Program of the National Institute of Neurological Disorders and Stroke,
NIH.
NR 68
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U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1068-9508
J9 CURR OPIN OTOLARYNGO
JI Curr. Opin. Otolaryngol. Head Neck Surg.
PD JUN
PY 2009
VL 17
IS 3
BP 160
EP 165
DI 10.1097/MOO.0b013e32832aef6f
PG 6
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 452XQ
UT WOS:000266574900004
PM 19337127
ER
PT J
AU Nowotny, M
Yang, W
AF Nowotny, Marcin
Yang, Wei
TI Structural and functional modules in RNA interference
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Review
ID DSRNA-BINDING DOMAIN; ARGONAUTE SILENCING COMPLEX; COLI
RIBONUCLEASE-III; CRYSTAL-STRUCTURE; PAZ DOMAIN; MOLECULAR-BASIS;
MESSENGER-RNA; MICROPROCESSOR COMPLEX; SUBSTRATE-SPECIFICITY;
DROSHA-DGCR8 COMPLEX
AB RNA interference (RNAi) uses small RNA molecules to regulate transcriptional and post-transcriptional gene expression. In recent years, a number of structural studies provided insights into the molecular architecture and mechanism of functional modules of RNAi. Mechanisms of nucleic acid recognition and cleavage have been revealed by structural studies of proteins and their nucleic acid complexes involved in RNA biogenesis, for example, Argonaute, PIWI, RNase III, Dicer, Drosha, and DGCR8. While quite a few questions remain, an excellent structural and mechanistic overview of RNAi processes has already emerged. In this review, we examine functional modules and their assemblies in RNAi processes.
C1 [Nowotny, Marcin] Int Inst Mol & Cell Biol, Lab Prot Struct, PL-02109 Warsaw, Poland.
[Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Nowotny, M (reprint author), Int Inst Mol & Cell Biol, Lab Prot Struct, 4 Ks Trojdena St, PL-02109 Warsaw, Poland.
EM mnowotny@iimcb.gov.pl; wei.yang@nih.gov
RI Yang, Wei/D-4926-2011
OI Yang, Wei/0000-0002-3591-2195
FU NIDDK; NIH
FX W Yang is supported by NIDDK, NIH intramural research program. M Nowotny
is supported by the Wellcome Trust International Senior Research
Fellowship and the EMBO Installation Grant. We thank Dr R Craigic for
editing the manuscript.
NR 49
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U2 13
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD JUN
PY 2009
VL 19
IS 3
BP 286
EP 293
DI 10.1016/j.sbi.2009.04.006
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 468BF
UT WOS:000267787600007
PM 19477631
ER
PT J
AU Miller, M
AF Miller, Maria
TI The Importance of Being Flexible: The Case of Basic Region Leucine
Zipper Transcriptional Regulators
SO CURRENT PROTEIN & PEPTIDE SCIENCE
LA English
DT Review
DE bZIP proteins; transcription control; intrinsic disorder; molecular
recognition motifs; induced protein folding
ID INTRINSICALLY UNSTRUCTURED PROTEINS; NATIVELY UNFOLDED PROTEINS;
DNA-BINDING DOMAIN; NUCLEAR-LOCALIZATION SIGNALS; COILED-COIL;
TRANSACTIVATION DOMAIN; C/EBP-BETA; CRYSTAL-STRUCTURE; STRUCTURAL BASIS;
MOLECULAR RECOGNITION
AB Large volumes of protein sequence and structure data acquired by proteomic studies led to the development of computational bioinformatic techniques that made possible the functional annotation and structural characterization of proteins based on their primary structure. It has become evident from genome-wide analyses that many proteins in eukaryotic cells are either completely disordered or contain long unstructured regions that are crucial for their biological functions. The content of disorder increases with evolution indicating a possibly important role of disorder in the regulation of cellular systems. Transcription factors are no exception and several proteins of this class have recently been characterized as premolten/molten globules. Yet, mammalian cells rely on these proteins to control expression of their 30,000 or so genes. Basic region: leucine zipper (bZIP) DNA-binding proteins constitute a major class of eukaryotic transcriptional regulators. This review discusses how conformational flexibility "built" into the amino acid sequence allows bZIP proteins to interact with a large number of diverse molecular partners and to accomplish their manifold cellular tasks in a strictly regulated and coordinated manner.
C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
RP Miller, M (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
EM millerm@ncifcrf.gov
RI Miller, Maria/I-1636-2013
OI Miller, Maria/0000-0003-0252-5348
FU NIH, National Cancer Institute, Center for Cancer Research
FX I thank my colleagues from MCL for help and discussions, and Michael
Gribskov for many useful suggestions and thoughtful comments on the
manuscript. This work was supported by the Intramural Research Program
of NIH, National Cancer Institute, Center for Cancer Research.
NR 218
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U1 4
U2 16
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-2037
J9 CURR PROTEIN PEPT SC
JI Curr. Protein Pept. Sci.
PD JUN
PY 2009
VL 10
IS 3
BP 244
EP 269
PG 26
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 458UF
UT WOS:000267049300004
PM 19519454
ER
PT J
AU Persky, S
Kaphingst, KA
McCall, C
Lachance, C
Beall, AC
Blascovich, J
AF Persky, Susan
Kaphingst, Kimberly A.
McCall, Cade
Lachance, Christina
Beall, Andrew C.
Blascovich, Jim
TI Presence Relates to Distinct Outcomes in Two Virtual Environments
Employing Different Learning Modalities
SO CYBERPSYCHOLOGY & BEHAVIOR
LA English
DT Article
ID REALITY; STUDENTS; SCIENCE; GAME
AB Presence in virtual learning environments (VLEs) has been associated with a number of outcome factors related to a user's ability and motivation to learn. The extant but relatively small body of research suggests that a high level of presence is related to better performance on learning outcomes in VLEs. Different configurations of form and content variables such as those associated with active (self-driven, interactive activities) versus didactic (reading or lecture) learning may, however, influence how presence operates and on what content it operates. We compared the influence of presence between two types of immersive VLEs (i.e., active versus didactic techniques) on comprehension and engagement-related outcomes. The findings revealed that the active VLE promoted greater presence. Although we found no relationship between presence and learning comprehension outcomes for either virtual environment, presence was related to information engagement variables in the didactic immersive VLE but not the active environment. Results demonstrate that presence is not uniformly elicited or effective across immersive VLEs. Educational delivery mode and environment complexity may influence the impact of presence on engagement.
C1 [Persky, Susan; Kaphingst, Kimberly A.; Lachance, Christina] NHGRI, Bethesda, MD 20892 USA.
[McCall, Cade; Beall, Andrew C.; Blascovich, Jim] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA.
RP Persky, S (reprint author), NHGRI, 31 Ctr Dr,Rm B1B54D, Bethesda, MD 20892 USA.
EM perskys@mail.nih.gov
FU Intramural NIH HHS [Z99 HG999999, Z01 HG200321-03]
NR 30
TC 10
Z9 10
U1 3
U2 9
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1094-9313
J9 CYBERPSYCHOL BEHAV
JI CyberPsychol. Behav.
PD JUN
PY 2009
VL 12
IS 3
BP 263
EP 268
DI 10.1089/cpb.2008.0262
PG 6
WC Communication; Psychology, Applied
SC Communication; Psychology
GA 455BH
UT WOS:000266730000003
PM 19366319
ER
PT J
AU Liljegren, SJ
Leslie, ME
Darnielle, L
Lewis, MW
Taylor, SM
Luo, RB
Geldner, N
Chory, J
Randazzo, PA
Yanofsky, MF
Ecker, JR
AF Liljegren, Sarah J.
Leslie, Michelle E.
Darnielle, Lalitree
Lewis, Michael W.
Taylor, Sarah M.
Luo, Ruibai
Geldner, Niko
Chory, Joanne
Randazzo, Paul A.
Yanofsky, Martin F.
Ecker, Joseph R.
TI Regulation of membrane trafficking and organ separation by the NEVERSHED
ARF-GAP protein
SO DEVELOPMENT
LA English
DT Article
DE Membrane trafficking; ARF-GAP; Abscission; Floral organ shedding; Flower
development; Arabidopsis; Golgi; Paramural; Exosome
ID GTPASE-ACTIVATING PROTEIN; TRANS-GOLGI NETWORK; ADP-RIBOSYLATION FACTOR;
ABSCISSION ZONE CELLS; DOMAIN FACTOR AGL15; ARABIDOPSIS-THALIANA;
V-ATPASE; INFLORESCENCE-DEFICIENT; VESICULAR TRAFFICKING; EARLY
ENDOSOMES
AB Cell separation, or abscission, is a highly specialized process in plants that facilitates remodeling of their architecture and reproductive success. Because few genes are known to be essential for organ abscission, we conducted a screen for mutations that alter floral organ shedding in Arabidopsis. Nine recessive mutations that block shedding were found to disrupt the function of an ADP-ribosylation factor-GTPase-activating protein (ARF-GAP) we have named NEVERSHED (NEV). As predicted by its homology to the yeast Age2 ARF-GAP and transcriptional profile, NEV influences other aspects of plant development, including fruit growth. Co-localization experiments carried out with NEV-specific antiserum and a set of plant endomembrane markers revealed that NEV localizes to the trans-Golgi network and endosomes in Arabidopsis root epidermal cells. Interestingly, transmission electron micrographs of abscission zone regions from wild-type and nev flowers reveal defects in the structure of the Golgi apparatus and extensive accumulation of vesicles adjacent to the cell walls. Our results suggest that NEV ARF-GAP activity at the trans-Golgi network and distinct endosomal compartments is required for the proper trafficking of cargo molecules required for cell separation.
C1 [Liljegren, Sarah J.; Darnielle, Lalitree; Lewis, Michael W.; Taylor, Sarah M.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
[Liljegren, Sarah J.; Leslie, Michelle E.] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA.
[Chory, Joanne] Salk Inst Biol Studies, Plant Biol Lab, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
[Luo, Ruibai; Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Geldner, Niko] Univ Lausanne, Dept Plant Mol Biol, UNIL Sorge, CH-1015 Lausanne, Switzerland.
[Yanofsky, Martin F.] Univ Calif San Diego, Div Biol Sci, Sect Cell & Dev Biol, San Diego, CA 92093 USA.
RP Liljegren, SJ (reprint author), Univ N Carolina, Dept Biol, CB 3280, Chapel Hill, NC 27599 USA.
EM liljegren@unc.edu
RI Ecker, Joseph/B-9144-2008;
OI Ecker, Joseph/0000-0001-5799-5895; Leslie, Michelle/0000-0003-1576-8816
FU NSF grant; UNC; NSF; USDA; HHMI; William R. Kenan Fellowship; UNC
Curriculum in Genetics and Molecular Biology; UNC Developmental Biology;
Intramural Program of the National Cancer Institute,; Department of
Health and Human Services
FX We thank M. Peifer, J. Reed, J. Kieber, M. Duncan, V. Bautch, S.
Patterson, V. Bankaitis and C. Jones for helpful discussions; V. Madden
( UNC Microscopy Services) and T. Perdue ( UNC Biology Microscopy) for
assistance with TEM, SEM and confocal microscopy; S. Guimil, C.
Habbersett, A. Imler, D. Reyes and R. Weaver for assistance with mutant
screens and mapping; P. Pinyopich for the nev- 3 allele; T. Jack, Y.
Eshed and J. Bowman for enhancer trap lines; and Monsanto for access to
Ler polymorphisms. This research was primarily supported by an NSF grant
and UNC startup funds to S. J. L.; the early stages of the project were
funded by grants from USDA to S. J. L., NSF and DOE to J. R. E., and NSF
to M. F. Y.; generation of the Wave markers was supported by funding
from NSF, USDA and HHMI to J. C. M. E. L. was supported by a William R.
Kenan Fellowship and the UNC Curriculum in Genetics and Molecular
Biology, and M. W. L. by the NIH- funded UNC Developmental Biology
training program. P. A. R. and R. L. are supported by the Intramural
Program of the National Cancer Institute, NIH, Department of Health and
Human Services. Deposited in PMC for release after 6 months.
NR 90
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U2 15
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 JUN 1
PY 2009
VL 136
IS 11
BP 1909
EP 1918
DI 10.1242/dev.033605
PG 10
WC Developmental Biology
SC Developmental Biology
GA 443WI
UT WOS:000265941100014
PM 19429787
ER
PT J
AU Geyer, CB
Inselman, AL
Sunman, JA
Bornstein, S
Handel, MA
Eddy, EM
AF Geyer, Christopher B.
Inselman, Amy L.
Sunman, Jeffrey A.
Bornstein, Sheila
Handel, Mary Ann
Eddy, Edward M.
TI A missense mutation in the Capza3 gene and disruption of F-actin
organization in spermatids of repro32 infertile male mice
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Testis; Spermatid; Spermatozoa; Spermiogenesis; Actin; Ectoplasmic
specialization; Spermiation; Tubulobulbar complex
ID CAPPING PROTEIN; TUBULOBULBAR COMPLEXES; RAT TESTIS; ECTOPLASMIC
SPECIALIZATIONS; SERTOLI-CELLS; GERM-CELLS; DEVELOPING ACROSOME;
CYTOSKELETAL CALYX; SPERMIOGENESIS; SPERMATOGENESIS
AB Males homozygous for the repro32 ENU-induced mutation produced by the Reproductive Genomics program at The Jackson Laboratory are infertile, have low epididymal sperm concentrations, and produce sperm with abnormally shaped heads and poor motility, The purpose of the present study was to identify the mutated gene in repro32 mice and to define the structural and functional changes causing infertility and the aberrant sperm phenotype. In repro32/repro32 mice, we discovered a failure to shed excess cytoplasm and disorganization of the middle piece of the flagellum at spermiation, resulting in the outer dense fibers being wrapped around the sperm head within a bag of cytoplasm. Using a candidate-gene approach, a mutation was identified in the spermatid-specific "capping protein (actin filament) muscle Z-line, alpha 3" gene (Capza3). CAPZA3 protein localization was altered in spermatids concurrent with altered localization of a unique CAPZB variant isoform and disruption of the filamentous actin (F-actin) network. These observations strongly suggest the missense mutation in Capza3 is responsible for the mutant phenotype of repro32/repro32 sperm and regulation of F-actin dynamics by a spermatogenic cell-specific CAPZ heterodimer is essential for removal of the cytoplasm and maintenance of midpiece integrity during spermiation in the mouse. Published by Elsevier Inc.
C1 [Geyer, Christopher B.; Inselman, Amy L.; Eddy, Edward M.] NIEHS, Labs Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
[Bornstein, Sheila; Handel, Mary Ann] Jackson Lab, Bar Harbor, ME 04609 USA.
RP Eddy, EM (reprint author), NIEHS, Labs Reprod & Dev Toxicol, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM eddy@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [ZC1-ES070076];
NIH, NICHD [P01 HD-42137]
FX We would like to extend our sincere appreciation to Drs. Fanny Odet and
Lisa Chadwick for helpful discussions, Gina Goulding and Linwood Koonce
for technical assistance, and to Drs. John Schimenti and Jason Mercer
for critical reading of the manuscript. This research was supported in
part by the Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences (ZC1-ES070076, EME) and a grant from
NIH, NICHD (P01 HD-42137, MAH).
NR 50
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U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUN 1
PY 2009
VL 330
IS 1
BP 142
EP 152
DI 10.1016/j.ydbio.2009.03.020
PG 11
WC Developmental Biology
SC Developmental Biology
GA 448ZP
UT WOS:000266300800014
PM 19341723
ER
PT J
AU Damiano, DL
AF Damiano, Diane L.
TI Muscle size matters
SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
LA English
DT Editorial Material
ID CEREBRAL-PALSY; SPASTIC DIPLEGIA; STRENGTH; CHILDREN
C1 NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bethesda, MD 20892 USA.
RP Damiano, DL (reprint author), NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bldg 10, Bethesda, MD 20892 USA.
RI Damiano, Diane/B-3338-2010
OI Damiano, Diane/0000-0002-2770-5356
NR 11
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0012-1622
J9 DEV MED CHILD NEUROL
JI Dev. Med. Child Neurol.
PD JUN
PY 2009
VL 51
IS 6
BP 416
EP 417
PG 2
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 443TS
UT WOS:000265934300002
PM 19416331
ER
PT J
AU Chia, CW
Carlson, OD
Kim, W
Shin, YK
Charles, CP
Kim, HS
Melvin, DL
Egan, JM
AF Chia, Chee W.
Carlson, Olga D.
Kim, Wook
Shin, Yu-Kyong
Charles, Cornelia P.
Kim, Hee Seung
Melvin, Denise L.
Egan, Josephine M.
TI Exogenous Glucose-Dependent Insulinotropic Polypeptide Worsens
Postprandial Hyperglycemia in Type 2 Diabetes
SO DIABETES
LA English
DT Article; Proceedings Paper
CT 67th Annual Meeting of the American-Diabetes-Association
CY JUN 22-26, 2007
CL Chicago, IL
SP Amer Diabet Assoc
ID GLUCAGON-LIKE PEPTIDE-1; GASTRIC-INHIBITORY POLYPEPTIDE; DEFECTIVE
AMPLIFICATION; 7-36 AMIDE; SECRETION; GIP; INCRETIN; RAT; EXPRESSION;
RECEPTORS
AB OBJECTIVE-Glucose-dependent insulinotropic polypeptide (GIP), unlike glucagon-like peptide (GLP)-1, lacks glucose-lowering properties in patients with type 2 diabetes. We designed this study to elucidate the underlying pathophysiology.
RESEARCH DESIGN AND METHODS-Twenty-two insulin-naive subjects with type 2 diabetes were given either synthetic human GIP (20 ng . kg(-1) . min(-1)) or placebo (normal saline) over 180 min, starting with the first bite of a mixed meal (plus 1 g of acetaminophen) on two separate occasions. Frequent blood samples were obtained over 6 h to determine plasma GIP, GLP-1, glucose, insulin, glucagon, resistin, and acetaminophen levels.
RESULTS-Compared with placebo, GIP induced an early postprandial increase in insulin levels. Intriguingly, GIP also induced an early postprandial augmentation in glucagon, a significant elevation in late postprandial glucose, and a decrease in late postprandial GLP-1 levels. Resistin and acetaminophen levels were comparable in both interventions. By immunocytochemistry, GIP receptors were present on human and mouse a-cells. In alpha TC1 cell line, GIP induced an increase in intracellular cAMP and glucagon secretion.
CONCLUSIONS-GIP, given to achieve supraphysiological plasma levels, still had an early, short-lived insulinotropic effect in type 2 diabetes. However, with a concomitant increase in glucagon, the glucose-lowering effect was lost. GIP infusion further worsened hyperglycemia postprandially, most likely through its suppressive effect on GLP-1. These findings make it unlikely that GIP or GIP receptor agonists will be useful in treating the hyperglycemia of patients with type 2 diabetes. Diabetes 58:1342-1349, 2009
C1 [Chia, Chee W.; Carlson, Olga D.; Kim, Wook; Shin, Yu-Kyong; Charles, Cornelia P.; Kim, Hee Seung; Melvin, Denise L.; Egan, Josephine M.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Egan, JM (reprint author), NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM eganj@grc.nia.nih.gov
FU Intramural NIH HHS
NR 36
TC 68
Z9 71
U1 0
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD JUN
PY 2009
VL 58
IS 6
BP 1342
EP 1349
DI 10.2337/db08-0958
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 449RK
UT WOS:000266347500012
PM 19276444
ER
PT J
AU Ward, MM
AF Ward, Michael M.
TI Access to Care and the Incidence of End-Stage Renal Disease Due to
Diabetes
SO DIABETES CARE
LA English
DT Article
ID HEALTH-CARE; SOCIOECONOMIC-STATUS; PREVENTABLE HOSPITALIZATIONS;
GLYCEMIC CONTROL; BLOOD-GLUCOSE; RISK-FACTORS; COMPLICATIONS;
POPULATION; AMPUTATION; MORTALITY
AB OBJECTIVE - Low socioeconomic status (SES) is associated with an increased risk of end-stage renal disease (ESRD) due to diabetes. Because ESRD is a preventable complication of diabetes, the association with SES may be related to limited access to treatment.
RESEARCH DESIGN AND METHODS - In this population-based ecological study, I examined the association between the incidence of ESRD attributed to diabetes and the proportion of hospitalizations with no insurance, Medicaid, or managed care insurance; residence in a primary care provider shortage area or rural area; and rate of hospitalizations for hyperglycemic complications, by ZIP code in California in 2001-2004.
RESULTS - The incidence of ESRD attributed to diabetes was higher in ZIP codes with higher proportions of hospitalizations with no insurance (r = 0.45; P < 0.0001) or Medicaid (r = 0.69; P < 0.0001) and in ZIP codes with higher rates of hospitalizations for hyperglycemic complications (r = 0.27; P < 0.0001). The incidence was lower in ZIP codes with higher proportions of hospitalizations with managed care insurance (r = -0.37; P < 0.0001) and was lower in primary care provider shortage areas and rural locations. In contrast, there were only weak associations between measures of access to care and the incidence of ESRD attributed to polycystic kidney disease, a condition that is not treatable.
CONCLUSIONS - The incidence of ESRD attributed to diabetes is strongly associated with area-based measures of access to care, Suggesting that access to treatment partly mediates the association between SES and the incidence of ESRD. Diabetes Care 32:1032-1036, 2009
C1 NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
National Institutes of Health
FX This work was supported by the intramural Research Program, National
Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health. The data reported here were been supplied by the
U.S. Renal Data System.
NR 25
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U1 1
U2 2
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 JUN
PY 2009
VL 32
IS 6
BP 1032
EP 1036
DI 10.2337/dc09-0017
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 452EG
UT WOS:000266522200012
PM 19460914
ER
PT J
AU Porter, SA
Massaro, JM
Hoffmann, U
Vasan, RS
O'Donnel, CJ
Fox, CS
AF Porter, Stacy A.
Massaro, Joseph M.
Hoffmann, Udo
Vasan, Ramachandran S.
O'Donnel, Christopher J.
Fox, Caroline S.
TI Abdominal Subcutaneous Adipose Tissue: A Protective Fat Depot?
SO DIABETES CARE
LA English
DT Article
ID INSULIN-RESISTANCE; WEIGHT-LOSS; RISK-FACTORS; OBESE WOMEN; HEART;
HYPERTENSION; SENSITIVITY; LIPOSUCTION; IMPROVEMENT; PREVENTION
AB OBJECTIVE - Obesity is associated with increased metabolic and cardiovascular risk. The ectopic fat hypothesis suggests that subcutaneous fat may be protective, but this theory has yet to be fully explored.
RESEARCH DESIGN AND METHODS - Participants from the Framingham Heart Study (n = 3,001, 48.5% women) were stratified by visceral adipose tissue (VAT) into sex-specific tertiles. Within these tertiles, age-adjusted abdominal subcutaneous adipose tissue (SAT) tertiles were examined in relation to cardiometabolic risk factors.
RESULTS - In the lowest VAT fertile, risk factor prevalence was low, although systolic blood pressure in women and rates of high triglycerides, impaired fasting glucose, hypertension, and the metabolic syndrome in men increased with increasing SAT tertile (all P < 0.04). In contrast, in the top VAT tertile, lower triglycerides were observed in men with increasing SAT (64.4% high triglycerides in SAT tertile 1 Vs. 52.7% in SAT tertile 3, P = 0.03). Similar observations were made for women, although results were not statistically significant (50.6% high triglycerides in SAT tertile 1 vs. 41.0% in tertile 3, P = 0.1.0). Results in the highest VAT tertile were notable for a lack of increase in the prevalence of low HDL in men and women and in rates of impaired fasting glucose in men with increasing subcutaneous fat, despite sizable differences in BMI across SAT tertiles (27.1 to 36.3 kg/m(2) [women]; 28.1 to 35.7 kg/m(2) [men]).
CONCLUSIONS - Although adiposity increases the absolute risk of metabolic and cardiovascular disease, abdominal subcutaneous fat is not associated with a linear increase in the prevalence of all risk factors among the obese, most notably, high triglycerides.
C1 [Porter, Stacy A.; Massaro, Joseph M.; Vasan, Ramachandran S.; O'Donnel, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Porter, Stacy A.] Harvard Univ, Sch Med, Boston, MA USA.
[Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Massaro, Joseph M.] Sch Publ Hlth, Div Biostat, Boston, MA USA.
[Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Vasan, Ramachandran S.] Boston Univ, Dept Cardiol & Prevent Med, Boston, MA 02215 USA.
[O'Donnel, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
EM foxca@nhlbi.nih.gov
OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Heart, Lung, and Blood Institute (NHLBI) [NO1-HC-251.95,
2K24HL04334]; PASTEUR; Harvard Medical School Office of Enrichment
FX Acknowledgments-This work was supported by the National Heart, Lung, and
Blood Institute (NHLBI) Framingham Heart Study (Grant NO1-HC-251.95).
S.A.P. is supported by the PASTEUR Program and the Harvard Medical
School Office of Enrichment Programs. R.S.V. is supported in part by
Grant 2K24HL04334 (NHLBI, National Institutes of Health).
NR 25
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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 JUN
PY 2009
VL 32
IS 6
BP 1068
EP 1075
DI 10.2337/dc08-2280
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 452EG
UT WOS:000266522200020
PM 19244087
ER
PT J
AU Billal, DS
Hotomi, M
Yan, SS
Fedorko, DP
Shimada, J
Fujihara, K
Yamanaka, N
AF Billal, Dewan Sakhawat
Hotomi, Muneki
Yan, Steve S.
Fedorko, Daniel P.
Shimada, Jun
Fujihara, Keiji
Yamanaka, Noboru
TI Loss of erythromycin resistance genes from strains of Streptococcus
pyogenes that have developed resistance to levofloxacin
SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
LA English
DT Article
DE Streptococcus pyogenes; Fluoroquinolone resistance; Erythromycin
resistance; Transconjugation
ID GROUP-A STREPTOCOCCI; UROPATHOGENIC ESCHERICHIA-COLI; MACROLIDE
RESISTANCE; ANTIMICROBIAL SUSCEPTIBILITY; STAPHYLOCOCCUS-AUREUS;
VANCOMYCIN; INDUCTION; JAPAN
AB In the past 2 to 3 decades, erythromycin resistance in Streptococcus pyogenes has been decreasing, whereas fluoroquinolone resistance (or reduction in its susceptibility) has been reported often. Although a shift of M-type prevalence and decreased pressure from macrolides have been suggested for the decrease in erythromycin resistance, we hypothesized that this might also be a result of increased antimicrobial pressure from fluoroquinolone use. Levofloxacin resistance for 4 erythromycin-resistant parent strains was induced in vitro. Their mutants became highly resistant to the fluoroquinolones but lost their erythromycin resistance trait. Erythromycin resistance was fully restored by transconjugation with respective parent strains with either mefA- or ermTR-mediated mechanisms. (C) 2009 Published by Elsevier Inc.
C1 [Billal, Dewan Sakhawat; Hotomi, Muneki; Shimada, Jun; Fujihara, Keiji; Yamanaka, Noboru] Wakayama Med Univ, Dept Otolaryngol, Wakayama 6418509, Japan.
[Yan, Steve S.] US FDA, Dept Hlth & Human Serv, Rockville, MD 20855 USA.
[Fedorko, Daniel P.] NIH, Dept Hlth & Human Serv, Ctr Clin, Bethesda, MD 20892 USA.
RP Yamanaka, N (reprint author), Wakayama Med Univ, Dept Otolaryngol, Wakayama 6418509, Japan.
EM ynobi@wakayama-med.ac.jp
NR 20
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0732-8893
J9 DIAGN MICR INFEC DIS
JI Diagn. Microbiol. Infect. Dis.
PD JUN
PY 2009
VL 64
IS 2
BP 225
EP 228
DI 10.1016/j.diagmicrobio.2009.01.034
PG 4
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 455WZ
UT WOS:000266800600017
PM 19345038
ER
PT J
AU Heishman, SJ
Evans, RJ
Singleton, EG
Levin, KH
Copersino, ML
Gorelick, DA
AF Heishman, Stephen J.
Evans, Rebecca J.
Singleton, Edward G.
Levin, Kenneth H.
Copersino, Marc L.
Gorelick, David A.
TI Reliability and validity of a short form of the Marijuana Craving
Questionnaire
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Marijuana craving; Cannabis; Reliability; Validity; Questionnaire
ID CANNABIS WITHDRAWAL; COEFFICIENT-ALPHA; DEPENDENCE; COCAINE; TOBACCO;
VALIDATION; INSTRUMENT; RELAPSE; HEROIN; ADULTS
AB Background:The Marijuana Craving Questionnaire (MCQ) is a valid and reliable, 47-item self-report instrument that assesses Marijuana craving along four dimensions: compulsivity, emotionality, expectancy, and Purposefulness. For use in research and clinical settings, we constructed a 12-item version of the MCQ by selecting three items from each of the four factors that exhibited the greatest within-factor internal consistency (Cronbach's alpha coefficient).
Methods: Adult marijuana users (n = 490), who had made at least one serious attempt to quit marijuana use but were not seeking treatment, completed the MCQ-Short Form (MCQ-SF) in a single session.
Results: Confirmatory factor analysis of the MCQ-SF indicated good fit with the 4-factor MCQ model. and the coefficient of congruence indicated moderate similarity in factor patterns and loadings between the MCQ and MCQ-SF. Homogeneity (unidimensionality and internal consistency) of MCQ-SF factors was also consistent with reliability values obtained in the initial validation of the MCQ.
Conclusions: Findings of psychometric Fidelity indicate that the MCQ-SF is a reliable and valid measure of the same multidimensional aspects of marijuana craving as the MCQ in Marijuana Users not seeking treatment. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Heishman, Stephen J.; Evans, Rebecca J.; Levin, Kenneth H.; Gorelick, David A.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
[Singleton, Edward G.] MayaTech Corp, Silver Spring, MD 20910 USA.
[Copersino, Marc L.] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02478 USA.
RP Heishman, SJ (reprint author), NIDA, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM heishman@nih.gov
OI Singleton, Edward G./0000-0003-3442-877X
FU NIH; National Institute on Drug Abuse (NIDA)
FX Funding for this study was provided by the Intramural Research Program
of the NIH, National Institute on Drug Abuse (NIDA). NIDA had no further
role in study design: in the collection, analysis, and interpretation of
data: in the writing of the report: or in the decision to Submit the
paper for publication.
NR 55
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD JUN 1
PY 2009
VL 102
IS 1-3
BP 35
EP 40
DI 10.1016/j.drugalcdep.2008.12.010
PG 6
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 447YQ
UT WOS:000266228400005
PM 19217724
ER
PT J
AU Buetow, KH
AF Buetow, Kenneth H.
TI An infrastructure for interconnecting research institutions
SO DRUG DISCOVERY TODAY
LA English
DT Review
AB Many researchers believe that personalized medicine is a potential solution to the well-known challenges facing the pharmaceutical industry worldwide today. Achieving the full promise of personalized medicine requires a new systems approach to biomedicine that will only be enabled by novel, interoperable IT infrastructures that facilitate simpler data access, data sharing, and enhanced collaboration. This article will describe how the technology developed in the cancer Biomedical Informatics Grid (R) (caBIG (R)) program (http://cabig.cancer.gov/) from the National Cancer Institute (NCI) is already enabling many research organizations to implement personalized medicine approaches for their basic and clinical research programs.
C1 NCI, Ctr Bioinformat & Informat Technol, Rockville, MD 20852 USA.
RP Buetow, KH (reprint author), NCI, Ctr Bioinformat & Informat Technol, Rockville, MD 20852 USA.
EM buetowk@nih.gov
NR 6
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U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1359-6446
J9 DRUG DISCOV TODAY
JI Drug Discov. Today
PD JUN
PY 2009
VL 14
IS 11-12
BP 605
EP 610
DI 10.1016/j.drudis.2009.03.011
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 463EX
UT WOS:000267413500010
PM 19508923
ER
PT J
AU Liu, AM
Patterson, AD
Yang, ZT
Zhang, XY
Liu, W
Qiu, FY
Sun, H
Krausz, KW
Idle, JR
Gonzalez, FJ
Dai, RK
AF Liu, Aiming
Patterson, Andrew D.
Yang, Zongtao
Zhang, Xinying
Liu, Wei
Qiu, Fayang
Sun, He
Krausz, Kristopher W.
Idle, Jeffrey R.
Gonzalez, Frank J.
Dai, Renke
TI Fenofibrate Metabolism in the Cynomolgus Monkey using Ultraperformance
Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry-Based
Metabolomics
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID ACTIVATED-RECEPTOR-ALPHA; RAT SKELETAL-MUSCLE; CLOFIBRIC ACID;
PEROXISOME PROLIFERATORS; SPECIES-DIFFERENCES; HEPATIC PEROXISOME;
GEMFIBROZIL; HEPATOCARCINOGENESIS; DISPOSITION; TOXICITY
AB Fenofibrate, widely used for the treatment of dyslipidemia, activates the nuclear receptor, peroxisome proliferator-activated receptor alpha. However, liver toxicity, including liver cancer, occurs in rodents treated with fibrate drugs. Marked species differences occur in response to fibrate drugs, especially between rodents and humans, the latter of which are resistant to fibrate-induced cancer. Fenofibrate metabolism, which also shows species differences, has not been fully determined in humans and surrogate primates. In the present study, the metabolism of fenofibrate was investigated in cynomolgus monkeys by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS)-based metabolomics. Urine samples were collected before and after oral doses of fenofibrate. The samples were analyzed in both positive-ion and negative-ion modes by UPLC-QTOFMS, and after data deconvolution, the resulting data matrices were subjected to multivariate data analysis. Pattern recognition was performed on the retention time, mass/charge ratio, and other metabolite-related variables. Synthesized or purchased authentic compounds were used for metabolite identification and structure elucidation by liquid chromatographytandem mass spectrometry. Several metabolites were identified, including fenofibric acid, reduced fenofibric acid, fenofibric acid ester glucuronide, reduced fenofibric acid ester glucuronide, and compound X. Another two metabolites (compound B and compound AR), not previously reported in other species, were characterized in cynomolgus monkeys. More importantly, previously unknown metabolites, fenofibric acid taurine conjugate and reduced fenofibric acid taurine conjugate were identified, revealing a previously unrecognized conjugation pathway for fenofibrate.
C1 [Liu, Aiming; Yang, Zongtao; Zhang, Xinying; Liu, Wei; Qiu, Fayang; Sun, He; Dai, Renke] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510663, Guangdong, Peoples R China.
[Idle, Jeffrey R.] Charles Univ Prague, Fac Med 1, Prague, Czech Republic.
[Patterson, Andrew D.; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, NIH, Bethesda, MD 20892 USA.
RP Dai, RK (reprint author), Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510663, Guangdong, Peoples R China.
RI Patterson, Andrew/G-3852-2012;
OI Patterson, Andrew/0000-0003-2073-0070; Idle, Jeff/0000-0002-6143-1520
FU National Institutes of Health National Cancer Institute [Z01
BC005562-20]; National High-tech RD Program [2006AA02Z339]; Guangzhou
Science and Technology Bureau [2006Z1-E4031, 2006P067]; Guangzhou
Development District [2006Ss-P067]
FX This work was supported in part by the National Institutes of Health
National Cancer Institute [Grant Z01 BC005562-20] ( Intramural Research
Program); the National High-tech R&D Program [Grant 2006AA02Z339]; the
Guangzhou Science and Technology Bureau [Grants 2006Z1-E4031, 2006P067];
and the Guangzhou Development District [Grant 2006Ss-P067].
NR 36
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U2 10
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD JUN
PY 2009
VL 37
IS 6
BP 1157
EP 1163
DI 10.1124/dmd.108.025817
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 446US
UT WOS:000266147500003
PM 19251819
ER
PT J
AU Rapisarda, A
Melillo, G
AF Rapisarda, Annamaria
Melillo, Giovanni
TI Role of the hypoxic tumor microenvironment in the resistance to
anti-angiogenic therapies
SO DRUG RESISTANCE UPDATES
LA English
DT Review
DE Angiogenesis; VEGF; Hypoxia; HIF-1; Bevacizumab; Cancer therapeutics;
Topotecan; mTOR inhibitors
ID ENDOTHELIAL GROWTH-FACTOR; INDUCIBLE FACTOR-1-ALPHA PROTEIN;
SMALL-MOLECULE INHIBITORS; CHEMOKINE RECEPTOR CXCR4; ANTIANGIOGENIC
THERAPY; MYELOID CELLS; FACTOR-I; TRANSCRIPTIONAL ACTIVATION; DEPENDENT
INHIBITION; MALIGNANT GLIOMAS
AB Angiogenesis, a key process for the growth of human cancers, has recently been exploited for the development of a novel class of cancer therapeutics that was thought to have wide applications and not to induce resistance in the clinical setting. Indeed, anti-angiogenic therapy has become an important option for the management of several human malignancies. However, a significant number of patients either do not respond to anti-angiogenic agents or fairly rapidly develop resistance. In addition, the benefit of anti-angiogenic therapy is relatively short-lived and the majority of patients eventually relapses and progresses. Several mechanisms of resistance to anti-angiogenic therapy have been recently proposed. The current review focuses on the role of intra-tumor hypoxia as a mechanism of resistance to anti-angiogenic agents and speculates on therapeutic approaches that might circumvent resistance and thereby improve clinical outcome. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Rapisarda, Annamaria; Melillo, Giovanni] NCI, Tumor Hypoxia Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Melillo, G (reprint author), NCI, DTP Tumor Hypoxia Lab, SAIC Frederick Inc, Bldg 432,Room 218, Frederick, MD 21702 USA.
EM melillog@mail.nih.gov
FU National Institutes of Health [N01-CO-12400]; National Cancer Institute
FX The authors would like to thank members of the Tumor Hypoxia Laboratory
and Dr. R.H. Shoemaker for helpful discussion. This project has been
funded in whole or in part with Federal funds from the National Cancer
Institute, National Institutes of Health, under Contract No.
N01-CO-12400. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This research
was supported [in part] by the Developmental Therapeutics Program, DCTD,
of the National Cancer Institute, NIH.
NR 94
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U1 1
U2 8
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1368-7646
J9 DRUG RESIST UPDATE
JI Drug Resist. Update
PD JUN
PY 2009
VL 12
IS 3
BP 74
EP 80
DI 10.1016/j.drup.2009.03.002
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 467YS
UT WOS:000267780400003
PM 19394890
ER
PT J
AU Alia-Klein, N
Goldstein, RZ
Tomasi, D
Woicik, PA
Moeller, SJ
Williams, B
Craig, IW
Telang, F
Biegon, A
Wang, GJ
Fowler, JS
Volkow, ND
AF Alia-Klein, Nelly
Goldstein, Rita Z.
Tomasi, Dardo
Woicik, Patricia A.
Moeller, Scott J.
Williams, Benjamin
Craig, Ian W.
Telang, Frank
Biegon, Anat
Wang, Gene-Jack
Fowler, Joanna S.
Volkow, Nora D.
TI Neural Mechanisms of Anger Regulation as a Function of Genetic Risk for
Violence
SO EMOTION
LA English
DT Article
DE MAOA; emotion regulation; anger; response to no; fMRI
ID MONOAMINE-OXIDASE-A; BRAIN ACTIVITY; ORBITOFRONTAL CORTEX;
AGGRESSIVE-BEHAVIOR; INHIBITORY CONTROL; AMYGDALA; GENOTYPE; MAOA;
PULVINAR; HUMANS
AB Genetic risk may predispose individuals to compromised anger regulation, potentially through modulation of brain responses to emotionally evocative stimuli. Emphatically expressed, the emotional word No can prohibit behavior through conditioning. In a recent functional magnetic resonance imaging study, the authors showed that healthy males attribute negative valence to No while showing a lateral orbitofrontal response that con-elated with their self-reported anger control. Here, the authors examined the influence of the monoamine oxidase A (MAOA) gene (low vs. high transcription variants) on brain response to No and in relationship to trait anger reactivity and control. The orbitofrontal response did not differ as a function of the genotype. Instead, carriers of the low-MAOA genotype had reduced left middle frontal gyros activation to No compared with the high variant. Furthermore, only for carriers of theup low-MAOA genotype, left amygdala and posterior thalamic activation to No increased with anger reactivity. Thus, vulnerability to aggression in carriers of the low-MAOA genotype is supported by decreased middle frontal response to No and the unique amygdala/thalamus association pattern in this group with anger reactivity but not anger control.
C1 [Alia-Klein, Nelly; Goldstein, Rita Z.; Tomasi, Dardo; Woicik, Patricia A.; Telang, Frank; Biegon, Anat; Wang, Gene-Jack; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Moeller, Scott J.] Univ Michigan, Dept Psychol, Ann Arbor, MI USA.
[Williams, Benjamin; Craig, Ian W.] Kings Coll London, London WC2R 2LS, England.
[Wang, Gene-Jack; Fowler, Joanna S.] Mt Sinai Sch Med, New York, NY USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
RP Alia-Klein, N (reprint author), Brookhaven Natl Lab, Dept Med, POB 5000, Upton, NY 11973 USA.
EM nellyklein@bnl.gov
RI Tomasi, Dardo/J-2127-2015; Moeller, Scott/L-5549-2016;
OI Moeller, Scott/0000-0002-4449-0844; Craig, Ian/0000-0002-4063-1005
FU NCRR NIH HHS [M01RR10710, M01 RR010710]; NIDA NIH HHS [K05 DA020001, K05
DA020001-04, K05DA020001]
NR 75
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U1 2
U2 12
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1528-3542
J9 EMOTION
JI Emotion
PD JUN
PY 2009
VL 9
IS 3
BP 385
EP 396
DI 10.1037/a0015904
PG 12
WC Psychology, Experimental
SC Psychology
GA 454BF
UT WOS:000266655900010
PM 19485616
ER
PT J
AU Lanari, C
Lamb, CA
Fabris, VT
Helguero, LA
Soldati, R
Bottino, MC
Giulianelli, S
Cerliani, JP
Wargon, V
Molinolo, A
AF Lanari, Claudia
Lamb, Caroline A.
Fabris, Victoria T.
Helguero, Luisa A.
Soldati, Rocio
Cecilia Bottino, Maria
Giulianelli, Sebastian
Pablo Cerliani, Juan
Wargon, Victoria
Molinolo, Alfredo
TI The MPA mouse breast cancer model: evidence for a role of progesterone
receptors in breast cancer
SO ENDOCRINE-RELATED CANCER
LA English
DT Review
ID EPIDERMAL-GROWTH-FACTOR; METHYL-N-NITROSOUREA; MEDROXYPROGESTERONE
ACETATE MPA; MAMMARY-TUMOR GROWTH; SPRAGUE-DAWLEY RATS; BALB/C FEMALE
MICE; ACTIVATED PROTEIN-KINASE; ESTROGEN-RECEPTOR; IN-VITRO; HORMONE
DEPENDENCE
AB More than 60% of all breast neoplasias are ductal carcinomas expressing estrogen (ER) and progesterone receptors (PR). By contrast, most of the spontaneous, chemically or mouse mammary tumor virus induced tumors, as well as tumors arising in genetically modified mice do not express hormone receptors. We developed a model of breast cancer in which the administration of medroxyprogesterone acetate to BALB/c female mice induces mammary ductal carcinomas with a mean latency of 52 weeks and an incidence of about 80%. These tumors are hormone-dependent (HD), metastatic, express both ER and PR, and are maintained by syngeneic transplants. The model has been further refined to include mammary carcinomas that evolve through different stages of hormone dependence, as well as several hormone-responsive cell lines. In this review, we describe the main features of this tumor model, highlighting the role of PR as a trigger of key signaling pathways mediating tumor growth. In addition, we discuss the relevance of this model in comparison with other presently used breast cancer models pointing out its advantages and limitations and how, this model may be suitable to unravel key questions in breast cancer.
