FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lowell, SY Poletto, CJ Graybeal, C Simonyan, K Ludlow, CL AF Lowell, Soren Y. Poletto, C. J. Graybeal, C. Simonyan, K. Ludlow, C. L. TI Cerebral activation patterns during swallowing and related tasks using functional magnetic resonance imaging SO DYSPHAGIA LA English DT Meeting Abstract C1 NIH, NINDS, Med Neurol Branch, Laryngeal & Speech Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD OCT PY 2007 VL 22 IS 4 BP 401 EP 401 PG 1 WC Otorhinolaryngology SC Otorhinolaryngology GA 219VN UT WOS:000250116400099 ER PT J AU Streubel, AH Klebanoff, MA AF Streubel, A. H. Klebanoff, M. A. TI Umbilical cord serum ferritin as a predictor of neurodevelopment at age five years SO EARLY HUMAN DEVELOPMENT LA English DT Meeting Abstract C1 [Streubel, A. H.; Klebanoff, M. A.] Natl Inst Hlth, NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. EM astreubel@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD OCT PY 2007 VL 83 SU 1 BP S154 EP S154 DI 10.1016/S0378-3782(07)70424-3 PG 1 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 232YS UT WOS:000251058200425 ER PT J AU Suomi, SJ AF Suomi, S. J. TI Gene-environment interactions and aggression in primates SO EARLY HUMAN DEVELOPMENT LA English DT Meeting Abstract C1 [Suomi, S. J.] Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. EM ss148k@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD OCT PY 2007 VL 83 SU 1 BP S33 EP S33 DI 10.1016/S0378-3782(07)70005-1 PG 1 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 232YS UT WOS:000251058200006 ER PT J AU Troisi, R Lagiou, P Trichopoulos, D Xu, B Chie, L Stanczyk, F Potischman, N Adami, HO Hoover, RN Hsieh, CC AF Troisi, R. Lagiou, P. Trichopoulos, D. Xu, B. Chie, L. Stanczyk, F. Potischman, N. Adami, H. -O. Hoover, R. N. Hsieh, C. -C. TI Cord estrogens, androgens, IGF-I and IGFBP-3 in chinese and US Caucasian neonates SO EARLY HUMAN DEVELOPMENT LA English DT Meeting Abstract C1 [Troisi, R.; Hoover, R. N.] Natl Inst Hlth, Natl Canc Inst, Dept Hlth & Human Serv, Div Canc Epedimiol & Genet, Bethesda, MD USA. [Troisi, R.] Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH USA. [Lagiou, P.] Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-10679 Athens, Greece. [Trichopoulos, D.; Adami, H. -O.; Hsieh, C. -C.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Xu, B.] Fudan Univ, Sch Publ Hlth, Dept Epidemiol, Shanghai, Peoples R China. [Chie, L.] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. [Stanczyk, F.] Univ Calif Los Angeles, Keck Sch Med, Reprod Endocrine Res Lab, Los Angeles, CA 90024 USA. [Potischman, N.] Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. [Adami, H. -O.; Hsieh, C. -C.] Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden. [Hsieh, C. -C.] Univ Massachusetts, Med Ctr, Dept Canc Biol, Worcester, MA USA. EM troisir@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD OCT PY 2007 VL 83 SU 1 BP S71 EP S71 DI 10.1016/S0378-3782(07)70134-2 PG 1 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 232YS UT WOS:000251058200135 ER PT J AU Dzikowski, R Li, F Amulic, B Eisberg, A Frank, M Patel, S Wellems, TE Deitsch, KW AF Dzikowski, Ron Li, Felomena Amulic, Borko Eisberg, Andrew Frank, Matthias Patel, Suchit Wellems, Thomas E. Deitsch, Kirk W. TI Mechanisms underlying mutually exclusive expression of virulence genes by malaria parasites SO EMBO REPORTS LA English DT Article DE malaria; antigenic variation; allelic exclusion; silencing; transcription ID PLASMODIUM-FALCIPARUM; ANTIGENIC VARIATION; TRYPANOSOMA-BRUCEI; ALLELIC EXCLUSION; TRANSCRIPTION; PROMOTERS; SURFACE; INTRON; RNA AB A fundamental yet poorly understood aspect of gene regulation in eukaryotic organisms is the mechanisms that control allelic exclusion and mutually exclusive gene expression. In the malaria parasite Plasmodium falciparum, this process regulates expression of the var gene family-a large, hypervariable repertoire of genes that are responsible for the ability of the parasite to evade the host immune system and for pathogenesis of the disease. A central problem in understanding this process concerns the mechanisms that limit expression to a single gene at a time. Here, we describe results that provide information on the mechanisms that control silencing and single gene expression and differentiate between several models that have recently been proposed. The results provide the first evidence, to our knowledge, supporting the existence of a postulated var-specific, subnuclear expression site and also reinforce the conclusion that var gene regulation is based on cooperative interactions between the two promoters of each var gene. C1 Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Int Med, New York, NY 10021 USA. Univ Tubingen, Dept Parasitol, D-72074 Tubingen, Germany. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Deitsch, KW (reprint author), Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, 1300 York Ave,Box 62, New York, NY 10021 USA. EM kwd2001@med.cornell.edu RI Patel, Suchit/E-5664-2012 FU NIAID NIH HHS [R01 AI052390]; NIGMS NIH HHS [T32 GM007739] NR 22 TC 80 Z9 80 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD OCT PY 2007 VL 8 IS 10 BP 959 EP 965 DI 10.1038/sj.embor.7401063 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 216NK UT WOS:000249884600017 PM 17762879 ER PT J AU Klein, E Laxminarayan, R Smith, DL Gilligan, CA AF Klein, Eili Laxminarayan, Ramanan Smith, David L. Gilligan, Christopher A. TI Economic incentives and mathematical models of disease SO ENVIRONMENT AND DEVELOPMENT ECONOMICS LA English DT Review ID STAPHYLOCOCCUS-AUREUS BACTEREMIA; HIV TRANSMISSION DYNAMICS; NONLINEAR INCIDENCE RATES; PUBLIC-HEALTH IMPACT; LENGTH-OF-STAY; ANTIBIOTIC-RESISTANCE; METHICILLIN-RESISTANT; EPIDEMIOLOGIC MODELS; INFECTIOUS-DISEASES; SAN-FRANCISCO AB The fields of epidemiological disease modeling and economics have tended to work independently of each other despite their common reliance on the language of mathematics and exploration of similar questions related to human behavior and infectious disease. This paper explores the benefits of incorporating simple economic principles of individual behavior and resource optimization into epidemiological models, reviews related research, and indicates how future cross-discipline collaborations can generate more accurate models of disease and its control to guide policy makers. C1 Resources Future Inc, Washington, DC 20036 USA. Fogarty Int Ctr, NIH, Bethesda, MD USA. Univ Cambridge, Dept Plant Sci, Modeling & Epidemiol Grp, Cambridge CB2 3EA, England. RP Laxminarayan, R (reprint author), Resources Future Inc, 1616 P St NW, Washington, DC 20036 USA. EM ramanan@rff.org RI Klein, Eili/C-3745-2012; Smith, David/L-8850-2013; OI Smith, David/0000-0003-4367-3849; Klein, Eili/0000-0002-1304-5289 NR 138 TC 38 Z9 41 U1 2 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-770X J9 ENVIRON DEV ECON JI Environ. Dev. Econ. PD OCT PY 2007 VL 12 BP 707 EP 732 DI 10.1017/S1355770X0700383X PN 5 PG 26 WC Environmental Studies SC Environmental Sciences & Ecology GA 227YP UT WOS:000250694200006 ER PT J AU Swartz, CD Parks, N Umbach, DM Ward, WO Schaaper, RM DeMarini, DM AF Swartz, Carol D. Parks, Nick Umbach, David M. Ward, William O. Schaaper, Roel M. DeMarini, David M. TI Enhanced mutagenesis of Salmonella tester strains due to deletion of genes other than uvrB SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE ames test; mutagenic potency; Delta uvrB; molybdenum cofactor; moeA; moaA ID ESCHERICHIA-COLI; BASE ANALOGS; TYPHIMURIUM; MUTAGENICITY; MUTANTS; REPAIR AB The standard Salmonella mutagenicify (Ames) tester strains are missing 15-119 genes due to the extended Delta(gal-bio-uvrB) mutations that render the strains excision-repair deficient (Delta uvrB). We constructed strains of Salmonella that are homologous to tester strains TA98 and TA100 except that in place of the uvrB deletion, they contain single-gene defects in either uvrB, moaA, moeA, or both uvrB and moeA. We then tested the following mutagens in these strains: 2-acetylaminofluorene, Glu-P-1, 4-aminobiphenyl, benzo[a]pyrene, MX, 1-nitropyrene, 6-hydroxylaminopurine (HAP), and 2-amino-6-hydroxylaminopurine (AHAP). We confirmed in Salmonella a previous finding in Escherichia coli. that the enhanced mutagenicity of the purine analogues HAP and AHAP is not due to the deletion of the uvrB gene but due to the deletion of moeA and/or moeA, which are involved in molybdenum cofactor biosynthesis. The spontaneous mutant frequency and induced mutagenic potency of mutagens due to the extended Delta uvrB mutation are due largely to the deletion of uvrB and to some extent of moeA/moaA at the frame-shift hisD3052 allele of TA98 but involve other genes in addition to uvrB and moeA/moaA at the base-substitution hisG46 allele of TA100. The extended Delta uvrB mutation does not prevent the detection of mutagens that would have been detected in a strain containing a single uvrB defect. Because of the deletion of moeA/moaA, the extended uvrB deletion generally enhanced spontaneous and induced mutagenicity, especially at the base-substitution allele. This enhanced sensitivity may underlay the severe health effects in humans who have mutations in molybdenum cofactor biosynthesis genes. Environ. Mal. Mutagen. 48:694-705, 2007. Published 2007 Wiley-Liss, Inc. C1 US EPA, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. Environm Careers Org, Boston, MA USA. Natl Inst Environm Hlth Sci, Biostat Branch, Natl Inst Hlth, DHHS, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Mol Genet Lab, Natl Inst Hlth, DHHS, Res Triangle Pk, NC USA. RP DeMarini, DM (reprint author), US EPA, Div Environm Carcinogenesis, B143-06, Res Triangle Pk, NC 27711 USA. EM demarini.david@epa.gov FU Intramural NIH HHS NR 21 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2007 VL 48 IS 8 BP 694 EP 705 DI 10.1002/em.20343 PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 222TZ UT WOS:000250321500009 PM 17896788 ER PT J AU Benbrahim-Tallaa, L Waterlandz, RA Dill, AL Webber, MM Waalkes, MP AF Benbrahim-Tallaa, Lamia Waterlandz, Robert A. Dill, Anna L. Webber, Mukta M. Waalkes, Michael P. TI Tumor suppressor gene inactivation during cadmium-induced malignant transformation of human prostate cells correlates with overexprression of de Novo DNA methyltransferase SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cadmium; carcinogenesis; DNA methylation; DNMT3b; p16; prostate; RASSF1A ID P16INK4A PROMOTER HYPERMETHYLATION; FEMALE LUNG-CANCER; EPITHELIAL-CELLS; METHYLATION STATUS; DNMT3B; EXPRESSION; 3B; OVEREXPRESSION; CARCINOGENESIS; NEOPLASIA AB BACKGROUND: Aberrant DNA methylation is common in carcinogenesis. The typical pattern appears to involve reduced expression of maintenance DNA methyltransferase, DNMT1, inducing genomic hypomethylation, whereas increased expression of de novo DNMT3a or 36 causes gene-specific hypermethylation. OBJECTIVES: During cadmium-induced malignant transformation, an unusual pattern of genomic hypermethylation occurred that we studied to provide insight into the roles of specific DNMTs in oncogenesis. METHODS: Gene expression and DNA methylation were assessed in control and chronic cadmium-transformed prostate epithelial cells (CTPE) using reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, methylation-specific PCR, and methyl acceptance assay. RESULTS: During the 10-weeks of cadmium exposure that induced malignant transformation, progressive increases in generalized DNMT enzymatic activity occurred that were associated with overexpression of DNMT3b without changes in DNMT1 expression. Increased DNMT3b expression preceded increased DNMT enzymatic activity. Procainamide, a specific DNMT1 inhibitor, reversed cadmium-induced genomic DNA hypermethylation. Reduced expression of the tumor suppressor genes, RASSF1A and p16 began about the time DNMT3b overexpression first occurred and progressively decreased thereafter. RASSF1A and p16 promoter regions were heavily methylated in CTPE cells, indicating silencing by hypermethylation, while the DNA demethylating agent, 5-aza-2'-deoxycytidine, reversed this silencing. DNMT1 inhibition only modestly increased RASSF1A and p16 expression in CTPE cells and did not completely reverse silencing. CONCLUSIONS: These data indicate that DNMT3b overexpression can result in generalized DNA hypermethylation and gene silencing but that DNMT1 is required to maintain these effects. The pattern of genomic DNA hypermethylation together with up-regulation of DNMT3b may provide a unique set of biomarkers to specifically identify cadmium-induced human prostate cancers. C1 NCI, Natl Inst Environm Hlth Sci, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect, Res Triangle Pk, NC USA. Baylor Coll Med, Childrens Nutr Res Ctr, Dept Pediat & Mol & Human Genet, Houston, TX USA. Michigan State Univ, Dept Med, Dept Zool, E Lansing, MI USA. RP Waalkes, MP (reprint author), NCI, NIEHS, Inorgan Carcinogenesis Sect, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU Intramural NIH HHS NR 31 TC 81 Z9 88 U1 0 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 OCT PY 2007 VL 115 IS 10 BP 1454 EP 1459 DI 10.1289/ehp.10207 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 216UQ UT WOS:000249904900037 PM 17938735 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI Dark matter in a deep-sea vent and in human mouth SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ALGA CYANIDIOSCHYZON-MEROLAE; GENOME SEQUENCE; BACTERIAL FLAGELLA; ESCHERICHIA-COLI; DIMETHYL SULFIDE; DIVISION TM7; SP. NOV.; DIVERSITY; WATER; ANNOTATION C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS [Z99 LM999999] NR 46 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD OCT PY 2007 VL 9 IS 10 BP 2385 EP 2391 DI 10.1111/j.1462-2920.2007.01434.x PG 7 WC Microbiology SC Microbiology GA 206ZY UT WOS:000249222600001 PM 17803764 ER PT J AU Breysse, J Anderson, J Dixon, S Galke, W Wilson, J AF Breysse, Jill Anderson, Jack Dixon, Sherry Galke, Warren Wilson, Jonathan TI Immediate and one-year post-intervention effectiveness of Maryland's lead law treatments SO ENVIRONMENTAL RESEARCH LA English DT Article DE Maryland lead law; visual inspection; dust lead loading; clearance testing ID CONTROL GRANT PROGRAM; DUST AB A 1994 Maryland law prescribes a lead-based paint risk reduction standard for pre-1950, privately owned rental housing. This standard, applied at each tenancy change, can be met by sampling to verify that dust lead loadings are within acceptable limits or by performing specific lead hazard reduction treatments, followed by an independent visual inspection without dust sampling. We evaluated the ability of visual inspection to predict treatment completion and dust lead loadings. Fifty-two Baltimore housing units were enrolled and received the law-specified treatments. Before treatment, study risk assessors conducted visual assessments and dust lead wipe sampling in each unit. After treatment, Maryland-certified visual inspectors conducted the law's required visual inspection, followed by the study risk assessors, who performed a separate visual assessment and collected dust wipe samples. One year later, study risk assessors performed another visual assessment and dust wipe sampling (n = 34). Dust lead loadings declined significantly immediately after prescribed lead treatments were implemented. Fifty-three percent, 20%, and 47% of units had at least one sample that exceeded 1995 EPA/HUD floor, window sill and window trough clearance guidance of 100, 500 and 800 mu g/ft(2), respectively. Overall, 73% of units had one or more immediate post-intervention single surface sample results exceeding the 1995 clearance values that were in effect at the time of the study. One-year post-intervention loadings remained significantly below pre-intervention levels for floors but not window sills or troughs. Visual assessments alone, without dust lead testing, did not ensure that prescribed treatments were completed or that dust lead loadings were below clearance values. (C) 2007 Elsevier Inc. All rights reserved. C1 Natl Ctr Healthy Housing, Columbia, MD 21044 USA. Healthy Housing Solut, Columbia, MD 21044 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. RP Breysse, J (reprint author), Natl Ctr Healthy Housing, 10320 Little Patuxent Pkwy,Suite 500, Columbia, MD 21044 USA. EM jbreysse@centerforhealthyhousing.org NR 19 TC 2 Z9 2 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD OCT PY 2007 VL 105 IS 2 BP 267 EP 275 DI 10.1016/j.envres.2007.04.002 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 218VC UT WOS:000250042200011 PM 17559831 ER PT J AU Cannell, JJ Vieth, R Umhau, JC Holick, MF Grant, WB Madronich, S Garland, CF Giovannucci, E AF Cannell, J. J. Vieth, R. Umhau, J. C. Holick, M. F. Grant, W. B. Madronich, S. Garland, C. F. Giovannucci, E. TI Epidemic influenza and vitamin D - Reply SO EPIDEMIOLOGY AND INFECTION LA English DT Letter ID ASSOCIATION; INFECTION; CHILDREN; HEALTH C1 Atascadero State Hosp, Atascadero, CA 93423 USA. Mt Sinai Hosp, Dept Med Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Physiol, Boston, MA 02215 USA. SUNARC, San Francisco, CA USA. Natl Ctr Atmospher Res, Div Atmospher Chem, Boulder, CO 80307 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Cannell, JJ (reprint author), Atascadero State Hosp, 10333 El Camino Real, Atascadero, CA 93423 USA. EM jcannell@dmhash.state.ca.us RI Grant, William/B-8311-2009; Madronich, Sasha/D-3284-2015; OI Grant, William/0000-0002-1439-3285; Madronich, Sasha/0000-0003-0983-1313; Cannell, John/0000-0001-9748-8740 NR 27 TC 0 Z9 0 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD OCT PY 2007 VL 135 IS 7 BP 1092 EP 1095 DI 10.1017/S0950268807008308 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 231JB UT WOS:000250941800005 ER PT J AU Cannell, JJ Vieth, R Umhau, JC Holick, MF Grant, WB Madronich, S Garland, CF Giovannucci, E AF Cannell, J. J. Vieth, R. Umhau, J. C. Holick, M. F. Grant, W. B. Madronich, S. Garland, C. F. Giovannucci, E. TI Epidemic influenza and vitamin D - Reply SO EPIDEMIOLOGY AND INFECTION LA English DT Letter ID ANTIMICROBIAL ACTIVITY; INFECTION; DISEASE; MOLECULES; PEPTIDES; PATTERNS C1 Atascadero State Hosp, Atascadero, CA 93423 USA. Mt Sinai Hosp, Dept Med Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Physiol, Boston, MA 02215 USA. SUNARC, San Francisco, CA USA. Natl Ctr Atmospher Res, Div Atmospher Chem, Boulder, CO 80307 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Cannell, JJ (reprint author), Atascadero State Hosp, 10333 El Camino Real, Atascadero, CA 93423 USA. EM jcannell@dmhash.state.ca.us RI Grant, William/B-8311-2009; OI Grant, William/0000-0002-1439-3285; Cannell, John/0000-0001-9748-8740 NR 14 TC 0 Z9 0 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD OCT PY 2007 VL 135 IS 7 BP 1097 EP 1098 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 231JB UT WOS:000250941800007 ER PT J AU Easterbrook, JD Kaplan, JB Vanasco, NB Reeves, WK Purcell, RH Kosoy, MY Glass, GE Watson, J Klein, SL AF Easterbrook, J. D. Kaplan, J. B. Vanasco, N. B. Reeves, W. K. Purcell, R. H. Kosoy, M. Y. Glass, G. E. Watson, J. Klein, S. L. TI A survey of zoonotic pathogens carried by Norway rats in Baltimore, Maryland, USA SO EPIDEMIOLOGY AND INFECTION LA English DT Article ID HEPATITIS-E VIRUS; UNITED-STATES; INNER-CITY; LYMPHOCYTIC CHORIOMENINGITIS; HEMORRHAGIC-FEVER; RATTUS-NORVEGICUS; RENAL SYNDROME; WILD RATS; INFECTION; BARTONELLA AB Norway rats (Rattus norvegicus) carry several zoonotic pathogens and because rats and humans live in close proximity in urban environments, there exists potential for transmission. To identify zoonotic agents carried by rats in Baltimore, Maryland, USA, we live-trapped 201 rats during 2005-2006 and screened them for a panel of viruses, bacteria, and parasites. Antibodies against Seoul virus (57 center dot 7%), hepatitis E virus (HEV, 73 center dot 5%), Leptospira interrogans (65 center dot 3%), Bartonella elizabethae (34 center dot 1%), and Rickettsia typhi (7 center dot 0%) were detected in Norway rats. Endoparasites, including Calodium hepatica (87 center dot 9%) and Hymenolepis sp. (34 center dot 4%), and ectoparasites (13 center dot 9%, primarily Laelaps echidninus) also were present. The risk of human exposure to these pathogens is a significant public health concern. Because these pathogens cause non-specific and often self-limiting symptoms in humans, infection in human populations is probably underdiagnosed. C1 Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA. ANLIS, Inst Nacl Enfermedades Resp E Coni, RA-8260 Blas Parera, Santa Fe, Argentina. Ctr Dis Control & Prevent, Atlanta, GA USA. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, Ft Collins, CO USA. RP Easterbrook, JD (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Microbiol & Immunol, 615 N Wolfe St, Baltimore, MD 21205 USA. EM jeasterb@jhsph.edu FU NIAID NIH HHS [R01 AI054995] NR 30 TC 68 Z9 69 U1 3 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD OCT PY 2007 VL 135 IS 7 BP 1192 EP 1199 DI 10.1017/S0950268806007746 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 231JB UT WOS:000250941800019 PM 17224086 ER PT J AU Hartman, AL Lyle, M Wayns, K Rogawski, M Gasior, M AF Hartman, Adam L. Lyle, M. Wayns, K. Rogawski, M. Gasior, M. TI The ketogenic diet is protective in the 6 Hz seizure model SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Hartman, Adam L.] Johns Hopkins Univ Hosp, John M Freeman Pediat Epilepsy Ctr, Baltimore, MD 21287 USA. [Hartman, Adam L.; Lyle, M.; Wayns, K.; Rogawski, M.; Gasior, M.] NIH, NINDS, Epilepsy Res Sect, Bethesda, MD 20892 USA. [Rogawski, M.] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [Gasior, M.] Cephalon Inc, W Chester, PA USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 99 EP 100 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900273 ER PT J AU Gaillard, WD Rosenberger, LR Ritzl, EK Moore, EN Berl, MM Pearl, PL Conry, JA Weinstein, SL Tsuchida, T Ritter, FJ Sato, S Theodore, WH AF Gaillard, William D. Rosenberger, L. R. Ritzl, E. K. Moore, E. N. Berl, M. M. Pearl, P. L. Conry, J. A. Weinstein, S. L. Tsuchida, T. Ritter, F. J. Sato, S. Theodore, W. H. TI Rates of success in language FMRI acquisition in children and adolescents with epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Gaillard, William D.; Rosenberger, L. R.; Moore, E. N.; Pearl, P. L.; Conry, J. A.; Weinstein, S. L.; Tsuchida, T.] Childrens Natl Med Ctr, Dept Neurosci, Washington, DC 20010 USA. [Gaillard, William D.; Rosenberger, L. R.; Ritzl, E. K.; Moore, E. N.; Sato, S.; Theodore, W. H.] NINDS, NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. [Ritzl, E. K.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Ritter, F. J.] Minnosota Epilepsy Grp, St Paul, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 168 EP 168 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900458 ER PT J AU Rosenberger, LR Knoedelseder, K Ritzl, EK Wohlschlaeger, AM Moore, EN Shamim, S Bagic, A Gaillard, WD Ottman, R Theodore, W AF Rosenberger, Lisa R. Knoedelseder, K. Ritzl, E. K. Wohlschlaeger, A. M. Moore, E. N. Shamim, S. Bagic, A. Gaillard, W. D. Ottman, R. Theodore, W. TI Abnormal auditory and verbal processing in autosomal dominant partial epilepsy with auditory features SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Rosenberger, Lisa R.; Moore, E. N.; Gaillard, W. D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Rosenberger, Lisa R.; Knoedelseder, K.; Ritzl, E. K.; Wohlschlaeger, A. M.; Moore, E. N.; Shamim, S.; Bagic, A.; Gaillard, W. D.; Theodore, W.] NINDS, NIH, Bethesda, MD 20892 USA. [Ottman, R.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Ritzl, E. K.] Johns Hopkins Univ Hosp, Baltimore, MD 21205 USA. [Wohlschlaeger, A. M.] Tech Univ Munich, D-8000 Munich, Germany. RI Ottman, Ruth/O-2371-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 175 EP 175 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900475 ER PT J AU Pearl, PL Taylor, J Trzcinski, S Sokohl, A Dustin, I Reeves-Tyer, P Herscovitch, P Carson, R Liew, C Shamim, S Quezado, Z Gibson, KM Theodore, A AF Pearl, Phillip L. Taylor, J. Trzcinski, S. Sokohl, A. Dustin, I. Reeves-Tyer, P. Herscovitch, P. Carson, R. Liew, C. Shamim, S. Quezado, Z. Gibson, K. M. Theodore, Andw. TI 11C-flumazenil pet imaging in patients with SSADH deficiency SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Pearl, Phillip L.; Taylor, J.; Trzcinski, S.; Sokohl, A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Dustin, I.; Reeves-Tyer, P.; Herscovitch, P.; Liew, C.; Shamim, S.; Quezado, Z.; Theodore, Andw.] NINDS, NIH, Bethesda, MD 20892 USA. [Carson, R.] Yale Univ, Sch Med, New Haven, CT USA. [Gibson, K. M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RI Carson, Richard/H-3250-2011; Quezado, Zenaide/O-4860-2016 OI Carson, Richard/0000-0002-9338-7966; Quezado, Zenaide/0000-0001-9793-4368 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 179 EP 179 DI 10.1016/B978-075067999-2/50012-7 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900484 ER PT J AU Freilich, ER Berl, MM Rosenberger, LR Moore, EN Weber, D Wohlschlager, AM Vaidya, C Ratner, N Gaillard, WD AF Freilich, Emily R. Berl, M. M. Rosenberger, L. R. Moore, E. N. Weber, D. Wohlschlager, A. M. Vaidya, C. Ratner, N. Gaillard, W. D. TI Receptive language activation and lateralization in the superior temporal gyrus in normal healthy children ages 4-12 SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Freilich, Emily R.; Berl, M. M.; Rosenberger, L. R.; Moore, E. N.; Weber, D.; Gaillard, W. D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Wohlschlager, A. M.; Gaillard, W. D.] NIH, NINDS, Clin Epilepsy Sect, Bethesda, MD 20892 USA. [Wohlschlager, A. M.] Tech Univ Munich, D-8000 Munich, Germany. [Vaidya, C.] Georgetown Univ, Washington, DC USA. [Ratner, N.] Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 232 EP 233 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900626 ER PT J AU Wu, SH Arevalo, JC Malthankar-Phatak, GH Hintz, TM McCloskey, DP Tessarollo, L Chao, MV Scharfman, HE AF Wu, Synphen H. Arevalo, J. C. Malthankar-Phatak, G. H. Hintz, T. M. McCloskey, D. P. Tessarollo, L. Chao, M. V. Scharfman, H. E. TI Molecular mechanisms of dentate gyrus granule cell resistance to seizure-induced damage SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Wu, Synphen H.; Arevalo, J. C.; Chao, M. V.] NYU, Sch Med, New York, NY USA. [Malthankar-Phatak, G. H.; Hintz, T. M.; McCloskey, D. P.; Scharfman, H. E.] Helen Hayes Hosp, W Haverstraw, NY USA. [Tessarollo, L.] Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 241 EP 241 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900649 ER PT J AU Jinde, S Cravens, CJ Nakazawa, K AF Jinde, Seiichiro Cravens, C. J. Nakazawa, K. TI Hippocampal CA3 NMDA receptors protect CA1 sub-field from excitotoxicity SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Jinde, Seiichiro; Cravens, C. J.; Nakazawa, K.] NIMH, NIH, UGCB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 251 EP 251 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900675 ER PT J AU Fritsch, B Stott, JJ Reis, J Braga, MF AF Fritsch, Brita Stott, J. J. Reis, J. Braga, M. F. TI Impaired neuroplasticity in the basolateral nucleus of the amygdala of kindled rats SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Fritsch, Brita; Stott, J. J.] NIH, NINDS, ERS, Bethesda, MD 20892 USA. [Reis, J.] NIH, NINDS, HCPS, Bethesda, MD 20892 USA. [Fritsch, Brita; Braga, M. F.] Univ Hlth Sci, Dept Anat, Uninformed Serv, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 258 EP 258 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900695 ER PT J AU Reis, J Cohen, LG Pearl, PL Gibson, KM Dustin, I Theodore, WH AF Reis, Janine Cohen, L. G. Pearl, P. L. Gibson, K. M. Dustin, I. Theodore, W. H. TI Transcranial magnetic stimulation reveals altered cortical excitability in succinic semialdehyde dehydrogenase deficiency SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Reis, Janine; Cohen, L. G.; Dustin, I.; Theodore, W. H.] NIH, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Pearl, P. L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Gibson, K. M.] Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Biochem Genet Lab, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 258 EP 258 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900696 ER PT J AU Theodore, WH Fotheringham, J Shamim, S Liew, C Dustin, I Sato, S Heiss, J Gaillard, WD Bruce, D Williams, E Vortmeyer, A Jacobson, S AF Theodore, William H. Fotheringham, J. Shamim, S. Liew, C. Dustin, I. Sato, S. Heiss, J. Gaillard, W. D. Bruce, D. Williams, E. Vortmeyer, A. Jacobson, S. TI HHV-6BAND temporal lobectomy outcome in patients with mesial tmporal sclerosis SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Shamim, S.; Liew, C.; Dustin, I.; Sato, S.; Gaillard, W. D.] NINDS, NIH, Clin Epidemiol Sect, Bethesda, MD 20892 USA. [Fotheringham, J.; Williams, E.; Jacobson, S.] NINDS, NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. [Heiss, J.; Vortmeyer, A.] NINDS, NIH, Neurosurg Branch, Bethesda, MD 20892 USA. [Gaillard, W. D.] CNMC, Dept Neurol, Washington, DC USA. [Bruce, D.] CNMC, Dept Neurosurg, Washington, DC USA. [Sato, S.] NINDS, NIH, EEG Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 275 EP 275 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900744 ER PT J AU Lawrence, JJ Rogawski, MA McBain, CJ AF Lawrence, J. J. Rogawski, M. A. McBain, C. J. TI The KV7/KCNQ/M channel opener ICA-027243 arrests interneuronal firing and reduces interneuron network synchrony in the hippocampus: Novel insights into the antiepileptic action of KV7 channel openers SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Lawrence, J. J.; McBain, C. J.] NICHD, LCSN, Bethesda, MD USA. [Rogawski, M. A.] Univ Calif Davis, Sacramento, CA 95817 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 361 EP 361 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900974 ER PT J AU Mayo, J Rosenberger, L Berl, M Ritzl, E Moore, E Wohlschlager, A Pearl, PL Conry, JA Weinstein, SL Sato, S Theodore, WH Gaillard, WD AF Mayo, Jessica Rosenberger, L. Berl, M. Ritzl, E. Moore, E. Wohlschlager, A. Pearl, P. L. Conry, J. A. Weinstein, S. L. Sato, S. Theodore, W. H. Gaillard, W. D. TI Language lateralization in left focus epilepsy as determined by four methods SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Mayo, Jessica; Rosenberger, L.; Berl, M.; Moore, E.; Pearl, P. L.; Conry, J. A.; Weinstein, S. L.; Gaillard, W. D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Rosenberger, L.; Ritzl, E.; Moore, E.; Wohlschlager, A.; Conry, J. A.; Sato, S.; Theodore, W. H.; Gaillard, W. D.] NINDS, NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. Univ Maryland, College Pk, MD 20742 USA. [Ritzl, E.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA. [Wohlschlager, A.] Tech Univ Munich, D-8000 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 393 EP 394 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917901059 ER PT J AU Gaillard, WD Blumenfeld, H Kobayashi, E Laufs, H AF Gaillard, William D. Blumenfeld, Hal Kobayashi, Eliane Laufs, Helmut TI Ictal and interictal FMRI SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 30-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Gaillard, William D.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Gaillard, William D.] NIH, NINDS, Clin Epilepsy Sect, Bethesda, MD 20892 USA. [Blumenfeld, Hal] Yale Univ, New Haven, CT USA. [Kobayashi, Eliane] Montreal Neurol Inst, Montreal, PQ, Canada. [Laufs, Helmut] UCL, Natl Soc Epilepsy, MRI Unit, Gerrards Cross, England. OI Laufs, Helmut/0000-0003-0030-2781 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 407 EP 407 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917901090 ER PT J AU Theodore, WH Parko, K Waterhouse, E Burneo, J AF Theodore, William H. Parko, Karen Waterhouse, Elizabeth Burneo, Jorge TI Disparities in epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Theodore, William H.] NIH, NINDS, Clin Epilepsy Sect, Bethesda, MD 20892 USA. [Parko, Karen] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Waterhouse, Elizabeth] VCU, Dept Neurol, Richmond, VA USA. [Burneo, Jorge] Univ Western Ontario, Dept Neurol, London, ON, Canada. [Parko, Karen] Navaho Area Indian Hlth Serv, Window Rock, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 407 EP 408 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917901093 ER PT J AU Koepp, MJ Basser, P Catani, M AF Koepp, Matthias J. Basser, Peter Catani, Marco TI Imaging brain connectivity SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Basser, Peter] NIH, Bethesda, MD 20892 USA. [Catani, Marco] Inst Psychiat, London, England. [Koepp, Matthias J.] Natl Hosp Nuerol & Neurosurg, London, England. RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 409 EP 409 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917901096 ER PT J AU Keren, A AF Keren, Arnon TI EPISTEMIC AUTHORITY, TESTIMONY AND THE TRANSMISSION OF KNOWLEDGE SO EPISTEME-A JOURNAL OF INDIVIDUAL AND SOCIAL EPISTEMOLOGY LA English DT Article AB I present an account of what it is to trust a speaker, and argue that the account can explain the common intuitions which structure the debate about the transmission view of testimony. According to the suggested account, to trust a speaker is to grant her epistemic authority on the asserted proposition, and hence to see her opinion as issuing a second order, preemptive reason for believing the proposition. The account explains the intuitive appeal of the basic principle associated with the transmission view of testimony: the principle according to which, a listener can normally obtain testimonial knowledge that p by believing a speaker who testifies that p only if the speaker knows that p. It also explains a common response to counterexamples to this principle: that these counterexamples do not involve normal cases of testimonial knowledge. C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Keren, A (reprint author), NIH, Dept Bioeth, Bethesda, MD 20892 USA. OI Keren, Arnon/0000-0002-4899-5495 NR 25 TC 9 Z9 9 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1742-3600 EI 1750-0117 J9 EPISTEME-J INDIV SOC JI Episteme PD OCT PY 2007 VL 4 IS 3 BP 368 EP 381 DI 10.3366/E1742360007000147 PG 14 WC Philosophy SC Philosophy GA V32UN UT WOS:000208976200010 ER PT J AU Lustig, Y Vagima, Y Goldshmidt, H Erlanger, A Ozeri, V Vince, J McConville, MJ Dwyer, DM Landfear, SM Michaeli, S AF Lustig, Yaniv Vagima, Yaron Goldshmidt, Hanoch Erlanger, Avigail Ozeri, Vered Vince, James McConville, Malcolm J. Dwyer, Dennis M. Landfear, Scott M. Michaeli, Shulamit TI Down-regulation of the trypanosomatid signal recognition particle affects the biogenesis of polytopic membrane proteins but not of signal peptide-containing proteins SO EUKARYOTIC CELL LA English DT Article ID ENDOPLASMIC-RETICULUM MEMBRANE; COLLOSOMA 7SL RNA; SACCHAROMYCES-CEREVISIAE; LEPTOMONAS-COLLOSOMA; DIFFERENTIAL REGULATION; FUNCTIONAL EXPRESSION; STABLE TRANSFECTION; LEISHMANIA-MEXICANA; TARGETING PATHWAY; BRUCEI AB Protein translocation across the endoplasmic reticulum is mediated by the signal recognition particle (SRP). In this study, the SRP pathway in trypanosomatids was down-regulated by two approaches: RNA interference (RNAi) silencing of genes encoding SRP proteins in Trypanosoma brucei and overexpression of dominant-negative mutants of 7SL RNA in Leptomonas collosoma. The biogenesis of both signal peptide-containing proteins and polytopic membrane proteins was examined using endogenous and green fluorescent protein-fused proteins. RNAi silencing of SRP54 or SRP68 in T. brucei resulted in reduced levels of polytopic membrane proteins, but no effect on the level of signal peptide-containing proteins was observed. When SRP deficiency was achieved in L. collosoma by overexpression of dominant-negative mutated 7SL RNA, a major effect was observed on polytopic membrane proteins but not on signal peptide-containing proteins. This study included two trypanosomatid species, tested various protein substrates, and induced depletion of the SRP pathway by affecting either the levels of SRP binding proteins or that of SRP RNA. Our results demonstrate that, as in bacteria but in contrast to mammalian cells, the trypanosome SRP is mostly essential for the biogenesis of membrane proteins. C1 Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel. Univ Melbourne, Dept Biochem & Mol Biol, Bio21 Mol Sci & Biotechnol Inst, Parkville, Vic 3052, Australia. NIH, NIAID, Parasit Dis Lab, Cell Biol Sect, Bethesda, MD 20892 USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. RP Michaeli, S (reprint author), Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel. EM michaes@mail.biu.ac.il OI Landfear, Scott/0000-0002-1643-6664 FU NIAID NIH HHS [R01 AI044138] NR 43 TC 10 Z9 10 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD OCT PY 2007 VL 6 IS 10 BP 1865 EP 1875 DI 10.1128/EC.00134-07 PG 11 WC Microbiology; Mycology SC Microbiology; Mycology GA 220XO UT WOS:000250190800016 PM 17715370 ER PT J AU Moschovi, M Stavrou, T Dessypris, N Skalkidis, I Karalis, D Reaman, GH Goldstein, AM Prodromou, N Tzortzatou-Stathopoulou, F Petridou, ET AF Moschovi, Maria Stavrou, Theodora Dessypris, Nick Skalkidis, Ilias Karalis, Dimitris Reaman, Gregory H. Goldstein, Alisa M. Prodromou, Neophytos Tzortzatou-Stathopoulou, Fotini Petridou, Eleni Th. TI Survival among children with medulloblastoma in Greece: gains from transition to chemotherapy and socio-economic differentials SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE chemotherapy; childhood; health services access; medulloblastoma; socio-economic differentials; survival ID NIJMEGEN BREAKAGE SYNDROME; RADIATION-THERAPY; POSTOPERATIVE CHEMOTHERAPY; CHILDHOOD MEDULLOBLASTOMA; ADJUVANT CHEMOTHERAPY; PEDIATRIC-ONCOLOGY; PROGNOSTIC-FACTORS; CANCER GROUP; TUMOR; TRIAL AB The objective of this study was to quantify improvements in survival due to chemotherapy among children with medulloblastorna treated during the last three decades at a university unit in Greece, compare these gains with figures derived from a specialized unit in the United States and explore the role of extrinsic factors affecting survival. The records of all children with medulloblastorna (n=50) treated at the University Childhood Oncology Unit in Athens, Greece during the period 1973-2003 were reviewed. The role on survival of socio-demographic factors was studied by modeling the data through Cox's proportional-hazards regression, controlling for the mode of treatment (chemotherapy, yes vs. no), whereas survival of children with medulloblastoma treated in Greece was compared with that of 76 children treated in a specialized center in the United States during a respective period. After adjustment for demographic factors, children with medulloblastorna who received adjuvant therapy in Greece had an approximately four times higher instantaneous rate of remaining alive than those who did not (P=0.05). The 5-year survival of children with medulloblastoma treated at specialized medical centers in Greece and the United States was 66 and 63%, respectively. Despite the comparable figure with that of an acceptable standard, however, there was a suggestion (P=0.07) that a rural place of residence in Greece is a poor prognostic indicator. Assuming inherently similar age of occurrence in urban and rural areas, children from rural areas in this study had a more advanced age at diagnosis than those residing in urban Greece (mean age: 7.9 vs. 6.6 years) with a 5-year survival of 57 and 73%, respectively. As expected, incorporation of adjuvant chemotherapy in the treatment of Greek children with medulloblastorna has yielded remarkable improvement in 5-year survival, comparable to that of technologically advanced countries. On the contrary, children residing in rural areas of the country seem to enjoy less favorable prognosis, possibly owing to delays in diagnosis or limited access to optimal treatment facilities. C1 Univ Athens, Sch Med, Dept Hyg & Epidemiol, Unit Prevent Med, Athens 11527, Greece. Univ Athens, Aghia Sophia Childrens Hosp, Dept Pediat 1, Hematol Oncol Unit, Athens 11527, Greece. Aghia Sophia Childrens Hosp, Neurosurg Unit, Athens, Greece. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Natl Canc Inst, Genet Epidemiol Branch, Bethesda, MD USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Petridou, ET (reprint author), Univ Athens, Sch Med, Dept Hyg & Epidemiol, Unit Prevent Med, 75 Mikras Asias Str, Athens 11527, Greece. EM epetrid@med.uoa.gr OI MOSCHOVI, MARIA/0000-0002-2982-8501 FU Intramural NIH HHS NR 32 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD OCT PY 2007 VL 16 IS 5 BP 460 EP 465 DI 10.1097/01.cej.0000243848.74609.9a PG 6 WC Oncology SC Oncology GA 208BJ UT WOS:000249294500012 PM 17923818 ER PT J AU van de Sluis, B Muller, P Klomp, LW Duran, K van Harn, T Chen, A Liu, PP Wijmenga, C AF van de Sluis, B. Muller, P. Klomp, L. W. Duran, K. van Harn, T. Chen, A. Liu, P. P. Wijmenga, C. TI Increased activity of hypoxia-inducible factor 1 leads to early embryonic lethality in Commd1 null mice SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Meeting Abstract C1 [van de Sluis, B.; Duran, K.; Wijmenga, C.] Univ Med Ctr Utrecht, Complex Genet Sect, DBG Dept Med Genet, Utrecht, Netherlands. [van de Sluis, B.; Muller, P.; Klomp, L. W.; van Harn, T.] Univ Med Ctr Utrecht, Lab Metab & Endocrine Dis, Utrecht, Netherlands. [Chen, A.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Liu, P. P.] NHGRI, Oncogenesis & Dev Sect, 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 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD OCT PY 2007 VL 19 IS 10 BP A59 EP A60 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 279LK UT WOS:000254356500173 ER PT J AU Steinbach, D Onda, M Voigt, A Dawczynski, K Wittig, S Hassan, R Gruhn, B Pastan, I AF Steinbach, Daniel Onda, Masanori Voigt, Astrid Dawczynski, Kristin Wittig, Susan Hassan, Raffit Gruhn, Bernd Pastan, Ira TI Mesothelin, a possible target for immunotherapy, is expressed in primary AML cells SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE acute myeloid leukemia; mesothelin; immunotherapy; therapeutic targets ID ACUTE MYELOID-LEUKEMIA; ANTITUMOR-ACTIVITY; SS1(DSFV)PE38; IMMUNOTOXIN; CANCER; GENES AB Background: Mesothelin is a promising candidate for tumor-specific therapy because of its limited expression in normal tissues and high expression in several cancers. The expression of the protein mesothelin in hematological malignancies has not yet been analyzed. SS1(dsFv)PE38 is a recombinant anti-mesothelin immunotoxin which is undergoing clinical evaluation in patients with mesothelin-expressing tumors. Methods and Results: In this study we show that the mesothelin protein is expressed in leukemic cells from children with acute myeloid leukemia (AML). This finding was confirmed by western blot, immunocytochemistry and real time polymerase chain reaction (PCR). Despite the expression of mesothelin, the patient samples were not sensitive to immunotoxin SS1(dsFv)PE38 in MTT assays. Conclusions: Primary AML cells express mesothelin but SS1(dsFv)PE38 is not active in killing these cells. Other approaches that utilize mesothelin as a target might be more effective and should be tested against AML cells. C1 Univ Ulm, Childrens Hosp, D-89075 Ulm, Germany. NIH, Mol Biol Lab, Bethesda, MD 20892 USA. Univ Jena, Childrens Hosp, D-6900 Jena, Germany. RP Steinbach, D (reprint author), Univ Ulm, Childrens Hosp, Eythstr 24, D-89075 Ulm, Germany. EM Daniel@Steinba.ch NR 14 TC 10 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD OCT PY 2007 VL 79 IS 4 BP 281 EP 286 DI 10.1111/j.1600-0609.2007.00928.x PG 6 WC Hematology SC Hematology GA 210AC UT WOS:000249428100002 PM 17803679 ER PT J AU Xu, ZL Kaplan, NL Taylor, JA AF Xu, Zongli Kaplan, Norman L. Taylor, Jack A. TI Tag SNP selection for candidate gene association studies using HapMap and gene resequencing data SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE environmental genome project; HapMap; gene resequencing; tag SNP; ethnic-mixed data; composite LD ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; LINKAGE DISEQUILIBRIUM; MULTIPLE POPULATIONS; SEQUENCE VARIATION; HAPLOTYPES; PATTERNS; COVERAGE; PROJECT; SAMPLE AB HapMap provides linkage disequilibrium (LD) information on a sample of 3.7 million SNPs that can be used for tag SNP selection in whole-genome association studies. HapMap can also be used for tag SNP selection in candidate genes, although its performance has yet to be evaluated against gene resequencing data, where there is near-complete SNP ascertainment. The Environmental Genome Project (EGP) is the largest gene resequencing effort to date with over 500 resequenced genes. We used HapMap data to select tag SNPs and calculated the proportions of common SNPs (MAF >= 0.05) tagged (rho(2)>= 0.8) for each of 127 EGP Panel 2 genes where individual ethnic information was available. Median gene-tagging proportions are 50, 80 and 74% for African, Asian, and European groups, respectively. These low gene-tagging proportions may be problematic for some candidate gene studies. In addition, although HapMap targeted nonsynonymous SNPs (nsSNPs), we estimate only similar to 30% of nonsynonymous SNPs in EGP are in high LD with any HapMap SNP. We show that gene-tagging proportions can be improved by adding a relatively small number of tag SNPs that were selected based on resequencing data. We also demonstrate that ethnic-mixed data can be used to improve HapMap gene-tagging proportions, but are not as efficient as ethnic-specific data. Finally, we generalized the greedy algorithm proposed by Carlson et al (2004) to select tag SNPs for multiple populations and implemented the algorithm into a freely available software package mPopTag. C1 Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. RP Taylor, JA (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, MD A3-05,111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM taylor@niehs.nih.gov OI xu, zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398 FU Intramural NIH HHS NR 27 TC 23 Z9 26 U1 2 U2 5 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 OCT PY 2007 VL 15 IS 10 BP 1063 EP 1070 DI 10.1038/sj.ejhg.5201875 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 215AB UT WOS:000249778400011 PM 17568388 ER PT J AU Martin, DL Postan, M Lucas, P Gress, R Tarleton, RL AF Martin, Diana L. Postan, Miriam Lucas, Philip Gress, Ronald Tarleton, Rick L. TI TGF-beta regulates pathology but not tissue CD8(+) T cell dysfunction during experimental Trypanosoma cruzi infection SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cytokines; cytotoxic; infectious diseases; parasitic-protozoan; T cells ID GROWTH-FACTOR-BETA; CUTTING EDGE; IN-VIVO; CYTOKINE PRODUCTION; INBRED MICE; SUSCEPTIBILITY; RESISTANCE; INFLAMMATION; TGF-BETA-1; DISEASE AB Infection with the protozoan parasite Trypanosoma cruzi leads to chronic infection, with parasite persistence primarily in muscle tissue. CD8(+) T cells isolated from muscle tissue of T cruzi-infected mice display decreased production of IFN-gamma in response to T cell receptor engagement. The expression of TGF-beta at the site of CD8(+) T cell dysfunction and parasite persistence suggested that this immunoregulatory cytokine might play a role in. these processes. Mice expressing a Tcell-specific dominant negative TGF-beta receptor type II (DNRII) were therefore infected with T cruzi. Infection of DNRII mice resulted in massive CD8(+) T cell proliferation, leading to increased numbers but decreased frequencies of antigen-specific CD8(+) T cells in the spleen compared to wild-type mice. However, TGF-beta unresponsiveness failed to restore effector functions of CD8(+) T cells isolated from muscle tissue. Histological examination of skeletal muscle from T cruzi-infected DNRII mice revealed an extensive cellular infiltrate, and DNRII mice displayed higher susceptibility to infection. Overall, while TGF-beta does not appear to be responsible for CD8+ T cell unresponsiveness in peripheral tissue in T cruzi-infected mice, these data suggest a role for TGF-beta in control of immunopathology in response to T cruzi infection. C1 Univ Georgia, Dept Cellular Biol, Athens, GA 30605 USA. Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30605 USA. Inst Salud Dr Carlos G Malbran ANLIS Malbran, Buenos Aires, DF, Argentina. Inst Nacl Parasiol Dr Mario Fatala Chaben, Adm Nacl Labs, Buenos Aires, DF, Argentina. NCI, NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Tarleton, RL (reprint author), Univ Georgia, Dept Cellular Biol, N310 Coverdell Bldg,500 D W Brooks Dr, Athens, GA 30605 USA. EM tarleton@cb.uga.edu FU NIAID NIH HHS [AI033106, AI022070] NR 37 TC 19 Z9 19 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2007 VL 37 IS 10 BP 2764 EP 2771 DI 10.1002/eji.200737033 PG 8 WC Immunology SC Immunology GA 222KD UT WOS:000250294100011 PM 17823982 ER PT J AU Parr-Brownlie, LC Poloskey, SL Flanagan, KK Eisenhofer, G Bergstrom, DA Walters, JR AF Parr-Brownlie, Louise C. Poloskey, Stacey L. Flanagan, Kalynda K. Eisenhofer, Graeme Bergstrom, Debra A. Walters, Judith R. TI Dopamine lesion-induced changes in subthalamic nucleus activity are not associated with alterations in firing rate or pattern in layer V neurons of the anterior cingulate cortex in anesthetized rats SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE basal ganglia; corticosubthalamic pathway; oscillations; Parkinson's disease; pyramidal neurons ID 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE PRIMATE MODEL; LIGHT MICROSCOPIC ANALYSIS; GLOBUS-PALLIDUS NEURONS; NIGRA PARS RETICULATA; BASAL GANGLIA OUTPUT; PARKINSONS-DISEASE; PREFRONTAL CORTEX; SUBSTANTIA-NIGRA; UNILATERAL LESION; PEDUNCULOPONTINE NUCLEUS AB Dysfunctional activity in the subthalamic nucleus (STN) is thought to underlie movement deficits of patients with Parkinson's disease. Alterations in STN firing patterns are also evident in the anesthetized rat model of Parkinson's disease, where studies show that loss of striatal dopamine and concomitant changes in the indirect pathway are associated with bursty and oscillatory firing patterns in STN output. However, the extent to which alterations in cortical activity contribute to changes in STN activity is unclear. As pyramidal neurons in the cingulate cortex project directly to the STN, cingulate output was assessed after dopamine lesion by simultaneously recording single-unit and local field potential (LFP) activities in STN and anterior cingulate cortex in control, dopamine-lesioned and non-lesioned hemispheres of urethane-anesthetized rats. Correlated oscillations were observed in cross-correlograms of spike trains from STN and cingulate layer V neurons with broad waveforms indicative of pyramidal neurons. One-2 weeks after dopamine cell lesion, firing rate, incidence of bursty and 0.3-2.5 Hz oscillatory activity of neurons and LFP power in the STN all increased significantly. In contrast, firing rate, incidence of bursty and 0.3-2.5 Hz oscillatory activity of cingulate layer V putative pyramidal neurons and power in cingulate LFPs did not differ significantly between dopamine-lesioned, non-lesioned or control hemispheres, despite significant loss of dopamine in the lesioned cingulate cortex. Data show that alterations in STN activity in the dopamine-lesioned hemisphere are not associated with alterations in neuronal activity in layer V of the anterior cingulate cortex in anesthetized rats. C1 NINDS, Neurophysiol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurosci Program, NIH, Bethesda, MD 20892 USA. RP Parr-Brownlie, LC (reprint author), NINDS, Neurophysiol Pharmacol Sect, NIH, 35 Convent Dr,Bldg 35 Room 1C 905, Bethesda, MD 20892 USA. EM parrbl@ninds.nih.gov OI Gonzales, Kalynda/0000-0001-7957-7125; Parr-Brownlie, Louise/0000-0002-3001-7669 FU Intramural NIH HHS NR 117 TC 21 Z9 23 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2007 VL 26 IS 7 BP 1925 EP 1939 DI 10.1111/j.1460-9568.2007.05814.x PG 15 WC Neurosciences SC Neurosciences & Neurology GA 214OY UT WOS:000249749200020 PM 17897398 ER PT J AU Rudebeck, PH Walton, ME Millette, BHP Shirley, E Rushworth, MFS Bannerman, DM AF Rudebeck, Peter H. Walton, Mark E. Millette, Benjamin H. P. Shirley, Elizabeth Rushworth, Matthew F. S. Bannerman, David M. TI Distinct contributions of frontal areas to emotion and social behaviour in the rat SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE anxiety; behaviour; emotion; rat ID ORBITAL PREFRONTAL CORTEX; SPONTANEOUS OBJECT RECOGNITION; ANTERIOR CINGULATE CORTEX; ORBITOFRONTAL CORTEX; RHESUS-MONKEYS; CYTOTOXIC LESIONS; DECISION-MAKING; REWARD VALUE; MEMORY; AMYGDALA AB Although the lesions of patients with impaired social behaviour encompass both orbitofrontal and anterior cingulate cortex (OFC and ACC), attempts to model such impairments in animals have focused on the OFC. However, recent neuroimaging attempts to identify the neural correlates of social interaction have emphasized the relative importance of ACC. Here we report the effect of circumscribed excitotoxic lesions of either OFC or ACC on ethological, unconditioned tests of emotion and social behaviour in the Lister hooded rat. OFC lesions altered emotional responsiveness to stimuli in non-social, fear-inducing situations (hyponeophagia test), and produced a small but statistically significant increase in aggression to other rats, but did not compromise other aspects of social interaction and appraisal. ACC lesions did, however, affect the utilization of social information. Specifically, ACC lesions diminished interest in other individuals and caused a relative reduction in memory for social stimuli. Whereas normal animals habituated to repeated presentations of the same individual, the poor performance of ACC animals entailed continued higher levels of responsiveness to repeated presentations of the same individual. The ACC impairment cannot simply be attributed to a general reduction in arousal, or a general impairment in recognition memory. Neither lesion affected anxiety per se (successive alleys test). Further analyses were conducted to investigate whether the changes in aggressive and social behaviour were related to different aspects of decision-making. Although the relationship between changes in social interaction and decision-making after ACC lesions is unclear, OFC impairments in emotionality were correlated with increased impulsive choice. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. RP Rudebeck, PH (reprint author), NIMH, Neuropsychol Lab, Bldg 49,Suite 1B-80,49 Convent Dr, Bethesda, MD 20892 USA. EM rudebeckp@mail.nih.gov RI Rudebeck, Peter/G-7931-2012; OI Rudebeck, Peter/0000-0002-1411-7555 FU Medical Research Council [G0600994]; Wellcome Trust [, 087736] NR 44 TC 56 Z9 57 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2007 VL 26 IS 8 BP 2315 EP 2326 DI 10.1111/j.1460-9568.2007.05844.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 221YC UT WOS:000250262300021 PM 17927774 ER PT J AU McCarron, JA Zoghbi, SS Shetty, HU Vermeulen, ES Wikstrom, HV Ichise, M Yasuno, F Halldin, C Innis, RB Pike, VW AF McCarron, Julie A. Zoghbi, Sami S. Shetty, H. Umesha Vermeulen, Eric S. Wikstrom, Hakan V. Ichise, Masanori Yasuno, Fumihiko Halldin, Christer Innis, Robert B. Pike, Victor W. TI Synthesis and initial evaluation of [C-11](R)-RWAY in monkey - a new, simply labeled antagonist radioligand for imaging brain 5-HT1A receptors with PET SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE 5-HT1A receptor; PET; radioligand; [ C-11]( R)-RWAY; Imaging ID IN-VIVO; RADIOACTIVE METABOLITES; HUMAN PLASMA; WAY-100635; QUANTIFICATION; BINDING; INHIBITION; WAY-100635; BEHAVIOR; LIGANDS AB Purpose We aimed to fulfill a need for a radioligand that may be simply labeled with carbon-11 for effective positron emission tomography (PET) imaging of brain 5-HT1A receptors. Methods Racemic RWAY (2,3,4,5,6,7-hexahydro-1-[4-[1-[4-(2-methoxyphenyl)piperazinyl]]-2-phenylbutyryl]-1H-azepine) has high affinity for 5-HT1A receptors. The enantiomers of RWAY and O-desmethyl-RWAY, synthesized from commercially available materials, were each labeled with carbon-11 by treating the respective O-desmethyl precursor with [C-11]iodomethane, and injected into rhesus monkey for measurement of regional brain uptake. The 5-HT1A selectivity of (R)-[C-11]RWAY was checked by administering WAY-100635, before and after radioligand administration. Radiometabolites of (R)-[C-11]RWAY in blood and urine were analyzed by HPLC with partial elucidation of their structures by LC-MS-MS. Results (R)-[C-11]RWAY was a 5-HT1A receptor antagonist exhibiting high brain uptake with regional distribution consistent with specific binding to 5-HT1A receptors. The similar affinity, (S)-[C-11]RWAY was a weak partial agonist at 5-HT1A receptors exhibiting similar brain peak uptake with much less 5-HT1A receptor-specific binding. The maximal ratio in receptor-rich cingulate gyrus to receptor-devoid cerebellum reached 6.4 at 87.5 min after injection of (R)-[C-11]RWAY. After treatment with WAY-100635 before or after (R)-[C-11]RWAY administration, radioactivity levels in 5-HT1A receptor-rich regions were reduced almost to that in cerebellum. Blood and urine radiometabolites were less lipophilic than parent and were not due to hydrolysis but to ring hydroxylations, oxidation, and dephenylation. Conclusion (R)-[C-11]RWAY is simply prepared and an effective antagonist for imaging brain 5-HT1A receptors. This radioligand resists hydrolysis in vivo, gives less lipophilic radiometabolites, and warrants further PET studies in human subjects. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Univ Groningen, Ctr Pharm, Dept Med Chem, Groningen, Netherlands. Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, Stockholm, Sweden. RP McCarron, JA (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA. EM mccarroj@mail.nih.gov FU Intramural NIH HHS NR 36 TC 12 Z9 12 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2007 VL 34 IS 10 BP 1670 EP 1682 DI 10.1007/s00259-007-0460-z PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 213EB UT WOS:000249647900018 PM 17579853 ER PT J AU Del Vecchio, S Zannetti, A Panico, MR Speranza, A Iommelli, F Papaccioli, A Sommella, J Lettieri, A Saviano, M Zaccaro, L Del Gatto, A Lang, L Pedone, C Salvatore, M AF Del Vecchio, S. Zannetti, A. Panico, M. R. Speranza, A. Iommelli, F. Papaccioli, A. Sommella, J. Lettieri, A. Saviano, M. Zaccaro, L. Del Gatto, A. Lang, L. Pedone, C. Salvatore, M. TI In vivo imaging of alpha(v) beta(3) integrin expression with a radiolabeled chimeric RGD peptide SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract CT 20th Annual Congress of the European-Association-of-Nuclear-Medicine CY 2007 CL Copenhagen, DENMARK SP European Assoc Nucl Med C1 [Del Vecchio, S.; Salvatore, M.] Univ Naples Federico 2, Naples, Italy. [Zannetti, A.; Panico, M. R.; Speranza, A.; Iommelli, F.; Papaccioli, A.; Sommella, J.; Lettieri, A.; Saviano, M.; Zaccaro, L.; Del Gatto, A.; Pedone, C.] CNR, Ist Biostruct & Bioimmagini, Naples, Italy. [Lang, L.] NIH, PET Dept, Bethesda, MD USA. RI Salvatore, Marco/K-8083-2016 OI Salvatore, Marco/0000-0001-9734-7702 NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2007 VL 34 SU 2 BP S200 EP S200 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 264JP UT WOS:000253283900385 ER PT J AU Kao, CK Xie, H Szajek, LP Liao, C Hsu, W Kao, P AF Kao, C. K. Xie, H. Szajek, L. P. Liao, C. Hsu, W. Kao, P. TI [F-18]-FBAU 3 ',5 '-dibenzoate as a potential lipophilic prodrug for Neurogenesis Imaging SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract CT 20th Annual Congress of the European-Association-of-Nuclear-Medicine CY 2007 CL Copenhagen, DENMARK SP European Assoc Nucl Med C1 [Kao, C. K.; Xie, H.; Liao, C.; Hsu, W.; Kao, P.] Tzu Chi Univ, Tzu Chi Coll Technol, Tzu Chi Gen Hosp, Hualien, Taiwan. [Szajek, L. P.] NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2007 VL 34 SU 2 BP S138 EP S138 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 264JP UT WOS:000253283900091 ER PT J AU Hajduch, J Paleta, O Kvicala, J Haufe, G AF Hajduch, Jan Paleta, Oldrich Kvicala, Jaroslav Haufe, Guenter TI Fluorinated furan-2(5H)-ones: Reactivity and stereoselectivity in Diels-Alder reactions SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY LA English DT Article DE cycloaddition; DFT calculations; Diels-Alder reactions; fluorinated heterocycles; lactones ID ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS; SECONDARY ORBITAL INTERACTIONS; CONSISTENT BASIS-SETS; CHEMICAL CONSEQUENCES; MALEIC-ANHYDRIDE; TANDEM ADDITIONS; PART 5; CYCLOPENTADIENE; DISPLACEMENT; SUBSTITUTION AB 3 -Fluorofuran-2(5H)-one (1) and three 3,4-difluorofuran-2(5H)-ones 2-4, alpha,beta-unsaturated lactones possessing fluorinated double bonds, were applied as dienophiles in Diels-Alder reactions with normal electron demand using diphenylisobenzofuran or cyclopentadiene as dienes. In the same reactions, furan or 2,3-dimethylbuta-1,3-diene were completely unreactive. Three structural factors of furan-2(5H)-ones appeared to have an effect on the reactivity, regioselectivity and diastereoselectivity of the [4+2] cycloadditions: the number of fluorine atoms attached to the double bond and the number and the bulkiness of alkyl substituents at the 5-position of the furan-2(5H)-one system. The monofluorinated furan-2(5H)-one 1 was generally more reactive than the difluorinated furan-2(5H) -ones 2-4. While the reactions of the furan-2(5H)-ones 2-4 with isobenzofuran exclusively gave exo products, those of the monofluorinated lactone 1 led to mixtures of endo and exo diastereoisomeric [4+2] cycloadducts, All fluorinated f uran-2(5H)-ones 1-4 formed mixtures of diastereoisomeric 1:1 and 1:2 adducts with cyclopentadiene. DFT calculations of the transition states of the above Diels-Alder reactions using the BMK functional, a third-generation hybrid functional tailored for transition state calculations, together with the polarization consistent aug-pc-2 basis set, confirmed the preferential formation of the exo adducts from difluorinated furan-2(5H)ones, while for nonfluorinated analogues a small but significant preference for the endo adducts was confirmed. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) C1 Inst Chem Technol, Dept Organ Chem, CR-16628 Prague 6, Czech Republic. Univ Munster, Inst Organ Chem, D-48149 Munster, Germany. RP Paleta, O (reprint author), NIDDK, Natl Inst Hlth, 8 Ctr Dr,Bldg 8, Bethesda, MD 20892 USA. EM janli@niddk.nih.gov; Paleta@vscht.cz; Jaroslav.Kvicala@vscht.cz; haufe@uni-muenster.de RI Kvicala, Jaroslav/K-4277-2012 NR 79 TC 11 Z9 11 U1 2 U2 13 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1434-193X J9 EUR J ORG CHEM JI Eur. J. Org. Chem. PD OCT PY 2007 IS 30 BP 5101 EP 5111 DI 10.1002/ejoc.200700543 PG 11 WC Chemistry, Organic SC Chemistry GA 225VA UT WOS:000250545100015 ER PT J AU Wu, HE Hong, JS Tseng, LF AF Wu, Hsiang-en Hong, Jau-Shyong Tseng, Leon F. TI Stereo selective action of (+)-morphine over (-)-morphine in attenuating the (-)-morphine-produced antinociception via the naloxone-sensitive sigma receptor in the mouse SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE sigma receptor; antianalgesia; antinociception; morphine; opioid; (mice) ID CONDITIONED PLACE PREFERENCE; OPIOID ANALGESIA; (&)-MORPHINAN SERIES; BRAIN MEMBRANES; SPINAL-CORD; MORPHINE; INVOLVEMENT; SYSTEM; ANTIANALGESIA; ANTAGONISM AB We have previously demonstrated that (+)-morphine and (-)-morphine given spinally stereoselectively attenuate the spinally-administered (-)morphine-produced tail-flick inhibition in the mouse. The phenomenon has been defined as antianalgesia. Present studies were then undertaken to determine if the systemic administration of (+)-morphine and (-)-morphine also stereoselectively attenuates the systemic (-)-motphine-produced tail-flick inhibition and the effects of (+)-morphine and (-)-morphine are mediated by the naloxone-sensitive sigma receptor activation in male CD-1 mice. Pretreatment with (+)-morphine at a dose of 0.01-10 ng/kg given subcutaneously dose-dependently attenuated the tail-flick inhibition produced by subcutaneously-administered (-)-morphine (5 mg/kg). Pretreatment with (-)-morphine (0.01-1.0 mg/kg) given subcutaneously also attenuates the (-)-morphine-produced tail-flick inhibition. The ED50 values for (+)-morphine and (-)-morphine for inhibiting the (-)-morphine-produced tail-flick inhibition were estimated to be 30.6 pg/kg and 97.5 mu g/kg, respectively. The attenuation of the (-)-morphine-produced tail-flick inhibition induced by (+)-morphine or (-)-morphine pretreatment was reversed by the pretreatment with (+)-naloxone or by the sigma receptor antagonist BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide) given subcutaneously. Pretreatment with (+)-pentazocine, a selective sigma receptor agonist, (1-10 mg/kg) given subcutaneously also attenuates (-)-morphine-produced tail-flick inhibition, which was restored by (+)-naloxone (4 mg/kg) or BD1047 (10 mg/kg) pretreated subcutaneously. It is concluded that (+)morphine exhibits extremely high stereoselective action over (-)-morphine given systemically in attenuating the systemic (-)-morphine-produced antinociception and the antianalgesic effect of (+)-morphine and (-)-morphine is mediated by activation of the naloxone-sensitive sigma receptor. (C) 2007 Elsevier B.V. All rights reserved. C1 Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA. NIEHS, NIH, Neuropharmacol Sect, Chem Pharmacol Lab, Res Triangle Pk, NC 27709 USA. RP Tseng, LF (reprint author), Med Coll Wisconsin, Dept Anesthesiol, Med Educ Bldg,Room M4308,8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM ltseng@mcw.edu FU Intramural NIH HHS; NIDA NIH HHS [DA12588, K01 DA024751, R01 DA012588, R01 DA012588-05] NR 18 TC 17 Z9 18 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 1 PY 2007 VL 571 IS 2-3 BP 145 EP 151 DI 10.1016/j.ejphar.2007.06.012 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 218VN UT WOS:000250043400009 PM 17617400 ER PT J AU Beesdo, K Bittner, A Pine, DS Stein, MB Hofler, M Lieb, R Wittchen, HU AF Beesdo, K. Bittner, A. Pine, D. S. Stein, M. B. Hoefler, M. Lieb, R. Wittchen, H. U. TI Social anxiety disorder: patterns of incidence and secondary depression risk SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol ID ADOLESCENTS C1 [Beesdo, K.; Bittner, A.; Hoefler, M.; Wittchen, H. U.] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-8027 Dresden, Germany. [Pine, D. S.] NIMH, Sect Emot Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Stein, M. B.] Univ Calif San Diego, Dept Psychiat, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Lieb, R.] Univ Basel, CH-4003 Basel, Switzerland. RI Beesdo-Baum, Katja/A-5793-2012; Wittchen, Hans-Ulrich/A-8507-2014 NR 3 TC 2 Z9 2 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S511 EP S512 DI 10.1016/S0924-977X(07)70788-5 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231901196 ER PT J AU Blair, R Finger, E Marsh, A AF Blair, R. Finger, E. Marsh, A. TI Neurocognition and neuroimaging in children with conduct disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol C1 [Blair, R.; Finger, E.; Marsh, A.] Natl Inst Hlth, Mood & Anxiety Disorders Program, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S175 EP S176 DI 10.1016/S0924-977X(07)70170-0 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231900007 ER PT J AU Elkashef, A Newton, T De la Garza, R Reid, M Mojsiak, J AF Elkashef, A. Newton, T. De la Garza, R. Reid, M. Mojsiak, J. TI Aripirazole for methamphetamine dependence; a phase I human safety study SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol ID D-AMPHETAMINE; ARIPIPRAZOLE C1 [Elkashef, A.] NIMH, Dept Hlth & Human Serv, Div Treatment Res, Bethesda, MD 20892 USA. [Newton, T.; De la Garza, R.] David Geffen Sch Med, Los Angeles, CA USA. [Reid, M.] NYU, Sch Med, New York, NY USA. [Mojsiak, J.] NIDA, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S550 EP S551 DI 10.1016/S0924-977X(07)70854-4 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231901262 ER PT J AU Mazzola, C Medalie, J Panlilio, L Solinas, M Drago, F Goldberg, S Yasar, S AF Mazzola, C. Medalie, J. Panlilio, L. Solinas, M. Drago, F. Goldberg, S. Yasar, S. TI URB597, fatty acid amide hydrolase inhibitor, improves long-term memory retention by PPARalpha and not by cannabinoid CB1 receptors SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol C1 [Mazzola, C.; Drago, F.] Univ Catania, Sch Med, Dept Expt Clin Pharmacol, Catania, Italy. [Medalie, J.; Panlilio, L.; Goldberg, S.] NIDA, NIH, IRP,Preclin Pharmacol Sect, Behav Neurosci Res Branch, Baltimore, MD USA. [Solinas, M.] Univ Poitiers, Lab Biol & Physiol Cellulaires, Poitiers, France. [Yasar, S.] Johns Hopkins Sch Med, Div Geriatr Med, Baltimore, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S251 EP S251 DI 10.1016/S0924-977X(07)70340-1 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231900177 ER PT J AU Vocci, F AF Vocci, F. TI Antabuse and modafinil in psycho stimulant abuse treatment SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol ID PLACEBO-CONTROLLED TRIAL C1 [Vocci, F.] NIMH, Div Pharmacotherapies & Med Consequences Drug A, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S183 EP S183 DI 10.1016/S0924-977X(07)70191-8 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231900028 ER PT J AU Zarate, C AF Zarate, C. TI Glutamate modulators in treatment resistant depression SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol ID MAJOR DEPRESSION; TRIAL C1 [Zarate, C.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S177 EP S178 DI 10.1016/S0924-977X(07)70176-1 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231900013 ER PT J AU Di Lorenzo, G Autorino, R Perdona, S De Laurentiis, M D'Armiento, M Cancello, G Mirone, V Imbimbo, C Longo, N Altieri, V Tortora, G Figg, WD De Placido, S AF Di Lorenzo, Giuseppe Autorino, Riccardo Perdona, Sisto De Laurentiis, Michele D'Armiento, Massimo Cancello, Giuseppe Mirone, Vincenzo Imbimbo, Ciro Longo, Nicola Altieri, Vincenzo Tortora, Gianpaolo Figg, William D. De Placido, Sabino TI Docetaxel, vinorelbine, and zoledronic acid as first-line treatment in patients with hormone refractory prostate cancer: A phase II study SO EUROPEAN UROLOGY LA English DT Article DE chemotherapy hormone refractory prostate cancer; prostate-specific antigen; toxicity ID ONCOLOGY GROUP; ESTRAMUSTINE PHOSPHATE; CLINICAL BENEFIT; CELL-LINES; IN-VITRO; CHEMOTHERAPY; CARCINOMA; TRIAL; COMBINATIONS; MITOXANTRONE AB Objectives: Combining antineoplastic agents is the key to improving the treatment options for men with hormone refractory prostate cancer (HRPC). The current study investigated the combination of docetaxel, vinorelbine, and zoledronic acid as a first-line treatment for HRPC. Methods: Patients were treated repeatedly with docetaxel (25 mg/mq) and vinorelbine (10 mg/mq) intravenously for three consecutive weeks followed by a 1-wk rest until disease progression or side effects. Zoledronic acid was administered every 4 wk. Changes in prostate- specific antigen (PSA) levels and objective responses were evaluated after two and three cycles, respectively. Toxicity and pain evaluation, based on pain intensity reduction and analgesic drug reduction, were assessed every cycle. Results: Forty men with HRPC (median age: 65 yr) were treated. Among 38 evaluable patients, complete and major PSA responses were observed in seven (18%) and 12 (32%), respectively; a partial objective response was observed in six of 15 (40%) patients with measurable disease. Neutropenia (25%) was the most important grade 3 haematologic toxicity observed. Only three patients (7.5%) reported grade 4 neutropenia. Nineteen patients (47.5%) achieved a reduction of pain intensity and analgesic drug use after two cycles. Median progression-free survival was 7 mo (95% CI: 2-10 mo), with a median overall survival of 17 mo (95% Cl: 6-22 mo). Conclusions: The combination of docetaxel, vinorelbine, and zoledronic acid is associated with improvement in biochemical, objective, and pain responses and is well tolerated as a first-line treatment for HRPC. C1 Univ Naples Federico 2, Dipartimento Endocrinol & Oncol Mol & Clin, Cattedra Oncol Med, Naples, Italy. Univ Naples 2, Urol Clin, Naples, Italy. Ist Nazl Tumori, Fdn G Pascale, UO Urol, Naples, Italy. Univ Naples Federico 2, Urol Clin, Naples, Italy. NCI, Mol Pharmacol Sect, Med Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Di Lorenzo, G (reprint author), Univ Naples Federico 2, Dipartimento Endocrinol & Oncol Mol & Clin, Cattedra Oncol Med, Naples, Italy. EM giuseppedilorenzoncol@hotmail.com OI Tortora, Giampaolo/0000-0002-1378-4962; MIRONE, Vincenzo/0000-0002-7639-2560 NR 34 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD OCT PY 2007 VL 52 IS 4 BP 1020 EP 1027 DI 10.1016/j.eururo.2007.02.060 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 215GZ UT WOS:000249797600016 PM 17360103 ER PT J AU Seppala, EH Autio, V Duggal, P Ikonen, T Stenman, UH Auvinen, A Bailey-Wilson, JE Tammela, TLJ Schleutker, J AF Seppala, Eija H. Autio, Ville Duggal, Priya Ikonen, Tarja Stenman, Ulf-Hakan Auvinen, Anssi Bailey-Wilson, Joan E. Tammela, Teuuo L. J. Schleutker, Johanna TI KLF6 IVS1 -27G > A variant and the risk of prostate cancer in Finland SO EUROPEAN UROLOGY LA English DT Article DE association study; benign prostate hyperplasia; cancer susceptibility; KLF6; prostate cancer ID TUMOR-SUPPRESSOR GENE; CELL-LINES; MUTATIONS; ABSENCE; GLIOBLASTOMAS; TRIAL AB Objectives: A recent report demonstrated that KLF6 IVS1 -27G > A substitution increases the transcription of alternatively spliced isoforms; this action was suggested to be associated with prostate cancer (pCA). To evaluate these findings among the Finnish population, a total of 3348 samples were analysed. Methods: The variant was genotyped in 164 patients with familial pCA, 852 patients with unselected pCA, 459 patients with benign prostate hyperplasia (BPH), 923 male population controls, and 950 men from a Finnish prostate- specific antigen (PSA) screening trial with PSA levels less than 1.0 ng/ml. Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated by using logistic regression to estimate pCA risk. Results: Association testing revealed no significant differences between familial prostate cancer patients and population controls (OR: 0.84; 95%CI, 0.56-1.28; p = 0.42), unselected cases and controls (OR: 0.95; 95%CI, 0.76-1.19; p = 0.63), or BPH cases and controls (OR: 1.12; 95%CI, 0.86-1.46; p = 0.39). pCA and BPH cases were also compared with PSA-screened controls. None of these analyses revealed any significant associations. Conclusion: Our results do not support the suggested association of KLF6 IVS1 -27G > A germline polymorphism with pCA risk and also suggest that the variant is not a risk allele for BPH in the Finnish population. C1 Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33014 Tampere, Finland. Tampere Univ Hosp, Res Unit, Tampere, Finland. NIH, NHGRI, Baltimore, MD USA. Univ Helsinki, Cent Hosp, Dept Clin Chem, FIN-00014 Helsinki, Finland. Finnish Canc Inst, Helsinki, Finland. Tampere Univ Hosp, Dept Urol, Tampere, Finland. Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. RP Schleutker, J (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33014 Tampere, Finland. EM Johanna.Schleutker@uta.fi OI Bailey-Wilson, Joan/0000-0002-9153-2920; Auvinen, Anssi/0000-0003-1125-4818 FU Intramural NIH HHS NR 22 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD OCT PY 2007 VL 52 IS 4 BP 1076 EP 1081 DI 10.1016/j.eururo.2006.11.019 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 215GZ UT WOS:000249797600023 PM 17125911 ER PT J AU Wetherington, CL AF Wetherington, Cora Lee TI Sex-gender differences in drug abuse: A shift in the burden of proof? SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE drug abuse; sex differences; gender differences; women; conclusion errors ID MENSTRUAL-CYCLE; COCAINE; RATS; VULNERABILITY; FEMALE; REINSTATEMENT; REPLACEMENT; ESTROGEN; WOMEN AB In the early years of NIDA-supported drug abuse research, much of the research on women was treatment related and conducted out of concern for their pregnancy status. Since then, drug abuse research on women has expanded to include females of all ages, including infants, children, and adolescents, both human and animal. This expansion has also extended to the study of male-female differences. In the early years of the expansion, National Institutes of Health study sections demanded a heavy burden of proof from drug abuse researchers who proposed to study male-female differences. The need for such research appeared not to have face validity. The tide has now changed with the growing body of literature attesting to its scientific and clinical validity. This change is often reflected in concerns expressed in study sections reviewing drug abuse grant applications that an applicant does not propose to analyze the data for sex-gender differences when in fact the literature suggests that such differences would be observed. Although the change has been slow, it suggests that the burden of proof is shifting from having to defend why sex-gender differences should be studied to having to defend why they should not. C1 Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. RP Wetherington, CL (reprint author), Natl Inst Drug Abuse, NIH, 6001 Execut Blvd,Room 4282,MSC 9555, Bethesda, MD 20892 USA. EM wetherington@nih.gov NR 27 TC 33 Z9 33 U1 1 U2 6 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD OCT PY 2007 VL 15 IS 5 BP 411 EP 417 DI 10.1037/1064-1297.15.5.411 PG 7 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 218VO UT WOS:000250043500001 PM 17924775 ER PT J AU Kochenderfer, JN Gress, RE AF Kochenderfer, J. N. Gress, R. E. TI A comparison and critical analysis of preclinical anticancer vaccination strategies SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review DE vaccination; tumor immunity; peptides; cytokines; T cells; adoptive T-cell therapy; CpG oligodeoxynucleotides ID CD8(+) T-CELLS; TYROSINASE-RELATED PROTEIN-2; COLONY-STIMULATING FACTOR; CPG-CONTAINING OLIGODEOXYNUCLEOTIDES; VIVO ANTITUMOR EFFICACY; TUMOR REJECTION ANTIGEN; DENDRITIC CELLS; METASTATIC MELANOMA; IN-VIVO; B16 MELANOMA AB Anticancer vaccines have been extensively studied in animal models and in clinical trials. While vaccination can lead to tumor protection in numerous murine models, objective tumor regressions after anticancer vaccination in clinical trials have been rare. B16 is a poorly immunogenic murine melanoma that has been extensively used in anticancer vaccination experiments. Because B16 has been widely used, different vaccination strategies can be compared. We reviewed the results obtained when B16 was treated with five common vaccine types: recombinant viral vaccines, DNA vaccines, dendritic cell vaccines, whole-tumor vaccines, and peptide vaccines. We also reviewed the results obtained when B16 was treated with vaccines combined with adoptive transfer of tumor antigen-specific T cells. We found several characteristics of vaccination regimens that were associated with antitumor efficacy. Many vaccines that incorporated xenogeneic antigens exhibited more potent anticancer activity than vaccines that were identical except that they incorporated the syngeneic version of the same antigen. Interleukin-2 enhanced the antitumor efficacy of several vaccines. Finally, several effective regimens generated large numbers of tumor antigen-specific CD8(+) T cells. Identification of vaccine characteristics that are associated with antitumor efficacy may aid in the development of more effective anticancer vaccination strategies. C1 NIH, Natl Canc Inst, Expt Transplant & Immunol Branch, Bethesda, MD 20892 USA. RP Kochenderfer, JN (reprint author), NIH, Natl Canc Inst, Expt Transplant & Immunol Branch, 10 Ctr Dr,CRC 3-3288, Bethesda, MD 20892 USA. EM kochendj@mail.nih.gov NR 64 TC 0 Z9 0 U1 1 U2 1 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD OCT PY 2007 VL 232 IS 9 BP 1128 EP 1139 DI 10.3181/0702-MR-42 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 216OL UT WOS:000249887500002 ER PT J AU Bundoc, VG Keane-Myers, A AF Bundoc, Virgilio G. Keane-Myers, Andrea TI IL-10 confers protection from mast cell degranulation in a mouse model of allergic conjunctivitis SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE allergic conjunctivitis; mast cell; mouse model; Compound 48/80 ID BETA-HEXOSAMINIDASE; DIRECT ACTIVATION; NITRIC-OXIDE; EXPRESSION; RELEASE; INTERLEUKIN-10; HISTAMINE; INHIBITION; CYTOKINE; PROTEINS AB IL-10 is a regulatory cytokine known to inhibit allergic and inflammatory events. Mast cells (MC) are effector cells which when stimulated release histamine, chemokines and cytokines that initiate the allergic inflammatory response. Recent studies have shown that IL-10 regulates MC function by affecting cytokine production and expression of Fc epsilon R1 in in vitro assays. Using IL-10 knockout (IL10KO) mice, we examined the effect of its absence on MC susceptibility to degranulation by the basic secretagogue, Compound 48/80 (C48/80). C48/80 is a receptor mimetic that directly activates G proteins and stimulates vigorous MC degranulation. For these studies we stimulated conjunctival MC with C48/80 and found that conjunctival MC of IL10KO mice exhibit increased degranulation compared with wild type mice. Reconstitution of IL10KO mice by adding rIL-10 24 h prior to challenge with C48/80 conferred increased resistance of MC to the degranulatory effects of C48/80. The protective effect therefore appears to be due to the presence of IL-10. This is the first in vivo rodent study which reports a novel role of IL-10 in stabilizing mast cells from degranulation by a secretagogue, by as of yet an unknown mechanism. (C) 2007 Published by Elsevier Ltd. C1 NIAID, NIH, Allerg Inflammat Sect, Lab Allerg Dis, Rockville, MD 20852 USA. RP Keane-Myers, A (reprint author), NIAID, NIH, Allerg Inflammat Sect, Lab Allerg Dis, 12441 Parklawn Dr,TW2 Bldg,Room 125, Rockville, MD 20852 USA. EM akeane@niaid.nih.gov NR 34 TC 19 Z9 23 U1 0 U2 0 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 OCT PY 2007 VL 85 IS 4 BP 575 EP 579 DI 10.1016/j.exer.2007.07.005 PG 5 WC Ophthalmology SC Ophthalmology GA 228FM UT WOS:000250713000020 PM 17765892 ER PT J AU Scroggins, BT Neckers, L AF Scroggins, Bradley T. Neckers, Len TI Post-translational modification of heat-shock protein 90: impact on chaperone function SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE acetylation; cancer; heat-shock protein; Hsp90; molecular chaperone; phosphorylation; post-translational modification; ubiquitinylation AB Heat-shock protein 90 (Hsp90) is a molecular chaperone required for the stability and function of many signaling proteins that are often activated, mutated or overexpressed in cancer cells and that underly cancer cell proliferation and survival. Hsp90 is a conformationally flexible protein that associates with a distinct set of cochaperones depending on ATP or ADP occupancy of an N-terminal binding pocket. Nucleotide exchange and ATP hydrolysis by Hsp90 itself, with the assistance of cochaperones, drive the Hsp90 chaperone machine to bind, chaperone and release client proteins. Cycling of the Hsp90 chaperone machine is critical to its function. Although ATP binding and hydrolysis have been convincingly implicated in regulating the Hsp90 cycle, growing evidence suggests that various post-translational modifications of Hsp90, including phosphorylation, acetylation and other modifications, provide an additional overlapping or parallel level of regulation. A more complete understanding of how these various protein modifications are regulated and interact with each other at the cellular level to modulate Hsp90 chaperone activity is critical to the design of novel approaches to inhibit this medically important molecular target. C1 [Scroggins, Bradley T.; Neckers, Len] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Bldg 10 CRC,Room 1-5940,9000 Rockville Pike, Bethesda, MD 20892 USA. EM len@helix.nih.gov NR 86 TC 24 Z9 24 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1746-0441 J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD OCT PY 2007 VL 2 IS 10 BP 1403 EP 1414 DI 10.1517/17460441.2.10.1403 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V12RW UT WOS:000207617300009 PM 23484535 ER PT J AU Chiou, CC Walsh, TJ Groll, AH AF Chiou, Christine C. Walsh, Thomas J. Groll, Andreas H. TI Clinical pharmacology of antifungal agents in pediatric patients SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE amphotericin; anidulafungin; antifungal agent; caspofungin; children; fluconazole; flucytosine; itraconazole; micafungin; mycoses; pharmacology; posaconazole; voriconazole ID LIPOSOMAL AMPHOTERICIN-B; INVASIVE FUNGAL-INFECTIONS; BIRTH-WEIGHT INFANTS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ITRACONAZOLE ORAL SOLUTION; STEM-CELL TRANSPLANTATION; MULTIPLE-DOSE PHARMACOKINETICS; AZOLE-REFRACTORY OROPHARYNGEAL; MULTICENTER RANDOMIZED-TRIAL; BONE-MARROW TRANSPLANTATION AB Invasive fungal infections have emerged as important causes of morbidity and mortality in profoundly immunocompromised children including cancer, transplant and intensive care unit patients. Present treatment strategies for these infections are limited by toxicity, drug interactions and expense. In order to overcome these limitations, new antifungal compounds are being developed, which may improve the therapeutic armamentarium for prevention and treatment of invasive mycoses in high-risk children. This article summarizes the clinical pharmacology of established and newly developed antifungal agents, including new triazoles and echinocandins in pediatric age groups. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Childrens Univ Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, Dept Pediat Hematol Oncol, D-48129 Munster, Germany. RP Groll, AH (reprint author), Childrens Univ Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, Dept Pediat Hematol Oncol, Albert Schweitzer Str 33, D-48129 Munster, Germany. EM grollan@ukmuenster.de RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 202 TC 12 Z9 13 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD OCT PY 2007 VL 8 IS 15 BP 2465 EP 2489 DI 10.1517/14656566.8.15.2465 PG 25 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 224DK UT WOS:000250426000003 PM 17931084 ER PT J AU Davies, KJA Ermak, G Rothermel, BA Pritchard, M Heitman, J Ahnn, J Henrique-Silva, F Crawford, D Canaider, S Strippoli, P Carinci, P Min, KT Fox, DS Cunningham, KW Bassel-Duby, R Olson, EN Zhang, Z Williams, RS Gerber, HP Perez-Riba, M Seo, H Cao, X Klee, CB Redondo, JM Maltais, LJ Bruford, EA Povey, S Molkentin, JD McKeon, FD Duh, EJ Crabtree, GR Cyert, MS de la Luna, S Estivill, X AF Davies, Kelvin J. A. Ermak, Gennady Rothermel, Beverley A. Pritchard, Melanie Heitman, Joseph Ahnn, Joohong Henrique-Silva, Flavio Crawford, Dana Canaider, Silvia Strippoli, Pierluigi Carinci, Paolo Min, Kyung-Tai Fox, Deborah S. Cunningham, Kyle W. Bassel-Duby, Rhonda Olson, Eric N. Zhang, Zhuohua Williams, R. Sanders Gerber, Hans-Peter Perez-Riba, Merce Seo, Hisao Cao, Xia Klee, Claude B. Redondo, Juan Miguel Maltais, Lois J. Bruford, Elspeth A. Povey, Sue Molkentin, Jeffery D. McKeon, Frank D. Duh, Elia J. Crabtree, Gerald R. Cyert, Martha S. de la Luna, Susana Estivill, Xavier TI Renaming the DSCR1/Adapt78 gene family as RCAN: regulators of calcineurin SO FASEB JOURNAL LA English DT Article DE calcipressin; oxidative stress; Down syndrome; Alzheimer disease; MCIP; NFAT ID SYNDROME CRITICAL REGION; DOWN-SYNDROME; DSCR1 ADAPT78; INHIBITS CALCINEURIN; ALZHEIMERS-DISEASE; IN-VIVO; PHOSPHATASE CALCINEURIN; CRYPTOCOCCUS-NEOFORMANS; INTERACTING PROTEIN-1; ENDOGENOUS INHIBITOR C1 Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Los Angeles, CA 90089 USA. Univ So Calif, Div Mol & Computat Biol, Los Angeles, CA 90089 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75230 USA. Monash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, Australia. Duke Univ, Med Ctr, Dept Mol Genet, Durham, NC USA. Duke Univ, Med Ctr, Dept Microbiol, Durham, NC 27710 USA. Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea. Univ Fed Sao Carlos, Dept Genet & Evolut, Sao Carlos, SP, Brazil. Albany Med Coll, Ctr Immunol & Microbial Dis, Albany, NY 12208 USA. Univ Bologna, Dept Histol Embryol & Appl Biol, Bologna, Italy. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Res Inst Children, New Orleans, LA USA. Childrens Hosp, Louisiana State Hlth Sci Ctr, Dept Pediat, New Orleans, LA USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75230 USA. Burnham Inst, Ctr Neurosci & Aging, La Jolla, CA 92037 USA. Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA. Inst Recerca Oncol, IDIBELL, Med & Mol Genet Ctr, Barcelona, Spain. Nagoya Univ, Environm Med Res Inst, Div Mol & Cellular Adaptat, Dept Endocrinol & Metab,Chikusa Ku, Nagoya, Aichi 464, Japan. NCI, Biochem Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. CNIC, Madrid, Spain. Jackson Lab, MGI, Mouse Genom Nomenclature Comm, Bar Harbor, ME 04609 USA. UCL, Dept Biol, Galton Lab, HUGO Gene Nomenclature Comm, London, England. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. ICREA, Barcelona, Spain. CRG, Genes & Dis Program, Gene Funct Grp, Barcelona, Spain. CRG, CeGen Barcelona Genotyping Node, Barcelona, Catalonia, Spain. Pompeu Fabra Univ, Dept Life Sci, Barcelona, Catalonia, Spain. RP Davies, KJA (reprint author), Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Los Angeles, CA 90089 USA. EM kelvin@usc.edu RI Estivill, Xavier/E-2957-2012; Henrique-Silva, Flavio/A-1937-2013; Estivill, Xavier/A-3125-2013; de la Luna, Susana/E-9553-2015; Redondo, Juan Miguel/H-6351-2015; OI Estivill, Xavier/0000-0002-0723-2256; de la Luna, Susana/0000-0001-7765-916X; Redondo, Juan Miguel/0000-0001-5779-9122; min, kyung-tai/0000-0003-0983-4258; Bruford, Elspeth/0000-0002-8380-5247 NR 51 TC 92 Z9 95 U1 2 U2 16 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 OCT PY 2007 VL 21 IS 12 BP 3023 EP 3028 DI 10.1096/fj.06-7246com PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 215BE UT WOS:000249781600004 PM 17595344 ER PT J AU Jia, SJ Omelchenko, M Garland, D Vasiliou, V Kanungo, J Spencer, M Wolf, Y Koonin, E Piatigorsky, J AF Jia, Sujuan Omelchenko, Marina Garland, Donita Vasiliou, Vasilis Kanungo, Jyotshnabala Spencer, Michael Wolf, Yuri Koonin, Eugene Piatigorsky, Joram TI Duplicated gelsolin family genes in zebrafish: a novel scinderin-like gene (scinla) encodes the major corneal crystallin SO FASEB JOURNAL LA English DT Article DE gene duplication; evolution; tissue-specific expression ID ACTIN-BINDING PROTEINS; FILAMENT-SEVERING PROTEIN; CHROMAFFIN CELL SCINDERIN; RAY-FINNED FISHES; GENOME DUPLICATION; LENS CRYSTALLINS; ALDEHYDE DEHYDROGENASE; RECOMBINANT SCINDERIN; REGULATORY PROTEIN; ANABLEPS-ANABLEPS AB We have previously identified a gelsolin-like protein ( C/L-gelsolin) as a corneal crystallin in zebrafish. Here we show by phylogenetic analysis that there are at least six genes encoding gelsolin-like proteins based on their gelsolin domains in zebrafish: gsna and gsnb group with the vertebrate gelsolin gene, scina and scinb group with the scinderin ( adseverin) gene, and scinla ( C/L-gelsolin) and scinlb are novel scinderin-like genes. RT-PCR showed that scinla, scinlb, and gsnb are preferentially expressed in the adult cornea whereas gsna is expressed to a similar extent in cornea, lens, brain, and heart; scina and scinb expression were detectable only in whole zebrafish and not in these adult tissues. Quantitative RT-PCR and 2-dimensional polyacrylamide gel electrophoresis followed by MALDI/TOF mass spectroscopy confirmed high expression of beta-actin and scinla, moderate expression of scinlb, and very low expression of gsna and gsnb in the cornea. Finally, transgenic zebrafish carrying a green fluorescent protein reporter transgene driven by a 4 kb scinla promoter fragment showed expression in the cornea, snout, dorsal fin, and tail fin of 3-day-old zebrafish larvae. Our data suggest that scinla and scinlb are diverged paralogs of the vertebrate scinderin gene and show that scinla encodes the zebrafish corneal crystallin previously called C/L-gelsolin. - Jia, S., Omelchenko, M., Garland, D., Vasiliou, V., Kanungo, J., Spencer, M., Wolf, Y., Koonin, E., Piatigorsky, J. Duplicated gelsolin family genes in zebrafish: a novel scinderin-like gene ( scinla) encodes the major corneal crystallin. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Retinal Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. NIH, Natl Lib Med, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Sch Pharm, Denver, CO 80262 USA. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, NIH, 7 Mem Dr,Bldg 7,Rm 100, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov FU NEI NIH HHS [EY11490] NR 70 TC 14 Z9 16 U1 2 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 OCT PY 2007 VL 21 IS 12 BP 3318 EP 3328 DI 10.1096/fj.07-8172com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 215BE UT WOS:000249781600032 PM 17548429 ER PT J AU Appella, E Anderson, CW AF Appella, Ettore Anderson, Carl W. TI Introduction: Post-translational modifications - S-palmitoylation, proline isomerization, disulfide bond isomerization SO FEBS JOURNAL LA English DT Editorial Material C1 NIH, Natl Canc Inst, Cell Biol Lab, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Appella, E (reprint author), NIH, Natl Canc Inst, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD OCT PY 2007 VL 274 IS 20 BP 5201 EP 5201 DI 10.1111/j.1742-4658.2007.06055.x PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 216MP UT WOS:000249882400001 ER PT J AU Peng, D Hu, WG Choudhury, BP Muszynski, A Carlson, RW Gu, XX AF Peng, Daxin Hu, Wei-Gang Choudhury, Biswa P. Muszynski, Artur Carlson, Russell W. Gu, Xin-Xing TI Role of different moieties from the lipooligosaccharide molecule in biological activities of the Moraxella catarrhalis outer membrane SO FEBS JOURNAL LA English DT Article DE lipooligosaccharide; moiety; Moraxella catarrhalis; outer membrane; role ID OBSTRUCTIVE PULMONARY-DISEASE; PHARYNGEAL EPITHELIAL-CELLS; BRANHAMELLA-CATARRHALIS; IMMUNE-RESPONSE; NEISSERIA-MENINGITIDIS; HAEMOPHILUS-INFLUENZAE; ACID TRANSFERASE; SERUM RESISTANCE; SEROTYPE-A; PROTEIN AB Lipooligosaccharide (LOS), a major component of the outer membrane of Moraxella catarrhalis, consists of two major moieties: a lipid A and a core oligosaccharide (OS). The core OS can be dissected into a linker and three OS chains. To gain an insight into the biological activities of the LOS molecules of M. catarrhalis, we used a random transposon mutagenesis approach with an LOS specific monoclonal antibody to construct a serotype A O35Elgt3 LOS mutant. MALDI-TOF-MS of de-O-acylated LOS from the mutant and glycosyl composition, linkage, and NMR analysis of its OS indicated that the LOS contained a truncated core OS and consisted of a Glc-Kdo(2) (linker)-lipid A structure. Phenotypic analysis revealed that the mutant was similar to the wild-type strain in its growth rate, toxicity and susceptibility to hydrophobic reagents. However, the mutant was sensitive to bactericidal activity of normal human serum and had a reduced adherence to human epithelial cells. These data, combined with our previous data obtained from mutants which contained only lipid A or lacked LOS, suggest that the complete OS chain moiety of the LOS is important for serum resistance and adherence to epithelial cells, whereas the linker moiety is critical for maintenance of the outer membrane integrity and stability to preserve normal cell growth. Both the lipid A and linker moieties contribute to the LOS toxicity. C1 Natl Inst Hlth, Natl Inst Deafness & Commun Disorders, Vaccine Res Sect, Rockville, MD USA. Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. RP Gu, XX (reprint author), 5 Res Court, Rm 2A31, Rockville, MD 20850 USA. EM guxx@nidcd.nih.gov OI Muszynski, Artur/0000-0003-3497-9977 FU Intramural NIH HHS NR 44 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD OCT PY 2007 VL 274 IS 20 BP 5350 EP 5359 DI 10.1111/j.1742-4658.2007.06060.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 216MP UT WOS:000249882400014 PM 17892485 ER PT J AU Scarpa, B Dunson, DB Giacchi, E AF Scarpa, Bruno Dunson, David B. Giacchi, Elena TI Bayesian selection of optimal rules for timing intercourse to conceive by using calendar and mucus SO FERTILITY AND STERILITY LA English DT Article DE Bayesian analysis; cervical mucus; conception; decision theory; fertility awareness; natural family planning; time to pregnancy ID URINARY HORMONE MEASUREMENTS; MENSTRUAL-CYCLE; FERTILE WINDOW; CERVICAL-MUCUS; ACHIEVE PREGNANCY; TWODAY ALGORITHM; OVULATION METHOD; CONCEPTION; PROBABILITY; INFERTILITY AB Objective: To find optimal clinical rules that maximize the probability of conception while limiting the number of intercourse days required. Design: Multicenter prospective study. Women were followed prospectively while they kept daily records of menstrual bleeding, intercourse, and mucus symptom characteristics. In some cycles, women sought to conceive, whereas in other cycles, they sought to avoid pregnancy. Setting: Four centers providing services on fertility awareness. Patient(s): One hundred ninety-one healthy women using the Billings Ovulation Method. Women were invited to enroll by their instructors if they satisfied the entry criteria. We excluded cycles in which mucus was not recorded on a day with intercourse. Intervention(s): None. Main Outcome Measure(s): Clinically identified pregnancies. There were 161 clinically identified pregnancies in 2,536 menstrual cycles from 191 women. Result(s): Our approach relies on a statistical model that relates daily predictors, such as type of mucus symptom, to the day-specific probabilities of conception. By using Bayesian methods to search over a large set of possible clinical rules, focusing on rules based on calendar and mucus, we found that simple rules that are based on days within the midcycle calendar interval that also have the most fertile-type mucus symptom present have high utility. Conclusion(s): Couples can shorten their time to pregnancy efficiently by timing intercourse on days that the most fertile-type mucus symptom is observed at the vulva. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ Padua, Dept Stat Sci, Padua, Italy. Univ Cattolica Sacro Cuore, Ctr Study & Res Nat Fertil Regulat, I-00168 Rome, Italy. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov NR 58 TC 6 Z9 7 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2007 VL 88 IS 4 BP 915 EP 924 DI 10.1016/j.fertnstert.2006.12.017 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 220YI UT WOS:000250192800023 PM 17601602 ER PT J AU Wittenberger, MD Catherino, WH Armstrong, AY AF Wittenberger, Michael D. Catherino, William H. Armstrong, Alicia Y. TI Role of embryo transfer in fellowship training SO FERTILITY AND STERILITY LA English DT Editorial Material ID INVITRO FERTILIZATION; PREGNANCY RATES; PROGRAM AB Our objective was to survey training in ET techniques among fellows, its perceived importance, and potential barriers to ET training during fellowship. Although ET training remains an important issue for most fellows and recent graduates, 44% of respondents did not receive this training during their fellowship. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. RP Armstrong, AY (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, E-3140,CRC 10 Ctr Dr, Bethesda, MD 20892 USA. EM aa257w@nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 10 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2007 VL 88 IS 4 BP 1014 EP 1015 DI 10.1016/j.fertnstert.2006.12.086 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 220YI UT WOS:000250192800043 PM 17412339 ER PT J AU Catherino, WH Mayers, CM Mantzouris, T Armstrong, AY Linehan, M Segars, JH AF Catherino, William H. Mayers, Chantal M. Mantzouris, Tammy Armstrong, Alicia Y. Linehan, Marston Segars, James H. TI Compensatory alterations in energy homeostasis characterized in uterine tumors from hereditary leiomyomatosis and renal cell cancer SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the American-Society-for-Reproductive-Medicine/51st Annual Meeting of the Canadian-Fertility-and-Andrology-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc DE hereditary leiomyomatosis and renal cell cancer; fumarate hydratase; leiomyoma; glycolysis; enolase; aldolase; pyruvate kinase; Krebs cycle ID DIFFERENTIALLY EXPRESSED GENES; FUMARASE DEFICIENCY; HYPOXIA; MUTATIONS; FIBROIDS; FH; ACTIVATION; ENCEPHALOPATHY; MITOCHONDRIAL; GLYCOLYSIS AB Objective: To determine the molecular alterations that maintain energy homeostasis in hereditary leiomyomatosis and renal cell cancer (HLRCC) uterine tumors with disrupted fumarate hydratase, compared with nonsyndromic uterine tumors. Design: Laboratory study. Setting: Tertiary academic university hospital. Patient(S): Eleven nonsyndromic leiomyoma-myometrium pairs and three HLRCC leiomyoma-myometrium pairs were obtained from patients who were recruited at national and military research centers in the United States. Intervention(s): Molecular analysis. Main Outcome Measure(S): Hereditary leiomyomatosis and renal cell cancer and nonsyndromic leiomyomas were compared with patient-matched myometrium for relative glycolysis and Krebs cycle gene expression. Result(s): By microarray analysis, we confirmed that fumarate hydratase messenger RNA (mRNA) was underexpressed in HLRCC fibroids, compared with matched myometrium. Consistent with the possibility that alterations in fumarate hydratase represented a change to a more anaerobic state, we found that HLRCC fibroids overexpressed genes such as phosphofructokinase, aldolase, phosphoglycerate kinase, enolase, and pyruvate kinase. Ex pression of these genes was not altered in nonsyndromic leiomyomas. Furthermore, there were no overt changes in expression of Krebs cycle enzyme gene expression, with the exception of fumarate hydratase. Conclusion(s): Our findings demonstrate that alterations in fumarate hydratase are compensated for by increases in glycolysis enzyme expression in HLRCC. (C)2007 by American Society for Reproductive Medicine. C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM catheriw@mail.nih.gov FU Intramural NIH HHS NR 42 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2007 VL 88 SU 2 BP 1039 EP 1048 DI 10.1016/j.fertnstert.2006.11.198 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 222XO UT WOS:000250331900003 PM 17383644 ER PT J AU Otto, M AF Otto, Michael TI Community-associated MRSA: a dangerous epidemic SO FUTURE MICROBIOLOGY LA English DT Editorial Material ID RESISTANT STAPHYLOCOCCUS-AUREUS; PANTON-VALENTINE LEUKOCIDIN C1 NIAID, NIH, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. RP Otto, M (reprint author), NIAID, NIH, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 NR 6 TC 10 Z9 10 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 J9 FUTURE MICROBIOL JI Future Microbiol. PD OCT PY 2007 VL 2 IS 5 BP 457 EP 459 DI 10.2217/17460913.2.5.457 PG 3 WC Microbiology SC Microbiology GA 224UD UT WOS:000250471100001 PM 17927464 ER PT J AU Nguyen, DD Maillard, MH Cotta-De-Almeida, V Mizoguch, E Klein, C Fuss, I Nagler, C Mizoguch, A Bhan, AK Snapper, SB AF Nguyen, Deanna D. Maillard, Michel H. Cotta-De-Almeida, Vinicius Mizoguch, Emiko Klein, Christoph Fuss, Ivan Nagler, Cathryn Mizoguch, Atsushi Bhan, Atul K. Snapper, Scott B. TI Lymphocyte-dependent and Th2 cytokine-associated colitis in mice deficient in Wiskott-Aldrich syndrome protein SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; ULCERATIVE-COLITIS; INTESTINAL INFLAMMATION; OXAZOLONE COLITIS; MURINE MODEL; IFN-GAMMA; IN-VITRO; INNATE; ANTIGEN AB Background & Aims: Controversy exists as to whether patients with inflammatory bowel disease have an underlying immunodeficiency. We have focused on a murine model of the Wiskott-Aldrich syndrome, an immunodeficiency in which autoimmunity can manifest in the form of an inflammatory bowel disease-like illness. Wiskott-Aldrich syndrome protein (WASP) deficiency in mice results in similar clinical features. Herein, we characterized the colitis in WASP-deficient mice. Methods: WASP-deficient mice were followed clinically and histologically. Immunologic studies were performed to determine the pathogenic cell population(s), the predominant cytokine expression pattern, and the role of cytokine(s) in colitis pathogenesis. Results: All WASP-deficient mice develop colitis by 6 months of age. Lymphocytes are required for disease induction, and CD4(+) T cells from WASP-deficient mice are sufficient to induce disease in lymphocyte-deficient hosts. Lamina propria preparations from WASP-deficient mice demonstrated elevations in interferon-gamma, interleukin (IL)-4, and IL-13 levels but decreased IL-6 and no difference in IL-17 expression in comparison with vvild-type controls. Treatment with neutralizing antibody to IL-4, but not to interferon-gamma, abrogated colitis development. However, mice deficient in both WASP and IL-4 showed no difference in histologic colitis scores at 24 weeks of age compared with WASP-deficient mice. Conclusions: These results demonstrate a critical role for lymphocytes and a relative T helper 2 cytokine predominance in the colitis associated with WASP-deficient mice. This is the only model of colitis with elevated T helper 2 cytokines and aberrant natural regulatory T cell function and is unique in having a human disease counterpart with similar defects. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Lausanne Med Sch, Dept Med, Div Gastroenterol & Hepatol, Lausanne, Switzerland. Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Rio De Janeiro, Brazil. Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany. NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Snapper, SB (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,Jackson 825C, Boston, MA 02114 USA. EM ssnapper@hms.harvard.edu RI Cotta-de-Almeida, Vinicius/G-3939-2012 FU NHLBI NIH HHS [HL59561, P01 HL059561-10, P01 HL059561]; NIAID NIH HHS [R56 AI050950, R01 AI081807, AI50950, R01 AI050950, R01 AI050950-03]; NIDDK NIH HHS [DK74454, T32DK007191, T32 DK007191, R03 DK074454, P30 DK043351, DK64351, DK64289, DK55678, DK47677, K08 DK064289, R01 DK064351, R01 DK055678, R01 DK047677, P30 DK043351-17] NR 43 TC 40 Z9 40 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2007 VL 133 IS 4 BP 1188 EP 1197 DI 10.1053/j.gastro.2007.07.010 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 218SW UT WOS:000250036200016 PM 17764675 ER PT J AU Oki, M Ma, L Wang, Y Hatanaka, A Miyazato, C Tatebayashib, K Nishitani, H Uchida, H Nishirnoto, T AF Oki, Masaya Ma, Li Wang, Yoriggang Hatanaka, Akira Miyazato, Chic Tatebayashib, Kazuo Nishitani, Hideo Uchida, Hiroyuki Nishirnoto, Takeharu TI Identification of novel suppressors for Mog1 implies its involvement in RNA metabolism, lipid metabolism and signal transduction SO GENE LA English DT Article DE Cid13; Crp79; Ntf2p/Nxt2; Ran; Ssp1 ID RAN-BINDING-PROTEIN; SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; CRYSTAL-STRUCTURE; MESSENGER-RNA; FISSION YEAST; NUCLEAR IMPORT; NTF2; HOMOLOG; GENE AB Mog1 is conserved from yeast to mammal, but its function is obscure. We isolated yeast genes that rescued a temperature-sensitive death of S. cerevisiae Scmog1 Delta, and of S. pombe Spmog1(ts). Scmog1 Delta was rescued by Opi3p, a phospholipid N-methyltransferase, in addition to S. cerevisiae Ran-homologue Gsp1p, and a RanGDP binding protein Ntf2p. On the other hand, Spmog1(ts) was rescued by Cid13 that is a poly (A) polymerase specific for suc22(+) mRNA encoding a subunit of ribonucleotide reductase, SspI that is a protein kinase involved in stress response pathway, and Crp79 that is required for mRNA export, in addition to Spi1, S. pombe Ran-homologue, and Nxt2, S. pombe homologue of Ntf2p. Consistent with the identification of those suppressors, lack of ScMog1p dislocates Opi3p from the nuclear membrane and all of Spmog1(ts) showed the nuclear accumulation of mRNA. Furthermore, SpMog1 was co-precipitated with Nxt2 and Cid13. (c) 2007 Elsevier B.V. All rights reserved. C1 Kyushu Univ, Grad Sch Med Sci, Dept Mol Biol, Fukuoka 812, Japan. Univ Tokyo, Inst Med Sci, Div Mol Cell Signaling, Tokyo 108, Japan. Univ Fukui, Fac Engn, Dept Appl Chem & Biotechnol, Fukui 910, Japan. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NIH, NICHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. Univ Hyogo, Grad Sch Life Sci, Lab Biol Signaling, Hyogo 678, Japan. RP Nishirnoto, T (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Mol Biol, Fukuoka 812, Japan. EM tnishi@molbiol.med.kyushu-u.ac.jp NR 36 TC 3 Z9 3 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 1 PY 2007 VL 400 IS 1-2 BP 114 EP 121 DI 10.1016/j.gene.2007.06.012 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 211QY UT WOS:000249539600014 PM 17651922 ER PT J AU Jeronimo, SMB Holst, AKB Jamieson, SE Francis, R Martins, DRA Bezerra, FL Ettinger, NA Nascimento, ET Monteiro, GR Lacerda, HG Miller, EN Cordell, HJ Duggal, P Beaty, TH Blackwell, JM Wilson, ME AF Jeronimo, S. M. B. Holst, A. K. B. Jamieson, S. E. Francis, R. Martins, D. R. A. Bezerra, F. L. Ettinger, N. A. Nascimento, E. T. Monteiro, G. R. Lacerda, H. G. Miller, E. N. Cordell, H. J. Duggal, P. Beaty, T. H. Blackwell, J. M. Wilson, M. E. TI Genes at human chromosome 5q31.1 regulate delayed-type hypersensitivity responses associated with Leishmania chagasi infection SO GENES AND IMMUNITY LA English DT Article DE delayed type hypersensitivity; visceral leishmaniasis; genetic control; chromosome 5q31.1 ID INTERFERON-GAMMA PRODUCTION; HLA CLASS-I; VISCERAL LEISHMANIASIS; NORTHEASTERN BRAZIL; KALA-AZAR; CUTANEOUS LEISHMANIASIS; IMMUNE-RESPONSE; PLUS BCG; MYCOBACTERIUM-TUBERCULOSIS; DISEQUILIBRIUM MEASURES AB Visceral leishmaniasis (VL) caused by Leishmania chagasi is endemic to northeast Brazil. A positive delayed-type hypersensitivity skin test response (DTH+) is a marker for acquired resistance to disease, clusters in families and may be genetically controlled. Twenty-three single nucleotide polymorphisms (SNPs) were genotyped in the cytokine 5q23.3-q31.1 region IRF1-IL5-IL13-IL4-IL9-LECT2-TGFBI in 102 families (323 DTH+; 190 DTH+; 123 VL individuals) from a VL endemic region in northeast Brazil. Data from 20 SNPs were analyzed for association with DTH+/- status and VL using family-based, stepwise conditional logistic regression analysis. Independent associations were observed between the DTH+ phenotype and markers in separate linkage disequilibrium blocks in LECT2 (OR 2.25; P = 0.005; 95% CI = 1.28-3.97) and TGFBI (OR 1.94; P = 0.003; 95% CI = 1.24-3.03). VL child/parent trios gave no evidence of association, but the DTH- phenotype was associated with SNP rs2070874 at IL4 (OR 3.14; P = 0.006; 95% CI = 1.38-7.14), and SNP rs30740 between LECT2 and TGFBI (OR 3.00; P = 0.042; 95% CI = 1.04-8.65). These results indicate several genes in the immune response gene cluster at 5q23.3-q31.1 influence outcomes of L. chagasi infection in this region of Brazil. C1 Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Univ Fed Rio Grande do Norte, Dept Biochem, Natal, RN, Brazil. Univ Iowa, VA Med Ctr, Dept Internal Med, Iowa City, IA USA. Univ Iowa, VA Med Ctr, Dept Microbiol, Iowa City, IA USA. Univ Iowa, VA Med Ctr, Dept Epidemiol, Iowa City, IA USA. Univ Iowa, VA Med Ctr, Dept Mol Biol Program, Iowa City, IA USA. Univ Cambridge, Sch Clin Med, Cambridge Inst Med Res, Cambridge, England. Univ Newcastle, Int Ctr Life, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England. NIH, Natl Human Genome Res Inst, Inherited Dis Res Branch, Bethesda, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Wilson, ME (reprint author), Univ Iowa, Dept Internal Med, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM mary-wilson@uiowa.edu RI Beaty, Terri/A-6032-2008; Jeronimo, Selma/M-8672-2014; Blackwell, Jenefer/H-3015-2015; OI Francis, Richard/0000-0003-1580-7934 FU Intramural NIH HHS; NIAID NIH HHS [AI048822, AI30639, AI45540, P50 AI030639, R01 AI045540, R01 AI048822, R01 AI076233]; NIGMS NIH HHS [T32 GM007337]; Wellcome Trust [, 074196] NR 66 TC 27 Z9 29 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 OCT PY 2007 VL 8 IS 7 BP 539 EP 551 DI 10.1038/sj.gene.6364422 PG 13 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 223OV UT WOS:000250382200003 PM 17713557 ER PT J AU Rafiq, S Frayling, TM Murray, A Hurst, A Stevens, K Weedon, MN Henley, W Ferrucci, L Bandinelli, S Corsi, AM Guralnik, JM Melzer, D AF Rafiq, S. Frayling, T. M. Murray, A. Hurst, A. Stevens, K. Weedon, M. N. Henley, W. Ferrucci, L. Bandinelli, S. Corsi, A-M Guralnik, J. M. Melzer, D. TI A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects SO GENES AND IMMUNITY LA English DT Article DE inflammation; genetics; ageing; epidemiology; interleukins ID GENOME-WIDE ASSOCIATION; POLYMORPHISMS; INCHIANTI; DISEASE; OBESITY AB Interleukin-6 (IL-6) is a key inflammatory cytokine, signalling to most tissues by binding to a soluble IL-6 receptor (sIL-6r), making a complex with gp130. We used 1273 subjects ( mean age 68 years) from the InCHIANTI Italian cohort to study common variation in the IL-6r locus and associations with interleukin 6 receptor (IL-6r), IL-6, gp130 and a battery of inflammatory markers. The rs4537545 single nucleotide polymorphism (SNP) tags the functional non-synonymous Asp358Ala variant (rs8192284) in IL-6r (r(2) 0.89, n = 343). Individuals homozygous for the rs4537545 SNP minor allele (frequency 40%) had a doubling of IL-6r levels (132.48 pg/ml, 95% CI 125.13-140.27) compared to the common allele homozygous group (68.31 pg/ml, 95% CI 65.35-71.41): in per allele regression models, the rs4537545 SNP accounted for 20% of the variance in sIL-6r, with P = 5.1 x 10(-62). The minor allele of rs4537545 was also associated with higher circulating IL-6 levels (P = 1.9 x 10(-4)). There was no association of this variant with serum levels of gp130 or with any of the studied pro- and anti-inflammatory markers. A common variant of the IL-6r gene results in major changes in IL-6r and IL-6 serum levels, but with no apparent effect on gp130 levels or on inflammatory status in the general population. C1 Peninsula Med Sch, Exeter EX2 5DW, Devon, England. Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. Univ Plymouth, Sch Math & Stat, Plymouth, Devon, England. NIA, Gerontol Res Ctr, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD USA. Italian Natl Res Council Aging, Lab Clin Epidemiol, Geriat Rehabil Unit, Florence, Italy. Univ Florence, Thrombosis Ctr, Tuscany Reg Hlth Agcy, Dept Med & Surg Crit Care,IOT, Florence, Italy. NIA, Lab Epidemiol Demog & Biometr, Bethesda, MD USA. RP Melzer, D (reprint author), Peninsula Med Sch, Barrack Rd, Exeter EX2 5DW, Devon, England. EM david.melzer@pms.ac.uk OI Murray, Anna/0000-0002-2351-2522; Rafiq, Sajjad/0000-0003-4873-4540; Melzer, David/0000-0002-0170-3838 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-821336, R01 AG024233, R01 AG24233-01, N01-AG-916413]; NIMHD NIH HHS [263 MD 821336, 263 MD 9164 13, R01 MD009164] NR 25 TC 58 Z9 58 U1 0 U2 5 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 OCT PY 2007 VL 8 IS 7 BP 552 EP 559 DI 10.1038/sj.gene.6364414 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 223OV UT WOS:000250382200004 PM 17671508 ER PT J AU Eck, P Erichsen, HC Taylor, JG Corpe, C Chanock, SJ Levine, M AF Eck, Peter Erichsen, Hans Christian Taylor, James G. Corpe, Christopher Chanock, Stephen J. Levine, Mark TI Genomic and functional analysis of the sodium-dependent vitamin C transporter SLC23A1-SVCT1 SO GENES AND NUTRITION LA English DT Article; Proceedings Paper CT International Conference on From Nutrigenomics to Personalized Nutrition CY NOV 01-04, 2005 CL Univ Illes Balears, Lab Biol Mole Nutr Biotecnol, Palma de Mallorca, SPAIN HO Univ Illes Balears, Lab Biol Mole Nutr Biotecnol DE vitamin C; SVCT1; SLC23A1; transport; Snp; nutrient recommendations C1 [Eck, Peter] AgResearch Ltd, Ruakura Res Ctr, Hamilton, New Zealand. [Eck, Peter; Corpe, Christopher; Levine, Mark] NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. [Erichsen, Hans Christian; Taylor, James G.; Chanock, Stephen J.] NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Eck, Peter] Nutrigenom New Zealand, Christchurch, New Zealand. RP Eck, P (reprint author), AgResearch Ltd, Ruakura Res Ctr, Hamilton, New Zealand. EM Peter.eck@agresearch.co.nz OI Eck, Peter/0000-0003-2371-9774; Taylor, James/0000-0002-4421-1809 NR 4 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1555-8932 J9 GENES NUTR JI Genes Nutr. PD OCT PY 2007 VL 2 IS 1 BP 143 EP 145 DI 10.1007/s12263-007-0040-7 PG 3 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 339EC UT WOS:000258559900039 PM 18850166 ER PT J AU Wersinger, SR Caldwell, HK Christiansen, M Young, WS AF Wersinger, S. R. Caldwell, H. K. Christiansen, M. Young, W. S., III TI Disruption of the vasopressin 1b receptor gene impairs the attack component of aggressive behavior in mice SO GENES BRAIN AND BEHAVIOR LA English DT Article DE agonistic behavior; maternal aggression; neuropeptide; predation; social motivation; V3 ID STRESS-RELATED DISORDERS; HAMSTERS MESOCRICETUS-AURATUS; FLANK-MARKING BEHAVIOR; SEXUAL-BEHAVIOR; INTERMALE AGGRESSION; PARA-CHLOROPHENYLALANINE; OLFACTORY BULBECTOMY; SOCIAL RECOGNITION; TESTOSTERONE PROPIONATE; PREDATORY AGGRESSION AB Vasopressin affects behavior via its two brain receptors, the vasopressin 1a and vasopressin 1b receptors (Avpr1b). Recent work from our laboratory has shown that disruption of the Avpr1b gene reduces intermale aggression and reduces social motivation. Here, we further characterized the aggressive phenotype in Avpr1b -/- (knockout) mice. We tested maternal aggression and predatory behavior. We also analyzed the extent to which food deprivation and competition over food increases intermale aggression. We quantified defensive behavior in Avpr1b -/- mice and later tested offensive aggression in these same mice. Our results show that attack behavior toward a conspecific is consistently reduced in Avpr1b -/- mice. Predatory behavior is normal, suggesting that the deficit is not because of a global inability to detect and attack stimuli. Food deprivation, competition for food and previous experience increase aggression in both Avpr1b +/+ and -/- mice. However, in these circumstances, the level of aggression seen in knockout mice is still less than that observed in wild-type mice. Defensive avoidance behaviors, such as boxing and fleeing, are largely intact in knockout mice. Avpr1b -/- mice do not display as many 'retaliatory' attacks as the Avpr1b +/+ mice. Interestingly, when territorial aggression was measured following the defensive behavior testing, Avpr1b -/- mice typically show less initial aggressive behavior than wild-type mice, but do show a significant increase in aggression with repeated testing. These studies confirm that deficits in aggression in Avpr1b -/- mice are limited to aggressive behavior involving the attack of a conspecific. We hypothesize that Avpr1b plays an important role in the central processing that couples the detection and perception of social cues (which appears normal) with the appropriate behavioral response. C1 SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. NIMH, DHHS, Sect Neural Gene Experss, NIH, Bethesda, MD 20892 USA. RP Wersinger, SR (reprint author), SUNY Buffalo, Dept Psychol, 348 Pk Hall, Buffalo, NY 14260 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU Intramural NIH HHS [Z01 MH002498-18]; NIMH NIH HHS [Z01-MH-002498-16, Z01 MH002498] NR 75 TC 64 Z9 67 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD OCT PY 2007 VL 6 IS 7 BP 653 EP 660 DI 10.1111/j.1601-183X.2006.00294.x PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 213JA UT WOS:000249661500008 PM 17284170 ER PT J AU Yan, Y Park, SS Janz, S Eckhardt, LA AF Yan, Yi Park, Sung Sup Janz, Siegfried Eckhardt, Laurel A. TI In a model of immunoglobulin heavy-chain (IGH)IMYC translocation, the igh 3 ' regulatory region induces MYC expression at the immature stage of B cell development SO GENES CHROMOSOMES & CANCER LA English DT Article ID C-MYC; SOMATIC HYPERMUTATION; SWITCH RECOMBINATION; INTRON ENHANCER; PROMOTER SHIFT; LINEAGE CELLS; LOCUS; ELEMENTS; GENE; END AB Reciprocal translocations involving the immunoglobulin loci and the cellular oncogene MYC are hallmark mutations of the human postgerminal center B cell neoplasm, Burkitt's lymphoma. They are occasionally found in other B cell lymphomas, as well. Translocations involving the heavy chain locus (IGH) place the MYC gene either in cis with both the intronic enhancer E L and the IGH 3' regulatory region (3'RR) or in cis with only the 3'RR. The result is deregulated MYC expression. Recent studies have led to some controversy as to when, during B lymphocyte development, IGH/MYC chromosome translocations take place. A related issue, relevant not only to lymphoma development but also to normal controls on IGH gene expression, is the stage, during B lymphocyte development, at which the 3'RR is capable of activating MYC expression. We have developed mice transgenic for a human MYC (hMYC) gene under control of the four core enhancers from the mouse Igh 3'RR. Unlike other transgenic mouse models where premature and inappropriate MYC expression disrupts normal B cell development, the hMYC transgene in these studies carries a mutation that prohibits MYC protein synthesis. As a result, hMYC expression can be analyzed in all of the normal B cell compartments. Our data show that hMYC is expressed almost exclusively in B-lineage cells and is induced to high levels as soon as bone marrow cells reach the immature B cell stage. (c) 2007 Wiley-Liss, Inc. C1 CUNY Hunter Coll, Dept Biol Sci, New York, NY 10021 USA. CUNY, Grad Ctr, Dept Biol Sci, New York, NY 10021 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. Korea Res Inst Biosci & Biotechnol, System Proteom Res Ctr, Taejon, South Korea. Carver Coll Med, Dept Pathol, Iowa City, IA USA. RP Eckhardt, LA (reprint author), CUNY Hunter Coll, Dept Biol Sci, 695 Pk Ave, New York, NY 10021 USA. EM eckhardt@genectr.hunter.cuny.edu FU NCRR NIH HHS [RR-0307]; NIAID NIH HHS [R01 AI030653-17, AI30653, R01 AI030653] NR 41 TC 12 Z9 13 U1 2 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 2007 VL 46 IS 10 BP 950 EP 959 DI 10.1002/gcc.20480 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 206OG UT WOS:000249192200008 PM 17639584 ER PT J AU Singh, G Klar, AJS AF Singh, Gurjeet Klar, Arnar J. S. TI A hypothesis for how chromosome 11 translocations cause psychiatric disorders SO GENETICS LA English DT Article ID DNA STRANDS; FISSION YEAST; SCHIZOPHRENIA; PSYCHOSIS; CELLS; SEGREGATION AB Despite extensive effort for many years, the etiology of major psychiatric diseases remains unknown. A recent study by Baysal et al. has argued against the ALG9 gene variants in causing psychosis. Due to its disruption by a balanced t(9p2,11q23) translocation that segregates with the disorder in a family, it was proposed to be a primary candidate gene causing psychosis. In addition, a recent review article by Pickard et al., entitled "Cytogenctics and gene discovery in psychiatric disorders," highlighted the importance of studies of chromosome rearrangements in finding disease-causing mutations. However, achieving the goal of finding genes by conventional association studies and by investigating chromosome rearrangements remains elusive. Here we discuss a fundamentally different explanation from the usual one considered by workers in the field concerning chromosome aberrations and psychoses etiology. We hypothesize how chromosome aberrations might. cause disease but the gene at the rearrangement breakpoint is irrelevant for the etiology. Moreover, we discuss subsequently published findings that help scrutinize validity of the two very different hypotheses considered in the psychiatric genetics field. In sum, we alert the readers to the complexities of interpreting phenotypes associated with rearrangements. C1 NCI, Gene Regulat & Chrosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Klar, AJS (reprint author), NCI, Gene Regulat & Chrosome Biol Lab, Ctr Canc Res, POB B,Bldg 539, Frederick, MD 21702 USA. EM klar@ncifcrf.gov FU Intramural NIH HHS NR 15 TC 2 Z9 2 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2007 VL 177 IS 2 BP 1259 EP 1262 DI 10.1534/genetics.107.077875 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 227LI UT WOS:000250657800053 PM 17720908 ER PT J AU Wenzel, LB Anderson, R Tucker, DC Palla, S Thomson, E Speechley, M Harrison, H Lewis-Jack, O Fadojutimi-Akinsiku, M Eckfeldt, JH Reiss, JA Rivers, CA Bookman, E Snively, BM McLaren, CE AF Wenzel, Lari B. Anderson, Roger Tucker, Diane C. Palla, Shana Thomson, Elizabeth Speechley, Mark Harrison, Helen Lewis-Jack, Ometha Fadojutimi-Akinsiku, Margaret Eckfeldt, John H. Reiss, Jacob A. Rivers, Charles A. Bookman, Ebony Snively, Beverly M. McLaren, Christine E. CA Hemochromatosis Iron Overload SRI TI Health-related quality of life in a racially diverse population screened for hemochromatosis: results from the Hemochromatosis and Iron Overload Screening (HEIRS) study SO GENETICS IN MEDICINE LA English DT Article DE quality of life; hemochromatosis; screening; iron overload; multi-ethnic population ID HEREDITARY HEMOCHROMATOSIS; PRIMARY-CARE; CANCER; IMPACT; QUESTIONNAIRE; ACCEPTABILITY; DIAGNOSIS; ATTITUDES; ADULTS AB Purpose: The HEIRS Study screened 101,168 primary care participants for iron overload-with serum transferrin saturation (TS), serum ferritin (SF), and C282Y and H63D mutations of the HFE gene. The objective of this study was to evaluate the impact of screening on participants' well-being. Methods: All C282Y homozygotes, participants with an elevated TS and SF concentration, and a control group of phenotype-genotype negative persons, with neither C282Y nor H63D mutations in the HFE gene were recalled for a clinical evaluation. Health-related quality of life was assessed before screening and approximately I week after receipt of the results. Health worries were assessed only at follow-up. Results: Participants (N = 1478) completed both initial and follow-up surveys. After adjusting for model covariates, phenotype and genotype combinations were statistically significant predictors of changes in psychological well-being (P = 0.0001) and general health (P = 0.0014). C282Y homozygotes with transient elevations in TS or SF were significantly more likely to worry about their health compared to study controls. Race, ethnicity, and preferred language subgroups differed on psychological wellbeing, general health, and health worry. Conclusion: Iron phenotype and HFE genotype are associated with health-related quality of life. Health worry was greatest among those considered genetically "at risk. " This may have important implications for multi-ethnic population-based screening studies in which genotype and phenotype are communicated. C1 Univ Calif Irvine, Dept Med, Ctr Hlth Policy Res, Irvine, CA 92697 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. NHGRI, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. London Hlth Sci Ctr, London, ON, Canada. Howard Univ, Dept Psychol, Washington, DC 20059 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Kaiser Permanente, Portland, OR USA. Univ Alabama, Microbiol Immunogenet Program, Birmingham, AL USA. NHLBI, Epidemiol & Biometry Program, NIH, DHHS, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA. RP Wenzel, LB (reprint author), Univ Calif Irvine, Dept Med, Ctr Hlth Policy Res, Irvine, CA 92697 USA. EM lwenzel@uci.edu FU NCRR NIH HHS [M01-RR10284, 5M01RR 00827-29]; NHLBI NIH HHS [N01-HC-05186, N01-HC-05188, N01-HC-05189, N01-HC-05192, N01-HC-05185, N01-HC-05191, N01-HC-05190] NR 19 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD OCT PY 2007 VL 9 IS 10 BP 705 EP 712 DI 10.1097/GIM.0b013e3181571f31 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 223IW UT WOS:000250364500006 PM 18073584 ER PT J AU Draghici, S Khatri, P Tarca, AL Amin, K Done, A Voichita, C Georgescu, C Romero, R AF Draghici, Sorin Khatri, Purvesh Tarca, Adi Laurentiu Amin, Kashyap Done, Arina Voichita, Calin Georgescu, Constantin Romero, Roberto TI A systems biology approach for pathway level analysis SO GENOME RESEARCH LA English DT Article ID FOCAL ADHESION KINASE; GENE-EXPRESSION DATA; CELL LUNG-CANCER; MICROARRAY DATA; BREAST-CANCER; APOPTOSIS; NETWORKS; TOOL; ASSOCIATION; PROFILES AB A common challenge in the analysis of genomics data is trying to understand the underlying phenomenon in the context of all complex interactions taking place on various signaling pathways. A statistical approach using various models is universally used to identify the most relevant pathways in a given experiment. Here, we show that the existing pathway analysis methods fail to take into consideration important biological aspects and may provide incorrect results in certain situations. By using a systems biology approach, we developed an impact analysis that includes the classical statistics but also considers other crucial factors such as the magnitude of each gene's expression change, their type and position in the given pathways, their interactions, etc. The impact analysis is an attempt to a deeper level of statistical analysis, informed by more pathway- specific biology than the existing techniques. On several illustrative data sets, the classical analysis produces both false positives and false negatives, while the impact analysis provides biologically meaningful results. This analysis method has been implemented as a Web- based tool, Pathway- Express, freely available as part of the Onto- Tools (http:// vortex. cs. wayne. edu). C1 Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. NICHD, Perinatol Res Branch, NIH, Detroit, MI 48201 USA. RP Draghici, S (reprint author), Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. EM sod@cs.wayne.edu RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 FU NCI NIH HHS [2P30 CA022453-24, 1R21CA100740-01, 1U01CA117478-01, P30 CA022453, R21 CA100740, U01 CA117478]; NCRR NIH HHS [1S10 RR017857-01, S10 RR017857]; NHGRI NIH HHS [1R01HG003491-01A1, R01 HG003491]; NIBIB NIH HHS [5R21EB00090-03, R21 EB000990]; NINDS NIH HHS [1R01NS045207-01, R01 NS045207] NR 50 TC 462 Z9 474 U1 3 U2 30 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2007 VL 17 IS 10 BP 1537 EP 1545 DI 10.1101/gr.6202607 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 216HN UT WOS:000249869200015 PM 17785539 ER PT J AU Goins, RT Moss, M Buchwald, D Guralnik, JM AF Goins, R. Turner Moss, Margaret Buchwald, Dedra Guralnik, Jack M. TI Disability among older American Indians and Alaska Natives: An analysis of the 2000 census public use microdata sample SO GERONTOLOGIST LA English DT Article DE American Indians and Alaska Natives; older adults; disability; US census ID ISSUES AB Purpose: We compared the prevalence of disability among older American Indians and Alaska Natives (AI/ANs) with that among their African American and White peers, then examined sociodemographic characteristics associated with disability among AI/ANs. Design and Methods: We analyzed the 5% 2000 Census Public Use Microdata Sample. We assessed disability by functional limitation, mobility disability, and self-care disability for four age groups (55-64, 65-74, 75-84, and 85 years or older). Results: For all age strata, AI/ANs reported the highest rates of functional limitation and African Americans the highest level of mobility disability. In the 55-to-64 age group, AI/ANs experienced the highest prevalence of self-care disability, and among those aged 65 years or older, African Americans reported the highest prevalence. Compared to Whites, the adjusted odds ratios for functional limitation, mobility disability, and self-care disability were significantly elevated in AI/ANs (1.62, 1.33, and 1.56, respectively) and African Americans (1.27, 1.54, and 1.56, respectively). For AI/ANs, being of increased age, being female, having lower educational attainment and household income, not being married or in the labor force, and residing in a metropolitan area were associated with disabilities. Implications: This study contributes to researchers' limited knowledge regarding disability among older AI/ANs. The lack of available empirical data poses obstacles to understanding the antecedents and consequences of disability for AI/ANs. More information on the nature and extent of disabilities among AI/AN elders would enhance the ability of advocates to document their needs and raise public awareness. Likewise, policy makers could enact prevention strategies and make comprehensive rehabilitative and long-term care services available to this population. C1 [Goins, R. Turner] W Virginia Univ, Ctr Aging, Morgantown, WV 26506 USA. [Goins, R. Turner] W Virginia Univ, Dept Community Med, Morgantown, WV 26506 USA. [Moss, Margaret] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [Buchwald, Dedra] Univ Washington, Dept Med, Seattle, WA USA. [Guralnik, Jack M.] Nat Inst Aging, Bethesda, MD USA. RP Goins, RT (reprint author), W Virginia Univ, Ctr Aging, POB 9127, Morgantown, WV 26506 USA. EM rgoitis@hsc.wvu.edu FU Intramural NIH HHS; NIA NIH HHS [K01 AG022336-01A2, 1 K01 AG022336-01A2, K01 AG022336] NR 21 TC 21 Z9 23 U1 0 U2 1 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2007 VL 47 IS 5 BP 690 EP 696 PG 7 WC Gerontology SC Geriatrics & Gerontology GA 272EN UT WOS:000253842800013 PM 17989411 ER PT J AU Pei, Z Pang, H Qian, L Yang, S Wang, TG Zhang, W Wu, X Dallas, S Wilson, B Reece, JM Miller, DS Hong, JS Block, ML AF Pei, Zhong Pang, Hao Qian, Li Yang, Sufen Wang, Tonggauang Zhang, Wei Wu, Xeufei Dallas, Shannon Wilson, Belinda Reece, Jeffrey M. Miller, David S. Hong, Jau-Shyong Block, Michelle L. TI MAC1 mediates LPS-induced production of superoxide by microglia: The role of pattern recognition receptors in dopaminergic neurotoxicity SO GLIA LA English DT Article DE MAC1; LPS; microglia; dopaminergic neurotoxicity; superoxide; reactive oxygen species; phagocytosis ID LIPOPOLYSACCHARIDE-BINDING PROTEIN; BACTERIAL-ENDOTOXIN EXPOSURE; TOLL-LIKE RECEPTOR-4; PARKINSONS-DISEASE; IN-VIVO; ACTIVATED MICROGLIA; TETRAZOLIUM SALT; HUMAN MONOCYTES; RAT MIDBRAIN; INFLAMMATION AB Microglia-derived superoxide is critical for the inflammation-induced selective loss of dopaminergic (DA) neurons, but the underlying mechanisms of microglial activation remain poorly defined. Using neuron-glia and microglia-enriched cultures from mice deficient in the MAC1 receptor (MAC1(-/-)), we demonstrate that lipopolysaccharide (LPS) treatment results in lower TNF alpha response, attenuated loss of DA neurons, and absence of extracellular superoxide production in MAC1(-/-) cultures. Microglia accumulated fluorescently labeled LPS in punctate compartments associated with the plasma membrane, intracellular vesicles, and the Golgi apparatus. Cytochalasin D (CD), an inhibitor of phagocytosis, blocked LPS internalization. However, Microglia derived from Toll-like receptor 4 deficient mice and MAC1(-/-) mice failed to show a significant decrease in intracellular accumulation of labeled LPS, when compared with controls. Pretreatment with the scavenger receptor inhibitor, fucoidan, inhibited 79% of LPS accumulation in microglia without affecting superoxide, indicating that LPS internalization and superoxide production are mediated by separate phagocytosis receptors. Together, these data demonstrate that MAC1 is essential for LPS-induced superoxide from microglia, implicating MAC1 as a critical trigger of microglial-derived oxidative stress during inflammation-mediated neurodegeneration. (c) 2007 Wiley-Liss, Inc. C1 NIEHS, Lab Pharmacol & Chem, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurol, Guangzhou 510275, Guangdong, Peoples R China. Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC USA. NIEHS, Confocal Microscopy Ctr, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Miller, DS (reprint author), NIEHS, Lab Pharmacol & Chem, Neuropharmacol Sect, MD F2-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM miller28@niehs.nih.gov FU NIEHS NIH HHS [1K99ES01549-01, K99 ES015409, K99 ES015409-01] NR 56 TC 44 Z9 45 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD OCT PY 2007 VL 55 IS 13 BP 1362 EP 1373 DI 10.1002/glia.20545 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 207FK UT WOS:000249236800007 PM 17654704 ER PT J AU Capello, F Scrimin, S Pillon, M Putnik, D Bornstein, MH Levrero, P Dufour, C Carli, M Axia, G AF Capello, F. Scrimin, S. Pillon, M. Putnik, D. Bornstein, M. H. Levrero, P. Dufour, C. Carli, M. Axia, G. TI Cognitive, motor and interaction development during a game in young patients with tumoral pathology SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA Italian DT Meeting Abstract CT 34th National Congress of the Italian-Association-of-Pediatric-Hematology CY OCT 21-23, 2007 CL Pavia, ITALY SP Italian Soc Pediat Hematol C1 [Capello, F.; Scrimin, S.; Axia, G.] Univ Padua, Dipartimento Psicol Sviluppo Socializzazione, Padua, Italy. [Putnik, D.; Bornstein, M. H.] NICHHD, Bethesda, MD 20892 USA. [Pillon, M.; Carli, M.] Univ Padua, Dipartimento Pediat, I-35128 Padua, Italy. [Levrero, P.; Dufour, C.] Osped Pediat Gaslini, Genoa, Italy. NR 0 TC 1 Z9 1 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 OCT PY 2007 VL 92 IS 6 SU 4 BP 40 EP 41 PG 2 WC Hematology SC Hematology GA 239MM UT WOS:000251522400090 ER PT J AU Allen, CT Ricker, JL Chen, Z Van Waes, C AF Allen, Clint T. Ricker, Justin L. Chen, Zhong Van Waes, Carter TI Role of activated nuclear factor-kappa B in the pathogenesis and therapy of squamous cell carcinoma of the head and neck SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Review DE nuclear factor-kappa B; signal transduction; head and neck squamous cell carcinoma; bortezomib; EGFR ID GROWTH-FACTOR RECEPTOR; PROINFLAMMATORY CYTOKINE EXPRESSION; PROTEASOME INHIBITOR PS-341; NECROSIS-FACTOR-ALPHA; CYCLIN D1 EXPRESSION; CASEIN KINASE-II; TRANSCRIPTION FACTORS; CONSTITUTIVE ACTIVATION; SIGNAL-TRANSDUCTION; CANCER-CELLS AB Background. Nuclear factor-kappa B (NF-kappa B), a transcription factor known to modulate expression of factors involved in inflammation, immunity, proliferation, and apoptosis, is constitutively activated and plays a role in pathogenesis and therapeutic resistance in head and neck squamous cell carcinoma (HNSCC). Understanding the molecular alterations leading to aberrant NF-kappa B activation in HNSCC may direct investigators to novel therapeutic targets. Methods. Results of laboratory and clinical studies are reviewed. Results. The structure, function, and activation of NF-kappa B, products of NF-kappa B target genes and their role in HNSCC oncogenesis, and current NF-kappa B modulating interventions are described. Conclusions. Aberrant NF-kappa B activation contributes to the expression of oncogenes and the malignant phenotype observed in HNSCC. NF-kappa B, along with providing a link between cancer and inflammation, may serve as an appropriate therapeutic target to inhibit tumor growth and sensitize cancer cells to established cytotoxic anticancer therapies. (c) 2007 Wiley Periodicals, Inc. C1 Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, 10 Ctr Dr,CRC 4-2732, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov NR 113 TC 67 Z9 67 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2007 VL 29 IS 10 BP 959 EP 971 DI 10.1002/hed.20615 PG 13 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 215KN UT WOS:000249807300010 PM 17405170 ER PT J AU Ando, M Asakura, T Ando, S Simons-Morton, B AF Ando, Mikayo Asakura, Takashi Ando, Shinichiro Simons-Morton, Bruce TI A psychoeducational program to prevent aggressive bjehavior among Japanese early adolescents SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE early adolescent; intervention; aggressive behavior; bullying; schools ID SCHOOL-BASED INTERVENTION; GOING PLACES PROGRAM; ANTISOCIAL-BEHAVIOR; VIOLENCE PREVENTION; CURRICULUM; IMPACT; TRIAL; YOUTH AB This study evaluates the impact of a school-based intervention program on aggressive behavior among junior high school students in Japan. One hundred and four seventh-graders were enrolled in the program and completed Time 1, Time 2, and Time 3 surveys. The program was implemented in two classes between Time I and Time 2 surveys (the first treatment group) and in two other classes between Time 2 and Time 3 surveys (the delayed treatment group). The program included four weekly lessons related to problem solving, stress management, and communication. The initial intervention group reported a significant increase in appropriate relationships with classmates. Aggressive behavior significantly decreased from Time I to Time 3 in both groups and from Time 2 to Time 3 in the delayed treatment group, but no treatment group effect was noted. Additional modification of the program may be needed to achieve decreases in aggressive behavior. C1 Tokyo Gakugei Univ, Hlth Sci Lab, Koganei, Tokyo 1848501, Japan. Ohkubo Hosp, Tokyo Metropolitan Hlth & Med Treatment Corp, Tokyo, Japan. NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA. RP Ando, M (reprint author), Tokyo Gakugei Univ, Hlth Sci Lab, 4-1-1 Nukuikita Machi, Koganei, Tokyo 1848501, Japan. EM mikayo@rc5.so-net.ne.jp RI ANDO, Mikayo/B-1378-2011 NR 43 TC 7 Z9 7 U1 1 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 2007 VL 34 IS 5 BP 765 EP 776 DI 10.1177/1090198106291965 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 226JI UT WOS:000250584900005 PM 17200095 ER PT J AU Gail, MH Pfeiffer, RM Brown, LM Zhang, L Ma, JL Pan, KF Liu, WD You, WC AF Gail, Mitchell H. Pfeiffer, Ruth M. Brown, Linda M. Zhang, Lian Ma, Jun-Ling Pan, Kai-Feng Liu, Wei-Dong You, Wei-Cheng TI Garlic, vitamin, and antibiotic treatment for Helicobacter pylori: A randomized factorial controlled trial SO HELICOBACTER LA English DT Letter ID PRECANCEROUS GASTRIC-LESIONS; INFECTION; PROGRESSION; REDUCE C1 NCI, Natl Inst Hlth, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Gail, MH (reprint author), NCI, Natl Inst Hlth, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 8032,MSC 7244, Bethesda, MD 20892 USA. RI Pfeiffer, Ruth /F-4748-2011 FU Intramural NIH HHS NR 8 TC 13 Z9 13 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD OCT PY 2007 VL 12 IS 5 BP 575 EP 578 DI 10.1111/j.1523-5378.2007.00528.x PG 4 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 203TE UT WOS:000248996100015 PM 17760729 ER PT J AU Landgren, O Caporaso, NE AF Landgren, Ola Caporaso, Neil E. TI New aspects in descriptive, etiologic, and molecular epidemiology of Hodgkin's lymphoma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID EPSTEIN-BARR-VIRUS; REED-STERNBERG CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; REGISTRY-BASED ANALYSIS; BREAST-CANCER RISK; CENTER B-CELL; RHEUMATOID-ARTHRITIS; 1ST-DEGREE RELATIVES; GENE REARRANGEMENTS; AUTOIMMUNE-DISEASES AB Epstein-Barr virus (EBV) has remained the main candidate suggested as the infection causing Hodgkin's lymphoma for several years. However, EBV genome has been found only within the tumor in about 20%-40% of Hodgkin's lymphoma cases with a prior diagnosis of infectious mononucleosis. Recently, autoimmune and related conditions have drawn attention to a potential role for immune-related and inflammatory conditions in the etiology and pathogenesis of the malignancy. Evidence from multiple affected families from case series, a twin study, a case-control study, and population-based registry studies implicate a role for genetic factors. Simultaneously, data from Eastern Asia and among Chinese immigrants in North America indicate increasing incidence trends for Hodgkin's lymphoma being associated with westernization. These results emphasize an interaction between environmental and genetic risk factors in Hodgkin's lymphoma. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Landgren, O (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd,Bldg EPS Room 7110, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov FU Intramural NIH HHS NR 107 TC 27 Z9 28 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2007 VL 21 IS 5 BP 825 EP + DI 10.1016/j.hoc.2007.07.001 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA 225CU UT WOS:000250495500005 PM 17908622 ER PT J AU Merion, RM Shearon, TH Berg, CL Everhart, JE Abecassis, MM Shaked, A Fisher, RA Trotter, JF Brown, RS Terrault, N Hayashi, PH Ghobrial, RM AF Merion, Robert M. Shearon, Tempie H. Berg, Carl L. Everhart, James E. Abecassis, Michael M. Shaked, Abraham Fisher, Robert A. Trotter, James F. Brown, Robert S. Terrault, Norah Hayashi, Paul H. Ghobrial, R. M. CA A2ALL Study Grp TI Hospitalization rates before and after adult-to-adult living donor or deceased donor liver transplantation SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Virginia, Charlottesville, VA USA. NIDDK, NIH, Bethesda, MD USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Penn, Philadelphia, PA 19104 USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Colorado, Denver, CO 80202 USA. Columbia Univ, New York, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Calif Los Angeles, Los Angeles, CA USA. RI Abecassis, Michael/F-7977-2011 NR 0 TC 1 Z9 1 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 OCT PY 2007 VL 46 IS 4 SU S MA 3 BP 234A EP 234A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400004 ER PT J AU Wakabayashi, Y Lippincott-Schwartz, J Arias, IM AF Wakabayashi, Yoshiyuki Lippincott-Schwartz, Jennifer Arias, Irwin M. TI Dynamic microtubules are required for constitutive canalicular trafficking of BSEP (ABCB11) in polarized WIF-139 cells and provide the "missing link" to the canalicular actin network SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NICHD, CBMB, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 34 BP 248A EP 248A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400035 ER PT J AU Lee, WM Rossoro, L Fontana, RJ Larson, AM Stravitz, RT Davern, TJ Hynan, LS Reisch, JS Robuck, PR AF Lee, William M. Rossoro, Lorenzo Fontana, Robert J. Larson, Anne M. Stravitz, Richard T. Davern, Timothy J. Hynan, Linda S. Reisch, Joan S. Robuck, Patricia R. TI Intravenous N-acetylcysteine improves spontaneous survival in early stage non-acetaminophen acute liver failure SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Univ Washington, Seattle, WA 98195 USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 7 Z9 7 U1 2 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 79 BP 268A EP 268A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400080 ER PT J AU Zaid, U Zhang, ZS Liang, TJ AF Zaid, Uwais Zhang, Zhensheng Liang, T. Jake TI In vitro and in vivo inhibition of HBV replication by peptide aptamers via disruption of the HBX-proteasome interaction SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIH, Liver Dis Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 109 BP 282A EP 282A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400110 ER PT J AU Di Bisceglie, AM Shiffman, ML Everson, GT Lindsay, KL Everhart, JE Wright, EC Lee, WM Lok, AS Bonkovsky, H Morgan, TR Dienstag, JL Ghany, M Morishima, C Snow, KK AF Di Bisceglie, Adrian M. Shiffman, Mitchell L. Everson, Gregory T. Lindsay, Karen L. Everhart, James E. Wright, Elizabeth C. Lee, William M. Lok, Anna S. Bonkovsky, Herbert Morgan, Timothy R. Dienstag, Jules L. Ghany, Marc Morishima, Chihiro Snow, Kristin K. TI Prolonged antiviral therapy with peginterferon to prevent complications of advanced liver disease associated with hepatitis C: Results of the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Denver, CO 80202 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDDKD, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX 75230 USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. Univ Calif Irvine, Gastroenterol Serv, Irvine, CA USA. VA Long Beach Healthcare Syst, Irvine, CA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIDDKD, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. New England Res Inst, Watertown, MA 02172 USA. RI Lok, Anna /B-8292-2009 NR 0 TC 23 Z9 23 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA LB1 BP 290A EP 290A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400128 ER PT J AU Abdelmalek, MF Suzuki, A Guy, C Johnson, RJ Diehl, AM AF Abdelmalek, Monal F. Suzuki, Ayako Guy, Cynthia Johnson, Richard J. Diehl, Anna Mae CA NASH Clinic Res Grp TI Fructose induced hyperuricemia as a causal mechanism for nonalcoholic fatty liver disease SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Duke Univ, Div Gastroenterol, Durham, NC 27706 USA. Univ Florida, Div Nephrol, Gainesville, FL 32611 USA. NIDDK, NIH, Baltimore, MD USA. NASH Clin Res Grp, Durham, England. RI Suzuki, Ayako/A-7656-2009 NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 128 BP 293A EP 293A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400134 ER PT J AU Hosui, A Hennighausen, L AF Hosui, Atsushi Hennighausen, Lothar TI The transcription factor STAT5 confines TGF-BETA levels in the liver and serves as a protective agent in liver fibrosis and cancer SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 152 BP 304A EP 304A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400158 ER PT J AU Feld, JJ Lutchman, GA Loomba, R Modi, AA Rotman, Y Nagabhyru, PR Ghany, M Heller, T Haynes-Williams, V Liang, TJ Neumann, AU Hoofnagle, JH AF Feld, Jordan J. Lutchman, Glen A. Loomba, Rohit Modi, Apurva A. Rotman, Yaron Nagabhyru, Pothu Raju Ghany, Marc Heller, Theo Haynes-Williams, Vanessa Liang, T. Jake Neumann, Avidan U. Hoofnagle, Jay H. TI Twice vs once weekly dosing of peginterferon alfa 2A in chronic HCV genotype 1 infection: Analysis of early viral kinetics SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, NIH, Liver Dis Branch, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 237 BP 343A EP 343A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400243 ER PT J AU Lindsay, KL Morishima, C Wright, EC Dienstag, JL Shiffman, ML Everson, GT Lok, AS Bonkovsky, HL Lee, WM Morgan, TR Ghany, M AF Lindsay, Karen L. Morishima, Chihiro Wright, Elizabeth C. Dienstag, Jules L. Shiffman, Mitchell L. Everson, Gregory T. Lok, Anna S. Bonkovsky, Herbert L. Lee, William M. Morgan, Timothy R. Ghany, Marc TI Systemic factors associated with virologic nonresponse to peginterferon/ribavirin retreatment of chronic hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 USC Keck Sch Med, Dept Med Gastroenterol, Los Angeles, CA USA. Univ Washington, Seattle, WA 98195 USA. New England Res Inst, Watertown, MA 02172 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Colorado, Denver, CO 80202 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Connecticut, Farmington, CT USA. Univ Texas, Dallas, TX 75230 USA. Univ Calif Irvine, Irvine, CA USA. NIDDK, NIH, Bethesda, MD USA. RI Lok, Anna /B-8292-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 320 BP 382A EP 382A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400326 ER PT J AU Rotman, Y Borg, BB Soza, A Loomba, R Modi, AA Feld, JJ Rivera, E Doo, E Heller, T Ghany, M Neumann, AU Liang, TJ Hoofnagle, JH AF Rotman, Yaron Borg, Brian B. Soza, Alejandro Loomba, Rohit Modi, Apurva A. Feld, Jordan J. Rivera, Elenito Doo, Edward Heller, Theo Ghany, Marc Neumann, Avidan U. Liang, T. Jake Hoofnagle, Jay H. TI Low dose peginterferon alfa-2a and ribavirin for chronic hepatitis C, genotype 2 & 3: Viral kinetics, efficacy and safety SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. Bar Ilan Univ, Goodman Fac Life Sci, Ramat Gan, Israel. RI Soza, Alejandro/C-2907-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 322 BP 383A EP 383A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400328 ER PT J AU Fujiwara, K Wang, RY Allison, RD Schechterly, C Marincola, FM Alter, H AF Fujiwara, Kei Wang, Richard Y. Allison, Robert D. Schechterly, Cathy Marincola, Francesco M. Alter, Harvey TI Investigation of residual hepatitis C virus (HCV) in presumed recovered subjects SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Natl Inst Hlth, Dept Transfus Med, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 OCT PY 2007 VL 46 IS 4 SU S MA 455 BP 441A EP 441A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400461 ER PT J AU Union, A Depla, E Meunier, JC Goossens, V Emerson, SU Priem, S Purcell, RH Maertens, G AF Union, Ann Depla, Erik Meunier, Jean-Christophe Goossens, Vera Emerson, Suzanne U. Priem, Sofie Purcell, Robert H. Maertens, Geert TI Human monoclonal antibodies recognizing a conserved HCV E1 domain effectively neutralize HCV in the cell culture (HCVCC) system SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Innogenet NV, Zwijnaarde, Belgium. NIAID, Lab Infect Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 479 BP 451A EP 452A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400485 ER PT J AU Shiina, M Rehermann, B AF Shiina, Masaaki Rehermann, Barbara TI Cell culture-produced hepatitis C virus impairs plasmacytoid dendritic cell maturation and function via direct interaction, but not infection SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 480 BP 452A EP 452A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400486 ER PT J AU Kuntzen, T Berical, A Lennon, N Heckerman, D Timm, J Adams, S zur Wiesch, JCS Carlson, J Ybung, S Kim, AY Kadie, C Lauer, GM Marincola, FM Chung, RT Bihl, FK Cerny, A Brander, C Spengler, U Birren, BW Walker, BD Lake-Bakaar, G Daar, ES Jacobson, IM Gomperts, ED Edlin, BR Donfield, SM Talal, A Marion, TN Henn, MR Allen, TM AF Kuntzen, Thomas Berical, Andrew Lennon, Niall Heckerman, David Timm, Joerg Adams, Sharon Schulze zur Wiesch, Julian C. Carlson, Jonathan Ybung, Sarah Kim, Arthur Y. Kadie, Carl Lauer, Georg M. Marincola, Francesco M. Chung, Raymond T. Bihl, Florian K. Cerny, Andreas Brander, Christian Spengler, Ulrich Birren, Bruce W. Walker, Bruce D. Lake-Bakaar, Gerond Daar, Eric S. Jacobson, Ira M. Gomperts, Edward D. Edlin, Brian R. Donfield, Sharyne M. Talal, Andrew Marion, Tony N. Henn, Matthew R. Allen, Todd M. TI HLA class I associated sequence polymorphisms in HCV reveal reproducible patterns of immune escape - Towards a comprehensive map of key residues for vaccine design SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr,Dept Infect Dis, Charlestown, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA USA. Microsoft Res, Redmond, WA USA. Essen Univ Hosp, Dept Virol, Essen, Germany. Natl Inst Hlth, Clin Ctr, HLA Lab, Bethesda, MD USA. Univ Klinikum Hamburg Eppendorf, Med Klin 1, Hamburg, 02115, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. Clin Moncucco, Swiss HCV Cohort Study, Lugano, Switzerland. Univ Bonn Hosp, Dept Internal Med 1, Bonn, 38163, Germany. Univ Tennessee, Ctr Hlth Sci, Hepatitis C Cooperat, Memphis, TN 10021 USA. Cornell Univ, Weill Med Coll, Ctr Study Hepatitis C, New York, NY 90024 USA. Univ Calif Los Angeles, Med Ctr, Div HIV Med, Los Angeles Biomed Res Inst Harbor, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Div Infect Dis, Los Angeles Biomed Res Inst Harbor, Los Angeles, CA 90027 USA. Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA USA. Rho Inc, Dept Biostat, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 487 BP 455A EP 455A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400493 ER PT J AU Gottwein, JM Scheel, T Jensen, TB Prento, J Knudsen, ML Eugen-Olsen, J Bukh, J AF Gottwein, Judith M. Scheel, Troels Jensen, Tanja Bertelsen Prento, Jannick Knudsen, Maria L. Eugen-Olsen, Jesper Bukh, Jens TI Development of JFH1-based intergenotypic cell culture systems of hepatitis C virus genotypes 1-5 and their use in studies of viral entry and neutralization SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Copenhagen Hosp, Dept Infect Dis, Hvidovre, Denmark. Univ Copenhagen Hosp, Clin Res Unit, Hvidovre, Denmark. Natl Inst Hlth, Lab Infect Dis, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 492 BP 457A EP 457A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400498 ER PT J AU Vander Borght, S Libbrecht, L Komuta, M Pirenne, J Nevens, F Thorgeirsson, SS Verslype, C Roskams, T AF Vander Borght, Sara Libbrecht, Louis Komuta, Mina Pirenne, Jacques Nevens, Frederik Thorgeirsson, Snorri S. Verslype, Chris Roskams, Tania TI Expression of multidrug resistance-associated protein 1 in hepatocellular carcinoma is associated with aggressive tumor phenotype and can reflect progenitor cell origin SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Hosp Leuven, Louvain, Belgium. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 644 BP 524A EP 524A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400650 ER PT J AU Teufel, A Westphal, H Zhao, YG Kanzler, S Galle, PR AF Teufel, Andreas Westphal, Heiner Zhao, Yangu Kanzler, Stephan Galle, Peter R. TI Liver specific Ldb 1 deletion results in enhanced liver cancer development SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 649 BP 526A EP 526A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400655 ER PT J AU Lee, YH Woo, HG Avital, I Judge, AD Durkin, M Ton, A Lee, JS Conner, EA Factor, V MacLachlan, I Thorgeirsson, SS AF Lee, Yun-Han Woo, Hyun Goo Avital, Itzhak Judge, Adam D. Durkin, Marian Ton, Anita Lee, Ju-Seog Conner, Elizabeth A. Factor, Valentina MacLachlan, Ian Thorgeirsson, Snorri S. TI Targeting histone deacetylation for treatment of hepatocellular carcinoma SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Protiva Biotherapeut Inc, Burnaby, BC, Canada. Univ Texas, MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 651 BP 527A EP 527A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400657 ER PT J AU Rehman, H Conner, HD Ramshesh, VK Theruvath, T Mason, RP Lemasters, JJ Zhong, Z AF Rehman, Hasibur Conner, Henry D. Ramshesh, Venkat K. Theruvath, Tom Mason, Ronald P. Lemasters, John J. Zhong, Zhi TI Ischemic preconditioning increases Mn-superoxide dismutase and prevents free radical-dependent mitochondrial depolarization in small-for-size liver grafts SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 667 BP 534A EP 534A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400673 ER PT J AU Chuang, YH Lian, ZXA Yang, GX Shu, SA Moritoki, Y Ridgway, WM Ansari, AA Kronenberg, M Flavell, RA Gao, B Gershwin, ME AF Chuang, Ya-Hui Lian, Zhe-Xiong A. Yang, Guo-Xiang Shu, Shang-An Moritoki, Yuki Ridgway, William M. Ansari, Aftab A. Kronenberg, Mitchell Flavell, Richard A. Gao, Bin Gershwin, M. Eric TI A critical role of invariant NKT cells in exacerbating the biliary lesions in a TGF-beta receptor II dominant-negative mouse model of primary biliary cirrhosis SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Calif Davis, Davis, CA 95616 USA. Univ Pittsburgh, Sch Med, Div Rheumatol & Immunol, Pittsburgh, PA 15260 USA. Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. La Jolla Inst Allergy & Immunol, La Jolla, CA USA. Howard Hughes Med Inst, Sect Immunobiol, New Haven, CT 06510 USA. NIAAA, Lab Physiol Studies, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 692 BP 545A EP 545A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400698 ER PT J AU Reshamwala, PA Kleiner, D Duan, ZG Wright, EC Fuss, I Gladwin, MT Holland, SM Malech, HL Metcalfe, DD Strober, W Hoofnagle, JH Liang, TJ Heller, T AF Reshamwala, Preeti A. Kleiner, David Duan, Zhigang Wright, Elizabeth C. Fuss, Ivan Gladwin, Mark T. Holland, Steven M. Malech, Harry L. Metcalfe, Dean D. Strober, Warren Hoofnagle, Jay H. Liang, T. Jake Heller, Theo TI Nodular regenerative hyperplasia: A clinicopathological evaluation SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 767 BP 577A EP 578A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401030 ER PT J AU Feld, JJ Shields, T Gladwin, MT Hildesheim, ME Nichols, JS Kleiner, D Liang, TJ Hoofnagle, JH Kato, GJ Heller, T AF Feld, Jordan J. Shields, Tammy Gladwin, Mark T. Hildesheim, Mariana E. Nichols, James S. Kleiner, David Liang, T. Jake Hoofnagle, Jay H. Kato, Gregory J. Heller, Theo TI Liver injury is associated with mortality in sickle cell disease SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, NIH, Liver Dis Branch, Bethesda, MD USA. NHLBI, NIH, Vasc Dis Branch, Bethesda, MD 20892 USA. NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 786 BP 586A EP 586A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401049 ER PT J AU Bambha, K Seaberg, EC Pierce, CB French, AL Strickler, HD Howard, AA Tien, PC Sharp, GB Augenbraun, M Kovacs, A Peters, MG AF Bambha, Kiran Seaberg, Eric C. Pierce, Christopher B. French, Audrey L. Strickler, Howard D. Howard, Andrea A. Tien, Phyllis C. Sharp, Gerald B. Augenbraun, Michael Kovacs, Andrea Peters, Marion G. TI Indirect serum markers of fibrosis predict mortality in women with HIV and HCV infections SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Stroger Hosp, CORE Ctr, Chicago, IL USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 883 BP 628A EP 629A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401146 ER PT J AU Mueller, T Marques, AM Sarrazin, C Wiese, M Halangk, J Witt, H Wasmuth, H Ahlenstiel, G Spengler, U Lammert, F Schott, E Weich, V Schreier, E Wiedenmann, B Berg, T AF Mueller, Tobias Marques, Andreas Mas Sarrazin, Christoph Wiese, Manfred Halangk, Juliane Witt, Heiko Wasmuth, Hartmut Ahlenstiel, Golo Spengler, Ulrich Lammert, Frank Schott, Eckart Weich, Viola Schreier, Eckart Wiedenmann, Betram Berg, Thomas TI Low-density lipoprotein receptor (LDLR) polymorphisms are associated with spontaneous and treatment-induced recovery from hepatitis C virus (HCV) infection SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Charite Univ Med Berlin, Med Klin Schwerpunkt Hepatol & Gastroenterol, Berlin, Germany. Robert Koch Inst, D-1000 Berlin, Germany. Univ Kliniken Saarlandes, Med Klin & Poliklin Innere Med 2, Homburg, Germany. Staedt Klinikum St Georg, Innere Med Klin 2, Leipzig, Germany. Univ Klinikum Aachen, Med Klin 3, Aachen, Germany. NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Klinikum Bonn, Med Klin 1, Bonn, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 885 BP 629A EP 630A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401148 ER PT J AU Loomba, R Rowley, A Wesley, R Liang, TJ Hoofnagle, JH Pucino, F Csako, G AF Loomba, Rohit Rowley, Ayana Wesley, Robert Liang, T. Jake Hoofnagle, Jay H. Pucino, Frank Csako, Gyorgy TI Pre-emptive lamivudine reduces the risk of chemotherapy-induced HBV-related morbidity and mortality in HBsAg-positive cancer patients: Meta-analysis SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NIH, Dept Pharm, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 945 BP 657A EP 657A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401208 ER PT J AU Haber, B Balistreri, WF Barton, B Gonzalez-Peralta, RP Goodman, ZD Jonas, MM Lobritto, SJ Mohan, P Molleston, JP Murray, KF Narkewicz, M Robuck, PR Rosenthal, P Schwarz, KB AF Haber, Barbara Balistreri, William F. Barton, Bruce Gonzalez-Peralta, Regino P. Goodman, Zachary D. Jonas, Maureen M. Lobritto, Steven J. Mohan, Parvathi Molleston, Jean P. Murray, Karen F. Narkewicz, Michael Robuck, Patricia R. Rosenthal, Philip Schwarz, Kathleen B. TI HCV autoimmunity in a US multi-center cohort of treatment naive children SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 CHOP, Philadelphia, PA 02115 USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Maryland Med Res Inst, Baltimore, MD USA. Univ Florida, Gainesville, FL 46204 USA. Childrens Hosp, Boston, MA USA. Columbia Univ, New York Presbyterian Hosp, New York, NY 80218 USA. George Washington Univ, Washington, DC USA. Indiana Univ, Sch Med, Indianapolis, IN 94143 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. Childrens Hosp, Denver, CO 20306 USA. NIDDK, NIH, Bethesda, MD USA. Univ Calif San Francisco, Childrens Hosp, San Francisco, CA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Armed Forces Inst Pathol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1092 BP 722A EP 723A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401355 ER PT J AU Clark, JM Van Natta, M Kleiner, D Chalasani, NP McCullogh, AJ Neuschwander-Tetri, BA Unalp, A Hoofnagle, JH Diehl, AM AF Clark, Jeanne M. Van Natta, Mark Kleiner, David Chalasani, Naga P. McCullogh, Arthur J. Neuschwander-Tetri, Brent A. Uenalp, Aynur Hoofnagle, Jay H. Diehl, Anna Mae TI Association of AST and ALT with liver histology in adults with NAFLD SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Johns Hopkins Univ, Baltimore, MD USA. NIDDK, NIH, Bethesda, MD USA. Indiana Univ, Indianapolis, IN 46204 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. St Louis Univ, St Louis, MO 63103 USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 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 OCT PY 2007 VL 46 IS 4 SU S MA 1126 BP 738A EP 738A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401389 ER PT J AU Lee, VD Kleiner, D Al-Osaimi, AM Argo, CK Northup, PG Berg, CL Pruett, TL Schmitt, TM Caldwell, SH AF Lee, Vanessa D. Kleiner, David Al-Osaimi, Abdullah M. Argo, Curtis K. Northup, Patrick G. Berg, Carl L. Pruett, Timothy L. Schmitt, Timothy M. Caldwell, Stephen H. TI Histological characteristics of patients with 'cryptogenic' cirrhosis and prior biopsy showing NASH SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Virginia, Charlottesville, VA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1138 BP 743A EP 744A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401401 ER PT J AU Kim, YJ Woo, HG Jung, YJ Kim, DH Park, BJ Yi, NJ Suh, KS Lee, KU Yoon, JH Thorgeirsson, SS Lee, HS AF Kim, Yoon Jun Woo, Hyun Goo Jung, Yong Jin Kim, Dong Hee Park, Bum Joon Yi, Nam-Joon Suh, Kyung-Suk Lee, Kuhn Uk Yoon, Jung-Hwan Thorgeirsson, Snorri S. Lee, Hyo-Suk TI Gene expression based recurrence prediction of HBV-related human hepatocellular carcinoma SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. Korea Res Inst Biosci & Biotechnol, Korea Bioinformat Ctr, Taejon, South Korea. Seoul Natl Univ Hosp, Dept Surg, Seoul 110744, South Korea. NCI, Expt Carcinogenesis Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RI Park, Byung-Joo/E-5438-2011; Lee, Hyo-Suk/J-5618-2012; Yi, Nam-Joon/J-5574-2012 OI Park, Byung-Joo/0000-0003-4630-4942; NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1244 BP 789A EP 789A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401507 ER PT J AU Budhu, A Jia, HL Forgues, M Liu, CG Goldstein, D Lam, A Zanetti, K Ye, QH Qin, LX Croce, C Tang, ZY Wang, X AF Budhu, Anuradha Jia, Hu-Liang Forgues, Marshonna Liu, Chang-Gong Goldstein, David Lam, Amy Zanetti, Krista Ye, Qing-Hai Qin, Lun-Xiu Croce, Carlo Tang, Zhao-You Wang, Xin TI A unique metastasis-related microrna expression signature is a prognostic indicator of survival and recurrence in hepatocellular carcinoma SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. Liver Canc Inst, Shanghai, Peoples R China. Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, Off Sci & Technol Partnerships, Canc Res Ctr, Bethesda, MD 20892 USA. EMMS Corp, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 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 OCT PY 2007 VL 46 IS 4 SU S MA 1249 BP 791A EP 791A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401512 ER PT J AU Coulouarn, C Factor, VM Thorgeirsson, SS AF Coulouarn, Cedric Factor, Valentiana M. Thorgeirsson, Snorri S. TI Transforming growth factor-beta gene expression signature predicts clinical outcome in cancer SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RI Coulouarn, Cedric/E-5472-2011 NR 0 TC 0 Z9 0 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 OCT PY 2007 VL 46 IS 4 SU S MA 1248 BP 791A EP 791A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401511 ER PT J AU Naranjo-Suarez, S Factor, VM Coulouarn, C Thorgeirsson, SS AF Naranjo-Suarez, Salvador Factor, Valentina M. Coulouarn, Cedric Thorgeirsson, Snorri S. TI Hypoxia induced gene expression signature in normal hepatocytes and human hepatocellular carcinoma SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NCI, NIH, Bethesda, MD 20892 USA. RI Coulouarn, Cedric/E-5472-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1263 BP 797A EP 797A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401526 ER PT J AU Kitisin, K Amin, R Tang, Y Volpe, EA Mendelson, JS Jogunoori, W Blake, TM Pishvaian, MJ Li, C Deng, CX Mueller, S Resom, H Mishra, B Evans, SR Shetty, K Zasloff, M Johnson, LB Mishra, L AF Kitisin, Krit Amin, Rupen Tang, Yi Volpe, Eugene A. Mendelson, Jonathan S. Jogunoori, Wilma Blake, Tiffany M. Pishvaian, Michael J. Li, Cuiling Deng, Chu-Xia Mueller, Susette Resom, Habtom Mishra, Bibhuti Evans, Stephen R. Shetty, Kirti Zasloff, Michael Johnson, Lynt B. Mishra, Lopa TI Human TGF-beta-regulated liver stem/progenitor cells in normal post transplant living donor recipients are altered in hepatocellular cancers SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. NIDDK, Genet Dev & Dis Branch, NIH, Washington, DC USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1273 BP 801A EP 802A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401536 ER PT J AU Yun, CH Pishvaian, MJ Tang, Y Kitisin, K Volpe, EA Mendelson, JS Jogunoori, W Li, C Deng, CX Mueller, S Ressom, H Rashid, A Sidawy, AN Evans, SR Shetty, K Zasloff, M Mishra, B Reddy, EP Johnson, LB Mishra, L AF Yun, Chohee Pishvaian, Michael J. Tang, Yi Kitisin, Krit Volpe, Eugene A. Mendelson, Jonathan S. Jogunoori, Wilma Li, Cuiling Deng, Chu-Xia Mueller, Susette Ressom, Habtom Rashid, Asif Sidawy, Anton N. Evans, Stephen R. Shetty, Kirti Zasloff, Michael Mishra, Bibhuti Reddy, E. P. Johnson, Lynt B. Mishra, Lopa TI Modulation of stemness in dysfunctional progenitor/stem cells alters cancer formation in the liver SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Georgetown Univ, Washington, DC USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Temple Univ, Philadelphia, PA 19122 USA. MD Anderson Canc Ctr, Houston, TX USA. NIH, Bethesda, MD 20892 USA. RI Reddy, E. Premkumar/F-6233-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1271 BP 801A EP 801A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401534 ER PT J AU Rochon, J Seeff, LB Fontana, RJ Liangpunsakul, S Hayashi, PH Davern, TJ McHutchison, JG AF Rochon, James Seeff, Leonard B. Fontana, Robert J. Liangpunsakul, Suthat Hayashi, Paul H. Davern, Timothy J. McHutchison, John G. TI A prospective study of the reliability of the RUCAM for assessing causality in drug-induced liver injury SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Duke Clin Res Inst, Durham, NC USA. Univ Connecticut, Farmington, CT USA. Univ N Carolina, Chapel Hill, NC USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Indiana Univ, Indianapolis, IN USA. NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1295 BP 811A EP 811A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401558 ER PT J AU Modi, AA Feld, JJ Park, Y Everhart, J Liang, TJ Hoofnagle, JH AF Modi, Apurva A. Feld, Jordan J. Park, Yoon Everhart, James Liang, T. Jake Hoofnagle, Jay H. TI Higher caffeine consumption is associated with milder fibrosis in patients with chronic liver diseases SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, Branch Liver Dis, Bethesda, MD USA. NIDDK, Epidemiol & Clin Trials Branch, NIH, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1341 BP 835A EP 835A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401604 ER PT J AU Matsumura, T Kato, T Hu, Z Imamura, M Hiraga, N Juteau, JM Vaillant, A Chayama, K Liang, TJ AF Matsumura, Takuya Kato, Takanobu Hu, Zongyi Imamura, Michio Hiraga, Nobuhiko Juteau, Jean-Marc Vaillant, Andrew Chayama, Kazuaki Liang, T. Jake TI Phosphorothioate oligonucleotide is a potent entry inhibitor of hepatitis C virus infection in vitro and in vivo SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIH, Liver Dis Branch, Bethesda, MD 20892 USA. Div Frontier Med Sci, Dept Med & Mol Sci, Hiroshima, Japan. REPLICor Inc, Laval, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1378 BP 852A EP 852A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401641 ER PT J AU Feld, JJ Ayers, M El-Ashry, D Mazzulli, T Tellier, R Heathcote, EJ AF Feld, Jordan J. Ayers, Melissa El-Ashry, Dahlia Mazzulli, Tony Tellier, Raymond Heathcote, E. Jenny TI Hepatitis B virus DNA prediction rules for hepatitis B e antigen-negative chronic hepatitis B SO HEPATOLOGY LA English DT Article ID SERUM HBV-DNA; CORE-PROMOTER; VIRAL REPLICATION; FULMINANT-HEPATITIS; NATURAL-HISTORY; PRECORE REGION; MUTATIONS; INFECTION; CARRIERS; SEROCONVERSION AB After hepatitis B e antigen (HBeAg) seroconversion, hepatitis B may become inactive or progress to HBeAg-negative hepatitis with persistent or intermittent alanine aminotransferase (ALT) elevation. The aim of this study was to prospectively identify factors predictive of the clinical course in HBeAg-negative chronic hepatitis B (CHB). Patients were stratified by ALT and HBeAg status and followed every 3 months for up to 5 years. Kaplan-Meier and Cox regression analysis using the change from normal ALT to elevated ALT as endpoints were performed to determine factors associated with ALT elevation/normalization. Seventy-four HBeAg-negative and 32 HBeAg-positive patients were prospectively evaluated. For HBeAg-negative patients, hepatitis B virus (HBV) DNA was predictive of future ALT. Only 1 patient with normal ALT and an HBV DNA value lower than 10,000 copies/mL developed an elevated ALT within the subsequent year, whereas 67% with an HBV DNA value greater than 100,000 copies/mL had a rise in ALT above normal within 1 year. Patients with a previous history of ALT elevation and longer follow-up at all levels of HBV DNA were more likely to experience ALT elevations. For HBeAg-negative patients with elevated ALT and all HBeAg-positive patients, HBV DNA did not predict future ALT. Other viral and host factors were not predictive of future ALT. Conclusion: HBeAg-negative CHB has a fluctuating course. HBV DNA values lower than 10,000 copies/mL predict persistently normal ALT for at least 1 year. Patients with HBV DNA values between 10,000 and 100,000 copies/mL can safely be followed at 6 monthly intervals, whereas HBV DNA values greater than 100,000 copies/mL are highly predictive of future ALT elevation and should prompt regular follow-up. C1 Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. NIH, NIDDKD, Liver Dis Branch, Bethesda, MD 20892 USA. RP Feld, JJ (reprint author), NIH, NIDDKD, 10 Ctr Dr,Room 9B16,MSC 1800, Bethesda, MD 20892 USA. EM feldj@niddk.nih.gov FU Intramural NIH HHS NR 39 TC 56 Z9 56 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 BP 1057 EP 1070 DI 10.1002/hep.21811 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WU UT WOS:000249910500016 PM 17654702 ER PT J AU Joy, DA Craig, DA Conn, JE AF Joy, D. A. Craig, D. A. Conn, J. E. TI Genetic variation tracks ecological segregation in Pacific island black flies SO HEREDITY LA English DT Article DE insular radiation; habitat shift; mitochondrial DNA; simuliidae; island biogeography ID SUBGENUS INSELIELLUM DIPTERA; MITOCHONDRIAL-DNA; CLADISTIC-ANALYSIS; GEOGRAPHICAL-DISTRIBUTION; NUCLEOTIDE SUBSTITUTIONS; PHENOTYPIC PLASTICITY; HAWAIIAN DROSOPHILA; HAPLOTYPES; SIMULIIDAE; SPECIATION AB Geographic isolation is widely viewed as a key component of insular radiations on islands. However, strong ecological affinities may also reinforce isolation and promote genetic divergence. The black fly fauna in the Society Islands French Polynesia is notable for the number of closely related endemic species (31), and the morphological and habitat diversity of the larvae. Here, we measure ecological and morphological differences within and between two closely related species, Simulium oviceps and Simulium dussertorum and relate these differences to genetic distance. Phylogenetic analyses of a 920 bp fragment of the cytochrome oxidase I (COI) gene revealed a well-supported, ecologically divergent S. oviceps clade (larvae found in rivers instead of cascades) that shows little morphological differentiation. For both S. oviceps and S. dussertorum, genetic distance among populations is related to larval habitat, with cascade populations showing greater isolation from each other than river populations. Our data support the hypothesis that larval ecological shifts have played a role in the radiation of this black fly fauna. C1 Univ Vermont, Dept Biol, Burlington, VT USA. Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada. New York State Dept Hlth, Wadsworth Ctr, Slingerlands, NY USA. RP Joy, DA (reprint author), NIAID, NIH, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy, Room 3E-20B, Rockville, MD 20850 USA. EM djoy@niaid.nih.gov OI Conn, Jan/0000-0002-5301-7020 NR 43 TC 16 Z9 16 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0018-067X J9 HEREDITY JI Heredity PD OCT PY 2007 VL 99 IS 4 BP 452 EP 459 DI 10.1038/sj.hdy.6801023 PG 8 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 214FH UT WOS:000249720900014 PM 17611492 ER PT J AU Batt, RE Smith, RA Louis, GMB Martin, DC Chapron, C Koninckx, PR Yeh, J AF Batt, R. E. Smith, R. A. Louis, G. M. Buck Martin, D. C. Chapron, C. Koninckx, P. R. Yeh, J. TI Mullerianosis SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE endometriosis; mullerianosis; mullerian choristoma; pathogenesis; pathology ID DEEPLY INFILTRATING ENDOMETRIOSIS; UTERUS-LIKE MASS; RENAL TISSUE; PERITONEAL ENDOMETRIOSIS; HEPATIC ENDOMETRIOSIS; URINARY-BLADDER; SMALL-INTESTINE; TETHERED CORD; DISEASE; ENDOCERVICOSIS AB Mullerianosis may be defined as an organoid structure of embryonic origin; a choristoma composed of mullerian rests - normal endometrium, normal endosalpinx, and normal endocervix - singly or in combination, incorporated within other normal organs during organogenesis. A choristoma is a mass of histologically normal tissue that is " not normally found in the organ or structure in which it is located" ( Choristoma, 2006). Mullerian choristomas are a subset of non- mullerian choristomas found throughout the body. Histologically, endometrial- mullerianosis and endometriosis are both composed of endometrial glands and stroma, but there the similarity ends. Their pathogenesis is different. Sampson faced the same difficulty with pathogenesis and nomenclature when he wrote: " The nomenclature of misplaced endometrial or mullerian lesions is a difficult one to decide upon." " The term mullerian would be inclusive and correct, but unfortunately it suggests an embryonic origin." Sampson then divided " misplaced endometrial or mullerian tissue" into " four or possibly five groups, according to the manner in which this tissue reached its ectopic location" ( Sampson, 1925). Sampson's classification of heterotopic or misplaced endometrial tissue is based on pathogenesis: 1) " direct or primary endometriosis" [ adenomyosis]; " a similar condition occurs in the wall of the tube from its invasion by the tubal mucosa" [ endosalpingiosis]; 2) " peritoneal or implantation endometriosis;" 3) " transplantation endometriosis;" 4) " metastatic endometriosis;" and 5) " developmentally misplaced endometrial tissue. ( I admit the possibility of such a condition, but have never been able to appreciate it.)" ( Sampson, 1925). It is precisely this condition " developmentally misplaced endometrial tissue," [ mullerianosis] that is the subject of this review. C1 SUNY Buffalo Coll, Dept Obstet Gynecol, Buffalo, NY 14260 USA. Sturdy Mem Hosp, Attleboro, MA USA. NICHHD, Epidemiol Branch, Rockville, MD USA. Univ Tennessee, Hlth Sci Ctr, Dept Obstet & Gynecol, Knoxville, TN 37996 USA. CHU Cochin St Vincent Paul, Dept Obstet & Gynecol, Paris, France. Univ Hosp Gaithuisberg, Dept Obstet & Gynecol, Louvain, Belgium. RP Batt, RE (reprint author), SUNY Buffalo Coll, 219 Bryant St, Buffalo, NY 14222 USA. EM rbatt@buffalo.edu OI Buck Louis, Germaine/0000-0002-1774-4490 NR 54 TC 32 Z9 32 U1 1 U2 3 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 EI 1699-5848 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD OCT PY 2007 VL 22 IS 10 BP 1161 EP 1166 PG 6 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 186CS UT WOS:000247757300011 PM 17616942 ER PT J AU Mirochnick, M Rodman, JH Robbins, B Fridland, A Gandia, J Hitti, J Bardeguez, A Rathore, MH Garcia, AG Cababasay, M Samson, P Mofenson, L Bryson, YJ Dorenbaum, A AF Mirochnick, M. Rodman, J. H. Robbins, B. L. Fridland, A. Gandia, J. Hitti, J. Bardeguez, A. Rathore, M. H. Garcia, A. Gonzalez Cababasay, M. Samson, P. Mofenson, L. Bryson, Y. J. Dorenbaum, A. TI Pharmacokinetics of oral zidovudine administered during labour: a preliminary study SO HIV MEDICINE LA English DT Article DE AIDS; antiretrovirals; pharmacokinetics; pregnancy ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERINATAL HIV-1 TRANSMISSION; VERTICAL TRANSMISSION; PREGNANT-WOMEN; COTE-DIVOIRE; PREVENTION; TRIAL; TOLERANCE; DELIVERY; CHILDREN AB Objectives The aim of this study was to determine whether oral zidovudine (ZDV) given during labour would provide a similar systemic exposure to the established intravenous regimen used to prevent mother-to-child transmission in HIV-infected pregnant women. Methods ZDV pharmacokinetic parameters following oral administration during labour were determined in 10 HIV-infected pregnant women in active labour. All subjects were converted to intravenous ZDV prior to delivery. Results In cohort 1 (n=6), subjects received 300 mg oral ZDV every 3 h for three doses. Oral therapy was well tolerated but plasma ZDV concentrations were substantially lower than previously reported with continuous intravenous therapy. Based on the pharmacokinetic results from cohort 1, women in cohort 2 (n=4) received an initial 600 mg dose followed by two 400 mg doses every 3 h. ZDV area under the curve and concentrations in cohort 2 increased approximately in proportion to the increase in dose but varied 6-7-fold. In both cohorts, ZDV pharmacokinetic parameters suggested erratic absorption. Conclusions While ZDV exposure improved with the increased dosing regimen, our sample size was small and larger studies are needed to establish whether oral ZDV administration during labour can consistently provide equivalent exposure to intravenous administration. C1 Boston Univ, Med Ctr, Sch Med, Dept Pediat, Boston, MA 02118 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. San Juan City Hosp, Dept Pediat, San Juan, PR USA. Univ Washington, Med Ctr, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Med & Dent New Jersey, Dept Obstet Gynecol & Womens Hlth, Newark, NJ 07103 USA. Univ Florida, Hlth Sci Ctr, Dept Pediat Infect Dis Immunol, Jacksonville, FL 32209 USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. NICHHD, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. RP Mirochnick, M (reprint author), Boston Univ, Med Ctr, Sch Med, Dept Pediat, 91 E Concord St,6th Floor, Boston, MA 02118 USA. EM markm@bu.edu OI Mofenson, Lynne/0000-0002-2818-9808 NR 19 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-2662 J9 HIV MED JI HIV Med. PD OCT PY 2007 VL 8 IS 7 BP 451 EP 456 DI 10.1111/j.1468-1293.2007.00495.x PG 6 WC Infectious Diseases SC Infectious Diseases GA 203TO UT WOS:000248997100006 PM 17760737 ER PT J AU Knutson, KM Mah, L Manly, CF Grafman, J AF Knutson, Kristine M. Mah, Linda Manly, Charlotte F. Grafman, Jordan TI Neural correlates of automatic beliefs about gender and race SO HUMAN BRAIN MAPPING LA English DT Article DE social cognition; emotion; behavior; attitudes; automatic processing; stereotypes; orbitofrontal cortex; prefrontal cortex; gender differences ID IMPLICIT ASSOCIATION TEST; ANTERIOR CINGULATE CORTEX; INFERIOR PREFRONTAL CORTEX; FALSE DISCOVERY RATE; FRONTAL-LOBE DAMAGE; ORBITOFRONTAL CORTEX; HUMAN AMYGDALA; SOCIAL COGNITION; FUNCTIONAL-ANATOMY; RACIAL PREJUDICE AB Functional MRI was used to identify the brain areas underlying automatic beliefs about gender and race, and suppression of those attitudes. Participants (n = 20; 7 females) were scanned at 3 tesla while performing the Implicit Association Test (IAT), an indirect measure of race and gender bias. We hypothesized that ventromedial prefrontal cortex areas (PFC) would mediate gender and racial stereotypic attitudes, and suppression of these beliefs would recruit dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC). Performance data on the IAT revealed gender and racial biases. Racial bias was correlated with an explicit measure of racism. Results showed activation of anteromedial PFC and rostral ACC while participants implicitly made associations consistent with gender and racial biases. In contrast, associations incongruent with stereotypes recruited DLPFC. Implicit gender bias was correlated with amygdala activation during stereotypic conditions. Results suggest there are dissociable roles for anteromedial and dorsolateral PFC circuits in the activation and inhibition of stereotypic attitudes. C1 NINDS, NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, NIH, Cognit Neurosci Sect, Bldg 10,Room 5C205,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Knutson, Kristine/0000-0003-4626-4514; Grafman, Jordan H./0000-0001-8645-4457 NR 100 TC 63 Z9 66 U1 5 U2 21 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD OCT PY 2007 VL 28 IS 10 BP 915 EP 930 DI 10.1002/hbm.20320 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 218BJ UT WOS:000249990700001 PM 17133388 ER PT J AU Donahue, R An, DS Kamata, M Mattapallil, J Poon, B Metzger, M Mao, SH Bonifacino, A Krouse, A Darlix, JL Baltimore, D Qin, FXF Chen, ISY AF Donahue, Robert An, Dong-Sung Kamata, Masakazu Mattapallil, Joseph Poon, Betty Metzger, Mark Mao, Si-Hua Bonifacino, Aylin Krouse, Allen Darlix, Jean-Luc Baltimore, David Qin, F. Xiao-Feng Chen, Irvin S. Y. TI Prolonged reduction of CCR5 expression in multiple hematopoietic cell lineages by RNA interference through CD34+cell transplant in non-human primates SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 15th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY OCT 27-30, 2007 CL Rotterdam, NETHERLANDS SP European Soc Gene & Cell Therapy C1 [Donahue, Robert; Metzger, Mark; Bonifacino, Aylin; Krouse, Allen] NHLBI, Hematol Branch, Rockville, MD USA. [Donahue, Robert; Metzger, Mark; Bonifacino, Aylin; Krouse, Allen] Univ Calif Los Angeles, AIDS Inst, David Geffen Sch Med, Los Angeles, CA USA. [Mattapallil, Joseph] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Darlix, Jean-Luc] Ecole Normale Super Lyon, Unit Virol Human, Lab Retro, F-69364 Lyon, France. [Baltimore, David] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Qin, F. Xiao-Feng] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. EM donahuer@nhlbi.nih.gov NR 0 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 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2007 VL 18 IS 10 BP 949 EP 949 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 222ZU UT WOS:000250339500026 ER PT J AU Wahren, B Brave, A Ljungberg, K Gudmundsdotter, L Boberg, A Cox, J Robb, M Marovich, M Earl, P Moss, B Nilsson, C Biberfeld, G Sandstrom, E AF Wahren, Britta Brave, Andreas Ljungberg, Karl Gudmundsdotter, Lindvi Boberg, Andreas Cox, Josephine Robb, Merlin Marovich, Mary Earl, Patricia Moss, Bernard Nilsson, Charlotta Biberfeld, Gunnel Sandstrom, Eric TI Potent cellular and humoral immunity against HIV-1 elicited preclinically and clinically by a DNA-prime/MVA-boost vaccine regimen SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 15th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY OCT 27-30, 2007 CL Rotterdam, NETHERLANDS SP European Soc Gene & Cell Therapy C1 [Wahren, Britta; Brave, Andreas; Ljungberg, Karl; Gudmundsdotter, Lindvi; Boberg, Andreas; Nilsson, Charlotta; Biberfeld, Gunnel] Karolinska Inst, Stockholm, Sweden. [Cox, Josephine; Robb, Merlin; Marovich, Mary] Walter Reed Army Inst Res, Rockville, MD USA. [Earl, Patricia; Moss, Bernard] NIH, NIAID, Lab Viral Dis, Bethesda, MD USA. [Sandstrom, Eric] Karolinska Univ Hosp, Stockholm, Sweden. EM Britta.Wahren@smi.ki.se 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 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2007 VL 18 IS 10 BP 962 EP 962 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 222ZU UT WOS:000250339500055 ER PT J AU Jorritsma, A Gomez-Eerland, R Dokter, M De Kasteele, WV Zoet, Y Doxiadis, I Rufer, N Romero, P Morgan, R Schumacher, T Haanen, J AF Jorritsma, Annelies Gomez-Eerland, Raquel Dokter, Maarten De Kasteele, Willeke Van Zoet, Yvonne Doxiadis, Ilias Rufer, Nathalie Romero, Pedro Morgan, Richard Schumacher, Ton Haanen, John TI Selecting highly affine and well-expressed TCRs for gene therapy of melanoma SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 15th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY OCT 27-30, 2007 CL Rotterdam, NETHERLANDS SP European Soc Gene & Cell Therapy C1 [Jorritsma, Annelies; Gomez-Eerland, Raquel; Dokter, Maarten; De Kasteele, Willeke Van; Schumacher, Ton; Haanen, John] Netherlands Canc Inst, Amsterdam, Netherlands. [Zoet, Yvonne; Doxiadis, Ilias] Leiden Univ, Med Ctr, Leiden, Netherlands. [Rufer, Nathalie; Romero, Pedro] Ludwig Inst Canc Res, Lausanne, Switzerland. [Morgan, Richard] NIH, Natl Canc Inst, Surg Branch, Bethesda, MD 20892 USA. 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 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2007 VL 18 IS 10 BP 980 EP 980 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 222ZU UT WOS:000250339500103 ER PT J AU Condiotti, R Grinshpun, A Peretz, S Chou, J Galun, E AF Condiotti, Reba Grinshpun, Albert Peretz, Sima Chou, Janice Galun, Eithan TI Correction of glycogen storage disease Ia in a murine model using a non-primate lentiviral vector SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 15th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY OCT 27-30, 2007 CL Rotterdam, NETHERLANDS SP European Soc Gene & Cell Therapy C1 [Condiotti, Reba; Grinshpun, Albert; Galun, Eithan] Hadassah Univ Hosp, Goldyne Savad Inst Gene Therapy, IL-91120 Jerusalem, Israel. [Peretz, Sima] Harlan Biotech Israel Ltd, SPF Anim Facilities, Rehovot, Israel. [Chou, Janice] NIH, NICHHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. EM reba@hadassah.org.il 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 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2007 VL 18 IS 10 BP 1072 EP 1073 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 222ZU UT WOS:000250339500347 ER PT J AU Du, KM Ji, Y Xie, JH Fu, M Sun, Y Jin, Y Sun, JL Yang, JH Zhang, Z Mao, Z Liu, DZ Qian, KC Zhao, TM AF Du, Ke-Ming Ji, Yun Xie, Jun-Hua Fu, Min Sun, Ying Jin, Ye Sun, Ji-Li Yang, Jian-Hao Zhang, Zheng Mao, Zhen Liu, Da-Zhuang Qian, Kai-Cheng Zhao, Tong-Mao TI HLA-A, -B, -DR haplotype frequencies from DNA typing data of 26,266 Chinese bone marrow donors SO HUMAN IMMUNOLOGY LA English DT Article DE HLA-A; -B; -DR; haplotype frequencies; probability of finding HLA-matched donor in China; bone marrow donor registry ID CORD BLOOD; ALLELES AB HLA phenotypes of 26,266 Chinese individuals who were recruited as potential hematopoietic stem cell donors by the Shanghai Red Cross Marrow Donor Registry, part of the China Marrow Donor Program, were determined for HLA-A, -B, and -DRB1 alleles at low to intermediate resolution using DNA-based typing methods. The large sample size of the study allowed accurate calculation of the Chinese HLA haplotype frequencies. The observed alleles correspond to 19 HLA-A, 44 -B, and 13 -DR split antigens. The serologic equivalents of HLA-A36, -A80, -B78, and -DR18 alleles were not observed. A total of 2,241 distinct HLA-A, -B, -DRB1 haplotypes were identified. Three-locus haplotype frequency was estimated using the maximum likelihood method. The lowest haplotype frequency that can be reliably estimated at a 95% confidence Level was 0.000057. Using this cutoff value, 1,220 haplotypes (54%) were statistically reliable and their cumulative haplotype frequency was 0.9730. The cumulative haplotype frequency of the remaining 1,021 haplotypes (46%) was 0.0270. A regression equation of p = 0.192 log N-0.576 was derived to estimate the probability (p) of finding an HLA-A, -B, -DR split antigens-matched donor in a pool of N Chinese donors. (c) 2007 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. C1 Shanghai Blood Ctr, Shanghai, Peoples R China. NIH, Bethesda, MD 20892 USA. RP Du, KM (reprint author), Shanghai Blood Ctr, Shanghai, Peoples R China. EM dkeming@hotmail.com NR 12 TC 13 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 2007 VL 68 IS 10 BP 854 EP 866 DI 10.1016/j.humimm.2007.04.006 PG 13 WC Immunology SC Immunology GA 227MZ UT WOS:000250662100008 PM 17961775 ER PT J AU Nal, N Ahmed, ZM Erkal, E Alper, OM Luleci, G Dinc, O Waryah, AM Ain, Q Tasneem, S Husnain, T Chattaraj, P Riazuddin, S Boger, E Ghosh, M Kabra, M Riazuddin, S Morell, RJ Friedman, TB AF Nal, Nevra Ahmed, Zubair M. Erkal, Engin Alper, Oezguel M. Lueleci, Gueven Dinc, Oktay Waryah, Ali Muhammad Ain, Quratul Tasneem, Saba Husnain, Tayyab Chattaraj, Parna Riazuddin, Saima Boger, Erich Ghosh, Marju Kabra, Madhulika Riazuddin, Sheikh Morell, Robert J. Friedman, Thomas B. TI Mutational spectrum of MYO15A: The large N-terminal extension of myosin XVA is required for hearing SO HUMAN MUTATION LA English DT Article DE DFNB3; hereditary deafness; genotype-phenotype; myosin; MYO15A ID BARDET-BIEDL-SYNDROME; CLASS-III MYOSIN; UNCONVENTIONAL MYOSIN; DEAFNESS DFNB3; CELL STEREOCILIA; HAIR BUNDLE; GENE; LOCALIZATION; EXPRESSION; CLONING AB Human MYO15A is located on chromosome 17p11.2, has 66 exons and encodes unconventional myosin XVA. Recessive mutations of MYO15A are associated with profound, nonsyndromic hearing loss DFNB3 in humans, and deafness and circling behavior in shaker 2 mice. In the inner ear, this motor protein is necessary for the development of hair cell stereocilia, which are actin-filled projections on the apical surface and the site of mechanotransduction of sound. The longest isoform of myosin XVA has 3,530 amino acid residues. Two isoform classes of MYO15A are distinguished by the presence or absence of 1,203 residues preceding the motor domain encoded by alternatively-spliced exon 2. It is not known whether this large N-terminal extension of myosin XVA is functionally necessary for hearing. We ascertained approximately 600 consanguineous families segregating hereditary hearing loss as a recessive trait and found evidence of linkage of markers at the DFNB3 locus to hearing loss in 38 of these families ascertained in Pakistan (n = 30), India (n = 6), and Turkey (n = 2). In this study, we describe 16 novel recessive mutations of MYO15A associated with severe to profound hearing loss segregating in 20 of these DFNB3-linked families. Importantly, two homozygous mutant alleles-c.3313G>T (p.E1105X) and c.3334de1G (p.G1112fsX1124) of MYO15A-located in exon 2 are associated with severe to profound hearing loss segregating in two families. These data demonstrate that isoform 1, containing the large N-terminal extension, is also necessary for normal hearing. C1 Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD 20850 USA. Akdeniz Univ, Dept Med Biol & Genet, Antalya, Turkey. Akdeniz Univ, Dept Otolaryngol, Antalya, Turkey. Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. All India Inst Med Sci, Dept Pediat, Genet Unit, New Delhi, India. RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. EM friedman@nidcd.nih.gov RI Husnain, Tayyab/G-3805-2015; SHEIKH, RIAZUDDIN/L-2406-2015; OI Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [1 ZO1DC000035-09, 1ZO1DC000039-09] NR 37 TC 41 Z9 41 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD OCT PY 2007 VL 28 IS 10 BP 1014 EP 1019 DI 10.1002/humu.20556 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 218TA UT WOS:000250036600013 PM 17546645 ER PT J AU Li, YM Tabatabai, L Lee, TL Hatakeyama, S Hyatna, C Chan, WY Looijenga, LHJ Lau, YFC AF Li, Yunmin Tabatabai, Laura Lee, Tin-Lap Hatakeyama, Shingo Hyatna, Chikara Chan, Wai-Yee Looijenga, Leendert H. J. Lau, Yun-Fai Chris TI The Y-encoded TSPY protein: a significant marker potentially plays a role in the pathogenesis of testicular germ cell tumors SO HUMAN PATHOLOGY LA English DT Article DE gonadoblastoma locus; Y chromosome; TSPY; diagnostic marker; 12p genes; testicular germ cell tumors ID CARCINOMA IN-SITU; ENVIRONMENTAL CONNECTION; GONADOBLASTOMA LOCUS; DYSGENETIC GONADS; PROSTATE-CANCER; CANDIDATE GENE; CHROMOSOME; EXPRESSION; DIFFERENTIATION; NEOPLASIA AB The testis-specific protein Y-encoded (TSPY) gene is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY) that predisposes dysgenetic gonads of intersex patients to gonadoblastoma development. TSPY is expressed at high levels in gonadoblastoma tissues, supporting its possible oncogenic function in this type of germ cell tumors. To explore the possibility that this Y chromosome gene is also involved in pathogenesis of the more common testicular germ cell tumors (TGCTs), we have conducted various expression studies using immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction analysis on 171 cases of TGCTs and selected normal testis controls. Our results demonstrated that TSPY protein is abundantly expressed in the precursor, carcinoma in situ or intratubular germ cell neoplasia unclassified, and seminoma, but only minimally or not expressed in various types of nonseminomas. TSPY coexpresses with established germ cell tumor markers (such as placental-like alkaline phosphatase, c-KIT, OCT4) and proliferative markers (such as Ki-67 and cyclin B 1) in the same tumor cells at both RNA and protein levels. Ectopic TSPYexpression in cultured cells up-regulates progrowth genes, including those at chromosome 12p 13, frequently gained/amplified in TGCTs. Our results suggest that TSPY, in combination with other markers, could be an important marker for diagnosis and subclassification of TGCTs and support its role in the pathogenesis of both gonadoblastoma and TGCTs. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, VA Med Ctr, Div Cell & Dev Genet, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, VA Med Ctr, Dept Pathol, San Francisco, CA 94121 USA. NCI, NIH, Hlth & Human Dev, Lab Clin Genom, Bethesda, MD 20892 USA. Hirosaki Univ, Sch Med, Dept Urol, Hirosaki, Aomori 036, Japan. Erasmus MC Univ Med Ctr, Dept Pathol, Rotherham 3015GE, S Yorkshire, England. Dr Daniel Den Hoed Canc Ctr, Josephine Nefkens Inst, NL-3008 AE Rotterdam, Netherlands. RP Lau, YFC (reprint author), Univ Calif San Francisco, VA Med Ctr, Div Cell & Dev Genet, Dept Med, 4150 Clement St, San Francisco, CA 94143 USA. EM chris.lau@ucsf.edu RI Lee, Tin-Lap/A-7853-2009; OI Lee, Tin-Lap/0000-0002-6654-0988; Lau, Yun-Fai /0000-0002-9119-7050 FU BLRD VA [I01 BX000865]; NCI NIH HHS [R21 CA152589]; NICHD NIH HHS [R01 HD038117, R01 HD038117-05] NR 56 TC 48 Z9 56 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 2007 VL 38 IS 10 BP 1470 EP 1481 DI 10.1016/j.humpath.2007.03.011 PG 12 WC Pathology SC Pathology GA 216WJ UT WOS:000249909400005 PM 17521702 ER PT J AU Moore, AB Castro, L Yu, L Zheng, X Di, X Sifre, MI Kissling, GE Newbold, RR Bortner, CD Dixon, D AF Moore, A. B. Castro, L. Yu, L. Zheng, X. Di, X. Sifre, M. I. Kissling, G. E. Newbold, R. R. Bortner, C. D. Dixon, D. TI Stimulatory and inhibitory effects of genistein on human uterine leiomyoma cell proliferation are influenced by the concentration SO HUMAN REPRODUCTION LA English DT Article DE apoptosis; cell proliferation; genistein; uterine leiomyoma (UtLM) cells; uterine smooth muscle cells (UtSMCs) ID BREAST-CANCER CELLS; ESTROGEN-RECEPTOR; MCF-7 CELLS; DIETHYLSTILBESTROL DES; DEPENDENT PATHWAY; GENE-EXPRESSION; IN-VITRO; EXPOSURE; GROWTH; PHYTOESTROGENS AB Background: Due to dietary exposure of women to genistein, a soy-derived phytoestrogen, and the estrogen responsiveness of uterine leiomyomas 'fibroids', we evaluated the effects of genistein ( 0.001-50 mu g/ml) on human uterine leiomyoma (UtLM) cells versus uterine smooth muscle cells (UtSMCs) in vitro. Methods: Light microscopy was used to determine the effects of genistein on cell morphology. Proliferation was assessed using a colorimetric assay and proliferating cell nuclear antigen (PCNA) immunocytochemistry. Flow cytometry was used to quantitate cells in the S-phase and those undergoing apoptosis. A fluorometric assay and confocal microscopy were used to detect caspase-3 activity and apoptotic bodies, respectively. Results: In UtLM cells, low concentrations (<= 1 mu g/ml) of genistein stimulated proliferation, increased PCNA labeling and the percentage of cells in the S- phase, but this did not occur in UtSMCs. Higher concentrations (>= 10 mu g/ml) of genistein adversely affected the morphology, significantly inhibited proliferation, decreased PCNA labeling, increased caspase-3 activity and induced apoptosis in both cell types. Conclusions: Genistein's effects are concentration-dependent in both cell lines. Lower concentrations elicit proliferative effects on UtLM cells only; whereas, higher concentrations alter morphology, inhibit proliferation, and increase caspase activity and apoptosis in both cell types, with the latter two effects being more extensive in UtSMCs. C1 NIH, NIEHS, Dept Hlth & Human Serv, Lab Expt Pathol,Comparat Pathobiol Grp, Res Triangle Pk, NC 27709 USA. NIH, NIEHS, DHHS, Lab Signal Transduct,Mol Endocrinol Grp, Res Triangle Pk, NC 27709 USA. NIH, NIEHS, DHHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIH, NIEHS, DHHS, Lab Mol Toxicol,Dev Endocrinol & Endocrine Disrup, Res Triangle Pk, NC 27709 USA. RP Dixon, D (reprint author), NIH, NIEHS, Dept Hlth & Human Serv, Lab Expt Pathol,Comparat Pathobiol Grp, Res Triangle Pk, NC 27709 USA. EM dixon@niehs.nih.gov FU Intramural NIH HHS [Z01 ES021196-14, Z99 ES999999] NR 52 TC 33 Z9 35 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD OCT PY 2007 VL 22 IS 10 BP 2623 EP 2631 DI 10.1093/humrep/dem185 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 223OZ UT WOS:000250382700007 PM 17725991 ER PT J AU Lien, LF Brown, AJ Ard, JD Loria, C Erlinger, TP Feldstein, AC Lin, PH Champagne, CM King, AC McGuire, HL Stevens, VJ Brantley, PJ Harsha, DW McBurnie, MA Appel, LJ Svetkey, LP AF Lien, Lillian F. Brown, Ann J. Ard, Jamy D. Loria, Catherine Erlinger, Thomas P. Feldstein, Adrianne C. Lin, Pao-Hwa Champagne, Catherine M. King, Abby C. McGuire, Heather L. Stevens, Victor J. Brantley, Phillip J. Harsha, David W. McBurnie, Mary Ann Appel, Lawrence J. Svetkey, Laura P. TI Effects of PREMIER lifestyle modifications on participants with and without the metabolic syndrome SO HYPERTENSION LA English DT Article; Proceedings Paper CT Annual Fall Conference of the American-Heart-Association-Council on High Blood Pressure Research CY OCT 11, 2004 CL Chicago, IL SP ISFE DE hypertension; metabolic syndrome; insulin resistance; lifestyle modification; DASH ID HIGH BLOOD-PRESSURE; LOW-FAT DIET; INSULIN-RESISTANCE; CLINICAL-TRIAL; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; RANDOMIZED-TRIAL; HYPERTENSION; OBESITY; PREVENTION AB Lifestyle modification can reduce blood pressure and lower cardiovascular risk. Established recommendations include weight loss, sodium reduction, and increased physical activity. PREMIER studied the effects of lifestyle interventions based on established recommendations alone and with the addition of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern. This analysis aimed to assess the interventions' impact on cardiometabolic variables in participants with, compared with those without, metabolic syndrome. The primary outcome was 6-month change in systolic blood pressure. Participants with prehypertension or stage-1 hypertension were randomly assigned to an advice only control group, a 6-month intensive behavioral intervention group of established recommendations (EST), or an established recommendations plus DASH group (EST + DASH). Metabolic syndrome was defined per National Cholesterol and Education Program Adult Treatment Panel III. We used general linear models to test intervention effects on change in blood pressure, lipids, and insulin resistance (homeostasis model assessment), in subgroups defined by the presence or absence of metabolic syndrome. Of 796 participants, 399 had metabolic syndrome. Both EST and EST + DASH reduced the primary outcome variable, systolic blood pressure. Within the EST + DASH group, those with and without metabolic syndrome responded similarly (P = 0.231). However, within EST, those with metabolic syndrome had a poorer response, with a decrease in systolic blood pressure of 8.4 mm Hg versus 12.0 mm Hg in those without metabolic syndrome (P = 0.002). Thus, metabolic syndrome attenuated the systolic blood pressure reduction of EST, but this attenuation was overcome in EST + DASH. Finally, diastolic blood pressure, lipids, and homeostasis model assessment responded similarly to both interventions regardless of metabolic syndrome status. Our data suggest that strategies for lowering BP in individuals with metabolic syndrome may be enhanced by recommendations to adopt the DASH dietary pattern. C1 Duke Univ, Med Ctr, Div Endocrinol Metab & Nutr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Hypertens Ctr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Div Nephrol, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA. Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Austin, TX 78712 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Johns Hopkins Med Inst, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Lien, LF (reprint author), Duke Univ, Med Ctr, Div Endocrinol Metab & Nutr, DUMC 2956, Durham, NC 27710 USA. EM lien0002@mc.duke.edu FU NHLBI NIH HHS [UO1 HL60571, UO1 HL60570, UO1 HL60573, UO1 HL60574, UO1 HL62828] NR 58 TC 60 Z9 62 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2007 VL 50 IS 4 BP 609 EP 616 DI 10.1161/HYPERTENSIONAHA.107.089458 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 212HN UT WOS:000249586900007 PM 17698724 ER PT J AU Cheung, N Sharrett, AR Klein, R Criqui, MH Islam, A Macura, KJ Cotch, MF Klein, BEK Wong, TY AF Cheung, Ning Sharrett, A. Richey Klein, Ronald Criqui, Michael H. Islam, Amirul Macura, Katarzyna J. Cotch, Mary Frances Klein, Barbara E. K. Wong, Tien Y. TI Aortic distensibility and retinal arteriolar narrowing - The multi-ethnic study of atherosclerosis SO HYPERTENSION LA English DT Article DE population science; microcirculation; arterial compliance; imaging; risk factors ID CORONARY-HEART-DISEASE; BLUE MOUNTAINS EYE; VESSEL DIAMETERS; DIABETIC-RETINOPATHY; MICROVASCULAR ABNORMALITIES; CARDIOVASCULAR RISK; BLOOD-PRESSURE; STIFFNESS; HYPERTENSION; COMMUNITIES AB Increased aortic stiffness and retinal arteriolar narrowing are subclinical vascular effects of chronic hypertension and predict future cardiovascular events. The relationship between these 2 vascular measures is uncertain and is examined in the Multi-Ethnic Study of Atherosclerosis. This cross-sectional analysis involves 3425 participants (aged 45 to 85 years) free of clinical cardiovascular disease. Retinal vascular caliber was quantified from digital retinal photographs using standardized protocols. Aortic distensibility was determined from chest MRI. After controlling for age, squared age, gender, race, study center, height, weight, heart rate, cigarette smoking, past and current systolic blood pressure, use of antihypertensive medications, diabetes, fasting glucose, lipid profile, and C-reactive protein, reduced aortic distensibility (first versus fourth distensibility quartile) was associated with increased odds of retinal arteriolar narrowing (odds ratio: 1.72; 95% CI: 1.15 to 2.58, comparing lowest to highest quartile of arteriolar caliber). Further adjustments for atherosclerotic measures (carotid intima-media thickness, coronary calcium score, and ankle brachial index) had minimal impact on this association (odds ratio: 1.70; 95% CI: 1.13 to 2.55). Reduced aortic distensibility was not associated with retinal venular caliber. We conclude that increased aortic stiffness is associated with retinal arteriolar narrowing, independent of measured blood pressure levels and vascular risk factors. These data suggest that changes in the microvasculature may play a role linking aortic stiffness with clinical cardiovascular events. C1 Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Wisconsin, Sch Med & Publ Hlth, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Madison, WI USA. Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. Natl Univ Singapore, Singapore Eye Res Inst, Yong Loo Lin Sch Med, Singapore 117548, Singapore. RP Wong, TY (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia. EM twong@unimelb.edu.au RI Cheung, Ning Danny/F-2043-2013; OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [ZIA EY000403-08, Z01 EY000403-06, Z01 EY000403-07, Z99 EY999999, ZIA EY000403-09, ZIA EY000403-10]; NHLBI NIH HHS [HL69979-03, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95169, R01 HL069979] NR 45 TC 61 Z9 62 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2007 VL 50 IS 4 BP 617 EP 622 DI 10.1161/HYPERTENSIONAHA.107.091926 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 212HN UT WOS:000249586900008 PM 17698721 ER PT J AU Ni, W Zhao, HW Murphy, DL Watts, SW AF Ni, Wei Zhao, Huawei Murphy, Dennis L. Watts, Stephanie W. TI Lack of the serotonin transporter does not prevent blood pressure increase in DOCA-salt hypertension SO HYPERTENSION LA English DT Meeting Abstract CT 61st Annual High Blood Pressure Reseach Conference CY SEP 26-29, 2007 CL Tucson, AZ C1 Michigan State Univ, E Lansing, MI 48824 USA. NIMH, 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 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2007 VL 50 IS 4 BP E124 EP E124 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 212HN UT WOS:000249586900397 ER PT J AU Yin, X Li, B Chen, H Catt, K AF Yin, Xing Li, Bo Chen, Hundar Catt, Kevin TI Differential signaling pathways in Ang II- and EGF-stimulated hepatic cells SO HYPERTENSION LA English DT Meeting Abstract CT 61st Annual High Blood Pressure Reseach Conference CY SEP 26-29, 2007 CL Tucson, AZ C1 NIDDK, NIH, Bethesda, MD USA. NICHD, NIH, Bethesda, MD 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 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2007 VL 50 IS 4 BP E98 EP E98 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 212HN UT WOS:000249586900262 ER PT J AU Zou, J Ji, Q Nagy, G AF Zou, Jie Ji, Qiang Nagy, George TI A comparative study of local matching approach for face recognition SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article DE aR database; face recognition; FERET database; local matching method ID FISHER LINEAR DISCRIMINANT; COMPONENT ANALYSIS; IMAGE RETRIEVAL; CLASSIFICATION; PCA; INFORMATION; EIGENFACES; ALGORITHMS; TEXTURE; MODELS AB In contrast to holistic methods, local matching methods extract facial features from different levels of locality and quantify them precisely. To determine how they can be best used for face recognition, we conducted a comprehensive comparative study at each step of the local matching process. The conclusions from our experiments include: 1) additional evidence that Gabor features are effective local feature representations and are robust to illumination changes; 2) discrimination based only on a small portion of the face area is surprisingly good; 3) the configuration of facial components does contain rich discriminating information and comparing corresponding local regions utilizes shape features more effectively than comparing corresponding facial components; 4) spatial multiresolution analysis leads to better classification performance; 5) combining local regions with Borda count classifier combination method alleviates the curse of dimensionality. We implemented a complete face recognition system by integrating the best option of each step. Without training, illumination compensation and without any parameter tuning, it achieves superior performance on every category of the FERET test: near perfect classification accuracy (99.5 %) on pictures taken on the same day regardless of indoor illumination variations, and significantly better than any other reported performance on pictures taken several days to more than a year apart. The most significant experiments were repeated on the AR database, with similar results. C1 Rensselaer Polytech Inst, Troy, NY 12180 USA. RP Zou, J (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. EM jzou@mail.nlm.nih.gov; qji@ecse.rpi.edu; nagy@ecse.rpi.edu NR 54 TC 146 Z9 159 U1 0 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1057-7149 EI 1941-0042 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD OCT PY 2007 VL 16 IS 10 BP 2617 EP 2628 DI 10.1109/TIP.2007.904421 PG 12 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 212RG UT WOS:000249613900018 PM 17926941 ER PT J AU Billadeau, DD Long, EO Lanier, LL AF Billadeau, Daniel D. Long, Eric O. Lanier, Lewis L. TI Paul J. Leibson 1952-2007 - Obituary SO IMMUNITY LA English DT Biographical-Item C1 Mayo Clin, Coll Med, Dept Immunol, Rochester, MN 55905 USA. Mayo Clin, Coll Med, Div Oncol Res, Rochester, MN 55905 USA. NIAID, Immunogenet Lab, Rockville, MD 20852 USA. Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA. RP Billadeau, DD (reprint author), Mayo Clin, Coll Med, Dept Immunol, Rochester, MN 55905 USA. EM billadeau.daniel@mayo.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2007 VL 27 IS 4 BP 531 EP 532 DI 10.1016/j.immuni.2007.09.004 PG 2 WC Immunology SC Immunology GA 225AY UT WOS:000250490700001 ER PT J AU Liu, Y Subrahmanyam, R Chakraborty, T Sen, R Desiderio, S AF Liu, Yun Subrahmanyam, Ramesh Chakraborty, Tirtha Sen, Ranjan Desiderio, Stephen TI A plant homeodomain in Rag-2 that binds hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangement SO IMMUNITY LA English DT Article ID V(D)J RECOMBINATION ACTIVITY; B-CELL; PHD FINGER; SIGNAL SEQUENCES; CHAIN GENE; C-TERMINUS; ACTIVE-SITE; PRE-B; PROTEINS; METHYLATION AB V(D)J recombination is initiated by the recombination activating gene (RAG) proteins RAG-1 and RAG-2. The ability of antigen-receptorgene segments to undergo V(D)J recombination is correlated with spatially- and temporallyrestricted chromatin modifications. We have found that RAG-2 bound specifically to histone H3 and that this binding was absolutely dependent on dimethylation or trimethylation at lysine 4 (H3K4me2 or H3K4me3). The interaction required a noncanonical plant homeodomain (PHD) that had previously been described within the noncore region of RAG-2. Binding of the RAG-2 PHD finger to chromatin across the IgH D-J(H)-C locus showed a strong correlation with the distribution of trimethylated histone H3 K4. Mutation of a conserved tryptophan residue in the RAG-2 PHD finger abolished binding to H3K4me3 and greatly impaired recombination of extrachromosomal and endogenous immunoglobulin gene segments. Together, these findings are consistent with the interpretation that recognition of hypermethylated histone H3 K4 promotes efficient V(D)J recombination in vivo. C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA. NIA, Lab Cell & Mol Biol, Baltimore, MD 21224 USA. RP Desiderio, S (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. EM sdesider@jhmi.edu RI Liu, Yun/I-5755-2012; Subrahmanyam, Ramesh/K-5503-2012 OI Liu, Yun/0000-0002-3917-0600; FU Intramural NIH HHS; NCI NIH HHS [CA16519, P01 CA016519] NR 70 TC 164 Z9 167 U1 2 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2007 VL 27 IS 4 BP 561 EP 571 DI 10.1016/j.immuni.2007.09.005 PG 11 WC Immunology SC Immunology GA 225AY UT WOS:000250490700008 PM 17936034 ER PT J AU Martin, MP Pascal, V Yeager, M Phair, J Kirk, GD Hoots, K O'Brien, SJ Anderson, SK Carrington, M AF Martin, Maureen P. Pascal, Veronique Yeager, Meredith Phair, John Kirk, Gregory D. Hoots, Keith O'Brien, Stephen J. Anderson, Stephen K. Carrington, Mary TI A mutation in KIR3DS1 that results in truncation and lack of cell surface expression SO IMMUNOGENETICS LA English DT Article DE KIR3DS1; truncation; cell surface expression; KIR gene polymorphism; KIR3DS; L1 locus; KIR expression; Human Genome Diversity Panel (HGDP) ID NK CELLS; RECEPTOR; AIDS; INFECTION; POLYMORPHISM; PROGRESSION; MUTAGENESIS; ALLELE; GENE; HLA AB The KIR gene cluster exhibits a high degree of polymorphism in terms of gene content as well as allelic polymorphism, and data suggest that it is evolving rapidly. The KIR3DL1 locus is one of the most polymorphic loci within this cluster and is unique in that it encodes an activating receptor KIR3DS1, as well as multiple inhibitory KIR3DL1 allotypes. Because KIR3DS1 has been implicated in a number of diseases, we tested for the presence of KIR3DS1 variants that might affect its expression and activating capacity. Preliminary FACS analysis indicated that indeed some individuals with the KIR3DS1 allele showed no cell surface expression of the molecule. Sequencing analysis identified a variant with a complex deletion/substitution mutation in exon 4 (which encodes the D1 extracellular domain), resulting in a premature stop codon. We subsequently genotyped 3,960 unrelated individuals and determined the frequencies of this allele across geographically distinct world populations. The data indicate that the null KIR3DS1 allele is uncommon, arose on a single haplotype, and spread across geographically distinct populations. C1 NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Canc & Inflammat Program, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Univ Texas, Hlth Sci Ctr, Gulf States Hemophilia Ctr, Houston, TX 77030 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. RP Carrington, M (reprint author), NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov RI Kirk, Gregory/A-8484-2009; Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 23 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD OCT PY 2007 VL 59 IS 10 BP 823 EP 829 DI 10.1007/s00251-007-0240-8 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 221CV UT WOS:000250205900006 PM 17687550 ER PT J AU Kuhns, DB Priel, DAL Gallin, JI AF Kuhns, Douglas B. Priel, Debra A. Long Gallin, John I. TI Induction of human monocyte interleukin (IL)-8 by fibrinogen through the Toll-like receptor pathway SO INFLAMMATION LA English DT Article DE monocytes; fibrinogen; IL-8; Toll-like receptor ID RECURRENT BACTERIAL-INFECTIONS; HYPORESPONSIVENESS; PATIENT AB Fibrinogen, in addition to its role in coagulation, is also an acute phase protein of inflammation. Treatment of adherent human monocytes with fibrinogen increases IL-8, IL-6, and TNF-alpha, but has no effect on MCP-1, IFN-beta, or IP-10. Treatment of monocytes with fibrinogen and C5a doubles IL-8 and IL-6 production, compared to fibrinogen alone. The increase in cytokine production was accompanied by a transient increase in IL-8 mRNA and increased NF-kappa B activity. Monocytes from an IRAK-4- and two NEMO-deficient patients had 80% reduced IL-8 responses to fibrinogen. Moreover, responses to fibrinogen were blocked with anti-CD14 antibody (MY4), a subunit of the LPS receptor. The data indicate that fibrinogen alone and fibrinogen plus C5a are potent inducers of cytokine production in monocytes, and that signaling by fibrinogen is mediated through the TLR-4 pathway. C1 NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. NCI Frederick, SAIC Frederick, Clin Serv Program, Ft Detrick, MD 21702 USA. RP Gallin, JI (reprint author), NIAID, NIH, Host Def Lab, Bldg 10,Rm 6-2551, Bethesda, MD 20892 USA. EM jgallin@cc.nih.gov FU NCI NIH HHS [N01 CA-12400] NR 10 TC 40 Z9 44 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-3997 J9 INFLAMMATION JI Inflammation PD OCT PY 2007 VL 30 IS 5 BP 178 EP 188 DI 10.1007/s10753-007-9035-1 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 219WI UT WOS:000250118500007 PM 17624583 ER PT J AU Lin, J Wilbur, WJ AF Lin, Jimmy Wilbur, W. John TI Syntactic sentence compression in the biomedical domain: facilitating access to related articles SO INFORMATION RETRIEVAL LA English DT Article DE sentence compression; extrinsic evaluation; PubMed; MEDLINE; genomics IR AB We explore a syntactic approach to sentence compression in the biomedical domain, grounded in the context of result presentation for related article search in the PubMed search engine. By automatically trimming inessential fragments of article titles, a system can effectively display more results in the same amount of space. Our implemented prototype operates by applying a sequence of syntactic trimming rules over the parse trees of article titles. Two separate studies were conducted using a corpus of manually compressed examples from MEDLINE: an automatic evaluation using BLEU and a summative evaluation involving human assessors. Experiments show that a syntactic approach to sentence compression is effective in the biomedical domain and that the presentation of compressed article titles supports accurate "interest judgments", decisions by users as to whether an article is worth examining in more detail. C1 Univ Maryland, Coll Informat Studies, College Pk, MD 20742 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Lin, J (reprint author), Univ Maryland, Coll Informat Studies, College Pk, MD 20742 USA. EM jimmylin@umd.edu; wilbur@ncbi.nlm.nih.gov NR 43 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1386-4564 EI 1573-7659 J9 INFORM RETRIEVAL JI Inf. Retr. PD OCT PY 2007 VL 10 IS 4-5 BP 393 EP 414 DI 10.1007/s10791-007-9029-5 PG 22 WC Computer Science, Information Systems SC Computer Science GA 213KD UT WOS:000249664800003 ER PT J AU Chen, KQ Huang, J Gong, WH Iribarren, P Dunlop, NM Wang, JM AF Chen, Keqiang Huang, Jian Gong, Wanghua Iribarren, Pablo Dunlop, Nancy M. Wang, Ji Ming TI Toll-like receptors in inflammation, infection and cancer SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE Toll-like receptors; ligands; signaling; inflammation; infection; cancer ID NF-KAPPA-B; CENTRAL-NERVOUS-SYSTEM; DOUBLE-STRANDED-RNA; ENTERICA SEROVAR TYPHIMURIUM; AIRWAY SMOOTH-MUSCLE; SURFACTANT PROTEIN-A; REGULATORY T-CELLS; INNATE IMMUNITY; DENDRITIC CELLS; HELICOBACTER-PYLORI AB Members of the Toll-like receptor (TLR) family play key roles in both innate and adaptive immune responses. TLR proteins enable host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharides, viral RNA, CPG-containing DNA, and flagellin, among others. TLRs are also apparently able to mediate responses to host molecules, including one defensin, ROS, HMGB I (high-mobility group box protein 1), surfactant protein A, fibrinogen, breakdown products of tissue matrix, heat shock proteins (hsp) and eosmophil-derived neurotoxin (EDN). Thus, TLR are involved in the development of many pathological conditions including infectious diseases, tissue damage, autoimmune and neurodegenerative diseases and cancer. In this review, the contribution of TLRs to diseases of the central nervous system (CNS), lung, gastrointestinal tract, kidney and skin as well as cancer is evaluated. We hope to provide new insight into the pathogenesis and progression of diseases and more importantly, into the potential for TLRs as targets of therapeutics. Published by Elsevier B.V. C1 NCI, Ctr Canc Res, Mol Immunoregulat Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. Shanghai Jiao Tong Univ, Sch Agr & Biol, Shanghai 201101, Peoples R China. NCI, SAIC, Basic Res Program, Frederick, MD 21702 USA. Natl Univ Cordoba, Fac Chem Sci, CIBICI CONICET, Dept Clin Biochem, Cordoba 5000, Spain. RP Chen, KQ (reprint author), NCI, Ctr Canc Res, Mol Immunoregulat Lab, Canc & Inflammat Program, Bldg 560,Room 31-76, Frederick, MD 21702 USA. EM kchen@mail.nciferf.gov FU NCI NIH HHS [N01 CO 12400] NR 136 TC 189 Z9 214 U1 6 U2 35 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD OCT PY 2007 VL 7 IS 10 BP 1271 EP 1285 DI 10.1016/j.intimp.2007.05.016 PG 15 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 204TT UT WOS:000249067600001 PM 17673142 ER PT J AU Carreon, T Kadlubar, FF Ruder, AM Schulte, PA Hayes, RB Waters, M Grant, DJ Boissy, R Beii, DA Hemstreet, GP Yin, S LeMasterS, GK Rothman, N AF Carreon, Tania Kadlubar, Fred F. Ruder, Avima M. Schulte, Paul A. Hayes, Richard B. Waters, Martha Grant, Delores J. Boissy, Robert Beii, Douglas A. Hemstreet, George P., III Yin, Songnian LeMasterS, Grace K. Rothman, Nathaniel TI "N-Acetyltransferases and the susceptibility to benzidine-induced bladder carcinogenesis" - Reply SO INTERNATIONAL JOURNAL OF CANCER LA English DT Letter ID ACETYLBENZIDINE; GLUCURONIDATION; BINDING; DNA; METABOLISM; CANCER; RAT; WORKERS; LIVER C1 NIOSH, Cincinnati, OH 45226 USA. Univ Cincinnati, Acad Hlth Ctr, Cincinnati, OH USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Natl Canc Inst, Rockville, MD USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ Nebraska Med Ctr, Omaha, NE USA. Chinese Acad Prevent Med, Beijing, Peoples R China. RP Carreon, T (reprint author), NIOSH, Hazard Evaluat & Field Studies, Div Surveillance, 4676 Columbia Pkwy,Mailstop R-15, Cincinnati, OH 45226 USA. EM carreota@ucmail.uc.edu RI Carreon, Tania/A-6548-2008; Waters, Martha/B-7441-2011; Ruder, Avima/I-4155-2012 OI Ruder, Avima/0000-0003-0419-6664 NR 15 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 1 PY 2007 VL 121 IS 7 BP 1637 EP 1639 DI 10.1002/ijc.22906 PG 3 WC Oncology SC Oncology GA 205JK UT WOS:000249109600032 PM 17583575 ER PT J AU Vrijheid, M Cardis, E Ashmore, P Auvinen, A Bae, JM Engels, H Gilbert, E Gulis, G Habib, RR Howe, G Kurtinaitis, J Malker, H Muirhead, CR Richardson, DB Rodriguez-Artalejo, F Rogel, A Schubauer-Berigan, M Tardy, H Telle-Lamberton, M Usel, M Veress, K AF Vrijheid, M. Cardis, E. Ashmore, P. Auvinen, A. Bae, J-M Engels, H. Gilbert, E. Gulis, G. Habib, R. R. Howe, G. Kurtinaitis, J. Malker, H. Muirhead, C. R. Richardson, D. B. Rodriguez-Artalejo, F. Rogel, A. Schubauer-Berigan, M. Tardy, H. Telle-Lamberton, M. Usel, M. Veress, K. TI Mortality from diseases other than cancer following low doses of ionizing radiation: results from the 15-Country Study of nuclear industry workers SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE radiation; ionizing; radiation effects; cohort studies; occupational diseases; cardiovascular diseases; digestive system diseases; respiratory tract diseases ID ATOMIC-BOMB SURVIVORS; CORONARY-HEART-DISEASE; BREAST-CANCER; NONCANCER MORTALITY; DEATH CERTIFICATES; RISK; RADIOTHERAPY; EXPOSURE; COHORT; REGISTRIES AB Background Ionizing radiation at very high (radio-therapeutic) dose levels can cause diseases other than cancer, particularly heart diseases. There is increasing evidence that doses of the order of a few sievert (Sv) may also increase the risk of non-cancer diseases. It is not known, however, whether such effects also occur following the lower doses and dose rates of public health concern. Methods We used data from an international (15-country) nuclear workers cohort study to evaluate whether mortality from diseases other than cancer is related to low doses of external ionizing radiation. Analyses included 275312 workers with adequate information on socioeconomic status, over 4 million person-years of follow-up and an average cumulative radiation dose of 20.7mSv; 11255 workers had died of non-cancer diseases. Results The excess relative risk (ERR) per Sv was 0.24 [95 CI (confidence intervals) -0.23, 0.78] for mortality from all non-cancer diseases and 0.09 (95 CI -0.43, 0.70) for circulatory diseases. Higher risk estimates were observed for mortality from respiratory and digestive diseases, but confidence intervals included zero. Increased risks were observed among the younger workers (attained age 50 years, identified post hoc) for all groupings of non-cancer causes of death, including external causes. It is unclear therefore whether these findings reflect real effects of radiation, random variation or residual confounding. Conclusions The most informative low-dose radiation study to date provides little evidence for a relationship between mortality from non-malignant diseases and radiation dose. However, we cannot rule out risks per unit dose of the same order of magnitude as found in studies at higher doses. C1 Int Agcy Res Canc, F-69372 Lyon 08, France. Hlth Canada, Radiat Protect Bur, Ottawa, ON K1A 0L2, Canada. Tampere Univ, FIN-33101 Tampere, Finland. STUK Radiat & Nucl Safety Author, Helsinki, Finland. Jeju Natl Univ, Coll Med, Dept Prevent Med, Chejudo, South Korea. CEN SCK, Radiat Protect Div, B-2400 Mol, Belgium. NCI, Radiat Epidemiol Branch, Div Epidemiol & Genet, Bethesda, MD 20892 USA. Trnava Univ, Dept Hyg & Epidemiol, Fac Hlth Care & Social Work, Trnava, Slovakia. Amer Univ Beirut, Fac Hlth Sci, Beirut, Lebanon. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. Vilnius State Univ, Inst Oncol, Lithuanian Canc Registry, Vilnius, Lithuania. Sundsvall Hosp, Midsweden Res & Dev Ctr, Sundsvall, Sweden. Hlth Protect Agcy, Radiat Protect Div, Didcot, Oxon, England. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ Autonoma Madrid, Sch Med, Dept Prevent Med & Publ Hlth, E-28049 Madrid, Spain. Inst Radioprotect & Surete Nucl, Fontenay Aux Roses, France. NIOSH, Cincinnati, OH 45226 USA. Off Cantonal Inspect & Relat Travail, Geneva, Switzerland. Semmelweis Univ, Dept Dermatol Venereol & Dermatooncol, H-1085 Budapest, Hungary. RP Vrijheid, M (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM vrijheid@iarc.fr RI Schubauer-Berigan, Mary/B-3149-2009; Gulis, Gabriel/E-4505-2013; Cardis, Elisabeth/C-3904-2017; Vrijheid, M/H-2702-2014; OI Schubauer-Berigan, Mary/0000-0002-5175-924X; Vrijheid, M/0000-0002-7090-1758; Auvinen, Anssi/0000-0003-1125-4818 NR 32 TC 64 Z9 78 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD OCT PY 2007 VL 36 IS 5 BP 1126 EP 1135 DI 10.1093/ije/dym138 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 227TO UT WOS:000250680900031 PM 17666424 ER PT J AU Carreon, JD Sherman, ME Guillen, D Solomon, D Herrero, R Jeronimo, J Wacholder, S Rodriguez, AC Morales, J Hutchinson, M Burk, RD Schiffman, M AF Carreon, Joseph D. Sherman, Mark E. Guillen, Diego Solomon, Diane Herrero, Rolando Jeronimo, Jose Wacholder, Sholom Rodriguez, Ana Cecilia Morales, Jorge Hutchinson, Martha Burk, Robert D. Schiffman, Mark TI CIN2 is a much less reproducible and less valid diagnosis than CIN3: Results from a histological review of population-based cervical samples SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE CIN2; CIN3; cervix; pathology ID HUMAN-PAPILLOMAVIRUS; INTRAEPITHELIAL NEOPLASIA; BETHESDA SYSTEM; UNITED-STATES; CYTOLOGY; WOMEN; RISK; ADENOCARCINOMA; MANAGEMENT; CANCER AB We wished to compare the relative reproducibility and validity of cervical intraepithelial neoplasia (CIN) 2 and CIN3 diagnoses. In a population-based cohort study (1993-2001) of human papillomavirus (HPV) and cervical neoplasia in Costa Rica, we compared community pathologists' diagnoses with those of the 2 independent reviewers from the United States (total, n = 357). As measures of validity, we correlated primary and review diagnoses with HPV positivity and cytological interpretations. Two review pathologists agreed with 84% and 81%, respectively, of initial diagnoses of CIN3 compared with 13% and 31% of CIN2. The CIN3 diagnoses made by review pathologists were 94% oncogenic HPV positive, compared with 72% of CIN2 diagnoses. Eighty-one percent of CIN3 diagnoses versus 61% of CIN2 were correlated with high-grade cytological interpretations. The CIN3 is a substantially more reproducible diagnosis that can be validated more frequently with HPV tests and cytological interpretations than CIN2. C1 NCI, Hormonal Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA. Albert Einstein Coll Med, Canc Res Ctr, Bronx, NY 10467 USA. RP Schiffman, M (reprint author), NCI, Hormonal Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 5011, Rockville, MD 20852 USA. EM schiffrnan@mail.nih.gov NR 19 TC 108 Z9 110 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 2007 VL 26 IS 4 BP 441 EP 446 DI 10.1097/pgp.ob013e31805152ab PG 6 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 213KV UT WOS:000249666700013 PM 17885496 ER PT J AU Robledo, C Zhang, J Troendle, J Barnhart, K Creinin, MD Westhoff, C Huang, X Frederick, M AF Robledo, C. Zhang, J. Troendle, J. Barnhart, K. Creinin, M. D. Westhoff, C. Huang, X. Frederick, M. TI Clinical indicators for success of misoprostol treatment after early pregnancy failure SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE bleeding; cervical os; early pregnancy failure; indicator; misoprostol; treatment success ID MANAGEMENT AB Objective: To identify clinical indicators for success of misoprostol treatment after early pregnancy failure. Methods: A total of 473 women with early pregnancy failure received 800 mu g of vaginal misoprostol on treatment day 1. At the follow-up visit on day 3, a second dose was given if expulsion was incomplete. On day 8, vacuum aspiration was offered if expulsion had not occurred. Ultrasonography was used as gold standard for success. A Classification and Regression Tree analysis was undertaken to derive two decision trees for the success of misoprostol treatment on study days 3 and 8. Results: Heavy bleeding after the first dose and an open cervical os were identified as clinical indicators of treatment success on day 3. Treatment success occurred in 84% of women with either or both indicators. Reporting passage of tissue after a second misoprostol dose and old blood in the vagina were potential indicators of treatment success or failure on day 8. A woman with either of these indicators has a 65% chance of treatment success after the second dose. Conversely, a woman with neither indicator on day 8 has a 94% chance of treatment failure. Conclusion: Standard clinical findings may be useful as indicators for success or failure of medical management of early pregnancy failure in settings with limited or no access to ultrasonography. More research to identify even better indicators is warranted. (C) 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA USA. Magee Womens Res Inst, Pittsburgh, PA USA. Columbia Univ, New York, NY USA. Clin Trials & Survey Corp, Baltimore, MD USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. EM zhangj@mail.nih.gov FU Intramural NIH HHS [Z01 HD008724-07]; NCATS NIH HHS [UL1 TR000005] NR 9 TC 11 Z9 13 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD OCT PY 2007 VL 99 IS 1 BP 46 EP 51 DI 10.1016/j.ijgo.2007.04.031 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 218LM UT WOS:000250017000015 PM 17599843 ER PT J AU Rogan, WJ Ragan, NB AF Rogan, Walter J. Ragan, N. Beth TI Some evidence of effects of environmental chemicals on the endocrine system in children SO INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH LA English DT Article; Proceedings Paper CT International Workshop on Childrens Environment in Central Europe - Threats and Chances CY NOV 21-24, 2006 CL Osnabruck, GERMANY SP DAKJ, Commiss Environm Issues, Kinderumwelt GmbH DE endocrine disruptors; environmental chemicals; lactation; thyroid function; sex ratio; puberty ID IN-UTERO EXPOSURE; POLYCHLORINATED-BIPHENYLS; SEXUAL-MATURATION; POLYBROMINATED BIPHENYL; ANOGENITAL DISTANCE; PHTHALATE EXPOSURE; THYROID-HORMONES; GIRLS; DURATION; DDE AB Pollutant chemicals that are widespread in the environment can affect endocrine function in laboratory experiments and in wildlife. Although human beings are commonly exposed to such pollutant chemicals, the exposures are generally low and clear effects on endocrine function from such exposures have been difficult to demonstrate. Human data including both exposure to the chemical agent and the endocrine outcome are reviewed here, including age at weaning, age at puberty, anogenital distance, and sex ratio at birth, and the strength of the evidence are discussed. Although endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real. Published by Elsevier GmbH. C1 NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, NIH, Mail Drop A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM rogan@niehs.nih.gov RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 FU Intramural NIH HHS [Z01 ES044006-07] NR 60 TC 29 Z9 33 U1 0 U2 7 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1438-4639 EI 1618-131X J9 INT J HYG ENVIR HEAL JI Int. J. Hyg. Environ. Health. PD OCT PY 2007 VL 210 IS 5 BP 659 EP 667 DI 10.1016/j.ijheh.2007.07.005 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 233AK UT WOS:000251062600024 PM 17870664 ER PT J AU Huff, J Ladou, J AF Huff, James Ladou, Joseph TI Aspartame bioassay findings portend human cancer hazards SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE aspartame ID SPRAGUE-DAWLEY RATS; CARCINOGENESIS BIOASSAYS; RAMAZZINI-FOUNDATION; ANIMAL TESTS; RISKS; EXPOSURE; PROGRAM; FEED AB The U.S. Food and Drug Administration (FDA) should reevaluate its position on aspartame as being safe under all conditions. Animal bioassay results predict human cancer risks, and a recent animal study confirms that there is a potential aspartame risk to humans. Aspartame is produced and packaged in China for domestic use and global distribution. Japan, France, and the United States are also major producers. No study of long-term adverse Occupational health effects on aspartame workers have been conducted. The FDA should consider sponsoring a prospective epidemiologic study of aspartame workers. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Calif San Francisco, Div Occupat & Environm Med, San Francisco, CA 94143 USA. RP Huff, J (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM huff1@niehs.nih.gov; joeladou@aol.com NR 33 TC 9 Z9 9 U1 5 U2 28 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD OCT-DEC PY 2007 VL 13 IS 4 BP 446 EP 448 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 232BV UT WOS:000250994000010 PM 18085058 ER PT J AU Abdo, KM Camargo, CA Davis, D Egilman, D Epstein, SS Froines, J Hattis, D Hooper, K Huff, J Infante, PF Jacobson, MF Teitelbaum, DT Tickner, JA AF Abdo, Kamal M. Camargo, Carlos A., Jr. Davis, Devra Egilman, David Epstein, Samuel S. Froines, John Hattis, Dale Hooper, Kim Huff, James Infante, Peter F. Jacobson, Michael F. Teitelbaum, Daniel Thau Tickner, Joel A. TI Letter to USFDA Commissioner SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Letter C1 Ctr Sci Publ Interest, Washington, DC 20009 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Pittsburgh, Inst Canc, Ctr Environm Oncol, Pittsburgh, PA 15232 USA. Brown Univ, Attleboro, MA 02703 USA. Univ Illinois, Sch Publ Hlth, Canc Prevent Coalit, Chicago, IL USA. Univ Calif Los Angeles, Ctr Environm & Occupat Hlth, Los Angeles, CA 90095 USA. NIOSH, Bethesda, MD 20892 USA. Clark Univ, George Perkins Marsh Inst, Worcester, MA 01610 USA. Calif Environm Protect Agcy, Calif Dept Tox Subst Control, Environm Chem Lab, Albany, CA 94710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. George Washington Univ, Sch Publ Hlth, Washington, DC 20052 USA. US Dept Labor, Hlth Stand Program, Occupat Safety & Hlth Adm, Washington, DC 20210 USA. NIEHS, Natl Toxicol Program, Bahama, NC 27503 USA. Colorado Sch Mines, Golden, CO 80401 USA. Univ Colorado, Hlth Sci Denver, Denver, CO 80202 USA. Univ Massachusetts, Dept Community Hlth & Sustainabil, Lowell Ctr Sustainable Prod, Lowell, MA 01854 USA. RP Jacobson, MF (reprint author), Ctr Sci Publ Interest, 1875 Connecticut Ave,Suite 300, Washington, DC 20009 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD OCT-DEC PY 2007 VL 13 IS 4 BP 449 EP 450 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 232BV UT WOS:000250994000011 PM 18085059 ER PT J AU Palau, MA Pham, TT Barnard, N Merino, MJ AF Palau, Mauricio A. Pham, Tina Thu Barnard, Nicola Merino, Maria J. TI Primary synovial sarcoma of the kidney with rhabdoid features SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE synovial sarcoma; kidney; rhabdoid morphology; SYT/SSX gene fusion ID SSX FUSION TRANSCRIPTS; MOLECULAR-DETECTION; SYT; TRANSLOCATION; IDENTIFICATION; ENTITY; IMPACT; TUMORS; GENES AB Synovial sarcoma is a soft tissue sarcoma with clearly defined histologic, immunophenotypic, and molecular features. It occurs predominantly in the extremities of young adults but has been reported in many other anatomic sites. Histologically, it is classified as biphasic, monophasic, and poorly differentiated. The latter category, which includes tumors with a rhabdoid morphology, has been associated with a more aggressive behavior. Generally, the biphasic variant does not pose any diagnostic problem because of its typical histologic appearance; in contrast, the monophasic and poorly differentiated variants may represent a diagnostic challenge because their microscopic features can be confused with those of other spindle cell tumors with rhabdoid features. The application of molecular techniques, such as reverse transcriptase polymerase chain reaction to detect the fusion transcript associated with the characteristic t(X; 18) translocation of synovial sarcoma, has enabled the confirmation of this diagnosis, even in cases of unusual localization, such as the one we present here. C1 NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA. NCI, NIH, Pathol Lab, Mol Diagnost Unit, Bethesda, MD USA. Robert Wood Johnson Univ Hosp, Brunswick, ME USA. RP Merino, MJ (reprint author), NCI, NIH, Pathol Lab, 9000 Rockville Pike,Bldg 10, Bethesda, MD 20892 USA. EM mjmerino@mail.nih.gov NR 33 TC 3 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD OCT PY 2007 VL 15 IS 4 BP 421 EP 428 DI 10.1177/1066896907302421 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 216VC UT WOS:000249906100018 PM 17913954 ER PT J AU Young, AE Fine, PM McCrery, R Wren, PA Richter, HE Brubaker, L Brown, MB Weber, AM AF Young, Amy E. Fine, Paul M. McCrery, Rebecca Wren, Patricia A. Richter, Holly E. Brubaker, Linda Brown, Morton B. Weber, Anne M. CA Pelvic Floor Disorders Network TI Spanish language translation of pelvic floor disorders instruments SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE pelvic floor disorders; Spanish translation; questionnaire; urinary incontinence; pelvic organ prolapse; fecal incontinence ID INCONTINENCE SEXUAL QUESTIONNAIRE; URINARY-INCONTINENCE; FECAL INCONTINENCE; ORGAN PROLAPSE; SEVERITY INDEX; HEALTH; VALIDATION; PREVALENCE; SYMPTOMS; VERSION AB The purpose of the study is to translate existing measures of pelvic symptoms and quality of life from English into Spanish, facilitating research participation of Hispanic/Latina women. The forward-backward translation protocol was applied then adjudicated by a concordance committee. The measures included the Pelvic Floor Distress Inventory (PFDI), Pelvic Floor Impact Questionnaire (PFIQ), Medical, Epidemiological, and Social Aspects of Aging (MESA) Questionnaire, Hunskaar Severity Measure, Fecal Incontinence Severity Index and modified Manchester Questionnaire, Pelvic Organ Prolapse/Urinary Incontinence Sexual Functioning Questionnaire (PISQ), and the Life Orientation Test (LOT). English and Spanish versions were administered to 50 Hispanic/Latina women with pelvic symptoms. Kappa correlations of items and correlation coefficients for scales were computed. Psychometric testing for translations demonstrated good (0.80-0.89), very good (0.90-0.95), or excellent (> 0.95) correlations for primary scales of the PFDI, PFIQ, MESA, Hunskaar, PISQ, and LOT. Strict translation techniques and testing yielded valid Spanish translations of instruments assessing pelvic symptoms/functional life impact in women with pelvic floor disorders. C1 Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Oakland Univ, Sch Hlth Sci, Rochester, MI 48063 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Loyola Univ, Ctr Med, Dept Obstet & Gynecol, Maywood, IL 60153 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. RP Young, AE (reprint author), Baylor Coll Med, Dept Obstet & Gynecol, 1706 Dryden,Suite 1100, Houston, TX 77030 USA. EM ayoung@bcm.tmc.edu FU NICHD NIH HHS [U10 HD41248, U01 HD41249, U10 HD041261, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41267, U10 HD41268, U10 HD41269] NR 20 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD OCT PY 2007 VL 18 IS 10 BP 1171 EP 1178 DI 10.1007/s00192-006-0297-1 PG 8 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 216IN UT WOS:000249871800008 PM 17576498 ER PT J AU Murphy, EC Ferris, FL O'Donnell, WR AF Murphy, Elizabeth C. Ferris, Frederick L., III O'Donnell, William R. TI An electronic medical records system for clinical research and the EMR-EDC interface SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Editorial Material ID DISEASE; THERAPY C1 NEI, NIH, CRC, Bethesda, MD 20892 USA. RP Murphy, EC (reprint author), NEI, NIH, CRC, Bldg 10,Room 3-2531, Bethesda, MD 20892 USA. EM murphyl@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999] NR 13 TC 13 Z9 14 U1 0 U2 2 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 OCT PY 2007 VL 48 IS 10 BP 4383 EP 4389 DI 10.1167/iovs.07-0345 PG 7 WC Ophthalmology SC Ophthalmology GA 214SE UT WOS:000249757600001 PM 17898254 ER PT J AU Su, SB Grajewski, RS Luger, D Agarwal, RK Silver, PB Tang, J Tuo, J Chan, CC Caspi, RR AF Su, Shao Bo Grajewski, Rafael S. Luger, Dror Agarwal, Rajeev K. Silver, Phyllis B. Tang, Jun Tuo, Jingsheng Chan, Chi-Chao Caspi, Rachel R. TI Altered chemokine profile associated with exacerbated autoimmune pathology under conditions of genetic interferon-gamma deficiency SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; COLLAGEN-INDUCED ARTHRITIS; IFN-GAMMA; T-CELLS; FUNCTIONAL-PROPERTIES; DENDRITIC CELLS; MICE; EXPRESSION; ENCEPHALOMYELITIS; DISEASE AB PURPOSE. A prior study showed that mice deficient in IFN-gamma (GKO) are more susceptible to experimental autoimmune uveitis ( EAU) than are wild-type (WT) mice. Histopathology of uveitic eyes revealed that the ocular infiltrate in GKO mice was dominated by neutrophils and eosinophils rather than by mononuclear cells, as in WT mice. The present study was conducted to explore the differential expression of chemokine( s) likely to account for the distinct inflammatory cell composition in uveitic eyes of WT and GKO mice. METHODS. Mice were immunized to induce EAU. Lymph nodes draining the site of the immunization and the eyes were collected at different time points for chemokine analysis. Microarray, real-time PCR and protein analyses were performed to examine the expression of chemokines in WT and GKO mice. RESULTS. Many chemokines were differentially upregulated in GKO versus WT mice. Expression of the Th1-associated chemokines CXCL10, CXCL9, CCL5, and CXCL11 was elevated in WT mice, whereas the Th2-associated chemokines CCL11, CCL17, and CCL1 and the Th17-associated chemokines CCL22 and CXCL2 were elevated in the GKO mice. Depletion of granulocytes abrogated EAU in both WT and GKO mice. CONCLUSIONS. These results suggest that Th1-associated chemokines play a critical role in the attraction of mononuclear cells to the eyes in the presence of IFN-gamma, while in the absence of this cytokine, Th2- and Th17-related chemokines may be the key elements for influx of granulocytes. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,10-10N222, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810; Caspi, Rachel/0000-0002-7140-7671 FU Intramural NIH HHS [Z01 EY000184-25] NR 57 TC 34 Z9 41 U1 0 U2 2 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 OCT PY 2007 VL 48 IS 10 BP 4616 EP 4625 DI 10.1167/iovs.07-0233 PG 10 WC Ophthalmology SC Ophthalmology GA 214SE UT WOS:000249757600032 PM 17898285 ER PT J AU Kottilil, S Jackson, JO Reitano, KN O'Shea, MA Roby, G Lloyd, M Yang, J Hallahan, CW Rehm, CA Arthos, J Lempicki, R Fauci, AS AF Kottilil, Shyam Jackson, Julia O. Reitano, Kristin N. O'Shea, Marie Angeline Roby, Gregg Lloyd, Margaret Yang, Jun Hallahan, Claire W. Rehm, Catherine A. Arthos, James Lempicki, Richard Fauci, Anthony S. TI Innate immunity in HIV infection - Enhanced susceptibility to CD9S-mediated natural killer cell death and turnover induced by HIV viremia SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 12th Conference on Retroviruses and Opportunistic Infections CY FEB 22-25, 2005 CL Boston, MA DE Fas; FasL; gene expression; HIV-1; natural killer cells ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; GENE-EXPRESSION; T-LYMPHOCYTES; NK CELLS; RHESUS MACAQUES; IN-VITRO; B-CELLS; RECEPTORS; INDIVIDUALS AB In the present study, we performed DNA microarray analyses and phenotypic and functional analyses in an effort to elucidate the mechanisms by which ongoing HIV replication affects the physiologic function of natural killer (NK) cells. Functional assays confirmed an increased propensity of NK cells from HIV infected viremic individuals to undergo Fas-mediated apoptosis but not CD 16-or NKG2D-mediated apoptosis. Serum levels of sFasL and expression of Ki67 on NK cells were markedly elevated in HIV infected viremic individuals when compared with those of HIV infected aviremic and HIV seronegative individuals. Our data demonstrate that ongoing HIV replication results in profound NK-cell abnormalities that are likely to be attributable to the effects of virus-induced immune activation. Of note is an increased susceptibility to cell death mediated by CD95-sFasL interactions. In addition, these NK cells, particularly the CD56(dim) CD16(bright) subset, undergo enhanced cell turnover in vivo, as demonstrated by intracellular Ki67 expression. C1 NIAID, Natl Inst Hlth, Immunoregulat Lab, Bethesda, MD 20892 USA. NIH, Clin Ctr Nursing Dept, Bethesda, MD USA. Sci Applicat Int Corp Frederick, Natl Canc Inst, NIH, Bethesda, MD USA. RP Kottilil, S (reprint author), NIAID, Natl Inst Hlth, Immunoregulat Lab, Bldg 10,Rm 11N204,9000 Rockville Pike, Bethesda, MD 20892 USA. EM skottilil@niaid.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU Intramural NIH HHS NR 38 TC 25 Z9 25 U1 0 U2 6 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 OCT 1 PY 2007 VL 46 IS 2 BP 151 EP 159 DI 10.1097/QAI.0b013e3180dc9909 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 215LO UT WOS:000249810100004 PM 17558334 ER PT J AU Lang, DL Salazar, LF Wingood, GM DiClemente, RJ Mikhail, I AF Lang, Delia L. Salazar, Laura F. Wingood, Gina M. DiClemente, Ralph J. Mikhail, Isis TI Associations between recent gender-based violence and pregnancy, sexually transmitted infections, condom use practices, and negotiation of sexual practices among HIV-positive women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE condom use; gender-based violence; pregnancy; seropositive women; sexually transmitted infections ID AFRICAN-AMERICAN WOMEN; HEALTH-RISK BEHAVIORS; DOMESTIC VIOLENCE; PHYSICAL ABUSE; PARTNER ABUSE; SUBSTANCE USE; CARE; VICTIMIZATION; PREVALENCE; DISEASES AB Background: This study sought to document the prevalence of recent gender-based violence (rGBV) among seropositive women and to determine the association between rGBV and pregnancy, sexually transmitted infections (STIs), condom use, and negotiation of sexual practices. Methods: A total of 304 seropositive women recruited from HIV clinics in the southeastern United States who reported being sexually active in the previous 6 months with 1 partner were included in analyses. Gender-based violence during the previous 3 months, condom use, and negotiation of sexual practices were assessed. Biologic samples for pregnancy and STI testing were collected. Results: A total of 10.2% of women reported a history of rGBV rGBV was related to inconsistent condom use practices, pregnancy, and abuse stemming from requests for condom use. No associations were found between rGBV and negotiation of sexual practices and STIs. Conclusions: The prevalence of rGBV among HIV positive women emphasizes the need for screening of abuse and highlights the need for the design and implementation of integrated intervention approaches necessary in addressing the needs of this population. C1 Emory Univ, Rollins Sch Hlth, Dept Hlth Behav & Hlth Educ, Atlanta, GA 30322 USA. Emory Univ, Emory Ctr AIDS Res, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Pediat, Div Infect Dis Epidemiol & Immunol, Atlanta, GA USA. Emory Univ, Sch Med, Dept Med Infect Dis, Atlanta, GA USA. NCI, Natl Inst Hlth, Epidemiol & Genet Res Program, Bethesda, MD 20892 USA. RP Lang, DL (reprint author), Emory Univ, Rollins Sch Hlth, Dept Hlth Behav & Hlth Educ, 1520 Clifton Rd,268, Atlanta, GA 30322 USA. EM dlang2@sph.emory.edu FU NIAID NIH HHS [AI027767]; NIMH NIH HHS [R01MH54412] NR 52 TC 22 Z9 22 U1 2 U2 8 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 OCT 1 PY 2007 VL 46 IS 2 BP 216 EP 221 DI 10.1097/QAI.0b013e31814d4dad PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 215LO UT WOS:000249810100013 PM 17693895 ER PT J AU Cleghorn, F Pape, JW Schechter, M Bartholomew, C Sanchez, J Jack, N Metch, BJ Hansen, M Allen, M Cao, H Montefiori, DC Tomaras, GD Gurunathan, S Eastman, DJ do Lago, RF Jean, S Lama, JR Lawrence, DN Wright, PF AF Cleghorn, Farley Pape, Jean W. Schechter, Mauro Bartholomew, Courtenay Sanchez, Jorge Jack, Noreen Metch, Barbara J. Hansen, Marianne Allen, Mary Cao, Huyen Montefiori, David C. Tomaras, Georgia D. Gurunathan, Sanjay Eastman, Donna J. do Lago, Regina F. Jean, Sonic Lama, Javier R. Lawrence, Dale N. Wright, Peter F. CA 026 Protocol Team NIAID HIV Vaccin TI Lessons from a multisite International trial in the Caribbean and South America of an HIV-1 Canarypox vaccine (ALVAC-HIV vCP1452) with or without boosting with MN rgp120 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; vaccine; canarypox; clinical trial; clade B; developing world ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSES; T-CELL; RECOMBINANT GP120; TYPE-1 VACCINE; FOWLPOX VIRUS; VOLUNTEERS; IMMUNOGENICITY; COMBINATION AB Background: The first multicenter, international National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored HIV vaccine trial took place in Brazil, Haiti, Peru and Trinidad. This randomized, double-blind, placebo-controlled, phase 2 trial evaluated the safety and immunogenicity of a clade B-derived, live canarypox HIV vaccine, vCP1452. vCP1452 was administered alone or with a heterologous boost of MN rgp 120 glycoprotein. The trial was pivotal in deciding whether these vaccines advanced to phase 3 efficacy trials. Methods: Forty seronegative volunteers per site were randomized to ALVAC alone, ALVAC plus MN rgp 120, or placebo in a 0, 1, 3, and 6 month schedule. Immunogenicity was assayed by chromium-release cytotoxic T lymphocyte (CTL) responses; interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays (ELISpot); lymphocyte proliferation assays (LPA); neutralization; and enzyme-linked immunosorbent assays (ELISA). Results: Enrollment and follow-up were excellent. Both vaccines were well tolerated. Neutralizing antibody to the laboratory-adapted MN strain was detected. Cellular immune responses, as measured by CTL, ELISpot, and LPA, did not differ between vaccines and placebos. Conclusions: The observation of disappointing immunogenicity in this and a parallel domestic study has informed future vaccine development. Equally important, challenges to doing an integrated trial across countries, cultures, languages, and differing at-risk populations were overcome. The identification of specific safety, ethical, logistic, and immunological issues in this trial established the foundation for current larger international studies. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Ctr HIV AIDS, Washington, DC USA. Inst Natl Lab & Rech GHESKIO, Port Au Prince, Haiti. Univ Fed Rio de Janeiro, Projeto Prraca Onze, Rio De Janeiro, Brazil. Med Res Fdn, Port of Spain, Trinid & Tobago. Asociac Civil Impacta Salud & Educ, Lima, Peru. HIV Vaccine Trials Network, Seattle, WA USA. NIAID, Natl Inst Hlth, Div Aids, Bethesda, MD 20892 USA. Calif Dept Hlth Serv, Richmond, CA USA. Duke Univ Med Ctr, Durham, NC USA. Sanofi Pasteur, Swiftwater, PA USA. Vaxgen Inc, Brisbane, CA USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. RP Wright, PF (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N LE-500,POB 19024, Seattle, WA 98109 USA. EM peter.wright@vanderbilt.edu RI Tomaras, Georgia/J-5041-2016; OI Allen, Mary/0000-0001-8163-0714 FU NIAID NIH HHS [U01 AI46725, U01 AI46747] NR 36 TC 30 Z9 31 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 OCT 1 PY 2007 VL 46 IS 2 BP 222 EP 230 DI 10.1097/QAI.0b013e318149297d PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 215LO UT WOS:000249810100014 PM 17693888 ER PT J AU Tang, SX Zhao, JQ Storhoff, JJ Norris, PJ Little, RF Yarchoan, R Stramer, SL Patno, T Domanus, M Dhar, A Mirkin, CA Hewlett, IK AF Tang, Shixing Zhao, Jiangqin Storhoff, James J. Norris, Philip J. Little, Richard F. Yarchoan, Robert Stramer, Susan L. Patno, Tim Domanus, Marc Dhar, Arindam Mirkin, Chad A. Hewlett, Indira K. TI Nanoparticle-based biobarcode amplification assay (BCA) for sensitive and early detection of human immunodeficiency type 1 capsid (p24) antigen SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; p24 antigen; nanoparticle; biobarcode; detection ID HEAT-DENATURED PLASMA; VIRUS TYPE-1; HIV-1 P24; ANTIRETROVIRAL THERAPY; SIGNAL AMPLIFICATION; DNA DETECTION; VIRAL-RNA; PROBES; PROTEINS; ANTIBODY AB Nanotechnology-based techniques are being widely evaluated in medical testing and could provide a new generation of diagnostic assays due to their high degrees of sensitivity, high specificity, multiplexing capabilities, and ability to operate without enzymes. In this article, we have modified a nanoparticle-based biobarcode amplification (BCA) assay for early and sensitive detection of HIV-1 capsid (p24) antigen by using antip24 antibody-coated microplates to capture viral antigen (p24) and streptavidin-coated nanoparticle-based biobarcode DNAs for signal amplification, followed by detection using a chip-based scanometric method. The modified BCA assay exhibited a linear dose-dependent pattern within the detection range of 0.1 to 500 pg/ml and was approximately 150-fold more sensitive than conventional enzyme-linked immunosorbent assay (ELISA). No false positive results were observed in 30 HIV-1-negative samples, while all 45 HIV-1 RNA positive samples were found HIV-1 p24 antigen positive by the BCA assay. In addition, the BCA assay detected HIV-1 infection 3 days earlier than ELISA in seroconversion samples. Preliminary evaluation based on testing a small number of samples indicates that the HIV-1 p24 antigen BCA may provide a new tool for sensitive and early detection of HIV 1 p24 antigen in settings where HIV-1 RNA testing is currently not routinely performed. C1 US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bethesda, MD 20892 USA. Nanosphere, N Brook, IL USA. Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. NCI, Natl Inst Hlth, HIV & AIDS Malilgnancy Branch, Bethesda, MD 20892 USA. Amer Red Cross, Biomed Serv Sci Support Off, Gaithersburg, MD USA. US FDA, NCI, Interagcy Oncol Task Force, Bethesda, MD 20014 USA. Northwestern Univ, Dept Chem, Evanston, IL USA. Northwestern Univ, Int Inst Nanotechnol, Evanston, IL USA. RP Tang, SX (reprint author), US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bldg 29B,Rm 4NN16,8800 Rcokville Pike, Bethesda, MD 20892 USA. EM shixing.tang@fda.hhs.gov; indira.hewlett@fda.hhs.gov RI Mirkin, Chad/E-3911-2010 NR 39 TC 49 Z9 54 U1 5 U2 28 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 OCT 1 PY 2007 VL 46 IS 2 BP 231 EP 237 DI 10.1097/QAI.0b013e31814a554b PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 215LO UT WOS:000249810100015 PM 17693896 ER PT J AU Hirvensalo, MH Cohen-Mansfield, J Rind, S Guralnik, J AF Hirvensalo, Mirja Hannele Cohen-Mansfield, Jiska Rind, Shlomit Guralnik, Jack TI Assessment of impairments that limit exercise and use of impairment information to generate an exercise SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Review DE functional limitation; exercise counseling; recommendations; functional tests ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE BATTERY; DWELLING OLDER-ADULTS; SUBSEQUENT DISABILITY; ELDERLY PATIENTS; MOBILITY; STRENGTH; RISK; PAIN; RECOMMENDATIONS AB Prescribing the correct exercise program is a challenge for older adults with multiple physiological impairments. The authors evaluated an assessment instrument that incorporates results of multiple categories of impairment, including strength, balance, gait, vision, and cognitive function. The physical therapist made judgments on the relative impact of 9 different impairments on specific exercises and on the total impact of all impairments on particular exercises. In a cohort age 75-85 y, functional limitations, impaired balance, pain, and low physical endurance were estimated to have the largest impact on the ability to carry out exercise activities, primarily walking, stair climbing, balance exercises, and stationary bicycling. The assessments revealed that the ability to exercise was related to objective measures of function, indicating that the therapist incorporated such objective measures into the impairment-impact rating. The impairment-impact assessment facilitates creating individualized exercise prescriptions for individuals with impairments. C1 Univ Jyvaskyla, Dept Sport Sci, Jyvaskyla 40014, Finland. Hebrew Home Greater Washington, Res Inst Aging, Rockville, MD 20825 USA. Adventist Rehabil Hosp, Outpatient Ctr, Silver Spring, MD 20903 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Hirvensalo, MH (reprint author), Univ Jyvaskyla, Dept Sport Sci, Jyvaskyla 40014, Finland. FU Intramural NIH HHS NR 32 TC 3 Z9 3 U1 0 U2 4 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD OCT PY 2007 VL 15 IS 4 BP 459 EP 479 PG 21 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA 222CN UT WOS:000250273800007 PM 18048948 ER PT J AU Shearer, WT Malech, HL Puck, JM AF Shearer, William T. Malech, Harry L. Puck, Jennifer M. TI Primary immunodeficiency: Meeting the challenges SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material C1 Texas Childrens Hosp, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. Texas Childrens Hosp, Allergy & Immunol Serv, Houston, TX 77030 USA. NIAID, Natl Inst Hlth, Genet Immunotherapy Sect, Host Def Lab, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Shearer, WT (reprint author), Texas Childrens Hosp, 6621 Fannin St MC FC330 01, Houston, TX 77030 USA. EM wtsheare@TexasChildrensHospital.org OI Malech, Harry/0000-0001-5874-5775 FU Intramural NIH HHS; NCRR NIH HHS [UL RR024131-01, RR0188]; NHLBI NIH HHS [HL78522, HL079533, HL72705]; NIAID NIH HHS [AI36211, AI069441, AI27551]; NICHD NIH HHS [HD41983, HD052102]; PHS HHS [RAT003084A] NR 22 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2007 VL 120 IS 4 BP 753 EP 755 DI 10.1016/j.jaci.2007.09.002 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 220LH UT WOS:000250157700005 PM 17931558 ER PT J AU Geha, RS Notarangelo, LD Casanova, JL Chapel, H Conley, ME Fischer, A Hammarstrom, L Nonoyama, S Ochs, HD Wedgwood, J AF Geha, Raif S. Notarangelo, Luigi D. Casanova, Jean-Laurent Chapel, Helen Conley, Mary Ellen Fischer, Alain Hammarstrom, Lennart Nonoyama, Shigeaki Ochs, Hans D. Wedgwood, Josiah TI Primary immunodeficiency diseases: An update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE primary immunodeficiency diseases; T cells; B cells; phagocytes; complement; immune dysregulation syndromes; innate immunity ID DEFICIENCY; MUTATION; EXPRESSION; CERNUNNOS; ROLES; CELLS AB Primary immunodeficiency diseases (PIDs) are a genetically heterogeneous group of disorders that affect distinct components of the innate and adaptive immune system, such as neutrophils, macrophages, dendritic cells, complement proteins, natural killer cells, and T and B lymphocytes. The study of these diseases has provided essential insights into the functioning of the immune system. More than 120 distinct genes have been identified, whose abnormalities account for more than 150 different forms of PID. The complexity of the genetic, immunologic, and clinical features of PID has prompted the need for their classification, with the ultimate goal of facilitating diagnosis and treatment. To serve this goal, an international committee of experts has met every 2 years since 1970. In its last meeting in Jackson Hole, Wyo, after 3 days of intense scientific presentations and discussions, the committee has updated the classification of PID, as reported in this article. C1 Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Inst Natl Sante & Rech Med, Lab Human Genet Infect Dis, Paris, France. John Radcliffe Hosp, Div Clin Immunol, Oxford OX3 9DU, England. St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA. INSERM U429, Hosp Necker Enfants Malades, Paris, France. Kavolinska Inst, Div Clin Immunol, Huddinge, Sweden. Natl Def Med Coll, Dept Pediat, Saitama, Japan. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Hosp Sick Children, Div Immunol & Allergy, Toronto, ON M5G 1X8, Canada. Kinderspital Zurich, Div Immunol, CH-8032 Zurich, Switzerland. NIAID, Natl Inst Hlth, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. RP Geha, RS (reprint author), Childrens Hosp, Div Immunol, 1 Blackfan Circle, Boston, MA 02115 USA. EM raif.geha@childrens.harvard.edu; luigi.notarangel@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 21 TC 263 Z9 283 U1 0 U2 14 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 OCT PY 2007 VL 120 IS 4 BP 776 EP 794 DI 10.1016/j.jaci.2007.08.053 PG 19 WC Allergy; Immunology SC Allergy; Immunology GA 220LH UT WOS:000250157700010 ER PT J AU Sever, ML Arbes, SJ Gore, JC Santangelo, RG Vaughn, B Mitchell, H Schal, C Zeldin, DC AF Sever, Michelle L. Arbes, Samuel J., Jr. Gore, J. Chad Santangelo, Richard G. Vaughn, Ben Mitchell, Herman Schal, Coby Zeldin, Darryl C. TI Cockroach allergen reduction by cockroach control alone in low-income urban homes: A randomized control trial SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE cockroaches; cockroach allergen; Bla g 1; Bla g 2; indoor allergens; intervention trial ID INTEGRATED PEST-MANAGEMENT; INNER-CITY HOMES; ENVIRONMENTAL INTERVENTION; ASTHMA; COMMUNITY; ABATEMENT; EXPOSURE; CHILDREN; BLA-G-1 AB Background: We previously reported significant reductions in cockroach allergen concentrations in urban homes by reducing cockroach infestations. Objective: To determine the effectiveness of pest control performed by professional entomologists, compared with commercial companies, in reducing cockroach allergen. Methods: This 3-arm randomized controlled trial enrolled 60 cockroach-infested homes in North Carolina. Homes were randomly assigned to a control group or 1 of 2 treatment groups. Treatment 1 had insecticide baits placed by entomologists from North Carolina State University. Treatment 2 received pest control from a randomly assigned commercial company. Vacuumed dust sampling and cockroach trapping were conducted at 0, 6, and 12 months. Dust samples were analyzed by ELISA. Results: In treatment 1 homes, there were significant reductions in geometric mean trap counts compared with control and treatment 2 homes at 12 months. Relative to control, significant 12-month reductions in Bla g 1 were evident in treatment I homes at all sampled sites, except bedroom floor. From baseline to month 12, geometric mean Bla g 1 concentrations (U/g) decreased from 64.2 to 5.6 in kitchen, 10.6 to 1.1 in living room, 10.7 to 1.9 on bedroom floor, and 3.6 to 2.3 in bed. Treatment 2 homes showed no significant 12-month allergen reductions versus control. Conclusion: Reductions in Bla g 1 in cockroach-infested homes can be achieved by reducing infestations; however, the magnitude of allergen reduction is dependent on the thoroughness and effectiveness of cockroach eradication efforts. Clinical implications: Elimination of cockroaches is an effective method for reducing exposure to cockroach allergen. C1 NIEHS, NIH, Div Intramural Res, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA. Rho Inc, Chapel Hill, NC USA. RP Zeldin, DC (reprint author), NIEHS, NIH, Div Intramural Res, POB 12233,MD D2-01, Res Triangle Pk, NC 27709 USA. EM zeldin@nielis.nih.gov RI Schal, Coby/A-8717-2010; OI Schal, Coby/0000-0001-7195-6358; Sever, Michelle/0000-0002-2435-1214 FU Intramural NIH HHS [Z01 ES025041-10] NR 16 TC 36 Z9 36 U1 1 U2 6 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 OCT PY 2007 VL 120 IS 4 BP 849 EP 855 DI 10.1016/j.jaci.2007.07.003 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 220LH UT WOS:000250157700019 PM 17825893 ER PT J AU Huestis, MA Darwin, WD Shimomura, E Lalani, SA Trinidad, DV Jenkins, AJ Cone, EJ Jacobs, AJ Smith, ML Paul, BD AF Huestis, Marilyn A. Darwin, W. David Shimomura, Eric Lalani, Shairose A. Trinidad, Daniel V. Jenkins, Amanda J. Cone, Edward J. Jacobs, Aaron J. Smith, Michael L. Paul, Buddha D. TI Cocaine and metabolites urinary excretion after controlled smoked administration SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID DIFFERENT ROUTES; BENZOYLECGONINE; ELIMINATION; STABILITY; ECGONINE; HUMANS; PLASMA C1 Natl Inst Drug Abuse, Natl Inst Hlth, Chem & Drug Metabol Intramural Res Program, Baltimore, MD 21224 USA. Armed Forces Inst Pathol, Off armed Forces Med Examiner, Div Forensic Toxicol, Rockville, MD USA. Off Cuyahoga Country Coroner, Cleveland, OH USA. Johns Hopkins Sch Med, Baltimore, MD USA. US Army Med Dept Board, Houston, TX USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Natl Inst Hlth, Chem & Drug Metabol Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000413-10] NR 16 TC 16 Z9 18 U1 0 U2 10 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 OCT PY 2007 VL 31 IS 8 BP 462 EP 468 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 222SX UT WOS:000250318600006 PM 17988460 ER PT J AU Abraham, TT Lowe, RH Pirnay, SO Darwin, WD Huestis, MA AF Abraham, Tsadik T. Lowe, Ross H. Pirnay, Stephane O. Darwin, William D. Huestis, Marilyn A. TI Simultaneous GC-El-MS determination of Delta 9-tetrahydrocannabinol, 11-hydroxy-Delta 9-tetrahydrocannabinol, and 11-nor-9-carboxy, Delta 9-tetrahydrocannabinol in human urine following tandem enzyme-alkaline hydrolysis SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID SOLID-PHASE EXTRACTION; CHROMATOGRAPHY-MASS SPECTROMETRY; CANNABIS-BASED MEDICINE; GAS-CHROMATOGRAPHY; DELTA(9)-TETRAHYDROCANNABINOL THC; CHEMICAL-IONIZATION; MAJOR METABOLITES; MULTIPLE-SCLEROSIS; ORAL APPLICATION; VALIDATED METHOD C1 NIDA, NIH, IRP, Chem & Drug Metabol, Baltimore, MD 21224 USA. Univ Paris 05, Fac Pharm, Neuropsychopharmacol Addict, CNRS,UMR7157, F-75010 Paris, France. RP Huestis, MA (reprint author), NIDA, NIH, IRP, Chem & Drug Metabol, 550 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000413-10] NR 40 TC 46 Z9 49 U1 3 U2 11 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 OCT PY 2007 VL 31 IS 8 BP 477 EP 485 PG 9 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 222SX UT WOS:000250318600008 PM 17988462 ER PT J AU Peer, CJ Shakleya, DM Younis, IR Kraner, JC Callery, PS AF Peer, Cody J. Shakleya, Diaa M. Younis, Islam R. Kraner, James C. Callery, Patrick S. TI Direct-injection mass spectrometric method for the rapid identification of fentanyl and norfentanyl in postmortem urine of six drug-overdose cases SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID HUMAN PLASMA; ELECTROSPRAY-IONIZATION; QUANTITATIVE-DETERMINATION; TRANSDERMAL DELIVERY; LIVER-TISSUE; LC-MS/MS; METABOLITES; SUPPRESSION; SUFENTANIL; EXTRACTION C1 W Virginia Univ, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. Off Chief Med Examiner, Charleston, WV 25302 USA. RP Callery, PS (reprint author), W Virginia Univ, Dept Basic Pharmaceut Sci, PO Box 9530, Morgantown, WV 26506 USA. EM pcallery@hsc.wvu.edu NR 31 TC 8 Z9 9 U1 1 U2 5 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 OCT PY 2007 VL 31 IS 8 BP 515 EP 521 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 222SX UT WOS:000250318600012 PM 17988466 ER PT J AU Rothney, MP Neumann, M Beziat, A Chen, KY AF Rothney, Megan P. Neumann, Megan Beziat, Ashley Chen, Kong Y. TI An artificial neural network model of energy expenditure using. nonintegrated acceleration signals SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE physical activity; actigraph; IDEEA monitor; accelerometer; indirect calorimeter ID PHYSICAL-ACTIVITY; TRIAXIAL ACCELEROMETER; COMPUTER-SCIENCE; VALIDATION; INC. AB Accelerometers are a promising tool for characterizing physical activity patterns in free living. The major limitation in their widespread use to date has been a lack of precision in estimating energy expenditure (EE), which may be attributed to the oversimplified time-integrated acceleration signals and subsequent use of linear regression models for EE estimation. In this study, we collected biaxial raw (32 Hz) acceleration signals at the hip to develop a relationship between acceleration and minute-to-minute EE in 102 healthy adults using EE data collected for nearly 24 h in a room calorimeter as the reference standard. From each 1 min of acceleration data, we extracted 10 signal characteristics (features) that we felt had the potential to characterize EE intensity. Using these data, we developed a feed-forward/back-propagation artificial neural network (ANN) model with one hidden layer (12 X 20 X I nodes). Results of the ANN were compared with estimations using the ActiGraph monitor, a uniaxial accelerometer, and the IDEEA monitor, an array of five accelerometers. After training and validation (leave-one-subject out) were completed, the ANN showed significantly reduced mean absolute errors (0.29 +/- 0. 