FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rosu-Myles, M Taylor, BJ Wolff, L AF Rosu-Myles, Michael Taylor, Barbara J. Wolff, Linda TI Loss of the tumor suppressor p15Ink4b enhances myeloid progenitor formation from common myeloid progenitors SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MOUSE BONE-MARROW; MYELODYSPLASTIC SYNDROMES; P15(INK4B) GENE; POOR-PROGNOSIS; C-KIT; EXPRESSION; HYPERMETHYLATION; DIFFERENTIATION; PROLIFERATION AB Objective. The tumor suppressor p15Ink4b (Ink4b) is a cell-cycle inhibitor that is inactivated in a high percentage of acute myeloid leukemia and myeloid dysplasia syndrome cases. Despite this, the role of Ink4b in hematopoiesis remains unclear. Here we examined the role of Ink4b in blood cell formation using Ink4b-deficient (Ink4b(-/-)) mice. Methods. We compared the bone marrow (BM) of Ink4b(-/-) and wild-type mice using flow cytometric, colony-forming unit and competitive repopulating assays (CRA). The proliferation, differentiation, self-renewal, and apoptosis of progenitor cells were further compared by in vitro and in vivo methods. Results. BM from Ink4b(-/-) mice contained increased numbers of granulocyte-monocyte progenitors and Gr-1(+) cells and showed a competitive advantage over wild-type cells in myeloid cell formation by CRA. Ink4b(-/-) progenitors did not demonstrate increased proliferation, self-renewing potential, or reduced apoptosis. Instead, Ink4b(-/-) common myeloid progenitors (CMPs) showed increased myeloid progenitor formation concomitant with reduced erythroid potential. Conclusions. This work establishes a role for Ink4b in regulating the differentiation of CMPs and indicates that loss of Ink4b enhances the formation of myeloid progenitors. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Wolff, L (reprint author), NCI, Canc Res Ctr, NIH, Bldg 37,Room 4124A,37 Convent Dr MSC 4263, Bethesda, MD 20892 USA. EM lwolff@helix.nih.gov FU Intramural NIH HHS NR 45 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 2007 VL 35 IS 3 BP 394 EP 406 DI 10.1016/j.exphem.2006.11.005 PG 13 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 141UV UT WOS:000244605200007 PM 17309820 ER PT J AU Packer, AN Muraro, PA AF Packer, Amy N. Muraro, Paolo A. TI Optimized clonotypic analysis of T-cell receptor repertoire in immune reconstitution SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; CEREBROSPINAL-FLUID; THYMIC OUTPUT; TRANSPLANTATION; DISEASE; EXPANSION; RESPONSES AB Objective. In recent years, T-cell receptor (TCR) sequencing analysis has proven an effective technique for the identification of T-cell populations of interest in cancer and autoimmunity, as well as for the characterization of peripheral immune repertoire reconstitution after hematopoietic stem cell transplantation (HSCT). However, despite its increased utilization, to our knowledge no group has investigated the minimum number of sequences necessary to accurately and efficiently describe the composition of TCR repertoire. The primary aim of this study was to optimize a procedure for clonotypic analysis of the TCR repertoire in patients undergoing autologous HSCT. Materials and Methods. TCR P-chain diversity was analyzed by DNA sequencing and CDR3 spectratyping CD8(+) T cells isolated from three patients with multiple sclerosis undergoing autologous HSCT. Samples were collected at baseline and 1 or 2 years post-HSCT. Results. Using DNA cloning and high throughput sequencing, we analyzed over 1500 in-frame TCR sequences, allowing us to evaluate how our measures of TCR repertoire diversity change with increasing numbers of sequences included in the analysis. Our findings show that by analyzing 75 to 100 in-frame sequences, we are able to estimate TCR diversity within 5.0% to 7.4% of the values obtained at endpoint analysis (213-312 sequences per sample). Conclusions. This study confirms the use of TCR sequencing as an effective technique for the characterization of immune renewal after autologous HSCT. In addition, we demonstrate for the first time convincing evidence to support the use of moderate sample sizes to accurately and efficiently evaluate TCR repertoire diversity. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Muraro, PA (reprint author), Imperial Coll Sch Med, Dept Cellular & Mol Neurosci, Div Neurosci & Mental Hlth, Fac Med, Room 8L 03,Lab Block,Charing Cross Campus,St Duns, London W6 8RP, England. EM p.muraro@imperial.ac.uk OI Muraro, Paolo/0000-0002-3822-1218 FU Intramural NIH HHS NR 17 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 2007 VL 35 IS 3 BP 516 EP 521 DI 10.1016/j.exphem.2006.11.007 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 141UV UT WOS:000244605200019 PM 17309832 ER PT J AU Carson, WE Allen, A Weiner, LM Cheever, MA Fox, BA Keilholz, U Wigginton, JM Sondel, PM Atkins, MB Hwu, P AF Carson, William E., III Allen, Andrew Weiner, Louis M. Cheever, Martin A. Fox, Bernard A. Keilholz, Ulrich Wigginton, Jon M. Sondel, Paul M. Atkins, Michael B. Hwu, Patrick TI Immunotherapy comes of age: overview of the 21(st) Annual Meeting and associated programs of the International Society for Biological Therapy of Cancer - Los Angeles, CA, USA, 27-29 October 2006 SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Editorial Material DE immunotherapy; International Society for Biological Therapy of Cancer; tumor AB This paper covers highlights from the International Society for Biological Therapy of Cancer (iSBTc) 21st Annual Meeting, including the associated iSBTc Primer on Tumor Immunology and Biological Therapy, and the iSBTc Mini-Symposium on the Biologic Effects of Targeted Therapies. The programs ran from 26 - 29 October 2006 and were held at the Hyatt Regency Century Plaza in Los Angeles, CA, USA. Focussed on the varying aspects of biological cancer therapies and tumor immunology, the iSBTc 21st Annual Meeting featured 131 scientific posters, 29 oral abstract presentations, 20 invited speaker lectures and 2 keynote addresses. The 21st Annual Meeting, Primer and Mini-Symposium were attended by > 400 clinicians and basic scientists from academia, industry and government. The iSBTc was founded in 1984 as the Society for Biological Therapy with 40 charter members. At present, the Society has > 500 members consisting primarily of MDs, PhDs, RNs and corporate representatives. Scientific and business meetings have been held annually since the Society's first Annual Meeting in 1986. C1 Ohio State Univ, Ctr Comprehens Canc, Dept Surg, Columbus, OH 43210 USA. Pharm Corp, San Francisco, CA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Earle A Chiles Res Inst, Portland, OR USA. Hosp Charite CBF, Berlin, Germany. Natl Canc Inst, Frederick, MD USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Carson, WE (reprint author), Ohio State Univ, Ctr Comprehens Canc, Dept Surg, N924 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. RI Carson, William/E-2846-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD MAR PY 2007 VL 7 IS 3 BP 419 EP 422 DI 10.1517/14712598.7.3.419 PG 4 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 142LU UT WOS:000244652200014 ER PT J AU Buxton, DB AF Buxton, Denis B. TI Nanotechnology in the diagnosis and management of heart, lung and blood diseases SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE cardiovascular; diagnostics; hematopoietic; imaging; pulmonary; therapy; tissue engineering ID ASSEMBLING PEPTIDE NANOFIBERS; COMPACTED DNA NANOPARTICLES; MRI CONTRAST AGENT; QUANTUM DOTS; CHITOSAN NANOPARTICLES; MAGNETIC NANOPARTICLES; TISSUE CONSTRUCTS; ENDOTHELIAL-CELLS; DELIVERY-SYSTEM; DENDRITIC CELLS AB Heart, lung and blood diseases exert an enormous toll, accounting for almost half of the deaths in the USA each year. In addition to the morbidity and mortality resulting from these diseases, there is also a high economic burden, estimated at US$560 billion for 2006. Nanotechnology offers a broad range of opportunities to improve diagnosis and therapy for cardiovascular, pulmonary and hematopoietic diseases, thereby decreasing these burdens. This review will focus on four areas of particular promise for the application of nanotechnology: imaging, diagnostics and biosensors, drug delivery and therapy, and tissue engineering and repair. The goal is to summarize the current state of science and technology in these areas and to look at future directions that the field is likely to move in to enhance the diagnosis and treatment of heart, lung and blood diseases. C1 NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Dis, Bethesda, MD 20892 USA. RP Buxton, DB (reprint author), NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Dis, 6701 Rockledge Dr,Bldg 10, Bethesda, MD 20892 USA. EM db225a@nih.gov OI Buxton, Denis/0000-0003-3077-6435 NR 72 TC 8 Z9 8 U1 0 U2 3 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAR PY 2007 VL 7 IS 2 BP 149 EP 160 DI 10.1586/14737159.7.2.149 PG 12 WC Pathology SC Pathology GA 150GK UT WOS:000245203500005 PM 17331063 ER PT J AU Ramprasad, S Radha, V Mathias, RA Majumder, PP Rao, MRS Rema, M AF Ramprasad, S. Radha, V. Mathias, R. A. Majumder, P. P. Rao, M. R. S. Rema, M. TI Rage gene promoter polymorphisms and diabetic retinopathy in a clinic-based population from South India SO EYE LA English DT Article DE diabetic retinopathy; RAGE polymorphism; -374 TA; -429 TC; 63 bp deletion ID CULTURED ENDOTHELIAL-CELLS; END-PRODUCTS GENE; ASSOCIATION; NEPHROPATHY; RECEPTOR; PREVALENCE; MICROALBUMINURIA; COMPLICATIONS; PROJECTIONS; REDUCTASE AB Purpose The main objective of this study was to evaluate if the -429T/C, -374T/A and 63 bp deletion polymorphisms in the RAGE gene are associated with diabetic retinopathy (DR) among Type 2 diabetic subjects in a clinic-based population from South India. Methods We screened 149 normal glucose tolerant subjects (NGT), 189 Type 2 diabetes subjects without retinopathy (DM) and 190 subjects with DR for these polymorphisms using the PCR-RFLP method. DR was diagnosed by grading color fundus photography. Logistic regression models were used to evaluate the association of individual polymorphisms with DR. Expectation maximization algorithms were implemented in haplotype tests of association to examine the combined effects of -429T/C and -374T/A polymorphisms on DR. Results The allelic frequencies of -429T are 0.83 in NGT, 0.84 in DM and 0.85 in DR subjects, and that of -374T are 0.93 in NGT, 0.92 in DM and 0.88 in DR subjects. The -374 polymorphism was found to be associated with non-proliferative retinopathy when this subgroup was compared to the DM group (OR 1.814, 95% CI = 1.005-3.273). However, this association was not obvious when both the subphenotypes of DR (the nonproliferative and proliferative DR groups) were studied jointly. We found no evidence for associations between the -429T/C polymorphism and the DR phenotype. Finally, extension to a 2-SNP haplotype did not reveal any significant statistical difference between the groups (P = 0.668). Conclusion In this study, we found a modest association with the -374T/A polymorphism in the nonproliferative DR subgroup. C1 Madras Diabet Res Fdn, Madras 600086, Tamil Nadu, India. Dr Diabet Specialities Ctr Gopalapuram, Madras, Tamil Nadu, India. NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Indian Stat Inst, Kolkata, India. Indian Inst Sci, Dept Biochem, Bangalore 560012, Karnataka, India. RP Rema, M (reprint author), Madras Diabet Res Fdn, 4 Conran Smith Rd, Madras 600086, Tamil Nadu, India. EM drrema@vsnl.com FU Intramural NIH HHS NR 37 TC 28 Z9 29 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X EI 1476-5454 J9 EYE JI Eye PD MAR PY 2007 VL 21 IS 3 BP 395 EP 401 DI 10.1038/sj.eye.6702239 PG 7 WC Ophthalmology SC Ophthalmology GA 141US UT WOS:000244604900016 PM 16440015 ER PT J AU Ptasinska, A Wang, SB Zhang, JH Wesley, RA Danner, RL AF Ptasinska, Anetta Wang, Shuibang Zhang, Jianhua Wesley, Robert A. Danner, Robert L. TI Nitric oxide activation of peroxisome proliferator-activated receptor gamma through a p38 MAPK signaling pathway SO FASEB JOURNAL LA English DT Article DE endothelial cells; gene expression; inflammation; peroxisome proliferator response element; vascular homeostasis ID VASCULAR ENDOTHELIAL-CELLS; PPAR-GAMMA; HUMAN NEUTROPHILS; EXPRESSION; INHIBITION; KINASE; TRANSDUCTION; SUPEROXIDE; MECHANISMS; SYNTHASE AB Both nitric oxide (NO center dot) and peroxisome proliferator-activated receptors (PPARs) protect the endothelium and regulate its function. Here, we tested for crosstalk between these signaling pathways. Human umbilical vein and hybrid EA.hy926 endothelial cells were exposed to S-nitrosoglutathione (GSNO) or diethylenetriamine NONOate (DETA NONOate). Electrophoretic mobility shift assays using PPAR-response element (PPRE) probe showed that NO center dot caused a rapid dose-dependent increase in PPAR gamma binding, an effect that was confirmed in vivo by chromatin inummoprecipitation. Conversely, N-G-monomethyl-L-arginine, a NOS inhibitor, decreased PPAR gamma binding. NO center dot-mediated PPAR gamma binding and NO center dot induction of cyclooxygenase-2 (COX-2), diacylglycerol (DAG) kinase alpha (DGK alpha), and heme oxygenase-1 (HO-1), genes with well-characterized PPRE motifs, were cGMP independent. NO center dot dose dependently activated p38 MAPK, and p38 MAPK inhibition with SB202190 or knockdown with siRNA was shown to block NO center dot activation of PPAR gamma. Likewise, p38 MAPK and PPAR gamma inhibitors or knockdown of either transcript all significantly blocked NO center dot induction of PPRE-regulated genes. PPAR gamma activation by p38 MAPK may contribute to the anti-inflammatory and cytoprotective effects of NO center dot in the vasculature. This crosstalk mechanism suggests new strategies for preventing and treating vascular dysfunction. C1 Ctr Clin, Crit Care Med Dept, NIH, Bethesda, MD 20892 USA. RP Danner, RL (reprint author), Ctr Clin, Crit Care Med Dept, NIH, Bethesda, MD 20892 USA. EM rdanner@cc.nih.gov FU Intramural NIH HHS NR 48 TC 48 Z9 48 U1 0 U2 7 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 MAR PY 2007 VL 21 IS 3 BP 950 EP 961 DI 10.1096/fj.06-6822com PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 142YE UT WOS:000244686400031 PM 17197391 ER PT J AU Okoli, I Oyeka, CA Kwon-Chung, KJ Theelen, B Robert, V Groenewald, JZ McFadden, DC Casadevall, A Boekhout, T AF Okoli, Ikechukwu Oyeka, Christie A. Kwon-Chung, Kyung J. Theelen, Bart Robert, Vincent Groenewald, Johannes Z. McFadden, Diane C. Casadevall, Arturo Boekhout, Teun TI Cryptotrichosporon anacardii gen. nov., sp nov., a new trichosporonoid capsulate basidiomycetous yeast from Nigeria that is able to form melanin on niger seed agar SO FEMS YEAST RESEARCH LA English DT Article DE Cryptotrichosporon anacardii; Cryptococcus neoformans; Trichosporonales; basidiomycetous yeast; taxonomic conflict; monophyly ID NEOFORMANS VAR. GATTII; CRYPTOCOCCUS-NEOFORMANS; NATURAL HABITAT; SEQUENCE-ANALYSIS; GENOME EVOLUTION; DECAYING WOOD; LIVING TREES; VIRULENCE; POLYSACCHARIDE; SYSTEMATICS AB Five yeast isolates obtained from cashew tree flowers in Nigeria resembled Cryptococcus neoformans phenotypically by producing brown pigmented colonies on niger seed agar, expressing a capsule, and being able to grow at 37 degrees C. However, rRNA gene sequences, including the 18S rRNA gene, the D1/D2 domains of the 26S rRNA gene and the ITS1+2 regions, suggested that these yeasts form a basal lineage within the Trichosporonales (Tremellomycetidae, Hymenomycetes, Basidiomycota, Fungi). Since the isolates could not be identified with any known genus and species within the Trichosporonales, we describe them as Cryptotrichosporon anacardii gen. et sp. nov. with CBS 9551(T) (=NRRL Y-27671) as the type strain. The taxonomic conflict between phenetic and molecular classification schemes within this group of fungi is discussed, and is resolved in favor of the latter. C1 Cent Bur Schimmelcultures, NL-3584 CT Utrecht, Netherlands. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Boekhout, T (reprint author), Cent Bur Schimmelcultures, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands. EM boekhout@cbs.knaw.nl RI Boekhout, Teun/F-1552-2010; Groenewald, Johannes/F-4667-2011 OI Boekhout, Teun/0000-0002-0476-3609; NR 42 TC 32 Z9 32 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1567-1356 J9 FEMS YEAST RES JI FEMS Yeast Res. PD MAR PY 2007 VL 7 IS 2 BP 339 EP 350 DI 10.1111/j.1567-1364.2006.00164.x PG 12 WC Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biotechnology & Applied Microbiology; Microbiology; Mycology GA 136MR UT WOS:000244228500017 PM 17002780 ER PT J AU Wittenberger, MD Hagerman, RJ Sherman, SL McConkie-Rosell, A Welt, CK Rebar, RW Corrigan, EC Simpson, JL Nelson, LM AF Wittenberger, Michael D. Hagerman, Randi J. Sherman, Stephanie L. McConkie-Rosell, Allyn Welt, Corrine K. Rebar, Robert W. Corrigan, Emily C. Simpson, Joe Leigh Nelson, Lawrence M. TI The FMR1 premutation and reproduction SO FERTILITY AND STERILITY LA English DT Review DE fragile X syndrome; FMR1; premutation; spontaneous premature ovarian failure; hypergonadotropic hypogonadism; primary hypogonadism; primary ovarian insufficiency; premature menopause; hypergonadotropic amenorrhea; low response to gonadotropin stimulation; diminished ovarian reserve; fragile X-associated tremor/ataxia syndrome; FXTAS; genetic counseling ID FRAGILE-X-SYNDROME; PREMATURE OVARIAN FAILURE; TREMOR/ATAXIA SYNDROME FXTAS; MENTAL-RETARDATION PROTEIN; PREIMPLANTATION GENETIC DIAGNOSIS; CGG REPEAT; FULL-MUTATION; INTENTION TREMOR; CYSTIC-FIBROSIS; GRAY ZONE AB Objective: To update clinicians on the reproductive implications of premutations in FMR1 (fragile X mental retardation 1). Fragile X syndrome, a cause of mental retardation and autism, is due to a full mutation (> 200 CGG repeats). Initially, individuals who carried the premutation (defined as more than 55 but less than 200 CGG repeats) were not considered at risk for any clinical disorders. It is now recognized that this was incorrect, specifically with respect to female reproduction. Design and Setting: Literature review and consensus building at two multidisciplinary scientific workshops. Conclusion(s): Convincing evidence now relates the FMR1 premutation to altered ovarian function and loss of fertility. An FMR1 mRNA gain-of-function toxicity may underlie this altered ovarian function. There are major gaps in knowledge regarding the natural history of the altered ovarian function in women who carry the FMR1 premutation, making counseling about reproductive plans a challenge. Women with premature ovarian failure are at increased risk of having an FMR1 premutation and should be informed of the availability of fragile X testing. Specialists in reproductive medicine can provide a supportive environment in which to explain the implications of FMR1 premutation testing, facilitate access to testing, and make appropriate referral to genetic counselors. C1 NICHHD, NIH, CRC, Intramural Res Program,Sect Womens Hlth Res,Dev E, Bethesda, MD 20892 USA. Univ Calif Davis, Med Ctr, Dept Pediat, MIND Inst, Sacramento, CA 95817 USA. Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Amer Soc Reprod Med, Birmingham, AL USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Nelson, LM (reprint author), NICHHD, NIH, CRC, Intramural Res Program,Sect Womens Hlth Res,Dev E, Room 1-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM Lawrence_Nelson@nih.gov OI Welt, Corrine/0000-0002-8219-5504 FU Intramural NIH HHS; PHS HHS [U10/CCU 92513] NR 101 TC 200 Z9 211 U1 6 U2 18 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 MAR PY 2007 VL 87 IS 3 BP 456 EP 465 DI 10.1016/j.fertnstert.2006.09.004 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 148OU UT WOS:000245085300002 PM 17074338 ER PT J AU Ventura, JL Fitzgerald, OR Koziol, DE Covington, SN Vanderhoof, VH Calis, KA Nelson, LM AF Ventura, June L. Fitzgerald, O. Ray Koziol, Deloris E. Covington, Sharon N. Vanderhoof, Vien H. Calis, Karim A. Nelson, Lawrence M. TI Functional well-being is positively correlated with spiritual well-being in women who have spontaneous premature ovarian failure SO FERTILITY AND STERILITY LA English DT Article DE premature ovarian failure; ovarian insufficiency; infertility; coping; depression; anxiety; spirituality; religion; functional well-being ID QUALITY-OF-LIFE; ILL ELDERLY-PATIENTS; CHRONIC ILLNESS; RELIGIOUS INVOLVEMENT; MEDICAL-STUDENTS; EMOTIONAL NEEDS; MORTALITY; ATTENDANCE; MENOPAUSE; HEALTH AB Objective: To examine the relationship between spiritual well-being and functional well-being in women who have spontaneous premature ovarian failure. Design: Cross-sectional. Setting: The Mark O. Hatfield Clinical Research Center at the US National Institutes of Health. Patient(s): Women diagnosed with spontaneous premature ovarian failure (N = 138) at a median age of 28 years. Intervention(s): Administration of validated self-reporting instruments. Main Outcome Measure(s): Functional Well-Being, Spiritual Well-Being, Meaning/Peace, and Faith scores. Result(s): We found a significant positive correlation between overall spiritual well-being and functional well-being scores. The Meaning/Peace subscale strongly correlated with functional well-being, explaining approximately 62% of the variance. In contrast, the Faith subscale was less strongly correlated with functional well-being, explaining only 7% of the variance. In multiple regression analysis evaluating the relative subscale contributions to functional well-being, only Meaning/Peace remained statistically significant. We found no significant associations between either spiritual well-being or functional well-being and age; age at diagnosis; time since diagnosis; or partner, children, or racial status. Conclusion(S): This study provides cross-sectional data supporting the need for prospective controlled studies. Strategies to improve spiritual well-being in the domains of meaning, purpose, and inner peace may provide a therapeutic approach to reduce the emotional suffering that accompanies the life-altering diagnosis of premature ovarian failure. (Fertil Steril (R) 2007;87:584-90. (c) 2007 by American Society for Reproductive Medicine.) C1 NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, NIH,CRC, Bethesda, MD 20892 USA. NIH, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. RP Nelson, LM (reprint author), NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, NIH,CRC, 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM lawrence_nelson@nih.gov FU Intramural NIH HHS NR 40 TC 6 Z9 6 U1 0 U2 4 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 MAR PY 2007 VL 87 IS 3 BP 584 EP 590 DI 10.1016/j.fertnstert.2006.07.1523 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 148OU UT WOS:000245085300021 PM 17258712 ER PT J AU Sheehan, FT Seisler, AR Siegel, KL AF Sheehan, Frances T. Seisler, Andrea R. Siegel, Karen Lohmann TI In vivo talocrural and subtalar kinematics: A non-invasive 3D dynamic MRI study SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE ankle; fast-PC; foot; Stieda process ID STANCE PHASE; ANKLE-JOINT; WALKING; MOTION; COMPLEX AB Background: To improve diagnostic accuracy, prevent injury, and reduce the effect of impairments on hindfoot function, an understanding of the combined in vivo kinematics of the talocrural and subtalar joints is critical. Therefore, the purpose of this study was to test the feasibility of quantifying talocrural and subtalar joint kinematics using fast-phase contrast (fast-PC) MRI, a noninvasive, in-vivo technique for the study of three-dimensional joint motion. Methods: Nine normal ankles and two ankles with a Stieda process were studied. Subjects were each placed supine in a 1.5 T MRI and asked to maintain a repeated dorsiflexion-plantarflexion movement while a full sagittal-oblique fast-PC dataset was acquired. The orientation and position of the calcaneus, talus, and tibia were individually quantified from these data. Results: The precision and accuracy of tracking calcaneal, talar, and tibial movement was excellent. The three-dimensional subtalar kinematics demonstrated that the talus and calcaneus do not move as a single unit. Most calcaneal-tibial supination occurred at the talocrural joint. The ankles with a Stieda process had markedly different kinematics from each other as well as from the normal group. Conclusions: This study demonstrated that fast-PC MRI is a viable, precise, and accurate technique for studying hindfoot kinematics and is potentially a useful clinical diagnostic tool. The findings call into question the earlier anatomical studies on which much of clinical practice on the foot and ankle is based. Since a clear link was found between anatomical variation and altered rearfoot kinematics, future study is warranted. C1 NIH, Bethesda, MD 20892 USA. RP Sheehan, FT (reprint author), NIH, Bldg 10,CRC 1-1469 10 Ctr Dr, Bethesda, MD 20892 USA. EM fsheehan@cc.nih.gov RI Siegel, Karen Lohmann/B-5898-2008; sheehan, frances/B-6962-2009; OI Siegel, Karen Lohmann/0000-0002-0788-6612 NR 27 TC 21 Z9 22 U1 1 U2 9 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD MAR PY 2007 VL 28 IS 3 BP 323 EP 335 DI 10.3113/FAI.2007.0323 PG 13 WC Orthopedics SC Orthopedics GA 140WF UT WOS:000244536700009 PM 17371656 ER PT J AU Johnson, JB Summer, W Cutler, RG Martin, B Hyun, DH Dixit, VD Pearson, M Nassar, M Tellejohan, R Maudsley, S Carlson, O John, S Laub, DR Mattson, MP AF Johnson, James B. Summer, Warren Cutler, Roy G. Martin, Bronwen Hyun, Dong-Hoon Dixit, Vishwa D. Pearson, Michelle Nassar, Matthew Tellejohan, Richard Maudsley, Stuart Carlson, Olga John, Sujit Laub, Donald R. Mattson, Mark P. TI Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE AQLQ; isoprostanes; peak expiratory flow; protein carbonyls; nitrotyrosine; BDNF; spirometry; tumor necrosis factor; oxidative stress ID CARDIOVASCULAR-DISEASE; AIRWAY INFLAMMATION; DIETARY RESTRICTION; NEUROTROPHIC FACTOR; LIPID-PEROXIDATION; WEIGHT-REDUCTION; SKELETAL-MUSCLE; RHESUS-MONKEYS; MEAL FREQUENCY; NITRIC-OXIDE AB Asthma is an increasingly common disorder responsible for considerable morbidity and mortality. Although obesity is a risk factor for asthma and weight loss can improve symptoms, many patients do not adhere to low calorie diets and the impact of dietary restriction on the disease process is unknown. A study was designed to determine if overweight asthma patients would adhere to an alternate day calorie restriction (ADCR) dietary regimen, and to establish the effects of the diet on their symptoms, pulmonary function and markers of oxidative stress, and inflammation. Ten subjects with BMI > 30 were maintained for 8 weeks on a dietary regimen in which they ate ad libitum every other day, while consuming less than 20% of their normal calorie intake on the intervening days. At baseline, and at designated time points during the 8-week study, asthma control, symptoms, and Quality of Life questionnaires (ACQ, ASUI, mini-AQLQ) were assessed and blood was collected for analyses of markers of general health, oxidative stress, and inflammation. Peak expiratory flow (PEF) was measured daily on awakening. Pre-and postbronchodilator spirometry was obtained at baseline and 8 weeks. Nine of the subjects adhered to the diet and lost an average of 8% of their initial weight during the study. Their asthma-related symptoms, control, and QOL improved significantly, and PEF increased significantly, within 2 weeks of diet initiation; these changes persisted for the duration of the study. Spirometery was unaffected by ADCR. Levels of serum beta-hydroxybutyrate were increased and levels of leptin were decreased on CR days, indicating a shift in energy metabolism toward utilization of fatty acids and confirming compliance with the diet. The improved clinical findings were associated with decreased levels of serum cholesterol and triglycerides, striking reductions in markers of oxidative stress (8-isoprostane, nitrotyrosine, protein carbonyls, and 4-hydroxynonenal adducts), and increased levels of the antioxidant uric acid. Indicators of inflammation, including serum tumor necrosis factor-alpha and brain-derived neurotrophic factor, were also significantly decreased by ADCR. Compliance with the ADCR diet was high, symptoms and pulmonary function improved, and oxidative stress and inflammation declined in response to the dietary intervention. These findings demonstrate rapid and sustained beneficial effects of ADCR on the underlying disease process in subjects with asthma, suggesting a novel approach for therapeutic intervention in this disorder. (c) 2006 Elsevier Inc. All rights reserved. C1 Louisiana State Univ, Med Ctr, Dept Surg, New Orleans, LA 70006 USA. Louisiana State Univ, Med Ctr, Dept Pulm Med, New Orleans, LA USA. Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD USA. Natl Inst Aging Intramural Res Program, Immunol Lab, Baltimore, MD USA. Natl Inst Aging Intramural Res Program, Diabet Sect, Baltimore, MD USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. Stanford Univ, Dept Surg, Palo Alto, CA 94304 USA. RP Johnson, JB (reprint author), Louisiana State Univ, Med Ctr, Dept Surg, New Orleans, LA 70006 USA. EM jim@jbjmd.com RI Mattson, Mark/F-6038-2012; OI nassar, matthew/0000-0002-5397-535X FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000315-05] NR 51 TC 182 Z9 185 U1 4 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 1 PY 2007 VL 42 IS 5 BP 665 EP 674 DI 10.1016/j.freeradbiomed.2006.12.005 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 145BC UT WOS:000244839300009 PM 17291990 ER PT J AU Patton, JT AF Patton, John T. TI Viral factories in rotavirus-infected cells: interactions between protein and RNA components SO FUTURE VIROLOGY LA English DT Article DE double-stranded RNA; nonstructural proteins; Reoviridae; rotavirus; single-particle cryoelectron microscopy; viral inclusion bodies; viroplasms ID GENOME REPLICATION; NSP5; VIROPLASM; VIRUS; HYPERPHOSPHORYLATION; PHOSPHORYLATION; ACTIVATION; COMPLEXES AB Rotavirus infection leads to the formation of large electron-dense inclusion bodies within the cytoplasm. These inclusions, termed viroplasms, represent viral factories in which the segmented double-stranded RNA genome of rotavirus is replicated and packaged into virion precursors. The two essential building blocks of the viroplasm are the nonstructural protein (NSP)2 octamer, a doughnut-shaped structure with RNA-binding and nucleosidetriphosphatase activities and dimers of the NSP5 phosphoprotein. Through the use of single-particle cryoelectron microscopy and 3D reconstruction, Jiang and colleagues obtained subnanometer images revealing that the two ligands, NSP5 and RNA, competitively bind to deep grooves spanning the surface of the NSP2 octamer. These results represent a major breakthrough in our understanding of the macromolecular interactions involved in the assembly and function of viral factories. C1 Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Rotavirus Mol Biol Unit, Infect Dis Lab, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Rotavirus Mol Biol Unit, Infect Dis Lab, 50 So Dr MSC 8026,Rm 6314, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov RI Patton, John/P-1390-2014 NR 18 TC 0 Z9 0 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 1746-0794 J9 FUTURE VIROL JI Future Virol. PD MAR PY 2007 VL 2 IS 2 BP 157 EP 161 DI 10.2217/17460794.2.2.157 PG 5 WC Virology SC Virology GA 209ZP UT WOS:000249426800010 ER PT J AU Hold, GL Rabkin, CS Chow, WH Smith, MG Gammon, MD Risch, HA Vaughan, TL McColl, KEL Lissowska, J Zatonski, W Schoenberg, JB Blot, WJ Mowat, NAG Fraumeni, JF El-Omar, EM AF Hold, Georgina L. Rabkin, Charles S. Chow, Wong-Ho Smith, Malcolm G. Gammon, Marilie D. Risch, Harvey A. Vaughan, Thomas L. McColl, Kenneth E. L. Lissowska, Jolanta Zatonski, Witold Schoenberg, Janet B. Blot, William J. Mowat, N. Ashley G. Fraumeni, Joseph F., Jr. El-Omar, Emad M. TI A functional polymorphism of toll-like receptor 4 gene increases risk of gastric carcinoma and its precursors SO GASTROENTEROLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-4; HELICOBACTER-PYLORI INFECTION; RESPIRATORY SYNCYTIAL VIRUS; ASP299GLY POLYMORPHISM; SEQUENCE VARIANTS; PROSTATE-CANCER; INNATE IMMUNITY; CROHNS-DISEASE; TLR4; RECOGNITION AB Background & Aims: TLR4 is a cell-surface signaling receptor involved in the recognition and host response to Helicobacter pylori. The TLR4+896A > G polymorphism linked with impaired reactivity to bacterial lipopolysaccharide may play a role in gastric carcinogenesis. Methods: We assessed associations with premalignant gastric changes in 149 relatives of gastric cancer patients, including 45 with hypochlorhydria and gastric atrophy. We also genotyped 2 independent Caucasian population-based case-control studies of upper gastrointestinal tract cancer, initially in 312 noncardia gastric carcinoma cases and 419 controls and then in 184 noncardia gastric carcinomas, 123 cardia carcinomas, 159 esophageal cancers, and 211 frequency-matched controls. Odds ratios were computed from logistic models and adjusted for potential confounding factors. Results: TLR4+896G carriers had an 11-fold (95% confidence interval [CI], 2.5-48) increased odds ratio (OR) for hypochlorhydria; the polymorphism was unassociated with gastric acid output in the absence of H pylori infection. Carriers also had significantly more severe gastric atrophy and inflammation. Seventeen percent of gastric carcinoma patients in the initial study and 15% of the noncardia gastric carcinoma patients in the replication study had 1 or 2 TLR4 variant alleles vs 8% of both control populations (combined OR = 2.3; 95% CI = 1.6-3.4). In contrast, prevalence of TLR4+896G was not significantly increased in esophageal squamous cell (2%, OR = 0.2) or adenocarcinoma. (9%, OR 1.4) or gastric cardia carcinoma (11%, OR 1.4). Conclusions: Our data suggest that the TLR4+896A > G polymorphism is a risk factor for noncardia gastric carcinoma and its precursors. The findings underscore the role of the host innate immune response in outcome of H pylori infection. C1 Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Univ Washington, Sch Publ Hlth, Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. M Sklodowska Curie Inst Oncol, Warsaw, Poland. New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. Int Epidemiol Inst, Rockville, MD USA. RP El-Omar, EM (reprint author), Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland. EM e.el-omar@abdn.ac.uk OI Lissowska, Jolanta/0000-0003-2695-5799 FU Chief Scientist Office [CZB/4/485]; Intramural NIH HHS NR 39 TC 165 Z9 173 U1 0 U2 10 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 MAR PY 2007 VL 132 IS 3 BP 905 EP 912 DI 10.1053/j.gastro.2006.12.026 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 149YH UT WOS:000245182300015 PM 17324405 ER PT J AU Eling, T Baek, SJ AF Eling, Thomas Baek, Seung Joon TI NAG-1/GDF-15: No evidence for an inhibitory role in colon cancer? Reply. SO GASTROENTEROLOGY LA English DT Letter ID EXPRESSION C1 NIEHS, Lab Mol Carcinogenesis, NIH, Res Triangle Pk, NC 27709 USA. Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37996 USA. RP Eling, T (reprint author), NIEHS, Lab Mol Carcinogenesis, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2007 VL 132 IS 3 BP 1205 EP 1205 DI 10.1053/j.gastro.2007.02.011 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 149YH UT WOS:000245182300046 ER PT J AU Stulberg, MJ Wright, PW Dang, H Hanson, RJ Miller, JS Anderson, SK AF Stulberg, M. J. Wright, P. W. Dang, H. Hanson, R. J. Miller, J. S. Anderson, S. K. TI Identification of distal KIR promoters and transcripts SO GENES AND IMMUNITY LA English DT Article DE human; NK cells; KIR; transcription ID NK CELL-RECEPTOR; NATURAL-KILLER NK; IG-LIKE RECEPTORS; GENE-CLUSTER; DNA METHYLATION; EXPRESSION; KIR2DL4; RECOGNITION; MOLECULES; HUMANS AB A more complete understanding of the transcriptional control of the human and murine class I MHC receptors will help to shed light on the mechanism of selective, stochastic, gene activation that operates in these gene families. Studies of the murine Ly49 class I MHC receptor genes have revealed an important role for distal transcripts originating upstream of the proximal promoter. To date, there have been no reports of distal promoters within the functionally analogous human KIR family of class I MHC receptors. In the current study, reverse transcriptase-polymerase chain reaction (RT-PCR) and RNase protection assays were used to reveal the presence of distal KIR transcripts initiating upstream of the previously characterized proximal KIR promoter. The intergenic promoter elements detected were associated with repetitive elements of the Alu and L1 families. Unlike the proximal KIR promoter, the distal promoter regions were not NK cell-specific. KIR genes expressed in a variegated manner produced a low level of distal transcripts containing a large 5' untranslated region. In contrast, the highly expressed KIR2DL4 gene possessed a higher level of spliced distal transcripts that were capable of producing KIR2DL4 protein. The identification of distal KIR promoter elements suggests that intergenic transcripts may influence the expression of KIR genes. C1 NCI Frederick, Ctr Canc Res, Lab expt Immunol, Ft Detrick, MD 21702 USA. NCI Frederick, SAIC Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA. Univ Minnesota, Div Hematol Oncol & Transplantat, Ctr Canc, Minneapolis, MN 55455 USA. RP Anderson, SK (reprint author), NCI Frederick, Ctr Canc Res, Lab expt Immunol, Bldg 560,Room 31-93, Ft Detrick, MD 21702 USA. EM andersonst@mail.nih.gov RI Anderson, Stephen/B-1727-2012; OI Anderson, Stephen/0000-0002-7856-4266; Miller, Jeffrey S/0000-0002-0339-4944 FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL55417]; PHS HHS [N01-C0-12400] NR 27 TC 23 Z9 23 U1 0 U2 0 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 MAR PY 2007 VL 8 IS 2 BP 124 EP 130 DI 10.1038/sj.gene.6364363 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 143JA UT WOS:000244715500005 PM 17159886 ER PT J AU Spady, TC Ostrander, EA AF Spady, Tyrone C. Ostrander, Elaine A. TI Canid genomics: Mapping genes for behavior in the silver fox SO GENOME RESEARCH LA English DT Editorial Material ID DOMESTIC DOG; LINKAGE MAP; EVOLUTION; CHROMOSOMES; MICROARRAY; SELECTION; TIMES C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS NR 34 TC 3 Z9 4 U1 1 U2 13 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 MAR PY 2007 VL 17 IS 3 BP 259 EP 263 DI 10.1101/gr.6055807 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 141IZ UT WOS:000244573300001 PM 17284673 ER PT J AU Hurle, B Swanson, W Green, ED AF Hurle, Belen Swanson, Willie Green, Eric D. CA NISC Comparative Sequencing TI Comparative sequence analyses reveal rapid and divergent evolutionary changes of the WFDC locus in the primate lineage SO GENOME RESEARCH LA English DT Article ID TRANSGLUTAMINASE SUBSTRATE DOMAIN; WHEY ACIDIC PROTEIN; SEMENOGELIN-II GENE; POSITIVE SELECTION; NATURAL-SELECTION; SEXUAL SELECTION; GENOMIC REGIONS; SEMINAL PLASMA; MATING SYSTEMS; HUMAN SEMEN AB The initial comparison of the human and chimpanzee genome sequences revealed 16 genomic regions with an unusually high density of rapidly evolving genes. One such region is the whey acidic protein (WAP) four-disulfide core domain locus ( or WFDC locus), which contains 14 WFDC genes organized in two subloci on human chromosome 20q13. WAP protease inhibitors have roles in innate immunity and/or the regulation of a group of endogenous proteolytic enzymes called kallikreins. In human, the centromeric WFDC sublocus also contains the rapidly evolving seminal genes, semenogelin 1 and 2 (SEMG1 and SEMG2). The rate of SEMG2 evolution in primates has been proposed to correlate with female promiscuity and semen coagulation, perhaps related to post-copulatory sperm competition. We mapped and sequenced the centromeric WFDC sublocus in 12 primate species that collectively represent four different mating systems. Our analyses reveal a 130-kb region with a notably complex evolutionary history that has included nested duplications, deletions, and significant interspecies divergence of both coding and noncoding sequences; together, this has led to striking differences of this region among primates and between primates and rodents. Further, this region contains six closely linked genes (WFDC12, PI3, SEMG1, SEMG2, SLPI, and MATN4) that show strong patterns of adaptive selection, although an unambiguous correlation between gene mutation rates and mating systems could not be established. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. NHGRI, NIH, Intramural Sequencing Ctr, Rockville, MD 20852 USA. RP Green, ED (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM egreen@nhgri.nih.gov FU Intramural NIH HHS; NCCDPHP CDC HHS [U48 DP000036, U48 DP000048] NR 59 TC 48 Z9 95 U1 1 U2 10 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 MAR PY 2007 VL 17 IS 3 BP 276 EP 286 DI 10.1101/gr.6004607 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 141IZ UT WOS:000244573300003 PM 17267810 ER PT J AU Peters, BA Croix, BS Sjoblom, T Cummins, JM Silliman, N Ptak, J Saha, S Kinzler, KW Hatzis, C Velculescu, VE AF Peters, Brock A. St. Croix, Brad Sjoblom, Tobias Cummins, Jordan M. Silliman, Natalie Ptak, Janine Saha, Saurabh Kinzler, Kenneth W. Hatzis, Christos Velculescu, Victor E. TI Large-scale identification of novel transcripts in the human genome SO GENOME RESEARCH LA English DT Article ID HIGHLY EXPRESSED GENES; SERIAL ANALYSIS; SEQUENCE; ANNOTATION; CDNAS; RNAS; MAP AB Although the sequencing of the human genome has been completed, the number and identity of genes contained within it remains to be fully determined. We used LongSAGE to analyze 660,357 human transcripts from human brain mRNA and identified expression of 17,409 known genes and > 15,000 different transcripts that were not annotated in genome databases. Analysis of a subset of these unannotated transcripts suggests that 85% were differentially expressed in various tissue types and that fewer than 20% would have been detected by ab initio gene predictions. These studies suggest that the human genome contains on the order of twice as many transcribed regions as are currently annotated and that experimental approaches will be required to fully elucidate the novel genes corresponding to these transcripts. C1 Johns Hopkins Univ, Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. Johns Hopkins Univ, Dept Pharmacol & Mol Sci, Baltimore, MD 21231 USA. NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, Frederick, MD 21702 USA. Nuvera Biosci, Woburn, MA 01801 USA. RP Velculescu, VE (reprint author), Johns Hopkins Univ, Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. EM velculescu@jhmi.edu RI Hatzis, Christos/M-3867-2015 OI Hatzis, Christos/0000-0002-8120-2290 FU NCI NIH HHS [CA121113, CA57345, CA62924, P50 CA062924, R01 CA057345, R01 CA121113, R37 CA057345] NR 30 TC 15 Z9 17 U1 0 U2 2 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 MAR PY 2007 VL 17 IS 3 BP 287 EP 292 DI 10.1101/gr.5486607 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 141IZ UT WOS:000244573300004 PM 17267814 ER PT J AU Bonome, T Samimi, G Radonovich, M Brady, J Ghosh, S Ng, SW Mok, SC Birrer, MJ AF Bonome, Tomas Samimi, Goli Radonovich, Michael Brady, John Ghosh, Sue Ng, Shu-wing Mok, Samuel C. Birrer, Michael J. TI Identification of a stromal gene expression signature predicting for survival in a cohort of patients with advanced high-grade serous ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2007 VL 104 IS 3 SU 1 BP S20 EP S21 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 144ZC UT WOS:000244834100042 ER PT J AU Cadungog, MG Bonome, T Giannakakis, A Zhang, L Chu, C Gimotty, P Birrer, M Coukos, G AF Cadungog, Mark G. Bonome, Tomas Giannakakis, Antonis Zhang, Lin Chu, Christina Gimotty, Phyllis Birrer, Michael Coukos, George TI Immune monitoring from tumor biopsy material in advanced ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2007 VL 104 IS 3 SU 1 BP S20 EP S20 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 144ZC UT WOS:000244834100041 ER PT J AU Merritt, WM Sood, AK Lin, YG Han, LY Kamat, AA Spannuth, WA Schmandt, R Coleman, RL Mok, SC Birrer, M AF Merritt, Willam M. Sood, Anil K. Lin, Yvonne G. Han, Liz Y. Kamat, Aparna A. Spannuth, Whitney A. Schmandt, Rosemarie Coleman, Robert L. Mok, Samuel C. Birrer, Michael TI Decreased expression of RNA interference machinery, Dicer and Drosha, is associated with poor outcome in patients with ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2007 VL 104 IS 3 SU 1 BP S4 EP S4 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 144ZC UT WOS:000244834100007 ER PT J AU Ozbun, L Bonome, T Radonovich, M Pise-Masison, C Brady, J Johnson, M Mok, S Birrer, MJ AF Ozbun, Laurent Bonome, Tomas Radonovich, Michael Pise-Masison, Cindy Brady, John Johnson, Michael Mok, Samuel Birrer, Michael J. TI Gene expression signature predicts for response to chemotherapy in advanced-stage serous papillary ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2007 VL 104 IS 3 SU 1 BP S18 EP S18 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 144ZC UT WOS:000244834100037 ER PT J AU Partridge, EE Kreimer, AR Buys, SS Reding, DJ Fouad, MN Riley, TL Greenlee, RT Williams, C Prorok, PC Xu, JL AF Partridge, Edward E. Kreimer, Aimee R. Buys, Saundra S. Reding, Douglas J. Fouad, Mona N. Riley, Thomas L. Greenlee, Robert T. Williams, Craig Prorok, Philip C. Xu, Jian-Lun TI Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: Results from 4 years of annual screening in a randomized trial SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. NCI, Rockville, MD USA. Huntsman Canc Inst, Salt Lake City, UT USA. Marshfield Clin Fdn Med Res & Educ, Res Fdn, Marshfield, WI USA. Informat Management Serv Inc, Rockville, MD USA. RI Kreimer, Aimee/H-1687-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2007 VL 104 IS 3 SU 1 BP S14 EP S15 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 144ZC UT WOS:000244834100029 ER PT J AU Hussain, N Feld, JJ Kleiner, DE Hoofnagle, JH Garcia-Eulate, R Ahlawat, S Koziel, DE Anderson, V Hilligoss, D Choyke, P Gallin, JI Liang, TJ Malech, HL Holland, SM Heller, T AF Hussain, Nadeem Feld, Jordan J. Kleiner, David E. Hoofnagle, Jay H. Garcia-Eulate, Reyes Ahlawat, Sushil Koziel, Deloris E. Anderson, Victoria Hilligoss, Dianne Choyke, Peter Gallin, John I. Liang, T. Jake Malech, Harry L. Holland, Steven M. Heller, Theo TI Hepatic abnormalities in patients with chronic granulomatous disease SO HEPATOLOGY LA English DT Article ID NODULAR REGENERATIVE HYPERPLASIA; PRIMARY BILIARY-CIRRHOSIS; PORTAL-HYPERTENSION; LIVER; ABSCESS AB Chronic granulomatous disease (CGD) is a rare congenital disorder characterized by repeated bacterial and fungal infections. Aside from a high incidence of liver abscess, little is known about hepatic involvement in CGD. The aim of this study was to describe the spectrum of liver abnormalities seen in CGD. The charts of 194 patients with CGD followed at the NIH were reviewed, with a focus on liver abnormalities. Liver enzyme elevations occurred on at least one occasion in 73% of patients during a mean of 8.9 years of follow-up. ALT elevations were generally transient. Although transient alkaline phosphatase (ALP) elevations were also common, persistent ALP elevations lasting up to 17.6 years were seen in 25% of patients. Liver abscess occurred in 35% of patients. Drug-induced hepatotoxicity was documented in 15% of patients but likely occurred more frequently. Hepatomegaly was found in 34% and splenomegaly in 56% of patients. Liver histology showed granulomata in 75% and lobular hepatitis in 90% of specimens. Venopathy of the portal vein was common (80%) and associated with splenomegaly. Venopathy of the central vein was also common (63%) and was associated with the number of abscess episodes. Nodular regenerative hyperplasia (NRH) was seen in 9 patients, including 6 of 12 autopsy specimens. Conclusion: Liver enzyme abnormalities occur frequently in patients with CGD. In addition to liver abscesses and granulomata, drug hepatotoxicity is likely underappreciated. Vascular lesions such as venopathy and-to a lesser extent-NRH are common. The cause and clinical consequences of venopathy await prospective evaluation. C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Ctr Biostat, Bethesda, MD 20892 USA. Georgetown Univ Hosp, Dept Gastroenterol, Washington, DC 20007 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Heller, T (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10,Room 9B16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM theller@nih.gov OI Malech, Harry/0000-0001-5874-5775; Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 26 TC 29 Z9 29 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 MAR PY 2007 VL 45 IS 3 BP 675 EP 683 DI 10.1002/hep.21524 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 144KJ UT WOS:000244794600015 PM 17326162 ER PT J AU Kovalenko, EI Abakushina, E Telford, W Kapoor, V Korchagina, E Khaidukov, S Molotkovskaya, I Sapozhnikov, A Vlaskin, P Bovin, N AF Kovalenko, Elena I. Abakushina, Elena Telford, William Kapoor, Veena Korchagina, Elena Khaidukov, Sergei Molotkovskaya, Irina Sapozhnikov, Alexander Vlaskin, Pavel Bovin, Nicolai TI Clustered carbohydrates as a target for natural killer cells: a model system SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article DE NK cell; neoglycoconjugate; saccharide; flow cytometry; caspase ID MEDIATED CYTOTOXICITY; K562 CELLS; CARCINOMA-CELLS; T-LYMPHOCYTES; NK CELLS; RECOGNITION; OLIGOSACCHARIDES; EXPRESSION; LYSIS; GLYCOSPHINGOLIPIDS AB Membrane-associated oligosaccharides are known to take part in interactions between natural killer (NK) cells and their targets and modulate NK cell activity. A model system was therefore developed using synthetic glycoconjugates as tools to modify the carbohydrate pattern on NK target cell surfaces. NK cells were then assessed for function in response to synthetic glycoconjugates, using both cytolysis-associated caspase 6 activation measured by flow cytometry and IFN-gamma production. Lipophilic neoglycoconjugates were synthesized to provide their easy incorporation into the target cell membranes and to make carbohydrate residues available for cell-cell interactions. While incorporation was successful based on fluorescence monitoring, glycoconjugate incorporation did not evoke artifactual changes in surface antigen expression, and had no negative effect on cell viability. Glycoconjugates contained Le(x), sulfated Le(x), and Le(y) sharing the common structure motif trisaccharide Le(x) were revealed to enhance cytotoxicity mediated specifically by CD16(+) CD56(+) NK cells. The glycoconjugate effects were dependent on saccharide presentation in a polymeric form. Only polymeric, or clustered, but not monomeric glycoconjugates resulted in alteration of cytotoxicity in our system, suggesting that appropriate presentation is critical for carbohydrate recognition and subsequent biological effects. C1 Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. NCI, NIH, Bethesda, MD 20892 USA. RP Kovalenko, EI (reprint author), Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Ul Mikklukho Maklaya 16-10, Moscow 117997, Russia. EM lenkovalen@mail.ru RI Kovalenko, Elena/S-2086-2016 FU Intramural NIH HHS; NIGMS NIH HHS [5-U54-GM062116] NR 36 TC 2 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD MAR PY 2007 VL 127 IS 3 BP 313 EP 326 DI 10.1007/s00418-006-0240-z PG 14 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 135XK UT WOS:000244187000008 PM 17226049 ER PT J AU Meshorer, E AF Meshorer, E. TI Chromatin in embryonic stem cell neuronal differentiation SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE chromatin; embrionic stem cells; DNA; histones; neuron; development; differentiation ID BRAIN CORTICAL-NEURONS; DNA METHYLATION; REPEAT LENGTH; TERMINAL DIFFERENTIATION; HISTONE DEACETYLASE; GENE-EXPRESSION; RAT-BRAIN; NUCLEAR ARCHITECTURE; VARIANT COMPOSITION; ADULT NEUROGENESIS AB Chromatin, the basic regulatory unit of the eukaryotic genetic material, is controlled by epigenetic mechanisms including histone modifications, histone variants, DNA methylation and chromatin remodeling. Cellular differentiation involves large changes in gene expression concomitant with alterations in genome organization and chromatin structure. Such changes are particularly evident in self-renewing pluripotent embryonic stem cells, which begin, in terms of cell fate, as a tabula rasa, and through the process of differentiation, acquire distinct identities. Here I describe the changes in chromatin that accompany neuronal differentiation, particularly of embryonic stem cells, and discuss how chromatin serves as the master regulator of cellular destiny. C1 NCI, NIH, Rockville, MD 20852 USA. Hebrew Univ Jerusalem, Dept Genet, IL-91904 Jerusalem, Israel. RP Meshorer, E (reprint author), NCI, NIH, Bldg 41,Room B508, Rockville, MD 20852 USA. EM meshoree@mail.nih.gov NR 104 TC 27 Z9 29 U1 0 U2 3 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD MAR PY 2007 VL 22 IS 3 BP 311 EP 319 PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 134NZ UT WOS:000244091400009 PM 17163405 ER PT J AU Hill, A Grossman, H Cohen, C Nadler, J Peeters, M AF Hill, Andrew Grossman, Howard Cohen, Cal Nadler, Jeff Peeters, Monika TI Modelling-based prediction of clinical benefits from etravirine in the TMC125-C223 trial SO HIV CLINICAL TRIALS LA English DT Article DE AIDS; CD4 count; clinical progression; etravirine; HIV RNA; non-nucleoside ID CD4 CELL COUNTS; IMMUNODEFICIENCY-VIRUS-INFECTION; PLACEBO-CONTROLLED TRIAL; ANTIRETROVIRAL DRUGS; HIV-1 INFECTION; HIV-1-INFECTED INDIVIDUALS; CUBIC MILLIMETER; DOUBLE-BLIND; ZIDOVUDINE; DIDANOSINE AB Objective: To predict the decrease in progression to AIDS or death based on the treatment benefit of etravirine over active control on CD4 counts and HIV RNA. Method: In the TMC125-C223 trial, treatment-experienced patients (n = 199, baseline median CD4 99 cells/mu L, HIV RNA 4.7 log(10) copies/mL) received optimized background treatment plus either etravirine 400 mg bid, etravirine 800 mg bid, or control. CD4 and HIV RNA data were used to predict progression to AIDS or death with two methods: regression method - data from clinical endpoint trials were used to correlate previous CD4 and HIV RNA treatment benefits with clinical progression; CD4 categorization method - data from the EuroSIDA cohort were used to predict rates of disease progression. Results: At week 48, CD4 counts rose by 49 cells/mu L for etravirine 800 mg bid versus 10 cells/mu L for control; HIV RNA fell by -1.0 and -0.14 log(10) at week 48 in the two groups. The regression method predicted a 39% comparative reduction in progression to AIDS/death from HIV RNA levels and a 33% reduction in progression from CD4 counts. The categorization method predicted a comparative reduction of 39% based on HIV RNA levels and a reduction of 31% based on CD4 counts. Conclusion: Based on the efficacy results from the TMC125-C223 trial, the benefits of etravirine 800 mg bid versus control in raising CD4 counts and suppressing HIV RNA are predicted to lower progression rates to AIDS/death by 31%-39% for etravirine treatment, using two independent methods. C1 Univ Liverpool, Pharmacol Res Labs, Liverpool L69 3GF, Merseyside, England. CRI New England, Boston, MA USA. NIH, Therapeut Res Program, Div AIDS, Bethesda, MD 20892 USA. Tibotec BVBA, Mechelen, Belgium. RP Hill, A (reprint author), Univ Liverpool, Pharmacol Res Labs, 70 Pembroke Pl, Liverpool L69 3GF, Merseyside, England. EM ahill1@tibbe.jnj.com NR 24 TC 0 Z9 0 U1 0 U2 0 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD MAR-APR PY 2007 VL 8 IS 2 BP 68 EP 76 DI 10.1310/hct0802-68 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 170WY UT WOS:000246698100002 PM 17507322 ER PT J AU Penzak, SR Kabuye, G Mugyenyi, P Mbamanya, F Natarajan, V Alfaro, RM Kityo, C Formentini, E Masur, H AF Penzak, S. R. Kabuye, G. Mugyenyi, P. Mbamanya, F. Natarajan, V. Alfaro, R. M. Kityo, C. Formentini, E. Masur, H. TI Cytochrome P4502B6 (CYP2B6) G516T influences nevirapine plasma concentrations in HIV-infected patients in Uganda SO HIV MEDICINE LA English DT Article DE Africa; CYP2B6; HIV; nevirapine; pharmacogenomics ID SINGLE-DOSE NEVIRAPINE; TO-CHILD TRANSMISSION; FUNCTIONAL-CHARACTERIZATION; CATALYTIC-ACTIVITY; RANDOMIZED-TRIAL; HUMAN LIVER; EFAVIRENZ; GENE; POLYMORPHISM; EXPRESSION AB Objective Polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been shown to influence nevirapine plasma concentrations in HIV-infected European Caucasians. Although nevirapine is used extensively in Africa, the influence of CYP2B6 genotype on nevirapine exposure has not been assessed in this population. We aimed to determine the influence of CYP2B6 genotype at position 516 on nevirapine trough concentrations in HIV-infected patients in Kampala, Uganda. Additional polymorphisms in the CYP and multidrug resistance protein-1 (MDR-1) genes were also assessed for their impact on nevirapine concentrations. Methods The following genotypes were determined in all subjects using polymerase chain reaction-restriction fragment length polymorphism: CYP2B6 G516T, MDR-1 C3435T and G2677T, CYP3A4(*)1B and CYP3A5(*)3. Nevirapine plasma concentrations were determined using high-performance liquid chromatography in 23 HIV-infected patients who were generally healthy and had been taking nevirapine 200 mg twice daily for at least 14 days. Analysis of variance with post hoc testing was used to compare nevirapine concentrations among CYP2B6 genotype groups. Results The median nevirapine trough concentration in individuals homozygous for the variant allele (TT) was 7607 ng/mL vs 4181 and 5559 ng/mL for GG and GT individuals, respectively (GG vs TT median ratio=1.82; P=0.011). The mean ratio for TT vs GG individuals (95% confidence interval) was 1.51 (1.18, 1.84). No associations were observed between the other polymorphisms studied and nevirapine concentrations. Conclusions CYP2B6 G516T significantly influenced nevirapine trough concentrations in HIV-infected patients in Uganda. Additional studies in larger patient populations are necessary to further define the potential clinical impact of these preliminary findings. C1 NIH, Dept Pharm, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Joint Clin Res Ctr, Kampala, Uganda. Sci Applicat Int Corp Frederick Inc, Frederick, MD USA. RP Penzak, SR (reprint author), NIH, Clin Pharmacokinet Res Lab, Clin Ctr Pharm Dept, Bldg 10,Room 1 N 257, Bethesda, MD 20892 USA. EM spenzak@cc.nih.gov NR 29 TC 78 Z9 82 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 MAR PY 2007 VL 8 IS 2 BP 86 EP 91 DI 10.1111/j.1468-1293.2007.00432.x PG 6 WC Infectious Diseases SC Infectious Diseases GA 143RI UT WOS:000244741200003 PM 17352764 ER PT J AU Kamel, F Enge, LS Gladen, BC Hoppin, JA Alavanja, MCR Sandler, DP AF Kamel, F. Enge, L. S. Gladen, B. C. Hoppin, J. A. Alavanja, M. C. R. Sandler, D. P. TI Neurologic symptoms in licensed pesticide applicators in the Agricultural Health Study SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article; Proceedings Paper CT 10th Meeting of the International-Neurotoxicology-Association CY JUN 06, 2005-JUL 01, 2006 CL Haikko, FINLAND SP Int Neurotoxicol Assoc DE insecticides; neurologic symptoms; organochlorine insecticides; organophosphate insecticides; pesticides; pesticide applicators ID ORGANOPHOSPHATE PESTICIDES; OCCUPATIONAL-EXPOSURE; FARM-WORKERS; ASSOCIATION; FARMWORKERS; INHIBITION; SEQUELAE; COHORT AB Exposure to high levels of many pesticides has both acute and long-term neurologic consequences, but little is known about the neurotoxicity of chronic exposure to moderate pesticide levels. We analysed cross-sectional data from 18 782 Caucasian, male, licensed pesticide applicators, enrolled in the Agricultural Health Study from 1993 to 1997. Applicators provided information on lifetime pesticide use, and 23 neurologic symptoms typically associated with pesticide intoxication. Increased risk of experiencing >= 10 symptoms during the year before enrollment was associated with cumulative pesticide use, personally mixing or applying pesticides, pesticide-related medical care, diagnosed pesticide poisoning, and events involving high personal pesticide exposure. Greatest risk was associated with use of organophosphate and organochlorine insecticides. Results were similar after stratification by pesticide use during the year before enrollment, or exclusion of applicators with a history of pesticide poisoning, or high-exposure events. Use of pesticide application methods likely to involve high personal exposure was associated with greater risk. Groups of symptoms reflecting several neurologic domains, including affect, cognition, autonomic and motor function, and vision, were also associated with pesticide exposure. These results suggest that neurologic symptoms are associated with cumulative exposure to moderate levels of organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning. C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Natl Inst Human Serv, Bethesda, MD 20892 USA. RP Kamel, F (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM kamel@mail.nih.gov OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018; Engel, Lawrence/0000-0001-9268-4830 FU Intramural NIH HHS NR 30 TC 54 Z9 55 U1 3 U2 17 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0960-3271 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD MAR PY 2007 VL 26 IS 3 BP 243 EP 250 DI 10.1177/0960327107070582 PG 8 WC Toxicology SC Toxicology GA 149ER UT WOS:000245130400012 PM 17439927 ER PT J AU Lange, EM Robbins, CM Gillanders, EM Zheng, SQL Xu, JF Wang, YF White, KA Chang, BL Ho, LA Trent, JM Carpten, JD Isaacs, WB Cooney, KA AF Lange, Ethan M. Robbins, Christiane M. Gillanders, Elizabeth M. Zheng, Siqun Lilly Xu, Jianfeng Wang, Yunfei White, Kirsten A. Chang, Bao-Li Ho, Lindsey A. Trent, Jeffrey M. Carpten, John D. Isaacs, William B. Cooney, Kathleen A. TI Fine-mapping the putative chromosome 17q21-22 prostate cancer susceptibility gene to a 10 cM region based on linkage analysis SO HUMAN GENETICS LA English DT Review DE prostate cancer; linkage analysis; early onset; subset analyses ID GENOME-WIDE SCAN; FAMILIES; DISEASE; PROHIBITIN; TARGET; TESTS; BRCA1; MEN AB Prostate cancer linkage studies have suggested the existence of a prostate cancer susceptibility gene on chromosome 17q21-22. We now report the results of an extended linkage analysis including 95 new multiplex prostate cancer families and 9 additional microsatellite markers resulting in a maximum LOD score of 2.99 at approximately 81-82 cM for all 453 pedigrees. Results from these 95 new pedigrees provide additional support for a chromosome 17q21-22 prostate cancer susceptibility gene. Inclusion of the 9 additional markers significantly reduced the size of the candidate region, as defined using a 1-LOD support interval, especially when focusing analyses on subsets of pedigrees with four or more confirmed affecteds or average age of diagnosis less than or equal to 65 years. A novel subset analysis of only those families (n = 147) that had four or more prostate cancer cases and an average age of prostate cancer diagnosis <= 65 years results in a maximum LOD score of 5.49 at 78 cM with a 1-LOD support interval of 10 cM. This large set of pedigrees with four more prostate cancer cases characterized by early-onset disease will serve as a useful resource for identifying the putative 17q21-22 prostate cancer susceptibility gene. C1 Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. Univ N Carolina, Dept Genet, Chapel Hill, NC USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. NHGRI, Bethesda, MD 20892 USA. Translat Genom Res Inst, Phoenix, AZ USA. Wake Forest Univ, Sch Med, Ctr Human Genome, Winston Salem, NC 27109 USA. RP Cooney, KA (reprint author), 7310 CCGC,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM kcooney@umich.edu FU NCI NIH HHS [CA79596] NR 19 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 2007 VL 121 IS 1 BP 49 EP 55 DI 10.1007/s00439-006-0274-2 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 135XL UT WOS:000244187100005 PM 17120048 ER PT J AU Vasireddy, V Uchida, Y Salem, N Kim, SY Mandal, MNA Reddy, GB Bodepudi, R Alderson, NL Brown, JC Hama, H Dlugosz, A Elias, PM Holleran, WM Ayyagari, R AF Vasireddy, Vidyullatha Uchida, Yoshikazu Salem, Norman, Jr. Kim, Soo Yeon Mandal, Md Nawajesh Ali Reddy, Geereddy Bhanuprakash Bodepudi, Ravi Alderson, Nathan L. Brown, Johnie C. Hama, Hiroko Dlugosz, Andrzej Elias, Peter M. Holleran, Walter M. Ayyagari, Radha TI Loss of functional ELOVL4 depletes very long-chain fatty acids (>= C28) and the unique omega-O-acylceramides in skin leading to neonatal death SO HUMAN MOLECULAR GENETICS LA English DT Article ID EPIDERMAL PERMEABILITY BARRIER; STRATUM-CORNEUM CERAMIDES; MACULAR DYSTROPHY; MASS-SPECTROMETRY; LIPIDS; SPHINGOLIPIDS; ORGANIZATION; ENVELOPE; MICE; ULTRASTRUCTURE AB Mutations in elongation of very long-chain fatty acid-4 (ELOVL4) are associated with autosomal dominant Stargardt-like macular degeneration (STGD3), with a five base-pair (5 bp) deletion mutation resulting in the loss of 51 carboxy-terminal amino acids and truncation of the protein. In addition to the retina, Elovl4 is expressed in a limited number of mammalian tissues, including skin, with unknown function(s). We generated a knock-in mouse model with the 5-bp deletion in the Elovl4 gene. As anticipated, mice carrying this mutation in the heterozygous state (Elovl4(+/del)) exhibit progressive photoreceptor degeneration. Unexpectedly, homozygous mice (Elovl4(del/del)) display scaly, wrinkled skin, have severely compromised epidermal permeability barrier function, and die within a few hours after birth. Histopathological evaluation of the Elovl4(del/del) pups revealed no apparent abnormality(ies) in vital internal organs. However, skin histology showed an abnormally-compacted outer epidermis [stratum corneum (SC)], while electron microscopy revealed deficient epidermal lamellar body contents, and lack of normal SC lamellar membranes that are essential for permeability barrier function. Lipid analyses of epidermis from Elovl4(del/del) mice revealed a global decrease in very long-chain fatty acids (VLFAs) (i.e., carbon chain >= C28) in both the ceramide/glucosylceramide and the free fatty-acid fractions. Strikingly, Elovl4(del/del) skin was devoid of the epidermal-unique omega-O-acylceramides, that are key hydrophobic components of the extracellular lamellar membranes in mammalian SC. These findings demonstrate that ELOVL4 is required for generating VLFA critical for epidermal barrier function, and that the lack of epidermal omega-O-acylceramides is incompatible with survival in a desiccating environment. C1 Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. Univ Calif San Francisco, Sch Med, Dept Dermatol, San Francisco, CA 94121 USA. Vet Adm Med Ctr, San Francisco, CA 94121 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. Natl Inst Nutr, Hyderabad 500007, Andhra Pradesh, India. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Appl Biosyst Inc, Framingham, MA 01701 USA. Univ Michigan, Dept Dermatol, Ann Arbor, MI 48105 USA. Univ Calif San Francisco, Sch Pharm, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. RP Ayyagari, R (reprint author), Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA. EM ayyagari@umich.edu FU NEI NIH HHS [R01 EY013198, P30 EY007003, R01 EY007060, EY07060, EY13198, F31 EY007003]; NIAMS NIH HHS [AR19098, R01 AR019098, AR051077, R01 AR051077, R01 AR045973, AR045973, R01 AR045973-07, AR39948]; PHS HHS [AY07003] NR 54 TC 113 Z9 115 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 1 PY 2007 VL 16 IS 5 BP 471 EP 482 DI 10.1093/hmg/ddl480 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 152HM UT WOS:000245352400003 PM 17208947 ER PT J AU Marini, JC Forlino, A Cabral, WA Barnes, AM San Antonio, JD Milgrom, S Hyland, JC Korkko, J Prockop, DJ De Paepe, A Coucke, P Symoens, S Glorieux, FH Roughley, PJ Lund, AM Kuurila-Svahn, K Hartikka, H Cohn, DH Krakow, D Mottes, M Schwarze, U Chen, D Yang, K Kuslich, C Troendle, J Dalgleish, R Byers, PH AF Marini, Joan C. Forlino, Antonella Cabral, Wayne A. Barnes, Aileen M. San Antonio, James D. Milgrom, Sarah Hyland, James C. Korkko, Jarmo Prockop, Darwin J. De Paepe, Anne Coucke, Paul Symoens, Sofie Glorieux, Francis H. Roughley, Peter J. Lund, Alan M. Kuurila-Svahn, Kaija Hartikka, Heini Cohn, Daniel H. Krakow, Deborah Mottes, Monica Schwarze, Ulrike Chen, Diana Yang, Kathleen Kuslich, Christine Troendle, James Dalgleish, Raymond Byers, Peter H. TI Consortium for osteogeneslis imperfecta mutations in the helical domain of type I collagen: Regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans SO HUMAN MUTATION LA English DT Review DE osteogenesis imperfecta; type I collagen; genotype-phenotype; proteoglycan binding; COL1A1; COL1A2 ID EHLERS-DANLOS-SYNDROME; RECEPTOR TYROSINE KINASES; COL1A1 NULL ALLELES; CONNECTIVE-TISSUE; MESSENGER-RNA; TRIPLE-HELIX; THERMAL-STABILITY; CELL ATTACHMENT; HEPARIN-BINDING; FIBRILS AB Osteogenesis imperfecta (01) is a generalized disorder of connective tissue characterized by fragile bones and easy susceptibility to fracture. Most cases of 01 are caused by mutations in type I collagen. We have identified and assembled structural mutations in type I collagen genes (COL1A1 and COL1A2, encoding the proal (1) and pro alpha 2(I) chains, respectively) that result in OI. Quantitative defects causing type 101 were not included. Of these 832 independent mutations, 682 result in substitution for glycine residues in the triple helical domain of the encoded protein and 150 alter splice sites. Distinct genotype-phenotype relationships emerge for each chain. One-third of the mutations that result in glycine substitutions in alpha 1 (I) are lethal, especially when the substituting residues are charged or have a branched side chain. Substitutions in the first 200 residues are nonlethal and have variable outcome thereafter, unrelated to folding or helix stability domains. Two exclusively lethal regions (helix positions 691-823 and 910-964) align with major ligand binding regions (MLBRs), suggesting crucial interactions of collagen monomers or fibrils with integrins, matrix metalloproteinases (MMPS), fibronectin, and cartilage oligomeric matrix protein (COMP). Mutations in COL1A2 are predominantly nonlethal (80%). Lethal substitutions are located in eight regularly spaced clusters along the chain, supporting a regional model. The lethal regions align with proteoglycan binding sites along the fibril, suggesting a role in fibril-matrix interactions. Recurrences at the same site in alpha 2(I) are generally concordant for outcome, unlike alpha 1 (1). Splice site mutations comprise 20% of helical mutations identified in OI patients, and may lead to exon skipping, intron inclusion, or the activation of cryptic splice sites. Splice site mutations in COL1A1 are rarely lethal; they often lead to frameshifts and the mild type I phenotype. In alpha 2(1), lethal exon skipping events are located in the carboxyl half of the chain. Our data on genotype-pheno type relationships indicate that the two collagen chains play very different roles in matrix integrity and that phenotype depends on intracellular and extracellular events. C1 NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. Univ Pavia, Dept Biochem A Castellani, I-27100 Pavia, Italy. Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Dept Med, Philadelphia, PA 19107 USA. Tulane Univ, Ctr Gene Therapy, New Orleans, LA 70118 USA. State Univ Ghent Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. Shriners Hosp Children, Genet Unit, Montreal, PQ, Canada. Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark. Vaasa Cent Hosp, Dept Otorhinolaryngol Head & Neck Surg, Vaasa, Finland. Turku Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, FIN-20520 Turku, Finland. Univ Oulu, Collagen Res Unit, Bioctr, Oulu, Finland. Univ Oulu, Dept Med Biochem & Mol Biol, Oulu, Finland. Cedars Sinai Res Inst, Inst Med Genet, Steven Spielberg Pediat Res Ctr, Los Angeles, CA USA. Univ Verona, Dept Mother & Child, I-37100 Verona, Italy. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. NICHD, Biometry & Math Stat Branch, NIH, Bethesda, MD USA. Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. RP Marini, JC (reprint author), NICHD, Bone & Extracellular Matrix Branch, NIH, Bldg 10,Rm 9S239,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov RI Dalgleish, Raymond/A-2893-2008; Forlino, Antonella/H-5385-2015; OI Dalgleish, Raymond/0000-0001-7667-187X; Forlino, Antonella/0000-0002-6385-1182; Byers, Peter H./0000-0001-7786-7030 FU NICHD NIH HHS [P01 HD022657, P01 HD022657-220002] NR 73 TC 293 Z9 313 U1 5 U2 24 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 MAR PY 2007 VL 28 IS 3 BP 209 EP 221 DI 10.1002/humu.20429 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 134QT UT WOS:000244099500001 PM 17078022 ER PT J AU Heinz, A Waters, AJ Taylor, RC Myers, CS Moolchan, ET Heishman, SJ AF Heinz, Adrienne Waters, Andrew J. Taylor, Richard C. Myers, Carol S. Moolchan, Eric T. Heishman, Stephen J. TI Effect of tobacco deprivation on the attentional blink in rapid serial visual presentation SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE tobacco deprivation; nicotine; attention; perception; attentional blink ID LOCUS-COERULEUS; NICOTINE; SMOKING; PERFORMANCE; IDENTIFICATION; MECHANISMS; RECEPTORS; AMYGDALA; SMOKERS; TARGETS AB When two targets are imbedded in rapid serial visual presentation (RSVP), identification of the second target (T2) is impaired if it occurs within 500 ms of the first target (T 1). This attentional blink (AB) is thought to involve interference of resources in processing T1 and T2. The deleterious effect of tobacco deprivation on attention has been documented, but no studies have examined the AB. Nonsmokers (n=30), 12-h tobacco-deprived smokers (n=30), and nondeprived smokers (n=30) were randomly assigned to perform the RSVP with one of three stimulus-duration conditions (96, 113, or 130 ms). Participants completed 48 RSVP trials. Each trial consisted of 16 individually presented words (T1, T2, and 14 distractors), and T2 lagged T1 at serial positions 1-8. Participants verbalized T1 and T2 in order immediately after each trial. Identification of T2 (for correct T1 trials) was impaired at early versus late lag positions, which was especially pronounced in the most difficult (96 ms) condition. There was no evidence for group differences on the AB; however, deprived smokers were worse identifying T1 in the 113-ms condition. These results suggest that the AB is influenced by stimulus duration, but not by 12 h of tobacco deprivation. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 Natl Inst Drug Abuse, Nicotine Psychopharmacol Unit, Clin Pharmacol & Therapeut Branch, NIH, Baltimore, MD 21224 USA. Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. RP Heishman, SJ (reprint author), Natl Inst Drug Abuse, Nicotine Psychopharmacol Unit, Clin Pharmacol & Therapeut Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM heishman@nih.gov FU Intramural NIH HHS NR 38 TC 4 Z9 4 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD MAR PY 2007 VL 22 IS 2 BP 89 EP 96 DI 10.1002/hup.826 PG 8 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 153MY UT WOS:000245440800004 PM 17266171 ER PT J AU Promislow, JHE Baird, DD Wilcox, AJ Weinberg, CR AF Promislow, J. H. E. Baird, D. D. Wilcox, A. J. Weinberg, C. R. TI Bleeding following pregnancy loss before 6 weeks' gestation SO HUMAN REPRODUCTION LA English DT Article DE pregnancy loss; menses; bleed length; spontaneous abortion ID SPONTANEOUS-ABORTION; EXPECTANT MANAGEMENT; BLOOD-LOSS; PATTERNS; WOMEN; MENORRHAGIA; URINE AB BACKGROUND: Pregnancy loss before 6 weeks' gestation is common, but little has been reported about the associated bleeding. We compared women's bleeding following a pregnancy loss before 6 weeks' gestation with their typical menstruation. METHODS: Women provided daily urine samples while trying to become pregnant and recorded the number of pads and tampons used each day. Thirty-six women had complete bleed data for a loss before 6 weeks' gestation and one or more non-pregnant cycles. RESULTS: Mean bleed length following a pregnancy loss was 0.4 days longer than the woman's average menstrual bleed (P = 0.01), primarily because of more days of light bleeding. Although there was no overall increase in the total number of pads plus tampons used, women with losses bled less than their typical menses following pregnancies of very short duration and more than usual for the pregnancies lasting the longest. CONCLUSIONS: Overall, the bleeding associated with pregnancy loss before 6 weeks' gestation is similar to menstrual bleeding and unlikely to be recognized as pregnancy loss. The intriguing finding that pregnancies of very short duration were associated with less bleeding than the woman's typical menses might reflect endometrial factors associated with loss. C1 NIEHS, Social & Sci Syst, Durham, NC 27703 USA. NIEHS, Epidemiol Branch, Durham, NC 27703 USA. NIEHS, Biostat Branch, Durham, NC 27703 USA. RP Promislow, JHE (reprint author), NIEHS, Social & Sci Syst, 1009 Slater Rd,Suite 120, Durham, NC 27703 USA. EM promisl1@niehs.nih.gov RI Baird, Donna/D-5214-2017; OI Baird, Donna/0000-0002-5544-2653; Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS [, NIH0011459185]; PHS HHS [NIH0011459185] NR 21 TC 9 Z9 10 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 MAR PY 2007 VL 22 IS 3 BP 853 EP 857 DI 10.1093/humrep/del417 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 147OG UT WOS:000245011700030 PM 17071824 ER PT J AU Wang, TJ Gona, P Larson, MG Levy, D Benjamin, EJ Tofler, GH Jacques, PF Meigs, JB Rifai, N Selhub, J Robins, SJ Newton-Cheh, C Vasan, RS AF Wang, Thomas J. Gona, Philimon Larson, Martin G. Levy, Daniel Benjamin, Emelia J. Tofler, Geoffrey H. Jacques, Paul F. Meigs, James B. Rifai, Nader Selhub, Jacob Robins, Sander J. Newton-Cheh, Christopher Vasan, Ramachandran S. TI Multiple biomarkers and the risk of incident hypertension SO HYPERTENSION LA English DT Article DE epidemiology; hypertension; C-reactive protein; plasminogen activator inhibitor-1; aldosterone; albuminuria ID C-REACTIVE PROTEIN; PLASMINOGEN-ACTIVATOR INHIBITOR-1; NATRIURETIC PEPTIDE LEVELS; URINARY ALBUMIN EXCRETION; BLOOD-PRESSURE TRACKING; AORTIC ENDOTHELIAL-CELLS; RENIN-ANGIOTENSIN SYSTEM; CARDIOVASCULAR RISK; PLASMA HOMOCYSTEINE; PRIMARY ALDOSTERONISM AB An understanding of mechanisms underlying the development of essential hypertension is critical for designing prevention and treatment strategies. Selected biomarkers may be elevated before the onset of hypertension, but previous studies are limited by cross-sectional designs or a focus on single biomarkers. We prospectively studied 1456 nonhypertensive individuals who had baseline measurement of 9 biomarkers: C-reactive protein (inflammation); fibrinogen (inflammation and thrombosis); plasminogen activator inhibitor-1 (fibrinolytic potential); aldosterone, renin, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptide (neurohormonal activity); homocysteine (renal function and oxidant stress); and urinary albumin/creatinine ratio (glomerular endothelial function). Incident hypertension, defined as blood pressure >= 140/90 mm Hg or antihypertensive therapy, developed in 232 participants over a mean follow-up of 3 years. After adjustment for clinical risk factors, the biomarker panel was significantly associated with incident hypertension (P = 0.002). Three (of 9) biomarkers were significantly related to incident hypertension on backward elimination (multivariable-adjusted odds ratios, per SD increment in biomarker): C-reactive protein (1.26; 95% CI: 1.05 to 1.51), plasminogen activator inhibitor-1 (1.28; 95% CI: 1.05 to 1.57), and urinary albumin/creatinine ratio (1.21; 95% CI: 1.02 to 1.43). The incidence of hypertension was 4.5, 6.4, and 9.9 per 100 person years for participants with 0, 1, and >= 2 elevated biomarkers, respectively (elevation defined as >= 1 SD above the mean). The threshold of >= 2 elevated biomarkers for predicting hypertension was associated with high specificity (0.92) but low sensitivity (0.15). Biomarkers of inflammation, reduced fibrinolytic potential, and low-grade albuminuria are jointly associated with the incidence of hypertension. These data support the premise that abnormalities in multiple biological pathways antedate the onset of overt hypertension. C1 Harvard Univ, Cardiol Div, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. Harvard Univ, Div Gen Med, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Royal N Shore Hosp, Sydney, NSW, Australia. Tufts Univ, Jean Mayer Dept Agr Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Lab Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Div Endocrinol Nutr & Diabet, Prevent Med Sect,Med Ctr, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Endocrinol Nutr & Diabet, Cardiol Sect,Med Ctr, Boston, MA 02118 USA. RP Wang, TJ (reprint author), Harvard Univ, Cardiol Div, Massachusetts Gen Hosp, Sch Med,Dept Med, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2K24-HL-04334, K23-HL-074077, N01-HC-25195] NR 69 TC 90 Z9 99 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2007 VL 49 IS 3 BP 432 EP 438 DI 10.1161/01.HYP.0000256956.61872.aa PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 136SU UT WOS:000244245200007 PM 17242302 ER PT J AU Zhang, R Cao, WW Zhou, QF Cha, JH Shung, KK Huang, YH AF Zhang, Rui Cao, Wenwu Zhou, Qifa Cha, Jung Hyui Shung, K. Kirk Huang, Yuhong TI Acoustic properties of alumina colloidal/polymer nano-composite film on silicon SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID MEDICAL IMAGING APPLICATIONS; ULTRASONIC TRANSDUCERS AB Alumina colloidal/polymer composite films on silicon substrates have been successfully fabricated using the sol-gel method, in which the crystallite sizes of alumina are between 20 and 50 nm. The density and ultrasonic phase velocities in these films with different alumina ratios from 14% to 32% were measured at the desired operating frequency. We have proved that the density, acoustic phase velocities, and hence the acoustic impedance of the nanocomposite films increase with the alumina content, which gives us another option of tailoring the acoustic impedance of the nano-composite film for making the matching layer of high-frequency medical ultrasonic transducers. C1 Harbin Inst Technol, Dept Phys, Harbin, Heilongjiang, Peoples R China. Penn State Univ, Mat Res Inst, University Pk, PA 16802 USA. Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. Chemat Technol Inc, Northridge, CA 91324 USA. RP Cao, WW (reprint author), Harbin Inst Technol, Dept Phys, Harbin, Heilongjiang, Peoples R China. EM cao@math.psu.edu RI Cao, Wenwu/F-6091-2012 OI Cao, Wenwu/0000-0002-2447-1486 FU NIBIB NIH HHS [P41-EB2182-07] NR 7 TC 8 Z9 9 U1 1 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD MAR PY 2007 VL 54 IS 3 BP 467 EP 469 DI 10.1109/TUFFC.2007.270 PG 3 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 140JA UT WOS:000244499600001 PM 17375816 ER PT J AU Beaven, MA AF Beaven, Michael A. TI Division of labor: Specialization of sphingosine kinases in mast cells SO IMMUNITY LA English DT Editorial Material ID 1-PHOSPHATE; SPHINGOSINE-1-PHOSPHATE; RECEPTORS AB Generation of sphingosine-1-phosphate by sphingosine kinases (SphKs) promotes allergic inflammatory diseases, but the roles of the individual SphK isoforms are unclear. Olivera et al. (2007) show that SphK2 regulates mast cell activation whereas SphK1 enhances susceptibility to antigen challenge in vivo. C1 Natl Heart Lung & Blood Inst, NIH, Bethesda, MD 20892 USA. RP Beaven, MA (reprint author), Natl Heart Lung & Blood Inst, NIH, Room 8N109Bldg 10, Bethesda, MD 20892 USA. EM beavenm@nhlbi.nih.gov NR 9 TC 8 Z9 8 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2007 VL 26 IS 3 BP 271 EP 273 DI 10.1016/j.immuni.2007.03.002 PG 3 WC Immunology SC Immunology GA 150PG UT WOS:000245228100001 PM 17376388 ER PT J AU Olivera, A Mizugishi, K Tikhonova, A Ciaccia, L Odom, S Proia, RL Rivera, J AF Olivera, Ana Mizugishi, Kiyomi Tikhonova, Anastassia Ciaccia, Laura Odom, Sandra Proia, Richard L. Rivera, Juan TI The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis SO IMMUNITY LA English DT Article ID FC-EPSILON-RI; PROTEIN-KINASE-C; KAPPA-B ACTIVATION; CYTOKINE PRODUCTION; CALCIUM MOBILIZATION; GENE-EXPRESSION; MICE DEFICIENT; RBL-2H3 CELLS; FYN KINASE; 1-PHOSPHATE AB Sphingosine-1-phosphate,a key mediator in immune cell trafficking, is elevated in the lungs of asthmatic patients and regulates pulmonary epithelium permeability. Stimulation of mast cells by allergens induces two mammalian sphingosine kinases (Sphk1 and Sphk2) to produce sphingosine-1-phosphate (S1P). Little is known about the individual role of these kinases in regulating immune cell function. Here we show that in mast cells, Sphk2 is required for production of S1P, for calcium influx, for activation of protein kinase C, and for cytokine production and degranulation. However, susceptibility to in vivo anaphylaxis is determined both by S1P within the mast cell compartment and by circulating S1P generated by Sphk1 predominantly from a non-mast cell source(s). Thus, sphingosine kinases are determinants of mast cell responsiveness, demonstrating a previously unrecognized relationship with anaphylaxis. C1 NIAMS, Mol Immunol & Inflammat Branch, Mol Inflammat Sect, NIH, Bethesda, MD 20892 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMS, Mol Immunol & Inflammat Branch, Mol Inflammat Sect, NIH, Bethesda, MD 20892 USA. EM riveraj@mail.nih.gov RI Proia, Richard/A-7908-2012; Tikhonova, Anastasia/F-1186-2015 NR 56 TC 141 Z9 144 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD MAR PY 2007 VL 26 IS 3 BP 287 EP 297 DI 10.1016/j.immuni.2007.02.008 PG 11 WC Immunology SC Immunology GA 150PG UT WOS:000245228100006 PM 17346996 ER PT J AU Laurence, A Tato, CM Davidson, TS Kanno, Y Chen, Z Yao, Z Blank, RB Meylan, F Siegel, R Hennighausen, L Shevach, EM O'Shea, JJ AF Laurence, Arian Tato, Cristina M. Davidson, Todd S. Kanno, Yuka Chen, Zhi Yao, Zhengju Blank, Rebecca B. Meylan, Francoise Siegel, Richard Hennighausen, Lothar Shevach, Ethan M. O'Shea, John J. TI Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation SO IMMUNITY LA English DT Article ID REGULATORY T-CELLS; AUTOIMMUNE INFLAMMATION; ANTIGEN RECEPTOR; HELPER-CELLS; JAK KINASES; BETA; DIFFERENTIATION; ACTIVATION; TOLERANCE; LYMPHOCYTES AB Recent work has identified a new subset of effector T cells that produces interleukin (IL)-17 known as T helper 17 (Th17) cells, which is involved in the pathophysiology of inflammatory diseases and is thought to be developmentally related to regulatory T (Treg) cells. Because of its importance for Treg cells, we examined the role of IL-2 in Th17 generation and demonstrate that a previously unrecognized aspect of IL-2 function is to constrain IL-17 production. Genetic deletion or antibody blockade of IL-2 promoted differentiation of the Th17 cell subset. Whereas STAT3 appeared to be a key positive regulator of ROR gamma t and IL-17 expression, absence of IL-2 or disruption of its signaling by deletion of the transcription factor STAT5 resulted in enhanced Th17 cell development. We conclude that in addition to the promotion of activation-induced cell death of lymphocytes and the generation of Treg cells, inhibition of Th17 polarization appears to be an important function of IL-2. C1 NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Tato, CM (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM tatoc@mail.nih.gov RI Laurence, Arian/A-8770-2009; Siegel, Richard/C-7592-2009; Kanno, Yuka/B-5802-2013; OI Laurence, Arian/0000-0003-0942-8292; Siegel, Richard/0000-0001-5953-9893; Kanno, Yuka/0000-0001-5668-9319 FU Intramural NIH HHS [Z99 AR999999] NR 42 TC 758 Z9 815 U1 6 U2 42 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2007 VL 26 IS 3 BP 371 EP 381 DI 10.1016/j.immuni.2007.02.009 PG 11 WC Immunology SC Immunology GA 150PG UT WOS:000245228100013 PM 17363300 ER PT J AU Lafont, BAP McGraw, CM Stukes, SA Buckler-White, A Plishka, RJ Byrum, RA Hirsch, VM Martin, MA AF Lafont, Bernard A. P. McGraw, Christopher M. Stukes, Sabriya A. Buckler-White, Alicia Plishka, Ronald J. Byrum, Russell A. Hirsch, Vanessa M. Martin, Malcolm A. TI The locus encoding an oligomorphic family of MHC-A alleles (Mane-A*06/Mamu-A*05) is present at high frequency in several macaque species SO IMMUNOGENETICS LA English DT Article DE pig-tailed macaques; MHC class I; locus; site specific primer-PCR (SSP-PCR) ID SIMIAN IMMUNODEFICIENCY VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; PEPTIDE-BINDING-SPECIFICITY; INFECTED RHESUS-MONKEYS; T-LYMPHOCYTE RESPONSES; CYNOMOLGUS MACAQUES; EVOLUTIONARY HISTORY; EPITOPES; IDENTIFICATION AB Several macaques species are used for HIV pathogenesis and vaccine studies, and the characterization of their major histocompatibility complex (MHC) class I genes is required to rigorously evaluate the cellular immune responses induced after immunization and/or infection. In this study, we demonstrate that the gene expressing the Mane-A*06 allele of pig-tailed macaques is an orthologue of the locus encoding the Mamu-A*05 allele family in rhesus macaques. Analysis of the distribution of this locus in a cohort of 63 pig-tailed macaques revealed that it encodes an oligomorphic family of alleles, highly prevalent (90%) in the pig-tailed macaque population. Similarly, this locus was very frequently found (62%) in a cohort of 80 Indian rhesus macaques. An orthologous gene was also detected in cynomolgus monkeys originating from four different geographical locations, but was absent in two African monkey species. Expression analysis in pig-tailed macaques revealed that the Mane-A*06 alleles encoded by this locus are transcribed at 10- to 20-fold lower levels than other MHC-A alleles (Mane-A*03 or Mane-A*10). Despite their conservation and high prevalence among Asian macaque species, the alleles of the Mane-A*06 family and, by extension their orthologues in rhesus and cynomolgus monkeys, may only modestly contribute to cellular immune responses in macaques because of their low level of expression. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD 20850 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. EM malm@niaid.nih.gov RI Lafont, Bernard/B-7236-2014 FU Intramural NIH HHS NR 51 TC 14 Z9 15 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAR PY 2007 VL 59 IS 3 BP 211 EP 223 DI 10.1007/s00251-007-0190-1 PG 13 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 134EP UT WOS:000244066300004 PM 17256149 ER PT J AU Shevach, EM Brinster, C DiPaolo, RA AF Shevach, E. M. Brinster, C. DiPaolo, R. A. TI Mechanisms of action of T regulatory cells in vivo SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-of-Immunology CY FEB 20-23, 2007 CL Glasgow, SCOTLAND SP British Soc Immunol C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 2007 VL 120 SU 1 BP 7 EP 7 PG 1 WC Immunology SC Immunology GA 134JT UT WOS:000244080000027 ER PT J AU Antunes, I Filby, A Hasenkrug, K Kassiotis, G AF Antunes, I. Filby, A. Hasenkrug, K. Kassiotis, G. TI Regulatory T cells in retroviral infection SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-of-Immunology CY FEB 20-23, 2007 CL Glasgow, SCOTLAND SP British Soc Immunol C1 Natl Inst Med Res, Div Immunoregulat, MRC, London NW7 1AA, England. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 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 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 2007 VL 120 SU 1 BP 12 EP 12 PG 1 WC Immunology SC Immunology GA 134JT UT WOS:000244080000048 ER PT J AU Hickman-Miller, H Takeda, K Murray, F Bennink, J Yewdell, J AF Hickman-Miller, H. Takeda, K. Murray, F. Bennink, J. Yewdell, J. TI Visualising early immune interactions after vaccinia virus infection in vivo SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-of-Immunology CY FEB 20-23, 2007 CL Glasgow, SCOTLAND SP British Soc Immunol C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20815 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 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 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 2007 VL 120 SU 1 BP 13 EP 13 PG 1 WC Immunology SC Immunology GA 134JT UT WOS:000244080000050 ER PT J AU Filby, A Antunes, I Marques, R Tolaini, M Iwashiro, M Kuribayashi, K Hasenkrug, K Kssiotis, G AF Filby, A. Antunes, I. Marques, R. Tolaini, M. Iwashiro, M. Kuribayashi, K. Hasenkrug, K. Kssiotis, G. TI Early and profound loss of high affinity T cell help during retroviral infection SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-of-Immunology CY FEB 20-23, 2007 CL Glasgow, SCOTLAND SP British Soc Immunol C1 Natl Inst Med Res, MRC, Div Immunoregulat, London NW7 1AA, England. Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. Mie Univ, Sch Med, Dept Bioregulat, Tsu, Mie 5148507, Japan. Tango Furusato Hosp, Kyoto 6293313, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 2007 VL 120 SU 1 BP 14 EP 14 PG 1 WC Immunology SC Immunology GA 134JT UT WOS:000244080000056 ER PT J AU Tudor, C Hitti, E Blackshear, PJ Clark, AR Saklatvala, J Dean, JLE AF Tudor, C. Hitti, E. Blackshear, P. J. Clark, A. R. Saklatvala, J. Dean, J. L. E. TI Identification of target mRNAs regulated by both p38 MAPK and tristetraprolin in murine macrophages SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-of-Immunology CY FEB 20-23, 2007 CL Glasgow, SCOTLAND SP British Soc Immunol C1 Univ London Imperial Coll Sci & Technol, Kennedy Inst, Div Rheumatol, Fac Med, London, England. Inst Biochem, Sch Med, D-30625 Hannover, Germany. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 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 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 2007 VL 120 SU 1 BP 16 EP 16 PG 1 WC Immunology SC Immunology GA 134JT UT WOS:000244080000062 ER PT J AU Ishmael, FT Fang, X Fan, J Blackshear, P Gorospe, M Cheadle, C Stellato, C AF Ishmael, F. T. Fang, X. Fan, J. Blackshear, P. Gorospe, M. Cheadle, C. Stellato, C. TI Role of the RNA-binding protein tristetraprolin in glucocorticoid-mediated gene regulation SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-of-Immunology CY FEB 20-23, 2007 CL Glasgow, SCOTLAND SP British Soc Immunol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NIA, NIH, Baltimore, MD 21224 USA. RI Stellato, Cristiana/P-3001-2015 OI Stellato, Cristiana/0000-0002-1294-8355 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 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 2007 VL 120 SU 1 BP 17 EP 17 PG 1 WC Immunology SC Immunology GA 134JT UT WOS:000244080000065 ER PT J AU Yang, D Oppenheim, JJ AF Yang, D. Oppenheim, J. J. TI Alarmins as endogenous effectors of innate immunity and enhancers of adaptive immunity SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-of-Immunology CY FEB 20-23, 2007 CL Glasgow, SCOTLAND SP British Soc Immunol C1 NCI, Basic Res Program, SAIC Frederick Inc, Canc Res Ctr,NIH, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Canc Res Ctr, NIH, Frederick, MD 21702 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 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 2007 VL 120 SU 1 BP 23 EP 23 PG 1 WC Immunology SC Immunology GA 134JT UT WOS:000244080000083 ER PT J AU Alderson, RF Smith, C Pastan, I Elvin, JG AF Alderson, R. F. Smith, C. Pastan, I. Elvin, J. G. TI CAT-3888 and CAT-8015: characterisation of immunotoxins for the treatment of CD22 related haematological malignancies SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-of-Immunology CY FEB 20-23, 2007 CL Glasgow, SCOTLAND SP British Soc Immunol C1 Cambridge Antibody Technol, Palo Alto, CA 94304 USA. NCI, Canc Res Ctr, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Cambridge Antibody Technol, Cambridge CB21 6GH, England. 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 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 2007 VL 120 SU 1 BP 87 EP 87 PG 1 WC Immunology SC Immunology GA 134JT UT WOS:000244080000337 ER PT J AU Wang, T Tian, LH Haino, M Gao, JL Lake, R Ward, Y Wang, HS Siebenlist, U Murphy, PM Kelly, K AF Wang, Tao Tian, Linhua Haino, Makoto Gao, Ji-Liang Lake, Ross Ward, Yvona Wang, Hongshan Siebenlist, Ulrich Murphy, Philip M. Kelly, Kathleen TI Improved antibacterial host defense and altered peripheral granulocyte homeostasis in mice lacking the adhesion class G protein receptor CD97 SO INFECTION AND IMMUNITY LA English DT Article ID LISTERIA-MONOCYTOGENES INFECTION; COLONY-STIMULATING FACTOR; KUPFFER CELL-INTERACTION; BONE-MARROW; NEUTROPHIL MIGRATION; EGF-TM7 RECEPTOR; DEFICIENT MICE; MOUSE CD97; G-CSF; LIVER AB CD97 is a member of the adhesion family of G protein-coupled receptors. Alternatively spliced forms of CD97 bind integrins alpha 5 beta 1 and alpha nu beta 3, decay accelerating factor, or dermatan sulfate. CD97 is expressed on myeloid cells at high levels and a variety of other cell types at lower levels. Little is known about the physiological function of CD97. To begin dissecting the function of CD97, we evaluated the immune response of CD97 null mice to systemic infection by Listeria monocytogenes. CD97 null mice were significantly more resistant to listeriosis than matched wild-type mice. A major determinant of the difference in survival appeared to be the comparatively more robust accumulation of granulocytes in the blood and in infected livers of CD97 null mice within 18 h of inoculation, correlating with a decrease in the number of bacteria. CD97 null mice also displayed a mild granulocytosis in the nonchallenged state. Because there is a strong suggestion that CD97 functions in an adhesive capacity, we examined the migratory properties of granulocytes in CD97 null mice. In chimeric animals, CD97 null and wild-type granulocytes migrated similarly, as determined by inflammation-induced emigration from the bone marrow and accumulation in the peritoneum. Granulocyte development in the bone marrow of CD97 null mice was comparable to that of wild-type mice, and CD97 deficiency did not appear to stimulate granulocytosis secondary to peripheral inflammation and resultant granulocyte colony-stimulating factor induction, unlike various other models of adhesion deficiencies. Our results suggest that CD97 plays a role in peripheral granulocyte homeostasis. C1 NCI, Cell & Canc Biol Branch, Ctr Canc Res, Gaithersburg, MD 20878 USA. NIAID, NIH, Host Def Lab, Gaithersburg, MD 20878 USA. NIAID, NIH, Immunoregulat Lab, Gaithersburg, MD 20878 USA. RP Kelly, K (reprint author), Bldg 37,Room 1068, Bethesda, MD 20892 USA. EM kkelly@helix.nih.gov FU Intramural NIH HHS NR 40 TC 24 Z9 24 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2007 VL 75 IS 3 BP 1144 EP 1153 DI 10.1128/IAI.00869-06 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 143PD UT WOS:000244733900008 PM 17158902 ER PT J AU Tilly, K Bestor, A Jewett, MW Rosa, P AF Tilly, Kit Bestor, Aaron Jewett, Mollie W. Rosa, Patricia TI Rapid clearance of Lyme disease spirochetes lacking OspC from skin SO INFECTION AND IMMUNITY LA English DT Article ID OUTER SURFACE-PROTEINS; BORRELIA-BURGDORFERI STRAINS; MAMMALIAN HOST; INFECTION; TICKS; EXPRESSION; CASSETTES; GENE; MICE AB We previously demonstrated that Borrelia burgdorferi requires OspC to colonize a mammalian host. To delineate this requirement, we analyzed the clearance of ospC mutant spirochetes and found that they were eliminated within 48 h. We conclude that B. burgdorferi uses OspC to resist innate host defenses immediately after transmission. C1 NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Tilly, K (reprint author), 903 S 4th St, Hamilton, MT 59840 USA. EM ktilly@niaid.nih.gov FU Intramural NIH HHS NR 24 TC 66 Z9 67 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2007 VL 75 IS 3 BP 1517 EP 1519 DI 10.1128/IAI.01725-06 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 143PD UT WOS:000244733900050 PM 17158906 ER PT J AU Simard, F Licht, M Besansky, NJ Lehmann, T AF Simard, Frederic Licht, Monica Besansky, Nora J. Lehmann, Tovi TI Polymorphism at the defensin gene in the Anopheles gambiae complex: Testing different selection hypotheses SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Anopheles gambiae; Africa; malaria; vector; arthropod; immunity; defensin; evolution; polymorphism; selection ID POLYMERASE CHAIN-REACTION; MALARIA VECTOR; PLASMODIUM-FALCIPARUM; IMMUNE-RESPONSE; MOSQUITO; PARASITE; POPULATION; ARABIENSIS; SEQUENCE; AFRICA AB Genetic variation in defensin, a gene encoding a major effector molecule of insects immune response was analyzed within and between populations of three members of the Anopheles gambiae complex. The species selected included the two anthropophilic species, An. gambiae and An. arabiensis and the most zoophilic species of the complex, An. quadriannulatus. The first species was represented by four populations spanning its extreme genetic and geographical ranges, whereas each of the other two species was represented by a single population. We found (i) reduced overall polymorphism in the mature peptide region and in the total coding region, together with specific reductions in rare and moderately frequent mutations (sites) in the coding region compared with non-coding regions, (ii) markedly reduced rate of non-synonymous diversity compared with synonymous variation in the mature peptide and virtually identical mature peptide across the three species, and (iii) increased divergence between species in the mature peptide together with reduced differentiation between populations of An. gambiae in the same DNA region. These patterns suggest a strong purifying selection on the mature peptide and probably the whole coding region. Because An. quadriannulatus is not exposed to human pathogens, identical mature peptide and similar pattern of polymorphism across species implies that human pathogens played no role as selective agents on this peptide. (c) 2006 Elsevier B.V. All rights reserved. C1 OCEAC, Yaounde, Cameroon. IRD, Yaounde, Cameroon. Ctr Dis Control & Prevent, Div Parasit Dis, Entomol Branch, Atlanta, GA 30341 USA. Univ Notre Dame, Dept Biol Sci, Ctr Trop Dis Res & Training, Notre Dame, IN 46556 USA. NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Simard, F (reprint author), OCEAC, POB 288, Yaounde, Cameroon. EM simard@ird.fr RI SIMARD, Frederic/J-9489-2016 OI SIMARD, Frederic/0000-0002-2871-5329 FU Intramural NIH HHS [Z99 AI999999] NR 44 TC 27 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD MAR PY 2007 VL 7 IS 2 BP 285 EP 292 DI 10.1016/j.megid.2006.11.004 PG 8 WC Infectious Diseases SC Infectious Diseases GA 138GP UT WOS:000244351400020 PM 17161659 ER PT J AU Kamau, L Munyekenye, GO Vulule, JM Lehmann, T AF Kamau, Luna Munyekenye, Godwil O. Vulule, John M. Lehmann, Tovi TI Evaluating genetic differentiation of Anopheles arabiensis in relation to larval habitats in Kenya SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Anopheles arabiensis; larval sites; gene flow; microsatellite loci; Kenya ID GAMBIAE COMPLEX; WESTERN KENYA; MALARIA VECTOR; POPULATION-STRUCTURE; COASTAL KENYA; AFRICA; MICROSATELLITE; TRANSMISSION; CULICIDAE; DIPTERA AB Anopheles arobiensis, an important vector of malaria in sub-Saharan Africa shows great versatility in utilizing a broad range of larval habitats. Most studies on the population genetic structure of this species have focused on adult mosquitoes collected mainly indoors and have found populations within relatively short distances to be panmictic. Various authors suggested that the incipient speciation between the chromosomal forms of Anopheles gambiae s.s. in West Africa involved adaptation to different habitats of larvae. To investigate if similar process occurs in An. arabiensis, we analyzed samples from four different larval habitats alongside a sample of adult mosquitoes collected indoors at eight microsatellite loci. We tested the hypothesis that An. arabiensis is subdivided into populations that are adapted to exploit different larval habitats. Overall, the level of genetic differentiation among the larval subpopulations was low with the mean pairwise Fst estimate based on information from all the loci being 0.0232 (P = 0.1691) although differentiation was only significant for comparisons between certain larval samples and the adult samples. In addition, there was strong evidence against subdivision among larvae when multilocus simultaneous assignment tests were used. These results do not provide sufficient support for the hypothesis that An. arabiensis is subdivided into subpopulations that specialize to exploit different larval habitats. (c) 2006 Published by Elsevier B.V. C1 Kenya Govt Med Res Ctr, Ctr Biotechnol Res & Dev, Nairobi 00200, Kenya. Kenya Govt Med Res Ctr, Ctr Vector Biol & Control Res, Kisumu 40100, Kenya. NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Kamau, L (reprint author), Kenya Govt Med Res Ctr, Ctr Biotechnol Res & Dev, POB 54840, Nairobi 00200, Kenya. EM lkamau@ke.cdc.gov NR 31 TC 6 Z9 7 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD MAR PY 2007 VL 7 IS 2 BP 293 EP 297 DI 10.1016/j.meegid.2006.11.006 PG 5 WC Infectious Diseases SC Infectious Diseases GA 138GP UT WOS:000244351400021 PM 17188943 ER PT J AU Oppenheim, J Yang, D AF Oppenheim, Joost Yang, De TI Characterization of endogenous peptides as alarmins SO INFLAMMATION RESEARCH LA English DT Meeting Abstract C1 NIH, NCI, LMI, CCR CIP, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD MAR PY 2007 VL 56 SU 2 BP S69 EP S69 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 151TO UT WOS:000245313900005 ER PT J AU Skarlatos, S AF Skarlatos, Sonia TI NHLBI/NIH resources for gene and cell-based therapies SO INFLAMMATION RESEARCH LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD MAR PY 2007 VL 56 SU 2 BP S197 EP S197 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 151TO UT WOS:000245313900290 ER PT J AU Eichacker, PQ Natanson, C AF Eichacker, Peter Q. Natanson, Charles TI Increasing evidence that the risks of rhAPC may outweigh its benefits SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID ACTIVATED PROTEIN-C; SEVERE SEPSIS; SAFETY; TRIAL C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 7D43, Bethesda, MD 20892 USA. EM peichacker@mail.cc.nih.gov NR 14 TC 44 Z9 48 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD MAR PY 2007 VL 33 IS 3 BP 396 EP 399 DI 10.1007/s00134-007-0556-8 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 140LJ UT WOS:000244506400002 PM 17325833 ER PT J AU Verbeek, R van Dongen, H Wawrousek, EF Amor, S van Noort, JM AF Verbeek, Richard van Dongen, Henrike Wawrousek, Eric F. Amor, Sandra van Noort, Johannes M. TI Induction of EAE by T cells specific for alpha B-crystallin depends on prior viral infection in the CNS SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE alpha B-crystallin; EAE; MS; SFV; T cells ID SEMLIKI-FOREST-VIRUS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; CANDIDATE AUTOANTIGEN; MICE; AUTOIMMUNITY; REPERTOIRE; EXPRESSION; SELF AB While myelin-reactive T cells are widely believed to play a pathogenic role in multiple sclerosis (MS), no substantial differences appear to exist in T-cell responses to myelin antigens between MS patients and healthy subjects. As an example, indistinguishable peripheral T-cell responses and serum antibody levels have been found in MS patients and healthy controls to alpha B-crystallin, a dominant antigen in MS-affected brain myelin. This suggests that additional factors are relevant in allowing myelin-reactive T cells to become pathogenic. In this study, we examined whether the inflammatory state of the CNS is relevant to the pathogenicity of alpha B-crystallin-specific T cells in mice. In normal mice, T-cell responses against alpha B-crystallin are limited by robust immunological tolerance. Reactive T cells were therefore generated in alpha B-crystallin-deficient mice, and these T cells were transferred into C57BL/6 recipients. While such a transfer in itself never induced any clinical signs of experimental autoimmune encephalomyelitis (EAE) in healthy recipient mice, acute EAE could be induced in animals that had been infected 7 days before with the avirulent A7(74) strain of Semliki Forest virus (SFV). SFV infection alone did not induce clinical disease, nor did it alter the expression levels of the target antigen. Our findings indicate that at least in mice, alpha B-crystallin-specific T cells can trigger EAE but only when prior viral infection has induced an inflammatory state in the CNS that helps recruit and activate T cells. C1 TNO, Dept Biosci, NL-2301 CE Leiden, Netherlands. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD USA. Biomed Primate Res Ctr, Dept Immunobiol, NL-2280 GH Rijswijk, Netherlands. RP van Noort, JM (reprint author), TNO, Dept Biosci, POB 2215, NL-2301 CE Leiden, Netherlands. EM hans.vannnoort@tno.nl RI Wawrousek, Eric/A-4547-2008; OI van Noort, Johannes/0000-0002-9060-5921 NR 30 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 2007 VL 19 IS 3 BP 277 EP 285 DI 10.1093/intimm/dxl144 PG 9 WC Immunology SC Immunology GA 139KA UT WOS:000244429500006 PM 17267417 ER PT J AU Butts, CL Shukair, SA Duncan, KM Bowers, E Horn, C Belyavskaya, E Tonelli, L Sternberg, EM AF Butts, Cherie L. Shukair, Shetha A. Duncan, Kristina M. Bowers, Eve Horn, Cash Belyavskaya, Elena Tonelli, Leonardo Sternberg, Esther M. TI Progesterone inhibits mature rat dendritic cells in a receptor-mediated fashion SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE antigen presenting/processing; dendritic cells; progesterone ID SEX-HORMONES; IMMUNE-RESPONSES; MATURATION; LYMPHOCYTES; ACTIVATION; SYSTEM; MOUSE; DIFFERENTIATION; GENERATION; EXPRESSION AB A variety of extraimmune system factors, including hormones, play a critical role in regulating immunity. Progesterone has been shown to affect immunity in rodents and humans, mainly at concentrations commensurate with pregnancy. These effects are primarily mediated via the progesterone receptor (PR), which acts as a transcription factor, although non-genomic effects of PR activation have been reported. In this study, we evaluated the effects of progesterone on rat dendritic cells (DCs) at ranges encompassing physiologic and pharmacologic concentrations to determine whether progesterone plays a role in modulating DC-mediated immune responses. DCs were derived by culturing rat bone marrow cells in granulocyte macrophage colony-stimulating factor and IL-4. Cells were analyzed for expression of PR using FACS analysis, real-time reverse transcriptase-PCR and fluorescent microscopy. Progesterone treatment of LPS-activated, mature bone marrow-derived dendritic cells (BMDCs) suppressed production of the pro-inflammatory response-promoting cytokines tumor necrosis factor-alpha and IL-1 beta in a dose-dependent manner but did not affect production of the pro-inflammatory response-inhibiting cytokine IL-10. Treatment of cells with progesterone also resulted in down-regulation of co-stimulatory molecule CD80 and MHC class II molecule RT1B expression. In addition, progesterone inhibited DC-stimulated proliferation of T cells. Suppression of pro-inflammatory response-promoting cytokine production by progesterone was prevented using the PR antagonist RU486. There was no dose-dependent effect of progesterone treatment on immature DC capacity to take up antigenic peptide. These data indicate that progesterone directly inhibits mature rat BMDC capacity to drive pro-inflammatory responses. This mechanism could contribute to or account for some of the differential expression of autoimmune/inflammatory disease in females. C1 NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM sternbee@mail.nih.gov OI Horn, Jeremy/0000-0003-0344-5913 FU Intramural NIH HHS NR 44 TC 69 Z9 80 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 2007 VL 19 IS 3 BP 287 EP 296 DI 10.1093/intimm/dxl145 PG 10 WC Immunology SC Immunology GA 139KA UT WOS:000244429500007 PM 17289656 ER PT J AU Wu, CF Bi, XL Yang, JY Zhan, JY Dong, YX Wang, JH Wang, JM Zhang, RW Li, M AF Wu, Chun Fu Bi, Xiu Li Yang, Jing Yu Zhan, Jia Yang Dong, Ying Xu Wang, Jin Hui Wang, Ji Min Zhang, Ruiwen Li, Xian TI Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE ginsenosides; protopanaxatriols; protopanaxadiols; NO; TNF-alpha; microglia ID NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; PROTEIN-KINASE; KAPPA-B; GINSENG; LIPOPOLYSACCHARIDE; MACROPHAGES; INDUCTION; APOPTOSIS; CELLS AB Ginsenosides, the main active components of ginseng, have been reported to exert neuroprotective effects in the central nervous system. In this report, the effects of ginsenoside-Rd and -Rb2, two protopanaxadiols, and ginsenoside-Rg1 and -Re, two protopanaxatriols, on the production of nitric oxide (NO) and TNF-alpha (TNF-alpha) by lipopolysaccharide (LPS)-activated N9 microglial cells were studied. All ginsenosides studied potently suppressed TNF-alpha production in LPS-activated N9 cells. Ginsenoside-Rgl and -Re, but not ginsenoside-Rb2 and -Rd, inhibited the production of NO in LPS-activated N9 cells. Ginsenosides inhibited the phosphorylation of c-Jun NH2-terminal kinase (JNK), c-Jun and extracellular signal-regulated kinase (ERK), The findings herein show that the inhibition of LPS-induced ERK1/2 and JNK activation may be a contributing factor to the main mechanisms by which ginsenosides inhibits RAW264.7. To clarify the mechanistic basis for its ability to inhibit TNF-a and NO induction, the effect of ginsenosides on transcription factor NF-kappa B protein level was also examined. These activities were associated with the down-regulation of inhibitor kappa B (I kappa B). These findings suggest that the inhibition of LPS-induced NO formation and TNF-alpha production in microglia by ginsenosides is due to its inhibition of NF-kappa B, which may be the mechanistic basis for the anti-inflammatory effects of ginsenosides. The significant suppressive effects of ginsenosides on proinflammatory responses of microglia implicate their therapeutic potential in neurodegenerative diseases accompanied by microglial activation. (c) 2006 Elsevier B.V. All rights reserved. C1 Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China. Shenyang Pharmaceut Univ, Dept Chem Nat Prod, Shenyang 110016, Peoples R China. NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21701 USA. Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL USA. RP Wu, CF (reprint author), Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China. EM wucf@syphu.edu.cn NR 27 TC 73 Z9 78 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD MAR PY 2007 VL 7 IS 3 BP 313 EP 320 DI 10.1016/j.intimp.2006.04.021 PG 8 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 142AS UT WOS:000244621400005 PM 17276889 ER PT J AU Landgren, O Pfeiffer, RM Stewart, L Gridley, G Mellemkjaer, L Hemminki, K Goldin, LR Travis, LB AF Landgren, Ola Pfeiffer, Ruth M. Stewart, Laveta Gridley, Gloria Mellemkjaer, Lene Hemminki, Kari Goldin, Lynn R. Travis, Lois B. TI Risk of second malignant neoplasms among lymphoma patients with a family history of cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE Hodgkin lymphoma non-Hodgkin lymphoma; chronic lymphocytic leukemia; susceptibility DNA repair mechanisms; second neoplasm; family history; familial aggregation ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; LUNG-CANCER; YOUNG-WOMEN; DISEASE; RADIOTHERAPY; THERAPY; TUMORS; CHEMOTHERAPY; DATABASE AB Radiotherapy and chemotherapy are known risk factors for second cancers after lymphoma. The role of genetic influences, however, remains largely unknown. We assessed risk of second cancers associated with family history of any cancer in 41,181 patients with Hodgkin lymphoma (HL) (n = 7,476), non-Hodgkin lymphoma (NHL) (n = 25,941), or chronic lymphocytic leukemia (CLL) (n = 7,764), using a large population-based database. Family history of cancer was based on a diagnosis of any cancer in 110,862 first-degree relatives. We found increased relative risk (RR) (1.81, 95% confidence interval (CI): 1.04-3.16) of breast cancer among HL patient with positive (vs. negative) family history of cancer. Among CLL patients with positive (vs. negative) family history of cancer, we observed elevated risks of bladder (RR = 3.53, 95% CI: 1.31-9.55) and prostate cancer (RR = 2.15, 95% CI: 1.17-3.94). For NHL patients with positive (vs. negative) family history of cancer, we observed non-significantly increased risk of non-melanoma skin cancer (RR = 1.94, 95% CI. 0.86-4.38) and lung cancer (RR = 1.99, 95% CI: 0.73-5.39). Our observations suggest that genetic factors, as measured by positive family history of cancer, may be influential risk-factors for selected second tumors following lymphoproliferative disorders. (c) 2006 Wiley-Liss, Inc. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. Karolinska Inst, Dept Biosci, Novum, S-10401 Stockholm, Sweden. German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. RP Landgren, O (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Bldg EPS Room 7110, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 35 TC 24 Z9 24 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 MAR 1 PY 2007 VL 120 IS 5 BP 1099 EP 1102 DI 10.1002/ijc.22414 PG 4 WC Oncology SC Oncology GA 131TK UT WOS:000243892700020 PM 17131330 ER PT J AU Pereira, MA Tao, LH Liu, Y Li, L Steele, VE Lubet, RA AF Pereira, Michael A. Tao, Lianhui Liu, Yue Li, Long Steele, Vernon E. Lubet, Ronald A. TI Modulation by budesonide of DNA methylation and mRNA expression in mouse lung tumors SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE budesonide; biomarkers; chemoprevention; DNA hypomethylation; lung cancer; mRNA expression; mouse lung tumors ID A/J MICE; PULMONARY CARCINOGENESIS; AEROSOLIZED BUDESONIDE; HYPOMETHYLATION; CANCER; CHEMOPREVENTION; PROGRESSION AB Biomarkers are being developed that can aid in the evaluation of cancer therapeutic and chemopreventive drugs. Two suggested biomarkers found in mouse lung tumors are DNA hypomethylation and alterations in mRNA expression of genes, such as 18S RNA, caspase 3, cyclin B2, cyclin E1, iNOS and survivin. Budesonide is very efficacious in preventing lung tumors in mice, so that its ability to modulate biomarkers in lung tumors was determined. Lung tumors were induced by vinyl carbamate in female strain A/J mice. Budesonide (2.0 mg/kg diet) was administered for 21 7 and 21 days or for 14 days followed by a 7-days' holding period prior to the killing of the mice at week 7. After 2 days of budesonide treatment, the size of the lung tumors was reduced. Tumor size continued to decrease during the 21 days of treatment. In the tumors, 2 days of treatment resulted in (i) increased methylation of DNA, reversing DNA hypomethylation, (ii) increased expression of 18S RNA and (iii) decreased mRNA expression of caspase 3, cyclin B2, cyclin El, iNOS and survivin. Termination of budesonide treatment at 7 days prior to killing did not affect the size of the tumors, but did result in increased mRNA expression of the 5 genes, approaching the expression level in tumors from control mice. Hence, budesonide rapidly decreased the size of lung tumors, reversed DNA hypomethylation and modulated mRNA expression of genes; with the molecular alterations requiring continued treatment with the drug for maintenance. (c) 2006 Wiley-Liss, Inc. C1 Ohio State Univ, Coll Med, Div Hematol & Oncol, Columbus, OH 43210 USA. NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Pereira, MA (reprint author), Ohio State Univ, Coll Med & Publ Hlth, Dept Internal Med, 300 W 10th Ave,1148 CHRI, Columbus, OH 43210 USA. EM michael.pereira@osumc.edu NR 17 TC 10 Z9 10 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 MAR 1 PY 2007 VL 120 IS 5 BP 1150 EP 1153 DI 10.1002/ijc.22468 PG 4 WC Oncology SC Oncology GA 131TK UT WOS:000243892700028 PM 17163412 ER PT J AU Morgan, RJ Synold, TW Gandara, D Muggia, F Scudder, S Reed, E Margolin, K Raschko, J Leong, L Shibata, S Tetef, M Vasilev, S McGonigle, K Longmate, J Yen, Y Chow, W Somlo, G Carroll, M Doroshow, JH AF Morgan, R. J., Jr. Synold, T. W. Gandara, D. Muggia, F. Scudder, S. Reed, E. Margolin, K. Raschko, J. Leong, L. Shibata, S. Tetef, M. Vasilev, S. McGonigle, K. Longmate, J. Yen, Y. Chow, W. Somlo, G. Carroll, M. Doroshow, J. H. TI Phase II trial of carboplatin and infusional cyclosporine with alpha-interferon in recurrent ovarian cancer: a California Cancer Consortium Trial SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE chemomodulation; chemotherapy; phase II ID REFRACTORY GYNECOLOGIC CANCER; MULTIDRUG-RESISTANCE; ONCOLOGY-GROUP; WHOLE-BLOOD; DRUG-RESISTANCE; CARCINOMA CELLS; MODULATION; CISPLATIN; EXPRESSION; ASSAY AB The purpose of this study was to estimate the response rate of 26-h continuous infusion cyclosporine A (CSA) combined with carboplatin (CBDCA) and subcutaneous alpha-interferon (IFN), in recurrent ovarian cancer (OC), and to measure their effects on CBDCA pharmacokinetics. OC patients relapsing following platinum-based chemotherapy received CBDCA area under the curve (AUC 3) with CSA and IFN, every 3 weeks. The pharmacokinetics of CSA and CBDCA were determined in a subset of patients. Thirty patients received 84 courses of therapy. Three partial responses were observed. Nine patients were stable for > 4 months. Toxicity was similar to that observed in our previously reported phase I study and consisted of myelosuppression, nausea, vomiting, and headache. The mean end of infusion CSA level (high-performance liquid chromatographic assay [HPLC]) was 1109 +/- 291 mu g/mL (mean +/- SD). CBDCA pharmacokinetics revealed a measured AUC of 3.61 versus a targeted AUC of 3, suggesting a possible effect of IFN on CBDCA levels versus errors in the estimation of CBDCA clearance using measured creatinine clearance. Steady-state levels of > 1 mu g/mL CSA (HPLC assay) are achievable in vivo. Insufficient clinical resistance reversal was observed in this study to warrant further investigation of this combination. C1 City Hope Natl Med Ctr, Div Med Oncol & Therapeut Res, Duarte, CA 91010 USA. Univ Calif Davis, Dept Med Oncol, Davis, CA 95616 USA. Univ So Calif, Dept Med Oncol, Los Angeles, CA USA. NCI, Med Branch, Bethesda, MD 20892 USA. City Hope Natl Med Ctr, Dept Biostat, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Dept Gynecol Oncol, Duarte, CA 91010 USA. RP Morgan, RJ (reprint author), City Hope Natl Med Ctr, Div Med Oncol & Therapeut Res, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM rmorgan@coh.org OI Longmate, Jeffrey/0000-0002-0869-7928; Muggia, Franco/0000-0003-0703-9146 FU NCI NIH HHS [CA 33572, CA 62505, CA 63265] NR 25 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD MAR-APR PY 2007 VL 17 IS 2 BP 373 EP 378 DI 10.1111/j.1525-1438.2007.00787.x PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 145SR UT WOS:000244885300009 PM 17362315 ER PT J AU DelParigi, A Chen, K Salbe, AD Hill, JO Wing, RR Reiman, EM Tataranni, PA AF DelParigi, A. Chen, K. Salbe, A. D. Hill, J. O. Wing, R. R. Reiman, E. M. Tataranni, P. A. TI Successful dieters have increased neural activity in cortical areas involved in the control of behavior SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE human brain; dietary restraint; successful dieting; prefrontal cortex ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX; BRAIN RESPONSES; WEIGHT-LOSS; SATIATION; HUNGER; HUMANS; PLEASANTNESS; ACTIVATION AB Objective: To investigate whether dietary restraint, a landmark of successful dieting, is associated with specific patterns of brain responses to the sensory experience of food and meal consumption. Design and subjects: Cross-sectional study of the brain's response to the sensory experience of food and meal consumption in nine successful dieters ( age: 38 +/- 7 years, body fat (%): 28 +/- 3) and 20 non-dieters ( age: 31 +/- 9 years, body fat (%): 33 +/- 9), all women. Measurements: Changes in brain activity in response to the sensory experience of food and meal consumption were assessed by using positron emission tomography and O-15 water as a radiotracer. Body fatness was assessed by dual X-ray absorptiometry. Subjective ratings of hunger and fullness were measured by visual analogue scale. Dietary restraint, disinhibition and hunger were assessed by the Three Factor Eating Questionnaire. Results: Successful dieters had a significantly higher level of dietary restraint compared to non-dieters. In response to meal consumption, successful dieters had a greater activation in the dorsal prefrontal cortex ( DPFC), dorsal striatum and anterior cerebellar lobe as compared to non-dieters. In response to the same stimulation, the orbitofrontal cortex (OFC) was significantly more activated in non-dieters as compared to successful dieters. Dietary restraint was positively correlated with the response in the DPFC and negatively with the response in the OFC. The responses in the DPFC and OFC were negatively intercorrelated. Conclusion: Cortical areas involved in controlling inappropriate behavioral responses, such as the DPFC, are particularly activated in successful dieters in response to meal consumption. The association between the degree of dietary restraint and the coordinated neural changes in the DPFC and OFC raises the possibility that cognitive control of food intake is achieved by modulating neural circuits controlling food reward. C1 NIH, Obes & Diabet Clin Res Sect, Phoenix, AZ USA. Banner Good Samaritan Med Ctr, Banner Good Samaritan PET Ctr, Phoenix, AZ USA. Univ Colorado, Ctr Hlth Sci, Ctr Human Nutr, Denver, CO 80202 USA. Miriam Hosp, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA. RP DelParigi, A (reprint author), John B Pierce Fdn Lab, 290 Congress Ave, New Haven, CT 06519 USA. EM adelparigi@jbpierce.org RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 NR 37 TC 117 Z9 119 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAR PY 2007 VL 31 IS 3 BP 440 EP 448 DI 10.1038/sj.ijo.0803431 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 140CL UT WOS:000244480100008 PM 16819526 ER PT J AU Maurovich-Horvat, P Massaro, J Fox, CS Moselewski, F O'Donnell, CJ Hoffmann, U AF Maurovich-Horvat, P. Massaro, J. Fox, C. S. Moselewski, F. O'Donnell, C. J. Hoffmann, U. TI Comparison of anthropometric, area- and volume-based assessment of abdominal subcutaneous and visceral adipose tissue volumes using multi-detector computed tomography SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE abdominal obesity; adipose tissue quantification; computed tomography ID CARDIOVASCULAR RISK-FACTORS; MAGNETIC-RESONANCE; INSULIN-RESISTANCE; FAT DISTRIBUTION; VASCULAR-DISEASE; BODY-COMPOSITION; FOLLOW-UP; OBESITY; MEN; WOMEN AB Purpose: Cross-sectional imaging may enable accurate localization and quantification of subcutaneous and visceral adipose tissue. The reproducibility of multi-detector computed tomography (MDCT)-based volumetric quantification of abdominal adipose tissue and the ability to depict age-and gender-related characteristics of adipose tissue deposition have not been reported. Methods: We evaluated a random subset of 100 Caucasian subjects ( age range: 37 - 83 years; 49% women) of the Framingham Heart Study offspring cohort who underwent MDCT scanning. Two readers measured subcutaneous and visceral adipose tissue volumes (SAV and VAV; cm(3)) and areas (SAA and VAA; cm(2)) as well as abdominal sagital diameter (SD) and waist circumference ( WC). Results: Inter-reader reproducibility was excellent ( relative difference: -0.34 +/- 0.52% for SAV and 0.59 +/- 0.93% for VAV, intraclass correlation (ICC) = 0.99 each). The mean SAA/VAA ratio was significantly different from the mean SAV/VAV ratio(2.0 +/- 1.2 vs 1.7 +/- 0.9; P < 0.001). The ratio of SAV/VAV was only weakly inversely associated with SD ( ICC = -0.32, P = 0.01) and not significantly associated with WC ( ICC = -0.14, P = 0.14) or body mass index ( ICC = -0.17, P = 0.09). The mean SAV/VAV ratio was significantly different between participants < 60 vs 460 years (1.9 +/- 1.0 vs 1.5 +/- 0.7; P < 0.001) and between men and women (1.2 +/- 0.5 vs 2.2 +/- 0.9; P < 0.001). Conclusion: This study demonstrates that MDCT-based volumetric quantification of abdominal adipose tissue is highly reproducible. In addition, our results suggest that volumetric measurements can depict age- and gender-related differences of visceral and subcutaneous abdominal adipose tissue deposition. Further research is warranted to assess whether volumetric measurements may substantially improve the predictive value of obesity measures for insulin resistance, type 2 diabetes mellitus and other diseases. C1 Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Semmelweis Univ, Dept Cardiovasc Surg, H-1085 Budapest, Hungary. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, 165 Charles River Plaza 400, Boston, MA 02114 USA. EM uhoffman@partners.org OI Massaro, Joseph/0000-0002-2682-4812; Maurovich-Horvat, Pal/0000-0003-0885-736X FU NHLBI NIH HHS [N01-HC-25195] NR 46 TC 137 Z9 143 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAR PY 2007 VL 31 IS 3 BP 500 EP 506 DI 10.1038/sj.ijo.0803454 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 140CL UT WOS:000244480100016 PM 16953256 ER PT J AU Touge, H Chikumi, H Igishi, T Kurai, J Makino, H Tamura, Y Takata, M Yoneda, K Nakamoto, M Suyama, H Gutkind, JS Shimizu, E AF Touge, Hirokazu Chikumi, Hiroki Igishi, Tadashi Kurai, Jun Makino, Haruhiko Tamura, Yoshisato Takata, Miyako Yoneda, Kazuhiko Nakamoto, Masaki Suyama, Hisashi Gutkind, J. Silvio Shimizu, Eiji TI Diverse activation states of RhoA in human lung cancer cells: Contribution of G protein coupled receptors SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE RhoA; lung cancer; YM-254890; G protein coupled receptors; in vivo Rho guanine nucleotide exchange assay ID GTP-BINDING PROTEIN; NUCLEOTIDE EXCHANGE FACTORS; AUTOCRINE GROWTH-FACTORS; SWISS 3T3-CELLS; SIGNAL-TRANSDUCTION; PEPTIDE RECEPTOR; TYROSINE PHOSPHORYLATION; IN-VIVO; BOMBESIN; GTPASES AB Rho GTPases play an essential role in the control of various cellular functions. Accumulating evidence suggests that RhoA overexpression contributes to human cancer development. However, the activation states of RhoA are poorly defined in cancer cells. In this study, we examined both the expression levels and the activation states of RhoA in various lung cancer cells by quantitative real-time reverse transcriptase-polymerase chain reaction and in vivo Rho guanine nucleotide exchange assay, respectively. Moreover, we dissected the signaling pathway from the cell surface receptors to RhoA using a broad-spectrum G protein coupled receptor (GPCR) antagonist, [D-Arg(1),D-Trp(5,7,9),Leu(11)]Substance P (SP), and a recently reported G alpha(q/11)-selective inhibitor, YM-254890. We found that RhoA was expressed highly in large cell carcinoma cells but only weakly in adenocarcinoma cells. The activation states of RhoA are considerably different from its expression profiles. We found that four of six small cell lung carcinoma (SCLC) cell lines exhibited a moderate to high activation rate of RhoA. The addition of [D-Arg(1),D-Trp(5,7,9),Leu(11)]SP reduced RhoA activity by almost 60% in H69 SCLC cells. The addition of YM-254890 had no effect on RhoA activity in H69 cells. Our results suggest that RhoA is activated in various lung cancer cells independent of its expression levels, and the high activation state of RhoA in SCLC cells mainly depends on a neuroendocrine peptide autocrine system which signals through G alpha(12) coupled GPCR to RhoA. This study provides new insights into RhoA signaling in lung cancer cells and may help in developing novel therapeutic strategies against lung cancer. C1 Tottori Univ, Fac Med, Dept Multidisciplinary Internal Med, Div Med Oncol & Mol Respirol, Yonago, Tottori 6830805, Japan. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Chikumi, H (reprint author), Tottori Univ, Fac Med, Dept Multidisciplinary Internal Med, Div Med Oncol & Mol Respirol, 36-1 Nishi Machi, Yonago, Tottori 6830805, Japan. EM chikumi@grape.med.tottori-u.ac.jp RI Gutkind, J. Silvio/A-1053-2009 NR 36 TC 10 Z9 12 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 2007 VL 30 IS 3 BP 709 EP 715 PG 7 WC Oncology SC Oncology GA 136IO UT WOS:000244216000020 PM 17273773 ER PT J AU Jones, FR Miller, G Gadea, N Meza, R Leon, S Perez, J Lescano, AG Pajuelo, J Caceres, CF Klausner, JD Coates, TJ AF Jones, F. R. Miller, G. Gadea, N. Meza, R. Leon, S. Perez, J. Lescano, A. G. Pajuelo, J. Caceres, C. F. Klausner, J. D. Coates, T. J. CA NIMH Collaborative HIV STI Prevent TI Prevalence of bacterial vaginosis among young women in low-income populations of coastal Peru SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE bacterial vaginosis; socially marginalized populations; sexually transmitted infections; human immunodeficiency virus; Peru ID VAGINAL FLORA; RISK-FACTOR; INFECTION; MICROBIOLOGY; EPIDEMIOLOGY; ASSOCIATION; DIAGNOSIS; CRITERIA; BVBLUE; BIRTH AB The goal of this study was to determine the prevalence of bacterial vaginosis (BV) in Peruvian women from socioeconomically deprived populations and to determine the association between BV and risk factors for sexually transmitted diseases (STDs). Women were administered an epidemiologic survey to determine sexual risk behaviour and they provided biological samples to test for BV and STDs. The prevalence of BV was high (27%) and was significantly associated with having a bacterial STD or trichomoniasis. Age, marital status, and a history of sex work, but not of sexual experience, frequency of intercourse, and unprotected intercourse, were associated with BV. As BV may be a marker for STDs, screening for STDs should be performed in individuals with BV to promote early detection and treatment of co-infecting sexually transmitted pathogens. C1 Naval Med Res Ctr Detachment, Bacterial Dis Program, Lima, Peru. Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA. Univ Peruana Cayetano Heredia, Lima, Peru. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. NIMH, Multisite Int Grp, Bethesda, MD 20892 USA. RP Jones, FR (reprint author), USN, Med Res Ctr, Biol Def Res Directorate, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM jonesf@nmrc.navy.mil RI Lescano, Andres/B-8479-2008; OI Lescano, Andres/0000-0001-9779-633X; Caceres, Carlos/0000-0002-8101-0790 FU NIMH NIH HHS [U10 MH061536, U10 MH61536] NR 35 TC 12 Z9 16 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD MAR PY 2007 VL 18 IS 3 BP 188 EP 192 DI 10.1258/095646207780132505 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 155OK UT WOS:000245587000011 PM 17362553 ER PT J AU Vijayasarathy, C Takada, Y Zeng, Y Bush, RA Sieving, PA AF Vijayasarathy, Camasamudram Takada, Yuichiro Zeng, Yong Bush, Ronald A. Sieving, Paul A. TI Retinoschisin is a peripheral membrane protein with affinity for anionic phospholipids and affected by divalent cations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID X-LINKED RETINOSCHISIS; JUVENILE RETINOSCHISIS; EXTRACELLULAR-MATRIX; CELL-ADHESION; MULLER CELLS; PHOTORECEPTOR; EXPRESSION; DISCOIDIN; BINDING; RETINA AB PURPOSE. Retinoschisin (RS) is a retina-specific, secreted protein implicated in X-linked juvenile retinoschisis and essential for the structural and functional integrity of the retina. This biochemical characterization and ultrastructural localization of RS in intact murine retina was performed to further understanding of the molecular basis of its function. METHODS. Subcellular fractions and fractions enriched in photoreceptor inner and outer segments were prepared from mouse retina by differential or density gradient ultracentrifugation. Immunoblot analysis was used to assess the expression of RS in various subcellular compartments and its fractionation into soluble phase on treatment of retinal cell membranes with several solubilizing reagents. RS-lipid interactions were evaluated by a protein-lipid overlay assay that used wild-type and mutant forms of RS discoidin domain glutathione S-transferase (GST) fusion proteins. The subcellular localization of RS in mouse retina was visualized by pre-embedding immunogold electron microscopy. Ultrastructure was evaluated by transmission electron microscopy. RESULTS. RS was intimately associated with cell membranes of the retina. It was found to cluster on the outer leaflet of the plasma membrane of the photoreceptor inner segments, which synthesize and secrete it. It was released from the membrane at high pH, which is characteristic of a peripheral membrane protein. It was extracted from the membrane by the nonionic detergent NP-40, together with glycerophospholipids. Protein-lipid overlay assays indicated a preferential interaction between RS and anioic phospholipids. Extraction of RS from the membrane was inhibited by divalent cations. Photoreceptor inner segment morphology was markedly affected in RS-/y mice, which failed to express RS protein. CONCLUSIONS. RS in intact retina is a peripheral membrane protein. Although distributed over the two membrane faces, RS is associated primarily with the outer leaflet of the inner segment plasma membrane through anionic phospholipids and divalent cations. RS's localization in photoreceptors and its biochemical properties suggest a functional role locally, at the site of secretion and membrane adhesion, in maintaining the photoreceptor inner segment stability and architecture. C1 NEI, STRRMD, NIH, Bethesda, MD 20892 USA. NIDCD, STRRMD, NIH, Bethesda, MD USA. RP Sieving, PA (reprint author), NEI, STRRMD, NIH, 31 Ctr Dr,Bldg 31,Room 6A03,MSC 2510, Bethesda, MD 20892 USA. EM camasamv@nidcd.nih.gov FU Intramural NIH HHS NR 32 TC 37 Z9 37 U1 1 U2 5 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 MAR PY 2007 VL 48 IS 3 BP 991 EP 1000 DI 10.1167/iovs.06-0915 PG 10 WC Ophthalmology SC Ophthalmology GA 142YF UT WOS:000244686500006 PM 17325137 ER PT J AU Ross, RJ Bojanowski, CM Wang, JJ Chew, EY Rochtchina, E Ferris, FL Mitchell, P Chan, CC Tuo, J AF Ross, Robert J. Bojanowski, Christine M. Wang, Jie Jin Chew, Emily Y. Rochtchina, Elena Ferris, Frederick L., III Mitchell, Paul Chan, Chi-Chao Tuo, Jingsheng TI The LOC387715 polymorphism and age-related macular degeneration: Replication in three case-control samples SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID COMPLEMENT FACTOR-H; BLUE-MOUNTAINS EYE; GENETIC ASSOCIATION; GENOMEWIDE-SCAN; RISK-FACTORS; EXTENDED FAMILIES; CHROMOSOME 10Q26; APOLIPOPROTEIN-E; COMMON VARIANTS; VISUAL-LOSS AB PURPOSE. Age-related macular degeneration (AMD) is a multifactorial blinding disease in the elderly. LOC387715 harbors single-nucleotide polymorphism that has an association with AMD. This study was conducted to confirm the association between LOC387715 and AMD and to refine estimates of the impact of this gene variation in using samples from three studies: an Australian population-based study and two U.S. clinic-based case-control studies. METHODS. Cases and controls were collected from a National Eye Institute (NEI) clinical protocol (n = 240), the Age-Related Eye Disease Study (AREDS; n = 488), and the Blue Mountains Eye Study (BMES; n = 851). After DNA extraction, subjects were genotyped for the LOC387715 Ala69Ser polymorphism (rs10490924). RESULTS. The combined NEI and AREDS samples yielded odds ratios (ORs) of 2.61 (95% CI 1.89-3.61, P = 1.42 X 10(-9)) and 8.59 (95% CI 4.49-16.5, P = 3.56 x 10(-13)) for the heterozygous and homozygous risk alleles, respectively. The corresponding odds ratios in the BMES sample were 1.69 (95% CI: 1.25-2.28, P = 0.0007) and 2.20 (95% CI: 1.05-4.62, P = 0.038) for the heterozygous and homozygous groups. Neither set of samples showed statistically significant interaction with smoking, although there appeared to be a trend of interaction between smoking and LOC387715 for risk of advanced AMD. CONCLUSIONS. Although these data from three case-control samples support an AMD genetic risk marker harbored within LOC387715, the nested case-control data from the population-based BMES samples showed lower estimates than from the clinic-based samples. This may be because the BMES samples consisted of largely early AMD cases while the clinic-based AMD samples consisted exclusively of advanced cases. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. Univ Sydney, Ctr Vis Res, Dept Ophthalmol, Westmead, NSW 2145, Australia. Univ Sydney, Westmead Millennium Inst, Westmead, NSW 2145, Australia. RP Tuo, J (reprint author), NEI, Immunol Lab, NIH, 10-10N103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tuoj@nei.nih.gov RI Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; OI Wang, Jie Jin/0000-0001-9491-4898; Tuo, Jingsheng/0000-0002-1372-7810 FU Intramural NIH HHS [ZIA EY000489-01, Z01 EY000418-04, Z99 EY999999] NR 43 TC 51 Z9 51 U1 0 U2 0 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 MAR PY 2007 VL 48 IS 3 BP 1128 EP 1132 DI 10.1167/iovs.06-0999 PG 5 WC Ophthalmology SC Ophthalmology GA 142YF UT WOS:000244686500025 PM 17325155 ER PT J AU Watts, DH Li, D Handelsman, E Tilson, H Paid, MV Toca, M Vajaranant, M Diaz, C Tuomala, R Thompson, B AF Watts, D. Heather Li, Daner Handelsman, Ed Tilson, Hugh Paid, Mai-V Toca, Marc Vajaranant, Mark Diaz, Clemente Tuomala, Ruth Thompson, Bruce TI Assessment of birth defects according to maternal therapy among infants in the women and infants transmission study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretrovirals; birth defects; HIV; pregnancy ID ANTIRETROVIRAL THERAPY; HIV-1-INFECTED WOMEN; INFECTED WOMEN; HYPOSPADIAS; EXPOSURE; SURVEILLANCE; PREGNANCY; RISK; COMBINATION; PREVENTION AB Background: To evaluate rate and types of birth defects according to timing of antiretroviral exposure among babies born to HIV-infected women. Methods: Anomalies identified during the prenatal, neonatal, or follow-up period were classified using criteria of the Antiretroviral Pregnancy Registry. Antiretroviral use was classified as none, second or third trimester only, or first trimester. Results: From January 1, 1990 through June 30, 2004, 2527 live births (LBs) occurred to 2353 women. Defects were identified in 90 babies for a rate of 3.56 defects per 100 LBs. The rate of defects was 3.19 per 100 LBs (24 of 752 LBs) with first-trimester antiretroviral exposure, 3.54 per 100 LBs (41 of 1158 LBs) with exposure later in pregnancy, and 4.05 of 100 LBs (25 of 617 LBs) with no antiretroviral use. Only genital abnormalities, specifically hypospadias, were significantly increased among babies born to women with first-trimester exposure to antiretrovirals (7 of 382 male LBs) compared with the 2 other groups (2 of 892 male LBs; P = 0.007). On logistic regression, use of zidovudine in the first trimester was associated with hypospadias (adjusted odds ratio = 10.68, 95% confidence interval: 2.11 to 54.13; P = 0.004). Conclusions: In general, data were reassuring, although the frequency of exposure to newer agents was limited. The increased risk of hypospadias after first-trimester exposure must be explored, because this association has not been detected previously. C1 NICHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Infants, NIH, Bethesda, MD 20892 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Univ N Carolina, Chapel Hill, NC USA. Baylor Coll Med, Houston, TX 77030 USA. Columbia Univ, New York, NY USA. Univ Illinois, Chicago, IL 60680 USA. Univ Puerto Rico, San Juan, PR 00936 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Watts, DH (reprint author), NICHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Infants, NIH, 6100 Execut Blvd,Room 4B11,MSC 7510, Bethesda, MD 20892 USA. EM heather.watts@nih.hhs.gov FU NCRR NIH HHS [RR 00188, RR 00645]; NIAID NIH HHS [U01 AI 34841, 1U01 AI 50274-01, N01 AI 85339, U01 AI 34858]; NICHD NIH HHS [U01 HD 41983, U01 HD 36117]; NIDA NIH HHS [U01 DA 15054, U01 DA 15053] NR 27 TC 37 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2007 VL 44 IS 3 BP 299 EP 305 DI 10.1097/QAI.0b013e31802e2229 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 141WT UT WOS:000244610400008 PM 17159659 ER PT J AU Malope, BI Pfeiffer, RM Mbisa, G Stein, L Ratshikhopha, EM O'Connell, DL Sitas, F MacPhail, P Whitby, D AF Malope, Babatyi I. Pfeiffer, Ruth M. Mbisa, Georgina Stein, Lara Ratshikhopha, Edith M. O'Connell, Dianne L. Sitas, Freddy MacPhail, Patrick Whitby, Denise TI Transmission of Kaposi sarcoma-associated herpesvirus between mothers and children in a South African population SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE coinfection; HIV; human herpesvirus-8; Kaposi sarcoma-associated herpesvirus ID HUMAN-HERPESVIRUS-8 INFECTION; TO-CHILD; DNA-SEQUENCES; UGANDAN CHILDREN; PREVALENCE; PERFORMANCE; HHV-8; HIV AB Background: To assess whether Kaposi sarcoma-associated herpesvirus (KSHV) with or without HIV coinfection in South African mothers is associated with higher KSHV seropositivity in their children. Methods: We tested sera from 1287 South African children and 1179 mothers using assays for KSHV lytic K8.1 and latent ORF73 antigens. We computed odds ratios (ORs) and 95% confidence intervals (CIs) to assess associations between KSHV serostatus and risk factors. Results: KSHV seroprevalence was 15.9% (204 of 1287 subjects) in children and 29.7% (350 of 1179 subjects) in mothers. The risk of KSHV seropositivity was significantly higher in children of KSHV-seropositive mothers compared with those of KSHV-seronegative mothers. The HIV status of mothers was marginally associated with an increased risk of KSHV seropositivity in their children (OR = 1.6, 95% CI: 1.0 to 2.6; P = 0.07). KSHV seroprevalence was significantly higher in HIV-infected subjects (P = 0.0005), and HIV-infected subjects had significantly higher lytic and latent KSHV antibody levels than HIV-negative subjects. Conclusions: The risk of acquisition of KSHV was higher among children of KSHV-seropositive mothers. Although KSHV seroprevalence was significantly higher in children and mothers who were infected with HIV, the HIV status of the mother was only marginally associated with an increased risk of KSHV seropositivity in the child. C1 NCI, Viral Epidemiol Sect, AIDS Vaccine Program, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. NSW Canc Council, Div Res, Sydney, NSW, Australia. Natl Hlth Lab Serv, Canc Epidemiol Res Grp, Johannesburg, South Africa. Univ Witwatersrand, Clin HIV Res Unit, Dept Med, Fac Hlth Sci, Johannesburg, South Africa. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Whitby, D (reprint author), NCI, Viral Epidemiol Sect, AIDS Vaccine Program, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. EM whitbyd@ncifcrf.gov RI Pfeiffer, Ruth /F-4748-2011; OI Sitas, Freddy/0000-0001-9679-1481 FU NCI NIH HHS [N01 CO 12400] NR 25 TC 39 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2007 VL 44 IS 3 BP 351 EP 355 DI 10.1097/QAI.0b013e31802f12ea PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 141WT UT WOS:000244610400016 PM 17195763 ER PT J AU Hare, ML Villarruel, AM AF Hare, Martha L. Villarruel, Antonia M. TI Cultural dynamics in HIV/AIDS prevention research among young people SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Editorial Material DE HIV prevention research; cultural dynamics; behavioral theory AB In September 2005, the National Institute of Nursing Research with the support of several other components of the National Institutes of Health held a workshop, '' Cultural Dynamics in HIV Biobehavioral Research. '' This special issue of the Journal of the Association of Nurses in AIDS Care contains a series of articles developed from that workshop. The articles are derived from those presentations that focused on prevention of infection. They do not contain an agenda or recommendations from the National Institute of Nursing Research or any other component of the National Institutes of Health. Rather, the purpose of this special issue is to share with a broad audience the exciting dialogue that began at the workshop and which the authors hope will continue for some time in the future. The articles represent an interdisciplinary and global perspective. Issues discussed include behavioral theory, intergenerational communication, historical trauma, modernization, research methodology, and the ethics of community clinic trials. C1 NINR, Bethesda, MD 20892 USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. RP Hare, ML (reprint author), NINR, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CA999999] NR 8 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-3290 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD MAR-APR PY 2007 VL 18 IS 2 BP 1 EP 4 DI 10.1016/j.jana.2007.01.006 PG 4 WC Nursing SC Nursing GA 161WX UT WOS:000246048600001 PM 17403490 ER PT J AU Dharajiya, N Choudhury, BK Bacsi, A Boldogh, I Alam, R Sur, S AF Dharajiya, Nilesh Choudhury, Barun K. Bacsi, Attila Boldogh, Istvan Alam, Rafeul Sur, Sanjiv TI Inhibiting pollen reduced nicotinamide adenine dinucleotide phosphate oxidase-induced signal by intrapulmonary administration of antioxidants blocks allergic airway inflammation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergy; inflammation; antioxidants; eosinophils; T(H)2 ID MUCIN GENE-EXPRESSION; LUNG INFLAMMATION; OXIDATIVE STRESS; ASTHMATIC-PATIENTS; REACTIVE OXYGEN; IN-VIVO; HYPERRESPONSIVENESS; MODEL; EOSINOPHILS; RECRUITMENT AB Background: Ragweed extract (RWE) contains NADPH oxidases that induce oxidative stress in the airways independent of adaptive immunity (signal 1) and augment antigen (signal 2)-induced allergic airway inflammation. Objective: To test whether inhibiting signal I by administering antioxidants inhibits allergic airway inflammation in mice. Methods: The ability of ascorbic acid (AA), N-acetyl cystenine (NAC), and tocopherol to scavenge pollen NADPH oxidase-generated reactive oxygen species (ROS) was measured. These antioxidants were administered locally to inhibit signal 1 in the airways of RWE-sensitized mice. Recruitment of inflammatory cells, mucin production, calcium-activated chloride channel 3, IL-4, and IL-13 mRNA expression was quantified in the lungs. Results: Antioxidants inhibited ROS generation by pollen NADPH oxidases and intracellular ROS generation in cultured epithelial cells. AA in combination with NAC or Tocopherol decreased RWE-induced ROS levels in cultured bronchial epithelial cells. Coadministration of antioxidants with RWE challenge inhibited 4-hydroxymmenal adduct formation, upregulation of Clca3 and IL-4 in lungs, mucin production, recruitment of eosinophils, and total inflammatory cells into the airways. Administration of antioxidants with a second RWE challenge also inhibited airway inflammation. However, administration of AA+NAC 4 or 24 hours after RWE challenge failed to inhibit allergic inflammation. Conclusion: Signal I plays a proinflammatory role during repeated exposure to pollen extract. We propose that inhibiting signal I by increasing antioxidant potential in the airways may be a novel therapeutic strategy to attenuate pollen-induced allergic airway inflammation. Clinical implications: Administration of antioxidants in the airways may constitute a novel therapeutic strategy to prevent pollen induced allergic airway inflammation. C1 Univ Texas, NHLBI, Proteom Ctr,Med Branch, Div Allergy & Immunol,Dept Internal Med, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. Univ Debrecen, Inst Immunol, H-4012 Debrecen, Hungary. Natl Jewish Med & Res Ctr, Denver, CO USA. RP Sur, S (reprint author), Univ Texas, Med Branch, Dept Internal Med & Microbiol, 8-104 Med Res Bldg,301 Univ Blvd, Galveston, TX 77555 USA. EM sasur@utmb.edu FU NCI NIH HHS [CA84461, R01 CA084461]; NHLBI NIH HHS [N01HV28184, N01 HV028184, N01 HV028184-13, N01-HV28184, R01 HL071163, R01 HL071163-01A2, R01 HL071163-02]; NIAID NIH HHS [P01 AI062885, P01 AI062885-01, P01 AI062885-02, P01 AI062885-03]; NIEHS NIH HHS [ES06676, P30 ES006676, P30 ES006676-09, P30 ES006676-10, P30 ES006676-11] NR 34 TC 38 Z9 41 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2007 VL 119 IS 3 BP 646 EP 653 DI 10.1016/j.jaci.2006.11.634 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 146HL UT WOS:000244925000018 PM 17336614 ER PT J AU Fletcher, CV DeVille, JG Samson, PM Moye, JH Church, JA Spiegel, HML Palumbo, P Fenton, T Smith, ME Graham, B Kraimer, JM Shearer, WT AF Fletcher, Courtney V. DeVille, Jaime G. Samson, Pearl M. Moye, John H., Jr. Church, Joseph A. Spiegel, Hans M. L. Palumbo, Paul Fenton, Terence Smith, M. Elizabeth Graham, Bobbie Kraimer, Joyce M. Shearer, William T. TI Nonlinear pharmacokinetics of high-dose recombinant fusion protein CD4-IgG(2) (PRO 542) observed in HIV-1-infected children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID ANTIBODIES C1 Univ Colorado, Hlth Sci Ctr, Dept Clin Pharm, Denver, CO 80202 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. Childrens Hosp, Keck Sch Med, Los Angeles, CA 90027 USA. Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. NIAID, Pediat Med Branch, Div Aids, Bethesda, MD 20892 USA. Social & Sci Syst Inc, Silver Spring, MD USA. Frontier Sci Fdn, Amherst, NY USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. RP Fletcher, CV (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Clin Pharm, 4200 E 9th Ave, Denver, CO 80202 USA. EM wtsheare@TexasChildrensHospital.org FU NCRR NIH HHS [M01 RR020359, K01 RR000188, M01 RR000043, M01 RR000071, M01 RR000188, M01 RR000188-380393, M01 RR000188-420393, M01 RR000240, M01 RR000533, M01 RR000645, M01 RR000865, M01 RR002172, RR-00043, RR-00071, RR-00188, RR-00240, RR-00533, RR-00645, RR-00865, RR-020359, RR-02172]; NIAID NIH HHS [AI-27550, AI-27551, AI-32921, AI-41089, AI-41110, AI-43084, AI-48278, AI-66329, P30 AI036211, R43 AI048278, R44 AI048278, U01 AI027550, U01 AI027551, U01 AI032921, U01 AI041089, U01 AI041110, U19 AI066329]; NICHD NIH HHS [HD-3-3162, U01 HD041983] NR 11 TC 13 Z9 14 U1 0 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 MAR PY 2007 VL 119 IS 3 BP 747 EP 750 DI 10.1016/j.jaci.2006.10.045 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 146HL UT WOS:000244925000033 PM 17336619 ER PT J AU Nakamura, N Eddy, EM AF Nakamura, Noriko Eddy, Edward M. TI Disulfide bonds of spermatogenic cell-specific type 1 hexokinase (HK1S) and sperm motility SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-of-Andrology CY APR 18-24, 2007 CL Tampa, FL SP Amer Soc Androl C1 Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2007 SU S MA 2 BP 36 EP 36 PG 1 WC Andrology SC Endocrinology & Metabolism GA 142LX UT WOS:000244652500005 ER PT J AU Schrager, MA Metter, EJ Simonsick, E Ble, A Bandinelli, S Lauretani, F Ferrucci, L AF Schrager, Matthew A. Metter, E. Jeffrey Simonsick, Eleanor Ble, Alessandro Bandinelli, Stefania Lauretani, Fulvio Ferrucci, Luigi TI Sarcopenic obesity and inflammation in the InCHIANTI study SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE sarcopenia; central obesity; proinflammatory cytokines ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; GROWTH-FACTOR-I; ADIPOSE-TISSUE; INSULIN-RESISTANCE; MUSCLE STRENGTH; SKELETAL-MUSCLE; PHYSICAL PERFORMANCE; OLDER PERSONS; FACTOR-ALPHA AB The aging process is often paralleled by decreases in muscle and increases in fat mass. At the extreme these two processes lead to a condition known as "sarcopenic obesity" (Roubenoff R. Ann NY Acad Sci 904: 553-557, 2000). Research suggests that inflammatory cytokines produced by adipose tissue, especially visceral fat, accelerate muscle catabolism and thus contribute to the vicious cycle that initiates and sustains sarcopenic obesity. We tested the hypothesis that obesity and poor muscle strength, hallmarks of sarcopenic obesity, are associated with high circulating levels of proinflammatory cytokines in a random sample of the residents of two municipalities in the Chianti geographic area (Tuscany, Italy). The study sample consisted of 378 men and 493 women 65 yr and older with complete data on anthropometrics, handgrip strength, and inflammatory markers. Participants were cross-classified according to sex-specific tertiles of waist circumference and grip strength and according to a cut point for obesity of body mass index >= 30 kg/m(2). After adjusting for age, sex, education, smoking history, physical activity, and history of comorbid diseases, components of sarcopenic obesity were associated with elevated levels of IL-6, C-reactive protein, IL-1 receptor antagonist, and soluble IL-6 receptor (P < 0.05). Our findings suggest that global obesity and, to a greater extent, central obesity directly affect inflammation, which in turn negatively affects muscle strength, contributing to the development and progression of sarcopenic obesity. These results suggest that proinflammatory cytokines may be critical in both the development and progression of sarcopenic obesity. C1 NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. Azienda Sanitaria Firenze, Geriatr Rehabil Unit, Florence, Italy. Tuscany Reg Hlth Agcy, Florence, Italy. RP Ferrucci, L (reprint author), NIA, Harbor Hosp, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999]; NIMHD NIH HHS [263 MD 821336, 263 MD 9164 13, R01 MD009164] NR 42 TC 188 Z9 196 U1 3 U2 12 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 MAR PY 2007 VL 102 IS 3 BP 919 EP 925 DI 10.1152/japplphysiol.00627.2006 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 143LF UT WOS:000244722400015 PM 17095641 ER PT J AU Zwaigenbaum, L Thurm, A Stone, W Baranek, G Bryson, S Iverson, J Kau, A Klin, A Lord, C Landa, R Rogers, S Sigman, M AF Zwaigenbaum, Lonnie Thurm, Audrey Stone, Wendy Baranek, Grace Bryson, Susan Iverson, Jana Kau, Alice Klin, Ami Lord, Cathy Landa, Rebecca Rogers, Sally Sigman, Marian TI Studying the emergence of autism spectrum disorders in high-risk infants: Methodological and practical issues SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE early identification; screening; longitudinal studies; prospective studies; infant; autism; child development; siblings ID PERVASIVE DEVELOPMENTAL DISORDERS; 1ST 6 MONTHS; MENTAL-RETARDATION; EARLY INTERVENTION; EARLY RECOGNITION; YOUNG-CHILDREN; FOLLOW-UP; LANGUAGE-DEVELOPMENT; BROADER PHENOTYPE; PARENTAL REPORTS AB Detecting early signs of autism is essential for timely diagnosis and initiation of effective interventions. Several research groups have initiated prospective studies of high-risk populations including infant siblings, to systematically collect data on early signs within a longitudinal design. Despite the potential advantages of prospective studies of young children at high-risk for autism, there are also significant methodological, ethical and practical challenges. This paper outlines several of these challenges, including those related to sampling (e.g., defining appropriate comparison groups), measurement and clinical implications (e.g., addressing the needs of infants suspected of having early signs). We suggest possible design and implementation strategies to address these various challenges, based on current research efforts in the field and previous studies involving high-risk populations. C1 McMaster Univ, Childrens Hosp, Dept Paediat, Hamilton, ON L8N 3Z5, Canada. NIMH, Div Pediat Translat Res & Treatment Dev, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Pediat, Nashville, TN USA. Vanderbilt Univ, Dept Psychol & Human Dev, Nashville, TN USA. Univ N Carolina, Div Occupat Sci, Chapel Hill, NC USA. Dalhousie Univ, Dept Pediat, Halifax, NS, Canada. Dalhousie Univ, Dept Psychol, Halifax, NS, Canada. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. NICHHD, Ctr Dev Biol & Perinatal Med, Bethesda, MD 20892 USA. Yale Univ, Yale Child Study Ctr, New Haven, CT USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. Kennedy Krieger Inst, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Zwaigenbaum, L (reprint author), McMaster Univ, Childrens Hosp, Dept Paediat, POB 2000, Hamilton, ON L8N 3Z5, Canada. EM zwaigenb@mcmaster.ca FU NICHD NIH HHS [R01 HD054979]; NIMH NIH HHS [R01 MH068398] NR 97 TC 112 Z9 114 U1 4 U2 25 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 MAR PY 2007 VL 37 IS 3 BP 466 EP 480 DI 10.1007/s10803-006-0179-x PG 15 WC Psychology, Developmental SC Psychology GA 142ZJ UT WOS:000244689500007 PM 16897376 ER PT J AU Vanderpool, CK Gottesman, S AF Vanderpool, Carin K. Gottesman, Susan TI The novel transcription factor SgrR coordinates the response to glucose-phosphate stress SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; SMALL RNA; GLUCOSE-TRANSPORTER; MESSENGER-RNA; PHOSPHOTRANSFERASE SYSTEM; GENE-EXPRESSION; REGULATORS; VECTORS; CLONING; OPERON AB SgrR is the first characterized member of a family of bacterial transcription factors containing an N-terminal DNA binding domain and a C-terminal solute binding domain. Previously, we reported genetic evidence that SgrR activates the divergently transcribed gene sgrS, which encodes a small RNA required for recovery from glucose-phosphate stress. In this study, we examined the regulation of sgrR expression and found that SgrR negatively autoregulates its own transcription in the presence and absence of stress. An SgrR binding site in the sgrR-sgrS intergenic region is required in vivo for both SgrR-dependent activation of sgrS and autorepression of sgrR. Purified SgrR binds specifically to sgrS promoter DNA in vitro; a mutation in the site required for in vivo activation and autorepression abrogates in vitro SgrR binding. A plasmid library screen identified clones that alter expression of a P-sgrS-lacZ fusion; some act by titrating endogenous SgrR. The yfdZ gene, encoding a putative aminotransferase, was identified in this screen; the yfdZ promoter contains an SgrR binding site, and transcriptional fusions indicate that yfdZ is activated by SgrR. Clones containing mlc, which encodes a glucose-specific repressor protein, also downregulate P-sgrS-IacZ. The mlc clones do not appear to titrate the SgrR protein, indicating that Mic affects sgrS expression by an alternative mechanism. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Vanderpool, CK (reprint author), Univ Illinois, Dept Microbiol, B213 CLSL,MC 110,601 S Goodwin Ave, Urbana, IL 61801 USA. EM cvanderp@life.uiuc.edu FU Intramural NIH HHS NR 22 TC 38 Z9 41 U1 0 U2 2 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 MAR PY 2007 VL 189 IS 6 BP 2238 EP 2248 DI 10.1128/JB.01689-06 PG 11 WC Microbiology SC Microbiology GA 147EG UT WOS:000244985600006 PM 17209026 ER PT J AU Ying, JF Chill, JH Louis, JM Bax, A AF Ying, Jinfa Chill, Jordan H. Louis, John M. Bax, Ad TI Mixed-time parallel evolution in multiple quantum NMR experiments: sensitivity and resolution enhancement in heteronuclear NMR SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE KcsA; mixed-time; multiple quantum NMR; NOESY; parallel evolution; resolution enhancement; RNA; sensitivity enhancement ID KCSA POTASSIUM CHANNEL; RESONANCE; PROTEINS; SPECTRA; C-13; SPECTROSCOPY; ASSIGNMENT; COUPLINGS; COHERENCE; PULSES AB A new strategy is demonstrated that simultaneously enhances sensitivity and resolution in three- or higher-dimensional heteronuclear multiple quantum NMR experiments. The approach, referred to as mixed-time parallel evolution (MT-PARE), utilizes evolution of chemical shifts of the spins participating in the multiple quantum coherence in parallel, thereby reducing signal losses relative to sequential evolution. The signal in a given PARE dimension, t(1), is of a non-decaying constant-time nature for a duration that depends on the length of t(2), and vice versa, prior to the onset of conventional exponential decay. Line shape simulations for the H-1-N-15 PARE indicate that this strategy significantly enhances both sensitivity and resolution in the indirect H-1 dimension, and that the unusual signal decay profile results in acceptable line shapes. Incorporation of the MT-PARE approach into a 3D HMQC-NOESY experiment for measurement of H-N-H-N NOEs in KcsA in SDS micelles at 50 degrees C was found to increase the experimental sensitivity by a factor of 1.7 +/- 0.3 with a concomitant resolution increase in the indirectly detected H-1 dimension. The method is also demonstrated for a situation in which homonuclear C-13-C-13 decoupling is required while measuring weak H3'-2'OH NOEs in an RNA oligomer. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Ying, JF (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 22 TC 14 Z9 14 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD MAR PY 2007 VL 37 IS 3 BP 195 EP 204 DI 10.1007/s10858-006-9120-z PG 10 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 133QX UT WOS:000244028700004 PM 17245527 ER PT J AU Geller, BM Zapka, J Hofvind, SSH Scharpantgen, A Giordano, L Ohuchi, N Ballard-Barbash, R AF Geller, Berta M. Zapka, Jane Hofvind, Solveig S. H. Scharpantgen, Astrid Giordano, Livia Ohuchi, Noriaki Ballard-Barbash, Rachel TI Communicating with women about mammography SO JOURNAL OF CANCER EDUCATION LA English DT Article ID DECISION-MAKING; BREAST-CANCER; HEALTH-CARE; COUNTRIES; SERVICES; INFORMATION; BENEFITS; DELIVERY AB Background/Methods. We report survey results of the types of tools used to communicate with women about breast cancer screening and the content areas included in each toot for member countries of the International Breast Cancer Screening Network (IBSN). Results. In addition to using pamphlets and invitation letters, new technologies are being used such as the Internet which allows for easy updating of information and can provide interactive modules. Several countries have addressed the needs of specific populations such as indigenous populations or blind women. All countries provide basic information, although they do not provide all the same information. Conclusion. More research is needed to understand what women need to make an informed decision about mammography and to learn what the best modalities are to provide this information. C1 Univ Vermont, Vermont Canc Ctr, Burlington, VT 05401 USA. Univ Massachusetts, Amherst, MA 01003 USA. Minist Hlth, Luxembourg, Luxembourg. CPO Peimonte, Turin, Italy. Tohoku Univ, Grad Sch Med, Sendai, Miyagi 980, Japan. NCI, Bethesda, MD 20892 USA. RP Geller, BM (reprint author), Univ Vermont, Vermont Canc Ctr, 1 S Prospect St, Burlington, VT 05401 USA. EM Berta.Geller@uvm.edu NR 22 TC 3 Z9 4 U1 0 U2 4 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 BP 25 EP 31 PG 7 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 192XK UT WOS:000248236900008 PM 17570805 ER PT J AU Bright, MA AF Bright, Mary Anne TI The National Cancer Institute's Cancer Information Service: A premiere cancer information and education resource for the nation SO JOURNAL OF CANCER EDUCATION LA English DT Article ID TRENDS SURVEY; HEALTH; INTERNET AB Through the National Cancer Act and its amendments (National Cancer Act, 1971; National Cancer Act Amendments, 1974), the U.S. Congress mandated that the National Cancer Institute (NCI)-the nation's lead agency for cancer information and research-provides accurate, up-to-date information about cancer to all segments of the U.S. population. In 1975, the NCI established the Cancer Information Service (CIS), a premieer resource for providing cancer information and education to the nation. The CIS is designed to maximize reach to the public by responding to the cancer needs of clients through several communication technologies, including a telephone service, e-mail, and real-time instant messaging. By offering cancer information to the public through one-on-one interactions with CIS information specialists, the CIS is in a unique position to fill the gap that lies between the preferred, interpersonal source of the health care provider and the actual, impersonal Internet. Cancer Information Service can play an important role in providing health care practitioners, health departments, caregivers, and researchers with up-to-date and accurate information about cancer and clinical trials. Currently, 10% of CIS callers are health professionals. Referring patients to the CIS can augment health practitioners' ability to convey important health information to patients. The CIS program uses NCI resources to educate clients on cancer prevention, early detection, treatment, and rehabilitation and smoking cessation in simple terms that they can understand. Additionally, the CIS works with organizations to develop educational programs and interventions to reach underserved populations. A unique component of this information and education program is its ability to contribute to the field of health communications research by collaborating in research studies throughout the U.S. Finally, since its inception in 1975, the CIS has assisted international organizations with starting a cancer information service and as such is seen as a "stem cell" from which many international CIS programs have derived. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Bright, MA (reprint author), NCI, NIH, 6116 Execut Blvd,MSC 8322,Room 3036, Bethesda, MD 20892 USA. EM brightma@mail.nih.gov NR 20 TC 22 Z9 22 U1 1 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 SU S BP S2 EP S7 PG 6 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 193XK UT WOS:000248308300002 PM 17571997 ER PT J AU Croyle, RT AF Croyle, Robert T. TI The National Cancer Institue's cancer information service: Dissemination of cancer information and education to the public - Foreword SO JOURNAL OF CANCER EDUCATION LA English DT Editorial Material C1 NCI, Div Canc Control & Populat Serv, Bethesda, MD 20892 USA. RP Croyle, RT (reprint author), NCI, Div Canc Control & Populat Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 SU S BP S1 EP S1 PG 1 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 193XK UT WOS:000248308300001 ER PT J AU Fleisher, L Kornfeld, J Davis, S Morra, ME Squiers, L AF Fleisher, Linda Kornfeld, Julie Davis, Sharon Morra, Marion E. Squiers, Linda TI The NCI's Cancer Information Service's Research Continuum Framework: Integrating research into cancer education practice (1999-2004) SO JOURNAL OF CANCER EDUCATION LA English DT Article ID MULTIPLE TAILORED MESSAGES; BREAST-CANCER; SMOKING-CESSATION; RANDOMIZED-TRIAL; DECISION-MAKING; CALLERS; WOMEN; DISSEMINATION; EXPERIENCE; AWARENESS AB Between 1999 and 2004, the National Cancer Institute's (NCI) Cancer Information Service's (CIS) Research Initiative supported over 50 research projects representing a broad range of activities from research capacity building, development, implementation to diffusion and dissemination. These research activities are represented in the CIS Research Continuum Framework which the authors describe through a number of short case studies. Based on the experiences and successes of the CIS, other professionals working in the cancer field might consider establishing collaborative relationships across the research continuum and participating in research that has relevancy to advances in cancer education. C1 Fox Chase Canc Ctr, Canc Informat Serv, Atlantic Reg, Cheltenham, PA 19012 USA. Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Canc Informat Serv,Coastal Reg, Coral Gables, FL 33124 USA. No Calif Canc Ctr, Canc Informat Serv, Calif Reg, Fremont, CA USA. Morra Commun, Milford, CT USA. NCI, Canc Informat Serv, NIH, Bethesda, MD 20892 USA. RP Fleisher, L (reprint author), Fox Chase Canc Ctr, Canc Informat Serv, Atlantic Reg, 510 Township Line Rd, Cheltenham, PA 19012 USA. EM Linda.Fleisher@fccc.edu NR 39 TC 4 Z9 4 U1 3 U2 4 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 SU S BP S41 EP S48 PG 8 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 193XK UT WOS:000248308300007 PM 17572000 ER PT J AU Kreps, GL Gustafson, D Salovey, P Perocchia, RS Wilbright, W Bright, MA Muha, C AF Kreps, Gary L. Gustafson, David Salovey, Peter Perocchia, Rosemarie Slevin Wilbright, Wayne Bright, Mary Anne Muha, Cathy TI The NCI Digital Divide Pilot Projects: Implications for cancer education SO JOURNAL OF CANCER EDUCATION LA English DT Article ID LOW-INCOME WOMEN; BREAST-CANCER; IMPACT; SYSTEM AB The National Cancer Institute (NCI) supported four innovative demonstration research projects, "The Digital Divide Pilot Projects," to test new strategies for disseminating health information via computer to vulnerable consumers. These projects involved active research collaborations between the NCI's Cancer Information Service (CIS) and regional cancer control researchers to field test new approaches for enhancing cancer communication in vulnerable communities. The projects were able to use computers to successfully disseminate relevant cancer information to vulnerable populations. These demonstration research projects suggested effective new strategies for using communication technologies to educate underserved populations about cancer prevention, control, and care. C1 George Mason Univ, Dept Commun, Fairfax, VA 22030 USA. Univ Wisconsin, Madison, WI 53706 USA. Yale Univ, New Haven, CT 06520 USA. Mem Sloan Kettering Canc Ctr, New York Reg Canc Informat Serv, New York, NY USA. Louisiana State Univ, Baton Rouge, LA 70803 USA. NCI, Canc Informat Serv, NIH, Bethesda, MD 20892 USA. RP Kreps, GL (reprint author), George Mason Univ, Dept Commun, Thompson Hall,MS 3D6, Fairfax, VA 22030 USA. EM gkreps@gmu.edu FU NCI NIH HHS [R01 CA068427] NR 21 TC 11 Z9 13 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 SU S BP S56 EP S60 PG 5 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 193XK UT WOS:000248308300009 PM 17572002 ER PT J AU Kreps, GL Bright, MA Fleisher, L Marcus, A Morra, ME Perocchia, RS AF Kreps, Gary L. Bright, Mary Anne Fleisher, Linda Marcus, Al Morra, Marion E. Perocchia, Rosemarie Slevin TI Future directions for the Cancer Information Service and cancer education SO JOURNAL OF CANCER EDUCATION LA English DT Article AB From its beginnings in the 1970s, the National Cancer Institute's (NCI's) Cancer Information Service (CIS) has developed as a vibrant program for providing health care professionals and the public with relevant cancer-related information through telephone, mail, and online communication. The CIS has become an important contributor to health communication and health education research. Through its network of community partnerships, it has disseminated relevant cancer information and health promotion programs to vulnerable and hard-to-reach populations. It has become a model for the development of health information and education programs around the world. However, the CIS is stilt growing; it is continually innovating and refining its programs and services. This concluding article examines the potential for increasing CIS contributions to cancer education and cancer control in the future. C1 George Mason Univ, Dept Commun, Fairfax, VA 22030 USA. NCI, Canc Informat Serv, NIH, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Atlantic Reg Canc Informat Serv, Philadelphia, PA 19111 USA. Univ Colorado, Ctr Canc, AMC Canc Res Ctr, Boulder, CO 80309 USA. Morra Commun, Milford, CT USA. Mem Sloan Kettering Canc Ctr, New York Reg Canc Informat Serv, New York, NY USA. RP Kreps, GL (reprint author), George Mason Univ, Dept Commun, 4400 Univ Dr,MS 3D6, Fairfax, VA 22030 USA. EM gkreps@gmu.edu NR 13 TC 3 Z9 3 U1 1 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 SU S BP S70 EP S73 PG 4 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 193XK UT WOS:000248308300011 PM 17572004 ER PT J AU La Porta, M Hagood, H Kornfeld, J Treiman, K AF La Porta, Madeline Hagood, Heather Kornfeld, Julie Treiman, Katherine TI Partnership as a means for reaching special populations: Evaluating the NCI's CIS Partnership Program SO JOURNAL OF CANCER EDUCATION LA English DT Article ID OUTREACH PROGRAM; SYNERGY AB Background. The National Cancer Institute's (NCI's) Cancer Information Service (CIS) Partnership Program involves collaboration with over 900 organizations and coalitions serving minority and medically underserved populations. Cancer Information Service collaborations are categorized into three types: networking, educational program, and program development partnerships. Methods. A survey of CIS partnership organizations (n=288). Results. Most respondents reported that partnerships with CIS are collaborative and make good use of their organization's skills and resources, and most perceive that the benefits of partnership outweigh any drawbacks. More than one-quarter say partnerships have not done a good job evaluating collaborative activities. Results vary among three types of partnerships. Conclusions. Evaluation of the CIS Partnership Program presents an opportunity to examine how a large-scale and multi-faceted partnership effort has been implemented, how it is evaluated, and initial indicators of program success. Organizations, health professionals, and community leaders interested in effective partnerships can use these findings to strengthen collaborations and maximize outcomes. C1 NCI, Natl Inst Hlth, Canc Informat Serv, Bethesda, MD 20892 USA. RP La Porta, M (reprint author), NCI, Natl Inst Hlth, Canc Informat Serv, 6116 Execut Blvd,MSC 8322, Bethesda, MD 20892 USA. EM laportam@mail.nih.gov NR 9 TC 7 Z9 7 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 SU S BP S35 EP S40 PG 6 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 193XK UT WOS:000248308300006 PM 17571999 ER PT J AU La Porta, M Hagood, H Kornfeld, J Treiman, K AF La Porta, Madeline Hagood, Heather Kornfeld, Julie Treiman, Katherine TI Evaluating the NCI's Cancer Information Service contact centers: Meeting and exceeding the expectations of the public SO JOURNAL OF CANCER EDUCATION LA English DT Article ID SEEKING BEHAVIORS; PROSTATE-CANCER; PARTNERS; IMPACT; NEEDS; MEN AB The National Cancer Institute's (NCI's) Cancer Information Service (CIS) provides cancer information to the public via 1-800-4-CANCER, a smoking quitline, and online. The 2003 National User Survey assessed satisfaction and outcomes among users contacting NCI's CIS by telephone and LiveHelp, an instant messaging service. Ninety-five percent of respondents were very satisfied/satisfied and 88% said their expectations had been met/exceeded. Users reported increased knowledge and self-efficacy. Most had discussed CIS information with a health professional or planned to do so. Of those who contacted CIS about smoking/tobacco use, 14% had quit and 35% cut back. The CIS provides a highly valued, effective service for patients and health professionals. C1 NCI, Natl Inst Hlth, Canc Informat Serv, Bethesda, MD 20892 USA. RP La Porta, M (reprint author), NCI, Natl Inst Hlth, Canc Informat Serv, 6116 Execut Blvd,MSC 8322, Bethesda, MD 20892 USA. EM laportam@mail.nih.gov NR 23 TC 9 Z9 9 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 SU S BP S18 EP S25 PG 8 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 193XK UT WOS:000248308300004 PM 17571996 ER PT J AU La Porta, M Hagood, H Patt, J Hodorowski, JK Treiman, K AF La Porta, Madeline Hagood, Heather Patt, Judy Hodorowski, Julie Keany Treiman, Katherine TI The NCI's Cancer Information Service: Meeting the public's cancer information needs via the Internet SO JOURNAL OF CANCER EDUCATION LA English DT Article AB The Cancer Information Service (CIS) of the National Cancer Institute (NCI) added e-mail and instant chat to its telephone service (1-800-4-CANCER, 1-877-44U-QUIT). While most CIS contacts are still via telephone, internet contacts have increased from 9000 in 2001 to over 20,000 in 2006. The NCI leveraged 30 years of CIS telephone experience to understand the needs of Internet information seekers. Online users are more likely to contact CIS on behalf of someone else. Instant chat users are younger and more educated than telephone users. They report high satisfaction levels, increased knowledge, and other positive effects from their interactions. Patients and their families can benefit from awareness of CIS online services and health care providers can be confident in directing them to CIS. C1 NCI, Canc Informat Serv, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Canc Informat Serv, New York Reg, New York, NY 10021 USA. RP La Porta, M (reprint author), NCI, Canc Informat Serv, NIH, 6116 Execut Blvd,MSC 8322, Bethesda, MD 20892 USA. EM laportam@mail.nih.gov NR 20 TC 6 Z9 6 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 SU S BP S26 EP S34 PG 9 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 193XK UT WOS:000248308300005 PM 17571998 ER PT J AU Morra, ME Thomsen, C Vezina, A Akkerman, D Bright, MA Dickens, C Hill, DJ Jefford, M AF Morra, Marion E. Thomsen, Chris Vezina, Anne Akkerman, Doreen Bright, Mary Anne Dickens, Catherine Hill, David J. Jefford, Michael TI The International Cancer Information Service: A worldwide resource SO JOURNAL OF CANCER EDUCATION LA English DT Article ID QUALITY-OF-LIFE; BREAST-CANCER; NEEDS; SURVIVORS; HELPLINE; IMPACT AB The need for accurate and relevant cancer information continues to grow worldwide. While healthcare professionals are the preferred source of cancer information, their time is limited, and patients are often not sure what to ask and their questions do not always come to mind in the physician's office. In its 30-year history, the National Cancer Institute's (NCI's) Cancer Information Service (CIS) has shown that it can increase users' confidence in their ability to seek more information, understand the causes and risk factors for cancer, and participate in decisions about their treatment. In 1996 the International Cancer Information Service Group (ICISG) was formed to facilitate the development of CIS programs throughout the world. A network of nearly 50 cancer organizations from 30 countries, the ICISG strives to provide its member organizations with standards and resources to ensure that the cancer information is of high quality, credible, and up-to-date and that it is delivered in a personal manner that complements and supports the patient/physician relationship. The ICISG offers worldwide resources that can augment the healthcare professionals' offering of information and support to cancer patients and their families. C1 Morra Commun, Milford, CT 06460 USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. Canc Council Victoria, Melbourne, Vic, Australia. NCI, Canc Informat Serv, NIH, Bethesda, MD 20892 USA. RP Morra, ME (reprint author), Morra Commun, 1 Platt St, Milford, CT 06460 USA. EM morram@earthlink.net NR 35 TC 8 Z9 8 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 SU S BP S61 EP S69 PG 9 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 193XK UT WOS:000248308300010 PM 17572003 ER PT J AU Perocchia, RS Galassi, A Jacobs, R Krauss, N LeMaitre, MK Rutledge, S AF Perocchia, Rosemarie Slevin Galassi, Annette Jacobs, Randy Krauss, Nancy LeMaitre, M. Kim Rutledge, Sue TI The NCI's Cancer Information Service staff training program: A foundation for excellence SO JOURNAL OF CANCER EDUCATION LA English DT Article ID RESOURCE; NATION AB The philosophy of the National Cancer Institute's (NCI) Cancer Information Service (CIS) staff training program is based on the premise that a solid relationship exists between staff performance and training. As a leading edge organization and the premiere cancer information service in the world, the CIS provides more training to its staff than many organizations. This factor is in part responsible for the program's success over the past 30 years, during which time the staff training program was revised to reflect a more comprehensive, performance-based approach. This paper describes the development of the curricula and the standards that are the foundation of the CIS program. C1 Mem Sloan Kettering Canc Ctr, New York Canc Informat Serv, New York, NY 10021 USA. NCI, Canc Informat Serv, NIH, Bethesda, MD 20892 USA. Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Coastal Reg Canc Informat Serv, Coral Gables, FL 33124 USA. Fox Chase Canc Ctr, Atlantic Reg Canc Informat Serv, Philadelphia, PA 19111 USA. Fred Hutchinson Canc Res Ctr, NW Reg Canc Informat Serv, Seattle, WA 98104 USA. RP Perocchia, RS (reprint author), Mem Sloan Kettering Canc Ctr, New York Canc Informat Serv, 1275 York Ave,Box 66, New York, NY 10021 USA. EM perocchr@mskcc.org NR 14 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 EI 1543-0154 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 SU S BP S8 EP S17 PG 10 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 193XK UT WOS:000248308300003 PM 17572005 ER PT J AU Squiers, L Bush, N Vanderpool, R Cofta-Woerpel, L Fabrizio, C AF Squiers, Linda Bush, Nigel Vanderpool, Robin Cofta-Woerpel, Ludmila Fabrizio, Cecilia TI Bridging the critical chasm between service and research: The Cancer Information Service's collaboratory SO JOURNAL OF CANCER EDUCATION LA English DT Article ID MULTIPLE TAILORED MESSAGES; LOW-INCOME WOMEN; BREAST-CANCER; VEGETABLE CONSUMPTION; INCREASING FRUIT; BEHAVIORS; AWARENESS; CALLERS AB As a collaboratory for cancer communication and education research, the National Cancer Institute's (NCIs) Cancer Information Service (CIS) is in an ideal position to bridge the critical chasm that exists between service and research. This article describes the CIS' current research program as well as the CIS Research Agenda launched in 2005. The CIS' progress in developing and supporting recently funded studies that address this agenda is detailed. The unique resources and opportunities available to researchers, public health practitioners, health care providers, and community-based organizations interested in developing collaborative cancer communication and cancer education studies with the CIS are identified and described and an invitation to collaborate is extended. C1 NCI, Canc Informat Serv Program, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, NW Reg Canc Informat Serv, Seattle, WA 98104 USA. Univ Kentucky, Mid S Reg Canc Informat Serv, Markey Canc Prevent & Control Program, Lexington, KY 40506 USA. Univ Texas, MD Anderson Canc Ctr, S Cent Reg Canc Informat Serv, Houston, TX 77030 USA. Yale Univ, Ctr Canc, New England Reg Canc Informat Serv, New Haven, CT 06520 USA. RP Squiers, L (reprint author), NCI, Canc Informat Serv Program, NIH, 6116 Execut Blvd,3029, Bethesda, MD 20892 USA. EM squiersl@mail.nih.gov FU NCI NIH HHS [N02 CO051106] NR 25 TC 5 Z9 5 U1 1 U2 2 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2007 VL 22 IS 1 SU S BP S49 EP S55 PG 7 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 193XK UT WOS:000248308300008 PM 17572001 ER PT J AU Paul, JD Powell, TM Thompson, M Benjamin, M Rodrigo, M Carlow, A Annavajjhala, V Shiva, S Dejam, A Gladwin, MT McCoy, JP Zalos, G Press, B Murphy, M Hill, JM Csako, G Waclawiw, MA Cannon, RO AF Paul, Jonathan D. Powell, Tiffany M. Thompson, Michael Benjamin, Moshe Rodrigo, Maria Carlow, Andrea Annavajjhala, Vidhya Shiva, Sruti Dejam, Andre Gladwin, Mark T. McCoy, J. Philip Zalos, Gloria Press, Beverly Murphy, Mandy Hill, Jonathan M. Csako, Gyorgy Waclawiw, Myron A. Cannon, Richard O., III TI Endothelial progenitor cell mobilization and increased intravascular nitric oxide in patients undergoing cardiac rehabilitation SO JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION LA English DT Article DE cardiac rehabilitation; EPCs; nitric oxide ID CORONARY-ARTERY-DISEASE; CARDIOVASCULAR RISK; TRAINING INCREASES; EXERCISE; ANGIOGENESIS; PREVENTION; APOPTOSIS; OUTCOMES; NUMBER; BLOOD AB PURPOSE: We investigated whether cardiac rehabilitation participation increases circulating endothelial progenitor cells (EPCs) and benefits vasculature in patients already on stable therapy previously shown to augment EPCs and improve endothelial function. METHODS: Forty-six of 50 patients with coronary artery disease completed a 36-session cardiac rehabilitation program: 45 were treated with HMG-CoA reductase inhibitor (statin) therapy >= 1 month (average baseline low-density lipoprotein cholesterol = 81 mg/dL). Mononuclear cells isolated from blood were quantified for EPCs by flow cytometry (CD133(+)/VEGFR-2(+) cells) and assayed in culture for EPC colony-forming units (CFUs). In 23 patients, EPCs were stained for annexin-V as a marker of apoptosis, and nitrite was measured in blood as an indicator of intravascular nitric oxide. RESULTS: Endothelial progenitor cells increased from 35 +/- 5 to 63 +/- 10 cells/mL, and EPC-CFUs increased from 0.9 +/- 0.2 to 3.1 +/- 0.6 per well (both P <.01), but 11 patients had no increase in either measure. Those patients whose EPCs increased from baseline showed significant increases in nitrite and reduction in annexin-V staining (both P <.01) versus no change in patients without increase in EPCs. Over the course of the program, EPCs increased prior to increase in nitrite in the blood. CONCLUSIONS: Cardiac rehabilitation in patients receiving stable statin therapy and with low-density lipoprotein cholesterol at goal increases EPC number, EPC survival, and endothelial differentiation potential, associated with increased nitric oxide in the blood. Although this response was observed in most patients, a significant minority showed neither EPC mobilization nor increased nitric oxide in the blood. C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Suburban Hosp, Bethesda, MD USA. RP Cannon, RO (reprint author), NIH, Dept Lab Med, Bldg 10,CRC,Room 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM cannonr@nih.gov FU Intramural NIH HHS NR 27 TC 44 Z9 47 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-7501 J9 J CARDIOPULM REHABIL JI J. Cardiopulm. Rehabil. Prev. PD MAR-APR PY 2007 VL 27 IS 2 BP 65 EP 73 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 157AL UT WOS:000245690900002 PM 17558240 ER PT J AU Boyarchuk, Y Salic, A Dasso, M Arnaoutov, A AF Boyarchuk, Yekaterina Salic, Adrian Dasso, Mary Arnaoutov, Alexei TI Bub1 is essential for assembly of the functional inner centromere SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SISTER-CHROMATID COHESION; CHROMOSOME SEGREGATION ROLES; SPINDLE CHECKPOINT PROTEINS; AURORA-B; KINETOCHORE LOCALIZATION; TOPOISOMERASE-II; PHOSPHATASE 2A; CENP-E; SHUGOSHIN; MITOSIS AB During mitosis, the inner centromeric region (ICR) recruits protein complexes that regulate sister chromatid cohesion, monitor tension, and modulate microtubule attachment. Biochemical pathways that govern formation of the inner centromere remain elusive. The kinetochore protein Bub1 was shown to promote assembly of the outer kinetochore components, such as BubR1 and CENP-F, on centromeres. Bub1 was also implicated in targeting of Shugoshin (Sgo) to the ICR. We show that Bub1 works as a master organizer of the ICR. Depletion of Bub1 from Xenopus laevis egg extract or from HeLa cells resulted in both destabilization and displacement of chromosomal passenger complex (CPC) from the ICR. Moreover, soluble Bub1 controls the binding of Sgo to chromatin, whereas the CPC restricts loading of Sgo specifically onto centromeres. We further provide evidence that Bub1 kinase activity is pivotal for recruitment of all of these components. Together, our findings demonstrate that Bub1 acts at multiple points to assure the correct kinetochore formation. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Cytol, St Petersburg 199004, Russia. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Dasso, M (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov; arnaouta@mail.nih.gov OI Dasso, Mary/0000-0002-5410-1371 FU Intramural NIH HHS [Z01 HD008740-06]; NICHD NIH HHS [Z01 HD008740] NR 42 TC 69 Z9 74 U1 0 U2 2 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 MAR PY 2007 VL 176 IS 7 BP 919 EP 928 DI 10.1083/jcb.200609044 PG 10 WC Cell Biology SC Cell Biology GA 150JB UT WOS:000245211200004 PM 17389228 ER PT J AU Juretic, N Urzua, U Munroe, DJ Jaimovich, E Riveros, N AF Juretic, Nevenka Urzua, Ulises Munroe, David J. Jaimovich, Enrique Riveros, Nora TI Differential gene expression in skeletal muscle cells after membrane depolarization SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; MESSENGER-RNA; SIGNALING PATHWAYS; CA2+ TRANSIENTS; 2-AMINOETHOXYDIPHENYL BORATE; TRISPHOSPHATE RECEPTORS; PROTEIN-PHOSPHORYLATION; TRANSCRIPTIONAL CONTROL; CALCIUM TRANSIENTS; EXERCISE AB Skeletal muscle is a highly plastic tissue with a remarkable capacity to adapt itself to challenges imposed by contractile activity. Adaptive response, that include hypertrophy and activation of oxidative mechanisins have been associated with transient changes in transcriptional activity of specific genes. To define the set of genes regulated by a depolarizing stimulus, we used 22 K mouse oligonucleotide microarrays. Total RNA from C2C12 myotubes was obtained at 2, 4, 18, and 24 h after high K+ stimulation. cDNA from control and depolarized samples was labeled with cyanine 3 or 5 dyes prior to microarray hybridization. Loess normalization followed by statistical analysis resulted in 423 differentially expressed genes using an unadjusted P-value <= 0.01 as cut off. Depolarization affects transcriptional activity of a limited number of genes, mainly associated with metabolism, cell communication and response to stress. A number of genes related to Ca2+ signaling pathways are induced at 4 h, reinforcing the potential role of Ca2+ in early steps of signal transduction that leads to gene expression. Significant changes in the expression of molecules involved in muscle cell structure were observed; K+-depolarization increased Tnni1 and Acta1 mRNA levels in both differentiated C2C12 and rat skeletal muscle cells in primary culture. Of these two, depolarization induced slow Ca2+ transients appear to have a role only in the regulation of Tnni1 transcriptional activity. We suggest that depolarization induced expression of a small set of genes may underlie Ca2+ dependent plasticity of skeletal muscle cells. C1 Univ Chile, Fac Med, Program Biol Celular & Mol, Inst Ciencias Biomed,Ctr Estudios Mol Celula, Santiago 7, Chile. Univ Chile, Fac Med, Inst Ciencias Biomed, Programa Biol Celular & Mol, Santiago 7, Chile. SAIC Frederick Inc, Lab Mol Technol, NCI, Frederick, MD USA. RP Riveros, N (reprint author), Univ Chile, Fac Med, Program Biol Celular & Mol, Inst Ciencias Biomed,Ctr Estudios Mol Celula, Casilla 70086, Santiago 7, Chile. EM nriveros@med.uchile.cl RI Urzua, Ulises/A-3982-2013; OI Urzua, Ulises/0000-0003-0522-5754 FU NCI NIH HHS [N01-CO-12400] NR 71 TC 28 Z9 29 U1 0 U2 1 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 MAR PY 2007 VL 210 IS 3 BP 819 EP 830 DI 10.1002/jcp.20902 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 130CF UT WOS:000243776100029 PM 17146758 ER PT J AU Perl, S Kotz, L Keil, M Patronas, NJ Stratakis, CA AF Perl, Shira Kotz, Linda Keil, Meg Patronas, Nicholas J. Stratakis, Constantine A. TI Calcified adrenals associated with perinatal adrenal hemorrhage and adrenal insufficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CALCIFICATION C1 NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, NIDDKD, InterInst Endocrinol Training Program, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bldg 10 CRC E,Room 1-3330,10 Ctr Dr MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [1 Z01 HD000642-04] NR 5 TC 4 Z9 4 U1 0 U2 0 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 MAR PY 2007 VL 92 IS 3 BP 754 EP 754 DI 10.1210/jc.2006-2026 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 143LA UT WOS:000244721900002 PM 17341573 ER PT J AU Timmers, HJLM Kozupa, A Eisenhofer, G Raygada, M Adams, KT Solis, D Lenders, JWM Pacak, K AF Timmers, Henri J. L. M. Kozupa, Anna Eisenhofer, Graeme Raygada, Margarita Adams, Karen T. Solis, Daniel Lenders, Jacques W. M. Pacak, Karel TI Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HEREDITARY PARAGANGLIOMA; GERMLINE MUTATIONS; SPORADIC PHEOCHROMOCYTOMAS; ELECTROCHEMICAL DETECTION; FAMILIAL PARAGANGLIOMA; GENE-MUTATIONS; SDHB GENE; PLASMA; MANAGEMENT; METANEPHRINES AB Context: Mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to malignant paraganglioma (PGL). Recognition of the SDHB phenotype in apparently sporadic PGL directs appropriate treatment and family screening. Objective: The objective of the study was to assess mutation-specific clinical and biochemical characteristics of SDHB-related PGL. Design: The study design was retrospective descriptive. Patients: Patients included 29 patients (16 males) with SDHB-related abdominal or thoracic PGL. Intervention: There was no intervention. Main Outcome Measures: Clinical presentations, plasma and urine concentrations of catecholamines and O-methylated metabolites, and genotype-phenotype correlations were measured. Results: Mean +/- SD age at diagnosis was 33.7 +/- 15.7 yr. Tumor-related pain was among the presenting symptoms in 54% of patients and was the sole symptom in 14%. Seventy-six percent had hypertension, and 90% lacked a family history of PGL. All primary tumors but one originated from extraadrenal locations. Mean +/- SD tumor size was 7.8 +/- 3.7 cm. In this referral-based study, 28% presented with metastatic disease and all but one eventually developed metastases after 2.7 +/- 4.1 yr. Ten percent had additional head and neck PGLs. The biochemical phenotype was consistent with hypersecretion of both norepinephrine and dopamine in 46%, norepinephrine only in 41%, and dopamine only in 3%. Ten percent had normal catecholamine (metabolite) levels, consistent with biochemically silent PGL. No obvious genotype-phenotype correlations were identified. Conclusions: SDHB-related PGL often presents as apparently sporadic PGL with symptoms related to tumor mass effect rather than to catecholamine excess. The predominant biochemical phenotype consists of hypersecretion of norepinephrine and/or dopamine, whereas 10% of tumors are biochemically silent. The clinical expression of these tumors cannot be predicted by the genotype. C1 NICHHD, Sect Med Neuroendocrinol, Reprod Biol & Med Branch, CRC, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. NIH, Lab Clin Genet, Bethesda, MD 20892 USA. Radboud Univ Nijmegen Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6500 HB Nijmegen, Netherlands. Radboud Univ Nijmegen Med Ctr, Dept Endocrinol, NL-6500 HB Nijmegen, Netherlands. RP Pacak, K (reprint author), NICHHD, Sect Med Neuroendocrinol, Reprod Biol & Med Branch, CRC, 10 Ctr Dr,Bldg 10,Room 1-E 3140,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Lenders, J.W.M./L-4487-2015 FU Intramural NIH HHS NR 38 TC 143 Z9 151 U1 0 U2 2 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 MAR PY 2007 VL 92 IS 3 BP 779 EP 786 DI 10.1210/jc.2006.2315 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 143LA UT WOS:000244721900006 PM 17200167 ER PT J AU Fleisch, AF Agarwal, N Roberts, MD Han, JC Theim, KR Vexler, A Troendle, J Yanovski, SZ Yanovski, JA AF Fleisch, Abby F. Agarwal, Neha Roberts, Mary D. Han, Joan C. Theim, Kelly R. Vexler, Albert Troendle, James Yanovski, Susan Z. Yanovski, Jack A. TI Influence of serum leptin on weight and body fat growth in children at high risk for adult obesity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID X-RAY ABSORPTIOMETRY; MASS INDEX; PLASMA LEPTIN; FASTING INSULIN; LONGITUDINAL CHANGES; ENERGY-EXPENDITURE; PHYSICAL-ACTIVITY; AFRICAN-AMERICAN; WHITE-CHILDREN; PIMA-INDIANS AB Objective: Our objective was to examine serum leptin prospectively as a predictor of weight and body fat growth in children at high risk for adult obesity. We hypothesized that leptin measurements would be positively associated with increased growth of adipose tissue because children with high baseline leptin for their body fat mass have greater leptin resistance and thus would have greater susceptibility to weight gain. Methods: Children ages 6 - 12 yr at high risk for adult obesity because of early-onset childhood overweight and/or parental overweight were recruited from 1996 - 2004. Growth in body mass index ( BMI) was studied in 197 children, and growth in total body fat mass was examined in 149 children over an average follow-up interval of 4.4 yr ( range, 1 - 8 yr). Longitudinal analyses accounted for sex, race, socioeconomic status, initial body composition, age, skeletal age, and physical activity and included all available interim visits for each individual so that a total of 982 subject visits were included in the analysis. Results: At baseline, 43% of children studied were overweight ( BMI >= 95th percentile); during follow-up, an additional 14% became overweight. Independent of initial body composition, baseline leptin was a statistically significant positive predictor of increased BMI ( P = 0.0147) and increased total body fat mass ( P < 0.007). Conclusions: High serum leptin, independent of body fat, may be an indicator of increased leptin resistance, which predisposes children at high risk for adult obesity to somewhat greater growth in weight and body fat during childhood. C1 NICHHD, Dev Endocrinol Branch, Unit Growth & Obes, NIH, Bethesda, MD 20892 USA. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, Dev Endocrinol Branch, Unit Growth & Obes, NIH, Hatfield CRC,ROom 1E-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01 HD000641] NR 59 TC 49 Z9 49 U1 0 U2 6 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 MAR PY 2007 VL 92 IS 3 BP 948 EP 954 DI 10.1210/jc2006-1390 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 143LA UT WOS:000244721900034 PM 17179198 ER PT J AU Bhasin, S Parker, RA Sattler, F Haubrich, R Alston, B Umbleja, T Shikuma, CM AF Bhasin, Shalender Parker, Robert A. Sattler, Fred Haubrich, Richard Alston, Beverly Umbleja, Triin Shikuma, Cecilia M. CA AIDS Clinical Trials Grp Protocol TI Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ADIPOSE-TISSUE DISTRIBUTION; CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; WEIGHT-LOSS; CONTROLLED-TRIAL; HIV-INFECTION; RISK-FACTORS; PERIPHERAL LIPODYSTROPHY; METABOLIC SYNDROME AB Background: Whole body and abdominal obesity are associated with increased risk of diabetes mellitus and heart disease. The effects of testosterone therapy on whole body and visceral fat mass in HIV-infected men with abdominal obesity are unknown. Objective: The objective of this study was to determine the effects of testosterone therapy on intraabdominal fat mass and whole body fat distribution in HIV-infected men with abdominal obesity. Methods: In this multicenter, randomized, placebo-controlled, double-blind trial, 88 HIV-positive men with abdominal obesity ( waist-to-hip ratio > 0.95 or mid-waist circumference > 100 cm) and total testosterone 125 - 400 ng/dl, or bioavailable testosterone less than 115 ng/dl, or free testosterone less than 50 pg/ml on stable antiretroviral regimen, and HIV RNA less than 10,000 copies per milliliter were randomized to receive 10 g testosterone gel or placebo daily for 24 wk. Fat mass and distribution were determined by abdominal computerized tomography and dual energy x-ray absorptiometry during wk 0, 12, and 24. We used an intention-to-treat approach and nonparametric statistical methods. Results: Baseline characteristics were balanced between groups. In 75 subjects evaluated, median percent change from baseline to wk 24 in visceral fat did not differ significantly between groups ( testosterone 0.3%, placebo 3.1%, P = 0.75). Total ( testosterone - 1.5%, placebo 4.3%, P = 0.04) and sc ( testosterone - 7.2%, placebo 8.1%, P < 0.001) abdominal fat mass decreased in testosterone-treated men, but increased in placebo group. Testosterone therapy was associated with significant decrease in whole body, trunk, and appendicular fat mass by dual energy x-ray absorptiometry ( all P < 0.001), whereas whole body and trunk fat increased significantly in the placebo group. The percent of individuals reporting a decrease in abdomen ( P = 0.01), neck ( P = 0.08), and breast size ( P = 0.01) at wk 24 was significantly greater in testosterone-treated than placebo-treated men. Testosterone-treated men had greater increase in lean body mass than placebo ( testosterone 1.3%, placebo - 0.3, P = 0.02). Plasma insulin, fasting glucose, and total high-density lipoprotein and low-density lipoprotein cholesterol levels did not change significantly. Testosterone therapy was well tolerated. Conclusions: Testosterone therapy in HIV-positive men with abdominal obesity and low testosterone was associated with greater decrease in whole body, total, and sc abdominal fat mass and a greater increase in lean mass compared to placebo. However, changes in visceral fat mass were not significantly different between groups. Further studies are needed to determine testosterone effects on insulin sensitivity and cardiovascular risk. C1 Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Med Ctr, Boston, MA 02118 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ So Calif, Los Angeles, CA 90033 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Univ Hawaii, Honolulu, HI 96817 USA. RP Bhasin, S (reprint author), Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Med Ctr, 670 Albany St,2nd Floor, Boston, MA 02118 USA. EM shalender.bhasin@bmc.org FU NIAID NIH HHS [AI38858] NR 55 TC 58 Z9 59 U1 0 U2 2 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 MAR PY 2007 VL 92 IS 3 BP 1049 EP 1057 DI 10.1210/jc.2006-2060 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 143LA UT WOS:000244721900048 PM 17164307 ER PT J AU Long, DN McGuire, S Levine, MA Weinstein, LS Germain-Lee, EL AF Long, Dominique N. McGuire, Sarah Levine, Michael A. Weinstein, Lee S. Germain-Lee, Emily L. TI Body mass index differences in pseudohypoparathyroidism type 1a versus pseudopseudohypoparathyroidism may implicate paternal imprinting of G alpha(s) in the development of human obesity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GS-ALPHA GENE; ALBRIGHT HEREDITARY OSTEODYSTROPHY; PROGRESSIVE OSSEOUS HETEROPLASIA; G(S)ALPHA KNOCKOUT MICE; PSEUDO-HYPOPARATHYROIDISM; TARGETED DISRUPTION; HORMONE RESISTANCE; SUBUNIT G(S)ALPHA; GNAS GENE; MUTATIONS AB Context: Obesity is a prominent feature of Albright hereditary osteodystrophy ( AHO), a disorder caused by heterozygous GNAS mutations that disrupt the stimulatoryGprotein alpha- subunit G alpha s. Because G alpha s is paternally imprinted in certain hormone target tissues, maternal inheritance of AHO leads to multihormone resistance [ pseudohypoparathyroidism type 1a ( PHP1a)], whereas paternal inheritance leads to AHO alone [ pseudopseudohypoparathyroidism ( pseudoPHP)]. Classically, the obesity in AHO is described as occurring similarly in both conditions. Setting: This observational study was conducted at the General Clinical Research Center, Johns Hopkins University School of Medicine; National Institutes of Health. Patients: Fifty- three patients with AHO ( 40 with PHP1a and 13 with pseudoPHP) and two with progressive osseous heteroplasia were studied. Main Outcome Measures: Main outcome measures were weight and height SD score ( SDS), body mass index ( BMI) percentiles, and BMI z- scores. Results: Patients with PHP1a had significantly greater mean weight SDS, BMI percentages, and BMI z- scores compared with patients with pseudoPHP. These differences in BMI were secondary to adipose content based on dual energy x-ray absorptiometry analysis. The mean BMI z- score +/- SEM for PHP1a was 2.31 +/- 0.18 compared with 0.65 +/- 0.31 in pseudoPHP ( P = 0.000032). Twenty- five of 40 ( 62.5%) patients with PHP1a had mean BMI z- scores greater than two SDS above the mean, whereas no patients with pseudoPHP had BMI z- scores in this range. Conclusions: Although the AHO phenotype for PHP1a and pseudoPHP has been thought to be similar, we have found that obesity is a more prominent feature in PHP1a than in pseudoPHP and that severe obesity is characteristic of PHP1a specifically. These findings may implicate paternal imprinting of G alpha s in the development of human obesity. C1 Johns Hopkins Univ, Sch Med, Dept Pediat, Div Pediat Endocrinol, Baltimore, MD 21287 USA. Cleveland Clin Fdn, Sect Pediat Endocrinol, Cleveland, OH 44195 USA. NIDDKD, Signal Transduct Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Germain-Lee, EL (reprint author), Johns Hopkins Univ Hosp, Dept Pediat, Div Pediat Endocrinol, CMSC 406,600 N Wolfe St, Baltimore, MD 21287 USA. EM egermain@jhmi.edu OI Levine, Michael/0000-0003-0036-7809 FU FDA HHS [R01 FD-R-002658]; Intramural NIH HHS [ZIA DK043302-16]; NCRR NIH HHS [M01 RR00052]; NIDDK NIH HHS [T32 DK007751] NR 40 TC 84 Z9 85 U1 0 U2 2 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 MAR PY 2007 VL 92 IS 3 BP 1073 EP 1079 DI 10.1210/jc.2006-1497 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 143LA UT WOS:000244721900051 PM 17164301 ER PT J AU Strober, W Fuss, I Mannon, P AF Strober, Warren Fuss, Ivan Mannon, Peter TI The fundamental basis of inflammatory bowel disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIVE ULCERATIVE-COLITIS; ENTERIC BACTERIAL-ANTIGENS; STEM-CELL TRANSPLANTATION; CROHNS-DISEASE; MAINTENANCE THERAPY; MONOCLONAL-ANTIBODY; ESCHERICHIA-COLI; DENDRITIC CELLS; T-CELLS; RANDOMIZED-TRIAL AB Two broad hypotheses have arisen regarding the fundamental nature of the pathogenesis of inflammatory bowel diseases (IBDs, which include ulcerative colitis and Crohn disease). The first contends that primary dysregulation of the mucosal immune system leads to excessive immunologic responses to normal microflora. The second suggests that changes in the composition of gut microflora and/or deranged epithelial barrier function elicits pathologic responses from the normal mucosal immune system. Here we examine these hypotheses and conclude that IBD is indeed characterized by an abnormal mucosal immune response but that microbial factors and epithelial cell abnormalities can facilitate this response. C1 NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bldg 10,CRC,Room 5-3940, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov NR 83 TC 677 Z9 703 U1 5 U2 84 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 MAR PY 2007 VL 117 IS 3 BP 514 EP 521 DI 10.1172/JCI30587 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 142PR UT WOS:000244662500006 PM 17332878 ER PT J AU Wynn, TA AF Wynn, Thomas A. TI Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID SYSTEMIC-SCLEROSIS; GROWTH-FACTOR; LIVER FIBROSIS; PULMONARY-FIBROSIS; HEPATIC-FIBROSIS; TISSUE FIBROSIS; IMMUNE-RESPONSE; CXC CHEMOKINES; CELL; ANGIOTENSIN AB Fibroproliferative diseases, including the pulmonary fibroses, systemic sclerosis, liver cirrhosis, cardiovascular disease, progressive kidney disease, and macular degeneration, are a leading cause of morbidity and mortality and can affect all tissues and organ systems. Fibrotic tissue remodeling can also influence cancer metastasis and accelerate chronic graft rejection in transplant recipients. Nevertheless, despite its enormous impact on human health, there are currently no approved treatments that directly target the mechanism(s) of fibrosis. The primary goals of this Review series on fibrotic diseases are to discuss some of the major fibroproliferative diseases and to identify the common and unique mechanisms of fibrogenesis that might be exploited in the development of effective antifibrotic therapies. C1 NIAID, Immunogenet Sect, NIH, Bethesda, MD 20892 USA. RP Wynn, TA (reprint author), NIAID, Immunogenet Sect, NIH, 50 South Dr,Room 6154,MSC 8003, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 NR 49 TC 562 Z9 600 U1 9 U2 58 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 MAR PY 2007 VL 117 IS 3 BP 524 EP 529 DI 10.1172/JCI31487 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 142PR UT WOS:000244662500007 PM 17332879 ER PT J AU Avila, AM Burnett, BG Taye, AA Gabanella, F Knight, MA Hartenstein, P Cizman, Z Di Prospero, NA Pellizzoni, L Fischbeck, KH Sumner, CJ AF Avila, Amy M. Burnett, Barrington G. Taye, Addis A. Gabanella, Francesca Knight, Melanie A. Hartenstein, Parvana Cizman, Ziga Di Prospero, Nicholas A. Pellizzoni, Livio Fischbeck, Kenneth H. Sumner, Charlotte J. TI Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; MOTOR-NEURON PROTEIN; VALPROIC ACID INCREASES; NEUROTROPHIC FACTORS; SINGLE NUCLEOTIDE; DETERMINING GENE; CLINICAL-TRIALS; MESSENGER-RNA; GROWTH CONES; MUSCLE AB The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by mutation of the telomeric survival motor neuron 1 (SMN1) gene with retention of the centromeric SMN2 gene. We sought to establish whether the potent and specific hydroxamic acid class of histone deacetylase (HDAC) inhibitors activates SMN2 gene expression in vivo and modulates the SMA disease phenotype when delivered after disease onset. Single intraperitoneal doses of 10 mg/kg trichostatin A (TSA) in nontransgenic and SMA model mice resulted in increased levels of acetylated H3 and H4 histones and modest increases in SMN gene expression. Repeated daily doses of TSA caused increases in both SMN2-derived transcript and SMN protein levels in neural tissues and muscle, which were associated with an improvement in small nuclear ribonucleoprotein (snRNP) assembly. When TSA was delivered daily beginning on PS, after the onset of weight loss and motor deficit, there was improved survival, attenuated weight loss, and enhanced motor behavior. Pathological analysis showed increased myofiber size and number and increased anterior horn cell size. These results indicate that the hydroxamic acid class of HDAC inhibitors activates SMN2 gene expression in vivo and has an ameliorating effect on the SMA disease phenotype when administered after disease onset. C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. CNR, Inst Cell Biol, Dulbecco Telethon Inst, Rome, Italy. RP Sumner, CJ (reprint author), NINDS, Neurogenet Branch, NIH, Bldg 35,Room 2A1010, Bethesda, MD 20892 USA. EM sumnerc@ninds.nih.gov FU Intramural NIH HHS; NINDS NIH HHS [K22 NS048199, K22-NS0048199-01]; Telethon [TCP02011] NR 60 TC 213 Z9 215 U1 1 U2 10 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 MAR PY 2007 VL 117 IS 3 BP 659 EP 671 DI 10.1172/JCI29562 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 142PR UT WOS:000244662500025 PM 17318264 ER PT J AU Meyer-Lindenberg, A Straub, RE Lipska, BK Verchinski, BA Goldberg, T Callicott, JH Egan, MF Huffaker, SS Mattay, VS Kolachana, B Kleinman, JE Weinberger, DR AF Meyer-Lindenberg, Andreas Straub, Richard E. Lipska, Barbara K. Verchinski, Beth A. Goldberg, Terry Callicott, Joseph H. Egan, Michael F. Huffaker, Stephen S. Mattay, Venkata S. Kolachana, Bhaskar Kleinman, Joel E. Weinberger, Daniel R. TI Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID AMP-REGULATED PHOSPHOPROTEIN; INNERVATED BRAIN-REGIONS; PREFRONTAL CORTEX; BASAL GANGLIA; IMMUNOCYTOCHEMICAL LOCALIZATION; DOPAMINE NEURONS; CEREBRAL-CORTEX; SCHIZOPHRENIA; STRIATUM; RAT AB Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32), encoded by PPP1R1B, is a pivotal integrator of information in dopaminoceptive neurons, regulating the response to neuroleptics, psychotomimetics, and drugs of abuse, and affecting striatal function and plasticity. Despite extensive preclinical work, there are almost no data on DARPP-32 function in humans. Here, we identify, through resequencing in 298 chromosomes, a frequent PPP1R1B haplotype predicting mRNA expression of PPP1R1B isoforms in postmortem human brain. This haplotype was associated with enhanced performance on several cognitive tests that depend on firontostriatal function. Multimodal imaging of healthy subjects revealed an impact of the haplotype on neostriatal volume, activation, and the functional connectivity of the prefrontal cortex. The haplotype was associated with the risk for schizophrenia in 1 family-based association analysis. Our convergent results identify a prefrontal-neostriatal system affected by variation in PPP1R1B and suggest that DARPP-32 plays a pivotal role in cognitive function and possibly in the pathogenesis of schizophrenia. C1 NIMH, Unit Syst Neurosci Psychiat, Genes Cognit & Psychosis Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIMH, Neuroimaging Core Facil, Genes Cognit & Psychosis Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Unit Syst Neurosci Psychiat, Genes Cognit & Psychosis Program, NIH,US Dept Hlth & Human Serv, Room 4S-235,10 Ctr Dr, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Callicott, Joseph/C-9102-2009; Meyer-Lindenberg, Andreas/H-1076-2011; Lipska, Barbara/E-4569-2017 OI Callicott, Joseph/0000-0003-1298-3334; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; FU Intramural NIH HHS NR 65 TC 137 Z9 140 U1 2 U2 7 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 MAR PY 2007 VL 117 IS 3 BP 672 EP 682 DI 10.1172/JCI30413 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 142PR UT WOS:000244662500026 PM 17290303 ER PT J AU Dahl, M Bauer, AK Arredouani, M Soininen, R Tryggvason, K Kleeberger, SR Kobzik, L AF Dahl, Morten Bauer, Alison K. Arredouani, Mohamed Soininen, Raija Tryggvason, Karl Kleeberger, Steven R. Kobzik, Lester TI Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MICROSOMAL EPOXIDE HYDROLASE; BIOLOGICALLY-ACTIVE OXYSTEROLS; OBSTRUCTIVE PULMONARY-DISEASE; OXIDATIVE STRESS; LUNG SURFACTANT; OZONATION PRODUCTS; BINDING-RECEPTOR; EPITHELIAL-CELLS; GENE-EXPRESSION; OZONE AB Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression in lungs of ozone-resistant mice suggested an additional role protecting against inhaled oxidants. After ozone exposure, MARCO(-/-) mice showed greater lung injury than did MARCO(+/+) mice. Ozone is known to generate oxidized, proinflammatory lipids in lung lining fluid, such as 5 beta,6 beta-epoxycholesterol (beta-epoxide) and 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (PON-GPC). Intratracheal instillation of either lipid caused substantial neutrophil influx in MARCO(-/-) mice, but had no effect in MARCO(+/+) mice. Normal AMs showed greater uptake in vitro of beta-epoxide compared with MARCO(-/-) AMs, consistent with SRA function in binding oxidized lipids. SR-AI/II-/- mice showed similar enhanced acute lung inflammation after beta-epoxide or another inhaled oxidant (aerosolized leachate of residual oil fly ash). In contrast, subacute ozone exposure did not enhance inflammation in SR-AI/II-/- versus SR-AI/II+/+ mice, reflecting increased AM expression of MARCO. These data identify what we believe to be a novel function for AM SRAs in decreasing pulmonary inflammation after oxidant inhalation by scavenging proinflammatory oxidized lipids from lung lining fluids. C1 Harvard Univ, Sch Med, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Res Triangle Pk, NC USA. Univ Oulu, Bioctr, Dept Med Biochem & Mol Biol, Oulu, Finland. Karolinska Inst, Dept Med Biochem & Biophys, Div Matrix Biol, Stockholm, Sweden. RP Kobzik, L (reprint author), Harvard Univ, Sch Med, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM lkobzik@hsph.harvard.edu RI Dahl, Morten/F-4219-2014 OI Dahl, Morten/0000-0002-6686-312X FU NIEHS NIH HHS [K22 ES014731-01, P30 ES000002, R01 ES011008, ES00002, ES011008] NR 52 TC 67 Z9 67 U1 2 U2 3 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 MAR PY 2007 VL 117 IS 3 BP 757 EP 764 DI 10.1172/JC129968 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 142PR UT WOS:000244662500035 PM 17332894 ER PT J AU Cheung, YY Kim, SY Yiu, WH Pan, CJ Jun, HS Ruef, RA Lee, EJ Westphal, H Mansfield, BC Chou, JY AF Cheung, Yuk Yin Kim, So Youn Yiu, Wai Han Pan, Chi-Jiunn Jun, Hyun-Sik Ruef, Robert A. Lee, Eric J. Westphal, Heiner Mansfield, Brian C. Chou, Janice Y. TI Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase-beta SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GLYCOGEN-STORAGE-DISEASE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; PHOSPHOHISTIDINE-ENZYME INTERMEDIATE; BONE-MARROW CELLS; ENDOPLASMIC-RETICULUM; HEXOSE-6-PHOSPHATE DEHYDROGENASE; TRANSMEMBRANE TOPOLOGY; GLUCOSE-HOMEOSTASIS; PROTEIN; TRANSPORTER AB Neutropenia and neutrophil dysfunction are common in many diseases, although their etiology is often unclear. Previous views held that there was a single ER enzyme, glucose-6-phosphatase-alpha (G6Pase-alpha), whose activity - limited to the liver, kidney, and intestine - was solely responsible for the final stages of gluconeogenesis and glycogenolysis, in which glucose-6-phosphate (G6P) is hydrolyzed to glucose for release to the blood. Recently, we characterized a second G6Pase activity, that of G6Pase-beta (also known as G6PC), which is also capable of hydrolyzing G6P to glucose but is ubiquitously expressed and not implicated in interprandial blood glucose homeostasis. We now report that the absence of G6Pase-beta led to neutropenia; defects in neutrophil respiratory burst, chemotaxis, and calcium flux; and increased susceptibility to bacterial infection. Consistent with this, G6Pase-beta-deficient (G6pc3(-/-)) mice with experimental peritonitis exhibited increased expression of the glucose-regulated proteins upregulated during ER stress in their neutrophils and bone marrow, and the G6pc3(-/-) neutrophils exhibited an enhanced rate of apoptosis. Our results define a molecular pathway to neutropenia and neutrophil dysfunction of previously unknown etiology, providing a potential model for the treatment of these conditions. C1 Chinese Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD USA. Correlog Syst Inc, Rockville, MD USA. NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bldg 10,Room 9D42, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov RI Jun, Hyun Sik/C-6799-2013 FU Intramural NIH HHS NR 49 TC 65 Z9 67 U1 0 U2 6 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 MAR PY 2007 VL 117 IS 3 BP 784 EP 793 DI 10.1172/JC130443 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 142PR UT WOS:000244662500038 PM 17318259 ER PT J AU Duan, SZ Ivashchenko, CY Whitesall, SE D'Alecy, LG Duquaine, DC Brosius, FC Gonzalez, FJ Vinson, C Pierre, MA Milstone, DS Mortensen, RM AF Duan, Sheng Zhong Ivashchenko, Christine Y. Whitesall, Steven E. D'Alecy, Louis G. Duquaine, Damon C. Brosius, Frank C., III Gonzalez, Frank J. Vinson, Charles Pierre, Melissa A. Milstone, David S. Mortensen, Richard M. TI Hypotension, lipodystrophy, and insulin resistance in generalized PPAR gamma-deficient mice rescued from embryonic lethality SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; DOMINANT-NEGATIVE MUTATIONS; BODY-FAT MASS; ADIPOSE-TISSUE; METABOLIC SYNDROME; BLOOD-PRESSURE; CELL-GROWTH; MUSCLE; HYPERTENSION; MOUSE AB We rescued the embryonic lethality of global PPAR gamma knockout by breeding Mox2-Cre (MORE) mice with floxed PPAR gamma mice to inactivate PPAR gamma in the embryo but not in trophoblasts and created a generalized PPAR gamma knockout mouse model, MORE-PPAR gamma knockout (MORE-PGKO) mice. PPAR gamma inactivation caused severe lipodystrophy and insulin resistance; surprisingly, it also caused hypotension. Paradoxically, PPAR gamma agonists had the same effect. We showed that another mouse model of lipodystrophy was hypertensive, ruling out the lipodystrophy as a cause. Further, high salt loading did not correct the hypotension in MOR.E-PGKO mice. In vitro studies showed that the vasculature from MORE-PGKO mice was more sensitive to endothelial-dependent relaxation caused by muscarinic stimulation, but was not associated with changes in eNOS expression or phosphorylation. In addition, vascular smooth muscle had impaired contraction in response to alpha-adrenergic agents. The renin-angiotensin-aldosterone system was mildly activated, consistent with increased vascular capacitance or decreased volume. These effects are likely mechanisms contributing to the hypotension. Our results demonstrated that PPAR gamma is required to maintain normal adiposity and insulin sensitivity in adult mice. Surprisingly, genetic loss of PPAR gamma function, like activation by agonists, lowered blood pressure, likely through a mechanism involving increased vascular relaxation. C1 Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA. William Beaumont Hosp, Dept Surg, Royal Oak, MI 48072 USA. Univ Michigan, Sch Med, Div Nephrol, Dept Internal Med, Ann Arbor, MI 48109 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Vasc Res Div, Boston, MA 02115 USA. Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Div Endocrinol Diabet & Metab, Ann Arbor, MI 48109 USA. RP Milstone, DS (reprint author), Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, 7726 Med Sci 2,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM milstone@rascal.med.harvard.edu; rmort@umich.edu OI 段, 胜仲/0000-0001-5399-7252 FU NHLBI NIH HHS [R01 HL083201, R01HL083201]; NICHD NIH HHS [R01 HD040895, R01HD040895]; NIDDK NIH HHS [DK20572, P60 DK020572] NR 56 TC 101 Z9 101 U1 0 U2 3 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 MAR PY 2007 VL 117 IS 3 BP 812 EP 822 DI 10.1172/JCI28859 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 142PR UT WOS:000244662500041 PM 17304352 ER PT J AU Harrington, SM Stock, F Kominski, AL Campbell, JD Hormazabal, JC Livio, S Rao, L Kotloff, KL Sow, SO Murray, PR AF Harrington, S. M. Stock, F. Kominski, A. L. Campbell, J. D. Hormazabal, J. C. Livio, S. Rao, L. Kotloff, K. L. Sow, S. O. Murray, P. R. TI Genotypic analysis of invasive Streptococcus pneumoniae from Mali, Africa, by semiautomated repetitive-element PCR and pulsed-field gel electrophoresis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SEQUENCE-BASED PCR; PNEUMOCOCCAL CONJUGATE VACCINE; POLYMERASE-CHAIN-REACTION; MICROBIAL TYPING SYSTEM; ENTEROCOCCUS-FAECIUM; UNITED-STATES; STAPHYLOCOCCUS-AUREUS; SEROTYPE DISTRIBUTION; CLINICAL-EVALUATION; DIVERSILAB SYSTEM AB As part of a large, ongoing study of invasive infections in pediatric patients in Bamako, Mali, 106 cases of invasive pneumococcal disease were identified from June 2002 to July 2003 (J. D. Campbell et al., Pediatr. Infect. Dis. J. 23:642-649, 2004). Of the 12 serotypes present, the majority of isolates were not contained in PCV7 (the 7-valent pneumococcal conjugate vaccine), including 1 isolate that was serotype 1, 12 isolates that were serotype 2, 58 isolates that were serotype 5, 7 isolates that were serotype 717, and 1 isolate that was serotype 12F. To determine whether clonal dissemination of the predominant serotypes had taken place, genotyping was performed on 100 S. pneumoniae isolates by using two methods: pulsed-field gel electrophoresis (PFGE) of Smal-digested genomic DNA, and the Bacterial Barcodes repetitive-element PCR (rep-PCR) method. Criteria for delineating rep-PCR genotypes were established such that isolates of different serotypes were generally not grouped together. The two methods were equally discriminatory within a given pneumococcal serotype. PFGE separated the isolates into 15 genotypes and 7 subtypes; rep-PCR separated isolates into 15 genotypes and 6 subtypes. Using either method, isolates within serotypes 2, 5, and 7 formed three large, separate clusters containing I genotype each. Both methods further distinguished related subtypes within serotypes 2 and 5. Interestingly, one of the PFGE subtypes of serotype 5 is indistinguishable from the Columbia(5)-19 clone circulating in Latin America since 1994. The data support that serotypes 2 and 5 were likely to be the result of dissemination of particular clones, some of which are responsible for invasive disease over a broad population range. C1 Natl Inst Hlth, Dept Lab Med, Bethesda, MD USA. Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Inst Salud Publ Chile, Dept Microbiol, Santiago, Chile. Ctr Vaccine Dev, Bamako, Mali. RP Harrington, SM (reprint author), Albany Med Ctr, Dept Pathol & Lab Med, MC-22,43 New Scotland Ave, Albany, NY 12208 USA. EM HarrinS@mail.amc.edu RI kotloff, karen/E-7768-2012 OI kotloff, karen/0000-0003-1808-6431 FU Intramural NIH HHS NR 38 TC 21 Z9 22 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2007 VL 45 IS 3 BP 707 EP 714 DI 10.1128/JCM.01871-06 PG 8 WC Microbiology SC Microbiology GA 148JU UT WOS:000245071500003 PM 17192418 ER PT J AU Yea, C Bukh, J Ayers, M Roberts, E Krajden, M Tellier, R AF Yea, Carmen Bukh, Jens Ayers, Melissa Roberts, Eve Krajden, Mel Tellier, Raymond TI Monitoring of hepatitis C virus quasispecies in chronic infection by matrix-assisted laser desorption ionization-time of flight mass spectrometry mutation detection SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HYPERVARIABLE REGION-1; SECONDARY STRUCTURE; PROTEIN; NEUTRALIZATION; GLYCOPROTEIN; CHIMPANZEES; PREVENTION; ANTIBODIES; EVOLUTION; VARIANTS AB Using both a mass spectrometry-based method and the classical method of cloning and sequencing, we demonstrated weekly changes in the hypervariable region 1 quasispecies of a chimpanzee infected with an infectious clone, coinciding with neutralizing antibody emergence. We also used the mass spectrometry method in the clinical follow-up of a chronically infected patient over a 5-year period. C1 Hosp Sick Children, Div Microbiol, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Div Gastroenterol, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Metab Res Program, Toronto, ON M5G 1X8, Canada. NIAID, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. Copenhagen Univ Hosp, Dept Infect Dis, Hvidovre, Denmark. British Columbia Ctr Dis Control, Vancouver, BC, Canada. RP Tellier, R (reprint author), Hosp Sick Children, Div Microbiol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM raymond.tellier@sickkids.ca FU Intramural NIH HHS NR 20 TC 8 Z9 10 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 MAR PY 2007 VL 45 IS 3 BP 1053 EP 1057 DI 10.1128/JCM.02512-06 PG 5 WC Microbiology SC Microbiology GA 148JU UT WOS:000245071500059 PM 17229863 ER PT J AU Kim, GP Colangelo, LH Wieand, HS Paik, S Kirsch, IR Wolmark, N Allegra, CJ AF Kim, George P. Colangelo, Linda H. Wieand, H. Samuel Paik, Soonmyung Kirsch, Ilan R. Wolmark, Norman Allegra, Carmen J. TI Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: A National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Symposium on Gastrointestinal Cancer of the American-Society-of-Clinical-Oncology CY JAN 27-29, 2005 CL Hollywood, FL SP Amer Soc Clin Oncol ID THYMIDYLATE SYNTHASE EXPRESSION; DNA MISMATCH REPAIR; SPORADIC COLORECTAL-CANCER; YOUNG-PATIENTS; CHEMOTHERAPY; FLUOROURACIL; SURVIVAL; P53; CARCINOMA; BENEFIT AB Purpose The role of high-degree microsatellite instability (MSI-H) as a marker to predict benefit from adjuvant chemotherapy remains unclear. Patients and Methods To help define its impact, we conducted an analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) patients who were randomly assigned to a surgery-alone group (untreated cohort) and patients assigned to an adjuvant fluorouracil (FU) -treated group (treated cohort). MSI-H and other potential markers were assessed (TGF-BRII, p53, thymidylate synthase, and Ki67). Results In all, 98 (18.1 %) of 542 patients exhibited MSI-H, and there was a strong inverse relationship between MSI-H and mutant p53 status (P <.001). The prognostic analyses showed increased recurrence-free survival (RFS) for MSI-H patients versus MSS/MSI-L patients (P =.10), but showed no difference in overall survival (OS; P =.67). There was a potential interaction between MSI-H and mutant p53 in terms of improved RFS (P =.03). In the predictive marker analysis, we observed no interaction between MSI status and treatment for either RFS (P =.68) or OS (P =.62). Hazard ratios (HR) for RFS for MSI-H versus MSS/MSI-L patients were 0.77 (95% Cl, 0.40 to 1.48) in the untreated-patients group and 0.60 (95% Cl, 0.30 to 1.19) in the treated-patients group. HRs for OS were 0.82 (95% Cl, 0.44 to 1.51) and 1.02 (95% Cl, 0.56 to 1.85) for the respective groups. There was a trend toward improved RFS in patients with MSI-H and mutant p53. Conclusion These results do not support the use of MSI-H as a predictive marker of chemotherapy benefit. C1 Mayo Clin Jacksonville, Natl Surg Adjuvant Breast & Bowel Project, Operat & Biostat Ctr, Jacksonville, FL 32224 USA. NCI, Genet Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Network Med Commun & Res, N Potomac, MD USA. RP Kim, GP (reprint author), Mayo Clin Jacksonville, Natl Surg Adjuvant Breast & Bowel Project, Operat & Biostat Ctr, Davis Bldg 8-E,4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM kim.george@mayo.edu FU NCI NIH HHS [P-U10CA-37377, U10CA-12027, U10CA-69651, U10CA-69974] NR 41 TC 187 Z9 195 U1 0 U2 5 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 MAR 1 PY 2007 VL 25 IS 7 BP 767 EP 772 DI 10.1200/JCO.2006.05.8172 PG 6 WC Oncology SC Oncology GA 145SK UT WOS:000244884600006 PM 17228023 ER PT J AU Scharf, O Colevas, AD AF Scharf, Orit Colevas, A. Dimitrios TI More thoughts on the reporting of adverse events in cancer clinical trials - Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CYCLOPHOSPHAMIDE; DOXORUBICIN; DOCETAXEL; BREAST C1 PSI Int Inc, Fairfax, VA USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Scharf, O (reprint author), PSI Int Inc, Fairfax, VA USA. NR 3 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 MAR 1 PY 2007 VL 25 IS 7 BP 918 EP 919 DI 10.1200/JCO.2006.09.8996 PG 2 WC Oncology SC Oncology GA 145SK UT WOS:000244884600039 ER PT J AU Yin, PD Kurup, SK Fischer, SH Rhee, HH Byrnes, GA Levy-Clarke, GA Buggage, RR Nussenblatt, RB Mican, JM Wright, ME AF Yin, Philip D. Kurup, Shree K. Fischer, Steven H. Rhee, Henry H. Byrnes, Gordon A. Levy-Clarke, Grace A. Buggage, Ronald R. Nussenblatt, Robert B. Mican, Joann M. Wright, Mary E. TI Progressive outer retinal necrosis in the era of highly active antiretroviral therapy: Successful management with intravitreal injections and monitoring with quantitative PCR SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE AIDS; HIV-1; varicella zoster virus; HAART; acute retinal necrosis syndrome; retinitis ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; VARICELLA-ZOSTER VIRUS; POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; CYTOMEGALOVIRUS RETINITIS; AIDS; VALGANCICLOVIR; COMBINATION; DISEASE; TRIAL AB Background: Progressive outer retinal necrosis (PORN) is an ocular disease in individuals with AIDS and is associated with substantial morbidity. The optimal management of PORN and its clinical course in the HAART era is unclear. Objective: We report a case of successfully managed PORN that provides insight into the monitoring and treatment of this disease. Study design: Intravitreal injections and intravenous therapy targeted towards varicella zoster virus (VZV) were used to treat PORN. HAART was initiated for HIV-1 therapy. Serial PCR for VZV was performed on aqueous humor to monitor the clinical course. Results: The presence of VZV DNA from aqueous humor correlated with clinical exacerbations of disease. Initiation of twice weekly intravitreal injections with dual antiviral drugs appeared to be an important therapeutic intervention that resulted in remission of PORN. Secondary prophylaxis against VZV was successfully withdrawn after HAART induced partial immune recovery. Conclusion: In addition to aggressive therapy with intravitreal injections, HAART and quantitative measurements of VZV DNA from aqueous humor have important roles in the management of PORN. A multidisciplinary approach involving specialists in infectious diseases, ophthalmology, and clinical microbiology will improve the chances for successful long-term outcomes. (C) 2007 Elsevier B.V. All rights reserved. C1 NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. IDSVA, Fairfax, VA USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIAID, Bethesda, MD 20892 USA. NEI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Yin, PD (reprint author), NCI, NIH, Dept Hlth & Human Serv, 9000 Rockville Pike,Bldg 10,10S255, Bethesda, MD 20892 USA. EM pdyin@mail.nih.gov NR 25 TC 20 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD MAR PY 2007 VL 38 IS 3 BP 254 EP 259 DI 10.1016/j.jcv.2006.12.012 PG 6 WC Virology SC Virology GA 149QE UT WOS:000245160900011 PM 17280866 ER PT J AU Schmitt, DP Allik, J McCrae, RR Benet-Martinez, V Alcalay, L Ault, L Austers, I Bennett, KL Bianchi, G Boholst, F Cunen, MAB Braeckman, J Brainerd, EG Gerard, L Caron, G Casullo, MM Cunningham, M Daibo, I De Backer, C DeSouza, E Diaz-Loving, R Diniz, G Durkin, K Echegaray, M Eremsoy, E Euler, HA Falzon, R Fisher, ML Foley, D Fry, DP Fry, S Ghayur, MA Giri, VN Golden, DL Grammer, K Grimaldi, L Halberstadt, L Hague, S Herrera, D Hertel, J Hoffmann, H Hooper, D Hradilekova, Z Hudek-Kene-evi, J Jaafar, J Jankauskaite, M Kabanagu-Stahel, H Kardum, I Khoury, N Kwon, H Laidra, K Laireiter, AR Lakerveld, D Lampert, A Lauri, M Lavallee, M Lee, SJ Leung, LC Locke, KD Locke, V Luksik, I Magaisa, I Marcinkeviciene, D Mata, A Mata, R McCarthy, B Mills, ME Mikhize, NJ Moreira, J Moreira, S Moya, M Munyae, M Noller, P Olimar, H Opre, A Panayiotou, A Petrovic, N Poels, K Popper, M Poulimenou, M P'yatokh, V Raymond, M Reips, UD Reneau, SE Rivera-Aragon, S Rowatt, WC Ruch, W Rus, VS Safir, MP Salas, S Sambataro, F Sandnabba, KN Schulmeyer, MK Schutz, A Scrimali, T Shackelford, TK Sharan, MB Shaver, PR Sichona, F Simonetti, F Sineshaw, T Sookdew, R Spelman, T Spyron, S Sumer, HC Sumer, N Supekova, M Szlendak, T Taylor, R Timmermans, B Tooke, W Tsaousis, I Tungaranza, FSK Van Overwalle, F Vandermassen, G Vanhoomissen, T Vanwesenbeeck, I Vasey, PL Verissimo, J Voracek, M Was, WWN Wang, TW Weiss, P Wijaya, A Woertman, L Youn, G Zupaneic, A AF Schmitt, David P. Allik, Juri McCrae, Robert R. Benet-Martinez, Veronica Alcalay, Lidia Ault, Lara Austers, Ivars Bennett, Kevin L. Bianchi, Gabriel Boholst, Fredrick Cunen, Mary Ann Borg Braeckman, Johan Brainerd, Edwin G. Gerard, Leo Caron, Gabrielle Casullo, Maria Martina Cunningham, Michael Daibo, Ikuo De Backer, Charlene DeSouza, Eros Diaz-Loving, Rolando Diniz, Glaucia Durkin, Kevin Echegaray, Marcela Eremsoy, Ekin Euler, Harald A. Falzon, Ruth Fisher, Maryanne L. Foley, Dolores Fry, Douglas P. Fry, Sirpa Ghayur, M. Arif Giri, Vjai N. Golden, Debra L. Grammer, Karl Grimaldi, Liria Halberstadt, Liria Hague, Shamsul Herrera, Dora Hertel, Janine Hoffmann, Heather Hooper, Danica Hradilekova, Zuzana Hudek-Kene-evi, Jasna Jaafar, Jas Jankauskaite, Margarita Kabanagu-Stahel, Heidi Kardum, Igor Khoury, Brigitte Kwon, Hayrran Laidra, Kaia Laireiter, Anton-Rupert Lakerveld, Dustin Lampert, Ada Lauri, Maryanne Lavallee, Marguerite Lee, Suk-Jae Leung, Luk Chung Locke, Kenneth D. Locke, Vance Luksik, Ivan Magaisa, Ishmael Marcinkeviciene, Dalia Mata, Andre Mata, Rui McCarthy, Barry Mills, Michael E. Mikhize, Nhlanhla J. Moreira, Joao Moreira, Sergio Moya, Miquel Munyae, M. Noller, Patricia Olimar, Hmoud Opre, Adrian Panayiotou, Alexia Petrovic, Nebojsa Poels, Karolien Popper, Miroslav Poulimenou, Maria P'yatokh, Volodymyr Raymond, Michel Reips, Ulf-Dietrich Reneau, Susan E. Rivera-Aragon, Sofia Rowatt, Wade C. Ruch, Willibald Rus, Velko S. Safir, Marilyn P. Salas, Sonia Sambataro, Fabio Sandnabba, Kenneth N. Schulmeyer, Marion K. Schutz, Astrid Scrimali, Tulio Shackelford, Todd K. Sharan, Mithila B. Shaver, Phillip R. Sichona, Francis Simonetti, Franco Sineshaw, Tilahun Sookdew, R. Spelman, Tom Spyron, Spyrow Sumer, H. Canan Sumer, Nebi Supekova, Marianna Szlendak, Tomasz Taylor, Robin Timmermans, Bert Tooke, William Tsaousis, Ioannis Tungaranza, F. S. K. Van Overwalle, Frank Vandermassen, Griet Vanhoomissen, Tim Vanwesenbeeck, Inc Vasey, Paul L. Verissimo, Joao Voracek, Martin Was, Wendy W. N. Wang, Ta-Wei Weiss, Peter Wijaya, Andik Woertman, Liesbeth Youn, Gahyun Zupaneic, Agata TI The geographic distribution of big five personality traits - Patterns and profiles of human self-description across 56 nations SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article DE personality traits; cross-cultural psychology; Big Five ID CROSS-CULTURAL RESEARCH; 5-FACTOR MODEL; METHODOLOGICAL ISSUES; RESPONSE STYLES; COUNTRIES; DIMENSIONS; EXTROVERSION; PSYCHOLOGY; VALIDITY; QUESTIONNAIRE AB The Big Five Inventory (BFI) is a self-report measure designed to assess the high-order personality traits of Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness. As part of the International Sexuality Description Project, the BFI was translated from English into 28 languages and administered to 17,837 individuals from 56 nations. The resulting cross-cultural data set was used to address three main questions: Does the factor structure of the English BFI fully replicate across cultures? How valid are the BFI trait profiles of individual nations'? And how are personality traits distributed throughout the world? The five-dimensional structure was robust across major regions of the world. Trait levels were related in predictable ways to self-esteem, sociosexuality, and national personality profiles. People from the geographic regions of South America and East Asia were significantly different in openness from those inhabiting other world regions. The discussion focuses on limitations of the current data set and important directions for future research. C1 Bradley Univ, Dept Psychol, Peoria, IL 61625 USA. Univ Tartu, EE-50090 Tartu, Estonia. NIA, Bethesda, MD 20892 USA. Univ Calif Riverside, Riverside, CA 92521 USA. Univ Louisville, Louisville, KY USA. Pontificia Univ Catolica Chile, Santiago, Chile. Univ Latvia, Riga, Latvia. Penn State Univ, University Pk, PA USA. RP Schmitt, DP (reprint author), Bradley Univ, Dept Psychol, Peoria, IL 61625 USA. EM dps@bradley.edu RI Sambataro, Fabio/E-3426-2010; Weiss, Petr/F-9516-2016; Moreira, Joao/C-4723-2008; Allik, Juri/D-5609-2009; Mata, Rui/K-8138-2015; Voracek, Martin/S-5865-2016; Ruch, Willibald/G-3124-2011; Grammer, Karl/A-5012-2011; Moya Morales, Miguel/B-4381-2011; Reips, Ulf-Dietrich/A-5177-2012; Benet-Martinez, Veronica/B-5398-2011; Raymond, Michel/C-9049-2015; Laidra, Kaia/D-4939-2017; OI Sambataro, Fabio/0000-0003-2102-416X; Weiss, Petr/0000-0003-2399-8005; Moreira, Joao/0000-0003-3465-7046; Allik, Juri/0000-0002-8358-4747; Mata, Rui/0000-0002-1679-906X; Voracek, Martin/0000-0001-6109-6155; Ruch, Willibald/0000-0001-5368-3616; Grammer, Karl/0000-0001-7801-6131; Moya Morales, Miguel/0000-0003-2421-7282; Benet-Martinez, Veronica/0000-0002-3352-9731; Laidra, Kaia/0000-0003-4371-1358; Mata, Andre/0000-0001-5087-4919; Luk, Chung Leung/0000-0002-1173-9420; Raymond, Michel/0000-0002-1714-6984; Schutz, Astrid/0000-0002-6358-167X NR 99 TC 264 Z9 270 U1 45 U2 173 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD MAR PY 2007 VL 38 IS 2 BP 173 EP 212 DI 10.1177/0022022106297299 PG 40 WC Psychology, Social SC Psychology GA 140TM UT WOS:000244529600005 ER PT J AU Kato, H Jochim, RC Lawyer, PG Valenzuela, JG AF Kato, Hirotomo Jochim, Ryan C. Lawyer, Phillip G. Valenzuela, Jesus G. TI Identification and characterization of a salivary adenosine deaminase from the sand fly Phlebotomus duboscqi, the vector of Leishmania major in sub-Saharan Africa SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE sand fly; saliva; ADA; adenosine deaminase; insect saliva; Phlebotomus ID LUTZOMYIA-LONGIPALPIS; SEQUENCE ALIGNMENT; PROTEINS; GLANDS AB Two transcripts coding for an adenosine deaminase (ADA) were identified by sequencing a Phlebotomus duboscqi salivary gland cDNA library. Adenosine deaminase was previously reported in the saliva of the sand fly Lutzomyia longipalpis but it was not present in the saliva of the sand flies Phlebotomus papatasi, P. argentipes, P. perniciosus and P. ariasi, suggesting that this enzyme is only present in the saliva of sand flies from the genus Lutzomyia. In the present work, we tested the hypothesis that the salivary gland transcript coding for ADA in Phlebotomus duboscqi, a sister species of Phlebotomus papatasi, produces an active salivary ADA. Salivary gland homogenates of P. duboscqi converted adenosine to inosine, suggesting the presence of ADA activity in the saliva of this species of sand fly; furthermore, this enzymatic activity was significantly reduced when using either salivary glands of recently blood-fed sand flies or punctured salivary glands, suggesting that this enzyme is secreted in the saliva of this insect. This enzymatic activity was absent from the saliva of P. papatasi. In contrast to other Phlebotomus sand flies, we did not find AMP or adenosine in P. duboscqi salivary glands as measured by HPLC-photodiode array. To confirm that the transcript coding for ADA was responsible for the activity observed in the saliva of this sand fly, we cloned this transcript into a prokaryotic expression vector and produced a soluble and active recombinant protein of approximately 60 kDa that was able to convert adenosine to inosine. Extracts of bacteria transformed with control plasmids did not show this activity. These results suggest that P. duboscqi transcripts coding for ADA are responsible for the activity detected in the salivary glands of this sand fly and that P. duboscqi acquired this activity independently from other Phlebotomus sand flies. This is another example of a gene recruitment event in salivary genes of blood-feeding arthropods that may be relevant for blood feeding and, because of the role of ADA in immunity, it may also play a role in parasite transmission. C1 NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Yamaguchi Univ, Fac Agr, Dept Vet Hyg, Yamaguchi 753, Japan. NIAID, Parasit Dis Lab, NIH, Rockville, MD 20852 USA. RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 2E-22C, Rockville, MD 20852 USA. EM jvalenzuela@niaid.nih.gov RI Kato, Hirotomo/A-4820-2012; Jochim, Ryan/C-6756-2013 OI Kato, Hirotomo/0000-0001-5429-9536; FU NIAID NIH HHS [1Z01AI00093202] NR 19 TC 18 Z9 19 U1 1 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD MAR 1 PY 2007 VL 210 IS 5 BP 733 EP 740 DI 10.1242/jeb.001289 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 142EU UT WOS:000244633000009 PM 17297134 ER PT J AU Waters, EA Weinstein, ND Colditz, GA Emmons, KA AF Waters, Erika A. Weinstein, Neil D. Colditz, Graham A. Emmons, Karen A. TI Reducing aversion to side effects in preventive medical treatment decisions SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-APPLIED LA English DT Article DE decision making; risk perception; risk communication; visual display; graphical display ID RISK COMMUNICATION; GRAPHICAL PERCEPTION; PROSPECT-THEORY; FORMATS; INFORMATION; DISPLAYS; CHOICE; UNCERTAINTY; AVOIDANCE; FREQUENCY AB Laypeople tend to be overly sensitive to side effects of treatments that prevent illness, possibly leading them to refuse beneficial therapies. This Internet-based study attempted to reduce such side effect aversion by adding graphic displays to the numerical risk probabilities. It also explored whether graphics reduce side effect aversion by making it easier for respondents to determine how the treatment might change their net cancer risk. Participants (N = 4,248) were presented with a hypothetical preventive treatment situation that was or was not accompanied by a small side effect. In both conditions, the net absolute risk reduction was 12%. Adding an array of stick figures to risk probabilities reduced side effect aversion substantially, but adding a bar graph was not beneficial. The ability of arrays to reduce side effect aversion was not attributable to greater accuracy in evaluating the treatment's net benefit. C1 Rutgers State Univ, Dept Psychol, Piscataway, NJ 08855 USA. Rutgers State Univ, Dept Human Ecol, Piscataway, NJ 08855 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Waters, EA (reprint author), NCI, Canc Prevent Fellowship Program, Div Canc Prevent, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM erika.a.waters@gmail.com RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Waters, Erika/0000-0001-7402-0133 NR 38 TC 45 Z9 45 U1 3 U2 12 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1076-898X J9 J EXP PSYCHOL-APPL JI J. Exp. Psychol.-Appl. PD MAR PY 2007 VL 13 IS 1 BP 11 EP 21 DI 10.1037/1076-898X.13.1.11 PG 11 WC Psychology, Applied SC Psychology GA 148GV UT WOS:000245063600002 PM 17385998 ER PT J AU Muniyappa, R Quon, MJ AF Muniyappa, Ranganath Quon, Michael J. TI Glucosamine and glycemic control SO JOURNAL OF FAMILY PRACTICE LA English DT Letter C1 NIH, Natl Ctr Complementary & Alternat Med, Div Intramural Res, Diabet Unit, Bethesda, MD 20892 USA. RP Muniyappa, R (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Div Intramural Res, Diabet Unit, Bldg 10, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 1 TC 1 Z9 1 U1 0 U2 0 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 MAR PY 2007 VL 56 IS 3 BP 192 EP 192 PG 1 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 191GG UT WOS:000248119000008 ER PT J AU White, PL Naugle, AL Jackson, CR Fedorka-Cray, PJ Rose, BE Pritchard, KM Levine, P Saini, PK Schroeder, CM Dreyfuss, MS Tan, R Holt, KG Harman, J Buchanan, S AF White, Patricia L. Naugle, Alecia L. Jackson, Charlene R. Fedorka-Cray, Paula J. Rose, Bonnie E. Pritchard, Katrine M. Levine, Priscilla Saini, Parmesh K. Schroeder, Carl M. Dreyfuss, Moshe S. Tan, Regina Holt, Kristin G. Harman, Jane Buchanan, Stephanie TI Salmonella Enteritidis in meat, poultry, and pasteurized egg products regulated by the US food safety and inspection service, 1998 through 2003 SO JOURNAL OF FOOD PROTECTION LA English DT Article ID UNITED-STATES; PHAGE TYPE-4; RESISTANT SALMONELLA; NONTYPHOIDAL SALMONELLA; ANTIBIOTIC-RESISTANCE; INFECTIONS; VIRULENCE; ESTABLISHMENTS; SURVEILLANCE; CALIFORNIA AB The U.S. Food Safety and Inspection Service (FSIS) tests for Salmonella in meat, poultry, and egg products through three regulatory testing programs: the Pathogen Reduction-Hazard Analysis and Critical Control Point (PR-HACCP) program, the ready-to-eat program for meat and poultry products, and the pasteurized egg products program. From 1998 through 2003, 293,938 samples collected for these testing programs were analyzed for the presence of Salmonella enterica serotypes. Of these samples, 12,699 (4.3%) were positive for Salmonella, and 167 (1.3%) of the positive samples (0.06% of all samples) contained Salmonella Enteritidis. The highest incidence of Salmonella Enteritidis was observed in ground chicken PR-HACCP samples (8 of 1,722 samples, 0.46%), and the lowest was found in steer-heifer PR-HACCP samples (0 of 12,835 samples). Salmonella Enteritidis isolates were characterized by phage type, pulsed-field gel electrophoretic pattern, and antimicrobial susceptibility. Phage typing of 94 Salmonella Enteritidis isolates identified PT13 (39 isolates) and PT8 (36 isolates) as the most common types. One isolate from a ready-to-eat ham product was characterized as PT4. Electrophoretic analysis of 148 Salmonella Enteritidis isolates indicated genetic diversity among the isolates, with 28 unique XbaI electrophoretic patterns identified. Of these 148 isolates, 136 (92%) were susceptible to each of 16 antimicrobials tested. Two isolates were resistant to ampicillin alone, and 10 isolates were resistant to two or more antimicrobials. Isolation of Salmonella Enteritidis from FSIS-regulated products emphasizes the need for continued consumer education on proper food handling and cooking practices and continued work to decrease the prevalence of Salmonella in meat, poultry, and pasteurized egg products. C1 USDA, Div Microbiol, Washington, DC 20250 USA. USDA, Human Hlth Sci Div, Washington, DC 20250 USA. USDA, Management Support Staff, Washington, DC 20250 USA. USDA, Risk Assessment Div, Off Publ Hlth Sci, Food Safety & Inspect Serv, Washington, DC 20250 USA. USDA, ARS, Bacterial Epidemiol & Antimicrobial Resistance Re, Athens, GA 30605 USA. USDA, Food Safety & Inspect Serv, Human Hlth Sci Div, Off Publ Hlth Sci, Atlanta, GA 30333 USA. NHLBI, Div Prevent & Populat Sci, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Dreyfuss, MS (reprint author), USDA, Div Microbiol, Washington, DC 20250 USA. EM moshe.dreyfuss@fsis.usda.gov NR 48 TC 23 Z9 24 U1 1 U2 9 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 2007 VL 70 IS 3 BP 582 EP 591 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 143QC UT WOS:000244736600007 PM 17388045 ER PT J AU Bonkovsky, HL Snow, KK Malet, PF Back-Madruga, C Fontana, RJ Sterling, RK Kulig, CC Di Bisceglie, AM Morgan, TR Dienstag, JL Ghany, MG Gretch, DR AF Bonkovsky, Herbert L. Snow, Kristin K. Malet, Peter F. Back-Madruga, Carla Fontana, Robert J. Sterling, Richard K. Kulig, Clark C. Di Bisceglie, Adrian M. Morgan, Timothy R. Dienstag, Jules L. Ghany, Marc G. Gretch, David R. CA HALT-C Trial Grp TI Health-related quality of life in patients with chronic hepatitis C and advanced fibrosis SO JOURNAL OF HEPATOLOGY LA English DT Article DE cirrhosis; fibrosis; health-related quality of life; hepatitis; viral type C; sexual functioning; sustained virological response ID VIRUS-INFECTION; PEGINTERFERON ALPHA-2A; SURVEY SF-36; WORK PRODUCTIVITY; PLUS RIBAVIRIN; INTERFERON; THERAPY; RELIABILITY; COMBINATION; REDUCTION AB Background/Aims: Although the antiviral and histological benefits of peginterferon/ribavirin therapy are well established, the effects on health-related quality of life (HRQOL) and sexual health are less certain. This study assessed HRQOL and sexual health in patients with advanced fibrosis or cirrhosis in the HALT-C Trial. Methods: Subjects completed SF-36 and sexual health questionnaires prior to and after 24 weeks of peginterferon/ribavirin therapy (n = 1144). Three hundred and seventy-three (33%) subjects were HCV RNA negative at week 20 and continued therapy through week 48; 258 were seen at week 72. One hundred and eighty achieved sustained virological responses (SVR) and 78 relapsed. Results: At baseline, patients had poorer scores for all eight SF-36 domains compared to healthy controls. Patients with cirrhosis had lower HRQOL scores than those with bridging fibrosis, as did patients with higher depression scores. SVR patients had significant improvements in seven domains, whereas relapsers had significant worsening in one domain. Sexual scores improved in SVR patients and decreased in relapsers (p = 0.03). In multivariate analyses, improvements in HRQOL and sexual scores were significantly associated with SVR but were less striking in patients with lower depression scores. Conclusions: Achievement of SVR after peginterferon/ribavirin therapy improves HRQOL and sexual health in chronic hepatitis C patients with advanced fibrosis or cirrhosis. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Dept Microbial & Struct Biol, Farmington, CT USA. New England Res Inst, Watertown, MA 02172 USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX USA. Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90089 USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. Virginia Commonwealth Univ, Hlth Syst, Div Gastroenterol Hepatol & Nutr, Hepatol Sect, Richmond, VA USA. Univ Colorado, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Denver, CO USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA 92717 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA USA. NIDDKD, Liver Dis Branch, Div Digest Dis & Nutr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Bonkovsky, HL (reprint author), Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. EM bonkovsky@uchc.edu FU NCRR NIH HHS [M01 RR000042, M01 RR000043, M01 RR000051, M01 RR000065, M01 RR000633, M01 RR000827, M01 RR001066, M01 RR006192, M01RR-00042, M01RR-00043, M01RR-00051, M01RR-00065, M01RR-00633, M01RR-00827, M01RR-01066, M01RR-06192]; NIDDK NIH HHS [N01-DK-9-2320, N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2327, N01-DK-9-2328] NR 50 TC 71 Z9 72 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2007 VL 46 IS 3 BP 420 EP 431 DI 10.1016/j.jhep.2006.10.009 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 144QU UT WOS:000244811900011 PM 17196293 ER PT J AU Rehermann, B Naoumov, NV AF Rehermann, Barbara Naoumov, Nikolai V. TI Immunological techniques in viral hepatitis SO JOURNAL OF HEPATOLOGY LA English DT Article DE hepatitis B virus; hepatitis C virus; T cell; B cell; lymphocyte; dendritic cell; antibody; proliferation; ELISpot; vaccine ID C-VIRUS-INFECTION; T-CELL RESPONSES; CYTOKINE FLOW-CYTOMETRY; EX-VIVO ANALYSIS; ELISPOT ASSAY; PERIPHERAL-BLOOD; IMMUNE-RESPONSE; B-CELLS; NONSTRUCTURAL PROTEIN-3; QUANTITATIVE-ANALYSIS AB The need to quantitate and monitor immune responses of large patient cohorts with standardized techniques is increasing due to the growing range of treatment options for hepatitis B and hepatitis C, the development of combination therapies, and candidate experimental vaccines for HCV. In addition, advances in immunological techniques have provided new tools for detailed phenotypic and functional analysis of cellular immune responses. At present, there is substantial variation in laboratory protocols, reagents, controls and analysis and presentation of results. Standardization of immunological assays would therefore allow better comparison of results amongst individual laboratories and patient cohorts. The EASL-sponsored and AASLD-endorsed Monothematic Conference on Clinical Immunology in Viral Hepatitis was held at the University College London, United Kingdom, Oct 7-8, 2006 to bring together investigators with research experience in clinical immunology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections for in-depth discussion, critical evaluation and standardization of immunological assays. This report summarizes the information presented and discussed at the conference, but is not intended to represent a consensus statement. Our aim is to highlight topics and issues that were supported by general agreement and those that were controversial, as well as to provide suggestions for future work. (c) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA. Univ Coll & Middlesex Sch Med, Inst Hepatol, London WC1E 6HX, England. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov; n.naoumov@ucl.ac.uk FU Intramural NIH HHS NR 77 TC 34 Z9 41 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2007 VL 46 IS 3 BP 508 EP 520 DI 10.1016/j.jhep.2007.01.002 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 144QU UT WOS:000244811900021 PM 17239482 ER PT J AU Sacha, JB Chung, C Rakasz, EG Spencer, SP Jonas, AK Bean, AT Lee, W Burwitz, BJ Stephany, JJ Loffredo, JT Allison, DB Adnan, S Hoji, A Wilson, NA Friedrich, TC Lifson, JD Yang, OO Watkins, DI AF Sacha, Jonah B. Chung, Chungwon Rakasz, Eva G. Spencer, Sean P. Jonas, Anna K. Bean, Alexander T. Lee, Wonhee Burwitz, Benjamin J. Stephany, Jason J. Loffredo, John T. Allison, David B. Adnan, Sama Hoji, Akihiko Wilson, Nancy A. Friedrich, Thomas C. Lifson, Jeffrey D. Yang, Otto O. Watkins, David I. TI Gag-specific CD8(+) T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 NEF PROTEIN; COMPLEX CLASS-I; GENE-EXPRESSION; ENVELOPE GLYCOPROTEINS; ANTIVIRAL ACTIVITY; TYPE-1 INFECTION; IMMUNE-RESPONSE; SIV REPLICATION; KINETICS AB CD8(+) T cells are a key focus of vaccine development efforts for HIV. However, there is no clear consensus as to which of the nine HIV proteins should be used for vaccination. The early proteins Tat, Rev, and Nef may be better CD8(+) T cell targets than the late-expressed structural proteins Gag, Pol, and Env. In this study, we show that Gag-specific CD8(+) T cells recognize infected CD4(+) T lymphocytes as early as 2 h postinfection, before proviral DNA integration, viral protein synthesis, and Nef-mediated MHC class I down-regulation. Additionally, the number of Gag epitopes recognized by CD8(+) T cells was significantly associated with lower viremia (p = 0.0017) in SIV-infected rhesus macaques. These results suggest that HIV vaccines should focus CD8(+) T cell responses on Gag. C1 Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53715 USA. Wisconsin Natl Primate Res Ctr, Madison, WI USA. Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA. Univ Calif Los Angeles, Geffen Sch Med, AIDS Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. NCI, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Watkins, DI (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, 555 Sci Dr, Madison, WI 53711 USA. EM watkins@primate.wisc.edu OI Allison, David/0000-0003-3566-9399 FU NCI NIH HHS [N01 CO012400, N01CO12400]; NCRR NIH HHS [C06 RR015459, C06 RR015459-01, C06 RR020141, P51 RR000167, P51 RR000167-43, RR 020141-01, RR 15459-01, P51 RR 000167]; NIAID NIH HHS [R01 AI 049120, R01 AI 052056, R01 AI049120, R01 AI049120-07, R01 AI052056, R37 AI052056, R37 AI052056-07] NR 41 TC 179 Z9 185 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2007 VL 178 IS 5 BP 2746 EP 2754 PG 9 WC Immunology SC Immunology GA 143PH UT WOS:000244734500026 PM 17312117 ER PT J AU Metenou, S Singuitan, AL Long, C Leke, RGF Taylor, DW AF Metenou, Simon Singuitan, Amorsolo L., Jr. Long, Carole Leke, Rose G. F. Taylor, Diane Wallace TI Fetal immune responses to Plasmodium falciparum antigens in a malaria-endemic region of Cameroon SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; CHONDROITIN SULFATE-A; CYTOKINE RESPONSES; INFECTED MOTHERS; IN-UTERO; CIRCUMSPOROZOITE PROTEIN; NEONATAL LYMPHOCYTES; TRYPANOSOMA-CRUZI; ANTIBODY-RESPONSE; CORD SERA AB Plasmodium falciparum infection during pregnancy can lead to the transplacental passage of malarial Ags that are capable of inducing acquired immune responses in the fetus. Studies have identified cytokines produced by malaria-specific cord blood (CB) T cells, but information on fetal B cells is limited. Thus, CB mommuclear cells from 120 Cameroonian newborns were cultured for 7 days in vitro and supernatants were assessed by ELISA for Abs to an extract of malarial schizonts (MA), recombinant apical merozoite Ag 1 (AMA-1), the 42-kDa C-terminal region of merozoite surface protein 1 (MSP-142), a B epitope of ring-infected erythrocyte surface Ag (RESA), and the dominant B epitope of the circumsporozoite protein (CSP). Only 12% of supernatants contained IgM to MA but 78% had IgG to one or more malarial Ags, with 53% having IgG to AMA-1, 38% to MSP-1(42),3% to RESA, and 0% to CSP. The Abs to AMA-1 and MSP-1(42) were predominantly IgGI and IgG3. CB mononuclear cells were also tested for the ability to secrete cytokines in response to MA and a pool of conserved MSP-1 T cell epitopes. Among the Ag-reactive samples, 39.3% produced only T142-type cytokines, whereas 60.6% produced a combination of Th1- and Th2-type cytokines. Although a Th2 bias was observed, the in utero cytokine environment was adequate to support isotype switching to cytophilic IgGs, the isotypes that are protective in adults. Because many infants living in a low transmission area are born with malaria-specific B and T cells, the influence of in utero priming on neonatal immunity merits further investigation. C1 Georgetown Univ, Dept Biol, Washington, DC 20057 USA. NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. Univ Yaounde 1, Fac Med & Biomed Sci, Ctr Biotechnol, Yaounde, Cameroon. RP Taylor, DW (reprint author), Asia Pacific Inst Trop Med & Infect Dis, John A Burns Sch Med, Dept Trop Med, 651 Ilalo St, Honolulu, HI 96813 USA. EM taylordw@georgetown.edu RI Metenou, Simon/C-1101-2013 FU FIC NIH HHS [5D43 TW 01264]; NIAID NIH HHS [U01 AI 43888, U01 AI035839] NR 44 TC 19 Z9 20 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 MAR 1 PY 2007 VL 178 IS 5 BP 2770 EP 2777 PG 8 WC Immunology SC Immunology GA 143PH UT WOS:000244734500029 PM 17312120 ER PT J AU Ehlting, C Lai, WS Schaper, F Brenndorfer, ED Matthes, RJ Heinrich, PC Ludwig, S Blackshear, PJ Gaestel, M Haussinger, D Bode, JG AF Ehlting, Christian Lai, Wi S. Schaper, Fred Brenndoerfer, Erwin D. Matthes, Raphaela-Jessica Heinrich, Peter C. Ludwig, Stephan Blackshear, Perry J. Gaestel, Matthias Haeussinger, Dieter Bode, Johannes G. TI Regulation of suppressor of cytokine signaling 3 (SOCS3) mRNA stability by TNF-alpha involves activation of the MKK6/p38(MAPK)/MK2 cascade SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AU-RICH ELEMENTS; SH2-CONTAINING PROTEIN; SEQUENCE FEATURES; GENE-EXPRESSION; KINASE PATHWAY; SH2 DOMAIN; P38 MAPK; DEGRADATION; TRISTETRAPROLIN; TRANSDUCTION AB The potential of some proinflammatory mediators to inhibit gp130-dependent STAT3 activation by enhancing suppressor of cytokine signaling (SOCS) 3 expression represents an important molecular mechanism admitting the modulation of the cellular response toward gp130-mediated signals. Thus, it is necessary to understand the mechanisms involved in the regulation of SOCS3 expression by proinflammatory mediators. In this study, we investigate SOCS3 expression initiated by the proinflammatory cytokine TNF-alpha. In contrast to IL-6, TNF-alpha increases SOCS3 expression by stabilizing SOCS3 mRNA. Activation of the MAPK kinase 6 (MKK6)/p38(MAPK)-cascade is required for TNF-alpha-mediated stabilization of SOCS3 mRNA and results in enhanced SOCS3 protein expression. In fibroblasts or macrophages deficient for MAPK-activated protein kinase 2 (MK2), a downstream MAPK target of the MKK6/p38(MAPK) cascade, basal SOCS3-expression is strongly reduced and TNF-alpha-induced SOCS3-mRNA stabilization is impaired, indicating that MK2 is crucial for the control of SOCS3 expression by p38(MAPK)-dependent signals. As a target for SOCS3 mRNA stability-regulating signals, a region containing three copies of a pentameric AUUUA motif in close proximity to a U-rich region located between positions 2422 and 2541 of the 3' untranslated region of SOCS3 is identified. One factor that could target this region is the zinc finger protein tristetraprolin (TTP), which is shown to be capable of destabilizing SOCS3 mRNA via this region. However, data from TTP-deficient cells suggest that TTP does not play an irreplaceable role in the regulation of SOCS3 mRNA stability by TNF-alpha. In summary, these data indicate that TNF-alpha regulates SOCS3 expression on the level of mRNA stability via activation of the MKK6/p38(MAPK) cascade and that the activation of MK2, a downstream target of p38(MAPK), is important for the regulation of SOCS3 expression. C1 Univ Dusseldorf, Dept Gastroenterol Hepatol & Infectiol, D-4000 Dusseldorf, Germany. Univ Klinikum, Rhein Westfal TH Aachen, Dept Biochem, Aachen, Germany. Univ Munster, Dept Mol Virol, D-4400 Munster, Germany. NIEHS, Lab Neurol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Off Clin Res, NIH, Res Triangle Pk, NC 27709 USA. Hannover Med Sch, Dept Biochem, D-3000 Hannover, Germany. RP Bode, JG (reprint author), Univ Dusseldorf, Dept Gastroenterol Hepatol & Infectiol, Moorenstr 5, D-4000 Dusseldorf, Germany. EM Johannes.Bode@t-online.de RI Schaper, Fred/F-1403-2013; OI Brenndorfer, Erwin Daniel/0000-0002-9189-7479 NR 60 TC 69 Z9 71 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2007 VL 178 IS 5 BP 2813 EP 2826 PG 14 WC Immunology SC Immunology GA 143PH UT WOS:000244734500034 PM 17312125 ER PT J AU Ettinger, R Sims, GP Robbins, R Withers, D Fischer, RT Grammer, AC Kuchen, S Lipsky, PE AF Ettinger, Rachel Sims, Gary P. Robbins, Rachel Withers, David Fischer, Randy T. Grammer, Amrie C. Kuchen, Stefan Lipsky, Peter E. TI IL-21 and BAFF/BLyS synergize in stimulating plasma cell differentiation from a unique population of human splenic memory B cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MARGINAL-ZONE; POLYCLONAL ACTIVATION; HUMAN SPLEEN; IN-VITRO; T-CELLS; EXPRESSION; RECEPTOR; SURVIVAL; ANTIGEN; COSTIMULATION AB Both constitutive Ig secretion by long-lived plasma cells (PC) and the recurrent differentiation of memory (mem) B cells into PC contribute to the maintenance of serologic mem. However, the relative contribution of each is unknown. In this study, we describe a novel population of human postswitched mem B cells that rapidly differentiate into PC and thus contribute to serologic mem. These IgG(+) B cells reside in the region of human spleen analogous to the murine marginal zone and have not previously been examined. These cells are highly responsive to IL-21 in the context of CD40 stimulation. Uniquely, IgG(+) marginal zone analog B cells are exquisitely sensitive to the combination of IL-21 and B cell-activating factor belonging to the TNF family (BAFF/BLyS) that synergize in the absence of further costimulation to induce up-regulation of B lymphocyte-induced maturation protein-1 and drive PC differentiation. Other cytokine combinations are not active in this regard. This is the first demonstration that this unique population of mem B cells can respond specifically and exclusively to IL-21 and BAFF/BLyS by differentiating into IgG-secreting PC, and thus contributing to serologic mem in an Ag-independent manner. C1 NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA. RP Ettinger, R (reprint author), NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA. EM ettingerr@mail.nih.gov RI Withers, David/C-7055-2015 OI Withers, David/0000-0003-3757-7594 FU Intramural NIH HHS NR 50 TC 93 Z9 95 U1 1 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 MAR 1 PY 2007 VL 178 IS 5 BP 2872 EP 2882 PG 11 WC Immunology SC Immunology GA 143PH UT WOS:000244734500040 PM 17312131 ER PT J AU Tilley, SL Jaradat, M Stapleton, C Dixon, D Hua, XY Erikson, CJ McCaskill, JG Chason, KD Liao, G Jania, L Koller, BH Jetten, AM AF Tilley, Stephen L. Jaradat, Maisa Stapleton, Cliona Dixon, Darlene Hua, Xiaoyang Erikson, Christopher J. McCaskill, Joshua G. Chason, Kelly D. Liao, Grace Jania, Leigh Koller, Beverly H. Jetten, Anton M. TI Retinold-related orphan receptor gamma controls immunoglobulin production and Th1/Th2 cytokine mance in the adaptive immune response to allergen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOID ORGAN DEVELOPMENT; NUCLEAR HORMONE-RECEPTOR; ROR-GAMMA; AIRWAY INFLAMMATION; T-CELLS; IMMUNOLOGICAL SYMPTOMS; THYMOCYTE SURVIVAL; NEGATIVE REGULATOR; DEFICIENT MICE; ACID RECEPTOR AB The retinoid-related orphan receptors (ROR) comprise a distinct subfamily of nuclear receptors with the capacity to act as both repressors and activators of transcription. ROR gamma, the most recently identified member of the ROR family, has been shown to be important for the development of normal lymphocyte compartments as well as organogenesis of some lymphoid organs. In this report, we examine the capacity of ROR gamma-deficient mice to develop an adaptive immune response to Ag using OVA-induced inflammation in mice as a model for allergic airway disease. In sham-treated mice lacking ROR gamma, low-grade pulmonary inflammation was observed and characterized by the perivascular accumulation of B and T lymphocytes, increased numbers of inflammatory cells in the lung lavage fluid, and polyclonal Ig activation. Following sensitization and challenge, the capacity of these animals to develop the allergic phenotype was severely impaired as evidenced by attenuated eosinophilic pulmonary inflammation, reduced numbers of CD4(+) lymphocytes, and lower Th2 cytokines/chemokine protein and mRNA expression in the lungs. IFN-gamma and IL-10 production was markedly greater in splenocytes from ROR gamma-deficient mice following in vitro restimulation with OVA compared with wild-type splenocytes, and a shift toward a Th1 immune response was observed in sensitized/challenged ROR gamma-deficient animals in vivo. These data reveal a critical role for ROR gamma in the regulation of Ig production and Th1/Th2 balance in adaptive immunity. C1 Univ N Carolina, Dept Med, Div Pulm & Crit Care Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. NIEHS, Lab Resp Biol, Cell Biol