C1 [Lanari, Claudia; Lamb, Caroline A.; Fabris, Victoria T.; Helguero, Luisa A.; Soldati, Rocio; Cecilia Bottino, Maria; Giulianelli, Sebastian; Pablo Cerliani, Juan; Wargon, Victoria; Molinolo, Alfredo] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, Lab Hormonal Carcinogenesis, Buenos Aires, CF, Argentina.
RP Molinolo, A (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RI Helguero, Luisa/B-1221-2013
OI Helguero, Luisa/0000-0001-8237-2390
FU Sales Foundation; SECYT; CONICET; Roemmers Foundation; Institute of
Dental and Craniofacial Research, National Institutes of Health,
Bethesda, MD, USA
FX This project has been supported by grants from the Sales Foundation, and
also by grants from SECYT, CONICET, and the Roemmers Foundation. Dr
Molinolo is supported by the Intramural Research Program of the
Institute of Dental and Craniofacial Research, National Institutes of
Health, Bethesda, MD, USA
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U1 0
U2 2
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD JUN
PY 2009
VL 16
IS 2
BP 333
EP 350
DI 10.1677/ERC-08-0244
PG 18
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 531MK
UT WOS:000272670200003
PM 19190078
ER
PT J
AU Timmers, HJLM
Gimenez-Roqueplo, AP
Mannelli, M
Pacak, K
AF Timmers, Henri J. L. M.
Gimenez-Roqueplo, Anne-Paule
Mannelli, Massimo
Pacak, Karel
TI Clinical aspects of SDHx-related pheochromocytoma and paraganglioma
SO ENDOCRINE-RELATED CANCER
LA English
DT Review
ID COMPLEX-II GENE; MITOCHONDRIAL RESPIRATORY-CHAIN; DEHYDROGENASE-B GENE;
RENAL-CELL CARCINOMA; GERM-LINE MUTATIONS; HEREDITARY PARAGANGLIOMA;
MALIGNANT PHEOCHROMOCYTOMAS; FAMILIAL PARAGANGLIOMA; SECRETING
PARAGANGLIOMA; SPORADIC PARAGANGLIOMA
AB Paragangliomas (PGLs) derive from either sympathetic chromaffin tissue in adrenal and extra-adrenal abdominal or thoracic locations, or from parasympathetic tissue of the head and neck Mutations of nuclear genes encoding subunits 13, C, and D of the mitochondrial enzyme succinate dehydrogenase (SDHB 1p35-p36 1, SDHC 1q21, SDHD 11q23) give rise to hereditary PGL syndromes PGL4, PGL3, and PGL1 respectively. The susceptibility gene for PGL2 on 11q13.1 remains unidentified Mitochondrial dysfunction due to SDHx mutations have been linked to tumorigenesis by upregulation of hypoxic and angiogenesis pathways, apoptosis resistance and developmental culling of neuronal precursor cells SDHB-, SDHC-, and SDHD-associated PGLs give rise to more or less distinct clinical phenotypes SDHB mutations mainly predispose to extra-adrenal, and to a lesser extent, adrenal PGLs, with a high malignant potential, but also head and neck paragangliomas (HNPGL). SDHD mutations are typically associated with multifocal HNPGL and usually benign adrenal and extra-adrenal PGLs SDHC mutations are a rare cause of mainly HNPGL. Most abdominal and thoracic SDHB-PGLs hypersecrete either norepinephrine or norepinephrine and dopamine. However, only some hypersecrete dopamine, are biochemically silent. The biochemical phenotype of SDHD-PGL has not been systematically studied For the localization of PGL, several positron emission tomography (PET) tracers are available. Metastatic SDHB-PGL is the best localized by [(18)F]-fluorodeoxyglucose PET The identification of SDHx mutations in patients with PGL is warranted for a tailor-made approach to the biochemical diagnosis, imaging, treatment, follow-up, and family screening.
C1 [Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6500 HB Nijmegen, Netherlands.
[Gimenez-Roqueplo, Anne-Paule] Hop Europeen Georges Pompidou, AP HP, Serv Genet, F-75015 Paris, France.
[Gimenez-Roqueplo, Anne-Paule] Univ Paris 05, F-75005 Paris, France.
[Gimenez-Roqueplo, Anne-Paule] Coll France, INSERM, U772, F-75231 Paris, France.
[Mannelli, Massimo] Univ Florence, Dept Clin Physiopathol, Endocrinol Unit, I-50139 Florence, Italy.
[Pacak, Karel] NICHHD, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA.
RP Timmers, HJLM (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, POB 9101, NL-6500 HB Nijmegen, Netherlands.
OI Mannelli, Massimo/0000-0002-8001-9857
FU NICHD/NIH; Institut National de la Sante et de la Recherche Medicale;
PHRC [AOM 06 179]; GIS-Institut des Maladies Rares
FX This research was supported by the Intramural Research Program of the
NICHD/NIH. Anne-Paule Gimenez-Roqueplo was supported by the Institut
National de la Sante et de la Recherche Medicale and by PHRC grant for
the COMETE Network (AOM 06 179) and the GIS-Institut des Maladies Rares
for the PGL NET network
NR 74
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U1 0
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD JUN
PY 2009
VL 16
IS 2
BP 391
EP 400
DI 10.1677/ERC-08-0284
PG 10
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 531MK
UT WOS:000272670200007
PM 19190077
ER
PT J
AU Ichikawa, S
Sorenson, AH
Austin, AM
Mackenzie, DS
Fritz, TA
Moh, A
Hui, SL
Econs, MJ
AF Ichikawa, Shoji
Sorenson, Andrea H.
Austin, Anthony M.
Mackenzie, Donald S.
Fritz, Timothy A.
Moh, Akira
Hui, Siu L.
Econs, Michael J.
TI Ablation of the Galnt3 Gene Leads to Low-Circulating Intact Fibroblast
Growth Factor 23 (Fgf23) Concentrations and Hyperphosphatemia Despite
Increased Fgf23 Expression
SO ENDOCRINOLOGY
LA English
DT Article
ID FAMILIAL TUMORAL CALCINOSIS; HOMOZYGOUS MISSENSE MUTATION;
N-ACETYLGALACTOSAMINYLTRANSFERASE; O-GLYCOSYLATION;
FIBROBLAST-GROWTH-FACTOR-23; KLOTHO; MICE; CLONING;
1,25-DIHYDROXYVITAMIN-D; HYPOPHOSPHATEMIA
AB Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia. The disease is caused by inactivating mutations in fibroblast growth factor 23 (FGF23), Klotho (KL), and uridine diphosphate-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). In vitro studies indicate that GALNT3 O-glycosylates a phosphaturic hormone, FGF23, and prevents its proteolytic processing, thereby allowing secretion of intact FGF23. In this study we generated mice lacking the Galnt3 gene, which developed hyperphosphatemia without apparent calcifications. In response to hyperphosphatemia, Galnt3-deficient mice had markedly increased Fgf23 expression in bone. However, compared with wild-type and heterozygous littermates, homozygous mice had only about half of circulating intact Fgf23 levels and higher levels of C-terminal Fgf23 fragments in bone. Galnt3-deficient mice also exhibited an inappropriately normal 1,25-dihydroxyvitamin D level and decreased alkaline phosphatase activity. Furthermore, renal expression of sodium-phosphate cotransporters and Kl were elevated in Galnt3-deficient mice. Interestingly, there were sex-specific phenotypes; only Galnt3-deficient males showed growth retardation, infertility, and significantly increased bone mineral density. In summary, ablation of Galnt3 impaired secretion of intact Fgf23, leading to decreased circulating Fgf23 and hyperphosphatemia, despite increased Fgf23 expression. Our findings indicate that Galnt3-deficient mice have a biochemical phenotype of tumoral calcinosis and provide in vivo evidence that Galnt3 plays an essential role in proper secretion of Fgf23 in mice. (Endocrinology 150: 2543-2550, 2009)
C1 [Ichikawa, Shoji; Sorenson, Andrea H.; Austin, Anthony M.; Mackenzie, Donald S.; Hui, Siu L.; Econs, Michael J.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA.
[Moh, Akira] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA.
[Econs, Michael J.] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Fritz, Timothy A.] NIDDKD, Sect Biol Chem, NIH, Bethesda, MD 20892 USA.
RP Econs, MJ (reprint author), Indiana Univ, Sch Med, Dept Med, 541 N Clin Dr,Clin Bldg 459, Indianapolis, IN 46202 USA.
EM mecons@iupui.edu
OI Econs, Michael/0000-0003-0940-1911
FU National Institutes of Health [R01 AR42228, S10 RR023710]; Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases
FX This work was supported by National Institutes of Health grants R01
AR42228 and S10 RR023710, and in part by the Intramural Research Program
of the National Institute of Diabetes and Digestive and Kidney Diseases.
NR 35
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U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD JUN
PY 2009
VL 150
IS 6
BP 2543
EP 2550
DI 10.1210/en.2008-0877
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 448IQ
UT WOS:000266256700011
PM 19213845
ER
PT J
AU Fiori, JL
Zhu, TN
O'Connell, MP
Hoek, KS
Indig, FE
Frank, BP
Morris, C
Kole, S
Hasskamp, J
Elias, G
Weeraratna, AT
Bernier, M
AF Fiori, Jennifer L.
Zhu, Tie-Nian
O'Connell, Michael P.
Hoek, Keith S.
Indig, Fred E.
Frank, Brittany P.
Morris, Christa
Kole, Sutapa
Hasskamp, Joanne
Elias, George
Weeraratna, Ashani T.
Bernier, Michel
TI Filamin A Modulates Kinase Activation and Intracellular Trafficking of
Epidermal Growth Factor Receptors in Human Melanoma Cells
SO ENDOCRINOLOGY
LA English
DT Article
ID ACTIN-BINDING PROTEIN; CBL-MEDIATED UBIQUITINYLATION; CALCIUM-SENSING
RECEPTOR; EGF RECEPTOR; DOWN-REGULATION; CYTOSKELETON; ENDOCYTOSIS;
PATHWAY; INTERNALIZATION; DEGRADATION
AB The actin-binding protein filamin A (FLNa) affects the intracellular trafficking of various classes of receptors and has a potential role in oncogenesis. However, it is unclear whether FLNa regulates the signaling capacity and/or down-regulation of the activated epidermal growth factor receptor (EGFR). Here it is shown that partial knockdown of FLNa gene expression blocked ligand-induced EGFR responses in metastatic human melanomas. To gain greater insights into the role of FLNa in EGFR activation and intracellular sorting, we used M2 melanoma cells that lack endogenous FLNa and a subclone in which human FLNa cDNA has been stably reintroduced(M2A7 cells). Both tyrosine phosphorylation and ubiquitination of EGFR were significantly lower in epidermal growth factor (EGF)-stimulated M2 cells when compared with M2A7 cells. Moreover, the lack of FLNa interfered with EGFR interaction with the ubiquitin ligase c-Cbl. M2 cells exhibited marked resistance to EGF-induced receptor degradation, which was very active in M2A7 cells. Despite comparable rates of EGF-mediated receptor endocytosis, internalized EGFR colocalized with the lysosomal marker lysosome-associated membrane protein-1 in M2A7 cells but not M2 cells, in which EGFR was found to be sequestered in large vesicles and subsequently accumulated in punctated perinuclear structures after EGF stimulation. These results suggest the requirement of FLNa for efficient EGFR kinase activation and the sorting of endocytosed receptors into the degradation pathway. (Endocrinology 150: 2551-2560, 2009)
C1 [Bernier, Michel] NIA, Clin Invest Lab, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[O'Connell, Michael P.; Weeraratna, Ashani T.] NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA.
[Indig, Fred E.; Frank, Brittany P.; Morris, Christa] NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
[Hoek, Keith S.] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland.
[Kole, Sutapa] MedStar Res Inst, Hyattsville, MD 20783 USA.
[Hasskamp, Joanne; Elias, George] Franklin Sq Hosp, Harry & Jeanette Weinberg Canc Inst, Baltimore, MD 21237 USA.
RP Bernier, M (reprint author), NIA, Clin Invest Lab, Biomed Res Ctr, NIH, 251 Bayview Blvd,Suite 100,Room 09B135, Baltimore, MD 21224 USA.
EM bernierm@mail.nih.gov
OI Bernier, Michel/0000-0002-5948-368X
FU National Institutes of Health, National Institute on Aging; MedStar
Research Institute
FX This work was supported entirely by the Intramural Research Program of
the National Institutes of Health, National Institute on Aging. A
portion of that support was through a research and development contract
with MedStar Research Institute.
NR 59
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U1 0
U2 3
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD JUN
PY 2009
VL 150
IS 6
BP 2551
EP 2560
DI 10.1210/en.2008-1344
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 448IQ
UT WOS:000266256700012
PM 19213840
ER
PT J
AU Heimeier, RA
Das, B
Buchholz, DR
Shi, YB
AF Heimeier, Rachel A.
Das, Biswajit
Buchholz, Daniel R.
Shi, Yun-Bo
TI The Xenoestrogen Bisphenol A Inhibits Postembryonic Vertebrate
Development by Antagonizing Gene Regulation by Thyroid Hormone
SO ENDOCRINOLOGY
LA English
DT Article
ID XENOPUS-LAEVIS TADPOLES; AFRICAN CLAWED FROG; RANA-PIPIENS;
ENVIRONMENTAL CHEMICALS; IN-VIVO; RECEPTOR SUPERFAMILY; EXPRESSION
CHANGES; METAMORPHOSIS; BRAIN; EXPOSURE
AB Bisphenol A (BPA), a chemical widely used to manufacture plastics, is estrogenic and capable of disrupting sex differentiation. However, recent in vitro studies have shown that BPA can also antagonize T-3 activation of the T-3 receptor. The difficulty in studying uterus-enclosed mammalian embryos has hampered the analysis on the direct effects of BPA during vertebrate development. This study proposed to identify critical T-3 pathways that may be disrupted by BPA based on molecular analysis in vivo. Because amphibian metamorphosis requires T-3 and encompasses the postembryonic period in mammals when T-3 action is most critical, we used this unique model for studying the effect of BPA on T-3-dependent vertebrate development at both the morphological and molecular levels. After 4 d of exposure, BPA inhibited T-3-induced intestinal remodeling in premetamorphic Xenopus laevis tadpoles. Importantly, microarray analysis revealed that BPA antagonized the regulation of most T-3-response genes, thereby explaining the inhibitory effect of BPA on metamorphosis. Surprisingly, most of the genes affected by BPA in the presence of T-3 were T-3-response genes, suggesting that BPA predominantly affected T-3-signaling pathways during metamorphosis. Our finding that this endocrine disruptor, well known for its estrogenic activity in vitro, functions to inhibit T3 pathways to affect vertebrate development in vivo and thus not only provides a mechanism for the likely deleterious effects of BPA on human development but also demonstrates the importance of studying endocrine disruption in a developmental context in vivo. (Endocrinology 150: 2964-2973, 2009)
C1 [Heimeier, Rachel A.; Das, Biswajit; Shi, Yun-Bo] NICHHD, Sect Mol Morphogenesis, Program Cell Regulat & Metab, NIH, Bethesda, MD 20892 USA.
[Buchholz, Daniel R.] Univ Cincinnati, Dept Biol Sci, Cincinnati, OH 45221 USA.
RP Shi, YB (reprint author), NICHHD, Sect Mol Morphogenesis, Program Cell Regulat & Metab, NIH, Bldg 18 T,Room 106, Bethesda, MD 20892 USA.
EM shi@helix.nih.gov
FU Intramural Research Program, National Institute of Child Health and
Human Development, National Institutes of Health
FX This work was supported in part by the Intramural Research Program,
National Institute of Child Health and Human Development, National
Institutes of Health.
NR 79
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Z9 57
U1 7
U2 24
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD JUN
PY 2009
VL 150
IS 6
BP 2964
EP 2973
DI 10.1210/en.2008-1503
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 448IQ
UT WOS:000266256700062
PM 19228888
ER
PT J
AU Newbold, RR
Jefferson, WN
Padilla-Banks, E
AF Newbold, Retha R.
Jefferson, Wendy N.
Padilla-Banks, Elizabeth
TI Prenatal Exposure to Bisphenol A at Environmentally Relevant Doses
Adversely Affects the Murine Female Reproductive Tract Later in Life
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE BPA; carcinogenesis; DES; development; diethylstilbestrol; endocrine
disruptors; ovary; reproduction; toxicology; uterus
ID IN-UTERO EXPOSURE; MOUSE GENITAL-TRACT; DEVELOPMENTAL EXPOSURE;
DIETHYLSTILBESTROL DES; ENDOCRINE DISRUPTORS; FETAL EXPOSURE; ESTROGEN
DIETHYLSTILBESTROL; PERINATAL EXPOSURE; OBESITY EPIDEMIC; MAMMARY-GLAND
AB BACKGROUND: Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a "high-volume production" chemical with widespread human exposure.
OBJECTIVES: In this study we investigated whether prenatal BIPA causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES.
METHODS: Timed pregnant CD-1 mice were treated on days 9-16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 mu g/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated.
RESULTS: Ovarian cysts were significantly increased in the 1-mu g/kg BPA group; ovarian cystadenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls.
CONCLUSIONS: These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation.
C1 [Newbold, Retha R.; Jefferson, Wendy N.; Padilla-Banks, Elizabeth] NIEHS, Dev Endocrinol & Endocrine Disruptor Sect, Mol Toxicol Lab, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Newbold, RR (reprint author), NIEHS, Dev Endocrinol & Endocrine Disruptor Sect, Mol Toxicol Lab, NIH,Dept Hlth & Human Serv, MD K2-15,POB 12233, Res Triangle Pk, NC 27709 USA.
EM newbold1@niehs.nih.gov
FU NIEHS, NIH
FX This research was supported by the Intramural Research Program of the
NIEHS, NIH.
NR 81
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Z9 95
U1 2
U2 30
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUN
PY 2009
VL 117
IS 6
BP 879
EP 885
DI 10.1289/ehp.0800045
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 451HZ
UT WOS:000266462600021
PM 19590677
ER
PT J
AU Rappaport, SM
Kim, S
Lan, Q
Vermeulen, R
Waidyanatha, S
Zhang, LP
Li, GL
Yin, SN
Hayes, RB
Rothman, N
Smith, MT
AF Rappaport, Stephen M.
Kim, Sungkyoon
Lan, Qing
Vermeulen, Roel
Waidyanatha, Suramya
Zhang, Luoping
Li, Guilan
Yin, Songnian
Hayes, Richard B.
Rothman, Nathaniel
Smith, Martyn T.
TI Evidence That Humans Metabolize Benzene via Two Pathways
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE benzene; biomonitoring; cancer risk; cytochrome P450; metabolism
ID URINARY BENZENE; TRANS,TRANS-MUCONIC ACID; ENVIRONMENTAL EXPOSURES;
PHYSIOLOGICAL MODEL; UNEXPOSED SUBJECTS; B6C3F1 MICE; ADDUCTS; LEUKEMIA;
RATS; WORKERS
AB BACKGROUND: Recent evidence has shown that humans metabolize benzene more efficiently at environmental air concentrations than at concentrations > 1 ppm. This led us to speculate that an unidentified metabolic pathway was mainly responsible for benzene metabolism at ambient levels.
OBJECTIVE: We statistically tested whether human metabolism of benzene is better fitted by a kinetic model having two pathways rather than one.
METHODS: We fit Michaelis-Menten-like models to levels of urinary benzene metabolites and the corresponding air concentrations for 263 nonsmoking Chinese females. Estimated benzene concentrations ranged from less than 0.001 ppm to 299 ppm, with 10th and 90th percentile values of 0.002 ppm and 8.97 ppm, respectively.
RESULTS: Using values of Akaike's information criterion obtained under the two models, we found strong statistical evidence favoring two metabolic pathways, with respective affinities (benzene air concentrations analogous to K(m) values) of 301 ppm for the low-affinity pathway (probably dominated by cytochrome P450 enzyme 2E1) and 0.594 ppm for the high-affinity pathway (unknown). The exposure-specific metabolite level predicted by our two-pathway model at nonsaturating concentrations was 184 mu M/ppm of benzene, a value close to an independent estimate of 194 mu M/ppm for a typical nonsmoking Chinese female. Our results indicate that a nonsmoking woman would metabolize about three times more benzene from the ambient environment under the two-pathway model (184 mu M/ppm) than under the one-pathway model (68.6 mu M/ppm). In fact, 73% of the ambient benzene dose would be metabolized via the unidentified high-affinity pathway.
CONCLUSION: Because regulatory risk assessments have assumed nonsaturating metabolism of benzene in persons exposed to air concentrations well above 10 ppm, our findings suggest that the true leukemia risks could be substantially greater than currently thought at ambient levels of exposure-about 3-fold higher among nonsmoking females in the general population.
C1 [Rappaport, Stephen M.; Zhang, Luoping; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Kim, Sungkyoon; Waidyanatha, Suramya] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA.
[Lan, Qing; Hayes, Richard B.; Rothman, Nathaniel] NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Li, Guilan] Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Poison Control, Beijing, Peoples R China.
RP Rappaport, SM (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
EM srappaport@berkeley.edu
RI Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
FU National Institute for Environmental Health Sciences [P42ES05948,
P30ES10126]; National Institutes of Health; National Cancer Institute;
[RO1ES06721]; [P42ES04705]
FX This research was supported by the National Institute for Environmental
Health Sciences through grants P42ES05948 and P30ES10126 to S.M.R. and
RO1ES06721 and P42ES04705 to M.T.S. and by funds from the intramural
research program of the National Institutes of Health, National Cancer
Institute.
NR 50
TC 41
Z9 42
U1 2
U2 11
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUN
PY 2009
VL 117
IS 6
BP 946
EP 952
DI 10.1289/ehp.0800510
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 451HZ
UT WOS:000266462600032
PM 19590688
ER
PT J
AU Ward, MH
Colt, JS
Metayer, C
Gunier, RB
Lubin, J
Crouse, V
Nishioka, MG
Reynolds, P
Buffler, PA
AF Ward, Mary H.
Colt, Joanne S.
Metayer, Catherine
Gunier, Robert B.
Lubin, Jay
Crouse, Vonda
Nishioka, Marcia G.
Reynolds, Peggy
Buffler, Patricia A.
TI Residential Exposure to Polychlorinated Biphenyls and Organochlorine
Pesticides and Risk of Childhood Leukemia
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE childhood cancer; dust; leukemia; organochlorine compounds; pesticides;
polychlorinated biphenyls
ID POLYBROMINATED DIPHENYL ETHERS; NON-HODGKIN-LYMPHOMA;
OCCUPATIONAL-EXPOSURE; AGRICULTURAL HEALTH; BLOOD DYSCRASIAS; TEMPORAL
TRENDS; YOUNG-CHILDREN; BREAST-MILK; CARPET DUST; HOUSE-DUST
AB BACKGROUND: Incidence of childhood leukemia in industrialized countries rose significantly during 1975-2004, and the reasons for the increase are not understood.
OBJECTIVES: We used carpet dust as an exposure indicator to examine the risk of childhood leukemia in relation to residential exposure to persistent organochlorine chemicals: six polychlorinated biphenyl (PCB) congeners and the pesticides alpha- and gamma-chlordane, pp'-DDT (dichlorodiphenyltrichloroethane), pp'-DDE (dichlorodiphenyidichloroethylene), methoxychlor, and pentachlorophenol.
METHODS: We conducted a population-based case-control study in 35 counties in northern and central California in 2001-2006. The study included 184 acute lymphocytic leukemia (ALL) cases 0-7 years of age and 212 birth certificate controls matched to cases by birth date, sex, race, and Hispanic ethnicity. We collected carpet dust samples from the room where the child spent the most time before diagnosis (similar date for controls) using a specialized vacuum.
RESULTS: Detection of any PCB congener in the dust conferred a 2-fold increased risk of ALL (odds ratio (OR) = 1.97; 95% confidence interval (CI), 1.22-3.17]. Compared with those in the lowest quartile of total PCBs, the highest quartile was associated with about a 3-fold risk (OR = 2.78; 95% CI, 1.41-5.48), and the positive trend was significant (p = 0.017). Significant positive trends in ALL risk were apparent with increasing concentrations of PCB congeners 118, 138, and 153. We bserved no significant positive associations for chlordane, DDT, DDE, methoxychlor, or pentachlorophenol. The associations with PCBs were stronger among non-Hispanic whites than among Hispanics despite similar distributions of PCB levels among controls in each racial/ethnic group.
CONCLUSIONS: Our findings suggest that PCBs, which are considered probable human carcinogens and cause perturbations of the immune system, may represent a previously unrecognized risk factor for childhood leukemia.
C1 [Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Metayer, Catherine; Buffler, Patricia A.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Gunier, Robert B.; Reynolds, Peggy] No Calif Canc Ctr, Berkeley, CA USA.
[Crouse, Vonda] Childrens Hosp Cent Calif, Madera, CA USA.
[Nishioka, Marcia G.] Battelle Mem Inst, Columbus, OH 43201 USA.
RP Ward, MH (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Rm 8006, Bethesda, MD 20892 USA.
EM wardm@mail.nih.gov
OI Gunier, Robert/0000-0001-5485-9919
FU National Cancer Institute (NCI); National Institutes of Health;
University of California-Berkeley [7590-S-04]; Battelle Memorial
Institute [7590-S-01]; Westar Inc [N02-CP-11015]; National Institute of
Environmental Health Sciences [R01ES009137, P-42-ES-04705-18]; NCI
[5R01CA092683-03]
FX This research was partially supported by the Intramural Research program
of the National Cancer Institute (NCI), National Institutes of Health,
and through NCI subcontracts 7590-S-04 (University of
California-Berkeley) and 7590-S-01 (Battelle Memorial Institute) under
NCI contract N02-CP-11015 (Westar Inc.). This research was also
financially supported by National Institute of Environmental Health
Sciences grants R01ES009137 and P-42-ES-04705-18 (University of
California and Berkeley) and NCI grant 5R01CA092683-03 (Colorado State
University).
NR 50
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U1 3
U2 27
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUN
PY 2009
VL 117
IS 6
BP 1007
EP 1013
DI 10.1289/ehp.0900583
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 451HZ
UT WOS:000266462600042
PM 19590698
ER
PT J
AU Koelle, K
Kamradt, M
Pascual, M
AF Koelle, Katia
Kamradt, Meredith
Pascual, Mercedes
TI Understanding the dynamics of rapidly evolving pathogens through
modeling the tempo of antigenic change: Influenza as a case study
SO EPIDEMICS
LA English
DT Article
DE Multi-strain model; RNA virus; Rapid evolution
AB Rapidly evolving pathogens present a major conceptual and mathematical challenge to our understanding of disease dynamics. For these pathogens, the simulation of disease dynamics requires the use of computational models that incorporate pathogen evolution. Currently, these models are limited by two factors. First, their computational complexity hinders their numerical analysis and the ease with which parameters can be statistically estimated. Second, their formulations are frequently not sufficiently general to allow for alternative immunological hypotheses to be considered. Here, we introduce a new modeling framework for rapidly evolving pathogens that lessens both of these limitations. At its core, the proposed framework differs from previous multi-strain models by modeling the tempo of antigenic change instead of the pathogen's genetic change. This shift in focus results in a new model of reduced computational complexity that can accommodate different immunological hypotheses. We demonstrate the utility of this antigenic tempo model in an application to influenza. We show that, under different parameterizations, the model can reproduce the qualitative findings of a diverse set of previously published flu models, despite being less computationally intensive. These advantages of the antigenic tempo model make it a useful alternative to address several outstanding questions for rapidly evolving pathogens. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Koelle, Katia; Kamradt, Meredith] Duke Univ, Dept Biol, Durham, NC 27708 USA.
[Koelle, Katia] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Koelle, Katia; Pascual, Mercedes] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Pascual, Mercedes] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Koelle, K (reprint author), Duke Univ, Dept Biol, Box 90338, Durham, NC 27708 USA.
EM katia.koelle@duke.edu
FU James S. McDonnell Foundation; Science and Technology Directorate,
Department of Homeland Security; Fogarty International Center, National
Institutes of Health; [NSF-EF-08-27416]
FX We thank J. Lloyd-Smith and S. Cobey for their helpful insights and
feedback, and Brian Finkelman for his 'phenodynamic' insights. Support
for K. K. and M. P. was provided by a Centennial fellowship of the James
S. McDonnell Foundation to M. P.; further support for K. K. and support
for M. K. was provided by grant NSF-EF-08-27416 and by the RAPIDD
program of the Science and Technology Directorate, Department of
Homeland Security, and the Fogarty International Center, National
Institutes of Health. MP is an investigator of the Howard Hughes Medical
Institute.
NR 33
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U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1755-4365
J9 EPIDEMICS-NETH
JI Epidemics
PD JUN
PY 2009
VL 1
IS 2
BP 129
EP 137
DI 10.1016/j.epidem.2009.05.003
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA V21UQ
UT WOS:000208232900008
PM 21352760
ER
PT J
AU Iseki, K
Ikeda, A
Kihara, T
Kawamoto, Y
Mezaki, T
Hanakawa, T
Hashikawa, K
Fukuyama, H
Shibasaki, H
AF Iseki, Kazumi
Ikeda, Akio
Kihara, Takeshi
Kawamoto, Yasuhiro
Mezaki, Takahiro
Hanakawa, Takashi
Hashikawa, Kazuo
Fukuyama, Hidenao
Shibasaki, Hiroshi
TI Impairment of the cortical GABAergic inhibitory system in catatonic
stupor: a case report with neuroimaging
SO EPILEPTIC DISORDERS
LA English
DT Article
DE catatonia; encephalitis; PET; SPECT; EEG
ID POSITRON EMISSION TOMOGRAPHY; BENZODIAZEPINE RECEPTORS; HUMAN-BRAIN;
BINDING; PET; ENCEPHALITIS; GABA
AB We report the case of a 32-year-old patient who presented with catatonic stupor during the course of acute aseptic encephalitis involving the right frontotemporal area. Flumazenil-PET performed during the stupor indicated decreased benzodiazepine receptor binding in the right frontotemporal area where glucose metabolism was preserved as revealed by FDG-PET. An injection of diazepam immediately ameliorated catatonic symptoms and reduced widespread high amplitude slow EEG activities with right frontotemporal predominance. Compared with a SPECT study performed a week earlier, there was no abnormal right-sided anteriorly predominant cerebral hyperperfusion after injection of diazepam. While neither flumazenil- nor FDG-PET could be repeated, and with the caveat that generalized convulsions occurred initially and epilepsia partialis continua was present for two weeks starting on the 23(rd) day after illness onset, these findings suggest that in our case the presentation with catatonic stupor may be related to impairment of the cortical GABAergic inhibitory system.
C1 [Ikeda, Akio] Kyoto Univ Hosp, Dept Neurol, Sakyo Ku, Kyoto 6068507, Japan.
[Iseki, Kazumi; Hanakawa, Takashi; Hashikawa, Kazuo; Fukuyama, Hidenao; Shibasaki, Hiroshi] Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Kyoto, Japan.
[Iseki, Kazumi] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD USA.
[Shibasaki, Hiroshi] Takeda Gen Hosp, Dept Neurol, Kyoto, Japan.
RP Ikeda, A (reprint author), Kyoto Univ Hosp, Dept Neurol, Sakyo Ku, 54 Shogoin Kawaharacho, Kyoto 6068507, Japan.
EM akio@kuhp.kyoto-u.ac.jp
OI Ikeda, Akio/0000-0002-0790-2598
NR 14
TC 8
Z9 10
U1 0
U2 1
PU JOHN LIBBEY EUROTEXT LTD
PI MONTROUGE
PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE
SN 1294-9361
J9 EPILEPTIC DISORD
JI Epileptic Disord.
PD JUN
PY 2009
VL 11
IS 2
BP 126
EP 131
DI 10.1684/epd.2009.0257
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 461GV
UT WOS:000267253600004
PM 19477714
ER
PT J
AU Afuola, F
Chang, CL
Li, QX
AF Afuola, Fasia
Chang, Chiou Ling
Li, Qing Xiao
TI EVALUATION OF ALTERNATIVES FOR WHEAT GERM OIL AS AN ENHANCER FOR MELON
FRUIT FLY LIQUID LARVAL REARING DIET
SO ETHNICITY & DISEASE
LA English
DT Article
AB Background. Wheat germ oil is one of the most significant ingredients used in preparing the liquid larval diet, which is used for rearing fruit flies and determining the larval production. Wheat germ oil is used by numerous research facilities and costs approximately >$100 per gallon.
Objective. The objective of this research study was to find an inexpensive oil that Could be used as an effective alternative for wheat germ oil and that would provide enough fatty acids for the larvae to develop normally. We hypothesized that the oil that contains the highest percentage of fatty acids and Vitamin E would be an effective alternative for the use of wheat germ oil.
Methods. The fruit flies known as the melon fruit flies, Bactrocera Cucurbitae, were selected for this research. Four different, inexpensive, commonly used oils, all containing approximately the same percent of total fat, were used for comparison and testing: corn oil, vegetable oil, canola oil, with 10% vitamin E, and canola oil with 20% vitamin E. For the research, we used five trays of fruit flies, each with a different oil and the control oil, wheat germ oil. We analyzed: larval duration, pupal recovery, pupal weight, adult emergence, adult fliers and percent mating.
Results. No significant differences were found in any category between wheat germ oil and the commonly used, inexpensive oils.
Conclusions. All the oils tested in this study had good potential to serve as Substitutes for wheat germ oil in the fruit fly larval rearing diet. We recommend corn oil as the first choice for an alternative to wheat germ oil.
C1 [Afuola, Fasia] NIDDK, NIH, Step Program, Bethesda, MD 20892 USA.
[Li, Qing Xiao] Univ Hawaii Manoa, Honolulu, HI 96822 USA.
RP Afuola, F (reprint author), NIDDK, NIH, Step Program, Bethesda, MD 20892 USA.
NR 1
TC 0
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U1 1
U2 1
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD SUM
PY 2009
VL 19
IS 2
SU 3
BP S33
EP S34
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 461WA
UT WOS:000267302200016
ER
PT J
AU Ferguson, F
Halpern-Felsher, BL
Hui, G
Norris, KC
Agodoa, LY
AF Ferguson, Frances
Halpern-Felsher, Bonnie L.
Hui, George
Norris, Keith C.
Agodoa, Lawrence Y.
TI NIDDK AND THE MINORITY BIOMEDICAL PIPELINE FOREWORD
SO ETHNICITY & DISEASE
LA English
DT Editorial Material
C1 [Ferguson, Frances; Agodoa, Lawrence Y.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Halpern-Felsher, Bonnie L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hui, George] Univ Hawaii Manoa, Honolulu, HI 96822 USA.
[Norris, Keith C.] Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA.
RP Ferguson, F (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
NR 2
TC 0
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U1 0
U2 0
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD SUM
PY 2009
VL 19
IS 2
SU 3
BP SI
EP SII
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 461WA
UT WOS:000267302200001
ER
PT J
AU Ruiz, JR
Gonzalez, HF
Gonzalez, MY
AF Ruiz, Javier R.
Gonzalez, Hector F.
Gonzalez, Monica Y.
TI METABOLIC SYNDROME AND SOFT DRINK CONSUMPTION
SO ETHNICITY & DISEASE
LA English
DT Article
AB Metabolic syndrome is a cluster of symptoms that, if left untreated may develop into worse health conditions, such as diabetes. This Study was clone to investigate whether excess glucose and carbohydrates affect the risk of developing metabolic syndrome. We studied members of the Latino population, which are known to be at high-risk of diabetes. For the purpose of this study, we used revised ATP III criteria, consisting of high BMI, high blood pressure, elevated triglycerides, low high-density lipoprotein (HDL)-cholesterol levels, and high fasting glucose levels. Our analysis was conducted by obtaining the data from a blood test and answers to an assessment tool. Using the revised ATP III criteria, 18 of the 53 patients had metabolic syndrome. Of those with metabolic syndrome, all but one reported drinking soda. These same patients had the highest risk values in each of the five different metabolic syndrome criteria. Of the 53 patients, only 8 reported not drinking any soda. The 8 patients with no soda intake were in the normal ranges for their BMI, glucose levels, and blood pressure readings. Of these eight patients, four did little or no exercise resulting in high triglyceride levels. HDL levels appeared to be unaffected by the soda intake.
C1 [Ruiz, Javier R.] NIH Intern, Bethesda, MD USA.
[Gonzalez, Hector F.; Gonzalez, Monica Y.] City Laredo Hlth Dept, Laredo, TX USA.
RP Ruiz, JR (reprint author), NIH Intern, Bethesda, MD USA.
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PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD SUM
PY 2009
VL 19
IS 2
SU 3
BP S21
EP S22
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 461WA
UT WOS:000267302200011
ER
PT J
AU Taylor, J
AF Taylor, Jennifer
TI Changes in the research landscape require a new approach, while
continuing to fund the highest scientific priorities
SO EUROPEAN HEART JOURNAL
LA English
DT Article
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
RP Taylor, J (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 1
U2 2
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 JUN
PY 2009
VL 30
IS 12
BP 1423
EP 1425
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 460VM
UT WOS:000267219300002
ER
PT J
AU Ryott, M
Wangsa, D
Heselmeyer-Haddad, K
Lindholm, J
Elmberger, G
Auer, G
Lundqvist, EA
Ried, T
Munck-Wikland, E
AF Ryott, Michael
Wangsa, Darawalee
Heselmeyer-Haddad, Kerstin
Lindholm, Johan
Elmberger, Goran
Auer, Gert
Lundqvist, Elisabeth Avall
Ried, Thomas
Munck-Wikland, Eva
TI EGFR protein overexpression and gene copy number increases in oral
tongue squamous cell carcinoma
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Mouth neoplasms; In situ hybridisation; Fluorescence;
Immunohistochemistry
ID EPIDERMAL-GROWTH-FACTOR; COMPARATIVE GENOMIC HYBRIDIZATION; FACTOR
RECEPTOR EXPRESSION; LUNG-CANCER; NECK-CANCER; PREDICTIVE FACTORS; HEAD;
RADIOTHERAPY; SENSITIVITY; GEFITINIB
AB New promising therapeutic agents targeting epidermal growth factor receptor (EGFR) have been developed although clinical information concerning EGFR status in oral tongue squamous cell carcinoma (OTSCC) is limited. We investigated EGFR protein expression and gene copy numbers in 78 pretreatment OTSCC paraffin samples. EGFR protein expression was found in all 78 tumours, of which 72% showed an intense staining. Fifty-four percent of the tumours had high (>= four gene copies) EGFR gene copy numbers. EGFR gene copy number was significantly associated with EGFR protein expression (P = 0.002). Pretreatment EGFR staining intensity tended to be associated with non-pathological complete remission after preoperative radiotherapy for Stage II OTSCC. No correlation was found between EGFR status and survival. EGFR FISH results were significantly (P = 0.003) higher in more advanced tumours (Stages II, III and IV) than in the tumours in Stage I. Non-smokers exhibited a significantly higher EGFR gene copy number and protein overexpression in Stages I and II OTSCC than smokers (P = 0.001, P = 0.009). In conclusion, EGFR was found to be over-expressed in all OTSCCs making this cancer type interesting for exploring new therapeutic agents targeting the EGFR receptor. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Ryott, Michael; Munck-Wikland, Eva] Karolinska Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, S-17176 Stockholm, Sweden.
[Wangsa, Darawalee; Lindholm, Johan; Elmberger, Goran; Auer, Gert] Karolinska Univ Hosp, Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden.
[Wangsa, Darawalee; Heselmeyer-Haddad, Kerstin; Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lundqvist, Elisabeth Avall] Karolinska Univ Hosp, Dept Gynaecol Oncol, S-17176 Stockholm, Sweden.
RP Ryott, M (reprint author), Karolinska Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, S-17176 Stockholm, Sweden.
EM michael.ryott@karolinska.se
RI Avall-Lundqvist, Elisabeth/C-9292-2009
FU Swedish Cancer Society; Cancer Society of Stockholm; Laryngfonden,
Karolinska Institutet; Intramural Research Programme of the NIH;
National Cancer Institute
FX This work was supported by the Swedish Cancer Society (Cancerfonden),
the Cancer Society of Stockholm (Cancerforreningen), Laryngfonden,
Karolinska Institutet and the Intramural Research Programme of the NIH,
National Cancer Institute. We gratefully thank Ann Olsson and Margaretha
Waern for excellent technical assistance.
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U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD JUN
PY 2009
VL 45
IS 9
BP 1700
EP 1708
DI 10.1016/j.ejca.2009.02.027
PG 9
WC Oncology
SC Oncology
GA 451XL
UT WOS:000266504100031
PM 19332367
ER
PT J
AU Wirfalt, E
Midthune, D
Reedy, J
Mitrou, P
Flood, A
Subar, AF
Leitzmann, M
Mouw, T
Hollenbeck, AR
Schatzkin, A
Kipnis, V
AF Wirfalt, E.
Midthune, D.
Reedy, J.
Mitrou, P.
Flood, A.
Subar, A. F.
Leitzmann, M.
Mouw, T.
Hollenbeck, A. R.
Schatzkin, A.
Kipnis, V.
TI Associations between food patterns defined by cluster analysis and
colorectal cancer incidence in the NIH-AARP diet and health study
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE food patterns; cluster analysis; colorectal cancer; prospective cohort
ID RETIRED-PERSONS DIET; LIFE-STYLE FACTORS; FREQUENCY QUESTIONNAIRES;
NUTRITIONAL EPIDEMIOLOGY; AMERICAN-ASSOCIATION; NATIONAL-INSTITUTES;
EATING PATTERNS; COLON-CANCER; RISK; COHORT
AB Background/Objectives: To examine associations between food patterns, constructed with cluster analysis, and colorectal cancer incidence within the National Institutes of Health-AARP Diet and Health Study.
Subjects/Methods: A prospective cohort, aged 50-71 years at baseline in 1995-1996, followed until the end of 2000. Food patterns were constructed, separately in men (n = 293 576) and women (n = 198 730), with 181 food variables (daily intake frequency per 1000 kcal) from a food frequency questionnaire. Four large clusters were identified in men and three in women. Cox proportional hazards regression examined associations between patterns and cancer incidence.
Results: In men, a vegetable and fruit pattern was associated with reduced colorectal cancer incidence (multivariate hazard ratio, HR: 0.85; 95% confidence interval, CI: 0.76, 0.94), when compared to less salutary food choices. Both the vegetable and fruit pattern and a fat-reduced foods pattern were associated with reduced rectal cancer incidence in men. In women, a similar vegetable and fruit pattern was associated with colorectal cancer protection (age-adjusted HR: 0.82; 95% CI: 0.70, 0.95), but the association was not statistically significant in multivariate analysis.
Conclusions: These results, together with findings from previous studies support the hypothesis that micronutrient dense, low-fat, high-fiber food patterns protect against colorectal cancer. European Journal of Clinical Nutrition (2009) 63, 707-717; doi: 10.1038/ejcn.2008.40; published online 6 August 2008
C1 [Wirfalt, E.] Lund Univ, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden.