10 kcal/min), mean squared errors (0.23 +/- 0.14 kcal(2)/min(2)), and difference in total EE (21 +/- 115 kcal/day), compared with both the IDEEA (P < 0.01) and a regression model for the ActiGraph accelerometer (P < 0.001). Thus ANN combined with raw acceleration signals is a promising approach to link body accelerations to EE. Further validation is needed to understand the performance of the model for different physical activity types under free-living conditions. C1 Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA. Vanderbilt Univ, Med Ctr, Dept Med, Div Gastroenterol, Nashville, TN USA. NIDDK, NIH, Clin Endocrinol Branch, Bethesda, MD USA. RP Rothney, MP (reprint author), CRC, 10 Ctr Dr MSC 1613,10 6-3940, Bethesda, MD 20892 USA. EM rothneym@niddk.nih.gov OI Chen, Kong/0000-0002-0306-1904 FU NCRR NIH HHS [RR-00095]; NHLBI NIH HHS [HL-082988]; NIDDK NIH HHS [DK-02973, DK-069465] NR 29 TC 74 Z9 76 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD OCT PY 2007 VL 103 IS 4 BP 1419 EP 1427 DI 10.1152/japplphysiol.00429.2007 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 219LX UT WOS:000250087800042 PM 17641221 ER PT J AU Thurm, A Lord, C Lee, LC Newschaffer, C AF Thurm, Audrey Lord, Catherine Lee, Li-Ching Newschaffer, Craig TI Predictors of language acquisition in preschool children with autism spectrum disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE autism; language; preschool; predictors; outcome ID PERVASIVE DEVELOPMENTAL DISORDERS; ADAPTIVE-BEHAVIOR SCALES; FRAGILE-X-SYNDROME; YOUNG-CHILDREN; JOINT ATTENTION; FOLLOW-UP; SYMPTOMS; INDIVIDUALS; IMITATION; DELAYS AB In 118 children followed from age 2 to 5 (59 with autism, 24 with PDD-NOS and 35 with non-spectrum developmental disabilities), age 2 and age 3 scores of non-verbal ability, receptive communication, expressive communication and socialization were compared as predictors of receptive and expressive language at age 5. Non-verbal cognitive ability at age 2 was generally the strongest predictor of age 5 language, while at age 3 communication scores were a stronger predictor of age 5 language for children with autism. Early joint attention as well as vocal and motor imitation skills were more impaired in children who did not develop language by age 5 (but had relatively strong non-verbal cognitive skills) than in children who did develop language by 5. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. Univ Michigan, Univ Michigan Austism & Commun Disorders Ctr UMAC, Ann Arbor, MI 48109 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Drexel Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Thurm, A (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, 10 Ctr Dr MSC 1255,Bldg 10,4N208, Bethesda, MD 20892 USA. EM athurm@mail.nih.gov FU NICHD NIH HHS [P01 HD035482, HD35482]; NIMH NIH HHS [MH066469, R01 MH066496] NR 51 TC 70 Z9 73 U1 4 U2 27 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD OCT PY 2007 VL 37 IS 9 BP 1721 EP 1734 DI 10.1007/s10803-006-0300-1 PG 14 WC Psychology, Developmental SC Psychology GA 213EV UT WOS:000249649900008 PM 17180717 ER PT J AU Srivastava, P Demarre, G Karpova, TS McNally, J Chattoraj, DK AF Srivastava, Preeti Demarre, Gaeelle Karpova, Tatiana S. McNally, James Chattoraj, Dhruba K. TI Changes in nucleoid morphology and origin localization upon inhibition or alteration of the actin homolog, MreB, of Vibrio cholerae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI CHROMOSOME; SEPARATE CELL HALVES; BACILLUS-SUBTILIS; CAULOBACTER-CRESCENTUS; BACTERIAL CYTOSKELETON; BINDING-PROTEIN; DNA SEGREGATION; IN-VIVO; REPLICATION; DISTINCT AB MreB is an actin homolog required for the morphogenesis of most rod-shaped bacteria and for other functions, including chromosome segregation. In Caulobacter crescentus and Escherichia coli, the protein seems to play a role in the segregation of sister origins, but its role in Bacillus subtilis chromosome segregation is less clear. To help clarify its role in segregation, we have here studied the protein in Vibrio cholerae, whose chromosome I segregates like the one in C crescentus and whose chromosome II like the one in E. coli or B. subtilis. The properties of Vibrio MreB were similar to those of its homologs in other bacteria in that it formed dynamic helical filaments, was essential for viability, and was inhibited by the drug A22. Wild-type (WT) cells exposed to A22 became spherical and larger. The nucleoids enlarged correspondingly, and the origin positions for both the chromosomes no longer followed any fixed pattern. However, the sister origins separated, unlike the situation in other bacteria. In mutants isolated as A22 resistant, the nucleoids in some cases appeared compacted even when the cell shape was nearly normal. In these cells, the origins of chromosome I were at the distal edges of the nucleoid but not all the way to the poles where they normally reside. The sister origins of chromosome II also separated less. Thus, it appears that the inhibition or alteration of Vibrio MreB can affect both the nucleoid morphology and origin localization. C1 NIH, NCI, Bethesda, MD 20892 USA. NIH, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA. NIH, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Chattoraj, DK (reprint author), NIH, NCI, 37 Convent Dr, Bethesda, MD 20892 USA. EM chattoraj@nih.gov FU Intramural NIH HHS NR 55 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 2007 VL 189 IS 20 BP 7450 EP 7463 DI 10.1128/JB.00362-07 PG 14 WC Microbiology SC Microbiology GA 219QP UT WOS:000250100000034 PM 17704222 ER PT J AU Liu, J McBride, MJ Subramaniam, S AF Liu, Jun McBride, Mark J. Subramaniam, Sriram TI Cell surface filaments of the gliding bacterium Flavobacterium johnsoniae revealed by cryo-electron tomography SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DIRECT VISUALIZATION; ELECTRON TOMOGRAPHY; CHITIN UTILIZATION; RECEPTOR ARRAYS; MOTILITY; CYTOPHAGA; LIPOPROTEIN; CLONING; GLDA AB Flavobacterium johnsoniae cells glide rapidly over surfaces by an as-yet-unknown mechanism. Using cryoelectron tomography, we show that wild-type cells display tufts of -5-nm-wide cell surface filaments that appear to be anchored to the inner surface of the outer membrane. These filaments are absent in cells of a nonmotile gldF mutant but are restored upon expression of plasmid-encoded GldF, a component of a putative ATP-binding cassette transporter. C1 NCI, NIH, Canc Res Ctr, Cell Biol Lab, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53201 USA. RP Subramaniam, S (reprint author), NCI, NIH, Canc Res Ctr, Cell Biol Lab, Bethesda, MD 20892 USA. EM mcbride@uwm.edu; ss1@nih.gov OI McBride, Mark/0000-0002-3798-6761 FU Intramural NIH HHS NR 25 TC 34 Z9 36 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 2007 VL 189 IS 20 BP 7503 EP 7506 DI 10.1128/JB.00957-07 PG 4 WC Microbiology SC Microbiology GA 219QP UT WOS:000250100000039 PM 17693495 ER PT J AU Johnson, MO Neilands, TB Dilworth, SE Morin, SF Remien, RH Chesney, MA AF Johnson, Mallory O. Neilands, Torsten B. Dilworth, Samantha E. Morin, Stephen F. Remien, Robert H. Chesney, Margaret A. TI The role of self-efficacy in HIV treatment adherence: Validation of the HIV treatment adherence self-efficacy scale (HIV-ASES) SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE HIV; AIDS; Adherence; Self-efficacy ID HEALTHY LIVING PROJECT; ANTIRETROVIRAL THERAPY; MEDICATION ADHERENCE; REPORTED ADHERENCE; RELIABILITY; BEHAVIOR; DISEASE; INTERVENTIONS; QUESTIONNAIRE; PREDICTORS AB Adherence to HIV treatment, including adherence to antiretroviral (ART) medication regimens, is paramount in the management of HIV. Self-efficacy for treatment adherence has been identified as an important correlate of medication adherence in the treatment of HIV and other medical conditions. This paper describes the validation of the HIV Treatment Adherence Self-Efficacy Scale (HIV-ASES) with two samples of HIV+ adults on ART. Factor analyses support subscales measuring Adherence Integration (eigenvalue = 6.12) and Adherence Perseverance (eigenvalue = 1.16), accounting for 61% of the variance in scale items. The HIV-ASES demonstrates robust internal consistency (rho s > .90) and 3-month (rs > .70) and 15-month (rs > .40) test-retest reliability. Concurrent validity analyses revealed relationships with psychosocial measures, ART adherence, clinical status, and healthcare utilization. Findings support the use of the HIV-ASES and provide guidance for further investigation of adherence self-efficacy in the context of treatment for HIV and other diseases. C1 Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94105 USA. New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA. Columbia Univ, New York, NY USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA. RP Johnson, MO (reprint author), Univ Calif San Francisco, Ctr AIDS Prevent Studies, 50 Beale St,Suite 1300, San Francisco, CA 94105 USA. EM Mallory.Johnson@ucsf.edu FU NIMH NIH HHS [P30 MH043520, R01 MH068208, R01 MH068208-04, R01MH068208, U10 MH057615, U10 MH057616, U10 MH057616-07, U10 MH057631, U10 MH057636, U10-MH57615, U10-MH57616, U10-MH57631, U10-MH57636] NR 57 TC 64 Z9 65 U1 1 U2 14 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD OCT PY 2007 VL 30 IS 5 BP 359 EP 370 DI 10.1007/s10865-007-9118-3 PG 12 WC Psychology, Clinical SC Psychology GA 198HU UT WOS:000248618400001 PM 17588200 ER PT J AU Ying, JF Grishaev, A Latham, MP Pardi, A Bax, A AF Ying, Jinfa Grishaev, Alexander Latham, Michael P. Pardi, Arthur Bax, Ad TI Magnetic field induced residual dipolar couplings of imino groups in nucleic acids from measurements at a single magnetic field SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE alignment; chemical shift; dipolar coupling; magnetic susceptibility anisotropy; RDC; tRNA(Val) ID SOLUTION NMR; BIOLOGICAL MACROMOLECULES; GLOBAL STRUCTURE; BINDING TAG; ALIGNMENT; DYNAMICS; PROTEINS; SPECTRA; DOMAIN; SPECTROSCOPY AB For base-paired nucleic acids, variations in (1)J(NH) and the imino H-1 chemical shift are both dominated by hydrogen bond length. In the absence of molecular alignment, the (1)J(NH) coupling for the imino proton then can be approximated by (1)J(NH) = (1.21Hz/ppm)delta(H) - 103.5 +/- 0.6 Hz, where delta(H) represents the chemical shift of the imino proton in ppm. This relation permits imino residual dipolar couplings (RDCs) resulting from magnetic susceptibility anisotropy (MSA) to be extracted from measurement of ((1)J(NH) + RDC) splittings at a single magnetic field strength. Magnetic field-induced RDCs were measured for tRNA(Val) and the alignment tensor determined from magnetic-field alignment of tRNA(Val) agrees well with the tensor calculated by summation of the MSA tensors of the individual nucleobases. C1 Natl Inst Hlth, NIDDK, Phys Chem Lab, Bethesda, MD 20892 USA. Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. RP Bax, A (reprint author), Natl Inst Hlth, NIDDK, Phys Chem Lab, Bethesda, MD 20892 USA. EM bax@nih.gov OI Latham, Michael/0000-0002-2209-5798 FU Intramural NIH HHS; NIAID NIH HHS [AI33098]; NIGMS NIH HHS [T32 GM65103] NR 38 TC 14 Z9 14 U1 1 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD OCT PY 2007 VL 39 IS 2 BP 91 EP 96 DI 10.1007/s10858-007-9181-7 PG 6 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 208FD UT WOS:000249304300002 PM 17680332 ER PT J AU Khosla, S Burr, D Cauley, J Dempster, DW Ebeling, PR Felsenberg, D Gagel, RF Gilsanz, V Guise, T Koka, S McCauley, LK McGowan, J Mckee, MD Mohla, S Pendrys, DG Raisz, LG Ruggiero, SL Shafer, DM Shum, L Silverman, SL Van Poznak, CH Watts, N Woo, SB Shane, E AF Khosla, Sundeep Burr, David Cauley, Jane Dempster, David W. Ebeling, Peter R. Felsenberg, Dieter Gagel, Robert F. Gilsanz, Vincente Guise, Theresa Koka, Sreenivas McCauley, Laurie K. McGowan, Joan Mckee, Marc D. Mohla, Suresh Pendrys, David G. Raisz, Lawrence G. Ruggiero, Salvatore L. Shafer, David M. Shum, Lillian Silverman, Stuart L. Van Poznak, Catherine H. Watts, Nelson Woo, Sook-Bin Shane, Elizabeth TI Bisphosphonate-associated osteonecrosis of the jaw: Report of a task force of the American Society for Bone and Mineral Research SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Editorial Material DE osteoporosis; bone; oral cavity; pain; metastases ID OPTICAL COHERENCE TOMOGRAPHY; MANDIBULAR OSTEORADIONECROSIS; COMPUTED-TOMOGRAPHY; RISK-FACTORS; RECOGNITION; PREVENTION; GUIDELINES; THERAPY; DISEASE; CANCER AB Introduction: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder. Materials and Methods: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate-associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed. Results and Conclusions: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between I in 10,000 and <1 in 100,000 patient-treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1-10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined. C1 Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Mayo Clin, Coll Med, ASBMR, Rochester, MN 55905 USA. Indiana Univ, Sch Med, Bloomington, IN 47405 USA. Columbia Univ, New York, NY 10027 USA. Univ Melbourne, Parkville, Vic 3052, Australia. Univ Hosp Benjamin Franklin, Franklin, TN USA. Univ Texas, Dallas, TX USA. Univ Virginia, ENDO, IBMS, Pagetss Fdn, Charlottesville, VA 22903 USA. Univ Michigan, Ann Arbor, MI 48109 USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. NIH, NIAMS, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Connecticut, NOF, Storrs, CT 06269 USA. Long Isl Jewish Med Ctr, New Hyde Pk, NY 11040 USA. NIDCR, NIH, Bethesda, MD 20892 USA. ACR, ASBMR, Minneapolis, MN USA. Univ Cincinnati, ISCD, AACE, Cincinnati, OH 45221 USA. Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. RP Khosla, S (reprint author), Columbia Univ Coll Phys & Surg, 630 W 168th St,PH8 W 864, New York, NY 10032 USA. RI Ebeling, Peter/A-9129-2012; Cauley, Jane/N-4836-2015; OI Cauley, Jane/0000-0003-0752-4408; Khosla, Sundeep/0000-0002-2936-4372 NR 48 TC 775 Z9 806 U1 15 U2 64 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2007 VL 22 IS 10 BP 1479 EP 1491 DI 10.1359/JBMR.0707ONJ PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 219KC UT WOS:000250082500001 PM 17663640 ER PT J AU Gupton, SL Eisenmann, K Alberts, AS Waterman-Storer, CM AF Gupton, Stephanie L. Eisenmann, Kathryn Alberts, Arthur S. Waterman-Storer, Clare M. TI mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration SO JOURNAL OF CELL SCIENCE LA English DT Article DE FRAP; FSM; adhesion; depolymerization; formin ID FLUORESCENT SPECKLE MICROSCOPY; DIAPHANOUS-RELATED FORMIN; EARLY MOLECULAR EVENTS; SRC TYROSINE KINASE; ARP2/3 COMPLEX; LEADING-EDGE; BUNDLING ACTIVITY; CAPPING PROTEIN; LIVING CELLS; BARBED ENDS AB Cell migration requires spatial and temporal regulation of filamentous actin (F-actin) dynamics. This regulation is achieved by distinct actin-associated proteins, which mediate polymerization, depolymerization, severing, contraction, bundling or engagement to the membrane. Mammalian Diaphanous-related (mDia) formins, which nucleate, processively elongate, and in some cases bundle actin filaments, have been extensively studied in vitro, but their function in the cell has been less well characterized. Here we study the role of mDia2 activity in the dynamic organization of F-actin in migrating epithelial cells. We find that mDia2 localizes in the lamella of migrating epithelial cells, where it is involved in the formation of a stable pool of cortical actin and in maintenance of polymerization competent free filament barbed ends at focal adhesions. Specific inhibition of mDia2 alters focal adhesion turnover and reduces migration velocity. We suggest that the regulation of filament assembly dynamics at focal adhesions may be necessary for the formation of a stable pool of cortical lamella actin and the proper assembly and disassembly dynamics of focal adhesions, making mDia2 an important factor in epithelial cell migration. C1 NHLBI, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. Van Andel Res Inst, Grand Rapids, MI 49503 USA. RP Waterman-Storer, CM (reprint author), Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. EM watermancm@nhlbi.nih.gov OI Waterman, Clare/0000-0001-6142-6775 FU NCI NIH HHS [CA107529]; NIGMS NIH HHS [F32 GM723313, F32 GM072331, GM67230]; NIH HHS [OD000435] NR 70 TC 86 Z9 88 U1 1 U2 4 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 OCT 1 PY 2007 VL 120 IS 19 BP 3475 EP 3487 DI 10.1242/jcs.006049 PG 13 WC Cell Biology SC Cell Biology GA 212GZ UT WOS:000249583600016 PM 17855386 ER PT J AU Pemberton, HN Franklyn, JA Boelaert, K Chan, SY Kim, DS Kim, C Cheng, SY Kilby, MD McCabe, CJ AF Pemberton, H. N. Franklyn, J. A. Boelaert, K. Chan, S. Y. Kim, D. S. Kim, C. Cheng, S. Y. Kilby, M. D. McCabe, C. J. TI Separase, securin and rad21 in neural cell growth SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID TUMOR-TRANSFORMING GENE; SISTER-CHROMATID SEPARATION; HUMAN PITUITARY-ADENOMAS; COHESIN SUBUNIT SCC1; THYROID TUMORIGENESIS; BINDING-FACTOR; C-MYC; PTTG; EXPRESSION; CLEAVAGE AB The key mitotic regulator securin is expressed at low levels in fetal brain compared with adult, and modulates the proliferation of human embryonic neuronal N-Tera2 (NT2) cells. We now examine the function and expression of securin's interacting partner separase, along with Rad21, the functional component of cohesin, which is cleaved by separase following interaction with securin. In contrast to securin, the cleaved forms of separase and Rad21 were highly expressed in human fetal cerebral cortex compared with adult. In a murine model of absent securin expression-the PTTG knock-out mouse-separase and Rad21 were over-expressed in multiple brain regions. In addition, cDNA array analysis of other key mitotic regulators additionally identified cyclin C and sestrin 2 to be induced in the brains of securin-null mice compared with wild type. Further, Rad21 mRNA expression was highly correlated with that of securin, separase, cyclin C and sestrin 2 in fetal brains. In embryonic neuronal NT2 cells, siRNA repression of separase failed to significantly alter cell turnover, whereas repression of securin expression resulted in increased levels of the activated forms of Rad21 and separase, and promoted cell proliferation. Our data suggest that the co-ordinated expression of separase, securin and Rad21 is fundamental for the developing brain. C1 Univ Birmingham, Queen Elizabeth Hosp, Div Med Sci, Birmingham B15 2TH, W Midlands, England. Univ Birmingham, Birmingham Womens Hosp, Birmingham B15 2TG, W Midlands, England. NCI, Gene Regulat Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP McCabe, CJ (reprint author), Univ Birmingham, Biomed Res Inst, Div Med Sci, Birmingham B15 2TH, W Midlands, England. EM mccabcjz@bham.ac.uk RI Chan, Shiao/C-8347-2011 FU Medical Research Council [G0601811, G0501548] NR 38 TC 8 Z9 8 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 2007 VL 213 IS 1 BP 45 EP 53 DI 10.1002/jcp.21086 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 208AK UT WOS:000249292000006 PM 17450531 ER PT J AU List, K Hobson, JP Molinolo, A Bugge, TH AF List, Karin Hobson, John P. Molinolo, Alfredo Bugge, Thomas H. TI Co-localization of the channel activating protease prostasin/(CAP1/PRSS8) with its candidate activator, matriptase SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID TRANSMEMBRANE SERINE-PROTEASE; HEPATOCYTE GROWTH-FACTOR; EPITHELIAL SODIUM-CHANNELS; EPIDERMAL BARRIER FUNCTION; BREAST-CANCER CELLS; CELLULAR-LOCALIZATION; MOLECULAR-CLONING; XENOPUS-OOCYTES; PROSTASIN; EXPRESSION AB Prostasin (CAPI/PRSS8) is a glycosyl phosphaticlylinositol-anchored membrane serine protease believed to be critical for the regulation of epithelial sodium channel (ENaC) activity. Prostasin is synthesized as an inactive zymogen that requires a site-specific encloproteolytic cleavage to be converted to an active protease. We have recently reported that the tumor-associated type 11 transmembrane serine protease, matriptase is necessary and sufficient for prostasin activation in the epidermis. In this study, the interrelationship between the two membrane serine proteases was investigated further by using enzymatic gene trapping combined with immunohistochemistry to delineate the spatial expression of matriptase and prostasin in mouse tissues. We utilized a knock-in mouse with a promoterless beta-galactosidase marker gene inserted into the matriptase locus, as a unique tool for precise assessment of endogenous matriptase expression. The spatial expression of matriptase and prostasin in mouse tissues was delineated by combining in situ P-galactosidase matriptase staining with immunohistochemical detection of prostasin. We report that prostasin displays a near-ubiquitous co-localization with its candidate activator matriptase in a variety of normal epithelia] tissues. These include simple, stratified, and pseudo-stratified epithelium of the integumentary system, digestive tract, respiratory tract, and urogenital tract. However, matriptase and prostasin expression segregates during epithelial multi-stage carcinogenesis to eventually become localized in separate compartments of the tumor. These data suggest that a matriptase-prostasin zymogen activation cascade may be functionally operative in multiple epithelial tissues, but matriptase promotes epithelial carcinogenesis independent of prostasin. (c) 2007 Wiley-Liss, Inc. C1 Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Room 211, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov FU Intramural NIH HHS NR 49 TC 60 Z9 62 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 2007 VL 213 IS 1 BP 237 EP 245 DI 10.1002/jcp.21115 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 208AK UT WOS:000249292000027 PM 17471493 ER PT J AU Charmandari, E Kino, T Ichijo, T Jubiz, W Mejia, L Zachman, K Chrousos, GP AF Charmandari, Evangelia Kino, Tomoshige Ichijo, Takamasa Jubiz, William Mejia, Liliana Zachman, Keith Chrousos, George P. TI A novel point mutation in helix 11 of the ligand-binding domain of the human glucocorticoid receptor gene causing generalized glucocorticoid resistance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CLINICAL PHENOTYPE; GR AB Background: Generalized glucocorticoid resistance is a rare condition characterized by partial, end- organ insensitivity to glucocorticoids, compensatory elevations in adrenocorticotropic hormone and cortisol secretion, and increased production of adrenal steroids with androgenic and/ or mineralocorticoid activity. We have identified a new case of glucocorticoid resistance caused by a novel mutation of the human glucocorticoid receptor ( hGR) gene and studied the molecular mechanisms through which the mutant receptor impairs glucocorticoid signal transduction. Methods and Results: We identified a novel, single, heterozygous nucleotide (T -> C) substitution at position 2209 (exon 9 alpha) of the hGR gene, which resulted in phenylalanine ( F) to leucine ( L) substitution at amino acid position 737 within helix 11 of the ligand- binding domain of the protein. Compared with the wild- type receptor, the mutant receptor hGR alpha F737L demonstrated a significant ligand-exposure time-dependent decrease in its ability to transactivate the glucocorticoid- inducible mouse mammary tumor virus promoter in response to dexamethasone and displayed a 2- fold reduction in the affinity for ligand, a 12- fold delay in nuclear translocation, and an abnormal interaction with the glucocorticoid receptor- interacting protein 1 coactivator. The mutant receptor preserved its ability to bind to DNA and exerted a dominant- negative effect on the wild- type hGR alpha only after a short duration of exposure to the ligand. Conclusions: The mutant receptor hGR alpha F737L causes generalized glucocorticoid resistance because of decreased affinity for the ligand, marked delay in nuclear translocation, and/ or abnormal interaction with the glucocorticoid receptor- interacting protein 1 coactivator. These findings confirm the importance of the C terminus of the ligand-binding domain of the receptor in conferring transactivational activity. C1 Natl Inst Hlth & Human Dev, Sect Pediat Endocrinol, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Natl Inst Hlth, Bethesda, MD USA. Univ Athens, Med Ctr, Dept Pediat 1, EL-11527 Athens, Greece. Fdn Valle Lili, Ctr Endocrinol, Cali, Colombia. RP Charmandari, E (reprint author), Natl Inst Hlth & Human Dev, Sect Pediat Endocrinol, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. EM evangelia.charmandari@googlemail.com RI Charmandari, Evangelia/B-6701-2011 FU Intramural NIH HHS NR 20 TC 35 Z9 36 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2007 VL 92 IS 10 BP 3986 EP 3990 DI 10.1210/jc.2006-2830 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 220HS UT WOS:000250148400035 PM 17635946 ER PT J AU Dixit, VD Yang, HW Sun, YX Weeraratna, AT Youm, YH Smith, RG Taub, DD AF Dixit, Vishwa Deep Yang, Hyunwon Sun, Yuxiang Weeraratna, Ashani T. Youm, Yun-Hee Smith, Roy G. Taub, Dennis D. TI Ghrelin promotes thymopoiesis during aging SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-HORMONE SECRETAGOGUE; T-CELL DEVELOPMENT; THYMIC INVOLUTION; MARROW-TRANSPLANTATION; MESSENGER-RNA; AGED MICE; STEM-CELL; RECEPTOR; ATROPHY; IL-7 AB The decline in adaptive immunity, T lymphocyte output, and the contraction of the TCR repertoire with age is largely attributable to thymic involution. The loss of thymic function with age may be due to diminished numbers of progenitors and the loss of critical cytokines and hormones from the thymic microenvironment. We have previously demonstrated that the orexigenic hormone ghrelin is expressed by immune cells and regulates T cell activation and inflammation. Here we report that ghrelin and ghrelin receptor expression within the thymus diminished with progressive aging. Infusion of ghrelin into 14-month-old mice significantly improved the age-associated changes in thymic architecture and thymocyte numbers, increasing recent thymic emigrants and improving TCR diversity of peripheral T cell subsets. Ghrelin-induced thymopoiesis during aging was associated with enhanced early thymocyte progenitors and bone marrow-derived Lin-Sca1(+)cKit(+) cells, while ghrelin- and growth hormone secretagogue receptor-deficient (GHS-R-deficient) mice displayed enhanced age-associated thymic involution. Leptin also enhanced thymopoiesis in aged but not young mice. Our findings demonstrate what we believe to be a novel role for ghrelin and its receptor in thymic biology and suggest a possible therapeutic benefit of harnessing this pathway in the reconstitution of thymic function in immunocompromised subjects. C1 NIA, Intramural Res Program, Immunol Lab, Clin Immunol Sect,NIH, Baltimore, MD 21224 USA. Louisiana State Univ, Pennington Biomed Res Ctr, Lab Neuroendocrine Immunol, Baton Rouge, LA 70803 USA. Baylor Coll Med, Roy M & Phyllis Gough Huffington Ctr Aging, Houston, TX 77030 USA. RP Taub, DD (reprint author), NIA, Intramural Res Program, Immunol Lab, Clin Immunol Sect,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vishwa.dixit@pbrc.edu; taubd@grc.nia.nih.gov FU Intramural NIH HHS; NIA NIH HHS [R01 AG018895, R01 AG019230, R01 AG18895-02, R01 AG19230-01] NR 57 TC 109 Z9 122 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2007 VL 117 IS 10 BP 2778 EP 2790 DI 10.1172/JCI30248 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 216QP UT WOS:000249894400010 PM 17823656 ER PT J AU Wilson, MS Elnekave, E Mentink-Kane, MM Hodges, MG Pesce, JT Ramalingam, TR Thompson, RW Kamanaka, M Flavell, RA Keane-Myers, A Cheever, AW Wynn, TA AF Wilson, Mark S. Elnekave, Eldad Mentink-Kane, Margaret M. Hodges, Marcus G. Pesce, John T. Ramalingam, Thirumalai R. Thompson, Robert W. Kamanaka, Masahito Flavell, Richard A. Keane-Myers, Andrea Cheever, Allen W. Wynn, Thomas A. TI IL-13R alpha 2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID REGULATORY T-CELLS; IN-VIVO; CYTOKINE PRODUCTION; TH2 RESPONSES; PULMONARY-FIBROSIS; HEPATIC-FIBROSIS; RECEPTOR ALPHA-2; IMMUNE-RESPONSE; ALLERGIC MICE; MURINE MODEL AB Development of persistent Th2 responses in asthma and chronic helminth infections are a major health concern. IL-10 has been identified as a critical regulator of Th2 immunity, but mechanisms for controlling Th2 effector function remain unclear. IL-10 also has paradoxical effects on Th2-associated pathology, with IL-10 deficiency resulting in increased Th2-driven inflammation but also reduced airway hyperreactivity (AHR), mucus hypersecretion, and fibrosis. We demonstrate that increased IL-13 receptor alpha 2 (IL-13R alpha 2) expression is responsible for the reduced AHR, mucus production, and fibrosis in BALB/c IL-10(-/-) mice. Using models of allergic asthma and chronic helminth infection, we demonstrate that IL-10 and IL-13R alpha 2 coordinately suppress Th2-mediated inflammation and pathology, respectively. Although IL-10 was identified as the dominant antiinflammatory mediator, studies with double IL-10/IL-13R alpha 2-deficient mice illustrate an indispensable role for IL-13R alpha 2 in the suppression of AHR, mucus production, and fibrosis. Thus, IL-10 and IL-13R alpha 2 are both required to control chronic Th2-driven pathological responses. C1 NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Immunol Sect, New Haven, CT USA. Inst Biomed Res, Rockville, MD USA. RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, 50 S Dr Room,6154, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 FU Intramural NIH HHS NR 62 TC 74 Z9 80 U1 1 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2007 VL 117 IS 10 BP 2941 EP 2951 DI 10.1172/JCI31546 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 216QP UT WOS:000249894400025 PM 17885690 ER PT J AU Mizugishi, K Li, CL Olivera, A Bielawski, J Bielawska, A Deng, CX Proia, RL AF Mizugishi, Kiyomi Li, Cuiling Olivera, Ana Bielawski, Jacek Bielawska, Alicja Deng, Chu-Xia Proia, Richard L. TI Maternal disturbance in activated sphingolipid metabolism causes pregnancy loss in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SPHINGOSINE 1-PHOSPHATE; EMBRYO IMPLANTATION; MOUSE PLACENTA; SPHINGOSINE-1-PHOSPHATE; CELLS; EXPRESSION; RECEPTOR; KINASE; KININOGEN; APOPTOSIS AB Uterine decidualization, a process that occurs in response to embryo implantation, is critical for embryonic survival and thus is a key event for successful pregnancy. Here we show that the sphingolipid metabolic pathway is highly activated in the deciduum during pregnancy and disturbance of the pathway by disruption of sphingosine kinase (Sphk) genes causes defective decidualization with severely compromised uterine blood vessels, leading to early pregnancy loss. Sphk-deficient female mice (Sphk1(-/-)Sphk2(+/-)) exhibited both an enormous accumulation of dihydrosphingosine and sphingosine and a reduction in phosphatidylethanolamine levels in pregnant uteri. These mice also revealed increased cell death in decidual cells, decreased cell proliferation in undifferentiated stromal cells, and massive breakage of decidual blood vessels, leading to uterine hemorrhage and early embryonic lethality. Thus, sphingolipid metabolism regulates proper uterine decidualization and blood vessel stability. Our findings also suggest that disturbance in sphingolipid metabolism may be considered as a cause of pregnancy loss in humans. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bldg 10,Rm 9D06,10 Ctr Dr,MSC 1821, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012; deng, chuxia/N-6713-2016 FU Intramural NIH HHS; NCRR NIH HHS [C06 RR018823] NR 52 TC 70 Z9 72 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2007 VL 117 IS 10 BP 2993 EP 3006 DI 10.1172/JCI30674 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 216QP UT WOS:000249894400030 PM 17885683 ER PT J AU Fauci, AS AF Fauci, Anthony S. TI A view from Washington through the eyes of an AAP physician-scientist SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIH, Bldg 31,Room 7A-03,31 Ctr Dr,MSC 2520, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2007 VL 117 IS 10 BP 3136 EP 3139 DI 10.1172/JCI33691 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 216QP UT WOS:000249894400045 PM 17909635 ER PT J AU Gravitt, PE van Doorn, LJ Quint, W Schiffman, M Hildesheim, A Glass, AG Rush, BB Hellman, J Sherman, ME Burk, RD Wang, SS AF Gravitt, Patti E. van Doorn, Leen Jan Quint, Wim Schiffman, Mark Hildesheim, Allan Glass, Andrew G. Rush, Brenda B. Hellman, Jared Sherman, Mark E. Burk, Robert D. Wang, Sophia S. TI Human papillomavirus (HPV) genotyping using paired exfoliated cervicovaginal cells and paraffin-embedded tissues to highlight difficulties in attributing HPV types to specific lesions SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LINE PROBE ASSAY; CERVICAL DYSPLASIA; PCR ASSAY; COLPOSCOPY; SPECIMENS; EFFICACY; CYTOLOGY; TRIAL; DNA AB Defining type-specific human papillomavirus (HPV) infections within cervical tissues is important for understanding the pathogenesis of cervical neoplasia and assessing the effectiveness of prophylactic vaccines with limited type-specific spectra. We compared HPV DNA-testing results from 146 matched exfoliated-cell and formalin-fixed-tissue specimens collected by cervicovaginal lavage (CVL) within 90 days of each other from women with histologically confirmed cervical intraepithelial lesions (CIN). The CVL specimens were HPV typed using a MY09/11 L1 consensus primer PCR method followed by dot blot hybridization. The tissue specimens were HPV typed using an SPF,0 line probe assay HPV detection system. Of the 146 specimen pairs with evidence of CIN in the tissue, 91.8% were positive for one or more HPV types in both the tissue and cellular specimens. Tissue sections were more likely to be HPV negative (P < 0.01). Typing directly from tissue sections resolved multiple infections detected in exfoliated cells to a single HPV type in only 46.9% of cases. Combined use of both specimen types to attribute lesions to HPV type 16 (HPV-16) and/or -18 led to 43.1% attributed to HPV-16 and/or -18 by both specimen types and 19.9% attributed to HPV-16 and/or -18 by one, but not both, specimen types. Unambiguous attribution of cervical lesions to a single, specific HPV type remains a difficult proposition. Use of multiple specimen types or the development of highly sensitive and robust in situ hybridization HPV-testing methods to evaluate the certainty of attribution of lesions to HPV types might provide insights in future efforts, including HPV vaccine trials. C1 Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. DDL Diagnost Labs, Voorburg, Netherlands. Natl Inst Hlth, Natl Canc Inst, Div Canc Epidemiol & Genet, Hormonal & Reproductive Epidemiol Branch, Bethesda, MD 20852 USA. Kaiser Permanente, Portland, OR USA. Dept Management Serv, Silver Spring, MD USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Gravitt, PE (reprint author), Johns Hopkins Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St Rm E6535, Baltimore, MD 21205 USA. EM pgravitt@jhsph.edu NR 18 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2007 VL 45 IS 10 BP 3245 EP 3250 DI 10.1128/JCM.00216-07 PG 6 WC Microbiology SC Microbiology GA 220KS UT WOS:000250156200014 PM 17699644 ER PT J AU Barlesi, F Giaccone, G Gallegos-Ruiz, MI Loundou, A Span, SW Lefesvre, P Kruyt, FAE Rodriguez, JA AF Barlesi, Fabrice Giaccone, Giuseppe Gallegos-Ruiz, Marielle I. Loundou, Anderson Span, Simone W. Lefesvre, Pierre Kruyt, Frank A. E. Rodriguez, Jose Antonio TI Global histone modifications predict prognosis of resected non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECURSIVE PARTITIONING ANALYSIS; B CALGB PROTOCOL-9633; ADJUVANT CHEMOTHERAPY; METHYLATION; MARKERS; CARBOPLATIN; PACLITAXEL; NSCLC; TRIAL AB Purpose Epigenetic modifications may contribute to the development and progression of cancer. We investigated whether epigenetic changes involving multiple histones influence prognosis of non - small-cell lung cancer (NSCLC) patients. Patients and Methods We used immunohistochemistry to assess histone 3 lysine 4 dimethylation (H3K4diMe), and acetylation of histone 2A lysine 5 ( H2AK5Ac), histone 2B lysine 12, histone 3 lysine 9 (H3K9Ac), and histone 4 lysine 8 in resected tumor samples of 138 NSCLC patients. Data were analyzed using a recursive partitioning analysis ( RPA). Results The RPA classified the patients into seven distinct prognostic groups based on TNM stage ( first node), histology, and histone modifications: H3K4diMe (< or >= 85% tumor cells), H3K9Ac (< or >= 68% tumor cells), and H2AK5Ac (< or >= 5% tumor cells). The seven groups were associated with significantly different disease-free ( P <.0001) and overall survival ( P <.0001). Interestingly, the four groups determined by stage I patients ( below the first node) displayed dramatic differences in survival ( median, 10 months in adenocarcinoma patients with H3K9Ac >= 68% v 147 months in nonadenocarcinoma patients with H3K4diMe >= 85%). A Cox model retained age and RPA groups as the sole independent factors significantly influencing overall survival. Conclusion The prognostic influence of epigenetic changes involving multiple histones, in particular H2A and H3, is greater in early NSCLC, and evaluation of these changes may help in selecting early-stage NSCLC patients for adjuvant treatment. Our observations provide a rationale for the use of a combination of standard chemotherapy with drugs interacting with histone modifications, such as histone deacetylase inhibitors. C1 Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands. Univ Aix Marseille 2, Assistance Publ Hop Marseille, Dept Stat, Marseille, France. Univ Aix Marseille 2, Assistance Publ Hop Marseille, Dept Thorac Oncol, Marseille, France. RP Giaccone, G (reprint author), NCI, Med Oncol Branch, CCR, 10 Ctr Dr,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 29 TC 148 Z9 150 U1 1 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2007 VL 25 IS 28 BP 4358 EP 4364 DI 10.1200/JCO.2007.11.2599 PG 7 WC Oncology SC Oncology GA 233EN UT WOS:000251073300008 PM 17906200 ER PT J AU Moore, MJ Au, HJ Parulekar, W AF Moore, Malcolm J. Au, Heather Jane Parulekar, Wendy TI Does a statistically significant survival benefit of erlotinib plus gemcitabine for advanced pancreatic cancer translate into clinical significance and value? - Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 Univ Toronto, Princess Margaret Hosp, NCI,Div Med Oncol & Hematol, Canada Clin Trials Grp Gastrointestinal Dis Commi, Toronto, ON, Canada. Queens Univ, NCI, Canada Clin Trials Grp, Kingston, ON, Canada. RP Moore, MJ (reprint author), Univ Toronto, Princess Margaret Hosp, NCI,Div Med Oncol & Hematol, Canada Clin Trials Grp Gastrointestinal Dis Commi, Toronto, ON, Canada. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2007 VL 25 IS 28 BP 4508 EP 4508 DI 10.1200/JCO.2007.13.1862 PG 1 WC Oncology SC Oncology GA 233EN UT WOS:000251073300037 ER PT J AU Ries, M Clarke, JT Whybra, C Mehta, A Loveday, KS Brady, RO Beck, M Schiffmann, R AF Ries, Markus Clarke, Joe T. Whybra, Catharina Mehta, Atul Loveday, Kenneth S. Brady, Roscoe O. Beck, Michael Schiffmann, Raphael TI Enzyme replacement in Fabry disease: Pharmacokinetics and pharmacodynamics of agalsidase alfa in children and adolescents SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Fabry disease; lysosomal disorders; enzyme replacement therapy ID CLINICAL-MANIFESTATIONS; THERAPY; GALACTOSIDASE; SAFETY; CERAMIDETRIHEXOSIDASE; DEFICIENCY; RECEPTORS; PHENOTYPE; INFUSION; EFFICACY AB This multicenter, open-label study evaluated pharmacokinetics, pharmacodynamics, and safety of agalsidase alfa in pediatric compared with adult patients with Fabry disease. The pharmacokinetic parameters of pediatric patients (19 boys, 5 girls, 6-18 years old; mean age, 11.8 years) were compared to those of adult male and female patients who participated in other clinical studies. All patients received agalsidase alfa at a dose of 0.2 mg/kg infused over 40 minutes every other week. Agalsidase alfa exhibited a biphasic serum elimination profile with a maximum serum concentration at the end of the 40-minute infusion; < 1% of the maximum concentration was detected 8 hours after dosing. In children, serum clearance was 2.0 to 9.4 mL/min/kg and tended to decrease with increasing age. The average clearance in children, 3.7 +/- 1.5 mL/min/kg (mean +/- SD), was significantly greater than that measured in 33 adults (2.3 +/- 0.7 mL/min/kg, P < .0001). Mean terminal elimination half-life of agalsidase alfa was prolonged in week 25 compared with baseline (150 vs 66 minutes) in 8 of 19 male children. The magnitude of the reduction of plasma globotriaosylceremide was similar in all age groups and was independent of area under the curve and other pharmacokinetic parameters. Except for clearance in younger patients, agalsidase alfa appears to have comparable pharmacokinetic and pharmacodynamic profiles in pediatric and adult Fabry patients of both genders. C1 Natl Inst Hlth, Bethesda, MD 20892 USA. NINDS, Natl Inst Hlth, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Mainz, Childrens Hosp, Ctr Lysosomal Storage Dis, D-6500 Mainz, Germany. Royal Free Hosp, London NW3 2QG, England. Shire HGT, Cambridge, MA USA. RP Schiffmann, R (reprint author), Natl Inst Hlth, Bldg 10,Rm 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. EM RS4e@nih.gov FU Intramural NIH HHS NR 32 TC 26 Z9 28 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD OCT PY 2007 VL 47 IS 10 BP 1222 EP 1230 DI 10.1177/0091270007305299 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 216IW UT WOS:000249872700001 PM 17698592 ER PT J AU Stojmircivic, A Yu, YK AF Stojmircivic, Aleksandar Yu, Yi-Kuo TI Information flow in interaction networks SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE Markov chains; random walks; matrices; proteins; networks; information theory ID PROTEIN-INTERACTION NETWORKS; HISTONE ACETYLTRANSFERASE COMPLEX; YEAST SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL REGULATION; FUNCTIONAL MODULES; PUTATIVE ACETYLTRANSFERASE; MOLECULAR NETWORKS; CELLULAR NETWORKS; INTERACTION MAP; BUDDING YEAST AB Interaction networks, consisting of agents linked by their interactions, are ubiquitous accross many disciplines of modern science. Many methods of analysis of interaction networks have been proposed, mainly concentrating on node degree distribution or aiming to discover clusters of agents that are very strongly connected between themselves. These methods are principally based on graph-theory or machine learning. We present a mathematically simple formalism for modelling context-specific information propagation in interaction networks based on random walks. The context is provided by selection of sources and destinations of information and by use of potential functions that direct the now towards the destinations. We also use the concept of dissipation to model the aging of information as it diffuses from its source. Using examples from yeast protein-protein interaction networks and some of the histone acetyltransferases involved in control of transcription, we demonstrate the utility of the concepts and the mathematical constructs introduced in this paper. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Yu, YK (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM yyu@ncbi.nlm.nih.gov OI Stojmirovic, Aleksandar/0000-0003-0957-6893 FU Intramural NIH HHS NR 88 TC 25 Z9 27 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD OCT PY 2007 VL 14 IS 8 BP 1115 EP 1143 DI 10.1089/cmb.2007.0069 PG 29 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 220MM UT WOS:000250160800007 PM 17985991 ER PT J AU Ghitza, UE Epstein, DH Schmittner, J Vahabzadeh, M Lin, JL Preston, KL AF Ghitza, Udi E. Epstein, David H. Schmittner, John Vahabzadeh, Massoud Lin, Jia-Ling Preston, Kenzie L. TI Randomized trial of prize-based reinforcement density for simultaneous abstinence from cocaine and heroin SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE contingency management; opiate; cocaine dependence; opiate dependence; methadone maintenance ID VOUCHER-BASED REINFORCEMENT; CONTINGENCY MANAGEMENT; 2ND-ORDER SCHEDULES; FOOD PRESENTATION; METHADONE-MAINTENANCE; SEEKING BEHAVIOR; FOLLOW-UP; DEPENDENCE; INJECTION; THERAPY AB To examine the effect of reinforcer density in prize-based abstinence reinforcement, heroin/cocaine users (N = 116) in methadone maintenance (100 mg/day) were randomly assigned to a noncontingent control group (NonC) or to I of 3 groups that earned prize draws for abstinence: manual drawing with standard prize density (MS) or computerized drawing with standard (CS) or high (CH) density. Probabilities (prizes/draw) were standard (50%) and high (78%); prize density was double blind. Mean prize values were CH, $286; CS, $167; MS, $139; and NonC, $171. Outcomes were % opioid/cocaine-negative urines during the 12-week intervention and then 8 weeks postintervention as well as diagnosis of dependence up to 6 months poststudy. CH had significantly more negative specimens than did NonC during intervention and had more than all groups during postintervention treatment: Mean % negative (95% confidence interval) during postintervention treatment adjusted for baseline drug use and dropout were CH, 55% (14%-90%); CS, 7% (1%-27%); MS, 4% (1%-12%); and NonC, 3% (1%-10%). Current cocaine dependence diagnoses after treatment were significantly lower in contingent compared with noncontingent groups. Computerized drawing with higher-density prizes enhanced reduction of cocaine use; abstinence reinforcement had long-term therapeutic benefits. C1 NIDA, Clin Pharmacol & Therapeut Branch, Treatment Sect,Dept Hlth & Human Serv, Intramural Res Program,NIH, Baltimore, MD 21224 USA. NIDA, Biomed Informat Sect, Adm Management Branch, IRP,NIH,DHHS, Baltimore, MD 21224 USA. RP Ghitza, UE (reprint author), NIDA, Clin Pharmacol & Therapeut Branch, Treatment Sect,Dept Hlth & Human Serv, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ghitzau@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS [Z01 DA000175-13] NR 44 TC 20 Z9 20 U1 4 U2 4 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2007 VL 75 IS 5 BP 765 EP 774 DI 10.1037/0022-006X.75.5.765 PG 10 WC Psychology, Clinical SC Psychology GA 214PG UT WOS:000249750000010 PM 17907858 ER PT J AU Arany, PR Flanders, KC DeGraff, W Cook, J Mitchell, JB Roberts, AB AF Arany, Praveen R. Flanders, Kathleen C. DeGraff, William Cook, John Mitchell, James B. Roberts, Anita B. TI Absence of Smad3 confers radioprotection through modulation of ERK-MAPK in primary dermal fibroblasts SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Article DE Smad3; transforming growth factor-beta; ionizing radiation; radioprotection; fibrosis ID PHOSPHORYLATED HISTONE H2AX; GROWTH-FACTOR-BETA; IONIZING-RADIATION; DNA-DAMAGE; SERINE 15; IN-SITU; EXPRESSION; PATHWAYS; CELLS; MICE AB Background: Transforming growth factor-beta 1 (TGF-beta 1), a key biological mediator following ionizing radiation, plays a role in a complex tissue reaction involved in local radiation-induced pathological damage. Knocking out Smad3 (S3KO), a downstream signaling intermediate in the TGF-beta pathway, in mice protects their skin from radiation damage as demonstrated by decreased epithelial acanthosis and dermal fibrosis as compared to Smad3 witd-type (S3WT) mice. Objective: The present study was designed to investigate the molecular mechanisms contributing to increased radioprotection in the absence of Smad3. Methods: Primary dermal fibroblasts derived from S3WT and KO mice were exposed to 5 Gy ionizing radiation in vitro. Western blot analyses, immunocytochemistry, and reporter transfections were used to dissect the radiation-induced events. Results: There was increased phosphorylation of ERK-MAPK, p53 and H2A.X in S3KO compared to the S3WT fibroblasts, implicating them in a key signaling cascade in response of these cells to radiation. Pro-fibrotic gene expression was decreased in S3KO fibroblasts post-irradiation. Conclusion: The absence of Smad3 may decrease radio- responsiveness by increasing activation of DNA damage sensing mechanisms and decreasing induction of profibrotic genes. Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology. C1 NCI, Lab Cel Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Harvard Univ, Sch Dent Med, Program Biol Sci Dental Med & Leader Med Sci, Boston, MA 02115 USA. Natl Canc Inst, NIH, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Natl Canc Inst, NIH, Bethesda, MD 20892 USA. RP Arany, PR (reprint author), NCI, Lab Cel Regulat & Carcinogenesis, Bldg 37,Room 5046B,37 Convent Dr, Bethesda, MD 20892 USA. EM arany@fas.harvard.edu; flanderk@dce41.nci.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 33 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD OCT PY 2007 VL 48 IS 1 BP 35 EP 42 DI 10.1016/j.jdermsci.2007.05.012 PG 8 WC Dermatology SC Dermatology GA 210FP UT WOS:000249442400004 PM 17624738 ER PT J AU Rogers, C Blatt, A Linehan, WM Pinto, P AF Rogers, Craig Blatt, Adam Linehan, W. Marston Pinto, Peter TI Robotic partial adrenalectomy for multifocal adrenal pheochromocytomas SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Rogers, Craig; Linehan, W. Marston; Pinto, Peter] Natl Canc Inst, Urol Oncol Branch, Bethesda, MD 20892 USA. [Blatt, Adam] Georgetown Univ, Sch Med, Dept Urol, Washington, DC 20057 USA. 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 0892-7790 J9 J ENDOUROL JI J. Endourol. PD OCT PY 2007 VL 21 SU 1 BP A127 EP A127 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 228UW UT WOS:000250759100567 ER PT J AU Rogers, C Singh, A Blatt, A AF Rogers, Craig Singh, Amar Blatt, Adam TI Robotic partial nephrectomy for complex renal tumors SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Rogers, Craig; Singh, Amar] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Blatt, Adam] Georgetown Univ, Sch Med, Dept Urol, Washington, DC 20057 USA. 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 0892-7790 J9 J ENDOUROL JI J. Endourol. PD OCT PY 2007 VL 21 SU 1 BP A145 EP A145 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 228UW UT WOS:000250759100645 ER PT J AU Rogers, C Linehan, WM Pinto, P AF Rogers, Craig Linehan, W. Marston Pinto, Peter TI Robotic radical nephrectomy for renal cell carcinoma in a horseshoe kidney with renal vein thrombus SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Rogers, Craig; Linehan, W. Marston; Pinto, Peter] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. 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 0892-7790 J9 J ENDOUROL JI J. Endourol. PD OCT PY 2007 VL 21 SU 1 BP A145 EP A145 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 228UW UT WOS:000250759100644 ER PT J AU Singh, A Singh, A Rogers, CG Bratslavsky, G Blatt, AM Linehan, WM Pinto, PA AF Singh, Amar Singh, Amar Rogers, Craig G. Bratslavsky, Gennady Blatt, Adam M. Linehan, W. Marston Pinto, Peter A. TI Robotic partial nephrectomy for renal hilar tumors SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Singh, Amar] Natl Canc Inst, NIH, Bethesda, MD 20892 USA. [Singh, Amar; Rogers, Craig G.; Bratslavsky, Gennady; Blatt, Adam M.; Linehan, W. Marston; Pinto, Peter A.] Natl Canc Inst, NIH, Urol Oncol Branch, Bethesda, MD 20892 USA. 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 0892-7790 J9 J ENDOUROL JI J. Endourol. PD OCT PY 2007 VL 21 SU 1 BP A223 EP A224 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 228UW UT WOS:000250759101317 ER PT J AU Tilburt, JC Goold, SD Siddiqui, N Mangrulkar, RS AF Tilburt, Jon C. Goold, Susan D. Siddiqui, Nazema Mangrulkar, Rajesh S. TI How do doctors use information in real-time? A qualitative study of internal medicine resident precepting SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE evidence-based medicine; graduate medical education; information-seeking behaviour; precepting; qualitative research ID HEALTH-CARE; THEORETICAL FRAMEWORK; SEEKING BEHAVIOR; DECISION-MAKING; PHYSICIANS; UNCERTAINTY; NEEDS; PROFESSIONALS; ENGINEERS AB Despite the importance of evidence-based medicine in medical education, little observational research exists on how doctors-in-training seek and use evidence from information resources in ambulatory care. To describe information exchange behaviour by internal medicine residents and attendings in ambulatory resident clinic precepting rooms. We observed resident behaviour and audiotaped resident-attending doctor interactions during precepting sessions. Participating residents included 70 of an eligible 89 residents and 28 of 34 eligible attendings from one large academic internal medicine residency programme in the Midwestern USA. Residents were observed during 95 separate precepting interactions at four ambulatory sites. Using a qualitative approach, we analysed transcripts and field notes of observed behaviours and interactions looking for themes of information exchange. Coders discussed themes which were refined using feedback from an interdisciplinary panel. Four themes of information exchange behaviour emerged: (i) questioning behaviours that were used as part of the communication process in which the resident and attending doctor could reason together; (ii) searching behaviour of non-human knowledge sources occurred in a minority of precepting interations; (iii) unsolicited knowledge offering and (iv) answering behaviours were important means of exchanging information. Most clinic interactions between resident and attending doctors relied heavily on spoken deliberation without resorting to the scientific literature or other published information resources. These observations suggest a range of factors that may moderate information exchange behaviour in the precepting context including relationships, space and efficiency. Future research should aim to more readily adapt information resources to the relationships and practice context of precepting. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. Univ Michigan Hlth Syst, Div Gen Internal Med, Dept Internal Med, Ann Arbor, MI USA. RP Tilburt, JC (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C 119, Bethesda, MD 20892 USA. EM jontilburt@yahoo.com OI Goold, Susan Dorr/0000-0002-0258-9774 NR 25 TC 6 Z9 6 U1 2 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1356-1294 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD OCT PY 2007 VL 13 IS 5 BP 772 EP 780 DI 10.1111/j.1365-2753.2006.00752.x PG 9 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA 207LX UT WOS:000249253700011 PM 17824871 ER PT J AU Curry, JD Schulz, D Guidos, CJ Danska, JS Nutter, L Nussenzweig, A Schlissel, MS AF Curry, John D. Schulz, Danae Guidos, Cynthia J. Danska, Jayne S. Nutter, Lauryl Nussenzweig, Andre Schlissel, Mark S. TI Chromosomal reinsertion of broken RSS ends during T cell development SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID V(D)J RECOMBINATION; GENOMIC INSTABILITY; B-CELL; JOINT FORMATION; IMMUNE-SYSTEM; TRANSPOSITION; RAG2; MICE; TRANSLOCATIONS; REARRANGEMENT AB The V( D) J recombinase catalyzes DNA transposition and translocation both in vitro and in vivo. Because lymphoid malignancies contain chromosomal translocations involving antigen receptor and protooncogene loci, it is critical to understand the types of " mistakes " made by the recombinase. Using a newly devised assay, we characterized 48 unique TCR beta recombination signal sequence ( RSS) end insertions in murine thymocyte and splenocyte genomic DNA samples. Nearly half of these events targeted " cryptic " RSS- like elements. In no instance did we detect target- site duplications, which is a hallmark of recombinase- mediated transposition in vitro. Rather, these insertions were most likely caused by either V( D) J recombination between a bona fide RSS and a cryptic RSS or the insertion of signal circles into chromosomal loci via a V( D) J recombination- like mechanism. Although wild- type, p53, p53 x scid, H2Ax, and ATM mutant thymocytes all showed similar levels of RSS end insertions, core- RAG2 mutant thymocytes showed a sevenfold greater frequency of such events. Thus, the noncore domain of RAG2 serves to limit the extent to which the integrity of the genome is threatened by mistargeting of V( D) J recombination. C1 Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Hosp Sick Children, Res Inst, Program Dev Biol, Toronto, ON M5G 1L7, Canada. Univ Toronto, Dept Immunol, Fac Med, Toronto, ON M5G 1L7, Canada. NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Schlissel, MS (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. EM mss@berkeley.edu FU NIAID NIH HHS [AI40227, R37 AI040227, R01 AI040227] NR 43 TC 18 Z9 19 U1 0 U2 7 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 OCT 1 PY 2007 VL 204 IS 10 BP 2293 EP 2303 DI 10.1084/jem.20070583 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 216HW UT WOS:000249870100008 PM 17785508 ER PT J AU Ku, CL von Bernuth, H Picard, C Zhang, SY Chang, HH Yang, K Chrabieh, M Issekutz, AC Cunningham, CK Gallin, J Holland, SM Roifman, C Ehl, S Smart, J Tang, M Barrat, FJ Levy, O McDonald, D Day-Good, NK Miller, R Takada, H Hara, T Al-Hajjar, S Al-Ghonaium, A Speert, D Sanlaville, D Li, XX Geissmann, F Vivier, E Marodi, L Garty, BZ Chapel, H Rodriguez-Gallego, C Bossuyt, X Abel, L Puel, A Casanova, JL AF Ku, Cheng-Lung von Bernuth, Horst Picard, Capucine Zhang, Shen-Ying Chang, Huey-Hsuan Yang, Kun Chrabieh, Maya Issekutz, Andrew C. Cunningham, Coleen K. Gallin, John Holland, Steven M. Roifman, Chaim Ehl, Stephan Smart, Joanne Tang, Mimi Barrat, Franck J. Levy, Ofer McDonald, Douglas Day-Good, Noorbibi K. Miller, Richard Takada, Hidetoshi Hara, Toshiro Al-Hajjar, Sami Al-Ghonaium, Abdulaziz Speert, David Sanlaville, Damien Li, Xiaoxia Geissmann, Frederic Vivier, Eric Marodi, Laszlo Garty, Ben-Zion Chapel, Helen Rodriguez-Gallego, Carlos Bossuyt, Xavier Abel, Laurent Puel, Anne Casanova, Jean-Laurent TI Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TOLL-LIKE RECEPTORS; MYELOID DIFFERENTIATION FACTOR-88; PLASMACYTOID DENDRITIC CELLS; IRAK4 KINASE-ACTIVITY; HERPES-SIMPLEX-VIRUS; C-REACTIVE PROTEIN; CUTTING EDGE; PNEUMOCOCCAL MENINGITIS; INNATE IMMUNITY; IL-1 RECEPTOR AB Human interleukin ( IL) 1 receptor - associated kinase 4 ( IRAK- 4) deficiency is a recently discovered primary immunodefi ciency that impairs Toll/ IL- 1R immunity, except for the Toll- like receptor ( TLR) 3 - and TLR4 - interferon ( IFN)-alpha/beta pathways. The clinical and immunological phenotype remains largely unknown. We diagnosed up to 28 patients with IRAK- 4 deficiency, tested blood TLR responses for individual leukocyte subsets, and TLR responses for multiple cytokines. The patients' peripheral blood mononuclear cells ( PBMCs) did not induce the 11 non- IFN cytokines tested upon activation with TLR agonists other than the nonspecific TLR3 agonist poly( I: C). The patients' individual cell subsets from both myeloid ( granulocytes, monocytes, monocyte- derived dendritic cells [ MDDCs], myeloid DCs [ MDCs], and plasmacytoid DCs) and lymphoid ( B, T, and NK cells) lineages did not respond to the TLR agonists that stimulated control cells, with the exception of residual responses to poly( I: C) and lipopolysaccharide in MDCs and MDDCs. Most patients ( 22 out of 28; 79%) suffered from invasive pneumococcal disease, which was often recurrent ( 13 out of 22; 59%). Other infections were rare, with the exception of severe staphylococcal disease ( 9 out of 28; 32%). Almost half of the patients died ( 12 out of 28; 43%). No death and no invasive infection occurred in patients older than 8 and 14 yr, respectively. The IRAK- 4 - dependent TLRs and IL- 1Rs are therefore vital for childhood immunity to pyogenic bacteria, particularly Streptococcus pneumoniae. Conversely, IRAK- 4 - dependent human TLRs appear to play a redundant role in protective immunity to most infections, at most limited to childhood immunity to some pyogenic bacteria. C1 INSERM, Lab Human Genet Infect Dis, U550, F-75015 Paris, France. Univ Paris 05, Necker Med Sch, F-75015 Paris, France. Tech Univ Dresden, Dept Pediat, D-01309 Dresden, Germany. Dalhousie Univ, Dept Pediat, Halifax, NS B3K 6R8, Canada. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. Univ Toronto, Hosp Sick Children, Div Immunol & Allergy, Dept Pediat, Toronto, ON M5G 1X8, Canada. Univ Freiburg, Ctr Pediat & Adolescent Med, D-79106 Freiburg, Germany. Royal Childrens Hosp, Parkville, Vic 3052, Australia. Dynavax Technol, Albany, CA 94710 USA. Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ S Florida, Dept Pediat, Div Allergy & Immunol, St Petersburg, FL 33701 USA. All Childrens Hosp, St Petersburg, FL 33701 USA. 3M Co, St Paul, MN 55144 USA. Kyushu Univ, Dept Pediat, Grad Sch Med Sci, Fukuoka 8128582, Japan. King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Riyadh 11211, Saudi Arabia. Child & Family Res Inst, Ctr Infect & Inflammatory Dis, Vancouver, BC V5Z 4H4, Canada. Hop Necker Enfants Malad, Immunodeficiency Invest Ctr, F-75015 Paris, France. Hop Necker Enfants Malad, Lab Histol Embryol & Cytogenet, Dept Mol Cytogenet, F-75015 Paris, France. Hop Necker Enfants Malad, Pediat Hematol Immunol Unit, F-75015 Paris, France. Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA. INSERM, U838, F-75015 Paris, France. Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, INSERM, CNRS, F-13288 Marseille, France. Debrecen Univ, Dept Infect & Pediat Immunol, Med & Hlth Sci Ctr, H-4032 Debrecen, Hungary. Schneider Childrens Med Ctr, Dept Pediat, IL-49202 Petah Tiqwa, Israel. John Radcliffe Hosp, Dept Immunol, Nuffield Dept Med, Oxford OX3 9DU, England. Hosp Univ Gran Canaria, Dept Immunol, Las Palmas Gran Canaria 35020, Spain. Univ Hosp Leuven, Expt Lab Med, B-3000 Louvain, Belgium. RP Casanova, JL (reprint author), INSERM, Lab Human Genet Infect Dis, U550, F-75015 Paris, France. EM casanova@necker.fr RI sanlaville, damien/M-4716-2014; KU, Cheng-Lung/L-6073-2015; OI sanlaville, damien/0000-0001-9939-2849; KU, Cheng-Lung/0000-0002-0643-2256; geissmann, frederic/0000-0001-5029-2468; Picard, Capucine/0000-0001-8788-5056 FU Medical Research Council [G0900867] NR 81 TC 231 Z9 239 U1 1 U2 17 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 OCT 1 PY 2007 VL 204 IS 10 BP 2407 EP 2422 DI 10.1084/jem.20070628 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 216HW UT WOS:000249870100017 PM 17893200 ER PT J AU Almeida, JR Price, DA Papagno, L Arkoub, ZA Sauce, D Bornstein, E Asher, TE Samri, A Schnuriger, A Theodorou, I Costagliola, D Rouzioux, C Agut, H Marcelin, AG Douek, D Autran, B Appay, V AF Almeida, Jorge R. Price, David A. Papagno, Laura Arkoub, Zaina Ait Sauce, Delphine Bornstein, Ethan Asher, Tedi E. Samri, Assia Schnuriger, Aurelie Theodorou, Ioannis Costagliola, Dominique Rouzioux, Christine Agut, Henri Marcelin, Anne-Genevieve Douek, Daniel Autran, Brigitte Appay, Victor TI Superior control of HIV-1 replication by CD8(+) T cells is reflected by their avidity, polyfunctionality, and clonal turnover SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DISEASE PROGRESSION; VIRAL LOAD; LYMPHOCYTE RESPONSES; PERSISTENT VIRUS; IN-VIVO; HLA-B; INFECTION; ESCAPE; EXPRESSION; MEMORY AB The key attributes of CD8(+) T cell protective immunity in human immunodeficiency virus ( HIV) infection remain unclear. We report that CD8(+) T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV- 1 replication in human histocompatibility leukocyte antigen ( HLA) - B27 patients. To understand further the nature of CD8(+) T cell - mediated antiviral efficacy, we performed a comprehensive study of CD8(+) T cells specific for the HLA- B27 - restricted epitope KK10 in chronic HIV- 1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27- KK10 - specific CD8(+) T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV- 1 replication. These data on the features of effective CD8(+) T cells in HIV infection may aid in the development of successful T cell vaccines. C1 INSERM, Cellular Immunol Lab, U543, Avenir Grp, F-75654 Paris 13, France. Univ Paris 06, Hop La Pitie Salpetriere, Virol Lab, UPRES EA2387, F-75013 Paris, France. Univ Paris 06, Hop La Pitie Salpetriere, U720, INSERM, F-75013 Paris, France. NIH, Human Immunol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. Univ Rene Descartes Paris 5, Virol Lab, Hop Necker Enfants Malad, F-75015 Paris, France. RP Appay, V (reprint author), INSERM, Cellular Immunol Lab, U543, Avenir Grp, F-75654 Paris 13, France. EM appay@chups.jussieu.fr RI schnuriger, aurelie/A-6628-2011; Price, David/C-7876-2013; sauce, delphine/H-1990-2014; Costagliola, Dominique/H-5849-2011; Marcelin, Anne-Genevieve/D-8272-2014; OI Price, David/0000-0001-9416-2737; sauce, delphine/0000-0003-4596-7373; Costagliola, Dominique/0000-0003-0765-0869; Marcelin, Anne-Genevieve/0000-0003-4808-8999; Ramos de Almeida, Jorge/0000-0002-5009-8478 FU Medical Research Council [G0501963] NR 53 TC 408 Z9 417 U1 2 U2 9 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 OCT 1 PY 2007 VL 204 IS 10 BP 2473 EP 2485 DI 10.1084/jem.20070784 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 216HW UT WOS:000249870100022 PM 17893201 ER PT J AU Coffay, AO AF Coffay, Agnes O. TI Smoking cessation: Tactics that make a big difference SO JOURNAL OF FAMILY PRACTICE LA English DT Article ID SUSTAINED-RELEASE BUPROPION; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-PRACTICE GUIDELINE; RECEPTOR PARTIAL AGONIST; PRIMARY-CARE; PLACEBO; NORTRIPTYLINE; EFFICACY; VARENICLINE; DEPENDENCE C1 NIH, NIDA, IRP, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Coffay, AO (reprint author), NIH, NIDA, IRP, Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM coffaya@mail.nih.gov FU Intramural NIH HHS NR 28 TC 3 Z9 3 U1 2 U2 2 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD OCT PY 2007 VL 56 IS 10 BP 817 EP 824 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 226KT UT WOS:000250588700008 PM 17908512 ER PT J AU Yang, LT Peng, H Zhu, ZL Li, G Huang, ZT Zhao, ZX Koup, RA Bailer, RT Wu, CY AF Yang, Litao Peng, Hui Zhu, Zhaoling Li, Gang Huang, Zitong Zhao, Zhixin Koup, Richard A. Bailer, Robert T. Wu, Changyou TI Persistent memory CD4(+) (and CD8(+) T-cell responses in recovered severe acute respiratory syndrome (SARS) patients to SARS coronavirus M antigen SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID SPIKE PROTEIN; NUCLEOCAPSID PROTEIN; PROTECTIVE IMMUNITY; IN-VIVO; MICE; IDENTIFICATION; COV; EPITOPES; VACCINE; LYMPHOCYTES AB The membrane (M) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is a major glycoprotein with multiple biological functions. In this study, we found that memory T cells against M protein were persistent in recovered SARS patients by detecting gamma interferon (IFN-gamma) production using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4(+) and CD8(+) T cells were involved in cellular responses to SARS-CoV IM antigen. Furthermore, memory CD8+ T cells displayed an effector memory cell phenotype expressing CD45RO(-) CCR7(-) CD62L(-). In contrast, the majority of IFN-gamma(+) CD4(+) T cells were central memory cells with the expression of CD45RO(+) CCR7(+) CD62L(-). The epitope screening from 30 synthetic overlapping peptides that cover the entire SARS-CoV IM protein identified four human T-cell immunodominant pepticles, p21-44, p65-91, p117-140 and p200-220. All four immunodominant pepticles could elicit cellular immunity with a predominance of CD8+ T-cell response. This data may have important implication for developing SARS vaccines. C1 Sun Yat Sen Univ, Zhongshan Med Sch, Dept Immunol, Guangzhou 510089, Peoples R China. Sun Yat Sen Univ, Affiliated Hosp 3, Guangzhou 510630, Peoples R China. Sun Yat Sen Univ, Affiliated Hosp 2, Guangzhou 510120, Peoples R China. NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Wu, CY (reprint author), Sun Yat Sen Univ, Zhongshan Med Sch, Dept Immunol, Guangzhou 510089, Peoples R China. EM changyou_wu@yahoo.com RI Peng, Hui/I-8579-2015 OI Peng, Hui/0000-0002-2646-129X FU Intramural NIH HHS [Z99 AI999999] NR 29 TC 17 Z9 17 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD OCT PY 2007 VL 88 BP 2740 EP 2748 DI 10.1099/vir.0.82839-0 PN 10 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 220LA UT WOS:000250157000016 PM 17872527 ER PT J AU de Melo, FHM Butera, D Medeiros, RS Andrade, LND Nonogaki, S Soares, FA Alvarez, RA Moura da Silva, AM Chammas, R AF de Melo, Fabiana H. M. Butera, Diego Medeiros, Raphael S. Andrade, Luciana N. de S. Nonogaki, Suely Soares, Fernando A. Alvarez, Richard A. Moura da Silva, Ana M. Chammas, Roger TI Biological applications of a chimeric probe for the assessment of galectin-3 ligands SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE galectin-3; galectin-3 ligands; L-PHA; aberrant glycosylation ID BETA-1-6 BRANCHED OLIGOSACCHARIDES; ASPARAGINE-LINKED OLIGOSACCHARIDES; TRYPANOSOMA-CRUZI INFECTION; COLI ALKALINE-PHOSPHATASE; HUMAN-BREAST; EPITHELIAL-CELLS; TUMOR PROGRESSION; ESCHERICHIA-COLI; BETA-1,6-BRANCHED OLIGOSACCHARIDES; DENDRITIC CELLS AB beta 1-6 branching of Winked oligosaccharides has been correlated with the progression of different cancers. The leukoagglutinins of Phaseolus vulgaris (L-PHA) have been used to study this pattern of glycosylation whose biological significance is incompletely understood. The animal lectin, galectin-3, also binds to structures recognized by L-PHA. To develop a functional tool for the in situ identification of this pattern of glycosylation, human galectin-3 was fused to bacterial alkaline phosphatase (gal3/AP). Gal3/AP recognized both A and B blood group saccharides (B > A) and lactosamine derivatives. Gal3/AP recognition depended at least in part on the Winked oligosaccharides of different glycoproteins. The presence and distribution of galectin-3 ligands were analyzed in both murine and human normal and tumor samples. Loss of apical expression of galectin-3 ligands was commonly found in carcinomas. Endothelial and inflammatory cells were enriched in galectin-3 ligands as compared with tumor cells; thus, gal3/AP is a suitable tool for studying tumor micro-environments. Comparative analysis of both gal3/AP and L-PHA binding patterns indicated that although similar, these patterns are not identical. The probe developed was useful for several immunoenzymatic assays and will allow the physiological and clinical significance of the expression pattern of galectin-3 ligands to be established. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. C1 Univ Sao Paulo, Fac Med, Expt Oncol Lab, BR-01246 Sao Paulo, Brazil. Inst Butantan, Lab Imunopatol, Sao Paulo, Brazil. Inst Adolfo Luts, Div Pathol, Sao Paulo, Brazil. Hosp AC Camargo Fund Antonio Prudente, Dept Pathol, Sao Paulo, Brazil. NIGMS, Consortium Funct Glycom, Oklahoma City, OK USA. Univ Sao Paulo, Ctr Cell Based Therapy Res, BR-14049 Ribeirao Preto, Brazil. RP Chammas, R (reprint author), Univ Sao Paulo, Fac Med, Expt Oncol Lab, Av Dr Aenaldo 455,Rm 4112, BR-01246 Sao Paulo, Brazil. EM rchammas@lim24.fm.usp.br RI Chammas, Roger/A-8004-2011; Moura-da-Silva, Ana/A-5247-2008; Melo, Fabiana/M-6460-2013; OI Chammas, Roger/0000-0003-0342-8726; Moura-da-Silva, Ana/0000-0003-1787-6634; Soares, Fernando Augusto/0000-0003-1647-7842 FU NIGMS NIH HHS [GM 62116] NR 66 TC 14 Z9 14 U1 0 U2 8 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD OCT PY 2007 VL 55 IS 10 BP 1015 EP 1026 DI 10.1369/jhc.7A7174.2007 PG 12 WC Cell Biology SC Cell Biology GA 210RH UT WOS:000249472800005 PM 17565118 ER PT J AU Yang, Q Kim, SK Sun, FZ Cui, J Larson, MG Vasan, RS Levy, D Schwartz, F AF Yang, Qiong Kim, Sung K. Sun, Fengzhu Cui, Jing Larson, Martin G. Vasan, Ramachandran S. Levy, Daniel Schwartz, Faina TI Maternal influence on blood pressure suggests involvement of mitochondrial DNA in the pathogenesis of hypertension: the Framingham Heart Study SO JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure genetics; maternal effect; mitochondrial inheritance; primary (essential) hypertension ID FAMILIAL AGGREGATION; Y-CHROMOSOME; ADAPTIVE SELECTION; GENERAL-POPULATION; GENETIC-VARIATION; TRANSFER-RNA; ASSOCIATION; DISEASE; RISK; GENOME AB Objective To investigate the contribution of the mitochondrial genome to hypertension and quantitative blood pressure (BP) phenotypes in the Framingham Heart Study cohort, a randomly ascertained, community- based sample. Methods Longitudinal BP values of 6421 participants (mean age, 53 years; 46% men) from 1593 extended families were used for analyses. In analyses of BP as a continuous trait, a variance components model with a variance component for maternal effects was used to estimate the mitochondrial heritability of the long- term average BP adjusted for age, sex, body mass index, and hypertension treatment. For analyses of BP as a categorical trait, a nonparametric test sensitive to excessive maternal inheritance was used to test for mitochondrial effect on long- term hypertension, defined as systolic BP of at least 140mmHg or diastolic BP of at least 90mmHg or use of antihypertensive medication in one- half or more of qualifying examinations. This test was based on 353 pedigrees comprised of 403 individuals informative for mitochondrial DNA contribution. Results The estimated fraction of hypertensive pedigrees potentially due to mitochondrial effects was 35.2% (95% confidence interval, 27 - 43%, P< 10(-10)). The mitochondrial heritabilities for multivariable- adjusted long- term average systolic BP and diastolic BP were, respectively, 5% (P< 0.02) and 4% (P=0.11). Conclusion Our data provide support for a maternal effect on hypertension status and quantitative systolic BP, consistent with mitochondrial influence. Additional studies are warranted to identify mitochondrial DNA variant(s) affecting BP. C1 Boston Univ, Sch Med, Genet Program, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Univ So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Schwartz, F (reprint author), Boston Univ, Sch Med, Genet Program, Dept Med, 715 Albany St,L320, Boston, MA 02118 USA. EM fschw@bu.edu RI Sun, Fengzhu /G-4373-2010; Yang, Qiong/G-5438-2014; OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC-25195, 2K24HL04334]; NIA NIH HHS [R01 AG-18412] NR 80 TC 28 Z9 29 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD OCT PY 2007 VL 25 IS 10 BP 2067 EP 2073 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 215AP UT WOS:000249780000016 PM 17885549 ER PT J AU Hollingsworth, JW Maruoka, S Li, ZW Potts, EN Brass, DM Garantziotis, S Fong, A Foster, WM Schwartz, DA AF Hollingsworth, John W. Maruoka, Shuichiro Li, Zhuowei Potts, Erin N. Brass, David M. Garantziotis, Stavros Fong, Alan Foster, W. Michael Schwartz, David A. TI Ambient ozone primes pulmonary innate immunity in mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-4; AIR-POLLUTION; GRAIN DUST; INFLAMMATORY RESPONSES; CUTTING EDGE; PPM OZONE; EXPOSURE; DISEASE; LUNG; ENDOTOXIN AB Exposure to ozone in air pollution in urban environments is associated with increases in pulmonary-related hospitalizations and mortality. Because ozone also alters clearance of pulmonary bacterial pathogens, we hypothesized that inhalation of ozone modifies innate immunity in the lung. To address our hypothesis, we exposed C57BL/6J mice to either free air or ozone, and then subsequently challenged with an aerosol of Escherichia coli LPS. Pre-exposure to ozone resulted in enhanced airway hyperreactivity, higher concentrations of both total protein and proinflammatory cytokines in lung lavage fluid, enhanced LPS-mediated signaling in lung tissue, and higher concentrations of serum IL-6 following inhalation of LPS. However, pre-exposure to ozone dramatically reduced inflammatory cell accumulation to the lower airways in response to inhaled LPS. The reduced concentration of cells in the lower airways was associated with enhanced apoptosis of both lung macrophages and systemic circulating monocytes. Moreover, both flow cytometry and confocal microscopy indicate that inhaled ozone causes altered distribution of TLR4 on alveolar macrophages and enhanced functional response to endotoxin by macrophages. These observations indicate that ozone exposure increases both the pulmonary and the systemic biologic response to inhaled LPS by priming the innate immune system. C1 Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. RP Hollingsworth, JW (reprint author), Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Box 3136, Durham, NC 27710 USA. EM holli017@mc.duke.edu RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU Intramural NIH HHS; NHLBI NIH HHS [HL91335]; NIAID NIH HHS [AI58161]; NIEHS NIH HHS [ES11961, ES12717] NR 49 TC 47 Z9 47 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2007 VL 179 IS 7 BP 4367 EP 4375 PG 9 WC Immunology SC Immunology GA 214QB UT WOS:000249752100010 PM 17878331 ER PT J AU Wildt, KF Sun, G Grueter, B Fischer, M Zamisch, M Ehlers, M Bosselut, R AF Wildt, Kathryn F. Sun, Guangping Grueter, Baerbel Fischer, Maria Zamisch, Monica Ehlers, Marc Bosselut, Remy TI The transcription factor Zbtb7b promotes CD4 expression by antagonizing runx-mediated activation of the CD4 silencer SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL DEVELOPMENT; ZINC-FINGER PROTEINS; THYMOCYTE DEVELOPMENT; LINEAGE COMMITMENT; POSITIVE SELECTION; GENE-EXPRESSION; LYMPHOCYTE DEVELOPMENT; NEGATIVE SELECTION; REGULATES CD4; DIFFERENTIATION AB The persistence of CD4 expression is a key event distinguishing the differentiation of MHC class II-restricted thymocytes into CD4 T cells from that of MHC class I-restricted thymocytes into CD8 T cells. The zinc finger transcription factor Zbtb7b (or cKrox or Thpok) is normally expressed in MHC class II-restricted thymocytes and promotes CD4 lineage choice. When expressed in MHC class I-restricted cells, Zbtb7b redirects these cells from their normal CD8 fate to CD4 differentiation, implying that it promotes, directly or not, sustained CD4 expression; the present study has investigated the mechanism of this effect. We demonstrate that, although Zbtb7b does not enhance CD4 expression on its own, it antagonizes the CD4 repression mediated by the transcription factor Runx3, which is normally up-regulated during CD8 differentiation and promotes CD4 silencing. Zbtb7b also antagonizes CD4 repression by the related protein Runx1, which is expressed in CD4 lineage cells. This antagonism is observed both in vitro and in vivo, is transcriptional, and requires domains of Zbtb7b that are essential to its ability to promote CD4 differentiation in vivo. Furthermore, Zbtb7b fails to antagonize Runx in cells treated with histone deacetylase inhibitors, suggesting that Zbtb7b acts by reducing the expression of thus far unknown factors that cooperate with Runx molecules to repress CD4. These findings demonstrate that the transcription factor Zbtb7b promotes CD4 expression by antagonizing Runx-mediated CD4 repression. C1 NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Res Ctr Juelich, Inst Neurosci & Biophys 1, Julich, Germany. German Rheumatism Res Ctr, Lab Tolerance & Autoimmun, Berlin, Germany. RP Bosselut, R (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bldg 37,Room 3015,37 Convent Dr, Bethesda, MD 20892 USA. EM remy@helix.nih.gov RI Ehlers, Marc/C-9441-2011 FU Intramural NIH HHS NR 47 TC 44 Z9 46 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 OCT 1 PY 2007 VL 179 IS 7 BP 4405 EP 4414 PG 10 WC Immunology SC Immunology GA 214QB UT WOS:000249752100015 PM 17878336 ER PT J AU Klaewsongkram, J Yang, Y Golech, S Katz, J Kaestner, KH Weng, NP AF Klaewsongkram, Jettanong Yang, Yinhua Golech, Susanne Katz, Jonathan Kaestner, Klaus H. Weng, Nan-Ping TI Kruppel-Like factor 4 regulates B cell number and activation-induced B cell proliferation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYCLIN D2; KLF4; DIFFERENTIATION; SUBSETS AB Kruppel-like factor 4 (KIN) is a transcription factor and functions in regulating cell differentiation, cell growth, and cell cycle. Although Klf4 is expressed in lymphocytes, its function in lymphocytes is unknown. In this study, we report that the levels of Klf4 expression were low in pro-B cells and continuously increased in pre-B and in mature B cells. Upon activation, Klf4 was rapidly decreased in mature B cells after 2 h of activation. A modest decrease in numbers of pre-B cells in bone marrow and mature B cells in spleen was observed in Klf4-deficient mice. In the absence of Klf4, fewer B cells entered the S phase of the cell cycle and completed cell division in response to the engagement of BCR and/or CD40 in vitro. Furthermore, the delay in entering the cell cycle is associated with decreased expression of cyclin D2 in B cells that lack Klf4 expression. We then demonstrated that KIN directly bound to the promoter of cyclin D2 and regulated its expression. These findings demonstrate that KIN regulates B cell number and activation-induced B cell proliferation through directly acting on the promoter of cyclin D2. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Chulalongkorn Univ, Fac Med, Dept Med, Div Clin Immunol & Allergy, Bangkok 10330, Thailand. RP Weng, NP (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM wengn@mail.nih.gov OI Klaewsongkram, Jettanong/0000-0001-6063-2403 FU Intramural NIH HHS [Z01 AG000757-10] NR 17 TC 32 Z9 34 U1 0 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 OCT 1 PY 2007 VL 179 IS 7 BP 4679 EP 4684 PG 6 WC Immunology SC Immunology GA 214QB UT WOS:000249752100045 PM 17878366 ER PT J AU DiPaolo, RJ Brinster, C Davidson, TS Andersson, J Glass, D Shevach, EM AF DiPaolo, Richard J. Brinster, Carine Davidson, Todd S. Andersson, John Glass, Deborah Shevach, Ethan M. TI Autoantigen-specific TGF beta-Induced Foxp3(+) regulatory T cells prevent Autoimmunity by inhibiting dendritic cells from activating autoreactive T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NONOBESE DIABETIC MICE; CUTTING EDGE; IN-VIVO; TRANSGENIC MICE; LYMPH-NODE; CD4(+); INDUCTION; GASTRITIS; SUPPRESS; DISEASE AB Several strategies are being designed to test the therapeutic potential of Ag-specific regulatory T cells to prevent or treat autoimmune diseases. In this study, we demonstrate that naive CD4(+)Foxp3(-) T cells specific for a naturally expressed autoantigen (H+/K+ ATPase) can be converted to Foxp3(+) T regulatory cells (Tregs) when stimulated in presence of TGF beta. TGF beta-induced Tregs (iTregs) have all the characteristics of naturally generated regulatory T cells in vitro, and more importantly, are effective at preventing organ-specific autoimmunity in a murine model of autoimmune gastritis. H+/K+ ATPase specific iTregs were able to inhibit the initial priming and proliferation of autoreactive T cells, and appear to do so by acting on H+/K+ ATPase presenting dendritic cells (DC). DC exposed to iTregs in vivo were reduced in their ability to stimulate proliferation and cytokine production by H+/K+ ATPase specific T cells. iTregs specifically reduced CD80 and CD86 expression on the surface of H+/K+ ATPase presenting DC in vitro. These studies reveal the therapeutic potential of Ag specific iTregs to prevent autoimmunity, and provide a mechanism by which this population of regulatory T cells, and perhaps others, mediate their suppressive effects in vivo. C1 NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov RI Andersson, John/A-4436-2009 FU Intramural NIH HHS NR 44 TC 125 Z9 128 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2007 VL 179 IS 7 BP 4685 EP 4693 PG 9 WC Immunology SC Immunology GA 214QB UT WOS:000249752100046 PM 17878367 ER PT J AU Zhang, H Snyder, KM Suhoski, MM Maus, MV Kapoor, V June, CH Mackall, CL AF Zhang, Hua Snyder, Kristen M. Suhoski, Megan M. Maus, Marcela V. Kapoor, Veena June, Carl H. Mackall, Crystal L. TI 4-1BB is superior to CD28 costimulation for generating CD8(+) cytotoxic lymphocytes for adoptive immunotherapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN-PRESENTING CELLS; EX-VIVO EXPANSION; CD8+ T-CELLS; IN-VIVO; EFFECTOR FUNCTION; DENDRITIC CELLS; RAPID EXPANSION; B-CELLS; VIRUS; RESPONSES AB Artificial APCs (aAPCs) genetically modified to express selective costimulatory molecules provide a reproducible, cost-effective, and convenient method for polyclonal and Ag-specific expansion of human T cells for adoptive immunotherapy. Among the variety of aAPCs that have been studied, acellular beads expressing anti-CD3/anti-CD28 efficiently expand CD4(+) cells, but not CD8(+) T cells. Cell-based aAPCs can effectively expand cytolytic CD8(+) cells, but optimal costimulatory signals have not been defined. 4-1BB, a costimulatory molecule expressed by a minority of resting CD8(+) T cells, is transiently up-regulated by all CD8(+) T cells following activation. We compared expansion of human cytolytic CD8(+) T cells using cell-based aAPCs providing costimulation via 4-1BB vs CD28. Whereas anti-CD3/anti-CD28 aAPCs mostly expand naive cells, anti-CD3/4-1BBL aAPCs preferentially expand memory cells, resulting in superior enrichment of Ag-reactive T cells which recognize previously primed Ags and efficient expansion of electronically sorted CD8(+) populations reactive toward viral or self-Ags. Using HLA-A2-Fc fusion proteins linked to 4-1BBL aAPCs, 3-log expansion of Ag-specific CD8(+) CTL was induced over 14 days, whereas similar Ag-specific CD8(+) T cell expansion did not occur using HLA-A2-Fc/anti-CD28 aAPCs. Furthermore, when compared with cytolytic T cells expanded using CD28 costimulation, CTL expanded using 4-1BB costimulation mediate enhanced cytolytic capacity due, in part, to NKG2D up-regulation. These results demonstrate that 4-1BB costimulation is essential for expanding memory CD8(+) T cells ex vivo and is superior to CD28 costimulation for generating Ag-specific products for adoptive cell therapy. C1 NCI, Dept Pediat Branch, Immunol Sect, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Mackall, CL (reprint author), NCI, Dept Pediat Branch, Immunol Sect, Bldg 10-CRC,IW-3940,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. EM cm35c@nih.gov FU Intramural NIH HHS; NCI NIH HHS [T32 CA009140, R01 CA105216, R01 CA105216-02] NR 53 TC 86 Z9 90 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2007 VL 179 IS 7 BP 4910 EP 4918 PG 9 WC Immunology SC Immunology GA 214QB UT WOS:000249752100070 PM 17878391 ER PT J AU Powell, DJ Felipe-Silva, A Merino, MJ Ahmadzadeh, M Allen, T Levy, C White, DE Mavroukakis, S Kreitman, RJ Rosenberg, SA Pastan, I AF Powell, Daniel J., Jr. Felipe-Silva, Aloisio Merino, Maria J. Ahmadzadeh, Mojgan Allen, Tamika Levy, Catherine White, Donald E. Mavroukakis, Sharon Kreitman, Robert J. Rosenberg, Steven A. Pastan, Ira TI Administration of a CD25-directed immunotoxin, LMB-2, to patients with metastatic melanoma induces a selective partial reduction in regulatory T cells in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; PSEUDOMONAS EXOTOXIN; CHAIN IMMUNOTOXIN; TUMOR-REGRESSION; FUSION PROTEIN; ANTI-TAC; PEPTIDE; IMMUNITY; LYMPHOCYTES; DEPLETION AB CD25(+)CD4(+) T regulatory (Treg) cells regulate peripheral self tolerance and possess the ability to suppress antitumor responses, which may in part explain the poor clinical response of cancer patients undergoing active immunization protocols. We have previously shown that in vitro incubation of human PBMC with LMB-2, a CD25-directed immunotoxin, significantly reduced CD25(+)FOXP3(+)CD4(+) Treg cells without impairing the function of the remaining lymphocytes. In the current study, eight patients with metastatic melanoma were treated with LMB-2 followed by MART-1 and gp100-specific peptide vaccination. LMB-2 administration resulted in a preferential, transient reduction in mean circulating CD25(+)CD4(+) T cell number, from 83 16 cells/mu l to a nadir of 17+/-5 cells/mu l, a 79.1% reduction. FOXP3 analysis revealed a less robust depletion with mean FOXP3(+)CD4(+) Treg cell number decreasing from 74+/-15 cells/mu l to 36+/-8 cells/mu l, a 51.4% reduction. FOXP3(+)CD4(+) Treg cells that survived LMB-2-mediated cytotoxicity expressed little or no CD25. Similar to the peripheral blood, immunohistochemical analysis showed a 68.9% mean reduction in FOXP3(+)CD4(+) Treg cell frequency in evaluable lesions. Despite inducing a reduction in Treg cell numbers in vivo, LMB-2 therapy did not augment the immune response to cancer vaccination and no patient experienced an objective response or autoimmunity. These data demonstrate the capacity of a CD25-directed immunotoxin to selectively mediate a transient partial reduction in circulating and tumor-infiltrating Treg cells in vivo, and suggest that more comprehensive Treg cell elimination may be required to bolster antitumor responses in patients with metastatic melanoma. C1 Clin Res Ctr, NIH, NCI, Surg Branch, Bethesda, MD 20892 USA. NIH, NCI, Surg Branch, Bethesda, MD 20892 USA. NIH, NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NIH, NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Powell, DJ (reprint author), Clin Res Ctr, NIH, NCI, Surg Branch, Rm 3W-3888,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM Daniel_Powell@nih.gov RI FELIPE-SILVA, ALOISIO/J-9295-2012 OI FELIPE-SILVA, ALOISIO/0000-0001-6668-7907 FU Intramural NIH HHS [Z01 SC003811-32] NR 53 TC 100 Z9 104 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 OCT 1 PY 2007 VL 179 IS 7 BP 4919 EP 4928 PG 10 WC Immunology SC Immunology GA 214QB UT WOS:000249752100071 PM 17878392 ER PT J AU Hama, Y Koyama, Y Urano, Y Choyke, PL Kobayashi, H AF Hama, Yukihiro Koyama, Yoshinori Urano, Yasuteru Choyke, Peter L. Kobayashi, Hisataka TI Two-color lymphatic mapping using Ig-conjugated near infrared optical probes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MAGNETIC RESONANCE LYMPHANGIOGRAPHY; BREAST-CANCER; QUANTUM DOTS; LYMPHEDEMA; EDEMA AB To map the drainage patterns of the lymphatic system, multicolor optical probes must be developed, which can be interstitially administered. These agents must be of sufficient size to be retained by the lymphatic system and permit the conjugation or incorporation of fluorescent probes with varying emission wavelengths. Quantum dots fulfill these criteria, but their potential toxicity limits their application to research settings. Here, we describe the synthesis of lymphatic optical probes based on Igs conjugated with Cy5.5 and Cy7 and demonstrate in animal models that these agents can map the lymphatic drainage patterns within axillary nodes draining both the breast and upper extremity, cervical nodes draining both the ear and upper extremity, and sentinel lymph nodes draining different anatomic locations. The ability to separately and simultaneously visualize the drainage patterns from two separate lymphatic vessels may have implications for the preoperative mapping of lymph nodes before lymph node resection. The biocompatibility of fluorescently labeled Igs in comparison to other nanoparticulate fluorophores improves the chances of clinical translation. This noninvasive and biocompatible multicolor method of optical lymphangiography may elucidate the complex human lymphatic system and reduce the risk of lymphedema after surgery for melanoma and other cancers. C1 NCI, Mol Imaging Program, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo, Japan. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, NIH, Ctr Canc Res, Bldg 10,Room 1B40,MSC 1088, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov RI Urano, Yasuteru/H-1380-2012 FU Intramural NIH HHS NR 21 TC 32 Z9 34 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2007 VL 127 IS 10 BP 2351 EP 2356 DI 10.1038/sj.jid.5700892 PG 6 WC Dermatology SC Dermatology GA 217FF UT WOS:000249933100013 PM 17522707 ER PT J AU Calabro, V Di Costanzo, A Festa, L Franci, V Galli, F Guerrini, L Morasso, M La Mantia, G AF Calabro, V. Di Costanzo, A. Festa, L. Franci, V. Galli, F. Guerrini, L. Morasso, M. La Mantia, G. TI P63 and Dlx3 reciprocal regulation: possible relevance in the molecular pathways underlying skin differentiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 05-08, 2007 CL Zurich, SWITZERLAND SP European Soc Dermatol Res C1 [Calabro, V.; Di Costanzo, A.; Festa, L.; Franci, V.; Galli, F.; La Mantia, G.] Univ Naples Federico 2, Naples, Italy. [Guerrini, L.] Univ Milan, I-20122 Milan, Italy. [Morasso, M.] NIH, NIAMS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2007 VL 127 SU 2 BP S63 EP S63 PG 1 WC Dermatology SC Dermatology GA 217FI UT WOS:000249933400378 ER PT J AU Gaffal, E Landsberg, J Kohlmeyer, J Tormo, D Wenzel, J Merlino, G Tuting, T AF Gaffal, E. Landsberg, J. Kohlmeyer, J. Tormo, D. Wenzel, J. Merlino, G. Tueting, T. TI Mutant CDK4 increases the penetrance and decreases the latency of UV-induced, metastasizing melanoma in the skin of C57BL/6 HGF mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 05-08, 2007 CL Zurich, SWITZERLAND SP European Soc Dermatol Res C1 [Gaffal, E.; Landsberg, J.; Kohlmeyer, J.; Tormo, D.; Wenzel, J.; Tueting, T.] Univ Bonn, D-5300 Bonn, Germany. [Merlino, G.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2007 VL 127 SU 2 BP S50 EP S50 PG 1 WC Dermatology SC Dermatology GA 217FI UT WOS:000249933400297 ER PT J AU Kim, AL Back, JH Zhu, Y Athar, M Tang, X Kopelovich, L Bickers, DR AF Kim, A. L. Back, J. H. Zhu, Y. Athar, M. Tang, X. Kopelovich, L. Bickers, D. R. TI Senescence driven by reactive oxygen species (ROS) via NF-kappa B suppresses UVB-induced skin photocarcinogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 05-08, 2007 CL Zurich, SWITZERLAND SP European Soc Dermatol Res C1 [Kim, A. L.; Back, J. H.; Zhu, Y.; Tang, X.; Bickers, D. R.] Columbia Univ, New York, NY USA. [Athar, M.] Univ Alabama, Birmingham, AL USA. [Kopelovich, L.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2007 VL 127 SU 2 BP S90 EP S90 PG 1 WC Dermatology SC Dermatology GA 217FI UT WOS:000249933400540 ER PT J AU Pfutzner, W Scheidemann, F Therrien, JP AF Pfutzner, W. Scheidemann, F. Therrien, J-P TI Bicistronic vectors for skin gene therapy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 05-08, 2007 CL Zurich, SWITZERLAND SP European Soc Dermatol Res C1 [Pfutzner, W.] Univ Marburg, Marburg, Germany. [Scheidemann, F.] Univ Munich, Munich, Germany. [Therrien, J-P] NIH, Natl Canc Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2007 VL 127 SU 2 BP S85 EP S85 PG 1 WC Dermatology SC Dermatology GA 217FI UT WOS:000249933400510 ER PT J AU Tang, X Kim, AL Kopelovich, L Bickers, DR Athar, M AF Tang, X. Kim, A. L. Kopelovich, L. Bickers, D. R. Athar, M. TI Genetic background and p53 gene-dose are major susceptibility factors for basal cell carcinomas (BCCs) in murine skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 05-08, 2007 CL Zurich, SWITZERLAND SP European Soc Dermatol Res C1 [Tang, X.; Kim, A. L.; Bickers, D. R.] Columbia Univ, New York, NY USA. [Kopelovich, L.] NCI, Bethesda, MD 20892 USA. [Athar, M.] Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2007 VL 127 SU 2 BP S96 EP S96 PG 1 WC Dermatology SC Dermatology GA 217FI UT WOS:000249933400573 ER PT J AU Lee, YJ Park, DJ Shin, CS Park, KS Kim, SY Lee, HK Park, YJ Cho, BY AF Lee, You Jin Park, Do Joon Shin, Chan Soo Park, Kyong Soo Kim, Seong Yeon Lee, Hong Kyu Park, Young Joo Cho, Bo Youn TI Microarray analysis of thyroid stimulating hormone, insulin-like growth factor-1, and insulin-induced gene expression in FRTL-5 thyroid cells SO JOURNAL OF KOREAN MEDICAL SCIENCE LA English DT Article DE oligonucleotide array sequence analysis; gene expression; thyroid; thyrotropin; insulin; insulin-like growth factor 1 ID RECEPTOR MESSENGER-RNA; SIGNALING PATHWAYS; THYROTROPIN; CARCINOMAS; GLUCAGON; DIFFERENTIATION; PROLIFERATION; MODULATION; PROTEINS; GOITERS AB To determine which genes are regulated by thyroid stimulating hormone (thyrotropin, TSH), insulin and insulin-like growth factor-1 (IGF-1) in the rat thyroid, we used the microarray technology and observed the changes in gene expression. The expressions of genes for bone morphogenetic protein 6, the glucagon receptor, and cyclin D1 were increased by both TSH and IGF-1; for cytochrome P450, 2c37, the expression was decreased by both. Genes for cholecystokinin, glucuronidase, beta, demethyl-Q 7, and cytochrome c oxidase, subunit VIIIa, were up-regulated; the genes for ribosomal protein L37 and ribosomal protein L4 were down-regulated by TSH and insulin. However, there was no gene observed to be regulated by all three: TSH, IGF-1, and insulin molecules studied. These findings suggest that TSH, IGF-1, and insulin stimulate different signal pathways, which can interact with one another to regulate the proliferation of thyrocytes, and thereby provide additional influence on the process of cellular proliferation. C1 Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Seoul, South Korea. Seoul Natl Univ, Seoul Natl Univ Hosp, Coll Med, Dept Internal Med, Seoul, South Korea. Seoul Natl Univ Hosp, Clin Res Inst, NHGRI, Seoul, South Korea. RP Park, YJ (reprint author), Seoul Natl Univ, Bundang Hosp, Dept Internal Med, 300 Gumi-dong, Bundang-gu, Seoul, South Korea. EM yjparkmd@snu.ac.kr RI KIM, SEONG YEON/E-4164-2012; Park, Do-Joon/J-2736-2012; Shin, Chan Soo/I-7320-2012; Park, Young Joo/J-4161-2012; Kim, Seong Yeon/J-5408-2012; Park, Kyong Soo/C-2265-2008 OI Shin, Chan Soo/0000-0002-5829-4465; Park, Young Joo/0000-0002-3671-6364; Park, Kyong Soo/0000-0003-3597-342X NR 26 TC 2 Z9 3 U1 0 U2 0 PU KOREAN ACAD MEDICAL SCIENCES PI SEOUL PA 302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA SN 1011-8934 J9 J KOREAN MED SCI JI J. Korean Med. Sci. PD OCT PY 2007 VL 22 IS 5 BP 883 EP 890 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 231ZM UT WOS:000250987700020 PM 17982240 ER PT J AU Rosenberg, HF AF Rosenberg, Helene F. TI Rational design of MyD88 inhibitors - new pathways to inflammatory control: an interview with Dr. Claudio Sette SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID MULTIPLE-SCLEROSIS C1 NIAID, Natl Inst Hlth, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Natl Inst Hlth, Lab Allerg Dis, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 4 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD OCT PY 2007 VL 82 IS 4 BP 811 EP 812 DI 10.1189/jlb.1306746 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 211JX UT WOS:000249521200004 ER PT J AU Ozarslan, E Basser, PJ AF Oezarslan, Evren Basser, Peter J. TI MR diffusion-"diffraction" phenomenon in multi-pulse-field-gradient experiments SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE MR; diffusion; diffraction; coherence; double; PGSE; PFG; pore size; distribution; general gradient waveform; matrix formalism; multiple scattering ID SPIN-ECHO ANALYSIS; RESTRICTED DIFFUSION; SPATIOTEMPORAL CORRELATIONS; VELOCITY CORRELATION; POROUS-MEDIA; WAVE-FORMS; NMR; FLUID AB Using pulsed-field-gradient (PFG) experiments, the sizes of the pores in ordered porous media can be estimated from the "diffraction" pattern that the signal attenuation curves exhibit. A different diffraction pattern is observed when the experiment is extended to a larger number (N) of diffusion gradient pulse pairs. Simulations to calculate signal values from arbitrary gradient waveforms are performed for diffusion in restricted geometries using a matrix operator formalism. The simulations suggest that the differences in the characteristics of the attenuation curves are expected to make it possible to measure smaller pore sizes, to. improve the accuracy of pore size measurements and potentially to distinguish different pore shapes using the N-PFG technique. Moreover, when an even number of PFG pairs is used, it is possible to observe the diffraction pattern at shorter diffusion times and measure an approximation to the average pore size even when the sample contains pores with a broad distribution of sizes. C1 NICHHD, Natl Inst Hlth, Sect Tissue Biophys & Biomimet, LIMB, Bethesda, MD 20892 USA. RP Ozarslan, E (reprint author), NICHHD, Natl Inst Hlth, Sect Tissue Biophys & Biomimet, LIMB, Bethesda, MD 20892 USA. EM evren@helix.nih.gov RI Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011 OI Ozarslan, Evren/0000-0003-0859-1311; FU Intramural NIH HHS [Z99 HD999999] NR 23 TC 61 Z9 61 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD OCT PY 2007 VL 188 IS 2 BP 285 EP 294 DI 10.1016/j.jmr.2007.08.002 PG 10 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 225RV UT WOS:000250536000011 PM 17723314 ER PT J AU Pelled, G Bergman, H Ben-Hur, T Goelman, G AF Pelled, Galit Bergman, Hagai Ben-Hur, Tamir Goelman, Gadi TI Manganese-enhanced MRI in a rat model of Parkinson's disease SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE manganese-enhanced MRI; Parkinson's disease; 6-hydroxydopamine; basal ganglia; functional connectivity; rat ID RESONANCE-IMAGING MEMRI; BASAL-GANGLIA; IN-VIVO; 6-HYDROXYDOPAMINE LESIONS; ENTOPEDUNCULAR NUCLEUS; FUNCTIONAL-ANATOMY; SUBSTANTIA-NIGRA; DOPAMINE NEURONS; BRAIN; PROJECTIONS AB Purpose: To measure intra- and inter-hemispheric connectivity within the basal ganglia (BG) nuclei in healthy and in unilateral 6-hydroxydopamine (6-OHDA) Parkinson disease rat model in order to test the BG interhemispheric connectivity hypothesis. Material and Methods: The manganese-enhanced MR] (MEMRI) method with direct injection of manganese chloride into the entopeduncular (EP), substantia nigra (SN), and the Habenula nuclei in unilateral 6-OHDA (N = 22) and sham-operated (N = 16) rat groups was used. MEMRI measurements were applied before, 3, 24, and 48 hours post-manganese injection. Signal enhancements in T1 -weighted images were compared between groups. Results: Manganese injection into the EP nucleus resulted with bihemispheric signal enhancements in the habenular complex (Hab) at both groups with stronger enhancements in the 6-OHDA group. It also exhibited lower sensorimotor cortex signal enhancement in the 6-OHDA rat group. SN manganese injection caused enhanced anteroventral thalamic and habenular nuclei signals in the 6-OHDA rat group. Manganese habenula injection revealed enhanced interpeduncular (IP) and raphe nuclei signals of the 6-OHDA rat group. Conclusion: Modulations in the effective intra- and interhemispheric BG connectivity in unilateral 6-OHDA Parkinson's disease (PD) rat model support the BG interhemispheric connectivity hypothesis and suggest a linkage between the dopaminergic and serotonergic systems in PD, in line with clinical symptoms. C1 Hadassah Hebrew Univ, Med Ctr, Dept Med Biophys & Nucl Med, Human Biol Res Ctr,MRI MRS Lab, Jerusalem, Israel. NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. Hadassah Hebrew Univ Hosp, Dept Neurol, Agnes Ginges Ctr Human Neurogenet, Jerusalem, Israel. RP Goelman, G (reprint author), Hadassah Hebrew Univ, Med Ctr, Dept Med Biophys & Nucl Med, Human Biol Res Ctr,MRI MRS Lab, Jerusalem, Israel. EM gadig@hadassah.org.il NR 65 TC 35 Z9 35 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD OCT PY 2007 VL 26 IS 4 BP 863 EP 870 DI 10.1002/jmri.21051 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216SH UT WOS:000249898800005 PM 17896372 ER PT J AU Gharib, AM Herzka, DA Ustun, AO Desai, MY Locklin, J Pettigrew, RI Stuber, M AF Gharib, Ahmed M. Herzka, Daniel A. Ustun, Ali O. Desai, Milind Y. Locklin, Julia Pettigrew, Roderic I. Stuber, Matthias TI Coronary MR angiography at 3T during diastole and systole SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE coronary MRA; 3T; systolic imaging; RR variability; parallel imaging ID MAGNETIC-RESONANCE ANGIOGRAPHY; ACQUISITION WINDOW; CARDIAC MOTION; ARTERIES; TIME; VARIABILITY AB Purpose: To investigate the impact of end-systolic imaging on quality of right coronary magnetic resonance angiography (MRA) in comparison to diastolic and to study the effect of RR interval variability on image quality. Materials and Methods: The right coronary artery (RCA) of 10 normal volunteers was imaged at 3T using parallel imaging (sensitivity encoding [SENSE]). Navigator-gated three-dimensional (3D) gradient echo was used three times: 1) end-systolic short acquisition (SS): 35-msec window; 2) diastolic short (DS): middiastolic acquisition using 35-msec window and 3) diastolic long, (DL): 75-msec diastolic acquisition window. Vectorcardiograrn (VCG) data was used to analyze RR variability. Vessel sharpness, length, and diameter were compared to each other and correlated with RR variablity Blinded qualitative image scores of the images were compared. Results: Quantitative and qualitative parameters were not significantly different and showed no significant correlation with RR varibality. Conclusion: Imaging the RCA at 3T during the end-systolic rest period using SENSE is possible without significant detrimental effect on image quality. Breaking away from the standard of imaging only during diastole can potentially improve image quality in tachycardic patients or used for simultaneous imaging during both periods in a single scan. C1 NHLBI, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. Philips Res N Amer, Bethesda, MD USA. Johns Hopkins Univ, Dept Radiol, Div MR Res, Baltimore, MD USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Med, Bethesda, MD USA. Johns Hopkins Univ, Dept Elect & Comp Engn, Bethesda, MD USA. RP Gharib, AM (reprint author), NHLBI, NIH, Clin Res Ctr, Bldg 10,Rm 3-5340,MSC 1263,10 Ctr Dr, Bethesda, MD 20892 USA. EM agharib@nhlbi.nih.gov RI Stuber, Matthias/B-2949-2010; Gharib, Ahmed/O-2629-2016; OI Stuber, Matthias/0000-0001-9843-2028; Gharib, Ahmed/0000-0002-2476-481X; Herzka, Daniel/0000-0002-9400-7814 FU Intramural NIH HHS [Z99 DK999999, ZIA DK075083-02] NR 24 TC 28 Z9 29 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD OCT PY 2007 VL 26 IS 4 BP 921 EP 926 DI 10.1002/jmri.21056 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216SH UT WOS:000249898800013 PM 17896391 ER PT J AU Sousa, AA Leapman, RD AF Sousa, Alioscka A. Leapman, Richard D. TI Quantitative STEM mass measurement of biological macromolecules in a 300 kV TEM SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE biological macromolecules; elastic scattering; hemocyanin; mass mapping; scanning transmission electron microscopy; STEM; tobacco mosaic virus ID TRANSMISSION ELECTRON-MICROSCOPY; FILAMENTS ASSEMBLED INVITRO; SCATTERING CROSS-SECTIONS; INTERMEDIATE FILAMENTS; SUBUNIT ORGANIZATION; ELASTIC-SCATTERING; EPIDERMAL KERATIN; MOLECULAR-MASS; DRY MASS; X-RAY AB For almost four decades, the scanning transmission electron microscope (STEM) has made significant contributions to structural biology by providing accurate determinations of the molecular masses of large protein assemblies that have arbitrary shapes and sizes. Nevertheless, STEM mass mapping has been implemented in very few laboratories, most of which have employed cold field-emission gun (FEG) electron sources operating at acceleration voltages of 100 kV and lower. Here we show that a 300 kV commercial transmission electron microscope (TEM) equipped with a thermally assisted Shottky FEG can also provide accurate STEM mass measurements. Using the recently published database of elastic-scattering cross sections from the National Institute of Standards and Technology, we show that the measured absolute mass values for tobacco mosaic virus and limpet hemocyanin didecamers agree with the known values to within better than 10%. Applying the established approach, whereby tobacco mosaic virus is added to a specimen as a calibration standard, we find that the measured molecular weight of the hemocyanin assemblies agrees with the known value to within 3%. This accuracy is achievable although only a very small fraction (similar to 0.002) of the incident probe current of 300 kV electrons is scattered onto the annular dark-field STEM detector. FEG TEMs operating at intermediate voltages (200-400 kV) are becoming common tools for determining the structure of frozen hydrated protein assemblies. The ability to perform mass determination with the same instrument can provide important complementary information about the numbers of subunits comprising the protein assemblies whose structure is being studied. C1 Natl Inst Biomed Imaging & Bioengn, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, Natl Inst Hlth, Bethesda, MD 20892 USA. EM leapmanr@mail.nih.gov FU Intramural NIH HHS NR 43 TC 15 Z9 15 U1 2 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD OCT PY 2007 VL 228 IS 1 BP 25 EP 33 DI 10.1111/j.1365-2818.2007.01819.x PG 9 WC Microscopy SC Microscopy GA 216NE UT WOS:000249883900003 PM 17910694 ER PT J AU Sommer, WH Rimondini, R Marquitz, M Lidstrom, J Siems, WE Bader, M Heilig, M AF Sommer, W. H. Rimondini, R. Marquitz, M. Lidstroem, J. Siems, W-E Bader, M. Heilig, M. TI Plasticity and impact of the central renin-angiotensin system during development of ethanol dependence SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE alcoholism; angiotensin converting enzyme inhibitor; animal model; transgenic rats; gene expression ID CORTICOTROPIN-RELEASING-FACTOR; CONVERTING ENZYME-INHIBITORS; ALCOHOL INTAKE; TRANSGENIC RATS; BRAIN ANGIOTENSIN; ANIMAL-MODELS; INTERMITTENT; CONSUMPTION; ANTAGONIST; PREFERENCE AB Pharmacological and genetic interference with the renin-angiotensin system (RAS) seems to alter voluntary ethanol consumption. However, understanding the influence of the RAS on ethanol dependence and its treatment requires modeling the neuroadaptations that occur with prolonged exposure to ethanol. Increased ethanol consumption was induced in rats through repeated cycles of intoxication and withdrawal. Expression of angiotensinogen, angiotensin-converting enzyme, and the angiotensin 11 receptor, AT1a, was examined by quantitative reverse transcription polymerase chain reaction. Increased ethanol consumption after a history of dependence was associated with increased angiotensinogen expression in medial prefrontal cortex but not in nucleus accumbens or amygdala. Increased angiotensinogen expression also demonstrates that the astroglia is an integral part of the plasticity underlying the development of dependence. The effects of low central RAS activity on increased ethanol consumption were investigated using either spirapril, a blood-brain barrier-penetrating inhibitor of angiotensin-converting enzyme, or transgenic rats (TGR(ASrAOGEN)680) with reduced central angiotensinogen expression. Spirapril reduced ethanol intake in dependent rats compared to controls. After induction of dependence, TGR(ASrAOGEN) 680 rats had increased ethanol consumption but to a lesser degree than Wistar rats with the same history of dependence. These data suggest that the central RAS is sensitized in its modulatory control of ethanol consumption in the dependent state, but pharmacological or genetic blockade of the system appears to be insufficient to halt the progression of dependence. C1 NIH, NIAAA, Lab Clin Translat Studies, Bethesda, MD 20892 USA. Univ Bologna, Dept Pharmacol, Bologna, Italy. Univ Jena, Dept Anat, D-6900 Jena, Germany. Leibniz Inst Mol Pharmacol, Berlin, Germany. Max Delbruck Ctr Mol Med, Berlin, Germany. RP Sommer, WH (reprint author), NIH, NIAAA, Lab Clin Translat Studies, Bldg 10,CRC,E1 5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM wolfgang.sommer@mail.nih.gov RI Rimondini, Roberto/B-2500-2010; OI Rimondini, Roberto/0000-0003-4099-513X; Bader, Michael/0000-0003-4780-4164 NR 47 TC 12 Z9 14 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED JI J. Mol. Med. PD OCT PY 2007 VL 85 IS 10 BP 1089 EP 1097 DI 10.1007/s00109-007-0255-5 PG 9 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 221AG UT WOS:000250198100006 PM 17823780 ER PT J AU Sellers, JR Knight, PJ AF Sellers, James R. Knight, Peter J. TI Folding and regulation in myosins II and V SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Review DE myosin; regulation; calcium; phosphorylation ID SMOOTH-MUSCLE MYOSIN; PHOSPHORYLATION-DEPENDENT REGULATION; LIGHT-CHAIN PHOSPHORYLATION; HEAVY-MEROMYOSIN; ATPASE ACTIVITY; IMAGE-RECONSTRUCTION; STRUCTURAL-CHANGES; STRIATED-MUSCLE; INHIBITED STATE; IONIC-STRENGTH AB The enzymatic activity of many myosins is regulated by various means including calcium binding, phosphorylation or binding of receptor molecules. In this review we compare and contrast the regulation of smooth muscle myosin II and myosin Va with particular emphasis on the structural basis for the regulation. Both myosins adopt folded compact conformations in their off states, but the details of the conformations are markedly different. In the regulated smooth muscle myosin II, the key feature is an asymmetric interaction between the two heads of the molecule with contributions of specific tail-head interactions. In myosin V the key feature is an interaction between the heads and the globular tail domain. C1 [Sellers, James R.] NHLBI, NIH, Lab Mol Physiol, Bethesda, MD 20892 USA. [Knight, Peter J.] Univ Leeds, Inst Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England. [Knight, Peter J.] Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England. RP Sellers, JR (reprint author), NHLBI, NIH, Lab Mol Physiol, Bldg 50,Room 3523, Bethesda, MD 20892 USA. EM sellersj@nhlbi.nih.gov FU Intramural NIH HHS; Wellcome Trust [076057] NR 63 TC 26 Z9 26 U1 3 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD OCT PY 2007 VL 28 IS 7-8 BP 363 EP 370 DI 10.1007/s10974-008-9134-0 PG 8 WC Cell Biology SC Cell Biology GA 300ZJ UT WOS:000255864100001 PM 18427938 ER PT J AU Takada, K Bermingham, A O'Keefe, BR Wamiru, A Beutler, JA Le Grice, SFJ Lloyd, J Gustafson, KR McMahon, JB AF Takada, Kentaro Bermingham, Alun O'Keefe, Barry R. Wamiru, Antony Beutler, John A. Le Grice, Stuart F. J. Lloyd, John Gustafson, Kirk R. McMahon, James B. TI An HIV RNase H inhibitory 1,3,4,5-tetragalloylapiitol from the African plant Hylodendron gabunensis SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID REVERSE-TRANSCRIPTASE; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; VIRUS; APIOSE; DNA AB A new compound, 1,3,4,5-tetragalloylapiitol (1), was isolated from the aqueous extract of the plant Hylodendron gabunensis and was found to be a potent inhibitor of RNase H enzymatic activity. The structure of 1 was elucidated by NMR analyses to be an apiitol (2) sugar moiety substituted with four gallic acid residues. Optical rotation measurements of the free sugar following basic hydrolysis indicated that the 3S absolute configuration was the same as that Of D-apiitol. Compound I inhibited HIV-1, HIV-2, and human RNase H with IC50 values of 0.24, 0.13, and 1.5 mu M, respectively, but it did not show inhibition of E. coli RNase H at 10 mu M. C1 NCI, Ctr Canc Res, Mol Targets Dev Programs, Ft Detrick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. NCI, CCR, Drug Resistance Program, Ft Detrick, MD 21702 USA. NIDDK, Protemoics & Mass Spectrometry Fac, Bethesda, MD USA. RP Gustafson, KR (reprint author), NCI, Ctr Canc Res, Mol Targets Dev Programs, Bldg 1052,Room 121, Ft Detrick, MD 21702 USA. EM gustafson@ncifcrf.gov RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 13 TC 16 Z9 19 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD OCT PY 2007 VL 70 IS 10 BP 1647 EP 1649 DI 10.1021/np0702279 PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 225ZA UT WOS:000250555700021 PM 17935297 ER PT J AU Mullasseril, P Dosemeci, A Lisman, JE Griffith, LC AF Mullasseril, Praseeda Dosemeci, Ayse Lisman, John E. Griffith, Leslie C. TI A structural mechanism for maintaining the 'on-state' of the CaMKII memory switch in the post-synaptic density SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE learning and memory; long-term potentiation; phosphatase; PP1; protein kinase ID PROTEIN-KINASE-II; LONG-TERM POTENTIATION; D-ASPARTATE RECEPTOR; SYNAPTIC PLASTICITY; AUTOPHOSPHORYLATION; PHOSPHORYLATION; PHOSPHATASE-1; SUBUNIT; IDENTIFICATION; TRANSLOCATION AB Ca2+/calmodulin-dependent protein kinase 11 (CaMKII) is activated by Ca2+ entry into neurons. Autophosphorylation of T286 is of special importance because it makes the enzyme active in the absence of Ca2+, providing a biochemical memory that is critical for plasticity. To understand the factors controlling the duration of this state of CaMKII, we studied dephosphorylation of CaMKII in the post-synaptic density (PSD), a structure that defines a neuronal subcompartment critical for plasticity. We found that PSD-resident PP1 can previous work showing that soluble PP2A cannot dephosph-orylate PSD CaMKII, provides a novel explanation for the in vivo persistence of T286 phosphorylation: after activated CaMKI I translocates from the cytoplasm to the PSD, structural constraints prevent phosphatases from dephosphorylating T286. These results also suggest that the PSD is more than a simple scaffold for synaptic proteins; it may act to regulate the activity of proteins by positioning them in orientations that either prevent or favor specific biochemical reactions. dephosphorylate many sites on CaMKII, but not the T286 site that produces Ca2+-independent activity. This, together with C1 Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. Brandeis Univ, Volen Ctr Complex Syst, Waltham, MA 02254 USA. Brandeis Univ, Natl Ctr Behav Genom, Waltham, MA 02254 USA. NINDS, NIH, Neurobiol Lab, Bethesda, MD 20892 USA. RP Lisman, JE (reprint author), Brandeis Univ, Dept Biol, MS008,415 S St, Waltham, MA 02454 USA. EM lisman@brandeis.edu OI Griffith, Leslie/0000-0003-3164-9876 FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM054408, R01 GM054408-12, R01 GM54408]; NINDS NIH HHS [R01 NS 27337, R01 NS027337, R01 NS050944, R01 NS50944] NR 44 TC 45 Z9 48 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2007 VL 103 IS 1 BP 357 EP 364 DI 10.1111/j.1471-4159.2007.04744.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 217LP UT WOS:000249949700032 PM 17877639 ER PT J AU Spina, S Murrell, JR Huey, ED Wassermann, EM Pietrini, P Grafman, J Ghetti, B AF Spina, Salvatore Murrell, Jill R. Huey, Edward D. Wassermann, Eric M. Pietrini, Pietro Grafman, Jordan Ghetti, Bernardino TI Corticobasal syndrome associated with the A9D Progranulin mutation SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE alien limb; apraxia; frontotemporal lobar degeneration; hemineglect; parietal lobe; Prograrunlin; TDP-43 ID FRONTOTEMPORAL LOBAR DEGENERATION; PROGRESSIVE SUPRANUCLEAR PALSY; ALZHEIMERS-DISEASE; IDEATIONAL APRAXIA; GENE-MUTATIONS; DEMENTIA; TAU; PATHOLOGY; FEATURES; INCLUSIONS AB Corticobasal syndrome is characterized by cortical dysfunction and L-dopa-unresponsive Parkinsonism, with asymmetrical onset of clinical presentation and evidence of atrophy and/or hypometabolism at neuroimaging. Recently, the heterogeneous pathologic substrate of corticobasal syndrome has been further expanded to include cases with pathologic diagnosis of frontotemporal lobar degeneration with ubiquitin/TDP-43 (TAR DNA binding protein 43)-positive inclusions associated with Progranulin (PGRN) mutations. We report a family in which several individuals have been affected with a dementia/movement disorder phenotype. The proband presented at age 45 with spontaneous left arm levitation, ideational apraxia, asymmetric parkinsonism, and dystonia. Subsequently, he developed limb-kinetic apraxia, left-side hemi-neglect, memory loss, and executive dysfunction. Magnetic resonance imaging and [(18)F]fluorodeoxyglucose-positron emission tomography studies revealed severe cerebral cortical atrophy and hypometabolism, which were significantly more pronounced in the parietal lobes (right > left). Neuropathologic examination displayed the highest degree of degeneration and ubiquitin/TDP-43 pathology in the proband's parietal areas. Genetic analysis revealed the presence of the c.26C>A PGRN mutation in I allele. This mutation has been reported in association with hereditary-dysphasic-disinhibition-dementia, Alzheimer-like dementia, progressive supranuclear palsy, and primary progressive aphasia. The peculiar findings observed in this patient indicate that the parietal lobe may represent the most vulnerable anatomical area in some of the PGRN-associated frontotemporal lobar degeneration with ubiquitin/TDP-43 -positive inclusion cases. C1 Indiana Univ, Sch Med, Dept Pathol, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Lab Med, Indianapolis, IN 46202 USA. Univ Siena, Dept Neurol & Behav Sci, I-53100 Siena, Italy. Natl Inst Hlth, Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Univ Pisa, Lab Clin Biochem & Mol Biol, Pisa, Italy. RP Ghetti, B (reprint author), Indiana Univ, Sch Med, Dept Pathol, Indiana Alzheimer Dis Ctr, Med Sci Bldg A138,635 Bamhill Dr, Indianapolis, IN 46202 USA. EM bghetti@iupui.edu OI Grafman, Jordan H./0000-0001-8645-4457 FU Intramural NIH HHS; NIA NIH HHS [P30AG10133] NR 54 TC 50 Z9 51 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD OCT PY 2007 VL 66 IS 10 BP 892 EP 900 DI 10.1097/nen.0b013e3181567873 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 220LW UT WOS:000250159200003 PM 17917583 ER PT J AU Depboylu, C Eiden, LE Weihe, E AF Depboylu, Candan Eiden, Lee E. Weihe, Eberhard TI Increased APOBEC3G expression is associated with extensive G-to-A hypermutation in viral DNA in rhesus macaque brain during lentiviral infection SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE antiretroviral treatment; hypermutations; inflammatory infiltrates; intrinsic immunity; macrophages; Neuro-AIDS; T-lymphocytes ID SIMIAN IMMUNODEFICIENCY VIRUS; MESSENGER-RNA LEVELS; CYTIDINE DEAMINATION; HIV-1 INFECTION; VIF PROTEIN; IN-VIVO; CELL; TYPE-1; REGIONS; MACROPHAGES AB APOBEC3G restricts retrovirus replication through inducing guanosine-to-adenosine (G-to-A) hypermutations in viral DNA. Its role in brain "intrinsic immunity" has not been elucidated nor has it been convincingly demonstrated which brain cell compartments produce this defense factor in human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), and antiretroviral therapy. Here, we investigated by immunohistochemistry and in situ hybridization the cell-specific regulation of APOBEC3G in rhesus macaque brains during infection with simian immunodeficiency virus (SIV) clone 813670, a primate model of HIV disease. We found that APOBEC3G protein and mRNA were exclusively expressed by some perivascular macrophages throughout the brain of noninfected and asymptomatic SIV-infected monkeys. Depending on virus burden, APOBEC3G was induced in microglia/ macrophage-derived cells and T-lymphocytes in late-stage SIV infection. Intracellularly, APOBEC3G was found in the cytoplasm and/or in the nucleus. APOBEC3G-positive cells were in close proximity to SIV gag-positive cells or were SIV-copositive. Induction of APOBEC3G was accompanied by G-to-A hypermutations in the gag and pol regions of retroviral DNA isolated from brain sections of AIDS-symptomatic monkeys. Although brain-directed treatment with antiretroviral 6-chloro-2',3'-dideoxyguanosine suppressed brain SIV burden, encephalitis and reduced cerebral APOBEC3G synthesis hypermutations were still detectable. Upregulation of APOBEC3G may restrict spread of SIV in the brain and thus limit brain damage during lentiviral infection. C1 Univ Marburg, Dept Mol Neurosci, Inst Anatomy & Cell Biol, D-35033 Marburg, Germany. Univ Marburg, Ctr Nervous Dis, Marburg, Germany. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Weihe, E (reprint author), Univ Marburg, Dept Mol Neurosci, Inst Anatomy & Cell Biol, Robert Kock Str 8, D-35033 Marburg, Germany. EM weihe@staff.uni-marburg.de OI Eiden, Lee/0000-0001-7524-944X NR 47 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD OCT PY 2007 VL 66 IS 10 BP 901 EP 912 DI 10.1097/nen.0b013e3181567a59 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 220LW UT WOS:000250159200004 PM 17917584 ER PT J AU Tsai, MJ Weng, CF Shyue, SK Liou, DY Chen, CH Chiu, CW Yang, TH Pan, HA Liao, RIH Kuo, HS Huang, MC Huang, WC Hoffer, BJ Cheng, H AF Tsai, May-Jywan Weng, Ching-Feng Shyue, Song-Kun Liou, Dann-Ying Chen, Chien-Hung Chiu, Chuan-Wen Yang, Tzu-Hsuan Pan, Hsu-An Liao, Roanna I-Hsin Kuo, Huai-Sheng Huang, Ming-Chao Huang, Wen-Cheng Hoffer, Barry J. Cheng, Henrich TI Dual effect of adenovirus-mediated transfer of BMP7 in mixed neuron-glial cultures: Neuroprotection and cellular differentiation SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE neuroprotection; cortical neurons; adenovirus; OP1; CGRP ID BONE MORPHOGENETIC PROTEINS; NITRIC-OXIDE; TGF-BETA; PROSTACYCLIN SYNTHASE; SIGNAL-TRANSDUCTION; LINEAGE COMMITMENT; ENDOTHELIAL-CELLS; DENDRITIC GROWTH; PROGENITOR CELLS; GENE-EXPRESSION AB Bone morphogenetic proteins (BMPs), members of the TGF-beta superfamily, have been implicated in nervous system development and in response to injury. Previous studies have shown that recombinant BMP7 can enhance dendritic growth and protect cultured neurons from oxidative stress. Because of the presence of extracellular BMP antagonists, BMP7 seems to act locally. Therefore, the present study uses BMP7 overexpression using adenovirus (Ad)-mediated gene transfer to examine its effect in mixed neuronal cultures. Enhanced BMP7 expression selectively induces neuronal CGRP expression in a time-dependent manner. BMP7 overexpression not only significantly protects cultures from H2O2 toxicity but reduces lipopolysaccharide (LPS) stimulation. Concurrently, it profoundly reduces microglial numbers, but increases oligodendroglial and endothelial cells. Together, low-dose and continuously expressed BMP7 is both neuroprotective and differentiation-inductive. (c) 2007 Wiley-Liss, Inc. C1 Taipei Vet Gen Hosp, Neural Regenerat Lab, Dept Neurosurg, Neurol Inst, Taipei 11217, Taiwan. Natl Dong Hwa Univ, Dept Biotechnol, Hualien, Taiwan. Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. NIDA, NIH, Baltimore, MD USA. Natl Yang Ming Univ, Inst Pharmacol, Taipei 112, Taiwan. Taipei Vet Gen Hosp, Neurol Inst, Ctr Neural Regenerat, Taipei, Taiwan. RP Cheng, H (reprint author), Taipei Vet Gen Hosp, Neural Regenerat Lab, Dept Neurosurg, Neurol Inst, 322 Shih Pai Rd,Sec 2, Taipei 11217, Taiwan. EM hc_cheng@vghtpe.gov.tw NR 45 TC 24 Z9 24 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT PY 2007 VL 85 IS 13 BP 2950 EP 2959 DI 10.1002/jnr.21395 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 222DD UT WOS:000250275400017 PM 17628501 ER PT J AU Timmers, HJLM Hadi, M Carrasquillo, JA Chen, CC Martiniova, L Whatley, M Ling, A Eisenhofer, G Adams, KT Pacak, K AF Timmers, Henri J. L. M. Hadi, Mohiuddin Carrasquillo, Jorge A. Chen, Clara C. Martiniova, Lucia Whatley, Millie Ling, Alexander Eisenhofer, Graeme Adams, Karen T. Pacak, Karel TI The effects of carbidopa on uptake of 6-F-18-fluoro-L-DOPA in PET of pheochromocytorna and extraadrenal abdominal paraganglioma SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE 6-fluoro-DOPA; 6-F-18-fluorodopamine; carbidopa; pheochromocytoma; paraganglioma; positron emission tomography; standardized uptake value; region of interest ID POSITRON-EMISSION-TOMOGRAPHY; F-18 DOPA PET; CARCINOID-TUMORS; NEUROENDOCRINE TUMORS; DECARBOXYLASE; VISUALIZATION; PRETREATMENT; BENIGN AB 6-F-18-fluoro-L-3,4-dihydroxyphenylalanine (F-18-DOPA) PET is a useful tool for the detection of certain neuroendocrine tumors, especially with the preadministration of carbidopa, an inhibitor of DOPA decarboxylase. Whether carbidopa also improves F-18-DOPA PET of adrenal pheochromocytomas and extraadrenal paragangliornas is unknown. The aim of this study was to investigate the sensitivity of F-18-DOPA PET in the detection of paraganglioma and its metastatic lesions and to evaluate whether tracer uptake by the tumors is enhanced by carbidopa. Methods: Two patients with nonmetastatic adrenal pheochromocytoma, and 9 patients with extraadrenal abdominal paraganglioma (1 nonmetastatic, 8 metastatic), underwent whole-body CT, MRI, baseline F-18-DOPA PET, and F-18-DOPA PET with oral preadministration of 200 mg of carbidlopa. The dynamics of tracer uptake by these lesions and the physiologic distribution of F-18-DOPA in normal tissues were recorded. Results: Seventy-eight lesions were detected by CT or MRI, 54 by baseline F-18-DOPA PET (P = 0.0022 vs. CT/MRI), and 57 by F-18-DOPA PET plus carbidopa (P = 0.0075 vs. CT/MRI, not statistically significant vs. baseline). In reference to findings on CT and MRI, the sensitivities of baseline F-18-DOPA PET were 47.4% for lesions and 55.6% for positive body regions, versus 50.0% (lesions) and 66.7% (regions) for F-18-DOPA PET plus carbidopa (neither is statistically significant vs. baseline). Compared with baseline, carbidopa detected additional lesions in 3 (27%) of 11 patients. Carbidopa increased the mean (+/- SD) peak standardized uptake value in index tumor lesions from 6.4 +/- 3.9 to 9.1 +/- 5.6 (P = 0.037). Pancreatic physiologic F-18-DOPA uptake, which may mask adrenal pheochromocytoma, is blocked by carbidopa. Conclusion: Carbidopa enhances the sensitivity of F-18-DOPA PET for adrenal pheochromocytomas and extraadrenal abdominal paraganglionnas by increasing the tumor-to-background ratio of tracer uptake. The sensitivity of F-18-DOPA PET for metastases of paraganglionna appears to be limited. C1 [Timmers, Henri J. L. M.; Martiniova, Lucia; Adams, Karen T.; Pacak, Karel] Natl Inst Child Hlth & Human Dev, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Endocrinol, Nijmegen, Netherlands. [Hadi, Mohiuddin; Carrasquillo, Jorge A.; Chen, Clara C.; Whatley, Millie] Natl Inst Hlth, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD USA. [Ling, Alexander] Natl Inst Hlth, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD USA. [Eisenhofer, Graeme] Natl Inst Hlth, Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Bethesda, MD USA. RP Pacak, K (reprint author), Natl Inst Child Hlth & Human Dev, Reprod Biol & Med Branch, 10 Ctr Dr,Bldg 10,CRC,RM 1-E 3140,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Carrasquillo, Jorge/E-7120-2010; Hadi, Mohiuddin/H-5682-2012 FU Intramural NIH HHS NR 27 TC 77 Z9 77 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 2007 VL 48 IS 10 BP 1599 EP 1606 DI 10.2967/jnumed.107.042721 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258UK UT WOS:000252894800028 PM 17873132 ER PT J AU Fowler, JS Kroll, C Ferrieri, R Alexoff, D Logan, J Dewey, SL Schiffer, W Schlyer, D Carter, P King, P Shea, C Xu, YW Muench, L Benveniste, H Vaska, P Volkow, ND AF Fowler, Joanna S. Kroll, Carsten Ferrieri, Richard Alexoff, David Logan, Jean Dewey, Stephen L. Schiffer, Wynne Schlyer, David Carter, Pauline King, Payton Shea, Colleen Xu, Youwen Muench, Lisa Benveniste, Helene Vaska, Paul Volkow, Nora D. TI PET studies of d-methamphetamine pharmacokinetics in primates: Comparison with l-methamphetamine and (-)-cocaine SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; methamphetamine; C-11; brain; peripheral organs ID EMISSION-TOMOGRAPHY PET; C-11 METHAMPHETAMINE; BRAIN DISTRIBUTION; COCAINE; BINDING; RADIOTRACERS; ASSOCIATION; MONKEYS; BABOON; MICE AB The methamphetamine molecule has a chiral center and exists as 2 enantiomers, d-methamphetamine (the more active enantiomer) and 1-methamphetamine (the less active enantiomer). d-Methamphetamine is associated with more intense stimulant effects and higher abuse liability. The objective of this study was to measure the pharmacokinetics of d-methamphetamine for comparison with both l-methamphetamine and (-)-cocaine in the baboon brain and peripheral organs and to assess the saturability and pharmacologic specificity of binding. Methods: d- and l-methamphetamine and (-)-cocaine were labeled with C-11 via alkylation of the norprecursors with C-11-methyl iodide using literature methods. Six different baboons were studied in 11 PET sessions at which 2 radiotracer injections were administered 2-3 h apart to determine the distribution and kinetics of C-11-d-methamphetamine in brain and peripheral organs. Saturability and pharmacologic specificity were assessed using pretreatment with d-methamphetamine, methylphenidate, and tetrabenazine. C-11-d-Methamphetamine pharmacokinetics were compared with C-11-l-methamphetamine and C-11-(-)-cocaine in both brain and peripheral organs in the same animal. Results: C-11-d- and l-methamphetamine both showed high uptake and widespread distribution in the brain. Pharmacokinetics did not differ between enantionners, and the cerebellum peaked earlier and cleared more quickly than the striatum for both. C-11-d-Methamphetamine distribution volume ratio was not substantially affected by pretreatment with methamphetamine, methylphenidate, or tetrabenazine. Both enantiomers showed rapid, high uptake and clearance in the heart and lungs and slower uptake and clearance in the liver and kidneys. A comparison of 11C-d-methamphetamine and C-11-(-)-cocaine showed that C-11-d-methamphetamine peaked later in the brain than did C-11-(-)-cocaine and cleared more slowly. The 2 drugs showed similar behavior in all peripheral organs examined except the kidneys and pancreas, which showed higher uptake for C-11-d-methamphetamine. Conclusion: Brain pharmacokinetics did not differ between d-and l-methamphetamine and thus cannot account for the more intense stimulant effects of d-methamphetamine. Lack of pharmacologic blockade by methamphetamine indicates that the PET image represents nonspecific binding, though the fact that methamphetamine is both a transporter substrate and an inhibitor may also play a role. A comparison of C-11-d-methamphetamine and C-11-(-)-cocaine in the same animal showed that the slower clearance of methamphetamine is likely to contribute to its previously reported longer-lasting stimulant effects relative to those of (-)-cocaine. High kidney uptake of d-methamphetamine or its labeled metabolites may account for the reported renal toxicity of d-methamphetamine in humans. C1 [Fowler, Joanna S.; Ferrieri, Richard; Alexoff, David; Logan, Jean; Dewey, Stephen L.; Schiffer, Wynne; Schlyer, David; Carter, Pauline; King, Payton; Shea, Colleen; Xu, Youwen; Benveniste, Helene; Vaska, Paul] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Fowler, Joanna S.] Mt Sinai Sch Med, New York, NY USA. [Fowler, Joanna S.] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA. [Kroll, Carsten] Johannes Gutenberg Univ Mainz, Mainz, Germany. [Muench, Lisa; Volkow, Nora D.] NIAAA, Rockville, MD 20852 USA. [Benveniste, Helene] SUNY Stony Brook, Hlth Sci Ctr, Dept Anesthesiol, Stony Brook, NY 11794 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Rockville, MD USA. RP Fowler, JS (reprint author), Brookhaven Natl Lab, Dept Med, Bldg 555,POB 5000, Upton, NY 11973 USA. EM fowler@bnl.gov OI Logan, Jean/0000-0002-6993-9994 FU NIDA NIH HHS [K05 DA020001, K05 DA020001-03, K05DA020001] NR 40 TC 26 Z9 26 U1 4 U2 11 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 2007 VL 48 IS 10 BP 1724 EP 1732 DI 10.2967/jnumed.107.040279 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258UK UT WOS:000252894800044 PM 17873134 ER PT J AU Jiang, CC Chiang, H Liao, CJ Lin, YJ Kuo, TF Shieh, CS Huang, YY Tuan, RS AF Jiang, Ching-Chuan Chiang, Hongsen Liao, Chun-Jen Lin, Yu-Ju Kuo, Tzong-Fu Shieh, Chang-Shun Huang, Yi-You Tuan, Rocky S. TI Repair of porcine articular cartilage defect with a biphasic osteochondral composite SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE autologous chondrocyte implantation; biphasic osteochondral composite ID FULL-THICKNESS DEFECTS; AUTOLOGOUS CHONDROCYTE TRANSPLANTATION; MESENCHYMAL STEM-CELLS; AUTOGENOUS PERIOSTEAL GRAFTS; CONTINUOUS PASSIVE MOTION; IN-VITRO; BIODEGRADABLE POLYMER; ENGINEERED CARTILAGE; JOINT SURFACES; MARROW-CELLS AB Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with beta-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress-relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone. (c) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Natl Taiwan Univ Hosp, Taipei, Taiwan. Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. Ind Technol Res Inst, Hsinchu, Taiwan. Natl Taiwan Univ, Vet Hosp, Taipei 10764, Taiwan. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, 50 S Dr,Bldg 50 Room 1523, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov OI Jiang, Ching-Chuan/0000-0001-7954-0875; Chiang, Hongsen/0000-0001-8781-5146; KUO, TZONG-FU/0000-0002-6328-8967 FU Intramural NIH HHS; NIAMS NIH HHS [AR Z01 41131] NR 59 TC 83 Z9 91 U1 2 U2 25 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD OCT PY 2007 VL 25 IS 10 BP 1277 EP 1290 DI 10.1002/jor.20442 PG 14 WC Orthopedics SC Orthopedics GA 213MF UT WOS:000249671000003 PM 17576624 ER PT J AU Khoromi, S Blackman, MR Kingman, A Patsalides, A Matherry, LA Adams, S Pilla, AA Max, MB AF Khoromi, Suzan Blackman, Marc R. Kingman, Albert Patsalides, Athos Matherry, Leigh Ann Adams, Sandra Pilla, Arthur A. Max, Mitchell B. TI Low intensity permanent magnets in the treatment of chronic lumbar radicular pain SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE magnet therapy; chronic lumbar radicular pain; chronic sciatica ID PLACEBO-CONTROLLED TRIAL; LOW-BACK-PAIN; DOUBLE-BLIND; STATIC MAGNETS; DIABETIC-NEUROPATHY; ACTION-POTENTIALS; PRIMARY-CARE; FIELDS; FIBROMYALGIA; DESIPRAMINE AB We assessed the pain-relieving efficacy of static magnetic fields produced by 200 Gauss (G) magnets compared with 50 G magnets in a double-blind, randomized, two-phase crossover study in patients with chronic lumbar radicular pain. The surface field strengths of the magnets were 200 and 50 G. Phase I included four random periods of two-week duration: two periods with 200 G, one period with 50 G, and one period of "no treatment." The magnets were positioned either vertically or horizontally in standard lumbosacral elastic corsets. Phase II consisted of two five-week periods with the most effective magnet from Phase I and its corresponding 50 or 200 G device. The primary outcome was average daily leg pain score (0-10 scale) in each period of Phase II. Thirty-eight of 40 randomized patients completed Phase I, and 28 of 31 Phase II participants completed the study. In Phase I, pain scores did not differ significantly between 200 and 50 G magnets. Phase H average leg pain scores tended to be lower with 200 vs. 50 G magnets (3.2 +/- 2.1 for 200 G vs. 3.9 +/- 2.2 for 50 G magnets [P = 0.08]) after excluding one unblinded patient. The relative treatment effect of the 200 G magnets appeared to increase throughout the five-week period. Although these data cannot rule out a chance effect, the positive trends suggest that larger, longer-duration, sham-controlled trials with 200 G magnets be considered in patients with chronic lumbar radicular pain. C1 NIMH, Sect Dev Genet Epidemiol, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20814 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Biomed Engn, New York, NY USA. RP Khoromi, S (reprint author), NIMH, Sect Dev Genet Epidemiol, Natl Ctr Complementary & Alternat Med, 35 Convent Dr,Bldg 35,1A102 MSC-3720, Bethesda, MD 20814 USA. EM khoromisu@mail.nih.gov NR 40 TC 8 Z9 9 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD OCT PY 2007 VL 34 IS 4 BP 434 EP 445 DI 10.1016/j.jpainsymman.2006.12.008 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 220MA UT WOS:000250159600013 PM 17618081 ER PT J AU Salto, S Heller, T Yoneda, M Takahashi, H Nakajima, A Liang, JT AF Salto, Satoru Heller, Theo Yoneda, Masato Takahashi, Hirokazu Nakajima, Atsushl Liang, Jake T. TI Lifestyle-related diseases of the digestive system: A new in vitro model of hepatitis C virion production: Application of basic research on hepatitis C virus to clinical medicine SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 80th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2007 CL Nagoya, JAPAN SP Japanese Pharmacol Soc DE life style-related disease; hepatitis C virus (HCV); replication; in vitro system; HCV-like particle; particle ID CELL-CULTURE; RNA REPLICATION; HEPATOCELLULAR-CARCINOMA; EFFICIENT REPLICATION; IMMUNE-RESPONSES; INSECT CELLS; CDNA-CLONE; PARTICLES; GENOME; LIVER AB The hepatitis C virus (HCV) is an enveloped virus with a single positive-strand RNA genome of about 9.6 kb. It is a major cause of liver disease worldwide. Clear understanding of the viral life cycle has been hampered by the lack of a robust cell culture system. While the development of the HCV replicon system was a major breakthrough, infectious virions could not be produced with the replicon system. Recently, several groups have reported producing HCV virions using in vitro systems. One of these is a replicon system, but with the special genotype 2a strain JFH-1. Another is a DNA transfection system, with the construct containing the cDNA of the known infectious HCV genotype 1b flanked by two ribozymes. The development of these models further extends the repertoire of tools available for the study of HCV biology, and in particular, they may help to elucidate the molecular details of hepatitis C viral assembly and release. This review discusses the progression of experimental strategies related to HCV and how these strategies may be applied to clinical medicine. C1 Yokohama City Univ, Sch Med, Div Gastroenterol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. NIDDK, Liver Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Salto, S (reprint author), Yokohama City Univ, Sch Med, Div Gastroenterol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM ssai1423@yokohama-cu.ac.jp NR 54 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 EI 1347-8648 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PD OCT PY 2007 VL 105 IS 2 BP 138 EP 144 DI 10.1254/jphs.FM0070040 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 225RW UT WOS:000250536100004 ER PT J AU Buehler, PW D'Agnillo, F Hoffman, V Alayash, AI AF Buehler, Paul W. D'Agnillo, Felice Hoffman, Victoria Alayash, Abdu I. TI Effects of endogenous ascorbate on oxidation, oxygenation, and toxicokinetics of cell-free modified hemoglobin after exchange transfusion in rat and guinea pig SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CROSS-LINKED HEMOGLOBIN; BOVINE HEMOGLOBIN; BLOOD-VOLUME; URIC-ACID; IN-VITRO; PHASE-I; CARRIERS; METHEMOGLOBIN; BIOSYNTHESIS; SUBSTITUTES AB Chemically modified hemoglobin (Hb) solutions are promising oxygen therapeutics; however, these agents are prone to intravascular oxidation. Using a 50% exchange transfusion ( ET) model with bovine polymerized hemoglobin (PolyHbBv), we examined heme oxidation, oxygenation markers, and toxicokinetics in rats, an ascorbic acid (AA)- producing species, and in guinea pigs, a non-AA-producing species. Plasma AA decreased by 50% in guinea pigs after ET, but it was unchanged in rats for the first 20 h post-ET. Both species cleared PolyHbBv from the circulation at similar rates. However, exposure to ferric PolyHbBv over time was 5-fold greater in the guinea pig. Mass spectrometry analysis of plasma revealed oxidative modifications within the tetrameric fraction of PolyHbBv in guinea pig. Oxygen equilibrium curves of PolyHbBv measured in plasma after ET were more left-shifted in guinea pigs compared with rats, consistent with increased ferric PolyHbBv formation. Renal hypoxia-inducible factor (HIF)-1 alpha, whose activity strictly depends on the partial pressure of oxygen increased over time, and it correlated inversely with circulating ferrous PolyHbBv in both species. Interestingly, HIF-1 alpha activity was greater in guinea pigs compared with rats at 72 h post-ET. Mean arterial pressure increases were also greater in guinea pigs; however, minimal differences in cardiac and renal pathology were observed in either species. The present findings suggest the importance of plasma AA in maintaining the stability of acellular Hb susceptible to oxidation, and they may be relevant to humans, which display a similar plasma/tissue antioxidant status to guinea pig. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. NIH, Div Vet Sci, Off Ctr Director, Bethesda, MD 20892 USA. RP Buehler, PW (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, 8800 Rockville Pike,Bldg 29,Rm 129, Bethesda, MD 20892 USA. EM paul.buehler@fda.hhs.gov NR 34 TC 44 Z9 44 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 2007 VL 323 IS 1 BP 49 EP 60 DI 10.1124/jpet.107.126409 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 212IF UT WOS:000249588900006 PM 17622572 ER PT J AU Marczak, ED Jinsmaa, Y Li, T Bryant, SD Tsuda, Y Okada, Y Lazarus, LH AF Marczak, Ewa D. Jinsmaa, Yunden Li, Tingyou Bryant, Sharon D. Tsuda, Yuko Okada, Yoshio Lazarus, Lawrence H. TI [N-Allyl-Dmt(1)]-Endomorphins are mu-opioid receptor antagonists lacking inverse agonist properties SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT International Narcotics Research Conference CY JUL 09-14, 2006 CL St Paul, MN ID BASAL SIGNALING ACTIVITY; ETHANOL-CONSUMPTION; NEUTRAL ANTAGONISTS; NARCOTIC DEPENDENCE; CHRONIC MORPHINE; KNOCKOUT MICE; UP-REGULATION; NEURAL CELLS; WILD-TYPE; NALOXONE AB [N-Allyl- Dmt(1)]-endomorphin-1 and -2 ([N-allyl-Dmt(1)]-EM-1 and -2) are new selective mu-opioid receptor antagonists obtained by N-alkylation with an allyl group on the amino terminus of 2 ', 6 '-dimethyl- L-tyrosine (Dmt) derivatives. To further characterize properties of these compounds, their intrinsic activities were assessed by functional guanosine 5 '-O-(3-[S-35] thiotriphosphate) binding assays and forskolin-stimulated cyclic AMP accumulation in cell membranes obtained from vehicle, morphine, and ethanol-treated SK-N-SH cells and brain membranes isolated from naive and morphine-dependent mice; their mode of action was compared with naloxone or naltrexone, which both are standard nonspecific opioid-receptor antagonists. [N-Allyl-Dmt(1)]-EM-1 and -2 were neutral antagonists under all of the experimental conditions examined, in contrast to naloxone and naltrexone, which behave as neutral antagonists only in membranes from vehicle-treated cells and mice but act as inverse agonists in membranes from morphine- and ethanol-treated cells as well as morphine- treated mice. Both endomorphin analogs inhibited the naloxone- and naltrexone-elicited withdrawal syndromes from acute morphine dependence in mice. This suggests their potential therapeutic application in the treatment of drug addiction and alcohol abuse without the adverse effects observed with inverse agonist alkaloid-derived compounds that produce severe withdrawal symptoms. C1 Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. Jilin Univ, Dept Chem, Changchun, Jilin, Peoples R China. Kobe Gakuin Univ, Dept Med Chem, Fac Pharmaceut Sci, Kobe, Hyogo 65121, Japan. Kobe Gakuin Univ, High Technol Res Ctr, Fac Pharmaceut Sci, Kobe, Hyogo 65121, Japan. RP Marczak, ED (reprint author), Natl Inst Environm Hlth Sci, Med Chem Grp, Lab Pharmacol & Chem, POB 12233,MD C304, Res Triangle Pk, NC USA. EM marczake@niehs.nih.gov FU Intramural NIH HHS NR 39 TC 11 Z9 11 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 2007 VL 323 IS 1 BP 374 EP 380 DI 10.1124/jpet.107.125807 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 212IF UT WOS:000249588900042 PM 17626793 ER PT J AU Ward, MM AF Ward, Michael M. TI Medical insurance, socioeconomic status, and age of onset of endstage renal disease in patients with lupus nephritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE medical insurance; socioeconomic status; health disparities; endstage renal disease; systemic lupus erythematosus ID PROGNOSTIC FACTORS; SINGLE-CENTER; ERYTHEMATOSUS; MORBIDITY; FAILURE; BIOPSY; COHORT; PERIOD; CARE AB Objective. Limited access to care may hasten progression to endstage renal disease (ESRD) in patients with lupus nephritis. We examined associations between type of medical insurance, socioeconomic status (SES), and age at onset of ESRD in a national, population-based cohort. Methods. Using the United States Renal Data System, incident cases of ESRD due to lupus nephritis in the US from January 1, 1996, to June 30, 2004, were examined in this cross-sectional study (n = 797 1). Age at onset of ESRD was compared among patients with different types of medical insurance and by SES. Results. In each ethnic croup, patients with private insurance were older at the onset of ESRD than those with no insurance or Medicaid. For example, whites with private insurance were on average 7.5 years older than those with no insurance and 8.2 years older than those with Medicaid. There were no differences in age at onset of ESRD between those with no insurance and those with Medicaid. SES, based on the socioeconomic characteristics of the patient's area of residence, was associated with age of onset of ESRD only in whites. Conclusion. Among patients with lupus nephritis who develop ESRD, those with private medical insurance are older when they begin ESRD treatment than those with Medicaid or no insurance. Given that medical insurance is unrelated to the age at onset of lupus nephritis, these findings suggest that progression to ESRD varies with medical insurance status, possibly because of differences in quality of care or access to care. C1 NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMS NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA. EM wardtm1@mail.nih.gov FU Intramural NIH HHS NR 19 TC 23 Z9 24 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2007 VL 34 IS 10 BP 2024 EP 2027 PG 4 WC Rheumatology SC Rheumatology GA 217OB UT WOS:000249956100014 PM 17696272 ER PT J AU Bouali, H Nietert, P Nowling, TM Pandey, J Dooley, MA Cooper, G Harley, J Kamen, DL Oates, J Gilkeson, G AF Bouali, Henda Nietert, Paul Nowling, Tamara M. Pandey, Janardan Dooley, Mary Anne Cooper, Glinda Harley, John Kamen, Diane L. Oates, Jim Gilkeson, Gary TI Association of the G-463A myeloperoxidase gene polymorphism with renal disease in African Americans with systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; myeloperoxidase; polymorphism; African American; lupus nephritis ID NITRIC-OXIDE SYNTHASE; PROMOTER POLYMORPHISMS; RISK; MICE; DNA; ATHEROSCLEROSIS; PEROXIDASES; EXPRESSION; KIDNEY; MPO AB Objective. Myeloperoxidase (MPO) is an enzyme expressed in neutrophils that is involved in tissue damage in inflammatory renal diseases. A functional G to A single-nucleotide polymorphism (SNP) is present at position -463 of the MPO promoter region and is associated with altered MPO expression. We hypothesized that the G-463A MPO SNP is a risk factor for developing lupus nephritis (LN) due to its potential influence on the inflammatory response. Methods. DNA from 229 patients with SLE and 277 controls from the Carolina Lupus cohort, 58 African American patients from the Sea Island Lupus Cohort, and 51 African American patients from the Lupus Multiplex Registry and Repository were genotyped by PCR. A linear regression model was used to examine relationships between the MPO genotype, case/control status, demographic characteristics, and LN. Results. There was no association of MPO genotype with systemic lupus erythematosus (SLE). However, the odds of developing LN were significantly higher among those with an A allele, compared to those without, in African American cases of all 3 cohorts. When the likelihood of developing LN was compared across MPO genotypes, the risk of developing LN was significantly higher among cases with a GA genotype versus GG (OR 2.11, 95% CI 1.12 to 3.97) and even higher with AA versus GG (OR 3.52, 95% CI 1.41 to 8.77). Conclusion. While the G-463A MPO SNP is not a risk factor for developing SLE, the low expressing A allele is a significant risk factor for developing LN that is gene dosage-dependent in African Americans. C1 Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. Univ N Carolina, Affiliated Hosp, Dept Med, Chapel Hill, NC 27515 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Gilkeson, G (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, 96 Jonathan Lucas St,Suite 912,POB 250623, Charleston, SC 29425 USA. EM gilkeson@musc.edu OI Nietert, Paul/0000-0002-3933-4986 FU NCRR NIH HHS [M01 RR001070-280263, M01 RR001070-220263, M01 RR001070-25A10263, M01 RR001070-240263, M01 RR001070, M01 RR001070-24S50263, M01 RR001070-25A1S20263, M01 RR001070-230263, M01 RR001070-260263, M01 RR001070-270263, M01 RR001070-25A1S10263]; NIAMS NIH HHS [P60 AR049459, AR47469, P30 AR053483] NR 49 TC 15 Z9 18 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2007 VL 34 IS 10 BP 2028 EP 2034 PG 7 WC Rheumatology SC Rheumatology GA 217OB UT WOS:000249956100015 PM 17896805 ER PT J AU Aronova, MA Kim, YC Harmon, R Sousa, AA Zhang, G Leapman, RD AF Aronova, M. A. Kim, Y. C. Harmon, R. Sousa, A. A. Zhang, G. Leapman, R. D. TI Three-dimensional elemental mapping of phosphorus by quantitative electron spectroscopic tomography (QuEST) SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE electron tomography; energy filtered transmission electron microscopy (EFTEM); electron energy loss spectroscopy; phosphorus; ribosome; nucleus; chromatin; 3-D reconstruction; quantitative elemental imaging ID ENERGY-LOSS SPECTROSCOPY; RECONSTRUCTION; MICROSCOPY; VISUALIZATION; MICROANALYSIS; DISTRIBUTIONS; PROJECTIONS; RESOLUTION; CHROMATIN; ALGORITHM AB We describe the development of quantitative electron spectroscopic tomography (QuEST), which provides 3-D distributions of elements on a nanometer scale. Specifically, it is shown that QuEST can be applied to map the distribution of phosphorus in unstained sections of embedded cells. A series of 2-D elemental maps is derived from images recorded in the energy filtering transmission electron microscope for a range of specimen tilt angles. A quantitative 3-D elemental distribution is then reconstructed from the elemental tilt series. To obtain accurate quantitative elemental distributions it is necessary to correct for plural inelastic scattering at the phosphorus L-2,L-3 edge, which is achieved by acquiring unfiltered and zero-loss images at each tilt angle. The data are acquired automatically using a cross correlation technique to correct for specimen drift and focus change between successive tilt angles. An algorithm based on the simultaneous iterative reconstruction technique (SIRT) is implemented to obtain quantitative information about the number of phosphorus atoms associated with each voxel in the reconstructed volume. We assess the accuracy of QuEST by determining the phosphorus content of ribosomes in a eukaryotic cell, and then apply it to estimate the density of nucleic acid in chromatin of the cell's nucleus. From our experimental data, we estimate that the sensitivity for detecting phosphorus is 20 atoms in a 2.7 nm-sized voxel. Published by Elsevier Inc. C1 NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Gatan Inc, Pleasanton, CA 94588 USA. RP Leapman, RD (reprint author), NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. EM leapmanr@mail.nih.gov FU Intramural NIH HHS [Z01 OD022012-03] NR 49 TC 30 Z9 30 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 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD OCT PY 2007 VL 160 IS 1 BP 35 EP 48 DI 10.1016/j.jsb.2007.06.008 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 215UN UT WOS:000249834600004 PM 17693097 ER PT J AU Sporn, AL Vermani, A Greenstein, DK Bobb, AJ Spencer, EP Clasen, LS Tossell, JW Stayer, CC Gochman, PA Lenane, MC Rapoport, JL Gogtay, N AF Sporn, Alexandra L. Vermani, Anoop Greenstein, Deanna K. Bobb, Aaron J. Spencer, Edgar P. Clasen, Liv S. Tossell, Julia W. Stayer, Catherine C. Gochman, Peter A. Lenane, Marge C. Rapoport, Judith L. Gogtay, Nitin TI Clozapine treatment of childhood-onset schizophrenia: Evaluation of effectiveness, adverse effects, and long-term outcome SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE clozapine; schizophrenia; childhood; treatment; concentration ID PLASMA-CONCENTRATIONS; CLINICAL-RESPONSE; DOUBLE-BLIND; K-SADS; CHILDREN; ADOLESCENTS; RESISTANT; NORCLOZAPINE; HALOPERIDOL; ASSOCIATION AB Objective: Clozapine is a unique atypical antipsychotic with superior efficacy in treatment-resistant schizophrenia. Plasma concentration of clozapine and its major metabolite N-desmethylclozapine (NDMC) as well as the ratio of NDMC to clozapine have been reported to be predictors of clozapine response. Here we evaluate these as well as other measures in an effort to find predictors of response to clozapine in our early-onset treatment-refractory population. Method: Fifty-four children and adolescents participated in double-blind (n = 22) or open-label (n = 32) clozapine trials. Clinical evaluations took place at baseline, week 6 on clozapine, and at 2- to 6-year follow-up. The data were analyzed in relation to demographics, age at onset, 10, clozapine dose, and plasma concentrations of prolactin, clozapine, NDMC, and NDMC/clozapine ratio. Stepwise regression and correlation analyses were performed to find predictors of treatment response. Results: Clinical improvement after 6 weeks of clozapine treatment, as measured by the percentage of improvement on the Brief Psychiatric Rating Scale and the Scale for the Assessment of Positive Symptoms, was strongly associated with the NDMC/clozapine ratio at the 6-week time point (Pearson correlation coefficient: r= 0.41; p <.01 for Brief Psychiatric Rating Scale and r= 0.43; p <.01 for Scale for the Assessment of Positive Symptoms). Although the rate of side effects was higher than that typically found in the adult population, it did not appear to be related to clozapine dose, clozapine or NDMC plasma concentrations, or NDMC/clozapine ratio. Outcome at long-term follow-up, as measured by Children's Global Assessment Scale, was associated with lesser illness severity at baseline and with greater improvement during the initial 6 weeks of clozapine treatment. Conclusions: The NDMC/clozapine ratio may be a valuable predictor of response to clozapine and may suggest new approaches to clozapine treatment. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Guys & St Thomas Hosp NHS Trust, Med Toxicol Lab, London, England. RP Sporn, AL (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr, New York, NY 10032 USA. EM als2168@columbia.edu RI Gogtay, Nitin/A-3035-2008 FU Intramural NIH HHS NR 50 TC 46 Z9 49 U1 5 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2007 VL 46 IS 10 BP 1349 EP 1356 DI 10.1097/chi.0b013e31812eed10 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 215IV UT WOS:000249802900013 PM 17885577 ER PT J AU Geller, AC Swetter, SM Brooks, K Demierre, MF Yaroch, AL AF Geller, Alan C. Swetter, Susan M. Brooks, Katie Demierre, Marie-France Yaroch, Amy L. TI Screening, early detection, and trends for melanoma: Current status (2000-2006) and future directions SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID SKIN SELF-EXAMINATION; CUTANEOUS MALIGNANT-MELANOMA; PRIMARY-CARE PHYSICIANS; SQUAMOUS-CELL CARCINOMA; HIGH-RISK; UNITED-STATES; CANCER PREVENTION; SUBSEQUENT MALIGNANCIES; DERMATOLOGICAL PRACTICE; SECONDARY-PREVENTION AB In the past 5 years, there have been notable strides toward the earlier recognition and discovery of melanoma, including new technologies to complement and augment the clinical examination and new insights to help clinicians recognize early melanoma. However, incidence and mortality rates throughout most of the developed world have risen over the past 25 years, while education and screening, potentially the best means for reducing the disease, continue to be severely underutilized. Much progress needs to be made to reach middle-aged and older men and persons of lower socioeconomic status who suffer a disproportionate burden of death from melanoma. Worldwide melanoma control must also be a priority, and comprehensive educational and screening programs should be directed to Northern Ireland and a number of Eastern European nations, whose 5-year survival rates range between 53% and 60%, mirroring those of the United States and Australia more than 40 years ago. Learning objective: After completing this learning activity, participants should be aware of the most recent melanoma epidemiologic data, both in the United States and internationally; worldwide early detection and screening programs., clinical strategies to recognize and improve the detection of early melanoma; the latest technologies for early detection of melanoma; and public and professional education programs designed to enhance early detection. C1 Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Stanford Univ, Vet Affairs Palo ALto Hlth Care Syst, Palo Alto, CA 94304 USA. Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Geller, AC (reprint author), Boston Univ, Sch Med, Dept Dermatol, DOB 801A,720 Harrison Ave, Boston, MA 02118 USA. EM ageller@bu.edu NR 152 TC 128 Z9 131 U1 0 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2007 VL 57 IS 4 BP 555 EP 572 DI 10.1016/j.jaad.2007.06.032 PG 18 WC Dermatology SC Dermatology GA 213VQ UT WOS:000249695600001 PM 17870429 ER PT J AU Norton, JA Jensen, RT AF Norton, Jeffrey A. Jensen, Robert T. TI Role of surgery in Zollinger-Ellison syndrome SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; LYMPH-NODE GASTRINOMA; SURGICAL-MANAGEMENT; NATURAL-HISTORY; DUODENAL GASTRINOMAS; PREDICTIVE FACTORS; TUMORS; LOCALIZATION; RESECTION; SURVIVAL C1 Stanford Univ, Dept Surg, Palo Alto, CA 94304 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. RP Norton, JA (reprint author), Stanford Univ, Ctr Med, Dept Surg, 300 Pasteur Dr H-3591, Stanford, CA 94305 USA. EM janorton@stanford.edu FU Intramural NIH HHS NR 28 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD OCT PY 2007 VL 205 IS 4 SU S BP S34 EP S37 DI 10.1016/j.jamcollsurg.2007.06.320 PG 4 WC Surgery SC Surgery GA 225ID UT WOS:000250509400006 PM 17916516 ER PT J AU Fried, LF Boudreau, R Lee, JS Chertow, G Kurella-Tamura, M Shlipak, MG Ding, J Sellmeyer, D Tylavsky, FA Simsonick, E Kritchevsky, SB Harris, TB Newman, AB AF Fried, Linda F. Boudreau, Robert Lee, Jung Sun Chertow, Glenn Kurella-Tamura, Manjula Shlipak, Michael G. Ding, Jingzhong Sellmeyer, Deborah Tylavsky, Frances A. Simsonick, Eleanor Kritchevsky, Stephen B. Harris, Tamara B. Newman, Anne B. CA Hlth, Aging Body Composition Study TI Kidney function as a predictor of loss of lean mass in older adults: Health, aging and body composition study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE kidney function; elderly; weight loss; body composition; sarcopenia ID MUSCLE PROTEIN BREAKDOWN; CHRONIC-RENAL-FAILURE; SKELETAL-MUSCLE; WEIGHT-LOSS; HEMODIALYSIS-PATIENTS; NUTRITIONAL-STATUS; DISEASE; INFLAMMATION; MORTALITY; MEN AB OBJECTIVES: To assess the association between kidney function and change in body composition in older individuals. DESIGN: Prospective cohort study. SETTING: Two sites, Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Three thousand twenty-six well-functioning, participants aged 70 to 79 in the Health, Aging and Body Composition Study. MEASUREMENTS: Body composition (bone-free lean mass and fat mass) was measured using dual x-ray absorptiometry annually for 4 years. Kidney function was measured at baseline according to serum creatinine (SCr). Comorbidity and inflammatory markers were evaluated as covariates in mixed-model, repeated-measures analysis. RESULTS: High SCr was associated with loss of lean mass in men but not women, with a stronger relationship in black men (P=.02 for difference between slopes for white and black men). In white men, after adjustment for age and comorbidity, higher SCr remained associated with loss of lean mass (-0.07 +/- 0.03 kg/y greater loss per 0.4 mg/dL (1 standard deviation (SD)), P=.009) but was attenuated after adjustment for inflammatory factors (-0.05 +/- 0.03 kg/y greater loss per SD, P=.10). In black men, the relationship between SCr and loss of lean mass (-0.19 +/- 0.04 kg/y per SD, P <.001) persisted after adjustment for inflammation and overall weight change. CONCLUSION: Impaired kidney function may contribute to loss of lean mass in older men. Inflammation appeared to mediate the relationship in white but not black men. Future studies should strive to elucidate mechanisms linking kidney disease and muscle loss and identify treatments to minimize loss of lean mass and its functional consequences. C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Renal Electrolyte Div, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. Univ Calif San Francisco, Div Endocrinol & Metab, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Nephrol, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Tennessee, Dept Biostat & Epidemiol, Memphis, TN USA. NIA, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. RP Fried, LF (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Univ Dr,Mailstop 111F-U, Pittsburgh, PA 15240 USA. EM Linda.Fried@va.gov RI Newman, Anne/C-6408-2013; Kurella Tamura, Manjula/C-8284-2014; OI Newman, Anne/0000-0002-0106-1150; Kurella Tamura, Manjula/0000-0001-5227-2479; Boudreau, Robert/0000-0003-0162-5187; Kritchevsky, Stephen/0000-0003-3336-6781 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 31 TC 13 Z9 13 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2007 VL 55 IS 10 BP 1578 EP 1584 DI 10.1111/j.1532-5415.2007.01398.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 215RA UT WOS:000249825500011 PM 17908060 ER PT J AU Stevens, LA Coresh, J Feldman, HI Greene, T Lash, JP Nelson, RG Rahman, M Deysher, AE Zhang, YP Schmid, CH Levey, AS AF Stevens, Lesley A. Coresh, Josef Feldman, Harold I. Greene, Tom Lash, James P. Nelson, Robert G. Rahman, Mahboob Deysher, Amy E. Zhang, Yaping Lucy Schmid, Christopher H. Levey, Andrew S. TI Evaluation of the modification of diet in renal disease study equation in a large diverse population SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; COCKCROFT-GAULT EQUATIONS; GFR-ESTIMATING EQUATIONS; SERUM CREATININE VALUES; BODY-MASS INDEX; PREDICTIVE PERFORMANCE; CHINESE PATIENTS; FORMULA; TRANSPLANTATION AB Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease. Performance of the Modification of Diet in Renal Disease (MDRD) Study equation varies substantially among populations. To describe the performance of the equation in a large, diverse population, estimated GFR (eGFR) was compared to measured GFR (mGFR) in a cross-sectional analysis of 5504 participants in 10 studies that included measurements of standardized serum creatinine and urinary clearance of iothalamate. At eGFR <60 ml/min per 1.73 m(2), the MDRD Study equation had lower bias and higher precision than at eGFR >= 60 ml/min per 1.73 m(2). The accuracy of the equation, measured by the percent of estimates that fell within 30% of mGFR, was similar for eGFR values above or below 60 ml/min per 1.73 m(2) (82% and 84%, respectively). Differences in performance among subgroups defined by age, sex, race, diabetes, transplant status, and body mass index were small when eGFR was <60 ml/min per 1.73 m(2). The MDRD Study equation therefore provides unbiased and reasonably accurate estimates across a wide range of subgroups when eGFR is <60 ml/min per 1.73 m(2). In individual patients, interpretation of GFR estimates near 60 ml/min per 1.73 m(2) should be interpreted with caution to avoid misclassification of chronic kidney disease in the context of the clinical setting. C1 Tufts Univ, New England Med Ctr, Div Nephrol, Boston, MA 02111 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Utah, Salt Lake City, UT USA. Univ Illinois, Chicago, IL USA. Natl Inst Hlth, Phoenix, AZ USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Stevens, LA (reprint author), Tufts Univ, New England Med Ctr, Div Nephrol, 750 Washington St,Box 391, Boston, MA 02111 USA. EM lstevens1@tufts-nemc.org RI Nelson, Robert/B-1470-2012; OI Schmid, Christopher/0000-0002-0855-5313 FU NIDDK NIH HHS [U01 DK 35073, U01 DK 053869, U01 DK 067651] NR 42 TC 315 Z9 334 U1 0 U2 8 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2007 VL 18 IS 10 BP 2749 EP 2757 DI 10.1681/ASN.2007020199 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 231YU UT WOS:000250985900018 PM 17855641 ER PT J AU Kim, BS Kim, SH Kim, SJ Jang, BS Kim, MB Oh, CK Kwon, YW Kwon, KS AF Kim, B-S Kim, S-H Kim, S-J Jang, B-S Kim, M-B Oh, C-K Kwon, Y-W Kwon, K-S TI An unusual complication of systemic lupus erythematosus: bacterial meningitis caused by Streptococcus agalactiae SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Letter ID INFECTIONS C1 Pusan Natl Univ, Sch Med, Dept Dermatol, Pusan 602739, South Korea. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Kwon, KS (reprint author), Pusan Natl Univ, Sch Med, Dept Dermatol, 1-10 Ami Dong, Pusan 602739, South Korea. EM kwonks@pusan.ac.kr NR 6 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0926-9959 J9 J EUR ACAD DERMATOL JI J. Eur. Acad. Dermatol. Venereol. PD OCT PY 2007 VL 21 IS 9 BP 1274 EP 1275 DI 10.1111/j.1468-3083.2007.02167.x PG 4 WC Dermatology SC Dermatology GA 215RG UT WOS:000249826100034 PM 17894731 ER PT J AU Grefsheim, SF Rankin, JA AF Grefsheim, Suzanne F. Rankin, Jocelyn A. TI Information needs and information seeking in a biomedical research setting: a study of scientists and science administrators SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID PRIMARY-CARE; CLINICAL QUESTIONS; PHYSICIANS; PRACTITIONERS; PROFESSIONALS; NETWORK AB Objective: An information needs study of clinical specialists and biomedical researchers was conducted at the US National Institutes of Health (NIH) to inform library services and contribute to a broader understanding of information use in academic and research settings. Methods: A random stratified sample by job category of 500 NIH scientists was surveyed by telephone by an independent consultant using a standardized information industry instrument, augmented with locally developed questions. Results were analyzed for statistical significance using t-tests and chi square. Findings were compared with published studies and an aggregated dataset of information users in business, government, and health care from Outsell. Results: The study results highlighted similarities and differences with other studies and the industry standard, providing insights into user preferences, including new technologies. NIH scientists overwhelmingly used the NIH Library (424/500), began their searches at the library's Website rather than Google (P = < 0.001), were likely to seek information themselves (474/500), and valued desktop resources and services. Conclusion: While NIH staff work in a unique setting, they share some information characteristics with other researchers. The findings underscored the need to continue assessing specialized needs and seek innovative solutions. The study led to improvements or expansion of services such as developing a Website search engine, organizing gene sequence data, and assisting with manuscript preparation. C1 NIH, Div Lib Serv, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, CDC Informat Ctr, Atlanta, GA 30333 USA. RP Grefsheim, SF (reprint author), NIH, Div Lib Serv, 10 Ctr Dr,MSC 1150, Bethesda, MD 20892 USA. EM grefshes@nih.gov; jrankin@cdc.gov NR 21 TC 13 Z9 14 U1 1 U2 15 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD OCT PY 2007 VL 95 IS 4 BP 426 EP 434 DI 10.3163/1536-5050.95.4.426 PG 9 WC Information Science & Library Science SC Information Science & Library Science GA 222DQ UT WOS:000250276700008 PM 17971890 ER PT J AU Chu, KC Miller, BA Springfield, SA AF Chu, Kenneth C. Miller, Barry A. Springfield, Sanya A. TI Measures of racial/ethnic health disparities in cancer mortality rates and the influence of socioeconomic status SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE race/ethnicity; health disparities; cancer; mortality; socioeconomic status ID UNITED-STATES; RECENT TRENDS; SURVIVAL; PATTERNS AB Objectives: In the 1990s, U.S. cancer mortality rates declined due to reductions in tobacco use among men and beneficial cancer interventions, such as mammography and Pap smears. We examined the cancer rates by racial/ethnic group, socioeconomic status and time period to identify disparities underlying the overall mortality trend. Methods: We examined racial/ethnic disparities by measuring excess cancer burden [rate ratio (RR) and ratio differences (RD)] and trends in their cancer rates for nine cancer sites. The trend (T) is calculated as a ratio of the average annual cancer mortality rate for 1995-2000 relative to the rate for 1990-1994 for three levels of poverty (counties with < 10% living below the poverty level, 10%-< 20% and >= 20%) for the major racial/ethnic populations. We also compared the trend for each racial/ethnic SES group to the trend for lowest SES white group (TD). Results: Blacks have RR disparities relative to whites for each cancer site examined, except for female lung cancer, while the other minorities had RR disparities for cervical cancer (RR > 1). There are increases in RR disparities from 1990-1994 to 1995-2000 (RD > 0) for colorectal cancer, prostate cancer and breast cancer for each racial/ethnic minority. Whites and blacks had declining trends for every SES group (T < 1) and positive high SES gradients (the highest SES group had the best trend and the lowest SES group had the worst trend) at each cancer site, except female lung cancer (T > 1). In contrast, American Indians/Alaska natives, Hispanics and Asians/Pacific Islanders had increasing trends for some of their cancer sites, and their trends did not have the SES gradients. Conclusions: Increases in racial/ethnic disparities (RD > 0) for colorectal, breast and prostate cancer were largest in the lowest SES groups. At some cancer sites, the highest SES group for minorities had worse trend results than the trends for the lowest SES white group (TD > 0). C1 NCI, Ctr Reduce Canc Hlth Disparities, Bethesda, MD 20892 USA. RP Chu, KC (reprint author), NCI, Ctr Reduce Canc Hlth Disparities, 1900 Rockville Pike,6116 Executive Blvd,Room 602, Bethesda, MD 20892 USA. EM kc10d@nih.gov NR 18 TC 90 Z9 91 U1 0 U2 8 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD OCT PY 2007 VL 99 IS 10 BP 1092 EP + PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 222DZ UT WOS:000250277600001 PM 17987912 ER PT J AU Zhang, P Guccione, JM Nicholas, SI Walker, JC Crawford, PC Shamal, A Acevedo-Bolton, G Guttman, MA Ozturk, C McVeigh, ER Saloner, DA Wallace, AW Ratcliffe, MB AF Zhang, Peng Guccione, Julius M. Nicholas, Susan I. Walker, Joseph C. Crawford, Philip C. Shamal, Amin Acevedo-Bolton, Gabriel Guttman, Michael A. Ozturk, Cengizhan McVeigh, Elliot R. Saloner, David A. Wallace, Arthur W. Ratcliffe, Mark B. TI Endoventricular patch plasty for dyskinetic anteroapical left ventricular aneurysm increases systolic circumferential shortening in sheep SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID VOLUME REDUCTION SURGERY; FINITE-ELEMENT-ANALYSIS; MECHANICAL DYSFUNCTION; BORDER ZONE; MR-IMAGES; MODEL; RESTORATION; CARDIOMYOPATHY; RECONSTRUCTION; MYOCARDIUM AB Objective: Endoventricular patch plasty ( Dor procedure) has gained favor as a surgical treatment for heart failure associated with large anteroapical myocardial infarction. We tested the hypotheses that the Dor procedure increases systolic circumferential shortening and longitudinal shortening in noninfarcted left ventricular regions in sheep. Methods: In 6 male Dorsett sheep, the left anterior descending coronary artery and its second diagonal branch were ligated 40% of the distance from the apex to the base. Sixteen weeks after myocardial infarction, a Dor procedure was performed with a Dacron patch that was 50% of the infarct neck dimension. Two weeks before and 2 and 6 weeks after the Dor procedure, animals underwent magnetic resonance imaging with tissue tagging in multiple short- axis and long- axis slices. Fully three- dimensional strain analyses were performed. All 6 end- systolic strain components were compared in regions 1 cm, 2 cm, 3 cm, and 4 cm below the valves, as well as in the anterior, posterior, and lateral left ventricular walls and the interventricular septum. Results: Circumferential shortening increased from before the Dor procedure to 6 weeks after repair in nearly every left ventricular region ( 13/ 16). The greatest regional change in circumferential shortening was found in the equatorial region or 2 cm below the base and in the posterior wall ( from 9.0% to 18.4%; P <.0001). Longitudinal shortening increased 2 weeks after the Dor procedure but then returned near baseline by 6 weeks after the Dor procedure. Conclusion: The Dor procedure significantly increases systolic circumferential shortening in nearly all noninfarcted left ventricular regions in sheep. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Dept Vet Affairs Med Ctr, San Francisco, CA USA. NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA. RP Guccione, JM (reprint author), San Francisco VA Med Ctr, Div Surg Serv, 4150 Clement St, San Francisco, CA 94121 USA. EM julius.guccione@med.va.gov RI Ozturk, Cengizhan/A-6177-2016 OI Ozturk, Cengizhan/0000-0002-6966-0774 FU NHLBI NIH HHS [R01 HL063348-01A1, R01 HL063348, R01 HL077921, R01 HL077921-01A2, R01-HL-63348, R01-HL-77921] NR 32 TC 21 Z9 23 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD OCT PY 2007 VL 134 IS 4 BP 1017 EP U80 DI 10.1016/j.jtcvs.2007.03.060 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 215IB UT WOS:000249800600029 PM 17903523 ER PT J AU Olivecrona, GK Gotberg, M Harnek, J Jacobson, KA Jern, S Erlinge, D AF Olivecrona, Goran K. Gotberg, Matthias Harnek, Jan Jacobson, Kenneth A. Jern, Sverker Erlinge, David TI The ADP receptor P2Y(1) mediates t-PA release in pigs during cardiac ischemia SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE ADP; P2Y1; t-PA; coronary; ischemia ID TISSUE-PLASMINOGEN ACTIVATOR; NITRIC-OXIDE; HYPERPOLARIZING FACTOR; MYOCARDIAL-ISCHEMIA; REACTIVE HYPEREMIA; RAT HEARTS; IN-VIVO; ENDOTHELIUM; PURINES; INDUCE AB Background The endothelial ADP receptor P2Y(1) is responsible for a large part of the reactive hyperemia following cardiac ischemia. Tissue plasminogen activator (t-PA) increases during reactive hyperemia. We postulated that the release of t-PA during reactive hyperemia could be mitigated through blocking the coronary endothelial P2Y(1) receptor. Methods t-PA was measured in peripheral arterial blood and locally in the venous blood from the coronary sinus in a porcine model. The stable ADP analogue 2-MeSADP (10(-5) M), alone or as co-infusion with a selective P2Y(1) receptor blocker, MRS2179 (10(-3) M) was locally delivered in the left anterior descending artery through the tip of a coronary angioplasty balloon. In separate pigs the coronary artery was occluded with the balloon for 10 min. During the first and tenth minute of coronary ischemia, 2.5 ml of MRS2179 (10(-3) M) was delivered distal to the occlusion in 8 pigs, 10 pigs were used as controls. Results 2-MeSADP increased levels of t-PA in the coronary sinus, which could be significantly inhibited by co-infusion with MRS2179. During cardiac ischemia and reperfusion, t-PA increased significantly, an effect that could be significantly inhibited by MRS2179. Conclusions Intra coronary administered MRS2179, a selective P2Y(1) receptor blocker, significantly reduces the increased levels of t-PA caused by both 2-MeSADP and cardiac ischemia in coronary arteries. Thus, ADP acting on the endothelial P2Y(1) receptor may mediate release of t-PA during ischemia and post-ischemic hyperemia, an effect that may counteract some of the platelet activating effects of ADP. C1 Lund Univ, Univ Lund Hosp, Dept Cardiol, S-22185 Lund, Sweden. Lund Univ, Dept Radiol, Lund, Sweden. NIH, Mol Recognit Sect, Bethesda, MD 20892 USA. Sahlgrens Univ Hosp, Heart & Lung Inst, Clin Expt Res Lab, S-41345 Gothenburg, Sweden. RP Erlinge, D (reprint author), Lund Univ, Univ Lund Hosp, Dept Cardiol, S-22185 Lund, Sweden. EM david.erlinge@med.lu.se RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999] NR 30 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD OCT PY 2007 VL 24 IS 2 BP 115 EP 122 DI 10.1007/s11239-007-0010-3 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 200WR UT WOS:000248794000006 PM 17294140 ER PT J AU Arlen, PM Skarupa, L Pazdur, M Seetharam, M Tsang, KY Grosenbach, DW Feldman, J Poole, DJ Litzinger, M Steinberg, SM Jones, E Chen, C Marte, J Parnes, H Wright, J Dahut, W Schlom, J Gulley, JL AF Arlen, Philip M. Skarupa, Lisa Pazdur, Mary Seetharam, Mahesh Tsang, Kwong Y. Grosenbach, Douglas W. Feldman, Jarett Poole, Diane J. Litzinger, Mary Steinberg, Seth M. Jones, Elizabeth Chen, Clara Marte, Jennifer Parnes, Howard Wright, John Dahut, William Schlom, Jeffrey Gulley, James L. TI Clinical safety of a viral vector based prostate cancer vaccine strategy SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostate-specific antigen; vaccines; granulocyte-macrophage colony-stimulating factor ID COLONY-STIMULATING FACTOR; PHASE-I; COMBINATION THERAPY; IMMUNE-RESPONSES; ANTIGEN; TRIAL; MITOXANTRONE; PREDNISONE; DOCETAXEL; LYMPHOMA AB Purpose: The primary objective of this phase I study was to evaluate the clinical safety of a vaccine using recombinant vaccinia virus (prime) and recombinant fowlpox virus (boost) in combination with granulocyte-macrophage colony-stimulating factor in patients with prostate cancer. The vaccines contained transgenes for prostate specific antigen, a triad of co-stimulatory molecules and a tumor antigen whose amino acid sequence had been modified to enhance its immunogenicity. Secondary end points were immunological and clinical responses, changes in prostate specific antigen velocity, and the kinetics of vaccinia virus clearance from the vaccination site, serum, peripheral blood mononuclear cells, urine and saliva. Materials and Methods: The 15 patients enrolled in this study had metastatic prostate cancer. Patients were given recombinant fowlpox-prostate specific antigen/triad of co-stimulatory molecules alone or recombinant vaccinia-prostate specific antigen/triad of co-stimulatory molecules followed by recombinant fowlpox-prostate specific antigen/triad of costimulatory molecules on a prime and boost schedule with or without recombinant-granulocyte-macrophage colony-stimulating factor protein or recombinant fowlpox-granulocyte-macrophage colony-stimulating factor vector. Prostate specific antigen specific immune responses were measured using an enzyme-linked immunosorbent spot assay for interferon-gamma production. Polymerase chain reaction for vaccinia DNA and a plaque assay for live virus were also used. Results: Some grade 2 toxicity was seen in patients who received a higher dose of recombinant fowlpox-granulocytemacrophage colony-stimulating factor but no toxicity exceeded grade 2. Viable vaccinia was detected after vaccination at the site swab of 1 of 4 patients analyzed. Prostate specific antigen specific immune responses were seen in 4 of 6 patients who were HLA-A2+ and decreases in serum prostate specific antigen velocity were observed in 9 of 15. Conclusions: Based on the safety and preliminary immunogenicity results of this trial we recommend initiating a randomized, phase II study of prostate specific antigen/triad of co-stimulatory molecules vaccines in patients with less advanced prostate cancer. C1 NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Div Canc Prevent, Canc Prevent & Evaluat Program,Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 8B09, Bethesda, MD 20892 USA. EM schlomj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS NR 20 TC 74 Z9 74 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2007 VL 178 IS 4 BP 1515 EP 1520 DI 10.1016/j.juro.2007.05.117 PN 1 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 212BI UT WOS:000249568200093 PM 17707059 ER PT J AU Williams, CR Tabios, R Linehan, WM Neckers, L AF Williams, Christopher R. Tabios, Ray Linehan, W. Marston Neckers, Len TI Intratumor injection of the hsp90 inhibitor 17AAG decreases tumor growth and induces apoptosis in a prostate cancer xenograft model SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; HSP90 heat-shock proteins; mice ID ANDROGEN RECEPTOR; ANTITUMOR AGENT; GELDANAMYCIN; PROTEIN; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; DEGRADATION; DERIVATIVES; COMPLEX; CELLS; BINDS AB Purpose: A role for heat shock protein 90 inhibitors in prostate cancer has been explored only in the context of systemic treatment of refractory metastatic disease. We hypothesized that intratumor administration of heat shock protein 90 inhibitors may have benefit for treating localized prostate cancer. Materials and Methods: Twice weekly intratumor injections of 50 mg/kg 17AAG (treatment group of 8 mice) or dimethyl sulfoxide (control group of 8) were performed in subcutaneously grown DU-145 prostate cancer xenografts for a total of 8 doses. Tumor size was monitored. An additional tumor nonintervention control group of 3 mice was maintained. Results: Seven of the 8 mice (88%) in the 17AAG group lived to study completion, of which 6 (86%) showed decreased tumor size and growth rate compared to those of vehicle treated controls (p < 0.05). Gross necropsy, and tumor histological and molecular evaluations were performed after sacrifice. No overt signs of systemic toxicity, evidence of distant metastases or peritumor tissue effects were noted. Histologically 17AAG treated tumors were characterized by marked necrosis, inflammation and complete destruction of cellular architecture. Intratumor 17AAG treatment also resulted in pharmacodynamic changes consistent with apoptosis. Conclusions: The current data demonstrate that intratumor administration of 17AAG promotes tumor growth inhibition, pertinent client protein responses and localized induction of apoptosis together with minimal clinical toxicity. These data support further preclinical evaluation of this treatment modality alone and in combination with other established noninvasive therapy for localized prostate cancer. C1 Univ Florida, Dept Surg, Div Urol, Jacksonville, FL 32209 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Williams, CR (reprint author), Univ Florida, Dept Surg, Div Urol, 653 W 8th St, Jacksonville, FL 32209 USA. EM Christopher.williams@jax.ufl.edu NR 19 TC 40 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2007 VL 178 IS 4 BP 1528 EP 1532 DI 10.1016/j.juro.2007.05.120 PN 1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 212BI UT WOS:000249568200095 PM 17707057 ER PT J AU Kercher, L Favara, C Striebel, JF LaCasse, R Chesebro, B AF Kercher, Lisa Favara, Cynthia Striebel, James F. LaCasse, Rachel Chesebro, Bruce TI Prion protein expression differences in microglia and astroglia influence scrapie-induced neurodegeneration in the retina and brain of transgenic mice SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; INFECTED MICE; INFLAMMATORY RESPONSE; NATURAL SCRAPIE; DAMAGED NEURONS; HAMSTER SCRAPIE; MESSENGER-RNA; LYMPH-NODES; GLIAL-CELLS; PRP AB Activated microglia and astroglia are known to be involved in a variety of neurodegenerative diseases, including prion diseases. In the present experiments, we studied activation of astroglia and microglia after intraocular scrapie infection in transgenic mice expressing prion protein (PrP) in multiple cell types (tg7 mice) or in neurons only (tgNSE mice). In this model, scrapie infection and protease-resistant PrP deposition occurs in the retinas of both strains of mice, but retinal degeneration is observed only in tg7 mice. Our results showed that the retinas of tg7 and tgNSE mice both had astroglial activation with increased chemokine expression during the course of infection. However, only tg7 retinas exhibited strong microglial activation compared to tgNSE retinas, which showed little microglial activation by biochemical or morphological criteria. Therefore, microglial PrP expression might be required for scrapie-induced retinal microglial activation and damage. Furthermore, microglial activation preceded retinal neurodegeneration in tg7 mice, suggesting that activated microglia might contribute to the degenerative process, rather than being a response to the damage. Surprisingly, brain differed from retina in that an altered profile of microglial activation markers was upregulated, and the profiles in the two mouse strains were indistinguishable. Microglial activation in the brain was associated with severe brain vactrolation and neurodegeneration, leading to death. Thus, retinal and brain microglia appeared to differ in their requirements for activation, suggesting that different activation pathways occur in the two tissues. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Chesebro, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM bchesebro@niaid.nih.gov NR 54 TC 15 Z9 17 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 OCT PY 2007 VL 81 IS 19 BP 10340 EP 10351 DI 10.1128/JVI.00865-07 PG 12 WC Virology SC Virology GA 212SP UT WOS:000249617400015 PM 17652390 ER PT J AU Yan, Y Knoper, RC Kozak, CA AF Yan, Yuhe Knoper, Ryan C. Kozak, Christine A. TI Wild mouse variants of envelope genes of Xenotropic/Polytropic mouse Gammaretroviruses and their XPR1 receptors elucidate receptor determinants of virus entry SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; CELL-SURFACE RECEPTOR; SPECIES MUS-CASTANEUS; GENUS MUS; MICE; SEQUENCES; RESISTANCE; INFECTION; SUSCEPTIBILITY; RETROVIRUSES AB Mouse xenotropic and polytropic leukemia viruses (XMVs and PMVs) are closely related gammaretroviruses that use the XPR1 receptor for entry. To identify amino acid residues in XPR1 important for virus entry, we tested mouse cells derived from evolutionarily divergent species for susceptibility to prototypical PMVs, XMVs, and the wild mouse isolate CasE#1. CasE#1 has a variant XMV/PMV host range, and sequence analysis of the CasE#1 env gene identifies segments related to PMVs and XMVs. Cells from the Asian mouse species Mus pahari show a unique pattern of susceptibility to these three viruses; these cells are susceptible to XMVs and CasE#1 but are resistant to PMVs, whereas NIH 3T3 cells show the reciprocal pattern, susceptibility to only PMVs. The M. pahari XPR1 gene differs from that of NIH 3T3 in the two extracellular loops (ECLs) previously shown to mediate virus entry (M. Marin, C. S. Tailor, A. Nouri, S. L. Kozak, and D. Kabat, J. Virol. 73:9362-9368, 1999, and N. S. Van Hoeven and A. D. Miller, Retrovirology 2:76, 2005). Using transfected hamster cells expressing chimeric and mutated XPR1s, we demonstrated that the susceptibility differences between NIH 3T3 and M. pahari cells are receptor mediated, that PMV entry requires residues in ECL3, that the CasE#1 entry determinant is in ECL4, and that determinants for XMV entry are in both ECL3 and ECL4. Additional substitutions in ECL3 and ECL4 modulate virus susceptibility and suggest that ECL3 and ECL4 may contribute to the formation of a single virus receptor site. The position of M. pahari at the base of the Mus phylogenetic tree indicates that XPR1-mediated susceptibility to XMVs is the ancestral type in this genus and that the phenotypic variants of mouse XPR1 likely arose in conjunction with exposure to gammaretrovirus infections and coevolutionary adaptations in the viral envelope. C1 NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Kozak, CA (reprint author), NIAID, NIH, Mol Microbiol Lab, Bldg,4 Rm 329,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM ckozak@niaid.nih.gov FU Intramural NIH HHS NR 39 TC 29 Z9 31 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2007 VL 81 IS 19 BP 10550 EP 10557 DI 10.1128/JVI.00933-07 PG 8 WC Virology SC Virology GA 212SP UT WOS:000249617400034 PM 17634227 ER PT J AU Joseph, T McAuliffe, J Lu, B Jin, H Kemble, G Subbarao, K AF Joseph, Tomy McAuliffe, Josephine Lu, Bin Jin, Hong Kemble, George Subbarao, Kanta TI Evaluation of replication and pathogenicity of avian influenza a h7 subtype viruses in a mouse model SO JOURNAL OF VIROLOGY LA English DT Article ID BRITISH-COLUMBIA; COMMERCIAL POULTRY; HUMAN-BEINGS; HEMAGGLUTININ; OUTBREAK; CONJUNCTIVITIS; CHICKENS; HUMANS; RECOMBINATION; PROTECTION AB Avian influenza A H7 subtype viruses pose a significant threat to human health because of their ability to transmit directly from domestic poultry to humans and to cause disease and, sometimes, death. Although it is important to develop vaccines against viruses of this subtype, very limited information is available on the immune response and pathogenesis of H7 viruses in animal models such as mice and ferrets. Ten H7 viruses were selected for possible vaccine development on the basis of their phylogenetic relationships and geographical locations. The virulence of the 10 viruses for mice and the immunogenicity of the viruses in mice and ferrets were evaluated to study the extent of antigenic relatedness and the level of cross-reactivity of antibodies. Most of the viruses showed similar patterns of cross-reactivity with mouse and ferret antisera. The Eurasian viruses elicited broadly cross-reactive antibodies that neutralized viruses from both Eurasian and North American lineages, but the converse was not true. A subset of the viruses was also evaluated for the ability to replicate and cause disease in BALB/c mice following intranasal administration. H7 subtype viruses were able to infect mice without adaptation and manifested different levels of lethality and kinetics of replication. On the basis of phylogenetic data, induction of broadly cross-neutralizing antibodies in mouse and ferret antisera, and their ability to replicate in mice, we have selected A/Netherlands/219/03 (subtype H7N7) and A/chicken/BC/CN-7/04 (subtype H7N3) viruses for vaccine development. The mouse model can be used for the preclinical evaluation of these vaccines against H7 subtype viruses. C1 NIAID, NIH, Infect Dis Lab, Bethesda, MD 20892 USA. MedImmune Vaccines Inc, Mountain View, CA 94043 USA. RP Subbarao, K (reprint author), Bldg 33,Room 3E-13C-1,33 N Dr,MSC 3203, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [K04 AI000155, Z01 AI000155] NR 31 TC 60 Z9 65 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2007 VL 81 IS 19 BP 10558 EP 10566 DI 10.1128/JVI.00970-07 PG 9 WC Virology SC Virology GA 212SP UT WOS:000249617400035 PM 17634234 ER PT J AU Igarashi, T Donau, OK Imamichi, H Nishimura, Y Theodore, TS Iyengar, R Erb, C Buckler-White, A Buckler, CE Martin, MA AF Igarashi, Tatsuhiko Donau, Olivia K. Imamichi, Hiromi Nishimura, Yoshiaki Theodore, Theodore S. Iyengar, Ranjini Erb, Christopher Buckler-White, Alicia Buckler, Charles E. Martin, Malcolm A. TI Although macrophage-tropic simian/human immunodeficiency viruses can exhibit a range of pathogenic phenotypes, a majority of isolates induce no clinical disease in immunocompetent macaques SO JOURNAL OF VIROLOGY LA English DT Article ID CAPRINE ARTHRITIS-ENCEPHALITIS; INFECTIOUS-ANEMIA VIRUS; RHESUS-MONKEYS; NEUTRALIZATION SENSITIVITY; CELLULAR-LOCALIZATION; ALVEOLAR MACROPHAGES; TISSUE MACROPHAGES; HIV-1 INFECTION; TYPE-1 ISOLATE; IN-VIVO AB Unlike prototypical lentiviruses like visna and caprine arthritis-encephalitis viruses, which are mainly macrophage tropic (M-tropic), primate lentiviruses primarily target CD4(+) T lymphocytes. We previously reported that during the late phase of highly pathogenic chimeric simian/human immunodeficiency virus (SHIV) infections of rhesus macaques, when CD4(+) T cells have been systemically eliminated, high levels of viremia are maintained from productively infected macrophages. The availability of several different M-tropic SHIVs from such late-stage immunocompromised animals provided the opportunity to assess whether they might contribute to the immune deficiency induced by their T-cell-tropic parental viruses or possibly cause a distinct disease based on their capacity to infect macrophages. Pairs of rhesus monkeys were therefore inoculated intravenously with six different M-tropic SHIV preparations, and their plasma viral RNA loads, circulating lymphocyte subset numbers, and eventual disease outcomes were monitored. Only one of these six M-tropic SHIVs induced any disease; the disease phenotype observed was the typical rapid, complete, and irreversible depletion of CD4(+) T cells induced by pathogenic SHIVs. An analysis of two asymptomatic monkeys, previously inoculated with an M-tropic SHIV recovered directly from alveolar macrophages, revealed that this inoculum targeted alveolar macrophages in vivo, compared to a T-cell-tropic virus, yet no clinical disease occurred. Although one isolate did, in fact, induce the prototypical rapid, irreversible, and complete loss of CD4(+) T cells, indicating that M-tropism and pathogenicity may not be inversely related, the majority of M-tropic SHIVs induced no clinical disease in immunocompetent macaques. C1 NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. Frederick Inc, Sci Applicat Int Corp, Ft Detrick, MD 21702 USA. RP Martin, MA (reprint author), NIAID, NIH, Mol Microbiol Lab, Bldg 4,Room 315, Bethesda, MD 20892 USA. EM mmartin@niaid.nih.gov FU Intramural NIH HHS NR 47 TC 5 Z9 5 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 OCT PY 2007 VL 81 IS 19 BP 10669 EP 10679 DI 10.1128/JVI.00517-07 PG 11 WC Virology SC Virology GA 212SP UT WOS:000249617400046 PM 17626082 ER PT J AU Franklin, SP Troyer, JL Terwee, JA Lyren, LM Boyce, WM Riley, SPD Roelke, ME Crooks, KR VandeWoude, S AF Franklin, S. P. Troyer, J. L. Terwee, J. A. Lyren, L. M. Boyce, W. M. Riley, S. P. D. Roelke, M. E. Crooks, K. R. VandeWoude, S. TI Frequent transmission of immunodeficiency viruses among bobcats and pumas SO JOURNAL OF VIROLOGY LA English DT Article ID LIONS PANTHERA-LEO; LENTIVIRUS INFECTION; HABITAT FRAGMENTATION; SOUTHERN CALIFORNIA; DOMESTIC CATS; AFRICAN LIONS; FELINE; WILD; PREVALENCE; DIVERGENCE AB With the exception of human immunodeficiency virus (HIV), which emerged in humans after cross-species transmissions of simian immunodeficiency viruses from nonhuman primates, immunodeficiency viruses of the family Lentiviridae represent species-specific viruses that rarely cross species barriers to infect new hosts. Among the Felidae, numerous immunodeficiency-like lentiviruses have been documented, but only a few cross-species transmissions have been recorded, and these have not been perpetuated in the recipient species. Lentivirus seroprevalence was determined for 79 bobcats (Lynx rufus) and 31 pumas (Puma concolor) from well-defined populations in Southern California. Partial genomic sequences were subsequently obtained from 18 and 12 seropositive bobcats and pumas, respectively. Genotypes were analyzed for phylogenic relatedness and genotypic composition among the study set and archived feline lentivirus sequences. This investigation of feline immunodeficiency virus infection in bobcats and pumas of Southern California provides evidence that cross-species infection has occurred frequently among these animals. The data suggest that transmission has occurred in multiple locations and are most consistent with the spread of the virus from bobcats to pumas. Although the ultimate causes remain unknown, these transmission events may occur as a result of puma predation on bobcats, a situation similar to that which fostered transmission of HIV to humans, and likely represent the emergence of a lentivirus with relaxed barriers to cross-species transmission. This unusual observation provides a valuable opportunity to evaluate the ecological, behavioral, and molecular conditions that favor repeated transmissions and persistence of lentivirus between species. C1 Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. Colorado State Univ, Dept Fis Wildlife & Conservat Biol, Ft Collins, CO 80523 USA. US Geol Survey, Carlsbad, CA 92011 USA. Univ Calif Davis, Wildlife Hlth Ctr, Davis, CA 95616 USA. Natl Pk Serv, Santa Monica Mountains Natl Recreat Area, Thousand Oaks, CA 91360 USA. Frederick Inc, NCI, SAIC, Lab Genom Divers, Frederick, MD 21702 USA. RP VandeWoude, S (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. EM suev@lamar.colostate.edu RI Troyer, Jennifer/B-8415-2012 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 52 TC 30 Z9 30 U1 0 U2 7 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 OCT PY 2007 VL 81 IS 20 BP 10961 EP 10969 DI 10.1128/JVI.00997-07 PG 9 WC Virology SC Virology GA 218MK UT WOS:000250019400013 PM 17670835 ER PT J AU Mehandru, S Vcelar, B Wrin, T Stiegler, G Joos, B Mohri, H Boden, D Galovich, J Tenner-Racz, M Racz, P Carrington, M Petropoulos, C Katinger, H Markowitz, M AF Mehandru, Saurabh Vcelar, Brigitta Wrin, Terri Stiegler, Gabriela Joos, Beda Mohri, Hiroshi Boden, Daniel Galovich, Justin Tenner-Racz, Mara Racz, Paul Carrington, Mary Petropoulos, Christos Katinger, Hermann Markowitz, Martin TI Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; ACTIVE ANTIRETROVIRAL THERAPY; HIV-1/SIV CHIMERIC VIRUS; CD4(+) T-LYMPHOCYTES; NEUTRALIZING ANTIBODIES; GASTROINTESTINAL-TRACT; MYOCARDIAL-INFARCTION; NEONATAL MACAQUES; CELL RESPONSES; VIRAL LOAD AB Three neutralizing monoclonal antibodies (MAbs), 2G12, 2F5, and 4E10, with activity in vitro and in vivo were administered in an open-label, nonrandomized, proof-of-concept study to attempt to prevent viral rebound after interruption of antiretroviral therapy (ART). Ten human immunodeficiency virus type I-infected individuals identified and treated with ART during acute and early infection were enrolled. The first six patients were administered 1.0 g of each of the three MAbs per infusion. The remaining four patients received 2G12 at 1.0 g/infusion and 2.0 g/infusion of 2175 and 4E10. The MAbs were well tolerated. Grade I post-partial thromboplastin time prolongations were noted. Viral rebound was observed in 8/10 subjects (28 to 73 days post-ART interruption), and 2/10 subjects remained aviremic over the course of the study. In seven of eight subjects with viral rebound, clear resistance to 2G12 emerged, whereas reductions in the susceptibilities of plasma-derived recombinant viruses to 2F5 and 4E10 were neither sustained nor consistently measured. Viral rebound was associated with a preferential depletion of CD4(+) T cells within the gastrointestinal tract. Though safe, the use of MAbs generally delayed, but did not prevent, virologic rebound. Consideration should be given to further pilot studies with alternative combinations of MAbs and perhaps additional novel treatment modalities. C1 Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Polymun Sci, A-1190 Vienna, Austria. Monogram Biosci Inc, San Francisco, CA USA. Univ Zurich Hosp, Hosp Epidemiol, Div Infect Dis, CH-8091 Zurich, Switzerland. Bernhard Nocht Inst Trop Med, D-20359 Hamburg, Germany. Frederick Inc, NCI, SAIC, Lab Genom Divers, Frederick, MD 21702 USA. Univ Nat Resources & Appl Life Sci, Inst Appl Microbiol, Vienna, Austria. RP Markowitz, M (reprint author), Aaron Diamond AIDS Res Ctr, 455 First Ave,7th Floor, New York, NY 10016 USA. EM mmarkowitz@adarc.org RI Joos, Beda/D-5547-2009; Infektiologie, USZ/A-6921-2011 OI Joos, Beda/0000-0002-3082-8875; FU Intramural NIH HHS; NCI NIH HHS [N01-CO12400, N01CO12400]; NCRR NIH HHS [UL1 RR024143, RR024143]; NIAID NIH HHS [AI41534, U01 AI041534] NR 57 TC 64 Z9 65 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 OCT PY 2007 VL 81 IS 20 BP 11016 EP 11031 DI 10.1128/JVI.01340-07 PG 16 WC Virology SC Virology GA 218MK UT WOS:000250019400018 PM 17686878 ER PT J AU Cho, WK Zhou, M Jang, MK Huang, K Jeong, SJ Ozato, K Brady, JN AF Cho, Won-Kyung Zhou, Meisheng Jang, Moon Kyoo Huang, Keven Jeong, Soo-Jin Ozato, Keiko Brady, John N. TI Modulation of the Brd4/P-TEFb interaction by the human T-Lymphotropic virus type I tax protein SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-POLYMERASE-II; LONG TERMINAL REPEAT; ELONGATION-FACTOR-B; CELL LEUKEMIA; P-TEFB; HTLV-I; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATOR; POSITIVE TRANSCRIPTION; REGULATORY SEQUENCES AB Positive transcription elongation factor (P-TEFb), which is composed of CDK9 and cyclin T1 plays an important role in cellular and viral gene expression. Our lab has recently demonstrated that P-TEFb is required for Tax transactivation of the viral long terminal repeat (LTR). P-TEFb is found in two major complexes: the inactive form, which is associated with inhibitory subunits 7SK snRNA and HEXIM1, and the active form, which is associated with, at least in part, Brd4. In this study, we analyzed the effect of Brd4 on human T-lymphotropic virus type 1 (HTLV-1) transcription. Overexpression of Brd4 repressed Tax transactivation of the HTLV-1 LTR in a dose-dependent manner. In vitro binding studies suggest that Tax and Brd4 compete for binding to P-TEFb through direct interaction with cyclin T1. Tax interacts with cyclin T1 amino acids 426 to 533, which overlaps the region responsible for Brd4 binding. In vivo, overexpression of Tax decreased the amount of 7SK snRNA associated with P-TEFb and stimulates serine 2 phosphorylation of the RNA polymerase II carboxyl-terminal domain, suggesting that Tax regulates the functionality of P-TEFb. Our results suggest the possibility that Tax may compete and functionally substitute for Brd4 in P-TEFb regulation. C1 NCI, NIH, Ctr Canc Res, Cellular Oncol Lab, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Cellular Oncol Lab, Tumor Virus Biol Sect, Bethesda, MD 20892 USA. NIH, NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. RP Brady, JN (reprint author), NCI, NIH, Ctr Canc Res, Cellular Oncol Lab, 41 Medlars Dr Bldg 41,Rm B201, Bethesda, MD 20892 USA. EM bradyj@mail.nih.gov FU Intramural NIH HHS NR 54 TC 21 Z9 21 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 OCT PY 2007 VL 81 IS 20 BP 11179 EP 11186 DI 10.1128/JVI.00408-07 PG 8 WC Virology SC Virology GA 218MK UT WOS:000250019400033 PM 17686863 ER PT J AU Inagaki, K Lewis, SM Wu, XL Ma, CR Munroe, DJ Fuess, S Storm, TA Kay, MA Nakai, H AF Inagaki, Katsuya Lewis, Susanna M. Wu, Xiaolin Ma, Congrong Munroe, David J. Fuess, Sally Storm, Theresa A. Kay, Mark A. Nakai, Hiroyuki TI DNA palindromes with a modest arm length of greater than or similar to s20 base pairs are a significant target for recombinant adeno-associated virus vector integration in the liver, muscles, and heart in mice SO JOURNAL OF VIROLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; YEAST SACCHAROMYCES-CEREVISIAE; SHORT INVERTED REPEATS; GENE AMPLIFICATION; HUMAN-CELLS; IN-VIVO; CHROMOSOMAL TRANSLOCATIONS; GENOME STABILITY; MOUSE-LIVER; FACTOR-IX AB Our previous study has shown that recombinant adeno-associated virus (rAAV) vector integrates preferentially in genes, near transcription start sites and CpG islands in mouse liver (H. Nakai, X. Wu, S. Fuess, T. A. Storm, D. Munroe, E. Montini, S. M. Burgess, M. Grompe, and M. A. Kay, J. Virol. 79:3606-3614, 2005). However, the previous method relied on in vivo selection of rAAV integrants and could be employed for the liver but not for other tissues. Here, we describe a novel method for high-throughput rAAV integration site analysis that does not rely on marker gene expression, selection, or cell division, and therefore it can identify rAAV integration sites in nondividing cells without cell manipulations. Using this new method, we identified and characterized a total of 997 rAAV integration sites in mouse liver, skeletal muscle, and heart, transduced with rAAV2 or rAAV8 vector. The results support our previous observations, but notably they have revealed that DNA palindromes with an arm length of greater than or similar to 20 bp (total length, greater than or similar to 40 bp) are a significant target for rAAV integration. Up to similar to 30% of total integration events occurred in the vicinity of DNA palindromes with an arm length of greater than or similar to 20 bp. Considering that DNA palindromes may constitute fragile genomic sites, our results support the notion that rAAV integrates at chromosomal sites susceptible to breakage or preexisting breakage sites. The use of rAAV to label fragile genomic sites may provide an important new tool for probing the intrinsic source of ongoing genomic instability in various tissues in animals, studying DNA palindrome metabolism in vivo, and understanding their possible contributions to carcinogenesis and aging. C1 Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Hosp Sick Children, Res Inst, Program Genet & Genome Biol, Toronto, ON M5G 1L8, Canada. SAIC Frederick Inc, NCI Frederick, Lab Mol Technol, Ft Detrick, MD 21702 USA. Stanford Univ, Sch Med, Dept Pediat & Genet, Stanford, CA 94305 USA. RP Nakai, H (reprint author), Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, W1244 BSTWR 200 Lothrop St, Pittsburgh, PA 15261 USA. EM nakaih@pitt.edu FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NHLBI NIH HHS [HL64274, R01 HL064274]; NIDDK NIH HHS [DK78388, R21 DK068636, R01 DK048252, R56 DK078388, R01 DK078388, DK68636] NR 60 TC 33 Z9 35 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 OCT PY 2007 VL 81 IS 20 BP 11290 EP 11303 DI 10.1128/JVI.00963-07 PG 14 WC Virology SC Virology GA 218MK UT WOS:000250019400044 PM 17686840 ER PT J AU Guo, F Cen, S Niu, MJ Yang, YL Gorelick, RJ Kleiman, L AF Guo, Fei Cen, Shan Niu, Meijuan Yang, Yiliang Gorelick, Robert J. Kleiman, Lawrence TI The interaction of APOBEC3G with human immunodeficiency virus type 1 nucleocapsid inhibits tRNA(3)(Lys) annealing to viral RNA SO JOURNAL OF VIROLOGY LA English DT Article ID ACID CHAPERONE ACTIVITY; PRIMER BINDING-SITE; REVERSE TRANSCRIPTION; VIF PROTEIN; ANTIVIRAL ACTIVITY; HIV-1 VIRIONS; IN-VITRO; GAG POLYPROTEIN; GENOMIC RNA; SOR GENE AB Human immunodeficiency virus type 1 (HIV-1) containing human APOBEC3G (hA3G) has a reduced ability to produce viral DNA in newly infected cells. At least part of this hA3G-facilitated inhibition is due to a cytidine deamination-independent reduction in the ability to initiate reverse transcription. HIV-1 nucleocapsid (NCp7) is required both for the incorporation of hA3G into virions and for the annealing between viral RNA and tRNA(3)(Lys), the primer tRNA for reverse transcription. Herein we present evidence that the interaction of hA3G with nucleocapsid is required for the inhibition of reverse transcription initiation. A tRNA(3)(Lys) priming complex was produced in vitro by the NCp7-facilitated annealing of tRNA(3)(Lys) to synthetic viral RNA in the absence or presence of hA3G. The effect of hA3G on the annealing of tRNA(3)(Lys) to viral RNA and the ability of tRNA(3)(Lys) to 3 initiate reverse transcription was measured. Our results show the following. (i) Electrophoretic band shift and primer binding site assays show that hA3G reduces the annealing of tRNA(3)(Lys) 44 and 60%, respectively, but does not disrupt the annealed complex once formed. (ii) hA3G inhibits tRNA(3)(Lys) priming 70 to 80%. (iii) Inhibition 3 of tRNA(3)(Lys) priming by hA3G requires an interaction between hA3G and NCp7 during annealing. Thus, annealing of tRNALys is insensitive to hA3G inhibition when facilitated by a zinc finger mutant of NCp7 unable 3 to interact with hA3G. NCp7-independent annealing of DNA to viral RNA also is insensitive to hA3G inhibition. These results indicate that hA3G does not sterically block IRNA vs annealing by binding to viral RNA. Annealing and priming are not affected by another RNA binding protein, QKI-6. C1 Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, McGill AIDS Ctr, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3T 1E2, Canada. SAIC Frederick Inc, NCI Frederick, Basic Res Program, Ft Detrick, MD 21702 USA. RP Kleiman, L (reprint author), Jewish Gen Hosp, Lady Davis Inst Med Res, 3755 Cote St Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM lawrence.kleiman@mcgill.ca FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 52 TC 85 Z9 87 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2007 VL 81 IS 20 BP 11322 EP 11331 DI 10.1128/JVI.00162-07 PG 10 WC Virology SC Virology GA 218MK UT WOS:000250019400046 PM 17670826 ER PT J AU Melendi, GA Zavala, F Buchholz, UJ Boivin, G Collins, PL Kleeberger, SR Polack, FP AF Melendi, Guillermina A. Zavala, Fidel Buchholz, Ursula J. Boivin, Guy Collins, Peter L. Kleeberger, Steven R. Polack, Fernando P. TI Mapping and characterization of the primary and anamnestic H-2(d)-restricted cytotoxic T-Lymphocyte response in mice against human metapneumovirus SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; PRIMARY INFECTION; TRACT DISEASE; BALB/C MICE; PROTEIN; EPITOPE; CELLS; IMMUNIZATION; PATHOGENESIS; ANTIBODIES AB Cytotoxic T lymphocytes (CTLs) are important for the control of virus replication during respiratory infections. For human metapneumovirus (hMPV), an H-2(d) -restricted CTL epitope in the M2-2 protein has been described. In this study, we screened the hMPV F, G, N, M, M2-1, and M2-2 proteins using three independent algorithms to predict H-2(d) CTL epitopes in BALB/c mice. A dominant epitope (GYIDDNQSI) in positions 81 to 89 of the antitermination factor M2-1 and a subdominant epitope (SPKAGLLSL) in N307-315 were detected during the anti-hMPV CTL response. Passive transfer of CD8(+) T-cell lines against M2-1(81-89) and N307-315 protected Ragl(-/-) mice against hMPV challenge. Interestingly, diversification of CTL targets to include multiple epitopes was observed after repetitive infections. A subdominant response against the previously described M2-2 epitope was detected after the third infection. An understanding of the CTL response against hMPV is important for developing preventive and therapeutic strategies against the virus. C1 Johns Hopkins Univ, Baltimore, MD 21205 USA. Fdn INFANT, Buenos Aires, DF, Argentina. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Mol Microbiol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Immunol, Baltimore, MD USA. Johns Hopkins Univ, Dept Int Hlth, Baltimore, MD USA. NIH, NIAID, Bethesda, MD 20892 USA. Univ Quebec, Cent Hosp, Res Ctr Infect Dis, Quebec City, PQ, Canada. NIH, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Polack, FP (reprint author), Johns Hopkins Univ, 615 N Wolfe St,E5202, Baltimore, MD 21205 USA. EM fpolick@jhsph.edu FU Intramural NIH HHS; NIAID NIH HHS [R01 AI054952, AI-054952, R21 AI054952] NR 28 TC 16 Z9 17 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 OCT PY 2007 VL 81 IS 20 BP 11461 EP 11467 DI 10.1128/JVI.02423-06 PG 7 WC Virology SC Virology GA 218MK UT WOS:000250019400059 PM 17670840 ER PT J AU Igarashi, T Iyengar, R Byrum, RA Buckler-White, A Dewar, RL Buckler, CE Lane, HC Kamada, K Adachi, A Martin, MA AF Igarashi, Tatsuhiko Iyengar, Ranjini Byrum, Russel A. Buckler-White, Alicia Dewar, Robin L. Buckler, Charles E. Lane, H. Clifford Kamada, Kazuya Adachi, Akio Martin, Malcolm A. TI Human immunodeficiency virus type 1 derivative with 7% simian immunodeficiency virus genetic content is able to establish infections in pig-tailed macaques SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS-MONKEYS; NEUTRALIZING ANTIBODIES; PERSISTENT INFECTION; HIV-1 INFECTION; CHIMERIC VIRUS; AIDS; CELLS; PROGRESSION; GENERATION; PREVENTION AB A human immunodeficiency virus type 1 (HIV-1) derivative (HIVNL-DT5R) containing sequences encoding a 7-amino-acid segment of CA and the entire vif gene from simian immunodeficiency virus (SIV) was previously shown to establish spreading infections in cultured macaque peripheral blood mononuclear cells. To assess its replicative and disease-inducing properties in vivo, HIVNL-DT5R was inoculated into pig-tailed macaques. HIVNL-DT5R generated plasma viremia in all five of the monkeys and elicited humoral responses against all of the HfV-1 structural proteins but did not cause CD4(+) T-lymphocyte depletion or clinical disease. Additional adaptation will be required to optimize infectivity in vivo. C1 NIH, NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. Bioqual, Rockville, MD 20850 USA. Sci Applicat Int Corp, Frederick Inc, Frederick, MD 21702 USA. NCI, NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Virol, Tokushima 770, Japan. RP Martin, MA (reprint author), NIH, NIAID, Mol Microbiol Lab, Bldg 4,Room 315,4 Ctr Dr, Bethesda, MD 20892 USA. EM malm@nih.gov FU NCRR NIH HHS [R24 RR016001, RR016001]; NIAID NIH HHS [AI040101, R01 AI040101] NR 27 TC 37 Z9 40 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 OCT PY 2007 VL 81 IS 20 BP 11549 EP 11552 DI 10.1128/JVI.00960-07 PG 4 WC Virology SC Virology GA 218MK UT WOS:000250019400070 PM 17670817 ER PT J AU Franklin, SP Troyer, JL TerWee, JA Lyren, LM Kays, RW Riley, SPD Boyce, WM Crooks, KR Vandewoude, S AF Franklin, Samuel P. Troyer, Jennifer L. TerWee, Julie A. Lyren, Lisa M. Kays, Roland W. Riley, Seth P. D. Boyce, Walter M. Crooks, Kevin R. Vandewoude, Sue TI Variability in assays used for detection of lentiviral infection in bobcats (Lynx rufus), pumas (Puma concolor) and ocelots (Leopardus pardalis) SO JOURNAL OF WILDLIFE DISEASES LA English DT Article DE bobcat; ELISA; FIV; immunoblot; lentivirus; ocelot; PCR; puma ID FELINE IMMUNODEFICIENCY VIRUS; LIONS PANTHERA-LEO; DOMESTIC CATS; AFRICAN LIONS; WILD; FIV; EPIDEMIOLOGY; POPULATION; DIVERGENCE; DIAGNOSIS AB Although lentiviruses similar to feline immunodeficiency virus (FIV) are known to infect numerous felid species, the relative utility of assays used for detecting lentiviral infection has not been compared for many of these hosts. We tested bobcats (Lynx rufus), pumas (Felis concolor), and ocelots (Leopardus pardalis) for exposure to lentivirus using five different assays: puma lentivirus (PLV), African lion lentivirus (LLV), and domestic cat FIV-based immunoblots, a commercially available enzyme-linked immunosorbent assay (ELISA) kit, and nested polymerase chain reaction (PCR). Puma lentivirus immunoblots identified more seropositive individuals than the other antibody-detection assays. The commercial ELISA provided a fair ability to recognize seropositive samples when compared with PLV immunoblot for screening bobcats and ocelots, but not pumas. Polymerase chain reaction identified fewer positive samples than PLV immunoblot for all three species. Immunoblot results were equivalent whether the sample tested was serum, plasma, or whole blood. The results from this study and previous investigations suggest that the PLV immunoblot has the greatest ability to detect reactive samples when screening wild felids of North America and is unlikely to produce false positive results. However, the commercial ELISA kit may provide an adequate alternative for screening of some species and is more easily adapted to field conditions. C1 Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. Western Ecol Res Ctr, US Geol Survey, Carlsbad, CA 92011 USA. New York State Museum & Sci Serv, Albany, NY 12230 USA. Univ Calif Davis, Wildlife Hlth Ctr, Davis, CA 95616 USA. Colorado State Univ, Dept Fish Wildlife & Conservat Biol, Ft Collins, CO 80523 USA. SAIC Frederick Inc, NCI Frederick, Lab Genom Diversity, Ft Detrick, MD 21702 USA. RP Franklin, SP (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, 1619 Campus Delivery, Ft Collins, CO 80523 USA. EM sam17franklin@hotmail.com RI Troyer, Jennifer/B-8415-2012 FU Intramural NIH HHS NR 34 TC 6 Z9 6 U1 0 U2 8 PU WILDLIFE DISEASE ASSOC, INC PI LAWRENCE PA 810 EAST 10TH ST, LAWRENCE, KS 66044-8897 USA SN 0090-3558 J9 J WILDLIFE DIS JI J. Wildl. Dis. PD OCT PY 2007 VL 43 IS 4 BP 700 EP 710 PG 11 WC Veterinary Sciences SC Veterinary Sciences GA 232QL UT WOS:000251034100016 PM 17984266 ER PT J AU Pinn, VW AF Pinn, Vivian W. TI Fourth annual NIH interdisciplinary women's health research symposium November 15, 2007 SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material C1 NIH, Off Res Womens Hlth, US Dept HHS, Bethesda, MD 20892 USA. RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, US Dept HHS, 6707 Democracy Blvd,Suite 400,MSC 5484, Bethesda, MD 20892 USA. EM PinnV@od1tm1.od.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2007 VL 16 IS 8 BP 1093 EP 1094 DI 10.1089/jwh.2007.AB01 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 225GW UT WOS:000250506100001 ER PT J AU Barker, ET Galambos, NL AF Barker, Erin T. Galambos, Nancy L. TI Body dissatisfaction, living away from parents, and poor social adjustment predict binge eating symptoms in young women making the transition to university SO JOURNAL OF YOUTH AND ADOLESCENCE LA English DT Article DE binge eating; body dissatisfaction; transition to university ID COLLEGE-WOMEN; ADOLESCENCE; DISORDERS; STUDENTS; TRAJECTORIES; ADULTHOOD; ESTEEM; HEALTH; RISK; LIFE AB The current study explored how body dissatisfaction and challenges associated with the transition to university predicted symptoms of binge eating. Participants were 101 female full-time first-year university students (M=18.3 years of age; SD=.50) who completed a background questionnaire and a web-based daily checklist assessing binge eating. Hierarchical Generalized Linear Modeling results showed that participants who were more dissatisfied with their bodies were three times as likely to report symptoms of binge eating compared to participants who were less dissatisfied. Participants who lived away from home were three times as likely to report symptoms of binge eating compared to participants living with parents. Finally, poor perceived social adjustment to the university context was associated with an increased likelihood of binge eating. Discussion calls for more research exploring the role that university challenges and adjustment play in predicting eating problems. C1 NICHHD, Bethesda, MD 20892 USA. Univ Alberta, Dept Psychol, Edmonton, AB, Canada. RP Barker, ET (reprint author), NICHHD, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. EM barkerer@mail.nih.gov NR 43 TC 17 Z9 18 U1 2 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0047-2891 J9 J YOUTH ADOLESCENCE JI J. Youth Adolesc. PD OCT PY 2007 VL 36 IS 7 BP 904 EP 911 DI 10.1007/s10964-006-9134-6 PG 8 WC Psychology, Developmental SC Psychology GA 212EY UT WOS:000249577600005 ER PT J AU Barker, ET Bornstein, MH Putnick, DL Hendricks, C Suwalsky, JTD AF Barker, Erin T. Bornstein, Marc H. Putnick, Diane L. Hendricks, Charlene Suwalsky, Joan T. D. TI Adolescent-mother agreement about adolescent problem behaviors: Direction and predictors of disagreement SO JOURNAL OF YOUTH AND ADOLESCENCE LA English DT Article DE adolescent-mother agreement; internalizing problems; externalizing problems ID INTERNALIZING PROBLEMS; PEER RELATIONSHIPS; PARENT; CHILD; DISCREPANCIES; SELF; PSYCHOPATHOLOGY; REINTERPRETATION; PERSPECTIVES; PERCEPTIONS AB Correlations between adolescent and parent reports of adolescent problems are low in magnitude. In community samples adolescents tend to report more problems than parents and in clinical samples adolescents tend to report fewer problems than parents. Indices of agreement may be biased if some adolescents in a given sample report more problems and others report fewer problems than parents. In the current study, order and mean agreement between adolescent and maternal reports of adolescent internalizing and externalizing problems, taking into account the direction of disagreement, was examined in a community sample of 133 young adolescents and their mothers. Two-thirds to three-quarters of adolescents reported more problems than mothers. Accounting for the direction of discrepancies resulted in improved agreement between adolescents and mothers and differing patterns of predictors of discrepancies. Additionally, the results demonstrate the need to control for relations between adolescent-reported problems and discrepancies when exploring predictors of discrepancies. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Barker, ET (reprint author), NICHHD, NIH, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. EM barkerer@mail.nih.gov RI Putnick, Diane/B-1707-2009; OI Putnick, Diane/0000-0002-6323-749X NR 50 TC 32 Z9 32 U1 4 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0047-2891 J9 J YOUTH ADOLESCENCE JI J. Youth Adolesc. PD OCT PY 2007 VL 36 IS 7 BP 950 EP 962 DI 10.1007/s10964-006-9164-0 PG 13 WC Psychology, Developmental SC Psychology GA 212EY UT WOS:000249577600009 ER PT J AU Cherubini, A Andres-Lacueva, C Martin, A Lauretani, F Di Lorio, A Bartali, B Corsi, A Bandinelli, S Mattson, MP Ferrucci, L AF Cherubini, Antonio Andres-Lacueva, Cristina Martin, Antonio Lauretani, Fulvio Di Lorio, Angelo Bartali, Benedetta Corsi, Annamaria Bandinelli, Stefania Mattson, Mark P. Ferrucci, Luigi TI Low plasma n-3 fatty acids and dementia in older persons: The InCHIANTI study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID DOCOSAHEXAENOIC ACID; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; LEARNING-ABILITY; MOUSE MODEL; DECLINE; RISK; DIET; OMEGA-3-FATTY-ACIDS; ROTTERDAM AB Background. N-3 fatty acids (FA) have an important role in brain development and function. However, there is conflicting evidence concerning the relationship between n-3 FA and dementia in older persons. Methods. In the Invecchiare in Chianti (InCHIANTT) study, we measured plasma FA by gas chromatography in 935 community-dwelling older persons randomly extracted from the population of two towns near Florence, Italy. Cognitive impairment was measured using the Mini-Mental Status Examination. Participants who scored <= 26 underwent a detailed clinical and neuropsychological evaluation. The diagnosis of dementia was based on Diagnostic and Statistical Manual of Mental Disorders, Third Revision (DSM-III-R) criteria. The population was divided in three groups: persons with normal cognitive function, persons with cognitive impairment not demented, and persons with dementia. Results. After adjustment for age, gender, education, body mass index, weight loss, smoking status, cholesterol and triglycerides levels, daily intake of alcohol, FA and total energy, cardiovascular disease, depression and other FA levels, participants with dementia had significantly lower n-3 FA levels (2.9% vs 3.2%; p <.05), particularly alpha-linolenic acid levels (0.34% vs 0.39%; p <.05), than did participants with normal cognitive function. Conclusions. Dementia is associated with low plasma n-3 FA relative concentrations. The possibility that higher n-3 FA intake is associated with a lower risk of cognitive impairment should be further investigated in prospective studies. C1 [Cherubini, Antonio] Univ Perugia, Dept Clin & Expt Med, Inst Gerontol & Geriat, I-06100 Perugia, Italy. [Andres-Lacueva, Cristina] Univ Barcelona, Referenca Tecnol Aliments Generalitat Catalunya, Dept Nutr & Food Sci Xarxa, E-08007 Barcelona, Spain. [Martin, Antonio] Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Lauretani, Fulvio; Bartali, Benedetta; Corsi, Annamaria] Reg Hlth Agcy Tuscany, Florence, Italy. [Di Lorio, Angelo] Univ G DAnnunzio, Dept Med & Sci Aging, Lab Clin Epidemol, Chieti, Italy. [Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriat Unit, Florence, Italy. [Mattson, Mark P.] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Cherubini, A (reprint author), Univ Perugia, Dept Clin & Expt Med, Inst Gerontol & Geriat, I-06100 Perugia, Italy. EM acherub@unipg.it RI Mattson, Mark/F-6038-2012; Andres-Lacueva, Cristina/J-3377-2012; Lauretani, Fulvio/K-5115-2016; OI Andres-Lacueva, Cristina/0000-0002-8494-4978; Lauretani, Fulvio/0000-0002-5287-9972; Cherubini, Antonio/0000-0003-0261-9897 FU Intramural NIH HHS [Z99 AG999999]; NIMHD NIH HHS [R01 MD009164] NR 42 TC 46 Z9 48 U1 0 U2 4 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD OCT PY 2007 VL 62 IS 10 BP 1120 EP 1126 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 272AF UT WOS:000253829100009 PM 17921425 ER PT J AU Prozialeck, WC Vaidya, VS Liu, J Waalkes, MP Edwards, JR Lamar, PC Bernard, AM Dumont, X Bonventre, JV AF Prozialeck, W. C. Vaidya, V. S. Liu, J. Waalkes, M. P. Edwards, J. R. Lamar, P. C. Bernard, A. M. Dumont, X. Bonventre, J. V. TI Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicity SO KIDNEY INTERNATIONAL LA English DT Article DE biomarkers; cadmium; Kim-1; nephrotoxicity; Clara cell protein (CC-16); metallothionein ID CLARA-CELL PROTEIN; URINARY METALLOTHIONEIN; RENAL INJURY; E-CADHERIN; INDUCED HEPATOTOXICITY; TOXICITY; EXPOSURE; RAT; BETA(2)-MICROGLOBULIN; MARKERS AB Cadmium ( Cd) exposure results in injury to the proximal tubule characterized by polyuria and proteinuria. Kidney injury molecule-1 ( Kim-1) is a transmembrane glycoprotein not normally detected in the mature kidney, but is upregulated and shed into the urine following nephrotoxic injury. In this study, we determine if Kim-1 might be a useful early biomarker of Cd nephrotoxicity. Male Sprague-Dawley rats were given daily injections of Cd for up to 12 weeks. Weekly urine samples were analyzed for Kim-1, protein, creatinine, metallothionein, and Clara cell protein CC-16. Significant levels of Kim-1 were detected in the urine by 6 weeks and continued to increase throughout the treatment period. This appearance of Kim-1 occurred 4-5 weeks before the onset of proteinuria, and 1-3 weeks before the appearance of metallothionein and CC-16. Higher doses of Cd gave rise to higher Kim-1 excretion. Reverse transcriptase-polymerase chain reaction ( RT-PCR) expression analysis showed that Kim-1 transcript levels were increased after 6 weeks at the low dose of Cd. Immunohistochemical analysis showed that Kim-1 was present in proximal tubule cells of the Cd-treated rats. Our results suggest that Kim-1 may be a useful biomarker of early stages of Cd-induced proximal tubule injury. C1 Midwestern Univ, Dept Pharmacol, Downers Grove, IL 60515 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Renal Div, Boston, MA 02115 USA. NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. Univ Catholique Louvain, Unit Ind Toxicol & Occupat Med, B-3054 Brussels, Belgium. Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. RP Prozialeck, WC (reprint author), Midwestern Univ, Dept Pharmacol, 555 31st St, Downers Grove, IL 60515 USA. EM wprozi@midwestern.edu RI BERNARD, Alfred/A-6511-2010 OI BERNARD, Alfred/0000-0003-3171-3743 FU Intramural NIH HHS; NIDDK NIH HHS [DK 074099, DK 039773, DK072831, R01 DK039773, R21 DK074099, R33 DK074099, R37 DK039773]; NIEHS NIH HHS [ES 006478, R00 ES016723, R00 ES016723-02, R01 ES006478] NR 82 TC 70 Z9 78 U1 6 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2007 VL 72 IS 8 BP 985 EP 993 DI 10.1038/sj.ki.5002467 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 219NB UT WOS:000250090800013 PM 17687258 ER PT J AU Brown, P Gipson, C AF Brown, Patricia Gipson, Chester TI A word from OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. [Gipson, Chester] USDA, APHIS, Washington, DC USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD OCT PY 2007 VL 36 IS 9 BP 14 EP 14 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 245VA UT WOS:000251965700004 PM 17311040 ER PT J AU Moh, A Iwamoto, Y Chai, GX Zhang, SSM Kano, A Yang, DD Zhang, W Wang, J Jacoby, JJ Gao, B Flavell, RA Fu, XY AF Moh, Akira Iwamoto, Yoshiki Chai, Gui-Xuan Zhang, Samual Shao-Min Kano, Arihiro Yang, Derek D. Zhang, Wenjun Wang, Jun Jacoby, Joerg J. Gao, Bin Flavell, Richard A. Fu, Xin-Yuan TI Role of STAT3 in liver regeneration: survival, DNA synthesis, inflammatory reaction and liver mass recovery SO LABORATORY INVESTIGATION LA English DT Article DE conditional knockout; CCl4; liver regeneration; partial hepatectomy; STAT ID RETINOL-BINDING PROTEIN; HEPATOCYTE CELL-CYCLE; ACUTE-PHASE RESPONSE; IN-VIVO; TRANSCRIPTION FACTORS; PARTIAL-HEPATECTOMY; FETAL DEVELOPMENT; CHOROID-PLEXUS; YOLK-SAC; KAPPA-B AB The hepatoprotective effect of interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) has been well documented. However, reports on the role of IL-6/STAT3 in liver regeneration are conflicting probably due to the fact that the model of Stat3 knockout mice were complicated with obesity and fatty liver, which may cause some secondary effects on liver regeneration. To study the direct role of STAT3 and to circumvent the problems of obesity and fatty liver in liver regeneration, we generated conditional STAT3 knockout in the liver (L-Stat(3-/-)) using a transthyretin-driven Cre-lox method. The L-Stat(3-/-) mice were born with the expected Mendelian frequency and showed no obesity or other obvious phenotype. After partial hepatectomy, mortality in the L-Stat(3-/-) mice was significantly higher than the littermate Stat3(f/+) controls in the early time points (< 24 h). Hepatocyte DNA synthesis in the survived L-Stat3(-/-) mice slightly decreased as compared with Stat3(f/+) mice at 40 h after partial hepatectomy, whereas similar hepatocyte DNA synthesis was found at other time points and liver mass could be completely recovered in the L-Stat(3-/-) mice. In another model of liver regeneration induced by subcutaneous injection of carbon tetrachloride (CCl4), hepatocyte DNA synthesis in the CCl(4-)treated L-Stat(3-/-) mice also decreased as compared with Stat3(f/+) mice at 40 h after injection but not at other time points. In addition, infiltration of neutrophils and monocyte increased in the liver of CCl4(-) treated L-Stat(3-/-) mice compared to wild-type mice. In conclusion, STAT3 is required for survival in the acute stage after 70% hepatectomy and plays a role in inflammatory reaction after hepatocyte necrosis. However, the hepatocytic STAT3 may have limited role in liver mass recovery although DNA synthesis may be impaired. C1 Indiana Univ, Sch Med, Dept Microbiol, Indianapolis, IN 46204 USA. Indiana Univ, Sch Med, Dept Immunol, Indianapolis, IN 46204 USA. Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46204 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. NIAAA, Sect Liver Biol, Lab Physiol Studies, Bethesda, MD USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06510 USA. Indiana Univ, Sch Med, Ctr Canc, Indianapolis, IN 46204 USA. RP Moh, A (reprint author), Indiana Univ, Sch Med, Dept Microbiol, 635 Barnhill Dr MS 420, Indianapolis, IN 46204 USA. EM xfu@iupui.edu FU NIAID NIH HHS [R01-AI34522]; NIAMS NIH HHS [R01-AR44906]; NIDDK NIH HHS [DK34989] NR 36 TC 49 Z9 53 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD OCT PY 2007 VL 87 IS 10 BP 1018 EP 1028 DI 10.1038/labinvest.3700630 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 211XQ UT WOS:000249557400006 PM 17660847 ER PT J AU Simonsen, L Taylor, RJ Viboud, C Miller, MA Jackson, LA AF Simonsen, Lone Taylor, Robert J. Viboud, Cecile Miller, Mark A. Jackson, Lisa A. TI Mortality benefits of influenza vaccination in elderly people: an ongoing controversy SO LANCET INFECTIOUS DISEASES LA English DT Review ID RESPIRATORY SYNCYTIAL VIRUS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; UNITED-STATES; PUBLIC-HEALTH; EFFICACY; COMMUNITY; POPULATION; REDUCTION; EPIDEMIC AB Influenza vaccination policy in most high-income countries attempts to reduce the mortality burden of influenza by targeting people aged at least 65 years for vaccination. However, the effectiveness of this strategy is under debate. Although placebo-controlled randomised trials show influenza vaccine is effective in younger adults, few trials have included elderly people, and especially those aged at least 70 years, the age-group that accounts for three-quarters of all influenza-related deaths. Recent excess mortality studies were unable to confirm a decline in influenza-related mortality since 1980, even as vaccination coverage increased from 1.5% to 65%. Paradoxically, whereas those studies attribute about 5% of all winter deaths to influenza, many cohort studies report a 50% reduction in the total risk of death in winter-a benefit ten times greater than the estimated influenza mortality burden. New studies, however, have shown substantial unadjusted selection bias in previous cohort studies. We propose an analytical framework for detecting such residual bias. We conclude that frailty selection bias and use of non-specific endpoints such as all-cause mortality have led cohort studies to greatly exaggerate vaccine benefits. The remaining evidence base is currently insufficient to indicate the magnitude of the mortality benefit, if any, that elderly people derive from the vaccination programme. C1 George Washington Univ, Sch Publ Hlth, Dept Global Hlth, Hlth Serv, Washington, DC 20037 USA. NIAID, NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. LTS Corp, Bethesda, MD USA. Grp Hlth Ctr Hlth Studies, Seattle, WA USA. RP Simonsen, L (reprint author), George Washington Univ, Sch Publ Hlth, Dept Global Hlth, Hlth Serv, 9000 Rockville Pike, Washington, DC 20037 USA. EM iphlxs@gwumc.edu OI Simonsen, Lone/0000-0003-1535-8526 NR 63 TC 280 Z9 291 U1 3 U2 18 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD OCT PY 2007 VL 7 IS 10 BP 658 EP 666 DI 10.1016/S1473-3099(07)70236-0 PG 9 WC Infectious Diseases SC Infectious Diseases GA 215OM UT WOS:000249818900017 PM 17897608 ER PT J AU Traynor, BJ Singleton, A AF Traynor, Bryan J. Singleton, Andrew TI Genome-wide association studies and ALS: are we there yet? SO LANCET NEUROLOGY LA English DT Editorial Material ID AMYOTROPHIC-LATERAL-SCLEROSIS C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD USA. Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA 22903 USA. RP Singleton, A (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Traynor, Bryan/G-5690-2010 FU Intramural NIH HHS NR 9 TC 3 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD OCT PY 2007 VL 6 IS 10 BP 841 EP 843 DI 10.1016/S1474-4422(07)70225-9 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 218SQ UT WOS:000250035600003 PM 17884667 ER PT J AU Rademakers, R Baker, M Gass, J Adamson, J Huey, ED Momeni, P Spina, S Coppola, G Karydas, AM Stewart, H Johnson, N Hsiung, GY Kelley, B Kuntz, K Steinbart, E Wood, EM Yu, CE Josephs, K Sorenson, E Womack, KB Weintraub, S Pickering-Brown, SM Schopeld, PR Brooks, WS van Deerlin, VM Snowden, J Clark, CM Kertesz, A Boylan, K Ghetti, B Neary, D Schellenberg, GD Beach, TG Mesulam, M Mann, D Grafman, J Mackenzie, IR Feldman, H Bird, T Petersen, R Knopman, D Boeve, B Geschwind, DH Miller, B Wszolek, Z Lippa, C Bigio, EH Dickson, D Graff-Radford, N Hutton, M AF Rademakers, Rosa Baker, Matt Gass, Jennifer Adamson, Jennifer Huey, Edward D. Momeni, Parastoo Spina, Salvatore Coppola, Giovanni Karydas, Anna M. Stewart, Heather Johnson, Nancy Hsiung, Ging-Yuek Kelley, Brendan Kuntz, Karen Steinbart, Ellen Wood, Elisabeth McCarty Yu, Chang-En Josephs, Keith Sorenson, Eric Womack, Kyle B. Weintraub, Sandra Pickering-Brown, Stuart M. Schopeld, Peter R. Brooks, William S. van Deerlin, Vivianna M. Snowden, Julie Clark, Christopher M. Kertesz, Andrew Boylan, Kevin Ghetti, Bernardino Neary, David Schellenberg, Gerard D. Beach, Thomas G. Mesulam, Marsel Mann, David Grafman, Jordan Mackenzie, Ian R. Feldman, Howard Bird, Thomas Petersen, Ron Knopman, David Boeve, Bradley Geschwind, Dan H. Miller, Bruce Wszolek, Zbigniew Lippa, Carol Bigio, Eileen H. Dickson, Dennis Graff-Radford, Neill Hutton, Mike TI Phenotypic variability associated with progranulin haploinsufficiency in patients with the common 1477C -> T (Arg493X) mutation: an international initiative SO LANCET NEUROLOGY LA English DT Article ID FRONTOTEMPORAL LOBAR DEGENERATION; NULL MUTATIONS; GENE-MUTATIONS; DEMENTIA; TAU; CHROMOSOME-17; INCLUSIONS; DISEASE; NEUROPATHOLOGY; PATHOLOGY AB Background The progranulin gene (GRN) is mutated in 5-10% of patients with frontotemporal lobar degeneration (FTLD) and in about 20% of patients with familial FTLD. The most common mutation in GRN is Arg493X. We aimed to establish the contribution of this mutation to FTLD and related disorders. Methods We measured the frequency of Arg493X in 3405 unrelated patients with various neurodegenerative diseases using Taqman single-nucleotide polymorphism (SNP) genotyping. Clinicopathological characterisation and shared haplotype analysis were done for 30 families with FTLD who carry Arg493X. To investigate the effect of potential modifying loci, we did linear regression analyses with onset age as the covariate for GRN variants, for genotypes of the apolipoprotein E gene (APOE), and for haplotypes of the microtubule-associated protein tau gene (MAPT). Findings Of 731 patients with FTLD, 16 (2%) carried Arg493X. This mutation was not detected in 2674 patients who did not have FTLD. In 37 patients with Arg493X from 30 families with FTLD, clinical diagnoses included frontotemporal dementia, primary progressive aphasia, corticobasal syndrome, and Alzheimer's disease. Range of onset age was 44-69 years. In all patients who came to autopsy (n=13), the pathological diagnosis was FTLD with neuronal inclusions that contained TAR DNA-binding protein or ubiquitin, but not tau. Neurofibrillary tangle pathology in the form of Braak staging correlated with overall neuropathology in the Arg493X carriers. Haplotype analyses suggested that Arg493X arose twice, with a single founder for 27 families. Linear regression analyses suggested that patients with SNP rs9897528 on their wild-type GRN allele have delayed symptom onset. Onset ages were not associated with the MAPT H1 or H2 haplotypes or APOE genotypes, but early memory deficits were associated with the presence of an APOE epsilon 4 allele. Interpretation Clinical heterogeneity is associated with GRN haploinsufficiency, and genetic variability on the wild-type GRN allele might have a role in the age-related disease penetrance of GRN mutations. C1 Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. NINDS, NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Neurol, Lubbock, TX 79409 USA. Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA. Univ Siena, I-53100 Siena, Italy. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Vancouver Gen Hosp, ALS Ctr, Vancouver, BC, Canada. Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimer Dis Ctr, Chicago, IL USA. Univ British Columbia, Div Neurol, Vancouver, BC V5Z 1M9, Canada. Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Washington, Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Med Neurol, Seattle, WA USA. Univ Washington, Dept Pharmacol, Seattle, WA USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX USA. Univ Manchester, Fac Med & Hlth Sci, Manchester, Lancs, England. Prince Wales Med Res Inst, Sydney, NSW, Australia. Univ Penn, Sch Med, Rush Alzheimers Dis Ctr, Dept Neurol, Philadelphia, PA 19104 USA. Univ Western Ontario, London, ON, Canada. Mayo Clin, Coll Med, Dept Neurol, Jacksonville, FL 32224 USA. Sun Hlth Res Inst, Sun City, AZ USA. Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada. Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Rademakers, R (reprint author), Mayo Clin, Coll Med, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM rademakers.rosa@mayo.edu RI Pickering-Brown, Stuart/D-4008-2009; OI Pickering-Brown, Stuart/0000-0003-1561-6054; Grafman, Jordan H./0000-0001-8645-4457; Dickson, Dennis W/0000-0001-7189-7917; Snowden, Julie/0000-0002-3976-4310; Womack, Kyle/0000-0002-6060-9075; Feldman, Howard/0000-0002-9258-4538 FU Intramural NIH HHS; Medical Research Council [G0400356]; NIA NIH HHS [P50 AG03006, P01 AG017216, P01 AG019724, P01 AG17586, P30 AG10133, P30 AG12300, P30 AG13854, P30 AG19610, P50 AG05136, P50 AG16574, R01 AG026251, R01 AG026938]; NINDS NIH HHS [P50 NS40256] NR 37 TC 126 Z9 128 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD OCT PY 2007 VL 6 IS 10 BP 857 EP 868 DI 10.1016/S14744422(07)70221-1 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 218SQ UT WOS:000250035600016 PM 17826340 ER PT J AU Di Prospero, NA Baker, A Jeffries, N Fischbeck, KH AF Di Prospero, Nicholas A. Baker, Angela Jeffries, Neal Fischbeck, Kenneth H. TI Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial SO LANCET NEUROLOGY LA English DT Article ID RATING-SCALE; PHARMACOKINETICS; HYPERTROPHY; GLUTATHIONE; DAMAGE; MODEL AB Background Friedreichs ataxia (FA) is a progressive, multisystem, degenerative disorder caused by a reduction in frataxin. Loss of frataxin results in mitochondrial dysfunction and oxidative damage in patients and model systems. Previous Studies have indicated that the antioxidant idebenone (5 mg/kg daily) reduces cardiac hypertrophy, but definite improvement in neurological function has not been shown. Methods 48 genetically confirmed FA patients, aged 9-17 years, were enrolled in a 6-month, randomised, double-blind, placebo-controlled study. The patients received placebo or one of three doses of idebenone (similar to 5 mg/kg, 15 mg/kg, and 45 mg/kg), stratified by body weight. The primary endpoint was change from baseline in urinary 8-hydroxy-2'-deoxyguanosine (80H2'dG), a marker of oxidative DNA damage. Secondary endpoints included changes in the. international cooperative ataxia rating scale (ICARS), the FA rating scale (FARS), and a survey of activities of daily living (ADL). This study is registered with ClinicalTrials.gov, number NCT00229632. Findings Idebenone was generally well tolerated with similar numbers of adverse events in each group. One child receiving high-dose idebenone developed neutropenia after 6 months, which resolved after discontinuation of treatment. 80H2'dG concentrations were not increased, and did not significantly change with idebenone treatment. Whereas an overall analysis did not show a significant difference in ICARS, FARS, or ADL total scores, there were indications of a dose-dependent response in the ICARS score. A second, pre-specified analysis, excluding patients who required wheelchair assistance, showed a significant improvement in ICARS (Bonferroni p=0.03) and suggested a dose-related response in ICARS, FARS, and ADL scores. Interpretation Treatment with higher doses of idebenone was generally well tolerated and associated with improvement in neurological function and ADL in patients with FA. The degree of improvement correlated with the dose of idebenone, suggesting that higher doses may be necessary to have a beneficial effect on neurological function. C1 NINDS, NIH, Neurogenet Branch, Bethesda, MD 20892 USA. NINDS, NIH, Off Clin Director, Bethesda, MD 20892 USA. RP Di Prospero, NA (reprint author), NINDS, NIH, Neurogenet Branch, 35 Convent Dr,Bldg 35,Room 2A-1008, Bethesda, MD 20892 USA. EM diprospern@ninds.nih.gov FU Intramural NIH HHS NR 23 TC 162 Z9 165 U1 1 U2 10 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD OCT PY 2007 VL 6 IS 10 BP 878 EP 886 DI 10.1016/S1474-4422(07)70220-X PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 218SQ UT WOS:000250035600018 PM 17826341 ER PT J AU Savani, BN Mielke, S Adams, S Uribe, M Rezvani, K Yong, ASM Zeilah, J Kurlander, R Srinivasan, R Childs, R Hensel, N Barrett, AJ AF Savani, B. N. Mielke, S. Adams, S. Uribe, M. Rezvani, K. Yong, A. S. M. Zeilah, J. Kurlander, R. Srinivasan, R. Childs, R. Hensel, N. Barrett, A. J. TI Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia SO LEUKEMIA LA English DT Article DE hematological malignancies; natural killer cells; KIR genotype; allogeneic stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; IMMUNOGLOBULIN-LIKE RECEPTOR; KIR GENES; NK CELLS; ALLOREACTIVITY; GENOTYPES; RELAPSE; GRAFT; GVHD AB Natural killer (NK) cells are the first lymphocytes to recover after allogeneic stem cell transplantation (SCT) and can exert powerful graft-versus-leukemia(GVL) effects determining transplant outcome. Conditions governing NK cell alloreactivity and the role of NK recovery in sibling SCT are not well defined. NK cells on day 30 post-transplant (NK30) were measured in 54 SCT recipients with leukemia and donor and recipient killer immunoglobulin-like receptor (KIR) genotype determined. In univariate analysis, donor KIR genes 2DL5A, 2DS1, 3DS1 ( positive in 46%) and higher numbers of inhibitory donor KIR correlated with higher NK30 counts and were associated with improved transplant outcome. NK30 counts also correlated directly with the transplant CD34 cell dose and inversely with the CD3+ cell dose. In multivariate analysis, the NK30 emerged as the single independent determinant of transplant outcome. Patients with NK30 > 150/mu l had less relapse (HR 18.3, P =0.039), acute graft-versus-host disease ( HR 3.2, P =0.03), non-relapse mortality ( HR 10.7, P =0.028) and improved survival ( HR 11.4, P =0.03). Results suggest that T cell-depleted SCT might be improved and the GVL effect enhanced by selecting donors with favorable KIR genotype, and by optimizing CD34 and CD3 doses. C1 NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. Natl Canc Inst, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Room 3-5320,10 Ctr Dr MSC 12, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov NR 30 TC 83 Z9 86 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2007 VL 21 IS 10 BP 2145 EP 2152 DI 10.1038/sj.leu.2404892 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 211XC UT WOS:000249555600009 PM 17673900 ER PT J AU Marrelec, G Horwitz, B Kim, J Pelegrini-Issac, M Benali, H Doyon, J AF Marrelec, Guillaume Horwitz, Barry Kim, Jieun Pelegrini-Issac, Melanie Benali, Habib Doyon, Julien TI Using partial correlation to enhance structural equation modeling of functional MRI data SO MAGNETIC RESONANCE IMAGING LA English DT Article DE fMRI; functional brain interactivity; effective connectivity; partial correlation; structural equation modeling ID GRANGER CAUSALITY; NETWORK ANALYSIS; FMRI DATA; BRAIN; CONNECTIVITY; INTERACTIVITY AB In functional magnetic resonance imaging (fMRI) data analysis, effective connectivity investigates the influence that brain regions exert on one another. Structural equation modeling (SEM) has been the main approach to examine effective connectivity. In this paper, we propose a method that, given a set of regions, performs partial correlation analysis. This method provides an approach to effective connectivity that is data driven, in the sense that it does not require any prior information regarding the anatomical or functional connections. To demonstrate the practical relevance of partial correlation analysis for effective connectivity investigation, we reanalyzed data previously published [Bullmore, Horwitz, Honey, Brammer, Williams, Sharma, 2000. How good is good enough in path analysis of fMRI data? NeuroImage 11, 289-301]. Specifically, we show that partial correlation analysis can serve several purposes. In a pre-processing step, it can hint at which effective connections are structuring the interactions and which have little influence on the pattern of connectivity. As a post-processing step, it can be used both as a simple and visual way to check the validity of SEM optimization algorithms and to show which assumptions made by the model are valid, and which ones should be further modified to better fit the data. (C) 2007 Elsevier Inc. All rights reserved. C1 INSERM, U678, F-75013 Paris, France. Univ Paris 06, Fac Med Pitie Salpetriere, F-75013 Paris, France. Univ Montreal, UNF, MIC, Montreal, PQ H3W 1W5, Canada. NIH, Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, Bethesda, MD 20892 USA. RP Marrelec, G (reprint author), CHU Pitie Salpetriere, INSERM, U678, 91 Blvd Hop, F-75634 Paris 13, France. EM marrelec@imed.jussieu.fr FU Intramural NIH HHS NR 27 TC 26 Z9 26 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD OCT PY 2007 VL 25 IS 8 BP 1181 EP 1189 DI 10.1016/j.mri.2007.02.012 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 220HV UT WOS:000250148700008 PM 17475433 ER PT J AU Weiser, KC Liu, B Hansen, GM Skapura, D Hentges, KE Yarlagadda, S Morse, HC Justice, MJ AF Weiser, Keith C. Liu, Bin Hansen, Gwenn M. Skapura, Darlene Hentges, Kathryn E. Yarlagadda, Sujatha Morse, Herbert C., III Justice, Monica J. TI Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma SO MAMMALIAN GENOME LA English DT Article ID ACUTE MYELOID-LEUKEMIA; B-CELL LEUKEMIA; INTEGRATION SITE; GENE-EXPRESSION; FUSION PROTEIN; DISEASE GENES; CANCER; ACTIVATION; TRANSCRIPTION; STRAINS AB AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NF kappa B, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at http://www.mouse-genome.bcm.tmc.edu/vision. C1 Baylor Coll Med, Interdept Program Cell & Mol Biol, Houston, TX 77030 USA. NIAID, NIH, Immunopathol Lab, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Human Mol Genet, Houston, TX 77030 USA. RP Justice, MJ (reprint author), Lexicon Genet Inc, 8800 Technol Forest Pl, The Woodlands, TX 77381 USA. EM mjustice@bcm.tmc.edu OI Morse, Herbert/0000-0002-9331-3705 FU Intramural NIH HHS; NCI NIH HHS [R01 CA063229, R01 CA63229] NR 68 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 2007 VL 18 IS 10 BP 709 EP 722 DI 10.1007/s00335-007-9060-2 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 224JI UT WOS:000250442900003 PM 17926094 ER PT J AU Forlino, A Kuznetsova, NV Marini, JC Leikin, S AF Forlino, Antonella Kuznetsova, Natalia V. Marini, Joan C. Leikin, Sergey TI Selective retention and degradation of molecules with a single mutant alpha 1(I) chain in the Brtl IV mouse model of OI SO MATRIX BIOLOGY LA English DT Article DE type I collagen; Osteogenesis Imperfecta; collagen secretion; reactive sulphide group ID CARBOXYL-TERMINAL PROPEPTIDE; EHLERS-DANLOS-SYNDROME; OSTEOGENESIS IMPERFECTA; PRO-ALPHA-1(I) CHAIN; TRIPLE-HELIX; MURINE MODEL; COL1A2 GENE; COLLAGEN; MUTATIONS; PROCOLLAGEN AB We investigated the secretion, matrix incorporation and interactions of molecules with one and two mutant alpha 1(I) collagen chains in the Brtl IV murine model for Osteogenesis Imperfecta, carrying a Gly-349 to Cys substitution in one col I al allele. We detected a significant deviation from the expected 25 and 50% content of the molecules with no (37-46%) and one (26-40%) mutant chains in skin and bone as well as in fibroblast and osteoblast cell culture media. Steady-state labeling with S-35-Cys demonstrated incomplete secretion of the mutant collagen in cell culture, particularly molecules containing one mutant chain. Pulse and pulse-chase experiments revealed slower secretion of the latter. An enlargement of endoplasmic reticulum in skin fibroblasts from Brtl IV mice, clearly visible by electron microscopy, supported the abnormal secretion identified by biochemical studies. We observed increased susceptibility of molecules with one mutant chain to proteolytic degradation in vitro, but we did not detect significant selective degradation in cell culture media. Mutant collagen molecules incorporated from the media into newly deposited fibers and into fully crosslinked and mature matrix in the same ratio as they were secreted. Specific labeling of reactive -SH demonstrated that about half of the Cvs349-SH groups in the mutant molecules were exposed and potentially available for aberrant interactions with other molecules inside or outside the cells. Based on these and our previous findings, we argue that the outcome in Brtl IV may be significantly affected by cellular stress and malfunction caused by the retention and degradation of newly synthesized mutant collagen. (c) 2007 Elsevier B.V/International Society of Matrix Biology. All rights reserved. C1 [Forlino, Antonella] Univ Pavia, Dept Biochem A Castellani, I-27100 Pavia, Italy. [Forlino, Antonella; Marini, Joan C.] NIH, NICHD, BEMB, Sect Connect Tissue Disorders, Bethesda, MD 20892 USA. [Kuznetsova, Natalia V.; Leikin, Sergey] NIH, NICHD, Sect Phys Biochem, Bethesda, MD 20892 USA. RP Forlino, A (reprint author), Univ Pavia, Dept Biochem A Castellani, Via Taramelli 3B, I-27100 Pavia, Italy. EM aforlino@unipv.it RI Leikin, Sergey/A-5518-2008; Forlino, Antonella/H-5385-2015 OI Leikin, Sergey/0000-0001-7095-0739; Forlino, Antonella/0000-0002-6385-1182 NR 31 TC 29 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD OCT PY 2007 VL 26 IS 8 BP 604 EP 614 DI 10.1016/j.matbio.2007.06.005 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 245HZ UT WOS:000251927000004 PM 17662583 ER PT J AU Drinkard, B Roberts, MD Ranzenhofer, LM Han, JC Yanoff, LB Merke, DP Savastano, DM Brady, S Yanovski, JA AF Drinkard, Bart Roberts, Mary D. Ranzenhofer, Lisa M. Han, Joan C. Yanoff, Lisa B. Merke, Deborah P. Savastano, David M. Brady, Sheila Yanovski, Jack A. TI Oxygen-uptake efficiency slope as a determinant of fitness in overweight adolescents SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE obesity; exercise test; nonoverweight; physical fitness ID CARDIORESPIRATORY FUNCTIONAL RESERVE; ANAEROBIC THRESHOLD; EXERCISE TOLERANCE; CHILDREN; OBESITY; PERFORMANCE; INDEX; AMERICAN; CAPACITY; VALIDITY AB Purpose: Peak oxygen uptake ((V) over dot O-2peak) is frequently difficult to assess in overweight individuals; therefore, submaximal measures that predict (V) over dot O-2peak are proposed as substitutes. Oxygen uptake efficiency slope (OUES) has been suggested as a submaximal measurement of cardiorespiratory fitness that is independent of exercise intensity. There are few data examining its value as a predictor of (V) over dot O-2peak in severely overweight adolescents. Methods: One hundred seven severely overweight (BMI Z 2.50 +/- 0.34) and 43 nonoverweight (BMI Z 0.13 +/- 0.84) adolescents, performed a maximal cycle ergometer test with respiratory gas-exchange measurements. OUES was calculated through three exercise intensities: lactate inflection point (OUES LI), 150% of lactate inflection point (OUES 150), and (V) over dot O-2peak (OUES PEAK). Results: When adjusted for lean body mass, (V) over dot O-2peak and OUES at all exercise intensities were lower in overweight subjects ((V) over dot O-2peak: 35.3 +/- 6.4 vs 46.8 +/- 7.9 mL.kg(-1) LBM.min(-1), P < 0.001; OUES LI: 37.9 +/- 10.0 vs 43.7 +/- 9.2 mL.kg(-1) LBM.min(-1).logL(-1) P < 0.001; OUES 150: 41.6 +/- 9.0 vs 49.8 +/- 11.1 mL.kg(-1) LBM.min(-1).logL(-1) P < 0.001; and OUES PEAK: 45.1 +/- 8.7 vs 52.8 +/- 9.6 mL-kg(-1) LBM.min(-1).logL(-1) P < 0.001). There was a significant increase in OUES with increasing exercise intensity in both groups (P < 0.001). OUES at all exercise intensities was a significant. predictor of (V) over dot O-2peak for both groups (r(2) = 0.35-0.83, P < 0.0001). However, limits of agreement for predicted (V) over dot O-2peak relative to actual (V) over dot O-2peak were wide (+/-478 to +/-670 mL.min(-1)). Conclusions: OUES differs significantly in overweight and nonoverweight adolescents. The wide interindividual variation and the exercise intensity dependence of OUES preclude its use in clinical practice as a predictor of (V) over dot O-2peak. C1 NICHHD, Unit Growth & Obes, Natl Inst Hlth, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Natl Inst Hlth, Mark O Hatfield Clin Res Ctr, Dept Rehabil Med, Bethesda, MD USA. NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obes, Natl Inst Hlth, Dev Endocrinol Branch, Bldg CRC Room 1-1330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM yanovskj@mail.nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z99 HD999999, Z01 HD000641-12]; NICHD NIH HHS [Z01 HD000641] NR 38 TC 24 Z9 26 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD OCT PY 2007 VL 39 IS 10 BP 1811 EP 1816 DI 10.1249/mss.0b013e31812e52b3 PG 6 WC Sport Sciences SC Sport Sciences GA 217RD UT WOS:000249964100018 PM 17909409 ER PT J AU Carlson, OD David, JD Schrieder, JM Muller, DC Jang, HJ Kim, BJ Egan, JM AF Carlson, Olga D. David, Jehan D. Schrieder, Jessica M. Muller, Dennis C. Jang, Hyeung-Jin Kim, Byung-Joon Egan, Josephine M. TI Contribution of nonesterified fatty acids to insulin resistance in the elderly with normal fasting but diabetic 2-hour postchallenge plasma glucose levels: the Baltimore Longitudinal Study of Aging SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID NECROSIS-FACTOR-ALPHA; HOMEOSTASIS MODEL ASSESSMENT; BETA-CELL FUNCTION; ADIPOSE-TISSUE; NONDIABETIC SUBJECTS; NATIONAL SAMPLE; SKELETAL-MUSCLE; TOLERANCE TEST; US ADULTS; HYPERGLYCEMIA AB Isolated postchallenge hyperglycemia (IPH) with normal fasting plasma glucose <100 mg/dL and plasma glucose with diabetic 2-hour plasma glucose >= 200 mg/dL after an oral glucose tolerance test (OGTT) is a common occurrence in the elderly. We sought to understand what unique characteristics this population might have that puts it at risk for this particular metabolic finding. We therefore conducted a longitudinal study of volunteers in the Baltimore Longitudinal Study of Aging (BLSA). All volunteers had an OGTT performed (75 g) on 2 or more occasions. We measured plasma levels of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), ghrelin, leptin, adiponectin, resistin, C-reactive protein, cytokines, and their soluble receptors, as well as nonesterified free fatty acids (NEFAs). We determined that 22 subjects in BLSA had IPH, accounting for 2.1% of the BLSA population. All 22 were older than 65 years. They were then matched by age, sex, and body mass index to 12 subjects who had isolated impaired glucose tolerance (IGT) and 15 subjects with normal glucose tolerance (NGT). All subjects had normal fasting glucose levels <100 mg/dL in accordance with the American Diabetes Association Expert Committee on the Classification and Diagnosis of Diabetes Mellitus criteria (2003). We found that subjects with IPH had similar plasma insulin levels to the other 2 groups, except at the 2-hour time when their insulin levels were higher than NGT (P <.05). Although there was a clear trend for differences in the insulinogenic index, the areas under the curves for insulin, systolic blood pressure, adiponectin, and C-reactive protein across the glucose tolerance categories revealed no statistical significance. Cytokines and their soluble receptors, gut hormones, and adipokines were similar in all 3 groups. The NEFA levels were significantly elevated in the fasting state (P <.05) in the IPH compared with NGT, with IGT intermediate between the other 2 groups. The rate of clearance of NEFAs after the OGTT decreased progressively from the NGT to the IPH group (in micromoles per liter per minute: NGT. 11.9 vs IGT, 7.6 vs IPH, 3.0). We conclude that the rate of suppression of lipolysis in the elderly determines the sensitivity of glucose uptake to insulin after OGTT. (c) 2007 Elsevier Inc. All rights reserved. C1 NIH, NIA, Diabet Sect, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIH, NIA, Diabet Sect, Baltimore, MD 21224 USA. EM eganj@grc.nia.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 46 TC 4 Z9 4 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 2007 VL 56 IS 10 BP 1444 EP 1451 DI 10.1016/j.metabol.2007.06.009 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 215XU UT WOS:000249843100023 PM 17884459 ER PT J AU Klinman, DM Currie, D Lee, G Grippe, V Merkel, T AF Klinman, Dennis M. Currie, Debra Lee, Gloria Grippe, Vanessa Merkel, Tod TI Systemic but not mucosal immunity induced by AVA prevents inhalational anthrax SO MICROBES AND INFECTION LA English DT Article DE anthrax; vaccine; protection ID BACILLUS-ANTHRACIS; CPG MOTIFS; PROTECTIVE ANTIGEN; RHESUS MACAQUES; VACCINE; INFECTION; MICE; OLIGODEOXYNUCLEOTIDES; IMMUNOGENICITY; IMMUNIZATION AB Improved vaccines and adjuvants are being developed to reduce the threat posed by a terrorist attack involving aerosolized anthrax spores. Nevertheless, uncertainty persists concerning the relative benefits of inducing mucosal vs systemic immunity to host survival following inhalational exposure to anthrax spores. This work examines the effect of delivering the licensed human vaccine (anthrax vaccine adsorbed, AVA) combined with a CpG oligodeoxynucleotide (ODN) adjuvant intraperitoneally or intranasally to A/J mice. Results indicate that protection from inhalational anthrax correlates with the induction of a strong systemic rather than mucosal immune response, and demonstrate that protection is significantly improved and accelerated by the addition of CpG ODN. (c) 2007 Elsevier Masson SAS. All rights reserved. C1 Natl Canc Inst, Expt Immunol Lab, Ft Detrick, MD 21702 USA. Ctr Biol Evaluat & Res, Food & Drug Adm, Lab Respirat & Special Pathogens, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), Natl Canc Inst, Expt Immunol Lab, Ft Detrick, MD 21702 USA. EM klinmand@niail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 28 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD OCT PY 2007 VL 9 IS 12-13 BP 1478 EP 1483 DI 10.1016/j.micinf.2007.08.002 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 238WU UT WOS:000251479900012 PM 17913545 ER PT J AU Zahn, CM Dunlow, SG Alvero, R Parker, JD Nace, MC Armstrong, AY AF Zahn, Christopher M. Dunlow, Susan G. Alvero, Ruben Parker, Jason D. Nace, M. Catherine Armstrong, Alicia Y. TI Too little time to teach? Medical student education and the resident work-hour restriction SO MILITARY MEDICINE LA English DT Article ID SLEEP-DEPRIVATION; TRAINING-PROGRAM; PERFORMANCE; SATISFACTION; LIMITATIONS; EXPERIENCE; OBSTETRICS; ATTITUDES; FATIGUE; SKILLS AB Objective: The purpose of this study was to examine the impact of the resident duty-hour restriction on medical student education through a survey of faculty, residents, and interns, with interns providing experience as students relative to implementation of work-hour restrictions. Methods: A survey was performed at two (one military and one civilian) obstetrics and gynecology residency programs, Additional surveys were obtained from an Association of Professors of Gynecology and Obstetrics workshop, which included military and nonmilitary attendees. Results: The majority of faculty reported spending 5 to 10 hours per week in medical education before and after implementation of the work-hour restriction. Residents reported less time teaching students after work-hour restrictions were instituted. Nearly all interns, responding about their clinical clerkship experience as students, believed their educational experience would have been improved if residents were more involved in teaching. Conclusion: This pilot study suggests residents are less involved in medical student education following implementation of the duty-hour restrictions. C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Dept Obstet & Gynecol, Washington, DC 20307 USA. Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Aurora, CO 80045 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20814 USA. RP Zahn, CM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. EM czahn@usuhs.mil FU Intramural NIH HHS NR 24 TC 9 Z9 9 U1 0 U2 0 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD OCT PY 2007 VL 172 IS 10 BP 1053 EP 1057 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 221UE UT WOS:000250252000009 PM 17985765 ER PT J AU Yi, L Zhou, ZH Ping, YF Chen, JH Yao, XH Feng, H Lu, JY Wang, JM Bian, XW AF Yi, Liang Zhou, Zhi-hua Ping, Yi-fang Chen, Jian-hong Yao, Xiao-hong Feng, Hua Lu, Jia-you Wang, Ji Ming Bian, Xiu-wu TI Isolation and characterization of stem cell-like precursor cells from primary human anaplastic oligoastrocytoma SO MODERN PATHOLOGY LA English DT Article DE oligoastrocytoma; cancer stem cell; CD133; nestin; differentiation ID ACUTE MYELOID-LEUKEMIA; BREAST-CANCER CELLS; BRAIN-TUMORS; SELF-RENEWAL; IN-VITRO; IDENTIFICATION; GLIOBLASTOMA; HIERARCHY; GLIOMAS AB A small population of stem cell-like precursors in solid tumors are linked to histological composition, progression, angiogenesis, metastasis, recurrence and drug resistance of a variety of malignant tumors. Oligoastrocytoma is the most common brain mixed glioma composed of mixed cells of oligodendroglial and astrocytic phenotypes. Identification and characterization of stem cell-like precursors in oligoastrocytoma may shed light on the oncogenesis of this unique type of tumor and assist in the design of novel therapeutic strategy. Here, tumor stem cell-like precursors were identified from primary human anaplastic oligoastrocytomas by labeling of the tumor sections with nestin and CD133. Tumor cells were cultured in vitro in stem cell medium with growth factors and the capacity of the surviving stem cell-like precursors to form tumor spheres was tested. The tumor spheres were further injected subcutaneously into nude mice to observe the contribution of stem cell-like precursors to histological composition and tumor progression. We found that primary human oligoastrocytoma tissues contained nestin(+)/CD133(+) stem cell-like precursors. These cells differentiated into tumor cells with both oligodendroglial and astrocytic characteristics and formed tumor spheres in vitro, which upon implantation in nude mice, grew into tumor nodules containing nestin (+)/CD133(+) cells at levels higher than in the primary tumor tissues. This study revealed for the first time that anaplastic human oligoastrocytomas contained stem cell-like precursors, which exhibit neural stem cell properties with tumorigenicity. These stem cell-like precursors may be responsible for the oligodendroglial and astrocytic components of human oligoastrocytoma and should be considered as therapeutic targets. C1 Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China. Third Mil Med Univ, Southwest Hosp, Dept Neurosurg, Chongqing 400038, Peoples R China. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Bian, XW (reprint author), Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China. EM bianxiuwu@263.net RI Bian, Xiuwu/F-1569-2011; yi, liang/K-6010-2012; Bian, Xiu-wu/D-4736-2017 OI Bian, Xiu-wu/0000-0003-4383-0197 NR 29 TC 48 Z9 63 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2007 VL 20 IS 10 BP 1061 EP 1068 DI 10.1038/modpathol.3800942 PG 8 WC Pathology SC Pathology GA 212GT UT WOS:000249583000007 PM 17660801 ER PT J AU Li, J Zhang, YH Sullivan, M Hong, LX Huang, L Lu, FL McCutchan, TF Su, XZ AF Li, Jian Zhang, Yanhui Sullivan, Margery Hong, Linxian Huang, Lei Lu, Fangli McCutchan, Thomas F. Su, Xin-zhuan TI Typing Plasmodium yoelii microsatellites using a simple and affordable fluorescent labeling method SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE genetic mapping; genotyping; rodent malaria parasite; simple sequence repeat ID M13-TAILED PRIMERS; MALARIA PARASITES; FALCIPARUM; MARKERS; SEQUENCES; GENOME; GENE; DNA AB The rodent malaria parasite Plasmodium yoelii has been an important animal model for studying malaria pathology and host-parasite interactions. Compared with other rodent malaria parasites such as Plasmodium chabaudi, however, genetic mapping studies on P. yoelii have been limited, partly due to the absence of genetic markers and the lack of well characterized phenotypes. Taking advantage of the available genome sequence, we initiated a project to develop a high-resolution microsatellite (MS) map for P. yoelii to study malaria disease phenotypes. Here we report screening the P. yoelii genome for simple sequence repeats and development of an inexpensive method (modified from a previously reported procedure) for typing malaria parasite MS: instead of labeling individual polymerase chain reaction primers, a single fluorescently labeled primer was used to type the MS markers. We evaluated various polymerase chain reaction cycling conditions and M13-tailed/labeled M13 primer ratios to establish a simple and robust procedure for typing P. yoelii MS markers. We also compared typing efficiencies between individually labeled primers and the M13-tailed single labeled primer method and found that the two approaches were comparable. Preliminary analyses of seven P. yoelii isolates deposited at MR4 with 77 MS showed that the markers were highly polymorphic and that the isolates belonged to two groups, suggesting potential common ancestry or laboratory contaminations among the isolates. The MS markers and the typing method provide important tools for genetic studies of P. yoelii. There is a good possibility that this method can be applied to type MS from other malaria parasites including important human pathogens Plasmodium falciparum and Plasmodium vivax. (c) 2007 Elsevier B.V. All rights reserved. C1 Xiamen Univ, Sch Life Sci, Lab Parasitol Res, Fujian 361005, Peoples R China. NIAID, NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510080, Guangdong, Peoples R China. RP Su, XZ (reprint author), Xiamen Univ, Sch Life Sci, Lab Parasitol Res, Fujian 361005, Peoples R China. EM xsu@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS [Z01 AI000892-07, Z99 AI999999] NR 26 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD OCT PY 2007 VL 155 IS 2 BP 94 EP 102 DI 10.1016/j.molbiopara.2007.06.003 PG 9 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 211UJ UT WOS:000249548500003 PM 17658627 ER PT J AU Bockhorst, J Lu, F Janes, JH Keebler, J Gamain, B Awadalla, P Su, XZ Samudrala, R Jojica, N Smith, JD AF Bockhorst, Joseph Lu, Fangli Janes, Joel H. Keebler, Jon Gamain, Benoit Awadalla, Philip Su, Xin-zhuan Samudrala, Ram Jojica, Nebojsa Smith, Joseph D. TI Structural polymorphism and diversifying selection on the pregnancy malaria vaccine candidate VAR2CSA SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE antigenic variation; malaria; Plasmodium falciparum; var genes ID CHONDROITIN-SULFATE-A; FALCIPARUM-INFECTED ERYTHROCYTES; PROTEIN-STRUCTURE PREDICTION; VAR GENE FAMILY; PLASMODIUM-FALCIPARUM; ANTIGENIC PROPERTIES; EVOLUTIONARY ORIGIN; PLACENTAL MALARIA; RECOMBINATION; ANTIBODIES AB VAR2CSA is the main candidate for a pregnancy malaria vaccine, but vaccine development may be complicated by sequence polymorphism. Here, we obtained partial or full-length var2CSA sequences from 106 parasites and applied novel computational methods and three-dimensional modeling to investigate VAR2CSA geographic variation and selection pressure. Our analysis reveals structural patterns of VAR2CSA sequence variation in which polymorphic sites group into segments of limited diversity. Within these segments, two or three basic types characterize a substantial majority of the parasite samples. Comparison to the primate malaria Plasmodium reichenowi shows that these basic types have ancient origins. Globally, var2CSA genes are comprised of a mosaic of these ancestral polymorphic segments that have recombined extensively between var2CSA alleles. Three-dimensional modeling reveals that polymorphic segments concentrate in flexible loops at characteristic locations in the six VAR2CSA Duffy binding-like (DBL) adhesion domains. Individual DBL domain surfaces have distinct patterns of diversifying selection, suggesting that limited and differing portions of each DBL domain are targeted by host antibody. Since standard phylogenetic tree analysis is inadequate for highly recombining genes like var2CSA, we developed a novel phylogenetic approach that incorporates recombination and tracks new mutations in segment types. In the resulting tree, P. reichenowi is confirmed as an outlier and African and Asian P. falciparum isolates have slightly diverged. These findings validate a new approach to modeling protein evolution in the presence of frequent recombination and provide a clearer understanding of how var gene products function as immunoevasive binding ligands. (c) 2007 Elsevier B.V. All rights reserved. C1 Seattle Biomed Res Inst, Seattle, WA 98109 USA. Microsoft Res, Seattle, WA USA. Univ Wisconsin, Milwaukee, WI 53201 USA. NIAID, NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA. Inst Pasteur, Unite Biol Interact Hote Parasite, Paris, France. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. RP Smith, JD (reprint author), Seattle Biomed Res Inst, 4 Nickerson St, Seattle, WA 98109 USA. EM joe.smith@sbri.org OI Gamain, Benoit/0000-0002-8255-2145; Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS NR 44 TC 70 Z9 70 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD OCT PY 2007 VL 155 IS 2 BP 103 EP 112 DI 10.1016/j.molbiopara.2007.06.007 PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 211UJ UT WOS:000249548500004 PM 17669514 ER PT J AU Kim, HS Kuwano, Y Zhan, M Pullmann, R Mazan-Mamczarz, K Li, HA Kedersha, N Anderson, P Wilce, MCJ Gorospe, M Wilce, JA AF Kim, Henry S. Kuwano, Yuki Zhan, Ming Pullman, Rudolf, Jr. Mazan-Mamczarz, Krystyna Li, Huai Kedersha, Nancy Anderson, Paul Wilce, Matthew C. J. Gorospe, Myriam Wilce, Jacqueline A. TI Elucidation of a C-rich signature motif in target mRNAs of RNA-Binding protein TIAR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ANTIGEN-RELATED PROTEIN; GENE-EXPRESSION; STRESS GRANULES; TRANSLATIONAL REPRESSION; 3'-UNTRANSLATED REGION; RECOGNITION MOTIFS; HUR; STABILITY; ELEMENT; ALPHA AB The RNA-binding protein TIAR (related to TIA-1 [T-cell-restricted intracellular antigen 1]) was shown to associate with subsets of mRNAs bearing U-rich sequences in their 3' untranslated regions. TIAR can function as a translational repressor, particularly in response to cytotoxic agents. Using unstressed colon cancer cells, collections of mRNAs associated with TIAR were isolated by immunoprecipitation (IP) of (TIAR-RNA) ribonucleoprotein (RNP) complexes, identified by microarray analysis, and used to elucidate a common signature motif present among TIAR target transcripts. The predicted TIAR motif was an unexpectedly cytosine-rich, 28- to 32-nucleotide-long element forming a stem and a loop of variable size with an additional side loop. The ability of TIAR to bind an RNA oligonucleotide with a representative C-rich TIAR motif sequence was verified in vitro using surface plasmon resonance. By this analysis, TIAR containing two or three RNA recognition domains (TIAR12 and TIAR123) showed low but significant binding to the C-rich sequence. In vivo, insertion of the C-rich motif into a heterologous reporter strongly suppressed its translation in cultured cells. Using this signature motif, an additional similar to 2,209 UniGene targets were identified (2.0% of the total UniGene database). A subset of specific mRNAs were validated by RNP IP analysis. Interestingly, in response to treatment with short-wavelength UV light (UVC), a stress agent causing DNA damage, each of these target mRNAs bearing C-rich motifs dissociated from TIAR. In turn, expression of the encoded proteins was elevated in a TIAR-dependent manner. In sum, we report the identification of a C-rich signature motif present in TIAR target mRNAs whose association with TIAR decreases following exposure to a stress-causing agent. C1 NIH, NIA IRP, Mol Cell Biol Lab, Baltimore, MD 21224 USA. Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia. NIH, NIA IRP, Res Resources Branch, Baltimore, MD 21228 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol & Immunol, Boston, MA 02115 USA. RP Gorospe, M (reprint author), NIH, NIA IRP, Mol Cell Biol Lab, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov OI Wilce, Jacqueline/0000-0002-8344-2626 FU Intramural NIH HHS; NIAID NIH HHS [AI33600, R01 AI033600, R56 AI033600]; NIAMS NIH HHS [R01 AR051472] NR 46 TC 49 Z9 51 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2007 VL 27 IS 19 BP 6806 EP 6817 DI 10.1128/MCB.01036-07 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 213CD UT WOS:000249642600019 PM 17682065 ER PT J AU Lu, NZ Collins, JB Grissom, SF Cidlowski, JA AF Lu, Nick Z. Collins, Jennifer B. Grissom, Sherry F. Cidlowski, John A. TI Selective regulation of bone cell apoptosis by translational isoforms of the glucocorticoid receptor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TISSUE-SPECIFIC COACTIVATOR; GENE-EXPRESSION; MOLECULAR-MECHANISMS; NUCLEAR RECEPTORS; ACTIVATION; IDENTIFICATION; OSTEOBLASTS; SPECIFICITY; SURFACES; ENZYME AB Glucocorticoids are widely used in the treatment of inflammatory and other diseases. However, high-dose or chronic administration often triggers troublesome side effects such as metabolic syndrome and osteoporosis. We recently described that one glucocorticoid receptor gene produces eight translational glucocorticoid receptor isoforms that have distinct gene-regulatory abilities. We show here that specific, but not all, glucocorticoid receptor isoforms induced apoptosis in human osteosarcoma. U-2 OS bone cells. Whole human genome microarray analysis revealed that the majority of the glucocorticoid target genes were selectively regulated by specific glucocorticoid receptor isoforms. Real-time PCR experiments confirmed that proapoptotic enzymes necessary for cell death, granzyme A and caspase-6, were induced by specific glueocorticoid receptor isoforms. Chromatin immunoprecipitation assays further suggested that glucocorticoid receptor isoform-dependent induction of proapoptotic genes was likely due to selective coregulator recruitment and chromatin modification. Interestingly, the capabilities to transrepress proinflammatory genes were similar among glucocorticoid receptor isoforms. Together, these findings provide new evidence that translational glucocorticoid receptor isoforms can elicit distinct glucocorticoid responses and may be useful for the development of safe glucocorticoids with reduced side effects. C1 NIEHS, Natl Inst Hlth, Dept Hlth & Human Serv, Lab Signal Transduct,Mol Endocrinol Grp, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Inst Hlth, Dept Hlth & Human Serv, Microarray Ctr, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Natl Inst Hlth, Dept Hlth & Human Serv, Lab Signal Transduct,Mol Endocrinol Grp, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU Intramural NIH HHS NR 35 TC 75 Z9 79 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2007 VL 27 IS 20 BP 7143 EP 7160 DI 10.1128/MCB.00253-07 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 219QN UT WOS:000250099800014 PM 17682054 ER PT J AU Mishra, K Rajb, DK Hazra, RK Dash, AP Supakar, PC AF Mishra, Kirti Rajb, Dipak K. Hazra, Rupenangshu K. Dash, Aditya P. Supakar, Prakash C. TI The development and evaluation of a single step multiplex PCR method for simultaneous detection of Brugia malayi and Wuchereria bancrofti SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE polymerase chain reaction; multiplex PCR; diagnosis; Brugia malayi; Wuchereria bancrofti ID POLYMERASE-CHAIN-REACTION; REACTION-BASED ASSAY; BLOOD-SAMPLES; DIFFERENTIAL-DIAGNOSIS; LYMPHATIC FILARIASIS; DNA; MOSQUITOS; INFECTION AB A single step novel multiplex polymerase chain reaction (PCR) has been developed for simultaneous detection of human filarial parasites, Brugia malayi and Wuchereria bancrofti, from blood samples and mosquitoes. The primers used were novel and have been tested with the parasite DNA amplifying 188bp (BM) and 129bp (WB) DNA fragments, specific to B. malayi and W. bancrofti, respectively, in a single reaction. The specificity of the PCR product was confirmed by DNA sequencing and slot blot hybridization assay. The test was found highly sensitive for both B. malayi and W. bancrofti by detecting the parasitaemia up to the level of one microfilaria per reaction. The assay was further evaluated on 98 blood samples and 144 mosquito samples collected from filarial endemic areas. The PCR was found to be more efficient in comparison to microscopy by detecting 8% and 5% more filarial parasites in field-collected blood and mosquito samples, respectively. This novel PCR that offers scope for simultaneous detection of both the parasites may be used as a diagnostic tool for the detection of filariasis in population and can be adopted for rapid surveillance and monitoring of mosquitoes for use in the effective control of filariasis. (c) 2007 Elsevier Ltd. All rights reserved. C1 Inst Life Sci, Bhubaneswar 751023, Orissa, India. NIAID, Rockville, MD 20852 USA. Reg Med Res Ctr, Bhubaneswar 751023, Orissa, India. Natl Inst Malaria Res, New Delhi 110054, India. RP Supakar, PC (reprint author), Inst Life Sci, Nalco Sq, Bhubaneswar 751023, Orissa, India. EM pcsupakar@hotmail.com NR 26 TC 18 Z9 18 U1 1 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD OCT-DEC PY 2007 VL 21 IS 5-6 BP 355 EP 362 DI 10.1016/j.mcp.2007.05.001 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 212QN UT WOS:000249612000006 PM 17560074 ER PT J AU Hahn, Y Jeong, S Lee, B AF Hahn, Yoonsoo Jeong, Sangkyun Lee, Byungkook TI Inactivation of MOXD2 and S100A15A by Exon deletion during human evolution SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE human; chimpanzee; exon deletion; gene inactivation ID DOPAMINE-BETA-HYDROXYLASE; SEQUENCE ALIGNMENT; CHIMPANZEE GENOME; PROTEIN FAMILY; GENE; MOUSE; DIVERGENCE; EXPRESSION; UPDATE; NOMENCLATURE AB We devised a bioinformatics method for systematic identification of putative human-specific exon-deletion mutations that occurred after the divergence of human and chimpanzee and experimentally verified 2 of the predicted mutations in MOXD2 and S100A15A genes. MOXD2 gene encodes a monooxygenase that is highly conserved in mammals and is mostly expressed in the olfactory epithelium in mouse. The presence of a deletion of the last 2 exons and a polymorphic nonsense mutation in exon 6 suggests that MOXD2 gene is inactive in humans. S100A15A is a member of the S100 family of calcium-binding proteins, the mouse ortholog of which is expressed during epidermal maturation. Human S100A15A gene is likely to be inactive because the start codon-bearing exon is deleted in human. We propose that modification or inactivation of MOXD2 and S100A15A genes have contributed to the loss of certain smell sense in humans and to the development of human skin. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Lee, B (reprint author), Chung Ang Univ, Coll Nat Sci, Dept Life Sci, Seoul 156756, South Korea. EM bk@nih.gov FU Intramural NIH HHS NR 49 TC 17 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD OCT PY 2007 VL 24 IS 10 BP 2203 EP 2212 DI 10.1093/molbev/msm146 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 224HB UT WOS:000250437000006 PM 17642472 ER PT J AU Shiao, MS Khil, P Camerini-Otero, RD Shiroishi, T Moriwaki, K Yu, HT Long, M AF Shiao, Meng-Shin Khil, Pavel Camerini-Otero, R. Daniel Shiroishi, Toshihiko Moriwaki, Kazuo Yu, Hon-Tsen Long, Manyuan TI Origins of new male germ-line functions from X-derived autosomal retrogenes in the mouse SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE mouse; retroposition; spermatogenesis; male functions ID MEIOTIC CHROMOSOME SYNAPSIS; GENE-EXPRESSION; DNA POLYMORPHISM; RETROPOSED GENE; SEX-CHROMOSOMES; ZFX GENE; DROSOPHILA; EVOLUTION; MICE; RNA AB Recent literature demonstrates that retrogenes tend to leave the X chromosome and integrate onto the autosomes and evolve male-biased expression patterns. Several selection-based evolutionary mechanisms have been proposed to explain this observation. Testing these selection-based models requires examining the evolutionary history and functional properties of new retrogenes, particularly those that show evidence of directional movement between the X and the autosomes (X-related retrogenes). This includes autosomal retrogenes with parental paralogs on the X chromosome (X-derived autosomal retrogenes) and those retrogenes integrated onto the X chromosomes (X-linked retrogenes). In order to understand why retrogenes tend to move nonrandomly in genomes, we examined the expression patterns and evolutionary mechanisms concerning gene pairs having young retrogenes-originating less than 20 MYA (after mouse-rat split). We demonstrate that these X-derived autosomal retrogenes evolved a more restricted male-biased expression pattern: they are expressed exclusively or predominantly in the testis, in particular, during the. late stages of sperm atogenesis. In contrast, the parental counterparts have relatively broad expression patterns in various tissues and spermatogenetic stages. We further observed that positive selection is targeting these X-derived autosomal retrogenes with novel male-biased expression patterns. This suggests that such retrogenes evolved new male germ-line functions that may be complementary to the functions of the parental paralogs, which themselves contribute little during spermatogenesis. Such evolutionary changes may be beneficial to the populations. Furthermore, most identified X-related retrogenes have recruited novel adjacent sequences as their untranslated regions (UTRs), suggesting that these UTRs, acquired de novo, may play an important role in establishing new regulatory mechanisms to carry out the new male germ-line functions. C1 Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. Natl Taiwan Univ, Inst Zool, Taipei 10764, Taiwan. NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD USA. Natl Inst Genet, Shizuoka, Japan. RIKEN, BioResources Ctr, Tsukuba, Ibaraki, Japan. Natl Taiwan Univ, Dept Life Sci, Taipei 10764, Taiwan. RP Long, M (reprint author), Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. EM ayu@ntu.edu.tw; mlong@uchicago.edu OI Khil, Pavel/0000-0002-4903-8777 FU NIGMS NIH HHS [R01GM65429-01A1, R01GM078070-01A1] NR 57 TC 18 Z9 18 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD OCT PY 2007 VL 24 IS 10 BP 2242 EP 2253 DI 10.1093/molbev/insm153 PG 12 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 224HB UT WOS:000250437000010 PM 17646254 ER PT J AU Koshkina, NV Khanna, C Mendoza, A Guan, H DeLauter, L Kleinerman, ES AF Koshkina, Nadezhda V. Khanna, Chand Mendoza, Arnulfo Guan, Hui DeLauter, Lindsey Kleinerman, Eugenie S. TI Fas-negative osteosarcoma tumor cells are selected during metastasis to the lungs: The role of the fas pathway in the metastatic process of osteosarcoma SO MOLECULAR CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; MURINE RENAL-CANCER; LIGAND INTERACTIONS; INDUCED APOPTOSIS; EXPRESSION; CARCINOMA; CD95; MICE; PROGRESSION; ACTIVATION AB Low expression of Fas by different tumors including osteosarcoma, correlates with poor prognosis. We found that osteosarcoma lung metastases from patients expressed negligible amounts of Fas, but primary tumors often expressed high Fas levels. The reason for this discrepancy is unknown. We hypothesized that because FasL is constitutively expressed in the lungs, Fas-positive (Fas(+)) tumor cells entering the lungs would bind with FasL and die from Fas-induced apoptosis, resulting in the "selection" of Fas-negative (Fas(-)) cells, which would eventually form metastases. To test this hypothesis, we injected K7 osteosarcoma cells, which express functional Fas in vitro, into mice and confirmed that its bone tumors were Fas(+), but lung metastases were Fas(-). Next, to inhibit Fas signaling without affecting Fas expression, we transfected these cells with a FADD-dominant negative (FDN) plasmid and developed K7/FDN cells. Metastases formed by K7/FDN cells contained Fas(+) tumor cells. Moreover, K7/FDN cells were retained in the lungs longer and formed more lung metastases than K7 cells. In addition, the incidence of lung metastases in FasL-deficient mice injected with K7 cells was higher than that in wild-type mice. Metastases from FasL-deficient mice but not from wild-type mice contained Fas(+) tumor cells. Based on that, we conclude that Fas- osteosarcoma cells are selected during lung metastases formation and that inhibition of Fas signaling in tumors or lack of FasL in the host environment allows the proliferation of Fas(+) osteosarcoma cells in the lungs and promotes metastases growth. Therefore, Fas may be considered as a new therapeutic target for osteosarcoma treatment. C1 Univ Texas, MD Anderson Canc Ctr, Childrens Canc Hosp, Houston, TX 77030 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Koshkina, NV (reprint author), Univ Texas, MD Anderson Canc Ctr, Div Pediat Res, Unit 853, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM nvkosliki@mdanderson.org FU NCI NIH HHS [R01 CA42992, CA16672] NR 35 TC 39 Z9 43 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2007 VL 5 IS 10 BP 991 EP 999 DI 10.1158/1541-7786.MCR-07-0007 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 224VE UT WOS:000250474000002 PM 17951400 ER PT J AU Ji, Y Prasad, NB Novotny, EA Kaur, S Elkahloun, A Chen, Y Zhang, RZ Chu, ML Agarwal, SK Marx, SJ Collins, FS Chandrasekharappa, SC AF Ji, Youngmi Prasad, Nijaguna B. Novotny, Elizabeth A. Kaur, Sukhbir Elkahloun, Abdel Chen, Yidong Zhang, Rui-Zhu Chu, Mon-Li Agarwal, Sunita K. Marx, Stephen J. Collins, Francis S. Chandrasekharappa, Settara C. TI Mouse embryo fibroblasts lacking the tumor suppressor menin show altered expression of extracellular matrix protein genes SO MOLECULAR CANCER RESEARCH LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; HISTONE METHYLTRANSFERASE COMPLEX; GROWTH-FACTOR-BETA; IDENTIFICATION; OSTEOBLAST; TYPE-1; INACTIVATION; PERIOSTIN; LEUKEMIA; PRODUCT AB Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant familial cancer syndrome characterized primarily by endocrine tumors of the parathyroids, anterior pituitary, and enteropancreatic endocrine tissues. Affected individuals carry a germ-line loss-of-f unction mutation of the MEN1 gene, and tumors arise after loss of the second allele. Homozygous loss of Men1 in the germ line of mice results in early embryonic lethality, with defective development of neural tube, heart, liver, and craniofacial structures. We generated immortalized wild-type (WT) and menin-null mouse embryo fibroblast (MEF) cell lines and evaluated their characteristics, including global expression patterns. The WT and menin-null cell lines were aneuploid, and the nulls did not display tumorigenic characteristics in soft agar assay. Expression arrays in menin-null MEFs revealed altered expression of several extracellular matrix proteins that are critical in organogenesis. Specifically, transcripts for fibulin 2 (FbIn2), periostin (Postn), and versican [chondroitin sulfate proteoglycan (Cspg2)], genes critical for the developing heart and known to be induced by transforming growth factor- (TGF-), were decreased in their expression in menin-null MEFs. FbIn2 expression was the most affected, and the reduction in menin-null MEFs for FbIn2, Postn, and Cspg2 was 16.18-, 5.37-, and 2.15-fold, respectively. Menin-null MEFs also showed poor response to TGF-beta-induced Smad3-mediated transcription in a reporter assay, supporting a role for menin in this pathway. Postn and Cspg2 expression in WT, unlike in null MEFs, increased on TGF-beta treatment. The expression changes associated with the loss of the tumor suppressor menin provide insights into the defective organogenesis observed during early embryonic development in Men1-null mouse embryos. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. RP Chandrasekharappa, SC (reprint author), NHGRI, Genome Technol Branch, NIH, 50 S Dr, Bethesda, MD 20892 USA. EM chandra@mail.nih.gov RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 FU Intramural NIH HHS; NIGMS NIH HHS [GM55625] NR 30 TC 13 Z9 13 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2007 VL 5 IS 10 BP 1041 EP 1051 DI 10.1158/1541-7786.MCR-06-0379 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 224VE UT WOS:000250474000006 PM 17951404 ER PT J AU Dosemeci, A Makusky, AJ Jankowska-Stephens, E Yang, X Slotta, DJ Markey, SP AF Dosemeci, Ayse Makusky, Anthony J. Jankowska-Stephens, Ewa Yang, Xiaoyu Slotta, Douglas J. Markey, Sanford P. TI Composition of the synaptic PSD-95 complex SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID POSTSYNAPTIC DENSITY FRACTION; PROTEIN-KINASE-II; TANDEM MASS-SPECTROMETRY; LONG-TERM POTENTIATION; LIQUID-CHROMATOGRAPHY; PROTEOMIC ANALYSIS; RAT-BRAIN; GLUTAMATE RECEPTORS; EXCITATORY SYNAPSES; DENDRITIC SPINES AB Postsynaptic density protein 95 (PSD-95), a specialized scaffold protein with multiple protein interaction domains, forms the backbone of an extensive postsynaptic protein complex that organizes receptors and signal transduction molecules at the synaptic contact zone. Large, detergent-insoluble PSD-95-based postsynaptic complexes can be affinity-purified from conventional PSD fractions using magnetic beads coated with a PSD-95 antibody. In the present study purified PSD-95 complexes were analyzed by LC/MS/MS. A semiquantitative measure of the relative abundances of proteins in the purified PSD-95 complexes and the parent PSD fraction was estimated based on the cumulative ion current intensities of corresponding peptides. The affinity-purified preparation was largely depleted of presynaptic proteins, spectrin, intermediate filaments, and other contaminants prominent in the parent PSD fraction. We identified 525 of the proteins previously reported in parent PSD fractions, but only 288 of these were detected after affinity purification. We discuss 26 proteins that are major components in the PSD-95 complex based upon abundance ranking and affinity co-purification with PSD-95. This subset represents a minimal list of constituent proteins of the PSD-95 complex and includes, in addition to the specialized scaffolds and N-methyl-D-aspartate (NMDA) receptors, an abundance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, small G-protein regulators, cell adhesion molecules, and hypothetical proteins. The identification of two Arf regulators, BRAG1 and BRAG2b, as co-purifying components of the complex implies pivotal functions in spine plasticity such as the reorganization of the actin cytoskeleton and insertion and retrieval of proteins to and from the plasma membrane. Another co-purifying protein (Q8BZM2) with two sterile alpha motif domains may represent a novel structural core element of the PSD. C1 NIMH, NIH, NINDS, Neurobiol Lab, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Markey, SP (reprint author), NIMH, NIH, NINDS, Neurobiol Lab, Bethesda, MD 20892 USA. EM markeys@mail.nih.gov FU Intramural NIH HHS [Z01 MH000279-25] NR 59 TC 85 Z9 86 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2007 VL 6 IS 10 BP 1749 EP 1760 DI 10.1074/mcp.M700040-MCP200 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 219NT UT WOS:000250092600008 PM 17623647 ER PT J AU Gay, EA Bienstock, RJ Lamb, PW Yakel, JL AF Gay, Elaine A. Bienstock, Rachelle J. Lamb, Patricia W. Yakel, Jerrel L. TI Structural determinates for apolipoprotein E-derived peptide interaction with the alpha 7 nicotinic acetylcholine receptor SO MOLECULAR PHARMACOLOGY LA English DT Article ID LIGAND-BINDING DOMAIN; THROMBIN-CLEAVAGE FRAGMENT; NICOTINIC RECEPTORS; CRYSTAL-STRUCTURE; AGONIST-BINDING; HOMOLOG ACHBP; AMINO-ACIDS; PROTEIN; NEUROTOXICITY; INFLAMMATION AB Neuronal nicotinic acetylcholine receptor ( nAChR) signaling has been implicated in a variety of normal central nervous system (CNS) functions as well as an array of neuropathologies. Previous studies have demonstrated both neurotoxic and neuroprotective actions of peptides derived from apolipoprotein E (apoE). It has been discovered that apoE-derived peptides inhibit native and recombinant alpha 7-containing nAChRs, indicating a direct interaction between apoE peptides and nAChRs. To probe the structure/function interaction between alpha 7 nAChRs and the apoE peptide apoE(141-148), experiments were conducted in Xenopus laevis oocytes expressing wild-type and mutated nAChRs. Mutation of Trp55 to alanine blocks apoE peptide-induced inhibition of acetylcholine (ACh)-mediated alpha 7 nAChR responses. Additional mutations at Trp55 suggest that hydrophobic interactions between the receptor and apoE(141-148) are essential for inhibition of alpha 7 nAChR function. A mutated apoE peptide also demonstrated decreased inhibition at alpha 7-W55A nAChRs as well as activity-dependent inhibition of both wild-type alpha 7 nAChRs and alpha 7-W55A receptors. Finally, a three- dimensional model of the alpha 7 nAChR was developed based on the recently refined Torpedo marmorata nACh receptor. A structural model is proposed for the binding of apoE(141-148) to the alpha 7 nAChR where the peptide binds at the interface between two subunits, near the ACh binding site. Similar to the functional data, the computational docking suggests the importance of hydrophobic interactions between the alpha 7 nAChR and the apoE peptide for inhibition of receptor function. The current data suggest a mode for apoE peptide binding that directly blocks alpha 7 nAChR activity and consequently may disrupt nAChR signaling. C1 NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Comp Sci Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM fakel@niehs.nih.gov OI Bienstock, Rachelle/0000-0001-5228-3610 FU Intramural NIH HHS [Z01 ES090089-11] NR 44 TC 15 Z9 15 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 2007 VL 72 IS 4 BP 838 EP 849 DI 10.1124/mol.107.035527 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 211YZ UT WOS:000249561500005 PM 17609418 ER PT J AU Jobson, AG Cardellina, JH Scudiero, D Kondapaka, S Zhang, H Kim, H Shoemaker, R Pommier, Y AF Jobson, Andrew G. Cardellina, John H., II Scudiero, Dominic Kondapaka, Sudhir Zhang, Hongliang Kim, Hijoo Shoemaker, Robert Pommier, Yves TI Identification of a bis-guanylhydrazone [4,4 '-diacetyldiphenylurea-bis(guanylhydrazone); NSC 109555] as a novel chemotype for inhibition of Chk2 kinase SO MOLECULAR PHARMACOLOGY LA English DT Article ID MOLECULAR INTERACTION MAP; DNA-DAMAGE CHECKPOINT; DOUBLE-STRAND BREAKS; THREONINE-68 PHOSPHORYLATION; G(2) ARREST; IN-VITRO; ACTIVATION; CELLS; CYCLE; P53 AB Chk2 is a protein kinase involved in the ATM-dependent checkpoint pathway (http://discover.nci.nih.gov/mim). This pathway is activated by genomic instability and DNA damage and results in either cell cycle arrest, to allow DNA repair to occur, or cell death ( apoptosis). Chk2 is activated by ATM-mediated phosphorylation and autophosphorylation and in turn phosphorylates its downstream targets ( Cdc25A, Cdc25C, BRCA1, p53, Hdmx, E2F1, PP2A, and PML). Inhibition of Chk2 has been proposed to sensitize p53-deficient cells as well as protect normal tissue after exposure to DNA-damaging agents. We have developed a drug-screening program for specific Chk2 inhibitors using a fluorescence polarization assay, immobilized metal ion affinity-based fluorescence polarization (IMAP). This assay detects the degree of phosphorylation of a fluorescently linked substrate by Chk2. From a screen of over 100,000 compounds from the NCI Developmental Therapeutics Program, we identified a bis-guanylhydrazone [4,4 '-diacetyldiphenylureabis( guanylhydrazone); NSC 109555] as a lead compound. In vitro data show the specific inhibition of Chk2 kinase activity by NSC 109555 using in vitro kinase assays and kinase-profiling experiments. NSC 109555 was shown to be a competitive inhibitor of Chk2 with respect to ATP, which was supported by docking of NSC 109555 into the ATP binding pocket of the Chk2 catalytic domain. The potency of NSC 109555 was comparable with that of other known Chk2 inhibitors, such as debromohymenialdisine and 2-arylbenzimidazole. These data define a novel chemotype for the development of potent and selective inhibitors of Chk2. This class of drugs may ultimately be useful in combination with current DNA-damaging agents used in the clinic. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Dev Therapeut Program, NIH, Frederick, MD 21701 USA. NCI, SAIC Frederick, NIH, Frederick, MD 21701 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO12400] NR 43 TC 41 Z9 42 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 2007 VL 72 IS 4 BP 876 EP 884 DI 10.1124/mol.107.035832 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 211YZ UT WOS:000249561500009 PM 17616632 ER PT J AU Spivak, CE Lupica, CR Oz, M AF Spivak, Charles E. Lupica, Carl R. Oz, Murat TI The endocannabinoid anandamide inhibits the function of alpha 4 beta 2 nicotinic acetylcholine receptors SO MOLECULAR PHARMACOLOGY LA English DT Article ID ENDOGENOUS CANNABINOID ANANDAMIDE; NEURONAL NICOTINIC RECEPTORS; T-TUBULE MEMBRANES; MEDIATED RESPONSES; XENOPUS OOCYTES; SYNTHETIC CANNABINOIDS; UNSTIRRED LAYER; K+ CHANNELS; FATTY-ACIDS; CALCIUM AB The effects of the endocannabinoid anandamide ( arachidonylethanolamide, AEA) on the function of alpha 4 beta 2 nicotinic acetylcholine receptors ( nAChR) stably expressed in SH-EP1 cells were investigated using the whole-cell patch-clamp technique. In the concentration range of 200 nM to 2 mu M, AEA significantly reduced the maximal amplitudes and increased the desensitization of acetylcholine (ACh)-induced currents. The effects of AEA could be neither replicated by the exogenous cannabinoid Delta(9)- tetrahydrocannabinol (1 mu M) nor reversed by the selective CB1 receptor antagonist 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)4- methyl-N-(piperidin-1-yl)-1H- pyrazole- 3carboxamide (SR- 141716A) (1 mu M). The actions of AEA were apparent when applied extracellularly but not during intracellular dialysis. Furthermore, the effects of AEA ACh currents were not altered by the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N, N, N ', N '-tetraacetic acid. The onset and washout of the AEA effects required several minutes ( 10 - 30 min), but the latter was significantly decreased in the presence of lipid-free bovine serum albumin (BSA). Moreover, BSA alone increased peak ACh current amplitudes and diminished desensitization rates in naive cells, suggesting a tonic modulation of alpha 4 beta 2 nAChR function by an endogenous AEA-like lipid. Further analysis of AEA effects on alpha 4 beta 2 nAChR-mediated currents, using a twostage desensitization model, indicated that the first forward rate constant leading to desensitization, k(1), increased nearly 30-fold as a linear function of the AEA concentration. In contrast, the observation that the other three rate constants were unaltered by AEA suggested that AEA raised the energy of the activated state. These results indicate that AEA directly inhibits the function of alpha 4 beta 2 nAChRs in a CB1 receptor- independent manner. C1 US Dept HHS, NIH, Natl Inst Drug Abuse,,Electrophysiol Res Unit, Intramural Res Program,Cellulr Neurobiol Branch, Baltimore, MD 21224 USA. RP Spivak, CE (reprint author), US Dept HHS, NIH, Natl Inst Drug Abuse,,Electrophysiol Res Unit, Intramural Res Program,Cellulr Neurobiol Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM cspivak@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 FU Intramural NIH HHS NR 45 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 2007 VL 72 IS 4 BP 1024 EP 1032 DI 10.1124/mol.107.036939 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 211YZ UT WOS:000249561500023 PM 17628012 ER PT J AU Ke, QG Xiao, YF Bradbury, JA Graves, JP DeGraff, LM Seubert, JM Zeldin, DC AF Ke, Qingen Xiao, Yong-Fu Bradbury, J. Alyce Graves, Joan P. DeGraff, Laura M. Seubert, John M. Zeldin, Darryl C. TI Electrophysiological properties of cardiomyocytes isolated from CYP2J2 transgenic mice SO MOLECULAR PHARMACOLOGY LA English DT Article ID SENSITIVE K+ CHANNELS; ARACHIDONIC-ACID METABOLISM; L-TYPE CA2+; EPOXYEICOSATRIENOIC ACIDS; HUMAN CYTOCHROME-P450; VENTRICULAR MYOCYTES; EPOXIDE HYDROLASE; MOLECULAR-CLONING; PROTEIN-KINASE; HEART AB CYP2J2 is abundant in cardiac tissue and active in the biosynthesis of eicosanoids such as epoxyeicosatrienoic acids (EETs). To determine the effects of CYP2J2 and its eicosanoid products in the heart, we characterized the electrophysiology of single cardiomyocytes isolated from adult transgenic (Tr) mice with cardiac-specific overexpression of CYP2J2. CYP2J2 Tr cardiomyocytes had a shortened action potential. At 90% repolarization, the action potential duration (APD) was 30.6+/-3.0 ms (n+/-22) in wild-type (Wt) cells and 20.2+/-2.3 ms (n+/-19) in CYP2J2 Tr cells (p+/-0.005). This shortening was probably due to enhanced maximal peak transient outward K+ currents ( I to, peak), which were 38.6+/-2.8 and 54.4+/-4.9 pA/pF in Wt and CYP2J2 Tr cells, respectively (p+/-0.05). In contrast, the late portion of the transient outward K+ current (I-to,I-280ms), the slowly inactivating outward K+ current (I-K,I-slow), and the voltage-gated Na+ current (I-Na) were not significantly altered in CYP2J2 Tr cells. N-Methylsulphonyl-6-(2-proparglyloxy-phenyl) hexanamide (MS-PPOH), a specific inhibitor of EET biosynthesis, significantly reduced I-to,I-peak and increased APD in CYP2J2 Tr cardiomyocytes but not in Wt cells. Intracellular dialysis with a monoclonal antibody against CYP2J2 also significantly reduced I-to,I-peak and increased APD in CYP2J2 Tr cardiomyocytes. Addition of 11,12-EET or 8-bromo- cAMP significantly reversed the MS-PPOH- or monoclonal antibody-induced changes in I-to,I-peak and APD in CYP2J2 Tr cells. Together, our data demonstrate that shortening of the action potential in CYP2J2 Tr cardiomyocytes is associated with enhanced I-to,I-peak via an EET-dependent, cAMP-mediated mechanism. C1 NIEHS, NIH, Div Intramural Res, Res Triangle Pk, NC 27709 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. RP Zeldin, DC (reprint author), NIEHS, NIH, Div Intramural Res, 111 TW Alexander Dr,Bldg 101,Room D236, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU Intramural NIH HHS [Z01 ES025034-13] NR 40 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 2007 VL 72 IS 4 BP 1063 EP 1073 DI 10.1124/mol.107.035881 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 211YZ UT WOS:000249561500027 PM 17652182 ER PT J AU Buckholtz, JW Sust, S Tan, HY Mattay, VS Straub, RE Meyer-Lindenberg, A Weinberger, DR Callicott, JH AF Buckholtz, J. W. Sust, S. Tan, H. Y. Mattay, V. S. Straub, R. E. Meyer-Lindenberg, A. Weinberger, D. R. Callicott, J. H. TI FMRI evidence for functional epistasis between COMT and RGS4 SO MOLECULAR PSYCHIATRY LA English DT Letter ID SCHIZOPHRENIA; GENOTYPE; POLYMORPHISMS; EXPRESSION; DOPAMINE; BRAIN; RISK C1 NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Div Intramural Res,Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. NIMH, Div Intramural Res, Dept Hlth & Human Serv, Neuroimaging Core Facil,Unit Dynam Imaging Genet, Bethesda, MD 20892 USA. NIMH, Neuroimaging Core Facil, Div Intramural res, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Buckholtz, JW (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Div Intramural Res,Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. EM callicottj@mail.nih.gov RI Buckholtz, Joshua /E-7299-2010; Callicott, Joseph/C-9102-2009 OI Buckholtz, Joshua /0000-0002-9418-8686; Callicott, Joseph/0000-0003-1298-3334 FU Intramural NIH HHS NR 10 TC 29 Z9 30 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2007 VL 12 IS 10 BP 893 EP 895 DI 10.1038/sj.mp.4002008 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 217AK UT WOS:000249920500003 PM 17895922 ER PT J AU Ishizuka, K Chen, J Taya, S Li, W Millar, JK Xu, Y Clapcote, S Hookway, C Morita, M Kamiya, A Tomoda, T Lipska, B Roder, J Pletnikov, M Porteous, D Silva, A Cannon, T Kaibuchi, K Brandon, N Weinberger, D Sawa, A AF Ishizuka, K. Chen, J. Taya, S. Li, W. Millar, J. K. Xu, Y. Clapcote, S. J. Hookway, C. Morita, M. Kamiya, A. Tomoda, T. Lipska, B. K. Roder, J. C. Pletnikov, M. Porteous, D. Silva, A. J. Cannon, T. D. Kaibuchi, K. Brandon, N. J. Weinberger, D. R. Sawa, A. TI Evidence that many of the DISC1 isoforms in C57BL/6J mice are also expressed in 129S6/SvEv mice SO MOLECULAR PSYCHIATRY LA English DT Letter ID SCHIZOPHRENIA; NEURODEVELOPMENT; GENES C1 Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Behav Sci, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Program Mol Psychiat, Baltimore, MD USA. NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Nagoya Univ, Grad Sch Med, Dept Cell Pharmacol, Nagoya, Aichi, Japan. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA USA. Univ Edinburgh, Med Genet Sect, Mol Med Ctr, Edinburgh, Midlothian, Scotland. Johns Hopkins Univ, Sch Med, Div Neurobiol, Baltimore, MD USA. Mt Sinai Hosp, Inst Res, Toronto, ON, Canada. Beckman Res Inst City Hope, Div Neurosci, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. Wyeth Discovery Neurosci, Schizophrenai & Bipolar Dept, Princeton, NJ USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD USA. RP Ishizuka, K (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. EM asawa1@jhmi.edu RI Porteous, David/C-7289-2013; Roder, John/G-6468-2013; kamiya, atsushi/L-8550-2016; OI Porteous, David/0000-0003-1249-6106; Silva, Alcino/0000-0001-5525-0494 FU Medical Research Council [G0100266, G0600214] NR 10 TC 32 Z9 35 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2007 VL 12 IS 10 BP 897 EP 899 DI 10.1038/sj.mp.4002024 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 217AK UT WOS:000249920500005 PM 17895924 ER PT J AU Sei, Y Ren-Patterson, R Li, Z Tunbridge, EM Egan, MF Kolachana, BS Weinberger, DR AF Sei, Y. Ren-Patterson, R. Li, Z. Tunbridge, E. M. Egan, M. F. Kolachana, B. S. Weinberger, D. R. TI Neuregulin1-induced cell migration is impaired in schizophrenia: association with neuregulin1 and catechol-o-methyltransferase gene polymorphisms SO MOLECULAR PSYCHIATRY LA English DT Article DE schizophrenia; neuregulin1; migration; ErbB lymphoblast; catechol-o-methyltransferase ID ERBB RECEPTORS; MESSENGER-RNA; GABAERGIC INTERNEURONS; SUSCEPTIBILITY GENES; NEURONAL MIGRATION; PREFRONTAL CORTEX; BIPOLAR DISORDER; MUTANT MICE; HUMAN BRAIN; EXPRESSION AB Neuregulin1 ( NRG1), a candidate susceptibility gene for schizophrenia, plays a critical role in neuronal migration and central nervous system development. However, its relation to schizophrenia pathogenesis is unknown. Here we show that B lymphoblasts migrate to NRG1 through the ErbB-signaling system as observed in neuronal cells. We assessed NRG1-induced cell migration in B lymphoblasts from patients with schizophrenia and found that NRG1-induced migration is significantly decreased compared with control individuals in two independent cohorts. This impaired migration is related at least in part to reduced AKT phosphorylation in the patients. Moreover, the magnitude of NRG1-induced migration is associated with polymorphisms of the NRG1 and catechol-o-methyltransferase genes and with an epistatic interaction of these genes. This study demonstrates that the migratory response of schizophrenia-derived cells to NRG1 is impaired and is associated with genetic variations in more than one schizophrenia susceptibility gene, providing a novel insight into potential neurodevelopmental mechanisms of schizophrenia. C1 NIMH, Blood Genom Lab, Genes Cognit & Psychosis Program, NIH,Clin Brain Disorder Branch, Bethesda, MD 20892 USA. Univ Oxford, Dept Psychiat, Warneford Hosp, Oxford OX1 2JD, England. RP Sei, Y (reprint author), NIMH, Blood Genom Lab, Genes Cognit & Psychosis Program, NIH,Clin Brain Disorder Branch, 10 Ctr Dr,Bldg 10,Rm 4S235,MSC1379, Bethesda, MD 20892 USA. EM seiy@mail.nih.gov; daniel.weinberger@mail.nih.gov OI Tunbridge, Elizabeth/0000-0002-2966-2281 FU Intramural NIH HHS NR 58 TC 44 Z9 46 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2007 VL 12 IS 10 BP 946 EP 957 DI 10.1038/sj.mp.4001994 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 217AK UT WOS:000249920500012 PM 17440436 ER PT J AU Fanous, AH Neale, MC Gardner, CO Webb, BT Straub, RE O'Neill, FA Walsh, D Riley, BP Kendler, KS AF Fanous, A. H. Neale, M. C. Gardner, C. O. Webb, B. T. Straub, R. E. O'Neill, F. A. Walsh, D. Riley, B. P. Kendler, K. S. TI Significant correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy SO MOLECULAR PSYCHIATRY LA English DT Article DE schizophrenia; schizotypy; genome scan; endophenotype; personality ID QUANTITATIVE-TRAIT LOCI; SUSCEPTIBILITY LOCUS; BIPOLAR DISORDER; PERSONALITY-DISORDERS; VULNERABILITY LOCUS; FOLLOW-UP; BORDERLINE PERSONALITY; GENE POLYMORPHISM; MAJOR DEPRESSION; ROSCOMMON FAMILY AB Prior family and adoption studies have suggested a genetic relationship between schizophrenia and schizotypy. However, this has never been verified using linkage methods. We therefore attempted to test for a correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy. The Irish study of high-density schizophrenia families comprises 270 families with at least two members with schizophrenia or poor-outcome schizoaffective disorder (n = 637). Non-psychotic relatives were assessed using the structured interview for schizotypy (n = 746). A 10-cM multipoint, non-parametric, autosomal genomewide scan of schizophrenia was performed in Merlin. A scan of a quantitative trait comprising ratings of DSM-III-R criteria for schizotypal personality disorder in non-psychotic relatives was also performed. Schizotypy logarithm of the odds (LOD) scores were regressed onto schizophrenia LOD scores at all loci, with adjustment for spatial autocorrelation. To assess empirical significance, this was also carried out using 1000 null scans of schizotypy. The number of jointly linked loci in the real data was compared to distribution of jointly linked loci in the null scans. No markers were suggestively linked to schizotypy based on strict Lander Kruglyak criteria. Schizotypy LODs predicted schizophrenia LODs above chance expectation genome wide (empirical P = 0.04). Two and four loci yielded nonparametric LOD (NPLs) > 1.0 and > 0.75, respectively, for both schizophrenia and schizotypy (genome-wide empirical P = 0.04 and 0.02, respectively). These results suggest that at least a subset of schizophrenia susceptibility genes also affects schizotypy in non-psychotic relatives. Power may therefore be increased in molecular genetic studies of schizophrenia if they incorporate measures of schizotypy in non-psychotic relatives. C1 George Washington Univ, Washington VA Med Ctr, Mental Hlth Serv Line, Schizophrenia Res Program, Washington, DC 20422 USA. Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC 20007 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23284 USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23284 USA. NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. Queens Univ Belfast, Belfast BT12 6BJ, Antrim, North Ireland. Hlth Res Board, Dublin, Ireland. RP Fanous, AH (reprint author), George Washington Univ, Washington VA Med Ctr, Mental Hlth Serv Line, Schizophrenia Res Program, 50 Irving St NW, Washington, DC 20422 USA. EM ahfanous@hsc.vcu.edu RI Neale, Michael/B-1418-2008; Webb, Bradley/B-1459-2009; OI Webb, Bradley/0000-0002-0576-5366; O'Neill, Francis Anthony/0000-0002-7531-7657 FU NIMH NIH HHS [IT-32 MH-20030, MH-41953, MH-45390, MH-52537, MH-65322] NR 80 TC 42 Z9 42 U1 3 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2007 VL 12 IS 10 BP 958 EP 965 DI 10.1038/sj.mp.4001996 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 217AK UT WOS:000249920500013 PM 17440434 ER PT J AU Chia, A Richert, N Ehrmantraut, M Ohayon, J Cantor, F Frank, J McFarland, H Bagnato, F AF Chia, A. Richert, N. Ehrmantraut, M. Ohayon, J. Cantor, F. Frank, J. McFarland, H. Bagnato, F. TI Characterisation of response to treatment with interferon beta-1b using contrast-enhancing lesions lesion frequency as a primary outcome measure: a 3-year monthly imaging study SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 23rd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/12th Annual Conference of Rehabilitation in MS CY OCT 11-14, 2007 CL Prague, CZECH REPUBLIC SP European Comm Treatment & Res Multiple Sclerosis C1 [Chia, A.; Richert, N.; Ehrmantraut, M.; Ohayon, J.; Cantor, F.; Frank, J.; McFarland, H.; Bagnato, F.] NINDS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD OCT PY 2007 VL 13 SU 2 BP S192 EP S192 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 238BX UT WOS:000251423400592 ER PT J AU Gaindh, D Jeffries, N Richert, N Ohayon, J Stern, S Frank, J McFarland, H Bagnato, F AF Gaindh, D. Jeffries, N. Richert, N. Ohayon, J. Stern, S. Frank, J. McFarland, H. Bagnato, F. TI The role of interferon beta 1 b in decreasing lesions size in patients with multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 23rd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/12th Annual Conference of Rehabilitation in MS CY OCT 11-14, 2007 CL Prague, CZECH REPUBLIC SP European Comm Treatment & Res Multiple Sclerosis C1 [Gaindh, D.; Jeffries, N.; Richert, N.; Ohayon, J.; Stern, S.; Frank, J.; McFarland, H.; Bagnato, F.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD OCT PY 2007 VL 13 SU 2 BP S193 EP S193 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 238BX UT WOS:000251423400594 ER PT J AU Ikonomidou, VN Pellegrini, S Evangelou, I Gallo, A Ohayon, J Stern, S Ehrmantraut, M Richert, ND McFarland, H Bagnato, F AF Ikonomidou, V. N. Pellegrini, S. Evangelou, I. Gallo, A. Ohayon, J. Stern, S. Ehrmantraut, M. Richert, N. D. McFarland, H. F. Bagnato, F. TI Measuring actual normal white matter and normal appearing white matter volume with tissue specific imaging SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 23rd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/12th Annual Conference of Rehabilitation in MS CY OCT 11-14, 2007 CL Prague, CZECH REPUBLIC SP European Comm Treatment & Res Multiple Sclerosis C1 [Ikonomidou, V. N.; Pellegrini, S.; Evangelou, I.; Gallo, A.; Ohayon, J.; Stern, S.; Ehrmantraut, M.; Richert, N. D.; McFarland, H. F.; Bagnato, F.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD OCT PY 2007 VL 13 SU 2 BP S178 EP S178 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 238BX UT WOS:000251423400549 ER PT J AU Niccolini, E Bagnato, F Scagnolari, C Bellomi, F Giannetti, P Millerforini, E Gasperini, C Pozzilli, C Antonelli, G Frontoni, M AF Niccolini, E. Bagnato, F. Scagnolari, C. Bellomi, F. Giannetti, P. Millerforini, E. Gasperini, C. Pozzilli, C. Antonelli, G. Frontoni, M. TI Differences in pharmacodynamic profile of interferon beta 1a between multiple sclerosis patients with diverse clinical outcome: a 3-year study SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 23rd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/12th Annual Conference of Rehabilitation in MS CY OCT 11-14, 2007 CL Prague, CZECH REPUBLIC SP European Comm Treatment & Res Multiple Sclerosis C1 Univ Roma La Sapienza, Rome, Italy. NIH, Bethesda, MD USA. RI SCAGNOLARI, CAROLINA/G-3837-2011 OI SCAGNOLARI, CAROLINA/0000-0003-1044-1478 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD OCT PY 2007 VL 13 SU 2 BP S63 EP S63 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 238BX UT WOS:000251423400176 ER PT J AU Richert, N Ostuni, I Stone, R Frank, J Bagnato, F Ohayon, J McFarland, H AF Richert, N. Ostuni, I. Stone, R. Frank, J. Bagnato, F. Ohayon, J. McFarland, H. TI Contrast enhancing lesion evolution followed by magnetisation transfer imaging in relapsing-remitting multiple sclerosis patients during treatment with Interferon beta-1b or glatiramer acetate. SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 23rd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/12th Annual Conference of Rehabilitation in MS CY OCT 11-14, 2007 CL Prague, CZECH REPUBLIC SP European Comm Treatment & Res Multiple Sclerosis C1 [Richert, N.; Ostuni, I.; Stone, R.; Frank, J.; Bagnato, F.; Ohayon, J.; McFarland, H.] Natl Inst Hlth, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD OCT PY 2007 VL 13 SU 2 BP S192 EP S193 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 238BX UT WOS:000251423400593 ER PT J AU Abrahamsson, SV Packer, AN Oh, U Burt, RK Martin, R Muraro, PA AF Abrahamsson, S. V. Packer, A. N. Oh, U. Burt, R. K. Martin, R. Muraro, P. A. TI Increased frequency of immuno-regulatory T-cells in patients with multiple sclerosis after haematopoietic stem cell transplantation SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 23rd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/12th Annual Conference of Rehabilitation in MS CY OCT 11-14, 2007 CL Prague, CZECH REPUBLIC SP European Comm Treatment & Res Multiple Sclerosis C1 Imperial Coll London, London, England. Univ Iowa, Iowa City, IA 52242 USA. Natl Inst Hlth, Bethesda, MD USA. Northwestern Univ, Chicago, IL USA. INIMS, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2007 VL 13 SU 2 BP S247 EP S247 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 238BX UT WOS:000251423400770 ER PT J AU Abrahamsson, SV Packer, AN Oh, U Burt, RK Murato, PA AF Abrahamsson, S. V. Packer, A. N. Oh, U. Burt, R. K. Murato, P. A. TI Effects of different immunosuppressive conditioning regimens on immune reconstitution after haematopoietic stem cell transplantation in patients with MS SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 23rd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/12th Annual Conference of Rehabilitation in MS CY OCT 11-14, 2007 CL Prague, CZECH REPUBLIC SP European Comm Treatment & Res Multiple Sclerosis C1 Imperial Coll London, London, England. Univ Iowa, Iowa City, IA 52242 USA. Natl Inst Hlth, Bethesda, MD USA. Northwestern Univ, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2007 VL 13 SU 2 BP S247 EP S247 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 238BX UT WOS:000251423400769 ER PT J AU Richardson, SP Bliem, B Lomarev, M Shamim, E Dang, N Hallett, M AF Richardson, S. Pirio Bliem, B. Lomarev, M. Shamim, E. Dang, N. Hallett, M. TI Changes in short afferent inhibition during phasic movement in focal dystonia SO MUSCLE & NERVE LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-of-Neuromuscular-and-electrodiagnostic-Medicine CY OCT 17-20, 2007 CL Phoenix, AZ SP Amer Assoc Neuromuscular & Electrodiagnost Med C1 NINDS, Study Supported Intramural Res Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2007 VL 36 IS 4 BP 555 EP 555 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 215XM UT WOS:000249842300022 ER PT J AU Waldman, M Kopp, JB AF Waldman, Meryl Kopp, Jeffrey B. TI Parvovirus-B19-associated complications in renal transplant recipients SO NATURE CLINICAL PRACTICE NEPHROLOGY LA English DT Review DE anemia; glomerular disease; kidney transplant; parvovirus B19; pure red cell aplasia ID PARVOVIRUS B19 INFECTION; RED-CELL APLASIA; ENDOCAPILLARY PROLIFERATIVE GLOMERULONEPHRITIS; MINOR CAPSID PROTEIN; REAL-TIME PCR; KIDNEY-TRANSPLANT; INTRAVENOUS IMMUNOGLOBULIN; NONSTRUCTURAL PROTEIN; UNIQUE REGION; ANEMIA AB Parvovirus B19 is a common human pathogen, causing erythema infectiosum in children, hydrops fetalis in pregnant women, and transient aplastic crisis in patients with chronic hemolytic anemia. Immunosuppressed patients can fail to mount an effective immune response to B19, resulting in prolonged or persistent viremia. Renal transplant recipients can develop symptomatic B19 infections as a result of primary infection acquired via the usual respiratory route or via the transplanted organ, or because of reactivation of latent or persistent viral infection. The most common manifestations of B19 infection in immunosuppressed patients are pure red cell aplasia and other cytopenias. Thus, this diagnosis should be considered in transplant recipients with unexplained anemia and reticulocytopenia or pancytopenia. Collapsing glomerulopathy and thrombotic microangiopathy have been reported in association with B19 infection in renal transplant recipients, but a causal relationship has not been definitively established. Prompt diagnosis of B19 infection in the renal transplant recipient requires a high index of suspicion and careful selection of diagnostic tests, which include serologies and polymerase chain reaction. Most patients benefit from intravenous immunoglobulin therapy and/or alteration or reduction of immunosuppressive therapy. Conservative therapy might be sufficient in some cases. C1 NIDDK, NIH, Kidney Dis Sect, Dept Hlth & Human Serv, Bethesda, MD 20814 USA. RP Waldman, M (reprint author), NIDDK, NIH, Kidney Dis Sect, Dept Hlth & Human Serv, 10 Ctr Dr,MSC 1455, Bethesda, MD 20814 USA. EM merylw@intra.niddk.nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X FU Intramural NIH HHS NR 99 TC 30 Z9 33 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8323 J9 NAT CLIN PRACT NEPHR JI Nat. Clin. Pract. Nephrol. PD OCT PY 2007 VL 3 IS 10 BP 540 EP 550 DI 10.1038/ncpneph0609 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 214BC UT WOS:000249710000009 PM 17895931 ER PT J AU Morse, CG Kovacs, JA AF Morse, Caryn G. Kovacs, Joseph A. TI Does atovaquone provide effective prophylaxis for Pneumocystis pneumonia in children with leukemia? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE atovaquone; leukemia; opportunistic; infection; Pneumocystis jirovecii; pneumonia ID CARINII-PNEUMONIA; TRIMETHOPRIM C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Room 2C145,Bldg 10,MSC 1662,10 Ctr Dr, Bethesda, MD 20892 USA. EM jkovacs@nih.gov OI Morse, Caryn/0000-0002-1177-4365 NR 5 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD OCT PY 2007 VL 4 IS 10 BP 566 EP 567 DI 10.1038/ncponc0927 PG 2 WC Oncology SC Oncology GA 214AQ UT WOS:000249708800005 PM 17700556 ER PT J AU Mailman, MD Feolo, M Jin, Y Kimura, M Tryka, K Bagoutdinov, R Hao, L Kiang, A Paschall, J Phan, L Popova, N Pretel, S Ziyabari, L Lee, M Shao, Y Wang, ZY Sirotkin, K Ward, M Kholodov, M Zbicz, K Beck, J Kimelman, M Shevelev, S Preuss, D Yaschenko, E Graeff, A Ostell, J Sherry, ST AF Mailman, Matthew D. Feolo, Michael Jin, Yumi Kimura, Masato Tryka, Kimberly Bagoutdinov, Rinat Hao, Luning Kiang, Anne Paschall, Justin Phan, Lon Popova, Natalia Pretel, Stephanie Ziyabari, Lora Lee, Moira Shao, Yu Wang, Zhen Y. Sirotkin, Karl Ward, Minghong Kholodov, Michael Zbicz, Kerry Beck, Jeffrey Kimelman, Michael Shevelev, Sergey Preuss, Don Yaschenko, Eugene Graeff, Alan Ostell, James Sherry, Stephen T. TI The NCBI dbGaP database of genotypes and phenotypes SO NATURE GENETICS LA English DT Editorial Material ID GENOMIC CONTROL; ASSOCIATION AB The National Center for Biotechnology Information has created the dbGaP public repository for individual-level phenotype, exposure, genotype and sequence data and the associations between them. dbGaP assigns stable, unique identifiers to studies and subsets of information from those studies, including documents, individual phenotypic variables, tables of trait data, sets of genotype data, computed phenotype-genotype associations, and groups of study subjects who have given similar consents for use of their data. C1 Natl Ctr Biotechnol Informat, NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Sherry, ST (reprint author), Natl Ctr Biotechnol Informat, NIH, Natl Lib Med, Bethesda, MD 20892 USA. EM sherry@ncbi.nlm.nih.gov OI Tryka, Kimberly/0000-0002-5399-4235 FU Intramural NIH HHS [Z99 LM999999] NR 6 TC 420 Z9 429 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2007 VL 39 IS 10 BP 1181 EP 1186 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 214KW UT WOS:000249737400003 PM 17898773 ER PT J AU Keinan, A Mullikin, JC Patterson, N Reich, D AF Keinan, Alon Mullikin, James C. Patterson, Nick Reich, David TI Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans SO NATURE GENETICS LA English DT Article ID HUMAN GENOME; HUMAN-POPULATIONS; LINKAGE DISEQUILIBRIUM; SEQUENCE; POLYMORPHISMS; SELECTION; PATTERNS; ISRAEL AB Large data sets on human genetic variation have been collected recently, but their usefulness for learning about history and natural selection has been limited by biases in the ways polymorphisms were chosen. We report large subsets of SNPs from the International HapMap Project(1,2) that allow us to overcome these biases and to provide accurate measurement of a quantity of crucial importance for understanding genetic variation: the allele frequency spectrum. Our analysis shows that East Asian and northern European ancestors shared the same population bottleneck expanding out of Africa but that both also experienced more recent genetic drift, which was greater in East Asians. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Broad Inst Harvard & MIT, Cambridge, MA 02139 USA. NIH, Natl Human Genome Res Inst, Genome Technol Branch, Bethesda, MD 20892 USA. RP Keinan, A (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM akeinan@genetics.med.harvard.edu FU Intramural NIH HHS; NHGRI NIH HHS [U01 HG004168] NR 29 TC 159 Z9 160 U1 2 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2007 VL 39 IS 10 BP 1251 EP 1255 DI 10.1038/ng2116 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 214KW UT WOS:000249737400021 PM 17828266 ER PT J AU Kozlov, SV Bogenpohl, JW Howell, MP Wevrick, R Panda, S Hogenesch, JB Muglia, LJ Van Gelder, RN Herzog, ED Stewart, CL AF Kozlov, Serguei V. Bogenpohl, James W. Howell, Maureen P. Wevrick, Rachel Panda, Satchin Hogenesch, John B. Muglia, Louis J. Van Gelder, Russell N. Herzog, Erik D. Stewart, Colin L. TI The imprinted gene Magel2 regulates normal circadian output SO NATURE GENETICS LA English DT Article ID PRADER-WILLI-SYNDROME; SUPRACHIASMATIC NUCLEUS; MOUSE; MICE; NECDIN; DISRUPTION; BRAIN; SNRPN; EXPRESSION; LETHALITY AB Mammalian circadian rhythms of activity are generated within the suprachiasmatic nucleus ( SCN). Transcripts from the imprinted, paternally expressed Magel2 gene, which maps to the chromosomal region associated with Prader-Willi Syndrome (PWS), are highly enriched in the SCN. The Magel2 message is circadianly expressed and peaks during the subjective day. Mice deficient in Magel2 expression entrain to light cycles and express normal running-wheel rhythms, but with markedly reduced amplitude of activity and increased daytime activity. These changes are associated with reductions in food intake and male fertility. Orexin levels and orexin-positive neurons in the lateral hypothalamus are substantially reduced, suggesting that some of the consequences of Magel2 loss are mediated through changes in orexin signaling. The robust rhythmicity of Magel2 expression in the SCN and the altered behavioral rhythmicity of null mice reveal Magel2 to be a clock-controlled circadian output gene whose disruption results in some of the phenotypes characteristic of PWS. C1 Washington Univ, Dept Biol, St Louis, MO 63130 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Univ Alberta, Dept Med Genet, Edmonton, AB T6G 2H7, Canada. Salk Inst Biol Studies, Regulat Biol Lab, La Jolla, CA 92037 USA. Genom Inst Novartis Res Fdn, San Diego, CA 92121 USA. Washington Univ, Sch Med, Dept Mol Biol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pharmacol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Stewart, CL (reprint author), Inst Med Biol, 03-03 Proteos,61 Biopolis Dr, Singapore 113867, Singapore. EM stewartc@ncifcrf.gov RI Panda, Satchidananda/J-6891-2012; OI Herzog, Erik/0000-0001-7209-5174; Wevrick, Rachel/0000-0002-3343-5794; Van Gelder, Russell/0000-0001-5368-3659 FU Intramural NIH HHS; NEI NIH HHS [EY14988]; NIMH NIH HHS [MH63104] NR 29 TC 77 Z9 80 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2007 VL 39 IS 10 BP 1266 EP 1272 DI 10.1038/ng2114 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 214KW UT WOS:000249737400024 PM 17893678 ER PT J AU Park, JH Adoro, S Lucas, PJ Sarafova, SD Alag, AS Doan, LL Erman, B Liu, XL Ellmeier, W Bosselut, R Feigenbaum, L Singer, A AF Park, Jung-Hyun Adoro, Stanley Lucas, Philip J. Sarafova, Sophia D. Alag, Amala S. Doan, Loretta L. Erman, Batu Liu, Xiaolong Ellmeier, Wilfried Bosselut, Remy Feigenbaum, Lionel Singer, Alfred TI 'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR SO NATURE IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; POSITIVELY SELECTED THYMOCYTES; CD4/CD8 LINEAGE DECISION; TRANSGENIC MICE; IN-VIVO; NEGATIVE SELECTION; HOMEOSTATIC PROLIFERATION; SURFACE EXPRESSION; GENE-EXPRESSION; GAMMA-CHAIN AB T cell immunity requires the long-term survival of T cells that are capable of recognizing self antigens but are not overtly autoreactive. How this balance is achieved remains incompletely understood. Here we identify a homeostatic mechanism that transcriptionally tailors CD8 coreceptor expression in individual CD8+ T cells to the self-specificity of their clonotypic T cell receptor (TCR). 'Coreceptor tuning' results from interplay between cytokine and TCR signals, such that signals from interleukin 7 and other common gamma-chain cytokines transcriptionally increase CD8 expression and thereby promote TCR engagement of self ligands, whereas TCR signals impair common gamma-chain cytokine signaling and thereby decrease CD8 expression. This dynamic interplay induces individual CD8+ T cells to express CD8 in quantities appropriate for the self-specificity of their TCR, promoting the engagement of self ligands, yet avoiding autoreactivity. C1 NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA. NCI, NIH, Expt Transplant & Immunol Branch, Bethesda, MD 20892 USA. Sabanci Univ, Fac Engn & Nat Sci, Biol Sci & Bioengn Program, Istanbul, Turkey. NCI, NIH, Immunol Cell Biol Branch, Bethesda, MD 20892 USA. Med Univ Veinna, Inst Immunol, Vienna, Austria. Canc Res & Dev Ctr, NCI, SAIC, Ft Detrick, MD 21702 USA. Davidson Coll, Dept Biol, Davidson, NC 28035 USA. RP Singer, A (reprint author), NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. EM singera@njh.gov OI Ellmeier, Wilfried/0000-0001-8192-8481 FU Austrian Science Fund FWF [Y 163]; Intramural NIH HHS NR 60 TC 99 Z9 100 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2007 VL 8 IS 10 BP 1049 EP 1059 DI 10.1038/ni1512 PG 11 WC Immunology SC Immunology GA 213UA UT WOS:000249691400019 PM 17873878 ER PT J AU Fauci, AS AF Fauci, Anthony S. TI The expanding global health agenda: a welcome development SO NATURE MEDICINE LA English DT Editorial Material ID INFECTIOUS-DISEASES; AIDS C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, 9000 Rockville Pike,Bldg 31,Room 7A-03, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 13 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2007 VL 13 IS 10 BP 1169 EP 1171 DI 10.1038/nm1646 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217XI UT WOS:000249980200031 PM 17917667 ER PT J AU Umetani, M Domoto, H Gormley, AK Yuhanna, IS Cummins, CL Javitt, NB Korach, KS Shaul, PW Mangelsdorf, DJ AF Umetani, Michihisa Domoto, Hideharu Gormley, Andrew K. Yuhanna, Ivan S. Cummins, Carolyn L. Javitt, Norman B. Korach, Kenneth S. Shaul, Philip W. Mangelsdorf, David J. TI 27-hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen SO NATURE MEDICINE LA English DT Article ID NITRIC-OXIDE SYNTHASE; CORONARY-HEART-DISEASE; B TYPE-I; HORMONE-THERAPY; RECEPTOR-BETA; POSTMENOPAUSAL WOMEN; OXIDATION-PRODUCTS; MASS-SPECTROMETRY; VASCULAR INJURY; PLUS PROGESTIN AB The cardioprotective effects of estrogen are mediated by receptors expressed in vascular cells. Here we show that 27- hydroxycholesterol ( 27HC), an abundant cholesterol metabolite that is elevated with hypercholesterolemia and found in atherosclerotic lesions, is a competitive antagonist of estrogen receptor action in the vasculature. 27HC inhibited both the transcription- mediated and the non- transcription- mediated estrogen- dependent production of nitric oxide by vascular cells, resulting in reduced estrogen- induced vasorelaxation of rat aorta. Furthermore, increasing 27HC levels in mice by diet- induced hypercholesterolemia, pharmacologic administration or genetic manipulation ( by knocking out the gene encoding the catabolic enzyme CYP7B1) decreased estrogen- dependent expression of vascular nitric oxide synthase and repressed carotid artery reendothelialization. As well as antiestrogenic effects, there were proestrogenic actions of 27HC that were cell- type specific, indicating that 27HC functions as an endogenous selective estrogen receptor modulator ( SERM). Taken together, these studies point to 27HC as a contributing factor in the loss of estrogen protection from vascular disease. C1 Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX 75390 USA. NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. NYU, Sch Med, Dept Med, New York, NY 10016 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Mangelsdorf, DJ (reprint author), Univ Texas, SW Med Ctr, Dept Pharmacol, 6001 Forest Pk Rd, Dallas, TX 75390 USA. EM davo.mango@utsouthwestern.edu OI Korach, Kenneth/0000-0002-7765-418X; Cummins, Carolyn/0000-0001-7603-6577 FU NHLBI NIH HHS [HL87564]; NIDDK NIH HHS [U19DK62434] NR 49 TC 162 Z9 166 U1 1 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2007 VL 13 IS 10 BP 1185 EP 1192 DI 10.1038/nm1641 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217XI UT WOS:000249980200034 PM 17873880 ER PT J AU Bi, YM Ehirchiou, D Kilts, TM Inkson, CA Embree, MC Sonoyama, W Li, L Leet, AI Seo, BM Zhang, L Shi, ST Young, MF AF Bi, Yanming Ehirchiou, Driss Kilts, Tina M. Inkson, Colette A. Embree, Mildred C. Sonoyama, Wataru Li, Li Leet, Arabella I. Seo, Byoung-Moo Zhang, Li Shi, Songtao Young, Marian F. TI Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche SO NATURE MEDICINE LA English DT Article ID MARROW STROMAL FIBROBLASTS; MESENCHYMAL STEM-CELLS; LABEL-RETAINING CELLS; HUMAN BONE-MARROW; IN-VITRO; PROGENITOR CELLS; MONOCLONAL-ANTIBODY; DEFICIENT MICE; TENASCIN-C; MOUSE AB The repair of injured tendons remains a great challenge, largely owing to a lack of in- depth characterization of tendon cells and their precursors. We show that human and mouse tendons harbor a unique cell population, termed tendon stem/ progenitor cells ( TSPCs), that has universal stem cell characteristics such as clonogenicity, multipotency and self- renewal capacity. The isolated TSPCs could regenerate tendon- like tissues after extended expansion in vitro and transplantation in vivo. Moreover, we show that TSPCs reside within a unique niche predominantly comprised of an extracellular matrix, and we identify biglycan ( Bgn) and fibromodulin ( Fmod) as two critical components that organize this niche. Depletion of Bgn and Fmod affects the differentiation of TSPCs by modulating bone morphogenetic protein signaling and impairs tendon formation in vivo. Our results, while offering new insights into the biology of tendon cells, may assist in future strategies to treat tendon diseases. C1 Natl Inst Dental & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Dept Physiol, Baltimore, MD 21201 USA. Johns Hopkins Univ, Div Pediat Orthopaed, Baltimore, MD 21287 USA. Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. RP Young, MF (reprint author), Natl Inst Dental & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, 30 Convent Dr 30-225 MSC 4320, Bethesda, MD 20892 USA. EM songtaos@usc.edu; myoung@dir.nidcr.nih.gov OI Inkson, Colette/0000-0003-1215-312X FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL061589, R01 HL61589-01]; NIAID NIH HHS [R21 AI078365] NR 50 TC 467 Z9 510 U1 7 U2 45 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2007 VL 13 IS 10 BP 1219 EP 1227 DI 10.1038/nm1630 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217XI UT WOS:000249980200038 PM 17828274 ER PT J AU Lai, CQ Leips, J Zou, W Roberts, JF Wollenberg, KR Parnell, LD Zeng, ZB Ordovas, JM Mackay, TFC AF Lai, Chao-Qiang Leips, Jeff Zou, Wei Roberts, Jessica F. Wollenberg, Kurt R. Parnell, Laurence D. Zeng, Zhao-Bang Ordovas, Jose M. Mackay, Trudy F. C. TI Speed-mapping quantitative trait loci using microarrays SO NATURE METHODS LA English DT Article ID MARKER; DNA AB We developed a rapid, economical method for high-resolution quantitative trait locus ( QTL) mapping using microarrays for selective genotyping of pooled DNA samples. We generated 21,207 F-2 flies from two inbred Drosophila melanogaster strains with known QTLs affecting lifespan, and hybridized DNA pools of young and old flies to microarrays. We used changes of gene frequency of 2,326 single-feature polymorphisms ( SFPs) to map previously identified and additional QTLs affecting lifespan. C1 Univ Maryland Baltimore Cty, Dept Biol Sci, Baltimore, MD 21250 USA. PGxHlth, New Haven, CT 06511 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. NCI, NIAID, Bioinformat & Sci IT Program, Off Technol Informat Syst, Bethesda, MD 20892 USA. Tufts Univ, USDA Human Nutr Res Ctr Aging Nutr & Genom, Boston, MA 02111 USA. N Carolina State Univ, WM Keck Behav Biol, Dept Genet, Raleigh, NC 27695 USA. N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA. RP Lai, CQ (reprint author), Univ Maryland Baltimore Cty, Dept Biol Sci, 711 Washington St, Baltimore, MD 21250 USA. EM chaoqiang.lai@ars.usda.gov OI Ordovas, Jose/0000-0002-7581-5680 FU NIGMS NIH HHS [GM45146, GM45344] NR 15 TC 28 Z9 31 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD OCT PY 2007 VL 4 IS 10 BP 839 EP 841 DI 10.1038/NMETH1084 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 214ZZ UT WOS:000249778200018 PM 17873888 ER PT J AU Read, JCA Cumming, BG AF Read, Jenny C. A. Cumming, Bruce G. TI Sensors for impossible stimuli may solve the stereo correspondence problem SO NATURE NEUROSCIENCE LA English DT Article ID BINOCULAR DISPARITY; VISUAL-CORTEX; ANTICORRELATED STEREOGRAMS; SURFACE ORIENTATION; NEURAL MECHANISMS; DEPTH-PERCEPTION; ENERGY-MODEL; MACAQUE; NEURONS; POSITION AB One of the fundamental challenges of binocular vision is that objects project to different positions on the two retinas ( binocular disparity). Neurons in visual cortex show two distinct types of tuning to disparity, position and phase disparity, which are the results of differences in receptive field location and profile, respectively. Here, we point out that phase disparity does not occur in natural images. Why, then, should the brain encode it? We propose that phase-disparity detectors help to work out which feature in the left eye corresponds to a given feature in the right. This correspondence problem is plagued by false matches: regions of the image that look similar, but do not correspond to the same object. We show that phase-disparity neurons tend to be more strongly activated by false matches. Thus, they may act as 'lie detectors', enabling the true correspondence to be deduced by a process of elimination. C1 Univ Newcastle, Inst Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Read, JCA (reprint author), Univ Newcastle, Inst Neurosci, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. EM j.c.a.read@ncl.ac.uk RI Read, Jenny/A-7493-2013 OI Read, Jenny/0000-0002-9029-5185 FU Intramural NIH HHS [NIH0013247660, Z01 EY000404-06] NR 46 TC 40 Z9 43 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD OCT PY 2007 VL 10 IS 10 BP 1322 EP 1328 DI 10.1038/nn1951 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 214FG UT WOS:000249720800020 PM 17828262 ER PT J AU Wang, WD AF Wang, Weidong TI Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins SO NATURE REVIEWS GENETICS LA English DT Review ID CROSS-LINK REPAIR; STALLED REPLICATION FORKS; ACUTE MYELOID-LEUKEMIA; DOUBLE-STRAND BREAKS; S-PHASE CHECKPOINT; GROUP-A GENE; HOMOLOGOUS RECOMBINATION; NUCLEAR-COMPLEX; FANCD2 MONOUBIQUITINATION; POSITIONAL CLONING AB Fanconi anaemia (FA) has recently become an attractive model to study breast cancer susceptibility (BRCA) genes, as three FA genes, FANCD1, FANCN and FANCJ, are identical to the BRCA genes BRCA2, PALB2 and BRIP1. Increasing evidence shows that FA proteins function as signal transducers and DNA-processing molecules in a DNA-damage response network. This network consists of many proteins that maintain genome integrity, including ataxia telangiectasia and Rad3 related protein (ATR), Bloom syndrome protein (BLM), and BRCA1. Now that the gene that is defective in the thirteenth and last assigned FA complementation group (FANCI) has been identified, I discuss what is known about FA proteins and their interactive network, and what remains to be discovered. C1 NIA, NIH, Baltimore, MD 21093 USA. RP Wang, WD (reprint author), NIA, NIH, 333 Cassell Dr, Baltimore, MD 21093 USA. EM wangw@grc.nia.nih.gov FU Intramural NIH HHS NR 106 TC 442 Z9 451 U1 4 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD OCT PY 2007 VL 8 IS 10 BP 735 EP 748 DI 10.1038/nrg2159 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 211XR UT WOS:000249557500011 PM 17768402 ER PT J AU Piomelli, D Astarita, G Rapaka, R AF Piomelli, Daniele Astarita, Giuseppe Rapaka, Rao TI A neuroscientist's guide to lipidomics SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID METABOTROPIC GLUTAMATE RECEPTORS; PLATELET-ACTIVATING-FACTOR; CANNABINOID CB1 RECEPTOR; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; DOCOSAHEXAENOIC ACID; ENDOGENOUS CANNABINOIDS; ARACHIDONIC-ACID; RAT-BRAIN; PHOSPHATIDYLSERINE RECEPTOR AB Nerve cells mould the lipid fabric of their membranes to ease vesicle fusion, regulate ion fluxes and create specialized microenvironments that contribute to cellular communication. The chemical diversity of membrane lipids controls protein traffic, facilitates recognition between cells and leads to the production of hundreds of molecules that carry information both within and across cells. With so many roles, it is no wonder that lipids make up half of the human brain in dry weight. The objective of neural lipidomics is to understand how these molecules work together; this difficult task will greatly benefit from technical advances that might enable the testing of emerging hypotheses. C1 Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA. Italian Inst Technol, I-16163 Genoa, Italy. Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Piomelli, D (reprint author), Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA. EM piomelli@uci.edu NR 126 TC 133 Z9 140 U1 5 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD OCT PY 2007 VL 8 IS 10 BP 743 EP 754 DI 10.1038/nrn2233 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 212GX UT WOS:000249583400011 PM 17882252 ER PT J AU Esteva-Font, C Ars, E Guillen-Gomez, E Campistol, JM Sanz, L Jimenez, W Knepper, MA Torres, F Torra, R Ballarin, JA Fernandez-Llama, P AF Esteva-Font, Cristina Ars, Elisabet Guillen-Gomez, Elena Campistol, Josep Maria Sanz, Laia Jimenez, Wladimiro Knepper, Mark Alan Torres, Ferran Torra, Roser Ballarin, Jose Aurelio Fernandez-Llama, Patricia TI Ciclosporin-induced hypertension is associated with increased sodium transporter of the loop of Henle (NKCC2) SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE aquaporins; cyclosporine; hypertension; NHE-3; NKCC2; renal sodium transporters ID THICK ASCENDING LIMB; NA-K-2CL COTRANSPORTER ABUNDANCE; RENAL AQUAPORINS; EXPRESSION; RAT; CELLS AB Background. Hypertension induced by cyclosporine is associated with renal sodium and water retention. Using immunoblotting of kidney homogenates, we investigated the regulation of sodium and water transport proteins in a rat model of cyclosporine-induced hypertension. Methods. Rats were treated with cyclosporine ( 25 mg/kg/day intraperitoneally) during 7 days. Control rats received vehicle. Results. Cyclosporine-treated rats had an increase in blood pressure with a decrease in renal sodium excretion compared with control rats. There were no differences either in sodium intake or in plasma creatinine levels between the two groups of rats. These data suggest that the decrease in sodium excretion in the cyclosporine-treated rats was due to an increase in renal sodium absorption. The densito-metric analysis of the renal immunoblot showed an increase in the Na-K-2Cl cotransporter of the loop of Henle (NKCC2) in cyclosporine-treated rats (178% +/- 36) compared with control rats (100% +/- 18; P < 0.05*). This protein rise was associated with an increase in the NKCC2 mRNA pointing to a transcriptional regulation of this sodium transporter. There were no statistically significant changes in the sodium proton exchange (NHE-3) of the proximal tubule although in this renal segment, aquaporin-1 was increased in cyclosporine-treated rats compared with control rats ( control 100% +/- 6 vs cyclosporine 119% +/- 6; P < 0.05). Conclusions. Our results pointed to the thick ascending limb of the loop of Henle as an important site of sodium retention in cyclosporine-induced hypertension. This data may have potential clinical implications for the treatment of hypertension induced by cyclosporine. C1 Univ Autonoma Barcelona, Fdn Puigvert, Mol Biol Lab, E-08193 Barcelona, Spain. Hosp Clin Barcelona, Renal Transplant Unit, Barcelona, Spain. Fdn Puigvert, Renal & Hypertens Unit, Barcelona, Spain. Hosp Clin Barcelona, Hormonal Lab, Barcelona, Spain. NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. Autonomous Univ Barcelona, Hosp Clin, Lab Biostat & Epidemiol, Clin Pharmacol Unit, E-08193 Barcelona, Spain. RP Fernandez-Llama, P (reprint author), Fdn Puigvert, Renal Unit & Hypertens, E-08025 Barcelona, Spain. EM pfernandezllama@fundacio-puigvert.es RI Torra, Roser/A-9983-2008; Torres, Ferran/D-1296-2011 OI Torra, Roser/0000-0001-8714-2332; Torres, Ferran/0000-0002-7355-7913 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 20 TC 16 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD OCT PY 2007 VL 22 IS 10 BP 2810 EP 2816 DI 10.1093/ndt/gfm390 PG 7 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 219UU UT WOS:000250114500017 PM 17595192 ER PT J AU Joy, A Nakada, M Seif-Naraghi, S Nakada, S Rennert, J Beaudry, C Sasse, J Tran, N Fortin, S Mariani, L Zenklusen, J Fine, H Feuerstein, BG Berens, M AF Joy, Anna Nakada, Mitsitoshi Seif-Naraghi, Sonya Nakada, Satoko Rennert, Jessica Beaudry, Christian Sasse, Jeanne Tran, Nhan Fortin, Shannon Mariani, Luigi Zenklusen, Jean Fine, Howard Feuerstein, Burt G. Berens, Michael TI Akt1 and 2 mediate malignant function in GBM SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Joy, Anna; Feuerstein, Burt G.] St Josephs Hosp, Med Ctr, Phoenix, AZ USA. [Nakada, Mitsitoshi; Seif-Naraghi, Sonya; Nakada, Satoko; Rennert, Jessica; Beaudry, Christian; Sasse, Jeanne; Tran, Nhan; Fortin, Shannon; Berens, Michael] Genom Res Inst, Phoenix, AZ USA. [Zenklusen, Jean; Fine, Howard] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 474 EP 474 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100039 ER PT J AU Jiang, W Cazacu, S Xiang, C Zenklusen, J Fine, H Berebs, M Armstrong, B Brodie, C Mikkelsen, T AF Jiang, Wei Cazacu, Simona Xiang, Cunli Zenklusen, Jean Fine, Howard Berebs, Michael Armstrong, Brock Brodie, Chaya Mikkelsen, Tom TI FK506 binding protein (FKBP5) mediates glioma cell growth and sensitivity to rapamycin treatment through regulating AKT and NF-kB signal transduction SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Jiang, Wei; Cazacu, Simona; Xiang, Cunli; Brodie, Chaya; Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Zenklusen, Jean; Fine, Howard] NIH, Bethesda, MD 20892 USA. [Berebs, Michael] TGen, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 482 EP 482 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100069 ER PT J AU Reilly, K Tuskan, R Fox, K Truffer, E Broman, K Tsang, S Munroe, D Akagi, K AF Reilly, Karlyne Tuskan, Robert Fox, Kristi Truffer, Erika Broman, Karl Tsang, Shirley Munroe, David Akagi, Keiko TI Genetic determinants of susceptibility to nervous system tumors in a mouse model of neurofibromatosis type 1 SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 Natl Canc Inst, Frederick, MD USA. [Fox, Kristi; Truffer, Erika; Tsang, Shirley; Munroe, David; Akagi, Keiko] SAIC, Frederick, MD USA. [Tsang, Shirley] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 500 EP 500 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100135 ER PT J AU Proescholdt, M Mayer, C Storr, EM Brawanski, A Merrill, M AF Proescholdt, Martin Mayer, Christina Stoerr, Eva-Maria Brawanski, Alexander Merrill, Marsha TI Hypoxia-inducible carbonic anhydrase IX enhances invasion of glioma cells in vitro SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Proescholdt, Martin; Mayer, Christina; Stoerr, Eva-Maria; Brawanski, Alexander] Univ Regensburg, Med Ctr, Regensburg, Germany. [Merrill, Marsha] Natl Inst Hlth, Surg Neurol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 510 EP 510 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100172 ER PT J AU Schiff, D Sarkaria, J Decker, P Buckner, J Galanis, E Dancey, J Giannini, C Brown, P Wiesenfeld, M Jaeckle, K AF Schiff, David Sarkaria, Jann Decker, Paul Buckner, Jan Galanis, Evanthia Dancey, Janet Giannini, Caterina Brown, Paul Wiesenfeld, Martin Jaeckle, Kurt TI Phase I study of temsirolimus (CCI-779) and sorafenib in recurrent glioblastoma: North central cancer treatment group (NCCTG) N0572 SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Schiff, David] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. [Sarkaria, Jann; Decker, Paul; Buckner, Jan; Galanis, Evanthia; Giannini, Caterina; Brown, Paul] Mayo Clin, Rochester, MN USA. [Dancey, Janet] Natl Canc Inst, Bethesda, MD USA. [Wiesenfeld, Martin] Cedar Rapids Oncol Project, Cedar Rapids, IA USA. [Jaeckle, Kurt] Mayo Clin, Jacksonville, FL 32224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 518 EP 518 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100203 ER PT J AU Wen, P Puduvalli, V Kuhn, J Reid, J Cloughesy, T Yung, W Drappatz, J Lamborn, K Gilbert, M Butowski, N Levin, V Chang, S Kesari, S Robbins, H McGovern, R Richon, V Frankel, S Ames, M Zweibel, J Prados, M AF Wen, Patrick Puduvalli, Vinay Kuhn, John Reid, Joel Cloughesy, Timothy Yung, Wka Drappatz, Jan Lamborn, Kathleen Gilbert, Mark Butowski, Nicholas Levin, Victor Chang, Susan Kesari, Santosh Robbins, Hi McGovern, Renee Richon, Victoria Frankel, Stanley Ames, Matthew Zweibel, James Prados, Michael TI Phase I study of vorinostat (suberoylanilide hydroxamic acid [SAHA]) in combination with temozolomide in patients with malignant gliomas (NABTC 04-03) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 15-18, 2007 CL Dallas, TX SP Soc Neuro Oncol C1 [Wen, Patrick; Drappatz, Jan; Kesari, Santosh] Brigham & Womes Canc Ctr, Boston, MA USA. [Puduvalli, Vinay; Yung, Wka; Gilbert, Mark; Levin, Victor] MD Anderson Canc Ctr, Houston, TX USA. [Kuhn, John] Univ Texas San Antonio, San Antonio, TX 78285 USA. [Reid, Joel; McGovern, Renee; Ames, Matthew] Mayo Clin, Rochester, MN USA. [Cloughesy, Timothy] Univ Calif Los Angeles, Los Angeles, CA USA. [Lamborn, Kathleen; Butowski, Nicholas; Chang, Susan; Prados, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Robbins, Hi] Univ Wisconsin, Madison, WI 53706 USA. [Zweibel, James] Natl Canc Inst, Washington, DC USA. RI Kesari, Santosh/E-8461-2013 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 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2007 VL 9 IS 4 BP 518 EP 518 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 218EP UT WOS:000249999100202 ER PT J AU Riudavets, MA Iacono, D Resnick, SM O'Brien, R Zonderman, AB Martin, LJ Rudow, G Pletnikova, O Troncoso, JC AF Riudavets, Miguel Angel Iacono, Diego Resnick, Susan M. O'Brien, Richard Zonderman, Alan B. Martin, Lee J. Rudow, Gay Pletnikova, Olga Troncoso, Juan C. TI Resistance to Alzheimer's pathology is associated with nuclear hypertrophy in neurons SO NEUROBIOLOGY OF AGING LA English DT Article DE normal cognition; stereology; nucleus; hypertrophy ID MILD COGNITIVE IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; RNA-CONTENT; DISEASE; DEMENTIA; CORTEX; SIZE; PLAQUES; BRAIN; NEURODEGENERATION AB This study focuses on the morphometric changes of neurons in asymptomatic Alzheimer's disease (AD), a state characterized by the presence of AD lesions in subjects without cognitive impairment. In autopsy brains, we used stereological methods to compare the cell body and nuclear volumes of anterior cingulate gyrus (ACG) and CAI hippocampal neurons in asymptomatic AD subjects (11 = 9), subjects with AD dementia (AD, n = 8), mild cognitive impairment (MCI, it = 9), and age-matched controls (controls, n = 9). In ACG, we observed a significant decrease in the neuronal volume of MCI and AD compared to controls; by contrast, no atrophy was present in asymptomatic AD. Moreover, we found a significant increase in nuclear volume in asymptomatic AD compared to controls (P < 0.00 1), MCI (P < 0.0 1) and AD (P < 0.00 1) brains. Similar results were found in the CA I region of the hippocampus. This nuclear hypertrophy may represent an early neuronal reaction to AP or Tau, or a compensatory mechanism which forestalls the progression of AD and a] lows the brain to resist the development of dementia. (c) 2007 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. RP Troncoso, JC (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Ross 558,720 Rutland Ave, Baltimore, MD 21205 USA. EM troncoso@jhmi.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS [Z01 AG000191-11]; NIA NIH HHS [AG16282, AG 05146, P50 AG005146, P50 AG005146-240030, P50 AG005146-249003, R01 AG016282, R01 AG016282-07]; NINDS NIH HHS [NS52098, R01 NS052098, R01 NS052098-01A1] NR 61 TC 52 Z9 53 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD OCT PY 2007 VL 28 IS 10 BP 1484 EP 1492 DI 10.1016/j.neurobiolaging.2007.05.005 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 204RX UT WOS:000249062800004 PM 17599696 ER PT J AU Lin, X Shim, H Cai, H AF Lin, Xian Shim, Hoon Cai, Huatibin TI Deficiency in the ALS2 gene does not affect the motor neuron degeneration in SOD1(G93A) transgenic mice SO NEUROBIOLOGY OF AGING LA English DT Article DE amyotrophic lateral sclerosis (ALS); ALS2; alsin SOD1; SOD1(G93A) mice ID MUTATION; PROTEIN; DEATH; RAB5 AB Dysfunction of the ALS2 gene has been linked to one form of juvenile onset autosomal recessive amyotrophic lateral sclerosis (ALS). Previous in vitro studies suggest that over-expression of ALS2 protects cells from mutant Cu/Zn superoxide dismutase (SOD1)-induced cytotoxicity. To test whether ALS2 plays a protective role against mutant SODI-mediated motor neuron degeneration in vivo, we examined the progression of motor neuron disease in SOD1 (G93A) mice on an ALS2 null background. Our data suggest that deficiency in the ALS2 gene does not affect the pathogenesis of SOD I G93A mice. (c) 2006 Elsevier Inc. All rights reserved. C1 NIA, Unit Transgenesis, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cai, H (reprint author), NIA, Unit Transgenesis, Neurogenet Lab, NIH, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA. EM caih@mail.nih.gov RI Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 FU Intramural NIH HHS [Z01 AG000959-04, Z99 AG999999] NR 9 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD OCT PY 2007 VL 28 IS 10 BP 1628 EP 1630 DI 10.1016/j.neurobiolaging.2006.07.014 PG 3 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 204RX UT WOS:000249062800017 PM 16973244 ER PT J AU Krueger, F Rostami, E Huey, ED Snyder, A Grafman, J AF Krueger, Frank Rostami, Elham Huey, Edward D. Snyder, Andrew Grafman, Jordan TI Evidence of an inferior total-order planning strategy in patients with frontotemporal dementia SO NEUROCASE LA English DT Article DE prefrontal cortex; planning; chores; artificial intelligence; partial-order ID FRONTAL-LOBE DEMENTIA; EVENT-RELATED FMRI; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; PICKS-DISEASE; DIAGNOSIS; DEFICITS; DEGENERATION; TOWER; IMPAIRMENTS AB We investigated planning abilities in patients with frontal temporal dementia (FTD) and normal controls (NC) using a chore location planning task. Planning tasks with increasing complexity could be either solved by constructing a linear total plan (total-order planning) or partially ordered sub-plans (partial-order planning). The NC group appeared to use partial-order planning, while the FTD group appeared to use total-order planning based on error pattern in performance, task-solution, and planning time. Our results are a reminder that besides social impairments, FTD patients also demonstrate higher-order cognitive impairment in domains such as planning and that these impairments may also have a profound effect upon the patients' day-to-day functioning. C1 [Krueger, Frank; Huey, Edward D.; Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Rostami, Elham] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. [Snyder, Andrew] Univ Chicago, Dept Econ, Chicago, IL 60637 USA. RP Grafman, J (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA. EM GrafmanJ@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 FU Intramural NIH HHS NR 58 TC 3 Z9 3 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1355-4794 J9 NEUROCASE JI Neurocase PD OCT-DEC PY 2007 VL 13 IS 5-6 BP 426 EP 437 DI 10.1080/13554790701881723 PG 12 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 309UE UT WOS:000256484900015 PM 18781442 ER PT J AU Unno, T Tanahashi, Y Matsuyama, H Yamada, M Wess, J Komori, S AF Unno, Toshiihro Tanahashi, Yasuyuki Matsuyama, Hayato Yamada, Masahisa Wess, Jurgen Komori, Seiichi TI Three distinct muscarinic pathways mediating the suppression of voltage-gated Ca(2+)channel currents in mouse intestinal smooth muscle cells SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract DE muscarinic receptor; voltage-gated Ca channels; carbachol; intestinal smooth muscle; knockout mouse C1 [Unno, Toshiihro; Matsuyama, Hayato; Komori, Seiichi] Gifu Univ, Dept Vet Med, Pharmacol Lab, Gifu, Japan. [Tanahashi, Yasuyuki] Gifu Univ, United Grad Sch Vet Sci, Dept Pathogenet Vet Sci, Gifu, Japan. [Yamada, Masahisa] RIKEN, Brain Sci Inst, Yamada Res Unit, Wako, Saitama, Japan. [Wess, Jurgen] Natl Inst Diabet & Digest & Kidney Dis, Lab Bioorgan Chem, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD OCT PY 2007 VL 19 SU 3 BP 47 EP 47 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 219SN UT WOS:000250105100122 ER PT J AU Komori, S Sakamoto, T Unno, T Kitazawa, T Taneike, T Yamada, M Wess, J AF Komori, Seiichi Sakamoto, Takashi Unno, Toshihiro Kitazawa, Takio Taneike, Tetsuro Yamada, Masahisa Wess, Jurgen TI Three distinct muscarinic signaling pathways for cationic channel activation in gut smooth muscle cells SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract DE muscarinic receptor; cationic channels; carbachol; intestinal smooth muscle; knockout mouse C1 [Komori, Seiichi; Unno, Toshihiro] Gifu Univ, Dept Vet Med, Pharmacol Lab, Gifu, Japan. [Sakamoto, Takashi] Gifu Univ, United Grad Sch Vet Sci, Dept Pathogenet Vet Sci, Gifu, Japan. [Yamada, Masahisa] RIKEN, Brain Sci Inst, Yamada Res Unit, Wako, Saitama, Japan. [Wess, Jurgen] Natl Inst Diabet & Digest & Kidney Dis, Lab Bioorgan Chem, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD OCT PY 2007 VL 19 SU 3 BP 48 EP 48 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 219SN UT WOS:000250105100124 ER PT J AU Bhattacharjee, AK Meister, LM Chang, L Bazinet, RP White, L Rapoport, SI AF Bhattacharjee, Abesh Kumar Meister, Lindsey M. Chang, Lisa Bazinet, Richard P. White, Laura Rapoport, Stanley I. TI In vivo imaging of disturbed pre- and post-synaptic dopaminergic signaling via arachidonic acid in a rat model of Parkinson's disease SO NEUROIMAGE LA English DT Article DE arachidonic acid; PLA2; D-2 receptors; D-Amphetamine; Parkinson's disease; quinpirole; substantia nigra; lesion ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; PHOSPHOLIPASE A(2) ACTIVATION; SUBSTANTIA-NIGRA LESIONS; UNANESTHETIZED RATS; BRAIN INCORPORATION; RECEPTOR STIMULATION; D-2 RECEPTORS; D-AMPHETAMINE; BLOOD-FLOW AB Background. Parkinson's disease involves loss of dopamine (DA)-producing neurons in the substantia nigra, associated with fewer pre-synaptic DA transporters (DATs) but more post-synaptic dopaminergic D-2 receptors in terminal areas of these neurons. Hypothesis: Arachidonic acid (AA) signaling via post-synaptic D2 receptors coupled to cytosolic phospholipase A(2) (cPLA(2)) will be reduced in terminal areas ipsilateral to a chronic unilateral substantia nigra lesion in rats given D-amphetamine, which reverses the direction of the DAT, but will be increased in rats given quinpirole, a D-2-receptor agonist. Methods: D-Amphetamine (5.0 mg/kg i.p.), quinpirole (1.0 mg/kg i.v.), or saline was administered to unanesthetized rats having a chronic unilateral lesion of the substantia nigra. AA incorporation coefficients, k* (radioactivity/integrated plasma radioactivity), markers of AA signaling, were measured using quantitative autoradiography in 62 bilateral brain regions following intravenous [1-C-14]AA. Results: In rats given saline (baseline), k* was elevated in 13 regions in the lesioned compared with intact hemisphere. Quinpirole increased k* in frontal cortical and basal ganglia regions bilaterally, more so in the lesioned than intact hemisphere. D-Amphetamine increased k* bilaterally but less so in the lesioned hemisphere. Conclusions: Increased baseline elevations of k* and increased responsiveness to quinpirole in the lesioned hemisphere are consistent with their higher D-2-receptor and cPLA(2) activity levels, whereas reduced responsiveness to D-amphetamine is consistent with dropout of pre-synaptic elements containing the DAT. In vivo imaging of AA signaling using dopaminergic drugs can identify pre- and post-synaptic DA changes in animal models of Parkinson's disease. Published by Elsevier Inc. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bhattacharjee, AK (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126, Bethesda, MD 20892 USA. EM abeshb@mail.nih.gov FU Intramural NIH HHS [, NIH0011382695]; PHS HHS [NIH0011382695] NR 69 TC 12 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2007 VL 37 IS 4 BP 1112 EP 1121 DI 10.1016/j.neuroimage.2007.06.012 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 214YF UT WOS:000249773600016 PM 17681816 ER PT J AU Scott, A Laing, N Mastaglia, F Needham, M Walter, M Dalakas, M Allcock, R AF Scott, A. Laing, N. Mastaglia, F. Needham, M. Walter, M. Dalakas, M. Allcock, R. TI Recombinant mapping of MHC susceptibility region in sporadic inclusion body myositis (sIBM) SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 12th International Congress of the World-Muscle-Society CY OCT 17-20, 2007 CL Giardini Naxos, ITALY SP World Muscle Soc C1 [Scott, A.; Allcock, R.] Univ Western Australia, Sch Surg & Pathol, Perth, WA, Australia. [Scott, A.; Laing, N.] Univ Western Australia, Western Australian Inst Med Res, Perth, WA, Australia. [Mastaglia, F.; Needham, M.] Univ Western Australia, Ctr Neuromuscular & Neurol Disorder, Perth, WA, Australia. [Dalakas, M.] Univ Munich, Friedrich Baur Inst, Dept Neurol, Munich, Germany. [Dalakas, M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2007 VL 17 IS 9-10 BP 853 EP 854 DI 10.1016/j.nmd.2007.06.309 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 221WL UT WOS:000250258000310 ER PT J AU Fischer, D Kley, R Strach, K Huebner, A Kress, W Udd, B Schroeder, R Eymard, B Fardeau, M Goldfarb, L Vorgerd, M Olive, M AF Fischer, D. Kley, R. Strach, K. Huebner, A. Kress, W. Udd, B. Schroeder, R. Eymard, B. Fardeau, M. Goldfarb, L. Vorgerd, M. Olive, M. TI Muscle imaging differentiates primary desminopathies from myofibrillar myopathies SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 12th International Congress of the World-Muscle-Society CY OCT 17-20, 2007 CL Giardini Naxos, ITALY SP World Muscle Soc C1 [Fischer, D.] Kantonsspital St Gallen, St Gallen, Switzerland. [Kley, R.; Vorgerd, M.] Univ Hosp Bergmannsheil, Dept Neurol, Bochum, Germany. [Strach, K.] Univ Hosp, Dept Radiol, Bonn, Germany. [Huebner, A.] Tech Univ Dresden, Childrens Hosp, D-8027 Dresden, Germany. [Kress, W.] Biozentrum, Inst Human Genet, Wurzburg, Germany. [Udd, B.] Vaasa Cent Hosp, Dept Neurol, Vaasa, Finland. [Schroeder, R.] Univ Cologne, Dept Biochem, Cologne, Germany. [Eymard, B.; Fardeau, M.] Grp Hosp Pitie Salpetriere, Inst Myol, F-75634 Paris, France. [Goldfarb, L.] NINDS, Bethesda, MD USA. [Olive, M.] Hosp Llobregat, IDIBELL, Inst Neuropathol, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2007 VL 17 IS 9-10 BP 879 EP 879 DI 10.1016/j.nmd.2007.06.392 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 221WL UT WOS:000250258000393 ER PT J AU van der Knaap, MS Schiffmann, R Scheper, GC AF van der Knaap, M. S. Schiffmann, R. Scheper, G. C. TI Conversion of a normal MRI into an MRI showing a cystic Leukoencephalopathy is not a known feature of vanishing white matter SO NEUROPEDIATRICS LA English DT Letter ID INITIATION-FACTOR EIF2B; SUBUNITS; DISEASE C1 [van der Knaap, M. S.; Scheper, G. C.] Vrije Univ Amsterdam Med Ctr, Dept Pediat Child Neurol, NL-1117 HV Amsterdam, Netherlands. [Schiffmann, R.] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA. RP van der Knaap, MS (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Pediat Child Neurol, De Boelelaan, NL-1117 HV Amsterdam, Netherlands. EM ms.vanderknaap@vumc.nl RI Scheper, Gert/D-7001-2014 NR 8 TC 1 Z9 1 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0174-304X J9 NEUROPEDIATRICS JI Neuropediatrics PD OCT PY 2007 VL 38 IS 5 BP 264 EP 264 DI 10.1055/s-2008-1046788 PG 1 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 282PX UT WOS:000254580800010 PM 18330844 ER PT J AU Fox, MA Jensen, CL Gallagher, PS Murphy, DL AF Fox, Meredith A. Jensen, Catherine L. Gallagher, Pamela S. Murphy, Dennis L. TI Receptor mediation of exaggerated responses to serotonin-enhancing drugs in serotonin transporter (SERT)-deficient mice SO NEUROPHARMACOLOGY LA English DT Article DE 5-hydroxy-L-tryptophan (5-HTP); serotonin 1a receptors (5-HT1A, Htr1a); serotonin 2a receptors (5-HT2A, Htr2a); serotonin 7 receptors (5-HT7, Htr7); serotonin syndrome; serotonin transporter (SERT) knockout mice ID KNOCK-OUT MICE; 5-HT TRANSPORTER; ANIMAL-MODEL; 8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN 8-OH-DPAT; ANTAGONIST SB-269970; HYPOTHERMIC RESPONSE; BEHAVIOR; BRAIN; LACKING; RATS AB Administration of serotonin-enhancing drugs induces a distinctive behavioral syndrome in rodents. We previously reported that mice with a targeted disruption of the serotonin transporter (SERT) display some of these behaviors spontaneously, in the absence of drug. In the current studies, we assessed the drug-induced serotonin syndrome in SERT wildlype (+/+), heterozygous (+/-) and knockout (-/-) mice. In SERT -/- mice, the monoamine oxidase inhibitor (MAOI) tranylcypromine (1 mg/kg) or the serotonin precursor 5-hydroXy-L-tryptophan (5-HTP; 80 mg/kg) led to markedly exaggerated serotonin syndrome behaviors relative to SERT +/+ mice, with an intermediate phenotype in SERT +/- mice. SERT +/+ mice developed significant serotonin syndrome behaviors only with the combination of the MAO-A/B inhibitor tranylcypromine (0.5 or 1 mg/kg) or the MAO-A-selective inhibitor clorgyline (1.2 mg/kg) plus 5-HTP. In evaluations of underlying mechanisms, pretreatment with the Htr1a receptor antagonist WAY 100635 (1 mg/kg), but not the Htr7 antagonist SB 269970 (3 mg/kg) or the Htr2a antagonist MDL 11,939 (5 mg/kg), markedly decreased the exaggerated 5-HTP-induced behaviors in SERT -/- mice. Subsequent experiments showed that the Htrla agonist 8-OH-DPAT (1 or 2 mg/kg) elicited serotonin syndrome behaviors in a dose-dependent manner, blocked by WAY 100635 (1 mg/kg), in mice of all three genotypes, confirming the role of Htrla receptors. The current data document markedly enhanced behavioral sensitivity to serotonin-enhancing drugs in SERT-deficient mice. These studies also show that the exaggerated behavioral responses observed in SERT +/- and -/- mice are mediated by postsynaptic Htrla receptors, and suggest intact postsynaptic Htr1a function in SERT -/- mice. (c) 2007 Published by Elsevier Ltd. C1 NIMH, Clin Sci Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Fox, MA (reprint author), NIMH, Clin Sci Lab, Natl Inst Hlth, Bldg 10,Room 3D41, Bethesda, MD 20892 USA. EM mfox@mail.nih.gov FU Intramural NIH HHS NR 59 TC 34 Z9 34 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD OCT PY 2007 VL 53 IS 5 BP 643 EP 656 DI 10.1016/j.neuropharm.2007.07.009 PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 228PD UT WOS:000250741000008 PM 17765930 ER PT J AU Gould, TD Einat, H O'Donnell, KC Picchini, AM Schloesser, RJ Manji, HK AF Gould, Todd D. Einat, Haim O'Donnell, Kelley C. Picchini, Alyssa M. Schloesser, Robert J. Manji, Husseini K. TI beta-catenin overexpression in the mouse brain phenocopies lithium-sensitive Behaviors SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE hyperactivity; Wnt pathway; mania; depression; animal model; lithium ID GLYCOGEN-SYNTHASE KINASE-3; FORCED SWIM TEST; METHAMPHETAMINE-INDUCED STEREOTYPY; TRANSGENIC MICE; EXPRESSION; CHLORIDE; PATHWAY; ZINC; INHIBITION; RATS AB Lithium inhibits glycogen synthase kinase-3 (GSK-3) at therapeutic concentrations; however, it is unclear if this inhibition and its downstream effects on specific signaling pathways are relevant to the treatment of bipolar disorder and depression. One of the targets of GSK-3 is the transcription factor beta-catenin. Normally active GSK-3 phosphorylates beta-catenin, leading to its degradation. Inhibition of GSK3 therefore increases beta-catenin. We have utilized transgenic mice to investigate the behavioral consequences of CNS beta-catenin overexpression. Transgenic mice overexpressing beta-catenin demonstrated behavioral changes similar to those observed following the administration of lithium, including decreased immobility time in the forced swim test (FST). Further, we show that although acute administration of lithium and overexpression of the beta-catenin transgene inhibits d-amphetamine-induced hyperlocomotion, neither lithium nor the beta-catenin transgene prevents d-amphetamine-induced sensitization, as measured by locomotor activity. Both lithium-treated and beta-catenin mice had an elevated response to d-amphetamine following multiple administrations of the stimulant, though the difference in absolute locomotion was maintained throughout the sensitization time-course. Neither acute lithium nor beta-catenin overexpression had an effect on d-amphetamine-induced stereotyped behavior. The results of this study, in which beta-catenin transgenic mice exhibited behaviors identical to those observed in lithium-treated mice, are consistent with the hypothesis that the behavioral effects of lithium in these models are mediated through its direct inhibition of GSK-3 and the consequent increase in beta-catenin. By associating the behavioral effects of lithium with beta-catenin levels, these data suggest that increasing beta-catenin might be a novel therapeutic strategy for mood disorders. C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, NIH, 35 Convent Dr,Bldg 35,Rm 1C-912, Bethesda, MD 20892 USA. EM manjih@mail.nih.gov RI Einat, Haim/A-7203-2009 FU Intramural NIH HHS NR 55 TC 96 Z9 100 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2007 VL 32 IS 10 BP 2173 EP 2183 DI 10.1038/sj.npp.1301338 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 211EB UT WOS:000249506000013 PM 17299510 ER PT J AU Epperson, CN Pittman, B Czarkowski, KA Stiklus, S Krystal, JH Grillon, C AF Epperson, Cynthia Neill Pittman, Brian Czarkowski, Kathryn Ann Stiklus, Stephanie Krystal, John Harrison Grillon, Christian TI Luteal-phase accentuation of acoustic startle response in women with premenstrual dysphoric disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE PMDD; startle; menstrual cycle; affect; valence; arousal ID POSTTRAUMATIC-STRESS-DISORDER; FEAR-POTENTIATED STARTLE; STRIA TERMINALIS; MENSTRUAL-CYCLE; BED NUCLEUS; NEUROACTIVE STEROIDS; PREPULSE INHIBITION; GABA(A) RECEPTOR; RAT HYPOTHALAMUS; ALLOPREGNANOLONE CONCENTRATIONS AB Alterations in central nervous system response to menstrual cycle-related fluctuations in neuroactive steroids are thought to underlie the emergence of negative affect in the luteal phase of the menstrual cycle in women with premenstrual dysphoric disorder (PMDD). Such changes in the neuroendocrine milieu may lead to heightened arousal and response to stress in women with PMDD. Using the acoustic startle paradigm, we sought to determine whether women with PMDD have an accentuated physiologic response to a mildly aversive stimulus during the luteal compared to follicular phase. Further, we also examined the impact of visual affective stimuli on acoustic startle response (ASR) magnitude. During the follicular and luteal phases of the menstrual cycle, acoustic stimuli (103 dB) were delivered to 15 women with PMDD and 14 healthy menstruating women of similar age. After obtaining baseline ASR, the procedure was repeated when subjects viewed pleasant, neutral and unpleasant pictures. There was a significant group by menstrual cycle phase interaction for baseline ASR magnitude, which can be attributed to the heightened startle magnitude in women with PMDD compared to healthy women during the luteal relative to the follicular phase. The direction and degree to which picture viewing modulated the startle magnitude did not vary by group or menstrual cycle phase. These data suggest that menstrual cycle phase has a powerful modulatory effect on physiologic reactivity in women with PMDD but not in healthy women. Physiologic response to affective stimuli appears to be intact in women with PMDD across the menstrual cycle. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA. Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA. NIMH, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. RP Epperson, CN (reprint author), Yale Univ, Sch Med, Dept Psychiat, Univ Towers,Suite 2H,100 York St, New Haven, CT 06511 USA. EM neill.epperson@yale.edu FU Intramural NIH HHS [Z01 MH002798-06]; NIMH NIH HHS [(KO2) MH73090, R01 MH064845, (K23) MH1830, R01 MH64845, K02 MH073090] NR 62 TC 36 Z9 36 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2007 VL 32 IS 10 BP 2190 EP 2198 DI 10.1038/sj.npp.1301351 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 211EB UT WOS:000249506000015 PM 17314917 ER PT J AU Cadet, JL Krasnova, IN AF Cadet, Jean Lud Krasnova, Irina N. TI Interactions of HIV and methamphetamine: Cellular and molecular mechanisms of toxicity potentiation SO NEUROTOXICITY RESEARCH LA English DT Review DE HIV; methamphetamine; neurotoxicity; microgliosis; apoptosis ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; TUMOR-NECROSIS-FACTOR; ACTIVE ANTIRETROVIRAL THERAPY; DISMUTASE TRANSGENIC MICE; INDUCED DOPAMINERGIC NEUROTOXICITY; INDUCED NEURONAL APOPTOSIS; NITRIC-OXIDE SYNTHASE; VPR INDUCES APOPTOSIS AB Methamphetamine (METH) is a highly addictive psychostimulant drug, whose abuse has reached epidemic proportions worldwide. METH use is disproportionally represented among populations at high risks for developing HIV infection or who are already infected with the virus. Psychostimulant abuse has been reported to exacerbate the cognitive deficits and neurodegenerative abnormalities observed in HIV-positive patients. Thus, the purpose of the present paper is to review the clinical and basic observations that METH potentiates the adverse effects of HIV infection. An additional purpose is to provide a synthesis of the cellular and molecular mechanisms that might be responsible for the increased toxicity observed in co-morbid patients. The reviewed data indicate that METH and HIV proteins, including gp120, gp41, Tat, Vpr and Nef, converge on various caspase-dependent death pathways to cause neuronal apoptosis. The role of reactive microgliosis in METH- and in HIV-induced toxicity is also discussed. C1 NIDA, Mol Neuropsychiat Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov FU Intramural NIH HHS NR 303 TC 27 Z9 30 U1 2 U2 6 PU F P GRAHAM PUBLISHING CO PI MOUNTAIN HOME PA PO BOX 370, MOUNTAIN HOME, TN 37684 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PD OCT PY 2007 VL 12 IS 3 BP 181 EP 204 PG 24 WC Neurosciences SC Neurosciences & Neurology GA 237OL UT WOS:000251384600004 PM 17967742 ER PT J AU Kim, D Kellman, P AF Kim, Daniel Kellman, Peter TI Improved cine displacement-encoded MRI using balanced steady-state free precession and time-adaptive sensitivity encoding parallel imaging at 3T SO NMR IN BIOMEDICINE LA English DT Article DE MRI; SENSE; strain; TSENSE; function; displacement; tagging; SSFP ID TO-NOISE RATIO; MAGNETIC-RESONANCE; MYOCARDIAL MOTION; PHASE-CONTRAST; TRACKING; HEART; DENSE; MODULATION; ECHOES; ERRORS AB Cine displacement-encoded MRI is a promising modality for quantifying regional myocardial function. However, it has two major limitations: low signal-to-noise ratio (SNR) and data acquisition efficiency. The purpose of this study was to incrementally improve the SNR and the data acquisition efficiency of cine displacement-encoded MRI through the combined use of balanced steady-state free precession (b-SSFP) imaging, 3T imaging, echo-combination image reconstruction, and time-adaptive sensitivity encoding (TSENSE) parallel imaging. Phantom experiments were performed to empirically determine the optimal excitation angle (alpha) and to estimate the measurement errors in the presence of 130 Hz peak-to-peak static magnetic field (B-0) variation. The optimal a was determined to be 20 degrees. The intrinsic phase correction in the echo-combination effectively reduced the phase error, which produced small displacement errors (0.11 versus 0.11 mm) and negligible strain errors (-0.001 versus -0.002). Six healthy volunteers were imaged in three short-axis levels of the heart to evaluate the SNR and the relative accuracy of strain calculations. Compared with the 24-heartbeat cine echo-planar imaging acquisition, the 24-heartbeat non-accelerated b-SSFP acquisition yielded approximately 65% higher SNR, and the 12-heartbeat twofold accelerated b-SSFP acquisition yielded approximately 28% higher SNR. The 12-heartbeat twofold accelerated b-SSFP acquisition yielded functional maps with spatial resolution of 3.6 x 3.6 mm, temporal resolution of 35 ms, and relatively high SNR (31.2 +/- 5.4 at end diastole; 19.9 +/- 3.6 at end systole; 10.3 +/- 1.1 at late diastole; mean SD). The left ventricular strain values between the non-accelerated and twofold accelerated b-SSFP acquisitions correlated strongly (slope = 0.99; bias = 0.00; R-2 = 0.91) and were in excellent agreement. The combined implementation of b-SSFP imaging, 3T imaging, echo-combination image reconstruction, and TSENSE parallel imaging can be used to incrementally improve the cine displacement-encoded MRI pulse sequence. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 NYU, Dept Radiol, New York, NY 10016 USA. NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA. RP Kim, D (reprint author), NYU, Dept Radiol, 650 1St Ave,600 A, New York, NY 10016 USA. EM dan.kim@med.nyu.edu NR 37 TC 16 Z9 16 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD OCT PY 2007 VL 20 IS 6 BP 591 EP 601 DI 10.1002/nbm.1126 PG 11 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 215MC UT WOS:000249811600004 PM 17211867 ER PT J AU Boswell, CA Brechbiel, MW AF Boswell, C. Andrew Brechbiel, Martin W. TI Development of radioimmunotherapeutic and diagnostic antibodies: an inside-out view SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Workshop on After Bench to Bedside - Impact on Cllinical Outcome CY 2007 CL La Jolla, CA DE Radioimmunotherapy; cancer diagnosis; antibodies; molecular imaging ID NON-HODGKINS-LYMPHOMA; PHASE-I TRIAL; POSITRON-EMISSION-TOMOGRAPHY; TARGETED-ALPHA-THERAPY; BREAST-CANCER XENOGRAFTS; RENAL-CELL CARCINOMA; COMBINED-MODALITY RADIOIMMUNOTHERAPY; RADIOLABELED MONOCLONAL-ANTIBODY; GROWTH-FACTOR RECEPTOR; ZR-89 IMMUNO-PET AB Only a handful of radiolabeled antibodies (Abs) have gained US Food and Drug Administration (FDA) approval for use in clinical oncology, including four immonodiagnostic agents and two targeted radio immunotherapeutic agents. Despite the advent of nonimmunogenic Abs and the availability of a diverse library of radionuclides, progress beyond early Phase II radioimmunotherapy (RIT) studies in solid tumors has been marginal. Furthermore, [F-18]fluorodeoxyglucose continues to dominate the molecular imaging domain, underscored by a decade-long absence of any newly approved Ab-based imaging agent (none since 1996). Why has the development of clinically successful Abs for RIT been limited to lymphoma? What obstacles must be overcome to allow the FDA approval of immuno-positron emission tomography (immuno-PET) imaging agents? How can we address the unique challenges that have thus far prevented the introduction of Abbased imaging agents and therapeutics for solid tumors? Many poor decisions have been made regarding radiolabeled Abs, but useful insight can be gained from these mistakes. The following review addresses the physical, chemical, biological, clinical, regulatory and financial limitations that impede the progress of this increasingly important class of drugs. Published by Elsevier Inc. C1 NIH, Natl Canc Inst, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NIH, Natl Canc Inst, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov OI Boswell, Charles/0000-0002-0426-9846 FU Intramural NIH HHS [Z01 SC006353-24] NR 173 TC 116 Z9 121 U1 3 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD OCT PY 2007 VL 34 IS 7 BP 757 EP 778 DI 10.1016/j.nucmedbio.2007.04.001 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 222WI UT WOS:000250328100007 PM 17921028 ER PT J AU Drevets, WC Thase, ME Moses-Kolko, EL Price, J Frank, E Kupfer, DJ Mathis, C AF Drevets, Wayne C. Thase, Michael E. Moses-Kolko, Eydie L. Price, Julie Frank, Ellen Kupfer, David J. Mathis, Chester TI Serotonin-1A receptor imaging in recurrent depression: replication and literature review SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Workshop on After Bench to Bedside - Impact on Clinical Outcome CY 2007 CL La Jolla, CA ID POSITRON-EMISSION-TOMOGRAPHY; MESSENGER-RNA EXPRESSION; ANTIDEPRESSANT DRUG-TREATMENT; 5-HT1A RECEPTOR; MAJOR DEPRESSION; HUMAN-BRAIN; MINERALOCORTICOID RECEPTOR; AUTORADIOGRAPHIC ANALYSES; BIPOLAR DEPRESSION; DORSAL HIPPOCAMPUS AB Introduction: Serotonin-1A receptor (5-HT(1A)R) function appears to be decreased in major depressive disorder (MDD) based on physiological responses to 5-HT(1A)R agonists in vivo and to 5-HT(1A)R binding in brain tissues postmortem or antemortem. We have previously assessed 5-HT(1A)R binding potential (BP) in depression using positron emission tomography (PET) and [carbonyl-(11)C]WAY-100635, and we have demonstrated reduced 5-HT(1A)R BP in the mesiotemporal cortex (MTC) and raphe in depressives with primary recurrent familial mood disorders (n=12) versus controls (n=8) [Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C. PET imaging of serotonin I A receptor binding in depression. Biol Psychiatry 1999;46(10):1375-87]. These findings were replicated by some, but not other, studies performed in depressed samples that were more generally selected using criteria for MDD. In the current study, we attempted to replicate our previous findings in an independent sample of subjects selected according to the criteria for primary recurrent depression applied in our prior study. Methods: Using PET and [carbonyl-(11)C]WAY-100635, 5-HT(1A)R BP was assessed in 16 depressed subjects and 8 healthy controls. Results: Mean 5-HT(1A)R BP was reduced by 26% in the MTC (P<.005) and by 43% in the raphe (P<.001) in depressives versus controls. Conclusions: These data replicate our original findings, which showed that BP was reduced by 27% in the MTC (P<.025) and by 42% in the raphe (P<.02) in depression. The magnitudes of these reductions in 5-HT(1A)R binding were similar to those found postmortem in 5-HT(1A)R mRNA concentrations in the hippocampus in MDD [Lopez JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547-73] and in 5-HT(1A)R-binding capacity in the raphe in depressed suicide victims [Arango V, Underwood MD, Boldrini M, Tamir H, Kassir SA, Hsiung S, Chen JJ, Mann JJ. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 2001-,25(6):892-903]. There exists disagreement within the literature, however, regarding the presence and direction of 5-HT(1A)R-binding abnormalities in depression, which may be explained in some cases by differences in anatomical location (e.g., [Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G. Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression -postmortem evidence for decreased serotonin activity. J Neurosci 1998;18(18):7394-401]) and in other cases by pathophysiological heterogeneity within MDD (e.g., some depressives hypersecrete cortisol, which would be expected to down-regulate 5-HT(1A)R expression [Lopez JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547-73]). Antidepressant drug treatment does not alter these abnormalities in 5-HTIAR binding [Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, Gunn RN, Grasby PM, Cowen PJ. Brain serotonin(1A) receptor binding measured by positron emission tomography with [(11)C]WAY-1 00635: effects of depression and antidepressant treatment. Arch Gen Psychiatry 2000;57(2):174-80; Moses-Kolko EL, Price JC, Thase ME, Meltzer CC, Kupfer DJ, Mathis CA, Bogers WD, Berman SR, Houck PR, Schneider TN, Drevets WC. Measurement of 5-HT(1A) receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [(11)C]WAY-100635. Synapse 2007;61(7):523-30] but may compensate for blunted 5-HT(1A)R function by increasing post-synaptic 5-HT(1A)R transmission [Chaput Y, de Montigny C, Blier P. Presynaptic and postsynaptic modifications of the serotonin system by long-terin administration of antidepressant treatments. An in vivo electrophysiologic study in the rat. Neuropsychopharmacology 1991;5(4):219-29]. C 2007 Elsevier Inc. All rights reserved. C1 MINH Mol Imaging Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 19213 USA. Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 19213 USA. Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. RP Drevets, WC (reprint author), NIH NIMH DIRP, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. EM drevetsw@mail.nih.gov FU Intramural NIH HHS [Z01 MH002788-06]; NIMH NIH HHS [K23 MH064561] NR 109 TC 212 Z9 221 U1 2 U2 31 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD OCT PY 2007 VL 34 IS 7 BP 865 EP 877 DI 10.1016/j.nuemedbio.2007.06.008 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 222WI UT WOS:000250328100016 PM 17921037 ER PT J AU Messaoudi, L Yang, YG Kinomura, A Stavreva, DA Yan, G Bortolin-Cavaille, ML Arakawa, H Buerstedde, JM Hainaut, P Cavaille, J Takata, M Van Dyck, E AF Messaoudi, Lydia Yang, Yun-Gui Kinomura, Aiko Stavreva, Diana A. Yan, Gonghong Bortolin-Cavaille, Marie-Line Arakawa, Hiroshi Buerstedde, Jean-Marie Hainaut, Pierre Cavaille, Jerome Takata, Minoru Van Dyck, Eric TI Subcellular distribution of human RDM1 protein isoforms and their nucleolar accumulation in response to heat shock and proteotoxic stress SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PML NUCLEAR-BODIES; RNA RECOGNITION MOTIF; SERINE-RICH DOMAINS; DNA-BINDING DOMAIN; SR PROTEINS; LOCALIZATION SIGNAL; SPLICING FACTORS; CELLULAR STRESS; POLYMERASE-II; RGG DOMAIN AB The RDM1 gene encodes a RNA recognition motif (RRM)-containing protein involved in the cellular response to the anti-cancer drug cisplatin in vertebrates. We previously reported a cDNA encoding the full-length human RDM1 protein. Here, we describe the identification of 11 human cDNAs encoding RDM1 protein isoforms. This repertoire is generated by alternative pre-mRNA splicing and differential usage of two translational start sites, resulting in proteins with long or short N-terminus and a great diversity in the exonic composition of their C-terminus. By using tagged proteins and fluorescent microscopy, we examined the subcellular distribution of full-length RDM1 (renamed RDM1), and other RDM1 isoforms. We show that RDM1 undergoes subcellular redistribution and nucleolar accumulation in response to proteotoxic stress and mild heat shock. In unstressed cells, the long N-terminal isoforms displayed distinct subcellular distribution patterns, ranging from a predominantly cytoplasmic to almost exclusive nuclear localization, suggesting functional differences among the RDM1 proteins. However, all isoforms underwent stress-induced nucleolar accumulation. We identified nuclear and nucleolar localization determinants as well as domains conferring cytoplasmic retention to the RDM1 proteins. Finally, RDM1 null chicken DT40 cells displayed an increased sensitivity to heat shock, compared to wild-type (wt) cells, suggesting a function for RDM1 in the heat-shock response. C1 Int Agcy Res Canc, F-69372 Lyon, France. Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Human Genet, Minami Ku, Hiroshima 7348553, Japan. NCI, Ctr Canc Res, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. Univ Toulouse 3, LBME, CNRS UMR 5099, IFR 109, F-31062 Toulouse, France. GSF, Inst Mol Radiobiol, D-85764 Neuherberg, Germany. RP Van Dyck, E (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France. EM vandyck@iarc.fr RI Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 NR 79 TC 7 Z9 8 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2007 VL 35 IS 19 BP 6571 EP 6587 DI 10.1093/nar/gkm753 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229TJ UT WOS:000250827000021 PM 17905820 ER PT J AU Spong, CY Landon, MB Gilbert, S Rouse, DJ Leveno, KJ Varner, MW Moawad, AH Simhan, HN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, AM O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM AF Spong, Catherine Y. Landon, Mark B. Gilbert, Sharon Rouse, Dwight J. Leveno, Kenneth J. Varner, Michael W. Moawad, Atef H. Simhan, Hyagriv N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall Peaceman, Alan M. O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. CA NICHD MFMU Network TI Risk of uterine rupture and adverse perinatal outcome at term after cesarean delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID VAGINAL BIRTH; TRIAL; LABOR; COMPLICATIONS; MORBIDITY; SECTION; WOMEN AB OBJECTIVE: Current information on the risk of uterine rupture after cesarean delivery has generally compared the risk after trial of labor to that occurring with an elective cesarean delivery without labor. Because anteparturn counseling cannot account for whether a woman will develop an indication requiring a repeat cesarean delivery or whether labor will occur before scheduled cesarean delivery, the purpose of this analysis was to provide clinically useful information regarding the risks of uterine rupture and adverse perinatal outcome for women at term with a history of prior cesarean delivery. METHODS: Women with a term singleton gestation and prior cesarean delivery were studied over 4 years at 19 centers. For this analysis, outcomes from five groups were'studied: trial of labor, elective repeat with no labor, elective repeat with labor (women presenting in early labor who subsequently underwent cesarean delivery), indicated repeat with labor, and indicated repeat without labor. All cases of uterine rupture were reviewed centrally to assure accuracy of diagnosis. RESULTS: A total of 39,117 women were studied. In term pregnant women with a prior cesarean delivery, the overall risk for uterine rupture was 0.32% (125 of 39,117), and the overall risk for serious adverse perinatal outcome (stillbirth, hypoxic ischemic encephalopathy, neonatal death) was 106 of 39,049 (0.27%). The uterine rupture risk for indicated repeat cesarean delivery (labor or without labor) was 7 of 6,080 (0.12%); the risk for elective (no indication) repeat cesarean delivery (labor or without labor) was 4 of 17,714 (0.02%). Indicated repeat cesarean delivery increased the risk of uterine rupture by a factor of 5 (odds ratio 5.1, 95% confidence interval 1.49-17.44). In the absence of an indication, the presence of labor also increased the risk of uterine rupture (4 of 2,721 [0.15%] compared with 0 of 14,993, P<.01). The highest rate of uterine rupture occurred in women undergoing trial of labor (0.74%, 114 of 15,323). CONCLUSION: At term, the risk of uterine rupture and adverse perinatal outcome for women with a singleton and prior cesarean delivery is low regardless of mode of delivery, occurring in 3 per 1,000 women. Maternal complications occurred in 3-8% of women within the five delivery groups. C1 NICHD, PPB, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Washington Univ, Ctr Biostat, Washington, DC USA. Univ Alabama Birmingham, Dept Obstet, Birmingham, AL USA. Univ Alabama Birmingham, Dept Gynecol, Birmingham, AL USA. Univ Texas San Antonio, SW Med Ctr, Dallas, TX 75230 USA. Univ Utah, Salt Lake City, UT USA. Univ Chicago, Chicago, IL 60637 USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Columbia Univ, New York, NY USA. Brown Univ, Providence, RI 02912 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Miami, Miami, FL 33152 USA. Univ Tennessee, Memphis, TN USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas San Antonio, Houston, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Spong, CY (reprint author), NICHD, PPB, NIH, 6100 Execut Blvd,Room 4B03 MSC 7510, Bethesda, MD 20892 USA. EM spongc@mail.nih.gov RI Varner, Michael/K-9890-2013; OI Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NICHD NIH HHS [HD21414, HD21410, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 8 TC 66 Z9 70 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2007 VL 110 IS 4 BP 801 EP 807 DI 10.1097/01.AOG.0000284622.71222.b2 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 217VA UT WOS:000249974200011 PM 17906012 ER PT J AU Varner, MW Thom, E Spong, CY Landon, MB Leveno, KJ Rouse, DJ Moawad, AH Simhan, HN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, A O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM AF Varner, Michael W. Thom, Elizabeth Spong, Catherine Y. Landon, Mark B. Leveno, Kenneth J. Rouse, Dwight J. Moawad, Atef H. Simhan, Hyagriv N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall Peaceman, Alan O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. CA NICHD Maternal-Fetal Med Units Net TI Trial of labor after one previous cesarean delivery for multifetal gestation SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med ID BIRTH AB OBJECTIVE: To estimate success rates and risks with a trial of labor after one previous cesarean delivery for multifetal gestation compared with one previous cesarean delivery for a singleton pregnancy. METHODS: Patients from the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network Cesarean Registry with one previous cesarean delivery and a current term singleton pregnancy were identified. Cases had one previous cesarean delivery for a multifetal pregnancy. Controls had one previous cesarean delivery for a singleton pregnancy. RESULTS: Of cases, 556 of 944 (58.9%) attempted a trial of labor. Of controls, 13,923 of 29,329 (47.5%) attempted a trial of labor. The trial of labor success rate was 85.6% among cases and 73.1% among controls (odds ratio 2.19, 950% confidence interval 1.72-2.78). Compared with trial of labor controls, cases had no statistically increased risk of transfusion, endometritis, intensive care unit admissions, uterine rupture, or perinatal complications. Cases in this analysis with a successful trial of labor were more likely to have previously had a successful vaginal birth after cesarean (37.1% compared with 14.1%, P<.001). CONCLUSION: Women with one previous cesarean delivery for a multifetal gestation have high trial of labor success rates and low complication rates. C1 Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. Ohio State Univ, Columbus, OH 43210 USA. SW Texas State Univ, Dallas, TX USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Chicago, Chicago, IL 60637 USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Columbia Univ, New York, NY USA. Brown Univ, Providence, RI 02912 USA. Univ Miami, Miami, FL 33152 USA. Univ Tennessee, Memphis, TN USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas San Antonio, Houston, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Varner, MW (reprint author), Univ Utah, Sch Med, Dept Obstet & Gynecol, 30 North 1900 East,Room 308, Salt Lake City, UT 84132 USA. EM mvarner@hsc.utah.edu RI Varner, Michael/K-9890-2013 OI Peaceman, Alan/0000-0002-4515-4850; Varner, Michael/0000-0001-9455-3973 FU NICHD NIH HHS [HD36801, HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 6 TC 6 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2007 VL 110 IS 4 BP 814 EP 819 DI 10.1097/01.AOG.0000280586.05350.9e PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 217VA UT WOS:000249974200013 PM 17906014 ER PT J AU Jeronimo, J Massad, LS Castle, PE Wacholder, S Schiffman, M AF Jeronimo, Jose Massad, L. Stewart Castle, Philip E. Wacholder, Sholom Schiffman, Mark CA NIH ASCCP Res Grp TI Interobserver agreement in the evaluation of digitized cervical images SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ASCUS-LSIL TRIAGE; HUMAN-PAPILLOMAVIRUS; CANCER; PRECANCER; WOMEN; RISK AB OBJECTIVE: To estimate the agreement among multiple expert colposcopists evaluating high-resolution digitized cervigrams taken from patients with a variety of human papillomavirus (HPV) infection states and previous cervigram interpretations. METHODS: Twenty expert colposcopists evaluated 939 digitized images of the uterine cervix obtained after the application of 5% acetic acid during the ASCUS-LSIL Triage Study. Twenty images selected to represent a broad range were graded by all the colposcopists. The remaining 919 pictures were distributed by stratified random sampling; such that each image was evaluated by two colposcopists and each expert evaluated 112 images with similar distributions of cervigram diagnoses and HPV DNA test results. We evaluated interrater agreement among the pairs of colposcopists and confirmed the conclusions using the 20 images they all graded. RESULTS: Pairs of colposcopists agreed on the diagnosis for only 56.8% of images. Similar agreement was seen regarding number of visible lesions (of low-grade or greater). This variability in ratings remained when the images were stratified by final histologic diagnosis or HPV status. The results were confirmed by the presence of large variability in ratings (ranging in some cases from normal to cancer) for the 20 images graded by all colposcopists. CONCLUSION: Colposcopic diagnosis using static images is poorly reproducible and might reflect similar problems in clinical practice. Researchers should question the use of colposcopic images as a reference standard for teaching and evaluating the presence or severity of disease. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. RP Jeronimo, J (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5010, Bethesda, MD 20852 USA. EM guibovij@mail.nih.gov NR 18 TC 26 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2007 VL 110 IS 4 BP 833 EP 840 DI 10.1097/01.AOG.0000281665.63550.8f PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 217VA UT WOS:000249974200016 PM 17906017 ER PT J AU Northen, AT Norman, GS Anderson, K Moseley, L DiVito, M Cotroneo, M Swain, M Bousleiman, S Johnson, F Dorman, K Milluzzi, C Tillinghast, JA Kerr, M Mallett, G Thom, E Pagliaro, S Anderson, GD AF Northen, Allison T. Norman, Gwendolyn S. Anderson, Kristine Moseley, Lisa DiVito, Michelle Cotroneo, Margaret Swain, Melissa Bousleiman, Sabine Johnson, Francee Dorman, Karen Milluzzi, Cynthia Tillinghast, Jo-Ann Kerr, Marcia Mallett, Gail Thom, Elizabeth Pagliaro, Susan Anderson, Garland D. CA NICHD MFMU Network TI Follow-up of children exposed in utero to 17 alpha-hydroxyprogesterone caproate compared with placebo SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CONGENITAL-MALFORMATIONS; PREGNANCY; PROGESTERONE; PROGESTOGENS; PROGESTINS; ANOMALIES; THERAPY; MOUSE; MALES AB OBJECTIVE: To assess whether there are evident adverse effects of 17 alpha-hydroxyprogesterone caproate after in utero exposure. METHODS: This study evaluated surviving children of mothers who participated in a multicenter placebocontrolled trial of weekly intramuscular 17 alpha-hydroxyprogesterone caproate, with a 2:1 allocation to 17 a-hydroxyprogesterone caproate and placebo, respectively. The guardian was interviewed about the child's general health. Children underwent a physical examination and developmental screen with the Ages and Stages Questionnaire. Gender-specific roles were assessed with the Preschool Activities Inventory. RESULTS: Of 348 eligible surviving children, 278 (80%) were avalilable for evaluation (194 in the 17 alpha-hydroxyprogestrone caproate group and 84 in the placebo group). The mean age at follow-up was 48 months. No significant differences were seen in health status or physical examination, including genital anomalies, between 17 alpha-hydroxyprogesterone caproate and placebo children. Scores for gender-specific roles (Preschool Activities Inventory) were within the normal range and similar between 17 alpha-hydroxyprogesterone caproate and placebo groups. CONCLUSION: 17 alpha-hydroxyprogesterone caproate seems to be safe for the fetus when administered in the second and third trimesters. C1 Univ Alabama, Ctr Womens Reprod Hlth, Dept Obstet, Birmingham, AL USA. Univ Alabama, Ctr Womens Reprod Hlth, Dept Gynecol, Birmingham, AL USA. Wayne State Univ, Detroit, MI USA. Univ Utah, Salt Lake City, UT USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Drexel Univ, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Columbia Univ, New York, NY USA. Ohio State Univ, Columbus, OH 43210 USA. Univ N Carolina, Chapel Hill, NC USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Brown Univ, Providence, RI 02912 USA. Univ Texas, Houston, TX USA. Northwestern Univ, Chicago, IL 60611 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. NICHD, Bethesda, MD USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Northen, AT (reprint author), Univ Alabama, Dept Obstet & Gynecol, 1500 6th Ave S CWRH 393, Birmingham, AL 35294 USA. EM anorthen@uab.edu FU NICHD NIH HHS [HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD36801, HD40485, HD40512, HD40544, HD40545, HD40560] NR 23 TC 50 Z9 52 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2007 VL 110 IS 4 BP 865 EP 872 DI 10.1097/01.AOG.0000281348.51499.bc PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 217VA UT WOS:000249974200020 PM 17906021 ER PT J AU Levens, ED DeCherney, AH AF Levens, Eric D. DeCherney, Alan H. TI Severe menorrhagia associated with thrombocytopenia SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID BLEEDING DISORDERS; ENDOMETRIAL ABLATION; WOMEN; TRANSPLANTATION; PLATELET C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Hlth, Walter Reed Army Med Ctr, Natl Naval Med Ctr, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. RP Levens, ED (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bldg 10,CRC,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM levense@mail.nih.gov OI Scheinberg, Phillip/0000-0002-9047-4538 NR 15 TC 7 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2007 VL 110 IS 4 BP 913 EP 917 DI 10.1097/01.AOG.0000279138.64895.2b PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 217VA UT WOS:000249974200027 PM 17906028 ER PT J AU Krstev, S Stewart, P Rusiecki, J Blair, A AF Krstev, S. Stewart, P. Rusiecki, J. Blair, A. TI Mortality among shipyard Coast Guard workers: a retrospective cohort study SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Review ID LUNG-CANCER; OCCUPATIONAL-EXPOSURE; NASOPHARYNGEAL CARCINOMA; ASBESTOS-EXPOSURE; PAINT-REMOVAL; RISK-FACTORS; MILD-STEEL; WELDERS; MESOTHELIOMA; WOOD AB Background: The mortality experience of 4702 ( 4413 men and 289 women) civilian workers in a US Coast Guard shipyard was evaluated. Methods: All workers employed at the shipyard between 1 January 1950 and 31 December 1964 were included in the study and were followed through 31 December 2001 for vital status. Detailed shipyard and lifetime work histories found in the shipyard personnel records and job descriptions were evaluated. Workers were classified as likely exposed to any potential hazardous substances. In addition, 20 job groups were created on likely similar exposures. Standardised mortality ratios (SMRs) were calculated based on the general population of the state and adjusted for age, calendar period, sex and race. Results: The follow-up was successful for 93.3% of the workers. Among all men employed in the shipyard, there was an excess of mortality from all causes of death (SMR 1.08; 95% CI 1.04 to 1.12), respiratory cancers (SMR 1.29; 95% CI 1.15 to 1.43), lung cancer ( SMR 1.26; 95% CI 1.12 to 1.41), mesothelioma (SMR 5.07; 95% CI 1.85 to 11.03) and emphysema (SMR 1.44; 95% CI 1.01 to 1.99) and a decrease for cardiovascular diseases (OR 0.95; 95% CI 0.90 to 1.00), vascular lesions of the central nervous system (SMR 0.80; 95% CI 0.67 to 0.96), cirrhosis of the liver (SMR 0.38; 95% CI 0.25 to 0.57) and external causes of death ( SMR 0.55; 95% CI 0.44 to 0.68). A similar pattern was observed for the men classified as exposed. No increasing trend of mortality was found with duration of employment in the shipyard, with the exception of mesothelioma (SMRs of 4.23 and 6.27 for < 10 years and >= 10 years, respectively). In occupations with at least three cases and with an SMR of >= 1.3, the authors observed a significantly elevated mortality for lung cancer among machinists (SMR 1.60; 95% CI 1.08 to 2.29) and shipfitters, welders and cutters (SMR 1.34; 95% CI 1.07 to 1.65) and for oral and nasopharyngeal cancers among wood workers (SMR 6.20; 95% CI 2.27 to 13.50). Conclusion: Employment in this Coast Guard shipyard revealed a small but significant excess mortality from all causes, lung cancer and mesothelioma, most of which is probably related to asbestos exposure. C1 NCI, Occupat & Environm Epidemiol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Inst Occupat & Radiol Hlth, Clin Ctr Serbia, Belgrade, Serbia. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Blair, A (reprint author), NCI, Occupat & Environm Epidemiol Branch, NIH, Dept Hlth & Human Serv, EPS Room 8008, Bethesda, MD 20892 USA. EM blaira@mail.nih.gov FU Intramural NIH HHS NR 62 TC 23 Z9 23 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD OCT PY 2007 VL 64 IS 10 BP 651 EP 658 DI 10.1136/oem.2006.029652 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 212HM UT WOS:000249586800004 PM 17881470 ER PT J AU Baker, SJ Rane, SG Reddy, EP AF Baker, S. J. Rane, S. G. Reddy, E. P. TI Hematopoietic cytokine receptor signaling SO ONCOGENE LA English DT Review DE hematopoiesis; cytokine receptors; Src kinases; JAKs; STATs ID COLONY-STIMULATING FACTOR; PROTEIN-TYROSINE-PHOSPHATASE; DNA-BINDING ACTIVITY; INTERLEUKIN-5 TRANSDUCE SIGNALS; INTERFERON-ALPHA/BETA RECEPTOR; CELL-SURFACE EXPRESSION; C-TERMINAL DOMAINS; GM-CSF RECEPTOR; ERYTHROPOIETIN RECEPTOR; MOLECULAR-CLONING AB Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Proper culmination of these diverse pathways forms the basis for an orderly generation of different cell types. Recent studies conducted over the past 10 - 15 years have revealed that hematopoietic cytokine receptor signaling is largely mediated by a family of tyrosine kinases termed Janus kinases ( JAKs) and their downstream transcription factors termed STATs ( signal transducers and activators of transcription). Aberration in these pathways, such as that caused by the recently identified JAK2V617F mutation, is an underlying cause for diseases such as leukemias and other myeloproliferative disorders. This recent discovery, when coupled with the fact that STATs are activated by oncoproteins such as BCR-ABL, underscores the importance of the JAK- STAT pathway in both normal cellular development and disease states. C1 Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. NIDDK, NIH, Diabet Branch, Bethesda, MD USA. RP Reddy, EP (reprint author), Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, 3307 N Broad St, Philadelphia, PA 19140 USA. EM reddy@temple.edu RI Reddy, E. Premkumar/F-6233-2011 FU NHLBI NIH HHS [5R01HL080666-02] NR 130 TC 142 Z9 149 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 2007 VL 26 IS 47 BP 6724 EP 6737 DI 10.1038/sj.onc.1210757 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 220HE UT WOS:000250147000005 PM 17934481 ER PT J AU Beck, RW Maguire, MG Bressler, NM Glassman, AR Lindblad, AS Ferris, FL AF Beck, Roy W. Maguire, Maureen G. Bressler, Neil M. Glassman, Adam R. Lindblad, Anne S. Ferris, Frederick L. TI Visual acuity as an outcome measure in clinical trials of retinal diseases SO OPHTHALMOLOGY LA English DT Article ID MACULAR DEGENERATION; VERTEPORFIN; RANIBIZUMAB; PROTOCOL AB Purpose: Visual acuity (VA) is the primary outcome measure in many studies involving eye diseases. A standard statistical approach for comparing a continuous measurement such as a VA letter score between 2 treatment groups is to perform a t test comparing the means. However, frequently a binary variable is created from the continuous VA letter score based on whether or not there has been a worsening (or gain) of 15 letters (equivalent to >= 3 lines), and a chi square or similar statistical test is performed to compare the proportions of success (or failure), between groups. The purpose of this article is to contrast these 2 approaches. Methods: Clinical trial reports of retinal disorders were used to compare results using mean change in the VA letter score versus binary proportions created from the VA letter score. Additionally, analyses were performed using generated data to gain a perspective on the magnitude of differences that might be expected between the 2 methods. Results: Studies from the literature showed that differences of 6% to 15% in >= 15-letter worsening corresponded to mean differences in letter scores between groups of 3.0 to 7.0 (approximately 0.6 to 1.4 lines). Analyses using generated data demonstrated that a mean improvement in the VA letter score of 5 corresponded to a doubling of the proportion of eyes with >= 15-letter improvement and a 28% relative reduction in the proportion of eyes with >= 15-letter worsening. Conclusions: How VA data should be analyzed in a clinical trial depends to large extent on the research question. The frequently used outcome of >= 15-letter change has several drawbacks, including loss of efficiency (need for a larger sample), misclassification of the outcome, and potential for a ceiling or floor effect. Therefore, for most clinical trials we believe that the primary outcome analysis should be a comparison of changes in the VA letter score, and created binary variables should be reported as secondary outcomes. This approach maximizes the information gained from the data and accommodates both improvement and worsening of acuity. C1 Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. EMMES Corp, Rockville, MD USA. NEI, Bethesda, MD 20892 USA. RP Beck, RW (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. NR 11 TC 59 Z9 59 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2007 VL 114 IS 10 BP 1804 EP 1809 DI 10.1016/j.ophtha.2007.06.047 PG 6 WC Ophthalmology SC Ophthalmology GA 214XU UT WOS:000249772500002 PM 17908590 ER PT J AU Nemesure, B Honkanen, R Hennis, A Wu, SY Leske, MC AF Nemesure, B. Honkanen, R. Hennis, A. Wu, S. Y. Leske, M. Cristina CA Barbados Eye Studies Grp TI Incident open-angle glaucoma and intraocular pressure SO OPHTHALMOLOGY LA English DT Article ID OCULAR HYPERTENSION TREATMENT; BARBADOS EYE; RISK-FACTORS; MEDICATION DELAYS; LENS OPACITIES; PSEUDOEXFOLIATION; POPULATION; PREVENTS; ONSET AB Purpose: To evaluate the role of baseline intraocular pressure (b-IOP) as a risk factor for incident open-angle glaucoma (OAG) in participants of African origin from the Barbados Eye Studies. Design: Population-based 9-year cohort study. Participants: Three thousand two hundred twenty-two persons examined during the study period who were free of glaucoma at baseline and at risk of developing OAG during the 9-year follow-up. Methods: Study protocols were standardized and included ophthalmic and other measurements, automated perimetry, applanation tonometry, fundus photography, and comprehensive ophthalmologic examination for those referred. The product-limit approach was used to estimate incidence. Relationships between b-IOP and incidence were evaluated by adjusted relative risk ratios (RRs) with 95% confidence intervals (CIs), based on Cox regression models. Main Outcome Measure: The 9-year incidence of OAG was based on both visual field and optic disc abnormalities, with ophthalmologic evaluations to exclude other possible causes. Results: The overall 9-year incidence of OAG was 4.4% (95% Cl, 3.7%-5.2%), and the mean (standard deviation) b-IOP among persons at risk was 18.0 mmHg (4.1). Among the 125 incident OAG cases, the mean b-IOP was 21.9 mmHg and 46% had b-IOP of >21 mmHg. In contrast, the nonincident group had a mean b-IOP of 17.8 mmHg and only 12% had b-IOP of >21 mmHg. Overall, OAG risk increased by 12% with each 1 -mmHg increase in IOP (RR, 1.12; 95% Cl, 1.08-1.16). Incidence steadily increased from 1.8% (95% Cl, 1.2%-2.7%) for persons with b-IOP of <= 7 mmHg (referent group) to 22.3% (95% Cl, 15.8%-31.1 %) for those with b-IOP > 25 mmHg, resulting in an adjusted RR of 13.1 (95% Cl, 7.1-24.1) among the latter group. The attributable risk for IOP of >25 mmHg was 19%. Using 21 mmHg as a cutoff, the RR was 7.9 (95% Cl, 3.8-16.2) and the attributable risk was 37%. Conclusions: After 9 years' follow-up, the risk of OAG was positively related to IOP levels at baseline. Although persons with b-IOP of >25 mmHg had a 13-fold RR of developing OAG, most cases arose with lower b-IOP. This study thus confirms the role of IOP as an influential risk factor, yet at the same time underscores its limitations in predicting OAG. C1 SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Ophthalmol, Stony Brook, NY 11794 USA. Minist Hlth, Bridgetown, Barbados. Univ W Indies, Res Inst Trop Med, Chron Dis Res Ctr, Bridgetown, Barbados. NEI, Bethesda, MD 20892 USA. RP Leske, MC (reprint author), SUNY Stony Brook, Dept Prevent Med, L3 HSC Room 086, Stony Brook, NY 11794 USA. EM cleske@notes.cc.sunysb.edu FU NEI NIH HHS [EY07617, EY07625] NR 25 TC 50 Z9 51 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2007 VL 114 IS 10 BP 1810 EP 1815 DI 10.1016/j.ophtha.2007.04.003 PG 6 WC Ophthalmology SC Ophthalmology GA 214XU UT WOS:000249772500003 PM 17583352 ER PT J AU Yanamoto, S Kawasaki, G Yoshitomi, I Iwamoto, T Hirata, K Mizuno, A AF Yanamoto, Souichi Kawasaki, Goro Yoshitomi, Izumi Iwamoto, Tsutomu Hirata, Kazunari Mizuno, Akio TI Clinicopathologic significance of EpCAM expression in squamous cell carcinoma of the tongue and its possibility as a potential target for tongue cancer gene therapy SO ORAL ONCOLOGY LA English DT Article DE EpCAM; invasion; metastasis; beta-catenin; RNA interference ID MONOCLONAL-ANTIBODY THERAPY; EP-CAM EXPRESSION; BREAST-CANCER; BETA-CATENIN; ANTIGEN EPCAM; ORAL-CANCER; PROGNOSTIC MARKER; RNA INTERFERENCE; TUMOR-CELLS; E-CADHERIN AB Epithelial. adhesion molecule (EpCAM) is a transmembrane glycoprotein involved in intercellular adhesion. In particular, EpCAM appears to be overexpressed by the majority of human epithelial. carcinomas, including colorectal, breast, head and neck, and hepatic carcinomas. We therefore hypothesized that EpCAM would be a good molecular target for cancer gene therapy. EpCAM protein expression in 48 primary tongue cancers and 10 normal oral mucosa was evaluated using anti-EpCAM immunohistochemistry, and correlation was examined with the clinico patho logic factors. In four human tongue cancer cell tines (SAS, HSC-2, OSC19 and OSC20), we investigated EpCAM expression by reverse transcription-polymerase chain reaction (RT-PCR). The invasive potential of cancer cells was evaluated using Matrigel invasion assay. Moreover, the effect of EpCAM inhibition was analyzed using RNA interference (RNAi). EpCAM overexpression was detected in 30 of 48 tongue cancers (62.5%), and was significantly higher in primary squamous cell carcinoma (SCC) of the tongue than in normal, oral mucosa. The expression of EpCAM was significantly associated with tumor size, regional lymph node metastasis, histological differentiation and invasion pattern. Cancer cell tines with higher EpCAM expression had more invasive potential. Moreover, RNAi-mediated EpCAM reduction decreased the invasion potential and proliferation activity. These results indicated that the overexpression of EpCAM was correlated with a more aggressive phenotype of tongue cancer. Moreover, we suggested that EpCAM could be a molecular target, and that RNAi targeting EpCAM could be useful for tongue cancer gene therapy. (c) 2006 Elsevier Ltd. Alt rights reserved. C1 Nagasaki Univ, Grad Sch Biomed Sci, Dept Oral & Maxillofacial Surg, Unit Translat Med Course Med & Dent Sci, Nagasaki 852, Japan. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. RP Yanamoto, S (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Dept Oral & Maxillofacial Surg, Unit Translat Med Course Med & Dent Sci, 1-7-1 Sakamoto, Nagasaki 852, Japan. EM syana@nagasaki-u.ac.jp NR 45 TC 53 Z9 59 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD OCT PY 2007 VL 43 IS 9 BP 869 EP 877 DI 10.1016/j.oraloncology.2006.10.010 PG 9 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 221JU UT WOS:000250224200003 PM 17207659 ER PT J AU Ogbureke, KUE Nikitakis, NG Warburton, G Ord, RA Sauk, JJ Waller, JL Fisher, LW AF Ogbureke, Kalu U. E. Nikitakis, Nikolaos G. Warburton, Gary Ord, Robert A. Sauk, John J. Waller, Jennifer L. Fisher, Larry W. TI Up-regulation of SIBLING proteins and correlation with cognate MMP expression in oral cancer SO ORAL ONCOLOGY LA English DT Article DE SIBLING proteins; DSPP; OPN; BSP; MMP-2; MMP-3; MMP-9; OSCC; immunohistochemistry ID SQUAMOUS-CELL-CARCINOMA; HUMAN BREAST-CANCER; BONE SIALOPROTEIN EXPRESSION; DENTIN MATRIX PROTEIN-1; HUMAN PROSTATE-CANCER; OSTEOPONTIN EXPRESSION; LUNG-CANCER; INVASION; METASTASES; INTEGRIN AB Various combinations of the SIBLING family of proteins have been found to be upregulated in many human cancers and have been Linked to different stages of tumor progression, including metastasis. Bone sialoprotein (BSP), osteopontin (OPN) and dentin matrix protein 1 (DMP1) specifically bind and activate MMP-2, MMP-3, and MMP-9, respectively. These proteases have also been shown to play important roles in oral squamous cell carcinoma (OSCQ invasion and metastasis. However, with the exception of OPN, there are no reports on the expression of the family of five SIBLING proteins in OSCC. This study examines the expression patterns of the SIBLING family (and MMP partners when known) in OSCC, correlating expression to outcome variables. Archived paraffin sections of 87 cases of primary OSCC. were screened by immunohistochemistry for the SIBLINGs and their MMP partners. Three SIBLINGs (BSP, DSPP, and OPN), were expressed in OSCC, while DMP1 and MEPE expression were never observed. Furthermore, BSP and OPN were always expressed with their known MMP partners, MMP-2 and MMP-3, respectively. Poorly differentiated tumors exhibited reduced or no immunoreactivity for BSP and OPN but increased immunoreactivity for DSPP. Seventy eight (90%) cases were positive for BSP and DSPP, while 79 cases (91%) were positive for OPN. Overall, 91% of the cases were positive for at least one SIBLING. There were no correlations between SIBLING expression and tumor size ("T"; of the Union Internationale Contre le Cancer [UICC]-TNM classification for OSCQ, and between SIBLING expression and lymph node spread for the T1/T2 tumors. The levels of DSPP expression for floor of mouth and retromotar region tumors were higher than for tongue tumors. Statistically significant correlations were, however, found between the expression Levels of BSP and MMP-2 (p < 0.0001), BSP and MMP-3 (p < 0.0001), and OPN and MMP-3 (p < 0.0024). We conclude that BSP, DSPP, and OPN are highly up-regulated in OSCC. White the production of these SIBLINGs is independent of T, they correlate with oral location of tumor, cognate MMP expression, and for DSPP, the degree of tumor differentiation. (c) 2006 Elsevier Ltd. All rights reserved. C1 Med Coll Georgia, Dept Oral Biol & Maxillofacial Pathol, Augusta, GA 30912 USA. Univ Maryland, Sch Dent, Greenebaum Canc Ctr, Dept Diagnost Sci & Pathol, Baltimore, MD 21201 USA. Univ Maryland, Dept Oral & Maxillofacial Surg, Baltimore, MD 21201 USA. Med Coll Georgia, Sch Grad Studies, Dept Biostat, Augusta, GA 30912 USA. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bethesda, MD 20892 USA. Univ Athens, Sch Dent, Dept Oral Med & Oral Pathol, Athens, Greece. RP Ogbureke, KUE (reprint author), Med Coll Georgia, Dept Oral Biol & Maxillofacial Pathol, AD1442,1120 15th Ave, Augusta, GA 30912 USA. EM kogbureke@mail.mcg.edu; NNikitakis@umarytand.edu; thewarburtons@verizon.net; rord@umarytand.edu; jsauk@umaryland.edu; jwatter@mail.mcg.edu; lfisher@dir.nidcr FU Intramural NIH HHS NR 44 TC 31 Z9 37 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD OCT PY 2007 VL 43 IS 9 BP 920 EP 932 DI 10.1016/i.oratoncology.2006.11.011 PG 13 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 221JU UT WOS:000250224200010 PM 17306612 ER PT J AU Hunter, DJ Zhang, YQ Niu, JB Felson, DT Kwoh, K Newman, A Kritchevsky, S Harris, T Carbone, L Nevitt, M AF Hunter, D. J. Zhang, Y. Q. Niu, J. B. Felson, D. T. Kwoh, K. Newman, A. Kritchevsky, S. Harris, T. Carbone, L. Nevitt, M. TI Patella malalignment, pain and patellofemoral progression: the Health ABC Study SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE patellofemoral osteoarthritis; patella alignment ID SYMPTOMATIC KNEE OSTEOARTHRITIS; RISK-FACTORS; FRAMINGHAM OSTEOARTHRITIS; RADIOGRAPHIC ASSESSMENT; JOINT-SPACE; BIOMECHANICS; PATTERNS; MOTION; REHABILITATION; ASSOCIATION AB Objective: Patellofemoral (PF) joint ostecarthritis (OA) is strongly correlated with lower extremity disability and knee pain. Risk factors for pain and structural progression in PF OA are poorly understood. Our objective was to determine the association between patella malalignment and its relation to pain severity, and PF OA disease progression. Methods: We conducted an analysis of data from the Health ABC knee OA study. Health ABC is a community based, multi-center cohort study of 3075 Caucasian and Black men and women aged 70-79 at enrollment. Weight bearing skyline knee X-rays were obtained in a subset (595) of subjects, with and without knee pain, at year 2 and year 5 (mean follow-up 36 months). Films were read paired, and PF osteophytes (OST) and joint space narrowing (JSN) were scored on a 0-3 scale using the Osteoarthritis Research Society International atlas. We defined progression of PF OA as any increase in JSN score. Three measures of patella malalignment were made: sulcus angle; patella tilt angle; and patella subluxation medially or laterally (bisect offset). Knee symptoms were assessed using a knee specific Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain subscale. We assessed the relationship between baseline patella malalignment and pain severity (linear regression for WOMAC) and compartment specific PF OA progression (logistic regression for dichotomous outcomes). We classified continuous measures of patella alignment into quartile groups. We performed multivariable adjusted logistic regression models, including age, gender and body mass index (BMI) to assess the relation of baseline patella alignment to the occurrence of PF JSN progression using generalized estimating equations (GEE). Results: The subjects had a mean age 73.6 (SD 2.9), BMI 28.8 (SD 4.9), 40.3% male, and 46% were Black. Medial displacement of the patella predisposed to medial JSN progression; odds for each quartile 1, 1.2, 1.2, 2.2 (P for trend = 0.03), whilst protecting from lateral JSN progression; odds for each quartile 1, 0.7, 0.6, 0.4 (P for trend = 0.0004). Increasing patella tilt protected from medial JSN progression; odds for each quartile 1, 0.8, 0.5, 0.2 (P < 0.0001) and trended to increasing pain severity (P = 0.09). Conclusion: Patella malalignment is associated with PF disease progression. Medial displacement and tilt of the patella predisposes to medial JSN progression, whilst lateral displacement is predictive of lateral JSN progression. The influence of patella malalignment has important implications since it is potentially modifiable through footwear, taping and/or knee bracing. (C) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN USA. UCSF, San Francisco, CA 94143 USA. RP Hunter, DJ (reprint author), Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, 715 Albany St,A203, Boston, MA 02118 USA. EM djhunter@bu.edu RI Hunter, David/A-4622-2010; Newman, Anne B./C-6408-2013 OI Hunter, David/0000-0003-3197-752X; Zhang, Yuqing/0000-0001-7954-1149; Felson, David/0000-0002-2668-2447; Niu, Jingbo/0000-0002-6170-1965; Newman, Anne B./0000-0002-0106-1150 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIAMS NIH HHS [AR47785, P60 AR047785, R03 AR051102, R03 AR051102-01, R03 AR051102-02, R03 AR051102-03, R03 AR51102-01] NR 48 TC 57 Z9 59 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD OCT PY 2007 VL 15 IS 10 BP 1120 EP 1127 DI 10.1016/j.joca.2007.03.020 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 217YL UT WOS:000249983100004 PM 17502158 ER PT J AU Ling, SM Conwit, RA Talbot, L Shermack, M Wood, JE Dredge, EM Weeks, MJ Abernethy, DR Metter, EJ AF Ling, S. M. Conwit, R. A. Talbot, L. Shermack, M. Wood, J. E. Dredge, E. M. Weeks, M. J. Abernethy, D. R. Metter, E. J. TI Electromyographic patterns suggest changes in motor unit physiology associated with early osteoarthritis of the knee SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE knee osteoarthritis; quadriceps muscle; motor unit; electromyography; mobility ID MUSCLE STRENGTH; OLDER-ADULTS; QUADRICEPS STRENGTH; WOMENS HEALTH; FIRING RATE; DECOMPOSITION; ACTIVATION; PEDOMETERS; ACCURACY; WEAKNESS AB Objective: To assess characteristics of active motor units (MUs) during volitional vastus medialis (VM) activation in adults with symptomatic knee osteoarthritis (OA) across the spectrum of radiographic severity and age-comparable healthy control volunteers. Methods: We evaluated 39 participants (age 65 3 years) in whom weight-bearing knee X-rays were assigned a Kellgren & Lawrence (KL) grade (18 with KL grade = 0; four each with KL grades = 1, 2 and 4; nine with grade 3). Electromyography (EMG) signals were simultaneously acquired using surface [surface EMG (S-EMG)] and intramuscular needle electrodes, and analyzed by decomposition-enhanced spike-triggered averaging to obtain estimates of size [surface-represented MU action potentials (S-MUAP) area], number [MU recruitment index (MURI)] and firing rates [MU firing rates (mFR)] of active MUs at 10%, 20%, 30% and 50% effort relative to maximum voluntary force [maximal voluntary isometric contraction (MVIC)] during isometric knee extension. Results: Knee extensor MVIC was lower in CA participants, especially at higher KL grades (P = 0.05). Taking the observed force differences into account, OA was also associated with activation of larger MUs (S-MUAP area/MVIC x %effort; P < 0.0001). In contrast, the estimated number of active units (MURI/MVIC x %effort) changed differently as effort increased from 10% to 50% and was higher with advanced CA (KIL = 3, 4) than controls (P = 0.0002). Conclusion: VM activation changes at the level of the MU with symptomatic knee OA, and this change is influenced by radiographic severity. Poor muscle quality may explain the pattern observed with higher KIL grades, but alternative factors (e.g., nerve or joint injury, physical inactivity or muscle composition changes) should be examined in early OA. (C) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 NIA, Clin Res Branch, IRP, NIH, Baltimore, MD 21225 USA. NINDS, Extramural Res Program, Bethesda, MD 20894 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20894 USA. Johns Hopkins Med Inst, Baltimore, MD 21224 USA. Harbor Hosp, Dept Orthoped Surg, Baltimore, MD 21225 USA. NIA, IRP, Clin Invest Lab, Baltimore, MD 21224 USA. RP Ling, SM (reprint author), Harbor Hosp, Staff Clinician, ASTRA Unit, 3001 S Hanover St, Baltimore, MD 21225 USA. EM lingsh@grc.nia.nih.gov FU Intramural NIH HHS [NIH0011070815, Z01 AG000908-07] NR 39 TC 17 Z9 19 U1 0 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD OCT PY 2007 VL 15 IS 10 BP 1134 EP 1140 DI 10.1016/j.joca.2007.03.024 PG 7 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 217YL UT WOS:000249983100006 PM 17543548 ER PT J AU Kurth, T Hedbom, E Shintani, N Sugimoto, M Chen, FH Haspl, M Martinovic, S Hunziker, EB AF Kurth, T. Hedbom, E. Shintani, N. Sugimoto, M. Chen, F. H. Haspl, M. Martinovic, S. Hunziker, E. B. TI Chondrogenic potential of human synovial mesenchymal stem cells in alginate SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE synovial cells; chondrogenesis; BMP-2; BMP-7; TGF-beta 1 ID PARTIAL-THICKNESS DEFECTS; IN-VITRO CHONDROGENESIS; MARROW STROMAL CELLS; GROWTH-FACTOR-BETA; ARTICULAR-CARTILAGE; PROGENITOR CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; II COLLAGEN; DIFFERENTIATION; MEMBRANE AB Objective: In a recent study, we demonstrated that mesenchymal stem cells (MSCs) derived from the synovial membranes of bovine shoulder joints could differentiate into chondrocytes when cultured in alginate. The purpose of the present study was to establish the conditions under which synovial MSCs derived from aging human donors can be induced to undergo chondrogenic differentiation using the same alginate system. Methods: MSCs were obtained by digesting the knee-joint synovial membranes of ostecarthritic human donors (aged 59-76 years), and expanded in monolayer cultures. The cells were then seeded at a numerical density of 4 x 10(6)/ml within discs of 2% alginate, which were cultured in serum-containing or serum-free medium (the latter being supplemented with 1% insulin, transferrin, selenium (ITS). The chondrogenic differentiation capacity of the cells was tested by exposing them to the morphogens transforming growth factor-betal (TGF-beta 1), TGF-beta 2, TGF-beta 3, insulin-like growth factor-1 (IGF-1), bone morphogenetic protein-2 (BMP-2) and BMP-7, as well as to the synthetic glucocorticoid dexamethasone. The relative mRNA levels of collagen types I and II, of aggrecan and of Sox9 were determined quantitatively by the real-time polymerase chain reaction (PCR). The extracellular deposition of proteoglycans was evaluated histologically after staining with Toluidine Blue, and that of type-II collagen by immunohistochemistry. Results: BMP-2 induced the chondrogenic differentiation of human synovial MSCs in a dose-dependent manner. The response elicited by BMP-7 was comparable. Both of these agents were more potent than TGF-beta 1. A higher level of BMP-2-induced chondrogenic differentiation was achieved in the absence than in the presence of serum. In the presence of dexamethasone, the BMP-2-induced expression of mRNAs for aggrecan and type-II collagen was suppressed; the weaker TGF-beta 1-induced expression of these chondrogenic markers was not obviously affected. Conclusions: We have demonstrated that synovial MSCs derived from the knee joints of aging human donors possess chondrogenic potential. Under serum-free culturing conditions and in the absence of dexamethasone, BMP-2 and BMP-7 were the most potent inducers of this transformation process. (C) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 Univ Bern, ITI Res Inst Dent & Skeletal Biol, CH-3010 Bern, Switzerland. NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. Univ Zagreb, Sch Med, Dept Orthopaed Surg, Zagreb 41001, Croatia. Univ Zagreb, Sch Med, Dept Anat, Zagreb 41001, Croatia. RP Hunziker, EB (reprint author), Univ Bern, ITI Res Inst Dent & Skeletal Biol, Murtenstr 35,POB 54, CH-3010 Bern, Switzerland. EM ernst.hunziker@iti.unibe.ch FU Intramural NIH HHS NR 44 TC 71 Z9 81 U1 2 U2 14 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD OCT PY 2007 VL 15 IS 10 BP 1178 EP 1189 DI 10.1016/j.joca.2007.03.015 PG 12 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 217YL UT WOS:000249983100012 PM 17502159 ER PT J AU Jagannathan, J Lonser, RR Stanger, RA Butman, JA Vortmeyer, AO Zalewski, CK Brewer, C Surowicz, C Kim, HJ AF Jagannathan, Jay Lonser, Russell R. Stanger, Richard A. Butman, John A. Vortmeyer, Alexander O. Zalewski, Christopher K. Brewer, Carmen Surowicz, Christal Kim, H. Jeffrey TI Cochlear implantation for hearing loss associated with bilateral endolymphatic sac tumors in von Hippel-Lindau disease SO OTOLOGY & NEUROTOLOGY LA English DT Article DE bilateral; cochlear implant; endolymphatic sac tumor; hearing loss; von Hippel-Lindau disease ID LOW-GRADE ADENOCARCINOMA; NEUROFIBROMATOSIS TYPE-2; SURGERY; ORIGIN AB Objective: Bilateral endolymphatic sac tumors (ELSTs) are associated with von Hippel-Lindau disease and often underlie significant audiovestibular morbidity, including hearing loss. Patient: This 44-year-old female von Hippel-Lindau disease patient presented with tinnitus, vertigo, and binaural hearing loss. Magnetic resonance and computed tomography imaging demonstrated bilateral ELSTs, and audiometry confirmed bilateral hearing loss. Intervention: The patient underwent staged resection of the ELSTs (left then right). After resection of the left ELST and during the same operation, a cochlear implant was placed. Main Outcome Measures: Clinical, audiometric, and imaging data. Results: Postoperatively, the patient had resolution of tinnitus and vertigo with a significant implant-aided improvement in hearing. Conclusion: Because of their unique anatomic and biologic features, resection of bilateral tumors and cochlear implantation in deaf ELST patients is a potential option to improve hearing and quality of life. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Dept Neurosurg, Charlottesville, VA 22908 USA. Natl Inst Deafness & Other Commun Disorders, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD USA. Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Bethesda, MD USA. Washington Hosp Ctr, Hearing & Speech Ctr, Washington, DC 20010 USA. Georgetown Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Washington, DC 20007 USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 13 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD OCT PY 2007 VL 28 IS 7 BP 927 EP 930 PG 4 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 216DN UT WOS:000249858400011 PM 17468670 ER PT J AU Saul, A Hensmann, M Sattabongkot, J Collins, WE Barnwell, JW Langermans, JAM Wu, Y Long, CA Dubovsky, F Thomas, AW AF Saul, A. Hensmann, M. Sattabongkot, J. Collins, W. E. Barnwell, J. W. Langermans, J. A. M. Wu, Y. Long, C. A. Dubovsky, F. Thomas, A. W. TI Immunogenicity in rhesus of the Plasmodium vivax mosquito stage antigen Pvs25H with Alhydrogel and Montanide ISA 720 SO PARASITE IMMUNOLOGY LA English DT Article DE Alhydrogel; aluminium hydroxide; Montanide ISA 720; Plasmodium vivax; Pvs25H; rhesus ID TRANSMISSION-BLOCKING ACTIVITY; VACCINE CANDIDATES PVS25; PAPUA-NEW-GUINEA; MALARIA VACCINE; ADJUVANT; ISA-720; SAFETY; TRIAL; ICC-1132; EFFICACY AB Pvs25 is an ookinete surface protein from Plasmodium vivax that is the target of transmission-blocking antibodies. Two immunogenicity trials in rhesus monkeys with a recombinant form of the protein, Pvs25H, were undertaken. Monkeys were vaccinated with Pvs25H adsorbed to Alhydrogel or emulsified in Montanide ISA 720 at 0, 4 and 27 weeks (study 1) or in Montanide ISA 720 at 0 and 18 weeks (study 2) with 1.5 or 15 mu g Pvs25H in 0.1 or 0.5 mL of emulsion (four combinations). Immunogenicity was assessed by ELISA and by membrane-feeding experiments using P. vivax-infected blood from human volunteers (studies 1 and 2) or from chimpanzees (study 1). Both vaccine trials generated antibodies that blocked transmission of P. vivax to mosquitoes. Antibody titres and transmission blocking were higher with Montanide ISA 720 than with Alhydrogel in the first trial and with the 15 mu g Pvs25H/0.5 mL ISA 720 combination in the second trial. C1 NIAID, Lab Malaria & Vector Res, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. GH Rijswijk, Biomed Primate Res Ctr, Dept Parasitol, Rijswijk, Netherlands. USA Med Component, Dept Entomol, Armed Forces Res Inst Med Sci, Bangkok, Thailand. CDC, Div Parasit Dis, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. PATH Malaria Vaccine Initiat, Bethesda, MD USA. RP Saul, A (reprint author), NIAID, Lab Malaria & Vector Res, Malaria Vaccine Dev Branch, NIH, Twinbrook 3,Room 1E-04,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM asaul@niaid.nih.gov RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 FU Intramural NIH HHS NR 21 TC 17 Z9 20 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD OCT PY 2007 VL 29 IS 10 BP 525 EP 533 DI 10.1111/j.1365-3024.2007.00971.x PG 9 WC Immunology; Parasitology SC Immunology; Parasitology GA 215RL UT WOS:000249826600004 PM 17883455 ER PT J AU Kontny, U Werner, S Mendoza, A Reichardt, W Hilger, R Erlacher, M Uhl, M Khanna, C Niemeyer, C AF Kontny, Udo Werner, Sebastian Mendoza, Arnulfo Reichardt, Wilfried Hilger, Ralf Erlacher, Miriam Uhl, Markus Khanna, Chand Niemeyer, Charlotte TI Activity of treosulfan against Ewing sarcoma cells in vitro and in vivo in an orthotopic mouse xenograft model SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 Univ Freiburg, Med Ctr, Div Pediat Hematol & Oncol, Freiburg, Germany. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Freiburg, Med Ctr, Div Expt Radiol, Freiburg, Germany. Univ Freiburg, Med Ctr, Dept Radiol, Freiburg, Germany. Univ Hosp Essen, Dept Internal Med, Essen, Germany. RI Reichardt, Wilfried/K-6727-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT 1 PY 2007 VL 49 IS 4 BP 410 EP 410 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 205LU UT WOS:000249116100046 ER PT J AU Ambros, PF Ambros, PF Ambros, IM Brodeur, GM Haber, M Khan, J Nakagawara, A Schleiermacher, G Speleman, F Spitz, R Cohn, SL Pearson, ADJ Maris, JM AF Ambros, Peter F. Ambros, Peter F. Ambros, Inge M. Brodeur, Garrett M. Haber, Michelle Khan, Javed Nakagawara, Akira Schleiermacher, Gudrun Speleman, Frank Spitz, Ruediger Cohn, Susan L. Pearson, Andrew D. J. Maris, John M. TI International consensus for neuroblastoma molecular diagnostics: Report from the International Neuroblastoms Risk Grouping (INRG) biology committee SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 Childrens Canc Res Inst, Vienna, Austria. Univ Penn, Sch Med, Dept Oncol, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Hosp, Childrens Canc Inst, Sydney, NSW, Australia. NCI, Oncogenom Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Chiba Canc Ctr, Inst Res, Dept Mol Biol & Oncol, Chiba, Japan. Inst Curie, Dept Pediat Oncol, Paris, France. State Univ Ghent Hosp, Ctr Genet Med, B-9000 Ghent, Belgium. Univ Cologne, Cologne, Germany. Univ Chicago, Inst Mol Pediat Sci, Chicago, IL 60637 USA. Royal Marsden Hosp, Dept Paed Oncol, Surrey, England. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT 1 PY 2007 VL 49 IS 4 BP 432 EP 433 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 205LU UT WOS:000249116100127 ER PT J AU Cavalli, F Eden, TOB Lemerle, J Magrath, I Sancho-Garnier, H Steliarova-Foucher, E Mortara, I Forget, C Tabah-Fisch, I Thaxter, G Harford, J Miklavec, T Divino, JJ Ribeiro, RC AF Cavalli, Franco Eden, Tim O. B. Lemerle, Jean Magrath, Ian Sancho-Garnier, Helene Steliarova-Foucher, Eva Mortara, Isabel Forget, Catherine Tabah-Fisch, Isabelle Thaxter, Geoffrey Harford, Joe Miklavec, Thomas Divino, Jose Julio Ribeiro, Raul C. TI Evaluation of pediatric oncology care in ten countries taking part in the my child matters program SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 UICC Int Union Canc, Bellinzona, Switzerland. Univ Manchester, Christie Hosp NHS Trust, Paediat & Adolescent Oncol Unit, Manchester, Lancs, England. Inst Gustave Roussy, Grp Franco Africain Oncol Pediat, Villejuif, France. INCTR, Brussels, Belgium. Sch Med Montpellier, Montpellier, France. IARC, Unit Descript Epidemiol, Lyon, France. UICC, Off Execut Director, Geneva, Switzerland. Sanofi Aventis, Corp Commun, Paris, France. Sanofi Aventis, Corp Commun, Paris, France. Sanofi Aventis, Global Oncol Franchise, Paris, France. CLIC Sargen Canc Care Children Serv, London, England. NCI, NIH, Bethesda, MD 20892 USA. Sanisphere Consulting & Surveys, Paris, France. UICC, Campaigns & Commun Cluster, Geneva, Switzerland. St Jude Childrens Hosp, Oncol Dept & Int Outreach, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT 1 PY 2007 VL 49 IS 4 BP 525 EP 525 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 205LU UT WOS:000249116100484 ER PT J AU Zimmet, P George, K Alberti, MM Kaufman, F Tajima, N Silink, M Arslanian, S Wong, G Bennett, P Shaw, J Caprio, S AF Zimmet, Paul George, K. Alberti, M. M. Kaufman, Francine Tajima, Naoko Silink, Martin Arslanian, Silva Wong, Gary Bennett, Peter Shaw, Jonathan Caprio, Sonia CA IDF Consensus Grp TI The metabolic syndrome in children and adolescents - an IDF consensus report SO PEDIATRIC DIABETES LA English DT Review DE cardiovascular risk; children; diabetes; metabolic syndrome; obesity ID WAIST CIRCUMFERENCE PERCENTILES; NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR RISK-FACTORS; 3RD NATIONAL-HEALTH; INTERNATIONAL DIABETES FEDERATION; CORONARY-HEART-DISEASE; TREATMENT PANEL-III; C-REACTIVE PROTEIN; BODY-MASS INDEX; INSULIN-RESISTANCE C1 Int Diabet Inst, Caulfield, Vic 3162, Australia. Int Diab Inst, Melbourne, Vic, Australia. St Marys Hosp, Dept Endocrinol & Metab Med, London, England. Childrens Hosp, Ctr Diabet Endocrinol & Metab, Los Angeles, CA 90027 USA. Jikei Univ, Sch Med, Div Diabet Metab & Endocrinol, Tokyo, Japan. Childrens Hosp Westmead, Inst Endocrinol & Diab, Sydney, NSW, Australia. Childrens Hosp Pittsburgh, Div Endocrinol, Pittsburgh, PA 15213 USA. Univ Hong Kong, Dept Paediat, Hong Kong, Peoples R China. NIH, NIDDK, Clin Res Branch, Phoenix, AZ USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT USA. RP Zimmet, P (reprint author), Int Diabet Inst, 250 Kooyong Rd, Caulfield, Vic 3162, Australia. EM pzimmet@idi.org.au RI Shaw, Jonathan/E-7388-2010 OI Shaw, Jonathan/0000-0002-6187-2203 NR 62 TC 579 Z9 617 U1 3 U2 41 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1399-543X EI 1399-5448 J9 PEDIATR DIABETES JI Pediatr. Diabetes PD OCT PY 2007 VL 8 IS 5 BP 299 EP 306 DI 10.1111/j.1399-5448.2007.00271.x PG 8 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 210CG UT WOS:000249433700008 PM 17850473 ER PT J AU Grave, GD Nelson, SA Walker, WA Moss, RL Dvorak, B Hamilton, FA Higgins, R Raju, TNK AF Grave, Gilman D. Nelson, Stefanie A. Walker, W. Allan Moss, R. Lawrence Dvorak, Bohuslav Hamilton, Frank A. Higgins, Rosemary Raju, Tonse N. K. TI New therapies and preventive approaches for necrotizing enterocolitis: Report of a research planning workshop SO PEDIATRIC RESEARCH LA English DT Editorial Material ID EPIDERMAL-GROWTH-FACTOR; BIRTH-WEIGHT INFANTS; REDUCES INTESTINAL APOPTOSIS; PERITONEAL DRAINAGE; NEONATAL-RATS; HUMAN-MILK; MODEL; PERFORATION; ADAPTATION; MODULATION AB The National Institute of Child Health and Human Development and the Digestive Diseases Interagency Coordinating Committee held a workshop, chaired by Dr. W. Allan Walker, on July 10-1 1. 2006 to identify promising leads in necrotizing enterocolitis (NEC) research. The goals of the workshop were to identify new approaches to the prevention and treatment of NEC, to define basic and translational mechanisms of potential approaches to NEC, and to develop recommendations for clinical studies to reduce the incidence of NEC. Workshop participants implicated prematurity, introduction of enteral feedings. gastrointestinal bacterial colonization, gut motility, proinflammatory cytokines. impaired gut blood flow, and various neonatal complications in the pathogenesis of NEC. They concluded that a unifying hypothesis encompassing these pathogenetic factors is the uncontrolled exuberant inflammatory response to bacterial colonization that characterizes the intestine of premature infants. The inflammatory cascade appears to offer multiple targets for interventions with a variety of anti-inflammatory agents. including human milk and probiotics. Because of the rapidity with which the inflammatory response gets out of control in infants with NEC, workshop participants agreed that searching for ways to prevent NEC will be more rewarding than trying to identify ways to treat the condition once it has become established. C1 NICHD, Endocrinol Nutr & Growth Branch, NIH, Bethesda, MD 20892 USA. NICHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. Sci Consulting Grp, Gaithersburg, MD 20878 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Musosal Immunol Lab, Boston, MA 02129 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA. Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ 85724 USA. NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. RP Grave, GD (reprint author), NICHD, Endocrinol Nutr & Growth Branch, NIH, 6100 Execut Blvd,Room 4B11, Bethesda, MD 20892 USA. EM graveg@mail.nih.gov NR 28 TC 95 Z9 100 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 2007 VL 62 IS 4 BP 510 EP 514 DI 10.1203/PDR.0b013e318142580a PG 5 WC Pediatrics SC Pediatrics GA 216FC UT WOS:000249862900026 PM 17667844 ER PT J AU Edison, RJ Berg, K Remaley, A Kelley, R Rotimi, C Stevenson, RE Muenke, M AF Edison, Robin J. Berg, Kate Remaley, Alan Kelley, Richard Rotimi, Charles Stevenson, Roger E. Muenke, Maximilian TI Adverse birth outcome among mothers with low serum cholesterol SO PEDIATRICS LA English DT Article DE cholesterol; preterm birth; birth defects; congenital defects; birth weight; embryonic and fetal development; lipoproteins ID LOW-DENSITY-LIPOPROTEIN; INTRAUTERINE GROWTH RESTRICTION; EARLY ATHEROSCLEROTIC LESIONS; HUMAN PLACENTA; APOLIPOPROTEIN-E; LIPID-METABOLISM; NORMAL-PREGNANCY; PLASMA-LIPIDS; MATERNAL HYPERCHOLESTEROLEMIA; PROGESTERONE SYNTHESIS AB OBJECTIVE. The objective of this study was to assess whether low maternal serum cholesterol during pregnancy is associated with preterm delivery, impaired fetal growth, or congenital anomalies in women without identified major risk factors for adverse pregnancy outcome. METHODS. Mother-infant pairs were retrospectively ascertained from among a cohort of 9938 women who were referred to South Carolina prenatal clinics for routine second-trimester serum screening. Banked sera were assayed for total cholesterol; < 10th percentile of assayed values ( 159 mg/dL at mean gestational age of 17.6 weeks) defined a "low total cholesterol" prenatal risk category. Eligible women were aged 21 to 34 years and nonsmoking and did not have diabetes; neonates were liveborn after singleton gestations. Total cholesterol values of eligible mothers were adjusted for gestational age at screening before risk group assignment. The study population included 118 women with low total cholesterol and 940 women with higher total cholesterol. Primary analyses used multivariate regression models to compare rates of preterm delivery, fetal growth parameters, and congenital anomalies between women with low total cholesterol and control subjects with mid-total cholesterol values < 10th percentile but < 90th percentile. RESULTS. Prevalence of preterm delivery among mothers with low total cholesterol was 12.7%, compared with 5.0% among control subjects with mid-total cholesterol. The association of low maternal serum cholesterol with preterm birth was observed only among white mothers. Term infants of mothers with low total cholesterol weighed on average 150 g less than those who were born to control mothers. A trend of increased microcephaly risk among neonates of mothers with low total cholesterol was found. Low maternal serum cholesterol was unassociated with risk for congenital anomalies. CONCLUSIONS. Total serum cholesterol < 10th population percentile was strongly associated with preterm delivery among otherwise low-risk white mothers in this pilot study population. Term infants of mothers with low total cholesterol weighed less than control infants among both racial groups. C1 NIH, NHGRI, US Dept HHS, Bethesda, MD 20892 USA. NIH, NHGRI, Med Genet Branch, Bethesda, MD USA. Natl Inst Hlth Clin Ctr, Bethesda, MD USA. Kenny Krieger Inst, Baltimore, MD USA. Howard Univ, NHGRI, Washington, DC USA. Greenwood Genet Ctr, Greenwood, SC 29646 USA. RP Muenke, M (reprint author), NIH, NHGRI, US Dept HHS, 35 Covent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov FU Intramural NIH HHS NR 83 TC 69 Z9 70 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2007 VL 120 IS 4 BP 723 EP 733 DI 10.1542/peds.2006-1939 PG 11 WC Pediatrics SC Pediatrics GA 216HV UT WOS:000249870000004 PM 17908758 ER PT J AU Vohr, BR Poindexter, BB Dusick, AM McKinley, LT Higgins, RD Langer, JC Poole, WK AF Vohr, Betty R. Poindexter, Brenda B. Dusick, Anna M. McKinley, Leslie T. Higgins, Rosemary D. Langer, John C. Poole, W. Kenneth CA Natl Inst Of Child Hlth Human Dev TI Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age SO PEDIATRICS LA English DT Article DE breast milk; extremely low birth weight; Bayley; outcomes ID VISUAL-ACUITY DEVELOPMENT; INTELLIGENCE QUOTIENT; PRETERM INFANTS; TERM INFANTS; HEALTHY; ACID; TRIAL; DIET AB BACKGROUND. We previously reported beneficial effects of breast milk ingestion by infants with extremely low birth weight in the NICU on developmental outcomes at 18 months' corrected age. The objective of this study was to determine whether these effects of breast milk in infants with extremely low birth weight persisted at 30 months' corrected age. METHODS. Nutrition data, including enteral and parenteral feeds, were prospectively collected, and 30 months' corrected age follow-up assessments were completed on 773 infants with extremely low birth weight who participated in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial. A total of 593 ingested some breast milk during the neonatal hospitalization, and 180 ingested none. Neonatal feeding characteristics and morbidities and 30-month interim history, neurodevelopmental outcomes, and growth parameters were analyzed. Children were divided into quintiles of breast milk volume to evaluate the effects of volume of human milk ingested during the NICU hospitalization. RESULTS. At 30 months, increased ingestion of breast milk was associated with higher Bayley Mental Developmental Index scores, higher Bayley behavior score percentiles for emotional regulation, and fewer rehospitalizations between discharge and 30 months. There were no differences in growth parameters or cerebral palsy. For every 10 mL/kg per day increase in breast milk, the Mental Developmental Index increased by 0.59 points, the Psychomotor Developmental Index by 0.56 points, and the total behavior percentile score by 0.99 points, and the risk of rehospitalization between discharge and 30 months decreased by 5%. CONCLUSIONS. Beneficial effects of ingestion of breast milk in the NICU persist at 30 months' corrected age in this vulnerable extremely low birth weight population. Continued efforts must be made to offer breast milk to all extremely low birth weight infants both in the NICU and after discharge. C1 Brown Med Sch, Dept Pediat, Providence, RI USA. Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. NICHHD, Ctr Dev Biol & Perinatal Med, Rockville, MD USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Vohr, BR (reprint author), Women & Infants Hosp Rhode Isl, 101 Dudley St, Providence, RI 02905 USA. EM betty_vohr@brown.edu FU NCRR NIH HHS [M01 RR 00070, M01 RR 00750, M01 RR 06022, M01 RR 08084]; NICHD NIH HHS [U10 HD21364, U01 HD36790, U10 HD21385, U10 HD21397, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27904, U10 HD34216, U10 HD40461, U10 HD40689] NR 23 TC 125 Z9 135 U1 3 U2 16 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2007 VL 120 IS 4 BP e953 EP e959 DI 10.1542/peds.2006-3227 PG 7 WC Pediatrics SC Pediatrics GA 216HV UT WOS:000249870000073 PM 17908750 ER PT J AU Sterling, TR Martire, T de Almeida, AS Ding, L Greenberg, DE Moreira, LA Elloumi, H Torres, APV Sant'Anna, CC Calazans, E Paraguassu, G Gebretsadik, T Shintani, A Miller, K Kritski, A Silva, JRLE Holland, SM AF Sterling, Timothy R. Martire, Terezinha de Almeida, Alexandre Silva Ding, Li Greenberg, David E. Moreira, Lorena Alves Elloumi, Houda Torres, Angelica P. V. Sant'Anna, Clemax Couto Calazans, Eliane Paraguassu, Geraldo Gebretsadik, Tebeb Shintani, Ayumi Miller, Kathleen Kritski, Afranio Lapa e Silva, Jose Roberto Holland, Steven M. TI Immune function in young children with previous pulmonary or miliary/meningeal tuberculosis and impact of BCG vaccination SO PEDIATRICS LA English DT Article; Proceedings Paper CT 102nd International Conference of the American-Thoracic-Society CY MAY 19-24, 2006 CL San Diego, CA SP Amer Thorac Soc DE M tuberculosis; tuberculosis; tuberculosis meningitis; miliary tuberculosis; BCG vaccine; MCP-1 ID EXTRAPULMONARY TUBERCULOSIS; MILIARY TUBERCULOSIS; SAN-FRANCISCO; MYCOBACTERIUM-TUBERCULOSIS; PUBLISHED LITERATURE; INTERFERON-GAMMA; MENINGITIS; RESPONSES; ADULTS; EFFICACY AB OBJECTIVE. Children <5 years old are at increased risk of miliary/meningeal tuberculosis, but the immunologic factors that place them at risk are unknown. BCG vaccine protects against miliary/meningeal tuberculosis, but the mechanism of protection is unknown. We assessed for abnormalities in immune response associated with miliary/meningeal or pulmonary tuberculosis in young children. PATIENTS AND METHODS. We conducted a case-control study among HIV-seronegative Brazilian children who were <5 years old. Case subjects had previous culture-confirmed or clinical miliary/meningeal tuberculosis. There were 2 sets of control subjects: those with culture-confirmed pulmonary tuberculosis and purified protein derivative-positive household contacts. All of the children had completed treatment. Peripheral blood mononuclear cells were stimulated ( phytohemagglutinin, phytohemagglutinin + interleukin 12, lipopolysaccharide, lipopolysaccharide + interferon-gamma, and purified protein derivative), and cytokine responses ( interleukin 1 beta, interleukin-4, interleukin-6, interleukin-8, interleukin 10, interleukin 12, interferon-gamma, tumor necrosis factor-alpha, and monocyte chemoattractant protein 1) were quantified by bead-based assay. Median cytokine responses were compared by the Kruskal-Wallis test. Multivariate analysis of variance accounted for multiple comparisons. RESULTS. There were 18 case subjects with miliary/meningeal tuberculosis, 28 pulmonary control subjects, and 29 purified protein derivative-positive control subjects. The median age was 4.2 years. There was no difference in case and control subjects by age, gender, race, BMI, or median CD4 count. Twelve ( 67%) of 18 case subjects, 26 ( 93%) of 28 pulmonary control subjects, and 28 ( 97%) of 29 purified protein derivative-positive subjects had received BCG vaccine. No cytokine defects were identified in case subjects with miliary/meningeal tuberculosis compared with either set of control subjects. Pulmonary control subjects had uniformly higher monocyte chemoattractant protein 1 levels than case subjects with miliary/meningeal tuberculosis and purified protein derivative-positive control subjects, both at rest and with lipopolysaccharide, lipopolysaccharide + interferon-gamma, and purified protein derivative stimulation. Pulmonary control subjects did not have a higher frequency of allele G in the -2518 monocyte chemoattractant protein 1 promoter polymorphism. Case subjects with miliary/meningeal tuberculosis who had received BCG vaccine ( n = 12) had lower stimulated interleukin 8 production than children who did not receive BCG vaccine ( n = 6). CONCLUSIONS. Children with previous miliary/meningeal tuberculosis did not have a major defect in the cytokine pathways studied. Increased monocyte chemoattractant protein 1 levels were associated with pulmonary disease, occurred despite BCG vaccination, and were not associated with a polymorphism in the monocyte chemoattractant protein 1 promoter. C1 Vanderbilt Univ, Med Ctr, Div Infect Dis, Sch Med,Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. Univ Fed Rio de Janeiro, Martagao Gesteira Pediat Inst, Rio De Janeiro, Brazil. Univ Fed Estado Rio de Janeiro, Div Pediat Pneumol, Rio De Janeiro, Brazil. NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. Hosp San Sebastian, Dept Pediat, Rio De Janeiro, Brazil. Hosp Sao Goncalo, Dept Pediat Neurosurg, Sao Goncalo, Brazil. Hosp Municipal Jesus, Dept Pediat Neurosurg, Rio De Janeiro, Brazil. RP Sterling, TR (reprint author), Vanderbilt Univ, Med Ctr, Div Infect Dis, Sch Med,Dept Med, A2209 Med Ctr N,1161 21st Ave S, Nashville, TN 37232 USA. EM timothy.sterling@vanderbilt.edu RI de Almeida, Alexandre/C-6023-2012 OI de Almeida, Alexandre/0000-0002-4062-2504 FU Intramural NIH HHS; NIAID NIH HHS [K23-AI01654] NR 38 TC 13 Z9 14 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2007 VL 120 IS 4 BP E912 EP e921 DI 10.1542/peds.2006-3150 PG 10 WC Pediatrics SC Pediatrics GA 216HV UT WOS:000249870000068 PM 17908747 ER PT J AU Savla, J Davey, A Costa, PT Whitfield, KE AF Savla, Jyoti Davey, Adam Costa, Paul T., Jr. Whitfield, Keith E. TI Replicating the NEO-PI-R factor structure in African-American older adults SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE five factor model; personality; procrustes rotation; African-American; older adults ID PERSONALITY-TRAITS; 5-FACTOR MODEL; CULTURES; PERSPECTIVE; UNIVERSAL; INVENTORY; PROFILES; ROTATION AB Personality structure of African-American older adults using the Baltimore Study of Black Aging (BSBA; N = 234; Age range 49-88, M = 67; 72% women; Education M = I I years) was compared with the census-matched normative NEO-PI-R factor structure. Principal components with Procrustes rotation was used to calculate factor, facet, and total congruence coefficients. Significant factor congruence coefficients at a 99% probability level or beyond were found, and only three facet-level congruence coefficients did not reach significance. With the exception of cross-loadings on a few facets, most primary and secondary loadings generally replicated the normative structure providing evidence that there are little differences among the African-American older adults and the largely European American normative structure. (c) 2007 Elsevier Ltd. All rights reserved. C1 Virginia Polytech Inst & State Univ, Ctr Gerontol, Blacksburg, VA 24061 USA. Temple Univ, Coll Hlth Profess, Philadelphia, PA 19122 USA. NIA, Baltimore, MD 21224 USA. Duke Univ, Durham, NC 27708 USA. RP Savla, J (reprint author), Virginia Polytech Inst & State Univ, Ctr Gerontol, 237 A Wallace Hall 0426, Blacksburg, VA 24061 USA. EM jsavla@vt.edu RI Savla, Jyoti/J-7125-2015; OI Savla, Jyoti/0000-0001-7142-3770; Costa, Paul/0000-0003-4375-1712 NR 23 TC 12 Z9 15 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD OCT PY 2007 VL 43 IS 5 BP 1279 EP 1288 DI 10.1016/j.paid.2007.03.019 PG 10 WC Psychology, Social SC Psychology GA 201VH UT WOS:000248860200026 ER PT J AU Schmidt, LA Santesso, DL Schulkin, J Segalowitz, SJ AF Schmidt, Louis A. Santesso, Diane L. Schulkin, Jay Segalowitz, Sidney J. TI Shyness is a necessary but not sufficient condition for high salivary cortisol in typically developing 10 year-old children SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE shyness; salivary cortisol; heart rate; children ID POSTTRAUMATIC-STRESS-DISORDER; BEHAVIORAL-INHIBITION; SOCIAL COMPETENCE; EARLY-CHILDHOOD; TEMPERAMENT; REACTIVITY; ATTACHMENT; EXCRETION; ANXIETY; FEAR AB Previous research has noted both high and low baseline cortisol levels in anxious personality styles. We examined the relations among shyness, baseline salivary cortisol, and resting heart rate in a non-clinical sample of 10-year-old children. As predicted, shyness was positively correlated with baseline salivary cortisol and resting heart rate, replicating and extending earlier work with preschool age children to middle childhood. However, post-hoc analyses revealed that the scatterplot of shyness and salivary cortisol was significantly triangular in shape, indicating that shyness was a necessary, but not sufficient, condition for high salivary cortisol at age 10. For children high in shyness, salivary cortisol levels ranged from low to high; for children low in shyness, salivary cortisol levels were low. This triangular pattern was not found for the association between shyness and resting heart rate, suggesting different roles of neuroendocrine and autonomic measures in relation to shyness. The potential roles of cortisol in the maintenance of shyness developmentally are discussed as are the broader implications for clarifying prior inconsistent results on the relation between temperament and cortisol in humans. The use of triangular data analytic strategies for interpreting relations between psychological variables and identification of risk and protective factors is also discussed. (c) 2007 Elsevier Ltd. All rights reserved. C1 McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON, Canada. Brock Univ, Dept Psychol, St Catharines, ON L2S 3A1, Canada. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. RP Schmidt, LA (reprint author), McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON, Canada. EM schmidtl@mcmaster.ca NR 28 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD OCT PY 2007 VL 43 IS 6 BP 1541 EP 1551 DI 10.1016/j.paid.2007.04.011 PG 11 WC Psychology, Social SC Psychology GA 214LG UT WOS:000249738500022 ER PT J AU Varnai, P Balla, T AF Varnai, Peter Balla, Tamas TI Visualization and manipulation of phosphoinositide dynamics in live cells using engineered protein domains SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Review DE Ca2+ channels; confocal microscopy; fluorescence; phospholipase C; phosphoinositide; phosphoinositide kinase; phosphoinositide phosphatase ID PLECKSTRIN-HOMOLOGY DOMAINS; OXYSTEROL-BINDING-PROTEIN; BRUTONS TYROSINE KINASE; ADP-RIBOSYLATION FACTOR; SINGLE LIVING CELLS; G-BETA-GAMMA; PLASMA-MEMBRANE; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; PHOSPHOLIPASE-C; INOSITOL 1,4,5-TRISPHOSPHATE AB There is hardly a membrane-associated molecular event that is not regulated by phosphoinositides, a minor but critically important class of phospholipids of cellular membranes. The rapid formation, elimination, and conversion of these lipids in specific membrane compartments are ensured by a wealthy number of inositol lipid kinases and phosphatases with unique localization and regulatory properties. The existence of multiple inositol lipid pools have been indicated by metabolic labeling studies, but the level of functional compartmentalization revealed by the identification of numerous protein effectors acted upon by phosphoinositides could not have been foreseen. The changing perception of inositides from just serving as lipid precursors of second messengers to becoming highly dynamic local membrane-bound regulators poses new challenges concerning the detection of their rapid localized changes. Moreover, it is increasingly evident that manipulation of lipids in highly defined compartments would be a highly superior approach to soaking the cells with a particular phosphoinositide when studying the local regulation of the lipid on any effectors. In this review, we will summarize our efforts to improve our tools in studying phosphoinositide dynamics and discuss our views on the values of these methods compared to other options currently used or being explored. C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD USA. Semmelweis Univ, Fac Med, Dept Physiol, Budapest, Hungary. RP Varnai, P (reprint author), NICHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A35,49 Convent Dr, Bethesda, MD USA. EM varnai@puskin.sote.hu; ballat@mail.nih.gov OI Balla, Tamas/0000-0002-9077-3335 FU Intramural NIH HHS NR 107 TC 30 Z9 30 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD OCT PY 2007 VL 455 IS 1 BP 69 EP 82 DI 10.1007/s00424-007-0270-y PG 14 WC Physiology SC Physiology GA 210MG UT WOS:000249459700007 PM 17473931 ER PT J AU Kim, S Lan, O Waidyanatha, S Chanock, S Johnson, BA Vermeulen, R Smith, MT Zhang, LP Li, GL Shen, M Yin, SN Rothman, N Rappaport, SM AF Kim, Sungkyoon Lan, Oing Waidyanatha, Suramya Chanock, Stephen Johnson, Brent A. Vermeulen, Roel Smith, Martyn T. Zhang, Luoping Li, Guilan Shen, Min Yin, Songnian Rothman, Nathaniel Rappaport, Stephen M. TI Genetic polymorphisms and benzene metabolism in humans exposed to a wide Range of air concentrations SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE benzene; CYP2E1; EPHX1; genetic polymorphisms; GSTT1; human; metabolism; MPO; NQO1; splines ID MICROSOMAL EPOXIDE HYDROLASE; GLUTATHIONE-S-TRANSFERASE; HUMAN LIVER-MICROSOMES; OXIDATIVE DNA-DAMAGE; HUMAN BONE-MARROW; NAD(P)H-QUINONE OXIDOREDUCTASE; IN-VITRO; URINARY BIOMARKERS; DT-DIAPHORASE; MOLECULAR EPIDEMIOLOGY AB Using generalized linear models with natural-spline smoothing functions, we detected effects of specific xenobiotic metabolizing genes and gene-environment interactions on levels of benzene metabolites in 250 benzene-exposed and 136 control workers in Tianjin, China (for all individuals, the median exposure was 0.512 p.p.m. and the 10th and 90th percentiles were 0.002 and 6.40 p.p.m., respectively). We investigated five urinary metabolites (E,E-muconic acid, S-phenylmercapturic acid, phenol, catechol, and hydroquinone) and nine polymorphisms in seven genes coding for key enzymes in benzene metabolism in humans (cytochrome P450 2E1 [CYP2E1, rs2031920], NAD(P)H: quinone oxidoreductase [NQO1, rs1800566 and rs4986998], microsomal epoxide hydrolase [EPHX1, rs1051740 and rs2234922], glutathione-S-transferases [GSTT1, GSTM1 and GSTP1(rs947894)] and myeloperoxidase [MPO, rs2333227]). After adjusting for covariates, including sex, age, and smoking status, NQO1*2 (rs1800566) affected all five metabolites, CYP2E1 (rs2031920) affected most metabolites but not catechol, EPHX1 (rs1051740 or rs2234922) affected catechol and S-phenylmercapturic acid, and GSTT1 and GSTM1 affected S-phenylmercapturic acid. Significant interactions were also detected between benzene exposure and all four genes and between smoking status and NQO1*2 and EPHX1 (rs1051740). No significant effects were detected for GSTP1 or MPO. Results generally support prior associations between benzene hematotoxicity and specific gene mutations, confirm earlier evidence that GSTT1 affects production of S-phenylmercapturic acid, and provide additional evidence that genetic polymorphisms in NQO1*2, CYP2E1, and EPHX1 (rs1051740 or rs2234922) affect metabolism of benzene in the human liver. C1 Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. NCI, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Canc Res Ctr, Bethesda, MD USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Poison Control, Beijing, Peoples R China. RP Rappaport, SM (reprint author), Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. EM stephen_rappaport@unc.edu RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU Intramural NIH HHS; NIEHS NIH HHS [P30 ES01896, P30 ES10126, P42 ES04705, P42 ES05948, R01 ES06721] NR 87 TC 33 Z9 36 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD OCT PY 2007 VL 17 IS 10 BP 789 EP 801 DI 10.1097/FPC.0b013e3280128f77 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 215JX UT WOS:000249805700001 PM 17885617 ER PT J AU Tanda, G Katz, JL AF Tanda, Gianluigi Katz, Jonathan L. TI Muscarinic preferential M-1 receptor antagonists enhance the discriminative-stimulus effects of cocaine in rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE cocaine; drug-discrimination behavior; muscarinic antagonist; M1, benztropine analogues; dopamine transporter; rats ID DOPAMINE UPTAKE INHIBITORS; NUCLEUS-ACCUMBENS; ANALOGS; AMPHETAMINE; BENZTROPINE; RADIOLIGAND AB Previous studies of benztropine analogues have found them to inhibit dopamine uptake like cocaine, but with less effectiveness than cocaine in producing behavioral effects related to drug abuse. Studies have assessed whether nonselective muscarinic antagonists decrease the effects of cocaine because many of the benztropine analogues are also muscarinic antagonists. As previous studies were conducted with nonselective muscarinic antagonists and the benztropine analogues show preferential affinity for the M, muscarinic receptor subtype, the present study examined interactions of cocaine and the preferential M, antagonists, telenzepine (TZP) and trihexyphenidyl (TXP) on subjective effects in rats trained to discriminate cocaine (10 mg/kg, i.p.) from saline injections. Cocaine dose-dependently increased the percentage of responses on the cocaine-appropriate lever, with full substitution at the training dose. In contrast neither UP nor TXP produced more than 25% cocaine-appropriate responding at any dose. Both M, antagonists produced significant leftward shifts in the cocaine dose-effect curve, TZP at 3.0 and TXP at 0.3 and 1.0 mg/kg. The present results indicate that preferential antagonist actions at muscarinic M, receptors enhance rather than attenuate the discriminative-stimulus effects of cocaine, and thus those actions unlikely contribute to the reduced cocaine-like effects of BZT analogues. Published by Elsevier Inc. C1 Natl Inst Drug Abuse, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. RP Katz, JL (reprint author), Natl Inst Drug Abuse, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gtanda@intra.nida.nih.gov; jkatz@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009 OI Tanda, Gianluigi/0000-0001-9526-9878 FU Intramural NIH HHS [Z99 DA999999, Z01 DA000105-18, Z01 DA000103-18] NR 17 TC 11 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD OCT PY 2007 VL 87 IS 4 BP 400 EP 404 DI 10.1016/j.pbb.2007.05.015 PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 208QD UT WOS:000249333400002 PM 17631384 ER PT J AU Thanos, PK Michaelides, M Benveniste, H Wang, GJ Volkow, ND AF Thanos, Panayotis K. Michaelides, Michael Benveniste, Helene Wang, Gene Jack Volkow, Nora D. TI Effects of chronic oral methylphenidate on cocaine self-administration and striatal dopamine D2 receptors in rodents SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE psychostimulant; addiction; impulsivity; dopamine transporters; attention deficit hyperactivity disorder; drug abuse ID DEFICIT HYPERACTIVITY DISORDER; POSITRON-EMISSION-TOMOGRAPHY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; GLUCOSE-METABOLISM; AUTOMATED ALGORITHM; NONHUMAN-PRIMATES; HARDERIAN GLANDS; ADOLESCENT RATS; GENE-REGULATION; HUMAN BRAIN AB Background: Methylphenidate (MP) and amphetamine, which are the mainstay for the treatment of ADHD, have raised concerns because of their reinforcing effects and the fear that their chronic use during childhood or adolescence could induce changes in the brain that could facilitate drug abuse in adulthood. Methods: Here we measured the effects of chronic treatment (8 months) with oral MP (1 or 2 mg/kg), which was initiated in periadolescent rats (postnatal day 30). Following this treatment, rats were tested on cocaine self-administration. In addition at 2 and 8 months of treatment we measured dopamine D2 receptor (D2R) availability in the striatum using [C-11]raclopride microPET (mu PET) imaging. Results: Animals treated for 8 months with 2 mg/kg of MP showed significantly reduced rates of cocaine self-administration at adulthood than vehicle treated rats. D2R availability in the striatum was significantly lower in rats after 2 months of treatment with MP (I and 2 mg/kg) but significantly higher after 8 months of MP treatment than in the vehicle treated rats. In vehicle treated rats D2R availability decreased with age whereas it increased in rats treated with MP. Because low D2R levels in the striatum are associated with a propensity for self-administration of drugs both in laboratory animals and in humans, this effect could underlie the lower rates of cocaine self-administration observed in the rats given 8 months of treatment with MP. Conclusions: Eight month treatment with oral MP beginning in adolescence decreased cocaine-self administration (I mg/kg) during adulthood which could reflect the increases in D2R availability observed at this life stage since D2R increases are associated with reduced propensity for cocaine self administration. In contrast, two month treatment with MP started also at adolescence decreased D2R availability, which could raise concern that at this life stage short treatments could possibly increase vulnerability to drug abuse during adulthood. These findings indicate that MP effects on D2R expression in the striatum are sensitive not only to length of treatment but also to the developmental stage at which treatment is given. Future studies evaluating the effects of different lengths of treatment on drug self-administration are required to assess optimal duration of treatment regimes to minimize adverse effects on the propensity for drug self administration. (c) 2007 Published by Elsevier Inc. C1 Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & NeuroImaging Lab, Upton, NY 11973 USA. NIAAA, Lab Neuroimaging, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & NeuroImaging Lab, Bldg 490, Upton, NY 11973 USA. EM thanos@bnl.gov RI Michaelides, Michael/K-4736-2013 OI Michaelides, Michael/0000-0003-0398-4917 FU Intramural NIH HHS NR 58 TC 57 Z9 57 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD OCT PY 2007 VL 87 IS 4 BP 426 EP 433 DI 10.1016/j.pbb.2007.05.020 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 208QD UT WOS:000249333400006 PM 17599397 ER PT J AU Winter, JC Rice, KC Amorosi, DJ Rabin, RA AF Winter, J. C. Rice, K. C. Amorosi, D. J. Rabin, R. A. TI Psilocybin-induced stimulus control in the rat SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE psilocybin; drug discrimination; rat; LSD; M100907; WAY-100635; ketanserin; bufotenine; 2C-T-7; MDMA; PCP ID LYSERGIC-ACID DIETHYLAMIDE; SEROTONERGIC-DOPAMINERGIC MEDIATION; DISCRIMINATIVE STIMULUS; HALLUCINOGENIC DRUGS; 5-HT2C RECEPTORS; LSD; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; ANTAGONISTS; MDMA; 2,5-DIMETHOXY-4-METHYLAMPHETAMINE AB Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. In the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. An intermediate degree of antagonism of psilocybin was observed following treatment with the 5-HT2A receptor antagonist, M100907. In contrast, no significant antagonism was observed following treatment with the 5-HT1A/7 receptor antagonist, WAY-100635, or the DAD, antagonist, remoxipride. Psilocybin generalized fully to DOM, LSD, psilocin, and, in the presence of WAY-100635, DMT while partial generalization was seen to 2C-T-7 and mescaline. LSD and MDMA partially generalized to psilocybin and these effects were completely blocked by M-100907; no generalization of PCP to psilocybin was seen. The present data suggest that psilocybin induces a compound stimulus in which activity at the 5-HT2A receptor plays a prominent but incomplete role. In addition, psilocybin differs from closely related hallucinogens such as 5-MeO-DMT in that agonism at 5-HT1A receptors appears to play no role in psilocybin-induced stimulus control. (c) 2007 Elsevier Inc. All rights reserved. C1 SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA. NIDDK, Med Chem Lab, Bethesda, MD 20892 USA. RP Winter, JC (reprint author), SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, 102 Farber Hall, Buffalo, NY 14214 USA. EM jcwinter@buffalo.edu FU NIDA NIH HHS [DA 03385, R01 DA003385, R01 DA003385-18, R56 DA003385] NR 61 TC 15 Z9 15 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD OCT PY 2007 VL 87 IS 4 BP 472 EP 480 DI 10.1016/j.pbb.2007.06.003 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 208QD UT WOS:000249333400011 PM 17688928 ER PT J AU Fenton, RA Knepper, MA AF Fenton, Robert A. Knepper, Mark A. TI Mouse models and the urinary concentrating mechanism in the new millennium SO PHYSIOLOGICAL REVIEWS LA English DT Review ID NEPHROGENIC DIABETES-INSIPIDUS; MEDULLARY COLLECTING DUCT; PROTEIN-KINASE-C; THICK ASCENDING LIMB; NITRIC-OXIDE SYNTHASE; EPITHELIAL SODIUM-CHANNEL; OSMOTIC WATER PERMEABILITY; NULL-MUTANT MICE; ANGIOTENSIN-CONVERTING ENZYME; CYTOSOLIC PHOSPHOLIPASE A(2) AB Our understanding of urinary concentrating and diluting mechanisms at the end of the 20th century was based largely on data from renal micropuncture studies, isolated perfused tubule studies, tissue analysis studies and anatomical studies, combined with mathematical modeling. Despite extensive data, several key questions remained to be answered. With the advent of the 21st century, a new approach, transgenic and knockout mouse technology, is providing critical new information about urinary concentrating processes. The central goal of this review is to summarize findings in transgenic and knockout mice pertinent to our understanding of the urinary concentrating mechanism, focusing chiefly on mice in which expression of specific renal transporters or receptors has been deleted. These include the major renal water channels (aquaporins), urea transporters, ion transporters and channels (NHE3, NKCC2, NCC, ENaC, ROMK, ClC-K1), G protein-coupled receptors (type 2 vasopressin receptor, prostaglandin receptors, endothelin receptors, angiotensin II receptors), and signaling molecules. These studies shed new light on several key questions concerning the urinary concentrating mechanism including: 1) elucidation of the role of water absorption from the descending limb of Henle in countercurrent multiplication, 2) an evaluation of the feasibility of the passive model of Kokko-Rector and Stephenson, 3) explication of the role of inner medullary collecting duct urea transport in water conservation, 4) an evaluation of the role of tubuloglomerular feedback in maintenance of appropriate distal delivery rates for effective regulation of urinary water excretion, and 5) elucidation of the importance of water reabsorption in the connecting tubule versus the collecting duct for maintenance of water balance. C1 Univ Aarhus, Inst Anat, Water & Salt Res Ctr, Aarhus, Denmark. NHLBI, Lab Kidney & Elect Metab, NIH, Bethesda, MD 20892 USA. RP Fenton, RA (reprint author), Univ Aarhus, Inst Anat, Water & Salt Res Ctr, Aarhus, Denmark. EM ROFE@ana.au.dk FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 299 TC 99 Z9 104 U1 0 U2 15 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD OCT PY 2007 VL 87 IS 4 BP 1083 EP 1112 DI 10.1152/physrev.00053.2006 PG 30 WC Physiology SC Physiology GA 219KA UT WOS:000250082300001 PM 17928581 ER PT J AU Burg, MB Ferraris, JD Dmitrieva, NI AF Burg, Maurice B. Ferraris, Joan D. Dmitrieva, Natalia I. TI Cellular response to hyperosmotic stresses SO PHYSIOLOGICAL REVIEWS LA English DT Review ID ACTIVATED-PROTEIN-KINASE; MEDULLARY COLLECTING DUCT; ENHANCER-BINDING PROTEIN; ALDOSE REDUCTASE GENE; THICK ASCENDING LIMB; CANINE KIDNEY-CELLS; NA+/MYO-INOSITOL COTRANSPORTER; GROWTH-FACTOR RECEPTOR; TRANSCRIPTION FACTOR TONEBP/OREBP; REGULATORY VOLUME INCREASE AB Cells in the renal inner medulla are normally exposed to extraordinarily high levels of NaCl and urea. The osmotic stress causes numerous perturbations because of the hypertonic effect of high NaCl and the direct denaturation of cellular macromolecules by high urea. High NaCl and urea elevate reactive oxygen species, cause cytoskeletal rearrangement, inhibit DNA replication and transcription, inhibit translation, depolarize mitochondria, and damage DNA and proteins. Nevertheless, cells can accommodate by changes that include accumulation of organic osmolytes and increased expression of heat shock proteins. Failure to accommodate results in cell death by apoptosis. Although the adapted cells survive and function, many of the original perturbations persist, and even contribute to signaling the adaptive responses. This review addresses both the perturbing effects of high NaCl and urea and the adaptive responses. We speculate on the sensors of osmolality and document the multiple pathways that signal activation of the transcription factor TonEBP/OREBP, which directs many aspects of adaptation. The facts that numerous cellular functions are altered by hyperosmolality and remain so, even after adaptation, indicate that both the effects of hyperosmolality and adaptation to it involve profound alterations of the state of the cells. C1 NHLBI, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM maurice_burg@nih.gov RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 FU Intramural NIH HHS NR 349 TC 320 Z9 327 U1 8 U2 67 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD OCT PY 2007 VL 87 IS 4 BP 1441 EP 1474 DI 10.1152/physrev.00056.2006 PG 34 WC Physiology SC Physiology GA 219KA UT WOS:000250082300009 PM 17928589 ER PT J AU Hearing, VJ AF Hearing, Vincent J. TI Regulating melanosome transfer: who's driving the bus? SO PIGMENT CELL RESEARCH LA English DT Article ID HUMAN SKIN; KERATINOCYTES; COLOR; MECHANISM; PATTERNS C1 NIH, Natl Canc Inst, Cell Biol Lab, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NIH, Natl Canc Inst, Cell Biol Lab, Bldg 10, Bethesda, MD 20892 USA. EM hearingv@nih.gov NR 16 TC 9 Z9 9 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD OCT PY 2007 VL 20 IS 5 BP 334 EP 335 DI 10.1111/j.1600-0749.2007.pcr402.x PG 2 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 210CF UT WOS:000249433600002 PM 17850503 ER PT J AU Wong, CCL Xu, T Rai, R Bailey, AO Yates, JR Wolf, YI Zebroski, H Kashina, A AF Wong, Catherine C. L. Xu, Tao Rai, Reena Bailey, Aaron O. Yates, John R., III Wolf, Yuri I. Zebroski, Henry Kashina, Anna TI Global analysis of Posttranslational protein arginylation SO PLOS BIOLOGY LA English DT Article ID N-TERMINAL ARGINYLATION; TANDEM MASS-SPECTRA; END RULE PATHWAY; BRAIN PROTEINS; SEQUENCES; PEPTIDES; ARGININE; SYSTEM; CELLS AB Posttranslational arginylation is critical for embryogenesis, cardiovascular development, and angiogenesis, but its molecular effects and the identity of proteins arginylated in vivo are largely unknown. Here we report a global analysis of this modification on the protein level and identification of 43 proteins arginylated in vivo on highly specific sites. Our data demonstrate that unlike previously believed, arginylation can occur on any N-terminally exposed residue likely defined by a structural recognition motif on the protein surface, and that it preferentially affects a number of physiological systems, including cytoskeleton and primary metabolic pathways. The results of our study suggest that protein arginylation is a general mechanism for regulation of protein structure and function and outline the potential role of protein arginylation in cell metabolism and embryonic development. C1 Univ Penn, Dept Biol Anim, Philadelphia, PA 19104 USA. Scripps Res Inst, La Jolla, CA USA. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. Rockefeller Univ, New York, NY 10021 USA. RP Kashina, A (reprint author), Univ Penn, Dept Biol Anim, Philadelphia, PA 19104 USA. EM akashina@vet.upenn.edu RI Xu, Tao/A-9353-2009 NR 34 TC 1 Z9 1 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD OCT PY 2007 VL 5 IS 10 BP 2231 EP 2242 DI 10.1371/journal.pbio.0050258 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 233EH UT WOS:000251072700014 ER PT J AU Kalluri, S Gilruth, P Rogers, D Szczur, M AF Kalluri, Satya Gilruth, Peter Rogers, David Szczur, Martha TI Surveillance of arthropod vector-borne infectious diseases using remote sensing techniques: A review SO PLOS PATHOGENS LA English DT Review ID GEOGRAPHIC INFORMATION-SYSTEMS; VALLEY FEVER EPIDEMICS; LYME-DISEASE; SATELLITE IMAGERY; ONCHOCERCIASIS CONTROL; POPULATION-DYNAMICS; HABITAT SUITABILITY; SLEEPING SICKNESS; IXODES-SCAPULARIS; EARTH-OBSERVATION AB Epidemiologists are adopting new remote sensing techniques to study a variety of vector-borne diseases. Associations between satellite-derived environmental variables such as temperature, humidity, and land cover type and vector density are used to identify and characterize vector habitats. The convergence of factors such as the availability of multi-temporal satellite data and georeferenced epidemiological data, collaboration between remote sensing scientists and biologists, and the availability of sophisticated, statistical geographic information system and image processing algorithms in a desktop environment creates a fertile research environment. The use of remote sensing techniques to map vector-borne diseases has evolved significantly over the past 25 years. In this paper, we review the status of remote sensing studies of arthropod vector-borne diseases due to mosquitoes, ticks, blackflies, tsetse flies, and sandflies, which are responsible for the majority of vector-borne diseases in the world. Examples of simple image classification techniques that associate land use and land cover types with vector habitats, as well as complex statistical models that link satellite-derived multi-temporal meteorological observations with vector biology and abundance, are discussed here. Future improvements in remote sensing applications in epidemiology are also discussed. C1 Raytheon Co, Upper Marlboro, MD USA. Univ Oxford, Dept Zool, TALA Res Grp, Oxford OX1 2JD, England. Natl Lib Med, Specialized Informat Serv, Bethesda, MD USA. RP Kalluri, S (reprint author), Raytheon Co, Upper Marlboro, MD USA. EM satya_kalluri@raytheon.com FU PHS HHS [467-MZ-202468] NR 89 TC 108 Z9 111 U1 7 U2 53 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2007 VL 3 IS 10 BP 1361 EP 1371 AR e116 DI 10.1371/journal.ppat.0030116 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 233TV UT WOS:000251114100001 PM 17967056 ER PT J AU Wang, JJ Wang, YH Wang, XM Sun, LG AF Wang, Jianjun Wang, Yuhong Wang, Xinming Sun, Liguang TI Penguins and vegetations on Ardley Island, Antarctica: evolution in the past 2,400 years SO POLAR BIOLOGY LA English DT Article ID CONTINENTAL ANTARCTICA; FECAL POLLUTION; ORGANIC-MATTER; CLIMATE-CHANGE; COLD DESERT; MARITIME; SEDIMENTS; STEROLS; POPULATIONS; RECORD AB The impact of penguins on vegetation cover is a frequently documented but not fully explained phenomenon, especially over geological time scales. To address this we collected two ornithogenic sediment cores from Ardley Island, Antarctica, and reconstructed historic variations of penguin population and different vegetations by using biomarkers fecal sterols and n-alkanols in the cores. The three major types of vegetations in the colony, namely coprophilic algae, moss and lichen, exhibited quite different trends, in concert with fluctuations in the penguin populations: a moderate penguin population is favorable for coprophilic algae and mosses, while lichen abundances decreased whenever penguin population increased, and vice versa. Cholestanol and alkanols biomarkers, in combination with bioelements, provided integrated information about the 2,400-year evolution of the penguin colony: historical penguins and vegetation populations, their fluctuations, and their interactions. C1 Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. State Ocean Adm, Inst Oceanog 3, Key Lab Global Change & Marine Atmospher Chem, Xiamen 361005, Fujian, Peoples R China. NCI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. Chinese Acad Sci, Guangzhou Inst Geochem, Guangzhou 510640, Peoples R China. Max Planck Inst Chem, Biogeochem Dept, D-55128 Mainz, Germany. RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. EM slg@ustc.edu.cn RI Wang, Xinming/A-7388-2014 OI Wang, Xinming/0000-0002-1982-0928 NR 34 TC 19 Z9 26 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0722-4060 J9 POLAR BIOL JI Polar Biol. PD OCT PY 2007 VL 30 IS 11 BP 1475 EP 1481 DI 10.1007/s00300-007-0308-9 PG 7 WC Biodiversity Conservation; Ecology SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 208GC UT WOS:000249306800011 ER PT J AU Miller, HI Henderson, DR AF Miller, Henry I. Henderson, David R. TI The FDA's risky risk-aversion SO POLICY REVIEW LA English DT Article C1 NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Naval Postgrad Sch, Monterey, CA USA. RP Miller, HI (reprint author), NIH, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU HOOVER INST PI STANFORD PA STANFORD UNIV, STANFORD, CA 94305-601 USA SN 0146-5945 J9 POLICY REV JI Policy Rev. PD OCT-NOV PY 2007 IS 145 BP 3 EP 27 PG 25 WC Political Science SC Government & Law GA 222JQ UT WOS:000250292800001 ER PT J AU Daugherty, SE Shugart, YY Platz, EA Fallin, MD Isaacs, WB Pfeiffer, RM Welch, R Huang, WY Reding, D Hayes, RB AF Daugherty, Sarah E. Shugart, Yin Yao Platz, Elizabeth A. Fallin, M. Daniele Isaacs, William B. Pfeiffer, Ruth M. Welch, Robert Huang, Wen-Yi Reding, Douglas Hayes, Richard B. TI Polymorphic variants in alpha-methylacyl-CoA racemase and prostate cancer SO PROSTATE LA English DT Article DE AMACR; prostate cancer; ibuprofen; branched chain fatty acids; haplotypes ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PHYTANIC ACID; MOLECULAR MARKER; OVER-EXPRESSION; LINKAGE PHASE; ASPIRIN USE; RISK; CYCLOOXYGENASE-2; ASSOCIATION; PREVENTION AB BACKGROUND. Alpha-methylacyl-CoA racemase (AMACR), which prepares branched chain fatty acids to be metabolized for energy and is implicated in the activation of the COX-inhibiting form of ibuprofen, is overexpressed in prostate cancer and its precursor lesions. Significant differences in AMACR allele frequencies have been reported for hereditary prostate cancer (HPC), but the relevance of AMACR in the context of its substrates have not been studied. METHODS. We conducted a nested case-control study of 1,318 prostate cancer cases and 1,842 controls from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Five non-synonymous (nsSNP) and two intronic AMACR polymorphisms were genotyped. Conditional logistic regression models were used to evaluate the associations between the genetic variants and prostate cancer. RESULTS. Overall, prostate cancer was not related to AMACR gene variants; however, risks for prostate cancer were significantly reduced among regular ibuprofen users who carried allele variants at four nsSNP loci (M9V, D175G, S201 L, and K277E; all P-trend, < 0.05) or carried the TGTGCG haplotype (OR = 0.65; 95% Cl 0.44-0.97). No AMACR-related associations were noted among nonregular ibuprofen users (all P-interaction > 0.33). CONCLUSION. AMACR gene variants were unrelated to prostate cancer overall in this study. The protective associations observed among ibuprofen users suggest that AMACR gene variants may enhance the chemopreventive effects of ibuprofen on prostate cancer risk. C1 Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Johns Hopkins Sch Med, James Buchanan Brady Urol Inst, Dept Urol, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr, Johns Hopkins Med Institut, Baltimore, MD USA. SAIC Frederick Inc, Adv Technol Program, Frederick, MD USA. Marshfield Clin Res Fdn, Marshfield, WI USA. RP Daugherty, SE (reprint author), Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM daughers@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; OI Hayes, Richard/0000-0002-0918-661X FU Intramural NIH HHS; NCI NIH HHS [T32 CA09314, N01-CO-12400] NR 42 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD OCT 1 PY 2007 VL 67 IS 14 BP 1487 EP 1497 DI 10.1002/pros.20635 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 218SP UT WOS:000250035500001 PM 17680641 ER PT J AU Zheng, WJ Brooks, BR Hummer, G AF Zheng, Wenjun Brooks, Bernard R. Hummer, Gerhard TI Protein conformational transitions explored by mixed elastic network models SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE elastic network model; protein conformational change; transition state; transition path; saddle point; myosin; kinesin ID MOLECULAR-DYNAMICS SIMULATIONS; MYOSIN MOTOR DOMAIN; MACROMOLECULAR MACHINES; DATABASE FRAMEWORK; ENERGY LANDSCAPES; MOTIONS; MECHANISM; KINESIN; POLYMERASES; FLEXIBILITY AB We develop a mixed elastic network model (MENM) to study large-scale conformational transitions of proteins between two (or more) known structures. Elastic network potentials for the beginning and end states of a transition are combined, in effect, by adding their respective partition functions. The resulting effective MENM energy function smoothly interpolates between the original surfaces, and retains the beginning and end structures as local minima. Saddle points, transition paths, potentials of mean force, and partition functions can be found efficiently by largely analytic methods. To characterize the protein motions during a conformational transition, we follow "transition paths" on the MENM surface that connect the beginning and end structures and are invariant to parameterizations of the model and the mathematical form of the mixing scheme. As illustrations of the general formalism, we study large-scale conformation changes of the motor proteins KIFIA kinesin and myosin H. We generate possible transition paths for these two proteins that reveal details of their conformational motions. The MEEM formalism is computationally efficient and generally applicable even for large protein systems that undergo highly collective structural changes. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM gcrhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013; OI Hummer, Gerhard/0000-0001-7768-746X; Zheng, Wenjun/0000-0002-6236-9765 FU Intramural NIH HHS NR 36 TC 96 Z9 98 U1 1 U2 14 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD OCT PY 2007 VL 69 IS 1 BP 43 EP 57 DI 10.1002/prot.21465 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 206NA UT WOS:000249189000005 PM 17596847 ER PT J AU Andrusier, N Nussinov, R Wolfson, HJ AF Andrusier, Nelly Nussinov, Ruth Wolfson, Haim J. TI FireDock: Fast interaction refinement in molecular docking SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE docking refinement; side-chain flexibility; linear programming; rigid-body minimization; binding free energy; protein-protein docking ID PROTEIN-PROTEIN DOCKING; SIDE-CHAIN CONFORMATIONS; MEAN-FIELD THEORY; HOT-SPOTS; PREDICTION; ALGORITHM; OPTIMIZATION; COMPLEXES; ENERGY; MODEL AB Here, we present FireDock, an efficient method for the refinement and rescoring of rigid-body docking solutions. The refinement process consists of two main steps: (1) rearrangement of the interface side-chains and (2) adjustment of the relative orientation of the molecules. Our method accounts for the observation that most interface residues that are important in recognition and binding do not change their conformation significantly upon complexation. Allowing full side-chain flexibility, a common procedure in refinement methods, often causes excessive conformational changes. These changes may distort preformed structural signatures, which have been shown to be important for binding recognition. Here, we restrict side-chain movements, and thus manage to reduce the false-positive rate noticeably. In the later stages of our procedure (orientation adjustments and scoring), we smooth the atomic radii. This allows for the minor backbone and side-chain movements and increases the sensitivity of our algorithm. FireDock succeeds in ranking a near-native structure within the top 15 predictions for 83% of the 30 enzyme-inhibitor test cases, and for 78% of the 18 semi-unbound antibody-antigen complexes. Our refinement procedure significantly improves the ranking of the rigid-body PatchDock algorithm for these cases. The FireDock program is fully automated. In particular, to our knowledge, FireDock's prediction results are comparable to current state-of-the-art refinement methods while its running time is significantly lower. The method is available at http:// bioinfo3d. cs. tau. ac. il/FireDock/. C1 Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Wolfson, HJ (reprint author), Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. EM wolfson@post.tau.ac.it RI Wolfson, Haim/A-1837-2011 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [1UC1AI067231] NR 58 TC 216 Z9 221 U1 2 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD OCT PY 2007 VL 69 IS 1 BP 139 EP 159 DI 10.1002/prot.21495 PG 21 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 206NA UT WOS:000249189000013 PM 17598144 ER PT J AU Detera-Wadleigh, SD Liu, CY Maheshwari, M Cardona, I Corona, W Akula, N Steele, CJM Badnerc, JA KundUa, M Kassem, L Potash, JB Gibbs, R Gershonc, ES McMahon, FJ AF Detera-Wadleigh, Sevilla D. Liu, Chun-yu Maheshwari, Manjula Cardona, Imer Corona, Winston Akula, Nirmala Steele, C. J. M. Badnerc, Judith A. KundUa, Mukta Kassem, Layla Potash, James B. Gibbs, Richard Gershonc, Elliot S. McMahon, Francis J. CA NIMH GIBDC TI Sequence variation in DOCK9 and heterogeneity in bipolar disorder SO PSYCHIATRIC GENETICS LA English DT Article DE allele; association; Cdc42; phenotypes; transmission ID GENETICS INITIATIVE PEDIGREES; GENOME-WIDE SEARCH; SUSCEPTIBILITY LOCUS; CHROMOSOME 13Q32; REGRESSION-ANALYSIS; COMPUTER-PROGRAM; LINKAGE ANALYSIS; DAOA/G30 LOCUS; POTENTIAL LOCI; PANIC DISORDER AB Background Linkage of bipolar disorder to a broad region on chromosome 13q has been supported in several studies including a meta-analysis on genome scans. Subsequent reports have shown that variations in the DAOA (G72) locus on 13q33 display association with bipolar disorder but these may not account for all of the linkage evidence in the region. Objective To identify additional susceptibility loci on 13q32-q33 by linkage disequilibrium mapping and explore the impact of phenotypic heterogeneity on association. Methods In the initial phase, 98 single nucleotide polymorphism (SNPs) located on 13q32-q33 were genotyped on 285 probands with bipolar disorder and their parents were drawn from families in the NIMH Genetics Initiative consortium for bipolar disorder (NIMH1-4) and two other series. Fine scale mapping using one family series (NIMH1-2) as the test sample was targeted on a gene that displayed the highest evidence of association. A secondary analysis of familial component phenotypes of bipolar disorder was conducted. Results Three of seven SNPs in DOCK9, a gene that encodes an activator of the Rho-GTPase Cdc42, showed significant excess allelic transmission (P=0.0477-0.00067). Fine scale mapping on DOCK9 yielded evidence of association at nine SNPs in the gene (P=0.02-0.006). Follow-up tests detected excess transmission of the same allele of rs1340 in two out of three other sets of families. The association signals were largely attributable to maternally transmitted alleles (rsl 927568: P= 0.000083; odds ratio = 3.778). A secondary analysis of familial component phenotypes of bipolar disorder detected significant association across multiple DOCK9 markers for racing thoughts, psychosis, delusion during mania and course of illness indicators. Conclusion These results suggest that DOCK9 contributes to both risk and increased illness severity in bipolar disorder. We found evidence for the effect of phenotypic heterogeneity on association. To our knowledge this is the first report to implicate DOCK9 or the Rho-GTPase pathway in the etiology of bipolar disorder. C1 NIMH, NIH, Bethesda, MD 20892 USA. US Dept HHS, NIH, Natl Inst Mental Hlth INtramural Res Program, Mood & Anxiety Program,Genet Basis Mood, Bethesda, MD USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Baylor Coll Med, Human Genome Sequencing Ctr, Dept Human Mol Genet, Houston, TX 77030 USA. Indiana Univ, Indianapolis, IN 46204 USA. Washington Univ, St Louis, MO USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif Irvine, Irvine, CA USA. Univ Iowa, Iowa City, IA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Rush Univ, Chicago, IL USA. RP Detera-Wadleigh, SD (reprint author), NIMH, NIH, Bldg 35 Room 1A205,35 Convent Dr, Bethesda, MD 20892 USA. EM deteras@mail.nih.gov RI McMahon, Francis/A-7290-2009; Liu, Chunyu/G-7561-2012; OI Liu, Chunyu/0000-0002-5986-4415; McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS; NIMH NIH HHS [R01 MH 59567, 1Z01 MH 002810-01, MH 59533, R01 MH 059548, R01 MH 059556, R01 MH 59534, R01 MH 59535, R01 MH 59545, R01 MH 59553, R01 MH 60068] NR 76 TC 13 Z9 15 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD OCT PY 2007 VL 17 IS 5 BP 274 EP 286 DI 10.1097/YPG.0b013e328133f352 PG 13 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 210VS UT WOS:000249484300004 PM 17728666 ER PT J AU Vythilingam, M Blair, KS McCaffrey, D Scaramozza, M Jones, M Nakic, M Mondillo, K Hadd, K Bonne, O Mitchell, DGV Pine, DS Charney, DS Blair, RJR AF Vythilingam, M. Blair, K. S. McCaffrey, D. Scaramozza, M. Jones, M. Nakic, M. Mondillo, K. Hadd, K. Bonne, O. Mitchell, D. G. V. Pine, D. S. Charney, D. S. Blair, R. J. R. TI Biased emotional attention in post-traumatic stress disorder: a help as well as a hindrance? SO PSYCHOLOGICAL MEDICINE LA English DT Article ID ANXIETY DISORDERS; AMYGDALA RESPONSE; LEXICAL ACCESS; WORD-FREQUENCY; RAPE VICTIMS; TRAUMA CUES; INFORMATION; PTSD; MEMORY; INDIVIDUALS AB Background. From a cognitive neuroscience perspective, the emotional attentional bias in posttraumatic stress disorder (PTSD) could be conceptualized either as emotional hyper-responsiveness or as reduced priming of task-relevant representations due to dysfunction in 'top-down' regulatory systems. We investigated these possibilities both with respect to threatening and positive stimuli among traumatized individuals with and without PTSD. Method. Twenty-two patients with PTSD, 21 trauma controls and 20 non-traumatized healthy participants were evaluated on two tasks. For one of these tasks, the affective Stroop task (aST), the emotional stimuli act as distracters and interfere with task performance. For the other, the emotional lexical decision task (eLDT), emotional information facilitates task performance. Results. Compared to trauma controls and healthy participants, patients with PTSD showed increased interference for negative but not positive distracters on the aST and increased emotional facilitation for negative words on the eLDT. Conclusions. These findings document that hyper-responsiveness to threat but not to positive stimuli is specific for patients with PTSD. C1 NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Med Ctr, Dept Psychiat, Jerusalem, Israel. Univ Western Ontario, Dept Psychiat, London, ON N6A 3K7, Canada. Univ Western Ontario, Dept Anat, London, ON N6A 3K7, Canada. Univ Western Ontario, Dept Cell Biol, London, ON N6A 3K7, Canada. CUNY Mt Sinai Sch Med, Off Dean, New York, NY 10029 USA. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, 15K N Dr, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov FU Intramural NIH HHS NR 44 TC 36 Z9 37 U1 4 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD OCT PY 2007 VL 37 IS 10 BP 1445 EP 1455 DI 10.1017/S003329170700092X PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 224EH UT WOS:000250429800007 PM 17559703 ER PT J AU Carrico, AW Johnson, MO Moskowitz, JT Neilands, TB Morin, SF Charlebois, ED Steward, WT Remien, RH Wong, FL Rotheram-Borus, MJ Lightfoot, MA Chesney, MA AF Carrico, Adam W. Johnson, Mallory O. Moskowitz, Judith T. Neilands, Torsten B. Morin, Stephen F. Charlebois, Edwin D. Steward, Wayne T. Remien, Robert H. Wong, F. Lennie Rotheram-Borus, Mary Jane Lightfoot, Marguerita A. Chesney, Margaret A. CA NIMH Healthy Living Project Team TI Affect regulation, stimulant use, and viral load among HIV-Positive persons on anti-retroviral therapy SO PSYCHOSOMATIC MEDICINE LA English DT Article DE adherence; affect; cocaine; depression; methamphetamine; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEDICATION ADHERENCE; DRUG-USE; PSYCHOLOGICAL STATES; DEPRESSIVE SYMPTOMS; METHAMPHETAMINE USE; INFECTED ADULTS; RISK-FACTORS; MEN; MODEL AB Objective: A substantial minority of HIV-positive individuals have comorbid affective or substance use disorders, which can interfere with effective medical management. The present study examined the associations among affect regulation, substance use, non-adherence to anti-retroviral therapy (ART), and immune status in a diverse sample of HIV-positive persons. Methods: A total of 858 HIV-positive participants self-reporting risk of transmitting HIV were enrolled in a randomized behavioral prevention trial and provided baseline blood samples to measure T-helper (CD4+) counts and HIV viral load. Results: Among individuals on ART, regular. stimulant users had a five-fold (0.70 log(10)) higher HIV viral load than those who denied regular stimulant use. The association between regular stimulant use and elevated HIV viral load remained after accounting for demographics, differences in CD4+ counts, and polysubstance use. In the final model, 1 unit increase in affect regulation (decreased severity of depressive symptoms as well as enhanced positive states of mind) was associated with a 23% decrease in the likelihood of reporting regular stimulant use and 15% decrease in the likelihood of being classified as nonadherent to ART. Regular stimulant users, in turn, were more than twice as likely to be nonadherent to ART. Even after accounting for the effects of nonadherence and CD4+ counts, regular stimulant use was independently associated with 50% higher HIV viral load. Conclusions: Increased mental health treatment as well as more intensive referrals to substance abuse treatment or 12-step self-help groups may be crucial to assist stimulant users with more effectively managing treatment for HIV/AIDS. C1 Univ Calif San Francisco, Hlth Psychol Program, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr AIDS Prevent Studies, NIMH, Healthy Living Project Team, San Francisco, CA 94143 USA. Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. New York State Psychiat Inst & Hosp, NIMH, Healthy Living Project Team, New York, NY 10032 USA. Univ Calif Los Angeles, Ctr Community Hlth, Los Angeles, CA USA. Natl Inst Hlth Ctr Complementary & Alternat Med, Milwaukee, WI USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Carrico, AW (reprint author), Univ Calif San Francisco, Hlth Psychol Program, 3333 California St,Suite 465,Box 0848, San Francisco, CA 94143 USA. EM adam.carrico@ucsf.edu FU NIMH NIH HHS [P30-MH43520, P30 MH043520, P30-MH058107, P30-MH062246, P30-MH57226, T32-MH019391, U10-MH57615, U10-MH57616, U10-MH57631, U10-MH57636] NR 52 TC 30 Z9 30 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD OCT PY 2007 VL 69 IS 8 BP 785 EP 792 DI 10.1097/PSY.0b013e318157b142 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 224VX UT WOS:000250476400012 PM 17942835 ER PT J AU Liu, J Sempos, C AF Liu, Jian Sempos, Christopher TI Foetal nutritional status and cardiovascular risk profile among children SO PUBLIC HEALTH NUTRITION LA English DT Article DE foetal nutritional status; cardiovascular risk; children; NHANES III; metabolic syndrome ID INSULIN-RESISTANCE SYNDROME; BIRTH-WEIGHT; BLOOD-PRESSURE; METABOLIC SYNDROME; MATERNAL FACTORS; BODY-MASS; OBESITY; DISEASE; ORIGINS; HEALTH AB Objective: To estimate the impact of foetal rutritional status on cardiovascular risk among children with the Foetal Nutritional Status Index (FNSI), calculated by dividing the child's birth weight (BW, kg) by the mother's height height (m(2)). Design: Cross-sectional survey analysis. Setting: A sample of children from the US Third National Health and Nutrition Examination Survey. Subjects: A total of 3109 children who were 5-11 years of age and had data oil BW and mother's height. Non-fasting blood samples were included. Results: Overall, the FNSI was positively associated with BW and negatively associated with mother's height (P < 0.0001). Within sex-specific quintiles of FNSI (third quintile as reference) adjusted for potential confounding variables, cardiovascular risk factors tended to be 'higher' in the lower quintiles for males while the opposite was true for females. Multivariate logistic regression analyses indicated that the odds for males in quintile 1 was 2.4 for having a low level of high-density lipoprotein cholesterol (P < 0.01) and 2.1 for having a cluster of cardiovascular risk factors (P = 0.01); for females, the odds of having a cluster of cardiovascular risk factors was approximately two times higher for those in the first and fifth quintiles, who also had 21 significantly higher prevalence of central obesity. Conclusions: The FNSI may be a potential proxy indicator of foetal nutritional status and it may be used to test specific hypotheses of whether foetal nutrition restriction or overnutrition programmes future cardiovascular risk. C1 Brock Univ, Dept Community Hlth Sci, St Catharines, ON L2S 3A1, Canada. NIH, Bethesda, MD 20892 USA. RP Liu, J (reprint author), Brock Univ, Dept Community Hlth Sci, AS 309,500 Glenridge Ave, St Catharines, ON L2S 3A1, Canada. EM jliu@brocku.ca NR 37 TC 4 Z9 4 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 EI 1475-2727 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD OCT PY 2007 VL 10 IS 10 BP 1067 EP 1075 DI 10.1017/S136898000768389X PG 9 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 225YV UT WOS:000250555100012 PM 17381940 ER PT J AU Medvedeva, NG Panyutin, IV Panyutin, IG Neumann, RD AF Medvedeva, Natalia G. Panyutin, Irina V. Panyutin, Igor G. Neumann, Ronald D. TI Phosphorylation of histone H2AX in radiation-induced micronuclei SO RADIATION RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; DNA-DAMAGE; CELL-LINES; PROTEIN; REPAIR; FOCI; CHROMOSOMES; INSTABILITY AB DNA double-strand breaks are thought to precede the formation of most radiation-induced micronuclei. Phosphorylation of the histone H2AX is an early indicator of DNA doublestrand breaks. Here we studied the phosphorylation status of the histone H2AX in micronuclei after exposure of cultured cells to ionizing radiation or treatment with colchicine. In human astrocytoma SF268 cells, after exposure to gamma radiation, the proportion of gamma-H2AX-positive to gamma-H2AX-negative micronuclei increases. The majority of the gamma-H2AX-positive mlcronuclei are centromere-negative. The number of gamma-H2AXpositive micronuclei continues to increase even 24 h postirradiation when most gamma-H2AX foci in the main nucleus have disappeared. In contrast, in normal human fibroblasts (BJ), the proportion of gamma-H2AX-positive to gamma-H2AX-negative micronuclei remains constant, and the majority of the centromere-negative cells are gamma-H2AX-negative. Treatment of both cell lines with colchicine results in mostly centromere-positive gamma-H2AX-negative micronuclei. Immunostaining revealed colocalization of MDC1 and ATM with gamma-H2AX foci in both main nuclei and micronuclei; however, other repair proteins, such as Rad50, 53BP1 and Rad17, that co-localized with gamma-H2AX foci in the main nuclei were not found in the micronuclei. Combination of the micronucleus assay with gamma-H2AX immunostaining provides new insights into the mechanisms of the formation and fate of micronuclei. (C) 2007 by Radiation Research Society. C1 NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Panyutin, IG (reprint author), NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, 9000 Rockville Pike,Bldg 10,Room IC492, Bethesda, MD 20892 USA. EM ipanyuting@mail.nih.gov FU Intramural NIH HHS NR 25 TC 24 Z9 27 U1 0 U2 0 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD OCT PY 2007 VL 168 IS 4 BP 493 EP 498 DI 10.1667/RR0788.1 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 215FL UT WOS:000249793600014 PM 17903033 ER PT J AU Machado-Vieira, R Soares, JC AF Machado-Vieira, Rodrigo Soares, Jair C. TI Treatment-resisstant mood disorders SO REVISTA BRASILEIRA DE PSIQUIATRIA LA Portuguese DT Article DE depressive disorder major; bipolar disorder; mood disorders; antidepressive agents; refractory period; psychological ID OPEN-LABEL TRIAL; RESISTANT MAJOR DEPRESSION; BIPOLAR DISORDER; PHARMACOLOGICAL-TREATMENT; DOUBLE-BLIND; LITHIUM; ANTIDEPRESSANT; BRAIN; PATHOPHYSIOLOGY; HIPPOCAMPAL AB Objective and Method: Mood disorders are the most prevalent psychiatric disorders. Despite new insights and advances on the neurobiological basis and therapeutic approaches for bipolar disorders and recurrent depression, elevated prevalence of recurrence, persistent sub-syndromal symptoms and treatment resistance are challenging aspects and need to be urgently addressed. The objective of this literature review is to evaluate the current concepts of treatment resistance and refractoriness in mood disorders. Results: Genetic factors, misdiagnosis, use of inappropriate pharmacological approaches, non-compliance and biological/psychosocial stressors account for dysfunctions in mood regulation, thus increasing the prevalence of refractory mood disorders. Regarding available treatments, the use of effective doses during an adequate period followed by augmentation with a second and/or third agent, and finally switching to other agent are steps frequently necessary to optimize efficacy. However in the treatment-resistant paradigm, drugs mimicking standard strategies, which target preferentially the monoaminergic system, can present reduced therapeutic effects. Thus, the search for new effective treatments for mood disorders is critical to decreasing the overall morbidity secondary to treatment resistance. Conclusion: Emerging strategies targeting brain plasticity pathways or 'plasticity enhancers', including antiglutamatergic drugs, glucocorticoid receptor antagonists and neuropeptides, have been considered promising therapeutic options for difficult-to-treat mood disorders. C1 NIMH, Programa Transtornos Humor & Ansiedade, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Psiquiatria, Chapel Hill, NC USA. RP Machado-Vieira, R (reprint author), 35 Convent Dr,bldg 35,Rm 1C-1010, Bethesda, MD 20892 USA. EM machadovieirar@terra.com.br RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 49 TC 3 Z9 4 U1 2 U2 3 PU ASSOC BRASILEIRA PSIQUIATRIA PI SAO PAULO PA SUBSCRIPTION DEPARTMENT, RUA PEDRO DE TOLEDO, 967 - CASA 01, SAO PAULO, SP 04039-032 A, BRAZIL SN 1516-4446 J9 REV BRAS PSIQUIATR JI Rev. Bras. Psiquiatr. PD OCT PY 2007 VL 29 SU 2 BP S48 EP S54 DI 10.1590/S1516-44462006005000058 PG 7 WC Psychiatry SC Psychiatry GA 233GY UT WOS:000251079800003 PM 17713691 ER PT J AU Huber, AM Dugan, EM Lachenbruch, PA Feldman, BM Perez, MD Zemel, LS Lindsley, CB Rennebohm, RM Wallace, CA Passo, MH Reed, AM Bowyer, SL Ballinger, SH Miller, FW Rider, LG AF Huber, A. M. Dugan, E. M. Lachenbruch, P. A. Feldman, B. M. Perez, M. D. Zemel, L. S. Lindsley, C. B. Rennebohm, R. M. Wallace, C. A. Passo, M. H. Reed, A. M. Bowyer, S. L. Ballinger, S. H. Miller, F. W. Rider, L. G. CA Juvenile Dermatomyositis Dis Activ TI The Cutaneous Assessment Tool: development and reliability in juvenile idiopathic inflammatory myopathy SO RHEUMATOLOGY LA English DT Article DE juvenile idiopathic inflammatory myopathy; juvenile dermatomyositis; skin disease; Cutaneous Assessment Tool; assessment ID DISEASE-ACTIVITY; SKIN INVOLVEMENT; DERMATOMYOSITIS; VALIDATION; PSORIASIS; CHILDREN AB Objectives. Clinical care and therapeutic trials in idiopathic inflammatory myopathies (IIM) require accurate and consistent assessment of cutaneous involvement. The Cutaneous Assessment Tool (CAT) was designed to measure skin activity and damage in IIM. We describe the development and inter-rater reliability of the CAT, and the frequency of lesions endorsed in a large population of juvenile IN patients. Methods. The CAT includes 10 activity, 4 damage and 7 combined lesions. Thirty-two photographic slides depicting IN skin lesions were assessed by 11 raters. One hundred and twenty-three children were assessed by 11 paediatric rheumatologists; at 10 centres. Inter-rater reliability was assessed using simple agreements and intra-class correlation coefficients (ICC). Results. Simple agreements in recognizing lesions as present or absent were generally high (0.5-1.0). ICCs for CAT lesions were moderate (0.4-0.75) in both slides and real patients. ICCs for the CAT activity and damage scores were 0.71 and 0.81, respectively. CAT activity scores ranged from 0 to 44 (median 7, potential range 0-96) and CAT damage scores ranged from 0 to 13 (median 1, potential range 0-22). The most common cutaneous lesions endorsed were periungual capillary loop changes (63%), Gottron's papules/sign (53%), heliotrope rash (49%) and malar/facial erythema (49%). Conclusions. Total CAT activity and damage scores have moderate to good reliability. Assessors generally agree on the presence of a variety of cutaneous lesions. The CAT is a promising, semi-quantitative tool to comprehensively assess skin disease activity and damage in IIM. C1 IWK Hlth Ctr, Div Pediat Rheumatol, Halifax, NS B3K 6R8, Canada. Dalhousie Univ, Halifax, NS, Canada. Washington Hosp Ctr, Washington, DC 20010 USA. DHHS, Ctr Biol Evaluat & Res, US FDA, Rockville, MD USA. Univ Toronto, Toronto, ON, Canada. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Texas Childrens Hosp, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Connecticut, Hartford, CT 06112 USA. Connecticut Childrens Med Ctr, Hartford, CT USA. Univ Kansas, Kansas City, KS USA. Ohio State Univ, Columbus, OH 43210 USA. British Columbia Childrens Hosp, Columbus, OH USA. Univ Washington, Seattle, WA 98195 USA. Childrens Hosp, Seattle, WA USA. Univ Cincinnati, Cincinnati, OH USA. Childrens Hosp, Cincinnati, OH 45229 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. NIEHS, Environm Autoimmun Grp, Res Triangle Pk, NC 27709 USA. RP Huber, AM (reprint author), IWK Hlth Ctr, Div Pediat Rheumatol, 5850 Univ Ave, Halifax, NS B3K 6R8, Canada. EM adam.huber@iwk.nshealth.ca RI Feldman, Brian/A-8586-2011; OI Sundel, Robert/0000-0002-0083-5695; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS [Z01 ES101081-06] NR 17 TC 19 Z9 24 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD OCT PY 2007 VL 46 IS 10 BP 1606 EP 1611 DI 10.1093/rheumatology/kem179 PG 6 WC Rheumatology SC Rheumatology GA 226XX UT WOS:000250622900020 PM 17890275 ER PT J AU Lada, AG Iyer, LM Rogozin, IB Aravind, L Pavlov, YI AF Lada, A. G. Iyer, L. M. Rogozin, I. B. Aravind, L. Pavlov, Yu. I. TI Incarnation of classical pro- and eukaryotic mechanisms of mutagenesis in hypermutagenesis and immunity of vertebrates SO RUSSIAN JOURNAL OF GENETICS LA English DT Review ID DNA-POLYMERASE-ETA; INDUCED CYTIDINE DEAMINASE; POLYNUCLEOTIDE (DEOXY)CYTIDINE DEAMINASES; VARIABLE LYMPHOCYTE RECEPTORS; CLASS-SWITCH RECOMBINATION; UVRA-POLA DERIVATIVES; PRONE REPAIR SYSTEM; RNA-EDITING ENZYME; YEAST REV1 PROTEIN; COLI B-R AB M.E. Lobashev has brilliantly postulated in 1947 that error-prone repair contribute to mutations in cells. This was shown to be true once the mechanisms of UV mutagenesis in Escherichia coli were deciphered. Induced mutations are generated during error-prone SOS DNA repair with the involvement of inaccurate DNA polymerases belonging to the Y family. Currently, several distinct mutator enzymes participating in spontaneous and induced mutagenesis have been identified. Upon induction of these proteins, mutation rates increase by several orders of magnitude. These proteins regulate the mutation rates in evolution and in ontogeny during immune response. In jawed vertebrates, somatic hypermutagenesis occurs in the variable regions of immunoglobulin genes, leading to affinity maturation of antibodies. The process is initiated by cytidine deamination in DNA to uracil by AID (Activation-Induced Deaminase). Further repair of uracil-containing DNA through proteins that include the Y family DNA polymerases causes mutations, induce gene conversion, and class switch recombination. In jawless vertebrates, the variable lymphocyte receptors (VLR) serve as the primary molecules for adaptive immunity. Generation of mature VLRs most likely depends on agnathan AID-like deaminases. AID and its orthologs in lamprey (PmCDA1 and PMCDA2) belong to the AID/APOBEC family of RNA/DNA editing cytidine deaminases. This family includes enzymes with different functions: APOBEC1 edits RNA, APOBEC3 restricts retroviruses. The functions of APOBEC2 and APOBEC4 have not been yet determined. Here, we report a new member of the AID/APOBEC family, APOBEC5, in the bacterium Xanthomonas oryzae. The widespread presence of RNA/DNA editing deaminases suggests that they are an ancient means of generating genetic diversity. C1 St Petersburg State Univ, Inst Biol, Dept Genet & Breeding, St Petersburg 196240, Russia. Natl Ctr Biotechnol Informat, Natl Inst Hlth, Natl Lib Med, Bethesda, MD 20894 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Dept Biochem & Mol Biol, Dept Pathol & Microbiol, Omaha, NE 68198 USA. RP Lada, AG (reprint author), St Petersburg State Univ, Inst Biol, Dept Genet & Breeding, St Petersburg 196240, Russia. EM biotambovez@mail.ru NR 103 TC 0 Z9 0 U1 0 U2 2 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 1022-7954 J9 RUSS J GENET+ JI Russ. J. Genet. PD OCT PY 2007 VL 43 IS 10 BP 1093 EP 1107 DI 10.1134/S1022795407100031 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 221PY UT WOS:000250241000003 ER PT J AU Cunningham, T AF Cunningham, Tshalka TI Discrimination in academia SO SCIENTIST LA English DT Letter C1 NIAID, Bethesda, MD 20892 USA. RP Cunningham, T (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM cunninghamt@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD OCT PY 2007 VL 21 IS 10 BP 20 EP 20 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 213VH UT WOS:000249694700012 ER PT J AU Williams, KA Hakim, FT Gress, RE AF Williams, Kirsten A. Hakim, Frances T. Gress, Ronald E. TI T cell immune reconstitution following lymphodepletion SO SEMINARS IN IMMUNOLOGY LA English DT Review DE immune reconstitution; lymphopenia; thymopoiesis; thymus; homeostatic peripheral expansion; GVHD; immunotherapy ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; RECEPTOR EXCISION CIRCLE; IN-VIVO; THYMIC FUNCTION; HOMEOSTATIC PROLIFERATION; CANCER REGRESSION; REGULATORY CELLS; GROWTH-HORMONE; CUTTING EDGE AB T cell reconstitution following lymphopenia from chemotherapy or stem cell transplant is often slow and incompetent, contributing to the development of infectious diseases, relapse, and graft-versus-host disease. This is due to the fact that de novo T cell production is impaired following cytoreductive regimens. T cells can be generated from two pathways: (1) thymus derived through active thymopoiesis and (2) peripherally expanded clones through homeostatic proliferation. During recovery from lymphopenia, the thymic pathway is commonly compromised in adults and T cells rely upon peripheral expansion to restore T cell numbers. This homeostatic proliferation exploits the high cytokine levels following lymphopenia to rapidly generate T cells in the periphery. Moreover, this early peripheral expansion of T cells can also be driven by exogenous antigen. This results in loss of T cell repertoire diversity and may predispose to auto- or allo-immunity. Alternatively, the high homeostatic proliferation following lymphopenia may facilitate expansion of anti-tumor immunity. Murine and human studies have provided insight into the cytokine and cellular regulators of these two pathways of T cell generation and the disparate portraits of T cell immunity created through robust thymopoiesis or peripheral expansion following lymphopenia. This insight has permitted the manipulation of the immune system to maximize anti-tumor immunity through lymphopenia and led to an appreciation of mechanisms that underlie graft versus host disease. Published by Elsevier Ltd. C1 [Williams, Kirsten A.; Hakim, Frances T.; Gress, Ronald E.] NIH, Natl Canc Inst, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Gress, RE (reprint author), NIH, Natl Canc Inst, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. EM gressr@exchange.nih.gov FU Intramural NIH HHS [Z99 CA999999, Z01 BC010525-04] NR 145 TC 160 Z9 166 U1 0 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD OCT PY 2007 VL 19 IS 5 BP 318 EP 330 DI 10.1016/j.smim.2007.10.004 PG 13 WC Immunology SC Immunology GA 249MB UT WOS:000252231400006 PM 18023361 ER PT J AU Ulrich, C O'Donnell, P Taylor, C Farrar, A Danis, M Grady, C AF Ulrich, Connie O'Donnell, Patricia Taylor, Carol Farrar, Adrienne Danis, Marion Grady, Christine TI Ethical climate, ethics stress, and the job satisfaction of nurses and social workers in the United States SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE registered nurses; social workers; ethical climate; ethics stress; job satisfaction; USA ID HEALTH-CARE; ORGANIZATIONAL JUSTICE; REGISTERED NURSES; MORAL DISTRESS; ISSUES; LIFE; CONFLICTS; TURNOVER; DILEMMAS; SCALE AB Nurses and social workers are fundamental to the delivery of quality health care across the continuum of care. As health care becomes increasingly complex, these providers encounter difficult ethical issues in patient care, perceive limited respect in their work, and are increasingly dissatisfied. However, the link between ethics-related work factors and job satisfaction and intent-to-leave one's job has rarely been considered. In this paper, we describe how nurses and social workers in the US view the ethical climate in which they work, including the degree of ethics stress they feel, and the adequacy of organizational resources to address their ethical concerns. Controlling for socio-demographics, we examined the extent to which these factors affect nurses and social workers' job satisfaction and their interest in leaving their current position. Data were from self-administered mail questionnaires of 1215 randomly selected nurses and social workers in four census regions of the US. Respondents reported feeling powerless (32.5%) and overwhelmed (34.7%) with ethical issues in the workplace and frustration (52.8%) and fatigue (40%) when they cannot resolve ethical issues. In multivariate models, a positive ethical climate and job satisfaction protected against respondents' intentions to leave as did perceptions of adequate or extensive institutional support for dealing with ethical issues. Black nurses were 3.21 times more likely than white nurses to want to leave their position. We suggest several strategies to reduce ethics stress and improve the ethical climate of the workplace for nurses and social workers. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Penn, Philadelphia, PA 19104 USA. Inova Hlth Syst, Ctr Eth, Falls Church, VA 22042 USA. Georgetown Univ, Ctr Bioeth, Washington, DC 20057 USA. NIH, Ctr Clin, Dept Social Work, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Ulrich, C (reprint author), Univ Penn, Philadelphia, PA 19104 USA. EM culrich@nursing.upenn.edu FU Intramural NIH HHS [Z01 CL010523-05] NR 54 TC 86 Z9 88 U1 1 U2 27 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD OCT PY 2007 VL 65 IS 8 BP 1708 EP 1719 DI 10.1016/j.socscimed.2007.05.050 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 222BP UT WOS:000250271400013 PM 17619068 ER PT J AU Marcos, J Shackleton, CHL Buddhikot, MM Porter, FD Watson, GL AF Marcos, Josep Shackleton, Cedric H. L. Buddhikot, Madhavee M. Porter, Forbes D. Watson, Gordon L. TI Cholesterol biosynthesis from birth to adulthood in a mouse model for 7-dehydrosterol reductase deficiency (Smith-Lemli-Opitz syndrome) SO STEROIDS LA English DT Article DE SLOS; cholesterol deficiency; dehydrocholesterol; mutant mouse model; sterol metabolism; Dhcr7 ID STEROL BIOSYNTHESIS; PRENATAL-DIAGNOSIS; DHCR7 MUTATION; INBORN-ERRORS; SIMVASTATIN; SUPPLEMENTATION; FIBROBLASTS; METABOLISM; FREQUENCY; PHENOTYPE AB Smith-Lemli-Opitz syndrome (SLOS) is caused by deficiency in the terminal step of cholesterol biosynthesis, which is catalyzed by 7 - dehydrocholesterol reductase (DHCR7). The disorder exhibits several phenotypic traits including dysmorphia. and mental retardation with a broad range of severity. Pathogenesis of SLOS is complex due to multiple roles of cholesterol and maybe further complicated by unknown effects of aberrant metabolites that arise when 7-dehydrocholesterol (7-DHC), the substrate for DHCR7, accumulates. A viable mouse model for SLOS has recently been developed, and here we characterize cholesterol metabolism in this model with emphasis on changes during the first few weeks of postnatal development. Cholesterol and 7-DHC were measured in "SLOS" mice and compared with measurements in normal mice. SLOS mice had measurable levels of 7-DHC at all ages tested (up to 1 year), while 7-DHC was below the threshold for detection in normal mice. in perinatal to weaning age SLOS mice, cholesterol and 7-DHC levels changed dramatically. Changes in brain and liver were independent; in brain cholesterol increased several fold while 7-DHC remained relatively constant, but in liver cholesterol first increased then decreased again while 7-DHC first decreased then increased. In older SLOS animals the ratio of 7-DHC/cholesterol, which is an index of biochemical severity, tended to approach, but not reach, normal. While these mice provide the best available genetic animal model for the study of SLOS pathogenesis and treatment, they probably will be most useful at early ages when the metabolic effects of the mutations are most dramatic. To correlate any experimental treatment with improved sterol metabolism will require age-matched controls. Finally, determining the mechanism by which these "SLOS" mice tend to normalize may provide insight into the future development of therapy. (c) 2007 Elsevier Inc. All rights reserved. C1 Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. NICHD, NIH, Heritable Disorders Branch, Bethesda, MD USA. RP Watson, GL (reprint author), Childrens Hosp, Oakland Res Inst, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA. EM gwatson@chori.org RI Marcos, Josep/F-3545-2015 OI Marcos, Josep/0000-0002-3624-108X FU Intramural NIH HHS; NCRR NIH HHS [S10 RR017854, S10 RR017854-01]; NICHD NIH HHS [R03 HD045302-02, R01 HD053036, R01 HD053036-01, R03 HD045302] NR 33 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-128X J9 STEROIDS JI Steroids PD OCT PY 2007 VL 72 IS 11-12 BP 802 EP 808 DI 10.1016/j.steroids.2007.07.002 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 215UL UT WOS:000249834400010 PM 17714750 ER PT J AU Fox, ER Alnabhan, N Penman, AD Butler, KR Taylor, HA Skelton, TN Mosley, TH AF Fox, Ervin R. Alnabhan, Nabhan Penman, Alan D. Butler, Kenneth R. Taylor, Herman A., Jr. Skelton, Thomas N. Mosley, Thomas H., Jr. TI Echocardiographic left ventricular mass index predicts incident stroke in African Americans - Atherosclerosis risk in communities (ARIC) study SO STROKE LA English DT Article DE African American; echocardiography; left ventricular mass; stroke ID CARDIOVASCULAR HEALTH; BLOOD-PRESSURE; FOLLOW-UP; PROGNOSTIC IMPLICATIONS; ESSENTIAL-HYPERTENSION; ISCHEMIC-STROKE; ELDERLY COHORT; ARTERY DISEASE; HEART-DISEASE; HYPERTROPHY AB Background and Purpose - Despite theories that link stroke to left ventricular mass, few large, population- based studies have examined the predictive value of echocardiographically derived left ventricular mass index ( LVMI) to incident stroke in African Americans. Methods - Participants in the Jackson cohort of the Atherosclerotic Risk in Communities study have had extensive baseline evaluations, have undergone echocardiography during the third examination ( 1993 - 1995), and have been followed up for incident cardiovascular disease including ischemic stroke. Results - The study population consisted of 1792 participants, of whom 639 ( 35.7%) were men and the mean +/- SD age was 58.8 +/- 5.7 years. Compared with those without ischemic stroke, those with ischemic stroke had a higher frequency of hypertension ( 85.6% vs 58.7%) and diabetes ( 46.9% vs 21.0%). Left ventricular hypertrophy was more prevalent in those with stroke ( 62.2% vs 38.6%). During a median follow- up of 8.8 years, 98 incident strokes occurred ( 6.5 per 1000 person- years). LVMI was independently associated with stroke after adjusting for age, sex, hypertension, systolic blood pressure, smoking, diabetes, total to HDL cholesterol ratio, body mass index, and low left ventricular ejection fraction ( adjusted hazard ratio per 10 g/ m(2.7) increment of LVMI = 1.15; 95% CI, 1.02 to 1.28). The relation remained statistically significant after adding left atrial size and mitral annular calcification to the multivariable model. Conclusions - In this large, population- based African American cohort, we found that echocardiographic LVMI was an independent predictor of incident ischemic stroke even after taking into account traditional clinical risk factors. C1 Univ Mississippi, Med Ctr, Dept Med, Jackson Heart Study, Jackson, MS 39216 USA. NHLBI, Jackson Hearth Study, Jackson, MS USA. RP Fox, ER (reprint author), Univ Mississippi, Med Ctr, Dept Med, Jackson Heart Study, 2500 N State St, Jackson, MS 39216 USA. EM efox@medicine.umsmed.edu FU NHLBI NIH HHS [N01 HC095171, N01HC55019, N01HC55016, N01HC95172, N01-HC-95172, N01-HC-55015, N01HC95170, N01-HC-55022, N01HC55015, N01 HC095170, N01 HC055016, N01 HC055018, N01-HC-95170, N01-HC-55018, N01HC55018, N01HC55021, N01-HC-55016, N01-HC-95171, N01HC55020, N01 HC055019, N01HC55022, N01-HC-55020, N01 HC055015, N01-HC-55019, N01HC95171, N01-HC-55021] NR 37 TC 18 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2007 VL 38 IS 10 BP 2686 EP 2691 DI 10.1161/STROKEAHA.107.485425 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 213VJ UT WOS:000249694900013 PM 17761924 ER PT J AU Phillips, SJ Dai, D Mitnitski, A Gubitz, GJ Johnston, KC Koroshetz, WJ Furie, KL Black, S Heiselman, DE AF Phillips, Stephen J. Dai, Dingwei Mitnitski, Arnold Gubitz, Gordon J. Johnston, Karen C. Koroshetz, Walter J. Furie, Karen L. Black, Sandra Heiselman, Darell E. CA GAIN Americas Investigators TI Clinical diagnosis of Lacunar stroke in the first 6 hours after symptom onset - Analysis of data from the glycine antagonist in neuroprotection (GAIN) Americas trial SO STROKE LA English DT Article DE lacunar infarction; stroke assessment; stroke classification; stroke outcome ID ACUTE ISCHEMIC-STROKE; SCALE RANDOMIZED EVIDENCE; ACUTE CEREBRAL INFARCTION; DIFFUSION-WEIGHTED MRI; COMPUTED-TOMOGRAPHY; CLASSIFICATION; HYPOTHESIS; COMMUNITY; ACCURACY; VALIDITY AB Background and Purpose - Although the pathophysiological heterogeneity of stroke may be highly relevant to the development of acute-phase therapies, discriminating between ischemic stroke subtypes soon after onset remains a challenge. We conducted a study of the accuracy of a clinical diagnosis of lacunar stroke in the first 6 hours after symptom onset. Methods - We analyzed data from 1367 patients in the Glycine Antagonist In Neuroprotection (GAIN) Americas trial. The Trial of ORG10172 in Acute Stroke Treatment (TOAST) category " small vessel (lacunar)" disease at day 7 or at hospital discharge was used as the reference standard to determine the accuracy of a diagnosis of a lacunar stroke made within 6 hours of symptom onset using the Oxfordshire Community Stroke Project (OCSP) classification " LACS." Outcome was analyzed by comparing the proportions of patients classified as " LACS" at baseline or " small vessel (lacunar)" at 7 days who were dead or dependent at 3 months. Results - The positive predictive value of an OCSP diagnosis of a lacunar stroke was 76% (95% CI: 69% to 81%; sensitivity 64% [95% CI: 58% to 70%]; specificity 96% [95% CI: 95% to 97%]; negative predictive value 93% [95% CI: 92% to 94%]; accuracy 91% [95% CI: 89% to 92%]). The 3-month outcomes of patients classified as either OCSP " LACS" within 6 hours of onset or TOAST " small vessel (lacunar)" at 7 days were not significantly different. Conclusions - An OCSP LACS diagnosis made within 6 hours of stroke onset is reasonably predictive of a final diagnosis of " small vessel (lacunar)" disease made using TOAST criteria and has a similar relationship to outcome at 3 months. C1 Dalhousie Univ, Queen Elizabeth II Hlt Sci Ctr, Halifax, NS, Canada. Dalhousie Univ, Dept Med, Halifax, NS, Canada. Dalhousie Univ, Dept Epidemiol & Community Hlth, Halifax, NS, Canada. Univ Virginia, Charlottesville, VA USA. NINDS, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Toronto, Toronto, ON, Canada. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. Akron Gen Med Ctr, Akron, OH USA. RP Phillips, SJ (reprint author), Div Neurol, Halifax Infirmary Room 3831,1796 Summer St, Halifax, NS B3H 3A7, Canada. EM stephen.phillips@dal.ca OI Black, Sandra/0000-0001-7093-8289 FU NINDS NIH HHS [R01 NS050192, R01 NS050192-02] NR 38 TC 9 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2007 VL 38 IS 10 BP 2706 EP 2711 DI 10.1161/STROKEAHA.107.487744 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 213VJ UT WOS:000249694900016 PM 17717313 ER PT J AU Mears, JA Ray, P Hinshaw, JE AF Mears, Jason A. Ray, Pampa Hinshaw, Jenny E. TI A corkscrew model for dynamin constriction SO STRUCTURE LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; PLECKSTRIN HOMOLOGY DOMAIN; SYNAPTIC VESICLE ENDOCYTOSIS; CRYSTAL-STRUCTURE; GTPASE ACTIVITY; ACIDIC PHOSPHOLIPIDS; MEMBRANE FISSION; COATED PITS; RAT DYNAMIN; SH3 DOMAIN AB Numerous vesiculation processes throughout the eukaryotic cell are dependent on the protein dynamin, a large GTPase that constricts lipid bilayers. We have combined X-ray crystallography and cryo-electron microscopy (cryo-EM) data to generate a coherent model of dynamin-mediated membrane constriction. GTPase and pleckstrin homology domains of dynamin were fit to cryo-EM structures of human dynamin helices bound to lipid in nonconstricted and constricted states. Proteolysis and immunogold labeling experiments confirm the topology of dynamin domains predicted from the helical arrays. Based on the fitting, an observed twisting motion of the GTPase, middle, and GTPase effector domains coincides with conformational changes determined by cryo-EM. We propose a corkscrew model for dynamin constriction based on these motions and predict regions of sequence important for dynamin function as potential targets for future mutagenic and structural studies. C1 NIDDKD, Natl Inst Hlth, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. RP Hinshaw, JE (reprint author), NIDDKD, Natl Inst Hlth, Lab Cell Biochem & Biol, 8 Ctr Dr,MSC 0851, Bethesda, MD 20892 USA. EM jennyh@helix.nih.gov FU Intramural NIH HHS [Z01 DK060100-12] NR 54 TC 69 Z9 71 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD OCT PY 2007 VL 15 IS 10 BP 1190 EP 1202 DI 10.1016/j.str.2007.08.012 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 221NZ UT WOS:000250235900007 PM 17937909 ER PT J AU Selleri, S Ruinio, C Sabatino, M Marincola, FM Wang, E AF Selleri, Silvia Ruinio, Cristiano Sabatino, Marianna Marincola, Francesco M. Wang, Ena TI Tumor microenvironment and the immune response SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID MESSENGER-RNA AMPLIFICATION; REGULATORY T-CELLS; METASTATIC MELANOMA; IN-VIVO; DENDRITIC CELLS; IMMUNOSUPPRESSIVE TREATMENT; PERIPHERAL-BLOOD; GENE-EXPRESSION; HUMAN CANCERS; IMMUNOTHERAPY AB Without clinical information, accurate follow-up, high-quality sample collection, and preservation, scientific conclusions are only based on theoretical assumptions that are unlikely to lead to clinical breakthroughs. In this article we discuss our understanding of the relationship between cancer cells and the host immune response. We emphasize the critical role that future clinical investigations, led by surgical oncologists, may have for the assessment of the validity of the disparate hypotheses so far formulated at the bench side. C1 [Selleri, Silvia; Sabatino, Marianna; Marincola, Francesco M.; Wang, Ena] NIH, Clin Ctr, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bethesda, MD 20892 USA. [Ruinio, Cristiano] Univ Studi Milano, Dept Human Morphol, I-20133 Milan, Italy. RP Wang, E (reprint author), NIH, Clin Ctr, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bldg 10, Bethesda, MD 20892 USA. EM ewang@cc.nih.gov NR 95 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 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD OCT PY 2007 VL 16 IS 4 BP 737 EP + DI 10.1016/j.soc.2007.07.002 PG 19 WC Oncology; Surgery SC Oncology; Surgery GA 243AZ UT WOS:000251768600004 PM 18022542 ER PT J AU Kan, HD Heiss, G Rose, KM Whitsel, E Lurmann, F London, SJ AF Kan, Haidong Heiss, Gerardo Rose, Kathryn M. Whitsel, Eric Lurmann, Fred London, Stephanie J. TI Traffic exposure and lung function in adults: the Atherosclerosis Risk in Communities study SO THORAX LA English DT Article ID URBAN AIR-POLLUTION; PULMONARY-FUNCTION; RESPIRATORY SYMPTOMS; AUTOMOBILE EXHAUST; HOSPITAL ADMISSION; CHILDHOOD ASTHMA; NITROGEN-DIOXIDE; CHILDREN; HEALTH; SMOKING AB Background: Traffic exposure is a major contributor to ambient air pollution for people living close to busy roads. The relationship between traffic exposure and lung function remains inconclusive in adults. Methods: A cross-sectional study was conducted to investigate the association between traffic exposure and lung function in the Atherosclerosis Risk in Communities (ARIC) study, a community based cohort of 15 792 middle aged men and women. Traffic density and distance to major roads were used as measures of traffic exposure. Results: After controlling for potential confounders including demographic factors, personal and neighbourhood level socioeconomic characteristics, cigarette smoking and background air pollution, higher traffic density was significantly associated with lower forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in women. Relative to the lowest quartile of traffic density, the adjusted differences across increasing quartiles were 5.1, -15.4 and -21.5 ml for FEV(1) (p value of linear trend across the quartiles = 0.041) and 1.2, -23.4 and -34.8 ml for FVC (p trend = 0.010). Using distance from major roads as a simpler index of traffic related air pollution exposure, the FEV(1) was -15.7 ml (95% CI -34.4 to 2.9) lower and the FVC was -24.2 ml (95% CI -46.2 to -2.3) lower for women living within 150 m compared with subjects living further away. There was no significant effect of traffic density or distance to major roads on lung function in men. The FEV(1)/FVC ratio was not significantly associated with traffic exposure in either men or women. Conclusions: This is the largest published study of traffic exposure and pulmonary function in adults to date. These results add to growing evidence that chronic exposure to traffic related air pollution may adversely affect respiratory health. C1 Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. Sonoma Technol Inc, Petaluma, CA USA. RP London, SJ (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS [Z01 ES043012-09]; NHLBI NIH HHS [N01-HC-55021, N01 HC55015, N01 HC55016, N01 HC55018, N01 HC55019, N01 HC55020, N01 HC55021, N01 HC55022, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55022]; NIEHS NIH HHS [Z01 ES043012] NR 59 TC 58 Z9 64 U1 1 U2 12 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD OCT PY 2007 VL 62 IS 10 BP 873 EP 879 DI 10.1136/thx.2006.073015 PG 7 WC Respiratory System SC Respiratory System GA 216HE UT WOS:000249868300009 PM 17442705 ER PT J AU Barton, HA Chiu, WA Setzer, RW Andersen, ME Bailer, AJ Bois, FY Dewoskin, RS Hays, S Johanson, G Jones, N Loizou, G MacPhail, RC Portier, CJ Spendiff, M Tan, YM AF Barton, Hugh A. Chiu, Weihsueh A. Setzer, R. Woodrow Andersen, Melvin E. Bailer, A. John Bois, Frederic Y. DeWoskin, Robert S. Hays, Sean Johanson, Gunnar Jones, Nancy Loizou, George MacPhail, Robert C. Portier, Christopher J. Spendiff, Martin Tan, Yu-Mei TI Characterizing uncertainty and variability in physiologically based pharmacokinetic models: State of the science and needs for research and implementation SO TOXICOLOGICAL SCIENCES LA English DT Article DE physiologically based pharmacokinetic modeling; uncertainty; population variability; nonlinear modeling; risk assessment; Bayesian models ID RISK-ASSESSMENT; SENSITIVITY-ANALYSIS; INHALATION EXPOSURE; METABOLISM; TOXICOKINETICS; COEFFICIENTS; SIMULATION; DIAZEPAM; EXERCISE; CHLORIDE AB Physiologically based pharmacokinetic (PBPK) models are used in mode-of-action based risk and safety assessments to estimate internal dosimetry in animals and humans. When used in risk assessment, these models can provide a basis for extrapolating between species, doses, and exposure routes or for justifying nondefault values for uncertainty factors. Characterization of uncertainty and variability is increasingly recognized as important for risk assessment; this represents a continuing challenge for both PBPK modelers and users. Current practices show significant progress in specifying deterministic biological models and nondeterministic (often statistical) models, estimating parameters using diverse data sets from multiple sources, using them to make predictions, and characterizing uncertainty and variability of model parameters and predictions. The International Workshop on Uncertainty and Variability in PBPK Models, held 31 Oct-2 Nov 2006, identified the state-of-the-science, needed changes in practice and implementation, and research priorities. For the short term, these include (1) multidisciplinary teams to integrate deterministic and nondeterministic/statistical models; (2) broader use of sensitivity analyses, including for structural and global (rather than local) parameter changes; and (3) enhanced transparency and reproducibility through improved documentation of model structure(s), parameter values, sensitivity and other analyses, and supporting, discrepant, or excluded data. Longer-term needs include (1) theoretical and practical methodological improvements for nondeterministic/statistical modeling; (2) better methods for evaluating alternative model structures; (3) peer-reviewed databases of parameters and covariates, and their distributions; (4) expanded coverage of PBPK models across chemicals with different properties; and (5) training and reference materials, such as cases studies, bibliographies/glossaries, model repositories, and enhanced software. The multidisciplinary dialogue initiated by this Workshop will foster the collaboration, research, data collection, and training necessary to make characterizing uncertainty and variability a standard practice in PBPK modeling and risk assessment. Key Words: physiologically based pharmacokinetic modeling; uncertainty; population variability; nonlinear modeling; risk assessment; Bayesian models. C1 US EPA, Natl Ctr Computat Toxicol, ORD, Res Triangle Pk, NC 27711 USA. US EPA, ORD, Natl Ctr Environm Assessment, Washington, DC 20460 USA. Hamner Inst Hlth Sci, Res Triangle Pk, NC 27709 USA. Miami Univ, Oxford, OH 45056 USA. Unite Toxicol Expt, Natl Environm Ind & Risques, F-60550 Vernuil En Halatte, France. Summit Toxicol, Lyons, CO 80540 USA. Karolinska Inst, Stockholm, Sweden. EC R Inc, Chapel Hill, NC 27517 USA. Hlth & Safety Lab, Buxton S17 9JN, England. US EPA, ORD, Natl Hlth & Environm Effects Lab, Res Triangle Pk, NC 27711 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Barton, HA (reprint author), US EPA, Natl Ctr Computat Toxicol, ORD, B205-01,109 TW Alexander Dr, Res Triangle Pk, NC 27711 USA. EM barton.hugh@epa.gov RI Portier, Christopher/A-3160-2010; Bois, Frederic/E-9241-2012; OI Portier, Christopher/0000-0002-0954-0279; Bois, Frederic/0000-0002-4154-0391; Andersen, Melvin/0000-0002-3894-4811; Johanson, Gunnar/0000-0002-8759-9567 FU Intramural NIH HHS NR 40 TC 64 Z9 64 U1 0 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2007 VL 99 IS 2 BP 395 EP 402 DI 10.1093/toxsci/kfm100 PG 8 WC Toxicology SC Toxicology GA 216NW UT WOS:000249885900003 PM 17483121 ER PT J AU Bell, DR Clode, S Fan, MQ Fernandes, A Foster, PMD Jiang, T Loizou, G MacNicoll, A Miller, BG Rose, M Tran, L White, S AF Bell, David R. Clode, Sally Fan, Ming Qi Fernandes, Alwyn Foster, Paul M. D. Jiang, Tao Loizou, George MacNicoll, Alan Miller, Brian G. Rose, Martin Tran, Lang White, Shaun TI Relationships between tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mRNAs, and toxicity in the developing male Wistar(Han) rat SO TOXICOLOGICAL SCIENCES LA English DT Article DE dioxin; sperm; developmental; toxicity; balanopreputial separation; puberty ID SPRAGUE-DAWLEY RATS; LONG-EVANS RATS; DIOXIN-LIKE COMPOUNDS; EQUIVALENCY FACTORS; AH RECEPTOR; EXPOSURE; MOUSE; MILK; TOXICOKINETICS; DIBENZOFURANS AB We compared the effects of a single acute dose, or chronic fetal exposure, to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the male reproductive system of the Wistar(Han) rat. Tissue samples were taken from dams on gestation day (GD)16 and GD21, and from offspring on postnatal days (PND)70 and 120. Steady-state concentration of TCDD was demonstrated in the chronic study: body burdens were comparable in both studies. Fetal TCDD concentrations were comparable after acute and chronic exposure, and demonstrate more potent toxicity after chronic versus acute dosing. In maternal liver, cytochrome P450 (CYP)1A1 and CYP1A2 RNA were induced. In fetus, there was induction of both CYP1A1 and CYP1A2 RNA at medium and high doses, but inadequate evidence for induction at low dose in either study. The low level induction of CYP1A1 RNA at low dose in fetus argues against AhR activation in fetus as a mechanism of toxicity of TCDD in causing delay in balanopreputial separation (BPS), and the greater induction of CYP1A1 RNA in PND70 offspring liver from chronically-dosed dams suggests that lactational transfer of TCDD is crucial to this toxicity. These data characterize the maternal and fetal disposition of TCDD, induction of CYP1A1 RNA as a measure of AhR activation, and suggest that lactational transfer of TCDD determines the difference in delay in BPS between the two studies. C1 Univ Nottingham, Sch Biol, Nottingham NG7 2RD, England. Covance Labs Ltd, Harrogate HG3 1PY, N Yorkshire, England. NIEHS, Res Triangle Pk, NC 27709 USA. Hlth & Safety Lab, Buxton SK17 9JN, Derby, England. Cent Sci Lab Environm Food & Hlth, York YO41 ILZ, N Yorkshire, England. Inst Occupat Med, Edinburgh EH14 4AP, Midlothian, Scotland. RP Bell, DR (reprint author), Univ Nottingham, Sch Biol, Univ Pk, Nottingham NG7 2RD, England. EM david.bell@nottingham.ac.uk OI Rose, Martin/0000-0001-7071-180X NR 41 TC 18 Z9 18 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2007 VL 99 IS 2 BP 591 EP 604 DI 10.1093/toxsci/kfm179 PG 14 WC Toxicology SC Toxicology GA 216NW UT WOS:000249885900021 PM 17656490 ER PT J AU Horn, TL Torres, KEO Naylor, JM Cwik, MJ Detrisac, CJ Kapetanovic, IM Lubet, RA Crowell, JA McCormick, DL AF Horn, Thomas L. Torres, Karen E. O. Naylor, Jennifer M. Cwik, Michael J. Detrisac, Carol J. Kapetanovic, Izet M. Lubet, Ronald A. Crowell, James A. McCormick, David L. TI Subchronic toxicity and toxicogenomic evaluation of tamoxifen citrate plus bexarotene in female rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE tamoxifen; bexarotene; preclinical toxicity; toxicogenomics; rat; chemoprevention ID T-CELL LYMPHOMA; ESTROGEN-RECEPTOR MODULATOR; SELECTIVE LIGAND LGD1069; UNION-OF-PHARMACOLOGY; MAMMARY-CARCINOMA; BREAST-CANCER; 9-CIS-RETINOIC ACID; ORAL BEXAROTENE; TRANSGENIC MICE; CLINICAL-TRIAL AB Tamoxifen (TAM) is a nonsteroidal antiestrogen that prevents estrogen receptor-positive breast cancer in rodents and humans. Bexarotene (BEX), a selective agonist for retinoid X receptors, inhibits mammary carcinogenesis in rodents. The present study was conducted to support the preclinical development of TAM (tamoxifen citrate) 1 BEX for use in breast cancer chemoprevention, and to investigate the influence of these agents on hepatic gene expression. Female CD rats (20 per group) received daily oral (gavage) exposure to TAM (0 or 60 mu g/kg/day) and/or BEX (0, 5, 15, or 45 mg/kg/day) for a minimum of 90 days. BEX induced mild, dose-related anemia and dose-related increases in serum alkaline phosphatase, cholesterol, triglycerides, and calcium levels, and increased platelet counts. TAM had no biologically significant effect on any clinical pathology parameter and did not alter the effects of BEX on these endpoints. Microscopic alterations induced by BEX included epidermal hyperplasia, hyperkeratosis (stomach), and cytoplasmic clearing (liver). Microscopic changes in TAM-treated rats were limited to mucous cell hypertrophy in the cervix and vagina. The toxicity of administration of the combination of TAM + BEX can generally be predicted on the basis of the toxicity of each drug as a single agent. BEX induced dose-related alterations in the expression of several genes involved in steroid, drug, and/or fatty acid metabolism; TAM did not alter these effects of BEX. Differential expression of genes involved in drug and lipid metabolism may underlie the observed effects of BEX on cholesterol and triglyceride levels and its effects on liver histology. C1 IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA. Charles River Labs Inc, Pathol Assoc, Chicago, IL 60612 USA. NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP McCormick, DL (reprint author), IIT, Res Inst, Life Sci Grp, 10 West 35th St, Chicago, IL 60616 USA. EM dmccormick@iitri.org FU NCI NIH HHS [N01-CN-35121, N01-CN-43304] NR 40 TC 4 Z9 4 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2007 VL 99 IS 2 BP 612 EP 627 DI 10.1093/toxsci/kfm181 PG 16 WC Toxicology SC Toxicology GA 216NW UT WOS:000249885900023 PM 17630414 ER PT J AU Karacsonyi, C Miguel, AS Puertollano, R AF Karacsonyi, Claudia Miguel, Anitza San Puertollano, Rosa TI Mucolipin-2 localizes to the Arf6-associated pathway and regulates recycling of GPI-APs SO TRAFFIC LA English DT Article DE Arf6; GPI; MCOLN2; MLIV; mucolipin; TRP ID PLASMA-MEMBRANE; ANCHORED PROTEINS; ARF6; ENDOSOMES; IV; CLATHRIN; ACCUMULATION; TRAFFICKING; FIBROBLASTS; ENDOCYTOSIS AB In mammals, the mucolipin family includes three members mucolipin-1, mucolipin-2, and mucolipin-3 (MCOLN1-3). While mutations in MCOLN1 and MCOLN3 have been associated with mucolipidosis type IV and the varitint-waddler mouse phenotype, respectively, little is known about the function and cellular distribution of MCOLN2. Here we show that MCOLN2 traffics via the Arf6-associated pathway and colocalizes with major histocompatibility protein class I (MHCI) and glycosylphosphatidylinositol-anchored proteins (GPI-APs), such as CD59 in both vesicles and long tubular structures. Expression of a constitutive active Arf6 mutant, or activation of endogenous Arf6 by transfection with EFA6 or treatment with aluminum fluoride, caused accumulation of MCOLN2 in enlarged vacuoles that also contain MHCI and CD59. In addition, overexpression of MCOLN2 promoted efficient activation of Arf6 in vivo, thus suggesting that MCOLN2 may have a role in the traffic of cargo through the Arf6-associated pathway. In support of this we found that overexpression of a MCOLN2 inactive mutant decreases recycling of CD59 to the plasma membrane. Therefore, our results indicate that MCOLN2 localizes to the Arf6-regulated pathway and regulates sorting of GPI-APs. C1 NHLBI, Lab Cell Biol, NIH, Bethesda, MD 20892 USA. RP Puertollano, R (reprint author), NHLBI, Lab Cell Biol, NIH, Bethesda, MD 20892 USA. EM puertolr@mail.nih.gov FU Intramural NIH HHS NR 40 TC 44 Z9 44 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-9219 J9 TRAFFIC JI Traffic PD OCT PY 2007 VL 8 IS 10 BP 1404 EP 1414 DI 10.1111/j.1600-0854.2007.00619.x PG 11 WC Cell Biology SC Cell Biology GA 210DG UT WOS:000249436300010 PM 17662026 ER PT J AU Lefrancois, P McCormick, PJ AF Lefrancois, Stephane McCormick, Peter J. TI The Arf GEF GBF1 is required for GGA recruitment to golgi membranes SO TRAFFIC LA English DT Article DE Arf1; GBF1; GGAs; golgi; lysosomes ID NUCLEOTIDE EXCHANGE FACTOR; SULFATED GLYCOPROTEIN-1 PROSAPOSIN; PROTEIN COMPLEX; COAT PROTEINS; ENDOSOME TRANSPORT; VHS DOMAINS; TRAFFICKING; FAMILY; LOCALIZATION; EXPRESSION AB The lysosomal trafficking of the mannose 6-phosphate receptor and sortilin require that the Golgi-localized, gamma-ear-containing, ADP ribosylation factor (Arf)-binding proteins (GGAs) be recruited to Golgi membranes where they bind a signal in the cytosolic tail of the receptors and recruit clathrin to form trafficking vesicles. GGA recruitment to membranes requires Arf1, a protein that cycles between a GDP-bound inactive state and GTP-bound active state. The guanine nucleotide exchange factors (GEFs) promote the formation of Arf-GTP, while the GTPase activating proteins induce hydrolysis of GTP to GDP. We provide evidence that the GEF, GBF1, colocalizes with the GGAs and interacts with the GGAs. Depletion of GBF1 or expression of an inactive mutant prevents recruitment of the GGAs to Golgi membranes and results in the improper sorting of cargo. In summary, we show that GBF1 is required for GGA recruitment to Golgi membranes and plays a role in the proper processing and sorting of lysosomal cargo. C1 Univ Montreal, Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada. NCI, Lab Cellular Oncol, Ctr Canc Res, Bethesda, MD 20892 USA. RP Lefrancois, P (reprint author), Univ Montreal, Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada. EM stephane.lefrancois@umontreal.ca RI McCormick, Peter/E-7387-2012 OI McCormick, Peter/0000-0002-2225-5181 NR 27 TC 8 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-9219 J9 TRAFFIC JI Traffic PD OCT PY 2007 VL 8 IS 10 BP 1440 EP 1451 DI 10.1111/j.1600-0854.2007.00623.x PG 12 WC Cell Biology SC Cell Biology GA 210DG UT WOS:000249436300013 ER PT J AU Kleinman, SH Glynn, SA Lee, TH Tobler, L Montalvo, L Todd, D Kiss, JE Shyamala, V Busch, MP AF Kleinman, Steven H. Glynn, Simone A. Lee, Tzong-Hae Tobler, Leslie Montalvo, Leilani Todd, Deborah Kiss, Joseph E. Shyamala, Venkatakrishna Busch, Michael P. CA Natl Heart Lung Blood Inst Retrovi TI Prevalence and quantitation of parvovirus B19 DNA levels in blood donors with a sensitive polymerase chain reaction screening assay SO TRANSFUSION LA English DT Article ID B19 DNA; HIGH-PURITY; TRANSFUSION; INFECTION; TRANSMISSION; INDIVIDUALS; PERSISTENCE; RECIPIENTS; EXPOSURE; PATIENT AB Blood donor parvovirus B19 DNA prevalence with sensitive nucleic acid test assays has recently been demonstrated to be higher than that found with assays designed to detect high viral titers in the plasma manufacturing sector. Stored plasma aliquots from 5020 donations collected between 2000 and 2003 at seven US blood centers were tested. Testing was performed with a real-time B19 DNA polymerase chain reaction (PCR; TaqMan, Applied Biosystems) assay with a 50 percent limit of detection (LOD) of 1.6 IU per mL (95% confidence interval [CI], 1.2-2.1 IU/mL) and a 95 percent LOD of 16.5 IU per mL (95% CI, 10.6-33.9 IU/mL). Confirmation and quantitation of B19 DNA was accomplished by retesting of two additional subaliquots. Confirmed-positive specimens were tested for the presence of anti-B19 immunoglobulin M (IgM) and IgG with FDA-licensed assays. B19 DNA prevalence was 0.88 percent (95% CI, 0.64%-1.2%). Among the 23 donations with B19 DNA titers of at least 20 IU per mL, the median DNA concentration was 105 IU per mL with an interquartile range of 42 to 481 IU per mL; the highest value was 1869 IU per mL. All B19 DNA-positive donations were positive for the presence of IgG and 10 (23%) were also positive for the presence of IgM; IgM seropositivity was associated with increasing DNA levels (p = 0.0013). Low-level B19 DNA was detected in nearly 1 percent of donations. The 23 percent of DNA-positive donations with both IgM and IgG B19 antibody most likely represent acute resolving infection, whereas those with IgG but no IgM are most consistent with a more chronic and possibly persistent phase of B19 infection. C1 Blood Syst Res Inst, San Francisco, CA USA. Inst Transfus Med, Pittsburgh, PA USA. Chiron Corp, Emeryville, CA USA. Digene Corp, Gaithersburg, MD USA. NHLBI, Bethesda, MD 20892 USA. RP Kleinman, SH (reprint author), 1650 Res Blvd, Rockville, MD 20850 USA. FU NHLBI NIH HHS [N01 HB 97077, N01 HB 47175, N01 HB 57181, N01 HB 97078, N01 HB 97079, N01 HB 97080, N01 HB 97081, N01 HB 97082] NR 26 TC 47 Z9 48 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2007 VL 47 IS 10 BP 1756 EP 1764 DI 10.1111/j.1537-2995.2007.01341.x PG 9 WC Hematology SC Hematology GA 213KI UT WOS:000249665300006 PM 17880600 ER PT J AU Stroncek, DF Fadeyi, E Adams, S AF Stroncek, David F. Fadeyi, Emmanuel Adams, Sharon TI Leukocyte antigen and antibody detection assays: Tools for assessing and preventing pulmonary transfusion reactions SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID ACUTE LUNG INJURY; POLYMERASE-CHAIN-REACTION; SEQUENCE-SPECIFIC PRIMERS; POLYCYTHEMIA RUBRA VERA; SSOP-LUMINEX METHOD; HLA CLASS-I; GENE-FREQUENCIES; RECEPTOR-III; NEONATAL NEUTROPENIA; MOLECULAR-BASIS AB Antibodies to neutrophil and HLA antigens can cause pulmonary transfusion reactions, and in some cases acute lung injury. When evaluating cases of pulmonary transfusion reactions, it is often necessary to test donors for neutrophil and HLA antibodies and also type the recipient for neutrophil and HLA antigens. A variety of enzyme-linked immunosorbent assay (ELISA) and flow cytometry-based solid phase assays are available to test for HLA class I and class II antibodies, but not neutrophil antibodies. Screening for neutrophil antibodies requires the preparation of panels of fresh neutrophils and testing in agglutination, immunofluorescence, or flow cytometry assays. Genotyping of HLA class I and II antigens is performed with a variety of sequence- specific primers, sequenced-specific oligonucleoticle probe, and sequence-based typing assays. Neutrophil-specific antigens HNA-1a, -1b, -1c, -4a, and -5a can be genotyped, but not HNA-2a or -3a. Phenotyping of HNA2a can be performed with CD177 monoclonal antibodies, but the gene encoding HNA-3a has not been identified, and the genomic basis for the HNA-2a-negative phenotype is not known. In conclusion, patients and donors involved with pulmonary transfusion reactions can be quickly typed for HLA antigens and tested for HLA antibodies, but testing for neutrophil antibodies and antigens requires the use of a reference laboratory. Published by Elsevier Inc. C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, 10 Ctr Dr,MSC-1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. EM dstroncek@mail.cc.nih.gov FU Intramural NIH HHS [Z01 CL002095-11] NR 66 TC 17 Z9 17 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 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD OCT PY 2007 VL 21 IS 4 BP 273 EP 286 DI 10.1016/j.tmrv.2007.05.003 PG 14 WC Hematology SC Hematology GA 219BH UT WOS:000250059200001 PM 17900489 ER PT J AU Alvarez, SE Milstien, S Spiegel, S AF Alvarez, Sergio E. Milstien, Sheldon Spiegel, Sarah TI Autocrine and paracrine roles of sphingosine-1-phosphate SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID EPIDERMAL-GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; SPHINGOSINE KINASE-1 EXPRESSION; STEROIDOGENIC FACTOR-I; PROGRAMMED CELL-DEATH; BREAST-CANCER CELLS; FC-EPSILON-RI; ENDOTHELIAL-CELLS; MAST-CELLS; CALCIUM MOBILIZATION AB Sphingosine-1-phosphate [W) is a bioactive sphingolipid metabolite that has been implicated in many biological processes, including cell migration, survival, proliferation, angiogenesis and immune and allergic responses. S1P levels inside cells are regulated tightly by the balance between its synthesis by sphingosine kinases and degradation by S1P Iyases and S1P phosphatases. Activation of sphingosine kinase by any of a variety of agonists increases S1P levels, which in turn can function intracellularly as a second messenger or in an autocrine and/or paracrine fashion to activate and signal through S1P receptors present on the surface of the cell. This review summarizes recent findings on the roles of S1P as a mediator of the actions of cytokines, growth factors and hormones. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM sspiegel@vcu.edu FU Intramural NIH HHS; NCI NIH HHS [R01CA61774]; NIAID NIH HHS [R01AI50094]; NIGMS NIH HHS [R37GM043880] NR 85 TC 171 Z9 175 U1 1 U2 12 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD OCT PY 2007 VL 18 IS 8 BP 300 EP 307 DI 10.1016/i.tem.2007.07.005 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 227DD UT WOS:000250636500002 PM 17904858 ER PT J AU Carey, MA Card, JW Voltz, JW Arbes, SJ Germolec, DR Korach, KS Zeldin, DC AF Carey, Michelle A. Card, Jeffrey W. Voltz, James W. Arbes, Samuel J., Jr. Germolec, Dori R. Korach, Kenneth S. Zeldin, Darryl C. TI It's all about sex: gender, lung development and lung disease SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID OBSTRUCTIVE PULMONARY-DISEASE; ESTROGEN-RECEPTOR-ALPHA; HORMONE REPLACEMENT THERAPY; ADULT-ONSET ASTHMA; AIRWAY HYPERRESPONSIVENESS; HUMAN-PAPILLOMAVIRUS; MENSTRUAL-CYCLE; CANCER; WOMEN; MICE AB Accumulating evidence suggests that gender affects the incidence, susceptibility and severity of several lung diseases. Gender also influences lung development and physiology. Data from both human and animal studies indicate that sex hormones might contribute to disease pathogenesis or serve as protective factors, depending on the disease involved. In this review, the influence of gender and sex hormones on lung development and pathology will be discussed, with specific emphasis on pulmonary fibrosis, asthma and cancer. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Zeldin, DC (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU Intramural NIH HHS [Z01 ES101885-03] NR 70 TC 103 Z9 104 U1 2 U2 10 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD OCT PY 2007 VL 18 IS 8 BP 308 EP 313 DI 10.1016/j.tem.2007.08.003 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 227DD UT WOS:000250636500003 PM 17764971 ER PT J AU Dufau, ML Tsai-Morris, CH AF Dufau, Maria L. Tsai-Morris, Chon-Hwa TI Gonadotropin-regulated testicular helicase (GRTH/DDX25): an essential regulator of spermatogenesis SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID MALE GERM-CELLS; DEAD-BOX PROTEINS; RNA HELICASE; ANDROGEN RECEPTOR; CHROMATOID BODY; MESSENGER-RNAS; TRANSLATION INITIATION; RAT TESTIS; MICRORNA PATHWAY; DROSOPHILA-VASA AB Male germ-cell maturation is orchestrated by a cascade of temporally regulated factors. Gonadotropin-regulated testicular helicase (GRTH/DDX25), a target of gonadotropin and androgen action, is a post-transcriptional regulator of key spermatogenesis genes. Male mice lacking GRTH are sterile, with spermatogenic arrest owing to the failure of round spermatids to elongate. GIRTH is a component of messenger ribonucleoprotein particles, which transport target mRNAs to the cytoplasm for storage in chromatoid bodies of spermatids; these messages are released for translation during spermatogenesis. GIRTH is also found in polyribosomes, where it regulates the translation of mRNAs encoding spermatogenesis factors. The association of GRTH mutations with male infertility underlines the importance of GRTH as a central, post-transcriptional regulator of spermatogenesis. C1 NICHHD, Sect Mol Endocrinol, NIH, Bethesda, MD 20892 USA. NICHHD, Res Reprod Branch, NIH, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), NICHHD, Sect Mol Endocrinol, NIH, Bethesda, MD 20892 USA. EM dufaum@mail.nih.gov NR 63 TC 32 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD OCT PY 2007 VL 18 IS 8 BP 314 EP 320 DI 10.1016/j.tem.2007.09.001 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 227DD UT WOS:000250636500004 PM 17889551 ER PT J AU Bernstein, HD AF Bernstein, Harris D. TI Are bacterial 'autotransporters" really transporters? SO TRENDS IN MICROBIOLOGY LA English DT Review ID TOXIN-B-SUBUNIT; OUTER-MEMBRANE; ESCHERICHIA-COLI; TRANSLOCATOR DOMAIN; EXTRACELLULAR TRANSPORT; SERINE-PROTEASE; IGA PROTEASE; SECRETION; PROTEINS; ADHESIN AB Autotransporters are bacterial outer membrane proteins that consist of a large N-terminal extracellular domain ('passenger domain') and a C-terminal beta-barrel domain ['beta domain'). The beta domain was originally proposed to function as a channel that transports its own passenger domain across the outer membrane. Results of recent structural, biochemical and molecular genetic studies, however, have challenged this idea. Here I describe an alternative model in which translocation of the passenger domain is mediated by an exogenous factor (possibly a newly identified factor necessary for assembly of outer membrane proteins called 'Omp85/YaeT'), whereas the beta domain only targets the protein to the outer membrane and serves as a membrane anchor. C1 NIDDKD, NIH, Genet Biochem Branch, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDKD, NIH, Genet Biochem Branch, Bldg 5,Room 201,5 Mem Dr, Bethesda, MD 20892 USA. EM harris_bernstein@nih.gov FU Intramural NIH HHS NR 39 TC 45 Z9 45 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD OCT PY 2007 VL 15 IS 10 BP 441 EP 447 DI 10.1016/j.tim.2007.09.007 PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 236VW UT WOS:000251332500003 PM 17935998 ER PT J AU Schmitt, JE Eyler, LT Giedd, JN Kremen, WS Kendler, KS Neale, MC AF Schmitt, J. Eric Eyler, Lisa T. Giedd, Jay N. Kremen, William S. Kendler, Kenneth S. Neale, Michael C. TI Review of twin and family studies on neuroanatomic phenotypes and typical neurodevelopment SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Review ID HUMAN BRAIN STRUCTURE; OLDER MALE TWINS; MONOZYGOTIC TWINS; GENETIC INFLUENCES; CORPUS-CALLOSUM; WORKING-MEMORY; SCHIZOPHRENIA; VOLUMES; SIZE; MORPHOLOGY AB T his article reviews the extant twin studies employing magnetic resonance imaging data (MRI), with an emphasis on studies of population-based samples. There have been approximately 75 twin reports using MRI, with somewhat under half focusing on typical brain structure. Of these, most are samples of adults. For large brain regions such as lobar volumes, the heritabilities of large brain volumes are consistently high, with genetic factors accounting for at least half of the phenotypic variance. The role of genetics in generating individual differences in the volumes of small brain regions is less clear, mostly due to a dearth of information, but rarely because of disagreement between studies. Multivariate analyses show strong genetic relationships between brain regions. Cortical regions involved in language, executive function, and emotional regulation appear to be more heritable than other areas. Studies of brain shape also show significant, albeit lower, genetic effects on population variance. Finally, there is evidence of significant genetically mediated relationships between intelligence and brain structure. At present, the majority of twin imaging studies are limited by sample sizes small by the standards of behavioral genetics; nevertheless the literature at present represents a pioneering effort in the pursuit of answers to many challenging neurobiological questions. C1 Virginia Commonwealth Univ, Med Coll Virginia, Virginia Inst Psychiat & Behavioral Genet, Richmond, VA 23298 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. VA San Diego Hlth Care Syst, MIRECC Program, VISN 22, San Diego, CA USA. NIMH, Pediat Imaging Unit, Bethesda, MD 20892 USA. Univ Calif San Diego, Ctr Behavioral Genom, San Diego, CA USA. RP Schmitt, JE (reprint author), Virginia Inst Psychiat & Behav Genet, 800 E Leigh St,POB98003, Richmond, VA USA. EM schmittje@vcu.edu RI Giedd, Jay/A-3080-2008; Neale, Michael/B-1418-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU NIA NIH HHS [R01 AG018386, AG-18384, AG-18386, AG-22381, AG-22982, R01 AG018384, R01 AG022381, R01 AG022982]; NIDA NIH HHS [DA-18673, R01 DA018673, R37 DA018673]; NIMH NIH HHS [MH-20030, MH-65322, R01 MH065322, T32 MH020030] NR 53 TC 54 Z9 54 U1 1 U2 10 PU AUSTRALIAN ACAD PRESS PI BOWEN HILLS PA 32 JEAYS ST, BOWEN HILLS, QLD 4006, AUSTRALIA SN 1832-4274 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD OCT PY 2007 VL 10 IS 5 BP 683 EP 694 DI 10.1375/twin.10.5.683 PG 12 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 222CW UT WOS:000250274700001 PM 17903108 ER PT J AU Romero, R AF Romero, Roberto TI Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Editorial Material ID FACTOR-KAPPA-B; HUMAN MYOMETRIAL CELLS; SMOOTH-MUSCLE-CELLS; AMNIOTIC-FLUID INTERLEUKIN-6; ASSISTED REPRODUCTION CYCLES; RANDOMIZED CONTROLLED-TRIAL; LIGHT-INDUCED FLUORESCENCE; SPERM ACROSOME REACTION; RECEPTOR MESSENGER-RNA; IN-VITRO FERTILIZATION C1 NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 237 TC 47 Z9 49 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD OCT PY 2007 VL 30 IS 5 BP 675 EP 686 DI 10.1002/uog.5174 PG 12 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 228MB UT WOS:000250732900002 PM 17899585 ER PT J AU Kusanovic, JP Espinoza, J Romero, R Goncalves, LF Nien, JK Soto, E Khalek, N Camacho, N Hendler, I Mittal, P Friel, LA Gotsch, F Erez, O Than, NG Mazaki-Tovi, S Schoen, ML Hassan, SS AF Kusanovic, J. P. Espinoza, J. Romero, R. Goncalves, L. F. Nien, J. K. Soto, E. Khalek, N. Camacho, N. Hendler, I. Mittal, P. Friel, L. A. Gotsch, F. Erez, O. Than, N. G. Mazaki-Tovi, S. Schoen, M. L. Hassan, S. S. TI Clinical significance of the presence of amniotic fluid 'sludge' in asymptomatic patients at high risk for spontaneous preterm delivery SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE amniotic fluid 'sludge'; chorioamnionitis; funisitis; microbial invasion of the amniotic cavity; preterm labor; preterm premature rupture of membranes; short cervix; spontaneous preterm delivery; transvaginal ultrasound ID UREAPLASMA-UREALYTICUM; INTRAAMNIOTIC INFECTION; TRANSVAGINAL ULTRASONOGRAPHY; CHORIOAMNION INFECTION; INTRAUTERINE INFECTION; INFLAMMATORY LESIONS; INTACT MEMBRANES; CERVICAL LENGTH; WEEKS GESTATION; UTERINE CERVIX AB Objectives To determine the clinical significance of the presence of amniotic fluid (AF) 'sludge' among asymptomatic patients at high risk for spontaneous preterm delivery. Methods This retrospective case-control study included 281 patients with (n = 66) or without (n = 215) AF 'sludge', who underwent transvaginal ultrasound examination between 13 and 29 completed weeks of gestation. Patients with threatened preterm labor, multiple gestation, fetal anomalies, placenta previa or uterine contractions were excluded. Results The prevalence of AF 'sludge' in the study population was 23.5% (66/281). The rates of spontaneous preterm delivery at < 28 weeks, < 32 weeks, < 35 weeks and < 37 weeks of gestation were 14.7% (29/197), 21.3% (46/216), 28.7% (62/216) and 42.1% (91/216), respectively. Patients with 'sludge' had: (1) a higher rate of spontaneous preterm delivery at < 28 weeks (46.5% (20/43) vs. 5.8% (9/154); P < 0.001), < 32 weeks (55.6% (25/45) vs. 12.3% (21/171); P < 0.001) and < 35 weeks (62.2% (28/45) vs. 19.9% (34/171); P < 0.001); (2) a higher frequency of clinical chorioamnionitis (15.2% (10/66) vs. 5.1% (11/215); P = 0.007), histologic chorioamnionitis (61.5% (40/65) vs. 28% (54/193); P < 0.001) and funisitis (32.3% (21/65) vs. 19.2% (37/193); P = 0.03); (3) a higher frequency of preterm prelabor rupture of membranes (PROM) (39.4% (26/66) vs. 13.5% (29/215); P < 0.001), lower gestational age at preterm PROM (median 24.7 (interquartile range (IQR), 22.3-28.1) weeks vs. 32.3 (IQR, 27.7-34.8) weeks; P < 0.001); and (4) shorter median ultrasound-to-delivery interval ('sludge' positive 127 days (95% CI, 120-134 days) vs. 'sludge' negative 161 days (95% CI, 153-169 days); P < 0.001) and ultrasound-to-preterm PROM interval ('sludge' positive 23 days (95% CI, 7-39 days) vs. 'sludge' negative 57 days (95% CI, 38-77 days); P = 0.003) than those without 'sludge'. AF 'sludge' was an independent explanatory variable for the occurrence of spontaneous preterm delivery at < 28 weeks, < 32 weeks and < 35 weeks, preterm PROM, microbial invasion of the amniotic cavity (MIAC) and histologic chorioamnionitis. Moreover, the combination of a cervical length < 25 mm and 'sludge' conferred an odds ratio of 14.8 and 9.9 for spontaneous preterm delivery at < 28 weeks and < 32 weeks, respectively. Conclusions AF 'sludge' is an independent risk factor for spontaneous preterm delivery, preterm PROM, MIAC and histologic chorioamnionitis in asymptomatic patients at high risk for spontaneous preterm delivery. Furthermore, the combination of 'sludge' and a short cervix confers a higher risk for spontaneous preterm delivery at < 28 weeks and < 32 weeks than a short cervix alone. Copyright (C) 2007 ISUOG. Published by John Wiley & Sons, Ltd. C1 NICHD, NIH, Dept Hlth & Human Dev, Perinatol Res Branch, Bethesda, MD USA. Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov FU Intramural NIH HHS [Z01 HD002400-16] NR 32 TC 52 Z9 53 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD OCT PY 2007 VL 30 IS 5 BP 706 EP 714 DI 10.1002/uog.4081 PG 9 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 228MB UT WOS:000250732900005 PM 17712870 ER PT J AU Romero, R Kusanovic, JP Espinoza, J Gotsch, F Nhan-Chang, CL Erez, O Kims, CJ Khalek, N Mittal, P Goncalves, LF Schaudinn, C Hassan, SS Costerton, JW AF Romero, R. Kusanovic, J. P. Espinoza, J. Gotsch, F. Nhan-Chang, C. L. Erez, O. Kims, C. J. Khalek, N. Mittal, P. Goncalves, L. F. Schaudinn, C. Hassan, S. S. Costerton, J. W. TI Picture of the month - What is amniotic fluid 'sludge'? SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article ID INTRAUTERINE CONTRACEPTIVE DEVICES; POLYMERASE-CHAIN-REACTION; CERVICAL-MUCUS PLUG; CLINICAL-SIGNIFICANCE; BACTERIAL BIOFILMS; PRETERM LABOR; OTITIS-MEDIA; UREAPLASMA-UREALYTICUM; ANTIBIOTIC-RESISTANCE; ASCENDING INFECTION C1 NICHD, NIH, DHHS, Perinatol Res Branch, Bethesda, MD USA. Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA. Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Hutzel Womens Hosp, Dept Pathol, Detroit, MI USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. Univ So Calif, Sch Dent, Ctr Biofilms, Los Angeles, CA 90089 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [Z01 HD002400-16] NR 49 TC 32 Z9 33 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD OCT PY 2007 VL 30 IS 5 BP 793 EP 798 DI 10.1002/uog.5173 PG 6 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 228MB UT WOS:000250732900021 PM 17899615 ER PT J AU Carter, HB Kettermann, A Ferrucci, L Landis, P Metter, EJ AF Carter, H. Ballentine Kettermann, Anna Ferrucci, Luigi Landis, Patricia Metter, E. Jeffrey TI Prostate-specific antigen velocity risk count assessment: A new concept for detection of life-threatening prostate cancer during window of curability SO UROLOGY LA English DT Article ID PSA VELOCITY; DEATH; MEN AB OBJECTIVES To determine whether the number of times the prostate-specific antigen (PSA) velocity (PSAV) exceeds a threshold (PSAV risk Count) is predictive of high-risk prostate cancer. METHODS The PSAV was determined in 717 men (606 without prostate cancer; 32 with high-risk prostate cancer defined as death from cancer, PSA level of 20 ng/mL or more, or a Gleason score of 8 or more; and 79 with prostate cancer who were alive or dead of another cause). Multiple PSAVs determined from three repeated measures from each subject during 10 to 20 years were used to determine the risk count by summing the number of times a subject exceeded a PSAV threshold. Cox proportional hazards regression analysis was used to evaluate the associations between the risk count and the probability of high-risk disease. The statistical tests were two-sided. RESULTS The probability of high-risk disease increased directly with the risk Count. After adjusting for age, PSA level, PSAV, and date of diagnosis, the PSAV risk Count was significantly associated with the development of high-risk prostate cancer (relative risk 1.41, 95% confidence interval 1.25 to 1.59 for a PSAV cutpoint 0.2 ng/mL/yr; relative risk 1.49, 95% confidence interval 1.29 to 1.71 for a PSAV cutpoint of 0.4 ng/mL/yr; P <0.001). CONCLUSIONS The PSAV risk count could be a useful method of interpreting a PSA history to help identify those men who will benefit from a diagnosis of prostate cancer at PSA levels associated with curable disease. C1 Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. NIA, NIH, Clin Res Branch, Baltimore, MD USA. RP Carter, HB (reprint author), Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst, Marburg 145,600 N Wolfe St, Baltimore, MD 21287 USA. EM hcarter@jhmi.edu FU Intramural NIH HHS [Z01 AG000015-49] NR 9 TC 34 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD OCT PY 2007 VL 70 IS 4 BP 685 EP 690 DI 10.1016/j.urology.2007.05.010 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 234FF UT WOS:000251145400015 PM 17991538 ER PT J AU Osaki, M Inoue, T Yamaguchi, S Inaba, A Tokuyasu, N Jeang, KT Oshimura, M Ito, H AF Osaki, Mitsuhiko Inoue, Toshiaki Yamaguchi, Shigeyuki Inaba, Aiko Tokuyasu, Naruo Jeang, Kuan-Teh Oshimura, Mitsuo Ito, Hisao TI MAD1 (mitotic arrest deficiency 1) is a candidate for a tumor suppressor gene in human stomach SO VIRCHOWS ARCHIV LA English DT Article DE MAD1; gastric carcinoma; tumor suppressor gene; immunohistochemistry; centrosome ID DNA-PLOIDY PATTERNS; SPINDLE CHECKPOINT; GASTRIC-CARCINOMA; MICROSATELLITE INSTABILITY; CELL-LINES; CANCER; PROTEINS; COMPLEX; BINDING; HYPERMETHYLATION AB Mitotic arrest deficiency 1 (MAD1) is a component of the spindle checkpoint factors that monitor fidelity of chromosomal segregation. We previously confirmed that the level of MAD1 protein was decreased in gastric carcinoma compared with non-tumoral mucosa by conducting proteome-based analyses (Nishigaki R, Osaki M, Hiratsuka M, Toda T, Murakami K, Jeang KT, Ito H, Inoue T, Oshimura M, Proteomics 5:3205-3213, 29). In this study, an immunohistochemical analysis was performed to examine MAD1 expression histologically in gastric mucosa and tumor. MAD1 was detected in the supranuclear portion of normal epithelial, intestinal metaplasia, and adenoma cells, but its expression was not restricted to any specific area in carcinoma cells. Lower levels of expression were noted in 16 (47.1%) of 34 adenomas and in 52 (60.5%) of 86 carcinomas, whereas all normal mucosae and intestinal metaplasias were grouped into cases with higher level of expression. Moreover, the expression of MAD1 was significantly lower in advanced carcinomas than early carcinomas and in intestinal than diffuse type, respectively (P < 0.05). Exogenous expression of wild-type MAD1, but not the mutant MAD1, inhibited cell proliferation and resulted in G2/M accumulation in MKN-1, a gastric carcinoma cell line. Taken together, our findings suggest that the MAD1 gene could be a candidate tumor suppressor gene and that down-regulation of MAD1 expression contribute to tumorigenesis in human stomach. C1 Tottori Univ, Fac Med, Dept Pathol & Microbiol, Div Organ Pathol, Yonago, Tottori 6838503, Japan. Tottori Univ, Grad Sch Med, Dept Biomed Sci, Div Mol Genet & Biofunct, Yonago, Tottori 6838503, Japan. Tottori Univ, Fac Med, Dept Mol & Cellular Biol, Div Human Genome Sci, Yonago, Tottori 6838503, Japan. NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Osaki, M (reprint author), Tottori Univ, Fac Med, Dept Pathol & Microbiol, Div Organ Pathol, 86 Nishi Cho, Yonago, Tottori 6838503, Japan. EM osamitsu@grape.med.tottori-u.ac.jp RI Jeang, Kuan-Teh/A-2424-2008 NR 42 TC 9 Z9 11 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD OCT PY 2007 VL 451 IS 4 BP 771 EP 779 DI 10.1007/s00428-007-0470-z PG 9 WC Pathology SC Pathology GA 215JG UT WOS:000249804000005 PM 17674037 ER PT J AU Askari, H Kaneski, CR Semino-Mora, C Desai, P Ang, A Kleiner, DE Perlee, LT Quezado, M Spollen, LE Wustman, BA Schiffmann, R AF Askari, Hasan Kaneski, Christine R. Semino-Mora, Cristina Desai, Priya Ang, Agnes Kleiner, David E. Perlee, Lorah T. Quezado, Martha Spollen, Linda E. Wustman, Brandon A. Schiffmann, Raphael TI Cellular and tissue localization of globotriaosylceramide in Fabry disease SO VIRCHOWS ARCHIV LA English DT Article DE glycolipids; immunohistochemistry; electron microscopy; lysosomal disorder; lysosome ID ENZYME REPLACEMENT; MONOCLONAL-ANTIBODIES; STORAGE DISEASES; COLLOIDAL GOLD; THERAPY; CELLS; DEPOSITS; GLYCOSPHINGOLIPIDS; ACCUMULATION; TRAFFICKING AB The pathogenesis of Fabry disease is poorly understood. We used a variety of immunohistological techniques to localize globotriaosylceramide, the main glycolipid that accumulates in Fabry disease. Globotriaosylceramide immunoreactivity in a heterogenous pattern was present in all organs examined of a patient on long-term enzyme replacement therapy. In the brain, immmunopositivity was found only in the parahippocampal region. Globotriaosylceramide immunostaining was present in the cell membrane and cytoplasm of endothelial cells, even in the absence of lysosomal inclusions. In kidney tissue, globotriaosylceramide colocalized with lysosomal, endoplasmic reticulum, and nuclear markers. Pre- and postembedding immunogold electron microscopy of skin biopsies and untreated patient cultured skin fibroblasts confirmed the presence of globotriaosylceramide in the cell membrane, in various cytoplasmic structures, and in the nucleus. Control organ tissues and cultured fibroblasts from five unaffected subjects were uniformly negative for globotriaosylceramide by immunohistochemistry and immunogold electron microscopy. We conclude that a substantial amount of lysosomal and extralysosomal globotriaosylceramide immunoreactivity remains in cells and tissues even after years of enzyme replacement therapy in Fabry disease. These findings are crucial for the understanding of the disease mechanism and suggest the usefulness of immunostaining for globotriaosylceramide as a means to assess response to novel, specific therapies. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Div Digest Dis, Gastrointestinal & Liver Studies Lab, Bethesda, MD 20814 USA. HistoRx, New Haven, CT USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Missouri Hosp & Clin, Dept Pathol, Columbia, MO USA. Amicus Therapeut, Cranbury, NJ USA. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. EM RS4e@nih.gov OI Kaneski, Christine/0000-0003-1453-2502; Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 47 TC 50 Z9 53 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD OCT PY 2007 VL 451 IS 4 BP 823 EP 834 DI 10.1007/s00428-007-0468-6 PG 12 WC Pathology SC Pathology GA 215JG UT WOS:000249804000010 PM 17674039 ER PT J AU Wang, PS Angermeyer, M Borges, G Bruffaerts, R Chiu, WT de Girolamo, G Fayyad, J Gureje, O Haro, JM Huang, YQ Kessler, RC Kovess, V Levinson, D Nakane, Y Browne, MAO Ormel, JH Posada-Villa, J Aguilar-Gaxiola, S Alonso, J Lee, S Heeringa, S Pennell, BE Chatterji, S Ustun, TB AF Wang, Philip S. Angermeyer, Matthias Borges, Guilherme Bruffaerts, Ronny Chiu, Wai Tat de Girolamo, Giovanni Fayyad, John Gureje, Oye Maria Haro, Josep Huang, Yueqin Kessler, Ronald C. Kovess, Viviane Levinson, Daphna Nakane, Yoshibumi Browne, Mark A. Oakley Ormel, Johan H. Posada-Villa, Jose Aguilar-Gaxiola, Sergio Alonso, Jordi Lee, Sing Heeringa, Steven Pennell, Beth-Ellen Chatterji, Somnatih Uestuen, T. Bedirhan CA WHO World Mental Hlth Survey Conso TI Delay and failure in treatment seeking after first onset of mental disorders in the World Health Organization's World Mental Health Survey Initiative SO WORLD PSYCHIATRY LA English DT Article DE treatment seeking; anxiety disorders; mood disorders; substance use disorders ID COMORBIDITY SURVEY REPLICATION; PSYCHIATRIC-DISORDERS; SOCIAL-CONSEQUENCES; TREATMENT CONTACT; UNITED-STATES; HELP-SEEKING; DEPRESSION; ANXIETY; MOOD; CARE AB Data are presented on patterns of failure and delay in making initial treatment contact after first onset of a mental disorder in 15 countries in the World Health Organization (WHO)'s World Mental Health (WMH) Surveys. Representative face-to-face household surveys were conducted among 76,012 respondents aged 18 and older in Belgium, Colombia, France, Germany, Israel, Italy, Japan, Lebanon, Mexico, the Netherlands, New Zealand, Nigeria, People's Republic of China (Beijing and Shanghai), Spain, and the United States. The WHO Composite International Diagnostic Interview (CIDI) was used to assess lifetime DSM-IV anxiety, mood, and substance use disorders. Ages of onset for individual disorders and ages of first treatment contact for each disorder were used to calculate the extent of failure and delay in initial help seeking. The proportion of lifetime cases making treatment contact in the year of disorder onset ranged from 0.8 to 36.4% for anxiety disorders, from 6.0 to 52.1 % for mood disorders, and from 0.9 to 18.6% for substance use disorders. By 50 years, the proportion of lifetime cases making treatment contact ranged from 15.2 to 95.0% for anxiety disorders, from 7.9 to 98.6% for mood disorders, and from 19.8 to 86.1% for substance use disorders. Median delays among cases eventually making contact ranged from 3.0 to 30.0 years for anxiety disorders, from 1.0 to 14.0 years for mood disorders, and from 6.0 to 18.0 years for substance use disorders. Failure and delays in treatment seeking were generally greater in developing countries, older cohorts, men, and cases with earlier ages of onset. These results show that failure and delays in initial help seeking are pervasive problems worldwide. Interventions to ensure prompt initial treatment contacts are needed to reduce the global burdens and hazards of untreated mental disorders. C1 [Wang, Philip S.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Angermeyer, Matthias] Univ Leipzig, Dept Psychiat, Leipzig, Germany. [Borges, Guilherme] Natl Inst Psychiat, Dept Epidemiol, Mexico City, DF, Mexico. [Bruffaerts, Ronny] Univ Hosp Gasthuisberg, Dept Neurosci & Psychiat, B-3000 Louvain, Belgium. [Chiu, Wai Tat; Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [de Girolamo, Giovanni] Dept Mental Hlth, Local Hlth Unit, Bologna, Italy. [Fayyad, John] IDRAAC, Beirut, Lebanon. [Gureje, Oye] Univ Coll Ibadan Hosp, Dept Psychiat, Ibadan, Nigeria. [Maria Haro, Josep] St Joan de Deu Mental Hlth Serv, Barcelona, Spain. [Huang, Yueqin] Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China. [Kovess, Viviane] MGEN Fdn Publ Hlth, Paris, France. [Levinson, Daphna] Minist Hlth, Res & Planning Mental Hlth Serv, Jerusalem, Israel. [Nakane, Yoshibumi] Nagasaki Int Univ Grad Sch, Div Human Sociol, Nagasaki, Japan. [Browne, Mark A. Oakley] Monash Univ, Fac Med Nursing & Hlth Sci, Sch Rural Hlth, Dept Rural & Indigenous Hlth, Clayton, Vic 3168, Australia. [Ormel, Johan H.] Netherlands Inst Mental Hlth & Addict, Utrecht, Netherlands. [Posada-Villa, Jose] Colegio Mayor Cundinamarca Univ, Saldiarraga Concha Fdn, Bogota, Colombia. [Aguilar-Gaxiola, Sergio] UC Davis Sch Med, Ctr Reducing Hlth Disparities, Sacramento, CA USA. [Alonso, Jordi] Inst Municipal Invest Med, Hlth Serv Res Unit, E-08003 Barcelona, Spain. [Lee, Sing] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Heeringa, Steven; Pennell, Beth-Ellen] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Chatterji, Somnatih; Uestuen, T. Bedirhan] WHO, Global Programme Evidence Hlth Policy, CH-1211 Geneva, Switzerland. RP Wang, PS (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd, Bethesda, MD 20892 USA. RI Alonso, Jordi/A-5514-2010; Ormel, Johan/C-6094-2013; Lee, Sing/O-2136-2015; Haro, Josep Maria/D-1423-2011 OI Alonso, Jordi/0000-0001-8627-9636; Haro, Josep Maria/0000-0002-3984-277X FU FIC NIH HHS [R03 TW006481]; NIDA NIH HHS [R01 DA016558]; NIMH NIH HHS [R01 MH069864, R01 MH070884, R13 MH066849, U01 MH060220] NR 51 TC 150 Z9 152 U1 12 U2 30 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 1723-8617 J9 WORLD PSYCHIATRY JI World Psychiatry PD OCT PY 2007 VL 6 IS 3 BP 177 EP 185 PG 9 WC Psychiatry SC Psychiatry GA 248DI UT WOS:000252131300016 PM 18188443 ER PT J AU van Bockel, D Price, DA Asher, TE Venturi, V Suzuki, K Warton, K Davenport, MP Cooper, DA Douek, DC Kelleher, AD AF van Bockel, David Price, David A. Asher, Tedi E. Venturi, Vanessa Suzuki, Kazuo Warton, Kristina Davenport, Miles P. Cooper, David A. Douek, Daniel C. Kelleher, Anthony D. TI Validation of RNA-based molecular clonotype analysis for virus-specific CD8+ T-cells in formaldehyde-fixed specimens isolated from peripheral blood SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE clonotype; repertoire; mRNA; T-cell; formaldehyde ID INFECTED H9 CELLS; IMMUNE-RESPONSES; TCR REPERTOIRE; FLOW-CYTOMETRY; VIRAL ESCAPE; PCR ANALYSIS; WHOLE-BLOOD; HIV; SAMPLES; AMPLIFICATION AB Recent advances in the field of molecular clonotype analysis have enabled detailed repertoire characterization of viably isolated antigen-specific T cell populations directly ex vivo. However, in the absence of a biologically contained FACS facility, peripheral blood mononuclear cell (PBMC) preparations derived from patients infected with agents such as HIV must be formaldehyde fixed to inactivate the pathogen; this procedure adversely affects nucleic acid template quality. Here, we developed and validated a method to amplify and sequence mRNA species derived from formaldehyde fixed PBMC specimens. Antigen-specific CD8+ cytotoxic T-lymphocyte populations were identified with standard fluorochrome-conjugated peptide-major histocompatibility complex class I tetramers refolded around synthetic peptides representing immunodominant epitopes from HIV p24 Gag (KRWII [M/L]GLNK/HLA B*2705) and CMV pp65 (NLVPMVATV/HLA A*0201 and TPRVTGGGAM/HLA B*0702), and acquired in separate laboratories with or without fixation. In the presence of proteinase K pre-treatment, the observed antigen-specific CD8+ T-cell repertoire determined by molecular clonotype analysis was statistically no different whether derived from fixed or unfixed PBMC. However, oligo-dT recovery methods were not suitable for use with fixed tissue as significant skewing of clonotypic representation was observed. Thus, we have developed a reliable RNA-based method for molecular clonotype analysis that is compatible with formaldehyde fixation and therefore suitable for use with primary human samples isolated by FACS outside the context of a biological safety level 3 containment facility. Crown Copyright (c) 2007 Published by Elsevier B.V. All rights reserved. C1 St Vincents Hosp, Ctr Immunol, Sydney, NSW 2010, Australia. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. NIAID, Vaccine Res Ctr, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. UNSW, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. Univ New S Wales, Ctr Vasc Res, Sydney, NSW, Australia. Corbett Res, Ctr Immunol, Sydney, NSW, Australia. RP van Bockel, D (reprint author), St Vincents Hosp, Ctr Immunol, HIV Immunovirol & Pathogenesis Program, Corner Boundary & W St, Darlinghurst, NSW 2010, Australia. EM d.vanbockel@cfi.unsw.edu.au RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Intramural NIH HHS [Z01 AI005033-06, Z99 AI999999]; Medical Research Council [G0501963] NR 36 TC 3 Z9 3 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD SEP 30 PY 2007 VL 326 IS 1-2 BP 127 EP 138 DI 10.1016/j.jim.2007.07.016 PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 218PD UT WOS:000250026500012 PM 17716684 ER PT J AU Lin, H Hejtmancik, JF Qi, YH AF Lin, Hui Hejtmancik, J. Fielding Qi, Yanhua TI A substitution of arginine to lysine at the COOH-terminus of MIP caused a different binocular phenotype in a congenital cataract family SO MOLECULAR VISION LA English DT Article ID MAJOR INTRINSIC PROTEIN; AQUAPORIN WATER PERMEABILITY; LENS DEVELOPMENT; GENETIC-LINKAGE; C-TERMINUS; MEMBRANE; JUNCTIONS; POLYPEPTIDE; EXPRESSION; PH AB Purpose: To detect the cataractogenetic mutation for a six-generation family of Chinese origin with autosomal dominant binocular polymorphic cataracts. Methods: A genome wide scan was performed using 382 fluorescent-labeled microsatellite markers. Multiple polymerase chain reaction (PCR) was performed according to the protocols previously described. Two-point linkage analysis was performed with the FASTLINK version of the MLINK in Linkage Program Package. The candidate gene was screened by direct sequencing. Results: The disease locus was mapped to a 61 cM region on chromosome 12 defined by D12S310 and D12S351 near the major intrinsic protein gene (MIP). The maximum two-point lod score of 5.44 was obtained at marker D12S83 at theta=0.00. Direct sequencing of the encoding region of the candidate gene revealed a novel missense mutation G>A in exon 4 at nucleotide 702, which caused the replacement of arginine to lysine at codon 233 (p.R233K). Conclusions: The change located in the alpha-helix domain of the COOH-terminus of MIP was determined to be associated with the binocular polymorphic cataract in this study. It suggests that arginine in this domain plays a crucial role in the function of the carboxyl-end of this protein and provides a helpful clue to further studies on completely understanding the physiological significance of MIP and its role in the formation of cataract. C1 Harbin Med Coll, Second Affiliated Hosp, Dept Ophthalmol, Harbin 150086, Peoples R China. NEI, NIH, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. RP Qi, YH (reprint author), Harbin Med Coll, Second Affiliated Hosp, Dept Ophthalmol, 246 Xuefu Rd, Harbin 150086, Peoples R China. EM qi_yanhua@yahoo.com NR 23 TC 29 Z9 30 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD SEP 30 PY 2007 VL 13 IS 203 BP 1822 EP 1827 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 223SN UT WOS:000250392700001 PM 17960133 ER PT J AU Freidlin, B Korn, EL AF Freidlin, Boris Korn, Edward L. TI Release of data from an ongoing randomized clinical trial for sample size adjustment or planning SO STATISTICS IN MEDICINE LA English DT Article DE bayesian analysis; interim analysis; administrative analysis; data monitoring committee; data release ID MONITORING COMMITTEES; PREVENTION TRIALS; INTERIM ANALYSES; ISSUES; RECALCULATION; REESTIMATION; DURATION; OUTCOMES; CANCER; SAFETY AB The determination of an appropriate sample size is a key issue in planning and designing randomized clinical trials. In settings with time-to-event or binary outcomes, the required sample size depends on the control-arm event (response) rate. An accurate estimate of this rate is not often available at the planning stage. Therefore, non-comparative control-arm or pooled-arm event rates from an ongoing trial are sometimes released for sample size adjustment or planning purposes. It is shown that such noncomparative data release may still contain information on the relative treatment benefit and may thus adversely affect the ongoing trial. A simple approach to minimizing the effect of the data release is suggested. Published in 2007 by John Wiley & Sons, Ltd. C1 NCI, Biometr Res Branch, Div Canc Traetment & Diagnosis, Bethesda, MD 20892 USA. RP Freidlin, B (reprint author), NCI, Biometr Res Branch, Div Canc Traetment & Diagnosis, 6130 Executive Blvd,EPN 8122,MSC 7434, Bethesda, MD 20892 USA. EM freidlinb@ctep.nci.nih.gov NR 45 TC 2 Z9 2 U1 0 U2 2 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 SEP 30 PY 2007 VL 26 IS 22 BP 4074 EP 4082 DI 10.1002/sim.2842 PG 9 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 208AS UT WOS:000249292800002 PM 17328095 ER PT J AU Husain, M Weisberg, AS Moss, B AF Husain, Matloob Weisberg, Andrea S. Moss, Bernard TI Resistance of a vaccinia virus A34R deletion mutant to spontaneous rupture of the outer membrane of progeny virions on the surface of infected cells SO VIROLOGY LA English DT Article DE viral membrane; poxvirus virions; vaccinia virus mutants ID EXTRACELLULAR ENVELOPED VIRUS; ACTIN-CONTAINING MICROVILLI; ENTRY-FUSION COMPLEX; ESSENTIAL COMPONENT; POXVIRUS ENTRY; PROTEIN; GENE; GLYCOPROTEIN; SPREAD; DISSEMINATION AB The extracellular form of vaccinia virus is referred to as an enveloped virion (EV) because it contains an additional lipoprotein membrane surrounding! the infectious mature virion (MV) that must be discarded prior to cell fusion and entry. Most EVs adhere to the surface of the parent cell and mediate spread of the infection to adjacent cells. Here we show that some attached EVs have ruptured envelopes. Rupture was detected by fluorescence microscopy of unfixed and unpermeabilized cells using antibodies to the F13 and L1 proteins, which line the inner side of the EV membrane and the outer side of the MV membrane, respectively. The presence of ruptured EV membranes was confirmed by immunogold transmission electron microscopy. EVs with broken membranes were present on several cell lines examined including one deficient in glycosaminoglycans, which are thought to play a role in breakage of the EV membrane prior to fusion of the MV No correlation was found between EVs with ruptured membranes and actin tail formation. Studies with several mutant viruses indicated that EV membranes lacking the A34 protein were unbroken. This result was consistent with other properties of A34R deletion mutants including resistance of the EV membrane to polyanions, small plaque formation and low infectivity that can be increased by disruption of the EV membrane by freezing and thawing,. Published by Elsevier Inc. C1 Natl Inst Hlth, NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Moss, B (reprint author), Natl Inst Hlth, NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS [Z01 AI000539-20] NR 36 TC 10 Z9 10 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 0042-6822 J9 VIROLOGY JI Virology PD SEP 30 PY 2007 VL 366 IS 2 BP 424 EP 432 DI 10.1016/j.virol.2007.05.015 PG 9 WC Virology SC Virology GA 214WR UT WOS:000249769400018 PM 17553539 ER PT J AU Kobayashi, S Toyooka, N Zhou, D Tsuneki, H Wada, T Sasaoka, T Sakai, H Nemoto, H Garraffo, HM Spande, TF Daly, JW AF Kobayashi, Soushi Toyooka, Naoki Zhou, Dejun Tsuneki, Hiroshi Wada, Tsutomu Sasaoka, Toshiyasu Sakai, Hideki Nemoto, Hideo Garraffo, H. Martin Spande, Thomas F. Daly, John W. TI Flexible synthesis of poison-frog alkaloids of the 5,8-disubstituted indolizidine-class. II: Synthesis of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and an epimer of 193E and pharmacological effects at neuronal nicotinic acetylcholine receptors SO BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID STEREOSELECTIVE-SYNTHESIS; SCHIZOPHRENIA AB Background: The 5,8-disubstituted indolizidines constitute the largest class of poison-frog alkaloids. Some alkaloids have been shown to act as noncompetitive blockers at nicotinic acetylcholine receptors but the proposed structures and the biological activities of most of the 5,8-disubstituted indolizidines have not been determined because of limited supplies of the natural products. We have therefore conducted experiments to confirm proposed structures and determine biological activities using synthetic compounds. Recently, we reported that one of this class of alkaloids, (-)-235B', acts as a noncompetitive antagonist for alpha 4 beta 2 nicotinic receptors, and its sensitivity is comparable to that of the classical competitive antagonist for this receptor, dihydro-beta-erythroidine. Results: The enantioselective syntheses of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and what proved to be an epimer of natural 193E, starting from common chiral lactams have been achieved. When we performed electrophysiological recordings to examine the effects of the synthetic alkaloids on two major subtypes of nicotinic receptors ( alpha 4 beta 2 and alpha 7) expressed in Xenopus laevis oocytes, (-)-231C effectively blocked alpha 4 beta 2 receptor responses ( IC50 value, 1.5 mu M) with a 7.0-fold higher potency than for blockade of alpha 7 receptor responses. In contrast, synthetic (-)-221I and (-)-epi-193E were more potent in blocking alpha 7 receptor responses ( IC50 value, 4.4 mu M and 9.1 mu M, respectively) than alpha 4 beta 2 receptor responses ( 5.3-fold and 2.0-fold, respectively). Conclusion: We achieved the total synthesis of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and an epimer of 193E starting from common chiral lactams, and the absolute stereochemistry of natural (-)-233D was determined. Furthermore, the relative stereochemistry of (-)-231C and (-)-221I was also determined. The present asymmetric synthesis of the proposed structure for 193E revealed that the C-8 configuration of natural 193E should be revised. C1 [Kobayashi, Soushi; Toyooka, Naoki; Zhou, Dejun; Tsuneki, Hiroshi; Wada, Tsutomu; Sasaoka, Toshiyasu; Sakai, Hideki; Nemoto, Hideo] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Toyama 9300194, Japan. [Garraffo, H. Martin; Spande, Thomas F.; Daly, John W.] NIDDK, Bioorgan Chem Lab, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. RP Toyooka, N (reprint author), Toyama Univ, Grad Sch Med & Pharmaceut Sci, Sugitani 2630, Toyama 9300194, Japan. EM d0560009@ems.u-toyama.ac.jp; d0560009@ems.u-toyama.ac.jp; zej4060@yahoo.co.jp; htsuneki@pha.u-toyama.ac.jp; twada-tym@umin.ac.jp; tsasaoka@pha.u-toyama.ac.jp; sakaih@pha.u-toyama.ac.jp; nemotoh@pha.u-toyama.ac.jp; garraffo@helix.nih.gov; thomassp@bdg8.niddk.nih.gov; jdaly@nih.gov NR 19 TC 9 Z9 9 U1 0 U2 6 PU BEILSTEIN-INSTITUT PI FRANKFURT AM MAIN PA TRAKEHNER STRASSE 7-9, FRANKFURT AM MAIN, 60487, GERMANY SN 1860-5397 J9 BEILSTEIN J ORG CHEM JI Beilstein J. Org. Chem. PD SEP 28 PY 2007 VL 3 AR 30 DI 10.1186/1860-5397-3-30 PG 6 WC Chemistry, Organic SC Chemistry GA 245VY UT WOS:000251968100002 PM 21931443 ER PT J AU Toyooka, N Zhou, D Nemoto, H Garraffo, HM Spande, TF Daly, JW AF Toyooka, Naoki Zhou, Dejun Nemoto, Hideo Garraffo, H. Martin Spande, Thomas F. Daly, John W. TI Flexible synthetic routes to poison-frog alkaloids of the 5,8-disubstituted indolizidine-class I: synthesis of common lactam chiral building blocks and application to the synthesis of (-)-203A, (-)-205A, and (-)-219F SO BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ENANTIOSELECTIVE SYNTHESIS; QUINOLIZIDINE ALKALOIDS; ASYMMETRIC-SYNTHESIS; DENDROBATES-PUMILIO; STEREOCHEMISTRY; CONVERSION; (-)-235B; KETONES AB Background: The 5,8-disubstituted indolizidines are the largest class of poison-frog alkaloids found in anuran skin, and are of considerable interest because of their inhibitory effects on the neuronal nicotinic acetylcholine receptors. Many synthetic strategies for the construction of this nucleus have been reported: however, a flexible route has not been reported to date. Results: Synthesis of lactam chiral building blocks for the flexible synthesis of the title alkaloids has been achieved using a Michael-type conjugate addition reaction to a chiral cyclic enamine ester as the key step in constructing the trisubstituted piperidine ring system. To demonstrate the usefulness of these chiral building blocks, syntheses of (-)-203A, (-)-205A from 1, and (-)-219F from 2 have been achieved. Conclusion: The total synthesis of (-)-203A, (-)-205A, and (-)-219F was achieved, and the absolute stereochemistry of natural 203A was determined to be 5S, 8R, 9S. In addition, the relative stereochemistry of natural 219F was determined. C1 [Toyooka, Naoki; Zhou, Dejun; Nemoto, Hideo] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Toyama 9300194, Japan. [Garraffo, H. Martin; Spande, Thomas F.; Daly, John W.] NIDDK, Bioorgan Chem Lab, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. RP Toyooka, N (reprint author), Toyama Univ, Grad Sch Med & Pharmaceut Sci, Sugitani 2630, Toyama 9300194, Japan. EM toyooka@pha.u-toyama.ac.jp; zej4060@yahoo.co.jp; nemotoh@pha.u-toyama.ac.jp; garraffo@helix.nih.gov; thomassp@bdg8.niddk.nih.gov; jdaly@nih.gov NR 28 TC 13 Z9 13 U1 0 U2 8 PU BEILSTEIN-INSTITUT PI FRANKFURT AM MAIN PA TRAKEHNER STRASSE 7-9, FRANKFURT AM MAIN, 60487, GERMANY SN 1860-5397 J9 BEILSTEIN J ORG CHEM JI Beilstein J. Org. Chem. PD SEP 28 PY 2007 VL 3 AR 29 DI 10.1186/1860-5397-3-29 PG 5 WC Chemistry, Organic SC Chemistry GA 245VY UT WOS:000251968100001 PM 17903239 ER PT J AU Tubb, MR Silva, RAGD Pearson, KJ Tso, P Liu, M Davidson, WS AF Tubb, Matthew R. Silva, R. A. Gangani D. Pearson, Kevin J. Tso, Patrick Liu, Min Davidson, W. Sean TI Modulation of apolipoprotein A-IV lipid binding by an interaction between the N and C termini SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH-DENSITY-LIPOPROTEINS; CORONARY-ARTERY-DISEASE; EXCHANGEABLE APOLIPOPROTEINS; CIRCULAR-DICHROISM; SLIDING CLAMP; APOA-IV; PLASMA; MICE; POLYMORPHISM; POLYMERASE AB Apolipoprotein A-IV (apoA-IV) is a 376-amino acid exchangeable apolipoprotein made in the small intestine of humans. Although it has many proposed roles in vascular disease, satiety, and chylomicron metabolism, there is no known structural basis for these functions. The ability to associate with lipids may be a key step in apoA-IV functionality. We recently identified a single amino acid, Phe(334), which seems to inhibit the lipid binding capability of apoA-IV. We also found that an intact N terminus was necessary for increased lipid binding of Phe334 mutants. Here, we identify Trp(12) and Phe(15) as the N-terminal amino acids required for the fast lipid binding seen with the F334A mutant. Furthermore, we found that individual disruption of putative amphipathic alpha-helices 3-11 had little effect on lipid binding, suggesting that the N terminus of apoA-IV may be the operational site for initial lipid binding. We also provide three independent pieces of experimental evidence supporting a direct intramolecular interaction between sequences near amino acids 12/15 and 334. This interaction could represent a unique "switch" mechanism by which apoA-IV changes lipid avidity in vivo. C1 Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH 45237 USA. NIA, Lab Exp Gerontol, NIH, Baltimore, MD 21224 USA. RP Davidson, WS (reprint author), Univ Cincinnati, Dept Pathol & Lab Med, 2120 Galbraith Rd, Cincinnati, OH 45237 USA. EM Sean.Davidson@UC.edu OI Tubb, Matthew/0000-0002-4543-2742 FU NHLBI NIH HHS [HL67093, HL82734] NR 39 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 28 PY 2007 VL 282 IS 39 BP 28385 EP 28394 DI 10.1074/jbc.M704070200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 213BY UT WOS:000249642100013 PM 17686771 ER PT J AU Das, S Chattopadhyay, R Bhakat, KK Boldogh, I Kohno, K Prasad, R Wilson, SH Hazra, TK AF Das, Soumita Chattopadhyay, Ranajoy Bhakat, Kishor K. Boldogh, Istvan Kohno, Kimitoshi Prasad, Rajendra Wilson, Samuel H. Hazra, Tapas K. TI Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOX-BINDING-PROTEIN; TRANSCRIPTION FACTOR YB-1; HUMAN DNA GLYCOSYLASES; CELL NUCLEAR ANTIGEN; Y-BOX; ULTRAVIOLET-LIGHT; ENDONUCLEASE-VIII; MAMMALIAN-CELLS; MESSENGER-RNA; UVA RADIATION AB The recently characterized enzyme NEIL2 (Nei-like-2), one of the four oxidized base-specific DNA glycosylases (OGG1, NTH1, NEIL1, and NEIL2) in mammalian cells, has poor base excision activity from duplex DNA. To test the possibility that one or more proteins modulate its activity in vivo, we performed mass spectrometric analysis of the NEIL2 immunocomplex and identified Y box-binding (YB-1) protein as a stably interacting partner of NEIL2. We show here that YB-1 not only interacts physically with NEIL2, but it also cooperates functionally by stimulating its base excision activity by 7-fold. Moreover, YB-1 interacts with the other NEIL2-associated BER proteins, namely, DNA ligase III alpha and DNA polymerase beta and thus could form a large multiprotein complex. YB-1, normally present in the cytoplasm, translocates to the nucleus during UVA-induced oxidative stress, concomitant with its increased association with and activation of NEIL2. NEIL2-initiated base excision activity is significantly reduced in YB-1-depleted cells. YB-1 thus appears to have a novel regulatory role in NEIL2-mediated repair under oxidative stress. C1 Univ Texas, Med Branch, Sealy Ctr Mol Med, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Occupat & Environm Hlth, Sch Med, Dept Mol Biol, Kitakyushu, Fukuoka 807, Japan. RP Hazra, TK (reprint author), 6-136 Med Res Bldg,Route 1079, Galveston, TX 77555 USA. EM tkhazra@utmb.edu RI Bhakat, Kishor/C-8072-2012 FU Intramural NIH HHS [Z01 ES050158-11, Z01 ES050159-11]; NCI NIH HHS [CA102271, CA81063, R01 CA081063, R01 CA102271]; NIA NIH HHS [P01 AG021830]; NIEHS NIH HHS [P01 ES06676, P30 ES006676]; PHS HHS [E508457] NR 56 TC 70 Z9 77 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 28 PY 2007 VL 282 IS 39 BP 28474 EP 28484 DI 10.1074/jbc.M704672200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 213BY UT WOS:000249642100021 PM 17686777 ER PT J AU Koh, Y Matsumi, S Das, D Amano, M Davis, DA Li, JF Leschenko, S Baldridge, A Shioda, T Yarchoan, R Ghosh, AK Mitsuya, H AF Koh, Yasuhiro Matsumi, Shintaro Das, Debananda Amano, Masayuki Davis, David A. Li, Jianfeng Leschenko, Sofiya Baldridge, Abigail Shioda, Tatsuo Yarchoan, Robert Ghosh, Arun K. Mitsuya, Hiroaki TI Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VIRUS TYPE-1 PROTEASE; STRUCTURE-BASED DESIGN; ACTIVE-SITE; IN-VITRO; INTERFACE PEPTIDES; DRUG-RESISTANCE; PROTEINASE; THERAPY; MONOMER; TMC114 AB Dimerization of HIV-1 protease subunits is essential for its proteolytic activity, which plays a critical role in HIV-1 replication. Hence, the inhibition of protease dimerization represents a unique target for potential intervention of HIV-1. We developed an intermolecular fluorescence resonance energy transfer-based HIV-1-expression assay employing cyan and yellow fluorescent protein-tagged protease monomers. Using this assay, we identified non-peptidyl small molecule inhibitors of protease dimerization. These inhibitors, including darunavir and two experimental protease inhibitors, blocked protease dimerization at concentrations of as low as 0.01 mu M and blocked HIV-1 replication with IC50 values of 0.0002-0.48 mu M. These agents also inhibited the proteolytic activity of mature protease. Other approved anti-HIV-1 agents examined except tipranavir, a CCR5 inhibitor, and soluble CD4 failed to block the dimerization event. Once protease monomers dimerize to become mature protease, mature protease is not dissociated by this dimerization inhibition mechanism, suggesting that these agents block dimerization at the nascent stage of protease maturation. The proteolytic activity of mature protease that managed to undergo dimerization despite the presence of these agents is likely to be inhibited by the same agents acting as conventional protease inhibitors. Such a dual inhibition mechanism should lead to highly potent inhibition of HIV-1. C1 Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Hematol, Kumamoto 8608556, Japan. Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Infect Dis, Kumamoto 8608556, Japan. NCI, NIH, Expt Retrovirol Sect, Bethesda, MD 20892 USA. NCI, NIH, Retroviral Dis Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. Purdue Univ, Dept Chem & Med Chem, W Lafayette, IN 47907 USA. Osaka Univ, Dept Viral Infect, Res Inst Microbial Dis, Osaka 5650871, Japan. RP Mitsuya, H (reprint author), Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Hematol, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM hmitsuya@helix.nih.gov RI Li, Jianfeng/F-5057-2014; Amano, Masayuki/N-7407-2016 OI Li, Jianfeng/0000-0002-8838-3872; Amano, Masayuki/0000-0003-0516-9502 FU Intramural NIH HHS; NIGMS NIH HHS [GM53386] NR 48 TC 69 Z9 71 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 28 PY 2007 VL 282 IS 39 BP 28709 EP 28720 DI 10.1074/jbc.M703938200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 213BY UT WOS:000249642100045 PM 17635930 ER PT J AU Fernando, R Foster, JS Bible, A Strom, A Pestell, RG Rao, M Saxton, A Baek, SJ Yamaguchi, K Donnell, R Cekanova, M Wimalasena, J AF Fernando, Romaine Foster, James S. Bible, Amber Stroem, Anders Pestell, Richard G. Rao, Mahadev Saxton, Arnold Baek, Seung Joon Yamaguchi, Kiyoshi Donnell, Robert Cekanova, Maria Wimalasena, Jay TI Breast cancer cell proliferation is inhibited by bad - Regulation of CYCLIN D1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-DAMAGE RESPONSE; CYCLE PROGRESSION; SIGNALING PATHWAY; E-CDK2 ACTIVATION; PHOSPHORYLATION; D1; APOPTOSIS; ESTROGEN; SURVIVAL; PROTEIN AB Recent investigations suggest that functions of the proapoptotic BCL2 family members, including BAD, are not limited to regulation of apoptosis. Here we demonstrate that BAD inhibits G(1) to S phase transition in MCF7 breast cancer cells independent of apoptosis. BAD overexpression inhibited G1 transit and cell growth as well as cyclin D1 expression. Inhibition of cyclin D1 expression was mediated through inhibition of transcription activated by AP1. Chromatin immunoprecipitation assays indicated that BAD is localized at the 12-O-tetradecanoylphorbol-13-acetate-response element (TRE) and cAMP-response element (CRE) in the cyclin D1 promoter. This was shown to reflect direct binding interactions of BAD with c-Jun, and this interaction inhibited the activity of AP1 complexes at TRE. BAD did not interact with phosphorylated forms of c-Jun. Our data suggest that inhibitory TRE/CRE-c-Jun-BAD complexes are present at the cyclin D1 promoter in quiescent cells. Estrogen stimulation displaced BAD from TRE/CRE elements in MCF7 cells, whereas BAD overexpression inhibited estrogen-induced cyclin D1 synthesis and cell proliferation. Inhibition of endogenous BAD in MCF7 cells markedly increased the proliferative fraction and DNA synthesis, activated Cdks, and increased cyclin D1 protein levels. This action of BAD required serine residues Ser(75) and Ser(99). Both phosphorylated and unphosphorylated forms of BAD localized to the nuclei of human breast epithelial cells. Thus, we demonstrate a novel role for BAD in cell cycle regulation dependent upon its phosphorylation state and independent of the BAD/BCL2 interaction and apoptosis. C1 Univ Tennessee, Med Ctr, Grad Sch Med, Knoxville, TN 37920 USA. Karolinska Inst, Novum, Dept Biosci, S-14157 Huddinge, Sweden. Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Med Oncol, Philadelphia, PA 19107 USA. NCI, Dept Oncol, Natl Inst Hlth, Washington, DC 20057 USA. Univ Tennessee, Dept Anim Sci, Knoxville, TN 37996 USA. Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37996 USA. RP Wimalasena, J (reprint author), Univ Tennessee, Med Ctr, Grad Sch Med, 1924 Alcoa Hwy, Knoxville, TN 37920 USA. EM jwimalas@mc.utmck.edu OI Baek, Seung/0000-0001-7866-7778; Cekanova, Maria/0000-0002-9651-1619 NR 41 TC 21 Z9 23 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 28 PY 2007 VL 282 IS 39 BP 28864 EP 28873 DI 10.1074/jbc.M700785200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 213BY UT WOS:000249642100061 PM 17670745 ER PT J AU Balaji, S Babu, MM Aravind, L AF Balaji, S. Babu, M. Madan Aravind, L. TI Interplay between network structures, regulatory modes and sensing mechanisms of transcription factors in the transcriptional regulatory network of E-coli SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transcriptional network; co-regulation network; sensing; mRNA half-life; evolution ID ESCHERICHIA-COLI K-12; GLOBAL ANALYSIS; SACCHAROMYCES-CEREVISIAE; DNA MICROARRAYS; GENE-REGULATION; EVOLUTION; SYSTEMS; MOTIFS; GENOME; YEAST AB Though the bacterial transcription regulation apparatus is distinct in terms of several structural and functional features from its eukaryotic counterpart, the gross structure of the transcription regulatory network (TRN) is believed to be similar in both superkingdoms. Here, we explore the fine structure of the bacterial TRN and the underlying "co-regulatory network" (CRN) to show that despite the superficial similarities to the TRN of the eukaryotic model organism yeast, the bacterial networks display entirely different organizational principles. In particular unlike in eukaryotes, hubs of the bacterial networks are both global regulators and integrators of diverse disparate transcriptional responses. These and other organizational differences might correlate with the fundamental differences in gene and promoter organization in the two superkingdoms, especially the presence of operons and regulons in bacteria. Further we explored to find the interplay, if any, between network structures, mode of regulatory interactions and signal sensing of transcription factors (TFs) in shaping up the bacterial transcriptional regulatory responses. For this purpose, we first classified TFs according to their regulatory mode (activator, repressor or dual regulator) and sensory mechanism (one-component systems responding to internal or external signals, TFs from two-component systems and chromosomal structure modifying TFs) in the bacterial model organism Escherichia coli and then we studied the overall evolutionary optimization of network structures. The incorporation of TFs in different hierarchical elements of the TRN appears to involve on a multi-dimensional selection process depending on regulatory and sensory modes of TFs in motifs, coregulatory associations between TFs of different functional classes and transcript half-lives. As a result it appears to have generated circuits that allow intricately regulated physiological state changes. We identified the biological significance of most of these optimizations, which can be further used as the basis to explore similar controls in other bacteria. We also show that, though on the larger evolutionary scale, unrelated TFs have evolved to become hubs, within lineages like gamma-proteobacteria there is strong tendency to retain hubs, as well as certain higher-order network modules that have emerged through lineage specific paralog duplications. (c) 2007 Elsevier Ltd. All rights reserved. C1 Natl Ctr Biotechnol Informat, Natl Inst Hlth, Natl Library Med, Bethesda, MD 20894 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RP Balaji, S (reprint author), Natl Ctr Biotechnol Informat, Natl Inst Hlth, Natl Library Med, Bethesda, MD 20894 USA. EM sbalaji@ncbi.nlm.nih.gov; madanm@mrc-lmb.cam.ac.uk FU Intramural NIH HHS [NIH0011790914, ]; Medical Research Council [MC_U105185859]; PHS HHS [NIH0011790914] NR 44 TC 44 Z9 44 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 28 PY 2007 VL 372 IS 4 BP 1108 EP 1122 DI 10.1016/j.jmb.2007.06.084 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 215NX UT WOS:000249817400022 PM 17706247 ER PT J AU Redmond, TM Weber, CH Poliakov, E Yu, S Gentleman, S AF Redmond, T. Michael Weber, Charles H. Poliakov, Eugenia Yu, Shirley Gentleman, Susan TI Effect of Leu/Met variation at residue 450 on isomerase activity and protein expression of RPE65 and its modulation by variation at other residues SO MOLECULAR VISION LA English DT Article ID LEBER CONGENITAL AMAUROSIS; RETINAL-PIGMENT EPITHELIUM; THERAPY RESTORES VISION; VISUAL CYCLE; LIPOFUSCIN FLUOROPHORES; MOUSE MODEL; MUTATIONS; GENE; DEGENERATION; ISOMEROHYDROLASE AB Purpose: RPE65 is the visual cycle retinol isomerase and missense mutations in its gene cause severe retinal dystrophies in man, due to lack of chromophore. While the rate of opsin regeneration in mouse is slower than in man, the methionine (M) variant of mouse RPE65 residue 450 (normally L) is associated with additionally lowered light sensitivity and with resistance to light damage in C57Bl/6 mice, consistent with lowered total activity. We wished to determine how this variant affects RPE65 and if it is modulated by other rodent-specific variations. Methods: Site-directed mutagenesis was used to make variant constructs in mouse and dog RPE65, which were tested for isomerase activity by transient transfection in 293-F cells. Results: The isomerase activity of dog RPE65 is slightly higher than mouse. Replacing L at aa450 with M reduces total activity of dog to approximately 70% and mouse to approximately 45% of respective wild type RPE65, and also reduces protein levels of both variants. Replacing K at aa446 in mouse with R, as in other species, reduces total activity in mouse RPE65, whereas the converse case, changing dog aa446 from R to K, increases activity. Exchanges of residues at aa457 and 459 had little overall effect. Human variants at two of these positions, L450R and T457N, had disparate effects, abolishing and augmenting activity, respectively. Conclusions: Wildtype dog RPE65 is more active than wildtype mouse RPE65, perhaps partially explaining the slower regeneration rate in the mouse. The effect of Met at aa450 is more severe in mouse RPE65 than in dog. The effects of variation at residues 446 (K or R) modulate variation at aa450. The sensitivity of aa450 to change is underscored by the abolition of activity in the pathogenic human L450R mutation. These results suggest that subtle species-specific residue changes may be involved in "tuning" of RPE65 activity to required evolutionary criteria. C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. RP Redmond, TM (reprint author), NEI, LRCMB, NIH, Bldg 7,Bldg 303,7 Mem Dr,MSC 0706, Bethesda, MD 20892 USA. EM redmond@helix.nih.gov OI Redmond, T. Michael/0000-0002-1813-5291 FU Intramural NIH HHS NR 32 TC 14 Z9 14 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD SEP 28 PY 2007 VL 13 IS 201-02 BP 1813 EP 1821 PG 9 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 223SL UT WOS:000250392500002 PM 17960118 ER PT J AU Huang, CC Lam, SN Acharya, P Tang, M Xiang, SH Hussan, SSU Stanfield, RL Robinson, J Sodroski, J Wilson, IA Wyatt, R Bewley, CA Kwong, PD AF Huang, Chih-chin Lam, Son N. Acharya, Priyamvada Tang, Min Xiang, Shi-Hua Hussan, Syed Shahzad-ul Stanfield, Robyn L. Robinson, James Sodroski, Joseph Wilson, Ian A. Wyatt, Richard Bewley, Carole A. Kwong, Peter D. TI Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4 SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; CORECEPTOR; BINDING; RECEPTORS; ENTRY; V3; DETERMINANTS; DOMAINS; REGION AB The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (alpha-helix) and 412d (extended-loop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA. RP Bewley, CA (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov; pdkwong@nih.gov FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [P30 AI060354, U19 AI067854, U19 AI067854-03] NR 28 TC 268 Z9 276 U1 5 U2 40 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 28 PY 2007 VL 317 IS 5846 BP 1930 EP 1934 DI 10.1126/science.1145373 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214US UT WOS:000249764300042 PM 17901336 ER PT J AU Zeisel, MB Fafi-Kremer, S Fofana, I Barth, H Stoll-Keller, F Doffoel, M Baumert, TF AF Zeisel, Mirjam B. Fafi-Kremer, Samira Fofana, Isabel Barth, Heidi Stoll-Keller, Francoise Doffoel, Michel Baumert, Thomas F. TI Neutralizing antibodies in hepatitis C virus infection SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE hepatitis C virus; virus-host cell interaction; viral entry; neutralizing antibodies ID HUMAN MONOCLONAL-ANTIBODIES; E2 ENVELOPE GLYCOPROTEIN; SINGLE-SOURCE OUTBREAK; SCAVENGER RECEPTOR-BI; IN-VITRO; IMMUNE-RESPONSES; VIRAL CLEARANCE; MEDIATED NEUTRALIZATION; HEPARAN-SULFATE; DENDRITIC CELLS AB Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays, the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of anti body-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodies for control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis. (c) 2007 The WJG Press. All rights reserved. C1 Univ Strasbourg 1, INSERM, Unite 748, F-67000 Strasbourg, France. Hop Univ Strasbourg, Serv Hepatogastroenterol, Strasbourg, France. NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Baumert, TF (reprint author), Univ Strasbourg 1, INSERM, Unite 748, 3 Rue Koeberle, F-67000 Strasbourg, France. EM thomas.baumert@viro-ulp.u-strasbg.fr RI Zeisel, Mirjam/E-9205-2016 OI Zeisel, Mirjam/0000-0003-1606-0131 NR 86 TC 32 Z9 37 U1 1 U2 8 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD SEP 28 PY 2007 VL 13 IS 36 BP 4824 EP 4830 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 210NG UT WOS:000249462300006 PM 17828813 ER PT J AU Neumann, HPH Vortmeyer, A Schmidt, D Werner, M Erlic, Z Cascon, A Bausch, B Januszewicz, A Eng, C AF Neumann, Hartmut P. H. Vortmeyer, Alexander Schmidt, Dieter Werner, Martin Erlic, Zoran Cascon, Alberto Bausch, Birke Januszewicz, Andrzej Eng, Charis TI Evidence of MEN-2 in the original description of classic pheochromocytoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MUTATIONS; GENE AB The first description of pheochromocytoma in 1886 has been attributed to Felix Frankel, who described an 18-year-old woman with bilateral adrenal "sarcoma and angio-sarcoma." We reviewed the publication and then approached and assessed relatives of the patient to update the findings with the use of current technology. In-depth review revealed that the histopathological findings were consistent with pheochromocytoma. Because the proband was young and had bilateral disease at diagnosis, we hypothesized that she had an inherited condition. The presence of germ-line RET mutations in four living relatives demonstrates that the original patient and her family had multiple endocrine neoplasia type 2 and provides molecular evidence that she had pheochromocytoma. C1 Univ Freiburg, Med Klin, Med Ctr, Dept Nephrol, D-79106 Freiburg, Germany. Univ Freiburg, Med Ctr, Dept Ophthalmol, D-79106 Freiburg, Germany. Univ Freiburg, Med Ctr, Dept Pathol, D-79106 Freiburg, Germany. NINDS, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Univ Padua, Sch Med, Dept Endocrinol, Padua, Italy. Ctr Nacl Invest Oncol, Hereditary Endocrine Canc Grp, Madrid, Spain. Inst Cardiol, Warsaw, Poland. Lerner Res Inst, Genom Med Inst, Cleveland, OH USA. Cleveland Clin Fdn, Taussig Canc Ctr, Cleveland, OH 44195 USA. RP Neumann, HPH (reprint author), Univ Freiburg, Med Klin, Med Ctr, Dept Nephrol, Hugstetter Str 55, D-79106 Freiburg, Germany. EM hartmut.neumann@uniklinik-freiburg.de RI Cascon, Alberto/G-3160-2014 OI Cascon, Alberto/0000-0003-2119-891X FU NICHD NIH HHS [R01HD39058-01, R01HD39058-01S1] NR 15 TC 41 Z9 43 U1 0 U2 6 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 SEP 27 PY 2007 VL 357 IS 13 BP 1311 EP 1315 DI 10.1056/NEJMoa071407 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 214BR UT WOS:000249711500007 PM 17898100 ER PT J AU Reboli, AC Wible, M Walsh, TJ AF Reboli, Annette C. Wible, Michele Walsh, Thomas J. TI Anidulafungin and fluconazole for candidiasis - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Cooper Univ Hosp, Camden, NJ 08103 USA. Wyeth Ayerst Res, Collegeville, PA 19426 USA. NCI, Bethesda, MD 20892 USA. RP Reboli, AC (reprint author), Cooper Univ Hosp, Camden, NJ 08103 USA. EM reboli-annette@cooperhealth.edu NR 2 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 SEP 27 PY 2007 VL 357 IS 13 BP 1348 EP 1348 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 214BR UT WOS:000249711500017 ER PT J AU Takafuji, V Forgues, M Unsworth, E Goldsmith, P Wang, XW AF Takafuji, V. Forgues, M. Unsworth, E. Goldsmith, P. Wang, X. W. TI An osteopontin fragment is essential for tumor cell invasion in hepatocellular carcinoma SO ONCOGENE LA English DT Article DE osteopontin; hepatocellular carcinoma; metastasis; cellular invasion; MMP-9; CD44 ID METASTASIS FORMATION; PROTEIN EXPRESSION; PLASMA OSTEOPONTIN; SURVIVAL; CANCER; CD44; TRANSGLUTAMINASE; BREAST; OVEREXPRESSION; PROGRESSION AB Tumor cell invasion is a primary event in the metastatic progression of hepatocellular carcinoma (HCC). Our recent results indicate a concordant elevated expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in primary metastatic HCC. This study hypothesizes an MMP-9-directed cleavage of OPN that biologically contributes to HCC metastasis. We found that MMP-9 cleaved OPN into specific fragments in vitro, of which three could be identified by Edman degradation amino-acid sequencing. On e of these fragments (OPN-5 kDa, residues 167-210) induced low-metastatic HCC cellular invasion via CD44 receptors, which was effectively blocked by the addition of small peptides within the region of OPN-5 kDa. In creased expression of an OPN splice variant (OPN-c) was associated with clinical metastatic HCC. Overexpression of OPN-c with physiological levels of MMP-9 enhanced cellular invasion and coincided with elevated OPN-5 kDa levels. Our data suggest that an alternative splicing event (OPN-c) promotes extracellular cleavage of OPN by MMP-9, thus releasing a distinct region of OPN (OPN-5 kDa) that is essential for HCC cellular invasion and appears to correlate with metastatic potential. The findings of this study may help to improve advanced-stage HCC prognosis and suggest the utility of small peptides for novel therapies. C1 NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Antibody & Protein Purificat Grp, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37-3044A,37 Convent Dr MSC 4258, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 FU Intramural NIH HHS NR 39 TC 98 Z9 102 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 27 PY 2007 VL 26 IS 44 BP 6361 EP 6371 DI 10.1038/sj.onc.1210463 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 214KY UT WOS:000249737600001 PM 17452979 ER PT J AU Kumar, V Olsen, CE Schaffer, SJC Parmar, VS Malhotra, SV AF Kumar, Vineet Olsen, Carl E. Schaffer, Susan J. C. Parmar, Virinder S. Malhotra, Sanjay V. TI Synthesis and applications of novel bis(ammonium) chiral ionic liquids derived from isomannide SO ORGANIC LETTERS LA English DT Article ID TRANSFER RADICAL POLYMERIZATION; MICHAEL ADDITION; ISOSORBIDE; SOLVENTS; DESIGN; ACIDS; POLYESTERS; SALTS; ACRYLATES; CATALYSTS AB Carbohydrate-based novel bis(ammonium) chiral ionic liquids have been synthesized by following a straightforward protocol using isomannide as the substrate. Their applications in chiral discrimination and optical resolution of racemates have been established. C1 Univ Hts, New Jersey Inst Technol, Dept Chem & Environm Sci, Newark, NJ 07102 USA. Univ Delhi, Dept Chem, Delhi 110007, India. Univ Copenhagen, Fac Life Sci, Dept Nat Sci, DK-1871 Frederiksberg, Denmark. Tech Univ Denmark, Dept Chem, DK-2800 Lyngby, Denmark. RP Kumar, V (reprint author), NCI, SAIC Frederick, 1050 Boyles St, Frederick, MD 21702 USA. EM virparmar@gmail.com; malhotrasa@mail.nih.gov RI Olsen, Carl/H-3031-2014 OI Olsen, Carl/0000-0002-2275-0596 NR 43 TC 50 Z9 50 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD SEP 27 PY 2007 VL 9 IS 20 BP 3905 EP 3908 DI 10.1021/ol071390y PG 4 WC Chemistry, Organic SC Chemistry GA 213WK UT WOS:000249697800012 PM 17725360 ER PT J AU Gulley, JL Madan, RA Arlen, PM AF Gulley, James L. Madan, Ravi A. Arlen, Philip M. TI Enhancing efficacy of therapeutic vaccinations by combination with other modalities SO VACCINE LA English DT Review DE immunotherapy; vaccine; clinical protocols; prostate cancer; prostate-specific antigen; cancer vaccine; combination therapy; hormone therapy; chemotherapy; radiation therapy; Anti-CTLA-4 ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; INDEPENDENT PROSTATE-CANCER; ANTITUMOR IMMUNE-RESPONSE; FAS-MEDIATED CYTOTOXICITY; RANDOMIZED PHASE-II; CELL VACCINES; TUMOR-CELLS; T-CELLS; IONIZING-RADIATION; GAMMA-INTERFERON AB Novel strategies are emerging from preclinical and clinical investigations for combining vaccines with conventional and experimental anticancer therapies. Several lines of research show that combining either radiation or certain chemotherapeutic agents with vaccine can alter the phenotype of tumor cells, rendering them more susceptible to T cell-mediated killing. Furthermore, there is emerging data suggesting that an immune response elicited by vaccine may augment the antitumor effectiveness of subsequent therapies. This article reviews and discusses therapeutic cancer strategies that employ vaccines sequentially or in combination with conventional cytotoxic therapies such as local radiation, chemotherapy, and hormone therapy, or immunopotentiating therapies such as anti-CTLA-4 monoclonal antibodies. Preliminary results of clinical studies using these combination strategies have demonstrated a postvaccination antigen cascade, prolonged time to disease progression, and preliminary evidence of improved overall survival. Large randomized studies are currently underway to further investigate these findings. C1 NCI, Canc Res Ctr, Tumor Immunol & Biol Lab, Clin Immunotherapy Grp,Natl Inst Hlth, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Canc Res Ctr, Tumor Immunol & Biol Lab, Clin Immunotherapy Grp,Natl Inst Hlth, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS [Z99 CA999999] NR 64 TC 50 Z9 51 U1 0 U2 2 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 SEP 27 PY 2007 VL 25 SU 2 BP B89 EP B96 DI 10.1016/j.vaccine.2007.04.091 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 232XO UT WOS:000251054700009 PM 17573164 ER PT J AU Tomasi, D Goldstein, RZ Telang, F Maloney, T Alia-Klein, N Caparelli, EC Volkow, ND AF Tomasi, D. Goldstein, R. Z. Telang, F. Maloney, T. Alia-Klein, N. Caparelli, E. C. Volkow, N. D. TI Widespread disruption in brain activation patterns to a working memory task during cocaine abstinence SO BRAIN RESEARCH LA English DT Article DE cocaine withdrawal; function MRI; PET ID POSITRON-EMISSION-TOMOGRAPHY; RAT PREFRONTAL CORTEX; CEREBRAL-BLOOD-FLOW; ACOUSTIC NOISE; DOPAMINERGIC MODULATION; NICOTINE WITHDRAWAL; PARKINSONS-DISEASE; DEPENDENT SUBJECTS; ATTENTION TASKS; 4 TESLA AB Cocaine abstinence is associated with impaired performance in cognitive functions including attention, vigilance and executive function. Here we test the hypothesis that cognitive dysfunction during cocaine abstinence reflects in part impairment of cortical and subcortical regions modulated by dopamine. We used functional magnetic resonance imaging (fMRI) to study brain activation to a verbal working memory task in cocaine abusers (n=16) and healthy controls (n=16). Compared to controls, cocaine abusers showed: (1) hypoactivation in the mesencephalon, where dopamine neurons are located, as well as the thalamus, a brain region involved in arousal; (2) larger deactivation in dopamine projection regions (putamen, anterior cingulate, parahippocampal gyrus, and amygdala); and (3) hyperactivation in cortical regions involved with attention (prefrontal and parietal cortices), which probably reflects increased attention and control processes as compensatory mechanisms. Furthermore, the working memory load activation was lower in the prefrontal and parietal cortices in cocaine abusers when compared with controls, which might reflect limited network capacity. These abnormalities were accentuated in the cocaine abusers with positive urines for cocaine at time of study (as compared to cocaine abusers with negative urines) suggesting that the deficits may reflect in part early cocaine abstinence. These findings provide evidence of impaired function of regions involved with executive control, attention and vigilance in cocaine abusers. This widespread neurofunctional disruption is likely to underlie the cognitive deficits during early cocaine abstinence and to reflect involvement of dopamine as well as other neurotransmitters. Published by Elsevier B.V. C1 Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Natl Inst Drug Abuse, Bethesda, MD USA. RP Tomasi, D (reprint author), Brookhaven Natl Lab, Dept Med, Bldg 490,30 Bell Ave, Upton, NY 11973 USA. EM tomasi@bnl.gov RI Tomasi, Dardo/J-2127-2015 FU NCRR NIH HHS [GCRC 5 M01 RR10710, M01 RR010710]; NIDA NIH HHS [1 K23 DA15517-01, K23 DA015517, R03 DA017070, R03 DA017070-01] NR 47 TC 71 Z9 71 U1 4 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 26 PY 2007 VL 1171 BP 83 EP 92 DI 10.1016/j.brainres.2007.06.102 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 222IH UT WOS:000250289100009 PM 17765877 ER PT J AU Wang, PS Simon, GE Avorn, J Azocar, F Ludman, EJ McCulloch, J Petukhova, MZ Kessler, RC AF Wang, Philip S. Simon, Gregory E. Avorn, Jerry Azocar, Francisca Ludman, Evette J. McCulloch, Joyce Petukhova, Maria Z. Kessler, Ronald C. TI Telephone screening, outreach, and care management for depressed workers and impact on clinical and work productivity outcomes - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COMORBIDITY SURVEY REPLICATION; PERFORMANCE QUESTIONNAIRE HPQ; HEALTH-ORGANIZATION HEALTH; SERIOUS MENTAL-ILLNESS; COLLABORATIVE CARE; UNITED-STATES; COST-EFFECTIVENESS; MAJOR DEPRESSION; SYMPTOMATOLOGY IDS; ANXIETY DISORDERS AB Context Although guideline-concordant depression treatment is clearly effective, treatment often falls short of evidence-based recommendations. Organized depression care programs significantly improve treatment quality, but employer purchasers have been slow to adopt these programs based on lack of evidence for cost-effectiveness from their perspective. Objective To evaluate the effects of a depression outreach-treatment program on workplace outcomes, a concern to employers. Design, Setting, and Participants A randomized controlled trial involving 604 employees covered by a managed behavioral health plan were identified in a 2-stage screening process as having significant depression. Patient treatment allocation was concealed and assessment of depression severity and work performance at months 6 and 12 was blinded. Employees with lifetime bipolar disorder, substance disorder, recent mental health specialty care, or suicidality were excluded. Intervention A telephonic outreach and care management program encouraged workers to enter outpatient treatment (psychotherapy and/or antidepressant medication), monitored treatment quality continuity, and attempted to improve treatment by giving recommendations to providers. Participants reluctant to enter treatment were offered a structured telephone cognitive behavioral psychotherapy. Main Outcome Measures Depression severity (Quick Inventory of Depressive Symptomatology, QIDS) and work performance (World Health Organization Health and Productivity Questionnaire [HPQ], a validated self-report instrument assessing job retention, time missed from work, work performance, and critical workplace incidents). Results Combining data across 6- and 12-month assessments, the intervention group had significantly lower QIDS self-report scores (relative odds of recovery, 1.4; 95% confidence interval, 1.1-2.0; P = .009), significantly higher job retention (relative odds, 1.7; 95% confidence interval, 1.1-3.3; P = .02), and significantly more hours worked among the intervention (beta = 2.0; P = .02; equivalent to an annualized effect of 2 weeks of work) than the usual care groups that were employed. Conclusions A systematic program to identify depression and promote effective treatment significantly improves not only clinical outcomes but also workplace outcomes. The financial value of the latter to employers in terms of recovered hiring, training, and salary costs suggests that many employers would experience a positive return on investment from outreach and enhanced treatment of depressed workers. C1 NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. United Behav Hlth, San Francisco, CA USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA 98101 USA. RP Wang, PS (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd,Room 7141,MSC 9629, Bethesda, MD 20892 USA. EM wangphi@mail.nih.gov FU NIMH NIH HHS [R01 MH061941, R01 MH061941-03, R01 MH61941] NR 83 TC 189 Z9 189 U1 4 U2 30 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 SEP 26 PY 2007 VL 298 IS 12 BP 1401 EP 1411 DI 10.1001/jama.298.12.1401 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 213WV UT WOS:000249698900019 PM 17895456 ER PT J AU You, ZB Wang, B Zitzman, D Azari, S Wise, RA AF You, Zhi-Bing Wang, Bin Zitzman, Dawnya Azari, Soraya Wise, Roy A. TI A role for conditioned ventral tegmental glutamate release in cocaine seeking SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cocaine; extinction; GABA; glutamate; self-administration; ventral tegmental area ID NUCLEUS-ACCUMBENS DOPAMINE; EXTRACELLULAR DOPAMINE; INVIVO MICRODIALYSIS; D-AMPHETAMINE; DRUG-SEEKING; REWARD; RATS; PIMOZIDE; NEURONS; EXTINCTION AB Initiation of cocaine self-administration in rats was associated with release of glutamate in the ventral tegmental area ( VTA). The glutamate release was transient, despite continued cocaine intake. Similar glutamate release was seen in rats earning, for the first time, unexpected saline rather than expected cocaine. VTA glutamate release was not seen in similarly trained rats earning saline instead of cocaine for the 13th time. VTA glutamate release was also seen in similarly trained rats that received yoked rather than earned cocaine injections on test day. VTA glutamate release was not seen in a group of rats that had never earned cocaine but had received yoked injections during the training period. Glutamate release was also not seen in a group of rats that received yoked injections but had no previous experience with cocaine. VTA GABA levels did not fluctuate during any aspect of cocaine seeking. Blockade of VTA glutamate receptors appeared to attenuate the rewarding effects of intravenous cocaine injections and blocked almost completely the conditioned responding normally seen during extinction trials. These findings indicate that VTA glutamate release is a conditioned response dependent on an associative process and is not a simple consequence of previous cocaine exposure. The findings implicate glutamate as at least one of the sources of VTA signals from reward-associated environmental stimuli. C1 NIDA, Intramural Res Program, NIH, Behav Neurosci Branch, Baltimore, MD 21224 USA. RP You, ZB (reprint author), NIDA, Intramural Res Program, NIH, Behav Neurosci Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM zyou@intra.nida.nih.gov RI Wise, Roy/A-6465-2012 FU Intramural NIH HHS NR 41 TC 70 Z9 70 U1 1 U2 5 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 SEP 26 PY 2007 VL 27 IS 39 BP 10546 EP 10555 DI 10.1523/JNEUROSCI.2967-07.2007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 214SB UT WOS:000249757300024 PM 17898226 ER PT J AU Makarova, KS Omelchenko, MV Gaidamakova, EK Matrosova, VY Vasilenko, A Zhai, M Lapidus, A Copeland, A Kim, E Land, M Mavromatis, K Pitluck, S Richardson, PM Detter, C Brettin, T Saunders, E Lai, B Ravel, B Kemner, KM Wolf, YI Sorokin, A Gerasimova, AV Gelfand, MS Fredrickson, JK Koonin, EV Daly, MJ AF Makarova, Kira S. Omelchenko, Marina V. Gaidamakova, Elena K. Matrosova, Vera Y. Vasilenko, Alexander Zhai, Min Lapidus, Alla Copeland, Alex Kim, Edwin Land, Miriam Mavromatis, Konstantinos Pitluck, Samuel Richardson, Paul M. Detter, Chris Brettin, Thomas Saunders, Elizabeth Lai, Barry Ravel, Bruce Kemner, Kenneth M. Wolf, Yuri I. Sorokin, Alexander Gerasimova, Anna V. Gelfand, Mikhail S. Fredrickson, James K. Koonin, Eugene V. Daly, Michael J. TI Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks SO PLOS ONE LA English DT Article ID STRAND ANNEALING PROTEINS; ESCHERICHIA-COLI; IONIZING-RADIATION; DNA-DAMAGE; COMPARATIVE GENOMICS; RADIODURANS R1; TRANSCRIPTIONAL REGULATORS; TARGETED MUTAGENESIS; BACILLUS-SUBTILIS; CRYOELECTRON MICROSCOPY AB Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to resistance; and strengthen the case for a role in survival of systems involved in manganese and iron homeostasis. C1 [Makarova, Kira S.; Omelchenko, Marina V.; Wolf, Yuri I.; Sorokin, Alexander; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Gaidamakova, Elena K.; Matrosova, Vera Y.; Vasilenko, Alexander; Zhai, Min; Daly, Michael J.] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. [Lapidus, Alla; Copeland, Alex; Kim, Edwin; Land, Miriam; Mavromatis, Konstantinos; Pitluck, Samuel; Richardson, Paul M.] US DOE, Joint Genome Inst, Walnut Creek, CA USA. [Detter, Chris; Brettin, Thomas; Saunders, Elizabeth] Los Alamos Natl Lab, US Dept Energy, Joint Genome Inst, Los Alamos, NM USA. [Lai, Barry; Ravel, Bruce; Kemner, Kenneth M.] Argonne Natl Lab, Div Environm Res, Argonne, IL 60439 USA. [Lai, Barry; Ravel, Bruce; Kemner, Kenneth M.] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA. [Gerasimova, Anna V.] Res Inst Genet & Select Ind Microorganisms, Moscow, Russia. [Gelfand, Mikhail S.] RAS, Inst Informat Transmiss Problems, Moscow 117901, Russia. [Gelfand, Mikhail S.] Moscow MV Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow, Russia. [Fredrickson, James K.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. RP Makarova, KS (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM makarova@ncbi.nlm.nih.gov; mdaly@usuhs.mil RI Land, Miriam/A-6200-2011; Gelfand, Mikhail/F-3425-2012; Lapidus, Alla/I-4348-2013 OI Land, Miriam/0000-0001-7102-0031; Lapidus, Alla/0000-0003-0427-8731 FU National Institutes of Health; National Library of Medicine; USUHS [DE-FG02-04ER63918]; U.S. Department of Energy (DOE), Office of Science, Office of Biological and Environmental Research; Environmental Remediation Sciences Program (ERSP); Air Force Office of Scientific Research [FA9550-07-1-0218]; DOE Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; Howard Hughes Medical Institute [55005610]; INTAS [05-8028]; Molecular and Cellular Virology program of the Russian Academy of Sciences FX The work of KSM, MVO, YIW, AS, and EVK was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. The work at USUHS was supported by grant DE-FG02-04ER63918 to MJD from the U.S. Department of Energy (DOE), Office of Science, Office of Biological and Environmental Research (BER), Environmental Remediation Sciences Program (ERSP); and by grant FA9550-07-1-0218 to MJD from the Air Force Office of Scientific Research. The work at the DOE-Joint Genome Institute was supported by the DOE Office of Science. Work at the Advanced Photon Source was supported by the DOE Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. The work of MSG and AVG was supported by grants from the Howard Hughes Medical Institute (55005610), INTAS (05-8028), and the Molecular and Cellular Virology program of the Russian Academy of Sciences. D. geothermalis was selected for genome sequencing by BER (http://www.science. doe.gov/ober/RFS-2.pdf) with MJD as the Principal Investigator. NR 171 TC 89 Z9 94 U1 4 U2 26 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 SEP 26 PY 2007 VL 2 IS 9 AR e955 DI 10.1371/journal.pone.0000955 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10HT UT WOS:000207455800033 PM 17895995 ER PT J AU Parikh, NI Hwang, SJ Larson, MG Cupples, LA Fox, CS Manders, ES Murabito, JM Massaro, JM Hoffmann, U O'Donnell, CJ AF Parikh, Nisha I. Hwang, Shih-Jen Larson, Martin G. Cupples, L. Adrienne Fox, Caroline S. Manders, Emily S. Murabito, Joanne M. Massaro, Joseph M. Hoffmann, Udo O'Donnell, Christopher J. TI Parental occurrence of premature cardiovascular disease predicts increased coronary artery and abdominal aortic calcification in the Framingham Offspring and Third Generation cohorts SO CIRCULATION LA English DT Article DE calcium; epidemiology; imaging; atherosclerosis; coronary disease; aorta ID ACUTE MYOCARDIAL-INFARCTION; CONVENTIONAL RISK-FACTORS; ISCHEMIC-HEART-DISEASE; FAMILY-HISTORY; SUBCLINICAL ATHEROSCLEROSIS; INDEPENDENT PREDICTOR; COMPUTED-TOMOGRAPHY; TASK-FORCE; CALCIUM; ADULTS AB Background-Parental premature cardiovascular disease (CVD) is a risk factor for coronary heart disease ( CHD). We related validated parental premature CVD with the subclinical measures of coronary artery (CAC) and abdominal aortic (AAC) calcification in the community. Methods and Results-We studied 2 generations of Framingham Heart Study subjects who underwent multidetector computed tomography measurements of CAC and AAC and who had 2 parents in the study. Subjects included 797 Framingham Offspring ( mean age, 63 years; 56% women) and 1238 Third Generation (Gen3) ( mean age, 46 years; 47% women) participants free of CVD. Generalized estimating equations adjusted for major CVD risk factors were used to relate validated parental premature CVD and CHD to CAC and AAC, defined by > 90th percentile age- and sex-specific cut points from a healthy subsample. Parental premature CVD was associated with CAC among Gen3 ( odds ratio=2.17 [1.41 to 3.33]; P < 0.001) and nonsignificantly among Offspring (odds ratio=1.42 [0.91 to 2.22]; P=0.12). Parental premature CHD was associated with CAC among Gen3 (odds ratio=2.22 [1.22 to 4.01]) but not Offspring. Parental premature CVD was not associated with AAC in either cohort. Parental premature CHD was associated with AAC among Gen3 (odds ratio=1.65 [0.99 to 2.75]; P=0.05) but not among Offspring. The magnitude of risk conferred was greater for paternal than maternal premature CVD. Conclusions-Parental premature CVD is associated with CAC, and premature CHD is associated with AAC, after adjustment for risk factors, particularly in younger middle-aged adults. Risk conferred by parental premature CVD on vascular calcification may be mediated through novel mechanisms not accounted for by classic CVD risk factors known to cause atherosclerosis. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), 73 Mt Wayte Ave 2, Framingham, MA 01702 USA. EM codonnell@nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Cupples, L. Adrienne/0000-0003-0273-7965; Murabito, Joanne/0000-0002-0192-7516 FU NHLBI NIH HHS [N01-HC-25195] NR 47 TC 69 Z9 69 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 25 PY 2007 VL 116 IS 13 BP 1473 EP 1481 DI 10.1161/CIRCULATIONAHA.107.705202 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 213VL UT WOS:000249695100007 PM 17785619 ER PT J AU Smith, DL Guerra, CA Snow, RW Hay, SI AF Smith, David L. Guerra, Carlos A. Snow, Robert W. Hay, Simon I. TI Standardizing estimates of the Plasmodium falciparum parasite rate SO MALARIA JOURNAL LA English DT Article ID MALARIA ATLAS PROJECT; ACQUIRED-IMMUNITY; INOCULATION RATE; RURAL AREA; TRANSMISSION; CHILDREN; AFRICA; RISK; AGE; PREVALENCE AB Background: The Plasmodium falciparum parasite rate (PfPR) is a commonly reported index of malaria transmission intensity. PfPR rises after birth to a plateau before declining in older children and adults. Studies of populations with different age ranges generally report average PfPR, so age is an important source of heterogeneity in reported PfPR data. This confounds simple comparisons of PfPR surveys conducted at different times or places. Methods: Several algorithms for standardizing PfPR were developed using 21 studies that stratify in detail PfPR by age. An additional 121 studies were found that recorded PfPR from the same population over at least two different age ranges; these paired estimates were used to evaluate these algorithms. The best algorithm was judged to be the one that described most of the variance when converting the PfPR pairs from one age-range to another. Results: The analysis suggests that the relationship between PfPR and age is predictable across the observed range of malaria endemicity. PfPR reaches a peak after about two years and remains fairly constant in older children until age ten before declining throughout adolescence and adulthood. The PfPR pairs were poorly correlated; using one to predict the other would explain only 5% of the total variance. By contrast, the PfPR predicted by the best algorithm explained 72% of the variance. Conclusion: The PfPR in older children is useful for standardization because it has good biological, epidemiological and statistical properties. It is also historically consistent with the classical categories of hypoendemic, mesoendemic and hyperendemic malaria. This algorithm provides a reliable method for standardizing PfPR for the purposes of comparing studies and mapping malaria endemicity. The scripts for doing so are freely available to all. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England. Kenyatta Natl Hosp Grounds, KEMRI Wellcome Trust Collaborat Programme, Ctr Geog Med, Malaria Publ Hlth & Epidemiol Grp, Nairobi 00100, Kenya. Univ Oxford, John Radcliffe Hosp, Ctr Trop Med, Oxford OX3 9DS, England. Univ Florida, Dept Zool, Gainesville, FL 32611 USA. Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA. RP Smith, DL (reprint author), NIH, Fogarty Int Ctr, Bldg 16,16 Ctr Dr, Bethesda, MD 20892 USA. EM davesmith@ufl.edu; carlos.guerraloaiza@zoo.ox.ac.uk; rsnow@nairobi.kemriwellcome.org; shay@nairobi.kemri-wellcome.org RI Smith, David/L-8850-2013; Hay, Simon/F-8967-2015; OI Smith, David/0000-0003-4367-3849; Hay, Simon/0000-0002-0611-7272; Snow, Robert/0000-0003-3725-6088 FU Wellcome Trust [076951, 079080, 079091] NR 39 TC 85 Z9 85 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD SEP 25 PY 2007 VL 6 AR 131 DI 10.1186/1475-2875-6-131 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 230JN UT WOS:000250872900001 PM 17894879 ER PT J AU Nemeth, MJ Topol, L Anderson, SM Yang, YZ Bodine, DM AF Nemeth, Michael J. Topol, Lilia Anderson, Stacie M. Yang, Yingzi Bodine, David M. TI Wnt5a inhibits canonical Wnt signaling in hematopoietic stem cells and enhances repopulation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell cycle; hematopoiesis; hematopoietic stem cell transplantation ID ACUTE MYELOID-LEUKEMIA; SELF-RENEWAL; BETA-CATENIN; IN-VIVO; CYCLE STATUS; GENE FAMILY; BONE-MARROW; DIFFERENTIATION; PATHWAY; ACTIVATION AB The mechanisms that regulate hematopoietic stem cell (HSC) fate decisions between proliferation and multilineage differentiation are unclear. Members of the Wnt family of ligands that activate the canonical Writ signaling pathway, which utilizes beta-catenin to relay the signal, have been demonstrated to regulate HSC function. In this study, we examined the role of noncanonical Writ signaling in regulating HSC fate. We observed that noncanonical Wnt5a inhibited Wnt3a-mediated canonical Writ signaling in HSCs and suppressed Wnt3a-mediated alterations in gene expression associated with HSC differentiation, such as increased expression of myc. Wnt5a increased short- and long-term HSC repopulation by maintaining HSCs in a quiescent Go state. From these data, we propose that Wnt5a regulates hematopoiesis by the antagonism of the canonical Writ pathway, resulting in a pool of quiescent HSCs. C1 NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Bodine, DM (reprint author), NHGRI, Genet & Mol Biol Branch, 49 Convent Dr,Room 4A04, Bethesda, MD 20892 USA. EM tedyaz@nhgri.nih.gov NR 38 TC 145 Z9 154 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 SEP 25 PY 2007 VL 104 IS 39 BP 15436 EP 15441 DI 10.1073/pnas.0704747104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 215KJ UT WOS:000249806900048 PM 17881570 ER PT J AU Dunn, BD Sakamoto, T Hong, MSS Sellers, JR Takizawa, PA AF Dunn, Brian D. Sakamoto, Takeshi Hong, Myoung-Soon S. Sellers, James R. Takizawa, Peter A. TI Myo4p is a monomeric myosin with motility uniquely adapted to transport mRNA SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CLASS-V MYOSINS; HAND-OVER-HAND; SACCHAROMYCES-CEREVISIAE; BINDING PROTEIN; TAIL DOMAIN; LEVER ARM; YEAST; LOCALIZATION; MOTOR; PROCESSIVITY AB The yeast Saccharomyces cerevisiae uses two class V myosins to transport cellular material into the bud: Myo2p moves secretory vesicles and organelles, whereas Myo4p transports mRNA. To understand how Myo2p and Myo4p are adapted to transport physically distinct cargos, we characterize Myo2p and Myo4p in yeast extracts, purify active Myo2p and Myo4p from yeast lysates, and analyze their motility. We find several striking differences between Myo2p and Myo4p. First, Myo2p forms a dimer, whereas Myo4p is a monomer. Second, Myo4p generates higher actin. lament velocity at lower motor density. Third, single molecules of Myo2p are weakly processive, whereas individual Myo4p motors are nonprocessive. Finally, Myo4p self-assembles into multimotor complexes capable of processive motility. We show that the unique motility of Myo4p is not due to its motor domain and that the motor domain of Myo2p can transport ASH1 mRNA in vivo. Our results suggest that the oligomeric state of Myo4p is important for its motility and ability to transport mRNA. C1 Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA. NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Takizawa, PA (reprint author), Yale Univ, Sch Med, Dept Cell Biol, 333 Cedar St, New Haven, CT 06520 USA. EM peter.takizawa@yale.edu FU NIGMS NIH HHS [GM073734, R01 GM073734, R01 GM073734-03] NR 56 TC 36 Z9 38 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP 24 PY 2007 VL 178 IS 7 BP 1193 EP 1206 DI 10.1083/jcb.200707080 PG 14 WC Cell Biology SC Cell Biology GA 215AO UT WOS:000249779800009 PM 17893244 ER PT J AU Paul, WE AF Paul, William E. TI Dendritic cells bask in the limelight SO CELL LA English DT Article ID PERIPHERAL LYMPHOID ORGANS; MICE; IDENTIFICATION AB Ralph Steinman is to receive the 2007 Albert Lasker Award for Basic Medical Research for his discovery of dendritic cells and his path- breaking work demonstrating their central role as the principal antigen- presenting cells of the immune system and key activators of T cell responses. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov NR 14 TC 2 Z9 2 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 21 PY 2007 VL 130 IS 6 BP 967 EP 970 DI 10.1016/j.cell.2007.09.001 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 225HK UT WOS:000250507500002 PM 17889637 ER PT J AU Yang, HY Yang, T Baur, JA Perez, E Matsui, T Carmona, JJ Lamming, DW Souza-Pinto, NC Bohr, VA Rosenzweig, A de Cabo, R Sauve, AA Sinclair, DA AF Yang, Hongying Yang, Tianle Baur, Joseph A. Perez, Evelyn Matsui, Takashi Carmona, Juan J. Lamming, Dudley W. Souza-Pinto, Nadja C. Bohr, Vilhelm A. Rosenzweig, Anthony de Cabo, Rafael Sauve, Anthony A. Sinclair, David A. TI Nutrient-sensitive mitochondrial NAD(+) levels dictate cell survival SO CELL LA English DT Article ID COLONY-ENHANCING FACTOR; LIFE-SPAN EXTENSION; NICOTINAMIDE ADENINE-DINUCLEOTIDE; CALORIE RESTRICTION; SACCHAROMYCES-CEREVISIAE; DEACETYLASE ACTIVITY; OXIDATIVE STRESS; SIR2 PROTEIN; ACETYL-COA; APOPTOSIS AB A major cause of cell death caused by genotoxic stress is thought to be due to the depletion of NAD+ from the nucleus and the cytoplasm. Here we show that NAD+ levels in mitochondria remain at physiological levels following genotoxic stress and can maintain cell viability even when nuclear and cytoplasmic pools of NAD+ are depleted. Rodents fasted for 48 hr show increased levels of the NAD+ biosynthetic enzyme Nampt and a concomitant increase in mitochondrial NAD+. Increased Nampt provides protection against cell death and requires an intact mitochondrial NAD+ salvage pathway as well as the mitochondrial NAD(+)- dependent deacetylases SIRT3 and SIRT4. We discuss the relevance of these findings to understanding how nutrition modulates physiology and to the evolution of apoptosis. C1 Cornell Univ, Weill Med Col, Dept Pharmacol, New York, NY 10021 USA. NIA, Lab Expt Gerontol, Inst Hlth, Baltimore, MD 21224 USA. NIA, Lab Mol Gerontol, Inst Hlth, Baltimore, MD 21224 USA. Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. RP Sinclair, DA (reprint author), Harvard Univ, Sch Med, Paul F Glenn Labs, Dept Pathol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM david_sinclair@hms.harvard.edu RI de Cabo, Rafael/E-7996-2010; Baur, Joseph/D-8163-2011; Souza-Pinto, Nadja/C-3462-2013; de Cabo, Rafael/J-5230-2016; OI , rafael/0000-0003-2830-5693; Souza-Pinto, Nadja/0000-0003-4206-964X; de Cabo, Rafael/0000-0002-3354-2442; Sinclair, David/0000-0002-9936-436X; Baur, Joseph/0000-0001-8262-6549 FU Intramural NIH HHS; NIA NIH HHS [R01 AG028730-01A1, P01 AG027916, P01 AG027916-010003, P01 AG027916-020003, P01 AG027916-030003, P01 AG027916-040003, P01 AG027916-04S10003, P01 AG027916-04S20003, R01 AG019719, R01 AG019719-06A1, R01 AG019719-07, R01 AG028730, R01 AG028730-02, R01AG028730]; NIDDK NIH HHS [R01 DK 073466, R01 DK073466]; NIGMS NIH HHS [R01 GM068072, R01GM068072] NR 63 TC 467 Z9 481 U1 7 U2 45 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 21 PY 2007 VL 130 IS 6 BP 1095 EP 1107 DI 10.1016/j.cell.2007.07.035 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 225HK UT WOS:000250507500018 PM 17889652 ER PT J AU Duan, X Chang, JH Ge, S Faulkner, RL Kim, JY Kitabatake, Y Liu, XB Yang, CH Jordan, JD Ma, DK Liu, CY Ganesan, S Cheng, HJ Ming, GL Lu, B Song, H AF Duan, Xin Chang, Jay H. Ge, Shaoyu Faulkner, Regina L. Kim, Ju Young Kitabatake, Yasuji Liu, Xiao-bo Yang, Chih-Hao Jordan, J. Dedrick Ma, Dengke K. Liu, Cindy Y. Ganesan, Sundar Cheng, Hwai-Jong Ming, Guo-li Lu, Bai Song, Hongjun TI Disrupted-in-schizophrenia 1 regulates integration of newly generated neurons in the adult brain SO CELL LA English DT Article ID GRANULE CELLS; DENTATE GYRUS; NEURITE OUTGROWTH; MOUSE HIPPOCAMPUS; BASAL DENDRITES; CEREBRAL-CORTEX; SCHIZOPHRENIA; DISC1; NEUROGENESIS; GENES AB Adult neurogenesis occurs throughout life in discrete regions of the adultmammalian brain. Little is known about the mechanism governing the sequential developmental process that leads to integration of new neurons from adult neural stem cells into the existing circuitry. Here, we investigated roles of Disrupted- In- Schizophrenia 1 ( DISC1), a schizophrenia susceptibility gene, in adult hippocampal neurogenesis. Unexpectedly, downregulation of DISC1 leads to accelerated neuronal integration, resulting in aberrant morphological development and mispositioning of new dentate granule cells in a cell- autonomous fashion. Functionally, newborn neurons with DISC1 knockdown exhibit enhanced excitability and accelerated dendritic development and synapse formation. Furthermore, DISC1 cooperates with its binding partner NDEL1 in regulating adult neurogenesis. Taken together, our study identifies DISC1 as a key regulator that orchestrates the tempo of functional neuronal integration in the adult brain and demonstrates essential roles of a susceptibility gene for major mental illness in neuronal development, including adult neurogenesis. C1 Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA. NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. NICHHD, Sect Neural Dev, NIH, Bethesda, MD 20892 USA. RP Ming, GL (reprint author), Johns Hopkins Univ, Sch Med, Inst Cell Engn, 733 N Broadway, Baltimore, MD 21205 USA. EM gming1@jhmi.edu; bailu@mail.nih.gov; shongju1@jhmi.edu RI Ming, Guo-li/J-7880-2013 FU NIA NIH HHS [AG024984, R01 AG024984, R01 AG024984-04]; NICHD NIH HHS [HD045757, R01 HD045757, R01 HD069184]; NINDS NIH HHS [NS047344, NS048271, R01 NS047344, R01 NS047344-05, R01 NS048271, R01 NS048271-04, R37 NS047344, R56 NS047344] NR 58 TC 360 Z9 382 U1 8 U2 46 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 21 PY 2007 VL 130 IS 6 BP 1146 EP 1158 DI 10.1016/j.cell.2007.07.010 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 225HK UT WOS:000250507500022 PM 17825401 ER PT J AU Yamaguchi, Y Brenner, M Hearing, VJ AF Yamaguchi, Yuji Brenner, Michaela Hearing, Vincent J. TI The regulation of skin pigmentation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID DNA-DAMAGE; ULTRAVIOLET-RADIATION; HUMAN MELANOCYTES; MASTER REGULATOR; MELANIN CONTENT; DIFFERENTIATION; MELANOSOME; TYROSINASE; HAIR; MELANOGENESIS C1 NCI, Natl Inst Hlth, Cell Biol Lab, Bethesda, MD 20892 USA. Osaka Univ, Grad Sch Med, Dept Dermatol, Osaka 5650871, Japan. RP Hearing, VJ (reprint author), Nagoya City Univ, Dept Geriatr & Environm Dermatol, Nagoya, Aichi 467, Japan. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008 FU Intramural NIH HHS NR 56 TC 167 Z9 177 U1 2 U2 22 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 SEP 21 PY 2007 VL 282 IS 38 BP 27557 EP 27561 DI 10.1074/jbc.R700026200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 210KR UT WOS:000249455600002 PM 17635904 ER PT J AU Chamberlain, PP Qian, X Stiles, AR Cho, J Jones, DH Lesley, SA Grabau, EA Shears, SB Spraggon, G AF Chamberlain, Philip P. Qian, Xun Stiles, Amanda R. Cho, Jaiesoon Jones, David H. Lesley, Scott A. Grabau, Elizabeth A. Shears, Stephen B. Spraggon, Glen TI Integration of inositol phosphate signaling pathways via human ITPK1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 1,3,4-TRISPHOSPHATE 5/6-KINASE; RAT-LIVER; HEXAKISPHOSPHATE; CELLS; 3,4,5,6-TETRAKISPHOSPHATE; PROTEINS; MODEL; PENTAKISPHOSPHATE; PURIFICATION; STIMULATION AB Inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) is a reversible, poly-specific inositol phosphate kinase that has been implicated as a modifier gene in cystic fibrosis. Upon activation of phospholipase C at the plasma membrane, inositol 1,4,5-trisphosphate enters the cytosol and is inter-converted by an array of kinases and phosphatases into other inositol phosphates with diverse and critical cellular activities. In mammals it has been established that inositol 1,3,4-trisphosphate, produced from inositol 1,4,5-trisphosphate, lies in a branch of the metabollic pathway that is separate from inositol 3,4,5,6-tetrakisphosphate, which inhibits plasma membrane chloride channels. We have determined the molecular mechanism for communication between these two pathways, showing that phosphate is transferred between inositol phosphates via ITPK1-bound nucleotide. Intersubstrate phosphate transfer explains how competing substrates are able to stimulate each others' catalysis by ITPK1. We further show that these features occur in the human protein, but not in plant or protozoan homologues. The high resolution structure of human ITPK1 identifies novel secondary structural features able to impart substrate selectivity and enhance nucleotide binding, thereby promoting intersubstrate phosphate transfer. Our work describes a novel mode of substrate regulation and provides insight into the enzyme evolution of a signaling mechanism from a metabolic role. C1 Genom Inst Novartis Res Fdn, San Diego, CA 92121 USA. NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Virginia Polytech Inst & State Univ, Dept Plant Pathol, Blacksburg, VA 24061 USA. RP Shears, SB (reprint author), Genom Inst Novartis Res Fdn, San Diego, CA 92121 USA. EM shears@niehs.nih.gov; gspraggo@gnf.org FU Intramural NIH HHS [Z01 ES080046-19, Z99 ES999999] NR 38 TC 18 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 21 PY 2007 VL 282 IS 38 BP 28117 EP 28125 DI 10.1074/jbc.M703121200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 210KR UT WOS:000249455600061 PM 17616525 ER PT J AU Bezrukov, SM Berezhkovskii, AM Szabo, A AF Bezrukov, Sergey M. Berezhkovskii, Alexander M. Szabo, Attila TI Diffusion model of solute dynamics in a membrane channel: Mapping onto the two-site model and optimizing the flux SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID ESCHERICHIA-COLI; SUGAR-TRANSPORT; OUTER-MEMBRANE; MALTOPORIN; LAMB; TRANSLOCATION; MECHANISM; BINDING; PROTEIN; PORES AB The steady-state flux through a singly occupied membrane channel is found for both discrete and continuum models of the solute dynamics in the channel. The former describes the dynamics as nearest-neighbor jumps between N sites, while the latter assumes that the molecule diffuses in a one-dimensional potential of mean force. For both models it is shown that the flux is the same as that for a simple two-site model with appropriately chosen rate constants, which contain all the relevant information about the more detailed dynamics. An interesting consequence of single occupancy is that the flux has a maximum as a function of the channel-solute interaction. If this interaction is too attractive, the molecule will never leave the channel, thus blocking it for the passage of other molecules. If it is too repulsive, the solute molecule will never enter the channel. Thus the flux vanishes in the two limits and, hence, has a maximum somewhere in-between. In the framework of the diffusion model, we find the optimal intrachannel potential of mean force that maximizes the flux using the calculus of variations. For a symmetric channel this potential is flat and occupies the entire channel. In the general case of an asymmetric channel, the optimal potential is obtained by tilting the optimal flat potential for the corresponding symmetric channel around the channel center, so that the solute is driven towards the reservoir with the lower solute concentration by a constant force. This implies that the flux is higher when the solute binding near the channel exit is stronger than that near the entrance. (c) 2007 American Institute of Physics. C1 NICHHD, Lab Phys & Struct Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. Natl Inst Hlth, Math & Stat Computing Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. NIDDK, Chem Phys Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), NICHHD, Lab Phys & Struct Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 FU Intramural NIH HHS NR 26 TC 37 Z9 37 U1 1 U2 11 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 21 PY 2007 VL 127 IS 11 AR 115101 DI 10.1063/1.2766720 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 213KZ UT WOS:000249667400067 PM 17887882 ER PT J AU Kiyatkin, EA Brown, PL AF Kiyatkin, E. A. Brown, P. L. TI I.V. Cocaine induces rapid, transient excitation of striatal neurons via its action on peripheral neural elements: Single-cell, iontophoretic study in awake and anesthetized rats SO NEUROSCIENCE LA English DT Article DE cocaine methiodide; somato-sensory stimuli; glutamate; visceral sensory nerves; sodium and potassium channels; drug-taking behavior ID FREELY MOVING RATS; VENTRAL TEGMENTAL AREA; CENTRAL-NERVOUS-SYSTEM; NUCLEUS-ACCUMBENS; INTRAVENOUS COCAINE; DOPAMINE UPTAKE; BEHAVING RATS; UNRESTRAINED RATS; UPTAKE INHIBITION; FIRING PATTERNS AB Cocaine's (COC) direct interaction with the dopamine (DA) transporter is usually considered the most important action underlying the psychomotor stimulant and reinforcing effects of this drug. However, some physiological, behavioral and psycho-emotional effects of COC are very rapid and brief and they remain intact during DA receptor blockade, suggesting possible involvement of peripheral non-DA neural mechanisms. To assess this issue, single-unit recording with microiontophoresis was used to examine changes in impulse activity of dorsal and ventral striatal neurons to i.v. COC (0.25-0.5 mg/kg) in the same rats under two conditions: awake with DA receptor blockade and anesthetized with urethane. In the awake preparation similar to 70% striatal neurons showed rapid and transient (latency similar to 6 s, duration similar to 15 s) COC-induced excitations. These effects were stronger in ventral than dorsal striatum. During anesthesia, these phasic effects were fully blocked and COC slowly decreased neuronal discharge rate. Cocaine-methiodide (COC-M), a derivative that cannot cross the blood-brain barrier, also caused phasic excitations in the awake, but not anesthetized condition. In contrast to regular COC, COC-M had no tonic effect on discharge rate in either preparation. Most striatal neurons that were phasically excited by both COC forms also showed short-latency excitations during tail-touch and tail-pinch in the awake preparation, an effect strongly attenuated during anesthesia. Finally, most striatal neurons that in awake conditions were phasically excited by somato-sensory stimuli and COC salts were also excited by iontophoretic glutamate (GLU). Although striatal neurons were sensitive to GLU in both preparations, the response magnitude at the same GLU current was higher in awake than anesthetized conditions. These data suggest that in awake animals i.v. COC, like somato-sensory stimuli, transiently excites striatal neurons via its action on peripheral neural elements and rapid neural transmission. While the nature of these neuronal elements needs to be clarified using other analytical techniques, they might involve voltage-gated K+ and Na+ channels, which have a high affinity for COC and are located on terminals of visceral sensory nerves that densely innervate peripheral vessels. Therefore, along with direct action on specific brain substrates, central excitatory effects of COC may occur via indirect action, involving afferents of visceral sensory nerves and rapid neural transmission. By providing a rapid sensory signal and triggering transient neural activation, such a peripherally triggered action might play a crucial role in the sensory effects of COC, thus contributing to learning and development of drug-taking behavior. Published by Elsevier Ltd on behalf of IBRO. C1 Natl Inst Hlth, Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Hlth, Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000445-07] NR 81 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD SEP 21 PY 2007 VL 148 IS 4 BP 978 EP 995 DI 10.1016/j.neuroscience.2007.07.013 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 216WF UT WOS:000249909000014 PM 17706878 ER PT J AU Miranda, PC Correia, L Salvador, R Basser, PJ AF Miranda, P. C. Correia, L. Salvador, R. Basser, P. J. TI Tissue heterogeneity as a mechanism for localized neural stimulation by applied electric fields SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; PERIPHERAL-NERVE STIMULATION; ELECTROMAGNETIC INDUCTION; VOLUME CONDUCTOR; CABLE EQUATION; EXCITATION; MODEL; BRAIN; CURRENTS; FIBERS AB We investigate the heterogeneity of electrical conductivity as a new mechanism to stimulate excitable tissues via applied electric fields. In particular, we show that stimulation of axons crossing internal boundaries can occur at boundaries where the electric conductivity of the volume conductor changes abruptly. The effectiveness of this and other stimulation mechanisms was compared by means of models and computer simulations in the context of transcranial magnetic stimulation. While, for a given stimulation intensity, the largest membrane depolarization occurred where an axon terminates or bends sharply in a high electric field region, a slightly smaller membrane depolarization, still sufficient to generate action potentials, also occurred at an internal boundary where the conductivity jumped from 0.143 S m(-1) to 0.333 S m(-1), simulating a white-matter-grey-matter interface. Tissue heterogeneity can also give rise to local electric field gradients that are considerably stronger and more focal than those impressed by the stimulation coil and that can affect the membrane potential, albeit to a lesser extent than the two mechanisms mentioned above. Tissue heterogeneity may play an important role in electric and magnetic 'far-field' stimulation. C1 Univ Lisbon, Fac Sci, Inst Biophys & Biomed Engn, P-1749 Lisbon, Portugal. NICHD, NIH, Sect Tissue Biophys & Biomimet, Bethesda, MD 20892 USA. RP Miranda, PC (reprint author), Univ Lisbon, Fac Sci, Inst Biophys & Biomed Engn, P-1749 Lisbon, Portugal. EM pcmiranda@fc.ul.pt RI Miranda, Pedro/A-5643-2013; Basser, Peter/H-5477-2011; Salvador, Ricardo/K-2301-2015 OI Miranda, Pedro/0000-0002-6793-8111; Salvador, Ricardo/0000-0003-1235-6533 FU Intramural NIH HHS NR 41 TC 36 Z9 37 U1 0 U2 12 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 21 PY 2007 VL 52 IS 18 BP 5603 EP 5617 DI 10.1088/0031-9155/52/18/009 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 209MQ UT WOS:000249393000009 PM 17804884 ER PT J AU Ghedin, E Wang, SL Spiro, D Caler, E Zhao, Q Crabtree, J Allen, JE Delcher, AL Guiliano, DB Miranda-Saavedra, D Angiuoli, SV Creasy, T Amedeo, P Haas, B El-Sayed, NM Wortman, JR Feldblyum, T Tallon, L Schatz, M Shumway, M Koo, H Salzberg, SL Schobel, S Pertea, M Pop, M White, O Barton, GJ Carlow, CKS Crawford, MJ Daub, J Dimmic, MW Estes, CF Foster, JM Ganatra, M Gregory, WF Johnson, NM Jin, JM Komuniecki, R Korf, I Kumar, S Laney, S Li, BW Li, W Lindblom, TH Lustigman, S Ma, D Maina, CV Martin, DMA McCarter, JP McReynolds, L Mitreva, M Nutman, TB Parkinson, J Peregrin-Alvarez, JM Poole, C Ren, QH Saunders, L Sluder, AE Smith, K Stanke, M Unnasch, TR Ware, J Wei, AD Weil, G Williams, DJ Zhang, YH Fraser-Liggett, C Slatko, B Blaxter, ML Scott, AL AF Ghedin, Elodie Wang, Shiliang Spiro, David Caler, Elisabet Zhao, Qi Crabtree, Jonathan Allen, Jonathan E. Delcher, Arthur L. Guiliano, David B. Miranda-Saavedra, Diego Angiuoli, Samuel V. Creasy, Todd Amedeo, Paolo Haas, Brian El-Sayed, Najib M. Wortman, Jennifer R. Feldblyum, Tamara Tallon, Luke Schatz, Michael Shumway, Martin Koo, Hean Salzberg, Steven L. Schobel, Seth Pertea, Mihaela Pop, Mihai White, Owen Barton, Geoffrey J. Carlow, Clotilde K. S. Crawford, Michael J. Daub, Jennifer Dimmic, Matthew W. Estes, Chris F. Foster, Jeremy M. Ganatra, Mehul Gregory, William F. Johnson, Nicholas M. Jin, Jinming Komuniecki, Richard Korf, Ian Kumar, Sanjay Laney, Sandra Li, Ben-Wen Li, Wen Lindblom, Tim H. Lustigman, Sara Ma, Dong Maina, Claude V. Martin, David M. A. McCarter, James P. McReynolds, Larry Mitreva, Makedonka Nutman, Thomas B. Parkinson, John Peregrin-Alvarez, Jose M. Poole, Catherine Ren, Qinghu Saunders, Lori Sluder, Ann E. Smith, Katherine Stanke, Mario Unnasch, Thomas R. Ware, Jenna Wei, Aguan D. Weil, Gary Williams, Deryck J. Zhang, Yinhua Fraser-Liggett, Claire Slatko, Barton Blaxter, Mark L. Scott, Alan L. TI Draft genome of the filarial nematode parasite Brugia malayi SO SCIENCE LA English DT Article ID CAENORHABDITIS-ELEGANS; C-ELEGANS; PAHANGI; EXPRESSION; MICROFILARIAE; IVERMECTIN; SEQUENCES; HOMOLOG; CLONING AB Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the similar to 90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict similar to 11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during similar to 350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design. C1 Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15261 USA. J Craig Venter Inst, Rockville, MD 20850 USA. Inst Genom Res, Rockville, MD 20850 USA. Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, London SW7 2AZ, England. Univ Dundee, Sch Life Sci Res, Dundee DD1 5EH, Scotland. New England Biolabs Inc, Div Parasitol, Ipswich, MA 01938 USA. Divergence Inc, St Louis, MO 63141 USA. Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland. Univ Edinburgh, Inst Immunol & Infect Res, Edinburgh EH9 3JT, Midlothian, Scotland. Lyon Coll, Div Sci, Batesville, AR 72501 USA. Australian Natl Univ, Sch Biochem & Mol Biol, Canberra, ACT 0200, Australia. New England Biolabs Inc, Div RNA Biol, Ipswich, MA 01938 USA. Univ Toledo, Dept Sci Biol, Toledo, OH 43606 USA. Univ Calif Davis, Div Biol Sci, Mol Biol Sect, Genome Ctr, Davis, CA 95616 USA. Smith Coll, Clark Sci Ctr, Northampton, MA 01063 USA. Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA. New York Blood Ctr, Lindsley F Kimball Res Inst, Mol Parasitol Lab, New York, NY 10021 USA. Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 1L7, Canada. Cambria Biosci, Woburn, MA 01801 USA. Univ Gottingen, Dept Bioinformat, D-37077 Gottingen, Germany. Univ Alabama, Div Geog Med, Birmingham, AL 35294 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Ghedin, E (reprint author), Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15261 USA. EM GhedinE@dom.pitt.edu RI Parkinson, John/A-4424-2008; Miranda-Saavedra, Diego/C-2707-2012; Martin, David/C-2984-2009; Angiuoli, Samuel/H-7340-2014; Blaxter, Mark/B-4113-2010; El-Sayed, Najib/K-7266-2015; Salzberg, Steven/F-6162-2011; Pop, Mihai/A-7987-2013; Barton, Geoffrey/C-6267-2011; OI Parkinson, John/0000-0001-9815-1189; Blaxter, Mark/0000-0003-2861-949X; El-Sayed, Najib/0000-0001-7970-3312; Salzberg, Steven/0000-0002-8859-7432; Pop, Mihai/0000-0001-9617-5304; Martin, David/0000-0002-8732-204X; Wortman, Jennifer/0000-0002-8713-1227; Schatz, Michael/0000-0002-4118-4446; Angiuoli, Samuel/0000-0001-9525-4350; Peregrin-Alvarez, Jose M/0000-0002-7184-832X; Zhang, Yinhua/0000-0003-0592-9153; Fraser, Claire/0000-0003-1462-2428; Barton, Geoffrey/0000-0002-9014-5355 FU NIAID NIH HHS [R01 AI048562, R01 AI048562-09, U01 AI048828, U01-AI50903]; NIEHS NIH HHS [R15 ES013128, R15 ES013128-01]; NLM NIH HHS [R01 LM006845, R01 LM006845-08, R01 LM007938, R01 LM007938-04] NR 28 TC 400 Z9 455 U1 13 U2 47 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 21 PY 2007 VL 317 IS 5845 BP 1756 EP 1760 DI 10.1126/science.1145406 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 212HD UT WOS:000249585900050 PM 17885136 ER PT J AU Elloumi, F Nason, M AF Elloumi, Fathi Nason, Martha TI SEARCHPATTOOL: a new method for mining the most specific frequent patterns for binding sites with application to prokaryotic DNA sequences SO BMC BIOINFORMATICS LA English DT Article ID NONCODING SEQUENCES; REGULATORY ELEMENTS; DISCOVERY; PREDICTION AB Background: Computational methods to predict transcription factor binding sites (TFBS) based on exhaustive algorithms are guaranteed to find the best patterns but are often limited to short ones or impose some constraints on the pattern type. Many patterns for binding sites in prokaryotic species are not well characterized but are known to be large, between 16-30 base pairs (bp) and contain at least 2 conserved bases. The length of prokaryotic species promoters (about 400 bp) and our interest in studying a small set of genes that could be a cluster of coregulated genes from microarray experiments led to the development of a new exhaustive algorithm targeting these large patterns. Results: We present Searchpattool, a new method to search for and select the most specific (conservative) frequent patterns. This method does not impose restrictions on the density or the structure of the pattern. The best patterns (motifs) are selected using several statistics, including a new application of a z-score based on the number of matching sequences. We compared Searchpattool against other well known algorithms on a Bacillus subtilis group of 14 input sequences and found that in our experiments Searchpattool always performed the best based on performance scores. Conclusion: Searchpattool is a new method for pattern discovery relative to transcription factor binding sites for species or genes with short promoters. It outputs the most specific significant patterns and helps the biologist to choose the best candidates. C1 NIAID, Res Technol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. NIAID, Off Clin Res, Biostat Res Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Elloumi, F (reprint author), NIAID, Res Technol Branch, Natl Inst Hlth, 9000 Rockville Pike,Blg 50-R5505, Bethesda, MD 20892 USA. EM elloumi.fathi@epa.gov; mnason@niaid.nih.gov NR 25 TC 0 Z9 0 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD SEP 20 PY 2007 VL 8 AR 354 DI 10.1186/1471-2105-8-354 PG 18 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 232AC UT WOS:000250989400002 PM 17883842 ER PT J AU Kim, CH Lee, BK AF Kim, Changhoon Lee, Byungkook TI Accuracy of structure-based sequence alignment of automatic methods SO BMC BIOINFORMATICS LA English DT Article ID PROTEIN-STRUCTURE ALIGNMENT; SECONDARY STRUCTURE; DATABASE; SUPERFAMILIES; CLASSIFICATION; SENSITIVITY; SELECTIVITY; ALGORITHMS; PHYLOGENY; BENCHMARK AB Background: Accurate sequence alignments are essential for homology searches and for building three-dimensional structural models of proteins. Since structure is better conserved than sequence, structure alignments have been used to guide sequence alignments and are commonly used as the gold standard for sequence alignment evaluation. Nonetheless, as far as we know, there is no report of a systematic evaluation of pairwise structure alignment programs in terms of the sequence alignment accuracy. Results: In this study, we evaluate CE, DaliLite, FAST, LOCK2, MATRAS, SHEBA and VAST in terms of the accuracy of the sequence alignments they produce, using sequence alignments from NCBI's human-curated Conserved Domain Database (CDD) as the standard of truth. We find that 4 to 9% of the residues on average are either not aligned or aligned with more than 8 residues of shift error and that an additional 6 to 14% of residues on average are misaligned by 1-8 residues, depending on the program and the data set used. The fraction of correctly aligned residues generally decreases as the sequence similarity decreases or as the RMSD between the C-alpha positions of the two structures increases. It varies significantly across CDD superfamilies whether shift error is allowed or not. Also, alignments with different shift errors occur between proteins within the same CDD superfamily, leading to inconsistent alignments between superfamily members. In general, residue pairs that are more than 3.0 angstrom apart in the reference alignment are heavily (>=25% on average) misaligned in the test alignments. In addition, each method shows a different pattern of relative weaknesses for different SCOP classes. CE gives relatively poor results for beta-sheet-containing structures (all-beta, alpha/beta, and alpha+beta classes), DaliLite for "others" class where all but the major four classes are combined, and LOCK2 and VAST for all-beta and "others" classes. Conclusion: When the sequence similarity is low, structure-based methods produce better sequence alignments than by using sequence similarities alone. However, current structure-based methods still mis-align 11-19% of the conserved core residues when compared to the human-curated CDD alignments. The alignment quality of each program depends on the protein structural type and similarity, with DaliLite showing the most agreement with CDD on average. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kim, CH (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bldg 37, Bethesda, MD 20892 USA. EM kimchan@mail.nih.gov; bk@nih.gov FU Intramural NIH HHS NR 41 TC 24 Z9 24 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD SEP 20 PY 2007 VL 8 AR 355 DI 10.1186/1471-2105-8-355 PG 17 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 226NV UT WOS:000250596700001 PM 17883866 ER PT J AU Arnold, AM Seymour, L Smylie, M Ding, K Ung, Y Findlay, B Lee, CW Djurfeldt, M Whitehead, M Ellis, P Goss, G Chan, A Meharchand, J Alam, Y Gregg, R Butts, C Langmuir, P Shepherd, F AF Arnold, Andrew M. Seymour, Lesley Smylie, Michael Ding, Keyue Ung, Yee Findlay, Brian Lee, Christopher W. Djurfeldt, Marina Whitehead, Marlo Ellis, Peter Goss, Glenwood Chan, Adrien Meharchand, Jacinta Alam, Yasmin Gregg, Richard Butts, Charles Langmuir, Peter Shepherd, Frances TI Phase II study of vandetanib or placebo in small-cell lung cancer patients after complete or partial response to induction chemotherapy with or without radiation therapy: National Cancer Institute of Canada clinical trials group study BR. 20 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ONCOLOGY-GROUP; DOUBLE-BLIND; MAINTENANCE; QLQ-C30; SCLC AB Purpose This double-blind randomized phase II trial examined whether vandetanib, an inhibitor of vascular endothelial and epidermal growth factor receptors, could prolong progression-free survival in responding patients with small-cell lung cancer. Patients and Methods Eligible patients with complete response (CR) or partial response (PR) to combination chemotherapy (+/- thoracic or prophylactic cranial radiation) received oral vandetanib 300 mg/d or matched placebo. With 100 patients and 77 events, the study had 80% power to detect an improvement in median progression-free survival from 4 to 6.5 months (one-sided, 10%-level test). Results Between May 2003 and March 2006, 107 patients were accrued; 46 had limited disease and 61 extensive disease. There were fewer patients with a performance status of 0 (n = 11 v 20), and fewer had CR to initial therapy (n = 4 v 8) in the vandetanib arm. Vandetanib patients had more toxicity and required more dose modifications for gastrointestinal toxicity and rash. Asymptomatic Corrected QT interval (QTC) prolongation was observed in eight vandetanib patients. Median progression-free survival for vandetanib and placebo was 2.7 and 2.8 months, respectively (hazard ratio [HR], 1.01; 80% Cl, 0.75 to 1.36; one-sided P = .51). Overall survival for vandetanib was 10.6 versus 11.9 months for placebo (HR, 1.43; 80% Cl, 1.00 to 2.05; one-sided P = 0.9). In planned subgroup analyses, a significant interaction was noted (P = .01): limited-stage vandetanib patients had longer overall survival (HR, 0.45; one-sided P = .07) and extensive-stage vandetanib patients shorter survival compared with placebo (HR, 2.27; one- sided P = .996). Conclusion Vandetanib failed to demonstrate efficacy as maintenance therapy for small-cell lung cancer. C1 NCI, Clin Trials Grp, Kingston, ON K7L 3N6, Canada. AstraZeneca, Wilmington, DE USA. RP Seymour, L (reprint author), NCI, Clin Trials Grp, 10 Stuart St, Kingston, ON K7L 3N6, Canada. EM lseymour@ctg.queensu.ca NR 26 TC 119 Z9 122 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2007 VL 25 IS 27 BP 4278 EP 4284 DI 10.1200/JCO.2007.12.3083 PG 7 WC Oncology SC Oncology GA 233EM UT WOS:000251073200021 PM 17878480 ER PT J AU Cai, LS Cuevas, J Temme, S Herman, MM Dagostin, C Widdowson, DA Innis, RB Pike, VW AF Cai, Lisheng Cuevas, Jessica Temme, Sebastian Herman, Mary M. Dagostin, Claudio Widdowson, David A. Innis, Robert B. Pike, Victor W. TI Synthesis and structure - Affinity relationships of new 4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N-dimethylbenzeneamine derivatives as ligands for human beta-amyloid plaques SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ALZHEIMERS-DISEASE; C-11 CYANIDE; IN-VIVO; NEUROFIBRILLARY TANGLES; MICROWAVE CONDITIONS; IMAGING AGENTS; BRAIN; IMIDAZO<1,2-A>PYRIDINES; RADIOSYNTHESIS; RADIOLIGANDS AB A new and extensive set of 4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N-dimethylbenzeneamine (IMPY) derivatives was synthesized and assayed for affinity toward human A beta plaques. 6-Ethylthio- (12h), 6-cyano-(12e), 6-nitro- (12f), and 6-p-methoxybenzylthio- (15d) analogues were discovered to have high affinity (K-I < 10 nM). However, introduction of a hydrophilic thioether group in the 6-position (15a-c, 15e-g) reduced or abolished affinity. In secondary N-methyl analogues, a bromo substiment in the adjacent ring position (14a) imparted high affinity (K-1 = 7.4 nM) whereas a methyl substituent did not (14c). The tolerance for nonhydrophilic thioether substituents in the 6-position opens up the possibility of developing new sensitive positron emission tomography radioligands for imaging human A beta plaques in Alzheimer's disease, especially in view of the amenability of thioethers to be labeled with carbon-11 or fluorine-18 through S-alkylation reactions. The structure-activity relationships revealed in this study extends insight into the topography of the binding site for IMPY-like ligands in human A beta plaques. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AY, England. RP Cai, LS (reprint author), NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. EM cail@-intra.nimh.nih.gov FU Intramural NIH HHS NR 54 TC 27 Z9 28 U1 1 U2 4 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 SEP 20 PY 2007 VL 50 IS 19 BP 4746 EP 4758 DI 10.1021/jm0702231 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 211CI UT WOS:000249501500018 PM 17722900 ER PT J AU Xu, H Baidoo, K Gunn, AJ Boswell, CA Milenic, DE Choyke, PL Brechbiel, MW AF Xu, Heng Baidoo, Kwamena Gunn, Andrew J. Boswell, C. Andrew Milenic, Diane E. Choyke, Peter L. Brechbiel, Martin W. TI Design, synthesis, and characterization of a dual modality positron emission tomography and fluorescence Imaging agent for monoclonal antibody tumor-targeted imaging SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MAGNETIC-RESONANCE; CONTRAST AGENT; CONJUGATION; RADIATION; REAGENT; PET/CT AB A novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A '') for sequestering radiometals (Y-86 or In-111) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the monoclonal antibody trastuzumab (Herceptin) was achieved by efficient thiol-maleimide chemistry, thereby yielding immunoconjugate 2. Analysis of 2 by flow cytometry and competitive binding assay demonstrates that immunoconjugate 2 binds to SKOV3 tumor cells comparably to native trastuzumab and, thus, may be used as a tumor-targeted monoclonal antibody probe for multimodality imaging. C1 NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room 1B40,10 Ctr Dr, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov OI Boswell, Charles/0000-0002-0426-9846 FU Intramural NIH HHS [Z01 SC006353-24, Z01 SC010051-11] NR 20 TC 51 Z9 52 U1 2 U2 11 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 SEP 20 PY 2007 VL 50 IS 19 BP 4759 EP 4765 DI 10.1021/jm070657w PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 211CI UT WOS:000249501500019 PM 17725340 ER PT J AU Wapner, RJ Sorokin, Y Mele, L Johnson, F Dudley, DJ Spong, CY Peaceman, AM Leveno, KJ Malone, F Caritis, SN Mercer, B Harper, M Rouse, DJ Thorp, JM Ramin, S Carpenter, MW Gabbe, SG AF Wapner, Ronald J. Sorokin, Yoram Mele, Lisa Johnson, Francee Dudley, Donald J. Spong, Catherine Y. Peaceman, Alan M. Leveno, Kenneth J. Malone, Fergal Caritis, Steve N. Mercer, Brian Harper, Margaret Rouse, Dwight J. Thorp, John M. Ramin, Susan Carpenter, Marshall W. Gabbe, Steven G. CA Natl Inst Child Hlth Human TI Long-term outcomes after repeat doses of antenatal corticosteroids SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med ID MATERNAL INJECTIONS; CONTROLLED-TRIAL; CEREBRAL-PALSY; FETAL SHEEP; SINGLE; BIRTH; EXPOSURE; DEXAMETHASONE; CHILDREN; COURSES AB Background Previous trials have shown that repeat courses of antenatal corticosteroids improve some neonatal outcomes in preterm infants but reduce birth weight and increase the risk of intrauterine growth restriction. We report long-term follow-up results of children enrolled in a randomized trial comparing single and repeat courses of antenatal corticosteroids. Methods Women at 23 through 31 weeks of gestation who remained pregnant 7 days after an initial course of corticosteroids were randomly assigned to weekly courses of betamethasone, consisting of 12 mg given intramuscularly and repeated once at 24 hours, or an identical-appearing placebo. We studied the children who were born after these treatments when they were between 2 and 3 years of corrected age. Prespecified outcomes included scores on the Bayley Scales of Infant Development, anthropometric measurements, and the presence of cerebral palsy. Results A total of 556 infants were available for follow-up; 486 children (87.4%) underwent physical examination and 465 (83.6%) underwent Bayley testing at a mean (+/-SD) corrected age of 29.3+/-4.6 months. There were no significant differences in Bayley results or anthropometric measurements. Six children (2.9% of pregnancies) in the repeat-corticosteroid group had cerebral palsy as compared with one child (0.5% of pregnancies) in the placebo group (relative risk, 5.7; 95% confidence interval, 0.7 to 46.7; P=0.12). Conclusions Children who had been exposed to repeat as compared with single courses of antenatal corticosteroids did not differ significantly in physical or neurocognitive measures. Although the difference was not statistically significant, the higher rate of cerebral palsy among children who had been exposed to repeat doses of corticosteroids is of concern and warrants further study. C1 Columbia Univ, Dept Obstet & Gynaecol, New York, NY 10032 USA. Drexel Univ, Philadelphia, PA 19104 USA. Wayne State Univ, Detroit, MI USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Utah, Salt Lake City, UT USA. NICHHD, Bethesda, MD 20892 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Alabama, Birmingham, AL USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas, Houston, TX USA. Brown Univ, Providence, RI 02912 USA. Vanderbilt Univ, Nashville, TN USA. RP Wapner, RJ (reprint author), Columbia Univ, Dept Obstet & Gynaecol, 622W 168th St,PH 16-66, New York, NY 10032 USA. OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850 FU NCRR NIH HHS [M01-RR-000080]; NICHD NIH HHS [HD27869, HD21410, HD27860, HD27915, HD27917, HD34116, HD34136, HD34208, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 36 TC 134 Z9 140 U1 1 U2 7 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 SEP 20 PY 2007 VL 357 IS 12 BP 1190 EP 1198 DI 10.1056/NEJMoa071453 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 211RM UT WOS:000249541000004 PM 17881751 ER PT J AU Plenge, RM Seielstad, M Padyukov, L Lee, AT Remmers, EF Ding, B Liew, A Khalili, H Chandrasekaran, A Davies, LRL Li, WT Tan, AKS Bonnard, C Ong, RTH Thalamuthu, A Pettersson, S Liu, CY Tian, C Chen, WV Carulli, JP Beckman, EM Altshuler, D Alfredsson, L Criswell, LA Amos, CI Seldin, MF Kastner, DL Klareskog, L Gregersen, PK AF Plenge, Robert M. Seielstad, Mark Padyukov, Leonid Lee, Annette T. Remmers, Elaine F. Ding, Bo Liew, Anthony Khalili, Houman Chandrasekaran, Alamelu Davies, Leela R. L. Li, Wentian Tan, Adrian K. S. Bonnard, Carine Ong, Rick T. H. Thalamuthu, Anbupalam Pettersson, Sven Liu, Chunyu Tian, Chao Chen, Wei V. Carulli, John P. Beckman, Evan M. Altshuler, David Alfredsson, Lars Criswell, Lindsey A. Amos, Christopher I. Seldin, Michael F. Kastner, Daniel L. Klareskog, Lars Gregersen, Peter K. TI TRAF1-C5 as a risk locus for rheumatoid arthritis - A genomewide study SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; WIDE ASSOCIATION; SHARED EPITOPE; SUSCEPTIBILITY GENES; MONOCLONAL-ANTIBODY; LINKAGE; FAMILIES; PTPN22; POWER; IDENTIFICATION AB Background Rheumatoid arthritis has a complex mode of inheritance. Although HLA-DRB1 and PTPN22 are well-established susceptibility loci, other genes that confer a modest level of risk have been identified recently. We carried out a genomewide association analysis to identify additional genetic loci associated with an increased risk of rheumatoid arthritis. Methods We genotyped 317,503 single-nucleotide polymorphisms (SNPs) in a combined case-control study of 1522 case subjects with rheumatoid arthritis and 1850 matched control subjects. The patients were seropositive for autoantibodies against cyclic citrullinated peptide (CCP). We obtained samples from two data sets, the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Results from NARAC and EIRA for 297,086 SNPs that passed quality-control filters were combined with the use of Cochran-Mantel-Haenszel stratified analysis. SNPs showing a significant association with disease (P<1 x 10(-8)) were genotyped in an independent set of case subjects with anti-CCP-positive rheumatoid arthritis (485 from NARAC and 512 from EIRA) and in control subjects (1282 from NARAC and 495 from EIRA). Results We observed associations between disease and variants in the major-histocompatibility-complex locus, in PTPN22, and in a SNP (rs3761847) on chromosome 9 for all samples tested, the latter with an odds ratio of 1.32 (95% confidence interval, 1.23 to 1.42; P=4 x 10(-14)). The SNP is in linkage disequilibrium with two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis factor receptor-associated factor 1) and C5 (encoding complement component 5). Conclusions A common genetic variant at the TRAF1-C5 locus on chromosome 9 is associated with an increased risk of anti-CCP-positive rheumatoid arthritis. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Davis, Rowe Program, Davis, CA 95616 USA. Biogen Idec, Cambridge, MA USA. NIAMSD, Bethesda, MD 20892 USA. N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. Karolinska Inst, Stockholm, Sweden. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Genome Inst Singapore, Singapore, Singapore. Brigham & Womens Hosp, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. RP Plenge, RM (reprint author), N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, 350 Community Dr, Manhasset, NY 11030 USA. RI Padyukov, Leonid/A-4890-2009; Altshuler, David/A-4476-2009; Pettersson, Sven/F-9511-2015; OI Padyukov, Leonid/0000-0003-2950-5670; Altshuler, David/0000-0002-7250-4107; Seielstad, Mark/0000-0001-5783-1401; Alfredsson, Lars/0000-0003-1688-6697; Li, Wentian/0000-0003-1155-110X; Klareskog, Lars/0000-0001-9601-6186 FU Intramural NIH HHS; NCRR NIH HHS [5-M01-RR-00079, M01 RR000079, M01 RR018535, M01-RR018535]; NIAID NIH HHS [K08 AI055314, K08 AI055314-01A1, K08 AI055314-02, K08 AI055314-03, K08 AI055314-04, K08 AI055314-05, K08-AI55314-3, R01 AI065841, R01-AI065841]; NIAMS NIH HHS [K24 AR002175, K24-AR02175, N01-AR22263, N01AR22263, R01 AR044422, R01 AR050267, R01-AR050267, R01-AR44422] NR 50 TC 504 Z9 522 U1 5 U2 20 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 SEP 20 PY 2007 VL 357 IS 12 BP 1199 EP 1209 DI 10.1056/NEJMoa073491 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 211RM UT WOS:000249541000005 PM 17804836 ER PT J AU Manson, JE Allison, MA Rossouw, JE AF Manson, JoAnn E. Allison, Matthew A. Rossouw, Jacques E. TI Estrogen therapy and coronary-artery calcification - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID DISEASE C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif San Diego, La Jolla, CA 92037 USA. NHLBI, Bethesda, MD 20892 USA. RP Manson, JE (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM jmanson@rics.bwh.harvard.edu NR 3 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 SEP 20 PY 2007 VL 357 IS 12 BP 1254 EP 1254 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 211RM UT WOS:000249541000017 ER PT J AU Harrington, PB Laurent, C Levinson, DF Levitt, P Markey, SP AF Harrington, Peter B. Laurent, Claudine Levinson, Douglas F. Levitt, Pat Markey, Sanford P. TI Bootstrap classification and point-based feature selection from age-staged mouse cerebellum tissues of matrix assisted laser desorption/ionization mass spectra using a fuzzy rule-building expert system SO ANALYTICA CHIMICA ACTA LA English DT Article DE fuzzy rule-building expert system; matrix assisted laser desorption/ionization; mass spectrometry; bootstrap Latin-partitions; mouse (Mus musculus domesticus); cerebellum tissue; biomarker ID NEURAL-NETWORKS; SPECTROMETRY; PROTEINS; SECTIONS; CALIBRATION; DESORPTION; REGRESSION; PROTEOMICS; PARSIMONY; PRINCIPLE AB A bootstrap method for point-based detection of candidate biomarker peaks has been developed from pattern classifiers. Point-based detection methods are advantageous in comparison to peak-based methods. Peak determination and selection are problematic when spectral peaks are not baseline resolved or on a varying baseline. The benefit of point-based detection is that peaks can be globally determined from the characteristic features of the entire data set (i.e., subsets of candidate points) as opposed to the traditional method of selecting peaks from individual spectra and then combining the peak list into a data set. The point-based method is demonstrated to be more effective and efficient using a synthetic data set when compared to using Mahalanobis distance for feature selection. In addition, probabilities that characterize the uniqueness of the peaks are determined. This method was applied for detecting peaks that characterize age-specific patterns of protein expression of developing and adult mouse cerebella from matrix assisted laser desorption/ionization (MALDI) mass spectrometry (MS) data. The mice comprised three age groups: 42 adults, 19 14-day-old pups, and 16 7-day-old pups. Three sequential spectra were obtained from each tissue section to yield 126, 57 and 48 spectra for adult, 14-day-old pup, and 7-day-old pup spectra, respectively. Each spectrum comprised 71,879 mass measurements in a range of 3.5-50 kDa. A previous study revealed that 846 unique peaks were detected that were consistent for 50% of the mice in each age group (C. Laurent, D.F. Levinson, S.A. Schwartz, P.B. Harrington, S.P. Markey, R.M. Caprioli, P. Levitt, Direct profiling of the cerebellum by MALDI MS: a methodological study in postnatal and adult mouse, J. Neurosci. Res. 81 (2005) 613-621.). A fuzzy rule-building expert system (FuRES) was applied to investigate the correlation of age with features in the MS data. FuRES detected two outlier pup-14 spectra. Prediction was evaluated using 100 bootstrap samples of 2 Latin-partitions (i.e., 50:50 split between training and prediction set) of the mice. The spectra without the outliers yielded classification rates of 99.1 +/- 0.1%, 90.1 +/- 0.8%, and 97.0 +/- 0.6% for adults, 14-day-old pups, and 7-day-old pups, respectively. At a 95% level of significance, 100 bootstrap samples disclosed 35 adult and 21 pup distinguishing peaks for separating adults from pups; and 8 14-day-old and 15 7-day-old predictive peaks for separating 14-day-old pup from 7-day-old pup spectra. A compressed matrix comprising 40,393 points that were outside the 95% confidence intervals of one of the two FuRES discriminants was evaluated and the classification improved significantly for all classes. When peaks that satisfied a quality criterion were integrated, the 55 integrated peak areas furnished significantly improved classification for all classes: the selected peak areas furnished classification rates of 100%, 97.3 +/- 0.6%, and 97.4 +/- 0.3% for adult, 14-day-old pups, and 7-day-old pups using 100 bootstrap Latin partitions evaluations with the predictions averaged. When the bootstrap size was increased to 1000 samples, the results were not significantly affected. The FuRES predictions were consistent with those obtained by discriminant partial least squares (DPLS) classifications. (C) 2007 Elsevier B.V. All rights reserved. C1 Ohio Univ, Ctr Intelligent Chem Instrumentat, Dept Chem & Biochem, Clippinger Labs, Athens, OH 45701 USA. NIMH, NIH, Lab Neurotoxicol, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Sch Med, Dept Pharmacol, Nashville, TN 37235 USA. RP Harrington, PB (reprint author), Ohio Univ, Ctr Intelligent Chem Instrumentat, Dept Chem & Biochem, Clippinger Labs, Athens, OH 45701 USA. EM Peter.Harrington@OHIO.edu OI Harrington, Peter/0000-0003-0268-8630 FU Intramural NIH HHS [Z01 MH000279-25]; NICHD NIH HHS [P30 HD015052, P30HD015052]; NIGMS NIH HHS [R01 GM058008, R01GM058008]; NIMH NIH HHS [K24 MH064197, K24MH064197, MH051456] NR 29 TC 11 Z9 11 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD SEP 19 PY 2007 VL 599 IS 2 BP 219 EP 231 DI 10.1016/j.aca.2007.08.007 PG 13 WC Chemistry, Analytical SC Chemistry GA 218NU UT WOS:000250023000007 PM 17870284 ER PT J AU Feinberg, MW Wara, AK Cao, Z Lebedeva, MA Rosenbauer, F Iwasaki, H Hirai, H Katz, JP Haspel, RL Gray, S Akashi, K Segre, J Kaestner, KH Tenen, DG Jain, MK AF Feinberg, Mark W. Wara, Akm Khyrul Cao, Zhuoxiao Lebedeva, Maria A. Rosenbauer, Frank Iwasaki, Hiromi Hirai, Hideyo Katz, Jonathan P. Haspel, Richard L. Gray, Susan Akashi, Koichi Segre, Julie Kaestner, Klaus H. Tenen, Daniel G. Jain, Mukesh K. TI The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation SO EMBO JOURNAL LA English DT Article DE hematopoietic progenitors; Kruppels; leukemia; monocyte differentiation; PU.1 ID COLONY-STIMULATING FACTOR; TRANSCRIPTION FACTOR PU.1; HEMATOPOIETIC STEM-CELLS; BINDING PROTEIN ALPHA; T-CELL; LINEAGE COMMITMENT; ERYTHROID-CELLS; C/EBP-ALPHA; FACTOR EKLF; GRANULOCYTE AB Monocyte differentiation involves the participation of line-age-restricted transcription factors, although the mechanisms by which this process occurs are incompletely defined. Within the hematopoietic system, members of the Kruppel-like family of factors ( KLFs) play essential roles in erythrocyte and T lymphocyte development. Here we show that KLF4/ GKLF is expressed in a monocyte- restricted and stage- specific pattern during myelopoiesis and functions to promote monocyte differentiation. Overexpression of KLF4 in HL- 60 cells confers the characteristics of mature monocytes. Conversely, KLF4 knockdown blocked phorbol ester- induced monocyte differentiation. Forced expression of KLF4 in primary common myeloid progenitors ( CMPs) or hematopoietic stem cells ( HSCs) induced exclusive monocyte differentiation in clonogenic assays, whereas KLF4 deficiency inhibited monocyte but increased granulocyte differentiation. Mechanistic studies demonstrate that KLF4 is a target gene of PU.1. Consistently, KLF4 can rescue PU.1-/- fetal liver cells along the monocytic lineage and can activate the monocytic- specific CD14 promoter. Thus, KLF4 is a critical regulator in the transcriptional network controlling monocyte differentiation. C1 Brigham & Womens Hosp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Inst Med, Boston, MA USA. Dana Farber Canc Inst, Dept Canc & Immunol & AIDS, Boston, MA USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Case Cardiovasc Res Inst, Cleveland, OH 44106 USA. RP Jain, MK (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM Mukesh.Jain2@case.edu OI Rosenbauer, Frank/0000-0001-7977-9421; Tenen, Daniel/0000-0002-6423-3888 FU NHLBI NIH HHS [K08 HL067755, HL 080174, HL-72952, HL-75427, HL-76754, HL03747, HL67755, HL69477, R01 HL069477, R01 HL072952, R01 HL075427, R01 HL076754, R01 HL080174] NR 44 TC 128 Z9 136 U1 0 U2 7 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 SEP 19 PY 2007 VL 26 IS 18 BP 4138 EP 4148 DI 10.1038/sj.emboj.7601824 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 213UF UT WOS:000249691900008 PM 17762869 ER PT J AU Emanuel, EJ Fuchs, VR Garber, AM AF Emanuel, Ezekiel J. Fuchs, Victor R. Garber, Alan M. TI Essential elements of a technology and outcomes assessment initiative SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HEALTH-CARE; INFORMATION C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. Stanford Univ, Dept Econ, Palo Alto, CA 94304 USA. Stanford Univ, Ctr Hlth Policy, Palo Alto, CA 94304 USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Emanuel, EJ (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM eemanuel@cc.nih.gov RI Garber, Alan/F-1476-2010 NR 17 TC 48 Z9 49 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 SEP 19 PY 2007 VL 298 IS 11 BP 1323 EP 1325 DI 10.1001/jama.298.11.1323 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 211LA UT WOS:000249524100022 PM 17878424 ER PT J AU Qian, L Xu, Z Zhang, W Wilson, B Hong, JS Flood, PM AF Qian, Li Xu, Zongli Zhang, Wei Wilson, Belinda Hong, Jau-Shyong Flood, Patrick M. TI Sinomenine, a natural dextrorotatory morphinan analog, is anti-inflammatory and neuroprotective through inhibition of microglial NADPH oxidase SO JOURNAL OF NEUROINFLAMMATION LA English DT Article ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; OXIDATIVE STRESS; ALKALOID SINOMENINE; PARKINSONS-DISEASE; NITRIC-OXIDE; DOPAMINERGIC-NEURONS; ACTIVATED MICROGLIA; TETRAZOLIUM SALT; GENE-EXPRESSION; RAT-BRAIN AB Background: The mechanisms involved in the induction and regulation of inflammation resulting in dopaminergic (DA) neurotoxicity in Parkinson's disease (PD) are complex and incompletely understood. Microglia-mediated inflammation has recently been implicated as a critical mechanism responsible for progressive neurodegeneration. Methods: Mesencephalic neuron-glia cultures and reconstituted cultures were used to investigate the molecular mechanisms of sinomenine (SN)-mediated anti-inflammatory and neuroprotective effects in both the lipopolysaccharide (LPS)-and the 1-methyl-4-phenylpyridinium (MPP+)-mediated models of PD. Results: SN showed equivalent efficacy in protecting against DA neuron death in rat midbrain neuron-glial cultures at both micro-and sub-picomolar concentrations, but no protection was seen at nanomolar concentrations. The neuroprotective effect of SN was attributed to inhibition of microglial activation, since SN significantly decreased tumor necrosis factor-alpha (TNF-alpha, prostaglandin E-2 (PGE(2)) and reactive oxygen species (ROS) production by microglia. In addition, from the therapeutic point of view, we focused on sub-picomolar concentration of SN for further mechanistic studies. We found that 10(-14) M of SN failed to protect DA neurons against MPP+-induced toxicity in the absence of microglia. More importantly, SN failed to show a protective effect in neuron-glia cultures from mice lacking functional NADPH oxidase (PHOX), a key enzyme for extracellular superoxide production in immune cells. Furthermore, we demonstrated that SN reduced LPS-induced extracellular ROS production through the inhibition of the PHOX cytosolic subunit p47phoxtranslocation to the cell membrane. Conclusion: Our findings strongly suggest that the protective effects of SN are most likely mediated through the inhibition of microglial PHOX activity. These findings suggest a novel therapy to treat inflammation-mediated neurodegenerative diseases. C1 Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Neuropharmacol Sect, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Flood, PM (reprint author), Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. EM qianl2@niehs.nih.gov; xuz@niehs.nih.gov; zw671104@yahoo.com; wilson3@niehs.nih.gov; hong3@niehs.nih.gov; pat_flood@dentistry.unc.edu OI xu, zongli/0000-0002-9034-8902 FU Intramural NIH HHS; NIDCR NIH HHS [DE-13079, P60 DE013079] NR 41 TC 59 Z9 66 U1 0 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD SEP 19 PY 2007 VL 4 AR 23 DI 10.1186/1742-2094-4-23 PG 14 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 230JQ UT WOS:000250873200001 PM 17880684 ER PT J AU Yao, LS Bax, A AF Yao, Lishan Bax, Ad TI Modulating protein alignment in a liquid-crystalline medium through conservative mutagenesis SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RESIDUAL DIPOLAR COUPLINGS; MOLECULAR ALIGNMENT; NMR-SPECTROSCOPY; BIOMOLECULAR NMR; DYNAMICS; MACROMOLECULES; UBIQUITIN; MOTIONS; GELS AB The Saupe matrix describing protein alignment in a liquid-crystalline medium contains five independent elements, enabling the generation of up to five linearly independent alignment conditions. Measurement of internuclear residual dipolar couplings by NMR spectroscopy under these conditions, orthogonal in five-dimensional alignment space, provides access to the amplitude, asymmetry, and direction of motions of the internuclear vector. It is demonstrated for the small protein domain GB3 (56 residues) that suitably orthogonal alignment conditions can be generated in a single liquid-crystalline medium of Pf1 phage, by generating a series of conservative mutants that have negligible impact on the time-averaged backbone structure of the domain. Mutations involve changes in the charge of several solvent-exposed side chains, as well as extension of the protein by either an N- or C-terminal Histag peptide, commonly used for protein purification. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov RI Yao, Lishan /C-6961-2009; yao, lishan/H-3662-2012 OI yao, lishan/0000-0003-1797-922X FU Intramural NIH HHS NR 21 TC 23 Z9 23 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 19 PY 2007 VL 129 IS 37 BP 11326 EP + DI 10.1021/ja073937+ PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 210OG UT WOS:000249464900015 PM 17718572 ER PT J AU Hansen, DF Yang, DW Feng, HQ Zhou, Z Wiesner, S Bai, YW Kay, LE AF Hansen, D. Flemming Yang, Daiwen Feng, Haniqiao Zhou, Zheng Wiesner, Silke Bai, Yawen Kay, Lewis E. TI An exchange-free measure of N-15 transverse relaxation: An NMR spectroscopy application to the study of a folding intermediate with pervasive chemical exchange SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; ROTATIONAL DIFFUSION ANISOTROPY; PROTEIN BACKBONE DYNAMICS; DENSITY-FUNCTION-ANALYSIS; LIQUID-CRYSTALLINE PHASE; 4-HELIX BUNDLE PROTEIN; MODEL-FREE APPROACH; HETERONUCLEAR NMR; SHIFT ANISOTROPY; SPIN RELAXATION AB A series of experiments are presented that provide an exchange-free measure of dipole-dipole N-15 transverse relaxation, R-dd, that can then be substituted for N-15 R-1p or R-2 rates in the study of internal protein dynamics. The method is predicated on the measurement of a series of relaxation rates involving H-1-N-15 longitudinal order, anti-phase H-1 and N-15 single-quantum coherences, and H-1-N-15 multiple quantum coherences; the relaxation rates of all coherences are measured under conditions of spin-locking. Results from detailed simulations and experiments on a number of protein systems establish that Rdd values are independent of exchange and systematic errors from dipolar interactions with proximal protons are calculated to be less than 1-2%, on average, for applications to perdeuterated proteins. Simulations further indicate that the methodology is rather insensitive to the exact level of deuteration so long as proteins are reasonably highly deuterated (> 50%). The utility of the methodology is demonstrated with applications involving protein L, ubiquitin, and a stabilized folding intermediate of apocytochrome b(562) that shows large contributions to N-15 R-1p relaxation from chemical exchange. C1 Univ Toronto, Dept Med Genet, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Biochem & Chem, Toronto, ON M5S 1A8, Canada. Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore. NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Kay, LE (reprint author), Univ Toronto, Dept Med Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada. EM kay@pound.med.utoronto.ca RI yang, daiwen/H-8408-2012 OI yang, daiwen/0000-0002-6804-0071 NR 76 TC 30 Z9 30 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 19 PY 2007 VL 129 IS 37 BP 11468 EP 11479 DI 10.1021/ja072717t PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 210OG UT WOS:000249464900045 PM 17722922 ER PT J AU Wacholder, S AF Wacholder, Sholom TI Untangling differences in cancer mortality rates: A closer look at race and education SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 NIH, Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. RP Wacholder, S (reprint author), NIH, Natl Canc Inst, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8046,MSC-7244, Rockville, MD 20892 USA. EM wacholds@mail.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 19 PY 2007 VL 99 IS 18 BP 1356 EP 1357 DI 10.1093/jnci/djm154 PG 2 WC Oncology SC Oncology GA 214EJ UT WOS:000249718500002 PM 17848665 ER PT J AU Lucia, MS Epstein, JI Goodman, PJ Darke, AK Reuter, VE Civantos, F Tangen, CM Parnes, HL Lippman, SM La Rosa, FG Kattan, MW Crawford, ED Ford, LG Coltman, CA Thompson, IM AF Lucia, M. Scott Epstein, Jonathan I. Goodman, Phyllis J. Darke, Amy K. Reuter, Victor E. Civantos, Francisco Tangen, Catherine M. Parnes, Howard L. Lippman, Scott M. La Rosa, Francisco G. Kattan, Michael W. Crawford, E. David Ford, Leslie G. Coltman, Charles A., Jr. Thompson, Ian M. TI Finasteride and high-grade prostate cancer in the prostate cancer prevention trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NEEDLE-BIOPSY; RADICAL PROSTATECTOMY; SPECIMENS; BENIGN; TISSUE; VOLUME; HYPERPLASIA; SENSITIVITY; CARCINOMAS; THERAPY AB Background The Prostate Cancer Prevention Trial (PCPT) reported a decreased incidence of prostate cancer overall but an increase in the incidence of high-grade prostate cancer with finasteride compared with placebo. We assessed whether the increased high-grade prostate cancer associated with finasteride in the PCPT was due to finasteride's potential effects oh tumor morphology or prostate size. Methods Prostate biopsies with Gleason score 8-10 (n = 90, finasteride; n 52, placebo) were examined histologically for hormonal effects, and those with Gleason score 7-10 (n 282, finasteride; n = 244, placebo) were examined for pathologic surrogates of disease extent. Prostate volumes were measured at biopsy. Samples from radical prostatectomies (n = 222, finasteride; n = 306, placebo) were examined for tumor grade and extent, and, where possible, grades at biopsy and prostatectomy were compared between the groups. Logistic regression was used to analyze differences between treatment groups with respect to pathologic criteria. All statistical tests were two-sided. Results Degenerative hormonal changes in high-grade biopsies were equivalent between the finasteride and placebo groups, but prostate volumes were lower in the finasteride group (median = 25.1 versus 34.4 cm(3), P <.001). Pathologic surrogates for tumor extent were lower with finasteride than with placebo, including mean percentage of positive cores (34% versus 38%, P =.016), mean tumor linear extent (greatest [4.4 versus 4.8 mm, P =.91 and aggregate [7.6 versus 9.2 mm, P =.13]), bilaterality (22.8% versus 30.6%, P=.046), and perineural invasion (14.2% versus 20.3%, P=.07). Among patients who had prostatectomy, the finasteride-associated increase in high-grade disease (Gleason score : 7) at biopsy (42.7% finasteride versus 25.4% placebo, P <.001) was diminished at prostatectomy (46.4% finasteride versus 38.6% placebo, P =.10). Biopsy identified a greater proportion of patients with high-grade disease present at prostatectomy in the finasteride group than in the placebo group (69.7% versus 50.5%, P=.01). The rate of upgrading (from low-grade cancer at biopsy to high-grade cancer at prostatectomy) and pathologic stage at prostatectomy were similar in both groups. Conclusions Effects of finasteride on prostate volume and selective inhibition of low-grade cancer, rather than effects on tumor morphology, may have contributed to the increase in high-grade cancers with finasteride in the PCPT. Although induction of high-grade cancer cannot be excluded, the results suggest that high-grade cancer was detected earlier and was less extensive in the finasteride group than in the placebo group. C1 Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD USA. Fred Hutchinson Canc Res Ctr, Seattle, WA USA. Mem Sloan Kettering Canc Ctr, New York, NY USA. Miami Univ, Sch Med, Miami, FL USA. Natl Canc Inst, Bethesda, MD USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX USA. Cleveland Clin Fdn, Dept Quantitative Hlth Sci, Cleveland, OH USA. SW Oncol Grp, San Antonio, TX USA. Univ Texas, Ctr Hlth Sci, San Antonio, TX USA. RP Lucia, MS (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pathol, 4200 E 9th Ave, Box B-216, Denver, CO 80262 USA. EM scott.lucia@uchsc.edu FU NCI NIH HHS [CA45808, CA35178, CA37429] NR 35 TC 157 Z9 159 U1 0 U2 7 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 SEP 19 PY 2007 VL 99 IS 18 BP 1375 EP 1383 DI 10.1093/jnci/djm117 PG 9 WC Oncology SC Oncology GA 214EJ UT WOS:000249718500009 PM 17848673 ER PT J AU Pine, SR Mechanic, LE Ambs, S Bowman, ED Chanock, SJ Loffredo, C Shields, PG Harris, CC AF Pine, Sharon R. Mechanic, Leah E. Ambs, Stefan Bowman, Elise D. Chanock, Stephen J. Loffredo, Christopher Shields, Peter G. Harris, Curtis C. TI Lung cancer survival and functional polymorphisms in MBL2, an innate-immunity gene SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MANNOSE-BINDING LECTIN; SINGLE NUCLEOTIDE POLYMORPHISMS; SQUAMOUS-CELL CARCINOMA; NITRIC-OXIDE SYNTHASE; SERINE PROTEASE-2; PROTEIN GENE; RISK; INFLAMMATION; DISEASE; TUMORIGENESIS AB Background The relationship among chronic inflammation, innate immunity, and cancer is well established. Mannose-binding lectin (MBL) is a key player in innate immunity. Five polymorphisms in the promoter and first exon of the MBL2 gene alter the expression and function of MBL in humans and are associated with inflammation-related disease susceptibility. These five polymorphisms create six well-characterized haplotypes that result in lower (i.e., LYB, LYC, HYD, and LXA) or higher (i.e., HYA and LYA) serum MBL concentrations. We investigated whether survival of patients with lung cancer was associated with these polymorphisms. Methods We used a multivariable Cox proportional hazards model to study the association between MBL2 polymorphisms and their haplotypes and diplotypes in 558 white and 173 African American patients with non-small-cell lung cancer in the Baltimore, MD, area and lung cancer mortality. Smoking history and race were obtained from interviews, tumor stage was obtained from medical records, and cause of death was obtained from the National Death Index. All statistical tests were two-sided. Results We found a statistically significant association between the X allele of the promoter Y/X polymorphism (which results in a lower serum MBL concentration) and improved lung cancer survival among white patients (risk ratio [13R] of death from lung cancer with X/X or X/Y genotype compared with Y/Y genotype = 0.61, 95% confidence interval [Cl] = 0.46 to 0.81) but not among African American patients (RR = 1.11, 95% Cl = 0.69 to 1.77). The associations among white patients were strongest in heavy smokers and were independent of stage. We also found a statistically significant interaction between the Y/X polymorphism and race for lung cancer survival (P-interaction = .019). The MBL2 LXA haplotype and XA/B diplotype, which are also associated with low serum MBL levels, were statistically significantly associated with improved lung cancer survival among white patients. Conclusion The functional Y/X polymorphism of the innate-immunity gene MBL2 and MBL2 haplotypes and diplotypes appear to be associated with lung cancer survival among white patients. C1 Lab Human Carcinogenes, Bethesda, MD USA. Sect Genomic Variation, Pediat Oncol Grp, Bethesda, MD USA. Natl Canc Inst, NIH, Bethesda, MD USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Canc Genet & Epidemiol Program, Washington, DC USA. RP Harris, CC (reprint author), NCI, NIH, Lab Human Carcinogenes, Rm 3068,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA. EM harrisc@mail.nih.gov RI Shields, Peter/I-1644-2012 FU Intramural NIH HHS NR 39 TC 28 Z9 29 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 19 PY 2007 VL 99 IS 18 BP 1401 EP 1409 DI 10.1093/jnci/djm128 PG 9 WC Oncology SC Oncology GA 214EJ UT WOS:000249718500012 PM 17848669 ER PT J AU Zhang, XY Yang, F Shim, JY Kirk, KL Anderson, DE Chen, XX AF Zhang, Xinyan Yang, Fan Shim, Joong-Youn Kirk, Kenneth L. Anderson, D. Eric Chen, Xiaoxin TI Identification of arsenic-binding proteins in human breast cancer cells SO CANCER LETTERS LA English DT Article DE arsenic; cysteine; breast cancer ID ESTROGEN-RECEPTOR-ALPHA; MAMMALIAN-CELLS; BETA-TUBULIN; METHIONINE AMINOPEPTIDASE; NICOTINIC RECEPTORS; ESCHERICHIA-COLI; MCF-7 CELLS; TRIOXIDE; KINASE; INHIBITION AB As a cancer chemotherapeutic drug, arsenic acts on numerous intracellular signal transduction pathways in cancer cells. However, its mechanism of actions is still not fully understood. Previous studies suggest that arsenic reacts with closely spaced cysteine (Cys) residues of proteins with high Cys content and accessible sulfhydryl (SH) groups. In this study, human breast cancer cell line MCF-7 was examined as a cellular model to explore arsenic-binding proteins and the mechanism of binding. An arsenic-biotin conjugate was synthesized by coupling the pentafluorophenol ester of biotin with p-aminophenylarsenoxide. Arsenic-binding proteins were eluted with streptavidin resin from arsenic-biotin treated MCF-7 cells, separated by polyacrylamide gel electrophoresis, and identified by matrix assisted laser desorption ionization mass spectrometry (MALDI-MS). Arsenic-binding properties of two of these proteins, beta-tubulin and pyruvate kinase M2 (PKM2), were studied further in vitro and the biological consequences of this binding was evaluated. Binding assay with Western blotting confirmed binding of beta-tubulin and PKM2 by arsenic in a concentration-dependent manner. Arsenic binding inhibited tubulin polymerization, but surprisingly had no effect on PKM2 activity. Molecular modeling showed that binding of Cys(12) alone or vicinal Cys residues (Cys(12) and Cys(213)) of beta-tubulin by arsenic blocked the active site for access of GTP, which is necessary for tubulin polymerization. On the contrary, all Cys residues of PKM2 were far away from the active site of the enzyme. In summary, this study confirmed beta-tubulin and PKM2 as arsenic-binding proteins in MCF-7 cells. Functional consequence of such binding may depend on whether arsenic binding causes conformational changes or blocks active sites of target proteins. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 NCI, NIH, Bethesda, MD 20892 USA. N Carolina Cent Univ, Julius L Chambers Biomed Biotechnol Res Inst, Canc Res Program, Durham, NC 27707 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Chen, XX (reprint author), NCI, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM fyang@mail.nih.gov; lchen@nccu.edu FU Intramural NIH HHS; NCI NIH HHS [U56 CA092077, U56 CA092077-05] NR 57 TC 41 Z9 42 U1 1 U2 17 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 SEP 18 PY 2007 VL 255 IS 1 BP 95 EP 106 DI 10.1016/j.canlet.2007.03.025 PG 12 WC Oncology SC Oncology GA 210XK UT WOS:000249488700011 PM 17499915 ER PT J AU Vislay-Meltzer, RL Stopfer, M AF Vislay-Meltzer, Rebecca L. Stopfer, Mark TI Olfactory coding: A plastic approach to timing precision SO CURRENT BIOLOGY LA English DT Editorial Material ID DEPENDENT SYNAPTIC PLASTICITY; DEVELOPING RETINOTECTAL SYSTEM; ODOR REPRESENTATIONS; MEMORY; DROSOPHILA; NEURONS; CELLS; LOBE C1 NIH, Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. RP Vislay-Meltzer, RL (reprint author), NIH, Natl Inst Child Hlth & Human Dev, 35 Lincoln Dr, Bethesda, MD 20892 USA. EM stopferm@mail.nih.gov RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 NR 17 TC 0 Z9 0 U1 0 U2 2 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 SEP 18 PY 2007 VL 17 IS 18 BP R797 EP R799 DI 10.1016/j.cub.2007.07.015 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 213CK UT WOS:000249643300011 PM 17878046 ER PT J AU de Gunst, MM Gallegos-Ruiz, MI Giaccone, G Rodriguez, JA AF de Gunst, Matheus M. Gallegos-Ruiz, Marielle I. Giaccone, Giuseppe Rodriguez, Jose Antonio TI Functional analysis of cancer-associated EGFR mutants using a cellular assay with YFP-tagged EGFR intracellular domain SO MOLECULAR CANCER LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; LUNG-CANCER; INCREASED SENSITIVITY; ERBB RECEPTORS; ACTIN-BINDING; IN-VIVO; GEFITINIB; MUTATIONS; ACTIVATION AB Background: The presence of EGFR kinase domain mutations in a subset of NSCLC patients correlates with the response to treatment with the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Although most EGFR mutations detected are short deletions in exon 19 or the L858R point mutation in exon 21, more than 75 different EGFR kinase domain residues have been reported to be altered in NSCLC patients. The phenotypical consequences of different EGFR mutations may vary dramatically, but the majority of uncommon EGFR mutations have never been functionally evaluated. Results: We demonstrate that the relative kinase activity and erlotinib sensitivity of different EGFR mutants can be readily evaluated using transfection of an YFP-tagged fragment of the EGFR intracellular domain (YFP-EGFR-ICD), followed by immunofluorescence microscopy analysis. Using this assay, we show that the exon 20 insertions Ins770SVD and Ins774HV confer increased kinase activity, but no erlotinib sensitivity. We also show that, in contrast to the common L858R mutation, the uncommon exon 21 point mutations P848L and A859T appear to behave like functionally silent polymorphisms. Conclusion: The ability to rapidly obtain functional information on EGFR variants of unknown relevance using the YFP-EGFR-ICD assay might prove important in the future for the management of NSCLC patients bearing uncommon EGFR mutations. In addition, our assay may be used to determine the response of resistant EGFR mutants to novel second-generation TKIs. C1 Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Amsterdam, Netherlands. NCI, Med Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. Univ Basque Country, Dept Genet Phys Anthropol & Anim Physiol, Leioa 48940, Spain. RP Rodriguez, JA (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Amsterdam, Netherlands. EM tdegunst@gmail.com; MGallegosRuiz@vumc.nl; giacconeg@mail.nih.gov; rodriguez_jan@hotmail.com RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 39 TC 13 Z9 13 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD SEP 18 PY 2007 VL 6 AR 56 DI 10.1186/1476-4598-6-56 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 229UF UT WOS:000250830200001 PM 17877814 ER PT J AU Yamanaka, O Saika, S Ohnishi, Y Kim-Mitsuyama, S Kamaraju, AK Ikeda, K AF Yamanaka, Osamu Saika, Shizuya Ohnishi, Yoshitaka Kim-Mitsuyama, Shokei Kamaraju, Anil K. Ikeda, Kazuo TI Inhibition of p38MAP kinase suppresses fibrogenic reaction in conjunctiva in mice SO MOLECULAR VISION LA English DT Article ID PIGMENT EPITHELIAL-CELLS; HUMAN SUBCONJUNCTIVAL FIBROBLASTS; ACTIVATED PROTEIN-KINASE; MESENCHYMAL TRANSITION; EXTRACELLULAR-MATRIX; LENS EPITHELIUM; FILTERING BLEB; BETA; SMAD; TRANSDIFFERENTIATION AB Purpose: To examine the effects of blocking p38 mitogen-activated protein kinase (MAPK) on post-injury conjunctival scarring in mice. Its effects on the behaviors of cultured subconjunctival fibroblasts were also investigated. Methods: An in vivo study was conducted using an adenoviral vector carrying a dominant-negative (DN)-p38MAPK gene. A circumferential incision was made in the equatorial conjunctiva by scissors in the right eye of generally anesthetized adult C57BL/6 mice. DN-p38MAPK-expressing adenoviral vector was topically applied. The left control eye received non-functioning adenoviral vector. At 2, 5, and 7 days (each, n=22) the eyes were processed for histological or immunohistochemical examination to evaluate the tissue scarring. The expressions of type-I collagen and growth factors were evaluated by real time-reverse transcriptase-polymerase chain reaction. The effects of p38MAPK inhibitor on the proliferation, migration, and fibrogenic gene/protein expression of cultured human fibroblasts were also studied. Results: The in vivo DN-p38MAPK gene introduction blocked the phospho-p38 expression with reduction of myofibroblast generation and suppression of mRNA expression of connective tissue growth factor (CTGF) and monocyte/macrophage chemoattractant protein-1 (MCP-1) in the mouse-injured conjunctiva. Blocking p38MAPK signal in the fibroblasts by a chemical inhibitor counteracted TGF beta 1's enhancement of expressions of type-I collagen, fibronectin, and CTGF. It also retarded cell migration, but cell proliferation was unchanged. Conclusions: Inhibiting p38MAPK signal impairs the fibrogenic reaction induced by the subconjunctival fibroblasts in vivo and in vitro, suggesting its potential effectiveness in preventing excessive scarring following glaucoma filtering surgery. C1 Wakayama Med Univ, Dept Ophthalmol, Wakayama 6410012, Japan. Kumamoto Univ, Grad Sch Med Sci, Dept Pharmacol & Mol Therapeut, Kumamoto, Japan. Natl Canc Inst, Lab Cell Regulat & Carcinogenesis, Bethesda, MD USA. Osaka City Univ, Grad Sch Med, Dept Anat, Osaka 558, Japan. RP Yamanaka, O (reprint author), Wakayama Med Univ, Dept Ophthalmol, 811-1 Kimiidera, Wakayama 6410012, Japan. EM yamanaka@wakayama-med.ac.jp NR 30 TC 19 Z9 22 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD SEP 18 PY 2007 VL 13 IS 190-93 BP 1730 EP 1739 PG 10 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 223SA UT WOS:000250391400004 PM 17960111 ER PT J AU Hummer, G AF Hummer, Gerhard TI Water pulls the strings in hydrophobic polymer collapse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID LONG-TIME DYNAMICS; COMPLEX-SYSTEMS; ELECTRON-TRANSFER; TRANSITION PATHS; FREE-ENERGY; PROTEINS; SIMULATIONS; KINETICS; STATES; MODEL C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 32 TC 6 Z9 6 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 18 PY 2007 VL 104 IS 38 BP 14883 EP 14884 DI 10.1073/pnas.0706633104 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214DB UT WOS:000249715100002 PM 17855565 ER PT J AU Bauer, J Xing, GX Yagi, H Sayer, JM Jerina, DM Ling, H AF Bauer, Jacob Xing, Guangxin Yagi, Haruhiko Sayer, Jane M. Jerina, Donald M. Ling, Hong TI A structural gap in Dpo4 supports mutagenic bypass of a major benzo[a]pyrene dG adduct in DNA through template misalignment SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; DNA replication; mutagenesis; translesion synthesis; polycyclic aromatic hydrocarbon ID POLYCYCLIC AROMATIC-HYDROCARBONS; DIOL EPOXIDE; LESION-BYPASS; ESCHERICHIA-COLI; SEQUENCE CONTEXT; ERROR-PRONE; DEOXYGUANOSINE ADDUCTS; BASE SUBSTITUTION; CRYSTAL-STRUCTURE; POLYMERASE-KAPPA AB Erroneous replication of lesions in DNA by DNA polymerases leads to elevated mutagenesis. To understand the molecular basis of DNA damage-induced mutagenesis, we have determined the x-ray structures of the Y-family polymerase, Dpo4, in complex with a DNA substrate containing a bulky DNA lesion and incoming nucleoticles. The DNA lesion is derived from an environmentally widespread carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BP). The potent carcinogen BP is metabolized to diol epoxides that form covalent adducts with cellular DNA. In the present study, the major BP diol epoxide adduct in DNA, BP-N-2-deoxyguanosine (BP-dG), was placed at a template-primer junction. Three ternary complexes reveal replication blockage, extension past a mismatched lesion, and a -1 frameshift mutation. In the productive structures, the bulky adduct is flipped/looped out of the DNA helix into a structural gap between the little finger and core domains. Sequestering of the hydrophobic BP adduct in this new substrate-binding site permits the DNA to exhibit normal geometry for primer extension. Extrusion of the lesion by template misalignment allows the base 5' to the adduct to serve as the template, resulting in a -1 frameshift. Subsequent strand realignment produces a mismatched base opposite the lesion. These structural observations, in combination with replication and mutagenesis data, suggest a model in which the additional substrate-binding site stabilizes the extrahelical nucleotide for lesion bypass and generation of base substitutions and -1 frameshift mutations. C1 Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada. NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ling, H (reprint author), Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada. EM hling4@uwo.ca RI Ling, Hong/E-3729-2010 FU Intramural NIH HHS; NIGMS NIH HHS [DMR0225180, GM0225180] NR 46 TC 51 Z9 52 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 SEP 18 PY 2007 VL 104 IS 38 BP 14905 EP 14910 DI 10.1073/pnas.0700717104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214DB UT WOS:000249715100008 PM 17848527 ER PT J AU Jang, HJ Kokrashvili, Z Theodorakis, MJ Carlson, OD Kim, BJ Zhou, J Kim, HH Xu, X Chan, SL Juhaszova, M Bernier, M Mosinger, B Margolskee, RF Egan, JM AF Jang, Hyeung-Jin Kokrashvili, Zaza Theodorakis, Michael J. Carlson, Olga D. Kim, Byung-Joon Zhou, Jie Kim, Hyeon Ho Xu, Xiangru Chan, Sic L. Juhaszova, Magdalena Bernier, Michel Mosinger, Bedrich Margolskee, Robert F. Egan, Josephine M. TI Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE enteroendocrine cells; gastrointestinal chemosensation; glucose sensor; incretin ID SWEET TASTE; ALPHA-GUSTDUCIN; ENTEROENDOCRINE CELLS; INSULIN-SECRETION; GLUCOSE-TOLERANCE; CATION CHANNEL; UMAMI TASTE; G-PROTEIN; BITTER; TRANSDUCTION AB Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GILP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express a-gustducin. Ingestion of glucose by alpha-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from alpha-gustducin null mice showed markedly defective GILP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses a-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for a-gustducin. We conclude that L cells of the gut "taste" glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut "taste cells" may provide an important treatment for obesity, diabetes and abnormal gut motility. C1 NIA, NIH, Baltimore, MD 21224 USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. RP Margolskee, RF (reprint author), NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM robert.margolskee@mssm.edu RI jang, hyeung jin/C-8022-2013; OI Bernier, Michel/0000-0002-5948-368X FU Intramural NIH HHS; NIDCD NIH HHS [DC003055, DC003155, DC007399, R01 DC003055, R01 DC003155, R21 DC007399] NR 42 TC 460 Z9 479 U1 9 U2 66 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 SEP 18 PY 2007 VL 104 IS 38 BP 15069 EP 15074 DI 10.1073/pnas.0706890104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214DB UT WOS:000249715100036 PM 17724330 ER PT J AU Marenco, S Siuta, MA Kippenhan, JS Grodofsky, S Chang, WL Kohn, P Mervis, CB Morris, CA Weinberger, DR Meyer-Lindenberg, A Pierpaoli, C Berman, KF AF Marenco, Stefano Siuta, Michael A. Kippenhan, J. Shane Grodofsky, Samuel Chang, Wei-Li Kohn, Philip Mervis, Carolyn B. Morris, Colleen A. Weinberger, Daniel R. Meyer-Lindenberg, Andreas Pierpaoli, Carlo Berman, Karen Faith TI Genetic contributions to white matter architecture revealed by diffusion tensor imaging in Williams syndrome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE development; LIMK1; neuronal growth cone; neuronal migration; tractography ID HUMAN BRAIN; CORPUS-CALLOSUM; WEIGHTED MRI; MORPHOLOGY; COGNITION; BEHAVIOR; ABNORMALITIES; GYRIFICATION; DEGENERATION; MORPHOMETRY AB Little is known about genetic regulation of the development of white matter. This knowledge is critical in understanding the pathophysiology of neurodevelopmental syndromes associated with altered cognition as well as in elucidating the genetics of normal human cognition. The hemideletion of approximate to 25 genes on chromosome 7q11.23 that causes Williams syndrome (WS) includes genes that regulate cytoskeletal dynamics in neurons, especially LIMK1 and CYLN2, and therefore offers the opportunity to investigate the role of these genes in the formation of white matter tracts. We used diffusion tensor imaging to demonstrate alteration in white matter fiber directionality, deviation in posterior fiber tract course, and reduced lateralization of fiber coherence in WS. These abnormalities are consistent with an alteration of the late stages of neuronal migration, define alterations of white matter structures underlying dissociable behavioral phenotypes in WS, and provide human in vivo information about genetic control of white matter tract formation. C1 NIH, NIMH,IRP, GCAP,CBDB, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, NIMH, IRP,CBDB, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. Univ Louisville, Dept Psychol & Brain Sci, Neurodev Sci Lab, Louisville, KY 40292 USA. Univ Nevada, Sch Med, Dept Pediat, Las Vegas, NV 89102 USA. NIH, IRP, GCAP,CBDB, Unit Syst Neurosci Psychiat, Bethesda, MD 20892 USA. NIH, Natl Inst Child Hlth & Human Dev, Sect Tissue Biophys & Biometr, Bethesda, MD 20892 USA. RP Marenco, S (reprint author), NIH, NIMH,IRP, GCAP,CBDB, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM marencos@mail.nih.gov RI Marenco, Stefano/A-2409-2008; Pierpaoli, Carlo/E-1672-2011; Meyer-Lindenberg, Andreas/H-1076-2011; OI Marenco, Stefano/0000-0002-2488-2365; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Grodofsky, Samuel/0000-0002-7484-7613 FU Intramural NIH HHS; NINDS NIH HHS [NS35102, R01 NS035102] NR 49 TC 57 Z9 57 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 18 PY 2007 VL 104 IS 38 BP 15117 EP 15122 DI 10.1073/pnas.0704311104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214DB UT WOS:000249715100044 PM 17827280 ER PT J AU Singh, AK Guion, P Sears-Crouse, N Ullman, K Smith, S Albert, PS Fichtinger, G Choyke, PL Xu, S Kruecker, J Wood, BJ Krieger, A Ning, H AF Singh, Anurag K. Guion, Peter Sears-Crouse, Nancy Ullman, Karen Smith, Sharon Albert, Paul S. Fichtinger, Gabor Choyke, Peter L. Xu, Sheng Kruecker, Jochen Wood, Bradford J. Krieger, Axel Ning, Holly TI Simultaneous integrated boost of biopsy proven, MRI defined dominant intra-prostatic lesions to 95 Gray with IMRT: early results of a phase I NCI study SO RADIATION ONCOLOGY LA English DT Article ID COMPARING 68 GY; INTRAPROSTATIC LESIONS; RADIATION-THERAPY; RANDOMIZED-TRIAL; DOSE-ESCALATION; CANCER; RADIOTHERAPY; BRACHYTHERAPY; TREAT; MEN AB Background: To assess the feasibility and early toxicity of selective, IMRT-based dose escalation (simultaneous integrated boost) to biopsy proven dominant intra-prostatic lesions visible on MRI. Methods: Patients with localized prostate cancer and an abnormality within the prostate on endorectal coil MRI were eligible. All patients underwent a MRI-guided transrectal biopsy at the location of the MRI abnormality. Gold fiducial markers were also placed. Several days later patients underwent another MRI scan for fusion with the treatment planning CT scan. This fused MRI scan was used to delineate the region of the biopsy proven intra-prostatic lesion. A 3 mm expansion was performed on the intra-prostatic lesions, defined as a separate volume within the prostate. The lesion + 3 mm and the remainder of the prostate + 7 mm received 94.5/75.6 Gray (Gy) respectively in 42 fractions. Daily seed position was verified to be within 3 mm. Results: Three patients were treated. Follow-up was 18, 6, and 3 months respectively. Two patients had a single intra-prostatic lesion. One patient had 2 intra-prostatic lesions. All four intra-prostatic lesions, with margin, were successfully targeted and treated to 94.5 Gy. Two patients experienced acute RTOG grade 2 genitourinary (GU) toxicity. One had grade 1 gastrointestinal (GI) toxicity. All symptoms completely resolved by 3 months. One patient had no acute toxicity. Conclusion: These early results demonstrate the feasibility of using IMRT for simultaneous integrated boost to biopsy proven dominant intra-prostatic lesions visible on MRI. The treatment was well tolerated. C1 [Singh, Anurag K.] Roswell Pk Canc Inst, Dept Radiat Med, Buffalo, NY 14263 USA. [Guion, Peter; Sears-Crouse, Nancy; Ullman, Karen; Smith, Sharon; Ning, Holly] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Fichtinger, Gabor] Queens Univ, Sch Comp, Kingston, ON, Canada. [Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Xu, Sheng; Kruecker, Jochen] Philips Res N Amer, Briarcliff Manor, NY USA. [Wood, Bradford J.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Krieger, Axel] Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA. RP Singh, AK (reprint author), Roswell Pk Canc Inst, Dept Radiat Med, Buffalo, NY 14263 USA. EM singhanu@yahoo.com; guionp@mail.nih.gov; ncrouse@mail.nih.gov; karenullman@mail.nih.gov; smiths@mail.nih.gov; albertp@mail.nih.gov; gabor@cs.queensu.ca; pchoyke@mail.nih.gov; Sheng.Xu@philips.com; jochen.kruecker@philips.com; bwood@mail.nih.gov; axel@jhu.edu; hning@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research [R01 EB002963-01] FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The Authors acknowledge the contribution of Louis L. Whitcomb Ph. D. of Johns Hopkins University, CO-PI of NIH Grant R01 EB002963-01, which supported the development of the APT-MRI device employed in the present study. Co-authors Gabor Fichtinger and Axel Krieger were also funded by the aforementioned NIH grant. NR 21 TC 47 Z9 47 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND J9 RADIAT ONCOL JI Radiat. Oncol. PD SEP 18 PY 2007 VL 2 AR 36 DI 10.1186/1748-717X-2-36 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 364OA UT WOS:000260343800002 PM 17877821 ER PT J AU Garolera, M Coppola, R Munoz, KE Elvevag, B Carver, FW Weinberger, DR Goldberg, TE AF Garolera, Maite Coppola, Richard Munoz, Karen E. Elvevag, Brita Carver, Frederick W. Weinberger, Daniel R. Goldberg, Terry E. TI Amygdala activation in affective priming: a magnetoencephalogram study SO NEUROREPORT LA English DT Article DE amygdala; emotion; magnetoencephalography; priming; synthetic aperture magnetometry; theta rhythm ID FACIAL EXPRESSIONS; FRONTAL-CORTEX; EMOTION; FEAR; SYNCHRONIZATION; BRAIN; RECOGNITION; RESPONSES; BAND; MEG AB We employed magnetoencephalography (MEG) to examine amygdala activity during a linguistic affective priming task. The experimental design included positive and negative word pairs. Using synthetic aperture magnetometry in the analysis of MEG data, we identified a left amygdala power increase in the theta frequency range during priming involving negative words. We found that the amygdala displayed a time-dependent intensification in responsiveness to negative stimuli, specifically between 150 and 400 ms after target presentation. This study provides evidence for theta power changes in the amygdala and demonstrates that the analysis of brain oscillations provides a powerful tool to explore mechanisms implicated in emotional processing. C1 NIMH, NIH, DHHS, IRP,Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NIMH, NIH, DHHS, IRPP,MEG Core Facil, Bethesda, MD USA. Hosp Terrassa, Barcelona, Spain. RP Elvevag, B (reprint author), NIMH, NIH, DHHS, IRP,Clin Brain Disorders Branch, Bethesda, MD 20892 USA. EM brita@elvevaag.net NR 28 TC 24 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 17 PY 2007 VL 18 IS 14 BP 1449 EP 1453 DI 10.1097/WNR.0b013e3282efa253 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 210UA UT WOS:000249479900008 PM 17712272 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI The young, not-so-young, and the 2007 Retrovirology Prize: call for nominations SO RETROVIROLOGY LA English DT Editorial Material ID SCIENCE; LIFE AB Recent findings suggest an aging scientific work force and an almost static publishing productivity in the United States. The Retrovirology Prize seeks to recognize and encourage the work of a midcareer retrovirologist between the ages of 45 and 60. The 2006 Retrovirology Prize was awarded to Dr. Joseph G. Sodroski. C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 6 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD SEP 17 PY 2007 VL 4 AR 64 DI 10.1186/1742-4690-4-64 PG 3 WC Virology SC Virology GA 224PY UT WOS:000250460100001 PM 17875209 ER PT J AU Lim, U Morton, LM Subar, AF Baris, D Stolzenberg-Solomon, R Leitzmann, M KipniS, V Mouwl, T Carro, L Schatzkin, A Hartge, P AF Lim, Unhee Morton, Lindsay M. Subar, Amy F. Baris, Daisu Stolzenberg-Solomon, Rachael Leitzmann, Michael KipniS, Victor Mouwl, Traci Carro, Leslie Schatzkin, Arthur Hartge, Patricia TI Alcohol, smoking, and body size in relation to incident Hodgkin's and non-Hodgkin's lymphoma risk SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol drinking; body height; Hodgkin disease; lymphoma; non-Hodgkin; motor activity; obesity; prospective studies; smoking ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PHYSICAL-ACTIVITY; UNITED-STATES; CIGARETTE-SMOKING; CANCER-RISK; MASS INDEX; ANTHROPOMETRIC CHARACTERISTICS; MALIGNANT-LYMPHOMA; SCANDINAVIAN MEN; POOLED ANALYSIS AB Studies associate alcohol consumption, cigarette smoking, and body size with the risk of overall or subtype lymphoma. Current data come mostly from case-control studies or prospective studies with few cases. In the prospective National Institutes of Health-former American Association of Retired Persons (NIH-AARP) Diet and Health Study, the authors assessed the above lifestyle factors via baseline questionnaire among 285,079 men and 188,905 women aged 50-71 years and ascertained histologically confirmed Hodgkin's lymphoma (n = 58) and non-Hodgkin's lymphoma (n = 1,381) cases through linkage with cancer registries from 1995 to 2000. Compared with nondrinkers, alcohol consumers had a lower risk for non-Hodgkin's lymphoma overall (for >28 drinks/week: adjusted relative risk (RR) = 0.77, 95% confidence interval (Cl): 0.59, 1.00; Arend among drinkers = 0.02) and for its main subtypes. Compared with never smokers, current smokers and recent quitters (<= 4 years ago) had higher risk of Hodgkin's lymphoma (RR = 2.25, 95% Cl: 1.04, 4.89; RR = 4.20, 95% Cl: 1.94, 9.09, respectively), whereas current or former smokers had lower risk of follicular non-Hodgkin's lymphoma (RR = 0.67, 95% Cl: 0.52, 0.86). Severe obesity (body mass index of >= 35: RR = 1.29, 95% Cl: 1.02, 1.64) and taller height (RR = 1.19, 95% Cl: 1.03,1.38) were associated moderately with non-Hodgkin's lymphoma. These findings add to the evidence that lifestyle factors and relevant anthropometric characteristics play a role in lymphoma etiology. C1 NCI, Div Canc Epidemiol, Nutr Epidemiol Branch, Rockville, MD 20852 USA. NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Lim, U (reprint author), NCI, Div Canc Epidemiol, Nutr Epidemiol Branch, 6120 Executive Blvd,EPS 320, Rockville, MD 20852 USA. EM limu@mail.nih.gov RI Morton, Lindsay/B-5234-2015 OI Morton, Lindsay/0000-0001-9767-2310 FU Intramural NIH HHS NR 69 TC 66 Z9 70 U1 2 U2 5 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 SEP 15 PY 2007 VL 166 IS 6 BP 697 EP 708 DI 10.1093/aje/kwm122 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 208OH UT WOS:000249328600010 PM 17596266 ER PT J AU Turner, J Biesecker, B Leib, J Biesecker, L Peters, KF AF Turner, Joyce Biesecker, Barbara Leib, Jennifer Biesecker, Leslie Peters, Kathryn F. TI Parenting children with Proteus syndrome: Experiences with, and adaptation to, courtesy stigma SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE courtesy stigma; stigma; coping; Protcus syndrome; parents; adaptation; psychosocial; genetic counseling ID GENETIC DISCRIMINATION; PTEN MUTATIONS; MANAGEMENT; DISABILITY; ILLNESS AB Courtesy stigima refers to the stigmatization an unaffected person experiences Clue to his or her relationship with a person who hears a stigma. Parents of children with genetic conditions are particularly, Vulnerable to courtesy stigma, but little research has been done to explore this phenomenon. The purpose of this study was to investigate the Courtesy stigma experiences of parents of children with proteus syndrome (PS) and related overgrowth conditions. Thematic analysis of transcripts from 31 parents identified three distinct themes: stigma experiences, social-crucitional reactions to stigmatizing encounters, and coping responses. Four 9 types of stigmatizing experiences were identified: intrusive inquires, staring and pointing, devaluing remarks, and social withdrawl. Additionally, we uncovered eight strategies parents used to cope with courtesy stigma: attributing cause, assigning meaning to social exchanges, concealing, with-drawing socially, taking the offensive, employing indifference, instructing and learning front family, and educating others. Parents' choices of strategy type were found to be context dependent and evolved over time. This is the first study to document the adaptive evolution of coping strategies to offset Courtesy stigma by parents of children with genetic conditions. These results provide groundwork for genetic counseling interventions aimed at addressing issues of courtesy stigma and further investigation of the phenomenon itself. Published 2007 Wiley-Liss, Inc. C1 NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. NHGRI, Social Behav Branch, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, Bethesda, MD USA. Penn State Univ, Ctr Dev & Hlth Genet, University Pk, PA 16802 USA. RP Turner, J (reprint author), NHGRI, NIH, Genet Dis Res Branch, 10 Ctr Dr,Bldg 10-3C710, Bethesda, MD 20892 USA. EM jturner1@mail.nih.gov FU Intramural NIH HHS NR 40 TC 10 Z9 11 U1 2 U2 8 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 SEP 15 PY 2007 VL 143A IS 18 BP 2089 EP 2097 DI 10.1002/ajmg.a.31904 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 207HM UT WOS:000249242200002 PM 17702022 ER PT J AU Lopez, BE Wink, DA Fukuto, JM AF Lopez, Brenda E. Wink, David A. Fukuto, Jon M. TI The inhibition of glyceraldehyde-3-phosphate dehydrogenase by nitroxyl (HNO) SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE nitroxyl; nitric oxide; glyceraldehyde-3-phosphate dehydrogenase; thiol; sulfinamide; glutathione; Angeli's salt ID TRANSCRIPTION FACTOR ACE1; NITRIC-OXIDE NO; NITROGEN-OXIDE; PROTEIN MODIFICATION; MEDIATED DISRUPTION; S-GLUTATHIONYLATION; CHEMISTRY; THIOL; MECHANISMS; OXIDATION AB Nitroxyl (HNO) has received recent and significant interest due to its novel and potentially important pharmacology. However, the chemical/biochemical mechanism(s) responsible for its biological activity remain to be established. Some of the most important biological targets for HNO are thiols and thiol proteins. Consistent with this, it was recently reported that HNO inhibits the glycolytic enzyme glyceralclehyde-3-phosphate dehydrogenase (GAPDH), a protein with a catalytically important cysteine thiol at its active site. Interestingly, it was reported that intracellular GAPDH inhibition occurred without significantly altering the cellular thiol redox status of glutathione. Herein, the nature of this reaction specificity was examined. HNO is found to irreversibly inhibit GAPDH in a manner that can be protected against by one of its substrates, glyceraldehyde-3-phosphate (G-3-P). These results are consistent with the idea that HNO has the ability to react with and oxidize a variety of intracellular thiols and the ease or facility of cellular re-reduction of the thiol targets can determine the target specificity. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Hlth Sci Ctr, Dept Pharmacol, Los Angeles, CA 90095 USA. NCI, Radiat Biol Branch, Tumor Biol Sect, Bethesda, MD 20892 USA. RP Fukuto, JM (reprint author), Univ Calif Los Angeles, Sch Med, Hlth Sci Ctr, Dept Pharmacol, Los Angeles, CA 90095 USA. EM jfukuto@mednet.ucla.edu NR 49 TC 34 Z9 34 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 15 PY 2007 VL 465 IS 2 BP 430 EP 436 DI 10.1016/j.abb.2007.06.017 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 212CB UT WOS:000249570100014 PM 17678614 ER PT J AU Liu, HF Zeeberg, BR Qu, G Koru, AG Ferrucci, A Kahn, A Ryan, MC Nuhanovic, A Munson, PJ Reinhold, WC Kane, DW Weinstein, JN AF Liu, Hongfang Zeeberg, Barry R. Qu, Gang Koru, A. Gunes Ferrucci, Alessandro Kahn, Ari Ryan, Michael C. Nuhanovic, Antej Munson, Peter J. Reinhold, William C. Kane, David W. Weinstein, John N. TI AffyProbeMiner: a web resource for computing or retrieving accurately redefined Affymetrix probe sets SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION MEASUREMENTS; ART.; GENERATIONS; MICROARRAYS; BIOLOGY; ARRAYS AB Motivation: Affymetrix microarrays are widely used to measure global expression of mRNA transcripts. That technology is based on the concept of a probe set. Individual probes within a probe set were originally designated by Affymetrix to hybridize with the same unique mRNA transcript. Because of increasing accuracy in knowledge of genomic sequences, however, a substantial number of the manufacturer's original probe groupings and mappings are now known to be inaccurate and must be corrected. Otherwise, analysis and interpretation of an Affymetrix microarray experiment will be in error. Results: AffyProbeMiner is a computationally efficient platform-independent tool that uses all RefSeq mature RNA protein coding transcripts and validated complete coding sequences in GenBank to (1) regroup the individual probes into consistent probe sets and (2) remap the probe sets to the correct sets of mRNA transcripts. The individual probes are grouped into probe sets that are ` transcript-consistent' in that they hybridize to the same mRNA transcript (or transcripts) and, therefore, measure the same entity (or entities). About 65.6% of the probe sets on the HG-U133A chip were affected by the remapping. Pre-computed regrouped and remapped probe sets for many Affymetrix microarrays are made freely available at the AffyProbeMiner web site. Alternatively, we provide a web service that enables the user to perform the remapping for any type of short-oligo commercial or custom array that has an Affymetrix-format Chip Definition File (CDF). Important features that differentiate AffyProbeMiner from other approaches are flexibility in the handling of splice variants, computational efficiency, extensibility, customizability and user-friendliness of the interface. C1 Natl Inst Hlth, Natl Canc Inst, Mol Pharmacol Lab, Genom & Bioinformat Grp, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC 20007 USA. Univ Maryland, Elect & Comp Engn & Inst Adv Studies, College Pk, MD 20742 USA. Univ Maryland, Dept Informat Syst, Baltimore, MD USA. Univ Maryland, Dept Comp Sci & Elect Engn, Baltimore, MD USA. George Mason Univ, Dept Bioinformat, Fairfax, VA USA. Natl Inst Hlth, Ctr Informat Technol, Div Computat Biosci, Math Stat Comp Lab, Bethesda, MD 20892 USA. SRA Intl, Fairfax, VA 22033 USA. RP Liu, HF (reprint author), Natl Inst Hlth, Natl Canc Inst, Mol Pharmacol Lab, Genom & Bioinformat Grp, Bethesda, MD 20892 USA. EM hl224@georgetown.edu; barry@discover.nci.nih.gov FU Intramural NIH HHS; NLM NIH HHS [R01 LM009959] NR 15 TC 52 Z9 52 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD SEP 15 PY 2007 VL 23 IS 18 BP 2385 EP 2390 DI 10.1093/bioinformatics/btm360 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 215OK UT WOS:000249818700005 PM 17660211 ER PT J AU Gilman, JM Bjork, JM Hommer, DW AF Gilman, Jodi M. Bjork, James M. Hommer, Daniel W. TI Parental alcohol use and brain volumes in early- and late-onset alcoholics SO BIOLOGICAL PSYCHIATRY LA English DT Article DE alcoholism; brain volumes; family history; intracranial volume; IQ; magnetic resonance imaging; neurodevelopment ID FETAL ALCOHOL; STRESS; CHILDREN; INTELLIGENCE; HYPOTHESIS; DISORDER; DRINKING; HISTORY; TRAITS; DAMAGE AB Background: Studies have shown that alcoholics have smaller brain volumes than non-alcoholic cohorts, but an effect of family history (FH) of heavy drinking on brain volume has not been demonstrated. We examined the relationship between an FH of heavy drinking and both brain shrinkage as measured by the ratio of brain volumes to intracranial volume (ICV) as well as maximal brain growth as measured by ICV in early-onset and late-onset alcoholics. Methods: With T1-weighted resonance imaging, we measured ICV, brain volume, and white and gray matter volume in adult treatment-seeking late-onset and early-onset alcoholics with either a positive or a negative FH of heavy alcohol use, and in healthy control subjects. We also calculated brain shrinkage using a ratio of soft tissue volumes to ICV. Results: The FH positive alcoholic patients had significantly smaller ICVs than FH negative patients, suggesting smaller premorbid brain growth. Brain shrinkage did not correlate with FH. Late-onset alcoholics showed a greater difference in ICV between FH positive and FH negative patients than early-onset alcoholics. Late-onset FH positive patients also had significantly lower IQ scores than late-onset FH negative patients, and IQ scores were correlated with ICV. Conclusions: These data provide evidence that parental alcohol use might increase risk for alcoholism in offspring in part by a genetic and/or environmental effect that might be related to reduced brain growth. C1 Hatfield Clin Res Ctr, NIH, Bethesda, MD 20892 USA. NIAAA, NIH, Lab Clin & Translat Studies, Sect Brain Electrophysiol & Imaging, Bethesda, MD USA. RP Gilman, JM (reprint author), Hatfield Clin Res Ctr, NIH, Room 1-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM gilmanj@mail.nih.gov OI Bjork, James/0000-0003-0593-3291 FU Intramural NIH HHS [Z01 AA000061-16, Z99 AA999999] NR 46 TC 18 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2007 VL 62 IS 6 BP 607 EP 615 DI 10.1016/j.biopsych.2006.10.029 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 209RD UT WOS:000249404800009 PM 17306776 ER PT J AU Job, MO Tang, A Hall, FS Sora, I Uhl, GR Bergeson, SE Gonzales, RA AF Job, Martin O. Tang, Amanda Hall, F. Scott Sora, Ichiro Uhl, George R. Bergeson, Susan E. Gonzales, Rueben A. TI Mu (mu) opioid receptor regulation of ethanol-induced dopamine response in the ventral striatum: Evidence of genotype specific sexual dimorphic epistasis SO BIOLOGICAL PSYCHIATRY LA English DT Article DE dopamine; genotype; knockout mice; microdialysis; nucleus accumbens; sexual dimorphism ID RAT NUCLEUS-ACCUMBENS; MORPHINE-INDUCED ANALGESIA; KNOCKOUT MICE; ALCOHOL-DRINKING; DEFICIENT MICE; BETA-ENDORPHIN; MICRODIALYSIS PROFILE; MOTOR-ACTIVITY; C57BL/6 MICE; DELTA AB Background: Ethanol stimulates the dopaminergic mesoaccumbal pathway, which is thought to play a role in ethanol reinforcement. Mu (mu)-opioid (MOP) receptors modulate accumbal dopamine activity, but it is not clear whether MOP receptors are involved in the mechanism of ethanol-stimulated accumbal dopamine release. Methods: We investigated the role that MOP receptors play in ethanol (2.0 g/kg)-stimulated accumbal dopamine release by using MOP receptor knockout mice (C57BL/6J-1 29SvEv and congenic C57BL/6J genotypes) along with blockade of MOP receptors with a mu 1 selective antagonist (naloxonazine). Results: Both gene deletion and pharmacological antagonism of the MOP receptor decreased ethanol-stimulated accumbal dopamine release compared with controls with female mice showing a larger effect in the C57BL/6J-129SvEv genotype. However, both male and female mice showed reduced ethanol-stimulated dopamine release in the congenic MOP receptor knockout mice (C57BL/6J). No differences in the time course of dialysate ethanol concentration were found in any of the experiments. Conclusions: The data demonstrate the existence of a novel interaction between genotype and sex in the regulation of ethanol-stimulated mesolimbic dopamine release by the MOP receptor. This implies that a more complete understanding of the epistatic influences on the MOP receptor and mesolimbic dopamine function may provide more effective pharmacotherapeutic interventions in the treatment of alcoholism. C1 Univ Texas, Coll Pharm, Div Pharmacol, PHAR Pharmacol, Austin, TX 78712 USA. Univ Texas, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA. NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD USA. Univ Texas, Neurobiol Sect, Austin, TX 78712 USA. Univ Texas, Sect Mol Genet & Microbiol, Austin, TX 78712 USA. RP Gonzales, RA (reprint author), Univ Texas, Coll Pharm, Div Pharmacol, PHAR Pharmacol, 1 Univ Stn A1915, Austin, TX 78712 USA. EM rgonzales@mail.utexas.edu RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 FU Intramural NIH HHS; NIAAA NIH HHS [AA 11852, AA 13486, L30 AA015308, L30 AA015308-02, R01 AA011852, R37 AA011852, T32 AA 97471, T32 AA007471, U01 AA013486] NR 65 TC 28 Z9 29 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2007 VL 62 IS 6 BP 627 EP 634 DI 10.1016/j.biopsych.2006.11.016 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 209RD UT WOS:000249404800011 PM 17336938 ER PT J AU Gorelick, DA AF Gorelick, David A. TI Regarding "Buprenorphine reduces alcohol drinking through activation of the nociceptin/orphanin FQ-NOP receptor system" SO BIOLOGICAL PSYCHIATRY LA English DT Letter ID CONDITIONED PLACE PREFERENCE; COCAINE; BLOCKS; RATS C1 Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. RP Gorelick, DA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM dgorelic@mail.nih.gov FU Intramural NIH HHS [Z01 DA000240-15] NR 8 TC 1 Z9 1 U1 0 U2 0 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 SEP 15 PY 2007 VL 62 IS 6 BP 702 EP 702 DI 10.1016/j.biopsych.2007.01.019 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 209RD UT WOS:000249404800021 PM 17531960 ER PT J AU Chung, JU Kim, SY Lim, JO Choi, HK Kang, SU Yoon, HS Ryu, H Kang, DW Lee, J Kang, B Choi, S Toth, A Pearce, LV Pavlyukovets, VA Lundberg, DJ Blumberg, PM AF Chung, Jae-Uk Kim, Su Yeon Lim, Ju-Ok Choi, Hyun-Kyung Kang, Sang-Uk Yoon, Hae-Seok Ryu, HyungChul Kang, Dong Wook Lee, Jeewoo Kang, Bomi Choi, Sun Toth, Attila Pearce, Larry V. Pavlyukovets, Vladimir A. Lundberg, Daniel J. Blumberg, Peter M. TI alpha-Substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE TRPV1 antagonists; analgesic ID HIGH-AFFINITY ANTAGONISTS; VANILLOID RECEPTOR; CAPSAICIN RECEPTORS; CHANNEL; REGION AB A series of alpha-Substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. alpha-Methyl substituted analogues showed potent and stereospecific antagonism to the action of capsaicin on rat TRPV1 heterologously expressed in Chinese hamster ovary cells. In particular, compounds 14 and 18, which possess the R-configuration, exhibited excellent potencies (respectively, K-i = 41 and 39.2 nM and K-i(ant) = 4.5 and 37 nM). (c) 2007 Published Elsevier Ltd. C1 Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 151742, South Korea. Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. Ewha Womans Univ, Natl Core Res Ctr Cell Signalling & Drug Discover, Seoul 120750, South Korea. NIH, Natl Canc Inst, Canc Res Ctr, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr RI Toth, Attila/F-4859-2010 OI Toth, Attila/0000-0001-6503-3653 FU Intramural NIH HHS NR 17 TC 21 Z9 21 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD SEP 15 PY 2007 VL 15 IS 18 BP 6043 EP 6053 DI 10.1016/j.bmc.2007.06.041 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 206PH UT WOS:000249194900005 PM 17629487 ER PT J AU Longo, DL AF Longo, Dan L. TI Watch out, MF! SO BLOOD LA English DT Editorial Material C1 NIA, Bethesda, MD 20892 USA. RP Longo, DL (reprint author), NIA, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2007 VL 110 IS 6 BP 1708 EP 1709 DI 10.1182/blood-2007-06-094896 PG 2 WC Hematology SC Hematology GA 213MM UT WOS:000249671700006 ER PT J AU Deleo, FR AF Deleo, Frank R. TI Attractive shedding SO BLOOD LA English DT Editorial Material ID INFLAMMATION C1 NIAID, Bethesda, MD 20892 USA. RP Deleo, FR (reprint author), NIAID, Bethesda, MD 20892 USA. OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS NR 5 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2007 VL 110 IS 6 BP 1711 EP 1712 DI 10.1182/blood-2007-06-096677 PG 2 WC Hematology SC Hematology GA 213MM UT WOS:000249671700009 PM 22993882 ER PT J AU Shepherd, BE Kiem, HP Lansdorp, PM Dunbar, CE Aubert, G LaRochelle, A Seggewiss, R Guttorp, P Abkowitz, JL AF Shepherd, Bryan E. Kiem, Hans-Peter Lansdorp, Peter M. Dunbar, Cynthia E. Aubert, Geraldine LaRochelle, Andre Seggewiss, Ruth Guttorp, Peter Abkowitz, Janis L. TI Hematopoietic stem-cell behavior in nonhuman primates SO BLOOD LA English DT Article ID TERM REPOPULATING CELLS; BLOOD CD34(+) CELLS; TELOMERE LENGTH; IN-VIVO; G-CSF; TRANSDUCTION; TRANSPLANTATION; TURNOVER; KINETICS; VECTORS AB Little is known about the behavior of hematopoietic stem cells (HSCs) in primates because direct observations and competitive-repopulation assays are not feasible. Therefore, we used 2 different and independent experimental strategies, the tracking of transgene expression after retroviral-mediated gene transfer (N = 11 baboons; N = 7 rhesus macaques) and quantitation of the average telomere length of granulocytes (N = 132 baboons; N = 14 macaques), together with stochastic methods, to study HSC kinetics in vivo. The average replication rate for baboon HSCs is once per 36 weeks according to gene-marking analyses and once per 23 weeks according to telomere-shortening analyses. Comparable results were derived from the macaque data. These rates are substantially slower than the average replication rates previously reported for HSCs in mice (once per 2.5 weeks) and cats (once per 8.3 weeks). Because baboons and macaques live for 25 to 45 years, much longer than mice (similar to 2 years) and cats (12-18 years), we can compute that HSCs undergo a relatively constant number (similar to 80-200) of lifetime replications. Thus, our data suggest that the self-renewal capacity of mammalian stem cells in vivo is defined and evolutionarily conserved. C1 Vanderbilt Univ, Dept Biostat, Nashville, TN USA. Fred Hutchinson Canc Res Inst, Seattle, WA USA. Univ British Columbia, Terry Fox Lab, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Stat, Seattle, WA 98195 USA. Univ Washington, Dept Med Hematol, Seattle, WA 98195 USA. RP Abkowitz, JL (reprint author), Univ Washington, Dept Med Hematol, Box 357710, Seattle, WA 98195 USA. EM janabk@u.washington.edu FU NHLBI NIH HHS [HL082933, HL53750, HL54881, P01 HL053750, P50 HL054881, R01 HL046598, R01 HL082933]; NIAID NIH HHS [AI29524, R01 AI029524, R21 AI029524] NR 51 TC 42 Z9 43 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2007 VL 110 IS 6 BP 1806 EP 1813 DI 10.1182/blood-2007-02-075382 PG 8 WC Hematology SC Hematology GA 213MM UT WOS:000249671700021 PM 17526860 ER PT J AU Bryceson, YT Rudd, E Zheng, CY Edner, J Ma, D Wood, SM Bechensteen, AG Boelens, JJ Celkan, T Farah, RA Hultenby, K Winiarski, J Roche, PA Nordenskjold, M Henter, JI Long, EO Ljunggren, HG AF Bryceson, Yenan T. Rudd, Eva Zheng, Chengyun Edner, Josefine Ma, Daoxin Wood, Stephanie M. Bechensteen, Anne Grete Boelens, Jaap J. Celkan, Tiraje Farah, Roula A. Hultenby, Kjell Winiarski, Jacek Roche, Paul A. Nordenskjold, Magnus Henter, Jan-Inge Long, Eric O. Ljunggren, Hans-Gustaf TI Defective cytotoxic lymphocyte degranulation in syntaxin-11-deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients SO BLOOD LA English DT Article ID FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; NATURAL-KILLER-CELLS; PERFORIN GENE-MUTATIONS; MEDIATED CYTOTOXICITY; NK CELLS; INHIBITORY RECEPTORS; GRANULE EXOCYTOSIS; DENDRITIC CELLS; IMMUNE-SYSTEM; CLASS-I AB Familial hemophagocytic lymphohistiocytosis (FHL) is typically an early onset, fatal disease characterized by a sepsislike illness with cytopenia, hepatosplenomegaly, and deficient lymphocyte cytotoxicity. Disease-causing mutations have been identified in genes encoding perforin (PRF1/FHL2), Munc13-4 (UNC13D/FHL3), and syntaxin-11 (STX11/FHL4). In contrast to mutations leading to loss of perforin and Munc13-4 function, it is unclear how syntaxin-11 loss-of-function mutations contribute to disease. We shove here that freshly isolated, resting natural killer (NK) cells and CD8(+) T cells express syntaxin-11. In infants, NK cells are the predominant perforin-containing cell type. NK cells from FHL4 patients fail to degranulate when encountering susceptible target cells. Unexpectedly, IL-2 stimulation partially restores degranulation and cytotoxicity by NK cells, which could explain the less severe disease progression observed in FHL4 patients, compared with FHL2 and FHL3 patients. Since the effector T-cell compartment is still immature in infants, our data suggest that the observed defect in NK-cell degranulation may contribute to the pathophysiology of FHL, that evaluation of NK-cell degranulation in suspected FHL patients may facilitate diagnosis, and that these new insights may offer novel therapeutic possibilities. C1 Karolinska Univ Hosp Solna, Karolinska Inst, Dept Women & Child Hlth, Childhood Canc Res Ctr, S-17176 Stockholm, Sweden. Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med, Ctr Infect Med, S-14186 Stockholm, Sweden. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Karolinska Univ Hosp Solna, Karolinska Inst, Dept Mol Med & Surg, Clin Genet Unit, S-17176 Stockholm, Sweden. Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. Ullevaal Univ Hosp, Dept Pediat, Oslo, Norway. Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Immunol Hematol & Bone Marrow Transplant BMT, Utrecht, Netherlands. Istanbul Univ, Cerrahpasa Fac Med, Dept Pediat Hematol Oncol, Istanbul, Turkey. Balamand Univ, St Georges Hosp, Dept Pediat, Beirut, Lebanon. Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, S-14186 Stockholm, Sweden. Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Clin Sci Intervent & Technol, Pediat Unit, S-14186 Stockholm, Sweden. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Henter, JI (reprint author), Karolinska Univ Hosp Solna, Karolinska Inst, Dept Women & Child Hlth, Childhood Canc Res Ctr, S-17176 Stockholm, Sweden. EM jan-inge.henter@ki.se; elong@nih.gov; hans-gustaf.ljunggren@ki.se RI Wood, Stephanie/D-3528-2012; Long, Eric/G-5475-2011; OI Wood, Stephanie/0000-0003-4224-759X; Long, Eric/0000-0002-7793-3728; Nordenskjold, Magnus/0000-0002-4974-425X; Bryceson, Yenan/0000-0002-7783-9934; Boelens, Jaap Jan/0000-0003-2232-6952 FU Intramural NIH HHS NR 62 TC 165 Z9 172 U1 0 U2 6 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 SEP 15 PY 2007 VL 110 IS 6 BP 1906 EP 1915 DI 10.1182/blood-2007-02-074468 PG 10 WC Hematology SC Hematology GA 213MM UT WOS:000249671700034 PM 17525286 ER PT J AU Rezvani, K Yong, ASM Savani, BN Mielke, S Keyvanfar, K Gostick, E Price, DA Douek, DC Barrett, AJ AF Rezvani, Katayoun Yong, Agnes S. M. Savani, Bipin N. Mielke, Stephan Keyvanfar, Keyvan Gostick, Emma Price, David A. Douek, Daniel C. Barrett, A. John TI Graft-versus-leukemia effects associated with detectable Wilms tumor-1-specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia SO BLOOD LA English DT Article ID TUMOR GENE WT1; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; MINIMAL RESIDUAL DISEASE; DONOR LEUKOCYTE INFUSIONS; POLYMERASE-CHAIN-REACTION; HOST-DISEASE; IMMUNE RECONSTITUTION; HEALTHY DONORS AB To determine whether the leukemia-associated Wilms tumor antigen (WT') contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL patients during the early phase of immune recovery after SCT (days 30-120). Seven of 10 patients had detectable WT1 expression in their peripheral blood (PB) before SCT by quantitative reverse-transcription polymerase chain reaction. Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining, WT1(+) CD8+ T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 31; P <.05). To monitor the kinetics of WT1(+) CD8+ T-cell responses and disease regression after SCT, absolute WT1(+) CD8+ T-cell numbers and WT1 expression were studied for each time point. The emergence of WT1(+) CD8+ T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect. Loss of WT1+ CD8+ T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P <.001). WT1+ CD8+ T cells had a predominantly effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma. Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL. C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Rezvani, K (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Rm 3-5410,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA. EM rezvanik@nhlbi.nih.gov RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Medical Research Council [G0501963] NR 64 TC 103 Z9 108 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2007 VL 110 IS 6 BP 1924 EP 1932 DI 10.1182/blood-2007-03-076844 PG 9 WC Hematology SC Hematology GA 213MM UT WOS:000249671700036 PM 17505014 ER PT J AU Pine, SR Guo, QX Yin, CH Jayabose, S Druschel, CM Sandoval, C AF Pine, Sharon R. Guo, Qianxu Yin, Changhong Jayabose, Somasundaram Druschel, Charlotte M. Sandoval, Claudio TI Incidence and clinical implications of GATA1mutations in newborns with Down syndrome SO BLOOD LA English DT Article ID ACUTE MEGAKARYOBLASTIC LEUKEMIA; TRANSIENT MYELOPROLIFERATIVE DISORDER; GATA1 MUTATIONS; NATURAL-HISTORY; ONCOLOGY-GROUP; CHILDREN; TRISOMY-21; PATIENT; BIOLOGY AB Somatic mutations in the GATA 1 gene are present in almost all cases of Down syndrome (DS)-associated acute megakaryo-blastic leukemia (AMKL) and transient leukemia (TL). An in utero origin of the GATA1 mutation suggests it is an early leukemogenic event. To determine the detectable incidence and clinical relevance of GATA1 mutations in IDS new-borns, we screened Guthrie cards from 590 DS infants for mutations in the GATA1 gene. Twenty-two (3.8%) of 585 evaluable infants harbored a predicted functional GATA1 mutation; 2 were identified exclusively within intron 1. Hispanic newborns were 2.6 times more likely to have a mutated GATA 1 gene than non-Hispanics (P=.02). Two newborns with a GATA1 mutation subsequently developed AMKL, and none of the infants without a functional GATA1 mutation were reported to have developed leukemia. In addition to screening for TL, a GATA1 mutation at birth might serve as a biomarker for an increased risk of DS-related AMKL. C1 New York Med Coll, Dept Pediat, Div Hematol Oncol, Maria Fareri Childerns Hosp, Valhalla, NY 10595 USA. New York Med Coll, Westchester Cty Med Ctr, Valhalla, NY 10595 USA. Congenital Malformat Registry New York State, Dept Hlth, Troy, NY USA. RP Pine, SR (reprint author), NCI, Human Carcinogenesis Lab, Bldg 37,Room 3060,37 Convent Dr, Bethesda, MD 20892 USA. EM claudio_sandoval@nymc.edu RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 22 TC 62 Z9 65 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2007 VL 110 IS 6 BP 2128 EP 2131 DI 10.1182/blood-2007-01-069542 PG 4 WC Hematology SC Hematology GA 213MM UT WOS:000249671700061 PM 17576817 ER PT J AU Hsieh, MM Linde, NS Wynter, A Metzger, M Wong, C Langsetmo, I Lin, A Smith, R Rodgers, GR Donahue, RE Klaus, SJ Tisdale, JF AF Hsieh, Matthew M. Linde, N. Seth Wynter, Aisha Metzger, Mark Wong, Carol Langsetmo, Ingrid Lin, Al Smith, Reginald Rodgers, Griffin R. Donahue, Robert E. Klaus, Stephen J. Tisdale, John F. TI HIF-prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques SO BLOOD LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR; RECOMBINANT-HUMAN-ERYTHROPOIETIN; ERYTHROID PRECURSOR CELLS; OXYGEN-TRANSPORT; BETA-THALASSEMIA; GENE-THERAPY; HEREDITARY PERSISTENCE; AUTOIMMUNE ANEMIA; NEWBORN-INFANTS; RENAL-FAILURE AB The hypoxia-inducible factor (HIF) pathway is crucial in mitigating the deleterious effects of oxygen deprivation. HIF-alpha is an essential component of the oxygen-sensing mechanisms and under normoxic conditions is targeted for degradation via hydroxylation by HIF-prolyl hydroxylases. Several HIF-prolyl hydroxylase inhibitors (PHIs) induced erythropoietin (epo) expression in vitro and in mice, with peak epo expression ranging from 5.6- to 207-fold above control animals. Furthermore, several PHIs induced fetal hemoglobin (HbF) expression in primary human erythroid cells in vitro, as determined by flow cytometry. One PHI, FG-2216, was further tested in a nonhuman primate model without and with chronic phlebotomy. FG-2216 was orally bioavallable and induced significant and reversible Epo induction in vivo (82- to 309-fold at 60 mg/kg). Chronic oral dosing in male rhesus macaques was well tolerated, significantly increased erythropolesis, and prevented anemia induced by weekly phlebotomy. Furthermore, mod- est increases in HbF-containing red cells and reticulocytes were demonstrated by flow cytometry, though significant increases in HbF were not demonstrated by high-pressure liquid chromatography (HPLC). HIF PHIs represent a novel class of molecules with broad potential clinical application for congenital and acquired anemias. C1 NIDDK, MCHB, NIH, Bethesda, MD 20892 USA. NHLBI, Rockville, MD USA. FibroGen, San Francisco, CA USA. RP Tisdale, JF (reprint author), NIDDK, MCHB, NIH, 9000 Rockville Pike,Bldg 10,9N 116, Bethesda, MD 20892 USA. EM johntis@mail.nih.gov FU Intramural NIH HHS NR 52 TC 117 Z9 124 U1 0 U2 16 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 SEP 15 PY 2007 VL 110 IS 6 BP 2140 EP 2147 DI 10.1182/blood-2007-02-073254 PG 8 WC Hematology SC Hematology GA 213MM UT WOS:000249671700063 PM 17557894 ER PT J AU Villagra, J Shiva, S Hunter, LA Machado, RF Gladwin, MI Kato, GJ AF Villagra, Jose Shiva, Sruti Hunter, Lori A. Machado, Roberto F. Gladwin, Mark I. Kato, Gregory J. TI Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin SO BLOOD LA English DT Article ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; UREMIC SYNDROME; ENDOTHELIAL-CELLS; FLOW-CYTOMETRY; SILDENAFIL; DEATH; DYSFUNCTION; INHIBITION; EXPRESSION; ADHESION AB Increased platelet activation is recognized in patients with sickle cell disease (SCD), but its pathogenesis and clinical relevance remain uncertain. Pulmonary arterial hypertension (PAH), an important complication of SCD, is characterized by a proliferative pulmonary vasculopathy, in situ thrombosis, and vascular dysfunction related to scavenging of nitric oxide (NO) by hemoglobin released into blood plasma during intravascular hemolysis. We investigated links between platelet activation, PAH and NO scavenging in patients with SCD. Platelet activation marked by activated fibrinogen receptor correlated to the severity of PAH (r = 0.58, P <.001) and to laboratory markers of intravascular hemolysis, such as reticulocyte count (r = 0.44, P =.02). In vitro exposure of platelets to pathologically relevant concentrations of cell-free hemoglobin promoted basal- and agonist-stimulated activation and blocked the inhibitory effects on platelet activation by an NO donor. In patients with SCD, administration of sildenafil, a phosphodiesterase-5 inhibitor that potentiates NO-dependent signaling, reduced platelet activation (P =.01). These findings suggest a possible interaction between hemolysis, decreased NO bioavailability, and pathologic platelet activation that might contribute to thrombosis and pulmonary hypertension in SCD, and potentially other disorders of intravascular hemolysis. This supports a role for NO-based therapeutics for SCD vasculopathy. This trial was registered at www.clinicaltrials.gov as no. NCT00352430. C1 NHLBI, Vasc Med Branch, Sickle Cell Vasc Dis Unit, NIH, Bethesda, MD 20892 USA. NHLBI, Dept Crit Care Med, Bethesda, MD 20892 USA. NHLBI, Dept Nursing, Ctr Clin, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Childrens Natl Med Ctr, Childerns Res Inst, Ctr Canc & Immunol Res, Washington, DC 20010 USA. RP Kato, GJ (reprint author), NHLBI, Vasc Med Branch, Sickle Cell Vasc Dis Unit, NIH, Bldg 10-CRC,Rm 5-5140,10 Ctr Dr,MSC 1476, Bethesda, MD 20892 USA. EM gkato@mail.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [Z99 HL999999, ZIA HL006014-02]; NCI NIH HHS [T32 CA060441, T32CA60441]; NICHD NIH HHS [5K12HD001399, K12 HD001399] NR 59 TC 137 Z9 139 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 SEP 15 PY 2007 VL 110 IS 6 BP 2166 EP 2172 DI 10.1182/blood-2006-12-061697 PG 7 WC Hematology SC Hematology GA 213MM UT WOS:000249671700066 PM 17536019 ER PT J AU Kem, R Chu, KC AF Kem, Ravie Chu, Kenneth C. TI Cambodian cancer incidence rates in california and washington, 1998-2002 SO CANCER LA English DT Article DE cambodians; cancer incidence ID AREA THYROID-CANCER; UNITED-STATES; AMERICAN WOMEN; ASIAN MIGRANTS; MORTALITY; VIRUS; RISK; EAST AB BACKGROUND. Among the many diverse Asian ethnic groups living in the US, Cambodian immigrants comprise a small fraction (1.8%) of the total Asian population. Because of their small numbers, Cambodian vital statistics are often combined into Southeast Asian (SA) cancer data consisting of Vietnamese, Thais, Laotians, and Hmong. METHODS. The 2000 Census counts were used for 2 Cambodian populations, Cambodians alone and Cambodians alone and in combination with any other racial/ethnic group for California and for Seattle (Puget Sound area), Washington. Then the cancer incidence rates were calculated using cancer cases from the California and Puget Sound cancer registries between 1998-2002. The 1998-2002 annual age-adjusted incidence rates, upper bound rates (based on the Cambodian alone population), lower bound rates (based on the Cambodians alone or in combination population) are reported and compared with the rates in the non-Hispanic White (NHW) population in these regions. RESULTS. The top 5 cancers in Cambodian males are lung and bronchus, liver, prostate, colorectal, and stomach cancers. The sites where the rates are higher in male Cambodians than NHW males are (in ascending rank) nasopharynx, liver, stomach, myeloma, and lung and bronchus. The top 5 cancers for female Cambodians are breast, lung, colon and rectum, cervix, and thyroid. The sites where female rates are greater than N1-fW female rates are (in ascending rank) nasopharynx, liver, stomach, cervix uteri, oral cavity, and thyroid. CONCLUSIONS. The challenges to address the health issues of Cambodians are complicated by historical events that caused their emigration to the US. Many of the immigrants are survivors of the holocaust in Cambodia. Health programs for Cambodians must deal with the consequences of these issues as well as cultural issues of language and religion in helping Cambodians to reduce their cancer disparities. C1 NCI, Ctr Reduce Canc Hlth Disparities, Disparities Res Branch, Bethesda, MD 20892 USA. Natl Canc Inst, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Pharmaceut Management Branch, Bethesda, MD USA. RP Chu, KC (reprint author), NCI, Ctr Reduce Canc Hlth Disparities, Disparities Res Branch, 6116 Execut Blvd,Room 602, Bethesda, MD 20892 USA. EM kc10d@nih.gov NR 22 TC 17 Z9 17 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 2007 VL 110 IS 6 BP 1370 EP 1375 DI 10.1002/cncr.22914 PG 6 WC Oncology SC Oncology GA 208FA UT WOS:000249304000027 PM 17654663 ER PT J AU Tang, B Yoo, N Vu, M Mamura, M Nam, JS Ooshima, A Du, Z Desprez, PY Anver, MR Michalowska, AM Shih, J Parks, WT Wakefield, LM AF Tang, Binwu Yoo, Naomi Vu, Mary Mamura, Mizuko Nam, Jeong-Seok Ooshima, Akira Du, Zhijun Desprez, Pierre-Yves Anver, Miriam R. Michalowska, Aleksandra M. Shih, Joanna Parks, W. Tony Wakefield, Lalage M. TI Transforming growth factor-beta can suppress tumorigenesis through effects on the putative cancer stem or early progenitor cell and committed progeny in a breast cancer xenograft model SO CANCER RESEARCH LA English DT Article ID IN-VITRO PROPAGATION; LOOP-HELIX PROTEINS; GENE-EXPRESSION; SIDE-POPULATION; MAMMARY-GLAND; TUMOR SUPPRESSION; EPITHELIAL-CELLS; SELF-RENEWAL; DIFFERENTIATION; PROGRESSION AB The transforming growth factor-beta (TGF-beta) pathway has tumor-suppressor activity in many epithelial tissues. Because TGF-beta is a potent inhibitor of epithelial cell proliferation, it has been widely assumed that this property underlies the tumor-suppressor effect. Here, we have used a xenograft model of breast cancer to show that endogenous TGF-beta has the potential to suppress tumorigenesis through a novel mechanism, involving effects at two distinct levels in the hierarchy of cellular progeny that make up the epithelial component of the tumor. First, TGF-beta reduces the size of the putative cancer stem or early progenitor cell population, and second it promotes differentiation of a more committed, but highly proliferative, progenitor cell population to an intrinsically less proliferative state. We further show that reduced expression of the type II TGF-beta receptor correlates with loss of luminal differentiation in a clinical breast cancer cohort, suggesting that this mechanism may be clinically relevant. At a molecular level, the induction of differentiation by TGF-beta involves down-regulation of Id1, and forced overexpression of Id1 can promote tumorigenesis despite persistence of the antiproliferative effect of TGF-beta. These data suggest new roles for the TGF-beta pathway in regulating tumor cell dynamics that are independent of direct effects on proliferation. C1 NCI, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. Calif Pacific Med Ctr, Geraldine Brush Canc Res Inst, San Francisco, CA 94115 USA. NCI, Pathol Histotechnol Lab, Frederick, MD 21701 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Wakefield, LM (reprint author), Gachon Univ Med Sci, Canc & Diabet Inst, Inchon 406840, South Korea. EM lw34g@nih.gov OI Mamura, Mizuko/0000-0003-4531-0144 FU Intramural NIH HHS [Z01 BC005785-12]; NCI NIH HHS [N01-CO-12400] NR 50 TC 63 Z9 67 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 SEP 15 PY 2007 VL 67 IS 18 BP 8643 EP 8652 DI 10.1158/0008-5472.CAN-07-0982 PG 10 WC Oncology SC Oncology GA 213PL UT WOS:000249679500029 PM 17875704 ER PT J AU Miao, ZH Player, A Shankavaram, U Wang, YH Zimonjic, DB Liao, ZY Liu, H Shimura, T Zhang, HL Meng, LH Zhang, YW Kawasaki, ES Popescu, NC Aladjem, MI Goldstein, DJ Weinstein, JN Pommier, Y AF Miao, Ze-Hong Player, Audrey Shankavaram, Urna Wang, Yong-Hong Zimonjic, Drazen B. Liao, Zhi-Yong Liu, Hong Shimura, Tsutornu Zhang, Hong-Liang Meng, Ling-Hua Zhang, Yong-Wei Kawasaki, Ernest S. Popescu, Nicholas C. Aladjem, Mirit I. Goldstein, David J. Weinstein, John N. Pommier, Yves TI Nonclassic functions of human topoisomerase I: Genome-wide and pharmacologic analyses SO CANCER RESEARCH LA English DT Article ID RNA-POLYMERASE-II; DNA TOPOISOMERASES; ANTIPROLIFERATIVE ACTIVITY; SACCHAROMYCES-CEREVISIAE; CLEAVAGE COMPLEXES; GENE-EXPRESSION; OXYGEN RADICALS; CAMPTOTHECIN; TRANSCRIPTION; ACTIVATION AB The biological functions of nuclear topoisomerase I (Top1) have been difficult to study because knocking out TOP1 is lethal in metazoans. To reveal the functions of human Top1, we have generated stable Top1 small interfering RNA (siRNA) cell lines from colon and breast carcinomas (HCT116-siTop1 and MCF-7-siTop1, respectively). in those clones, Top1 is reduced similar to 5-fold and Top2 alpha compensates for Top1 deficiency. A prominent feature of the siTop1 cells is genomic instability, with chromosomal aberrations and histone gamma-H2AX foci associated with replication defects. siTop1 cells also show rDNA and nucleolar alterations and increased nuclear volume. Genome-Mde transcription profiling revealed 55 genes with consistent changes in siTop1 cells. Among them, asparagine synthetase (ASNS) expression was reduced in siTop1 cells and in cells with transient Top1 down-regulation. Conversely, Top1. complementation increased ASNS, indicating a causal link between Top1 and ASNS expression. Correspondingly, pharmacologic profiling showed L-asparaginase hypersensitivity in the siTop1 cells. Resistance to camptothecin, indenoisoquinoline, aphidicolin, hydroxyurea, and staurosporine and hypersensitivity to etoposide and actinomycin D show that Top1, in addition to being the target of camptothecins, also regulates DNA replication, rDNA stability, and apoptosis. Overall, our studies show the pleiotropic nature of human Top1 activities. In addition to its classic DNA nicking-closing functions, Top1 plays critical nonclassic roles in genomic stability, gene-specific transcription, and response to various anticancer agents. The reported cell lines and approaches described in this article provide new tools to perform detailed functional analyses related to Top1 function. C1 NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Off Sci & Technol Partnerships, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Bethesda, MD 20892 USA. NIH, NIDDKD, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NIH, Mol Pharmacol Lab, Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI ZHANG, YONGWEI/E-6252-2012; Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 NR 49 TC 60 Z9 60 U1 0 U2 4 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 SEP 15 PY 2007 VL 67 IS 18 BP 8752 EP 8761 DI 10.1158/0008-5472.CAN-06-4554 PG 10 WC Oncology SC Oncology GA 213PL UT WOS:000249679500041 PM 17875716 ER PT J AU Sokolov, MV Dickey, JS Bonner, WM Sedelnikova, OA AF Sokolov, Mykyta V. Dickey, Jennifer S. Bonner, William M. Sedelnikova, Olga A. TI gamma-H2AX in bystander cells - Not just a radiation-triggered event, a cellular response to stress mediated by intercellular communication SO CELL CYCLE LA English DT Article DE bystander effect; ionizing radiation,gamma-H2AX; DNA damage; stress ID DOUBLE-STRAND BREAKS; TARGETED CYTOPLASMIC IRRADIATION; PRIMARY HUMAN FIBROBLASTS; DNA-DAMAGE; MAMMALIAN-CELLS; ALPHA-PARTICLES; CHROMOSOMAL-ABERRATIONS; MICROBEAM IRRADIATION; IONIZING-RADIATION; SIGNALING MOLECULE AB The recent years have witnessed a rapid accumulation of experimental data showing that ionizing radiation elicits a plethora of biological effects in unirradiated cells receiving bystander signals from hit cells. This so-called radiation-induced bystander effect (RIBE) manifests in various ways including changes in gene expression, genetic and epigenetic alterations, as well as increases in cell transformation and cell death. Our group and others found that DNA double-stranded breaks (DSBs), directly measured by gamma-H2AX focus formation assay, accumulate in bystander cells in a number of experimental systems such as human cultured cells, human three-dimensional tissue models and in mice. In addition, we recently found that various other sources of cell stress, including media from cancerous cells resulted in a DNA damage response (DDR) in normal human cells that is reminiscent of RIBE. These results suggest that the RIBE may be part of a more general stress response, however, the molecular mechanism underpinning the formation of DNA DSBs in bystander cells is still unclear. This extra view points to some possibilities that might explain why DDR in human cells can be observed under bystander conditions. C1 Ctr Canc Res, NCI, Mol Pharmacol Lab, Bethesda, MD 20895 USA. RP Sedelnikova, OA (reprint author), Ctr Canc Res, NCI, Natl Inst Hlth, Mol Pharmacol Lab, 900 Rockville Pike,Room 5050,Bldg 37, Bethesda, MD 20895 USA. EM sedelnio@mail.nih.gov FU Intramural NIH HHS NR 40 TC 70 Z9 70 U1 0 U2 5 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP 15 PY 2007 VL 6 IS 18 BP 2210 EP 2212 PG 3 WC Cell Biology SC Cell Biology GA 233IW UT WOS:000251085600003 PM 17881892 ER EF