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 TC 58 Z9 62 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 Z9 138 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 TC 182 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 Z9 7 U1 0 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 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 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. 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 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 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 0145-6008 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 ER 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 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 22A EP 22A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100047 ER 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 TC 0 Z9 0 U1 1 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 41A EP 41A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100122 ER 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. 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 58A EP 58A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100193 ER 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 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 67A EP 67A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100228 ER 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 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 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 ER 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 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 68A EP 68A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100231 ER 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. 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 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. 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 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 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 76A EP 76A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100264 ER 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 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 [Talani, G.; Lovinger, D. M.] 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 82A EP 82A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100289 ER 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 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 [Jun, S.; Talani, G.; Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 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 ER 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 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 [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. 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 86A EP 86A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100303 ER PT J AU Camp, MC Ihne, JL Holmes, A AF Camp, Marguerite C. 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 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 [Camp, Marguerite C.; Ihne, Jessica L.; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 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 92A EP 92A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100329 ER PT J AU Falk, D Mattson, M Fertig, J Ryan, M Litten, R AF Falk, D. 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 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 CSR Inc, Arlington, VA 22201 USA. 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 114A EP 114A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100416 ER 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. 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 117A EP 117A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100428 ER 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. 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 120A EP 120A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100440 ER 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. 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 120A EP 120A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100441 ER 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. 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 124A EP 124A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100457 ER 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. 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 138A EP 138A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100513 ER 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. NR 0 TC 0 Z9 0 U1 1 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 138A EP 138A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100512 ER 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. 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 145A EP 145A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100541 ER 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. 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 160A EP 160A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100599 ER 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. NR 0 TC 0 Z9 0 U1 1 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 219A EP 219A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100836 ER 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. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2009 VL 33 IS 6 BP 227A EP 227A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100866 ER 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. 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 227A EP 227A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100867 ER 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. 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 244A EP 244A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100933 ER 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. 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 246A EP 246A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100940 ER PT J AU White, AM Hingson, RW AF White, A. M. 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. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2009 VL 33 IS 6 BP 255A EP 255A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100976 ER 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. 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 258A EP 258A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100990 ER 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. 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 260A EP 260A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335100996 ER PT J AU Grant, BF Saha, TD Stinson, FS AF Grant, B. F. Saha, T. D. Stinson, F. S. 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. 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 268A EP 268A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335101023 ER PT J AU Murray, P AF Murray, Peggy 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. 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 281A EP 281A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335101076 ER 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. 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 288A EP 288A PG 1 WC Substance Abuse SC Substance Abuse GA 449MQ UT WOS:000266335101103 ER 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. 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:000266335101109 ER 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 TC 2 Z9 2 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 TC 27 Z9 27 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 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 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 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 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 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: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 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 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 TC 2 Z9 2 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 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 TC 15 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 TC 38 Z9 39 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). NR 31 TC 4 Z9 4 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. NR 40 TC 13 Z9 13 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 TC 8 Z9 9 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 TC 14 Z9 15 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 TC 104 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 TC 12 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 TC 6 Z9 6 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 TC 26 Z9 29 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 TC 36 Z9 39 U1 1 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 TC 42 Z9 42 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 TC 52 Z9 54 U1 1 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 TC 23 Z9 24 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 TC 22 Z9 22 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 TC 158 Z9 162 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD 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 TC 1 Z9 1 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 TC 43 Z9 44 U1 5 U2 9 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 TC 22 Z9 22 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 TC 19 Z9 19 U1 0 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 TC 80 Z9 84 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 TC 26 Z9 26 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 NR 140 TC 54 Z9 55 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 TC 65 Z9 68 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 TC 65 Z9 65 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 TC 23 Z9 27 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 TC 54 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 TC 89 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 TC 53 Z9 57 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 TC 15 Z9 15 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 Z9 0 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 Z9 0 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. NR 8 TC 1 Z9 1 U1 0 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 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. NR 33 TC 24 Z9 25 U1 0 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 TC 27 Z9 28 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 NR 46 TC 2 Z9 3 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 TC 26 Z9 30 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 TC 25 Z9 27 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 TC 28 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 TC 5 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