[Midthune, D.; Reedy, J.; Mitrou, P.; Subar, A. F.; Leitzmann, M.; Mouw, T.; Schatzkin, A.; Kipnis, V.] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Mitrou, P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Flood, A.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA.
[Hollenbeck, A. R.] AARP, Washington, DC USA.
RP Wirfalt, E (reprint author), Lund Univ, Dept Clin Sci Malmo, Entrance 72, SE-20502 Malmo, Sweden.
EM elisabet.wirfalt@med.lu.se
FU NIH, National Cancer Institute; Swedish Cancer Foundation [05 0128];
Swedish Council for Working Life and Social Research [2005-1703]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute. 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. We are
indebted to the participants in the NIH-AARP Diet and Health Study for
their outstanding cooperation. Funding was also received from the
Swedish Cancer Foundation (contract 05 0128 to EW) and the Swedish
Council for Working Life and Social Research (contract 2005-1703 to EW).
NR 46
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U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0954-3007
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD JUN
PY 2009
VL 63
IS 6
BP 707
EP 717
DI 10.1038/ejcn.2008.40
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 452WN
UT WOS:000266572000001
PM 18685556
ER
PT J
AU Forman, MR
Borkowf, CB
Cantwell, MM
Steck, S
Schatzkin, A
Albert, PS
Lanza, E
AF Forman, M. R.
Borkowf, C. B.
Cantwell, M. M.
Steck, S.
Schatzkin, A.
Albert, P. S.
Lanza, E.
TI Components of variation in serum carotenoid concentrations: the Polyp
Prevention Trial
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE carotenoids; serum; repeated measurements; Polyp Prevention Trial
ID FOOD-COMPOSITION DATABASE; BETA-CAROTENE; PLASMA CAROTENOIDS;
ALPHA-TOCOPHEROL; DIETARY INTERVENTION; INTESTINAL-ABSORPTION;
SEASONAL-VARIATIONS; FRUIT INTAKE; HIGH-FIBER; LOW-FAT
AB Objectives: The intra- and interindividual variations and season and center effects were estimated from a series of serum carotenoid concentrations in the Polyp Prevention Trial (PPT) participants.
Subjects/Methods: Fasting blood was collected annually for 4 years in all 1905 participants, and a subcohort of 901 participants were selected within each (of eight) center(s), by gender and dietary arm of the study, for measurement of five major carotenoid peaks. Using variance of component methods, the variation in serum carotenoid concentrations about the underlying mean was partitioned into explanatory components attributed to various sources.
Results: The contributions of the inter- and intraindividual variances to the overall variation in carotenoid concentrations were in the range of 61-70 and 20-35%, respectively, whereas center and center-by-season effects provided 2.6-9.5 and 0.2-1.4%, respectively. The highest percent (35%) of intraindividual variation was exhibited by lycopene, and the highest percent (70% apiece) of interindividual variation was exhibited by lutein/zeaxanthin and beta-carotene. Serum lycopene had the highest ratio of intra- to interindividual variation of 0.57, whereas lutein had the lowest ratio of 0.29. We estimate that the ratio of intra- to interindividual variance around the mean carotenoid concentration can be reduced greatly by collecting 3-4 compared to 1 blood measurement in large-scale trials like the PPT.
Conclusion: In the largest study of components of variation in individuals at high risk for colorectal cancer, the largest contributors to variation in serum carotenoid concentrations were intra- and interindividual effects followed by center and center-by-season effects. European Journal of Clinical Nutrition (2009) 63, 763-770; doi:10.1038/ejcn.2008.26; published online 16 April 2008
C1 [Forman, M. R.; Cantwell, M. M.] Natl Canc Inst, Lab Biosyst & Canc, Ctr Canc Res, Bethesda, MD USA.
[Borkowf, C. B.; Lanza, E.] NCI, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Steck, S.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Schatzkin, A.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Albert, P. S.] Natl Canc Inst, Div Canc Treatment & Diag, Bethesda, MD USA.
RP Forman, MR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Unit 1340, 1155 Herman Pressler, Houston, TX 77030 USA.
EM mforman@mdanderson.org
RI Steck, Susan/G-5736-2013
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U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0954-3007
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD JUN
PY 2009
VL 63
IS 6
BP 763
EP 770
DI 10.1038/ejcn.2008.26
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 452WN
UT WOS:000266572000008
PM 18414504
ER
PT J
AU Olafsdottir, E
Aspelund, T
Sigurdsson, G
Thorsson, B
Benediktsson, R
Harris, TB
Launer, LJ
Eiriksdottir, G
Gudnason, V
AF Olafsdottir, Elin
Aspelund, Thor
Sigurdsson, Gunnar
Thorsson, Bolli
Benediktsson, Rafn
Harris, Tamara B.
Launer, Lenore J.
Eiriksdottir, Gudny
Gudnason, Vilmundur
TI Unfavourable risk factors for type 2 diabetes mellitus are already
apparent more than a decade before onset in a population-based study of
older persons: from the Age, Gene/Environment Susceptibility-Reykjavik
Study (AGES-Reykjavik)
SO EUROPEAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Cohort study; Epidemiology; Type 2 diabetes; Older persons; Long term
risk evaluation of T2DM; AGES-Reykjavik
ID CORONARY-HEART-DISEASE; IMPAIRED GLUCOSE-TOLERANCE; METABOLIC SYNDROME;
LIFE-STYLE; PREVALENCE; MODEL; MORTALITY; WOMEN; MEN; US
AB We evaluated midlife risk factors of developing type 2 diabetes mellitus (T2DM) in late life in a population-based study of older persons. A cohort of 2,251 persons, aged 65-96, participated in AGES-Reykjavik in 2002-2004; all attended the Reykjavik Study 26 years earlier, at the mean age of 50. Based on glucometabolic status in 2002-2004 the participants are divided into a normoglycemic control group (n = 1,695), an impaired fasting glucose (IFG) group (n = 313) and T2DM group (n = 243). Change in risk parameters from midlife is evaluated retrospectively in these three groups. Since examined earlier 14.3% of men and 8.2% of women developed T2DM. A family history of diabetes was reported in 39.5% of T2DM compared to 19.3% in both IFG and normoglycemics. The T2DM and IFG groups currently have higher levels of fasting triglycerides, greater body mass index (BMI) and higher systolic blood pressure than normoglycemics and this difference was already apparent in midlife. In late life, two or more metabolic syndrome criteria are present in 60% of the T2DM groups compared to 25% in normoglycemic groups. T2DM with impaired cardiovascular health is more marked in women than men when compared with normoglycemics. Family history and higher levels of BMI, triglycerides and systolic blood pressure in midlife are associated with the development of T2DM in late life, suggesting risk can be evaluated long before onset. A continued rise in risk factors throughout life allows for more aggressive measures in preventing or delaying development of T2DM and its effect on cardiovascular health.
C1 [Olafsdottir, Elin; Aspelund, Thor; Thorsson, Bolli; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
[Sigurdsson, Gunnar; Benediktsson, Rafn; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Sigurdsson, Gunnar; Benediktsson, Rafn] Landspitali Univ Hosp, Reykjavik, Iceland.
[Aspelund, Thor] Univ Iceland, Fac Sci, Reykjavik, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] Natl Inst Aging, Intramural Res Program, Bethesda, MD 20892 USA.
RP Olafsdottir, E (reprint author), Iceland Heart Assoc, Holtasmari 1, IS-201 Kopavogur, Iceland.
EM elinolafs@hjarta.is
RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason,
Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084
FU National Institutes of Health [NO1-AG-1-2100]; National Institute on
Aging Intramural Research Program; Icelandic Government; Icelandic Heart
Association
FX The study is supported by National Institutes of Health contract
NO1-AG-1-2100, the National Institute on Aging Intramural Research
Program, the Icelandic Government and the Icelandic Heart Association.
NR 28
TC 9
Z9 9
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0393-2990
J9 EUR J EPIDEMIOL
JI Eur. J. Epidemiol.
PD JUN
PY 2009
VL 24
IS 6
BP 307
EP 314
DI 10.1007/s10654-009-9343-x
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 448CO
UT WOS:000266240500005
PM 19412572
ER
PT J
AU Murphy, G
Thornton, J
McManus, R
Swan, N
Ryan, B
Hughes, DJ
O'Morain, CA
O'Sullivan, M
AF Murphy, Gwen
Thornton, Jacinta
McManus, Ross
Swan, Niall
Ryan, Barbara
Hughes, David J.
O'Morain, Colm A.
O'Sullivan, Maria
TI Association of gastric disease with polymorphisms in the
inflammatory-related genes IL-1B, IL-1RN, IL-10, TNF and TLR4
SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY
LA English
DT Article
DE gastritis; Helicobacter pylori; intestinal metaplasia; interleukin-1
beta; interleukin-10; toll-like receptor 4; tumour necrosis factor-alpha
ID HELICOBACTER-PYLORI INFECTION; TOLL-LIKE RECEPTOR-4; INCREASED RISK;
INTERLEUKIN-1 POLYMORPHISMS; HAPLOTYPE RECONSTRUCTION; FUNCTIONAL
POLYMORPHISM; PRECANCEROUS LESIONS; ATROPHIC GASTRITIS; CHINESE
POPULATION; DUODENAL-ULCER
AB Objectives This study aimed to investigate if single nucleotide polymorphisms (SNPs) in a series of inflammatory genes were associated with the development of the most common pathologies thought to precede gastric cancer development namely; Helicobacter pylori (H. pylon)-associated gastritis and intestinal metaplasia.
Methods A total of 250 patients were genotyped for 11 SNPs in the IL-1B, IL-1RN, TNF, TLR4 and IL-10 genes. The study population comprised H. pylori uninfected ('normal' control patients (n=96), H. pylori-positive gastritis (n=91) and intestinal metaplasia patients (n = 63). Genotyping was performed using Taqman allelic discrimination assays. Odds ratios for gastric disease groups were adjusted for potential confounding factors.
Results No differences were identified in frequency of carriage, or homozygosity, for any of the 'risk' alleles investigated across the patient groups. No evidence was found to suggest an association with increased risk of developing either chronic gastritis or intestinal metaplasia with SNPs in the IL-1B, IL-1RN, TNF, TLR4 and IL-10 genes or haplotypes tested.
Conclusion This study found no evidence of an association with increased risk of developing either chronic gastritis or intestinal metaplasia with the SNPs or haplotypes tested. Eur J Gastroenterol Hepatol 21:630-635 (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Hughes, David J.; O'Morain, Colm A.; O'Sullivan, Maria] Adelaide & Meath Hosp, Trinity Ctr Hlth Sci, Dept Clin Med, Dublin 24, Ireland.
[Murphy, Gwen] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA.
[Murphy, Gwen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Thornton, Jacinta; McManus, Ross] St James Hosp, Trinity Coll, Dublin Mol Med Ctr, Dublin, Ireland.
[Swan, Niall] Adelaide & Meath Hosp, Trinity Ctr Hlth Sci, Dept Pathol, Dublin 24, Ireland.
[Ryan, Barbara] Adelaide & Meath Hosp, Trinity Ctr Hlth Sci, Dept Gastroenterol, Dublin 24, Ireland.
RP O'Sullivan, M (reprint author), Adelaide & Meath Hosp, Trinity Ctr Hlth Sci, Dept Clin Med, Dublin 24, Ireland.
EM maria.o.sullivan@tcd.ie
RI Murphy, Gwen/G-7443-2015;
OI McManus, Ross/0000-0002-0529-9617
FU Health Research Board (Ireland); Meath Foundation, Dublin, Ireland
FX The authors acknowledge the support of the Health Research Board
(Ireland) and the Meath Foundation, Dublin, Ireland.
NR 35
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U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0954-691X
J9 EUR J GASTROEN HEPAT
JI Eur. J. Gastroenterol. Hepatol.
PD JUN
PY 2009
VL 21
IS 6
BP 630
EP 635
DI 10.1097/MEG.0b013e3283140eea
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 446RF
UT WOS:000266138100005
PM 19295440
ER
PT J
AU Choi, SJ
Marazita, ML
Hart, PS
Sulima, PP
Field, LL
McHenry, TG
Govil, M
Cooper, ME
Letra, A
Menezes, R
Narayanan, S
Mansilla, MA
Granjeiro, JM
Vieira, AR
Lidral, AC
Murray, JC
Hart, TC
AF Choi, Sun J.
Marazita, Mary L.
Hart, P. Suzanne
Sulima, Pawel P.
Field, L. Leigh
McHenry, Toby Goldstein
Govil, Manika
Cooper, Margaret E.
Letra, Ariadne
Menezes, Renato
Narayanan, Somnya
Mansilla, Maria Adela
Granjeiro, Jose M.
Vieira, Alexandre R.
Lidral, Andrew C.
Murray, Jeffrey C.
Hart, Thomas C.
TI The PDGF-C regulatory region SNP rs28999109 decreases promoter
transcriptional activity and is associated with CL/P
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE PDGF-C; SNP; CL/P; promoter activity
ID GROWTH-FACTOR-C; NONSYNDROMIC CLEFT-LIP; RETINOIC ACID; CANDIDATE GENES;
ALPHA-RECEPTOR; LONG ARM; PALATE; EGR-1; IDENTIFICATION; EXPRESSION
AB Human linkage and association studies suggest a gene(s) for nonsyndromic cleft lip with or without cleft palate (CL/P) on chromosome 4q31-q32 at or near the platelet-derived growth factor-C (PDGF-C) locus. The mouse Pdgfc(-/-) knockout shows that PDGF-C is essential for palatogenesis. To evaluate the role of PDGF-C in human clefting, we performed sequence analysis and SNP genotyping using 1048 multiplex CL/P families and 1000 case-control samples from multiple geographic origins. No coding region mutations were identified, but a novel -986 C>T SNP (rs28999109) was significantly associated with CL/P (P=0.01) in cases from Chinese families yielding evidence of linkage to 4q31-q32. Significant or near-significant association was also seen for this and several other PDGF-C SNPs in families from the United States, Spain, India, Turkey, China, and Colombia, whereas no association was seen in families from the Philippines, and Guatemala, and case-controls from Brazil. The -986T allele abolished six overlapping potential transcription regulatory motifs. Transfection assays of PDGF-C promoter reporter constructs show that the -986T allele is associated with a significant decrease (up to 80%) of PDGF-C gene promoter activity. This functional polymorphism acting on a susceptible genetic background may represent a component of human CL/P etiology. European Journal of Human Genetics (2009) 17, 774-784; doi: 10.1038/ejhg.2008.245; published online 17 December 2008
C1 [Choi, Sun J.; Sulima, Pawel P.; Hart, Thomas C.] Natl Inst Dent & Craniofacial Res, Human Craniofacial Genet Sect, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Marazita, Mary L.; McHenry, Toby Goldstein; Govil, Manika; Cooper, Margaret E.; Letra, Ariadne; Menezes, Renato; Narayanan, Somnya; Vieira, Alexandre R.] Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Dept Oral Biol, Pittsburgh, PA USA.
[Hart, P. Suzanne] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Field, L. Leigh] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
[Mansilla, Maria Adela; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Granjeiro, Jose M.] Univ Fed Fluminense, Dept Cell & Mol Biol, Rio De Janeiro, Brazil.
[Lidral, Andrew C.] Univ Iowa, Dept Orthodont, Iowa City, IA USA.
RP Hart, TC (reprint author), Natl Inst Dent & Craniofacial Res, Human Craniofacial Genet Sect, Craniofacial & Skeletal Dis Branch, NIH, Bldg 10,Room 5N 102,10 Ctr Dr, Bethesda, MD 20892 USA.
EM thart@mail.nih.gov
RI Granjeiro, Jose/D-8289-2012; Sulima, Pawel/H-8649-2012
OI Granjeiro, Jose/0000-0002-8027-8293;
FU National Institutes of Health [R01-DE09886, R01-DE012472, R37-DE08559,
R01-DE016148, R01-DE014667, P50-DE016215, N01-HG-65403]; National
Institute of Dental and Craniofacial Research [Z01-DE000711]
FX We acknowledge and express their sincere appreciation to all individuals
who participated in these studies. The staff and collaborators at each
study site were critical for successful completion of these studies: Dr
You-e Liu and Dr Dan-ning Hu China), Dr Ajit Ray India), Dr Tuncbilek
Turkey), Carla Brandon, Kathy Bardi, Judith Resick, Dr Katherine
Neiswanger, Dr Joseph Losee Pittsburgh, USA), Dr Consuelo
Valencia-Ramirez, Dr Mauricio Camargo, Dr Mauricio Arcos-Burgos, Dora
Rivera Colombia), Sybill Naidoo, Dr Rick Martin, Dr Alex Kane St Louis,
USA). Operation Smile International, Operation Smile Philippines, the
HOPE Foundation, Bill and Kathy Magee, Edith Villanueva, Buena
Nepomuceno, Henrietta Gamboa, Salie Onggada, Rachel Lim, and Gloria
Melocoton were all critical to sample collection in the Philippines.
These studies were supported by National Institutes of Health Grants
R01-DE09886, R01-DE012472, R37-DE08559, R01-DE016148, R01-DE014667,
P50-DE016215; and by the Intramural Program of the National Institute of
Dental and Craniofacial Research Z01-DE000711. Some of the genotyping
was provided by the 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 N01-HG-65403.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institute of
Dental and Craniofacial Research or the National Institutes of Health.
NR 47
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U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JUN
PY 2009
VL 17
IS 6
BP 774
EP 784
DI 10.1038/ejhg.2008.245
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 448VC
UT WOS:000266289100013
PM 19092777
ER
PT J
AU Barbosa, EG
Bega, LAS
Beatriz, A
Sarkar, T
Hamel, E
do Amaral, MS
de Lima, DP
AF Barbosa, Euzebio G.
Bega, Luis A. S.
Beatriz, Adilson
Sarkar, Taradas
Hamel, Ernest
do Amaral, Marcos S.
de Lima, Denis Pires
TI A diaryl sulfide, sulfoxide, and sulfone bearing structural similarities
to combretastatin A-4
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Diaryl sulfide; Diaryl sulfoxide; Diaryl sulfone; Combretastatin A-4;
Cytotoxicity; Tubulin polymerization
ID TUBULIN POLYMERIZATION; ANTINEOPLASTIC AGENTS; ANTIMITOTIC AGENTS;
GROWTH; DERIVATIVES; SEPARATION; COMPLEXES; PHOSPHATE; ANALOGS; POTENT
AB Studies examining various spacer groups that link the two aromatic rings of combretastatin A-4 (CA4) have shown that the biological activity of analogs does not require the cis-stilbene configuration of CA4. Oxygen or nitrogen, carbonyl, methylene and ethylene spacers, for example, are present in CA4 analogs that show good activity. Up to now sulfur was not tested for this purpose. In this article we describe the synthesis of sulfide, sulfoxide and sulfone spacers between two aromatic rings comparable to those of CA4. We also compared them with CA4 for inhibitory effects on cell growth, tubulin polymerization, and the binding of [(3)H]colchicine to tubulin. We found that the sulfide is highly active and may be a lead compound for the preparation of antitumor compounds. (C) 2008 Elsevier Masson SAS. All rights reserved.
C1 [Barbosa, Euzebio G.; Bega, Luis A. S.; Beatriz, Adilson; de Lima, Denis Pires] Univ Fed Mato Grosso do Sul, Dept Quim, CCET, Lab LP4, BR-79070900 Campo Grande, MS, Brazil.
[Sarkar, Taradas; Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[do Amaral, Marcos S.] Univ Fed Mato Grosso do Sul, Dept Fis, CCET, LAB2M, BR-79070900 Campo Grande, MS, Brazil.
RP de Lima, DP (reprint author), Univ Fed Mato Grosso do Sul, Dept Quim, CCET, Lab LP4, CP 549, BR-79070900 Campo Grande, MS, Brazil.
EM dlima@nin.ufms.br
RI Barbosa, Euzebio/G-4059-2012; Beatriz, Adilson/H-9394-2012; de Lima,
Denis/D-7039-2014; Suassuna e Bega, Luis Augusto/E-8166-2015;
OI Beatriz, Adilson/0000-0001-6864-6092; de Lima,
Denis/0000-0002-6023-4867; Suassuna e Bega, Luis
Augusto/0000-0002-2844-2404; Serrou do Amaral,
Marcos/0000-0001-8101-6933
FU FUNDECT-MS; CAPES; PROPP-UFMS; FINEP; Kardol Industria Quimica Ltda.
(Brazil); LOE-UFC (Brazil)
FX The authors owe a debt of gratitude to the following Brazilian research
agencies: FUNDECT-MS, CAPES, PROPP-UFMS, FINEP for financial support and
scholarships. We are also grateful to Kardol Industria Quimica Ltda.
(Brazil) for providing some reagents and, LOE-UFC (Brazil) for carrying
out the additional cytotoxic tests. Euzebio thanks and dedicates this
work to Nazinha.
NR 21
TC 22
Z9 26
U1 0
U2 8
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD JUN
PY 2009
VL 44
IS 6
BP 2685
EP 2688
DI 10.1016/j.ejmech.2008.12.018
PG 4
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 445DV
UT WOS:000266030800043
PM 19135763
ER
PT J
AU Sverzellati, N
Calabro, E
Randi, G
La Vecchia, C
Marchiano, A
Kuhnigk, JM
Zompatori, M
Spagnolo, P
Pastorino, U
AF Sverzellati, N.
Calabro, E.
Randi, G.
La Vecchia, C.
Marchiano, A.
Kuhnigk, J-M.
Zompatori, M.
Spagnolo, P.
Pastorino, U.
TI Sex differences in emphysema phenotype in smokers without airflow
obstruction
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
DE Cigarette smoking; computed tomography; emphysema; sex
ID DOSE SPIRAL CT; PULMONARY-DISEASE; COMPUTED-TOMOGRAPHY; LUNG-CANCER;
GENDER-DIFFERENCES; COPD; QUANTIFICATION; SEVERITY; SMOKING; AGE
AB Data on sex differences in emphysema are limited to chronic obstructive pulmonary disease. We aimed to verify whether such differences also exist in smokers without airflow obstruction, weighting their influence on the relationship between emphysema and clinical features.
We evaluated both clinical and multidetector computed tomography (MDCT) data of 1,011 heavy smokers recruited by a lung cancer screening project. MDCT scans were analysed with software allowing lobar quantification of emphysema features. For these measures, multiple regression models were applied to assess the effect of patients sex, after allowance for age, body mass index (BMI), smoking history, forced expiratory volume in 1 s (FEV1) and forced vital capacity.
The final study cohort consisted of 957 smokers without airflow obstruction. Compared with males, females exhibited an emphysema phenotype less extensive in each pulmonary lobe, characterised by smaller emphysematous areas and less concentrated in the core of the lung. However, in females, the increase of emphysema with age was more pronounced and displayed a more significant relationship with FEV1% decline; conversely, in males there was a stronger association with the decrease in BMI.
Males and females respond differently to the type and location of lung damage due to tobacco exposure. In smokers, sex influences the relationship between emphysema and clinical features.
C1 [Sverzellati, N.; Zompatori, M.] Univ Parma, Dept Clin Sci, Div Radiol, I-43100 Parma, PR, Italy.
[Calabro, E.; Pastorino, U.] NCI, Div Thorac Surg, Bethesda, MD 20892 USA.
[Marchiano, A.] NCI, Div Radiol, Bethesda, MD 20892 USA.
[Randi, G.; La Vecchia, C.] Univ Milan, Mario Negri Inst, Milan, Italy.
[Randi, G.; La Vecchia, C.] Univ Milan, Inst Med Stat & Biometry GA Maccacaro, Milan, Italy.
[Spagnolo, P.] Univ Modena & Reggio Emilia, Dept Resp Dis, Res Ctr Rare Lung Dis MaRP, Reggio Emilia, Italy.
[Kuhnigk, J-M.] Fraunhofer MEVIS Inst Med Image Comp, Bremen, Germany.
RP Sverzellati, N (reprint author), Univ Parma, Osped Maggiore Parma, Dipartimento Sci Clin, Sez Radiol, V Gramsci 14, I-43100 Parma, PR, Italy.
EM nicolasve@tiscali.it
RI Pastorino, Ugo/C-2712-2017;
OI Pastorino, Ugo/0000-0001-9974-7902; SVERZELLATI,
Nicola/0000-0002-4820-3785; La Vecchia, Carlo/0000-0003-1441-897X
FU Italian Association for Research on Cancer (AIRC); Lombardia-Cariplo
Foundation (both Milan, Italy)
FX The present study was supported by grants from the Italian Association
for Research on Cancer (AIRC) and Lombardia-Cariplo Foundation (both
Milan, Italy).
NR 36
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Z9 28
U1 0
U2 0
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
J9 EUR RESPIR J
JI Eur. Resp. J.
PD JUN
PY 2009
VL 33
IS 6
BP 1320
EP 1328
DI 10.1183/09031936.00109808
PG 9
WC Respiratory System
SC Respiratory System
GA 461VX
UT WOS:000267301800013
PM 19164351
ER
PT J
AU Zhao, L
Ma, WX
Fariss, RN
Wong, WT
AF Zhao, Lian
Ma, Wenxin
Fariss, Robert N.
Wong, Wai T.
TI Retinal vascular repair and neovascularization are not dependent on
CX3CR1 signaling in a model of ischemic retinopathy
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retina; microglia; ischemia; neovascularization; CX3CR1; vascular
repair; oxygen-induced retinopathy
ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; MOUSE
RETINA; MICROGLIAL CELLS; FRACTALKINE; CHEMOKINE; MACROPHAGES;
EXPRESSION; ERYTHROPOIETIN; ANGIOGENESIS
AB Proliferative retinal neovascularization occurring in response to ischemia is a common mechanism underlying many retinal diseases. In recent studies, retinal microglia have been shown to influence pathological neovascularization, likely through an exchange of cellular signals with associated vascular elements. CX3CR1 is a chemokine receptor located specifically on microglia; its ligand, CX3CL1 (also known as fractalkine or neurotactin) displays pro-angiogenic activity both in in vivo and in vitro. Discovering the regulatory role, if any, that CX3CR1 signaling may have in ischemic retinopathy will shed light on the molecular nature of microglial-vascular interactions and clarify potential targets for future therapy. In this study, we examined this question by inducing and comparing ischemic vascular changes in transgenic mice in which CX3CR1 signaling is either preserved or ablated. Using a well-known oxygen-induced retinopathy (OIR) model, we induced ischemic retinopathy in transgenic mice in which the gene for CX3CR1 has been replaced by green fluorescent protein (GFP) and their wild type controls. CX3CR1(+/+), CX3CR1(+/GFP); and CX3CR1(GFP/GFP) transgenic mice were exposed to 75% oxygen for 5 days starting from postnatal day (P) 7, and then transferred back to room air. At P12 and P17, the extents of vascular repair and neovascularization, and associated changes in retinal microglia distribution, were quantified and compared between mice of different genotypes. Neuronal loss in the retina following ischemia was also evaluated in paraffin sections. Our results show that: (1) CX3CR1 signaling is not required for normal vascular, microglial, and neuronal development in the retina in the first postnatal week, (2) the processes of retinal vascular repair and neovascularization following ischemia occur similarly with and without CX3CR1 signaling, (3) microglia redistribution in the retina and their association with vascular elements occurring concurrently is independent of CX3CR1, and (4) CX3CR1 does not influence the extent of neuronal cell loss in the retina following ischemia. Taken together, our findings indicate that the regulatory signals exchanged between microglia and vascular elements in the ischemic retinopathy animal model are unlikely to involve CX3CR1. These results have implications on therapeutic approaches to, pathological neovascularization involving the modulation of chemokine signaling in general, and the regulation of CX3CR1 signaling specifically. Published by Elsevier Ltd.
C1 [Zhao, Lian; Ma, Wenxin; Wong, Wai T.] NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA.
[Zhao, Lian] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
RP Wong, WT (reprint author), NEI, Off Sci Director, NIH, 7 Mem Dr,Room 217, 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, Intramural Division
FX The authors would like to acknowledge Drs. Maria Campos and Jen-Yue Tsai
in the NEI Biological Imaging Core and the staff in the NEI Histology
Core for technical assistance, and Katharine Liang and Yunqing Wang for
critical comments on the manuscript. This work is supported by the
National Eye Institute, Intramural Division.
NR 35
TC 21
Z9 21
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUN
PY 2009
VL 88
IS 6
BP 1004
EP 1013
DI 10.1016/j.exer.2008.12.013
PG 10
WC Ophthalmology
SC Ophthalmology
GA 449EC
UT WOS:000266312600002
PM 19176215
ER
PT J
AU Montori-Grau, M
Minor, R
Lerin, C
Allard, J
Garcia-Martinez, C
de Cabo, R
Gomez-Foix, AM
AF Montori-Grau, Marta
Minor, Robin
Lerin, Caries
Allard, Joanne
Garcia-Martinez, Celia
de Cabo, Rafael
Gomez-Foix, Anna M.
TI Effects of aging and calorie restriction on rat skeletal muscle glycogen
synthase and glycogen phosphorylase
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Glycogen synthase phosphorylation site 3a (Ser641/0); G(M); RG(L);
Protein phosphatase 1 regulatory subunit 3A; Protein phosphatase 1
regulatory subunit 3C; Protein phosphatase 1 regulatory subunit 5 (R5)
ID PROTEIN PHOSPHATASE-1; GLUCOSE-METABOLISM; INSULIN-RESISTANCE; TARGETING
SUBUNIT; MESSENGER-RNA; EXERCISE; OVEREXPRESSION; DISPOSAL; TISSUES;
CELLS
AB Calorie restriction's (CR) effects on age-associated changes in glycogen-metabolizing enzymes were studied in rat soleus (SOL) and tibialis anterior (TA) muscles. Old (24 months) compared to young (6 months) rats maintained ad libitum on a standard diet had reduced glycogen synthase (GS) activity, lower muscle GS protein levels, increased phosphorylation of GS at site 3a with less activation in SOL. Age-associated impairments in GS protein and activation-phosphorylation were also shown in TA. There was an age-associated reduction in glycogen phosphorylase (GP) activity level in SOL, while brain/muscle isoforms (B/M) of GP protein levels were higher. GP activity and protein levels were preserved, but GP was inactivated in TA with age. Glycogen content was unchanged in both muscles. CR did not alter GS or GP activity/protein levels in young rats. CR hindered age-related decreases in GS activity/protein, unrelated to GS mRNA levels, and GS inactivation-phosphorylation; not on GP. In older rats, CR enhanced glycogen accumulation in SOL Short-term fasting did not recapitulate CR effects in old rats. Thus, the predominant age-associated impairments on skeletal muscle GS and GP activities occur in the oxidative SOL muscle of rats, and CR can attenuate the loss of GS activity/activation and stimulate glycogen accumulation. (C) 2009 Published by Elsevier Inc.
C1 [Minor, Robin; Allard, Joanne; de Cabo, Rafael] NIA, Lab Expt Gerontol, Intramural Res Program, NIH,Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Montori-Grau, Marta; Garcia-Martinez, Celia; Gomez-Foix, Anna M.] Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol,IBUB, CIBER Diabet & Enfermedades Metabol Asociadas, E-08028 Barcelona, Spain.
[Lerin, Caries] Johns Hopkins Univ, Dept Cell Biol, Baltimore, MD 21205 USA.
RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, Intramural Res Program, NIH,Gerontol Res Ctr, Box 10,5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM decabora@grc.nia.nih.gov; agomezfoix@ub.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; Montori Grau,
Marta/0000-0001-5707-5407; , rafael/0000-0003-2830-5693
FU Ministerio de Ciencia y Tecnologia (MCyT) [SAF2006-07228]; CIBER de
Diabetes y Enfermedades Metabolicas Asociadas; Ministerio de Educacion y
Ciencia, Spain
FX This work was supported by Grants SAF2006-07228 from the Ministerio de
Ciencia y Tecnologia (MCyT) and CIBER de Diabetes y Enfermedades
Metabolicas Asociadas which is an ISCIII project, Spain, and in part by
the Intramural Research Program of the National Institute on Aging, USA.
CGM was the recipient of a Ramon y Cajal fellowship from the Ministerio
de Educacion y Ciencia, Spain.
NR 52
TC 5
Z9 5
U1 0
U2 4
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 JUN-JUL
PY 2009
VL 44
IS 6-7
BP 426
EP 433
DI 10.1016/j.exger.2009.03.005
PG 8
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 465LA
UT WOS:000267584900011
PM 19341787
ER
PT J
AU Zou, SG
Carey, JR
Liedo, P
Ingram, DK
Muller, HG
Wang, JL
Yao, F
Yu, BB
Zhou, AH
AF Zou, Sige
Carey, James R.
Liedo, Pablo
Ingram, Donald K.
Mueller, Hans-Georg
Wang, Jane-Ling
Yao, Fang
Yu, Binbing
Zhou, Anhong
TI The prolongevity effect of resveratrol depends on dietary composition
and calorie intake in a tephritid fruit fly
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Dietary restriction; Calorie restriction; Lifespan; Anastrepha ludens;
Aging intervention
ID LIFE-SPAN; DROSOPHILA-MELANOGASTER; ANASTREPHA-LUDENS; RESTRICTION;
LONGEVITY; REPRODUCTION; ACTIVATORS; SIRTUINS; SURVIVAL; COHORT
AB Several studies have shown that resveratrol can extend lifespan in yeast, worm, fruit fly and short-lived fish, as well as mice under a high-fat diet, probably acting through molecular pathways similar to dietary restriction. However, the putative prolongevity effect of resveratrol has not been observed in other studies. To evaluate the robustness of the prolongevity effects of resveratrol, we designed a nutritional study to address the question, Under what nutritional conditions does resveratrol affect lifespan and reproduction? We fed 2592 individual tephritid fruit fly of the species, Anastrepha ludens, 24 diets of different sugaryeast ratios supplemented with or without 100 mu M resveratrol. Sex-specific survival and daily egg laying in females were recorded. Resveratrol was found to have no or little effect on lifespan of males in all the treatments, as well as on lifespan and reproduction of females. Only under one diet combination, resveratrol appears to increase mean lifespan of females but not at a statistically significant level after multiple comparison adjustment. These findings suggest that the prolongevity effect of resveratrol is at most limited to a narrow range of dietary composition and calorie content in this fruit fly. Coupled with a recent study indicating that resveratrol does not extend lifespan of mice fed the standard diet, our findings further question the ability of resveratrol to increase lifespan in organisms under normal conditions. Published by Elsevier Inc.
C1 [Zou, Sige] NIA, Funct Genom Unit, Lab Expt Gerontol, Baltimore, MD 21224 USA.
[Carey, James R.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Liedo, Pablo] Colegio Frontera Sur, Tapachula, Chiapas, Mexico.
[Ingram, Donald K.] Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA.
[Mueller, Hans-Georg; Wang, Jane-Ling] Univ Calif Davis, Dept Stat, Davis, CA 95616 USA.
[Yao, Fang] Univ Toronto, Dept Stat, Toronto, ON M5S 3G3, Canada.
[Yu, Binbing] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Zhou, Anhong] Utah State Univ, Dept Biol & Irrigat Engn, Logan, UT 84322 USA.
RP Zou, SG (reprint author), NIA, Funct Genom Unit, Lab Expt Gerontol, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM zous@grc.nia.nih.gov
RI Trejo, Yesenia/D-9257-2012; Liedo, Pablo/E-9313-2010
OI Liedo, Pablo/0000-0002-0004-1721
FU Intramural NIH HHS [Z99 AG999999, Z01 AG000365-03]; NIA NIH HHS [P01
AG008761, P01 AG022500, P01-AG022500-01, P01-AG08761-10, R01 AG025218]
NR 26
TC 31
Z9 31
U1 0
U2 5
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 JUN-JUL
PY 2009
VL 44
IS 6-7
BP 472
EP 476
DI 10.1016/j.exger.2009.02.011
PG 5
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 465LA
UT WOS:000267584900018
PM 19264118
ER
PT J
AU Parr-Brownlie, LC
Poloskey, SL
Bergstrom, DA
Walters, JR
AF Parr-Brownlie, Louise C.
Poloskey, Stacey L.
Bergstrom, Debra A.
Walters, Judith R.
TI Parafascicular thalamic nucleus activity in a rat model of Parkinson's
disease
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Low threshold calcium spike (LTS) bursts; Thalamosubthalamic pathway;
Intralaminar thalamic nucleus; Basal ganglia; Parkinson's disease; Slow
wave oscillations; Dopamine; Subthalamic nucleus
ID NIGRA PARS RETICULATA; BASAL GANGLIA OUTPUT; GLOBUS-PALLIDUS INTERNUS;
MACACA-MULATTA THALAMUS; SUBTHALAMIC NUCLEUS; NEURONAL-ACTIVITY;
PEDUNCULOPONTINE NUCLEUS; DOPAMINERGIC LESION; ELECTROPHYSIOLOGICAL
PROPERTIES; NIGROSTRIATAL PATHWAY
AB Parkinson's disease is associated with increased oscillatory firing patterns in basal ganglia output, which are thought to disrupt thalamocortical activity. However, it is unclear how specific thalamic nuclei are affected by these changes in basal ganglia activity. The thalamic parafascicular nucleus (PFN) receives input from basal ganglia Output nuclei and directly projects to the subthalamic nucleus (STN), striatum and cortex; thus basal ganglia-mediated changes on PFN activity may further impact basal ganglia and cortical functions. To investigate the impact of increased oscillatory activity in basal ganglia output on PFN activity after dopamine cell lesion, PFN single-unit and local field potential activities were recorded in neurologically intact (control) rats and in both non-lesioned and dopamine lesioned hemispheres of unilateral 6-hydroxydopamine lesioned rats anesthetized With urethane. Firing rates were unchanged 1-2 weeks after lesion; however, significantly fewer spontaneously active PFN neurons were evident. Firing pattern assessments after lesion showed that a larger proportion of PFN spike trains had 0.3-2.5 Hz oscillatory activity and significantly fewer spike trains exhibited low threshold calcium spike (LTS) bursts. In paired recordings, more PFN-STN spike oscillations were significantly correlated, but as these oscillations were in-phase, results are inconsistent with feedforward control of PFN activity by inhibitory oscillatory basal ganglia output. Furthermore, the decreased incidence of ITS bursts is incompatible with inhibitory basal ganglia output inducing rebound bursting in PFN after dopamine lesion. Together, results show that robust oscillatory activity observed in basal ganglia output nuclei after dopamine cell lesion does not directly drive changes in PFN oscillatory activity. Published by Elsevier Inc.
C1 [Parr-Brownlie, Louise C.; Poloskey, Stacey L.; Bergstrom, Debra A.; Walters, Judith R.] NINDS, Neurophysiol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
RP Parr-Brownlie, LC (reprint author), Univ Otago, Dept Physiol, POB 913, Dunedin, New Zealand.
EM parrbl@ninds.nih.gov
OI Parr-Brownlie, Louise/0000-0002-3001-7669
FU NINDS; NIH
FX The Intramural Research Program of the NINDS, NIH supported this
research. We Would like to thank Assoc. Prof Brian Hyland for his
helpful discussions on this manuscript.
NR 99
TC 20
Z9 21
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
J9 EXP NEUROL
JI Exp. Neurol.
PD JUN
PY 2009
VL 217
IS 2
BP 269
EP 281
DI 10.1016/j.expneurol.2009.02.010
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 450GM
UT WOS:000266389000007
PM 19268664
ER
PT J
AU Race, B
Meade-White, K
Race, R
Baumann, F
Aguzzi, A
Chesebro, B
AF Race, Brent
Meade-White, Kimberly
Race, Richard
Baumann, Frank
Aguzzi, Adriano
Chesebro, Bruce
TI Prion protein on astrocytes or in extracellular fluid impedes
neurodegeneration induced by truncated prion protein
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Astroglia; Glycophosphatidylinositol anchor; Granule cell neurons;
Neurodegeneration; Prion; Truncated prion protein
ID N-TERMINAL TRUNCATION; PRP KNOCKOUT MICE; SCRAPIE AGENT; NULL MICE;
EXPRESSION; DEFICIENT; TOXICITY; DISEASE; LACKING; DEATH
AB Prion protein (PrP) is a host-encoded membrane-anchored glycoprotein which is required for susceptibility to prion disease. PrP may also be important for normal brain functions such as hippocampal spatial memory. Previously transgenic mice expressing amino terminally truncated mouse PrP (Delta 32-134) spontaneously developed a fatal disease associated with degeneration of cerebellar granular neurons as well as vacuolar degeneration of deep cerebellar and brain stem white matter. This disease could be prevented by co-expression of wild-type (WT) mouse PrP on neurons or oligodendroglia. In the present experiments we Studied Delta 32-134 PrP transgenic mice with WT PrP expression restricted to astroglia, an abundant CNS cell-type important for neuronal viability. Expression of WT PrP in astroglia was sufficient to rescue 50% of mice from disease and prolonged Survival by 200 days in the other 50%. We also found that transgenic mice expressing full-length Soluble anchorless PrP had increased Survival by 100 days. Together these two results indicated that rescue from neurodegeneration induced by Delta 32-134 PrP might involve interactions between neurons expressing truncated PrP and nearby astrocytes expressing WT PrP or extracellular fluid containing soluble WT PrP. Published by Elsevier Inc.
C1 [Race, Brent; Meade-White, Kimberly; Race, Richard; Chesebro, Bruce] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Baumann, Frank; Aguzzi, Adriano] Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland.
RP Race, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM raceb@niaid.nih.gov
RI Aguzzi, Adriano/A-3351-2008;
OI Aguzzi, Adriano/0000-0002-0344-6708
FU NIH; MAID
FX This research was supported by the Intramural Research Program of the
NIH, MAID. The authors thank Cynthia Favara and Lori Lubke for work with
histopathology, Lynne Raymond and Nicolette Arndt for assistance with
animal breeding and husbandry, Anita Mora and Gary Hettrick for graphics
assistance, and Drs. Sonja Best,john Portis, Byron Caughey, Sue Priola
and Karin Peterson for helpful discussions concerning the manuscript.
NR 29
TC 5
Z9 5
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
J9 EXP NEUROL
JI Exp. Neurol.
PD JUN
PY 2009
VL 217
IS 2
BP 347
EP 352
DI 10.1016/j.expneurol.2009.03.017
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 450GM
UT WOS:000266389000015
PM 19332059
ER
PT J
AU Scaife, MD
Neschadim, A
Fowler, DH
Medin, JA
AF Scaife, Matthew D.
Neschadim, Anton
Fowler, D. H.
Medin, J. A.
TI Novel application of lentiviral vectors towards treatment of
graft-versus-host disease
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Review
DE allogeneic bone marrow transplantation (allo-BMT); cell fate control
gene therapy (CFCGT); donor lymphocyte infusion (DLI); gene therapy;
graft-versus-host disease (GvHD); hematopoietic cell transplantation
(HCT); lentivirus; suicide gene therapy
ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; MEDIATED
GENE-TRANSFER; THYMIDINE KINASE GENE; HUMAN T-CELLS; PERIPHERAL-BLOOD
LYMPHOCYTES; DONOR LEUKOCYTE INFUSIONS; CHRONIC MYELOID-LEUKEMIA;
SUICIDE GENE; IN-VIVO
AB Allogeneic transplantation of hematopoietic stem cells and lymphocytes is a curative treatment for malignant and non-malignant disease. However, the primary complication limiting the safety of transplantation is graft-versus-host disease (GvHD), which is mediated by donor T cells. Strategies for pre- and post-transplant manipulation of graft cells are not yet optimal for balancing GvHD severity with beneficial Graft-versus-Leukemia (GvL) effects. Emerging cell fate control gene therapy (CFCGT)-based strategies, such as 'suicide' gene therapy for donor T cell regulation, can supplement existing transplantation approaches by providing a safety element to reduce GvHD. Past uses of CFCGT in the clinic have provided proof-of-principle that GvHD can be controlled by such a strategy. However, there exists a need for improved transgene delivery and suicide control systems. Recently, lentiviral vectors (LVs) have emerged as effective gene delivery vehicles for the clinic. Combining lentiviral gene delivery with newer generations of 'suicide' systems that possess improved enzyme/prodrug specificities, activities, and reduced immunogenicity, could provide the necessary degree of control required to more successfully manage GvHD. Improving the safety of transplantation through successful CFCGT will serve to expand the potential donor pool and the spectrum of disorders that can be treated by this therapeutic schema.
C1 [Medin, J. A.] Ontario Canc Inst, Toronto, ON M4X 1K9, Canada.
[Scaife, Matthew D.; Neschadim, Anton; Medin, J. A.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
[Fowler, D. H.] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Medin, JA (reprint author), Ontario Canc Inst, 500 Sherbourne St, Toronto, ON M4X 1K9, Canada.
EM jmedin@uhnres.utoronto.ca
OI Neschadim, Anton/0000-0003-1750-9703
NR 107
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Z9 6
U1 0
U2 1
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 JUN
PY 2009
VL 9
IS 6
BP 749
EP 761
DI 10.1517/14712590903002021
PG 13
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA 459ZK
UT WOS:000267152600007
PM 19456209
ER
PT J
AU Giubellino, A
Linehan, WM
Bottaro, DP
AF Giubellino, Alessio
Linehan, W. Marston
Bottaro, Donald P.
TI Targeting the Met signaling pathway in renal cancer
SO EXPERT REVIEW OF ANTICANCER THERAPY
LA English
DT Review
DE HGF; HPRC; Met; RCC; renal cell carcinoma; targeted therapy; TFE3
ID HEPATOCYTE GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; HOGG-DUBE-SYNDROME;
ACTIVATOR INHIBITOR-1B HAI-1B; TYROSINE KINASE RECEPTOR;
HIPPEL-LINDAU-DISEASE; FACTOR SCATTER FACTOR; SINGLE-CHAIN FORM; CELL
CARCINOMA; C-MET
AB Renal cell carcinoma (RCC), the most common form of kidney cancer, accounts for 3% of all adult malignancies and its incidence has significantly increased over the last 20 years. RCC claims 13,000 lives annually in the USA and more than 100,000 worldwide. A better understanding of the molecular basis of RCC has facilitated the development of novel and more selective therapeutic approaches. An important role in RCC oncogenesis is played by the receptor for HGF, Met, which has attracted considerable attention, more recently as a molecular target for cancer therapy, and several drugs selectively targeting this pathway are now in clinical trials. This review will focus on efforts to understand the role of the Met signaling pathway in renal cancer and how this has contributed to the development of potent and selective drug candidates.
C1 [Giubellino, Alessio; Linehan, W. Marston; Bottaro, Donald P.] NCI, Urol Oncol Branch, CCR, Bethesda, MD 20892 USA.
RP Bottaro, DP (reprint author), NCI, Urol Oncol Branch, CCR, Bldg 10 CRC W,Room 2-5239,10 Ctr Dr,MSC 1107, Bethesda, MD 20892 USA.
EM dbottaro@helix.nih.gov
RI Bottaro, Donald/F-8550-2010;
OI Bottaro, Donald/0000-0002-5057-5334; Giubellino,
Alessio/0000-0002-5352-0662
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. The authors
have no other relevant affiliations or financial involvement with any
organization or entity with afinancial interest in orfinancial conflict
with the subject matter or materials discussed in the manuscript
apartfrom those disclosed.
NR 125
TC 28
Z9 33
U1 0
U2 0
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1473-7140
J9 EXPERT REV ANTICANC
JI Expert Rev. Anticancer Ther
PD JUN
PY 2009
VL 9
IS 6
BP 785
EP 793
DI 10.1586/ERA.09.43
PG 9
WC Oncology
SC Oncology
GA 461AI
UT WOS:000267234900017
PM 19496715
ER
PT J
AU Bolton, DL
Roederer, M
AF Bolton, Diane L.
Roederer, Mario
TI Flow cytometry and the future of vaccine development
SO EXPERT REVIEW OF VACCINES
LA English
DT Review
DE antigen-specific immune response; multiparameter flow cytometry;
polyfunctional T cell; vaccine
ID T-CELL RESPONSES; PLASMACYTOID DENDRITIC CELLS; ANTIBODY-SECRETING
CELLS; IN-VIVO; B-CELLS; MEDIATED CYTOTOXICITY; FLUOROMETRIC ASSESSMENT;
MONOCLONAL-ANTIBODIES; CYTOKINE RESPONSES; EFFECTOR FUNCTIONS
AB Vaccine research increasingly aims to understand the fundamental mechanisms of protection afforded by licensed and candidate vaccines. Historically, nearly all licensed vaccines have relied on measures of humoral immunity to provide correlates of protection, but cellular immunity is important for protection afforded by some vaccines and will be required for vaccines against TB and malaria. Common means of assessing vaccine-induced immune responses include measuring the frequency and functions of antigen-specific lymphocytes. While diverse assays can provide this information, flow cytometry is unique in its ability to simultaneously report other features of antigen-specific cellular responses. Here, we review the application of flow cytometry to characterizing three areas of immune responses to vaccines or diseases. First, analysis of cellular (T-cell) responses is more mature: polychromatic flow cytometric analysis of T-cell function has already yielded important insight into correlates of protection. Second, antibody and antigen-specific B-cell detection by flow cytometry are being actively developed; to date, these assays are not yet widely used. Finally, flow cytometry can also be used to analyze the contribution of innate immunity to vaccine efficacy and disease pathogenesis.
C1 [Bolton, Diane L.; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Roederer, M (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA.
EM dbolton@nih.gov; roederer@nih.gov
RI Chiang, Vincent, Ming-Hsien/D-4312-2016
OI Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, NIH
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, NIH. The authors
have no other relevant affiliations or financial involvement with any
organization or entity with afinancial interest in or financial conflict
with the subject matter or materials discussed in the manuscript apart
from those disclosed.
NR 76
TC 22
Z9 23
U1 0
U2 9
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1476-0584
J9 EXPERT REV VACCINES
JI Expert Rev. Vaccines
PD JUN
PY 2009
VL 8
IS 6
BP 779
EP 789
DI 10.1586/ERV.09.41
PG 11
WC Immunology
SC Immunology
GA 457TV
UT WOS:000266957500018
PM 19485757
ER
PT J
AU Anderson, BJ
Holmbeck, G
Iannotti, RJ
Mckay, SV
Lochrie, A
Volkening, LK
Laffel, L
AF Anderson, Barbara J.
Holmbeck, Grayson
Iannotti, Ronald J.
McKay, Siripoom V.
Lochrie, Amanda
Volkening, Lisa K.
Laffel, Lori
TI Dyadic Measures of the Parent-Child Relationship During the Transition
to Adolescence and Glycemic Control in Children With Type 1 Diabetes
SO FAMILIES SYSTEMS & HEALTH
LA English
DT Article
DE adolescence; type 1 diabetes; glycemic control; dyadic family variables;
conflict
AB To identify aspects of family behavior associated with glycemic control in youth with type I diabetes mellitus during the transition to adolescence, the authors studied 121 9- to 14-year-olds (M = 12.1 yrs) and their parents, who completed the Diabetes Family Conflict Scale (DFCS) and the Diabetes Family Responsibility Questionnaire (DFRQ). From the DFRQ, the authors derived 2 dyadic variables, frequency of agreement (exact parent and child concurrence about who was responsible for a task) and frequency of discordance (opposite parent and child reports about responsibility). The authors divided the cohort into Younger (n = 57, M = 10.6 yrs) and Older (n = 64, M = 13.5 yrs) groups. Family conflict was significantly related to glycemic control in the entire cohort and in both the Younger and Older groups. However, only in the Younger group was Agreement related to glycemic control, with higher Agreement associated with better glycemic control. Findings suggest that Agreement about sharing of diabetes responsibilities may be an important target for family-based interventions aiming to optimize glycemic control in preteen youth.
C1 [Anderson, Barbara J.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA.
[Holmbeck, Grayson] Loyola Univ Chicago, Chicago, IL USA.
[Iannotti, Ronald J.] NICHHD, Bethesda, MD 20892 USA.
[Lochrie, Amanda] Nemours Childrens Clin, Jacksonville, FL USA.
[Volkening, Lisa K.; Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Anderson, BJ (reprint author), Texas Childrens Hosp, Baylor Coll Med, 1100 Bates St, Houston, TX 77030 USA.
EM bja@bcm.tmc.edu
FU National Institutes of Health, National Institute of Child Health and
Human Development; Children's Memorial Hospital, Chicago
[N01-HD-4-3363]; Texas Children's Hospital, Houston, Texas
[N01-HD-4-3362]; Nemours Children's Clinic, Jacksonville, Florida
[N01-HD-4-3361]; Joslin Diabetes Center, Boston [N01-HD-4-3364]; James
Bell Associates, Arlington, Virginia [N01-HD-3-3360]
FX This research was supported by the intramural research program of the
National Institutes of Health, National Institute of Child Health and
Human Development. The following investigators and institutions made up
the steering committee of the Family Management of Childhood Diabetes
multisite trial: Jill Weissberg-Benchell, PhD, and Grayson Holmbeck, PhD
(Contract N01-HD-4-3363), Children's Memorial Hospital, Chicago; Bruce
Simons-Morton, EdD, Tonja R. Nansel, PhD, Ronald J. Iannotti, PhD, and
Rusan Chen, PhD, National Institute of Child Health and Human
Development, Bethesda, Maryland; Barbara Anderson, PhD (Contract
N01-HD-4-3362), Texas Children's Hospital, Houston, Texas; Tim Wysocki,
PhD, and Amanda Lochrie, PhD (Contract N01-HD-4-3361), Nemours
Children's Clinic, Jacksonville, Florida; Lori Laffel, MD, MPH, Deborah
Butler, MSW, Korey Hood, PhD, and Lisa Volkening, MA (Contract
N01-HD-4-3364), Joslin Diabetes Center, Boston; and Cheryl McDonnell,
PhD, and MaryAnn D'Elio (Contract N01-HD-3-3360), James Bell Associates,
Arlington, Virginia.
NR 48
TC 39
Z9 39
U1 8
U2 12
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1091-7527
J9 FAM SYST HEALTH
JI Fam. Syst. Health
PD JUN
PY 2009
VL 27
IS 2
BP 141
EP 152
DI 10.1037/a0015759
PG 12
WC Health Care Sciences & Services; Family Studies; Public, Environmental &
Occupational Health
SC Health Care Sciences & Services; Family Studies; Public, Environmental &
Occupational Health
GA V19PR
UT WOS:000208084800003
PM 19630455
ER
PT J
AU West, NP
Chow, FME
Randall, EJ
Wu, J
Chen, J
Ribeiro, JMC
Britton, WJ
AF West, Nicholas P.
Chow, Frances M. E.
Randall, Elizabeth J.
Wu, Jing
Chen, Jian
Ribeiro, Jose M. C.
Britton, Warwick J.
TI Cutinase-like proteins of Mycobacterium tuberculosis: characterization
of their variable enzymatic functions and active site identification
SO FASEB JOURNAL
LA English
DT Article
DE secreted enzymes; activity
ID PATHOGENIC MYCOBACTERIA; EXTRACELLULAR LIPASE; SEQUENCE ALIGNMENT;
LIPOLYTIC ENZYMES; CULTURE FILTRATE; BOVIS BCG; PURIFICATION;
MACROPHAGES; ESTERASE; DATABASE
AB Discovery and characterization of novel secreted enzymes of Mycobacterium tuberculosis are important for understanding the pathogenesis of one of the most important human bacterial pathogens. The proteome of M. tuberculosis contains over 400 potentially secreted proteins, the majority of which are uncharacterized. A family of seven cutinase-like proteins (CULPs) was identified by bioinformatic analysis, expressed and purified from Escherichia coli, and characterized in terms of their enzymatic activities. These studies revealed a functional diversity of enzyme classes based on differential preferences for substrate chain length. One member, Culp1, exhibited strong esterase activity, 40-fold higher than that of Culp6, which had strong activity as a lipase. Another, Culp4, performed moderately as an esterase and weakly as a lipase. Culp6 lipase activity was optimal above pH 7.0, and fully maintained to pH 8.5. None of the CULP members exhibited cutinase activity. Site-directed mutagenesis of each residue of the putative catalytic triad in Culp6 confirmed that each was essential for activity toward all fatty acid chain lengths of nitrophenyl esters and lipolytic function. Culp1 and Culp2 were present only in culture supernatants of M. tuberculosis, while Culp6, which is putatively essential for mycobacterial growth, was retained in the cell wall, suggesting the proteins play distinct roles in mycobacterial biology.-West, N. P., Chow, F. M. E., Randall, E. J., Wu, J., Chen, J., Ribeiro, J. M. C., Britton, W. J. Cutinase-like proteins of Mycobacterium tuberculosis: characterization of their variable enzymatic functions and active site identification. FASEB J. 23, 1694-1704 (2009)
C1 [West, Nicholas P.; Chow, Frances M. E.; Randall, Elizabeth J.; Britton, Warwick J.] Centenary Inst Canc Med & Cell Biol, Mycobacterial Res Program, Newtown, NSW 2042, Australia.
[Wu, Jing; Chen, Jian] Jiangnan Univ, State Key Lab Food Sci & Technol, Wuxi, Jiangsu, Peoples R China.
[Wu, Jing; Chen, Jian] Jiangnan Univ, Sch Biotechnol, Wuxi, Jiangsu, Peoples R China.
[Wu, Jing; Chen, Jian] Jiangnan Univ, Key Lab Ind Biotechnol, Wuxi, Jiangsu, Peoples R China.
[Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Britton, Warwick J.] Univ Sydney, Dept Med, Sydney, NSW 2006, Australia.
RP West, NP (reprint author), Centenary Inst Canc Med & Cell Biol, Mycobacterial Res Program, Locked Bag 6, Newtown, NSW 2042, Australia.
EM n.west@centenary.org.au
RI West, Nicholas/C-3119-2008;
OI Ribeiro, Jose/0000-0002-9107-0818
FU Intramural NIH HHS; NIAID NIH HHS [HHSN266200400091C]; PHS HHS
[HHSN266200400091C]
NR 52
TC 40
Z9 40
U1 0
U2 4
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 JUN
PY 2009
VL 23
IS 6
BP 1694
EP 1704
DI 10.1096/fj.08-114421
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 453ZW
UT WOS:000266652400009
PM 19225166
ER
PT J
AU Shen, H
Kuo, CC
Chou, J
Delvolve, A
Jackson, SN
Post, J
Woods, AS
Hoffer, BJ
Wang, Y
Harvey, BK
AF Shen, Hui
Kuo, Chi-Chung
Chou, Jenny
Delvolve, Alice
Jackson, Shelley N.
Post, Jeremy
Woods, Amina S.
Hoffer, Barry J.
Wang, Yun
Harvey, Brandon K.
TI Astaxanthin reduces ischemic brain injury in adult rats
SO FASEB JOURNAL
LA English
DT Article
DE antioxidant; stroke; neuroprotection; apoptosis; glutamate
ID FOCAL CEREBRAL-ISCHEMIA; ALGA HAEMATOCOCCUS-PLUVIALIS; PENAEUS-MONODON
FABRICIUS; NIVALIS BAUER WILLE; OXIDATIVE STRESS; RAINBOW-TROUT; DIETARY
SUPPLEMENTATION; SYNTHETIC ASTAXANTHIN; ANTIOXIDANT ACTIVITY;
ONCORHYNCHUS-MYKISS
AB Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.-Shen, H., Kuo, C.-C., Chou, J., Delvolve, A., Jackson, S. N., Post, J., Woods, A. S., Hoffer, B. J., Wang, Y., Harvey, B. K. Astaxanthin reduces ischemic brain injury in adult rats. FASEB J. 23, 1958-1968 (2009)
C1 [Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N.; Post, Jeremy; Woods, Amina S.; Hoffer, Barry J.; Wang, Yun; Harvey, Brandon K.] NIDA, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
RP Harvey, BK (reprint author), NIDA, NIH, Intramural Res Program, Ste 200,Rm 06A729,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM bharvey@intra.nida.nih.gov
FU Intramural Research Program at the National Institute on Drug Abuse
(USA)
FX This work was supported by the Intramural Research Program at the
National Institute on Drug Abuse (USA). We thank Mr. Douglas Howard and
Dr. Guann-Juh Chen for their technical assistance, Dr. Michael Tlusty
for his photograph of the lobsters and his input on ATX in crustaceans,
and Dr. Marc Halterman for his review and comments on the manuscript.
NR 63
TC 52
Z9 61
U1 0
U2 15
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 JUN
PY 2009
VL 23
IS 6
BP 1958
EP 1968
DI 10.1096/fj.08-123281
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 453ZW
UT WOS:000266652400034
PM 19218497
ER
PT J
AU Jaskolski, M
Alexandratos, JN
Bujacz, G
Wlodawer, A
AF Jaskolski, Mariusz
Alexandratos, Jerry N.
Bujacz, Grzegorz
Wlodawer, Alexander
TI Piecing together the structure of retroviral integrase, an important
target in AIDS therapy
SO FEBS JOURNAL
LA English
DT Review
DE AIDS; antiretroviral drugs; DNA integration; HIV; integrase
ID SARCOMA-VIRUS INTEGRASE; HIV-1 REVERSE-TRANSCRIPTASE; DNA-BINDING
DOMAIN; REFINED SOLUTION STRUCTURE; TO-AUTOINTEGRATION FACTOR; TERMINAL
HHCC DOMAIN; ACTIVE-SITE BINDING; PHOTO-CROSS-LINKING; CATALYTIC DOMAIN;
TYPE-1 INTEGRASE
AB Integrase ( IN) is one of only three enzymes encoded in the genomes of all retroviruses, and is the one least characterized in structural terms. IN catalyzes processing of the ends of a DNA copy of the retroviral genome and its concerted insertion into the chromosome of the host cell. The protein consists of three domains, the central catalytic core domain flanked by the N-terminal and C-terminal domains, the latter being involved in DNA binding. Although the Protein Data Bank contains a number of NMR structures of the N-terminal and C-terminal domains of HIV-1 and HIV-2, simian immunodeficiency virus and avian sarcoma virus IN, as well as X-ray structures of the core domain of HIV-1, avian sarcoma virus and foamy virus IN, plus several models of two-domain constructs, no structure of the complete molecule of retroviral IN has been solved to date. Although no experimental structures of IN complexed with the DNA substrates are at hand, the catalytic mechanism of IN is well understood by analogy with other nucleotidyl transferases, and a variety of models of the oligomeric integration complexes have been proposed. In this review, we present the current state of knowledge resulting from structural studies of IN from several retroviruses. We also attempt to reconcile the differences between the reported structures, and discuss the relationship between the structure and function of this enzyme, which is an important, although so far rather poorly exploited, target for designing drugs against HIV-1 infection.
C1 [Alexandratos, Jerry N.; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Jaskolski, Mariusz] Adam Mickiewicz Univ Poznan, Fac Chem, Dept Crystallog, Poznan, Poland.
[Jaskolski, Mariusz; Bujacz, Grzegorz] Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, Poznan, Poland.
[Bujacz, Grzegorz] Tech Univ Lodz, Inst Tech Biochem, PL-90924 Lodz, Poland.
RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
EM wlodawer@nih.gov
FU National Cancer Institute; Intramural Research Program of the NIH;
Center for Cancer Research
FX would like to thank A. Gustchina, A. M. Skalka and M. Andrake for
fruitful discussions, and P. Cherepanov for providing us with a
manuscript and data prior to their publication. This project was
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. The research of
M. Jaskolski was supported by a Faculty Scholar fellowship from the
National Cancer Institute.
NR 108
TC 50
Z9 51
U1 0
U2 8
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD JUN
PY 2009
VL 276
IS 11
BP 2926
EP 2946
DI 10.1111/j.1742-4658.2009.07009.x
PG 21
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 443TU
UT WOS:000265934500005
PM 19490099
ER
PT J
AU Taylor, DR
Silberstein, E
AF Taylor, Deborah R.
Silberstein, Erica
TI Innate immunity and hepatitis C virus: eluding the host cell defense
SO FRONTIERS IN BIOSCIENCE
LA English
DT Article
DE Interferon; Hepatitis; Signaling; Liver; Genotypes; Innate Immunity;
Review
ID NONSTRUCTURAL 5A PROTEIN; BLOOD MONONUCLEAR-CELLS; RECEPTOR
MESSENGER-RNA; NITRIC-OXIDE SYNTHASE; DOUBLE-STRANDED-RNA;
SENSITIVITY-DETERMINING REGION; INTERFERON-ALPHA THERAPY; CHRONIC
LIVER-DISEASES; RIBOSOME ENTRY SITE; E2 ENVELOPE PROTEIN
AB Interferon-alpha (IFN-alpha) mono-therapy is largely ineffective for most of the hepatitis C virus (HCV)-infected patients that receive it. The addition of ribavirin to IFN therapy has increased the response rate dramatically. While many factors are implicated in determining the success rate for IFN therapy, viral genotype seems to play a crucial role. Examining differences in viral gene sequences has and will continue to advance our understanding as to how HCV and other viruses circumvent the IFN response. Here we review the different ways that HCV evades the immune response elicited by IFN.
C1 [Taylor, Deborah R.; Silberstein, Erica] CBER FDA, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA.
RP Taylor, DR (reprint author), CBER FDA, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Lab Hepatitis & Related Emerging Agents, 8800 Rockville Pike,HFM-310,NIH Bldg 29,131, Bethesda, MD 20892 USA.
EM Deborah.Taylor@FDA.HHS.gov
NR 100
TC 7
Z9 7
U1 0
U2 2
PU FRONTIERS IN BIOSCIENCE INC
PI MANHASSET
PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY
DR, MANHASSET, NY 11030 USA
SN 1093-9946
J9 FRONT BIOSCI
JI Front. Biosci.
PD JUN
PY 2009
VL 14
BP 4950
EP 4961
DI 10.2741/3579
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 497LP
UT WOS:000270061300010
PM 19482597
ER
PT J
AU Lee, PR
Fields, RD
AF Lee, Philip R.
Fields, R. Douglas
TI Regulation of myelin genes implicated in psychiatric disorders by
functional activity in axons
SO FRONTIERS IN NEUROANATOMY
LA English
DT Review
DE oligodendrocyte; axon; activity; schizophrenia; depression; white
matter; ATP; LIF
AB Myelination is a highly dynamic process that continues well into adulthood in humans. Several recent gene expression studies have found abnormal expression of genes involved in myelination in the prefrontal cortex of brains from patients with schizophrenia and other psychiatric illnesses. Defects in myelination could contribute to the pathophysiology of psychiatric illness by impairing information processing as a consequence of altered impulse conduction velocity and synchrony between cortical regions carrying out higher level cognitive functions. Myelination can be altered by impulse activity in axons and by environmental experience. Psychiatric illness is treated by psychotherapy, behavioral modification, and drugs affecting neurotransmission, raising the possibility that myelinating glia may not only contribute to such disorders, but that activity-dependent effects on myelinating glia could provide one of the cellular mechanisms contributing to the therapeutic effects of these treatments. This review examines evidence showing that genes and gene networks important for myelination can be regulated by functional activity in axons.
C1 [Fields, R. Douglas] NICHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA.
RP Fields, RD (reprint author), NICHD, Nervous Syst Dev & Plast Sect, NIH, Bldg 35,Room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA.
EM fieldsd@mail.nih.gov
FU NICHD
FX This work was supported by NICHD funds for intramural research.
NR 72
TC 17
Z9 17
U1 0
U2 8
PU FRONTIERS RES FOUND
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5129
J9 FRONT NEUROANAT
JI Front. Neuroanat.
PD JUN 1
PY 2009
VL 3
AR 4
DI 10.3389/neuro.05.004.2009
PG 8
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA V21DS
UT WOS:000208188900001
PM 19521541
ER
PT J
AU Tsutsumi, S
Beebe, K
Neckers, L
AF Tsutsumi, Shinji
Beebe, Kristin
Neckers, Len
TI Impact of heat-shock protein 90 on cancer metastasis
SO FUTURE ONCOLOGY
LA English
DT Review
DE 17AAG; 17DMAG; cell adhesion; cell motility; geldanamycin; Hsp90;
metastasis; molecular chaperone; neoangiogenesis
ID FOCAL-ADHESION KINASE; GROWTH-FACTOR RECEPTOR; HYPOXIA-INDUCIBLE
FACTOR-1-ALPHA; UROKINASE PLASMINOGEN-ACTIVATOR; HSP90 MOLECULAR
CHAPERONE; INTEGRIN-LINKED KINASE; HUMAN-BREAST-CANCER; FACTOR-I
RECEPTOR; CELL MOTILITY; TYROSINE KINASE
AB Cancer metastasis is the result of complex processes, including alteration of cell adhesion/motility in the microenvironment and neoangiogenesis, that are necessary to support cancer growth in tissues distant from the primary tumor. The molecular chaperone heat-shock protein 90 (Hsp90), also termed the 'cancer chaperone', plays a crucial role in maintaining the stability and activity of numerous signaling proteins involved in these processes. Small-molecule Hsp90 inhibitors display anticancer activity both in vitro and in vivo, and multiple Phase 11 and Phase III clinical trials of several structurally distinct Hsp90 inhibitors are currently underway. In this review, we will highlight the importance of Hsp90 in cancer metastasis and the therapeutic potential of Hsp90 inhibitors as antimetastasis drugs.
C1 [Tsutsumi, Shinji; Beebe, Kristin; Neckers, Len] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Neckers, L (reprint author), NCI, Urol Oncol Branch, 9000 Rockville Pike,Bldg 10 CRC,1-5940, Bethesda, MD 20892 USA.
EM len@helix.nih.gov
FU Intramural NIH HHS [Z01 SC010074-12, Z99 CA999999]; NCI NIH HHS [Z01
BC011032-01]
NR 106
TC 35
Z9 38
U1 0
U2 6
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
J9 FUTURE ONCOL
JI Future Oncol.
PD JUN
PY 2009
VL 5
IS 5
BP 679
EP 688
DI 10.2217/FON.09.30
PG 10
WC Oncology
SC Oncology
GA 467LA
UT WOS:000267739200014
PM 19519207
ER
PT J
AU Heller, T
Hoofnagle, J
Liang, TJ
Rehermann, B
AF Heller, Theo
Hoofnagle, Jay
Liang, T. Jake
Rehermann, Barbara
TI Acute Hepatitis C
SO GASTROENTEROLOGY
LA English
DT Letter
C1 [Heller, Theo; Hoofnagle, Jay; Liang, T. Jake; Rehermann, Barbara] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Heller, T (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
NR 5
TC 2
Z9 2
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2009
VL 136
IS 7
BP 2411
EP 2411
DI 10.1053/j.gastro.2009.04.042
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 454CK
UT WOS:000266659100047
PM 19409987
ER
PT J
AU Edlin, BR
Shu, MA
Winkelstein, E
Jarlais, DCD
Busch, MP
Rehermann, B
O'Brien, TR
Talal, AH
Tobler, LH
Zeremski, M
Beeder, AB
AF Edlin, Brian R.
Shu, Marla A.
Winkelstein, Emily
Jarlais, Don C. Des
Busch, Michael P.
Rehermann, Barbara
O'Brien, Thomas R.
Talal, Andrew H.
Tobler, Leslie H.
Zeremski, Marija
Beeder, Ann B.
TI More Rare Birds, and the Occasional Swan
SO GASTROENTEROLOGY
LA English
DT Letter
ID INJECTION-DRUG USERS; HEPATITIS-C VIRUS; IMMUNE-RESPONSES;
SAN-FRANCISCO; HCV
C1 [Edlin, Brian R.; Shu, Marla A.; Winkelstein, Emily] SUNY Downstate Coll Med, Dept Med, Brooklyn, NY USA.
[Edlin, Brian R.; Talal, Andrew H.; Zeremski, Marija] Weill Cornell Med Coll, Dept Med, Ctr Study Hepatitis C, New York, NY USA.
[Edlin, Brian R.; Busch, Michael P.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Jarlais, Don C. Des] Beth Israel Deaconess Med Ctr, Baron Edmond de Rothschild Chem Dependency Inst, New York, NY 10003 USA.
[Busch, Michael P.; Tobler, Leslie H.] Blood Syst Res Inst, San Francisco, CA USA.
[Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD USA.
[O'Brien, Thomas R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Beeder, Ann B.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA.
[Beeder, Ann B.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA.
RP Edlin, BR (reprint author), SUNY Downstate Coll Med, Dept Med, Brooklyn, NY USA.
OI Edlin, Brian/0000-0001-8172-8797
FU CSAT SAMHSA HHS [H79-TI12103]; Intramural NIH HHS; NCI NIH HHS
[N01-CO-12400, N01CO12400, N02-CP-91027]; NCRR NIH HHS [M01 RR000047,
M01-RR000047, UL1 RR024996, UL1-RR024996]; NIDA NIH HHS [R01 DA003574,
R01 DA009532, R01 DA012109, R01 DA013245, R01 DA016159, R01 DA021550,
R01-DA021550, R01-DA03574, R01-DA09532, R01-DA13245, R01-DA16159]
NR 10
TC 3
Z9 3
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2009
VL 136
IS 7
BP 2412
EP 2414
DI 10.1053/j.gastro.2009.04.040
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 454CK
UT WOS:000266659100049
PM 19414076
ER
PT J
AU Furusawa, T
Ko, JH
Birger, Y
Bustin, M
AF Furusawa, Takashi
Ko, Jung-Ho
Birger, Yehudit
Bustin, Michael
TI Expression of nucleosomal protein HMGN1 in the cycling mouse hair
follicle
SO GENE EXPRESSION PATTERNS
LA English
DT Article
DE Chromatin; HMGN; p63; Hair follicle
ID STEM-CELLS; CHROMOSOMAL-PROTEINS; COMPREHENSIVE GUIDE; MORPHOGENESIS;
DISTINCT; CLASSIFICATION; CHROMATIN; LIMB; P63
AB Here we examine the expression pattern of HMGN1, a nucleosome binding protein that affects chromatin structure and activity, in the hair follicle and test whether loss of HMGN1 affects the development or cycling of the follicle. We find that at the onset of hair follicle development, HMGN1 protein is expressed in the epidermal placode and in aggregated dermal fibroblasts. In the adult hair follicle, HMGN1 is specifically expressed in the basal layer of epidermis, in the outer root sheath, in the hair bulb, but not in the inner root sheath and hair shaft. The expression pattern of HMGN1 is very similar to p63, suggesting a role for HMGN1 in the transiently amplifying cells. We also find HMGN1 expression in some, but not all hair follicle stem cells as detected by its colocalization with Nestin and with BrdU label-retaining cells. The appearance of the skin and hair follicle of Hmgn1(-/-) mice was indistinguishable from that of their Hmgn1(+/+) littermates. We found that in the hair follicle the expression of HMGN2 is very similar to HMGN1 suggesting functional redundancy between these closely related HMGN variants. Published by Elsevier B.V.
C1 [Furusawa, Takashi; Ko, Jung-Ho; Birger, Yehudit; Bustin, Michael] NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Bustin, M (reprint author), NCI, Prot Sect, Lab Metab, NIH, Bldg 37,Room 3122,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bustin@helix.nih.gov
RI Bustin, Michael/G-6155-2015
FU National Cancer Institute, NIH
FX We thank Susan H. Garfield and Stephen M. Wincovitch (Laboratory of
Experimental Carcinogenesis, Center for Cancer Research, National Cancer
Institute) for help with the confocal microscopy, Michael Falduto and
Scott Magnuson (GenUs BioSystems Inc., Northbrook, TILT) for micro array
data analysis, and the NIH Fellows Editorial Board for constructive
criticisms of the paper. Trhe monoclonal antibody against Nestin
developed by Dr. THockfieldT was obtained from the Developmental Studies
Hybridoma Bank maintained by The University of Iowa, Department of
Biological Sciences, Iowa City, IA 52242. The research was supported by
the intramural program of the National Cancer Institute, NIH.
NR 23
TC 5
Z9 5
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-133X
J9 GENE EXPR PATTERNS
JI Gene Expr. Patterns
PD JUN
PY 2009
VL 9
IS 5
BP 289
EP 295
DI 10.1016/j.gep.2009.03.002
PG 7
WC Developmental Biology; Genetics & Heredity
SC Developmental Biology; Genetics & Heredity
GA 465RV
UT WOS:000267605400005
PM 19303948
ER
PT J
AU Nizza, DT
Gawrisch, K
AF Nizza, David T.
Gawrisch, Klaus
TI A layer model of ethanol partitioning into lipid membranes
SO GENERAL PHYSIOLOGY AND BIOPHYSICS
LA English
DT Article
DE Ethanol; Lipid bilayer; Partitioning; Headspace gas chromatography
ID NONELECTROLYTE PARTITION; WATER; LIPOSOMES; BINDING; SPHINGOMYELIN;
CHOLESTEROL; INTERFACE; LECITHIN; BILAYERS; NMR
AB The effect of membrane composition on ethanol partitioning into lipid bilayers was assessed by headspace gas chromatography. A series of model membranes with different compositions have been investigated. Membranes were exposed to a physiological ethanol concentration of 20 mmol/l. The concentration of membranes was 20 wt% which roughly corresponds to values found in tissue. Partitioning depended on the chemical nature of polar groups at the lipid/water interface. Compared to phosphatidylcholine, lipids with headgroups containing phosphatidylglycerol, phosphatidylserine, and sphingomyelin showed enhanced partitioning while headgroups containing phosphatidylethanolamine resulted in a lower partition coefficient. The molar partition coefficient was independent of a membrane's hydrophobic volume. This observation is in agreement with our previously published NMR results which showed that ethanol resides almost exclusively within the membrane/water interface. At an ethanol concentration of 20 mmol/l in water, ethanol concentrations at the lipid/water interface are in the range from 30-15 mmol/l, corresponding to one ethanol molecule per 100-200 lipids.
C1 [Nizza, David T.; Gawrisch, Klaus] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 5625 Fishers Ln,Rm 3N07, Bethesda, MD 20892 USA.
EM gawrisch@helix.nih.gov
FU Intramural Research Program of NIAAA; NTH
FX This work was supported by the Intramural Research Program of NIAAA,
NTH.
NR 18
TC 7
Z9 7
U1 0
U2 6
PU GENERAL PHYSIOL AND BIOPHYSICS
PI BRATISLAVA
PA INST OF MOLEC PHYSIOL GENETICS SLOVAK ACAD OF SCI VLARSKA 5, 83334
BRATISLAVA, SLOVAKIA
SN 0231-5882
J9 GEN PHYSIOL BIOPHYS
JI Gen. Physiol. Biophys.
PD JUN
PY 2009
VL 28
IS 2
BP 140
EP 145
DI 10.4149/gpb_2009_02_140
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Physiology
SC Biochemistry & Molecular Biology; Biophysics; Physiology
GA 470WW
UT WOS:000268014100005
PM 19592710
ER
PT J
AU Oleksyk, TK
Shrestha, S
Truelove, AL
Goedert, JJ
Donfield, SM
Phair, J
Mehta, S
O'Brien, SJ
Smith, MW
AF Oleksyk, T. K.
Shrestha, S.
Truelove, A. L.
Goedert, J. J.
Donfield, S. M.
Phair, J.
Mehta, S.
O'Brien, S. J.
Smith, M. W.
TI Extended IL10 haplotypes and their association with HIV progression to
AIDS
SO GENES AND IMMUNITY
LA English
DT Article
DE AIDS; HIV progression; IL-10 protein; IL10 gene; promoter haplotypes
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SINGLE NUCLEOTIDE POLYMORPHISMS;
INTERLEUKIN-10 GENE PROMOTER; DISEASE PROGRESSION; HUMAN MACROPHAGES;
TYPE-1 INFECTION; IL-10 PRODUCTION; VIRAL-INFECTION; SUSCEPTIBILITY;
EXPRESSION
AB Interleukin-10 (IL-10) is a pleiotropic cytokine with both immunosuppressive and immunostimulatory functions. Its roles in infections and autoimmunity may have resulted in selective pressures on polymorphisms within the gene, leading to genomic coexistence of several semi-conserved haplotypes involved with diverse pathogen interactions during genomic evolution. Previous studies focused either exclusively on promoter haplotypes or on individual SNPs. We genotyped 21 single nucleotide polymorphisms in the human IL10 gene and examined this variation compared to other mammalian species sequences. Haplotype heterogeneity in human populations is centered around 'classic' 'proximal' promoter polymorphisms: -592, -819 and -1082. High-producing GCC haplotypes are by far the most numerous and diverse group, the intermediate IL-10 producing ACC-inclusive haplotypes seem to be related most closely to the ancestral haplotype, and the ATA-inclusive haplotypes cluster a separate branch with strong bootstrap support. We looked at associations of corresponding haplotypes with HIV progression. A haplotype trend regression confirmed that individuals carrying the low-producing ATA-inclusive haplotypes in European Americans progress to AIDS faster, and most likely explain the role of IL10. Our findings are consistent with the hypothesis that existing polymorphisms in this gene may reflect a balance of historic adaptive responses to autoimmune, infectious and other disease agents. Genes and Immunity (2009) 10, 309-322; doi:10.1038/gene.2009.9; published online 19 March 2009
C1 [Oleksyk, T. K.; Truelove, A. L.; Smith, M. W.] NCI, Basic Res Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA.
[Shrestha, S.] Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Goedert, J. J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Donfield, S. M.] Rho Inc, Dept Biostat, Chapel Hill, NC USA.
[Phair, J.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA.
[Mehta, S.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[O'Brien, S. J.] NCI, Lab Genom Div, NIH, Frederick, MD 21701 USA.
[Smith, M. W.] NCI, Genet & Genom Program, Adv Technol Program, Lab Genom Divers,SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Smith, MW (reprint author), NCI, Genet & Genom Program, Adv Technol Program, Lab Genom Divers,SAIC Frederick Inc, Frederick, MD 21702 USA.
EM smithmw@mail.nih.gov
RI Smith, Michael/B-5341-2012; Taras, Oleksyk/J-8805-2013
OI Taras, Oleksyk/0000-0002-8148-3918
FU National Cancer Institute; National Institutes of Health [N01-CO-12400]
FX We thank the patients and staff of all the participating cohorts in the
study. We thank Drs Cheryl Winkler, Michael Dean and Mary Carrington for
helpful insights in developing the ideas for this paper. We are also
grateful to Bailey Kessing, Michael Malasky and Mary Thompson for their
assistance. We thank Maritta Grau and Allen Kane of Scientific
Publications, Graphics and Media, SAIC-Frederick Inc., for help with the
study preparation. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does it mention of trade names, commercial products, or
organizations, which imply the endorsement by the US government. The
project included in this paper has been funded in whole or in part with
federal funds from the National Cancer Institute, National Institutes of
Health, under contract N01-CO-12400.
NR 69
TC 26
Z9 26
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
J9 GENES IMMUN
JI Genes Immun.
PD JUN
PY 2009
VL 10
IS 4
BP 309
EP 322
DI 10.1038/gene.2009.9
PG 14
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 452UO
UT WOS:000266566900003
PM 19295541
ER
PT J
AU Yee, LJ
Im, K
Borg, B
Yang, H
Liang, TJ
AF Yee, L. J.
Im, K.
Borg, B.
Yang, H.
Liang, T. J.
CA Virahep C Study
TI Interleukin-6 haplotypes and the response to therapy of chronic
hepatitis C virus infection
SO GENES AND IMMUNITY
LA English
DT Article
DE hepatitis C; race; therapy; response; African American
ID PEGINTERFERON ALPHA-2B; AMERICAN PATIENTS; RIBAVIRIN; ASSOCIATION;
POLYMORPHISMS; GENOTYPE-1; GENE
AB Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide. Treatment of HCV with pegylated interferon-alpha-2a is successful in eradicating virus from only 30 to 80% of those treated. Interleukin-6 (IL-6) is an important cytokine involved in the immune response to infectious agents and in vitro studies suggest that host genetic variation, particularly haplotypes, may affect IL-6 expression. We examined the contribution of haplotypes in the IL-6 gene on sustained viral response (SVR) to the therapy for chronic HCV infection. We observed the IL-6 T-T-G-G-G-G-C-A-G-A haplotype to be associated with a lower risk of achieving SVR among Caucasian Americans (CAs) ((relative risk) RR = 0.80; 95% CI: 0.66-0.98; P = 0.0261). Using a sliding window approach, the rs1800797-(G)-rs1800796-(G)-rs1800795-( G) haplotype was associated with a reduced chance of SVR (RR = 0.79; 95% CI: 0.66-0.94; P = 0.0081), as was the rs1800796-(G)-rs1800795-(G)-rs2069830-(C) haplotype (RR = 0.78; 95% CI: 0.66-0.94; P = 0.0065) among CAs. Overall, the rs1800797-(G)-rs1800796(G)-rs1800795-(G) haplotype was independently associated with a reduced chance of SVR (RR 0.78; 95% CI: 0.62-1.0; P = 0.0489) after adjustment for potential confounding factors. Our findings further illustrate the complexity of IL-6 genetic regulation and the potential importance of haplotypes on IL-6 expression. Our findings provide additional support for the potential importance of genetic variation in the IL-6 gene and the response to HCV therapy. Genes and Immunity (2009) 10, 365-372; doi:10.1038/gene.2009.26; published online 23 April 2009
C1 [Yee, L. J.; Im, K.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Im, K.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA.
[Borg, B.; Liang, T. J.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
[Yang, H.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
RP Yee, LJ (reprint author), Univ Pittsburgh, Dept Epidemiol, A511 Crabtree Hall, Pittsburgh, PA 15261 USA.
EM YeeL@edc.pitt.edu; JakeL@bdg10.niddk.nih.gov
FU National Center on Minority Health and Health Disparities (NCMHD) [U01
DK60329, U01 DK60340, U01 DK60324, U01 DK60344, U01 DK60327, U01
DK60335, U01 DK60352, U01 DK60342, U01 DK60345, U01 DK60309, U01
DK60346, U01 DK60349, U01 DK60341]; NIDDKNational Center for Research
Resources (NCRR); NIH; Center for Cancer Research; New York Presbyterian
[M01 RR00645]; University of California, San Francisco [M02 RR000079];
University of Maryland [M01 RR16500]; University of Michigan [M01
RR000042]; University of North Carolina [M01 RR00046]; National
Institutes of Health Clinical Research Career Development [1KL2
RR024154-02]
FX This clinical study was a co-operative agreement funded by the NIDDK and
co-funded by the National Center on Minority Health and Health
Disparities (NCMHD), with a Co-operative Research and Development
Agreement (CRADA) with Roche Laboratories Inc., Grant numbers: U01
DK60329, U01 DK60340, U01 DK60324, U01 DK60344, U01 DK60327, U01
DK60335, U01 DK60352, U01 DK60342, U01 DK60345, U01 DK60309, U01
DK60346, U01 DK60349 and U01 DK60341. Other support: National Center for
Research Resources (NCRR), Intramural Research Program of the NIH,
NIDDK, Center for Cancer Research, General Clinical Research Centers
Program Grants: M01 RR00645 (New York Presbyterian), M02 RR000079
(University of California, San Francisco), M01 RR16500 (University of
Maryland), M01 RR000042 (University of Michigan) and M01 RR00046
(University of North Carolina). In addition support for Dr Leland J Yee
was provided by a National Institutes of Health Clinical Research Career
Development Award Grant (1KL2 RR024154-02).
NR 18
TC 17
Z9 17
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
J9 GENES IMMUN
JI Genes Immun.
PD JUN
PY 2009
VL 10
IS 4
BP 365
EP 372
DI 10.1038/gene.2009.26
PG 8
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 452UO
UT WOS:000266566900009
PM 19387461
ER
PT J
AU Uchimura, T
Komatsu, Y
Tanaka, M
McCann, KL
Mishina, Y
AF Uchimura, Takashi
Komatsu, Yoshihiro
Tanaka, Momo
McCann, Kelly L.
Mishina, Yuji
TI Bmp2 and Bmp4 Genetically Interact to Support Multiple Aspects of Mouse
Development Including Functional Heart Development
SO GENESIS
LA English
DT Article
DE haploid insufficiency; ventricular septum defect; mitral valve;
tricaspid valve; microphthalmia
ID NEURAL CREST CELLS; MORPHOGENETIC PROTEIN-RECEPTOR; CARDIAC OUTFLOW
TRACT; PRIMORDIAL GERM-CELLS; DOUBLE-MUTANT MICE; ENDOCARDIAL CUSHION;
FOREBRAIN DEVELOPMENT; ALK3/BMPR1A RECEPTOR; EMBRYOGENESIS; GASTRULATION
AB Bone morphogenetic proteins (BMPs) have multiple roles during embryogenesis. Current data indicate that the dosage of BMPs is tightly regulated for normal development in mice. Since Bmp2 or Bmp4 homozygous mutant mice show early embryonic lethality, we generated compound heterozygous mice for Bmp2 and Bmp4 to explore the impact of lowered dosage of these BMP ligands. Genotyping pups bred between Bmp2 and Bmp4 heterozygous mice revealed that the ratio of adult compound heterozygous mice for Bmp2 and Bmp4 is much lower than expected. During embryogenesis, the compound heterozygous embryos showed several abnormalities, including defects in eye formation, body wall closure defects, and ventricular septal defects (VSD) in the heart. However, the ratio of the compound heterozygous embryos was the same as expected. Caesarean sections at E18.5 revealed that half of the compound heterozygotes died soon after birth, and the majority of the dead individuals exhibited VSD. Survivors were able to grow to adults, but their body weight was significantly lower than control littermates. They demonstrated progressive abnormalities in the heart, eventually showing a branched leaflet in atrioventricular valves. These results suggest that the dosage of both BMP2 and 4 is critical for functional heart formation during embryogenesis and after birth. genesis 47:374-384, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Komatsu, Yoshihiro; Mishina, Yuji] Univ Michigan, Dept Biol & Mat Sci, Sch Dent, Ann Arbor, MI 48109 USA.
[Uchimura, Takashi; Komatsu, Yoshihiro; Tanaka, Momo; Mishina, Yuji] Natl Inst Environm Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA.
[McCann, Kelly L.; Mishina, Yuji] NIEHS, Knock Out Core, NIH, Res Triangle Pk, NC 27709 USA.
RP Mishina, Y (reprint author), Univ Michigan, Dept Biol & Mat Sci, Sch Dent, 1011 N Univ Ave 4222A Dent, Ann Arbor, MI 48109 USA.
EM mishina@umich.edu
FU Intramural Research Program of the NIEHS/NIH; RIKEN Brain Science
Institute
FX Contract grant sponsor: Intramural Research Program of the NIEHS/NIH;
Contract grant sponsor: RIKEN Brain Science Institute (to Y.M.)
NR 53
TC 30
Z9 30
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1526-954X
J9 GENESIS
JI Genesis
PD JUN
PY 2009
VL 47
IS 6
BP 374
EP 384
DI 10.1002/dvg.20511
PG 11
WC Developmental Biology; Genetics & Heredity
SC Developmental Biology; Genetics & Heredity
GA 462KW
UT WOS:000267352400003
PM 19391114
ER
PT J
AU Scott, GJ
Ray, MK
Ward, T
McCann, K
Peddada, S
Jiang, FX
Mishina, Y
AF Scott, Gregory J.
Ray, Manas K.
Ward, Toni
McCann, Kelly
Peddada, Shyamal
Jiang, Fang-Xu
Mishina, Yuji
TI Abnormal Glucose Metabolism in Heterozygous Mutant Mice for a Type I
Receptor Required for BMP Signaling
SO GENESIS
LA English
DT Article
DE bone morphogenetic protein (BMP); bone morphogenetic protein receptor
(BMPR); insulin; intraperitoneal glucose tolerance test (IPGTT);
diabetes; heterozygous mutant mice; heterozygous phenotype; pancreas
ID BONE MORPHOGENETIC PROTEIN; INSULIN-SECRETION; PANCREATIC-ISLETS;
GENE-EXPRESSION; BETA-CELLS; CROSS-TALK; TARGET; INDUCTION
AB BMPR1A and its high-affinity ligand BMP4 have recently been shown to be expressed in the beta-cells of the pancreas. Here, we report the abnormalities of heterozygous mice for Bmpr1a in glucose metabolism during the course of intraperitoneal glucose tolerance test. The heterozygous mice had increased blood glucose levels throughout the first 2.5 h after the administration of glucose. Analysis of glucose-stimulated insulin secretion (GSIS) indicates that insulin secretion in the heterozygous mice is compromised, and induction of secreted insulin by stimulation is substantially lower compared with the wild-type controls. No apparent abnormalities in pancreas, thyroid, and liver were seen upon histological examination. Real-time PCR results of selected genes showed an increase in the mRNA level of Ins1 and 1ns2 in the heterozygous group. These results indicate that the glucose-sensing pathway in these heterozygous mice is altered because of the heterozygosity in Bmpr1a. Together, our data suggest that BMP signaling through BMPR1A plays an important role in glucose metabolism and possibly working through the GSIS pathway. genesis 47:385-391, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Scott, Gregory J.; Ray, Manas K.; Ward, Toni; McCann, Kelly; Mishina, Yuji] NIEHS, Knock Out Core, Res Triangle Pk, NC 27709 USA.
[Peddada, Shyamal] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Jiang, Fang-Xu] Western Australian Inst Med Res, Ctr Diabet Res, Beta Cell Dev & Regenerat Program, Perth, WA, Australia.
[Mishina, Yuji] NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA.
[Mishina, Yuji] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA.
RP Ray, MK (reprint author), NIEHS, Knock Out Core, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM ray6@niehs.nih.gov
RI Peddada, Shyamal/D-1278-2012
FU NIH; National Institute of Environmental Health Sciences
FX Contract grant sponsor: Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences
NR 27
TC 12
Z9 13
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1526-954X
J9 GENESIS
JI Genesis
PD JUN
PY 2009
VL 47
IS 6
BP 385
EP 391
DI 10.1002/dvg.20513
PG 7
WC Developmental Biology; Genetics & Heredity
SC Developmental Biology; Genetics & Heredity
GA 462KW
UT WOS:000267352400004
PM 19358156
ER
PT J
AU Shriner, D
AF Shriner, Daniel
TI Mapping multiple quantitative trait loci under Bayes error control
SO GENETICS RESEARCH
LA English
DT Article; Proceedings Paper
CT 6th Annual Meeting of the Complex Trait Consortium
CY MAY 26-29, 2007
CL Braunschweig, GERMANY
ID FALSE DISCOVERY RATE; GENOME-SCAN; GENETIC DISSECTION; COMPLEX TRAITS;
EXPERIMENTAL CROSSES; LINKAGE ANALYSIS; MODEL SELECTION; QTL;
EXPRESSION; PROPORTION
AB In mapping of quantitative trait loci (QTLs). performing hypothesis tests of linkage to a phenotype of interest across all entire genome involves multiple comparisons. Furthermore, linkage among, loci induces correlation among tests. Under Many Multiple comparison frameworks. these problems are exacerbated when Mapping Multiple QTLs. Traditionally, significance thresholds have been subjectively set to control the probability of detecting at least one false Positive outcome, although Such thresholds are known to result in excessively low power to detect true positive outcomes. Recently, false discovery rate (FDR)-controlling procedures have been developed that yield more power both by relaxing the stringency of the significance threshold and by retaining more power For a given significance threshold. However, these procedures have been shown to perform poorly for mapping QTLs, principally because they ignore recombination fractions between markers. Here, I describe a procedure that accounts for recombination fractions and extends FDR control to Include simultaneous Control of the false non-discovery rate, i.e. the overall error rate is controlled. This procedure is developed in the Bayesian framework using a direct posterior probability approach. Data-driven significance thresholds are determined by minimizing the expected loss. The procedure is equivalent to jointly maximizing positive and negative predictive values. In the context of mapping QTLs For experimental crosses, the procedure is applicable to mapping main effects, gene-gene interactions and gene-environment interactions.
C1 NIH, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
RP Shriner, D (reprint author), NIH, Ctr Res Genom & Global Hlth, Bldg 12A,Room 4047,12 S Dr,MSC 5635, Bethesda, MD 20892 USA.
EM shrinerda@mail.nih.gov
FU Intramural NIH HHS; NIDDK NIH HHS [T32 DK062710, DK062710]
NR 45
TC 0
Z9 0
U1 0
U2 1
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0016-6723
EI 1469-5073
J9 GENET RES
JI Genet. Res.
PD JUN
PY 2009
VL 91
IS 3
BP 147
EP 159
DI 10.1017/S001667230900010X
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 478WU
UT WOS:000268620100001
PM 19589185
ER
PT J
AU Silveira, TS
Martins, JL
Abreu, F
Silva, KT
Aranova, M
da Silva-Neto, ID
Kachar, B
Lins, U
AF Silveira, T. S.
Martins, J. L.
Abreu, F.
Silva, K. T.
Aranova, M.
da Silva-Neto, I. D.
Kachar, B.
Lins, U.
TI Grazing and digestion of magnetotactic bacteria by ciliates
SO GEOCHIMICA ET COSMOCHIMICA ACTA
LA English
DT Meeting Abstract
CT 19th Annual VM Goldschmidt Conference
CY JUN 21, 2009
CL Davos, SWITZERLAND
C1 [Silveira, T. S.; Martins, J. L.; Abreu, F.; Silva, K. T.; Lins, U.] Univ Fed Rio de Janeiro, Inst Microbiol Prof Paulo de Goes, BR-21941590 Rio De Janeiro, Brazil.
[Aranova, M.] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
[da Silva-Neto, I. D.] Univ Fed Rio de Janeiro, Inst Biol, BR-21941590 Rio De Janeiro, Brazil.
[Kachar, B.] NIDCD, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM ulins@micro.ufrj.br
RI Domingos da Silva Neto, inacio/H-1614-2015; Lins, Ulysses/N-7282-2015
OI Lins, Ulysses/0000-0002-1786-1144
NR 2
TC 0
Z9 0
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0016-7037
J9 GEOCHIM COSMOCHIM AC
JI Geochim. Cosmochim. Acta
PD JUN
PY 2009
VL 73
IS 13
BP A1225
EP A1225
PG 1
WC Geochemistry & Geophysics
SC Geochemistry & Geophysics
GA 460YS
UT WOS:000267229903137
ER
PT J
AU Farley, J
Fuchiuji, S
Darcy, KM
Tian, CQ
Hoskins, WJ
McGuire, WP
Hanjani, P
Warshal, D
Greer, BE
Belinson, J
Birrer, MJ
AF Farley, John
Fuchiuji, Sartoru
Darcy, Kathleen M.
Tian, Chunqiao
Hoskins, William J.
McGuire, William P.
Hanjani, Parviz
Warshal, David
Greer, Benjamin E.
Belinson, Jerome
Birrer, Michael J.
TI Associations between ERBB2 amplification and progression-free survival
and overall survival in advanced stage, suboptimally-resected epithelial
ovarian cancers: A Gynecologic Oncology Group study
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE ERBB2; Gene amplification; Ovary; Carcinogenesis; FISH
ID HER-2/NEU EXPRESSION; GENE AMPLIFICATION; PROGNOSTIC-SIGNIFICANCE;
BREAST-CANCER; ENDOMETRIAL CARCINOMA; TISSUE MICROARRAYS;
CONTINGENCY-TABLES; OVEREXPRESSION; ONCOGENE; C-ERBB-2
AB Objective(s). The Gynecologic Oncology Group (GOG) examined the association between ERBB2 amplification and clinical covariates, tumor response, disease status post-chemotherapy, progression-free survival (PFS), and overall survival (OS) in epithelial ovarian cancer (EOC).
Methods. Women with suboptimally-resected, advanced stage EOC who participated in GOG-111, a multicenter randomized phase III trial of cyclophosphamide + cisplatin versus paclitaxel + cisplatin, and provided a tumor block through the companion protocol GOG-9404 were eligible. ERBB2 amplification was examined using fluorescence in situ hybridization (FISH) with probes for ERBB2 and the centromere of chromosome 17 (CEP17).
Results. ERBB2 amplification, defined as > 2 copies of ERBB2/CEP17, was a rare event in EOC with 7% (9/133) of women exhibiting between 2.2 and 33.7 copies of ERBB2/CEP17, and was not associated with patient age, race, GOG performance status, stage, cell type, grade, measurable disease status, volume of ascites, tumor response or disease status post-chemotherapy. Women with > 2 verses <= 2 copies of ERBB2/CEP17 did not have a reduced risk of disease progression (hazard ratio [HR] = 0.56; 95% confidence interval [CI] = 0.27-1.16; p = 0.120) or death (HR = 0.57; 95% CI = 0.26-1.23; p = 0.152), and ERBB2 amplification was not an independent prognostic factor for PFS or OS. ERBB2 amplification, defined as > 4 copies of ERBB2/nuclei, was observed in 9% (12/133) of women with levels ranging from 4.2 to 49.2 copies of ERBB2/nuclei, and was associated with older age and Volume of ascites, but not with the other clinical covariates or outcome.
Conclusion(s). ERBB2 amplification is a rare event and has no predictive or prognostic value in suboptimally-resected, advanced stage EOC treated with platinum-based combination chemotherapy. (C) 2009 Published by Elsevier Inc.
C1 [Farley, John] Uniformed Serv Univ Hlth Sci, Dept Obstet, Bethesda, MD 20814 USA.
[Farley, John] Uniformed Serv Univ Hlth Sci, Dept Gynecol, Bethesda, MD 20814 USA.
[Fuchiuji, Sartoru] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Darcy, Kathleen M.; Tian, Chunqiao] GOG Stat & Data Ctr, Buffalo, NY 14263 USA.
[Hoskins, William J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[McGuire, William P.] Franklin Sq Hosp Ctr, Harry & Jeanette Weinberg Canc Inst, Baltimore, MD 21237 USA.
[Hanjani, Parviz] Abington Mem Hosp, Abington, PA 19001 USA.
[Warshal, David] Cooper Univ Hosp, Dept Obstet & Oncol, Camden, NJ 08103 USA.
[Greer, Benjamin E.] Univ Washington, Dept Gynecol Oncol, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Belinson, Jerome] Cleveland Clin Fdn, Dept Gynecol, Cleveland, OH 44195 USA.
[Birrer, Michael J.] Ctr Canc Res, Bethesda, MD 20892 USA.
RP Birrer, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey 9072,55 Fruit St, Boston, MA 02114 USA.
EM mbirrer@partners.org
FU National Cancer Institute [CA 27469, CA 37517]
FX This study was supported by National Cancer Institute grants of the
Gynecologic Oncology Group Administrative Office (CA 27469) and the
Gynecologic Oncology Group Statistical Office (CA 37517). The following
Gynecologic Oncology Group (GOG) institutions participated in this
Study: University of Alabama School of Medicine, Abington Memorial
Hospital, University of Rochester Medical Center, Walter Reed Army
Medical Center, Wayne State University, Colorado Gynecologic Oncology
Group RC., University of California at Los Angeles, University of
Washington, Milton S. Hershey Medical Center, Georgetown University
Hospital, Wake Forest University School of Medicine, University of
California Medical Center at Irvine, University of Kentucky, The
Cleveland Clinic Foundation, Johns Hopkins Oncology Center, Eastern
Pennsylvania Gyn/Onc Center, P.C., Cooper Hospital/University Medical
Center, Columbus Cancer Council, University of Massachusetts Medical
Center, University of Oklahoma, and Tacoma General Hospital, as well as
the following resigned or terminated GOG member institutions: Oregon
Health Sciences University, University of Southern California at Los
Angeles and Stanford University Medical Center.
NR 39
TC 20
Z9 20
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD JUN
PY 2009
VL 113
IS 3
BP 341
EP 347
DI 10.1016/j.ygyno.2009.02.009
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 449HB
UT WOS:000266320300010
PM 19272639
ER
PT J
AU Wierda, G
Roberts, P
Brown, R
Wilson, H
O'Connor, A
Czuczman, S
Busman, A
Xiong, H
Krivoshik, P
Enschede, H
AF Wierda, G.
Roberts, P.
Brown, R.
Wilson, H.
O'Connor, A.
Czuczman, S.
Busman, A.
Xiong, H.
Krivoshik, P.
Enschede, H.
TI PHARMACOKINETICS, SAFETY AND ANTI-TUMOR ACTIVITY OF ABT-263 IN PATIENTS
WITH RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL
LYMPHOCYTIC LYMPHOMA
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the European-Hematology-Association
CY JUN 04-07, 2009
CL Berlin, GERMANY
SP European Hematol Assoc
C1 [Wierda, G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Roberts, P.] Royal Melbourne Hosp, Parkville, Vic 3050, Australia.
[Brown, R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wilson, H.] NCI, NIH, Bethesda, MD 20892 USA.
[O'Connor, A.] Columbia Univ, Med Ctr, New York, NY USA.
[Czuczman, S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Busman, A.; Xiong, H.; Krivoshik, P.; Enschede, H.] Abbott Labs, Abbott Pk, IL 60064 USA.
NR 0
TC 3
Z9 3
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUN
PY 2009
VL 94
MA 0350
BP 138
EP 138
PG 1
WC Hematology
SC Hematology
GA 457MA
UT WOS:000266931900352
ER
PT J
AU Wiestner, A
Njuguna, N
Vire, B
McCoy, P
Wilson, W
Pittaluga, S
Aue, G
AF Wiestner, A.
Njuguna, N.
Vire, B.
McCoy, P., Jr.
Wilson, W.
Pittaluga, S.
Aue, G.
TI LENALIDOMIDE INDUCED UPREGULATION OF CD80 ON LEUKEMIC CELLS CORRELATES
WITH T-CELL ACTIVATION, THE RAPID ONSET OF A CYTOKINE RELEASE SYNDROME
AND CLEARANCE OF TUMOR CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the European-Hematology-Association
CY JUN 04-07, 2009
CL Berlin, GERMANY
SP European Hematol Assoc
C1 [Wiestner, A.; Njuguna, N.; Vire, B.; Aue, G.] NHLBI, HB, NIH, Bethesda, MD 20892 USA.
[McCoy, P., Jr.] NHLBI, Flow Cytometry Core Facil, Bethesda, MD 20892 USA.
[Wilson, W.] NCI, CCR, Bethesda, MD 20892 USA.
[Pittaluga, S.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUN
PY 2009
VL 94
MA 0363
BP 144
EP 145
PG 2
WC Hematology
SC Hematology
GA 457MA
UT WOS:000266931900365
ER
PT J
AU Kristinsson, SY
Bjorkholm, M
Andersson, TML
Eloranta, S
Dickman, PW
Goldin, LR
Blimark, C
Mellqvist, UH
Wahlin, A
Turesson, I
Landgren, O
AF Kristinsson, S. Y.
Bjorkholm, M.
Andersson, T. M. L.
Eloranta, S.
Dickman, P. W.
Goldin, L. R.
Blimark, C.
Mellqvist, U. H.
Wahlin, A.
Turesson, I.
Landgren, O.
TI PATTERNS OF SURVIVAL AND CAUSES OF DEATH FOLLOWING A DIAGNOSIS OF
MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE: A POPULATION-BASED
STUDY
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the European-Hematology-Association
CY JUN 04-07, 2009
CL Berlin, GERMANY
SP European Hematol Assoc
C1 [Kristinsson, S. Y.; Bjorkholm, M.] Karolinska Univ Hosp, Stockholm, Sweden.
[Andersson, T. M. L.; Eloranta, S.; Dickman, P. W.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Goldin, L. R.; Landgren, O.] NCI, NIH, Bethesda, MD 20892 USA.
[Blimark, C.; Mellqvist, U. H.] Sahlgrenska Univ Hospit, Dep Med, Sect Hematol & Coagulat, Gothenburg, Sweden.
[Wahlin, A.] Umea Univ Hosp, Ctr Canc, Sect Hematol, S-90185 Umea, Sweden.
[Turesson, I.] Malmo Univ Hosp, Dept Med, Sect Hematol, Malmo, Sweden.
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
NR 0
TC 0
Z9 0
U1 0
U2 2
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUN
PY 2009
VL 94
MA 0391
BP 157
EP 157
PG 1
WC Hematology
SC Hematology
GA 457MA
UT WOS:000266931900393
ER
PT J
AU Kirschbaum, M
Popplewell, L
Nademanee, A
Pullarkat, V
Delioukina, M
Zain, J
Matsuoka, D
Pulone, B
Frankel, P
Forman, S
Espinoza-Delgado, I
Newman, E
AF Kirschbaum, M.
Popplewell, L.
Nademanee, A.
Pullarkat, V.
Delioukina, M.
Zain, J.
Matsuoka, D.
Pulone, B.
Frankel, P.
Forman, S.
Espinoza-Delgado, I.
Newman, E.
TI A PHASE 2 STUDY OF VORINOSTAT (SUBEROYLANILIDE HYDROXAMIC ACID, SAHA) IN
RELAPSED OR REFRACTORY INDOLENT NOW HODGKIN'S LYMPHOMA. A CALIFORNIA
CANCER CONSORTIUM STUDY
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the European-Hematology-Association
CY JUN 04-07, 2009
CL Berlin, GERMANY
SP European Hematol Assoc
C1 [Kirschbaum, M.; Popplewell, L.; Nademanee, A.; Pullarkat, V.; Delioukina, M.; Zain, J.; Matsuoka, D.; Pulone, B.; Frankel, P.; Forman, S.; Newman, E.] City Hope Natl Canc Ctr, Duarte, CA USA.
[Espinoza-Delgado, I.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 4
Z9 4
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUN
PY 2009
VL 94
MA 0409
BP 166
EP 166
PG 1
WC Hematology
SC Hematology
GA 457MA
UT WOS:000266931900411
ER
PT J
AU Cokic, P
Han, J
Mojsilovic, S
Beleslin-Cokic, B
Mirkovic, K
Kraguljac-Kurtovic, N
Damjanovic, S
Gotic, M
Skoda, R
Puri, R
Noguchi, C
Schechter, A
AF Cokic, P.
Han, J.
Mojsilovic, S.
Beleslin-Cokic, B.
Mirkovic, K.
Kraguljac-Kurtovic, N.
Damjanovic, S.
Gotic, M.
Skoda, R.
Puri, R.
Noguchi, C.
Schechter, A.
TI GENE EXPRESSION PROFILING OF CD34(+) CELLS IN MYELOPROLIFERATIVE
DISORDERS BY CDNA MICROARRAY TECHNOLOGY
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the European-Hematology-Association
CY JUN 04-07, 2009
CL Berlin, GERMANY
SP European Hematol Assoc
C1 [Cokic, P.; Mojsilovic, S.] Inst Med Res, Belgrade, Serbia.
[Han, J.; Puri, R.] Div Cellular & Gene Therapie, Tumor Vaccines & Biotechnol Branch, Bethesda, MD USA.
[Beleslin-Cokic, B.; Mirkovic, K.; Damjanovic, S.] Inst Endocrinol Diabet & Dis Metab, Sch Med, Belgrade, Serbia.
[Kraguljac-Kurtovic, N.; Gotic, M.] Clin Ctr Serbia, Inst Hematol, Belgrade, Serbia.
[Skoda, R.] Univ Basel Hosp, Dept Biomed Expt Hematol, CH-4031 Basel, Switzerland.
[Noguchi, C.; Schechter, A.] Natl Inst Diabet & Digest & Kid, Mol Med Branch, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUN
PY 2009
VL 94
SU 2
MA 0874
BP 352
EP 352
PG 1
WC Hematology
SC Hematology
GA 457MA
UT WOS:000266931900873
ER
PT J
AU Bjorkholm, J
Derolf, AR
Ekstrand, C
Kristinsson, SY
Andreasson, B
Birgegard, G
Linder, O
Malm, C
Markevarn, B
Nilsson, A
Samuelsson, J
Granath, F
Landgren, O
AF Bjorkholm, J.
Derolf, A. R.
Ekstrand, C.
Kristinsson, S. Y.
Andreasson, B.
Birgegard, G.
Linder, O.
Malm, C.
Markevarn, B.
Nilsson, A.
Samuelsson, J.
Granath, F.
Landgren, O.
TI RISK FOR AML/MDS TRANSFORMATION IN PHILADELPHIA NEGATIVE CHRONIC
MYELOPROLIFERATIVE NEOPLASMS - A POPULATION-BASED NESTED CASE-CONTROL
STUDY IN SWEDEN
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the European-Hematology-Association
CY JUN 04-07, 2009
CL Berlin, GERMANY
SP European Hematol Assoc
C1 [Bjorkholm, J.; Derolf, A. R.; Ekstrand, C.; Kristinsson, S. Y.; Granath, F.] Karolinska Univ Hosp, Stockholm, Sweden.
[Landgren, O.] NCI, NIH, Bethesda, MD 20892 USA.
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
NR 0
TC 2
Z9 2
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUN
PY 2009
VL 94
MA 1065
BP 438
EP 438
PG 1
WC Hematology
SC Hematology
GA 457MA
UT WOS:000266931901174
ER
PT J
AU Focosi, D
Carson, K
Evens, A
Richey, E
Habermann, T
Seymour, J
Laubach, J
Bawn, S
Gordon, L
Winter, J
Vose, J
Zelenetz, A
Mamtani, R
Raisch, D
Dorshimer, G
Rosen, S
Muro, K
Gottardi-Littell, N
Talley, R
Sartor, O
Green, D
Major, E
Bennett, C
Petrini, M
AF Focosi, D.
Carson, K.
Evens, A.
Richey, E.
Habermann, T.
Seymour, J.
Laubach, J.
Bawn, S.
Gordon, L.
Winter, J.
Vose, J.
Zelenetz, A.
Mamtani, R.
Raisch, D.
Dorshimer, G.
Rosen, S.
Muro, K.
Gottardi-Littell, N.
Talley, R.
Sartor, O.
Green, D.
Major, E.
Bennett, C.
Petrini, M.
TI PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY FOLLOWING RITUXIMAB THERAPY
IN HIV NEGATIVE PATIENTS: A REPORT OF 56 CASES FROM THE RESEARCH ON
ADVERSE DRUG EVENT AND REPORTS (RADAR) PROJECT
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the European-Hematology-Association
CY JUN 04-07, 2009
CL Berlin, GERMANY
SP European Hematol Assoc
C1 [Focosi, D.; Petrini, M.] Univ Pisa, Pisa, Italy.
[Carson, K.] Washington Univ, Sch Med, St Louis, MO USA.
[Evens, A.; Richey, E.; Gordon, L.; Winter, J.; Rosen, S.; Muro, K.; Gottardi-Littell, N.; Sartor, O.; Green, D.; Bennett, C.] Northwestern Univ, Chicago, IL 60611 USA.
[Habermann, T.] Mayo Clin, Coll Med, Rochester, MN USA.
[Seymour, J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Seymour, J.] Univ Melbourne, Melbourne, Vic, Australia.
[Laubach, J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bawn, S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Vose, J.; Zelenetz, A.; Mamtani, R.] New York Presbyterian Hosp, Cornell Med Ctr, New York, NY USA.
[Raisch, D.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Dorshimer, G.] Univ Penn Hlth Syst, Philadelphia, PA USA.
[Talley, R.] Kansas City Canc Ctr, Kansas City, MO USA.
[Major, E.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUN
PY 2009
VL 94
MA 1099
BP 445
EP 445
PG 1
WC Hematology
SC Hematology
GA 457MA
UT WOS:000266931901188
ER
PT J
AU Hill, A
Rother, R
Wang, X
Sapsford, R
Collinson, P
Gaze, D
Morris, S
Scally, A
Quinn-Senger, K
Richards, S
Bessler, M
Kelly, R
Hillmen, P
Galdwin, M
AF Hill, A.
Rother, R.
Wang, X.
Sapsford, R.
Collinson, P.
Gaze, D.
Morris, S.
Scally, A.
Quinn-Senger, K.
Richards, S.
Bessler, M.
Kelly, R.
Hillmen, P.
Galdwin, M.
TI ECULIZUMAB REDUCES PULMONARY HYPERTENSION THROUGH INHIBITION OF
HAEMOLYSIS-ASSOCIATED NITRIC OXIDE CONSUMPTION IN PATIENTS WITH
PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the European-Hematology-Association
CY JUN 04-07, 2009
CL Berlin, GERMANY
SP European Hematol Assoc
C1 [Hill, A.] Bradford Royal Infirm, Bradford BD9 6RJ, W Yorkshire, England.
[Wang, X.] NHLBI, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA.
[Sapsford, R.] Leeds Gen Infirm, Leeds, W Yorkshire, England.
[Collinson, P.; Gaze, D.] Univ London St Georges Hosp, London, England.
[Morris, S.] Univ Pittsburgh, Pittsburgh, PA USA.
[Richards, S.; Kelly, R.; Hillmen, P.] St Jamess Inst Oncol, Leeds, W Yorkshire, England.
[Bessler, M.] Washington Univ, St Louis, MO USA.
[Galdwin, M.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUN
PY 2009
VL 94
MA 1110
BP 450
EP 450
PG 1
WC Hematology
SC Hematology
GA 457MA
UT WOS:000266931901199
ER
PT J
AU Tamarozzi, MB
Soares, SG
Sa-Nunes, A
Saggioro, FP
Bordin, JO
Garcia, AG
Rego, EM
AF Tamarozzi, M. B.
Soares, S. G.
Sa-Nunes, A.
Saggioro, F. P.
Bordin, J. O.
Garcia, A. G.
Rego, E. M.
TI ANIMAL MODELS FOR THE TWO HYPOTHESES OF TRALI PATHOLOGY
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the European-Hematology-Association
CY JUN 04-07, 2009
CL Berlin, GERMANY
SP European Hematol Assoc
C1 [Tamarozzi, M. B.; Saggioro, F. P.; Garcia, A. G.; Rego, E. M.] USP, Sch Med, Ribeirao Preto, Brazil.
[Soares, S. G.] Invent Biotecnol, Ribeirao Preto, Brazil.
[Sa-Nunes, A.] NIAID, NIH, Bethesda, MD 20892 USA.
[Bordin, J. O.] Univ Fed Sao Paulo, Sao Paulo, Brazil.
RI Sa-Nunes, Anderson/D-8667-2012; Rego, Eduardo/A-1058-2012
OI Sa-Nunes, Anderson/0000-0002-1859-4973; Rego,
Eduardo/0000-0003-1567-4086
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUN
PY 2009
VL 94
MA 1120
BP 455
EP 455
PG 1
WC Hematology
SC Hematology
GA 457MA
UT WOS:000266931901210
ER
PT J
AU Schrag, D
Virnig, BA
Warren, JL
AF Schrag, Deborah
Virnig, Beth A.
Warren, Joan L.
TI Linking Tumor Registry and Medicaid Claims to Evaluate Cancer Care
Delivery
SO HEALTH CARE FINANCING REVIEW
LA English
DT Article
ID DISPARITIES; POPULATION; SURVIVAL; ENROLLMENT; DIAGNOSIS; TRENDS; STAGE
AB The utility of Medicaid claims for studying cancer care is not known. Our objective was to evaluate how well Medicaid claims capture diagnostic and treatment information recorded by the California Cancer Registry (CCR). We compared cancer treatment from Medicaid claims with CCR data, using 1988-2000 cases matched with 1997-1998 Medicaid enrollment data. Medicaid claims corroborated diagnoses for 73 percent of breast and 68 percent of colorectal cancers in CCR. Medicaid claims confirmed surgery for 67 percent of CCR's breast cancers. We found that Medicaid claims have moderate sensitivity for identifying cancer diagnoses and surgery. Linked registry-Medicaid data can identify indigent patients and the timing of Medicaid coverage.
C1 [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02116 USA.
[Virnig, Beth A.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA.
[Warren, Joan L.] NCI, Bethesda, MD 20892 USA.
RP Schrag, D (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02116 USA.
EM deb_schrag@dfci.harvard.edu
NR 26
TC 7
Z9 8
U1 0
U2 0
PU CENTERS FOR MEDICARE & MEDICAID SERVICES
PI BALTIMORE
PA 7500 SECURITY BOULEVARD, BALTIMORE, MD 21244-1850 USA
SN 0195-8631
J9 HEALTH CARE FINANC R
JI Health Care Finan. Rev.
PD SUM
PY 2009
VL 30
IS 4
BP 61
EP 73
PG 13
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 485EO
UT WOS:000269104000005
PM 19719033
ER
PT J
AU O'Connell, JB
McCarthy, PM
Sopko, G
Filippatos, GS
Pina, IL
Konstam, MA
Young, JB
Miller, LW
Mehra, MR
Roland, E
Blair, JEA
Farrar, DJ
Gheorghiade, M
AF O'Connell, John B.
McCarthy, Patrick M.
Sopko, George
Filippatos, Gerasimos S.
Pina, Ileana L.
Konstam, Marvin A.
Young, James B.
Miller, Leslie W.
Mehra, Mandeep R.
Roland, Edmond
Blair, John E. A.
Farrar, David J.
Gheorghiade, Mihai
TI Mechanical circulatory support devices for acute heart failure
syndromes: considerations for clinical trial design
SO HEART FAILURE REVIEWS
LA English
DT Article
DE Heart failure; Trials; Devices
ID VENTRICULAR ASSIST DEVICE; HOSPITALIZED-PATIENTS; RISK STRATIFICATION;
IMPROVED OUTCOMES; CARDIAC SUPPORT; UNITED-STATES; SERUM SODIUM;
OPTIMIZE-HF; TRANSPLANTATION; MORTALITY
AB Mechanical circulatory support (MCS) devices are a guideline-recommended treatment option for a small subset of advanced heart failure patients. MCS has the potential to become more prominent in the management of Acute Heart Failure Syndromes (AHFS) as device technology advances and as clinical trials consistently discover neutral or harmful effects with pharmacologic therapies hypothesized to be beneficial in this population. While it is now possible to identify AHFS patients who are at high risk of death, the therapeutic options available to improve their long-term outcomes are limited. MCS therapy in this population offers a "bridge to recovery" strategy; these patients may have viable myocardium that responds favorably to the influence of MCS on neurohormones, cytokines, and/or reverse remodeling. Patients at high risk for mortality who have a substantial likelihood of benefiting from MCS can be easily identified using standard clinical criteria developed from large observational databases. MCS technology is rapidly evolving, and risks related to implantation are declining. It is evident that rigorous clinical trial testing of the potential risks, benefits, and economic implications of MCS in patients with AHFS will need to be conducted before the "routine" application of this aggressive therapy. This paper examines the rationale for conducting trials of MCS devices in patients with AHFS, and it explores considerations for patient selection and appropriate endpoints. This manuscript was generated from discussions on this issue during the third international meeting of the International Working Group on AHFS held in Washington, DC, April 8-9, 2006.
C1 [O'Connell, John B.; McCarthy, Patrick M.; Blair, John E. A.; Gheorghiade, Mihai] Northwestern Univ, Ctr Heart Failure, Bluhm Cardiovasc Inst, Feinberg Sch Med, Chicago, IL 60611 USA.
[Sopko, George] Natl Heart Lung & Blood & Lung Inst, Bethesda, MD USA.
[Filippatos, Gerasimos S.] Univ Athens, Athens, Greece.
[Pina, Ileana L.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Konstam, Marvin A.] Tufts Univ New England Med Ctr, Boston, MA USA.
[Young, James B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Miller, Leslie W.] Univ Minnesota, Minneapolis, MN USA.
[Mehra, Mandeep R.] Univ Maryland, Baltimore, MD 21201 USA.
[Roland, Edmond] Agence Francaise Secur Sanit Prod Sante, Paris, France.
[Farrar, David J.] Thoratec Corp, Pleasanton, CA USA.
RP O'Connell, JB (reprint author), Northwestern Univ, Ctr Heart Failure, Bluhm Cardiovasc Inst, Feinberg Sch Med, 201 E Huron St,Galter 11-20, Chicago, IL 60611 USA.
EM joconnell@northwestern.edu
RI Lainscak, Mitja/F-3237-2015;
OI Mehra, Mandeep/0000-0001-8683-7044
FU Sigma Tau; Abbott; Astellas; Scios; CV Therapeutics; Otsuka; Novartis;
CHF Solutions; Protein Design Labs; CardioDynamics; RenaMedBio;
Medtronic; Guidant; Thoratec; Cytokinetics
FX The third international meeting of the International Working Group on
AHFS was funded by: Sigma Tau, Abbott, Astellas, Scios, CV Therapeutics,
Otsuka, Novartis, CHF Solutions, Protein Design Labs, CardioDynamics,
RenaMedBio, Medtronic, Guidant, Thoratec, and Cytokinetics.
NR 36
TC 2
Z9 2
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1382-4147
J9 HEART FAIL REV
JI Heart Fail. Rev.
PD JUN
PY 2009
VL 14
IS 2
BP 101
EP 112
DI 10.1007/s10741-008-9097-7
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 425GR
UT WOS:000264625500008
PM 18548344
ER
PT J
AU Tucker, MA
AF Tucker, Margaret A.
TI Melanoma Epidemiology
SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Melanoma; Risk factors; Nevi; UV; Genetics
ID CUTANEOUS MALIGNANT-MELANOMA; NEVUS DENSITY; MC1R VARIANTS; SUN
EXPOSURE; RISK-FACTORS; POOLED ANALYSIS; GENETIC-DETERMINANTS;
ASSOCIATION ANALYSIS; FAMILIAL MELANOMA; MUTATION CARRIERS
AB Melanoma is a complex, heterogeneous cancer that continues to increase in incidence. Multiple studies have consistently identified major host and environmental risk factors for melanoma. Nevi, particularly dysplastic nevi, confer much higher risks than most pigmentary characteristics. Ultraviolet radiation exposure is the predominant environmental risk factor for melanoma. Recently, both rare high risk susceptibility genes and common polymorphic genes contributing to melanoma risk have been identified.
C1 [Tucker, Margaret A.] NCI, Human Genet Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Tucker, Margaret A.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Tucker, MA (reprint author), NCI, Human Genet Program, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7122, Bethesda, MD 20892 USA.
EM tuckerp@mail.nih.gov
RI Tucker, Margaret/B-4297-2015
FU NCI, NIH
FX This work was supported by the Intramural Research Program, NCI, NIH.
NR 61
TC 62
Z9 64
U1 2
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8588
J9 HEMATOL ONCOL CLIN N
JI Hematol. Oncol. Clin. North Am.
PD JUN
PY 2009
VL 23
IS 3
BP 383
EP +
DI 10.1016/j.hoc.2009.03.010
PG 14
WC Oncology; Hematology
SC Oncology; Hematology
GA 458ME
UT WOS:000267027100002
PM 19464592
ER
PT J
AU Lok, AS
Everhart, JE
Chung, RT
Kim, HY
Everson, GT
Hoefs, JC
Greenson, JK
Sterling, RK
Lindsay, KL
Lee, WM
Di Bisceglie, AM
Bonkovsky, HL
Ghany, MG
Morishima, C
AF Lok, Anna S.
Everhart, James E.
Chung, Raymond T.
Kim, Hae-Young
Everson, Gregory T.
Hoefs, John C.
Greenson, Joel K.
Sterling, Richard K.
Lindsay, Karen L.
Lee, William M.
Di Bisceglie, Adrian M.
Bonkovsky, Herbert L.
Ghany, Marc G.
Morishima, Chihiro
CA Halt-C Trial Grp
TI Evolution of Hepatic Steatosis in Patients with Advanced Hepatitis C:
Results from the Hepatitis C Antiviral Long-Term Treatment Against
Cirrhosis (HALT-C) Trial
SO HEPATOLOGY
LA English
DT Article
ID FIBROSIS PROGRESSION; INSULIN-RESISTANCE; UNTREATED PATIENTS; INFECTION;
THERAPY; INTERFERON; HISTORY
AB Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC) but there are no large longitudinal studies describing the progression of steatosis in CHC. We examined changes in steatosis on serial biopsies among CHC patients participating in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All 1050 patients in the trial had advanced fibrosis at baseline biopsy and were documented not to have had a sustained virological response to peginterferon and ribavirin. Most (94%) patients had genotype 1 infection. At least one protocol follow-up biopsy was read on 892 patients, and 699 had the last biopsy performed 3.5 years after randomization. At enrollment, 39% had cirrhosis and 61% had bridging fibrosis; 18%, 41%, 31%, and 10% had steatosis scores of 0, 1, 2, and 3 or 4, respectively. The mean steatosis score decreased in the follow-up biopsies in both the interferon-treated patients and controls with no effect of treatment assignment (P = 0.66). A decrease in steatosis score by >= 1 point was observed in 30% of patients and was associated with both progression to cirrhosis and continued presence of cirrhosis (P = 0.02). Compared to patients without a decrease in steatosis, those with a decrease in steatosis had worse metabolic parameters at enrollment, and were more likely to have a decrease in alcohol intake, improvement in metabolic parameters, and worsening liver disease (cirrhosis, esophageal varices, and deterioration in liver function). Conclusion: Serial biopsies demonstrated that in patients with CHC, steatosis recedes during progression from advanced fibrosis to cirrhosis. Decreased alcohol intake and improved metabolic parameters are associated with a decline in steatosis and may modulate hepatitis C progression. (HEPATOLOGY 2009;49:1828-1837.)
C1 [Lok, Anna S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA.
[Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA.
[Kim, Hae-Young] New England Res Inst, Watertown, MA 02172 USA.
[Everson, Gregory T.] Univ Colorado Denver, Sch Med, Aurora, CO USA.
[Hoefs, John C.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
[Greenson, Joel K.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA.
[Sterling, Richard K.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA.
[Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Sch Med, Los Angeles, CA 90033 USA.
[Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA.
[Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Infect Dis, Dallas, TX 75390 USA.
[Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA.
[Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA.
[Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA.
[Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA.
RP Lok, AS (reprint author), Univ Michigan Hlth System, Div Gastroenterol, 3912 Taubman Ctr,SPC 5362, Ann Arbor, MI 48109 USA.
EM aslok@med.umich.edu
RI Lok, Anna /B-8292-2009;
OI Yang, Shuman/0000-0002-9638-0890
FU National Institute of Diabetes & Digestive & Kidney Diseases [P60
DK020572]; National Institute of Allergy and Infectious Diseases
(NIAID); National Cancer Institute; National Center for Minority Health
and Health Disparities; National Center for Research Resources, National
Institutes of Health; Hoffmann-La Roche, Inc.
FX This study was supported by the National Institute of Diabetes &
Digestive & Kidney Diseases (contract numbers are listed below).
Additional support was provided by the National Institute of Allergy and
Infectious Diseases (NIAID), the National Cancer Institute, the National
Center for Minority Health and Health Disparities and by General
Clinical Research Center grants from the National Center for Research
Resources, National Institutes of Health (grant numbers are listed
below). Additional funding to conduct this study was supplied by
Hoffmann-La Roche, Inc., through a Cooperative Research and Development
Agreement (CRADA) with the National Institutes of Health. The insulin
assays were performed in the Michigan Diabetes Research and Training
Center, which is supported by National Institute of Diabetes & Digestive
& Kidney Diseases grant P60 DK020572.
NR 27
TC 28
Z9 28
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUN
PY 2009
VL 49
IS 6
BP 1828
EP 1837
DI 10.1002/hep.22865
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 456KY
UT WOS:000266846400009
PM 19291787
ER
PT J
AU Welzel, TM
Morgan, TR
Bonkovsky, HL
Naishadham, D
Pfeiffer, RM
Wright, EC
Hutchinson, AA
Crenshaw, AT
Bashirova, A
Carrington, M
Dotrang, M
Sterling, RK
Lindsay, KL
Fontana, RJ
Lee, WM
Di Bisceglie, AM
Ghany, MG
Gretch, DR
Chanock, SJ
Chung, RT
O'Brien, TR
AF Welzel, Tania Mara
Morgan, Timothy R.
Bonkovsky, Herbert L.
Naishadham, Deepa
Pfeiffer, Ruth M.
Wright, Elizabeth C.
Hutchinson, Amy A.
Crenshaw, Andrew T.
Bashirova, Arman
Carrington, Mary
Dotrang, Myhanh
Sterling, Richard K.
Lindsay, Karen L.
Fontana, Robert J.
Lee, William M.
Di Bisceglie, Adrian M.
Ghany, Marc G.
Gretch, David R.
Chanock, Stephen J.
Chung, Raymond T.
O'Brien, Thomas R.
CA Halt-C Trial Grp
TI Variants in Interferon-Alpha Pathway Genes and Response to Pegylated
Interferon-Alpha2a Plus Ribavirin for Treatment of Chronic Hepatitis C
Virus Infection in the Hepatitis C Antiviral Long-Term Treatment Against
Cirrhosis Trial
SO HEPATOLOGY
LA English
DT Article
ID SINGLE NUCLEOTIDE POLYMORPHISM; PEGINTERFERON ALPHA-2A; VIRAL-INFECTION;
PROTEIN-KINASE; THERAPY; PKR; MXA; ASSOCIATION; EXPRESSION; ROLES
AB Combination treatment with pegylated-interferon-alpha (PEG IFN-alpha) and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological response (SVR) in only about half of patients. Because genes involved in the interferon-alpha pathway may affect antiviral responses, we analyzed the relationship between variants in these genes and SVR among participants in the Hepatitis C Antiviral Long-Term treatment Against Cirrhosis (HALT-C) trial. Patients had advanced chronic hepatitis C that had previously failed to respond to interferon-based treatment. Participants were treated with peginterferonce-alpha 2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered nonresponders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon-alpha pathway. This analysis compares genotypes for participants with an SVR to nonresponders. The primary analysis was restricted to European American participants because a priori statistical power was low among the small number (n = 131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with IFNAR1 IVSI-22G (adjusted odds ratio, 0.57; P = 0.02); IFNAR2 Ex2-33C (adjusted odds ratio, 2.09; P = 0.02);JAK1 IVS22 + 112T (adjusted odds ratio, 1.66; P = 0.04); and ADAR Ex9 + 14A (adjusted odds ratio, 1.67; P = 0.03). For the TYK2-2256A promoter region variant, a borderline association was present among European American participants (OR, 1.51; P = 0.05) and a strong relationship among, African American patients; all 10 with SVR who were genotyped for TYK2-2256 carried the A variant compared with 68 of 120 (57%) nonresponders (P = 0.006). Conclusion. Genetic polymorphisms in the interferon-alpha pathway may affect responses to antiviral therapy of chronic hepatitis C. (HEPATOLOGY 2009;49:1847-1858.)
C1 [Welzel, Tania Mara; Pfeiffer, Ruth M.; Chanock, Stephen J.; O'Brien, Thomas R.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA.
[Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA.
[Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA.
[Wright, Elizabeth C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Hutchinson, Amy A.; Crenshaw, Andrew T.] NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, Adv Technol Program,SAIC Frederick Inc, Frederick, MD 21701 USA.
[Bashirova, Arman] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Carrington, Mary] NCI Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD USA.
[Dotrang, Myhanh] Comp Sci Corp, Rockville, MD USA.
[Sterling, Richard K.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA.
[Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA.
[Fontana, Robert J.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA.
[Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA.
[Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA.
[Gretch, David R.] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA.
[Chung, Raymond T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA.
RP O'Brien, TR (reprint author), 6120 Execut Blvd,Room 6111,MSC 7246, Rockville, MD 20892 USA.
EM obrient@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011
FU National Institute of Diabete & Digestive & Kidney Diseases; National
Institute of Allergy and Infectious Diseases (NIAID); National Cancer
Institute; National Center for Minority Health and Health Disparities;
National Center for Research Resources; National Institutes of Health;
Hoffmann-La Roche, Inc.
FX The HALT-C Trial was supported by the National Institute of Diabete &
Digestive & Kidney Diseases (contract numbers are listed below).
Additional support was provided by the National Institute of Allergy and
Infectious Diseases (NIAID), the National Cancer Institute, the National
Center for Minority Health and Health Disparities and by General
Clinical Research Center grants from the National Center for Research
Resources, National Institutes of Health (grant numbers are listed
below). Additional funding for HALT-C was supplied by Hoffmann-La Roche,
Inc. through a Cooperative Research and Development Agreement (CRADA)
with the National Institutes of Health. Supported by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Division of Cancer Epidemiology and Genetics This is
publication #32 of the HALT-C Trial.
NR 28
TC 52
Z9 54
U1 0
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUN
PY 2009
VL 49
IS 6
BP 1847
EP 1858
DI 10.1002/hep.22877
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 456KY
UT WOS:000266846400011
PM 19434718
ER
PT J
AU Finnegan, L
Winklbaur, B
Fischer, G
Olofsson, M
Welle-Strand, G
AF Finnegan, Loretta
Winklbaur, Bernadette
Fischer, Gabriele
Olofsson, May
Welle-Strand, Gabrielle
TI New Approaches in the Treatment of Opioid Dependency During the
Pregnancy
SO HEROIN ADDICTION AND RELATED CLINICAL PROBLEMS
LA English
DT Article
ID NEONATAL ABSTINENCE SYNDROME; BUPRENORPHINE; METHADONE; WOMEN; BORN;
MOTHERS
C1 [Finnegan, Loretta] Finnegan Consulting LLC, Perinatal Addict & Womens Hlth, Bethesda, MD USA.
[Finnegan, Loretta] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA.
[Winklbaur, Bernadette; Fischer, Gabriele] Med Univ Vienna, Dept Psychiat & Psychotherapy, Vienna, Austria.
[Olofsson, May] Copenhagen Univ Hosp, Family Ctr, Hvidovre, Denmark.
[Welle-Strand, Gabrielle] Univ Oslo, Norwegian Directorate Hlth, N-0316 Oslo, Norway.
[Welle-Strand, Gabrielle] Univ Oslo, Norwegian Ctr Addict Res, N-0316 Oslo, Norway.
RP Finnegan, L (reprint author), Finnegan Consulting Inc, Winward Harbor Unit, E-1700 Ocean Dr, Avalon, NJ 08202 USA.
EM finnegal337@aol.com
RI Fischer, Gabriele/B-3048-2013
NR 33
TC 4
Z9 4
U1 0
U2 2
PU PACINI EDITORE
PI PISA
PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY
SN 1592-1638
J9 HEROIN ADDICT REL CL
JI Heroin Addict. Relat. Clin. Probl.
PD JUN
PY 2009
VL 11
IS 2
BP 47
EP 57
PG 11
WC Substance Abuse
SC Substance Abuse
GA 508KE
UT WOS:000270928900006
ER
PT J
AU Zhu, XG
Cheng, SY
AF Zhu, X-G.
Cheng, S-Y.
TI Modeling Thyroid Cancer in the Mouse
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Review
DE thyroid cancer; thyroid hormone; mouse models
ID HORMONE-BETA-RECEPTOR; TISSUE-SPECIFIC EXPRESSION; TRANSGENIC MICE;
PAPILLARY CARCINOMAS; RET/PTC1 ONCOGENE; RAS ONCOGENE; TARGETED
EXPRESSION; RET PROTOONCOGENE; TUMOR PROGRESSION; CHROMOSOMAL
TRANSLOCATION
AB Thyroid carcinomas, the most common endocrine tumors in humans, have an increasing incidence in the U.S. and worldwide. There are four major types of thyroid cancers: papillary, follicular, anaplastic, and medullary carcinomas. In recent years, significant progress has been made in the identification of genetic alterations in thyroid carcinomas, particularly, papillary and medullary thyroid cancers. Mouse models of thyroid cancer are valuable tools in elucidating molecular genetic changes underlying thyroid carcinogenesis and in identifying potential molecular targets for therapeutic intervention. Representative mouse models of papillary, follicular, and medullary carcinomas are reviewed here with particular emphasis on those for follicular thyroid carcinomas. Challenges for further development in the modeling of thyroid cancer will also be discussed.
C1 [Zhu, X-G.; Cheng, S-Y.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
FU Center for Cancer Research; National Cancer Institute; National
Institutes of Health
FX We regret any reference omissions due to length limitation. We wish to
thank all colleagues and collaborators who have contributed to the work
described in this review. The present research was supported by the
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health. We are deeply indebted
to Drs. Pilar Santisteban, Sissy Jhaing, and Mark Willingham for the
critical reading of the manuscript and valuable suggestions.
NR 111
TC 9
Z9 9
U1 0
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
EI 1439-4286
J9 HORM METAB RES
JI Horm. Metab. Res.
PD JUN
PY 2009
VL 41
IS 6
SI SI
BP 488
EP 499
DI 10.1055/s-0029-1215572
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 464GM
UT WOS:000267493400013
PM 19358084
ER
PT J
AU Richards, AB
Morris, RW
Ward, S
Schmitz, S
Rothmond, DA
Noble, PL
Woodward, RA
Winslow, JT
Weickert, CS
AF Richards, A. Brent
Morris, Richard W.
Ward, Sarah
Schmitz, Stephanie
Rothmond, Debora A.
Noble, Pam L.
Woodward, Ruth A.
Winslow, James T.
Weickert, Cynthia Shannon
TI Gonadectomy negatively impacts social behavior of adolescent male
primates
SO HORMONES AND BEHAVIOR
LA English
DT Article
DE Social dominance; Sex hormones; Testosterone; Puberty; Fear; Object
novelty; Social novelty; Social brain
ID ESTROGEN-RECEPTOR-ALPHA; MALE RHESUS-MONKEYS; MAJOR MENTAL-ILLNESS;
MACACA-MULATTA; GONADOTROPIN-SECRETION; INDIVIDUAL-DIFFERENCES; PLASMA
TESTOSTERONE; PREFRONTAL CORTEX; GONADAL-HORMONES; DOMINANCE RANK
AB Social behavior changes dramatically during primate adolescence. However, the extent to which testosterone and other gonadal hormones are necessary for adolescent social behavioral development is unknown. In this study, we determined that gonadectomy significantly impairs social dominance in naturalistic settings and changes reactions to social stimuli in experimental settings. Rhesus macaques were castrated (n = 6) or sham operated (n = 6) at age 2.4 years, group-housed for 2 years, and ethograms were collected weekly. During adolescence the gonadally intact monkeys displayed a decrease in subordinate behaviors and an increase in dominant behaviors, which ultimately related to a rise in social status and rank in the dominance hierarchy. We measured monkey's reactions to emotional faces (fear, threat, neutral) of conspecifics of three ages (adult, peer, infant). Intact monkeys were faster to retrieve a treat in front of a threatening or infant face, while castrated monkeys did not show a differential response to different emotional faces or ages. No group difference in reaction to an innate fear-eliciting object (snake) was found. Approach and proximity responses to familiar vs unfamiliar conspecifics were tested, and intact monkeys spent more time proximal to a novel conspecific as compared to castrates who tended to spend more time with a familiar conspecific. No group differences in time spent with novel or familiar objects were found. Thus, gonadectomy resulted in the emergence of significantly different responses to social stimuli, but not non-social stimuli. Our work suggests that intact gonads, which are needed to produce adolescent increases in circulating testosterone, impact social behavior during adolescences in primates. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Richards, A. Brent; Ward, Sarah; Schmitz, Stephanie; Rothmond, Debora A.; Weickert, Cynthia Shannon] NIMH, MiNDS Unit, Bethesda, MD 20892 USA.
[Morris, Richard W.; Rothmond, Debora A.; Weickert, Cynthia Shannon] Univ New S Wales, Schizophrenia Res Inst, Sydney, NSW, Australia.
[Morris, Richard W.; Rothmond, Debora A.; Weickert, Cynthia Shannon] Prince Wales Med Res Inst, Sydney, NSW, Australia.
[Noble, Pam L.; Winslow, James T.] NIMH, IRP Nonhuman Primate Core, Bethesda, MD USA.
[Woodward, Ruth A.] NICHD, Poolesville, MD USA.
RP Weickert, CS (reprint author), Prince Wales Med Res Inst, UNSW Dept Psychiat, Corner Barker & Easy St, Randwick, NSW 2031, Australia.
EM cyndi@powmri.edu.au
RI Shannon Weickert, Cynthia/G-3171-2011;
OI Morris, Richard/0000-0002-5018-1239
FU Intramural NIH HHS [NIH0010048825]; PHS HHS [NIH0010048825]
NR 60
TC 13
Z9 13
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0018-506X
J9 HORM BEHAV
JI Horm. Behav.
PD JUN
PY 2009
VL 56
IS 1
BP 140
EP 148
DI 10.1016/j.yhbeh.2009.03.021
PG 9
WC Behavioral Sciences; Endocrinology & Metabolism
SC Behavioral Sciences; Endocrinology & Metabolism
GA 456KV
UT WOS:000266846100018
PM 19361511
ER
PT J
AU Hayakawa, J
Ueda, T
Lisowski, L
Hsieh, MM
Washington, K
Phang, O
Metzger, M
Krouse, A
Donahue, RE
Sadelain, M
Tisdale, JF
AF Hayakawa, Jun
Ueda, Takahiro
Lisowski, Leszek
Hsieh, Matthew M.
Washington, Kareem
Phang, Oswald
Metzger, Mark
Krouse, Allen
Donahue, Robert E.
Sadelain, Michel
Tisdale, John F.
TI Transient In Vivo beta-Globin Production After Lentiviral Gene Transfer
to Hematopoietic Stem Cells in the Nonhuman Primate
SO HUMAN GENE THERAPY
LA English
DT Article
ID BLOOD PROGENITOR CELLS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; REPOPULATING
CELLS; EFFICIENT TRANSDUCTION; THALASSEMIA-INTERMEDIA; HEMOGLOBIN
DISORDERS; VECTOR TRANSDUCTION; CD34(+) CELLS; SIMIAN CELLS; HUMAN
GENOME
AB Inherited disorders of globin synthesis remain desirable targets for hematopoietic stem cell (HSC)-based therapies. Gene transfer using retroviral vectors offers an alternative to allogeneic HSC transplantation by the permanent integration of potentially therapeutic genes into primary autologous HSCs. Although proof of principle has been demonstrated in humans, this approach has been met by formidable obstacles, and large-animal models have become increasingly important for the preclinical development of gene addition strategies. Here we report lentiviral gene transfer of the human beta-globin gene under the control of the globin promoter and large fragments of the globin locus control region (LCR) in the nonhuman primate. Using an HIV-1, vesicular stomatitis virus glycoprotein G (VSV-G)-pseudotyped vector, modified to overcome a species-specific restriction to HIV-1, gene transfer to colony-forming units (CFU) derived from mobilized peripheral blood (PB) rhesus CD34(+) cells was 84.4 +/- 2.33%. Erythroid cells derived from transduced rhesus CD34(+) cells expressed human beta-globin at high levels as assessed by flow cytometry with a human beta-globin-specific antibody. Two rhesus macaques (RQ3586 and RQ3583) were transplanted with mobilized PB CD34(+) cells transduced with our modified HIV vector at a multiplicity of infection of 80. High gene transfer rates to CFUs were achieved in vitro (RQ3586, 87.5%; RQ3583, 83.3%), with efficient human beta-globin expression among erythroid progeny generated in vitro. Early posttransplantation, gene transfer rates of 5% or higher were detectable and confirmed by genomic Southern blotting, with equivalent-level human beta-globin expression detected by flow cytometry. Long-term gene marking levels among mononuclear cells and granulocytes assessed by quantitative polymerase chain reaction gradually decreased to about 0.001% at 2 years, likely due to additional HIV-1 restrictive elements in the rhesus macaque. No evidence of clonal hematopoiesis has occurred in our animals in up to 2 years. Current efforts are aimed at developing a lentiviral vector capable of efficiently transducing both human and rhesus HSCs to allow preclinical modeling of globin gene transfer.
C1 [Hayakawa, Jun; Ueda, Takahiro; Lisowski, Leszek; Hsieh, Matthew M.; Washington, Kareem; Phang, Oswald; Metzger, Mark; Krouse, Allen; Donahue, Robert E.; Sadelain, Michel; Tisdale, John F.] NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Tisdale, JF (reprint author), NHLBI, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N116,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM johntis@mail.nih.gov
FU NIDDK at the NIH; NHLBI at the NIH; Leonardo Giambrone Foundation
FX This research was supported by the Intramural Research Program of the
NIDDK and NHLBI at the NIH and the Leonardo Giambrone Foundation. The
authors thank Martha Kirby for cell sorting and D. Eric Anderson for
mass spectroscopy. The authors also thank Drs. Isabelle Riviere and Ken
Cornetta for helpful discussion on vector production, and Jason Plotkin
for assistance with vector construction.
NR 57
TC 6
Z9 6
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD JUN
PY 2009
VL 20
IS 6
BP 563
EP 572
DI 10.1089/hum.2008.186
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 455BG
UT WOS:000266729800003
PM 19222366
ER
PT J
AU Jones, S
Peng, PD
Yang, SC
Hsu, C
Cohen, CJ
Zhao, YB
Abad, J
Zheng, ZL
Rosenberg, SA
Morgan, RA
AF Jones, Stephanie
Peng, Peter D.
Yang, Shicheng
Hsu, Cary
Cohen, Cyrille J.
Zhao, Yangbing
Abad, John
Zheng, Zhili
Rosenberg, Steven A.
Morgan, Richard A.
TI Lentiviral Vector Design for Optimal T Cell Receptor Gene Expression in
the Transduction of Peripheral Blood Lymphocytes and Tumor-Infiltrating
Lymphocytes
SO HUMAN GENE THERAPY
LA English
DT Article
ID POLYMERASE-CHAIN-REACTION; HIV-INFECTED INDIVIDUALS; ADOPTIVE
IMMUNOTHERAPY; RETROVIRAL VECTOR; TRANSGENE EXPRESSION; METASTATIC
MELANOMA; CANCER REGRESSION; IN-VIVO; THERAPY; TCR
AB Lentiviral vectors containing promoters of distinct origins, that is, strong viral promoters (cytomegalovirus [CMV] and murine stem cell virus [MSCV]), a cellular promoter (phosphoglycerate kinase [PGK]), and two composite promoters (CAG [a composite promoter sequence comprised of the CMV enhancer and portions of the chicken beta-actin promoter and the rabbit beta-globin gene] and SV40/CD43), were used to evaluate green fluorescent protein (GFP) reporter gene expression in human primary peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs). In PBLs, vectors containing the MSCV promoter were found to be optimal for expression in both minimally stimulated and highly activated lymphocytes. The stability of gene expression was monitored for up to 7 weeks in culture and the MSCV promoter-containing vector was found to be comparable to the cellular PGK promoter-containing vector. The MSCV promoter-containing lentiviral vector was also the most active in transduced TILs and these cells retained biological activity as measured by antimelanoma antigen reactivity. Using the knowledge gained in comparing individual promoters, a series of two-gene-containing lentiviral vectors was constructed in an attempt to produce the alpha and beta chains of antitumor antigen T cell receptors (TCRs). Dual-promoter or internal ribosome entry site (IRES)-containing vector designs were evaluated and found to be unable to produce both chains of the TCR in amounts that led to significant biological activity. In contrast, if the alpha and beta chains were linked by a 2A ribosomal skip peptide, both proper TCR chain pairing and biologically activity were observed. This paper emphasizes the need to optimize both promoter function and protein synthesis in constructs that require stoichiometric production of multiple protein subunits.
C1 [Jones, Stephanie; Peng, Peter D.; Yang, Shicheng; Hsu, Cary; Cohen, Cyrille J.; Zhao, Yangbing; Abad, John; Zheng, Zhili; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Morgan, RA (reprint author), 10 Ctr Dr,Bldg 10,CRC 3W-3864, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX The authors thank the members of the FACS and TIL laboratories (Surgery
Branch) for providing technical support and maintenance of tumor cells
from patients. In addition, the authors thank Boro Dropulic and
colleagues at Lentigen (Baltimore, MD) for assistance in the molecular
cloning and production of the anti-p53 TCR lentiviral vectors. This work
was supported by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research.
NR 42
TC 31
Z9 32
U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD JUN
PY 2009
VL 20
IS 6
BP 630
EP 640
DI 10.1089/hum.2008.048
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 455BG
UT WOS:000266729800010
PM 19265475
ER
PT J
AU Layman, WS
McEwen, DP
Beyer, LA
Lalani, SR
Fernbach, SD
Oh, E
Swaroop, A
Hegg, CC
Raphael, Y
Martens, JR
Martin, DM
AF Layman, W. S.
McEwen, D. P.
Beyer, L. A.
Lalani, S. R.
Fernbach, S. D.
Oh, E.
Swaroop, A.
Hegg, C. C.
Raphael, Y.
Martens, J. R.
Martin, D. M.
TI Defects in neural stem cell proliferation and olfaction in Chd7
deficient mice indicate a mechanism for hyposmia in human CHARGE
syndrome
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID PROTEIN-INTERACTION NETWORK; GLUTATHIONE S-TRANSFERASES; SMELL
IDENTIFICATION TEST; PHENOTYPIC SPECTRUM; KALLMANN-SYNDROME;
HYPOGONADOTROPIC HYPOGONADISM; CHOANAL ATRESIA; HAIR-CELLS; INNER-EAR;
MUTATIONS
AB Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies. The clinical features of CHARGE syndrome are highly variable and incompletely penetrant. Olfactory dysfunction is a common feature in CHARGE syndrome and has been potentially linked to primary olfactory bulb defects, but no data confirming this mechanistic link have been reported. On the basis of these observations, we hypothesized that loss of Chd7 disrupts mammalian olfactory tissue development and function. We found severe defects in olfaction in individuals with CHD7 mutations and CHARGE, and loss of odor evoked electro-olfactogram responses in Chd7 deficient mice, suggesting reduced olfaction is due to a dysfunctional olfactory epithelium. Chd7 expression was high in basal olfactory epithelial neural stem cells and down-regulated in mature olfactory sensory neurons. We observed smaller olfactory bulbs, reduced olfactory sensory neurons, and disorganized epithelial ultrastructure in Chd7 mutant mice, despite apparently normal functional cilia and sustentacular cells. Significant reductions in the proliferation of neural stem cells and regeneration of olfactory sensory neurons in the mature Chd7(Gt/+) olfactory epithelium indicate critical roles for Chd7 in regulating neurogenesis. These studies provide evidence that mammalian olfactory dysfunction due to Chd7 haploinsufficiency is linked to primary defects in olfactory neural stem cell proliferation and may influence olfactory bulb development.
C1 [Layman, W. S.; Martin, D. M.] Univ Michigan, Med Ctr, Dept Human Genet, Ann Arbor, MI 48109 USA.
[McEwen, D. P.; Martens, J. R.] Univ Michigan, Med Ctr, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Beyer, L. A.; Raphael, Y.] Univ Michigan, Med Ctr, Dept Otolaryngol, Ann Arbor, MI 48109 USA.
[Martin, D. M.] Univ Michigan, Med Ctr, Dept Pediat, Ann Arbor, MI 48109 USA.
[Lalani, S. R.; Fernbach, S. D.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Oh, E.; Swaroop, A.] NEI, NNRL, NIH, Bethesda, MD 20892 USA.
[Hegg, C. C.] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA.
RP Martin, DM (reprint author), Univ Michigan, Med Ctr, Dept Human Genet, 3520A Med Sci Res Bldg 1, Ann Arbor, MI 48109 USA.
EM donnamm@umich.edu
OI Martin, Donna/0000-0002-8070-2007; Swaroop, Anand/0000-0002-1975-1141
FU National Institutes of Health [RO1 NS054784, RO1 DC009410, RO1 DC009606,
T32 DC00011]; Amendt Heller Award from the University of Michigan
Department of Pediatrics
FX This work was supported by the National Institutes of Health (RO1
NS054784 to D. M. M., RO1 DC009410 to D. M. M. and Y.R. and RO1 DC009606
to J.R.M.), the Amendt Heller Award from the University of Michigan
Department of Pediatrics to D. M. M. and a Hearing Balance and Chemical
Senses Training Grant from the National Institutes of Health (T32
DC00011 to W.S.L.).
NR 73
TC 47
Z9 49
U1 0
U2 1
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 JUN 1
PY 2009
VL 18
IS 11
BP 1909
EP 1923
DI 10.1093/hmg/ddp112
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 444AH
UT WOS:000265951600002
PM 19279158
ER
PT J
AU Masmoudi, H
Hewitt, SA
Petrick, N
Myers, KJ
Gavrielides, MA
AF Masmoudi, Hela
Hewitt, Stephen M.
Petrick, Nicholas
Myers, Kyle J.
Gavrielides, Marios A.
TI Automated Quantitative Assessment of HER-2/neu Immunohistochemical
Expression in Breast Cancer
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Biomarker; breast cancer; computer-aided immunohistochemistry; digital
microscopy; HER2/neu; pathology
ID IN-SITU HYBRIDIZATION; TRIAL COMPARING DOXORUBICIN; RANDOMIZED
CLINICAL-TRIALS; COLOR PIXEL CLASSIFICATION; SURGICAL ADJUVANT BREAST;
CELLULAR IMAGING-SYSTEM; TISSUE MICROARRAYS; PROGNOSTIC-SIGNIFICANCE;
PROTEIN OVEREXPRESSION; CARDIAC DYSFUNCTION
AB The expression of the HER-2/neu (HER2) gene, a member of the epidermal growth factor receptor family, has been shown to be a valuable prognostic indicator for breast cancer. However, interobserver variability has been reported in the evaluation of HER2 with immunohistochemistry. It has been suggested that automated computer-based evaluation can provide a consistent and objective evaluation of HER2 expression. In this manuscript, we present an automated method for the quantitative assessment of HER2 using digital microscopy. The method processes microscopy images from tissue slides with a multistage algorithm, including steps of color pixel classification, nuclei segmentation, and cell membrane modeling, and extracts quantitative, continuous measures of cell membrane staining intensity and completeness. A minimum cluster distance classifier merges the features to classify the slides into HER2 categories. An evaluation based on agreement analysis with pathologist-derived HER2 scores, showed good agreement with the provided truth. Agreement varied within the different classes with highest agreement (up to 90%) for positive (3+) slides, and lowest agreement (72%-78%) for equivocal (2+) slides which contained ambiguous scoring. The developed automated method has the potential to be used as a computer aid for the immunohistochemical evaluation of HER2 expression with the objective of increasing observer reproducibility.
C1 [Petrick, Nicholas; Myers, Kyle J.; Gavrielides, Marios A.] NIBIB, CDRH, Lab Assessment Med Imaging Syst, US FDA, Silver Spring, MD 20903 USA.
[Masmoudi, Hela] George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA.
[Hewitt, Stephen M.] NCI, Tissue Array Res Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gavrielides, MA (reprint author), NIBIB, CDRH, Lab Assessment Med Imaging Syst, US FDA, Silver Spring, MD 20903 USA.
EM marios.gavrielides@fda.gov
OI Hewitt, Stephen/0000-0001-8283-1788
NR 67
TC 41
Z9 42
U1 0
U2 4
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
EI 1558-254X
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD JUN
PY 2009
VL 28
IS 6
BP 916
EP 925
DI 10.1109/TMI.2009.2012901
PG 10
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 454IV
UT WOS:000266676500012
PM 19164073
ER
PT J
AU Dawson, H
Solano-Aguilar, G
Beal, M
Beshah, E
Vangimalla, V
Jones, E
Botero, S
Urban, JF
AF Dawson, Harry
Solano-Aguilar, Gloria
Beal, Madeline
Beshah, Ethiopia
Vangimalla, Vandana
Jones, Eudora
Botero, Sebastian
Urban, Joseph F., Jr.
TI Localized Th1-, Th2-, T Regulatory Cell-, and Inflammation-Associated
Hepatic and Pulmonary Immune Responses in Ascaris suum-Infected Swine
Are Increased by Retinoic Acid
SO INFECTION AND IMMUNITY
LA English
DT Article
ID VITAMIN-A SUPPLEMENTATION; RECEPTOR-ALPHA; IN-VIVO; DEFICIENT MICE;
MAST-CELLS; POLYRIBOCYTIDYLIC ACID; ALLERGEN CHALLENGE; MEXICAN
CHILDREN; MOUSE MODEL; EXPRESSION
AB Pigs infected with Ascaris suum or controls were given 100 mu g (low-dose) or 1,000 mu g (high-dose) all-trans retinoic acid (ATRA)/kg body weight in corn oil or corn oil alone per os on days after inoculation (DAI) -1, -1, and -3 with infective eggs. Treatment with ATRA increased interleukin 4 (IL4) and IL12p70 in plasma of infected pigs at 7 DAI and augmented bronchoalveolar lavage (BAL) eosinophilia observed at 7 and 14 DAI. To explore potential molecular mechanisms underlying these observations, a quantitative real-time reverse transcription (RT)-PCR array was used to examine mRNA expression in tissue. Ascaris-infected pigs had increased levels of liver mRNA for T-helper-2 (Th2)-associated cytokines, mast cell markers, and T regulatory (Treg) cells, while infected pigs given ATRA had higher IL4, IL13, CCL11, CCL26, CCL17, CCL22, and TPSB1 expression. Gene expression for Th1-associated markers (IFNG, IL12B, and TBX21), the CXCR3 ligand (CXCL9), IL1B, and the putative Treg marker TNFRSF18 was also increased. Expression of IL4, IL13, IL1B, IL6, CCL11, and CCL26 was increased in the lungs of infected pigs treated with ATRA. To determine a putative cellular source of eosinophil chemoattractants, alveolar macrophages were treated with IL4 and/or ATRA in vitro. IL4 induced CCL11, CCL17, CCL22, and CCL26 mRNA, and ATRA increased the basal and IL4-stimulated expression of CCL17 and CCL22. Thus, ATRA augments a diverse Th1-, Th2-, Treg-, and inflammation-associated response in swine infected with A. suum, and the increased BAL eosinophilia may be related to enhanced induction of eosinophil chemokine activity by alveolar macrophages.
C1 [Dawson, Harry; Solano-Aguilar, Gloria; Beshah, Ethiopia; Vangimalla, Vandana; Botero, Sebastian; Urban, Joseph F., Jr.] ARS, USDA, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA.
[Beal, Madeline] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Jones, Eudora] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Dawson, H (reprint author), ARS, USDA, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, Rm 224,Bldg 307C,BARC E,10300 Baltimore Ave, Beltsville, MD 20705 USA.
EM Harry.Dawson@ars.usda.gov
RI Dawson, Harry/H-8242-2013;
OI Urban, Joseph/0000-0002-1590-8869
NR 80
TC 26
Z9 27
U1 0
U2 3
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 JUN
PY 2009
VL 77
IS 6
BP 2576
EP 2587
DI 10.1128/IAI.00827-07
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 447HO
UT WOS:000266182400035
PM 19332534
ER
PT J
AU Abreu, MT
von Tirpitz, C
Hardi, R
Kaatz, M
Van Assche, G
Rutgeerts, P
Bisaccia, E
Goerdt, S
Hanauer, S
Knobler, R
Mannon, P
Mayer, L
Ochsenkuhn, T
Sandborn, WJ
Parenti, D
Lee, K
Reinisch, W
AF Abreu, Maria T.
von Tirpitz, Christian
Hardi, Robert
Kaatz, Martin
Van Assche, Gert
Rutgeerts, Paul
Bisaccia, Emil
Goerdt, Sergi
Hanauer, Stephen
Knobler, Robert
Mannon, Peter
Mayer, Lloyd
Ochsenkuhn, Thomas
Sandborn, William J.
Parenti, Dennis
Lee, Kevin
Reinisch, Walter
CA Crohn's Dis Photopheresis Study
TI Extracorporeal Photopheresis for the Treatment of Refractory Crohn's
Disease: Results of an Open-label Pilot Study
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE extracorporeal photopheresis; 8-methoxypsoralen; anti-TNF therapy;
immunomodulators; Crohn's disease
ID VERSUS-HOST-DISEASE; INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS;
CERTOLIZUMAB PEGOL; APOPTOTIC CELLS; LONG-TERM; PHOTOCHEMOTHERAPY;
INFLIXIMAB; RESPONSES; LYMPHOMA
AB Background: Extracorporeal photopheresis (ECP) is effective in immune-mediated disorders. A prospective, uncontrolled pilot study was conducted to evaluate the safety and efficacy of ECP in patients with active Crohn's disease (CD) who were refractory to or intolerant of immunosuppressants and/or anti-TNF therapies.
Methods: Patients with moderate-to-severely active CD (Crohn's Disease Activity Index [CDAI] 220-450 points) underwent 12 weeks of ECP treatment (Weeks 1-4: twice weekly, every week; Weeks 5-12: twice weekly, every other week). Clinical response was defined as a decrease in the CDAI of : 100 points or remission (CDAI < 150 points) at Week 12. Patients who responded at Week 12 could receive an additional 12 weeks of ECP treatment (twice weekly, every other week) in an extension Study.
Results: Twenty-eight patients were enrolled with a mean baseline CDAI score of 314 (range 207-457). At Week 12, 14 patients (50%) responded; 13 patients responded within 6 weeks. Seven patients (25%) attained remission by Week 12. Three of 5 patients with open fistulae at baseline had fistula closure. Response was similar among patients naive to anti-TNF agents and patients who had previously been refractory or intolerant to anti-TNF agents. Of the 12 patients who entered the extension study, 9 (75%) maintained their response at Week 24.
Conclusions: In patients with moderate-to-severely active CD who were refractory to or intolerant of immunosuppressants and/or anti-TNF agents, ECP was well tolerated and induced clinical response (50%) and remission (25%) in patients. Most patients were able to maintain a response with Continued treatments.
C1 [Abreu, Maria T.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[von Tirpitz, Christian] Univ Ulm, Dept Digest Dis, Ulm, Germany.
[Hardi, Robert] Chevy Chase Clin Res, Chevy Chase, MD USA.
[Kaatz, Martin] Univ Jena, Dept Gastroenterol, Jena, Germany.
[Van Assche, Gert; Rutgeerts, Paul] Univ Leuven, Dept Internal Med, Dept Gastroenterol, Louvain, Belgium.
[Bisaccia, Emil] Morristown Mem Hosp, Morristown, NJ USA.
[Goerdt, Sergi] Univ Mannheim, Dept Gastroenterol, Mannheim, Germany.
[Hanauer, Stephen] Univ Chicago, Div Gastroenterol Hepatol & Nutr, Chicago, IL 60637 USA.
[Knobler, Robert] Univ Vienna, Dept Dermatol, Vienna, Austria.
[Mannon, Peter] NIAID, Bethesda, MD 20892 USA.
[Mayer, Lloyd] Mt Sinai Sch Med, Inst Immunol, New York, NY USA.
[Ochsenkuhn, Thomas] Univ Munich, Dept Gastroenterol, Munich, Germany.
[Sandborn, William J.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Parenti, Dennis; Lee, Kevin] Therakos Inc, Exton, PA USA.
[Reinisch, Walter] Univ Vienna, Dept Gastroenterol, Vienna, Austria.
RP Abreu, MT (reprint author), POB 016960, Miami, FL 33101 USA.
EM MAbreu1@med.miami.edu
NR 39
TC 25
Z9 25
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1078-0998
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD JUN
PY 2009
VL 15
IS 6
BP 829
EP 836
DI 10.1002/ibd.20833
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 454HT
UT WOS:000266673700010
PM 19130617
ER
PT J
AU Zia, FZ
White, JD
AF Zia, Farah Z.
White, Jeffrey D.
TI Untitled
SO INTEGRATIVE CANCER THERAPIES
LA English
DT Letter
ID CANCER
C1 [Zia, Farah Z.; White, Jeffrey D.] NCI, NIH, Bethesda, MD 20892 USA.
RP Zia, FZ (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
NR 4
TC 2
Z9 2
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1534-7354
J9 INTEGR CANCER THER
JI Integr. Cancer Ther.
PD JUN
PY 2009
VL 8
IS 2
BP 113
EP 114
DI 10.1177/1534735409339437
PG 2
WC Oncology; Integrative & Complementary Medicine
SC Oncology; Integrative & Complementary Medicine
GA 464KK
UT WOS:000267503600002
PM 19691176
ER
PT J
AU Pastwa, E
Somiari, RI
Malinowski, M
Somiari, SB
Winters, TA
AF Pastwa, Elzbieta
Somiari, Richard I.
Malinowski, Mariusz
Somiari, Stella B.
Winters, Thomas A.
TI In vitro non-homologous DNA end joining assays-The 20th anniversary
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Review
DE Anticancer drugs; DNA double-strand breaks; DNA repair; In vitro assays;
Non-homologous DNA end joining
ID DOUBLE-STRAND BREAKS; DEPENDENT PROTEIN-KINASE; HUMAN CELL-EXTRACTS;
V(D)J RECOMBINATION; PHOSPHODIESTERASE TDP1; REPAIR PATHWAY; EGG
EXTRACTS; KU RECRUITS; IV COMPLEX; LIGASE-IV
AB DNA double-strand breaks (DSBs) are the most serious forms of DNA damage in cells. Unrepaired or misrepaired DSBs account for some of the genetic instabilities that lead to mutations or cell death, and consequently, to cancer predisposition. In human cells non-homologous DNA end joining (NHEJ) is the main repair mechanism of these breaks. Systems for DNA end joining study have been developing during the last 20 years. New assays have some advantages over earlier in vitro DSBs repair assays because they are less time-consuming, allow the use of clinical material and examination of the joining DNA ends produced physiologically in mammalian cells. Proteins involved in NHEJ repair pathway can serve as biomarkers or molecular targets for anticancer drugs. Results of studies on NHEJ in cancer could help to select potent repair inhibitors that may selectively sensitize tumor cells to ionizing radiation (IR) and chemotherapy. Here, we review the principles and practice of in vitro NHEJ assays and provide some insights into the future prospects of this assay in cancer diagnosis and treatment. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Pastwa, Elzbieta] Med Univ Lodz, Dept Mol Genet, PL-92215 Lodz, Poland.
[Somiari, Richard I.] ITSI Biosci, Johnstown, PA 15901 USA.
[Malinowski, Mariusz] Med Univ Lodz, Dept Mol & Med Biophys, PL-92215 Lodz, Poland.
[Somiari, Stella B.] Windber Res Inst, Cell Biol Unit, Windber, PA 15963 USA.
[Winters, Thomas A.] NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Pastwa, E (reprint author), Med Univ Lodz, Dept Mol Genet, Mazowiecka 6-8, PL-92215 Lodz, Poland.
EM epastwa@csk.umed.lodz.pl
RI Perez , Claudio Alejandro/F-8310-2010
OI Perez , Claudio Alejandro/0000-0001-9688-184X
FU Polish Ministry of Science and Higher Education [401-117-32]; Medical
University of Lodz [502-19-677, 503-00-78-3]
FX This work was supported in part by grant 401-117-32 from the Polish
Ministry of Science and Higher Education and by grants 502-19-677 and
503-00-78-3 from the Medical University of Lodz.
NR 64
TC 15
Z9 15
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1357-2725
J9 INT J BIOCHEM CELL B
JI Int. J. Biochem. Cell Biol.
PD JUN
PY 2009
VL 41
IS 6
BP 1254
EP 1260
DI 10.1016/j.biocel.2008.11.007
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 425WU
UT WOS:000264669300007
PM 19110069
ER
PT J
AU Boffetta, P
Rabkin, CS
Gridley, G
AF Boffetta, Paolo
Rabkin, Charles S.
Gridley, Gloria
TI A cohort study of cancer among sarcoidosis patients
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE sarcoidosis; kidney cancer; colon cancer; rectal cancer; lung cancer;
epidemiology
ID RISK
AB Sarcoidosis is a chronic inflammatory condition that may increase the risk of cancer, but limited information is available on occurrence of cancer in these patients. We compared the incidence of cancer among 2,013 White and 3,755 Black male patients admitted to Veterans hospitals in the United States during 1969-1996 with a diagnosis of sarcoidosis, with that of 2,792,503 White and 662,204 Black nonsarcoidosis patients admitted to the same hospitals. Patients suffering from pulmonary and autoimmune diseases were excluded from the study, as was the first year of follow-up after first admission for sarcoidosis. A total of 241 malignant neoplasms were diagnosed in sarcoidosis patients [relative risk 0.99, 95% confidence interval (CI) 0.87-1.13]. The risks of rectal cancer (relative risk 2.12; 95% CI 1.27-3.52), colon cancer (relative risk 1.55; 95% CI 0.99-2.43) and kidney cancer (relative risk 1.84; 95% CI 1.02-3.33) were increased in sarcoidosis patients when compared with other Veterans hospital patients, whereas the risk of lung cancer was decreased (relative risk 0.60; 95% CI 0.42-0.85). The risk of kidney cancer remained elevated 10 years after first admission. Results were generally consistent among ethnic groups, although the increased risk of colon and kidney cancer was observed only in White patients. These results provide further evidence for an increased risk of specific cancers in patients with sarcoidosis, but do not support any additional increase in overall cancer risk. (C) 2009 Wiley-Liss, Inc.
C1 [Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France.
[Rabkin, Charles S.; Gridley, Gloria] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Boffetta, P (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France.
EM boffetta@iarc.fr
NR 20
TC 18
Z9 19
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUN 1
PY 2009
VL 124
IS 11
BP 2697
EP 2700
DI 10.1002/ijc.24261
PG 4
WC Oncology
SC Oncology
GA 442NT
UT WOS:000265848600023
PM 19230028
ER
PT J
AU Morton, LM
Wang, SS
Richesson, DA
Schatzkin, A
Hollenbeck, AR
Lacey, JV
AF Morton, Lindsay M.
Wang, Sophia S.
Richesson, Douglas A.
Schatzkin, Arthur
Hollenbeck, Albert R.
Lacey, James V., Jr.
TI Reproductive factors, exogenous hormone use and risk of lymphoid
neoplasms among women in the National Institutes of Health-AARP Diet and
Health Study Cohort
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE lymphoma; non-Hodgkin; diffuse large B-cell lymphoma; estrogen;
progestin; hormone replacement therapy; menopause; oral contraceptives;
hysterectomy
ID NON-HODGKIN-LYMPHOMA; REPLACEMENT THERAPY; INTERLYMPH-CONSORTIUM;
UNITED-STATES; CANCER-RISK; DISEASE; CHILDBEARING; PREGNANCY;
ASSOCIATIONS; ESTROGENS
AB Reasons for higher incidence of lymphoid neoplasms among men than women are unknown. Because female sex hormones have immunomodulatory effects, reproductive factors and exogenous hormone use may affect risk for lymphoid malignancies. Previous epidemiologic studies on this topic have yielded conflicting results. Within the National Institutes of Health-AARP Diet and Health Study cohort, we prospectively analyzed detailed, questionnaire-derived information on menstrual and reproductive factors and use of oral contraceptives and menopausal hormone therapy among 134,074 US women. Using multivariable proportional hazards regression models, we estimated relative risks (RRs) for 85 plasma cell neoplasms and 417 non-Hodgkin lymphomas (NHLs) identified during follow-up from 1996 to 2002. We observed no statistically significant associations between plasma cell neoplasms, NHL, or the 3 most common NHL subtypes and age at menarche, parity, age at first birth, oral contraceptive use or menopausal status at baseline. For menopausal hormone therapy use, overall associations between NHL and unopposed estrogen and estrogen plus progestin were null, with the potential exception of an inverse association (RR = 0.49, 95% CI, 0.25-0.96) between use of unopposed estrogen and diffuse large B-cell lymphoma (DLBCL), the most common NHL subtype, among women with a hysterectomy. These data do not support an important role for reproductive factors or exogenous hormones in modulating lymphomagenesis. (C) 2008 Wiley-Liss, Inc.
C1 [Morton, Lindsay M.; Wang, Sophia S.; Richesson, Douglas A.; Schatzkin, Arthur; Lacey, James V., Jr.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Morton, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 7040,MSC 7238, Rockville, MD 20852 USA.
EM mortonli@mail.nih.gov
RI Morton, Lindsay/B-5234-2015
OI Morton, Lindsay/0000-0001-9767-2310
FU National Cancer Institute; NIH; DHHS
FX National Cancer Institute, NIH, DHHS (Intramural Research Program).
NR 42
TC 25
Z9 25
U1 1
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUN 1
PY 2009
VL 124
IS 11
BP 2737
EP 2743
DI 10.1002/ijc.24248
PG 7
WC Oncology
SC Oncology
GA 442NT
UT WOS:000265848600028
PM 19253366
ER
PT J
AU Kessler, RC
Avenevoli, S
Costello, EJ
Green, JG
Gruber, MJ
Heeringa, S
Merikangas, KR
Pennell, BE
Sampson, NA
Zaslavsky, AM
AF Kessler, Ronald C.
Avenevoli, Shelli
Costello, E. Jane
Green, Jennifer Greif
Gruber, Michael J.
Heeringa, Steven
Merikangas, Kathleen R.
Pennell, Beth-Ellen
Sampson, Nancy A.
Zaslavsky, Alan M.
TI Design and field procedures in the US National Comorbidity Survey
Replication Adolescent Supplement (NCS-A)
SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH
LA English
DT Article
DE psychiatric epidemiology; child-adolescent mental disorder; National
Comorbidity Survey (NCS)
ID SAMPLES
AB An overview is presented of the design and field procedures of the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a US face-to-face household survey of the prevalence and correlates of DSM-IV mental disorders. The survey was based on a dual-frame design that included 904 adolescent residents of the households that participated in the US National Comorbidity Survey Replication (85.9% response rate) and 9244 adolescent students selected from a nationally representative sample of 320 schools (74.7% response rate). After expositing the logic of dual-frame designs, comparisons are presented of sample and population distributions on Census socio-demographic variables and, in the school sample, school characteristics. These document only minor differences between the samples and the population. The results of statistical analysis of the bias-efficiency trade-off in weight trimming are then presented. These show that modest trimming meaningfully reduces mean squared error. Analysis of comparative sample efficiency shows that the household sample is more efficient than the school sample, leading to the household sample getting a higher weight relative to its size in the consolidated sample relative to the school sample. Taken together, these results show that the NCS-A is an efficient sample of the target population with good representativeness on a range of socio-demographic and geographic variables. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Kessler, Ronald C.; Green, Jennifer Greif; Gruber, Michael J.; Sampson, Nancy A.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Avenevoli, Shelli] NIMH, Div Dev Translat Res, Bethesda, MD USA.
[Costello, E. Jane] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Ctr Dev Epidemiol, Durham, NC 27706 USA.
[Heeringa, Steven; Pennell, Beth-Ellen] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48109 USA.
[Merikangas, Kathleen R.] NIMH, Sect Dev Genet Epidemiol, Intramural Res Branch, Bethesda, MD USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM Kessler@hcp.med.harvard.edu
FU National Institute of Mental Health [U01-MH60220, R01-MH66627,
R01-MH070884, R13-MH066849, R01-MH069864, R01-MH077883]; National
Institute on Drug Abuse (NIDA) [R01-DA016558]; Substance Abuse and
Mental Health Services Administration (SAMHSA); Robert Wood Johnson
Foundation [044780]; John W. Alden Trust; Fogarty International Center
of the National Institutes of Health [R03-TW006481]
FX The National Comorbidity Survey Replication Adolescent Supplement
(NCS-A) is supported by the National Institute of Mental Health (NIMH;
U01-MH60220 and R01-MH66627) with supplemental support from the National
Institute on Drug Abuse (NIDA), the Substance Abuse and Mental Health
Services Administration (SAMHSA), the Robert Wood Johnson Foundation
(RWJF; Grant 044780), and the John W. Alden Trust. The views and
opinions expressed in this report are those of the authors and should
not be construed to represent the views of any of the sponsoring
organizations, agencies, or US Government. A complete list of NCS-A
publications can be found at http://www. hcp.med.harvard.edu/ncs. Send
correspondence to ncs@ hcp.med.harvard.edu. The NCS-A is carried out in
conjunction with the World Health Organization World Mental Health (WMH)
Survey Initiative. We thank the staff of the WMH Data Collection and
Data Analysis Coordination Centers for assistance with instrumentation,
fieldwork, and consultation on data analysis. The WMH Data Coordination
Centers have received support from NIMH (R01-MH070884, R13-MH066849,
R01-MH069864, R01-MH077883), NIDA (R01-DA016558), the Fogarty
International Center of the National Institutes of Health (FIRCA
R03-TW006481), the John D. and Catherine T. MacArthur Foundation, the
Pfizer Foundation, and the Pan American Health Organization. The WMH
Data Coordination Centers have also received unrestricted educational
grants from Astra Zeneca, Bristol-MyersSquibb, Eli Lilly and Company,
GlaxoSmithKline, Ortho-McNeil, Pfizer, Sanofi-Aventis, and Wyeth. A
complete list of WMH publications can be found at
http://www.hcp.med.harvard.edu/wmh/.
NR 21
TC 28
Z9 28
U1 2
U2 5
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1049-8931
J9 INT J METH PSYCH RES
JI Int. J. Methods Psychiatr. Res.
PD JUN
PY 2009
VL 18
IS 2
BP 69
EP 83
DI 10.1002/mpr.279
PG 15
WC Psychiatry
SC Psychiatry
GA 462VZ
UT WOS:000267387200001
ER
PT J
AU Stenholm, S
Alley, D
Bandinelli, S
Griswold, ME
Koskinen, S
Rantanen, T
Guralnik, JM
Ferrucci, L
AF Stenholm, S.
Alley, D.
Bandinelli, S.
Griswold, M. E.
Koskinen, S.
Rantanen, T.
Guralnik, J. M.
Ferrucci, L.
TI The effect of obesity combined with low muscle strength on decline in
mobility in older persons: results from the InCHIANTI Study
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE aged; disability; longitudinal studies; muscle strength; physical
function
ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE BATTERY; BODY-MASS INDEX;
SARCOPENIC OBESITY; WEIGHT-LOSS; SUBSEQUENT DISABILITY; KNEE
OSTEOARTHRITIS; WALKING LIMITATION; MUSCULAR STRENGTH; GAIT SPEED
AB Objective: Both obesity and muscle impairment are increasingly prevalent among older persons and negatively affect health and physical functioning. However, the combined effect of coexisting obesity and muscle impairment on physical function decline has been little studied. We examined whether obese persons with low muscle strength experience significantly greater declines in walking speed and mobility than persons with only obesity or low muscle strength.
Design: Community-dwelling adults aged >= 65 years (n = 930) living in the Chianti geographic area (Tuscany, Italy) were followed for 6 years in the population-based InCHIANTI study.
Measurements: On the basis of baseline measurements (1998-2000), obesity was defined as body mass index (BMI) >= 30 kg/m(2) and low muscle strength as lowest sex-specific tertile of knee extensor strength. Walking speed and self-reported mobility disability (ability to walk 400m or climb one flight of stairs) were assessed at baseline and at 3-and 6-year follow-up.
Results: At baseline, obese persons with low muscle strength had significantly lower walking speed compared with all other groups (P <= 0.05). In longitudinal analyses, obese participants with low muscle strength had steeper decline in walking speed and high risk of developing new mobility disability over the 6-year follow-up compared with those without obesity or low muscle strength. After the age of 80, the differences between groups were substantially attenuated. The differences seen in walking speed across combination of low muscle strength and obesity groups were partly explained by 6-year changes in muscle strength, BMI and waist circumference.
Conclusions: Obesity combined with low muscle strength increases the risk of decline in walking speed and developing mobility disability, especially among persons <80 years old. International Journal of Obesity (2009) 33, 635-644; doi: 10.1038/ijo.2009.62; published online 21 April 2009
C1 [Stenholm, S.; Ferrucci, L.] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21225 USA.
[Stenholm, S.; Koskinen, S.] Natl Inst Hlth & Welf, Div Welf & Hlth Policies, Helsinki, Finland.
[Alley, D.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
[Bandinelli, S.] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Griswold, M. E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Rantanen, T.] Univ Jyvaskyla, Dept Hlth Sci, Finnish Ctr Interdisciplinary Gerontol, Jyvaskyla, Finland.
[Guralnik, J. M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA.
RP Stenholm, S (reprint author), NIA, Clin Res Branch, Longitudinal Studies Sect, Harbor Hosp 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA.
EM stenholmsm@mail.nih.gov
RI Stenholm, Sari/G-6940-2011; Rantanen, Taina/O-6579-2016
OI Rantanen, Taina/0000-0002-1604-1945
FU Italian Ministry of Health; US National Institute on Aging [263 MD 9164,
263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; Intramural
Research Program of the National Institute on Aging; National Institutes
of Health; Baltimore, Maryland, USA; Finnish Academy [125494 SS]; Robert
Wood Johnson Foundation (DA)
FX The InCHIANTI study baseline (1998-2000) was supported as a 'targeted
project' (ICS110.1/ RF97.71) by the Italian Ministry of Health and, in
part, by the US National Institute on Aging (Contracts: 263 MD 9164 and
263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the
US National Institute on Aging (Contracts: N.1-AG-1-1 and
N.1-AG-1-2111); the InCHIANTI Follow-up 2 (2004-2006) was financed by
the US National Institute on Aging (Contract: N01-AG-5-0002); supported,
in part, by the Intramural Research Program of the National Institute on
Aging, National Institutes of Health, Baltimore, Maryland, USA. This
work was also supported by grants from the Finnish Academy (no. 125494
SS) and the Robert Wood Johnson Foundation (DA). None of the sponsoring
institutions interfered with the collection, analysis, presentation or
interpretation of the data reported here.
NR 43
TC 75
Z9 77
U1 1
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
J9 INT J OBESITY
JI Int. J. Obes.
PD JUN
PY 2009
VL 33
IS 6
BP 635
EP 644
DI 10.1038/ijo.2009.62
PG 10
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 458LM
UT WOS:000267022700005
PM 19381155
ER
PT J
AU Pachauri, A
Yadav, H
Jain, S
Bisen, PS
Chapperwal, A
Marotta, F
Minelli, E
Prasad, GBKS
AF Pachauri, Akash
Yadav, Hariom
Jain, Shalini
Bisen, Prakash S.
Chapperwal, Anand
Marotta, Francesco
Minelli, E.
Prasad, Godavarthi B. K. S.
TI Hypoglycemic Effect of Diabegon: A Polyherbal Preparation in Normal and
Type 2 Diabetic Rats and Human Subjects
SO INTERNATIONAL MEDICAL JOURNAL
LA English
DT Article
DE diabetes mellitus; diabegon; oxidative stress; glucose; hyperlipidemia
ID INSULIN RESISTANCE; MEDICINAL-PLANTS; MECHANISM; MELLITUS
AB Background: The diabegon is used as a folk medicine for treatment of diabetes in India, which contains 19 plant extracts. In the present study, the hypoglycemic effect of diabegon was evaluated on normal and high fructose induced diabetes in rats as well as in diabetic patients.
Methods: The study was divided into two experiments; viz. experiment 1, was conducted for evaluation of hypoglycaemic effect and deciding the appropriate dose of drug with reference to body weight in animals. The blood glucose lowering activity of diabegon were studied in normal and high fructose induced diabetes in rats, after oral administration of at doses of 100, 150 and 200 mg/kg body weight and compared the effect with standard antidiabetic drugs viz. Glibenclamide and Rosiglitazone. The blood samples were collected from the tail vein before and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 24 hours after drug administration and blood glucose was analysed by glucometer and insulin was estimated with ELISA kit. Experiment 2, was performed with 16 normal and 20 type 2 male diabetic patients with 100 mg/kg body weight of drug dose and also compared the effect with glibenclamide and rosiglitazone. The blood samples were collected before and at 2, 4, 6 and 8 hours after drug administration. The diabetes was checked by oral glucose tolerance test in both animals and human subjects.
Results: The diabegon exhibited dose dependent reduction of blood glucose and increased insulin production, in both normal and diabetic animals and human subjects as compared with that of standard drugs glibenclamide and rosiglitazone. On the basis of results of present study, it may be concluded that diabegon exhibited an ace hypoglycaemic activity at the dose of 100 mg/kg body weight also, and this activity may act by stimulating pancreatic beta-cells for insulin production and/or increasing insulin sensitivity by extra-pancreatic action.
Conclusions: On the basis of result from present study it is concluded that, diabegon is a potent antidiabetic herbal preparation which can use as folk antidiabetic preparation. The detailed elaborated effect and mode of action needs further study.
C1 [Pachauri, Akash; Yadav, Hariom; Prasad, Godavarthi B. K. S.] Jiwaji Univ, Sch Studies Biochem, Gwalior 474011, Madhya Pradesh, India.
[Jain, Shalini] NIDDK, NIH, Bethesda, MD USA.
[Bisen, Prakash S.] MS Bisen Biotech & Biopharma Pvt Ltd, R&D Div, Gwalior, India.
[Marotta, Francesco; Minelli, E.] Univ Milan, WHO Ctr Biotech & Trad Med, I-20122 Milan, Italy.
RP Prasad, GBKS (reprint author), Jiwaji Univ, Sch Studies Biochem, Gwalior 474011, Madhya Pradesh, India.
EM gbksprasad@gmail.com
NR 16
TC 0
Z9 0
U1 2
U2 3
PU JAPAN INT CULTURAL EXCHANGE FOUNDATION
PI TOKYO
PA 2-15-5-207, SHOTO, SHIBUYA-KU, TOKYO, 150-0046, JAPAN
SN 1341-2051
J9 INT MED J
JI Int. Med. J.
PD JUN
PY 2009
VL 16
IS 2
BP 117
EP 124
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 464JW
UT WOS:000267502200007
ER
PT J
AU Nunez-Troconis, J
Delgado, M
Gonzalez, J
Mindiola, R
Velasquez, J
Conde, B
Whitby, D
Munroe, DJ
AF Nunez-Troconis, Jose
Delgado, Mariela
Gonzalez, Julia
Mindiola, Raimy
Velasquez, Jesvy
Conde, Betty
Whitby, Denise
Munroe, David J.
TI Prevalence and risk factors of human papillomavirus infection in
asymptomatic women in a Venezuelan urban area.
SO INVESTIGACION CLINICA
LA English
DT Article
DE Prevalence; Human Papillomavirus; hybrid capture 2; Venezuela
ID CERVICAL-CANCER; HPV VACCINES; COSTA-RICA; EPIDEMIOLOGY; WORLDWIDE;
NEOPLASIA
AB The purpose of this study was to investigate the prevalence and risk factors of genital human papillomavirus (HPV) infection in asymptomatic women, using the HPV DNA Hybrid Capture 2 (HC2) test. Three hundred and two women who attended the Out-Patient Gynecological Clinic of a tertiary level hospital, in a Venezuelan urban area, were selected for the study. A pap smear, a cervical swab for HC2 and gynecological exam were performed to each patient. The HC2 testing showed that 47 samples (15.6%) were positive to HPV. Forty patients (13.2%) were positive to high risk-HPV (HR-HPV) and 11 (3.6%) were positive to low-risk-HPV (LR-HPV). The prevalence of HPV infections was higher for women under 35 years (51.1%; p < 0.02), and decreased to 6.4% for women >= 65 years old. Women who had not finished high school had a higher prevalence of HPV infection (p < 0.035). Twenty six (42.6%) of 6.1 pathological Pap smears were positives to HPV infection. A statistically significant difference was found when HPV infection was compared in normal and abnormal Pap smear (HSIL+LSIL; p<0.0001). Twenty four of 56 (43%) women with diagnosis of LSIL, and 2(40%) of 5 with diagnosis of HSIL were positive for HPV infection. A statistically significant difference was found when we compared HPV infection in negative Pap smears and those with LSIL (p<0.001). The present study found that the prevalence of HPV infection in asymptomatic Venezuelan women who attended a tertiary level hospital was 15.6%. HPV infection was more frequent in young adult, and in women with low educational level.
C1 [Nunez-Troconis, Jose] Univ Zulia, Manuel Noriega Trigo Hosp, Dept Obstet & Gynecol, Fac Med, Maracaibo 4011, Venezuela.
[Delgado, Mariela; Gonzalez, Julia] Maracaibo Policlin, Maracaibo, Venezuela.
[Mindiola, Raimy; Velasquez, Jesvy] Univ Zulia, Reg Lab Virol Reference, Fac Med, Maracaibo 4011, Venezuela.
[Munroe, David J.] SAIC Frederick Inc, Lab Mol Technol, Natl Canc Inst Frederick, Frederick, MD USA.
RP Nunez-Troconis, J (reprint author), Apartado 525, Maracaibo 4001 A, Venezuela.
EM jnunezt@cantv.net
FU NCI NIH HHS [N01-CO-12400]
NR 31
TC 3
Z9 5
U1 0
U2 4
PU INST INVESTIGACION CLINICA
PI MARACAIBO
PA APARTADO 23, MARACAIBO 4001-A, VENEZUELA
SN 0535-5133
J9 INVEST CLIN
JI Invest. Clin.
PD JUN
PY 2009
VL 50
IS 2
BP 203
EP 212
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 460EI
UT WOS:000267170600007
PM 19662815
ER
PT J
AU Austin, BA
Liu, BY
Li, ZQ
Nussenblatt, RB
AF Austin, Bobbie Ann
Liu, Baoying
Li, Zhuqing
Nussenblatt, Robert B.
TI Biologically Active Fibronectin Fragments Stimulate Release of MCP-1 and
Catabolic Cytokines from Murine Retinal Pigment Epithelium
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID CHOROIDAL NEOVASCULAR MEMBRANES; HTRA1 PROMOTER POLYMORPHISM; COMPLEMENT
FACTOR-H; MACULAR DEGENERATION; MATRIX METALLOPROTEINASES; BRUCHS
MEMBRANE; RHEUMATOID-ARTHRITIS; JAPANESE POPULATION; DRUSEN FORMATION;
SYNOVIAL-FLUID
AB PURPOSE. High-temperature requirement serine protease (HTRA1) was identified as a candidate age-related macular degeneration gene in multiple genetic studies in humans. To date, no functional studies have shown a mechanism for HTRA1 to instigate ocular tissue abnormalities. In the present study, the authors focused on a substrate of HTRA1, fibronectin, because fibronectin fragments (Fnfs) stimulate biochemical events in other age-related degenerative diseases that are analogous to changes associated with age-related macular degeneration (AMD). The purpose of the study was to determine whether Fnfs stimulate the release of proinflammatory and catabolic cytokines from murine retinal pigment epithelium (RPE).
METHODS. Fibronectin was purified from murine serum by gelatin cross-linked agarose chromatography and subsequently was enzymatically digested with alpha-chymotrypsin. The bioactivity of Fnfs was verified by measuring levels of IL-6 and TNF-alpha in Fnf-exposed murine splenocytes. To analyze the effect of Fnfs on RPE, cytokine and chemokine levels in RPE culture supernatants were assayed by ELISA.
RESULTS. IL-6 and TNF-alpha proinflammatory cytokines were released from primary murine splenocytes in proportion to the dose and length of Fnf treatment, indicating that alpha-chymotryptic digests of fibronectin are biologically active. Fnf treatment of murine RPE cells stimulated the release of microgram and nanogram levels of IL-6, MMP-3, MMP-9, and MCP-1, whereas only picogram levels were detected in untreated cells.
CONCLUSIONS. Fnfs stimulate the release of proinflammatory cytokines, matrix metalloproteinases, and monocyte chemoattractant protein from murine RPE cells. This observation indicated that Fnfs could contribute to ocular abnormalities by promoting inflammation, catabolism, and monocyte chemo-attraction. (Invest Ophthalmol Vis Sci. 2009; 50: 2896-2902) DOI: 10.1167/iovs.08-2495
C1 [Austin, Bobbie Ann; Liu, Baoying; Li, Zhuqing; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA.
RP Nussenblatt, RB (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10-10N113, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
FU National Eye Institute Intramural Research Training Award
FX Supported by a National Eye Institute Intramural Research Training
Award.
NR 77
TC 21
Z9 23
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2009
VL 50
IS 6
BP 2896
EP 2902
DI 10.1167/iovs.08-2495
PG 7
WC Ophthalmology
SC Ophthalmology
GA 450ME
UT WOS:000266403800049
PM 19151387
ER
PT J
AU Subramaniam, S
AF Subramaniam, Sriram
TI 3D structure of native HIV-1 gp120 trimers and mechanisms of cellular
entry
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Subramaniam, Sriram] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 100
BP 23
EP 23
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700003
ER
PT J
AU Bewley, CA
Lam, SN
Huang, CC
Acharya, P
Tang, M
Wyatt, R
Kwong, PD
AF Bewley, Carole A.
Lam, Son N.
Huang, Chih-Chin
Acharya, Priyamvada
Tang, Min
Wyatt, Richard
Kwong, Peter D.
TI Chemokine Receptor CCR5 Mediates Resistance to West Nile Virus Infection
in Mouse and Man
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Bewley, Carole A.; Lam, Son N.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 101
BP 24
EP 24
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700004
ER
PT J
AU Lagenaur, LA
Villarroel, VA
Berger, EA
AF Lagenaur, Laurel A.
Villarroel, Vadim A.
Berger, Edward A.
TI sCD4-17b, an Engineered Bifunctional HIV-1 Neutralizing Protein: Potent
Cross Clade Activity and Potential Microbicide Use
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Lagenaur, Laurel A.; Villarroel, Vadim A.; Berger, Edward A.] NIAID, NIH, Bethesda, MD 20892 USA.
[Lagenaur, Laurel A.] Osel Inc, Santa Clara, CA 95054 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 105
BP 28
EP 28
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700008
ER
PT J
AU Lisco, A
AF Lisco, Andrea
TI The anti-herpetic drug acyclovir suppresses HIV-1 in
herpesvirus-infected human tissues after conversion into a nucleoside
reverse transcriptase inhibitor
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Lisco, Andrea] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Intercellular Interact, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 113
BP 36
EP 36
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700016
ER
PT J
AU Lee, K
Martin, TD
Ambrose, Z
Mulky, A
KewalRamani, VN
AF Lee, Kyeongeun
Martin, Thomas D.
Ambrose, Zandrea
Mulky, Alok
KewalRamani, Vineet N.
TI CA-Dependent HIV-1 Nuclear Import Relies on Transportin-SR2
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Lee, Kyeongeun; Martin, Thomas D.; Ambrose, Zandrea; Mulky, Alok; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 117
BP 40
EP 40
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700020
ER
PT J
AU Douek, DC
AF Douek, Daniel C.
TI Differential CD4 T cell subset depletion at mucosal sites in HIV
infection
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Douek, Daniel C.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 122
BP 45
EP 45
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700025
ER
PT J
AU O'Brien, SJ
AF O'Brien, Stephen J.
TI AIDS Restriction Genes-Genome Wide Association Study
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [O'Brien, Stephen J.] NCI, Lab Genom Divers, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 123
BP 46
EP 46
DI 10.1097/01.qai.0000351080.97332.99
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700026
ER
PT J
AU Gao, XJ
AF Gao, Xiaojiang
TI Immunogenetic polymorphisms and their effects on AIDS progression
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Gao, Xiaojiang] NCI, Canc & Inflammat Program, SAIC Frederick, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 125
BP 48
EP 48
DI 10.1097/01.qai.0000351082.04956.ff
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700028
ER
PT J
AU Chen, WZ
AF Chen, Weizao
TI Human domain antibodies against HIV-1 as exceptionally potent
cross-reactive neutralizers
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Chen, Weizao] NCI, CCR Nanobiol Program, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 128
BP 51
EP 51
DI 10.1097/01.qai.0000351085.27827.57
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700030
ER
PT J
AU Daniels, SI
Davis, DA
Yarchoan, R
AF Daniels, Sarah I.
Davis, David A.
Yarchoan, Robert
TI Inhibition of HIV-1 Release by Cell Permeable Peptides
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Daniels, Sarah I.; Davis, David A.; Yarchoan, Robert] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 130
BP 53
EP 53
DI 10.1097/01.qai.0000351087.35450.5a
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700032
ER
PT J
AU Lee, K
Takemura, T
Xue, YJ
Mulky, A
KewalRamani, VN
AF Lee, Kyeongeun
Takemura, Taichiro
Xue, Yujing
Mulky, Alok
KewalRamani, Vineet N.
TI Cell-cycle dependent HIV-1 killing is mediated through the viral
protease
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Lee, Kyeongeun; Takemura, Taichiro; Xue, Yujing; Mulky, Alok; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 134
BP 57
EP 57
DI 10.1097/01.qai.0000351091.02278.78
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700036
ER
PT J
AU Fauci, AS
AF Fauci, Anthony S.
TI alpha 4 beta 7: A Newly Discovered Receptor for HIV
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 146
BP 69
EP 69
DI 10.1097/01.qai.0000351102.63266.3a
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700048
ER
PT J
AU Engels, EA
AF Engels, Eric A.
TI HIV and cancer: current trends and insights
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Engels, Eric A.] NCI, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 150
BP 73
EP 73
DI 10.1097/01.qai.0000351106.16632.95
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700052
ER
PT J
AU Santiago, ML
Montano, M
Benitez, R
Messer, RJ
Yonemoto, W
Chesebro, B
Hasenkrug, KJ
Greene, WC
AF Santiago, Mario L.
Montano, Mauricio
Benitez, Robert
Messer, Ronald J.
Yonemoto, Wes
Chesebro, Bruce
Hasenkrug, Kim J.
Greene, Warner C.
TI Apobec3: A Modern Twist to A Classic Retroviral Mystery
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Santiago, Mario L.; Montano, Mauricio; Benitez, Robert; Yonemoto, Wes; Greene, Warner C.] Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
[Greene, Warner C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Messer, Ronald J.; Chesebro, Bruce; Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 154
BP 77
EP 77
DI 10.1097/01.qai.0000351109.01385.de
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700056
ER
PT J
AU Pavlakis, GN
Valentin, A
Rosati, M
von Gegerfelt, A
Patel, V
Bergamaschi, C
Ganeru, B
Usami, O
Kulkarni, V
Jalah, R
Alicea, C
Felber, BK
AF Pavlakis, George N.
Valentin, Antonio
Rosati, Margherita
von Gegerfelt, Agneta
Patel, Vainav
Bergamaschi, Cristina
Ganeru, Brunda
Usami, Osamu
Kulkarni, Viraj
Jalah, Rashmi
Alicea, Candido
Felber, Barbara K.
TI Getting the Right Immune Response to HIV: Evaluation of Protective
Immune Responses After Vaccination of Rhesus Macaques
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Pavlakis, George N.; Valentin, Antonio; Rosati, Margherita; von Gegerfelt, Agneta; Patel, Vainav; Bergamaschi, Cristina; Ganeru, Brunda; Usami, Osamu] NCI, Human Retrovirus Sect, Frederick, MD 21701 USA.
[Kulkarni, Viraj; Jalah, Rashmi; Alicea, Candido; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 170
BP 94
EP 94
DI 10.1097/01.qai.0000351125.41288.0c
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700072
ER
PT J
AU Gang, W
de Leeuw, E
Zou, GZ
Rajabi, M
Pazgier, M
Yuan, WR
Li, J
Lubkowski, J
Lu, WY
AF Gang, Wei
de Leeuw, Erik
Zou, Guozhang
Rajabi, Mohsen
Pazgier, Marzena
Yuan, Weirong
Li, Jing
Lubkowski, Jacek
Lu, Wuyuan
TI Human defensins - small in size but big in functionality
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Gang, Wei; de Leeuw, Erik; Zou, Guozhang; Rajabi, Mohsen; Pazgier, Marzena; Yuan, Weirong; Li, Jing; Lu, Wuyuan] Univ Maryland, Sch Med, Lab Synthet Prot Chem, Div Basic Sci & Vaccine Res,Inst Human Virol, Baltimore, MD 21201 USA.
[Pazgier, Marzena; Lubkowski, Jacek] NCI, Macromol Assembly Struct & Cell Signaling Sect, NIH, Frederick, MD 21702 USA.
RI Pazgier, Marzena/B-7295-2012
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 173
BP 97
EP 97
DI 10.1097/01.qai.0000351128.87030.ed
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700075
ER
PT J
AU Zhu, Q
Belyakov, IM
Klinman, D
Berzofsky, JA
AF Zhu, Qing
Belyakov, Igor M.
Klinman, Dennis
Berzofsky, Jay A.
TI Mechanisms by which synergistic combinations of TLR ligands enhance T
cell responses to vaccines
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Zhu, Qing; Belyakov, Igor M.; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Klinman, Dennis] NCI, Expt Immunol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 175
BP 99
EP 99
DI 10.1097/01.qai.0000351130.94653.e0
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700077
ER
PT J
AU Schlom, J
Hodge, JW
Tsang, KY
Palena, C
Greiner, JW
Madan, RA
Gulley, JL
AF Schlom, Jeffrey
Hodge, James W.
Tsang, Kwong-Yok
Palena, Claudia
Greiner, John W.
Madan, Ravi A.
Gulley, James L.
TI Vector-based Vaccines for Cancer Therapy
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Schlom, Jeffrey; Hodge, James W.; Tsang, Kwong-Yok; Palena, Claudia; Greiner, John W.; Madan, Ravi A.; Gulley, James L.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RI Hodge, James/D-5518-2015; Gulley, James/K-4139-2016
OI Hodge, James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912
NR 1
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 176
BP 100
EP 100
DI 10.1097/01.qai.0000351237.66357.3f
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700078
ER
PT J
AU Nabel, GJ
AF Nabel, Gary J.
TI Rational Vaccine Design and the Development of an AIDS Vaccine
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 179
BP 103
EP 103
DI 10.1097/01.qai.0000351134.09833.3a
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700081
ER
PT J
AU Monaco, A
Sabatino, M
Pos, Z
Stroncek, DF
Wang, E
Gallo, RC
Lewis, GK
Tornesello, ML
Buonaguro, FM
Marincola, FM
Buonaguro, L
AF Monaco, A.
Sabatino, M.
Pos, Z.
Stroncek, D. F.
Wang, E.
Gallo, R. C.
Lewis, G. K.
Tornesello, M. L.
Buonaguro, F. M.
Marincola, F. M.
Buonaguro, L.
TI Morphogenomic immune responsiveness to preventive/therapeutic vaccines
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Monaco, A.; Sabatino, M.; Pos, Z.; Stroncek, D. F.; Wang, E.; Marincola, F. M.] NIH, Immunogenet Sect, Dept Transf Med, Ctr Clin, Bethesda, MD 20892 USA.
[Gallo, R. C.; Lewis, G. K.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Tornesello, M. L.; Buonaguro, F. M.; Buonaguro, L.] Ist Nazl Tumori Fond G Pascale, Lab Viral Oncogenesis, Naples, Italy.
[Tornesello, M. L.; Buonaguro, F. M.; Buonaguro, L.] Ist Nazl Tumori Fond G Pascale, Immunotherapies & AIDS Reference Ctr, Naples, Italy.
RI Tornesello, Maria Lina/A-1564-2009; Monaco, Alessandro/O-5338-2015
OI Tornesello, Maria Lina/0000-0002-3523-3264; Monaco,
Alessandro/0000-0002-9941-7003
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 183
BP 107
EP 107
DI 10.1097/01.qai.0000351138.02209.40
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700084
ER
PT J
AU Hendrickson, SL
Kingsley, LA
Ruiz-Pesini, E
Poole, JC
Jacobson, LP
Palella, FJ
Bream, JH
Wallace, DC
O'Brien, SJ
AF Hendrickson, Sher L.
Kingsley, Lawrence A.
Ruiz-Pesini, Eduardo
Poole, Jason C.
Jacobson, Lisa P.
Palella, Frank J.
Bream, Jay H.
Wallace, Douglas C.
O'Brien, Stephen J.
TI Mitochondrial DNA Haplogroups Influence Lipoatrophy After Highly Active
Antiretroviral Therapy
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE lipoatrophy; mitochondrial haplogroup; mitochondrial toxicity; NRTI
ID REVERSE-TRANSCRIPTASE INHIBITORS; IMMUNODEFICIENCY-VIRUS-INFECTION;
HIV-ASSOCIATED LIPODYSTROPHY; MULTICENTER AIDS COHORT; RISK-FACTORS;
HIV-1-INFECTED PATIENTS; PERIPHERAL NEUROPATHY; REGRESSION-MODELS;
ANTIVIRAL DRUGS; DISEASE RISK
AB Although highly active antiretroviral therapy (HAART) has been extremely effective in lowering AIDS incidence among patients infected with HIV, certain drugs included in HAART can cause serious mitochondrial toxicities. One of the most frequent adverse events is lipoatrophy, which is the loss of subcutaneous fat in the face, arms, buttocks, and/or legs as an adverse reaction to nucleoside reverse transcriptase inhibitors. The clinical symptoms of lipoatrophy resemble those of inherited mitochondrial diseases, which suggest that host mitochondrial genotype may play a role in susceptibility. We analyzed the association between mitochondrial haplogroup and severity of lipoatrophy in HIV infected European American patients on HAART in the Multicenter AIDS cohort Study and found that mitochondrial haplogroup H was strongly associated with increased atrophy [arms: P = 0.007, odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.17 to 2.69; legs: P = 0.037, OR = 1.54, 95% CI = 1.03 to 2.31; and buttocks: P = 0.10, OR = 1.41 95% CI = 0.94 to 2.12]. We also saw borderline significance for haplogroup T as protective against lipoatrophy (P = 0.05, OR = 0.52, 95% CI = 0.20 to 1.00). These data suggest that mitochondrial DNA haplogroup may influence the propensity for lipoatrophy in patients receiving nucleoside reverse transcriptase inhibitors.
C1 [Hendrickson, Sher L.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA.
[Kingsley, Lawrence A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA.
[Kingsley, Lawrence A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Ruiz-Pesini, Eduardo] Univ Zaragoza, Fundac ARAID, Dept Bioquim Biol Mol & Celular, CIBERER ISCIII, E-50009 Zaragoza, Spain.
[Poole, Jason C.; Wallace, Douglas C.] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Ctr Mol & Mitochondrial Med & Genet, Irvine, CA 92717 USA.
[Poole, Jason C.; Wallace, Douglas C.] Univ Calif Irvine, Ctr Mol & Mitochondrial Med & Genet, Dept Biol Chem, Irvine, CA 92717 USA.
[Poole, Jason C.; Wallace, Douglas C.] Univ Calif Irvine, Ctr Mol & Mitochondrial Med & Genet, Dept Pediat, Irvine, CA 92717 USA.
[Jacobson, Lisa P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Palella, Frank J.] Univ Chicago, Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60637 USA.
[Bream, Jay H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
RP Hendrickson, SL (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA.
EM hendricksons@mail.nih.gov
FU NCRR NIH HHS [5-M01-RR-00722, M01 RR000425, M01 RR000722, M01
RR000722-23, M01 RR00425, S07 RR018241-01]; NIA NIH HHS [AG16573,
AG24373, AG25638, F32 AG025638, F32 AG025638-02, P50 AG016573, R01
AG024373, R01 AG024373-05]; NIAID NIH HHS [U01 AI035039, U01
AI035039-07, U01 AI035039-08, U01 AI035039-09, U01 AI035039-09S1, U01
AI035039-10, U01 AI035039-11, U01 AI035039-12, U01 AI035039-13, U01
AI035039-14, U01 AI035039-15, U01 AI035039-16, U01 AI035039-17, U01
AI035040, U01 AI035040-08, U01 AI035040-10, U01 AI035040-11, U01
AI035040-11S1, U01 AI035040-12, U01 AI035040-13, U01 AI035040-14, U01
AI035040-15, U01 AI035040-16, U01 AI035040-17, U01 AI035041, U01
AI035041-07, U01 AI035042, U01 AI035042-08, U01 AI035043, U01 AI037613,
U01 AI037613-08, U01 AI037984, U01-AI-35039, U01-AI-35040, U01-AI-35041,
U01-AI-35042, U01-AI-35043, U01-AI-37613, U01-AI-37984]; NIDDK NIH HHS
[DK73691, R01 DK073691, R01 DK073691-04]; NINDS NIH HHS [NS21328, R01
NS021328, R01 NS021328-16]
NR 59
TC 44
Z9 45
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN 1
PY 2009
VL 51
IS 2
BP 111
EP 116
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 451IJ
UT WOS:000266463600001
PM 19339895
ER
PT J
AU Buonaguro, L
Tornesello, ML
Gallo, RC
Marincola, FM
Lewis, GK
Buonaguro, FM
AF Buonaguro, L.
Tornesello, M. L.
Gallo, R. C.
Marincola, F. M.
Lewis, G. K.
Buonaguro, F. M.
TI Peripheral blood mononuclear cells activated by HIV-VLPs in correlation
with HIV-1 seropositivity status
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Buonaguro, L.; Tornesello, M. L.; Buonaguro, F. M.] Ist Nazl Tumori Fond G Pascale, Lab Viral Oncogenesis & Immunotherapies, Naples, Italy.
[Buonaguro, L.; Tornesello, M. L.; Buonaguro, F. M.] Ist Nazl Tumori Fond G Pascale, AIDS Reference Ceneter, Naples, Italy.
[Gallo, R. C.; Lewis, G. K.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Marincola, F. M.] NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RI Tornesello, Maria Lina/A-1564-2009
OI Tornesello, Maria Lina/0000-0002-3523-3264
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 210
BP 137
EP 137
DI 10.1097/01.qai.0000351166.03102.bb
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700113
ER
PT J
AU Felber, BK
Valentin, A
von Gegerfelt, A
Rosati, M
Pate, V
Miteloudis, G
Alicea, C
Bergamaschi, C
Jalah, R
Kha, A
Draghia-Akli, R
Pavlakis, GN
AF Felber, Barbara K.
Valentin, A.
von Gegerfelt, A.
Rosati, M.
Pate, V.
Miteloudis, G.
Alicea, C.
Bergamaschi, C.
Jalah, R.
Kha, A.
Draghia-Akli, R.
Pavlakis, G. N.
TI Persistent virological benefit in SIV-infected macaques upon therapeutic
vaccination with DNA vectors by in vivo constant-current electroporation
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 11th Annual International Meeting of the Institute-of-Human-Virology
CY SEP 11-13, 2008
CL Univ Maryland Sch Med, Inst Human Virol, Bethesda, MD
SP Inst Human Virol
HO Univ Maryland Sch Med, Inst Human Virol
C1 [Felber, Barbara K.; Alicea, C.; Jalah, R.] NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA.
[Valentin, A.; von Gegerfelt, A.; Rosati, M.; Pate, V.; Miteloudis, G.; Bergamaschi, C.; Pavlakis, G. N.] NCI, Human Retrovirus Sect, Frederick, MD 21702 USA.
[Kha, A.; Draghia-Akli, R.] VGX Pharmaceut Inc, The Woodlands, TX 77381 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2009
VL 51
SU 2
MA 224
BP 151
EP 151
DI 10.1097/01.qai.0000351180.61412.0b
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 645RY
UT WOS:000281483700127
ER
PT J
AU Watts, DH
Huang, S
Cohn, SE
Smith, L
Hitti, J
AF Watts, D. Heather
Huang, Sharon
Cohn, Susan E.
Smith, Laura
Hitti, Jane
TI Repeat Pregnancies Among HIV-Infected Women Enrolled in Clinical Trial
PACTG1022
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Letter
ID CONTRACEPTION; RATES; COHORT
C1 [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
[Huang, Sharon] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA.
[Cohn, Susan E.] Univ Rochester, Sch Med, Dept Med, Rochester, NY USA.
[Smith, Laura] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Hitti, Jane] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
RP Watts, DH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
FU Intramural NIH HHS [Z99 HD999999]; NIAID NIH HHS [U01 AI041110-06, U01
AI041110-07, U01 AI068616-04, U01 AI068616-02, U01 AI068616-04S4, U01
AI068632, U01 AI068616-04S1, U01 AI068616, U01 AI068616-01, U01
AI068616-04S3, U01 AI068616-04S2, U01 AI041110-08, U01 AI068616-03, U01
AI041110, U01 AI041110-09]; NICHD NIH HHS [N01 HD033345,
HHSN267200800001C]; NIDDK NIH HHS [HHSN267200800001G]
NR 12
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN 1
PY 2009
VL 51
IS 2
BP 231
EP 233
PG 3
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 451IJ
UT WOS:000266463600018
PM 19465826
ER
PT J
AU Hardin, MG
Ernst, M
AF Hardin, Michael G.
Ernst, Monique
TI Functional Brain Imaging of Development-Related Risk and Vulnerability
for Substance Use in Adolescents
SO JOURNAL OF ADDICTION MEDICINE
LA English
DT Review
DE ontogeny; limbic system; drug experimentation; reward; inhibitory
control; working memory; development trajectories; brain maturation
ID SPATIAL WORKING-MEMORY; ALCOHOL-USE DISORDERS; EVENT-RELATED FMRI;
RESPONSE-INHIBITION; ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX;
DECISION-MAKING; COGNITIVE-DEVELOPMENT; ANTERIOR CINGULATE;
NUCLEUS-ACCUMBENS
AB The adolescent period is characterized by Substantial behavioral changes, including increases in novelty seeking and risk taking, which may facilitate substance use and experimentation. These behavioral changes co-occur with widespread structural and functional neural developments. Ontogenic changes affecting the neural circuitry subserving inhibitory control and reward-related processes are particularly relevant to adolescent risk-taking behavior. Impairment or immaturity of these processes is shown to contribute to enhanced risk for substance abuse. Additionally, the direct neural action of drugs of abuse in adolescents may have more severe consequences than in adults because of the additional potential effects on development. Functional neuroimaging research is beginning to examine the neural correlates of reward and inhibitory processes in adolescents. However, the Study of the consequences of exposure to drugs of abuse oil brain function in adolescents is lagging. This review summarizes the functional neuroimaging literature that can inform conceptualizations of risk and consequences of substance use in adolescence.
C1 [Hardin, Michael G.; Ernst, Monique] NIMH, Sec Dev & Affect Neurosci, NIH, Bethesda, MD 20892 USA.
[Hardin, Michael G.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
RP Ernst, M (reprint author), 15K N Dr, Bethesda, MD 20892 USA.
EM crnstm@mail.nih.gov
FU National Institute of Mental Heath
FX Supported by the Intramural Research program at the National Institute
of Mental Heath.
NR 99
TC 20
Z9 20
U1 3
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1932-0620
J9 J ADDICT MED
JI J. Addict. Med.
PD JUN
PY 2009
VL 3
IS 2
BP 47
EP 54
PG 8
WC Substance Abuse
SC Substance Abuse
GA 452BT
UT WOS:000266515300001
PM 20161036
ER
PT J
AU Speer, AM
Benson, BE
Kimbrell, TK
Wassermann, EM
Willis, MW
Herscovitch, P
Post, RM
AF Speer, A. M.
Benson, B. E.
Kimbrell, T. K.
Wassermann, E. M.
Willis, M. W.
Herscovitch, P.
Post, R. M.
TI Opposite effects of high and low frequency rTMS on mood in depressed
patients: Relationship to baseline cerebral activity on PET
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Repetitive transcranial magnetic stimulation; Depression; Positron
emission tomography; Regional cerebral blood flow; Hypoperfusion;
Hyperperfusion
ID TRANSCRANIAL MAGNETIC STIMULATION; CONTROLLED-TRIAL; GLUCOSE-METABOLISM;
MAJOR DEPRESSION; DOUBLE-BLIND; RESISTANT DEPRESSION; EFFICACY; TMS;
DISORDER; SAFETY
AB Background: Optimal parameters of rTMS for antidepressant efficacy in general, or within patients, have not been adequately delineated.
Methods: Using a double-blind, sham-controlled, cross-over design, 22 adult patients with treatment refractory major depression (n=9; bipolar disorder, depressed phase) were randomized to active rTMS (20-14z or 1-Hz) or sham rTMS conditions and given 5 rTMS treatments per week for two weeks. Repetitive TMS was administered at 100% of motor threshold for 1600 pulses over the left prefrontal cortex using a figure-eight coil. Patients initially randomized to sham rTMS were then exposed to two weeks of active rTMS with each frequency under blinded conditions. Those who received active 20-Hz and 1-Hz rTMS were crossed over to the opposite frequency for two weeks. Improvement in Hamilton Depression ratings were assessed after each two-week treatment phase. PET imaging was used to evaluate the patient's baseline absolute regional cerebral activity (blood flow and metabolism) as potential predictor of clinical response.
Results: Changes in depression severity on 1-Hz and 20-Hz rTMS were inversely correlated. PET scans with baseline hypoperfusion (but not hypometabolism) were associated with better improvement on 20-Hz rTMS as predicted.
Limitations: The magnitude of the clinical change with either frequency at 100% motor threshold was not robust, and larger studies with higher intensities of rTMS for longer durations of time should be explored.
Conclusions: High and low frequency rTMS exerts differential effects on depressed mood within individual subjects. The brain activity predictors and correlates of an optimal antidepressant response to rTMS remain to be better defined. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Speer, A. M.; Benson, B. E.; Post, R. M.] NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Kimbrell, T. K.] VA Med Ctr, N Little Rock, AR USA.
[Wassermann, E. M.] NINDS, NIH, Bethesda, MD 20892 USA.
[Willis, M. W.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA.
[Herscovitch, P.] NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA.
RP Post, RM (reprint author), George Washington Sch Med & Bipolar Collaborat, 5415 W Cedar Lane,Suite 201B, Bethesda, MD 20814 USA.
EM robert.post@speakeasy.net
FU Intramural NIH HHS [Z99 MH999999]
NR 33
TC 57
Z9 63
U1 1
U2 4
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 JUN
PY 2009
VL 115
IS 3
BP 386
EP 394
DI 10.1016/j.jad.2008.10.006
PG 9
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 449RL
UT WOS:000266347600013
PM 19027962
ER
PT J
AU Vinh, DC
Freeman, AF
Shea, YR
Malech, HL
Abinun, M
Weinberg, GA
Holland, SM
AF Vinh, Donald C.
Freeman, Alexandra F.
Shea, Yvonne R.
Malech, Harry L.
Abinun, Mario
Weinberg, Geoffrey A.
Holland, Steven M.
TI Mucormycosis in chronic granulomatous disease: Association with
iatrogenic immunosuppression
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID KETOACIDOSIS; ZYGOMYCOSIS
C1 [Vinh, Donald C.; Malech, Harry L.; Holland, Steven M.] NIAID, Dept Lab Med, NIH, Bethesda, MD 20892 USA.
[Shea, Yvonne R.] NIH, Microbiol Serv, Dept Lab Med, Bethesda, MD 20892 USA.
[Freeman, Alexandra F.] NCI, Lab Clin Infect Dis, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Abinun, Mario] Newcastle Upon Tyne Hosp NHS Fdn Trust, Dept Paediat Immunol, Newcastle Upon Tyne, Tyne & Wear, England.
[Weinberg, Geoffrey A.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
RP Vinh, DC (reprint author), NIAID, Dept Lab Med, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM smh@nih.gov
OI Malech, Harry/0000-0001-5874-5775; VINH, DONALD/0000-0003-1347-7767
FU Intramural NIH HHS [Z01 AI000646-16]; NCI NIH HHS [N01-CO-12400,
N01CO12400]
NR 9
TC 11
Z9 12
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JUN
PY 2009
VL 123
IS 6
BP 1411
EP 1413
DI 10.1016/j.jaci.2009.02.020
PG 3
WC Allergy; Immunology
SC Allergy; Immunology
GA 455WO
UT WOS:000266799100038
PM 19368967
ER
PT J
AU de Castro, A
Concheiro, M
Shakleya, DM
Huestis, MA
AF de Castro, Ana
Concheiro, Marta
Shakleya, Diaa M.
Huestis, Marilyn A.
TI Simultaneous Quantification of Methadone, Cocaine, Opiates, and
Metabolites in Human Placenta by Liquid Chromatography-Mass Spectrometry
SO JOURNAL OF ANALYTICAL TOXICOLOGY
LA English
DT Article; Proceedings Paper
CT SOFT Annual Meeting 2008
CY OCT 25-31, 2008
CL Phoenix, AZ
ID UMBILICAL-CORD TISSUE; AMNIOTIC-FLUID; ILLICIT DRUGS; ORAL FLUID;
NEONATAL WITHDRAWAL; TREATMENT PROGRAM; DEPENDENT WOMEN; FETAL EXPOSURE;
MS/MS ANALYSIS; MECONIUM
C1 [Huestis, Marilyn A.] Natl Inst Drug Abuse, Biomed Res Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[de Castro, Ana] Univ Santiago de Compostela, Forens Toxicol Serv, Inst Legal Med, Santiago De Compostela 15782, Spain.
RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Biomed Res Ctr, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
RI DE CASTRO, ANA/M-5159-2015
OI DE CASTRO, ANA/0000-0002-9832-012X
FU Intramural NIH HHS [ZIA DA000433-11]
NR 55
TC 21
Z9 21
U1 1
U2 3
PU PRESTON PUBL INC
PI NILES
PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA
SN 0146-4760
J9 J ANAL TOXICOL
JI J. Anal. Toxicol.
PD JUN
PY 2009
VL 33
IS 5
BP 243
EP 252
PG 10
WC Chemistry, Analytical; Toxicology
SC Chemistry; Toxicology
GA 452XF
UT WOS:000266573800002
PM 19671243
ER
PT J
AU Waybright, TJ
Terlizzi, DE
Ferrier, MD
AF Waybright, Timothy J.
Terlizzi, Daniel E.
Ferrier, M. Drew
TI Chemical characterization of the aqueous algistatic fraction of barley
straw (Hordeum vulgare) inhibiting Microcystis aeruginosa
SO JOURNAL OF APPLIED PHYCOLOGY
LA English
DT Article
DE Algae; Algal growth inhibition; Barley straw; Chemical characterization;
Inhibitor; Microcystis aeruginosa; Polyphenols
ID ALGAL CONTROL; ANTIALGAL ACTIVITY; GROWTH; RESERVOIR; EXTRACTS; TANNINS;
WATER; BLOOMS; PLANTS; ASSAY
AB The algistatic properties of aqueous barley straw (Hordeum vulgare) extracts have been observed in laboratory studies and in situ. This reported algistatic property has been used by farmers and horticulturists to control algal blooms in various systems and has become standard practice in some areas. However, both inhibition and stimulation of algal growth in freshwater and marine species have been demonstrated. While the number of taxa known to be inhibited by barley straw has increased, comparatively little has been done to isolate and classify the compound(s) responsible for this algistatic effect. A microplate assay system using Microcystis aeruginosa was developed to isolate and identify the inhibitory components of barley straw extract. M. aeruginosa was selected for the bioassay because it is consistently inhibited by barley straw extract in studies conducted by our laboratory and others. The 24-well plate assay utilizes in vivo fluorescence monitoring with a TECAN GENios plate reader to determine chlorophyll-a levels in each culture. Fractionation and partial chemical characterization of inhibitory extracts suggests that the inhibitors are polyphenolics with molecular weights (MW) between 1,000 and 3,000 Da. Percolation of the aqueous extract through a Polyamide CC6 resin or through various MW cutoff filters resulted in the loss of algistatic activity, which confirms this assertion, while hydrolysis resulted in little change in the activity profile. Fractionation by HPLC methods yielded a highly potent multi-compound fraction, showing toxicity at 353 mg L(-1) and algistatic activity between 11.1 and 3.53 mg L(-1).
C1 [Waybright, Timothy J.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA.
[Waybright, Timothy J.; Ferrier, M. Drew] Hood Coll, Frederick, MD 21701 USA.
[Terlizzi, Daniel E.] Univ Maryland, Sea Grant Extens Program, Ctr Marine Biotechnol, Baltimore, MD 21202 USA.
RP Waybright, TJ (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA.
EM waybrighttj@mail.nih.gov
NR 33
TC 28
Z9 29
U1 3
U2 40
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0921-8971
J9 J APPL PHYCOL
JI J. Appl. Phycol.
PD JUN
PY 2009
VL 21
IS 3
BP 333
EP 340
DI 10.1007/s10811-008-9373-x
PG 8
WC Biotechnology & Applied Microbiology; Marine & Freshwater Biology
SC Biotechnology & Applied Microbiology; Marine & Freshwater Biology
GA 437PE
UT WOS:000265498600010
ER
PT J
AU Timohhina, N
Guzun, R
Tepp, K
Monge, C
Varikmaa, M
Vija, H
Sikk, P
Kaambre, T
Sackett, D
Saks, V
AF Timohhina, Natalia
Guzun, Rita
Tepp, Kersti
Monge, Claire
Varikmaa, Minna
Vija, Heiki
Sikk, Peeter
Kaambre, Tuuli
Sackett, Dan
Saks, Valdur
TI Direct measurement of energy fluxes from mitochondria into cytoplasm in
permeabilized cardiac cells in situ: some evidence for mitochondrial
interactosome
SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
LA English
DT Article
DE Respiration; Cardiomyocytes; Mitochondria; Creatine kinase; Creatine;
Phosphocreatine; Tubulin
ID RAT-HEART MITOCHONDRIA; ADENINE-NUCLEOTIDE TRANSLOCASE; CREATINE-KINASE;
OXIDATIVE-PHOSPHORYLATION; OUTER-MEMBRANE; SKELETAL-MUSCLE; ADP
DIFFUSION; INTRACELLULAR DIFFUSION; RESPIRATORY-CHAIN; PHYSICAL-ACTIVITY
AB The aim of this study was to measure energy fluxes from mitochondria in isolated permeabilized cardiomyocytes. Respiration of permeabilized cardiomyocytes and mitochondrial membrane potential were measured in presence of MgATP, pyruvate kinase - phosphoenolpyruvate and creatine. ATP and phosphocreatine concentrations in medium surrounding cardiomyocytes were determined. While ATP concentration did not change in time, mitochondria effectively produced phosphocreatine (PCr) with PCr/O-2 ratio equal to 5.68 +/- 0.14. Addition of heterodimeric tubulin to isolated mitochondria was found to increase apparent Km for exogenous ADP from 11 +/- 2 A mu M to 330 A +/- 47 A mu M, but creatine again decreased it to 23 A +/- 6 A mu M. These results show directly that under physiological conditions the major energy carrier from mitochondria into cytoplasm is PCr, produced by mitochondrial creatine kinase (MtCK), which functional coupling to adenine nucleotide translocase is enhanced by selective limitation of permeability of mitochondrial outer membrane within supercomplex ATP Synthasome-MtCK-VDAC-tubulin, Mitochondrial Interactosome.
C1 [Guzun, Rita; Monge, Claire; Saks, Valdur] Univ Grenoble 1, INSERM, Lab Fundamental & Appl Bioenerget, U884, F-38041 Grenoble 9, France.
[Timohhina, Natalia; Tepp, Kersti; Varikmaa, Minna; Vija, Heiki; Sikk, Peeter; Kaambre, Tuuli; Saks, Valdur] NICPB, Lab Bioenerget, Tallinn, Estonia.
[Sackett, Dan] NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA.
RP Saks, V (reprint author), Univ Grenoble 1, INSERM, Lab Fundamental & Appl Bioenerget, U884, 2280 Rue Piscine,BP53X, F-38041 Grenoble 9, France.
EM Valdur.Saks@ujf-grenoble.fr
RI Sikk, Peeter/A-9538-2008; Kaambre, Tuuli/A-9536-2008; SAKS,
Valdur/A-8466-2008; Monge, Claire/E-2933-2012; Timohhina,
Natalja/A-8530-2011; Tepp, Kersti/A-4829-2012
OI Kaambre, Tuuli/0000-0001-5755-4694; Tepp, Kersti/0000-0001-7367-6632
FU Agence Nationale de la Recherche, France [ANR-07-BLAN-0086-01]; Estonian
Science Foundation [7117, 7823]
FX This work was supported by grant from Agence Nationale de la Recherche,
France, project ANR-07-BLAN-0086-01 and by grants N 7117 and 7823 from
Estonian Science Foundation. The authors thank Dr. Tatiana Rostovtseva,
Laboratory of Physical and Structural Biology, NICHD, NIH, Bethesda, MD,
USA for active and stimulating discussions.
NR 98
TC 38
Z9 38
U1 0
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0145-479X
EI 1573-6881
J9 J BIOENERG BIOMEMBR
JI J. Bioenerg. Biomembr.
PD JUN
PY 2009
VL 41
IS 3
BP 259
EP 275
DI 10.1007/s10863-009-9224-8
PG 17
WC Biophysics; Cell Biology
SC Biophysics; Cell Biology
GA 483PQ
UT WOS:000268980200006
PM 19597977
ER
PT J
AU Zhu, XX
Fan, JW
Baorto, DM
Weng, CH
Cimino, JJ
AF Zhu, Xinxin
Fan, Jung-Wei
Baorto, David M.
Weng, Chunhua
Cimino, James J.
TI A review of auditing methods applied to the content of controlled
biomedical terminologies
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Review
DE Terminology; Auditing method; Quality factor; Knowledge source; Manual;
Automated; Systematic; Heuristic
ID MEDICAL LANGUAGE SYSTEM; UMLS SEMANTIC NETWORK; OBJECT-ORIENTED
DATABASE; QUALITY-ASSURANCE; KNOWLEDGE; HEALTH; REPRESENTATION;
VOCABULARIES; DEFINITIONS; ONTOLOGIES
AB Although controlled biomedical terminologies have been with us for centuries, it is only in the last couple of decades that close attention has been paid to the quality of these terminologies. The result of this attention has been the development of auditing methods that apply formal methods to assessing whether terminologies are complete and accurate. We have performed an extensive literature review to identify published descriptions of these methods and have created a framework for characterizing them. The framework considers manual, systematic and heuristic methods that use knowledge (within or external to the terminology) to measure quality factors of different aspects of the terminology content (terms, semantic classification, and semantic relationships). The quality factors examined included concept orientation, consistency, non-redundancy, soundness and comprehensive coverage. We reviewed 130 studies that were retrieved based on keyword search on publications in PubMed, and present our assessment of how they fit into our framework. We also identify which terminologies have been audited with the methods and provide examples to illustrate each part of the framework. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Zhu, Xinxin; Fan, Jung-Wei; Weng, Chunhua; Cimino, James J.] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA.
[Baorto, David M.] New York Presbyterian Hosp, New York, NY USA.
[Cimino, James J.] NIH, Ctr Clin, Lab Informat Dev, Bethesda, MD 20892 USA.
RP Zhu, XX (reprint author), Columbia Univ, Dept Biomed Informat, 622 W 168th St,VC-5, New York, NY 10032 USA.
EM Katie.Zhu@dbmi.columbia.edu
OI Weng, Chunhua/0000-0002-9624-0214; Cimino, James/0000-0003-4101-1622
FU National Institutes of Health (NIH) Clinical Center; National Library of
Medicine (NLM)
FX Dr. Cimino was supported in part by funds from the intramural research
program at the National Institutes of Health (NIH) Clinical Center and
the National Library of Medicine (NLM).
NR 130
TC 26
Z9 27
U1 2
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD JUN
PY 2009
VL 42
IS 3
BP 413
EP 425
DI 10.1016/j.jbi.2009.03.003
PG 13
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 454KZ
UT WOS:000266682100002
PM 19285571
ER
PT J
AU Vizenor, LT
Bodenreider, O
McCray, AT
AF Vizenor, Lowell T.
Bodenreider, Olivier
McCray, Alexa T.
TI Auditing associative relations across two knowledge sources
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Biomedical terminologies; Associative relationships; Auditing methods;
Unified Medical Language System (UMLS)
ID MEDICAL LANGUAGE SYSTEM; UMLS SEMANTIC NETWORK; DESCRIPTION LOGIC;
ONTOLOGY; TERMINOLOGY; DESIGN; MODEL
AB Objectives: This paper proposes a novel semantic method for auditing associative relations in biomedical terminologies. We tested our methodology on two Unified Medical Language System (UMLS) knowledge sources.
Methods: We use the UMLS semantic groups as high-level representations of the domain and range of relationships in the Metathesaurus and in the Semantic Network. A mapping created between Metathesaurus relationships and Semantic Network relationships forms the basis for comparing the signatures of a given Metathesaurus relationship to the signatures of the semantic relationship to which it is mapped. The consistency of Metathesaurus relations is studied for each relationship.
Results: Of the 177 associative relationships in the Metathesaurus, 84 (48%) exhibit a high-degree of consistency with the corresponding Semantic Network relationships. Overall, 63% of the 1.8 M associative relations in the Metathesaurus are consistent with relations in the Semantic Network.
Conclusion: The semantics of associative relationships in biomedical terminologies should be defined explicitly by their developers. The Semantic Network would benefit from being extended with new relationships and with new relations for some existing relationships. The UMLS editing environment could take advantage of the correspondence established between relationships in the Metathesaurus and the Semantic Network. Finally, the auditing method also yielded useful information for refining the mapping of associative relationships between the two sources. Published by Elsevier Inc.
C1 [Bodenreider, Olivier] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA.
[Vizenor, Lowell T.] Comp Task Grp Inc, Buffalo, NY USA.
[Bodenreider, Olivier] Harvard Univ, Sch Med, Boston, MA USA.
RP Bodenreider, O (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike MS 3841 Bldg 38A,Rm B1N28U, Bethesda, MD 20894 USA.
EM olivier@nlm.nih.gov
FU National Institutes of Health (NIH); National Library of Medicine (NLM)
FX The authors thank the anonymous reviewers for their thoughtful and
extensive comments. This research was supported in part by the
Intramural Research Program of the National Institutes of Health (NIH),
National Library of Medicine (NLM).
NR 47
TC 6
Z9 6
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
EI 1532-0480
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD JUN
PY 2009
VL 42
IS 3
SI SI
BP 426
EP 439
DI 10.1016/j.jbi.2009.01.004
PG 14
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 454KZ
UT WOS:000266682100003
PM 19475724
ER
PT J
AU Mougin, F
Bodenreider, O
Burgun, A
AF Mougin, Fleur
Bodenreider, Olivier
Burgun, Anita
TI Analyzing polysemous concepts from a clinical perspective: Application
to auditing concept categorization in the UMLS
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Biomedical terminologies; Auditing methods; Unified Medical Language
System (UMLS); Polysemy; Semantic categorization
ID MEDICAL LANGUAGE SYSTEM; SEMANTIC NETWORK; DATABASE
AB Objectives: Polysemy is a frequent issue in biomedical terminologies. In the Unified Medical Language System (UMLS), polysemous terms are either represented as several independent concepts, or clustered into a single, multiply-categorized concept. The objective of this study is to analyze polysemous concepts in the UMLS through their categorization and hierarchical relations for auditing purposes.
Methods: We used the association of a concept with multiple Semantic Groups (SGs) as a surrogate for polysemy. We first extracted multi-SG (MSG) concepts from the UMLS Metathesaurus and characterized them in terms of the combinations of SGs with which they are associated. We then clustered MSG concepts in order to identify major types of polysemy. We also analyzed the inheritance of SGs in MSG concepts. Finally, we manually reviewed the categorization of the MSG concepts for auditing purposes.
Results: The 1208 MSG concepts in the Metathesaurus are associated with 30 distinct pairs of SGs. We created 75 semantically homogeneous clusters of MSG concepts, and 276 MSG concepts could not be clustered for lack of hierarchical relations. The clusters were characterized by the most frequent pairs of semantic types of their constituent MSG concepts. MSG concepts exhibit limited semantic compatibility with their parent and child concepts. A large majority of MSG concepts (92%) are adequately categorized. Examples of miscategorized concepts are presented.
Conclusion: This work is a systematic analysis and manual review of all concepts categorized by multiple SGs in the UMLS. The correctly-categorized MSG concepts do reflect polysemy in the UMLS Metathesaurus. The analysis of inheritance of SGs proved useful for auditing concept categorization in the UMLS. Published by Elsevier Inc.
C1 [Bodenreider, Olivier] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA.
[Mougin, Fleur] Univ Bordeaux 2, LESIM, INSERM, ISPED,U593, F-33076 Bordeaux, France.
[Burgun, Anita] Univ Rennes 1, EA 3888, IFR 140, Fac Med, F-35014 Rennes, France.
RP Bodenreider, O (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike,MS 3841 Bldg 38A,Rm B1N28U, Bethesda, MD 20894 USA.
EM olivier@nlm.nih.gov
FU National Institutes of Health (NIH); National Library of Medicine (NLM)
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (NIH), National Library of Medicine
(NLM).
NR 27
TC 4
Z9 4
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD JUN
PY 2009
VL 42
IS 3
BP 440
EP 451
DI 10.1016/j.jbi.2009.03.008
PG 12
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 454KZ
UT WOS:000266682100004
PM 19303057
ER
PT J
AU Baorto, D
Li, L
Cimino, JJ
AF Baorto, David
Li, Li
Cimino, James J.
TI Practical experience with the maintenance and auditing of a large
medical ontology
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Terminology; Medical Entities Dictionary; Maintenance; Semantic network;
Auditing; Vocabulary; Ontology
ID ENTITIES DICTIONARY; TERMINOLOGIES; INFORMATION; KNOWLEDGE; SYSTEM
AB The Medical Entities Dictionary (MED) has served as a unified terminology at New York Presbyterian Hospital and Columbia University for more than 20 years. It was initially created to allow the clinical data from the disparate information systems (e.g., radiology, pharmacy, and multiple laboratories, etc.) to be uniquely codified for storage in a single data repository, and functions as a real time terminology server for clinical applications and decision support tools. Being conceived as a knowledge base, the MED incorporates relationships among local terms, between local terms and external standards, and additional knowledge about terms in a semantic network structure. Over the past two decades, we have sought to develop methods to maintain, audit and improve the content of the MED, such that it remains true to its original design goals. This has resulted in a complex, multi-faceted process, with both manual and automated components. In this paper, we describe this process, with examples of its effectiveness. We believe that our process provides lessons for others who seek to maintain complex, concept-oriented controlled terminologies. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Baorto, David; Li, Li] New York Presbyterian Hosp, New York, NY 10032 USA.
[Cimino, James J.] Dept Biomed Informat, New York, NY 10032 USA.
[Cimino, James J.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Baorto, D (reprint author), New York Presbyterian Hosp, 622 W 168th St,VC-5, New York, NY 10032 USA.
EM baorto@dbmi.columbia.edu
OI Cimino, James/0000-0003-4101-1622
FU NIH Clinical Center; National Library of Medicine
FX Dr. Cimino is supported by intramural research funds from the NIH
Clinical Center and the National Library of Medicine.
NR 20
TC 19
Z9 19
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD JUN
PY 2009
VL 42
IS 3
BP 494
EP 503
DI 10.1016/j.jbi.2009.03.005
PG 10
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 454KZ
UT WOS:000266682100008
PM 19285569
ER
PT J
AU de Coronado, S
Wright, LW
Fragoso, G
Haber, MW
Hahn-Dantona, EA
Hartel, FW
Quan, SL
Safran, T
Thomas, N
Whiteman, L
AF de Coronado, Sherri
Wright, Lawrence W.
Fragoso, Gilberto
Haber, Margaret W.
Hahn-Dantona, Elizabeth A.
Hartel, Francis W.
Quan, Sharon L.
Safran, Tracy
Thomas, Nicole
Whiteman, Lori
TI The NCI Thesaurus quality assurance life cycle
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Controlled terminology; Biomedical vocabulary; Ontology development;
Quality assurance; Biomedical informatics; Cancer information
ID DESIDERATA; CACORE
AB The National Cancer Institute Enterprise Vocabulary Services (NCI EVS) uses a wide range of quality assurance (QA) techniques to maintain and extend NCI Thesaurus (NCIt). NCIt is a reference terminology and biomedical ontology used in a growing number of NCI and other systems that extend from translational and basic research through clinical care to public information and administrative activities. Both automated and manual QA techniques are employed throughout the editing and publication cycle, which includes inserting and editing NCIt in NCI Metathesaurus. NCI EVS conducts its own additional periodic and ongoing content QA. External reviews, and extensive evaluation by and interaction with EVS partners and other users, have also played an important part in the QA process. There have always been tensions and compromises between meeting the needs of dependent systems and providing consistent and well-structured content; external QA and feedback have been important in identifying and addressing such issues. Currently, NCI EVS is exploring new approaches to broaden external participation in the terminology development and QA process. Published by Elsevier Inc.
C1 [de Coronado, Sherri; Wright, Lawrence W.; Fragoso, Gilberto; Haber, Margaret W.; Hartel, Francis W.] Ctr Bioinformat, NCI, Rockville, MD 20852 USA.
[Hahn-Dantona, Elizabeth A.; Quan, Sharon L.; Thomas, Nicole; Whiteman, Lori] Lockheed Martin Corp, Fairfax, VA 22301 USA.
[Safran, Tracy] NCI, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
RP de Coronado, S (reprint author), 113 Brookline St, Moraga, CA 94556 USA.
EM decorons@mail.nih.gov
NR 35
TC 17
Z9 17
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD JUN
PY 2009
VL 42
IS 3
BP 530
EP 539
DI 10.1016/j.jbi.2009.01.003
PG 10
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 454KZ
UT WOS:000266682100011
PM 19475726
ER
PT J
AU Bodenreider, O
Peters, LB
AF Bodenreider, Olivier
Peters, Lee B.
TI A graph-based approach to auditing RxNorm
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Biomedical terminologies; Auditing methods; RxNorm; Quality assurance;
Graphs
ID UMLS
AB Objectives: RxNorm is a standardized nomenclature for clinical drug entities developed by the National Library of Medicine. In this paper, we audit relations in RxNorm for consistency and completeness through the systematic analysis of the graph of its concepts and relationships.
Methods: The representation of multi-ingredient drugs is normalized in order to make it compatible with that of single-ingredient drugs. All meaningful paths between two nodes in the type graph are computed and instantiated. Alternate paths are automatically compared and manually inspected in case of inconsistency.
Results: The 115 meaningful paths identified in the type graph can be grouped into 28 groups with respect to start and end nodes. Of the 19 groups of alternate paths (i.e., with two or more paths) between the start and end nodes, 9 (47%) exhibit inconsistencies. Overall, 28 (24%) of the 115 paths are inconsistent with other alternate paths. A total of 348 inconsistencies were identified in the April 2008 version of RxNorm and reported to the RxNorm team, of which 215 (62%) had been corrected in the January 2009 version of RxNorm.
Conclusion: The inconsistencies identified involve missing nodes (93), missing links (17), extraneous links (237) and one case of mix-up between two ingredients. Our auditing method proved effective in identifying a limited number of errors that had defeated the quality assurance mechanisms currently in place in the RxNorm production system. Some recommendations for the development of RxNorm are provided. Published by Elsevier Inc.
C1 [Bodenreider, Olivier; Peters, Lee B.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA.
RP Bodenreider, O (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike,MS 3841 Bldg 38A,Rm B1N28U, Bethesda, MD 20894 USA.
EM olivier@nlm.nih.gov
FU National Institutes of Health (NIH); National Library of Medicine (NLM);
Stuart Nelson
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (NIH), National Library of Medicine
(NLM). The authors wish to thank the RxNorm development team at NLM. In
particular, we wish to thank Tammy Powell for providing useful feedback
on the inconsistencies identified in this study and Stuart Nelson for
his support.
NR 21
TC 3
Z9 3
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD JUN
PY 2009
VL 42
IS 3
BP 558
EP 570
DI 10.1016/j.jbi.2009.04.004
PG 13
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 454KZ
UT WOS:000266682100014
PM 19394440
ER
PT J
AU Cimino, JJ
Hayamizu, TF
Bodenreider, O
Davis, B
Stafford, GA
Ringwald, M
AF Cimino, James J.
Hayamizu, Terry F.
Bodenreider, Olivier
Davis, Brian
Stafford, Grace A.
Ringwald, Martin
TI The caBIG terminology review process
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Terminology; Ontology; Auditing; Evaluation
ID NCI THESAURUS; GENE ONTOLOGY; IMPLEMENTATION; LOINC
AB The National Cancer Institute (NCI) is developing an integrated biomedical informatics infrastructure, the cancer Biomedical Informatics Grid (caBIG (R)), to support collaboration within the cancer research community. A key part of the caBIG architecture is the establishment of terminology standards for representing data. In order to evaluate the suitability of existing controlled terminologies, the caBIG Vocabulary and Data Elements Workspace (VCDE WS) working group has developed a set of criteria that serve to assess a terminology's Structure, content, documentation, and editorial process. This paper describes the evolution of these criteria and the results of their use in evaluating four standard terminologies: the Gene Ontology (GO), the NCI Thesaurus (NCIt), the Common Terminology for Adverse Events (known as CTCAE), and the laboratory portion of the Logical Objects, Identifiers, Names and Codes (LOINC). The resulting caBIG criteria are presented as a matrix that may be applicable to any terminology standardization effort. Published by Elsevier Inc.
C1 [Cimino, James J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA.
[Bodenreider, Olivier] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA.
[Hayamizu, Terry F.; Stafford, Grace A.; Ringwald, Martin] Jackson Lab, Bar Harbor, ME 04609 USA.
[Davis, Brian] 3rd Millenium Inc, Waltham, MA USA.
RP Cimino, JJ (reprint author), NIH, Lab Informat Dev, Ctr Clin, Room 6-2551,10 Ctr Dr, Bethesda, MD 20892 USA.
EM ciminoj@mail.nih.gov
OI Cimino, James/0000-0003-4101-1622
FU National Cancer Institute; National Institutes of Health [GS-35F-0306J];
NIH Clinical Center; National Library of Medicine (NLM)
FX Drs. Bodenreider, Cimino, Davis, Hayamizu, Ringwald, and Stafford were
supported in whole or in part by federal funds from the National Cancer
Institute, National Institutes of Health, under Contract No.
GS-35F-0306J. Drs. Bodenreider and Cimino were supported in part by
funds from the intramural research program at the NIH Clinical Center
and the National Library of Medicine (NLM).
NR 30
TC 17
Z9 18
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD JUN
PY 2009
VL 42
IS 3
BP 571
EP 580
DI 10.1016/j.jbi.2008.12.003
PG 10
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 454KZ
UT WOS:000266682100015
PM 19154797
ER
PT J
AU MacArthur, R
Leister, W
Veith, H
Shinn, P
Southall, N
Austin, CP
Inglese, J
Auld, DS
AF MacArthur, Ryan
Leister, William
Veith, Henrike
Shinn, Paul
Southall, Noel
Austin, Christopher P.
Inglese, James
Auld, Douglas S.
TI Monitoring Compound Integrity With Cytochrome P450 Assays and qHTS
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE HTS; compound storage; DMSO; quantitative HTS
ID STORAGE-CONDITIONS; STABILITY; DMSO; LIBRARY; WATER; SYSTEM;
DIMETHYLSULPHOXIDE; METABOLISM; EVOLUTION
AB The authors describe how room temperature storage of a 1120-member compound library prepared in either DMSO or in a hydrated-DMSO/water (67/33) mixture affects the reproducibility of potency values as monitored using cytochrome P450 1A2 and 2D6 isozyme assays. The bioluminescent assays showed Z' factors of 0.71 and 0.62, with 17% and 32% of the library found as active against the CYP 1A2 and 2D6 isozymes, respectively. The authors tested the library using quantitative high-throughput screening to generate potency values for every library member, which was measured at 7 time intervals spanning 37 weeks. They calculated the minimum significant ratio (MSR) from these potency values at each time interval and found that for the library stored in DMSO, the CYP 1A2 and 2D6 assay MSRs progressed from approximately 2.0 to 5.0. The hydrated conditions showed similar performance in both MSR progression and analytical quality control results. Based on this study, the authors recommend that DMSO samples be stored in 1536-well plates for <4 months at room temperature. Furthermore, the study illustrates the degree and time scale of apparent compound potency changes due to sample storage. (Journal of Biomolecular Screening 2009: 538-546)
C1 [MacArthur, Ryan; Leister, William; Veith, Henrike; Shinn, Paul; Southall, Noel; Austin, Christopher P.; Inglese, James; Auld, Douglas S.] NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Auld, DS (reprint author), NIH, NIH Chem Genom Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM dauld@mail.nih.gov
RI Southall, Noel/H-8991-2012
OI Southall, Noel/0000-0003-4500-880X
FU National Institutes of Health; National Human Genome Research Institute
FX We thank Lino Ofiaza for archiving and retrieval of temperature and
humidity records from the automated screening facility. This research
was supported by the Molecular Libraries Initiative of the NIH Roadmap
for Medical Research and the Intramural Research Program of the National
Human Genome Research Institute, National Institutes of Health.
NR 37
TC 12
Z9 13
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD JUN
PY 2009
VL 14
IS 5
BP 538
EP 546
DI 10.1177/1087057109336954
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 457GA
UT WOS:000266915300014
PM 19483146
ER
PT J
AU Wang, F
Stewart-Maynard, KM
Cruceanu, M
Qualley, DF
Mitra, M
Gorelick, RJ
Rouzina, I
Musier-Forsyth, K
Williams, MC
AF Wang, Fei
Stewart-Maynard, Kristen M.
Cruceanu, Margareta
Qualley, Dominic F.
Mitra, Mithun
Gorelick, Robert J.
Rouzina, Ioulia
Musier-Forsyth, Karin
Williams, Mark C.
TI Nucleic Acid Interaction Kinetics Modulate the Chaperone Activity of
Retroviral Nucleocapsid Proteins
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Wang, Fei; Cruceanu, Margareta; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
[Stewart-Maynard, Kristen M.] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA.
[Stewart-Maynard, Kristen M.] Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA.
[Qualley, Dominic F.; Mitra, Mithun; Musier-Forsyth, Karin] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA.
[Qualley, Dominic F.; Mitra, Mithun; Musier-Forsyth, Karin] Ohio State Univ, Dept Biochem, Columbus, OH 43210 USA.
[Gorelick, Robert J.] NCI Frederick, SAIC Frederick Inc, Basic Res Program, AIDS Vaccine Program, Frederick, MD 21702 USA.
[Rouzina, Ioulia] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
EM mark@neu.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2009
VL 26
IS 6
MA 28
BP 805
EP 805
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 448ZO
UT WOS:000266300700040
ER
PT J
AU Kim, T
Marquez, VE
Shapiro, BA
AF Kim, Taejin
Marquez, Victor E.
Shapiro, Bruce A.
TI Carbocyclic Sugars Constrained to North and South Conformations
Stabilize and Control RNA Conformations
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Kim, Taejin; Shapiro, Bruce A.] NCI, CCRNP, Frederick, MD 21702 USA.
[Marquez, Victor E.] NCI, Med Chem Lab, Frederick, MD 21702 USA.
EM bshapiro@ncifcrf.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2009
VL 26
IS 6
MA 54
BP 819
EP 819
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 448ZO
UT WOS:000266300700066
ER
PT J
AU Shapiro, BA
AF Shapiro, Bruce A.
TI Computational Design Strategies for RNA Nanostructures
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Shapiro, Bruce A.] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
EM bshapiro@ncifcrf.gov
NR 7
TC 4
Z9 5
U1 0
U2 1
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2009
VL 26
IS 6
MA 56
BP 820
EP 820
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 448ZO
UT WOS:000266300700068
ER
PT J
AU Kasprzak, W
Bindewald, E
Kim, TJ
Shapiro, BA
AF Kasprzak, Wojciech
Bindewald, Eckart
Kim, Tae-Jin
Shapiro, Bruce A.
TI Exploration of Structural Building Block Properties for RNA
Nanostructures
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Kasprzak, Wojciech; Bindewald, Eckart] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Kim, Tae-Jin; Shapiro, Bruce A.] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
EM bshapiro@ncifcrf.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2009
VL 26
IS 6
MA 58
BP 821
EP 822
PG 2
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 448ZO
UT WOS:000266300700070
ER
PT J
AU Aravind, L
AF Aravind, L.
TI The "Protein-scape" of Eukaryotic Chromatin
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Aravind, L.] Natl Inst Heath, Computat Biol Branch, Natl Lib Med, NCBI, Bethesda, MD 20894 USA.
EM aravind@ncbi.nlm.nih.gov
NR 0
TC 7
Z9 7
U1 0
U2 0
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2009
VL 26
IS 6
MA 88
BP 843
EP 843
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 448ZO
UT WOS:000266300700099
ER
PT J
AU Clore, GM
AF Clore, G. Marius
TI Visualizing Lowly-populated Regions of the Free Energy Landscape of
Macromolecular Complexes by Paramagnetic Relaxation Enhancement
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
ID BINDING; NMR
C1 [Clore, G. Marius] NIDDK, Chem Phys Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
NR 4
TC 1
Z9 1
U1 0
U2 0
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2009
VL 26
IS 6
MA 98
BP 848
EP 848
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 448ZO
UT WOS:000266300700109
ER
PT J
AU del Sol, A
Arauzo-Bravo, MJ
Nussinov, R
AF del Sol, Antonio
Arauzo-Bravo, Marcos J.
Nussinov, Ruth
TI Network Robustness and Modularity of Protein Structures in the
Identification of Key Residues for Allosteric Communications
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [del Sol, Antonio; Arauzo-Bravo, Marcos J.] Fujirebio Inc, Div Res & Dev, Bioinformat Res Unit, Hachioji, Tokyo 1920031, Japan.
[Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
EM antdelsol@gmail.com
RI Marcos, Arauzo-Bravo/A-1706-2011
OI Marcos, Arauzo-Bravo/0000-0002-3264-464X
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2009
VL 26
IS 6
MA 116
BP 861
EP 861
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 448ZO
UT WOS:000266300700127
ER
PT J
AU Baldwin, GS
Brooks, NJ
Robson, RE
Wynveen, A
Goldar, A
Leikin, S
Seddon, JM
Kornyshev, AA
AF Baldwin, Geoff S.
Brooks, Nicholas J.
Robson, Rebecca E.
Wynveen, Aaron
Goldar, Arach
Leikin, Sergey
Seddon, John M.
Kornyshev, Alexei A.
TI DNA Double Helices Recognize Mutual Sequence Homology in a Protein Free
Environment
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
ID RECOMBINATION; YEAST
C1 [Baldwin, Geoff S.] Univ London Imperial Coll Sci Technol & Med, Div Mol Biosci, London SW7 2AZ, England.
[Brooks, Nicholas J.; Robson, Rebecca E.; Wynveen, Aaron; Goldar, Arach; Seddon, John M.; Kornyshev, Alexei A.] Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AZ, England.
[Leikin, Sergey] NICHHD, Sect Phys Biochem, NIH, DHHS, Bethesda, MD 20892 USA.
EM g.baldwin@imperial.ac.uk
RI Brooks, Nicholas/H-3717-2011
NR 12
TC 0
Z9 0
U1 0
U2 2
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2009
VL 26
IS 6
MA 143
BP 880
EP 880
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 448ZO
UT WOS:000266300700154
ER
PT J
AU Tillius, TD
Parker, SCJ
Hansen, L
Abaan, HO
Margulies, EH
AF Tillius, Thomas D.
Parker, Stephen C. J.
Hansen, Loren
Abaan, Hatice Ozel
Margulies, Elliott H.
TI Evolutionary Constraint on DNA Structure in the Human Genome
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Tillius, Thomas D.] Boston Univ, Dept Chem, Boston, MA 02215 USA.
[Tillius, Thomas D.; Parker, Stephen C. J.; Hansen, Loren] Boston Univ, Program Bioinformat, Boston, MA 02215 USA.
[Hansen, Loren] Natl Ctr Biotechnol Info, Bethesda, MD USA.
[Abaan, Hatice Ozel; Margulies, Elliott H.] NHGRI, NIH, Bethesda, MD 20892 USA.
EM tullius@bu.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2009
VL 26
IS 6
MA 146
BP 882
EP 883
PG 2
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 448ZO
UT WOS:000266300700157
ER
PT J
AU Sidorova, N
Muradymov, S
Rau, DC
AF Sidorova, Nina
Muradymov, Shakir
Rau, Donald C.
TI Specific versus Nonspecific DNA Binding of the Restriction Endonuclease
EcoRV Measured by Self-Cleavage Assay
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Sidorova, Nina; Muradymov, Shakir; Rau, Donald C.] NICHD, Lab Phys & Struct Biol, PPB, NIH, Bethesda, MD 20892 USA.
EM sidorova@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2009
VL 26
IS 6
MA 167
BP 896
EP 897
PG 2
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 448ZO
UT WOS:000266300700178
ER
EF