Sect, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Tilley, SL (reprint author), Univ N Carolina, Dept Med, Div Pulm & Crit Care Med, 8033 Burnett Womack,CB 7219, Chapel Hill, NC 27599 USA. EM stephen_tilley@med.unc.edu FU Intramural NIH HHS; NHLBI NIH HHS [HL 071802] NR 52 TC 22 Z9 25 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 MAR 1 PY 2007 VL 178 IS 5 BP 3208 EP 3218 PG 11 WC Immunology SC Immunology GA 143PH UT WOS:000244734500078 PM 17312169 ER PT J AU Kapikian, AZ Hoshino, Y AF Kapikian, Albert Z. Hoshino, Yasutaka TI To serotype or not to serotype: That is still the question SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID NATURAL ROTAVIRUS INFECTION; 1ST 2 YEARS; ASYMPTOMATIC INFECTION; SERUM ANTIBODIES; YOUNG-CHILDREN; VACCINE; PROTECTION; EFFICACY; SAFETY; INFANTS C1 NIAID, UD, ES, Infect Dis Lab,NIH, Bethesda, MD 20892 USA. RP Kapikian, AZ (reprint author), NIAID, UD, ES, Infect Dis Lab,NIH, 50 South Dr,MSC 8026, Bethesda, MD 20892 USA. EM akapikian@niaid.nih.gov NR 51 TC 9 Z9 9 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2007 VL 195 IS 5 BP 611 EP 614 DI 10.1086/510862 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 136RV UT WOS:000244242700001 PM 17262698 ER PT J AU Marshall, V Parks, T Bagni, R Wang, CD Samols, MA Hu, JH Wyvil, KM Aleman, K Little, RF Yarchoan, R Renne, R Whitby, D AF Marshall, Vickie Parks, Thomas Bagni, Rachel Wang, Cheng Dian Samols, Mark A. Hu, Jianhong Wyvil, Kathleen M. Aleman, Karen Little, Richard F. Yarchoan, Robert Renne, Rolf Whitby, Denise TI Conservation of virally encoded MicroRNAs in kaposi sarcoma-associated herpesvirus in primary effusion lymphoma cell lines and in patients with kaposi sarcoma or multicentric Castleman disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID DNA-SEQUENCES; PERIPHERAL-BLOOD; HUMAN-HERPESVIRUS-8; EXPRESSION; PROTEIN; IDENTIFICATION; INFECTION; UGANDA; GENES; KSHV AB Background. MicroRNAs are small noncoding RNAs that posttranscriptionally regulate gene expression. Kaposi sarcoma ( KS)-associated herpesvirus ( KSHV) encodes 12 distinct microRNA genes, all of which are located within the latency-associated region that is highly expressed in all KSHV-associated malignancies. Methods. We amplified, cloned, and sequenced a 2.8-kbp-long region containing a cluster of 10 microRNAs plus a 646-bp fragment of K12/T0.7 containing the remaining 2 microRNAs from 5 primary effusion lymphoma derived cell lines and from 17 patient samples. The patients included 2 with classic KS, 12 with AIDS-KS ( 8 from the United States, 1 from Europe, 3 from Africa, and 4 from Central/South America), and 2 with multicentric Castleman disease ( MCD). Additionally, we analyzed the K1, open reading frame 75, and K15 genes to determine KSHV subtypes, and we performed a phylogenetic analysis. Results. Phylogenetic analysis of the 2.8-kbp microRNA region revealed 2 distinct clusters of sequences: a major ( A/C) and a variant ( B/Q) cluster. The variant cluster included sequences from 3 patients of African origin and both patients with MCD. Some microRNAs were highly conserved, whereas others had changes that could affect processing and, therefore, biological activity. Conclusions. These data demonstrate that KSHV microRNA genes are under tight selection in vivo and suggest that they contribute to the biological activity and possibly the pathogenesis of KSHV-associated malignancies. C1 NCI, Viral Epidemiol Sect, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21701 USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA. Univ Florida, UF Shands Canc Ctr, Gainesville, FL USA. RP Whitby, D (reprint author), NCI, Viral Epidemiol Sect, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21701 USA. EM whitbyd@ncifcrf.gov FU NCI NIH HHS [R21 CA097939, R01 CA88763] NR 44 TC 59 Z9 64 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2007 VL 195 IS 5 BP 645 EP 659 DI 10.1086/511434 PG 15 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 136RV UT WOS:000244242700008 PM 17262705 ER PT J AU Huang, TTK Horlick, MN AF Huang, Terry T-K Horlick, Mary N. TI Trends in childhood obesity research: A brief analysis of NIH-supported efforts SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID OVERWEIGHT; DISEASE; CONSEQUENCES; HYPERTENSION; GROWTH AB Childhood obesity is an increasing health threat. The National Institutes of Health (NIH)is the primary funding agency for research into the causes, mechanisms, consequences, and prevention and treatment of childhood obesity. Using the NIH Strategic Plan for Obesity Research as the framework, this article summarizes the research that has been funded in the past five years as well as new research areas with great potential. C1 NICHHD, Endocrinol Nutr & Growth Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Huang, TTK (reprint author), NICHHD, Endocrinol Nutr & Growth Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. NR 9 TC 16 Z9 16 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 2007 VL 35 IS 1 BP 148 EP + DI 10.1111/j.1748-720X.2007.00119.x PG 7 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 140ZG UT WOS:000244544900012 PM 17341223 ER PT J AU Rosenberg, HF AF Rosenberg, Helene F. TI The Shwartzman reaction repealed SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID NK T-CELLS C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 5 TC 0 Z9 0 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 MAR PY 2007 VL 81 IS 3 BP 623 EP 624 DI 10.1189/jlb.1306298 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 140LE UT WOS:000244505800008 ER PT J AU Miller, FG Veatch, RM AF Miller, Franklin G. Veatch, Robert M. TI Symposium on equipoise and the ethics of clinical trials SO JOURNAL OF MEDICINE AND PHILOSOPHY LA English DT Editorial Material C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov; veatchr@georgetown.edu NR 0 TC 3 Z9 3 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-5310 J9 J MED PHILOS JI J. Med. Philos. PD MAR-APR PY 2007 VL 32 IS 2 BP 77 EP 78 DI 10.1080/03605310701255701 PG 2 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 162FE UT WOS:000246071400001 ER PT J AU Miller, FG Brody, H AF Miller, Franklin G. Brody, Howard TI Clinical equipoise and the incoherence of research ethics SO JOURNAL OF MEDICINE AND PHILOSOPHY LA English DT Article DE clinical equipoise; exploitation; randomized controlled trials; risk-benefit assessment ID PLACEBO-CONTROLLED TRIALS; INVESTIGATOR; ORTHODOXY; TENSION; MYTHS AB The doctrine of clinical equipoise is appealing because it appears to permit physicians to maintain their therapeutic obligation to offer optimal medical care to patients while conducting randomized controlled trials (RCT). The appearance, however, is deceptive. In this article we argue that clinical equipoise is defective and incoherent in multiple ways. First, it conflates the sound methodological principle that RCTs should begin with an honest null hypothesis with the questionable ethical norm that participants in these trials should never be randomized to an intervention known to be inferior to standard treatment. Second, the claim that RCTs preserve the therapeutic obligation of physicians this represents the patient-centered orientation of medical care. Third, the appeal to clinical equipoise as a basic principle of risk-benefit assessment for RCTs is incoherent. Finally, the difficulties with clinical equipoise cannot be resolved by viewing it as a presumptive principle subject to exceptions. In the final sections of the article, we elaborate on the non-exploitation framework for the ethics clinical research and indicate issues that warrant further inquiry. C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 36 TC 37 Z9 38 U1 1 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-5310 J9 J MED PHILOS JI J. Med. Philos. PD MAR-APR PY 2007 VL 32 IS 2 BP 151 EP 165 DI 10.1080/03605310701255750 PG 15 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 162FE UT WOS:000246071400006 PM 17454420 ER PT J AU Moscarelli, M Rupp, A AF Moscarelli, Massimo Rupp, Agnes TI Untitled SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Editorial Material C1 Harvard Univ, Sch Med, Int Ctr Mental Hlth Policy & Econ, Cambridge, MA 02138 USA. NIMH, Econ Programme, Div Epidemiol & Serv Res, Rockville, MD 20857 USA. RP Moscarelli, M (reprint author), Harvard Univ, Sch Med, Int Ctr Mental Hlth Policy & Econ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT CENTER MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD MAR PY 2007 VL 10 IS 1 BP 1 EP 2 PG 2 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA 155GQ UT WOS:000245566300001 ER PT J AU Schlander, M Schwarz, O Roijen, LHV Jensen, PS Persson, U Santosh, P Trott, GE AF Schlander, Michael Schwarz, Oliver Roijen, Leona Hakkaart-Van Jensen, Peter S. Persson, Ulf Santosh, Paramala Trott, Goetz-Erik CA MTA Cooperative Grp TI Achieving normalization of core symptoms: Cost-effectiveness of ADHD treatment strategies in the international context SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Meeting Abstract C1 Inst Innovat & Valuat Hlth Care, D-65760 Eschborn, Germany. Univ Heidelberg, Heidelberg, Germany. Univ Appl Econ Sci Ludwigshafen, Ludwigshafen, Germany. Heilbronn Univ, Heilbronn, Germany. Erasmus MC, Inst Med Technol Assessment, Rotterdam, Netherlands. Columbia Univ, New York, NY USA. Swedish Inst Hlth Econ, Lund, Sweden. Great Ormond St Hosp Sick Children, Inst Child Hlth, London, England. Univ Wurzburg, Wurzburg, Germany. NIMH, Bethesda, MD 20892 USA. RI Santosh, Paramala/B-7303-2008 NR 0 TC 1 Z9 1 U1 0 U2 1 PU INT CENTER MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD MAR PY 2007 VL 10 SU 1 BP S38 EP S38 PG 1 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA 166OQ UT WOS:000246388800086 ER PT J AU Schlander, M Schwarz, O Roijen, LHV Jensen, PS Persson, U Santosh, P Trott, GE AF Schlander, Michael Schwarz, Oliver Roijen, Leona Hakkaart-Van Jensen, Peter S. Persson, Ulf Santosh, Paramala Trott, Goetz-Erik CA MTA Cooperative Grp TI Improving functional impairment in major life activities: Cost-effectiveness of ADHD treatment strategies in the international context SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Meeting Abstract C1 Inst Innovat & Valuat Hlth Care, D-65760 Eschborn, Germany. Univ Heidelberg, Heidelberg, Germany. Univ Appl Econ Sci Ludwigshafen, Ludwigshafen, Germany. Heilbronn Univ, Heilbronn, Germany. Erasmus MC, Inst Med Technol Assessment, Rotterdam, Netherlands. Columbia Univ, New York, NY USA. Swedish Inst Hlth Econ, Lund, Sweden. Great Ormond St Hosp Sick Children, London, England. Univ Wurzburg, Wurzburg, Germany. NIMH, Bethesda, MD 20892 USA. RI Santosh, Paramala/B-7303-2008 NR 0 TC 1 Z9 1 U1 0 U2 1 PU INT CENTER MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD MAR PY 2007 VL 10 SU 1 BP S38 EP S38 PG 1 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA 166OQ UT WOS:000246388800085 ER PT J AU Schlander, M Schwarz, O Roijen, LHV Jensen, PS Persson, U Santosh, P Trott, GE AF Schlander, Michael Schwarz, Oliver Roijen, Leona Hakkaart-Van Jensen, Peter S. Persson, Ulf Santosh, Paramala Trott, Goetz-Erik CA MTA Cooperative Grp TI Cost-effectiveness of ADHD treatment strategies in the international context-impact of therapeutic objectives and comorbidity SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Meeting Abstract C1 Inst Innovat & Valuat Hlth Care, D-65760 Eschborn, Germany. Univ Heidelberg, Heidelberg, Germany. Univ Appl Econ Sci Ludwigshafen, Ludwigshafen, Germany. Heilbronn Univ, Heilbronn, Germany. Erasmus MC, Inst Med Technol Assessment, Rotterdam, Netherlands. Columbia Univ, New York, NY USA. Swedish Inst Hlth Econ, Lund, Sweden. Great Ormond St Hosp Sick Children, Inst Child Hlth, London, England. Univ Wurzburg, Wurzburg, Germany. NIMH, Bethesda, MD 20892 USA. RI Santosh, Paramala/B-7303-2008 NR 0 TC 1 Z9 1 U1 0 U2 1 PU INT CENTER MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD MAR PY 2007 VL 10 SU 1 BP S37 EP S37 PG 1 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA 166OQ UT WOS:000246388800084 ER PT J AU Li, YF Polgar, O Okada, M Esser, L Bates, SE Xia, D AF Li, Yong-Fu Polgar, Orsolya Okada, Masaki Esser, Lothar Bates, Susan E. Xia, Di TI Towards understanding the mechanism of action of the multidrug resistance-linked half-ABC transporter ABCG2: A molecular modeling study SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article DE molecular modeling; structure; ABC transporter; ABCG2 ID CYSTIC-FIBROSIS GENE; MEMBRANE-PROTEINS; SUBSTRATE-SPECIFICITY; ESCHERICHIA-COLI; ATP HYDROLYSIS; HUMAN PLACENTA; GXXXG MOTIF; BINDING; EXPRESSION; IDENTIFICATION AB The ATP-binding cassette protein ABCG2 is a member of a broad family of ABC transporters with potential clinical importance as a mediator of multidrug resistance. We carried out a homology and knowledge-based, and mutationally improved molecular modeling study to establish a much needed structural framework for the protein, which could serve as guidance for further genetic, biochemical, and structural analyses. Based on homology with known structures of both full-length and nucleotide-binding domains (NBD) of ABC transporters and structural knowledge of integral membrane proteins, an initial model of ABCG2 was established. Subsequent refinement to conform to the lipophilic index distributions in the transmembrane domain (TMD) and to the results of site-directed mutagenesis experiments led to an improved model. The complete ABCG2 model consists of two identical subunits facing each other in a closed conformation. The dimeric interface in the nucleotide-binding domain (NBD) involves a characteristic nucleotide sandwich and the interface in the TMD consists of the TM helices 1-3 of one subunit and the helices 5 and 6 of the other. The interface between the NBD and the TMD is bridged by the conserved structural motif between TM2 and TM3, the intracellular domain 1 (ICD1), and the terminal beta-strand (S6) of the central beta-sheet in the NBD. The apparent flexibility of the ICD1 may play a role in transmitting conformational changes from the NBD to the TMD or from the TMD to the NBD. Published by Elsevier Inc. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Xia, D (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 2122C, Bethesda, MD 20892 USA. EM dixia@helix.nih.gov FU Intramural NIH HHS NR 65 TC 34 Z9 37 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1093-3263 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD MAR PY 2007 VL 25 IS 6 BP 837 EP 851 DI 10.1016/j.jmgm.2006.08.005 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA 158PG UT WOS:000245802900011 PM 17027309 ER PT J AU Greenbaum, JA Andersen, PH Blythe, M Bui, HH Cachau, RE Crowe, J Davies, M Kolaskar, AS Lund, O Morrison, S Mumey, B Ofran, Y Pellequer, JL Pinilla, C Ponomarenko, JV Raghava, GPS van Regenmortel, MHV Roggen, EL Sette, A Schlessinger, A Sollner, J Zand, M Peters, B AF Greenbaum, Jason A. Andersen, Pernille Haste Blythe, Martin Bui, Huynh-Hoa Cachau, Raul E. Crowe, James Davies, Matthew Kolaskar, A. S. Lund, Ole Morrison, Sherrie Mumey, Brendan Ofran, Yanay Pellequer, Jean-Luc Pinilla, Clemencia Ponomarenko, Julia V. Raghava, G. P. S. van Regenmortel, Marc H. V. Roggen, Erwin L. Sette, Alessandro Schlessinger, Avner Sollner, Johannes Zand, Martin Peters, Bjoern TI Towards a consensus on datasets and evaluation metrics for developing B-cell epitope prediction tools SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Review DE B-cell epitopes; epitope prediction; algorithms; immunology databases; data standardization; bioinformatics; software tools; tool development ID PROTEIN BINDING-SITES; LOCATION; ANTIBODIES; DATABASE; DETERMINANTS; ANTIGENICITY; BENCHMARKING; PEPTIDES; RESIDUES; VACCINES AB A B-cell epitope is the three-dimensional structure within an antigen that can be bound to the variable region of an antibody. The prediction of B-cell epitopes is highly desirable for various immunological applications, but has presented a set of unique challenges to the bioinformatics and immunology communities. Improving the accuracy of B-cell epitope prediction methods depends on a community consensus on the data and metrics utilized to develop and evaluate such tools. A workshop, sponsored by the National Institute of Allergy and Infectious Disease (NIAID), was recently held in Washington, DC to discuss the current state of the B-cell epitope prediction field. Many of the currently available tools were surveyed and a set of recommendations was devised to facilitate improvements in the currently existing tools and to expedite future tool development. An underlying theme of the recommendations put forth by the panel is increased collaboration among research groups. By developing common datasets, standardized data formats, and the means with which to consolidate information, we hope to greatly enhance the development of B-cell epitope prediction tools. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 La Jolla Allergy & Immunol, IEDB, Immune Epitope Database & Anal Resource, La Jolla, CA USA. Tech Univ Denmark, Bioctr, Ctr Biol Sequence Anal, Immunol Bioinformat Grp, DK-2800 Lyngby, Denmark. Edward Jenner Inst Vaccine Res, Bioinformat Dept, Newbury, Berks, England. NCI, Frederick Canc Res & Dev Ctr, Frederick Biomed Supercomp Ctr, Frederick, MD USA. Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Microbiol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Immunol, Nashville, TN 37232 USA. John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England. Univ Pune, Bioinformat Ctr, Pune, Maharashtra, India. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Montclair State Univ, Dept Comp Sci, Bozeman, MT USA. Tel Aviv Univ, Fac Life Sci, Dept Biochem, Ramat Aviv, Israel. CEA Valrho, Ctr Marcoule, DSV, DIEP,SBTN, F-30207 Bagnols Sur Ceze, France. Univ Calif San Diego, San Diego Supercomp Ctr, San Diego, CA 92103 USA. Inst Microbial Technol, Bioinformat Ctr, Sector 39A, Changdigarh, India. Ecole Super Biotechnol Strasbourg Parc Innovat, F-67412 Illkirch Graffenstaden, France. Novozymes AS, Dept Pharma Prot Dev, Mol Biotechnol, DK-2880 Bagsvaerd, Denmark. Columbia Univ, Ctr Computat Biol, Dept Biochem & Mol Biophys, New York, NY 10027 USA. Emergentec, A-1010 Vienna, Austria. Univ Rochester, Med Ctr, Ctr Biodef Immune Modeling, Rochester, NY 14627 USA. RP Greenbaum, JA (reprint author), La Jolla Allergy & Immunol, IEDB, Immune Epitope Database & Anal Resource, La Jolla, CA USA. EM jgbaum@liai.org RI Lund, Ole/F-4437-2014; Zand, Martin/A-8612-2015; Ponomarenko, Julia/K-8105-2015; Raghava, Gajendra/B-1717-2009; Pellequer, Jean-Luc/L-6855-2013; OI Lund, Ole/0000-0003-1108-0491; Zand, Martin/0000-0002-7095-8682; Crowe, James/0000-0002-0049-1079; Raghava, Gajendra/0000-0002-8902-2876 FU NCRR NIH HHS [P41 RR-01081] NR 41 TC 112 Z9 121 U1 4 U2 25 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD MAR-APR PY 2007 VL 20 IS 2 BP 75 EP 82 DI 10.1002/jmr.815 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 163OI UT WOS:000246169000001 PM 17205610 ER PT J AU Liu, AY Wua, CQ Yu, KF Yuan, WS AF Liu, Aiyi Wua, Chengqing Yu, Kai F. Yuan, Weishi TI Completeness and unbiased estimation of mean vector in the multivariate group sequential case SO JOURNAL OF MULTIVARIATE ANALYSIS LA English DT Article DE bias; interim analysis; mean squared error; medical trials; minimum variance; multiple endpoints; restricted completeness; truncation-adaptation ID MULTIPLE END-POINTS; CLINICAL-TRIALS; F-TESTS; DESIGN AB We consider estimation after a group sequential test about a multivariate normal mean, such as a chi(2) test or a sequential version of the Bonferroni procedure. We derive the density function of the sufficient statistics and show that the sample mean remains to be the maximum likelihood estimator but is no longer unbiased. We propose an alternative Rao-Blackwell type unbiased estimator. We show that the family of distributions of the sufficient statistic is not complete, and there exist infinitely many unbiased estimators of the mean vector and none has uniformly minimum variance. However, when restricted to truncation-adaptable statistics, completeness holds and the Rao-Blackwell estimator has uniformly minimum variance. Published by Elsevier Inc. C1 NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, Rockville, MD 20852 USA. US FDA, Rockville, MD 20857 USA. Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China. RP Liu, AY (reprint author), NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, 6100 Execut Blvd, Rockville, MD 20852 USA. EM liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 NR 28 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0047-259X J9 J MULTIVARIATE ANAL JI J. Multivar. Anal. PD MAR PY 2007 VL 98 IS 3 BP 505 EP 516 DI 10.1016/j.jmva.2006.01.001 PG 12 WC Statistics & Probability SC Mathematics GA 118AF UT WOS:000242913700005 ER PT J AU Takada, K Choi, BW Rashid, MA Gamble, WR Cardellina, JH Van, QN Lloyd, JR McMahon, JB Gustafson, KR AF Takada, Kentaro Choi, Byoung W. Rashid, Mohammad A. Gamble, William R. Cardellina, John H., II Van, Que N. Lloyd, John R. McMahon, James B. Gustafson, Kirk R. TI Structural assignment of poecillastrins B and C, macrolide lactams from the deep-water Caribbean sponge Poecillastra species SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID CYTOTOXIC MACROLIDES; V-ATPASES; BAFILOMYCINS; NMR; CONCANAMYCINS; CHONDROPSINS; LOBATAMIDES; INHIBITORS; DISCOVERY; PROBE AB Two new chondropsin-type macrolide lactams, poecillastrins B (1) and C (2), were isolated from aqueous extracts of the marine sponge Poecillastra sp. These trace metabolites were isolated in low yield (400-600 mu g), and their structures were determined primarily by analysis of NMR data acquired using a cyrogenically cooled probe. High-quality 1D and 2D NMR data sets allowed complete assignment of the spectroscopic data and defined the new structures as 35-membered ring analogues of poecillastrin A (3). Compounds 1 and 2 showed potent cytotoxic activity against a human melanoma tumor cell line (LOX) with an IC50 value of less than 1 mu g/mL. C1 NCI, Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA. RP Gustafson, KR (reprint author), NCI, Ctr Canc Res, Mol Targets Dev Program, Bldg 1052,Room 121, Frederick, MD 21702 USA. EM gustafson@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01 CO 12400] NR 18 TC 8 Z9 8 U1 2 U2 4 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 MAR PY 2007 VL 70 IS 3 BP 428 EP 431 DI 10.1021/np0604984 PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 149AN UT WOS:000245118800020 PM 17378533 ER PT J AU Newman, DJ Cragg, GM AF Newman, David J. Cragg, Gordon M. TI Natural products as sources of new drugs over the last 25 years SO JOURNAL OF NATURAL PRODUCTS LA English DT Review ID DIVERSITY-ORIENTED SYNTHESIS; STREPTOMYCES-COELICOLOR GENOME; SEVERE CHRONIC PAIN; BACTERIAL SYMBIONTS; MARKET; DISCOVERY; CHEMISTRY; RECEPTOR; LIBRARIES; DESIGN AB This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003. In the case of all approved agents the time frame has been extended to include the 25(1)/(2) years from 01/1981 to 06/2006 for all diseases worldwide and from 1950 (earliest so far identified) to 06/2006 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a "natural product mimic" or "NM" to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 155 small molecules, 73% are other than "S" (synthetic), with 47% actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the antiinfective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore we consider that this area of natural product research should be expanded significantly. C1 Natl Canc Inst, Div Canc Treatment & Diag, Dev Therapeut Program, Nat Prod Branch, Frederick, MD 21702 USA. RP Newman, DJ (reprint author), Natl Canc Inst, Div Canc Treatment & Diag, Dev Therapeut Program, Nat Prod Branch, POB B, Frederick, MD 21702 USA. EM newmand@mail.nih.gov RI Jansen, Nils/G-1835-2011 NR 96 TC 2147 Z9 2227 U1 96 U2 616 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 EI 1520-6025 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2007 VL 70 IS 3 BP 461 EP 477 DI 10.1021/np068054v PG 17 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 149AN UT WOS:000245118800027 PM 17309302 ER PT J AU Goetz, CG Kubota, K Stebbins, GT DeLeeuw, W Bronte-Stewart, H Elble, R Hallett, M Nutt, J Ramig, L Sanger, T Wu, A Kraus, PH Blasucci, LM Shamim, EA Taylor, CB AF Goetz, C. G. Kubota, K. Stebbins, G. T. DeLeeuw, W. Bronte-Stewart, H. Elble, R. Hallett, M. Nutt, J. Ramig, L. Sanger, T. Wu, A. Kraus, P. H. Blasucci, L. M. Shamim, E. A. Taylor, C. B. TI Parkinson's disease at-home testing battery: Reliability of data collection and transmission of objective motor data from home to a central study center SO JOURNAL OF NEURAL TRANSMISSION LA English DT Meeting Abstract CT 5th Congress Deutsche-Parkinson-Gesellschaft CY MAR 07-10, 2007 CL Ulm, GERMANY SP Deutsch Parkinson Gesell C1 Rush Univ, Med Ctr, Chicago, IL 60612 USA. Intel Corp, Hillsboro, OR USA. Stanford Univ, Stanford, CA 94305 USA. So Illinois Univ, Sch Med, Springfield, MA USA. NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Colorado, Boulder, CO 80309 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Bochum, Bochum, Germany. Stanford Med Ctr, Stanford, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD MAR PY 2007 VL 114 IS 3 BP XVIII EP XIX PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 140DU UT WOS:000244485200079 ER PT J AU Zhao, WQ Lu, B AF Zhao, Wei-Qin Lu, Bai TI Expression of annexin A2 in GABAergic interneurons in the normal rat brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE depolarization; extracellular matrix; gene expression; growth cone; secretion.; trigeminal nuclei ID TISSUE-PLASMINOGEN ACTIVATOR; II TETRAMER; CELL-SURFACE; GENE-EXPRESSION; LATE-PHASE; GROWTH; HETEROTETRAMER; PLASTICITY; P36; PHOSPHORYLATION AB Expression of the Ca2+-dependent phospholipids binding protein annexin A2 (ANX2) in the brain is thought to be largely associated with brain pathological conditions such as tumor, inflammation, and neurodegeneration. The recent findings that ANX2 heterotetramer is involved in learning and neuronal activities necessitates a systematic investigation of the physiological expression of ANX2 in the brain. With combination of in situ hybridization and immunohistochemistry, ANX2 mRNA and protein were specifically detected in a group of GABAergic interneurons throughout the brain. Although ANX2 was absent from the interior of pyramidal neurons, it was found on the membrane and seemly the extracellular space of those neurons, where they closely co-localized with glutamate decarboxylase terminals. In cultured developing neurons, ANX2 was present at high concentrations in the growth cones co-distributing with several growth-associated proteins such as growth associated protein 43 (GAP43), turned on after division/Ulip/CRMP (TUC-4), tubulin, and tissue-plasminogen activator. It then became predominantly distributed on the membrane and mostly in axonal branches as neurons grew and extended synaptic networks. ANX2 was also secreted from cultured neurons, in a membrane-bound form that was Ca2+-dependent, which was significantly increased by neuronal depolarization. These results may have implications in the function and regulatory mechanism of ANX2 in the normal brain. C1 Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. Blanchette Rockefeller Neurosci Inst, Rockville, MD USA. NICHD, Sect Neural Dev & Plast, NIH, Bethesda, MD USA. RP Zhao, WQ (reprint author), Northwestern Univ, Dept Neurobiol & Physiol, 2205 Tech Dr,Hogan 5-110, Evanston, IL 60208 USA. EM w-zhao@northwestern.edu RI Lu, Bai/A-4018-2012 NR 49 TC 8 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2007 VL 100 IS 5 BP 1211 EP 1223 DI 10.1111/j.1471-4159.2006.04311.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 134WN UT WOS:000244115200007 PM 17316400 ER PT J AU Hyun, DH Hunt, ND Emerson, SS Hernandez, JO Mattson, MP de Cabo, R AF Hyun, Dong-Hoon Hunt, Nicole D. Emerson, Scott S. Hernandez, Joe O. Mattson, Mark P. de Cabo, Rafael TI Up-regulation of plasma membrane-associated redox activities in neuronal cells lacking functional mitochondria SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE mitochondrial deficiency; oxidative stress; plasma membrane redox system ID COENZYME-Q REDUCTASE; CALORIE RESTRICTION; ELECTRON-TRANSPORT; OXIDATIVE DAMAGE; NEURODEGENERATIVE DISEASES; ASCORBATE STABILIZATION; ANTIOXIDANT PROTECTION; HL-60 CELLS; RAT-LIVER; VITAMIN-E AB Mitochondria-deficient cells (rho(o) cells) survive through enhanced glycolytic metabolism in the presence of pyruvate and uridine. The plasma membrane redox system (PMRS) contains several NAD(P)H-related enzymes and plays a key role in maintaining the levels of NAD(+)/NADH and reduced coenzyme Q. In this study, rho(o) cells were used to investigate how the PMRS is regulated under conditions of mitochondrial dysfunction. rho(o) cells exhibited a lower oxygen consumption rate and higher levels of lactate than parental cells, and were more sensitive to glycolysis inhibitors (2-deoxyglucose and iodoacetamide) than control cells. However, they were more resistant to H2O2, consistent with increased catalase activity and decreased oxidative damage (protein carbonyls and nitrotyrosine). PM-associated redox enzyme activities were enhanced in rho(o) cells compared to those in control cells. Our data suggest that all PMRS enzymes and biomarkers tested are closely related to the ability of the PMs to maintain redox homeostasis. These results illustrate that an up-regulated PM redox activity can protect cells from oxidative stress as a result of an improved antioxidant capacity, and suggest a mechanism by which neurons adapt to conditions of impaired mitochondrial function. C1 NIA, Intramural Res Program, Neurosci Lab, NIH, Baltimore, MD 21224 USA. NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP de Cabo, R (reprint author), NIA, Intramural Res Program, Neurosci Lab, NIH, Baltimore, MD 21224 USA. EM decabora@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; Mattson, Mark/F-6038-2012; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS NR 69 TC 42 Z9 42 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2007 VL 100 IS 5 BP 1364 EP 1374 DI 10.1111/j.1471-4159.2006.04411.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 134WN UT WOS:000244115200020 PM 17250676 ER PT J AU Hartmann, J Kiewert, C Duysen, EG Lockridge, O Greig, NH Klein, J AF Hartmann, Joachim Kiewert, Cornelia Duysen, Ellen G. Lockridge, Oksana Greig, Nigel H. Klein, Jochen TI Excessive hippocampal acetylcholine levels in acetylcholinesterase-deficient mice are moderated by butyrylcholinesterase activity SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; bambuterol; BW284c51; central cholinergic system; dementia with Lewy bodies; microdialysis ID ALZHEIMERS-DISEASE; LEWY BODIES; CHOLINESTERASE-INHIBITORS; CHOLINERGIC SYSTEM; KNOCKOUT MICE; DEMENTIA; RECEPTOR; MICRODIALYSIS; DIFFUSION; COGNITION AB Central cholinergic systems are involved in a plethora of brain functions and are severely and selectively damaged in neurodegenerative diseases such as Alzheimer's disease and dementia with Lewy bodies. Cholinergic dysfunction is treated with inhibitors of acetylcholinesterase (AChE) while the role of butyrylcholinesterase (BChE) for brain cholinergic function is unclear. We have used in vivo microdialysis to investigate the regulation of hippocampal acetylcholine (ACh) levels in mice that are devoid of AChE (AChE-/- mice). Extracellular ACh levels in the hippocampus were 60-fold elevated in AChE-/- mice compared with wild-type (AChE+/+) animals. In AChE-/- mice, calcium-free conditions reduced hippocampal ACh levels by 50%, and infusion of tetrodotoxin by more than 90%, indicating continuous ACh release. Infusion of a selective AChE inhibitor (BW284c51) caused a dose-dependent, up to 16-fold increase of extracellular ACh levels in AChE+/+ mice but did not change ACh levels in AChE-/- mice. In contrast, infusion of a selective inhibitor of BChE (bambuterol) caused up to fivefold elevation of ACh levels in AChE-/- mice, but was without effect in AChE+/+ animals. These results were corroborated with two other specific inhibitors of AChE and BChE, tolserine and bis-norcymserine, respectively. We conclude that lack of AChE causes dramatically increased levels of extracellular ACh in the brain. Importantly, in the absence of AChE, the levels of extracellular ACh in the brain are controlled by the activity of BChE. These results point to a potential usefulness of BChE inhibitors in the treatment of central cholinergic dysfunction in which brain AChE activity is typically reduced. C1 TTUHSC, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX 79106 USA. Univ Nebraska, Med Ctr, Eppley Inst, Omaha, NE 68198 USA. NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Klein, J (reprint author), TTUHSC, Sch Pharm, Dept Pharmaceut Sci, 1300 Coulter Dr, Amarillo, TX 79106 USA. EM jochen.klein@ttuhsc.edu RI Klein, Jochen/B-9730-2008; OI Klein, Jochen/0000-0001-6971-3381; Duysen, Ellen/0000-0002-0128-9032 FU NIA NIH HHS [1R03AG25045] NR 44 TC 61 Z9 64 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2007 VL 100 IS 5 BP 1421 EP 1429 DI 10.1111/j.1471-4159.2006.04347.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 134WN UT WOS:000244115200025 PM 17212694 ER PT J AU Quarles, RH AF Quarles, Richard H. TI Myelin-associated glycoprotein (MAG): past, present and beyond SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE multiple sclerosis; myelin; myelin-associated glycoprotein; neuropathy; oligodendrocyte; Schwann cell ID PERIPHERAL NERVOUS-SYSTEM; CELL-ADHESION MOLECULE; LACKING COMPLEX GANGLIOSIDES; MULTIPLE-SCLEROSIS LESIONS; FYN TYROSINE KINASE; SIALIC-ACID; ANTI-MAG; NEURITE OUTGROWTH; BASIC-PROTEIN; SCHWANN-CELLS AB The myelin-associated glycoprotein (MAG) is a type I transmembrane glycoprotein localized in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths where it functions in glia-axon interactions. It contains five immunoglobulin (Ig)-like domains and is in the sialic acid-binding subgroup of the Ig superfamily. It appears to function both as a ligand for an axonal receptor that is needed for the maintenance of myelinated axons and as a receptor for an axonal signal that promotes the differentiation, maintenance and survival of oligodendrocytes. Its function in the maintenance of myelinated axons may be related to its role as one of the white matter inhibitors of neurite outgrowth acting through a receptor complex involving the Nogo receptor and/or gangliosides containing 2,3-linked sialic acid. MAG is expressed as two developmentally regulated isoforms with different cytoplasmic domains that may activate different signal transduction pathways in myelin-forming cells. MAG contains a carbohydrate epitope shared with other glycoconjugates that is a target antigen in autoimmune peripheral neuropathy associated with IgM gammopathy and has been implicated in a dying back oligodendrogliopathy in multiple sclerosis. C1 NINDS, Myelin & Brain Dev Sect, NIH, Bethesda, MD 20892 USA. RP Quarles, RH (reprint author), NINDS, Myelin & Brain Dev Sect, NIH, 5625 Fishers Lane,Rm 4S-30,MSC 9407, Bethesda, MD 20892 USA. EM quarlesr@ninds.nih.gov FU Intramural NIH HHS NR 134 TC 107 Z9 109 U1 1 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2007 VL 100 IS 6 BP 1431 EP 1448 DI 10.1111/j.1471-4159.2006.04319.x PG 18 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 143KS UT WOS:000244720700001 PM 17241126 ER PT J AU Cheng, AW Coksaygan, T Tang, HY Khatri, R Balice-Gordon, RJ Rao, MS Mattson, MP AF Cheng, Aiwu Coksaygan, Turhan Tang, Hongyan Khatri, Rina Balice-Gordon, Rita J. Rao, Mahendra S. Mattson, Mark P. TI Truncated tyrosine kinase B brain-derived neurotrophic factor receptor directs cortical neural stem cells to a glial cell fate by a novel signaling mechanism SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE brain-derived neurotrophic factor; truncated form of tyrosine kinase B1; neural stem cells; neurogenesis; glial progenitor cells; neural development; neural differentiation; protein kinase C ID CENTRAL-NERVOUS-SYSTEM; ADULT-MOUSE BRAIN; PROGENITOR CELLS; TRKB RECEPTORS; RADIAL GLIA; SUBVENTRICULAR ZONE; EMBRYONIC FOREBRAIN; CEREBRAL-CORTEX; IN-VITRO; DIFFERENTIAL EXPRESSION AB During development of the mammalian cerebral cortex neural stem cells (NSC) first generate neurons and subsequently produce glial cells. The mechanism(s) responsible for this developmental shift from neurogenesis to gliogenesis is unknown. Brain-derived neurotrophic factor (BDNF) is believed to play important roles in the development of the mammalian cerebral cortex; it enhances neurogenesis and promotes the differentiation and survival of newly generated neurons. Here, we provide evidence that a truncated form of the BDNF receptor tyrosine kinase B (trkB-t) plays a pivotal role in directing embryonic mouse cortical NSC to a glial cell fate. Expression of trkB-t promotes differentiation of NSC toward astrocytes while inhibiting neurogenesis both in cell culture and in vivo. The mechanism by which trkB-t induces astrocyte genesis is not simply the result of inhibition of full-length receptor with intrinsic tyrosine kinase activity signaling. Instead, binding of BDNF to trkB-t activates a signaling pathway (involving a G-protein and protein kinase C) that induced NSC to become glial progenitors and astrocytes. Thus, the increased expression of trkB-t in the embryonic cerebral cortex that occurs coincident with astrocyte production plays a pivotal role in the developmental transition from neurogenesis to gliogenesis. Our findings suggest a mechanism by which a single factor (BDNF) regulates the production of the two major cell types in the mammalian cerebral cortex. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Univ Penn, Sch Med, Dept Neurosci, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Cheng, AW (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM chengai@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 81 TC 38 Z9 43 U1 0 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 MAR PY 2007 VL 100 IS 6 BP 1515 EP 1530 DI 10.1111/j.1471-4159.2006.07337.x PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 143KS UT WOS:000244720700008 PM 17286628 ER PT J AU Ochedalski, T Subburaju, S Wynn, PC Aguilera, G AF Ochedalski, T. Subburaju, S. Wynn, P. C. Aguilera, G. TI Interaction between oestrogen and oxytocin on hypothalamic-pituitary-adrenal axis activity SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE ACTH; corticosterone; corticotrophin-releasing factor (CRF); oxytocin; oestrogen; restraint stress ID CORTICOTROPIN-RELEASING HORMONE; FEMALE RATS; BRAIN OXYTOCIN; PARAVENTRICULAR NUCLEUS; OVARIAN-STEROIDS; GONADAL-STEROIDS; GENE-EXPRESSION; CATECHOLAMINE RESPONSES; PERIPHERAL RELEASE; SUPRAOPTIC NUCLEUS AB In addition to its role in reproduction, oxytocin has central actions modulating behavioural and hypothalamic-pituitary-adrenal (HPA) axis responses during late pregnancy and lactation. The hypothesis that ovarian hormones modulate the effects of oxytocin on HPA axis activity was studied in 7-day ovariectomised rats receiving oestradiol with or without progesterone replacement and intracerebroventricular (i.c.v) minipump infusion of oxytocin (100 ng/h). In an initial experiment, i.c.v. oxytocin had no effect on basal or restraint-stimulated plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations or hypothalamic corticotrophin-releasing factor (CRF) mRNA expression with low oestradiol replacement alone but it had a stimulatory effect in the presence of low oestradiol and progesterone. To investigate further whether oestradiol modulates central actions of oxytocin, rats received low dioestrous (low), pro-oestrous (medium) or pregnancy (high) oestradiol replacement levels, yielding plasma concentrations of < 5, 17.3 +/- 4.5 and 258 +/- 32 pg/ml, respectively, with or without i.c.v. oxytocin. Oestradiol caused dose-dependent increases in basal plasma ACTH and corticosterone concentrations but decreased the ACTH response to restraint stress. In parallel to the changes in basal plasma ACTH, high oestrogen increased basal CRF hnRNA, CRF mRNA in the paraventricular nucleus and pro-opiomelanocortin (POMC) mRNA in the pituitary gland, while decreasing restraint stress-stimulated levels. Intracerebroventricular administration of oxytocin reduced basal and stress-stimulated plasma ACTH, hypothalamic CRF hnRNA (30 min), CRF mRNA and pituitary POMC mRNA (4 h) levels parallel to the increases induced by elevating plasma oestradiol. The present study demonstrates the converse effects of oestradiol on basal and restraint stress-stimulated basal HPA axis activity, and that the ability of central oxytocin to inhibit HPA axis activity depends on the levels of circulating oestradiol. C1 NICHD, Sect Endocrine Physiol, DEB, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHD, Sect Endocrine Physiol, DEB, NIH Bldg 10,Room 10N 262,Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM greti_aguilera@nih.gov NR 61 TC 57 Z9 59 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD MAR PY 2007 VL 19 IS 3 BP 189 EP 197 DI 10.1111/j.1365-2826.2006.01525.x PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 132WS UT WOS:000243974200005 PM 17280592 ER PT J AU Kopnisky, KL Bao, J AF Kopnisky, Kathy L. Bao, Jing TI HIV Preclinical-Clinical Therapeutics Research: Central Nervous System approaches SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Article; Proceedings Paper CT NIMH HIV Preclinical/Clinical Therapeutics Research Meeting CY MAY 15-16, 2006 CL Bethesda, MD SP NIMH DE neuroAIDS; treatment; therapeutics development; brain; CNS; drug delivery; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; DEMENTIA; ERA AB The prevalence of HIV-associated brain disorders is reportedly increasing due, in part, to the prolonged life span of individuals who are surviving well on highly active antiretroviral treatments (HAART). While clinicians report CNS-related deficits that are more subtle in presentation than the frank dementia evident in the pre-HAART era, the milder presentation continues to substantively reduce an individual's quality of life. The development of novel drugs or therapeutic strategies for treating HIV-related CNS disease is important as most investigators agree that the brain is a sanctuary for latent virus, local viral recrudescence. and associated brain inflarnmatory responses. The prolonged chronic and curnulative effects on the brain of living with HIV-related inflammatory processes, antiretroviral treatments, and their long-term side effects, toxicities, and brain-related aging processes collectively indicate that the burden of CNS and PNS complications will increase profoundly during the upcoming years. Considering the high expense for new drugs entering CNS-related clinical trials and their ultimately low success rate, the NIMH convened a meeting entitled, HIV Preclinical-Clinical Therapeutics Research Meeting, to discuss the current and proposed novel approaches for neuroAIDS drug development and clinical practices. The purposes of the meeting were twofold: to identify the most promising approaches for future neuroAIDS therapeutics development research and to discuss optimal structures and partnerships with industry that may facilitate the successful movement of compounds from the bench to the bedside. Several themes can be derived from the sessions and are highlighted below for preclinical, translational and clinical neuroAIDS therapeutics research. C1 Ctr Mental Hlth Res AIDS, NIH, Rockville, MD 20852 USA. RP Kopnisky, KL (reprint author), Ctr Mental Hlth Res AIDS, NIH, 6001 Execut Blvd Room 6205 MSC 9619, Rockville, MD 20852 USA. EM kkopnisk@mail.nih.gov NR 15 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD MAR PY 2007 VL 2 IS 1 BP 1 EP 4 DI 10.1007/s11481-006-9056-9 PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 201YW UT WOS:000248869500001 PM 18040818 ER PT J AU Conforto, AB Cohen, LG dos Santos, RL Scaff, M Marie, SKN AF Conforto, Adriana Bastos Cohen, Leonardo G. dos Santos, Renata Laurenti Scaff, Milberto Marie, Suely Kazue Nagahashi TI Effects of somatosensory stimulation on motor function in chronic cortico-subcortical strokes SO JOURNAL OF NEUROLOGY LA English DT Article DE rehabilitation; cerebrovascular disorders; transcutaneous electrical nerve stimulation; motor skills; recovery of function ID HAND FUNCTION; PLASTICITY; CORTEX; ADULT AB Somatosensory stimulation enhances aspects of motor function in patients with chronic, predominantly subcortical infarcts. We investigated the effects of somatosensory stimulation on motor function in stroke patients with predominantly cortical involvement in the middle cerebral artery territory in a double-blind, pseudorandomized crossover trial. Motor performance was evaluated with the Jebsen-Taylor test before, after 2-hour somatosensory stimulation, and after subsequent motor training (n = 11). In one experimental session, patients were submitted to median nerve stimulation (MNS) and in the other session, to control stimulation (CS). The order of the sessions was counterbalanced across patients. Improvement in performance in the Jebsen-Taylor test after somatosensory stimulation and after motor training was significantly greater in the MNS session than in the CS session. Additionally, patients who received MNS in the second session maintained the beneficial effects of training 30 days later. A single MNS session improves hand motor function in patients with chronic cortico-subcortical strokes and appears to favor consolidation of training effects. Somatosensory stimulation may be an adjuvant tool for stroke rehabilitation in patients with cortical lesions. C1 Univ Sao Paulo, Hosp Clin, Dept Neurol, BR-05403000 Sao Paulo, Brazil. NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Conforto, AB (reprint author), Univ Sao Paulo, Hosp Clin, Dept Neurol, Av Dr Eneas de Carvalho Aguiar 255-5131, BR-05403000 Sao Paulo, Brazil. EM abconf@usp.br RI Marie, Suely/D-1870-2012 NR 14 TC 65 Z9 68 U1 0 U2 11 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD MAR PY 2007 VL 254 IS 3 BP 333 EP 339 DI 10.1007/s00415-006-0364-z PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 145AF UT WOS:000244837000009 PM 17345047 ER PT J AU Gelderblom, H Londono, D Bai, YH Cabral, ES Quandt, J Hornung, R Martin, R Marques, A Cadavid, D AF Gelderblom, Harald Londono, Diana Bai, Yunhong Cabral, Erik S. Quandt, Jacqueline Hornung, Ron Martin, Roland Marques, Adriana Cadavid, Diego TI High production of CXCL13 in blood and brain during persistent infection with the relapsing fever spirochete Borrelia turicatoe SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE B cells; Borrelia; CXCL13; interleukin-10; neuroborreliosis; relapsing fever; T cells ID MOUSE-BRAIN; LYME NEUROBORRELIOSIS; NEUROTROPIC STRAIN; GERMINAL CENTER; EXPRESSION; DISEASE; SYSTEM; LOCALIZATION; LIPOPROTEINS; BURGDORFERI AB Relapsing fever (RF) is a multisystemic borrelial infection with frequent neurologic involvement referred to as neuroborreliosis. The absence of an effective antibody response results in persistent infection. To study the consequences to the brain of persistent infection with the RF spirochete Borrelia turicatae, we studied B cell (igh6-/-) and B and T (Rag1-/-) cell-deficient mice inoculated with isogenic serotypes 1 (Bt1) or 2 (Bt2). We foun that Btl was more tissue tropic than Bt2, not only for brain but also for heart. Igh6-/- mice developed more severe clinical disease than Rag1-/- mice. 130-infected brains had widespread microgliosis/brain macrophage activation despite localization of spirochetes in the leptomeninges rather than the brain parenchyma itself. Oligoarray analysis revealed that CXCL13 was the most upregulated gene in the brain of 130-infiected lgh6-/- mice. CXCL13 was also the most abundant of the chemokines we measured in infected blood. Persistent infection did not result in injury to the brain. Treatment with exogenous interleukin-10 reduced microgliosis in the brain and production of CXCL13 in the blood. We concluded that brain involvement in B cell-deficient mice persistently infected with B. turicatae is characterized by prominent microgliosis and production of CXCL13 without detectable injury. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Emerging Pathogens, Newark, NJ USA. NIAID, Clin Studies Unit, Lab Clin Infect Dis, Bethesda, MD 20892 USA. NINDS, Cellular Immunol Sect, Neuroimmunol Branch, Bethesda, MD USA. NCI, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Cadavid, D (reprint author), 185 S Orange Ave,MSB H506, Newark, NJ 07103 USA. EM cadavidi@umdnj.edu FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 33 TC 19 Z9 19 U1 0 U2 1 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 MAR PY 2007 VL 66 IS 3 BP 208 EP 217 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 173DB UT WOS:000246852600005 PM 17356382 ER PT J AU Harris-Love, ML Perez, MA Chen, R Cohen, LG AF Harris-Love, Michelle L. Perez, Monica A. Chen, Robert Cohen, Leonardo G. TI Interhemispheric inhibition in distal and proximal arm representations in the primary motor cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; SPLIT-BRAIN MONKEYS; CORTICOSPINAL PROJECTIONS; SUPPLEMENTARY MOTOR; HAND; RESPONSES; EXCITABILITY; FACILITATION; CONNECTIONS; MECHANISMS AB Interhemispheric inhibition in distal and proximal arm representations in the primary motor cortex. J Neurophysiol 97: 2511-2515, 2007. First published January 10, 2007; doi:10.1152/jn. 01331.2006. Interhemispheric inhibitory interactions (IHI) operate between homologous distal hand representations in primary motor cortex (M1). It is not known whether proximal arm representations exhibit comparable effects on their homologous counterparts. We studied IHI in different arm representations, targeting triceps brachii (TB, n = 13), first dorsal interosseous (FDI, n = 13), and biceps brachii (BB, n = 7) muscles in healthy volunteers. Transcranial magnetic stimulation test stimuli ( TS) were delivered to M1 contralateral to the target muscle preceded 10 ms by a conditioning stimulus (CS) to the opposite M1 at 110-150% resting motor threshold (RMT). IHI was calculated as the ratio between motor-evoked potential (MEP) amplitudes in conditioned relative to unconditioned trials. Mean RMTs were 38.9, 46.9, and 46.0% of stimulator output in FDI, TB, and BB muscles, respectively. IHI was 0.45 +/- 0.41 (FDI), 0.78 +/- 0.38 (TB), and 0.52 +/- 0.32 (BB, P < 0.01) when test MEP amplitudes were matched and 0.28 +/- 0.17 (FDI) and 0.85 +/- 0.31 (TB, P < 0.05) when TS intensities expressed as percentage RMT were matched. Significant IHI (P < 0.05) was identified with minimal CS intensities ( expressed as percentage stimulator output) in the 30 s for FDI, 60 s for TB, and 40 s for BB. Additionally, a CS of roughly 120% RMT suppressed the test MEP but not a test H-reflex in BB, suggesting IHI observed in BB is likely mediated by a supraspinal mechanism. We conclude that IHI differs between different arm muscle representations, comparable between BB and FDI but lesser for TB. This finding suggests the amount of IHI between different arm representations does not strictly follow a proximal-to-distal gradient, but may be related to the role of each muscle in functional movement synergies. C1 NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20892 USA. Univ Toronto, Div Neurol, Toronto, ON, Canada. Univ Toronto, Toronto Western Res Inst, Toronto, ON, Canada. RP Cohen, LG (reprint author), NINDS, Human Cortical Physiol Sect, NIH, 10 Ctr Dr,MSC 1428,Bldg 10,Rm 5N226, Bethesda, MD 20892 USA. EM cohen1@ninds.nih.gov RI Chen, Robert/B-3899-2009; Harris-Love, Michelle/J-1388-2014 OI Chen, Robert/0000-0002-8371-8629; Harris-Love, Michelle/0000-0001-5571-3858 FU Intramural NIH HHS NR 27 TC 48 Z9 48 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 2007 VL 97 IS 3 BP 2511 EP 2515 DI 10.1152/jn.01331.2006 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 145KW UT WOS:000244864900060 PM 17215494 ER PT J AU Backman, CM Shan, LF Zhang, YJ Hoffer, BJ Tomac, AC AF Backman, Cristina M. Shan, Lufei Zhang, YaJun Hoffer, Barry J. Tomac, Andreas C. TI Alterations in prodynorphin, proenkephalin, and GAD67 mRNA levels in the aged human putamen: Correlation with Parkinson's disease SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE enkephalin; dynorphin; human; post-mortem; midbrain; striatum ID STRIATAL DOPAMINE TRANSPORTER; POSITRON EMISSION TOMOGRAPHY; HUMAN BASAL GANGLIA; SUBSTANCE-P; GENE-EXPRESSION; MET-ENKEPHALIN; HUMAN-BRAIN; PREPROENKEPHALIN; RECEPTORS; MARMOSET AB A real-time quantitative PCR approach was used to quantify mRNA levels corresponding to the neuropeptides enkephalin, dynorphin, and the 67-kDa isoform of glutamic acid decarboxylase (GAD67) in the human putamen from young and aged individuals as well as from aged patients affected by Parkinson's disease (PD). cDNA-specific primers were designed to amplify GAD67, proenkephalin (pENK), prodynorphin (pDYN), and the housekeeping genes glyceraldehydes-3-phosphate dehydrogenase (GAPDH) and guanine nucleotide binding protein, beta-pepticle 2-like I (GNB2LI). GAPDH and GNB2LI mRNA levels were similarly expressed among the groups and were therefore used as endogenous reference genes. Normalized data showed that mRNA levels for both pENK and pDYN were reduced in the putamen of aged controls and aged individuals affected by PD, compared with young controls. In addition, we showed that GAD67 mRNA levels did not change during aging and PD. Further analyses showed no differences in mRNA levels, for pENK, pDYN, or GAD67 mRNA, between PD patients and aged matched controls. These findings contrast with animal models of parkinsonism, for which expression of pDYN, pENK, and GAD67 mRNA has been reported to change after striatal dopamine denervation. Compensatory mechanisms and regional differences within the human putamen as well as the severity index of the disease, clinical diagnosis, and response to phalmacological therapy are possible reasons for these results. The present study suggests that alteration of neuropepticle pathways in the human putamen may be involved in the functional deterioration of parts of the extrapyramidal system during aging. (c) 2007 Wiley-Liss,Inc(dagger) C1 NIDA, Cellular Neurobiol Sect, Cellular Neurobiol Branch, NIH, Baltimore, MD 21224 USA. RP Backman, CM (reprint author), NIDA, Cellular Neurobiol Sect, Cellular Neurobiol Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM cbackman@mail.nih.gov RI backman, cristina/C-1276-2013 FU Intramural NIH HHS; NIMH NIH HHS [R24-MH068855] NR 32 TC 7 Z9 7 U1 0 U2 4 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 MAR PY 2007 VL 85 IS 4 BP 798 EP 804 DI 10.1002/jnr.21164 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 149PK UT WOS:000245158800012 PM 17203488 ER PT J AU Tweedie, D Milman, A Holloway, HW Li, YZ Harvey, BK Shen, H Pistell, PJ Lahiri, DK Hoffer, BJ Wang, Y Pick, CG Greig, NH AF Tweedie, David Milman, Anat Holloway, Harold W. Li, Yazhou Harvey, Brandon K. Shen, Hui Pistell, Paul J. Lahiri, Debomoy K. Hoffer, Barry J. Wang, Yun Pick, Chaim G. Greig, Nigel H. TI Apoptotic and behavioral sequelae of mild brain trauma in mice SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE traumatic brain injury; mild (mTBI); apoptosis; amyloid-beta precursor protein; apoptosis inducing factor (AIF); cytochrome-c; Bax ID AMYLOID PRECURSOR PROTEINS; COGNITIVE DEFICITS; ALZHEIMERS-DISEASE; CELL-DEATH; RAT-BRAIN; CASPASE ACTIVATION; INBRED STRAINS; HEAD-INJURY; BETA; IMPAIRMENT AB Mild traumatic brain injury (mTBI) is a not uncommon event in adolescents and young adults. Although it does not result in clear morphological brain defects, it is associated with long-term cognitive, emotional, and behavioral problems. Herein, we characterized the biochemical and behavioral changes associated with experimental mTBI in mice that may act as either targets or surrogate markers for interventional therapy. Specifically, mTBI was induced by 30-g and 50-g weight drop, and at 8 and 72 hr thereafter markers of cellular apoptosis-caspase-3, Bax, apoptosis-inducing factor (AIF), and cytochrome-c (Cyt-c)-were quantified by Western blot analysis in hippocampus ipsilateral to the impact. Levels of amyloid-P precursor protein (APP) were also measured, and specific behavioral tests-passive avoidance, open field, and forced swimming (Porsolt) paradigms-were undertaken to assess learning, emotionality, and emotional memory. In the absence of hemorrhage or infarcts, as assessed by triphenyltetrazolium chloride staining, procaspase-3 and Bax levels were markedly altered following mTBI at both times. No cleaved caspase-3 was detected, and levels of AIF and Cyt-c, but not APP, were significantly changed at 72 hr. Mice subjected to mTBI were indistinguishable from controls by neurological examination at 1 and 24 hr, and by passive avoidance/open field at 72 hr, but could be differentiated in the forced swimming paradigm. In general, this model mimics the diffuse effects of mTBI on brain function associated with the human condition and highlights specific apoptotic proteins and a behavioral paradigm as potential markers for prospective interventional strategies. (c) 2007 Wiley-Liss,Inc. C1 NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. NIDA, Neural Protect & Regenerat Sect, Mol Neuropsychiat Branch, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Lab Expt Gerontol, Intramural Res Program, Baltimore, MD 21224 USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46204 USA. NIDA, Cellular Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM greign@grc.nia.nih.gov RI Harvey, Brandon/A-5559-2010; Pick, Chaim/D-4789-2009 FU Intramural NIH HHS; NIA NIH HHS [R01AG023055] NR 56 TC 51 Z9 52 U1 0 U2 5 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 MAR PY 2007 VL 85 IS 4 BP 805 EP 815 DI 10.1002/jnr.21160 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 149PK UT WOS:000245158800013 PM 17243171 ER PT J AU Riley, WT Beasley, J Sowell, A Behar, A AF Riley, William T. Beasley, Jeannette Sowell, Allison Behar, Albert TI Effects of a web-based food portion training program on food portion estimation SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE computer-assisted instruction; dietary assessment; education-internet; nutrition education research ID FREQUENCY QUESTIONNAIRE; SIZE; ACCURACY; PHOTOGRAPHY; VALIDITY; STANDARD; AIDS AB Objective: Assess the effects of a prototype computerized food portion tutorial (CFPT). Design: Participants were randomly assigned to estimate portion sizes for selected food items either prior to or following CFPT training (between groups), and those estimating before CFPT training re-estimated portions after training (within groups). Setting: Research offices. Participants: Seventy-six adult participants without dietary restrictions. Intervention: The CFPT is a Web-based food portion training program that displays varied portions of 23 food items with user-controtlable reference objects and viewing angles. Main Outcome Measures: Estimated vs. weighed portions of food items selected for a meal. Analysis: Nonparametric tests were performed on estimated vs. weighed portion differences and on accuracy ratios between and within groups. Results: A significant difference was found between conditions, both within and between groups, on the discrepancy between estimated and weighed portions for a number of the food items. Training exposure, however, resulted primarily in a shift from underestimation to overestimation, not more accurate estimation. Implications for Research and Practice: The CFPT produced a significant impact on food portion estimation but appeared to sensitize participants to underestimation errors, leading to overestimation errors. Computerization of food portion training programs holds promise for providing cost-efficient portion estimation training but requires further development and evaluation before being considered for clinical use. C1 PICS Inc, Reston, VA USA. RP Riley, WT (reprint author), NIMH, 6001 Execut Blvd,Room 6226,MSC 9615, Bethesda, MD 20892 USA. EM wriley@mail.nih.gov OI Beasley, Jeannette/0000-0002-9343-6895 FU NIDDK NIH HHS [R43 DK061079, DK61079, R43 DK061079-01, R44 DK061079] NR 22 TC 11 Z9 11 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD MAR-APR PY 2007 VL 39 IS 2 BP 70 EP 76 DI 10.1016/j.jneb.2006.08.028 PG 7 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 150MV UT WOS:000245221800004 PM 17346654 ER PT J AU Fitzgibbon, M Gans, KM Evans, WD Viswanath, K Johnson-Taylor, WL Krebs-Smith, SM Rodgers, AB Yaroch, AL AF Fitzgibbon, Marian Gans, Kim M. Evans, W. Douglas Viswanath, K. Johnson-Taylor, Wendy L. Krebs-Smith, Susan M. Rodgers, Anne B. Yaroch, Amy L. TI Communicating healthy eating: Lessons learned and future directions SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article; Proceedings Paper CT Workshop on Diet and Communication - What Can Communication Science Tell Us about Promoting Optimal Dietary Behavior CY JUL, 2005 CL Bethesda, MD DE nutrition; communication; diet; behavior change ID VEGETABLE CONSUMPTION; PUBLIC-HEALTH; PLANNED BEHAVIOR; SOCIAL ECOLOGY; NUTRITION; PROMOTION; POLICY; FRUIT; CAMPAIGNS; INTERVENTION AB Achieving and maintaining wide-scale positive dietary change is a complex and formidable endeavor, given the current food environment. Moreover, for positive change to occur, nutrition messages should be communicated in a scientifically precise, yet practical and motivating manner. This challenge was the impetus for the organization of a 2-day workshop hosted by the National Cancer Institute (NCI) and the Division of Nutrition Research Coordination (DNRC), both of the National Institutes of Health (NIH). The conference included communication, nutrition, and behavioral scientists, market researchers, media advocates, journalists, and public policy experts. Discussions regarding communication efforts and the best methods to craft, deliver, and evaluate the impact of nutrition messages illustrated both the challenges and the opportunities we face. During the discussions, important recommendations for nutrition communicators and interventionists emerged, based on existing knowledge from the communications field, lessons learned thus far, and noted gaps in our knowledge. C1 Univ Illinois, Jesse Brown VA Med Ctr, Chicago, IL 60608 USA. Univ Illinois, Dept Med, Chicago, IL 60608 USA. Brown Univ, Inst Community Hlth Promot, Providence, RI 02912 USA. RTI Int, Washington, DC USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. NIH, Natl Canc Inst, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. NIH, Natl Canc Inst, Hlth Promot Res Branch, Bethesda, MD 20892 USA. RP Fitzgibbon, M (reprint author), Univ Illinois, Jesse Brown VA Med Ctr, 1747 W Roosevelt Rd, Chicago, IL 60608 USA. EM mlf@uic.edu NR 70 TC 23 Z9 23 U1 5 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD MAR-APR PY 2007 VL 39 IS 2 SU S BP S63 EP S71 DI 10.1016/j.jneb.2006.08.017 PG 9 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 151JZ UT WOS:000245287600013 PM 17336811 ER PT J AU Johnson-Taylor, WL Yaroch, AL Krebs-Smith, SM Rodgers, AB AF Johnson-Taylor, Wendy L. Yaroch, Amy L. Krebs-Smith, Susan M. Rodgers, Anne B. TI What can communication science tell us about promoting optimal dietary behavior? SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Editorial Material DE dietary behaviors; communication AB Four of the 10 leading causes of death can be attributed to poor dietary behaviors. Nutrition professionals continue to stuggle with the most effective ways to deliver nutrition messages that will result in changes in dietary behavior. On July 14-15, 2005, the National Cancer Institute and the Division of Nutrition Research Coordination, both of the National Institutes of Health, hosted a meeting to explore the state of the science concerning this issue. This paper provides an introduction to that meeting and the articles that resulted from it. C1 NIH, Publ Hlth Nutr & Hlth Policy Advisor, Div Nutr Res Coordinat, Dept Hlth & Human Sci, Bethesda, MD 20892 USA. Natl Canc Ctr, Hlth Promot Res Branch, NIH, Bethesda, MD 20892 USA. Natl Canc Ctr, Risk Factor Monitoring Methods Branch, NIH, Bethesda, MD 20892 USA. RP Johnson-Taylor, WL (reprint author), NIH, Publ Hlth Nutr & Hlth Policy Advisor, Div Nutr Res Coordinat, Dept Hlth & Human Sci, 2 Democracy Plaza,Room 635,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA. EM wj50v@nih.gov NR 18 TC 9 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 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD MAR-APR PY 2007 VL 39 IS 2 SU S BP S1 EP S4 DI 10.1016/j.neb.2006.05.011 PG 4 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 151JZ UT WOS:000245287600001 PM 17336799 ER PT J AU Sankofa, J Johnson-Taylor, WL AF Sankofa, John Johnson-Taylor, Wendy L. TI News coverage of diet-related health disparities experienced by black Americans: A steady diet of misinformation SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article; Proceedings Paper CT Workshop on Diet and Communication - What Can Communication Science Tell Us about Promoting Optimal Dietary Behavior CY JUL, 2005 CL Bethesda, MD DE racial health disparities; dietary behavior; news media ID FAST-FOOD; SUPERMARKETS; CONSUMPTION; ENVIRONMENT; COMMUNITY; IMPACT AB Compared to their white counterparts, black Americans experience greater morbidity and mortality across a range of diet-related diseases and conditions, including heart disease, type II diabetes, cancer, stroke, and obesity. Many factors influence dietary behaviors among blacks, including those associated with socioeconomics, Culture, racism, psychology, and health care quality and access. However, when reporting about the health status and dietary behavior of black Americans, the mainstream print media pursues a largely one-dimensional focus on behavioral and cultural factors. This approach tends to disregard or minimize other factors that influence health behaviors. Health scientists and journalists must be careful to include discussion of the other factors if they want to become a part of the solution to minimize diet-related disparities. C1 NIH, Bethesda, MD 20892 USA. RP Johnson-Taylor, WL (reprint author), Publ Hlth Nutr & Hlth Policy Advisor, 2 Democracy Plaza,Room 635,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA. EM wj50v@nih.gov NR 37 TC 4 Z9 4 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD MAR-APR PY 2007 VL 39 IS 2 SU S BP S41 EP S44 DI 10.1016/j.jneb.2006.08.014 PG 4 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 151JZ UT WOS:000245287600007 PM 17336804 ER PT J AU Hennig, B Ormsbee, L Bachas, L Silverstone, A Milner, J Carpenter, D Thompson, C Suk, WA AF Hennig, Bernhard Ormsbee, Lindell Bachas, Leonidas Silverstone, Allen Milner, John Carpenter, David Thompson, Claudia Suk, William A. TI Introductory comments: nutrition, environmental toxins and implications in prevention and intervention of human diseases SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE environmental chemicals; persistent organic pollutants (POPs); diet-related chronic disease; toxins C1 Univ Kentucky, Coll Agr, Mol & Cell Nutr Lab, Lexington, KY 40536 USA. Univ Kentucky, Grad Ctr Nutrit Sci & Toxicol, Lexington, KY 40536 USA. Univ Kentucky, Dept Civil Engn, Lexington, KY 40536 USA. Univ Kentucky, Dept Chem, Lexington, KY 40536 USA. SUNY Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY 13210 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. SUNY Albany, Inst Hlth & Environm, Rensselaer, NY 12144 USA. NIEHS, Ctr Risk & Integrated Sci, NIH, Res Triangle Pk, NC 27709 USA. RP Hennig, B (reprint author), Univ Kentucky, Coll Agr, Mol & Cell Nutr Lab, Lexington, KY 40536 USA. EM bhennig@uky.edu RI Ormsbee, Lindell/C-4814-2009; OI Bachas, Leonidas/0000-0002-3308-6264 FU NIEHS NIH HHS [P42 ES007380] NR 5 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD MAR PY 2007 VL 18 IS 3 BP 161 EP 162 DI 10.1016/j.jnutbio.2006.12.004 PG 2 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 143MY UT WOS:000244727700003 PM 17296487 ER PT J AU Seifried, HE AF Seifried, Harold E. TI Oxidative stress and antioxidants: a link to disease and prevention? SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Workshop on Nutrition and Superfund Chemical Toxicity CY NOV 18, 2005 CL Univ Kentucky, Lexington, KY SP Superfund Basic Res Program HO Univ Kentucky DE antioxidants; beta-carotene; cancer; environmental pollutants; prevention ID BETA-CAROTENE; CANCER PREVENTION; LUNG-CANCER; RANDOMIZED-TRIAL; ALPHA-TOCOPHEROL; RISK; VITAMINS; DIET; HEAD AB The thrust of this presentation takes a more programmatic approach and gives an overview of the programs at the NIH and the NCI that have a broad nutritional and basic science undercurrent and outline. Also discussed briefly are some areas of general concern that are under investigation in the nutrition group and are included in the group's outreach efforts among professional and academic organizations. The overarching focus of these efforts is to stress the importance of nutrition as a potential modulator of health/disease risks associated with genetic predisposition and environmentally induced disease from diet, lifestyle and exposure to pollutants. (c) 2007 Elsevier Inc. All rights reserved. C1 NCI, Nutrit Sci Res Grp, Div Canc Prevent, HHS,NIH, Rockville, MD 20852 USA. RP Seifried, HE (reprint author), NCI, Nutrit Sci Res Grp, Div Canc Prevent, HHS,NIH, Rockville, MD 20852 USA. EM harold.seifried@nih.hhs.gov NR 17 TC 21 Z9 21 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD MAR PY 2007 VL 18 IS 3 BP 168 EP 171 DI 10.1016/j.jnutbio.2006.12.003 PG 4 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 143MY UT WOS:000244727700005 PM 17296489 ER PT J AU Warburton, G Nikitakis, NG Roberson, P Marinos, NJ Wu, TX Sauk, JJ Ord, RA Wahl, SM AF Warburton, Gary Nikitakis, Nikolas G. Roberson, Patrick Marinos, Nancy J. Wu, Tianxia Sauk, John J., Jr. Ord, Robert A. Wahl, Sharon M. TI Histopathological and lymphangiogenic parameters in relation to lymph node metastasis in early stage oral squamous cell carcinoma SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NECK DISSECTION; FACTOR-C; PROGNOSTIC FACTORS; FACTOR RECEPTOR-3; INVASIVE FRONT; VEGF-C; PATHOLOGICAL FEATURES; TUMOR ANGIOGENESIS; OCCULT METASTASES AB Purpose: Lymph node metastasis from oral squamous cell carcinoma (SCC) correlates with a poor prognosis. Therefore, accurate assessment of lymph node status is crucial in treatment planning. Furthermore, prediction of delayed neck metastasis (DNM), especially in early stage tumors with a clinically negative (NO) neck, will determine the need for neck dissection or irradiation. In this study, we assess various clinical, histopathological and lymphangiogenic parameters in early stage oral SCC and their association with DNM. Materials and Methods: Clinical, histological, and immunohistochemical analyses were undertaken for 29 patients with T1N0M0 or T2N0M0 oral SCC affecting the tongue or floor of mouth and correlated with the development of DNM. Results: Tumor thickness, nuclear pleomorphism, pattern of invasion, and immunohistochemical expression of the lymphangiogenesis-associated molecules VEGFR-3 and VEGF-C were associated with DNM. Conclusions: Analysis of these parameters may help to identify patients who would benefit from a neck dissection or irradiation by predicting the likelihood of lymph node metastasis. (C) 2007 American Association of Oral and Maxillofacial Surgeons. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Dent, Dept Oral & Maxillofacial Surg, Baltimore, MD 21201 USA. Univ Maryland, Sch Dent, Dept Diagnost Sci & Pathol, Baltimore, MD 21201 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Natl Inst Dent & Craniofacial Res, Div Populat & Hlth Promot Sci, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. EM smwahl@maill.nih.gov NR 70 TC 35 Z9 38 U1 1 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 2007 VL 65 IS 3 BP 475 EP 484 DI 10.1016/j.joms.2005.12.074 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 144XU UT WOS:000244830600018 PM 17307596 ER PT J AU Rodriguez-Canales, J Hanson, JC Tangrea, MA Erickson, HS Albert, PS Wallis, BS Richardson, AM Pinto, PA Linehan, WM Gillespie, JW Merin, MJ Libutti, SK Woodson, KG Emmert-Buck, MR Chuaqui, RF AF Rodriguez-Canales, J. Hanson, J. C. Tangrea, M. A. Erickson, H. S. Albert, P. S. Wallis, B. S. Richardson, A. M. Pinto, P. A. Linehan, W. M. Gillespie, J. W. Merin, M. J. Libutti, S. K. Woodson, K. G. Emmert-Buck, M. R. Chuaqui, R. F. TI Identification of a unique epigenetic sub-microenvironment in prostate cancer SO JOURNAL OF PATHOLOGY LA English DT Article DE GSTP1; methylation; tumour microenvironment; tumour stroma; prostate carcinoma ID LASER CAPTURE MICRODISSECTION; TUMOR PROGRESSION; INTRAEPITHELIAL NEOPLASIA; EPITHELIAL PLASTICITY; PROMOTER METHYLATION; DNA METHYLATION; BREAST-CANCER; STROMAL CELLS; GLUTATHIONE; GENE AB The glutathione S-transferase P1 (GSTP1) gene promoter is methylated in tumour cells in more than 90% of prostate carcinomas. Recently, GSTP1 promoter methylation was identified in tumour-associated stromal cells in addition to the tumour epithelium. To define the extent and location of stromal methylation, epigenetic mapping using pyrosequencing quantification of GSTP1 promoter methylation and an anatomical three-dimensional reconstruction of an entire human prostate specimen with cancer were performed. Normal epithelium and stroma, tumour epithelium, and tumour-associated stromal cells were laser capture-microdissected from multiple locations throughout the gland. As expected, the GSTP1 promoter in both normal epithelium and normal stromal cells distant from the tumour was not methylated and the tumour epithelium showed consistently high levels of promoter methylation throughout. However, tumour-associated stromal cells were found to be methylated only in a localized and distinct anatomical sub-field of the tumour, revealing the presence of an epigenetically unique microenvironment within the cancer. Morphologically, the sub-field consisted of typical, non-reactive stroma, representing a genomic alteration in cells that appeared otherwise histologically normal. Similar epigenetic anatomical mapping of a control prostate gland without cancer showed low background methylation levels in all cell types throughout the specimen. These data suggest that stromal cell methylation can occur in a distinct sub-region of prostate cancer and may have implications for understanding tumour biology and clinical intervention. Published in 2007 by John Wiley & Sons, Ltd. C1 NCI, NIH, Pathogenet Unit, Pathol Lab,Adv Technol Ctr,Ctr Canc Res, Gaithersburg, MD 20877 USA. NCI, NIH, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, NIH, Biometr Res Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, NIH, Urol Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA. NCI, NIH, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, NIH, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, NIH, Pathogenet Unit, Pathol Lab,Adv Technol Ctr,Ctr Canc Res, Rm 109D,8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM buckm@mail.nih.gov FU Intramural NIH HHS NR 36 TC 38 Z9 41 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAR PY 2007 VL 211 IS 4 BP 410 EP 419 DI 10.1002/path.2133 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 141YL UT WOS:000244615000004 PM 17278115 ER PT J AU Han, YM Romero, R Kim, YM Kim, JS Richani, K Friel, LA Kusanovic, JP Jeanty, C Vitale, S Nien, JK Espinoza, J Kim, CJ AF Han, Y. M. Romero, R. Kim, Y. M. Kim, J-S Richani, K. Friel, L. A. Kusanovic, J. P. Jeanty, C. Vitale, S. Nien, J. K. Espinoza, J. Kim, C. J. TI Surfactant protein-A mRNA expression by human fetal membranes is increased in histological chorioamnionitis but not in spontaneous labour at term SO JOURNAL OF PATHOLOGY LA English DT Article DE surfactant protein-A; chorioamniotic membrane; chorioamnionitis; qRT-PCR; in situ hybridization; parturition ID HUMAN AMNIOTIC-FLUID; ALVEOLAR MACROPHAGES; PREMATURE RUPTURE; SP-A2 GENES; LUNG; PHAGOCYTOSIS; LOCALIZATION; PARTURITION; MORBIDITY; INFECTION AB Surfactant protein-A (SP-A) is produced by the fetal lung, participates in innate immunity, and has been proposed to play a role in the initiation of parturition in mice. Amniotic fluid SP-A concentration increases as a function of gestational age, and SP-A protein has been demonstrated in human chorioamniotic membranes. This study was conducted to determine whether parturition at term, gestational age and chorioamnionitis in preterm delivery (PTD) are associated with changes in the expression of SP-A in the chorioamniotic membranes. Chorioamniotic membranes were obtained from women at term and women with PTD (n = 58). SP-A mRNA and protein expression was detected in amniotic epithelial cells, chorionic trophoblasts and macrophages by in situ hybridization and immunohistochemistry. Quantitative real-time reverse transcription-PCR demonstrated predominant expression of SP-A1 mRNA, whose expression was 17.4-fold higher in patients with PTD with chorioamnionitis (n = 15) than in those without (n = 13) (p = 0.018). While no difference was observed in SP-A1 mRNA expression in the chorioamniotic membranes of women at term not in labour (n = 16) and those in tabour (n = 14) (p = 0.87), the expression in term membranes was higher than that of membranes from women with PTD without chorioamnionitis (p = 0.003). Analysis of JAR choriocarcinoma cells demonstrated SP-A1 mRNA expression that was up-regulated following lipopolysaccharide treatment. Furthermore, monocytic cell lines (THP-1 and U937) and peripheral blood monocytes (CD14(+)/CD115(+)) obtained from pregnant women also expressed SP-A1 mRNA and protein, suggesting the presence of autocrine/paracrine activation in vivo. Interestingly, a mid-trimester amniotic fluid sample obtained from a case of tracheal atresia contained SP-A (3.13 mu g/ml), indicating the presence of SP-A of extrapulmonary origin. These findings suggest not only that SP-A expression is a part of the innate immune response deployed during chorioamniotic inflammation, but also that chorioamniotic membranes are a source of SP-A in the amniotic fluid with advancing gestation. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. C1 NICHD, NIH, Perinatol Res Branch, DHHS, Detroit, MI 48201 USA. NICHD, NIH, Perinatol Res Branch, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Romero, R (reprint author), NICHD, NIH, Perinatol Res Branch, DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov; cjki@med.wayne.edu FU Intramural NIH HHS NR 33 TC 19 Z9 20 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAR PY 2007 VL 211 IS 4 BP 489 EP 496 DI 10.1002/path.2131 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 141YL UT WOS:000244615000013 PM 17273989 ER PT J AU Lovvorn, HN Boyle, S Shi, G Shyr, Y Wills, ML Perantoni, AO de Caestecker, M AF Lovvorn, Harold N., III Boyle, Scott Shi, Genbin Shyr, Yu Wills, Marcia L. Perantoni, Alan O. de Caestecker, Mark TI Wilms' tumorigenesis is altered by misexpression of the transcriptional co-activator, CITED1 SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Wilm's tumor; CITED1; melanocyte-specific gene 1; mesenchymal-to-epithelial conversion ID GROWTH-FACTOR-BETA; METANEPHRIC MESENCHYME; SIGNALING PATHWAYS; NUCLEAR-PROTEIN; GENE-EXPRESSION; TUMOR; SMAD4; MSG1; KIDNEY; CANCER AB Purpose: Wilms' tumors arise from arrested differentiation of renal progenitor cells. CITED1 is a transcriptional regulator that blocks the metanephric mesenchymal-to-epithelial conversion and is expressed in the blastema of both the developing kidney and Wilms' tumors. We hypothesized that alterations of CITED1-dependent signaling promote persistence of blastema and thereby subject these pluripotent cells to future oncogenic events. Methods: We used a retroviral delivery system to overexpress the full-length CITED I (F/L) protein and 2 deletion mutants lacking either of its known functional domains, Delta SID (Smad-4 Interacting Domain) and Delta CR2 (Conserved Region 2; the CITED1 transactivation domain), in a human Wilms' tumor cell line that endogenously expresses CITED1. In vitro effects on cellular proliferation and apoptosis were assayed. In vivo effects on tumorigenesis, growth, proliferation, and apoptosis were determined after heterotransplantation into immunodeficient mice (n = 15 per cell line). Results: In vitro, overexpression of CITED1-F/L significantly increased, whereas overexpression of the functionally inactivating mutant, CITED1-Delta CR2, significantly reduced cellular proliferation relative to the other lines (P <.0001). In vivo, Wilms' tumor incidence was significantly reduced in animals injected with cells overexpressing the mutant CITED1-Delta CR2 (7%) compared with CITED1-F/L (40%, P=.03) and CITED1-Delta SID (60%, P <.002). Similarly, mean tumor volume was least in the CITED1-Delta CR2 animals when compared with CITED1-F/L (P=.03) and CITED1-Delta SID animals (P <.005). Furthermore, the CITED1-Delta CR2 tumor showed the least cellular proliferation. Misexpression of CITED I did not affect apoptosis either in vitro or in vivo. Conclusions: Overexpression of CITED1 in a human Wilms' tumor cell line significantly increases proliferation in vitro, whereas mutation of its functionally critical transactivation domain (Delta CR2) significantly reduces proliferation. This mutation further perturbs tumorigenesis and tumor growth after heterotransplantation into immunodeficient mice. We speculate that overexpression of CITED1 promotes expansion of a rapidly proliferating population of blastema and thereby induces an unstable environment highly susceptible to future oncogenic events. (c) 2007 Elsevier Inc. All rights reserved. C1 Vanderbilt Univ, Childrens Hosp, Dept Pediat Surg, Sch Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Div Nephrol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pediat Pathol, Nashville, TN 37232 USA. NCI, Lab Comparat Carcinogenesis, Ft Detrick, MD 21702 USA. RP Lovvorn, HN (reprint author), Vanderbilt Univ, Childrens Hosp, Dept Pediat Surg, Sch Med, 221 Kirkland Hall, Nashville, TN 37232 USA. EM harold.lovvorn@vanderbilt.edu FU NCI NIH HHS [K99 CA135695, K99 CA135695-01] NR 33 TC 10 Z9 10 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD MAR PY 2007 VL 42 IS 3 BP 474 EP 481 DI 10.1016/j.jpedsurg.2006.10.054 PG 8 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 147KW UT WOS:000245002900005 PM 17336183 ER PT J AU Lee, JC Lai, BT Kozak, JJ Gray, HB Winkler, JR AF Lee, Jennifer C. Lai, Bert T. Kozak, John J. Gray, Harry B. Winkler, Jay R. TI alpha-Synuclein tertiary contact dynamics SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID A-BETA COMPONENT; CONTROLLED INTRACHAIN REACTIONS; UNFOLDED POLYPEPTIDE-CHAINS; FOLDING SPEED LIMIT; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; CYTOCHROME-C; PRECURSOR PROTEIN; ELECTRON-TRANSFER; ENERGY-TRANSFER AB Tertiary contact formation rates in alpha-synuclein, an intrinsically disordered polypeptide implicated in Parkinson's disease, have been determined from measurements of diffusion-limited electron-transfer kinetics between triplet-excited tryptophan:3-nitrotyrosine pairs separated by 10, 12, 55, and 90 residues. Calculations based on a Markovian lattice model developed to describe intrachain diffusion dynamics for a disordered polypeptide give contact quenching rates for various loop sizes ranging from 6 to 48 that are in reasonable agreement with experimentally determined values for small loops (10-20 residues). Contrary to expectations, measured contact rates in alpha-synuclein do not continue to decrease as the loop size increases (>= 35 residues), and substantial deviations from calculated rates are found for the pairs W4-Y94, Y39-W94, and W4-Y136. The contact rates for these large loops indicate much shorter average donor-acceptor separations than expected for a random polymer. C1 Depaul Univ, Chicago, IL 60604 USA. NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. CALTECH, Beckman Inst, Pasadena, CA 91125 USA. RP Kozak, JJ (reprint author), Depaul Univ, 243 S Wabash Ave, Chicago, IL 60604 USA. EM kozak@depaul.edu; winklerj@caltech.edu; hbgray@caltech.edu RI Lee, Jennifer/E-9658-2015 OI Lee, Jennifer/0000-0003-0506-8349 FU NIDDK NIH HHS [DK19038, R01 DK019038, R37 DK019038]; NIGMS NIH HHS [R01 GM068461-05, GM068461, R01 GM068461] NR 42 TC 45 Z9 46 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD MAR 1 PY 2007 VL 111 IS 8 BP 2107 EP 2112 DI 10.1021/jp068604y PG 6 WC Chemistry, Physical SC Chemistry GA 138FM UT WOS:000244348500026 PM 17279794 ER PT J AU Meunier, S Kwon, J Russmann, H Ravindran, S Mazzocchio, R Cohen, L AF Meunier, Sabine Kwon, Jeongyi Russmann, Heike Ravindran, Shashi Mazzocchio, Riccardo Cohen, Leonardo TI Spinal use-dependent plasticity of synaptic transmission in humans after a single cycling session SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SOLEUS H-REFLEX; POST-ACTIVATION DEPRESSION; LOW-FREQUENCY DEPRESSION; LONG-TERM POTENTIATION; VISUO-MOTOR SKILL; PRESYNAPTIC INHIBITION; IA AFFERENTS; HOMOSYNAPTIC DEPRESSION; LOCOMOTOR PLASTICITY; TRANSMITTER RELEASE AB The spinal cord is able to express use-dependent plasticity, as demonstrated in spinalized cats following treadmill training. In humans, spinal use-dependent plasticity is inferred from modifications in the size of H reflex, which are often more prominent after skilled motor training. Plasticity can develop at synaptic connections between afferent fibres and/or descending tracts and motoneurones or interneurones interposed in the spinal pathways. Here we explore whether skilled training induces a change in synaptic efficacy at the synapse between Ia afferents and soleus (Sol) motoneurones. Synaptic efficacy can be modulated presynaptically through changes of the probability of transmitter release (homosynaptic depression, HD). The frequency-related depression of the Sol H reflex, thought to reflect HD, was tested at rest, before and after one single skilled (14 subjects) or non-skilled (9 subjects) cycling training session. Performance improved in both groups but to a larger extent with skilled training, while HD increased immediately after and the day following skilled training in the absence of changes with non-skilled training. These results support the view that spinal cord function is able to encode a local motor memory. C1 NINCDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. NINCDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. INSERM, UMRS 731, F-75651 Paris, France. Univ Paris 06, UMRS 731, F-75013 Paris, France. Catholic Univ Korea, St Vincent Hosp, Suwon 442723, South Korea. Univ Siena, Sez Neurofisiol Clin, Dipartimento Sci Neurol & Comportamento, I-53100 Siena, Italy. RP Meunier, S (reprint author), Univ Paris 06, INSERM, U731, Grp Hosp Pitie Salpetriere, 47 Bd Hop, F-75651 Paris 13, France. EM meunier.sabine@free.fr RI meunier, sabine/G-7622-2014; Mazzocchio, Riccardo/H-4223-2012 OI meunier, sabine/0000-0002-6167-4602; Mazzocchio, Riccardo/0000-0002-0628-2868 FU Intramural NIH HHS NR 62 TC 44 Z9 44 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAR 1 PY 2007 VL 579 IS 2 BP 375 EP 388 DI 10.1113/jphysiol.2006.122911 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 141JU UT WOS:000244575400009 PM 17170047 ER PT J AU Woods, AS Wang, HYJ Jackson, SN AF Woods, Amina S. Wang, Hay-Yan J. Jackson, Shelley N. TI Sulfation, the up-and-coming post-translational modification: Its role and mechanism in protein-protein interaction SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE sulfation; noncovalent interactions; salt bridges; guanidium group ID TYROSINE SULFATION; MASS-SPECTROMETRY; PHOSPHATE; RESIDUES; ARGININE; BINDING; FIBRONECTIN; ADHESION; FEATURES AB Tyrosine sulfation is a post-translational modification entailing covalent attachment of sulfate to tyrosine residues. It takes place in the trans-Golgi, is necessary for the bioactivity of some proteins, and improves their ability to interact with other proteins. In the present work, we show that a protein containing a sulfated tyrosine with a delocalized negative charge forms a salt bridge with another protein if it has two or more adjacent arginine residues containing positive delocalized charges. These noncovalent complexes are so stable that, when submitted to collision induced dissociation, the peptides forming the complex dissociate. Just one covalent bond fragments, the covalent bond between the tyrosine oxygen and the SO3 sulfur, and is represented by the appearance of a new peak (basic peptide + SO3), suggesting that in some instances covalent bonds will break down before the noncovalent bonds between the arginine guanidinium and SO3 dissociate. The data implies that the dissociation pathway is preferred; however, fragmentation between tyrosine and the sulfate residue is a major pathway. C1 NIDA, IRP, NIH, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), NIDA, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 30 TC 17 Z9 17 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAR PY 2007 VL 6 IS 3 BP 1176 EP 1182 DI 10.1021/pr060529g PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 142GW UT WOS:000244638400026 PM 17256885 ER PT J AU Heinz, A Epstein, DH Preston, KL AF Heinz, Adrienne Epstein, David H. Preston, Kenzie L. TI Spiritual/religious experiences and in-treatment outcome in an inner-city program for heroin and cocaine dependence SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE addiction; religion; spirituality; substance abuse; treatment ID SUBSTANCE-ABUSE PATIENTS; SELF-HELP GROUPS; ADDICTION TREATMENT; RECOVERY PROCESS; SPIRITUALITY; HEALTH; RELIGIOSITY; ORGANIZATIONS; MEDIATORS; CLINICIAN AB Although spirituality is an integral component of some of the most popular approaches to substance abuse treatment, there is little empirical evidence for a causal relationship between spirituality and treatment success. In the present study, 169 (121 male) opiate-or cocaine-abusing treatment seekers completed the Index of Spiritual Experience (INSPIRIT), a questionnaire that assesses both spirituality and religiosity. Responses were analyzed in terms of demographic variables and in-treatment outcome, which was determined by treatment retention and drug screens from observed biweekly urine collections. Religious/spiritual beliefs were common in these participants and were associated with in-treatment outcome: total INSPIRIT score was weakly correlated (r=.16, p <.04) with number of subsequent cocaine-negative urines, and participants reporting that they frequently spent time on religious/spiritual activities showed significantly better outcomes in terms of subsequent drug use and treatment retention. Women and African Americans were more likely than men and non-African Americans to report religious and spiritual beliefs or experiences on several individual items, and African Americans had higher INSPIRIT scores than Caucasians. The results suggest that spiritual and religious experience plays a role in substance abuse recovery and that demographic characteristics should be considered in the design of spiritually oriented behavioral interventions. C1 Natl Inst Drug Abuse, Intramural Res Program, Clin Pharmacol & Treatment Branch, Baltimore, MD USA. RP Heinz, A (reprint author), Univ Illinois, 1007 W Harrison St,M-C 285, Chicago, IL 60607 USA. EM aheinz3@uic.edu RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 41 TC 12 Z9 12 U1 2 U2 11 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD MAR PY 2007 VL 39 IS 1 BP 41 EP 49 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 161ZX UT WOS:000246057000005 PM 17523584 ER PT J AU Cohen, LK AF Cohen, Lois K. TI Addressing global health research in the national interest SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Editorial Material C1 Natl Inst Dent & Craniofacial Res, NIH, US Dept Hlth & Human Resources, Bethesda, MD USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SPR PY 2007 VL 67 IS 2 BP 67 EP 68 DI 10.1111/j.0022-4006.2007.00012.x PG 2 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 169AZ UT WOS:000246566400001 PM 17557675 ER PT J AU Jensen, PS Youngstrom, EA Steiner, H Findling, RL Meyer, RE Malone, RP Carlson, GA Coccaro, EF Aman, MG Blair, J Dougherty, D Ferris, C Flynn, L Green, E Hoagwood, K Hutchinson, J Laughren, T Leve, LD Novins, DK Vitiello, B AF Jensen, Peter S. Youngstrom, Eric A. Steiner, Hans Findling, Robert L. Meyer, Roger E. Malone, Richard P. Carlson, Gabrielle A. Coccaro, Emil F. Aman, Michael G. Blair, James Dougherty, Donald Ferris, Craig Flynn, Laurie Green, Evelyn Hoagwood, Kimberly Hutchinson, Janice Laughren, Tom Leve, Leslie D. Novins, Douglas K. Vitiello, Benedetto TI Consensus report on impulsive aggression as a symptom across diagnostic categories in child psychiatry: Implications for medication studies SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE impulsivity; aggression; clinical trials; assessment ethics ID INTERMITTENT EXPLOSIVE DISORDER; DISRUPTIVE BEHAVIOR DISORDERS; RANDOMIZED CLINICAL-TRIAL; ANTISOCIAL-BEHAVIOR; AUTISTIC-CHILDREN; CONDUCT DISORDER; TREATMENT RECOMMENDATIONS; PROACTIVE AGGRESSION; JUVENILE-OFFENDERS; SOCIAL-CONTEXT AB Objective: To determine whether impulsive aggression (IA) is a meaningful clinical construct and to ascertain whether it is sufficiently similar across diagnostic categories, such that parallel studies across disorders might constitute appropriate evidence for pursuing indications. If so, how should IA be assessed, pharmacological studies designed, and ethical issues addressed? Method: Experts from key stakeholder communities, including academic clinicians, researchers, practicing clinicians, U.S. Food and Drug Administration, National Institute of Mental Health, industry sponsors, and patient and family advocates, met for a 2-day consensus conference on November 4 and 5, 2004. After evaluating summary presentations on current research evidence, participants were assigned to three workgroups, examined core issues, and generated consensus guidelines in their areas. Workgroup recommendations were discussed by the whole group to reach consensus, and then further iterated and condensed into this report postconference by the authors. Results: Conference participants agreed that IA is a substantial public health and clinical concern, constitutes a key therapeutic target across multiple disorders, and can be measured with sufficient precision that pharmacological studies are warranted. Additional areas of consensus concerned types of measures, optimal study designs, and ethical imperatives. Conclusion: Derived from scientific evidence and clinical experience, these consensus-driven recommendations can guide the design of future studies. C1 Columbia Univ, Ctr Advancement Childrens Menatl Hlth, NYSPI, Unit 78, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Best Practice Project Management Inc, Bethesda, MD USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Chicago, Sch Med, Chicago, IL 60637 USA. Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. NIMH, NIH, Bethesda, MD 20892 USA. Wake Forest Hlth Sci, Wake Forest, NC USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Attent Deficit Disorders Assoc, Chicago, IL USA. Howard Univ Hosp, Washington, DC USA. US FDA, Rockville, MD 20857 USA. Oregon Social Learning Ctr, Eugene, OR 97401 USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. RP Jensen, PS (reprint author), Columbia Univ, Ctr Advancement Childrens Menatl Hlth, NYSPI, Unit 78, 1051 Riverside Dr, New York, NY 10032 USA. EM pj131@columbia.edu OI Jensen, Peter/0000-0003-2387-0650; Leve, Leslie/0000-0003-3061-4524 NR 63 TC 68 Z9 69 U1 3 U2 13 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 MAR PY 2007 VL 46 IS 3 BP 309 EP 322 DI 10.1097/CHI.0b013e31802f1454 PG 14 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 139JT UT WOS:000244428800006 PM 17314717 ER PT J AU Dickstein, DP Nelson, EE McClure, EB Grimley, ME Knopf, L Brotman, MA Rich, BA Pine, DS Leibenluft, E AF Dickstein, Daniel P. Nelson, Eric E. McClure, Erin B. Grimley, Mary E. Knopf, Lisa Brotman, Melissa A. Rich, Brendan A. Pine, Daniel S. Leibenluft, Ellen TI Cognitive flexibility in phenotypes of pediatric bipolar disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE bipolar disorder; neuropsychological tests; cognition ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MAGNETIC-RESONANCE SPECTROSCOPY; DEFICIT HYPERACTIVITY DISORDER; ORBITAL PREFRONTAL CORTEX; VOXEL-BASED MORPHOMETRY; SCHOOL-AGE-CHILDREN; ORBITOFRONTAL CORTEX; RESPONSE-INHIBITION; EXECUTIVE FUNCTION; BASAL GANGLIA AB Objective: Clinicians and researchers debate whether children with chronic, nonepisodic irritability should receive the diagnosis of bipolar disorder (BD). To address this debate, we evaluated cognitive flexibility, or the ability to adapt to changing contingencies, in three groups of children: narrow-phenotype BD (NP-BD; full-duration manic episodes of elevated/expansive mood; N = 50; 13.1 +/- 2.9 years), severe mood dysregulation (SMD; chronic, nonepisodic irritability; N = 44; 12.2 +/- 2.1 years), and healthy controls (N = 43; 13.6 +/- 2.4 years). Cognitive flexibility is relevant to symptoms of BD involving dysfunctional reward systems (e.g., excessive goal-directed activity and pleasure-seeking in mania; anhedonia in depression). Method: We studied simple and compound reversal stages of the intra-/extradimensional shift task and change task that involves inhibiting a prepotent response and substituting a novel response. Results: On the simple reversal, NP-BD youths were significantly more impaired than both the SMD group and controls. On the compound reversal, NP-BD and SMD youths performed worse than controls. On the change task, NP-BD youths were slower to adapt than SMD subjects. Conclusions: Phenotypic differences in cognitive flexibility may reflect different brain/behavior mechanisms in these two patient populations. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Div Intramural Res Program, Bethesda, MD 20892 USA. RP Dickstein, DP (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, Div Intramural Res Program, 9000 Rockville Pike MSC 2670 Bldg 15K Room 204, Bethesda, MD 20892 USA. EM Dicksted@mail.nih.gov RI Nelson, Eric/B-8980-2008; Brotman, Melissa/H-7409-2013; Dickstein, Daniel/L-3210-2016 OI Nelson, Eric/0000-0002-3376-2453; Dickstein, Daniel/0000-0003-1647-5329 FU Intramural NIH HHS; NIMH NIH HHS [K22 MH74945] NR 66 TC 70 Z9 71 U1 7 U2 12 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 MAR PY 2007 VL 46 IS 3 BP 341 EP 355 DI 10.1097/chi.0b013e31802d0b3d PG 15 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 139JT UT WOS:000244428800009 PM 17314720 ER PT J AU Stryker, JE Yaroch, AL Moser, RP Atienza, A Glanz, K AF Stryker, Jo Ellen Yaroch, Amy L. Moser, Richard P. Atienza, Audie Glanz, Karen TI Prevalence of sunless tanning product use and related behaviors among adults in the United States: Results from a national survey SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SUN; LOTIONS AB Little is known about the use of sunless tanning products in the United States. This report describes the prevalence and correlates of sunless tanning use, comparing exclusive sunless tanners, exclusive indoor tanners, both sunless and indoor tanners, and non-tanners with respect to sociodemographic and sun protection behaviors. C1 Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. RP Stryker, JE (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, 1518 Clifton Rd NE,Rm 572, Atlanta, GA 30322 USA. EM jestryk@sph.emory.edu NR 10 TC 44 Z9 44 U1 1 U2 1 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 MAR PY 2007 VL 56 IS 3 BP 387 EP 390 DI 10.1016/j.jaad.2006.08.051 PG 4 WC Dermatology SC Dermatology GA 141XP UT WOS:000244612700004 PM 17097362 ER PT J AU Cowen, EW AF Cowen, Edward W. TI Epidermal growth factor receptor inhibitors: A new era of drug reactions in a new era of cancer therapy - Commentary SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material ID ADVANCED PANCREATIC-CANCER; SOLID TUMORS; NECK-CANCER; SKIN; CETUXIMAB; FOLLICULITIS; COMBINATION; MANAGEMENT; GEFITINIB; BINDING C1 NCI, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, CCR, NIH, 10 Ctr Dr,MSC 1908,Bldg 10,Room 12N238, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov NR 29 TC 10 Z9 11 U1 0 U2 1 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 MAR PY 2007 VL 56 IS 3 BP 514 EP 517 DI 10.1016/j.jaad.2006.11.004 PG 4 WC Dermatology SC Dermatology GA 141XP UT WOS:000244612700026 PM 17184876 ER PT J AU Kastenmayer, RJ Perdue, KA AF Kastenmayer, Robin J. Perdue, Kathy A. TI Variation in organ volumes of matched BALB/c mice by microcomputed tomography analysis SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID RAY COMPUTED-TOMOGRAPHY AB High-resolution microcomputed tomography technology has allowed researchers to use live mice to address questions that previously could be answered only at necropsy. Serial analyses of the same mouse allow tissue changes to be followed over time. The ability to follow a single mouse noninvasively can decrease the total number of mice required for the study. The magnitude of inter-mouse variation for matched mice undergoing microcomputed tomography has not been determined previously. We selected lung and contrast-enhanced stomach as tissues of standard size and anatomical structure that were hypothesized to vary minimally between mice. The analyses of the tissue volumes from matched mice showed considerable variation among mice, among multiple sequential scans of the same mouse, and even among multiple evaluations of the same scan. More variation occurred with repeated scans of the same mouse (intramouse variation) than between mice (intermouse variation). In addition, significant variation and obvious bias was detected between the 2 scan evaluators. These data suggest that to obtain the widest range of possible values, among which the true value would be found, multiple analyses of multiple scans of the same mouse must lie performed by multiple scan evaluators. C1 NIAID, Comparat Med Branch, NIH, Rockville, MD USA. RP Kastenmayer, RJ (reprint author), NIAID, Comparat Med Branch, NIH, Rockville, MD USA. EM rkastenmayer@niaid.nih.gov FU Intramural NIH HHS NR 15 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD MAR PY 2007 VL 46 IS 2 BP 7 EP 12 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 151XU UT WOS:000245325200001 PM 17343346 ER PT J AU McDermott, MM Hoff, F Ferrucci, L Pearce, WH Guralnik, JM Tian, L Liu, KA Schneider, JR Sharma, L Tan, J Criqui, MH AF McDermott, Mary M. Hoff, Frederick Ferrucci, Luigi Pearce, William H. Guralnik, Jack M. Tian, Lu Liu, Kiang Schneider, Joseph R. Sharma, Leena Tan, Jin Criqui, Michael H. TI Lower extremity ischemia, calf skeletal muscle characteristics, and functional impairment in peripheral arterial disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE physical functioning; peripheral vascular disease; intermittent claudication; sarcopenia ID ANKLE-BRACHIAL INDEX; INTERMITTENT CLAUDICATION; LEG SYMPTOMS; ATHEROSCLEROSIS; CLASSIFICATION; OSTEOARTHRITIS; ASSOCIATION; DISABILITY; DIAGNOSIS; CRITERIA AB OBJECTIVES: To determine whether lower ankle brachial index (ABI) levels are associated with lower calf skeletal muscle area and higher calf muscle percentage fat in persons with and without lower extremity peripheral arterial disease (PAD). DESIGN: Cross-sectional. SETTING: Three Chicago-area medical centers. PARTICIPANTS: Four hundred thirty-nine persons with PAD (ABI < 0.90) and 265 without PAD (ABI 0.90-1.30). MEASUREMENTS: Calf muscle cross-sectional area and the percentage of fat in calf muscle were measured using computed tomography at 66.7% of the distance between the distal and proximal tibia. Physical activity was measured using an accelerometer. Functional measures included the 6-minute walk, 4-meter walking speed, and the Short Physical Performance Battery (SPPB). RESULTS: Adjusting for age, sex, race, comorbidities, and other potential confounders, lower ABI values were associated with lower calf muscle area (ABI < 0.50, 5,193 mm(2); ABI 0.50-0.90, 5,536 mm(2); ABI 0.91-1.30, 5,941 mm(2); P for trend <.001). These significant associations remained after additional adjustment for physical activity. In participants with PAD, lower calf muscle area in the leg with higher ABI was associated with significantly poorer performance in usual- and fast-paced 4-meter walking speed and on the SPPB, adjusting for ABI, physical activity, percentage fat in calf muscle, muscle area in the leg with lower ABI, and other confounders (P <.05 for all comparisons). CONCLUSION: These data support the hypothesis that lower extremity ischemia has a direct adverse effect on calf skeletal muscle area. This association may mediate previously established relationships between PAD and functional impairment. C1 Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Radiol, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. NIA, Lab Clin Epidemiol, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Evanston NW Hosp, Div Vasc Surg, Dept Surg, Chicago, IL USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. RP McDermott, MM (reprint author), 676 N St Clair,Suite 200, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU Intramural NIH HHS [Z99 AG999999]; NCRR NIH HHS [M01 RR000048, RR-00048]; NHLBI NIH HHS [R01 HL064739, R01 HL071223, R01-HL58099, R01-HL64739, R01-HL71223] NR 28 TC 65 Z9 65 U1 0 U2 6 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 MAR PY 2007 VL 55 IS 3 BP 400 EP 406 DI 10.1111/j.1532-5412.2007.01092.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 140QA UT WOS:000244519400012 PM 17341243 ER PT J AU Manini, TM Visser, M Won-Park, S Patel, KV Strotmeyer, ES Chen, HP Goodpaster, B De Rekeneire, N Newman, AB Simonsick, EM Kritchevsky, SB Ryder, K Schwartz, AV Harris, TB AF Manini, Todd M. Visser, Marjolein Won-Park, Seok Patel, Kushang V. Strotmeyer, Elsa S. Chen, Hepei Goodpaster, Bret De Rekeneire, Nathalie Newman, Anne B. Simonsick, Eleanor M. Kritchevsky, Stephen B. Ryder, Kathy Schwartz, Ann V. Harris, Tamara B. CA Hlth Aging Body Composition Study TI Knee extension strength cutpoints for maintaining mobility SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE strength thresholds; disability; elderly; gait speed; physical reserve ID LOWER-EXTREMITY PERFORMANCE; MUSCLE MASS; BODY-COMPOSITION; GAIT SPEED; PHYSICAL ACTIVITIES; OLDER-ADULTS; ASSOCIATION; DISABILITY; HEALTH; WOMEN AB OBJECTIVES: To identify levels of knee extensor strength that are associated with high and low risk of incident severe mobility limitation (SML) in initially well-functioning older adults. DESIGN: Prospective cohort study. SETTING: University clinic center. PARTICIPANTS: One thousand three hundred fifty-five men and 1,429 women (aged 73.6 +/- 2.85) who reported no mobility limitation. MEASUREMENTS: Unilateral knee extensor isokinetic strength of participants was obtained. Participants were followed over a median of 5.90 years for the onset of SML, defined as two consecutive reports of a lot of difficulty or inability to walk one-quarter of a mile or climb 10 steps. Deciles of knee extension strength relative to body weight were evaluated to identify cutpoints most predictive of incident SML. Cutpoints were then compared with prevalence of having slow gait speed (< 1.22 m/s) and mortality. RESULTS: Two sex-specific knee extension strength cutpoints were found. High and low risk of SML corresponded to less than 1.13 newton-meters (Nm)/kg (1st decile) and more than 1.71 Nm/kg (6th decile) in men and less than 1.01 Nm/kg (3rd decile) and more than 1.34 Nm/kg (7th decile) in women, respectively. Moderate risk was defined as being between the low- and high-risk cutpoints. Individuals with knee extension strength in the high- and moderate-risk categories were more likely to have a gait speed less than 1.22 m/s (hazard ratio (HR)=7.00, 95% confidence interval (CI)=5.47-8.96 and HR=2.14 7.00, 95% CI=1.73-2.64, respectively) and had a higher risk of death (HR=1.77, 95% CI=1.41-2.23 and HR=1.51, 95% CI=1.24-1.84, respectively) than individuals in the low-risk category. Adjustment for demographic factors, health behaviors, and medical conditions did not alter these associations. CONCLUSION: Knee extensor strength cutpoints provide objective markers to identify initially well-functioning older adults at high and low risk of future mobility limitation. C1 Vrije Univ Amsterdam, Med Ctr, Inst Aging, Dept Aging & Geriatr Res, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Inst Hlth Sci, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands. Pochon CHA Univ, Dept Med, Seoul, South Korea. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Endocrinol & Metab, Pittsburgh, PA USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. NIA, Intramural Res Program, Baltimore, MD 21224 USA. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA. RP Manini, TM (reprint author), Univ Florida, Dept Aging & Geriatr Res, POB 112610, Gainesville, FL 32611 USA. EM tmanini@aging.ufl.edu RI Newman, Anne/C-6408-2013; Strotmeyer, Elsa/F-3015-2014; OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036; 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 29 TC 77 Z9 79 U1 2 U2 5 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 MAR PY 2007 VL 55 IS 3 BP 451 EP 457 DI 10.1111/j.1532-5415.2007.01087.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 140QA UT WOS:000244519400020 PM 17341251 ER PT J AU Lawler, SP Reimer, L Thiemann, T Fritz, J Parise, K Feliz, D Elnaiem, DE AF Lawler, Sharon P. Reimer, Lisa Thiemann, Tara Fritz, John Parise, Katy Feliz, Dave Elnaiem, Dia-Eldin TI Effects of vegetation control on mosquitoes in seasonal freshwater wetlands SO JOURNAL OF THE AMERICAN MOSQUITO CONTROL ASSOCIATION LA English DT Article DE Culex tarsalis; disking; seasonal wetlands ID MANAGEMENT STRATEGIES; HABITATS AB Wetland restorations benefit wildlife, but wetland vegetation may promote mosquitoes. We studied the effects of removing joint grass (Paspalum distichum L.) on the abundance and distribution of immature mosquitoes in seasonal freshwater wetlands in California. In 4 > 4-ha plots and one 29.8-ha field, joint grass was removed via herbicide and disking. Four untreated plots and one 4.1-ha field were controls. Fields were sampled every 7-14 days in early autumn by taking 75 dips along levees, plus a 25-dip circular transect 6 m from field edges. Untreated plots had 7 times more larvae and 20 times more pupae than did vegetation-removal plots. Similar densities of mosquitoes were found along, edges and within fields. C1 Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. Univ Calif Davis, Ctr Vectorborne Dis Res, Davis, CA 95616 USA. Sacramento Yolo Mosquito & Vector Control Dist, Elk Grove, CA 95624 USA. Calif Dept Fish & Game, Yolo Bypass Wildlife Area, Davis, CA 95616 USA. NIAID, NIH, Rockville, MD 20852 USA. RP Lawler, SP (reprint author), Univ Calif Davis, Dept Entomol, 1 Shields Ave, Davis, CA 95616 USA. FU FIC NIH HHS [K01 TW008778] NR 11 TC 6 Z9 7 U1 1 U2 8 PU AMER MOSQUITO CONTROL ASSOC PI EATONTOWN PA P O BOX 234, EATONTOWN, NJ 07724-0234 USA SN 8756-971X J9 J AM MOSQUITO CONTR JI J. Am. Mosq. Control Assoc. PD MAR PY 2007 VL 23 IS 1 BP 66 EP 70 DI 10.2987/8756-971X(2007)23[66:EOVCOM]2.0.CO;2 PG 5 WC Entomology SC Entomology GA 159LF UT WOS:000245866500010 PM 17536370 ER PT J AU Wang, HYJ Jackson, SN Woods, AS AF Wang, Hay-Yan J. Jackson, Shelley N. Woods, Amina S. TI Direct MALDI-MS analysis of cardiolipin from rat organs sections SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID TRAP MASS-SPECTROMETRY; ELECTROSPRAY-IONIZATION; BARTH-SYNDROME; STRUCTURAL-CHARACTERIZATION; FRAGMENTATION PROCESSES; TANDEM QUADRUPOLE; OXIDATIVE STRESS; APOPTOSIS; PHOSPHATIDYLSERINE; PURIFICATION AB Cardiolipins (CL) are mitochondria specific lipids. They play a critical role in ATP synthesis mediated by oxidative phosphorylation. Abnormal CL distribution is associated with several disease states. MALDI-MS and MALDI-MS/MS were used to demonstrate in situ analysis and characterization of CL from tissue sections of organs containing high concentrations of mitochondria. Once the experimental parameters were established, a survey of CL distribution in heart, liver, kidney, leg muscle, and testis was undertaken. The major CL specie in the heart muscle, leg muscle, liver, and kidney is the (18:2)(4) CL, while liver and kidney also contain a minor specie, (18:2)(3)/(18:1) CL. The major CL specie in testis is the (16:0)(4) CL. The CL species distribution in various organs appeared to be in agreement with prior reports. Overall, proper matrix selection, tissue section handling, instrument tuning, and the inclusion of cesium ion in matrix ensured successful in situ MALDI-MS and MALDI-MS/MS analysis of CL. Upon modification and standardization, this method could be streamlined for rapid pathological diagnosis with short turnaround time in clinical settings. C1 NIDA, Abuse Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), NIDA, Abuse Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 26 TC 49 Z9 51 U1 4 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD MAR PY 2007 VL 18 IS 3 BP 567 EP 577 DI 10.1016/j.jasms.2006.10.023 PG 11 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 141NT UT WOS:000244586300023 PM 17157526 ER PT J AU Fenton, RA Knepper, MA AF Fenton, Robert A. Knepper, Mark A. TI Urea and renal function in the 21st century: Insights from knockout mice SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID MEDULLARY COLLECTING DUCT; TRANSPORTER UT-B; URINARY CONCENTRATING ABILITY; THICK ASCENDING LIMB; KIDD BLOOD-GROUP; RAT-KIDNEY; WATER TRANSPORT; GLOMERULAR-FILTRATION; MAMMALIAN KIDNEY; INNER MEDULLA AB Since the turn of the 21st century, gene knockout mice have been created for all major urea transporters that are expressed in the kidney: the collecting duct urea transporters UT-A1 and UT-A3, the descending thin limb isoform UT-A2, and the descending vasa recta isoform UT-B. This article discusses the new insights that the results from studies in these mice have produced in the understanding of the role of urea in the urinary concentrating mechanism and kidney function. Following is a summary of the major findings: (1) Urea accumulation in the inner medullary interstitium depends on rapid transport of urea from the inner medullary collecting duct (IMCD) lumen via UT-A1 and/or UT-A3; (2) as proposed by Robert Berliner and colleagues in the 1950s, the role of IMCD urea transporters in water conservation is to prevent a urea-induced osmotic diuresis; (3) the absence of IMCD urea transport does not prevent the concentration of NaCl in the inner medulla, contrary to what would be predicted from the passive countercurrent multiplier mechanism in the form proposed by Kokko and Rector and Stephenson; (4) deletion of UT-B (vasa recta isoform) has a much greater effect on urinary concentration than deletion of UT-A2 (descending limb isoform), suggesting that the recycling of urea between the vasa recta and the renal tubules quantitatively is less important than classic countercurrent exchange; and (5) urea reabsorption from the IMCD and the process of urea recycling are not important elements of the mechanism of protein-induced increases in GFR. In addition, the clinical relevance of these studies is discussed, and it is suggested that inhibitors that specifically target collecting duct urea transporters have the potential for clinical use as potassium-sparing diuretics that function by creation of urea-dependent osmotic diuresis. C1 Aarhus Univ, Inst Anat, Water & Salt Res Ctr, DK-8000 Aarhus, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Fenton, RA (reprint author), Aarhus Univ, Inst Anat, Water & Salt Res Ctr, Bldg 2333-234, DK-8000 Aarhus, Denmark. EM rofe@ana.au.dk FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21] NR 87 TC 54 Z9 54 U1 0 U2 13 PU AMERICAN SOCIETY 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 MAR PY 2007 VL 18 IS 3 BP 679 EP 688 DI 10.1681/ASN.2006101108 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 159NS UT WOS:000245873400007 PM 17251384 ER PT J AU Ghosh, K Tiwari, RC AF Ghosh, Kaushik Tiwari, Ram C. TI Prediction of US cancer mortality counts using semiparametric Bayesian techniques SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Dirichlet process; health statistics; local linear model; local quadratic model; Markov chain Monte Carlo; state-space model; time series ID NONPARAMETRIC PROBLEMS; MIXTURES; MODEL AB We present two models for the short-term prediction of the number of deaths arising from common cancers in the United States. The first is a local linear model, in which the slope of the segment joining the number of deaths for any two consecutive time periods is assumed to be random with a nonparametric distribution, which has a Dirichlet process prior. For slightly longer prediction periods, we present a local quadratic model. This extension of the local linear model includes an additional "acceleration" term that allows it to quickly adjust to sudden changes in the time series. The proposed models can be used to obtain the predictive distributions of the future number of deaths, as well their means and variances through Markov chain Monte Carlo techniques. We illustrate our methods by runs on data from selected cancer sites. C1 New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA. NCI, Stat Res & Applicat Branch, Bethesda, MD 20892 USA. RP Ghosh, K (reprint author), New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA. EM ghosh@njit.edu; tiwarir@mail.nih.gov NR 20 TC 8 Z9 9 U1 0 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2007 VL 102 IS 477 BP 7 EP 15 DI 10.1198/016214506000000762 PG 9 WC Statistics & Probability SC Mathematics GA 138KH UT WOS:000244361000002 ER PT J AU Baker, SG AF Baker, Stuart G. TI Untitled SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2007 VL 102 IS 477 BP 394 EP 394 DI 10.1198/016214506000000654 PG 1 WC Statistics & Probability SC Mathematics GA 138KH UT WOS:000244361000033 ER PT J AU Sullivan, PS McNaghten, AD Begley, E Hutchinson, A Cargill, VA AF Sullivan, Patrick S. McNaghten, A. D. Begley, Elin Hutchinson, Angela Cargill, Victoria A. TI Enrollment of racial/ethnic minorities and women with HIV in clinical research studies of HIV medicines SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE HIV; clinical investigation; African Americans ID AFRICAN-AMERICANS; TUSKEGEE-SYPHILIS; CONSPIRACY BELIEFS; UNITED-STATES; TRIALS; PARTICIPATION; DISPARITIES; HIV/AIDS; COMMUNITY; ATTITUDES AB Purpose: Inclusion of women and racial/ethnic minorities is a requirement for federally supported clinical research, but data on clinical research participation from women and racial/ethnic minorities with HIV are few. To describe participation in clinical research of HIV medicines among women and racial/ethnic minorities, and associated factors, we used data from a cross-sectional behavioral surveillance interview project conducted in 15 U.S. states. Methods: Data were from 6,892 persons living with HIV infection, recruited in facilities in seven U.S. states and using population-based methods in eight other states, between 2000-2004. We calculated self-reported participation in a clinical research study of HIV medicines, factors associated with self-reported study participation among men and women, and reasons for not participating in a study among nonparticipants. Main Findings: Overall, 17% of respondents had ever participated in a clinical research study. For men, the odds of participation were lower for black or Hispanic men (versus white men) and were higher for men whose risk for HIV infection was male-male sex (versus men with male-female sex risk) and for men with AIDS. For men who had not participated in a study, black men were more likely than white men to report not participating in a study because they were unaware of available studies or were not offered enrollment (75% vs. 69%), and because they did not want to be a "guinea pig" (11% vs. 8%). Among women, participation was not associated with race/ethnicity or risk for HIV infection but was associated with living in an area with an NIH- or CDC- supported clinical research network. HIV-intected women were more likely than HIV-infected men with comparable modes of HIV acquisition to have participated in a study. Conclusions: Among persons with HIV interviewed in these 15 states, self-reported participation in clinical research studies was higher among women than men, but racial/ethnic minority men were less likely to report study participation. Our data suggest that clinicians and researchers should make increased efforts to offer study participation to racial and ethnic minority men. C1 Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA 30333 USA. NIH, Bethesda, MD 20892 USA. RP Sullivan, PS (reprint author), Ctr Dis Control & Prevent, Div HIV AIDS Prevent, 1600 Clifton Rd NE,MS E46, Atlanta, GA 30333 USA. EM pss0@cdc.gov OI Sullivan, Patrick/0000-0002-7728-0587 NR 26 TC 40 Z9 40 U1 1 U2 4 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 MAR PY 2007 VL 99 IS 3 BP 242 EP 250 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 144YT UT WOS:000244833200007 PM 17393948 ER PT J AU Mittal, P Goncalves, LF Kusanovic, JP Espinoza, J Lee, W Nien, JK Soto, E Romero, R AF Mittal, Pooja Goncalves, Luis F. Kusanovic, Juan Pedro Espinoza, Jimmy Lee, Wesley Nien, Jyh Kae Soto, Eleazar Romero, Roberto TI Objective evaluation of Sylvian fissure development by multiplanar 3-dimensional ultrasonography SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE fetal brain; sylvian fissure; 3-dimensional ultrasonography ID FETAL-BRAIN; 4-DIMENSIONAL ULTRASOUND; PRENATAL ULTRASOUND; SULCAL DEVELOPMENT; DIAGNOSIS; ANOMALIES; FETUSES; MIDLINE; CORTEX; VIEW AB Objective. Evaluation of fetal cerebral cortex sulcation is important for the prenatal diagnosis of neuronal migration disorders. Although abnormal sylvian fissure morphologic features are frequently observed in these conditions, the diagnosis of an abnormal sylvian fissure relies on subjective interpretation of ultrasonographic images. This study was performed to develop an objective ultrasonographic parameter for sylvian fissure evaluation. Methods. This cross-sectional study included 202 normal singleton pregnancies without fetal anomalies. Using multiplanar, 3-dimensional ultrasonography, the sylvian fissure midpoint was identified. The sylvian fissure-to-parietal bone distance (SPB) was measured from the midpoint to the inner surface of the parietal bone, perpendicular to the falx cerebri. Bland-Altman plots were used to determine intraobserver and interobserver agreement. Regression analysis was used to evaluate the correlation between SPB measurements and gestational age. Results. Two hundred (99%) of 202 pregnancies had a visible sylvian fissure, identifiable as early as 12 weeks of gestation. The mean SPB values at 12 and 41 weeks were 2.1 and 14.3 mm, respectively. Intraobserver and interobserver mean differences between paired measurements were 0.01 mm (95% limits of agreement, -0.41 to 0.43 mm) and 0.05 mm (95% limits of agreement, -1.79 to 1.90 mm), respectively. A linear correlation was observed between the SPB and gestational age (multiple R = 0.91; R-2 = 0.82 [SPB = -2.85 + 0.42 x gestational age]). Conclusions. (1) The SPB can be reproducibly measured from 12 weeks of gestation to term; and (2) a strong positive correlation was observed between the SPB and gestational age. C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Hutzel Womens Hosp, NICHD,Perinatol Res Branch, NIH,DHHS, Detroit, MI 48201 USA. William Beaumont Hosp, Div Fetal Imaging, Royal Oak, MI 48072 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD,Perinatol Res Branch, NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS [Z01 HD002401-15] NR 29 TC 10 Z9 12 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR PY 2007 VL 26 IS 3 BP 347 EP 353 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 142TU UT WOS:000244673900009 PM 17324984 ER PT J AU Geldmacher, C Currier, JR Herrmann, E Haule, A Kuta, E McCutchan, F Njovu, L Geis, S Hoffmann, O Maboko, L Williamson, C Birx, D Meyerhans, A Cox, J Hoelscher, M AF Geldmacher, Christof Currier, Jeffrey R. Herrmann, Eva Haule, Antelmo Kuta, Ellen McCutchan, Francine Njovu, Lilian Geis, Steffen Hoffmann, Oliver Maboko, Leonard Williamson, Carolyn Birx, Deborah Meyerhans, Andreas Cox, Josephine Hoelscher, Michael TI CD8 T-cell recognition of multiple epitopes within specific gag regions is associated with maintenance of a low steady-state viremia in human immunodeficiency virus type 1-seropositive patients SO JOURNAL OF VIROLOGY LA English DT Article ID ACUTE HIV-1 INFECTION; VIRAL LOAD; RESPONSES; LYMPHOCYTES; SUBTYPE; ESCAPE; PLASMA; PROTEINS; CD4(+); AIDS AB The importance of HLA class I-restricted CD8 T-cell responses in the control of human immunodeficiency virus (HIV) infection is generally accepted. While several studies have shown an association of certain HLA class I alleles with slower disease progression, it is not fully established whether this effect is mediated by HIV-specific CD8 T-cell responses restricted by these alleles. In order to study the influence of the HLA class I alleles on the HIV-specific CD8 T-cell response and on viral control, we have assessed HIV-specific epitope recognition, plasma viral load, and expression of HILA class I alleles in a cohort of HIV-seropositive bar workers. Possession of the HLA class I alleles 135801, B8101, and B0702 was associated with a low median viral load and simultaneously with a broader median recognition of Gag epitopes compared to all other HLA alleles (twofold increase) (P = 0.0035). We further found an inverse linear relationship between the number of Gag epitopes recognized and the plasma viral load (R = -0.36; P = 0.0016). Particularly, recognition of multiple epitopes within two regions of Gag (amino acids [aa] 1 to 75 and aa 248 to 500) was associated with the maintenance of a low steady-state viremia, even years after acute infection. C1 Univ Munich, Dept Infect Dis & Trop Med, D-80799 Munich, Germany. Referral Hosp, Mbeya Med Res Programme, Mbeya, Tanzania. US Mil HIV Res Program, Rockville, MD 20851 USA. Univ Cape Town, Inst Infect Dis & Mol Med, Div Med Virol, ZA-7925 Cape Town, South Africa. Univ Saarland, Inst Virol, D-66421 Homburg, Germany. Univ Saarland, Dept Internal Med, D-66421 Homburg, Germany. RP Geldmacher, C (reprint author), NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. EM cgeldmacher@mmrp.org RI Herrmann, Eva/E-8215-2010; Hoelscher, Michael/D-3436-2012; Meyerhans, Andreas/D-3382-2014; OI Meyerhans, Andreas/0000-0003-0620-5317; , Carolyn/0000-0003-0125-1226 NR 34 TC 101 Z9 103 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 MAR PY 2007 VL 81 IS 5 BP 2440 EP 2448 DI 10.1128/JVI.01847-06 PG 9 WC Virology SC Virology GA 138RM UT WOS:000244380000034 PM 17182686 ER PT J AU Wang, JH Janas, AM Olson, WJ KewalRamani, VN Wu, L AF Wang, Jian-Hua Janas, Alicia M. Olson, Wendy J. KewalRamani, Vineet N. Wu, Li TI CD4 coexpression regulates DC-SIGN-mediated transmission of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; HIV-1 NEF PROTEIN; T-CELLS; PRODUCTIVE INFECTION; PRIMATE LENTIVIRUSES; EFFICIENTLY TRANSMIT; LANGERHANS CELLS; DOWN-REGULATION; EXPRESSION; LYMPHOCYTES AB Dendritic cells (DCs) potently stimulate the cell-cell transmission of human immunodeficiency virus type I (HIV-1). However, the mechanisms that underlie DC transmission of HIV-1 to CD4(+) T cells are not fully understood. DC-SIGN, a C-type lectin, efficiently promotes HIV-1 trans infection. DC-SIGN is expressed in monocyte-derived DCs (MDDCs), macrophage subsets, activated B lymphocytes, and various mucosal tissues. MDDC-mediated HIV-1 transmission to CD4(+) T cells involves DC-SIGN-dependent and -independent mechanisms. DC-SIGN transmission of HIV-1 depends on the donor cell type. HIV-1 Nef can upregulate DC-SIGN expression and promote DC-T-cell clustering and HIV-1 spread. Nef also downregulates CD4 expression; however, the effect of the CD4 downmodulation on DC-mediated HIV-1 transmission has not been examined. Here, we report that CD4 expression levels correlate with inefficient HIV-1 transmission by monocytic cells expressing DC-SIGN. Expression of CD4 on Raji B cells strongly impaired DC-SIGN-mediated HIV-1 transmission to T cells. By contrast, enhanced HIV-1 transmission was observed when CD4 molecules on MDDCs and DC-SIGN-CD4-expressing cell lines were blocked with specific antibodies. Coexpression of CD4 and DC-SIGN in Raji cells promoted the internalization and intracellular retention of HIV-1. Interestingly, internalized HIV-1 particles were sorted and confined to late endosomal compartments that were positive for CD63 and CD81. Furthermore, in HIV-1-infected MDDCs, significant downregulation of CD4 by Nef expression correlated with enhanced viral transmission. These results suggest that CD4, which is present at various levels in DC-SIGN-positive primary cells, is a key regulator of HIV-1 transmission. C1 Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA. Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Wu, L (reprint author), Med Coll Wisconsin, Dept Microbiol & Mol Genet, 8701 Watertown Plank Rd,BSB 203, Milwaukee, WI 53226 USA. EM liwu@mcw.edu RI Wu, Li/E-4330-2011 OI Wu, Li/0000-0002-5468-2487 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI 068493, R01 AI068493] NR 64 TC 40 Z9 42 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 MAR PY 2007 VL 81 IS 5 BP 2497 EP 2507 DI 10.1128/JVI.01970-06 PG 11 WC Virology SC Virology GA 138RM UT WOS:000244380000039 PM 17151103 ER PT J AU Snapinn, KW Holmes, EC Young, DS Bernard, KA Kramer, LD Ebel, GD AF Snapinn, Katherine W. Holmes, Edward C. Young, David S. Bernard, Kristen A. Kramer, Laura D. Ebel, Gregory D. TI Declining growth rate of West Nile virus in North America SO JOURNAL OF VIROLOGY LA English DT Article AB To determine the demographic history of West Nile virus (WNV) in North America, we employed a coalescent method to envelope coding region data sets for the NY99 and WN02 genotypes. Although the observed genetic diversities in both genotypes were of approximately the same age, the mean rate of epidemiological growth of the WN02 population was approximately three times that of the NY99 population, a finding compatible with the recent dominance of the former genotype. However, there has also been a marked decrease in the recent growth rate of WN02, suggesting that WNV has reached its peak prevalence in North America. C1 Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. New York State Dept Hlth, Arbovirus Labs, Wadsworth Ctr, Slingerlands, NY 12159 USA. SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY 12144 USA. Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. EM ech15@psu.edu RI Ebel, Gregory/D-8324-2017; OI Holmes, Edward/0000-0001-9596-3552 FU NIAID NIH HHS [N01 AI025490, N01 AI 25490, N01AI25490]; PHS HHS [U50/CCU 223671-02] NR 9 TC 54 Z9 57 U1 0 U2 5 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 MAR PY 2007 VL 81 IS 5 BP 2531 EP 2534 DI 10.1128/JVI.02169-06 PG 4 WC Virology SC Virology GA 138RM UT WOS:000244380000043 PM 17182695 ER PT J AU Husain, M Weisberg, AS Moss, B AF Husain, Matloob Weisberg, Andrea S. Moss, Bernard TI Sequence-independent targeting of transmembrane proteins synthesized within vaccinia virus factories to nascent viral membranes SO JOURNAL OF VIROLOGY LA English DT Article ID GOLGI INTERMEDIATE COMPARTMENT; ENDOPLASMIC-RETICULUM; VIRION MORPHOGENESIS; ESSENTIAL COMPONENT; EARLY STEP; ENTRY; BIOGENESIS; EXPORT; STAGE; GENE AB The primary membrane of vaccinia virus, as well as those of other poxviruses, forms within a discrete cytoplasmic factory region. We recently determined the existence of an operative pathway from the endoplasmic reticulum within the virus factory to nascent viral membranes and demonstrated that a viral protein could be diverted from this pathway to Golgi membranes by the addition of COPII-binding sites (M. Husain, A. S. Weisberg, and B. Moss, Proc. Nat1. Acad. Sci. USA, 103:19506-19511, 2006). Here we describe an investigation of the structural features that are required for transit of proteins to the viral membrane. Deletion of either the N-terminal domain or the C-terminal cytoplasmic tail from the conserved A9 protein did not prevent its incorporation into viral membranes, whereas deletion of the transmembrane domain resulted in its distribution throughout the cytoplasm. Nevertheless, replacement of the A9 transmembrane domain with the corresponding region of a nonpoxvirus transmembrane protein or of a vaccinia virus extracellular envelope protein allowed viral membrane targeting, indicating no requirement for a specific amino acid sequence. Remarkably, the epitope-tagged A9 transmembrane domain alone, as well as a heterologous transmembrane domain lacking a poxvirus sequence, was sufficient for viral membrane association. The data are consistent with a sequence-independent pathway in which transmembrane proteins that are synthesized within the virus factory and lack COPII or other binding sites that enable conventional endoplasmic reticulum exiting are incorporated into nascent viral membranes. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS NR 38 TC 17 Z9 18 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 MAR PY 2007 VL 81 IS 6 BP 2646 EP 2655 DI 10.1128/JVI.02631-06 PG 10 WC Virology SC Virology GA 145FN UT WOS:000244850800011 PM 17192302 ER PT J AU Tilton, JC Luskin, MR Johnson, AJ Manion, M Hallahan, CW Metcalf, JA McLaughlin, M Davey, RT Connors, M AF Tilton, John C. Luskin, Marlise R. Johnson, Alison J. Manion, Maura Hallahan, Claire W. Metcalf, Julia A. McLaughlin, Mary Davey, Richard T., Jr. Connors, Mark TI Changes in paracrine interleukin-2 requirement, CCR7 expression, fre uency, and cytokine secretion of human immunodeficiency virus-specific CD4(+) T cells are a consequence of antigen load SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; ACUTE HIV-1 INFECTION; HEPATITIS-C; PROLIFERATIVE RESPONSES; HIV-1-INFECTED SUBJECTS; MEDIATED-IMMUNITY; CD8-T-CELL MEMORY; TYPE-1 INFECTION; CD4-T-CELL HELP; PLASMA VIREMIA AB Virus-specific CD4(+) T-cell responses are thought to be required for the induction and maintenance of many effective CD8(+) T-cell and B-cell immune responses in experimental animals and humans. Although the presence of human immunodeficiency virus (HM-specific CD4(+) T cells has been documented in patients at all stages of HIV infection, many fundamental questions regarding their frequency and function remain. A 10-color, 12-parameter How cytometric panel was utilized to examine the frequency, memory phenotype (CD27, CCR7, and CD45RA), and cytokine production (interleukin-2 [IL-2], gamma interferon, and tumor necrosis factor alpha) of CD+ T cells specific for HIV antigens as well as for adenovirus, Epstein-Barr virus (EBV), influenza H1N1 virus, influenza H3N2 virus, cytomegalovirus, varicella-zoster virus (VZV), and tetanus toxoid in normal controls, long-term nonprogressors (LTNP), and HIN-infected patients with progressive disease on or off therapy. The HIV-specifie CD4(+) T-cell responses in LTNP and patients on therapy were similar in frequency, phenotype, and cytokine production to responses directed against adenovirus, EBV, influenza virus, and VZV. HIV-specific CD4(+) T cells from patients off antiretroviral therapy demonstrated a shift towards a CCR7(-) CD45RA(-) phenotype and a reduced percentage of IL-2-producing cells. The alterations in cytokine production during HIV viremia were found to be intrinsic to the HIV-specific CD4(+) T cells and caused a requirement for IL-2 supplied exogenously for proliferation to occur. These observations suggest that many previously described changes in HIV-specific CD4(+) T-cell function and phenotype are a consequence of high levels of antigen in viremic patients. In addition, defects in function and phenotype of HIV-specific CD4(+) T cells are not readily discernible in the context of antiretroviral therapy but rather are similar to responses to other viruses. C1 NIAID, LIR, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Connors, M (reprint author), NIAID, LIR, Immunoregulat Lab, NIH, Bldg 10,Rm 11B-09,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM mconnors@niaid.nih.gov NR 51 TC 50 Z9 52 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 MAR PY 2007 VL 81 IS 6 BP 2713 EP 2725 DI 10.1128/JVI.01830-06 PG 13 WC Virology SC Virology GA 145FN UT WOS:000244850800017 PM 17182676 ER PT J AU McCann, KL Imani, F AF McCann, Kelly L. Imani, Farhad TI Transforming growth factor beta enhances respiratory syncytial virus replication and tumor necrosis factor alpha induction in human epithelial cells SO JOURNAL OF VIROLOGY LA English DT Article ID BRONCHOALVEOLAR LAVAGE FLUID; TNF-ALPHA; TGF-BETA; ASTHMA EXACERBATIONS; EXPRESSION; STIMULATION; ASSOCIATION; FIBROSIS; PROTEIN; POLYMORPHISMS AB Asthma is characterized as a chronic inflammatory disease associated with significant tissue remodeling. Patients with asthma are more susceptible to virus-induced exacerbation, which subsequently can lead to increased rates of hospitalization and mortality. While the most common cause of asthma-related deaths is respiratory viral infections, the underlying factors in the lung environment which render asthmatic subjects more susceptible to viral exacerbation are not yet identified. Since transforming growth factor beta (TGF-beta) is a critical cytokine for lung tissue remodeling and asthma phenotype, we have focused on the effects of TGF-beta on viral replication and virus-induced inflammation. Treatment of human epithelial cells with TGF-beta increased respiratory syncytial virus (RSV) replication by approximately fourfold. Tumor necrosis factor alpha (TNF-alpha) mRNA and protein expression were also significantly increased above levels with RSV infection alone. The increase in RSV replication and TNF-alpha expression after TGF-beta treatment was concomitant with an increase in virus-induced p38 mitogen-activated protein kinase activation. Our data reveal a novel effect for TGF-beta on RSV replication and provide a potential mechanism for the exaggerated inflammatory response observed in asthmatic subjects during respiratory viral infections. C1 NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Imani, F (reprint author), NIEHS, Lab Resp Biol, NIH, MD 2-01,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM imani@niehs.nih.gov FU Intramural NIH HHS NR 46 TC 23 Z9 25 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 MAR PY 2007 VL 81 IS 6 BP 2880 EP 2886 DI 10.1128/JVI.02583-06 PG 7 WC Virology SC Virology GA 145FN UT WOS:000244850800032 PM 17202225 ER PT J AU Bouamr, F Houck-Loomis, BR De Los Santos, M Casaday, RJ Johnson, MC Goff, SP AF Bouamr, Fadila Houck-Loomis, Brian R. De Los Santos, Martha Casaday, Rebecca J. Johnson, Marc C. Goff, Stephen P. TI The C-terminal portion of the Hrs protein interacts with Tsg101 and interferes with human immunodeficiency virus type 1 Gag particle production SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; TYROSINE KINASE SUBSTRATE; RECEPTOR DOWN-REGULATION; ROUS-SARCOMA-VIRUS; MULTIVESICULAR BODY; EARLY ENDOSOMES; ESCRT-I; SORTING COMPLEX; UBIQUITIN LIGASES; LATE DOMAIN AB The human immunodeficiency virus type 1 (HIV-1) Gag protein recruits Tsg101 to facilitate HIV-1 particle budding and release. In uninfected cells, the Hrs protein recruits the ESCRT-I complex to the endosome, also through an interaction with Tsg101, to promote the sorting of host proteins into endosomal vesicles and multivesicular bodies. Here, we show that the overexpression of the C-terminal fragment of Hrs (residues 391 to 777) or Hrs mutants lacking either the N-terminal FYVE domain (mutant dFYVE) or the PSAP (residues 348 to 351) motif (mutant ASAA) all efficiently inhibit HIV-1 Gag particle production. Expression of the dFYVE or ASAA mutants of Hrs had no effect on the release of Moloney murine leukemia virus. Coimmunoprecipitation analysis showed that the expression of Hrs mutant dFYVE or ASAA significantly reduced or abolished the HIV-1 Gag-Tsg101 interaction. Yeast-two hybrid assays were used to identify two new and independent Tsg101 binding sites, one in the Hrs coiled-coil domain and one in the proline/glutamic acid-rich domain. Scanning electron microscopy of HeLa cells expressing HIV-1 Gag and the Hrs ASAA mutant showed viral particles arrested in "lump-like" structures that remained attached to the cell surface. Together, these data indicate that fragments of Hrs containing the C-terminal portion of the protein can potently inhibit HIV-1 particle release by efficiently sequestering Tsg101 away from the Gag polyprotein. C1 Columbia Univ Coll Phys & Surg, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, New York, NY 10032 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY 14853 USA. Howard Hughes Med Inst, New York, NY 10032 USA. RP Goff, SP (reprint author), Columbia Univ Coll Phys & Surg, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA. EM goff@cancercenter.columbia.edu RI Goff, Stephen/K-6337-2014 OI Goff, Stephen/0000-0003-0693-5547 FU NCI NIH HHS [CA 20081, R37 CA 30488, R37 CA030488, R01 CA020081] NR 56 TC 22 Z9 22 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 MAR PY 2007 VL 81 IS 6 BP 2909 EP 2922 DI 10.1128/JVI.01413-06 PG 14 WC Virology SC Virology GA 145FN UT WOS:000244850800035 PM 17182674 ER PT J AU Yancik, R Ershler, W Satariano, W Hazzard, W Cohen, HJ Ferruci, L AF Yancik, Rosemary Ershler, William Satariano, William Hazzard, William Cohen, Harvey J. Ferruci, Luigi TI Report of the National Institute on Aging Task Force on Comorbidity SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material C1 NIA, NIH, Geriat & Clin Gerontol Program, Geriatr Branch, Bethesda, MD 20892 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Duke Univ, Med Ctr, Ctr Study Aging, Durham, NC USA. RP Yancik, R (reprint author), NIA, NIH, Geriat & Clin Gerontol Program, Geriatr Branch, 7201 Wisconsin Ave,Suite 3C307, Bethesda, MD 20892 USA. EM yancikr@nia.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 4 TC 78 Z9 78 U1 1 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 MAR PY 2007 VL 62 IS 3 BP 275 EP 280 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 228WM UT WOS:000250763300006 PM 17389724 ER PT J AU Lash, TL Mor, V Wieland, D Ferrucci, L Satariano, W Silliman, RA AF Lash, Timothy L. Mor, Vincent Wieland, Darryl Ferrucci, Luigi Satariano, William Silliman, Rebecca A. TI Methodology, design, and analytic techniques to address measurement of comorbid disease SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT National-Institiute-on-Aging-Funded-Comorbidity Conference CY MAR, 2005 CL Altanta, GA SP Natl Inst Aging Funded Comorbid ID BREAST-CANCER PATIENTS; MEDICAL-RECORD; NONDIFFERENTIAL MISCLASSIFICATION; NEIGHBORHOOD ENVIRONMENT; SENSITIVITY-ANALYSIS; ALZHEIMERS-DISEASE; OBSERVATIONAL DATA; SYSTEMATIC-ERRORS; PHYSICAL FUNCTION; ALAMEDA COUNTY AB Background. Measurement of comorbidity affects all variable axes that are considered in health care research: confounding, modifying, independent, and dependent variable. Comorbidity measurement particularly affects research involving older adults because they bear the disproportionate share of the comorbidity burden. Methods. We examine how well researchers can expect to segregate study participants into those who are healthier and those who are less healthy, given the variable axis for which they are measuring comorbidity, the comorbidity measure they select, and the analytic method they choose. We also examine the impact of poor measurement of comorbidity. Results. Available comorbidity measures make use of medical records, self-report, physician assessments, and administrative databases. Analyses using these scales introduce uncertainties that can be framed as measurement error or misclassification problems, and can be addressed by extant analytic methods. Newer analytic methods make efficient use of multiple sources of comorbidity information. Conclusions. Consideration of the comorbidity measure, its role in the analysis, and analogous measurement error problems will yield an analytic solution and an appreciation for the likely direction and magnitude of the biases introduced. C1 Boston Univ, Sch Med, Geriatr Sect, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. Brown Univ, Sch Med, Dept Community Hlth, Providence, RI 02912 USA. Univ S Carolina, Sch Med, Dept Med, Columbia, SC 29208 USA. NIA, Baltimore, MD 21224 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA. RP Lash, TL (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol, 715 Albany St TE3, Boston, MA 02118 USA. EM tlash@bu.edu FU Intramural NIH HHS [Z99 AG999999] NR 37 TC 51 Z9 51 U1 2 U2 2 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 MAR PY 2007 VL 62 IS 3 BP 281 EP 285 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 228WM UT WOS:000250763300007 PM 17389725 ER PT J AU Karlamangla, A Tinetti, M Guralnik, J Studenski, S Wetle, T Reuben, D AF Karlamangla, Arun Tinetti, Mary Guralnik, Jack Studenski, Stephanie Wetle, Terrie Reuben, David TI Comorbidity in older adults: Nosology of impairment, diseases, and conditions SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID CORONARY-HEART-DISEASE; TREATMENT PANEL-III; C-REACTIVE PROTEIN; DEPRESSIVE SYMPTOMS; DIABETES DURATION; ALLOSTATIC LOAD; DRIED BLOOD; MORTALITY; RISK; MEN AB Older adults generally have multiple medical problems as well as subclinical changes in several physiologic systems. This special article presents a framework (based on the World Health Organization International Classification of Functioning, Disability, and Health) for organizing comorbid processes and diseases to facilitate research and assist clinicians caring for older adults. The nosology begins with physiologic systems (e.g., cardiovascular, endocrine) and assesses each system in several domains (e.g., coronary blood flow, systemic blood pressure, and cardiac function in the cardiovascular system). Functioning in each domain can range from high-functioning, even protective, zones (e.g., high levels of high-density-lipoprotein cholesterol) to severe dysfunction (as in end-stage disease). The approach has four advantages. First, it explicitly recognizes that decrements in health begin before onset of symptomatic disease. Second, it accommodates the full range of possible performance for each system instead of measuring only negative aspects. Third, it avoids arbitrary diagnostic thresholds. Fourth, it sets up an exhaustive and mutually exclusive classification system that can stimulate development of summary indices of total comorbidity burden for both research and clinical settings. As the knowledge base grows, the nosology can be updated to add new domains and refine extant ones. C1 Univ Calif Los Angeles, Div Geriatr, David Geffen Sch Med, Los Angeles, CA 90095 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. NIA, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RP Karlamangla, A (reprint author), Univ Calif Los Angeles, Div Geriatr, David Geffen Sch Med, 10945 Le Conte 2339, Los Angeles, CA 90095 USA. EM akariamangla@mednet.ucla.edu NR 40 TC 49 Z9 51 U1 0 U2 2 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 MAR PY 2007 VL 62 IS 3 BP 296 EP 300 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 228WM UT WOS:000250763300009 PM 17389727 ER PT J AU Wu, CC Pritsch, T Bickels, J Wienberg, T Malawer, MM AF Wu, Chia-Chun Pritsch, Tamir Bickels, Jacob Wienberg, Tierney Malawer, Martin M. TI Two incision synovectomy and radiation treatment for diffuse pigmented villonodular synovitis of the knee with extra-articular component SO KNEE LA English DT Article DE knee; pigmented villonodular synovitis; radiotherapy; synovectomy; adjuvant therapy ID PARTIAL ARTHROSCOPIC SYNOVECTOMY; GIANT-CELL TUMOR; LARGE JOINTS; DIAGNOSIS; MANAGEMENT; THERAPY; SYSTEM; MRI AB Diffuse pigmented villonodular synovitis (PVNS) of the knee is a rare, locally aggressive disease. Since 1995 the senior author has been treating patients with diffuse intra- and extra-articular PVNS of the knee with a bimodality treatment protocol, consisting of anterior and posterior open synovectomies in conjunction with external-beam radiation. The purpose of this study was to describe the surgical technique, evaluate our protocol's efficacy in limiting local recurrences, and assess its functional implications and associated morbidities. The medical records of nine consecutive patients were analyzed. Functional results were measured using the Knee Society score. The mean follow-up was 67 months (range 37-103 months). Eight patients were disease free and one patient had local recurrence, which was extra-articular, localized and non-progressive. The mean knee rating and functional rating had significantly improved from 65.2 and 70 preoperatively to 93.7 and 96.6 postoperatively respectively. Maximal knee flexion ranged from 90 degrees to 130 degrees, and only 3 patients developed flexion contractures of 5 degrees. In conclusion our bimodality protocol of anterior and posterior open synovectomies, in conjunction with external-beam radiation, limited the recurrence of diffuse intra- and extra-articular PVNS of the knee. All patients showed good-to-excel lent functional outcomes and were able to return to their previous level of activity. (c) 2006 Elsevier B.V. All rights reserved. C1 Washington Canc Inst, Dept Orthoped Oncol, Washington, DC 20010 USA. Georgetown Univ, Washington, DC USA. NCI, Pediat & Surg Div, Bethesda, MD 20892 USA. Tel Aviv Sourasky Med Ctr, Natl Unit Orthoped Oncol, Tel Aviv, Israel. Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Orthopaed, Taipei, Taiwan. RP Pritsch, T (reprint author), Washington Canc Inst, Dept Orthoped Oncol, C2173,110 Irving St NW, Washington, DC 20010 USA. EM Pritscht@yahoo.com NR 35 TC 16 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0968-0160 J9 KNEE JI Knee PD MAR PY 2007 VL 14 IS 2 BP 99 EP 106 DI 10.1016/j.knee.2006.10.014 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 151RC UT WOS:000245307300004 PM 17161949 ER PT J AU Kim, UK Drayna, D AF Kim, Un-kyung Drayna, Dennis TI Current strategies for finding human disease genes SO KOREAN JOURNAL OF GENETICS LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; POSITIONAL CLONING; HUMAN GENOME; KOREAN POPULATION; HAPLOTYPE BLOCKS; CROHNS-DISEASE; COMPLEX TRAIT; TWIN REGISTRY; SUSCEPTIBILITY; ASSOCIATION C1 NIDCD, NIH, Bethesda, MD 20892 USA. Kyungpook Natl Univ, Dept Biol, Taegu, South Korea. RP Drayna, D (reprint author), NIDCD, NIH, Bethesda, MD 20892 USA. EM drayna@nidcd.nih.gov NR 34 TC 9 Z9 9 U1 0 U2 1 PU GENETICS SOC KOREA PI SEOUL PA SEOUL NATL UNIV, DEPT BIOLOGY, COLL EDUCATION, SINLIMDONG SAN 56-1, KWANAKGU, SEOUL 151-742, SOUTH KOREA SN 0254-5934 J9 KOREAN J GENETIC JI Korean J. Genet. PD MAR PY 2007 VL 29 IS 1 BP 1 EP 9 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 156KR UT WOS:000245647300001 ER PT J AU Knoepp, SM Carney, JA Mihn, MC Bei, T Stergiopoulos, S Stratakis, CA Zembowicz, A AF Knoepp, S. M. Carney, J. A. Mihn, M. C. Bei, T. Stergiopoulos, S. Stratakis, C. A. Zembowicz, A. TI Loss of expression of a carney complex gene, protein kinase a regulatory subunit 1a, in sporadic and carney complex-associated pigmented epithelioid melanocytoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 419 BP 95A EP 95A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935300420 ER PT J AU Kuhn, E Teller, L Piana, S Rosai, J Merino, MJ AF Kuhn, E. Teller, L. Piana, S. Rosai, J. Merino, M. J. TI Clonality of papillary thyroid cancer. Clinical implications SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 CCAPO, Milan, Italy. NCI, Bethesda, MD 20892 USA. CDI, Milan, Italy. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 455 BP 103A EP 103A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935300456 ER PT J AU Hartmann, DP Kallakury, BVS Luka, J Apella, EA Azumi, N AF Hartmann, D. P. Kallakury, B. V. S. Luka, J. Apella, E. A. Azumi, N. TI Progressive increase in PPM1D/wip-1 protein expression in normal mucosa, tubular adenoma, and low- and high-grade colorectal adenocarcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Georgetown Univ Hosp, Washington, DC 20007 USA. Bioworld Consulting Labs, New Windsor, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 523 BP 117A EP 117A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935300523 ER PT J AU Li, L Bourne, PA Yao, JL di Sant'Agnese, P Zhuang, Z Yin, C Wu, C Huang, J AF Li, L. Bourne, P. A. Yao, J. L. di Sant'Agnese, P. A. Zhuang, Z. Yin, C. Wu, C. Huang, J. TI Myosin VI, a mediator of the p53-depenclent cell survival pathway, is overexpressed in adenocarcinoma of the prostate SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Univ Rochester, Med Ctr, Rochester, NY 14642 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 718 BP 159A EP 159A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301141 ER PT J AU Nigwekar, P Wu, C Yao, JL Bourne, PA Li, J Zhuang, Z di Sant'Agnese, PA Walters, DC Huang, J AF Nigwekar, P. Wu, C. Yao, J. L. Bourne, P. A. Li, J. Zhuang, Z. di Sant'Agnese, P. A. Walters, D. C. Huang, J. TI Nucleophosmin, a critical regulator of cell proliferation, is overexpressed in prostate SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Natl Inst Hlth, Bethesda, MD 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 756 BP 166A EP 167A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301179 ER PT J AU Qian, J Liu, L Ma, J Meiers, I Lang, K Hewitt, SM Wilson, TH Rittmaster, RS Bostwick, DG AF Qian, J. Liu, L. Ma, J. Meiers, I. Lang, K. Hewitt, S. M. Wilson, T. H. Rittmaster, R. S. Bostwick, D. G. TI The 5-alpha-reductase inhibitor dutasteride decreases cancer volume and induces multiple phenotypic changes in the human prostate SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Bostwick Labs, Glen Allen, VA USA. NIH, NCI, Bethesda, MD 20892 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 778 BP 171A EP 172A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301201 ER PT J AU Rodriguez-Canales, J Hanson, JC Tangrea, MA Erickson, HS Albert, PA Wallis, BS Richardson, AM Pinto, PA Linehan, WM Gillespie, JW Merino, MJ Libutti, SK Woodson, KW Emmert-Buck, MR Chuaqui, RF AF Rodriguez-Canales, J. Hanson, J. C. Tangrea, M. A. Erickson, H. S. Albert, P. A. Wallis, B. S. Richardson, A. M. Pinto, P. A. Linehan, W. M. Gillespie, J. W. Merino, M. J. Libutti, S. K. Woodson, K. W. Emmert-Buck, M. R. Chuaqui, R. F. TI Identification of a unique epigenetic sub-microenvironment in prostate cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 785 BP 173A EP 173A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301208 ER PT J AU Shaheduzzaman, S Gao, C Wang, Z Furusato, B Petrovics, G Srikantan, V Ravindranath, L Nau, M Chen, Y Chen, Y Cullen, J McLeod, DG Sesterhenn, I Vahey, M Srivastava, S AF Shaheduzzaman, S. Gao, C. Wang, Z. Furusato, B. Petrovics, G. Srikantan, V. Ravindranath, L. Nau, M. Chen, Y. Chen, Y. Cullen, J. McLeod, D. G. Sesterhenn, I. Vahey, M. Srivastava, S. TI Epithelial cell transcriptome of poorly and moderately differentiated prostate cancers SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 CPDR, Rockville, MD USA. AFIP, Washington, DC USA. WRAMC, Washington, DC USA. NIH, NHGRI, Bethesda, MD 20892 USA. WRAIR, Rockville, MD 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 792 BP 174A EP 175A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301215 ER PT J AU Shaheduzzaman, S Vishwanath, A Furusato, B Cullen, J Chen, Y Banez, L Nau, M Ravindranath, L Kim, KH Mohammed, A Chen, Y Ehrich, M Srikantan, V Sesterhenn, I McLeod, DG Vahey, M Petrovics, G Dobi, A Srivastava, S AF Shaheduzzaman, S. Vishwanath, A. Furusato, B. Cullen, J. Chen, Y. Banez, L. Nau, M. Ravindranath, L. Kim, K. H. Mohammed, A. Chen, Y. Ehrich, M. Srikantan, V. Sesterhenn, I. McLeod, D. G. Vahey, M. Petrovics, G. Dobi, A. Srivastava, S. TI Mechanisms of downregulation of Lactotransferrin (LTF) in prostate cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 CPDR, Rockville, MD USA. AFIP, Washington, DC USA. WRAMC, Washington, DC USA. NIH, NHGRI, Bethesda, MD 20892 USA. WRAIR, Rockville, MD USA. Sequenom Inc, San Diego, CA 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 793 BP 175A EP 175A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301216 ER PT J AU Val, D Gulley, JL Pinto, P Schlom, J Linehan, WM Merino, MJ AF Val, D. Gulley, J. L. Pinto, P. Schlom, J. Linehan, W. M. Merino, M. J. TI Morphologic changes in prostate cancer samples following intraprostatic PSA-based vaccine administration SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 825 BP 181A EP 181A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301248 ER PT J AU Galgano, MT Castle, PE Stoler, MH AF Galgano, M. T. Castle, P. E. Stoler, M. H. TI Can HPV 16 typing adjudicate the accuracy of cervical biopsy interpretation? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Univ Virginia, Charlottesville, VA USA. Natl Canc Inst, NIH, DHHS, Bethesda, MD 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 901 BP 198A EP 198A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301324 ER PT J AU Posligua, L Malpica, A Deavers, M Merino, M Silva, E AF Posligua, L. Malpica, A. Deavers, M. Merino, M. Silva, E. TI The alleged low-grade leiomyosarcomas of the female genital tract: Metastatic lesions or independent primary tumors? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 MD Anderson Canc Ctr, Houston, TX USA. Natl Inst Hlth, Bethesda, MD 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 961 BP 210A EP 210A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301384 ER PT J AU Val, D Stratton, P Neumann, RD Linehanx, WM Merino, MJ AF Val, D. Stratton, P. Neumann, R. D. Linehanx, W. M. Merino, M. J. TI The morphologic spectrum of smooth muscle tumors in the hereditary leimyomatosis and renal cell cancer (HLRCC) syndrome. Its clinical significance SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. CC, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 990 BP 216A EP 216A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301413 ER PT J AU Bian, S Jiang, L Vivero, A Pittaluga, S Raffeld, M Jaffe, ES AF Bian, S. Jiang, L. Vivero, A. Pittaluga, S. Raffeld, M. Jaffe, E. S. TI B-cell lymphomas with marked tissue eosinophilia and plasmacytoid differentiation, a study of 25 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. Singapore Gen Hosp, Singapore 0316, Singapore. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1073 BP 234A EP 234A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301496 ER PT J AU Feldman, AL Arber, DA Raffeld, M Burke, JS Pittaluga, S Warnke, R Jaffe, ES AF Feldman, A. L. Arber, D. A. Raffeld, M. Burke, J. S. Pittaluga, S. Warnke, R. Jaffe, E. S. TI Clonal relationship between follicular lymphoma and Histiocytic/Dendritic cell neoplasms occurring in the same patient SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Stanford Univ, Stanford, CA 94305 USA. Alta Bates Summit Med Ctr, Berkeley, CA 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1098 BP 240A EP 240A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301521 ER PT J AU Gradowski, J Swerdlow, S Surti, U Jaffe, ES Pittaluga, S Prakash, S AF Gradowski, J. F. Swerdlow, S. H. Surti, U. Jaffe, E. S. Pittaluga, S. Prakash, S. TI Follicular lymphoma with plasmacytic differentiation: Fluorescence immunophenotypic and interphase cytogenetic characterization SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NCI, Bethesda, MD 20892 USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1106 BP 241A EP 242A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935301529 ER PT J AU Begnami, M Santi, M Rushing, EJ Quezado, M AF Begnami, M. Santi, M. Rushing, E. J. Quezado, M. TI Evaluation of chromosome 7 alterations including epidermal growth factor amplification status in pediatric meningiomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. Childrens Hosp, Washington, DC USA. AFIP, Washington, DC 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1360 BP 296A EP 296A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935302194 ER PT J AU Begnami, MD Soares, FA Quezado, M AF Begnami, M. D. Soares, F. A. Quezado, M. TI Chromosome 7 polysomy detected by chromogenic in situ hybridization (CISH) is a common finding in sporadic chordomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. AC Camargo, Sao Paulo, Brazil. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1361 BP 296A EP 296A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935302195 ER PT J AU Chevez-Barrios, P Zhou, M Shen, D Chew, EY Green, WR Chan, CC AF Chevez-Barrios, P. Zhou, M. Shen, D. Chew, E. Y. Green, W. R. Chan, C. C. TI Ophthalmic Von Hippel-Lindau disease: Expression of clusterin SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Methodist Hosp, Houston, TX 77030 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1392 BP 303A EP 303A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935302226 ER PT J AU Galli, SB Tsokos, M AF Galli, S. B. Tsokos, M. TI Expression of XIAP protein in neuroblastomas and ewing sarcoma family tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1436 BP 312A EP 312A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935302270 ER PT J AU Kamatani, H Kumagai, N Tanaka, T Kawamura, S Hewitt, SM Franks, TJ Travis, WD Jen, J Fukuoka, J AF Kamatani, H. Kumagai, N. Tanaka, T. Kawamura, S. Hewitt, S. M. Franks, T. J. Travis, W. D. Jen, J. Fukuoka, J. TI Lack of desmoglein 2 is an indicator of cancer progression and a poor prognostic factor in stage 1 non-small cell lung cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Toyama Univ Hosp, Toyama 930, Japan. NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. AFIP, Washington, DC 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1491 BP 324A EP 324A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935302325 ER PT J AU Merino, MJ Carter, D Linehan, WM Nguyen, D Quezado, M AF Merino, M. J. Carter, D. Linehan, W. M. Nguyen, D. Quezado, M. TI Novel benign pulmonary and chest wall lesions as part of the Von Hippel Lindau syndrome mimicking metastatic renal cell carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1503 BP 326A EP 326A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935302338 ER PT J AU Puttaswamy, S Fukuoka, J Fujii, T Shilo, K Franks, TJ Hewitt, S Travis, WD Jen, J AF Puttaswamy, S. Fukuoka, J. Fujii, T. Shilo, K. Franks, T. J. Hewitt, S. Travis, W. D. Jen, J. TI p27(kip1) loss correlates with poor prognosis in lung adenocarcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Toyama Univ, Toyama 930, Japan. Toranomon Gen Hosp, Tokyo, Japan. Armed Forces Inst Pathol, Washington, DC 20306 USA. NIH, NCI, Bethesda, MD 20892 USA. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1514 BP 329A EP 329A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935302349 ER PT J AU Rassaei, N Tavora, F Ozhudak, I Chu, WS Jaynes, E Sobin, L Travis, WD Jen, J Shilo, K Franks, TJ AF Rassaei, N. Tavora, F. Ozhudak, I. Chu, W-S Jaynes, E. Sobin, L. Travis, W. D. Jen, J. Shilo, K. Franks, T. J. TI Thyroid transcription factor-1 (TTF-1) expression in pulmonary neuroendocrine carcinomas: Clone-based variability SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 AFIP, Washington, DC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1515 BP 329A EP 329A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935302350 ER PT J AU Silva, A Carter, D Begnami, M Henschke, CI Vasquez, M Merino, MJ AF Silva, A. Carter, D. Begnami, M. Henschke, C. I. Vasquez, M. Merino, M. J. TI Evaluation of gene amplification and protein expression of epidermal growth factor receptor (EGFR) by CISH, FISH and IHC in lung adenocarcinoma (ADC) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Natl Canc Inst, Bethesda, MD USA. Weill Cornell Med Ctr, New York, NY USA. RI FELIPE-SILVA, ALOISIO/J-9295-2012 OI FELIPE-SILVA, ALOISIO/0000-0001-6668-7907 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1527 BP 331A EP 332A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935302362 ER PT J AU Yoshizawa, A Fukuoka, J Shilo, A Franks, TJ Hewitt, SM Fujii, T Jen, J Travis, WD Conlon-Cardo, C AF Yoshizawa, A. Fukuoka, J. Shilo, A. Franks, T. J. Hewitt, S. M. Fujii, T. Jen, J. Travis, W. D. Conlon-Cardo, C. TI Clinical significance of p-AKT pathway in non-small cell lung cancer (NSCLC) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Toyama Univ Hosp, Toyama, Japan. Armed Forces Inst Pathol, Washington, DC 20306 USA. NIH, NCI, Bethesda, MD USA. Toranomon Gen Hosp, Tokyo, Japan. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1543 BP 335A EP 335A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935302378 ER PT J AU Begnami, M Quezado, M Wincovitch, S Garfield, S Merino, MJ AF Begnami, M. Quezado, M. Wincovitch, S. Garfield, S. Merino, M. J. TI Evaluation of nucleic acid index (NAI) in the spectrum of thyroid lesions SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 2007 VL 87 SU 1 MA 1590 BP 345A EP 345A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 146LG UT WOS:000244935302426 ER PT J AU Gauthier, I Ding, K Winton, T Shepherd, FA Livingston, R Johnson, DH Rigas, JR Whitehead, M Graham, B Seymour, L AF Gauthier, I. Ding, K. Winton, T. Shepherd, F. A. Livingston, R. Johnson, D. H. Rigas, J. R. Whitehead, M. Graham, B. Seymour, L. TI Impact of hemoglobin levels on outcomes of adjuvant chemotherapy in resected non-small cell lung cancer: The JBR.10 trial experience SO LUNG CANCER LA English DT Article DE Hb levels; adjuvant chemotherapy; NSCLC; clinical outcomes ID SOUTHWEST-ONCOLOGY-GROUP; PHASE-II TRIAL; RANDOMIZED-TRIAL; PLUS CISPLATIN; EPOETIN-ALPHA; ANEMIA; SURVIVAL; VINORELBINE; ERYTHROPOIETIN; RADIOTHERAPY AB Background: Cisplatin-induced anemia may correlate with adverse events, poor quality of life (QoL), decreased adjuvant chemotherapy (ACT) dose intensity, shorter relapse-free survival (RFS) or overall survival (OS). Methods: The JBR.10 trial demonstrated significantly longer survival with adjuvant cisplatin and vinorelbine (n = 242) compared to observation (n = 240) in patients with resected NSCLC [Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et at. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352(25):2640-2]. This exploratory analysis evaluates the predictive value of baseline (in all patients) and during-treatment (in ACT arm only) hemoglobin (Hb) levels on OS and RFS when adjusted for prognostic factors. Baseline (in all patients) and during treatment (in ACT arm only) Hb levels were also correlated with adverse events, QoL, morbidity and ACT dose intensity. Results: Baseline Hb did not predict RFS or OS. However, there was a trend to shorter OS (p = 0.1) when baseline Hb was < 120 g/L. Lower baseline Hb predicted increased hospitalization (p = 0.04) and worse QoL (SOB item, p = 0.03) but had no impact on adverse events or dose intensity. There was a trend to longer RFS (p = 0.08) in patients with tower nadir during-treatment Hb and to longer OS (p = 0.06) and RFS (p = 0.08) in patients with maximum during-treatment Hb drop > 30% that was not maintained when ACT dose intensity was included in the model. Maximum during-treatment Hb drop > 30% correlated with increased lethargy (p = 0.003) and worse QoL (fatigue item, p = 0.07). Conclusions: Lower baseline and during-treatment Hb levels seem associated with poorer QoL, fatigue and increased hospitalization. There is a trend for shorter OS in patients with lower baseline Hb levels. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. SW Oncol Grp, Seattle, WA USA. Eastern Cooperat Oncol Grp, Nashville, TN USA. Canc & Leukemia Grp B, Chicago, IL USA. RP Gauthier, I (reprint author), NCI, Clin Trials Grp, Ottawa Hosp Reg Canc Ctr, 501 Smyth Rd,Box 944, Ottawa, ON K1H 8L6, Canada. EM igauthier@ottawahospital.on.ca RI Johnson, David/A-7437-2009 NR 34 TC 7 Z9 10 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD MAR PY 2007 VL 55 IS 3 BP 357 EP 363 DI 10.1016/j.lungcan.2006.10.021 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 147JA UT WOS:000244998000014 PM 17141357 ER PT J AU Grover, J Lee, ER Mounkes, LC Stewart, CL Roughley, PJ AF Grover, J. Lee, E. R. Mounkes, L. C. Stewart, C. L. Roughley, P. J. TI The consequence of PRELP overexpression on skin SO MATRIX BIOLOGY LA English DT Article DE PRELP; leucine-rich repeat protein; skin; transgenic mouse ID RICH REPEAT PROTEIN; ARTICULAR-CARTILAGE; CONNECTIVE TISSUES; IDENTIFICATION; EXPRESSION; BIGLYCAN; DECORIN; BINDS AB PRELP is a member of the small leucine-rich repeat proteoglycan family that is abundantly expressed in many cartilages compared to other connective tissues. To study the consequence of PRELP overexpression in tissues where it is normally expressed at low abundance, transgenic mice were generated in which the human PRELP transgene was placed under control of the CMV promoter. A connective tissue phenotype was observed in the skin, where the organization of collagen fibrils in the dermis was perturbed and the thickness of the hypodermal fat layer was diminished. (c) 2006 Elsevier B.V./Intemational Society of Matrix Biology. All rights reserved. C1 Shriners Hosp Children, Genet Unit, Montreal, PQ H3G 1A6, Canada. McGill Univ, Dept Surg, Montreal, PQ H3A 2T5, Canada. Shriners Hosp Children, Electron Microscopy Unit, Montreal, PQ, Canada. Natl Canc Inst, Canc & Dev Biol lab, Frederick, MD USA. RP Roughley, PJ (reprint author), Shriners Hosp Children, Genet Unit, 1529 Cedar Ave, Montreal, PQ H3G 1A6, Canada. EM proughley@shriners.mcgill.ca NR 14 TC 6 Z9 6 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 MAR PY 2007 VL 26 IS 2 BP 140 EP 143 DI 10.1016/j.matbio.2006.10.005 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 141NX UT WOS:000244586700009 PM 17123807 ER PT J AU Harrigan, JA Fan, J Momand, J Perrino, FW Bohr, VA Wilson, DM AF Harrigan, Jeanine A. Fan, Jinshui Momand, Jamil Perrino, Fred W. Bohr, Vilhelm A. Wilson, David M., III TI WRN exonuclease activity is blocked by DNA termini harboring 3 ' obstructive groups SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE exonuclease; WRN; Werner syndrome; 3 ' damage repair ID WERNER-SYNDROME PROTEIN; HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE; HUMAN APURINIC ENDONUCLEASE; P53 PROTEIN; RECOMBINANT PROTEINS; HUMAN-DISEASE; MAJOR HUMAN; HUMAN-CELLS; REPAIR; DAMAGE AB Reactive oxygen species, generated either by cellular respiration or upon exposure to environmental agents such as ionizing radiation (IR), attack DNA to form a variety of oxidized base and sugar modifications. Accumulation of oxidative DNA damage has been associated with age-related disease as well as the aging process. Single-strand breaks harboring oxidative 3' obstructive termini, e.g. 3' phosphates and 3' phosphoglycolates, must be removed prior to DNA repair synthesis or ligation. In addition, 3' tyrosyl-linked protein damage, resulting from therapeutic agents such as camptothecin (CPT), must be processed to initiate repair. Several nucleases participate in DNA repair and the excision of 3' obstructive ends. As the protein defective in the segmental progeroid Werner syndrome (WRN) possesses 3'-5' exonuclease activity, and Werner syndrome cells are hypersensitive to IR and CPT, we examined for WRN exonuclease activity on 3' blocking lesions. Moreover, we compared side-by-side the activity of four prominent human 3'-5' exonucleases (WRN, APE1, TREX1, and p53) on substrates containing 3' phosphates, phosphoglycolates, and tyrosyl residues. Our studies reveal that while WRN degrades 3' hydroxyl containing substrates in a non-processive manner, it does not excise 3' phosphate, phosphoglycolate, or tyrosyl groups. In addition, we found that APE1 was most active at excising 3' blocking termini in comparison to the disease-related exonucleases TREX1, WRN, and p53 under identical physiological reaction conditions, and that TREX1 was the most powerful 3'-5' exonuclease on undamaged oligonucleotide substrates. Published by Elsevier Ireland Ltd. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Calif State Univ Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90032 USA. Wake Forest Univ, Dept Biochem, Winston Salem, NC 27157 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov; wilsonda@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000743-04]; NIGMS NIH HHS [R01 GM069962-03, R01 GM069962, GM069962] NR 62 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD MAR PY 2007 VL 128 IS 3 BP 259 EP 266 DI 10.1016/j.mad.2006.12.005 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 144KB UT WOS:000244793800003 PM 17224176 ER PT J AU Klabunde, CN Harlan, LC Warren, JL AF Klabunde, Carrie N. Harlan, Linda C. Warren, Joan L. TI Data sources for measuring comorbidity: Response to Klabunde et al. October 2006 Medical Care - Response to letter from Dr. Steven T. Fleming SO MEDICAL CARE LA English DT Letter ID CLAIMS C1 NCI, Rockville, MD USA. RP Klabunde, CN (reprint author), NCI, Rockville, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 2007 VL 45 IS 3 BP 274 EP 275 DI 10.1097/01.mlr.0000254512.13177.cc PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 143MJ UT WOS:000244725900015 ER PT J AU Bailey, JJ Hodges, M Church, TR AF Bailey, James J. Hodges, Morrison Church, Timothy R. TI Decision to implant a cardioverter defibrillator after myocardial infarction: The role of ejection fraction v. other risk factor markers SO MEDICAL DECISION MAKING LA English DT Article DE arrhythmia; implantable cardioverter defibrillator; risk stratification; myocardial infarction; sudden cardiac death ID SUDDEN CARDIAC DEATH; HEART-RATE-VARIABILITY; SIGNAL-AVERAGED ELECTROCARDIOGRAM; VENTRICULAR PREMATURE COMPLEXES; CORONARY-ARTERY-DISEASE; T-WAVE ALTERNANS; ARRHYTHMIC EVENTS; PROGNOSTIC-SIGNIFICANCE; BAROREFLEX SENSITIVITY; FOLLOW-UP AB Background. The Multicenter Automatic Defibrillator Implantation Trial showed that in post-myocardial infarction patients with a left ventricular ejection fraction (EF) <= 0.30, an implantable cardioverter defibrillator (ICD) resulted in a 31% relative reduction in the risk of death when compared with a conventional therapy group. Whether further refinement in risk estimation could be achieved with additional clinical testing to qualify patients for primary prevention with ICDs remains problematic. Methods. The authors analyzed Cardiac Arrhythmia Suppression Trial registry data to estimate sensitivity and specificity of EF ventricular premature frequency, and nonsustained ventricular tachycardia for predicting death. They combined the results with similar data from the literature and used summarizing receiver operating characteristic (meta-ROC) curves to estimate overall operational values for sensitivity and specificity for each clinical test. They estimated aggregate values for prior probability to project risks when tests were used singly and in combination. Results. The authors used arrhythmia markers and heart rate variability to further stratify low-EF patients (prior risk = 20.3%); proportionately, 20.4% were predicted at high risk (>30%) and 40.5% at low risk (<10%). When heart rate variability is normal, those at high risk reduced proportionately to 9.2%, and those at low risk increased to 51.6%. Conclusions. The combined use of noninvasive markers for arrhythmia substrate and altered autonomic tone can improve risk stratification in low EF without optimal betab-lock therapy, whereas for those with optimal beta-block therapy, markers for arrhythmia substrate alone work. Ancillary use of electrophysiologic stimulation can improve results. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Minneapolis Heart Inst Fdn, Minneapolis, MN USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RP Bailey, JJ (reprint author), NIH, Ctr Informat Technol, Bldg 12A,Room 2007,MSC 5620,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jjbailey@helix.nih.gov OI Church, Timothy R./0000-0003-3292-5035 NR 46 TC 3 Z9 3 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAR-APR PY 2007 VL 27 IS 2 BP 151 EP 160 DI 10.1177/0272989X06297392 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 154ZL UT WOS:000245547200008 PM 17409365 ER PT J AU McMillan, KM Rogers, BP Koay, CG Laird, AR Price, RR Meyerand, ME AF McMillan, Kathryn M. Rogers, Baxter P. Koay, Cheng Guan Laird, Angela R. Price, Ronald R. Meyerand, M. Elizabeth TI An objective method for combining multi-parametric MRI datasets to characterize malignant tumors SO MEDICAL PHYSICS LA English DT Article ID APPARENT DIFFUSION-COEFFICIENT; EXPERIMENTAL CEREBRAL-ISCHEMIA; MAGNETIC-RESONANCE; TISSUE CHARACTERIZATION; WEIGHTED MRI; BLOOD-VOLUME; BOLD MRI; GLIOMAS; PERFUSION; SPECTROSCOPY AB Medical imaging has made significant contributions to the characterization of malignant tumors. In many cases, however, maps from multiple modalities may be required for more complete tumor mapping. In this manuscript we propose an objective method for combining multiple imaging datasets with the goal of characterizing malignant tumors. We refer to the proposed technique as the percent overlap method (POM). To demonstrate the power and flexibility of the POM analysis, we present four patients with recurrent glioblastoma multiforme. Each patient had multiple magnetic resonance imaging procedures resulting in seven different parameter maps. Chemical shift imaging was used to provide three metabolite ratio maps (Cho:NAA, Cho:Cre, Lac:Cre). A perfusion scan provided regional cerebral blood volume and permeability maps. Diffusion and carbogen-based hypoxia mapping data were also acquired. Composite maps were formed for each patient using POM, then were compared to results from the ISODATA clustering technique. The POM maps of likely recurrent tumor regions were found to be consistent with the ISODATA clustering method. This manuscript presents an objective method for combining parameters from multiple physiologic imaging techniques into a single composite map. The accuracy of the map depends strongly on the sensitivity of the chosen imaging parameters to the disease process at the time of image acquisition. Further validation of this method may be achieved by correlation with histological data. (c) 2007 American Association of Physicists in Medicine. C1 Vanderbilt Univ, Dept Radiol, Nashville, TN 37232 USA. Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. Vanderbilt Univ, Inst Imaging Sci, Nashville, TN 37232 USA. NICHD, LIMB, STBB, NIH, Bethesda, MD USA. Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX 78229 USA. Univ Wisconsin, Dept Phys Med, Madison, WI 53706 USA. RP McMillan, KM (reprint author), Vanderbilt Univ, Dept Radiol, 221 Kirkland Hall, Nashville, TN 37232 USA. EM kathryn.mcmillan@vanderbilt.edu RI Laird, Angela/B-5800-2010; Rogers, Baxter/B-7897-2010 FU NCI NIH HHS [2R25 CA092043-06]; NINDS NIH HHS [5F31 NS046168-02] NR 25 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAR PY 2007 VL 34 IS 3 BP 1053 EP 1061 DI 10.1118/1.2558301 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 148NT UT WOS:000245082600022 PM 17441252 ER PT J AU Zonios, DI Falloon, J Huang, CY Chaitt, D Bennett, JE AF Zonios, Dimitrios I. Falloon, Judith Huang, Chiung-Yu Chaitt, Doreen Bennett, John E. TI Cryptococcosis and idiopathic CD4 lymphocytopenia SO MEDICINE LA English DT Article ID UNEXPLAINED OPPORTUNISTIC INFECTIONS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PNEUMOCYSTIS-CARINII PNEUMONIA; VIRUS-NEGATIVE PATIENTS; T-LYMPHOCYTOPENIA; HIV-INFECTION; AMPHOTERICIN-B; DISSEMINATED TUBERCULOSIS; PULMONARY CRYPTOCOCCOMA; MAINTENANCE THERAPY AB We reviewed the cases of 11 patients with cryptococcosis and idiopathic CD4 lymphocytopenia (ICL) referred to our institution in the previous 12 years, as well as 42 similar cases reported in the literature, to assess the characteristics of the infection in this population. Cryptococcosis in 53 patients with ICL had features in common with cryptococcosis in previously normal patients. ICL patients had a slight male predominance (1.2:1) and a median age of presentation of 41 years (range, 4.5-85 yr). Initial cerebrospinal fluid findings showed glucose below 40 mg/dL in 60% of the patients, a median pleocytosis of 59 white blood cells/mm(3) (range, 0-884), and protein of 156 mg/dL (range, 25-402 mg/dL). The median CD4 count at diagnosis of ICL and at the last available measurement was 82 (range, 7-292) and 132 (range, 13-892) cells/mm(3), respectively, for an average follow-up of 32 months in 46 patients. Unlike previously normal patients with cryptococcosis, those with ICL had an excess incidence of dermatomal zoster (7 episodes in 46 ICL cases). Pneumocystis pneumonia was rare (1 case), casting doubt on the need for prophylaxis in patients with ICL. A favorable outcome (cured or improved) may be more common in ICL patients than in previously normal patients with cryptococcal meningitis and no predisposing factors. Identification of ICL in patients who were apparently normal before the onset of cryptococcosis appears to be useful because it predicts a favorable outcome. Patients with cryptococcal infection and ICL have an increased likelihood of developing dermatomal zoster. The long-term follow-up of these patients offers some reassurance regarding favorable prognosis. C1 NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Zonios, DI (reprint author), NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Clin Ctr Room 11C304, Bethesda, MD 20892 USA. EM zoniosd@niaid.nih.gov NR 82 TC 40 Z9 41 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAR PY 2007 VL 86 IS 2 BP 78 EP 92 DI 10.1097/md.0b013e31803b52f5 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 146UM UT WOS:000244960200003 PM 17435588 ER PT J AU Utian, WH Archer, DF Bachmann, GA Gallagher, JC Grodstein, F Heiman, JR Henderson, VW Hodis, HN Karas, RH Lobo, RA Manson, JE Reid, RL Schmidt, PJ Stuenkel, CA AF Utian, Wulf H. Archer, David F. Bachmann, Gloria A. Gallagher, J. Christopher Grodstein, Francine Heiman, Julia R. Henderson, Victor W. Hodis, Howard N. Karas, Richard H. Lobo, Rogerio A. Manson, JoAnn E. Reid, Robert L. Schmidt, Peter J. Stuenkel, Cynthia A. CA NAMS TI Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of The North American Menopause Society SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Review DE menopause; perimenopause; estrogen; progestogen; hormone therapy; vasomotor symptoms; vaginal atrophy; coronary heart disease; venous thromboembolism; stroke; diabetes mellitus; breast cancer; osteoporosis; depression; dementia; cognitive decline; premature menopause; bioidentical hormones; NAMS ID HORMONE-REPLACEMENT THERAPY; CONJUGATED EQUINE ESTROGENS; INITIATIVE RANDOMIZED-TRIAL; QUALITY-OF-LIFE; DOSE TRANSDERMAL ESTRADIOL; PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; BONE-MINERAL DENSITY; BREAST-CANCER RISK; ACUTE MYOCARDIAL-INFARCTION AB Objective: To update the evidence-based position statement published by The North American Menopause Society (NAMS) in 2004 regarding recommendations for estrogen and progestogen use in peri- and postmenopausal women. Design: NAMS followed the general principles established for evidence-based guidelines to create this updated document. An Advisory Panel of clinicians and researchers expert in the field of women's health was enlisted to review the 2004 NAMS position statement, compile supporting statements, and reach consensus on recommendations. The Panel's recommendations were reviewed and approved by the NAMS Board of Trustees. The position statements published by NAMS do not represent "practice standards" that would be codified and held up as standards by regulating bodies and insurance agencies. Rather, they are prevailing opinion pieces in a best effort attempt to incorporate current evidence into practical clinical recommendations. Results: With the primary goal being to evaluate the risk-benefit ratio of peri- and postmenopausal estrogen therapy (ET) and estrogen-progestogen therapy (EPT) for both disease prevention and treatment of menopause-related symptoms, current evidence allowed for a clear distinction between areas of consensus and areas for which the Panel determined that there was inadequate evidence for any conclusion to be reached. The document lists all of these areas along with clear explanatory comments. A comprehensive list of key references is provided. The absence of evidence is also recognized in the list of needs for further research recommended by the Panel. Conclusions: Current evidence supports the use of ET or EPT for menopause-related symptoms and disease prevention in appropriate populations of peri- and postmenopausal women. C1 NAMS, Cleveland, OH 44101 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Eastern Virginia Med Sch, Conrad Clin Res Ctr, Norfolk, VA 23501 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. Creighton Univ, Med Ctr, Omaha, NE USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Indiana Univ, Kinsey Inst Res Sex Gender & Reprod, Bloomington, IN USA. Stanford Univ, Stanford, CA 94305 USA. Univ So Calif, Keck Sch Med, Div Cardiovasc Med, Atherosclerosis Res Unit, Los Angeles, CA USA. Tufts Univ, Sch Med, Tufts New England Med Ctr, Womens Heart Ctr, Boston, MA USA. Tufts Univ, Sch Med, Tufts New England Med Ctr, Mol Cardiol Res Ctr, Boston, MA USA. Columbia Univ, Med Ctr, New York, NY USA. Harvard Univ, Sch Med, Div Prevent Med, Boston, MA USA. Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. Queens Univ, Dept Reprod Endocrinol & Infertil, Kingston, ON, Canada. NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. Univ Calif La Jolla, Div Endocrinol & Metab, La Jolla, CA USA. RP Utian, WH (reprint author), NAMS, POB 94527, Cleveland, OH 44101 USA. EM info@menopause.org NR 147 TC 98 Z9 100 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAR-APR PY 2007 VL 14 IS 2 BP 168 EP 182 DI 10.1097/gme.0b013e31803167ab PG 15 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 145OG UT WOS:000244873800004 ER PT J AU Tesauro, M Rizza, S Iantorno, M Campia, U Cardillo, C Lauro, D Leo, R Turriziani, M Cocciolillo, GC Fusco, A Panza, JA Scuteri, A Federici, M Lauro, R Quon, MJ AF Tesauro, Manfredi Rizza, Stefano Iantorno, Micaela Campia, Umberto Cardillo, Carmine Lauro, Davide Leo, Roberto Turriziani, Mario Cocciolillo, Giulio Cesare Fusco, Angelo Panza, Julio A. Scuteri, Angelo Federici, Massimo Lauro, Renato Quon, Michael J. TI Vascular, metabolic, and inflammatory abnormalities in normoglycemic offspring of patients with type 2 diabetes mellitus SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID C-REACTIVE PROTEIN; INSULIN-RESISTANCE ATHEROSCLEROSIS; ENDOTHELIAL DYSFUNCTION; MEDIATED VASODILATION; 1ST-DEGREE RELATIVES; BRACHIAL-ARTERY; DEFICIENT MICE; NITRIC-OXIDE; ADIPONECTIN; SENSITIVITY AB Endothelial dysfunction, insulin resistance, and elevated levels of circulating proinflammatory markers are among the earliest detectable abnormalities in people at risk for atherosclerosis. Accelerated atherosclerosis is a leading contributor to morbidity and mortality in type 2 diabetes mellitus, a complex genetic disorder. Therefore, we hypothesized that normoglycemic offspring of patients with type 2 diabetes mellitus (NOPD) may have impaired vascular and metabolic function related to an enhanced proinflammatory state. We compared NOPD (n = 51) with matched healthy control subjects without family history of diabetes (n = 35). Flow- and nitroglycerin-mediated brachial artery vasodilation were assessed by ultrasound to evaluate endothelium-dependent and -independent vascular function. Each subject also underwent an oral glucose tolerance test to evaluate metabolic function. Fasting levels of plasma adiponectin and circulating markers of inflammation (high-sensitivity C-reactive protein, CD40 ligand, interleukin 1 beta, tumor necrosis factor a, vascular cell adhesion molecule 1, and intracellular adhesion molecule) were measured. Both NOPD and the control group had fasting glucose and insulin levels well within the reference range. However, results from oral glucose tolerance test and quantitative insulin sensitivity check index revealed that NOPD were insulin resistant with significantly impaired flow- and nitroglycerin-mediated dilation compared with the control group. Adiponectin levels were lower, whereas many circulating markers of inflammation were higher, in NOPD compared with the control group. Normoglycemic offspring of patients with type 2 diabetes mellitus have impaired vascular and metabolic function accompanied by an enhanced proinflammatory state that may contribute to their increased risk of diabetes and its vascular complications. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Roma Tor Vergata, Dept Internal Med, Atherosclerosis Ctr, Rome, Italy. Univ Cattolica Sacro Cuore, Dipartimento Med Interna, Rome, Italy. NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Washington Hosp Ctr, Cardiovasc Res Inst, Washington, DC 20010 USA. IRCCS, UO Geriatr, INRCA, Rome, Italy. RP Tesauro, M (reprint author), Univ Roma Tor Vergata, Dept Internal Med, Atherosclerosis Ctr, Rome, Italy. EM mtesauro@tiscali.it RI Quon, Michael/B-1970-2008; Federici, Massimo/G-9940-2012; OI Federici, Massimo/0000-0003-4989-5194; Campia, Umberto/0000-0002-7894-3565; Quon, Michael/0000-0002-9601-9915; Lauro, Davide/0000-0002-8597-4415; Quon , Michael /0000-0002-5289-3707 NR 40 TC 20 Z9 22 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAR PY 2007 VL 56 IS 3 BP 413 EP 419 DI 10.1016/j.metabol.2006.10.026 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 139HC UT WOS:000244421900018 PM 17292732 ER PT J AU Cascales, E Buchanan, SK Duche, D Kleanthous, C Lloubes, R Postle, K Riley, M Slatin, S Cavard, D AF Cascales, Eric Buchanan, Susan K. Duche, Denis Kleanthous, Colin Lloubes, Roland Postle, Kathleen Riley, Margaret Slatin, Stephen Cavard, Daniele TI Colicin biology SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID A LYSIS PROTEIN; C-TERMINAL DOMAIN; OUTER-MEMBRANE RECEPTOR; BACTERIOCIN-RELEASE-PROTEIN; PORE-FORMING DOMAIN; FILAMENTOUS PHAGE INFECTION; PLANAR LIPID-BILAYERS; COMPLETE NUCLEOTIDE-SEQUENCE; CELL-ENVELOPE INTEGRITY; HUMAN GROWTH-HORMONE C1 CNRS, UPR9027, Lab Ingn Syst Macromol, IBSM, F-13402 Marseille 20, France. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ York, Dept Biol, York YO10 5YW, N Yorkshire, England. Penn State Univ, Eberly Coll Sci, Dept Biochem & Mol Biol, Althouse Lab 301, University Pk, PA 16802 USA. Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA. RP Cascales, E (reprint author), CNRS, UPR9027, Lab Ingn Syst Macromol, IBSM, 31 Chemin Joseph Aiguier, F-13402 Marseille 20, France. EM cascales@ibsm.cnrs-mrs.fr RI CASCALES, Eric/G-7420-2011; OI Postle, Kathleen/0000-0001-9451-777X FU Biotechnology and Biological Sciences Research Council [BB/C516236/1]; Intramural NIH HHS; NIAID NIH HHS [R01 AI064588-02, R01 AI064588, R01 AI064588-01A2]; Wellcome Trust NR 719 TC 412 Z9 418 U1 18 U2 100 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD MAR PY 2007 VL 71 IS 1 BP 158 EP 229 DI 10.1128/MMBR.00036-06 PG 72 WC Microbiology SC Microbiology GA 147ZR UT WOS:000245044800006 PM 17347522 ER PT J AU Norris, V den Blaauwen, T Cabin-Flaman, A Doi, RH Harshey, R Janniere, L Jimenez-Sanchez, A Jin, DJ Levin, PA Mileykovskaya, E Minsky, A Saier, M Skarstad, K AF Norris, Vic den Blaauwen, Tanneke Cabin-Flaman, Armelle Doi, Roy H. Harshey, Rasika Janniere, Laurent Jimenez-Sanchez, Alfonso Jin, Ding Jun Levin, Petra Anne Mileykovskaya, Eugenia Minsky, Abraham Saier, Milton, Jr. Skarstad, Kirsten TI Functional taxonomy of bacterial hyperstructures SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID ESCHERICHIA-COLI CHROMOSOME; DIVISION PROTEIN FTSZ; PENICILLIN-BINDING PROTEINS; DOUBLE-STRAND BREAKS; ELONGATION-FACTOR TU; ACTIN-LIKE PROTEINS; BACILLUS-SUBTILIS; CELL-DIVISION; CLOSTRIDIUM-THERMOCELLUM; DNA-REPLICATION C1 Univ Rouen, Dept Sci, F-76821 Mont St Aignan, France. Genopole, Epigen Project, F-91000 Evry, France. Univ Amsterdam, Swammerdam Inst Life Sci, NL-1098 SJ Amsterdam, Netherlands. Univ Calif Davis, Davis, CA 95616 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. INRA, Lab Genet Microbienne, F-78352 Jouy En Josas, France. Univ Extremadura, Fac Sci, Dept Genet, E-06080 Badajoz, Spain. NCI, Gen Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. Washington Univ, Dept Biol, St Louis, MO 63130 USA. Univ Texas, Sch Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. Norwegian Radium Hosp, Inst Canc Res, Dept Cell Biol, N-0310 Oslo, Norway. RP Norris, V (reprint author), Univ Rouen, Dept Sci, F-76821 Mont St Aignan, France. EM vjn@univ-rouen.fr FU Intramural NIH HHS; NIGMS NIH HHS [GM 64671, R01 GM064671, R01 GM064671-05] NR 292 TC 47 Z9 48 U1 1 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD MAR PY 2007 VL 71 IS 1 BP 230 EP 253 DI 10.1128/MMBR.00035-06 PG 24 WC Microbiology SC Microbiology GA 147ZR UT WOS:000245044800007 PM 17347523 ER PT J AU Knoepp, SM Carney, JA Mihm, MC Bei, T Stergiopoulos, S Stratakis, CA Zembowicz, A AF Knoepp, S. M. Carney, J. A. Mihm, M. C. Bei, T. Stergiopoulos, S. Stratakis, C. A. Zembowicz, A. TI Loss of expression of a carney complex gene, protein kinase a regulatory subunit 1a, in sporadic and carney complex-associated pigmented epithelioid melanocytoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Mayo Clin, Rochester, MN USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 419 BP 95A EP 95A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922400420 ER PT J AU Kuhn, E Teller, L Piana, S Rosai, J Merino, MJ AF Kuhn, E. Teller, L. Piana, S. Rosai, J. Merino, M. J. TI Clonality of papillary thyroid cancer. Clinical implications SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 CCAPO, Milan, Italy. NCI, Bethesda, MD 20892 USA. CDI, Milan, Italy. 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 455 BP 103A EP 103A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922400456 ER PT J AU Hartmann, DP Kallakury, BVS Luka, J Apella, EA Azumi, N AF Hartmann, D. P. Kallakury, B. V. S. Luka, J. Apella, E. A. Azumi, N. TI Progressive increase in PPM1D/wip-1 protein expression in normal mucosa, tubular adenoma, and low- and high-grade colorectal adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 George Washington Univ Hosp, Washington, DC USA. Bioworld Consulting Labs, New Windsor, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 523 BP 117A EP 117A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922400523 ER PT J AU Li, L Bourne, PA Yao, JL Sant'Agnese, PA Zhuang, Z Yin, C Wu, C Huang, J AF Li, L. Bourne, P. A. Yao, J. L. di Sant'Agnese, P. A. Zhuang, Z. Yin, C. Wu, C. Huang, J. TI Myosin VI, a mediator of the p53-dependent cell survival pathway, is overexpressed in adenocarcinoma of the prostate SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Univ Rochester, Med Ctr, Rochester, NY 14642 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 718 BP 159A EP 159A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922401141 ER PT J AU Nigwekar, P Wu, C Yao, JL Bourne, PA Li, J Zhuang, Z Agnese, PAD Walters, DC Huang, J AF Nigwekar, P. Wu, C. Yao, J. L. Bourne, P. A. Li, J. Zhuang, Z. di Sant Agnese, P. A. Walters, D. C. Huang, J. TI Nucleophosmin, a critical regulator of cell proliferation, is overexpressed in prostate cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Natl Inst Hlth, Bethesda, MD 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 756 BP 166A EP 167A PG 2 WC Pathology SC Pathology GA 146GL UT WOS:000244922401179 ER PT J AU Qian, J Liu, L Ma, J Meiers, I Lang, K Hewitt, SM Wilson, TH Rittmaster, RS Bostwick, DG AF Qian, J. Liu, L. Ma, J. Meiers, I. Lang, K. Hewitt, S. M. Wilson, T. H. Rittmaster, R. S. Bostwick, D. G. TI The 5-alpha-reductase inhibitor dutasteride decreases cancer volume and induces multiple phenotypic changes in the human prostate SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Bostwick Labs, Glen Allen, VA 20892 USA. NCI, HIH, Bethesda, MD USA. Glaxosmithkline Inc, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 778 BP 171A EP 172A PG 2 WC Pathology SC Pathology GA 146GL UT WOS:000244922401201 ER PT J AU Rodriguez-Canales, J Hanson, JC Tangrea, MA Erickson, HS Albert, PA Wallis, BS Richardson, AM Pinto, PA Linehan, WM Gillespie, JW Merino, MJ Libutti, SK Woodson, KW Emmert-Buck, MR Chuaqui, RF AF Rodriguez-Canales, J. Hanson, J. C. Tangrea, M. A. Erickson, H. S. Albert, P. A. Wallis, B. S. Richardson, A. M. Pinto, P. A. Linehan, W. M. Gillespie, J. W. Merino, M. J. Libutti, S. K. Woodson, K. W. Emmert-Buck, M. R. Chuaqui, R. F. TI Identification of a unique epigenetic sub-microenvironment in prostate cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 785 BP 173A EP 173A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922401208 ER PT J AU Shaheduzzaman, S Gao, C Wang, Z Furusato, B Petrovics, G Srikantan, V Ravindranath, L Nau, M Chen, Y Chen, Y Cullen, J McLeod, DG Sesterhenn, I Vahey, M Srivastava, S AF Shaheduzzaman, S. Gao, C. Wang, Z. Furusato, B. Petrovics, G. Srikantan, V. Ravindranath, L. Nau, M. Chen, Y. Chen, Y. Cullen, J. McLeod, D. G. Sesterhenn, I. Vahey, M. Srivastava, S. TI Epithelial cell transcriptome of poorly and moderately differentiated prostate cancers SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 CPDR, Rockville, MD USA. WRAMC, Washington, DC USA. NIH, Bethesda, MD 20892 USA. WRAIR, Rockville, MD 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 792 BP 174A EP 175A PG 2 WC Pathology SC Pathology GA 146GL UT WOS:000244922401215 ER PT J AU Shaheduzzaman, S Vishwanath, A Furusato, B Cullen, J Chen, Y Banez, L Nau, M Ravindranath, L Kim, KH Mohammed, A Chen, Y Ehrich, M Srikantan, V Sesterhenn, I McLeod, DG Vahey, M Petrovics, G Dobi, A Srivastava, S AF Shaheduzzaman, S. Vishwanath, A. Furusato, B. Cullen, J. Chen, Y. Banez, L. Nau, M. Ravindranath, L. Kim, K. H. Mohammed, A. Chen, Y. Ehrich, M. Srikantan, V. Sesterhenn, I. McLeod, D. G. Vahey, M. Petrovics, G. Dobi, A. Srivastava, S. TI Mechanisms of downregulation of lactotransferrin (LTF) in prostate cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 CPDR, Rockville, MD USA. AFIP, Washington, DC USA. WRAMC, Washington, DC USA. NIH, NHGRI, Bethesda, MD 20892 USA. WRAIR, Rockville, MD USA. Sequenom Inc, San Diego, CA 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 793 BP 175A EP 175A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922401216 ER PT J AU Val, D Gulley, JL Pinto, P Schlom, J Linehan, WM Merino, MJ AF Val, D. Gulley, J. L. Pinto, P. Schlom, J. Linehan, W. M. Merino, M. J. TI Morphologic changes in prostate cancer samples following intraprostatic PSA-Based vaccine administration SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 825 BP 181A EP 181A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922401248 ER PT J AU Galgano, MT Castle, PC Stoler, MH AF Galgano, M. T. Castle, P. C. Stoler, M. H. TI Can HPV 16 typing adjudicate the accuracy of cervical biopsy interpretation? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Univ Virginia, Charlottesville, VA USA. Natl Canc Inst, NIH, DHHS, Bethesda, MD 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 901 BP 198A EP 198A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922401324 ER PT J AU Posligua, L Malpica, A Deavers, M Merino, M Silva, E AF Posligua, L. Malpica, A. Deavers, M. Merino, M. Silva, E. TI The alleged low-grade leiomyosarcomas of the female genital tract: Metastatic lesions or independent primary tumors? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 MD Anderson Canc Ctr, Houston, TX USA. Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 961 BP 210A EP 210A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922401384 ER PT J AU Val, D Stranon, P Neumann, RD Linehan, WM Merino, MJ AF Val, D. Stranon, P. Neumann, R. D. Linehan, W. M. Merino, M. J. TI The morphologic spectrum of smooth muscle tumors in the hereditary leimyomatosis and renal cell cancer (HLRCC) syndrome. Its clinical significance SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. CC, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 990 BP 216A EP 216A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922401413 ER PT J AU Bian, S Jiang, L Vivero, A Pittaluga, S Raffeld, M Jaffe, ES AF Bian, S. Jiang, L. Vivero, A. Pittaluga, S. Raffeld, M. Jaffe, E. S. TI B-cell lymphomas with marked tissue eosinophilia and plasmacytoid differentiation, a study of 25 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. Singapore Gen Hosp, Singapore 0316, Singapore. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1073 BP 234A EP 234A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922401496 ER PT J AU Feldman, AL Arber, DA Raffeld, M Burke, JS Pittaluga, S Warnke, R Jaffe, ES AF Feldman, A. L. Arber, D. A. Raffeld, M. Burke, J. S. Pittaluga, S. Warnke, R. Jaffe, E. S. TI Clonal relationship between follicular lymphoma and histiocytic/dendritic cell neoplasms occurring in the same patient SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Natl Canc Inst, Bethesda, MD USA. Stanford Univ, Stanford, CA 94305 USA. Alta Bates Summit Med Ctr, Berkeley, CA USA. RI Feldman, Andrew/D-5028-2012 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1098 BP 240A EP 240A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922401521 ER PT J AU Gradowski, JF Swerdlow, SH Surti, U Jaffe, ES Pittaluga, S Prakash, S AF Gradowski, J. F. Swerdlow, S. H. Surti, U. Jaffe, E. S. Pittaluga, S. Prakash, S. TI Follicular lymphoma with plasmacytic differentiation: Fluorescence immunophenotypic and interphase cytogenetic characterization SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Natl Canc Inst, Bethesda, MD USA. Womens Hosp Med Ctr, Pittsburgh, PA 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1106 BP 241A EP 242A PG 2 WC Pathology SC Pathology GA 146GL UT WOS:000244922401529 ER PT J AU Begnami, M Santi, M Rushing, EJ Quezado, M AF Begnami, M. Santi, M. Rushing, E. J. Quezado, M. TI Evaluation of chromosome 7 alterations including epidermal growth factor amplification status in pediatric meningiomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. Childrens Hosp, Washington, DC USA. AFIP, Washington, DC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1360 BP 296A EP 296A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922402194 ER PT J AU Begnami, MD Soares, FA Quezado, M AF Begnami, M. D. Soares, F. A. Quezado, M. TI Chromosome 7 polysomy detected by chromogenic in situ hybridization (CISH) is a common finding in sporadic chordomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. AC Camargo, Sao Paulo, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1361 BP 296A EP 296A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922402195 ER PT J AU Chevcz-Barrios, P Zhou, M Shen, D Chew, EY Green, WR Chan, CC AF Chevcz-Barrios, P. Zhou, M. Shen, D. Chew, E. Y. Green, W. R. Chan, C. C. TI Ophthalmic Von Hippel-Lindau disease: Expression of clusterin SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Methodist Hosp, Houston, TX 77030 USA. Natl Inst Hlth, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1392 BP 303A EP 303A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922402226 ER PT J AU Galli, S Tyokos, M AF Galli, S. B. Tyokos, M. TI Expression of XIAP protein in neuroblastomas and Ewing sarcoma family tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1436 BP 312A EP 312A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922402270 ER PT J AU Kamatani, H Kumagai, N Tanaka, T Kawamura, S Hewitt, SM Franks, TJ Travis, WD Jen, J Fukuoka, J AF Kamatani, H. Kumagai, N. Tanaka, T. Kawamura, S. Hewitt, S. M. Franks, T. J. Travis, W. D. Jen, J. Fukuoka, J. TI Lack of desmoglein 2 is an indicator of cancer progression and a poor prognostic factor in stage 1 non-small cell lung cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Toyama Univ Hosp, Toyama 930, Japan. NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. AFIP, Washington, DC 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1491 BP 324A EP 324A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922402325 ER PT J AU Merino, MJ Carter, D Linehan, WM Nguyen, D Quezado, M AF Merino, M. J. Carter, D. Linehan, W. M. Nguyen, D. Quezado, M. TI Novel benign pulmonary and chest wall lesions as part of the von hippel lindau syndrome mimicking metastatic renal cell carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1503 BP 326A EP 326A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922402337 ER PT J AU Rassaei, N Tavora, F Ozbudak, I Chu, WS Jaynes, E Sobin, L Travis, WD Jen, J Shilo, K Franks, TJ AF Rassaei, N. Tavora, F. Ozbudak, I. Chu, W-S Jaynes, E. Sobin, L. Travis, W. D. Jen, J. Shilo, K. Franks, T. J. TI Thyroid transcription factor-1 (TTF-1) expression in pulmonary neuroendocrine carcinomas: Clone-based variability SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 AFIP, Washington, DC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NIH, Bethesda, MD 20892 USA. RI Ozbudak, Irem /C-4815-2016 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1515 BP 329A EP 329A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922402349 ER PT J AU Silva, A Carter, D Begnami, M Henschke, CI Vasquez, M Merino, MJ AF Silva, A. Carter, D. Begnami, M. Henschke, C. I. Vasquez, M. Merino, M. J. TI Evaluation of gene amplification and protein expression of epidermal growth factor receptor (EGFR) by CISH, FISH and IHC in lung adenocarcinoma (ADC) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Weill Cornell Med Ctr, New York, NY 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1527 BP 331A EP 332A PG 2 WC Pathology SC Pathology GA 146GL UT WOS:000244922402361 ER PT J AU Yoshizawa, A Fukuoka, J Shilo, K Franks, TJ Hewitt, S Fujii, T Jen, J Travis, WD Cordon-Cardo, C AF Yoshizawa, A. Fukuoka, J. Shilo, K. Franks, T. J. Hewitt, S. M. Fujii, T. Jen, J. Travis, W. D. Cordon-Cardo, C. TI Clinical significance of p-AKT pathway in non-small cell lung cancer (NSCLC) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Toyama Univ Hosp, Toyama, Japan. AFIP, Washington, DC USA. NCI, NIH, Bethesda, MD 20892 USA. Toranomon Gen Hosp, Tokyo, Japan. 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1543 BP 335A EP 335A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922402377 ER PT J AU Begnami, M Quezado, M Wincovitch, S Garfield, S Merino, M AF Begnami, M. Quezado, M. Wincovitch, S. Garfield, S. Merino, M. J. TI Evaluation of nucleic acid index (NAI) in the spectrum ofThyroid lesions SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2007 VL 20 SU 2 MA 1590 BP 345A EP 345A PG 1 WC Pathology SC Pathology GA 146GL UT WOS:000244922402425 ER PT J AU Chernukhin, I Shamsuddin, S Kang, SY Bergstrom, R Kwon, YW Yu, WQ Whitehead, J Mukhopadhyay, R Docquier, F Farrar, D Morrison, I Vigneron, M Wu, SY Chiang, CM Loukinov, D Lobanenkov, V Ohlsson, R Klenova, E AF Chernukhin, Igor Shamsuddin, Shaharum Kang, Sung Yun Bergstrom, Rosita Kwon, Yoo-Wook Yu, WenQiang Whitehead, Joanne Mukhopadhyay, Rituparna Docquier, France Farrar, Dawn Morrison, Ian Vigneron, Marc Wu, Shwu-Yuan Chiang, Cheng-Ming Loukinov, Dmitri Lobanenkov, Victor Ohlsson, Rolf Klenova, Elena TI CTCF interacts with and recruits the largest subunit of RNA polymerase II to CTCF target sites genome-wide SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INSULATOR PROTEIN CTCF; C-MYC GENE; METHYLATION-FREE DOMAINS; ZINC-FINGER FACTOR; BETA-GLOBIN LOCUS; TRANSCRIPTION FACTOR; CHROMATIN INSULATOR; CONTROL REGION; IMPRINTED EXPRESSION; ENHANCER BLOCKING AB CTCF is a transcription factor with highly versatile functions ranging from gene activation and repression to the regulation of insulator function and imprinting. Although many of these functions rely on CTCF-DNA interactions, it is an emerging realization that CTCF-dependent molecular processes involve CTCF interactions with other proteins. In this study, we report the association of a subpopulation of CTCF with the RNA polymerase II (Pot II) protein complex. We identified the largest subunit of Pot II (LS Pot II) as a protein significantly colocalizing with CTCF in the nucleus and specifically interacting with CTCF in vivo and in vitro. The role of CTCF as a link between DNA and LS Pot II has been reinforced by the observation that the association of LS Pot II with CTCF target sites in vivo depends on intact CTCF binding sequences. "Serial" chromatin immunoprecipitation (ChIP) analysis revealed that both CTCF and LS Pot II were present at the P-globin insulator in proliferating HD3 cells but not in differentiated globin synthesizing HD3 cells. Further, a single wild-type CTCF target site (N-Myc-CTCF), but not the mutant site deficient for CTCF binding, was sufficient to activate the transcription from the promoterless reporter gene in stably transfected cells. Finally, a ChIP-on-ChIP hybridization assay using microarrays of a library of CTCF target sites revealed that many intergenic CTCF target sequences interacted with both CTCF and LS Pot II. We discuss the possible implications of our observations with respect to plausible mechanisms of transcriptional regulation via a CTCFmediated direct link of LS Pot II to the DNA. C1 Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England. Uppsala Univ, Dept Genet & Dev, Evolut Biol Ctr, S-75236 Uppsala, Sweden. NIAID, Mol Pathol Sect, LIP, NIH, Bethesda, MD 20892 USA. ESBS, UMR 7175, CNRS, ULP, F-67412 Illkirch Graffenstaden, France. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. RP Klenova, E (reprint author), Univ Essex, Dept Biol Sci, Cent Campus,Wivenhoe Pk, Colchester CO4 3SQ, Essex, England. EM klenovae@essex.ac.uk RI Shamsuddin, Shaharum/A-7907-2011; Whitehead, Joanne/A-8597-2008 OI Shamsuddin, Shaharum/0000-0001-9997-7740; Whitehead, Joanne/0000-0002-9602-2081 FU Intramural NIH HHS; Medical Research Council [G0401088]; NCI NIH HHS [CA103867, R01 CA103867, R01 CA124760]; Worldwide Cancer Research [99-0514] NR 68 TC 81 Z9 83 U1 0 U2 1 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 MAR PY 2007 VL 27 IS 5 BP 1631 EP 1648 DI 10.1128/MCB.01993-06 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 137PW UT WOS:000244305500008 PM 17210645 ER PT J AU Shin, BS Acker, MG Maag, D Kim, JR Lorsch, JR Dever, TE AF Shin, Byung-Sik Acker, Michael G. Maag, David Kim, Joo-Ran Lorsch, Jon R. Dever, Thomas E. TI Intragenic suppressor mutations restore GTPase and translation functions of a eukaryotic initiation factor 5B Switch II mutant SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ELONGATION-FACTOR TU; ESCHERICHIA-COLI; INITIATION; BINDING; SWITCH; GDP; HYDROLYSIS; ACTIVATION; SUBUNITS; RIBOSOME AB Structural studies of GTP-binding proteins identified the Switch I and Switch II elements as contacting the gamma-phosphate of GTP and undergoing marked conformational changes upon GTP versus GDP binding. Movement of a universally conserved Gly at the N terminus of Switch II is thought to trigger the structural rearrangement of this element. Consistently, we found that mutation of this Gly in the Switch II element of the eukaryotic translation initiation factor 5B (eIF5B) from Saccharomyces cerevisiae impaired cell growth and the guanine nucleotide-binding, GTPase, and ribosomal subunit joining activities of eIF5B. In a screen for mutations that bypassed the critical requirement for this Switch II Gly in eIF5B, intragenic suppressors were identified in the Switch I element and at a residue in domain II of eIF5B that interacts with Switch II. The intragenic suppressors restored yeast cell growth and eIF5B nucleotide-binding, GTP hydrolysis, and subunit joining activities. We propose that the Switch II mutation distorts the geometry of the GTP-binding active site, impairing nucleotide binding and the eIF5B domain movements associated with GTP binding. Accordingly, the Switch I and domain II suppressor mutations induce Switch II to adopt a conformation favorable for nucleotide binding and hydrolysis and thereby reestablish coupling between GTP binding and eIF5B domain movements. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. RP Dever, TE (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, 6 Ctr Dr,Bldg 6A,Rm B1A-03, Bethesda, MD 20892 USA. EM tdever@nih.gov OI Dever, Thomas/0000-0001-7120-9678; Lorsch, Jon/0000-0002-4521-4999 FU Intramural NIH HHS NR 27 TC 9 Z9 9 U1 0 U2 1 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 MAR PY 2007 VL 27 IS 5 BP 1677 EP 1685 DI 10.1128/MCB.01258-06 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 137PW UT WOS:000244305500011 PM 17189426 ER PT J AU Sharma, S Stumpo, DJ Balajee, AS Bock, CB Lansdorp, PM Brosh, RM Blackshear, PJ AF Sharma, Sudha Stumpo, Deborah J. Balajee, Adayabalam S. Bock, Cheryl B. Lansdorp, Peter M. Brosh, Robert M., Jr. Blackshear, Perry J. TI RECQL, a member of the RecQ family of DNA helicases, suppresses chromosomal instability SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID WERNER-SYNDROME FIBROBLASTS; ROTHMUND-THOMSON-SYNDROME; BLOOMS-SYNDROME GENE; HOMOLOGOUS RECOMBINATION; SACCHAROMYCES-CEREVISIAE; PANCREATIC-CANCER; MOLECULAR-CLONING; SYNDROME PROTEIN; CELL-LINES; S-PHASE AB The mouse gene Recql is a member of the RecQ subfamily of DEx-H-containing DNA helicases. Five members of this family have been identified in both humans and mice, and mutations in three of these, BLM, WRN, and RECQL4, are associated with human diseases and a cellular phenotype that includes genomic instability. To date, no human disease has been associated with mutations in RECQL and no cellular phenotype has been associated with its deficiency. To gain insight into the physiological function of RECQL, we disrupted Recql in mice. RECQL-deficient mice did not exhibit any apparent phenotypic differences compared to wild-type mice. Cytogenetic analyses of embryonic fibroblasts from the RECQL-deficient mice revealed aneuploidy, spontaneous chromosomal breakage, and frequent translocation events. In addition, the RECQL-deficient cells were hypersensitive to ionizing radiation, exhibited an increased load of DNA damage, and displayed elevated spontaneous sister chromatid exchanges. These results provide evidence that RECQL has a unique cellular role in the DNA repair processes required for genomic integrity. Genetic background, functional redundancy, and perhaps other factors may protect the unstressed mouse from the types of abnormalities that might be expected from the severe chromosomal aberrations detected at the cellular level. C1 NIEHS, Lab Neurobiol, Res Triangle Pk, NC 27709 USA. NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Duke Univ, Ctr Med, Durham, NC 27710 USA. British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC, Canada. Columbia Univ, Coll Phys & Surg, Ctr Radiol Res, Dept Radiat Oncol, New York, NY 10032 USA. NIA, Lab Mol Gerontol, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIEHS, Lab Neurobiol, A2-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM broshr@grc.nia.nih.gov OI Sharma, Sudha/0000-0003-2765-2482 FU Intramural NIH HHS NR 59 TC 65 Z9 65 U1 1 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 MAR PY 2007 VL 27 IS 5 BP 1784 EP 1794 DI 10.1128/MCB.01620-06 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 137PW UT WOS:000244305500020 PM 17158923 ER PT J AU Klokk, TI Kurys, P Elbi, C Nagaich, AK Hendarwanto, A Slagsvold, T Chang, CY Hager, GL Saatcioglu, F AF Klokk, Tove I. Kurys, Piotr Elbi, Cem Nagaich, Akhilesh K. Hendarwanto, Anindya Slagsvold, Thomas Chang, Ching-Yi Hager, Gordon L. Saatcioglu, Fahri TI Ligand-specific dynamics of the androgen receptor at its response element in living cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CARBOXYL-TERMINAL REGIONS; NUCLEAR HORMONE-RECEPTORS; GLUCOCORTICOID-RECEPTOR; PROSTATE-CANCER; BINDING DOMAIN; IN-VIVO; TRANSCRIPTIONAL ACTIVATION; GENE-EXPRESSION; DNA-BINDING; PROGESTERONE-RECEPTOR AB Androgens have key roles in normal physiology and in male sexual differentiation as well as in pathological conditions such as prostate cancer. Androgens act through the androgen receptor (AR), which is a ligand-modulated transcription factor. Antiandrogens block AR function and are widely used in disease states, but little is known about their mechanism of action in vivo. Here, we describe a rapid differential interaction of AR with target genomic sites in living cells in the presence of agonists which coincides with the recruitment of BRM ATPase complex and chromatin remodeling, resulting in transcriptional activation. In contrast, the interaction of antagonist-bound or mutant AR with its target was found to be kinetically different: it was dramatically faster, occurred without chromatin remodeling, and resulted in the lack of transcriptional inhibition. Fluorescent resonance energy transfer analysis of wild-type AR and a transcriptionally compromised mutant at the hormone response element showed that intramolecular interactions between the N and C termini of AR play a key functional role in vivo compared to intermolecular interactions between two neighboring ARs. These data provide a kinetic and mechanistic basis for regulation of gene expression by androgens and antiandrogens in living cells. C1 Univ Oslo, Dept Mol Biosci, N-0316 Oslo, Norway. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. RP Hager, GL (reprint author), Univ Oslo, Dept Mol Biosci, Postboks 1041, N-0316 Oslo, Norway. EM hagerg@dce41.nci.nih.gov; fahris@imbv.uiono NR 85 TC 78 Z9 81 U1 1 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 MAR PY 2007 VL 27 IS 5 BP 1823 EP 1843 DI 10.1128/MCB.01297-06 PG 21 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 137PW UT WOS:000244305500023 PM 17189428 ER PT J AU Lewis-Tuffin, LJ Jewell, CM Bienstock, RJ Collins, JB Cidlowski, JA AF Lewis-Tuffin, Laura J. Jewell, Christine M. Bienstock, Rachelle J. Collins, Jennifer B. Cidlowski, John A. TI Human glucocorticoid receptor beta binds RU-486 and is transcriptionally active SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACCURATE DOCKING; GENE-EXPRESSION; IMAGING AGENTS; ISOFORM; RESISTANCE; CELLS; ASTHMA; CORTICOSTEROIDS; ANTIPROGESTINS; IDENTIFICATION AB Human glucocorticoid receptor (hGR) is expressed as two alternately spliced C-terminal isoforms, alpha and beta. In contrast to the canonical hGR alpha, hGR beta is a nucleus-localized orphan receptor thought not to bind ligand and not to affect gene transcription other than by acting as a dominant negative to hGR alpha. Here we used confocal microscopy to examine the cellular localization of transiently expressed fluorescent protein-tagged hGR beta in COS-1 and U-2 OS cells. Surprisingly, yellow fluorescent protein (YFP)-hGR beta was predominantly located in the cytoplasm and translocated to the nucleus following application of the glucocorticoid antagonist RU-486. This effect of RU-486 was confirmed with transiently expressed wild-type hGR beta. Confocal microscopy of coexpressed YFP-hGR beta and cyan fluorescent protein-hGR alpha in COS-1 cells indicated that the receptors move into the nucleus independently. Using a ligand binding assay, we confirmed that hGR beta bound RU-486 but not the hGR alpha ligand dexamethasone. Examination of the cellular localization of YFP-hGR beta in response to a series of 57 related compounds indicated that RU-486 is thus far the only identified ligand that interacts with hGR beta. The selective interaction of RU-486 with hGR beta was also supported by molecular modeling and computational docking studies. Interestingly, microarray analysis indicates that hGR beta, expressed in the absence of hGR alpha, can regulate gene expression and furthermore that occupation of hGR beta with the antagonist RU-486 diminishes that capacity despite the lack of helix 12 in the ligand binding domain. C1 NIEHS, Lab Signal Transduct, 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. NIEHS, Microarray Facil, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, POB 12233,MD F3-07, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov OI Bienstock, Rachelle/0000-0001-5228-3610 NR 38 TC 98 Z9 102 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 MAR PY 2007 VL 27 IS 6 BP 2266 EP 2282 DI 10.1128/MCB.01439-06 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 147LD UT WOS:000245003600024 PM 17242213 ER PT J AU Ying, H Araki, O Furuya, F Kato, Y Cheng, SY AF Ying, Hao Araki, Osamu Furuya, Fumlhiko Kato, Yasuhito Cheng, Sheue-Yarm TI Impaired adipogenesis caused by a mutated thyroid hormone alpha 1 receptor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID THYROID-HORMONE RECEPTOR; BROWN ADIPOSE-TISSUE; C-ERBA-BETA; MESSENGER-RNA; TRANSCRIPTIONAL ACTIVITY; GENERALIZED RESISTANCE; NUCLEAR RECEPTORS; LIGAND-BINDING; MOUSE MODEL; GENE AB Thyroid hormone (T3) is critical for growth, differentiation, and maintenance of metabolic homeostasis. Mice with a knock-in mutation in the thyroid hormone receptor alpha gene (TR alpha 1PV) were created previously to explore the roles of mutated TR alpha 1 in vivo. TR alpha 1PV is a dominant negative mutant with a frameshift mutation in the carboxyl-terminal 14 amino acids that results in the loss of T3 binding and transcription capacity. Homozygous knock-in TR alpha 1(PV/PV) mice are embryonic lethal, and heterozygous TR alpha 1(PV/+) mice display the striking phenotype of dwarfism. These mutant mice provide a valuable tool for identifying the defects that contribute to dwarfism. Here we show that white adipose tissue (WAT) mass was markedly reduced in TR alpha 1(PV/+) mice. The expression of peroxisome proliferator-activated receptor gamma (PPAR gamma), the key regulator of adipogenesis, was repressed at both mRNA and protein levels in WAT of TR alpha 1(PV/+) mice. Moreover, TR alpha 1(PV/+) acted to inhibit the transcription activity of PPAR gamma by competition with PPAR gamma for binding to PPAR gamma response elements and for heterodimerization with the retinoid X receptors. The expression of TR alpha 1PV blocked the T3-dependent adipogenesis of 3T3-L1 cells and repressed the expression of PPAR gamma. Thus, mutations of TR alpha 1 severely affect adipogenesis via cross talk with PPAR gamma signaling. The present study suggests that defects in adipogenesis could contribute to the phenotypic manifestation of reduced body weight in TR alpha 1(PV/+) mice. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural NIH HHS NR 50 TC 52 Z9 54 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2007 VL 27 IS 6 BP 2359 EP 2371 DI 10.1128/MCB.02189-06 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 147LD UT WOS:000245003600030 PM 17220280 ER PT J AU Fringer, JM Acker, MG Fekete, CA Lorsch, JR Dever, TE AF Fringer, Jeanne M. Acker, Michael G. Fekete, Christie A. Lorsch, Jon R. Dever, Thomas E. TI Coupled release of eukaryotic translation initiation factors 5B and 1A from 80S ribosomes following subunit joining SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID START-SITE SELECTION; ESCHERICHIA-COLI; RNA-BINDING; FACTOR IF2; FACTORS 1A; IN-VIVO; YEAST; COMPLEX; CODON; EIF3 AB The translation initiation GTPase eukaryotic translation initiation factor 513 (eIF5B) binds to the factor eIFIA and catalyzes ribosomal subunit joining in vitro. We show that rapid depletion of eIF5B in Saccharomyces cerevisiae results in the accumulation of eIFIA and mRNA on 40S subunits in vivo, consistent with a defect in subunit joining. Substituting Ala for the last five residues in eIF1A (eIFIA-5A) impairs eIF5B binding to eIF1A in cell extracts and to 40S complexes in vivo. Consistently, overexpression of eIF5B suppresses the growth and translation initiation defects in yeast expressing eIF1A-5A, indicating that eIF1A helps recruit eIF5B to the 40S subunit prior to subunit joining. The GTPase-deficient eIF5B-T439A mutant accumulated on 80S complexes in vivo and was retained along with eIF1A on 80S complexes formed in vitro. Likewise, eIF5B and eIFIA remained associated with 80S complexes formed in the presence of nonhydrolyzable GDPNP, whereas these factors were released from the 80S complexes in assays containing GTP. We propose that eIFIA facilitates the binding of eIF5B to the 40S subunit to promote subunit joining. Following 80S complex formation, GTP hydrolysis by eIF5B enables the release of both eIF5B and eIF1A, and the ribosome enters the elongation phase of protein synthesis. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. RP Dever, TE (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 6A-Rm B1A-03,6 Ctr Dr, Bethesda, MD 20892 USA. EM tdever@nih.gov OI Dever, Thomas/0000-0001-7120-9678; Lorsch, Jon/0000-0002-4521-4999 FU Intramural NIH HHS NR 38 TC 34 Z9 34 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 MAR PY 2007 VL 27 IS 6 BP 2384 EP 2397 DI 10.1128/MCB.02254-06 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 147LD UT WOS:000245003600032 PM 17242201 ER PT J AU Karavanova, I Vasudevan, K Cheng, J Buonanno, A AF Karavanova, Irina Vasudevan, Kuzhalini Cheng, Jun Buonanno, Andres TI Novel regional and developmental NMDA receptor expression patterns uncovered in NR2C subunit-beta-galactosidase knock-in mice SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID GLUTAMATE-RECEPTOR; MESSENGER-RNA; GLIAL-CELLS; DIFFERENTIAL DISTRIBUTION; SYNAPTIC-TRANSMISSION; HIPPOCAMPAL-NEURONS; CORTICAL-NEURONS; PURKINJE-CELLS; ION CHANNELS; RAT AB NMDA receptor "knock-in" mice were generated by inserting the nuclear P-galactosidase reporter at the NR2C subunit translation initiation site. Novel cell types and dynamic patterns of NR2C expression were identified using these mice, which were unnoticed before because reagents that specifically recognize NR2C-containing receptors are nonexistent. We identified a transition zone from NR2C-expressing neurons to astrocytes in an area connecting the retrosplenial cortex and hippocampus. We demonstrate that NR2C is expressed in a subset of S10013-positive/GFAP-negative glial cells in the striation, olfactory bulb and cerebral cortex. We also demonstrate novel areas of neuronal expression such as retrosplenial cortex, thalamus, pontine and vestibular nuclei. In addition, we show that during cerebellar development NR2C is expressed in transient caudal-rostral gradients and parasagittal bands in subsets of granule ceUs residing in the internal granular layer, further demonstrating heterogeneity of granule neurons. These results point to novel functions of NR2C-containing NMDA receptors. (c) 2006 Elsevier Inc. All rights reserved. C1 NICHHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Buonanno, A (reprint author), NICHHD, Mol Neurobiol Sect, NIH, Bldg 35,Room 2C-1000,35 Lincoln Dr, Bethesda, MD 20892 USA. EM buonanno@helix.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD000711-16] NR 57 TC 45 Z9 49 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAR PY 2007 VL 34 IS 3 BP 468 EP 480 DI 10.1016/j.mcn.2006.12.001 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 146BJ UT WOS:000244909200017 PM 17276696 ER PT J AU Kalamegham, R Sturgill, D Siegfried, E Oliver, B AF Kalamegham, Rasika Sturgill, David Siegfried, Esther Oliver, Brian TI Drosophila mojoless, a retroposed GSK-3, has functionally diverged to acquire an essential role in male fertility SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE germ cell; male sterile; gene duplication; GSK-3; adaptive evolution; retroposition; male germ line ID GLYCOGEN-SYNTHASE KINASE-3; CELL SELF-RENEWAL; ZESTE-WHITE 3; GENE-EXPRESSION; X-CHROMOSOME; DUPLICATE GENES; EVOLUTION; MELANOGASTER; ALIGNMENT; SEQUENCE AB Retroposition is increasingly recognized as an important mechanism for the acquisition of new genes. We show that a glycogen synthase kinase-3 gene, shaggy (sgg), retroposed at least 50 MYA in the Drosophila genus to generate a new gene, mojoless (mjl). We have extensively analyzed the function of mjl and examined its functional divergence from the parental gene sgg in Drosophila melanogaster. Unlike Sgg, which is expressed in many tissues of both sexes, Mjl is expressed specifically in the male germ line, where it is required for male germ line survival. Our analysis indicates that mjl has acquired a specific function in the maintenance of male germ line viability. However, it has not completely lost its ancestral biochemical function and can partially compensate for loss of the parental gene sgg when ectopically expressed in somatic cells. We postulate that mjl has undergone functional diversification and is now under stabilizing selection in the Drosophila genus. C1 NIDDKD, NIH, Lab Cellular & Dev Biol, Bethesda, MD 20892 USA. Penn State Univ, Dept Biochem Mol Biol & Microbiol, University Pk, PA 16802 USA. RP Kalamegham, R (reprint author), NIDDKD, NIH, Lab Cellular & Dev Biol, Bethesda, MD 20892 USA. EM rasika@niddk.nih.gov FU Intramural NIH HHS [Z01 DK015600-12] NR 64 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 MAR PY 2007 VL 24 IS 3 BP 732 EP 742 DI 10.1093/molbev/msl201 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 142PM UT WOS:000244662000012 PM 17179138 ER PT J AU Pybus, OG Rambaut, A Belshaw, R Freckleton, RP Drummond, AJ Holmes, EC AF Pybus, Oliver G. Rambaut, Andrew Belshaw, Robert Freckleton, Robert P. Drummond, Alexei J. Holmes, Edward C. TI Phylogenetic evidence for deleterious mutation load in RNA viruses and its contribution to viral evolution SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE virus; deleterious mutation; phylogeny ID NUCLEOTIDE SUBSTITUTIONS; PURIFYING SELECTION; POSITIVE EPISTASIS; GENE; FITNESS; ROBUSTNESS; GENOMES; HIV-1; RATES; HOST AB Populations of RNA viruses are often characterized by abundant genetic variation. However, the relative fitness of these mutations is largely unknown, although this information is central to our understanding of viral emergence, immune evasion, and drug resistance. Here we develop a phylogenetic method, based on the distribution of nonsynonymous and synonymous changes, to assess the relative fitness of polymorphisms in the structural genes of 143 RNA viruses. This reveals that a substantial proportion of the amino acid variation observed in natural populations of RNA viruses comprises transient deleterious mutations that are later purged by purifying selection, potentially limiting virus adaptability. We also demonstrate, for the first time, the existence of a relationship between amino acid variability and the phylogenetic distribution of polymorphisms. From this relationship, we propose an empirical threshold for the maximum viable deleterious mutation load in RNA viruses. C1 Univ Oxford, Dept Zool, Oxford, England. Univ Auckland, Dept Comp Sci, Auckland 1, New Zealand. Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Pybus, OG (reprint author), Univ Oxford, Dept Zool, Oxford, England. EM oliver.pybus@zoo.ox.ac.uk RI Drummond, Alexei/A-3209-2010; pybus, oliver/B-2640-2012; OI Drummond, Alexei/0000-0003-4454-2576; Pybus, Oliver/0000-0002-8797-2667; Freckleton, Robert/0000-0002-8338-864X; Rambaut, Andrew/0000-0003-4337-3707; Holmes, Edward/0000-0001-9596-3552 NR 32 TC 72 Z9 73 U1 0 U2 13 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 MAR PY 2007 VL 24 IS 3 BP 845 EP 852 DI 10.1093/molbev/msm001 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 142PM UT WOS:000244662000022 PM 17218639 ER PT J AU Wu, KM Liu, MR Li, AP Donninger, H Rao, M Jiao, XM Lisanti, MP Cvekl, A Birrer, M Pestell, RG AF Wu, Kongming Liu, Manran Li, Anping Donninger, Howard Rao, Mahadev Jiao, Xuanmao Lisanti, Michael P. Cvekl, Ales Birrer, Michael Pestell, Richard G. TI Cell fate determination factor DACH1 inhibits c-Jun-induced contact-independent growth SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ACTIVATED PROTEIN-KINASES; SERUM RESPONSE ELEMENT; ANDROGEN RECEPTOR; SIGNAL-TRANSDUCTION; CYCLE PROGRESSION; TRANSCRIPTIONAL ACTIVATION; DROSOPHILA-DACHSHUND; TUMOR-DEVELOPMENT; BINDING-PROTEIN; ACTIN DYNAMICS AB The cell fate determination factor DACH1 plays a key role in cellular differentiation in metazoans. DACH1 is engaged in multiple context-dependent complexes that activate or repress transcription. DACH1 can be recruited to DNA via the Six1/Eya bipartite transcription (DNA binding/coactivator) complex. c-Jun is a critical component of the activator protein (AP)-1 transcription factor complex and can promote contact-independent growth. Herein, DACH1 inhibited c-Jun-induced DNA synthesis and cellular proliferation. Excision of c-Jun with Cre recombinase, in c-jun(f1/f1) 3T3 cells, abrogated DACH1-mediated inhibition of DNA synthesis. c-Jun expression rescued DACH1-mediated inhibition of cellular proliferation. DACH1 inhibited induction of c-Jun by physiological stimuli and repressed c-jun target genes (cyclin A, beta-PAK, and stathmin). DACH1 bound c-Jun and inhibited AP-1 transcriptional activity. c-jun and c-fos were transcriptionally repressed by DACH1, requiring the conserved N-terminal (dac and ski/sno [DS]) domain. c-fos transcriptional repression by DACH1 requires the SRF site of the c-fos promoter. DACH1 inhibited c-jun transactivation through the delta domain of c-Jun. DACH1 coprecipitated the histone deacetylase proteins (HDAC1, HDAC2, and NCoR), providing a mechanism by which DACH1 represses c-Jun activity through the conserved delta domain. An oncogenic v-Jun deleted of the delta domain was resistant to DACH1 repression. Collectively, these studies demonstrate a novel mechanism by which DACH1 blocks c-Jun-mediated contact-independent growth through repressing the c-Jun delta domain. C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Albert Einstein Coll Med, Dept Ophthalmol & Visual Sci & Mol Genet, New York, NY 10461 USA. RP Pestell, RG (reprint author), Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA. EM richard.pestell@jefferson.edu RI Cvekl, Ales/B-2427-2013; Lisanti, Michael/C-6866-2013 FU NCI NIH HHS [R01 CA070896, P30 CA056036, P30CA56036, R01 CA075503, R01 CA086072, R01CA70896, R01CA75503, R01CA86072]; NEI NIH HHS [EY12200, R01 EY012200] NR 69 TC 36 Z9 39 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR PY 2007 VL 18 IS 3 BP 755 EP 767 DI 10.1091/mbc.E06-09-0793 PG 13 WC Cell Biology SC Cell Biology GA 143YE UT WOS:000244761500008 PM 17182846 ER PT J AU Shankavaram, UT Reinhold, WC Nishizuka, S Major, S Morita, D Chary, KK Reimers, MA Scherf, U Kahn, A Dolginow, D Cossman, J Kaldjian, EP Scudiero, DA Petricoin, E Liotta, L Lee, JK Weinstein, JN AF Shankavaram, Uma T. Reinhold, William C. Nishizuka, Satoshi Major, Sylvia Morita, Daisaku Chary, Krishna K. Reimers, Mark A. Scherf, Uwe Kahn, Ari Dolginow, Douglas Cossman, Jeffrey Kaldjian, Eric P. Scudiero, Dominic A. Petricoin, Emanuel Liotta, Lance Lee, Jae K. Weinstein, John N. TI Transcript and protein expression profiles of the NCI-60 cancer cell panel: an integromic microarray study SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ANTICANCER DRUG SCREEN; GENE-EXPRESSION; MOLECULAR PHARMACOLOGY; MESSENGER-RNA; LINES; DISCOVERY; CHEMOSENSITIVITY; DIFFERENTIATION; INFORMATION; RESISTANCE AB To evaluate the utility of transcript profiling for prediction of protein expression levels, we compared profiles across the NCl-60 cancer cell panel, which represents nine tissues of origin. For that analysis, we present here two new NCl-60 transcript profile data sets (A based on Affymetrix HG-U95 and HG-U133A chips; Affymetrix, Santa Clara, CA) and one new protein profile data set (based on reverse-phase protein lysate arrays). The data sets are available online at http://discover.nci.nih.gov in the CelllMiner program package. Using the new transcript data in combination with our previously published cDNA array and Affymetrix HU6800 data sets, we first developed a "consensus set" of transcript profiles based on the four different microarray platforms. Using that set, we found that 65% of the genes showed statistically significant transcript-protein correlation, and the correlations were generally higher than those reported previously for panels of mammalian cells. Using the predictive analysis of microarray nearest shrunken centroid algorithm for functional prediction of tissue of origin, we then found that (a) the consensus mRNA set did better than did data from any of the individual mRNA platforms and (b) the protein data seemed to do somewhat better (P = 0.027) on a gene-for-gene basis in this particular study than did the consensus mRNA data, but both did well. Analysis based on the Gene Ontology showed protein levels of structure-related genes to be well predicted by mRNA levels (mean r = 0.71). Because the transcript-based technologies are more mature and are currently able to assess larger numbers of genes at one time, they continue to be useful, even when the ultimate aim is information about proteins. C1 NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Off Informat Technol, Rockville, MD 20857 USA. Gene Log Inc, Gaithersburg, MD USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21701 USA. George Mason Univ, Manassas, VA USA. RP Weinstein, JN (reprint author), NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM weinstein@dtpax2.ncifcrf.gov FU Intramural NIH HHS NR 41 TC 198 Z9 202 U1 4 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAR PY 2007 VL 6 IS 3 BP 820 EP 832 DI 10.1158/1535-7163.MCT-06-0650 PG 13 WC Oncology SC Oncology GA 148NO UT WOS:000245082100004 PM 17339364 ER PT J AU Tryndyak, VP Kovalchuk, O Muskhelishvili, L Montgomery, B Rodriguez-Juarez, R Melnyk, S Ross, SA Beland, FA Pogribny, IP AF Tryndyak, Volodymyr P. Kovalchuk, Olga Muskhelishvili, Levan Montgomery, Beverly Rodriguez-Juarez, Rocio Melnyk, Stepan Ross, Sharon A. Beland, Frederick A. Pogribny, Igor P. TI Epigenetic reprogramming of liver cells in tamoxifen-induced rat hepatocarcinogenesis SO MOLECULAR CARCINOGENESIS LA English DT Article DE tamoxifen; rat; hepatocarcinogenesis; DNA hypomethylation; cell proliferation ID DNA-POLYMERASE-BETA; HISTONE METHYLTRANSFERASES; HEPATOCELLULAR-CARCINOMA; HIGH-FREQUENCY; BREAST-CANCER; AURORA-A; METHYLATION; PROLIFERATION; DEFICIENCY; EXPRESSION AB Tamoxifen, a nonsteroidal anti-estrogen, is a potent genotoxic hepatocarcinogen in rats; with both tumor initiating and promoting properties. Recently it has been demonstrated that genotoxic carcinogens, in addition to exerting genotoxic effects, often cause epigenetic alterations and these induced epigenetic changes may play important mechanistic role in carcinogenesis. In the present study, we investigated the role of tamoxifen-induced epigenetic changes in hepatocarcinogenic process. The results of the study showed that exposure of female F344 rats to tamoxifen resulted in progressive loss of CpG methylation in regulatory sequences of long interspersed nucleotide elements (LINE-1) and prominent increase in expression of LINE-1 elements and c-myc proto-oncogene. The accumulation of tamoxifen-induced DNA lesions was accompanied by the decreased level of Rad51, Ku70, and DNA polymerase beta (Pol beta) proteins that play a crucial role in maintenance of genomic stability. Furthermore, feeding rats with tamoxifen-containing diet led to increased regenerative cell proliferation, as indicated by the increased level of Ki67 and proliferating cell nuclear antigen (PCNA) proteins. These data indicate that exposure of animals to genotoxic hepatocarcinogen tamoxifen led to early phenotypical alterations in livers characterized by emergence of epigenetically reprogrammed cells with a specific cancer-related epigenetic phenotype prior to tumor formation. (c) 2007 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 56 TC 29 Z9 32 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 2007 VL 46 IS 3 BP 187 EP 197 DI 10.1002/mc.20263 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 141RX UT WOS:000244597500003 PM 17219426 ER PT J AU Luo, SJ Cai, QX David, VA Zhang, L Martelli, P Lim, NTL Ferrand, N Chin, SC Gaubert, P Ramos, MJ O'Brien, SJ Antunes, A Johnson, WE AF Luo, Shu-Jin Cai, Qing-Xiu David, Victor A. Zhang, Li Martelli, Paolo Lim, Norman T-L. Ferrand, Nuno Chin, Shih-Chien Gaubert, Philippe Ramos, Maria Joao O'Brien, Stephen J. Antunes, Agostinho Johnson, Warren E. TI Isolation and characterization of microsatellite markers in pangolins (Mammalia, Pholidota, Manis spp.) SO MOLECULAR ECOLOGY NOTES LA English DT Article DE Manis; microsatellite; pangolin; Pholidota AB Thirty-four polymorphic dinucleotide microsatellite loci were developed in the Malayan pangolin Manis javanica. Of the 34 markers, 32 and 18 were also amplified, respectively, in the Chinese pangolin (Manis pentadactyla) and the African tree pangolin (Manis tricuspis). Analysis of 24 Malayan, 12 Chinese and 2 African tree pangolins showed high levels of variability (heterozygosity ranging from 0.321 to 0.708). These are the first available microsatellite markers in Pholidota and will be an invaluable tool for evolutionary and conservation genetic studies in pangolins. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. Univ Minnesota, Dept Fisheries Wildlife & Conservat Biol, St Paul, MN 55108 USA. Beijing Normal Univ, Key Lab Biodivers Sci & Ecol Engn, Minist Educ, Beijing 100875, Peoples R China. Ocean Pk, Aberdeen, Hong Kong, Peoples R China. Natl Univ Singapore, Dept Biol Sci, Systemat & Ecol Lab, Singapore 117543, Singapore. UP, CIBIO, Ctr Invest Biodivers & Recursos Genet, P-4485661 Vairao, Portugal. Univ Porto, Fac Ciencias, Dept Zool & Anthropol, P-4099002 Oporto, Portugal. Taipei Zoo, Taipei 1168, Taiwan. Inst Rech Dev, UR136, F-45072 Orleans 2, France. Univ Porto, Fac Ciencias, Dept Quim, REQUIMTE, P-4169007 Oporto, Portugal. RP Antunes, A (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM aantunes@ncifcrf.gov; johnsonw@mail.ncifcrf.gov RI MNHN/CNRS/UPMC/IRD, UMR BOREA/B-2312-2012; REQUIMTE, AL/H-9106-2013; REQUIMTE, TCB/M-6190-2013; REQUIMTE, UCIBIO/N-9846-2013; Ferrand, Nuno /E-6085-2014; Scientific output, CIIMAR/E-5122-2012; Ramos, Maria/D-6183-2013; Johnson, Warren/D-4149-2016; Lim, Norman/P-4940-2016; OI Ferrand, Nuno /0000-0002-2408-4195; Scientific output, CIIMAR/0000-0001-6270-2153; Ramos, Maria/0000-0002-7554-8324; Johnson, Warren/0000-0002-5954-186X; Lim, Norman/0000-0001-7350-6975; Gaubert, Philippe/0000-0002-1375-9935 NR 7 TC 2 Z9 5 U1 4 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1471-8278 J9 MOL ECOL NOTES JI Mol. Ecol. Notes PD MAR PY 2007 VL 7 IS 2 BP 269 EP 272 DI 10.1111/j.1471-8286.2006.01577.x PG 4 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 140QL UT WOS:000244520600024 ER PT J AU Waits, LP Buckley-Beason, VA Johnson, WE Onorato, D McCarthy, T AF Waits, Lisette P. Buckley-Beason, Valerie A. Johnson, Warren E. Onorato, Dave McCarthy, Tom TI A select panel of polymorphic microsatellite loci for individual identification of snow leopards (Panthera uncia) SO MOLECULAR ECOLOGY NOTES LA English DT Article DE microsatellites; noninvasive genetic sampling; Panthera uncia; snow leopard ID ESTIMATING POPULATION-SIZE; CAT FELIS-CATUS; MOLECULAR TRACKING; DNA; FECES; BEARS AB Snow leopards (Panthera uncia) are elusive endangered carnivores found in remote mountain regions of Central Asia. New methods for identifying and counting snow leopards are needed for conservation and management efforts. To develop molecular genetic tools for individual identification of hair and faecal samples, we screened 50 microsatellite loci developed for the domestic cat (Felis catus) in 19 captive snow leopards. Forty-eight loci were polymorphic with numbers of alleles per locus ranging from two to 11. The probability of observing matching genotypes for unrelated individuals (2.1 x 10(-11)) and siblings (7.5 x 10(-5)) using the 10 most polymorphic loci was low, suggesting that this panel would easily discriminate among individuals in the wild. C1 Univ Idaho, Dept Fish & Wildlife Resources, Moscow, ID 83844 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Int Snow Leopard Trust, Seattle, WA 98103 USA. RP Waits, LP (reprint author), Univ Idaho, Dept Fish & Wildlife Resources, Moscow, ID 83844 USA. EM lwaits@uidaho.edu RI Johnson, Warren/D-4149-2016 OI Johnson, Warren/0000-0002-5954-186X NR 16 TC 6 Z9 10 U1 3 U2 18 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1471-8278 J9 MOL ECOL NOTES JI Mol. Ecol. Notes PD MAR PY 2007 VL 7 IS 2 BP 311 EP 314 DI 10.1111/j.1471-8286.2006.01591.x PG 4 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 140QL UT WOS:000244520600036 ER PT J AU Klootwijk, E Manoli, I Galeano, B Sun, MS Ciccone, C Bond, W Darvish, D Krasnewich, D Gahl, WA Huizing, M AF Klootwijk, E. Manoli, I. Galeano, B. Sun, M. S. Ciccone, C. Bond, W. Darvish, D. Krasnewich, D. Gahl, W. A. Huizing, M. TI N-Acetylmannosamine treatment rescues GNE knock-in mice from severe neonatal glomerular hematuria and podocytopathy: Insights for hereditary inclusion body myopathy. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 NHGRI, MGB, NIH, Bethesda, MD 20892 USA. HIBM Res Grp, Encino, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 241 EP 242 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500017 ER PT J AU Lukose, L Markello, T AF Lukose, L. Markello, T. TI Acute presentation of beta-ketothiolase deficiency: An illustrative case for glucose administration in pediatric advanced life support (PALS). SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Childrens Natl Med Ctr, Div Med Genet & Metab, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 242 EP 242 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500018 ER PT J AU Adams, DR Sloan, JL Gropman, AL Baker, EH Venditti, CP AF Adams, D. R. Sloan, J. L. Gropman, A. L. Baker, E. H. Venditti, C. P. TI Long term follow-up of survivors of "metabolic stroke" associated with methylmalonic aciduria. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 246 EP 246 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500023 ER PT J AU Blech-Hermoni, Y Goker-Alpan, O Goldin, E LaMarca, ME Sidransky, E AF Blech-Hermoni, Y. Goker-Alpan, O. Goldin, E. LaMarca, M. E. Sidransky, E. TI Localization of glucocerebrosidase and alpha-synuclein in hippocmpal neurons from a gba null mouse. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 MA 9 BP 247 EP 248 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500029 ER PT J AU Forit-Montgomery, EE Ocak, I Choyke, P Heller, T Kleta, R Edwards, H Mohan, P Guay-Woodford, L Daryanani, K Quezado, Z Gahl, WA Gunay-Aygun, M AF Forit-Montgomery, Esperanza E. Ocak, Iclal Choyke, Peter Heller, Theo Kleta, Robert Edwards, Hailey Mohan, Parvathi Guay-Woodford, Lisa Daryanani, Kailash Quezado, Zenaide Gahl, William A. Gunay-Aygun, Metal TI Autosomal dominant polveystic kidney disease (ADPKD) mimicking autosomal recessive polycystic kidney disease (ARPKD) with congenital hepatic fibrosis (CHF) and portal hypertension (PH). SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Univ Alabama, Birmingham, AL USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 251 EP 251 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500040 ER PT J AU Gropman, AL O'Brien, K Sloan, J Baker, E Venditti, CP AF Gropman, Andrea L. O'Brien, Kevin Sloan, Jennifer Baker, Eva Venditti, Charles P. TI Neuroimaging findings post renal transplant in an adult with cobalamin-responsive methylmalonic academia. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. George Washington Univ Hlth Sci, Washington, DC USA. NIH, Clin Ctr Radiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 252 EP 252 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500045 ER PT J AU Held, PK Westbroek, W Helip-Wooley, A Ayub, M Huizing, M Gahl, WA AF Held, P. K. Westbroek, W. Helip-Wooley, A. Ayub, M. Huizing, M. Gahl, W. A. TI Hermansky pudlak proteins interact within biogenesis of lysosome-related organelle complex-2. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 NHGRI, Sect Human Biochem Genet, Med Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 253 EP 254 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500049 ER PT J AU Hruska, KS LaMarca, ME Ziegler, SG Stubblefield, B Portnoy, ME Green, ED Sidransky, E AF Hruska, K. S. LaMarca, M. E. Ziegler, S. G. Stubblefield, B. Portnoy, M. E. Green, E. D. Sidransky, E. TI Analysis of conserved regulatory elements in the glucocerebrosidase gene locus. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 254 EP 254 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500052 ER PT J AU Huizing, M Klootwijk, E Savelkou, PJ Ciccone, C Krasnewich, D Gahl, WA AF Huizing, M. Klootwijk, E. Savelkou, P. J. Ciccone, C. Krasnewich, D. Gahl, W. A. TI Allele-specific silencing of the dominant disorder sialuria by small interfering RNA. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 254 EP 255 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500053 ER PT J AU Kayser, MA Suwannarat, P Introne, W Austin, HA Tuchman, M Tinloy, B Klein, C O'Brien, K Bernardini, I Gahl, WA Kleta, R AF Kayser, Michael A. Suwannarat, Pim Introne, Wendy Austin, Howard A. Tuchman, Maya Tinloy, Bradford Klein, Cornelia O'Brien, K. Bernardini, Isa Gahl, William A. Kleta, Robert TI Can a common SNP in the organic anion transporter MRP4/ABCC4 influence homogentisic acid secretion and the severity of ochronosis in alkaptonuria? SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 NHGRI, MGB, SHBG, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 255 EP 255 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500054 ER PT J AU Askari, H Kaneski, CR Semino-Mora, C Ang, A Wustman, B Schiffmann, R AF Askari, H. Kaneski, C. R. Semino-Mora, C. Ang, A. Wustman, B. Schiffmann, R. TI Cellular and tissue localization of globotriaosyleeramide in Fabry disease. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 NINDS, Dev & Metab Neurol Branco, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Lab Gastrointestinal & Liver Studies, Bethesda, MD 20814 USA. HistoRx Inc, New Haven, CT USA. Amicus Therapeut Inc, Cranbury, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 261 EP 261 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500074 ER PT J AU Wassif, CA Brownson, KE Wilson, WK Starost, MF Porter, FD AF Wassif, C. A. Brownson, K. E. Wilson, W. K. Starost, M. F. Porter, F. D. TI HEM dysplasia and ichthyosis are laminopathies rather than inborn errors of cholesterol synthesis. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) CY MAR 25-28, 2007 CL Nashville, TN SP Soc Inherited Metabol Disorders C1 NICHD, HDB, Bethesda, MD USA. Rice Univ, Houston, TX 77251 USA. NIH, OD, ORS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 264 EP 264 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500084 ER PT J AU Murray, GJ Anver, MR Kennedy, MA Quirk, JM Schiffmann, R AF Murray, Gary J. Anver, Miriam R. Kennedy, Maureen A. Quirk, Jane M. Schiffmann, Raphael TI Cellular and tissue distribution of intravenously administered agalsidase alfa SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE enzyme replacement therapy; lysosomal storage disease; Fabry disease; immunohistochemistry; alpha-Galactosidase A ID ENZYME REPLACEMENT THERAPY; GROWTH FACTOR-II; FABRY-DISEASE; PROTEIN TRANSDUCTION; NERVE-FIBERS; RAT-TISSUES; GALACTOSIDASE; MICE; SAFETY; RECEPTORS AB alpha-Galactosidase A is the lysosomal hydrolase that is deficient in patients with Fabry disease. Intravenous infusion of agalsidase alfa, a preparation of alpha-Galactosidase A, is used for enzyme replacement therapy (ERT) in patients with Fabry disease. Although ERT appears to show some beneficial effects, most patients show only a modest response. We investigated using immunohistochemistry the relative tissue and cellular distribution of agalsidase alfa after a single intravenous injection in a mouse knockout model of Fabry disease. Specific immunostaining for agalsidase alfa was found only in liver, kidney, heart, testes, adrenal gland, spleen and bone marrow. There was no difference in distribution of the infused enzyme distribution among tissues sampled 4, 24, and 48 h post-injection. The intracellular localization of immunopositivity varied considerably between organs with vascular endothelium being the most commonly positive site. alpha-Galactosidase A specific activity in tissue homogenates matched the relative extent of agalsidase alfa immunostaining distribution in the same organs. We conclude that intravenously injected agalsidase alfa has a very heterogeneous systemic distribution using all immunostaining technique. Published by Elsevier Inc. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick Inc, Pathol Histotechnol Lab, Frederick, MD 21701 USA. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM RS4e@nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO-12400]; NINDS NIH HHS [Z01 NS002984-07] NR 30 TC 22 Z9 22 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2007 VL 90 IS 3 BP 307 EP 312 DI 10.1016/j.ymgme.2006.11.008 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 149XF UT WOS:000245179500094 PM 17188539 ER PT J AU Nagashima, T Maruyama, T Furuya, M Kajitani, T Uchida, H Masuda, H Ono, M Arase, T Ozato, K Yoshimura, Y AF Nagashima, Takashi Maruyama, Tetsuo Furuya, Masataka Kajitani, Takashi Uchida, Hiroshi Masuda, Hirotaka Ono, Masanori Arase, Toru Ozato, Keiko Yoshimura, Yasunori TI Histone acetylation and subcellular localization of chromosomal protein BRD4 during mouse oocyte meiosis and mitosis SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE BRD4; bromodomain; histone acetylation; meiosis; oocyte ID PAPILLOMAVIRUS E2 PROTEIN; BROMODOMAIN PROTEIN; PREIMPLANTATION DEVELOPMENT; DEPENDENT TRANSCRIPTION; MITOTIC CHROMOSOMES; CHROMATIN-STRUCTURE; MAMMALIAN OOCYTES; GENE-EXPRESSION; H4 ACETYLATION; P-TEFB AB Most specific and general transcription factors (TFs) become dissociated from hypoacetylated mitotic chromosomes, which may contribute to transcriptional silencing during mitosis. Only some chromosomal proteins, such as bromodomain containing protein 4 (BRD4), have a potential to associate with mitotic chromosomes in a histone acetylation-dependent manner. It remains to be fully demonstrated whether similar displacement of nuclear factors takes place in meiotic oocytes whose chromosomes become globally deacetylated. To address this, we here examined the subcellular localization of BRD4 in conjunction with the acetylation status of histones in mouse oocytes. Immunofluorescence studies revealed that BRD4 preferentially localized to mitotic chromosomes in early embryos. In contrast, not only endogenous BRD4 but also exogenous BRD4 overexpressed by mRNA microinjection were displaced from meiotic chromosomes whose histones H3 and H4 were deacetylated. Treatment with trichostatin A (TSA), an inhibitor of histone deacetylases, induced histone hyperacetylation of meiotic chromosomes from which endogenous BRD4, however, remained dissociated. Finally, meiotic chromosomal localization of BRD4 could be achieved by BRD4 overexpression together with TSA-induced histone hyperacetylation. These results indicate that, unlike mitosis, histone acetylation is necessary but not sufficient for chromosomal localization of BRD4 during meiosis, suggesting that meiotic oocytes may have additional mechanism(s) for displacement of chromosomal proteins and TFs. C1 Keio Univ, Sch Med, Dept Obstet & Gynecol, Tokyo 1608582, Japan. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Maruyama, T (reprint author), Keio Univ, Sch Med, Dept Obstet & Gynecol, 35 Shinanomachi, Tokyo 1608582, Japan. EM tetsuo@sc.itc.keio.ac.jp OI Ono, Masanori/0000-0001-9249-6813 NR 45 TC 19 Z9 20 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD MAR PY 2007 VL 13 IS 3 BP 141 EP 148 DI 10.1093/molehr/gal115 PG 8 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 142PP UT WOS:000244662300001 PM 17267518 ER PT J AU Wang, HS Clarke, SH AF Wang, Hongsheng Clarke, Stephen H. TI Association of the pre-B cell receptor (BCR) expression level with the quality of pre-BII cell differentiation reveals hierarchical pre-BCR function SO MOLECULAR IMMUNOLOGY LA English DT Article DE IL-7; hemokinin 1; V(H)12; positive selection ID IMMUNOGLOBULIN HEAVY-CHAINS; SURROGATE LIGHT-CHAIN; MOUSE BONE-MARROW; ALLELIC EXCLUSION; D-MU; ENDOPLASMIC-RETICULUM; DEFICIENT MICE; MARGINAL ZONE; ACTIVATION; GENE AB The expression of a pre-B cell receptor (pre-BCR) is required for allelic exclusion and pre-BII cell differentiation. V-H 12 mu H chains are unusual in that they form pre-BCRs and mediate allelic exclusion, but most cannot drive pre-BII cell differentiation. To explain this paradox, we examined pre-BCR functions and pre-BII cell differentiation in mice expressing mu H chain transgenes encoding a B cell-permissible V(H)12 mu H chain (designated 10/G4(6-1)), and a non-permissible V(H)12 mu H chain (designated 8/G0). Compared with 10/G4 pre-BCRs, 8/G0 pre-BCRs are expressed at low levels on the cell surface. 8/G0 pre-BCRs mediate allelic exclusion, but 8/G0 pre-BII cells are defective in proliferation and expression of survival factors Bcl-2, BCI-X-L and hemokinin 1 (HK1). Increasing 8/G0 mu H chain production restores HKI transcription and improves proliferation of pre-BII cells as well as later stage B cell development. These data reveal a hierarchy of pre-BCR function that determines the development and plasticity of early B cells. (c) 2006 Elsevier Ltd. All riahts reserved. C1 Univ N Carolina, Dept Immunol & Microbiol, Chapel Hill, NC 27599 USA. NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. RP Clarke, SH (reprint author), Univ N Carolina, Dept Immunol & Microbiol, CB7290,804 MEJB, Chapel Hill, NC 27599 USA. EM shl@med.unc.edu FU NIAID NIH HHS [AI29576, AI43587] NR 38 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAR PY 2007 VL 44 IS 7 BP 1765 EP 1774 DI 10.1016/j.molimm.2006.07.301 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 129WB UT WOS:000243759700033 PM 17007932 ER PT J AU Morley, SC Sung, J Sun, GP Martelli, MP Bunnell, SC Bierer, BE AF Morley, S. Celeste Sung, Janice Sun, Guang-Ping Martelli, Maria Paola Bunnell, Stephen C. Bierer, Barbara E. TI Gelsolin overexpression alters actin dynamics and tyrosine phosphorylation of lipid raft-associated proteins in Jurkat T cells SO MOLECULAR IMMUNOLOGY LA English DT Article DE gelsolin; T cells; signal transduction; cytoskeleton; lipid rafts ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; IMMUNE SYNAPSE FORMATION; SOLUBLE F-ACTIN; SIGNAL-TRANSDUCTION; IMMUNOLOGICAL SYNAPSE; ANTIGEN RECEPTOR; CYTOSKELETON; ACTIVATION; LYMPHOCYTES; POLYMERIZATION AB Upon T cell receptor engagement, both the actin cytoskeleton and substrates of tyrosine phosphorylation are remodeled to create a signaling complex at the interface of the antigen-presenting cell and responding T cell. While T cell signaling has been shown to regulate actin reorganization, the mechanisms by which changes in actin dynamics affect early T cell signaling have not been fully explored. Using gelsolin, an actin-binding protein with capping and severing activities, and latrunculin, an actin-depolymerizing agent, we have further investigated the interplay between actin dynamics and the regulation of T cell signaling. Overexpression of gelsolin altered actin dynamics in Jurkat T cells, and alteration of actin dynamics correlated with dysregulation of tyrosine phosphorylation of raft-associated substrates. This perturbation of tyrosine phosphorylation was correlated with inhibition of activation-dependent signaling pathways regulating Erk-1/2 phosphorylation, NF-AT transcriptional activation and IL-2 production. Modification of actin by the depolymerizing agent latrunculin also altered the tyrosine phosphorylation patterns of proteins associated with lipid rafts, and pre-treatment with latrunculin inhibited anti-CD3 mAb-mediated NF-AT activation. Thus, our data indicate that actin cytoskeletal dynamics modulate the tyrosine phosphorylation of raft-associated proteins and subsequent downstream signal transduction. (c) 2006 Elsevier Ltd. All rights reserved. C1 Natl Heart Lund & Blood Inst, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Morley, SC (reprint author), St Louis Childrens Hosp, Div Pediat Infect Dis, 1 Childrens Pl, St Louis, MO 63110 USA. EM morley_c@kids.wustl.edu RI Martelli, Maria Paola/I-5618-2012 FU Intramural NIH HHS; NCI NIH HHS [T32 CA009141, T32 CA009141-23, T32 CA009141-24, T32 CA09141] NR 45 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAR PY 2007 VL 44 IS 9 BP 2469 EP 2480 DI 10.1016/j.molimm.2006.09.024 PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 143YA UT WOS:000244761100033 PM 17178161 ER PT J AU Bauer, B Hartz, AMS Miller, DS AF Bauer, Bjorn Hartz, Anika M. S. Miller, David S. TI Tumor necrosis factor alpha and endothelin-1 increase P-glycoprotein expression and transport activity at the blood-brain barrier SO MOLECULAR PHARMACOLOGY LA English DT Article ID NF-KAPPA-B; RAT-BRAIN; SIGNAL-TRANSDUCTION; CNS INFLAMMATION; OXIDATIVE STRESS; FACTOR RECEPTORS; DRUG-RESISTANCE; PROXIMAL TUBULE; UP-REGULATION; IN-VIVO AB The ATP-driven drug efflux pump, P-glycoprotein, is a critical and selective element of the blood-brain barrier and a primary impediment to pharmacotherapy of central nervous system (CNS) disorders. Thus, an understanding of how P-glycoprotein function is regulated has the potential to improve CNS therapy. We recently demonstrated rapid ( minutes) and reversible inactivation of P-glycoprotein in rat brain capillaries signaled through tumor necrosis factor-alpha (TNF-alpha) and endothelin-1 (ET-1), components of the brain's innate immune response. In this study, we examined the longer-term consequences of continuous exposure of rat brain capillaries to low levels of TNF-alpha and ET-1. Exposing brain capillaries to TNF-alpha or ET-1 caused a rapid decrease in P-glycoprotein transport activity with no change in transporter protein expression. This was followed by a 2- to 3-h plateau at the low activity level and then by a sharp increase in both transport activity and protein expression. After 6 h, transport activity and transporter protein expression was double that of control samples. TNF-alpha signaled through TNFR1, which in turn caused ET release and action through ET A and ET B receptors, nitric-oxide synthase, protein kinase C and nuclear factor-kappa B (NF-kappa B) and finally increased P-glycoprotein expression and transport activity. Assuming similar effects occur in vivo, the present results imply a tightening of the selective blood-brain barrier with chronic inflammation and thus reduced efficacy of CNS-acting drugs that are P-glycoprotein substrates. Moreover, involvement of NF-kappa B raises the possibility that other effectors acting through this transcription factor may have similar effects on this key blood-brain barrier transporter. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Miller, DS (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, 111 TW Alexander Dr,POB 12233,MD F2-03, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov FU Intramural NIH HHS NR 40 TC 152 Z9 158 U1 2 U2 8 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 MAR PY 2007 VL 71 IS 3 BP 667 EP 675 DI 10.1124/mol.106.029512 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 137KB UT WOS:000244290400005 PM 17132686 ER PT J AU Johnson, AA Marchand, C Patil, SS Costi, R Di Santo, R Burke, TR Pommier, Y AF Johnson, Allison A. Marchand, Christophe Patil, Sachindra S. Costi, Roberta Di Santo, Roberto Burke, Terrence R., Jr. Pommier, Yves TI Probing HIV-1 integrase inhibitor binding sites with position-specific integrase-DNA cross-linking assays SO MOLECULAR PHARMACOLOGY LA English DT Article ID VIRUS TYPE-1 INTEGRASE; BETA-DIKETO ACIDS; ACTIVE-SITE; CATALYTIC DOMAIN; STRAND TRANSFER; DRUG DESIGN; VIRAL-DNA; REPLICATION; RESISTANCE; PROTEIN AB HIV-1 integrase binds site-specifically to the ends of the viral cDNA. We used two HIV-1 integrase-DNA cross-linking assays to probe the binding sites of integrase inhibitors from different chemical families and with different strand transfer selectivities. The disulfide assay probes cross-linking between the integrase residue 148 and the 5'-terminal cytosine of the viral cDNA, and the Schiff base assay probes cross-linking between an integrase lysine residue and an abasic site placed at selected positions in the viral cDNA. Cross-linking interference by eight integrase inhibitors shows that the most potent cross-linking inhibitors are 3'-processing inhibitors, indicating that cross-linking assays probe the donor viral cDNA ( donor binding site). In contrast, strand transfer-selective inhibitors provide weak cross-linking interference, consistent with their binding to a specific acceptor ( cellular DNA) site. Docking and crystal structure studies illustrate specific integrase-inhibitor contacts that prevent cross-linking formation. Four inhibitors that prevented Schiff base cross-linking to the conserved 3'-terminal adenine position were examined for inhibition at various positions within the terminal 21 bases of the viral cDNA. Two of them selectively inhibited upper strand cross-linking, whereas the other two had a more global effect on integrase-DNA binding. These findings have implications for elucidating inhibitor binding sites and mechanisms of action. The cross-linking assays also provide clues to the molecular interactions between integrase and the viral cDNA. C1 NIH, Mol Pharmacol Lab, Canc Res Ctr, Natl Canc Inst, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21701 USA. Univ Roma La Sapienza, Inst Pasteur, Fdn Cenci Bolognetti, Dipartimento Studi Farmaceut, Rome, Italy. RP Pommier, Y (reprint author), NIH, Mol Pharmacol Lab, Canc Res Ctr, Natl Canc Inst, Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Burke, Terrence/N-2601-2014; Marchand, Christophe/D-8559-2016; OI COSTI, Roberta/0000-0002-1314-9029; Di Santo, Roberto/0000-0002-4279-7666 FU Intramural NIH HHS NR 41 TC 23 Z9 25 U1 0 U2 4 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 MAR PY 2007 VL 71 IS 3 BP 893 EP 901 DI 10.1124/mol.106.030817 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 137KB UT WOS:000244290400029 PM 17172465 ER PT J AU Smolka, MN Buhler, M Schumann, G Klein, S Hu, XZ Moayer, M Zimmer, A Wrase, J Flor, H Mann, K Braus, DF Goldman, D Heinz, A AF Smolka, M. N. Buehler, M. Schumann, G. Klein, S. Hu, X-Z Moayer, M. Zimmer, A. Wrase, J. Flor, H. Mann, K. Braus, D. F. Goldman, D. Heinz, A. TI Gene-gene effects on central processing of aversive stimuli SO MOLECULAR PSYCHIATRY LA English DT Article DE fMRI; COMT; 5-HTT; genetics; emotion; amygdala ID CATECHOL-O-METHYLTRANSFERASE; SEROTONIN TRANSPORTER; HUMAN AMYGDALA; FUNCTIONAL POLYMORPHISM; BIPOLAR DISORDER; IN-VIVO; GENOTYPE; COMT; DOPAMINE; 5-HTTLPR AB Emotional reactivity and regulation are fundamental to human behavior. As inter-individual behavioral variation is affected by a multitude of different genes, there is intense interest to investigate gene - gene effects. Functional sequence variation at two genes has been associated with response and resiliency to emotionally unpleasant stimuli. These genes are the catechol-O-methyltransferase gene ( COMT Val(158)Met) and the regulatory region (5-HTTLPR) of the serotonin transporter gene. Recently, it has been proposed that 5-HTT expression is not only affected by the common S/L variant of 5-HTTLPR but also by an A to G substitution. Using functional magnetic resonance imaging, we assessed the effects of COMT Val(158)Met and both 5-HTT genotypes on brain activation by standardized affective visual stimuli ( unpleasant, pleasant, and neutral) in 48 healthy subjects. Based on previous studies, the analysis of genotype effects was restricted to limbic brain areas. To determine allele-dose effects, the number of COMT Met(158) alleles (i.e., lower activity of COMT) and the number of 5-HTT low expressing alleles ( S and G) was correlated with the blood oxygen level-dependent ( BOLD) response to pleasant or unpleasant stimuli compared to neutral stimuli. We observed an additive effect of COMT and both 5-HTT polymorphisms, accounting for 40% of the inter-individual variance in the averaged BOLD response of amygdala, hippocampal and limbic cortical regions elicited by unpleasant stimuli. Effects of 5-HTT and COMT genotypes did not affect brain processing of pleasant stimuli. These data indicate that functional brain imaging may be used to assess the interaction of multiple genes on the function of neuronal networks. C1 Univ Med Berlin, Dept Psychiat & Psychotherapy, Charite, D-10117 Berlin, Germany. Tech Univ Dresden, Dept Psychiat, D-8027 Dresden, Germany. Cent Inst Mental Hlth, D-6800 Mannheim, Germany. Univ Tubingen, Grad Sch Neural & Behav Sci, Tubingen, Germany. Kings Coll London, Inst Psychiat, Sect Addict Biol, London WC2R 2LS, England. NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. Univ Hamburg, Dept Psychiat, Hamburg, Germany. RP Heinz, A (reprint author), Univ Med Berlin, Dept Psychiat & Psychotherapy, Charite, Charite Campus Mitte,Schumannstr 20-21, D-10117 Berlin, Germany. EM andreas.heinz@charite.de RI Smolka, Michael/B-4865-2011; Vollstadt-Klein, Sabine/C-6744-2012; Goldman, David/F-9772-2010; OI Smolka, Michael/0000-0001-5398-5569; Vollstadt-Klein, Sabine/0000-0002-6210-672X; Goldman, David/0000-0002-1724-5405; Flor, Herta/0000-0003-4809-5398 NR 68 TC 119 Z9 121 U1 2 U2 8 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 MAR PY 2007 VL 12 IS 3 BP 307 EP 317 DI 10.1038/sj.mp.4001946 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 141DX UT WOS:000244559000014 PM 17211439 ER PT J AU Burke, JD Morris, JC AF Burke, John Douglas Morris, John C. TI Retroviral vectors encoding a reverse transcription-activated transgene efficiently limit expression of the gene to target cells SO MOLECULAR THERAPY LA English DT Article ID THYMIDINE KINASE GENE; MAMMALIAN-CELLS; LEUKEMIA-VIRUS; BRAIN-TUMORS; PRODUCER CELLS; EX-VIVO; THERAPY; INITIATION; RNA; REPLICATION AB Recombinant retroviral vectors are indispensable tools for the study of gene function and for therapeutic gene transfer owing to their ability to transfer and stably express foreign genes in target cells. A limitation of these vectors, however, is the difficulty in generating stable vector producer cell (VPC) lines when the vectors encode cytotoxic proteins. We developed a series of Moloney murine leukemia virus-based vectors encoding a reverse transcription-activated transgene. These vectors preclude gene expression in the producer cells, yet allow lines for transgene expression in target cells. The vectors were generated by cloning the gene of interest in reverse orientation either just upstream of the viral 30 long terminal repeat (LTR) or in the U3 region of the 3'LTR. An exogenous promoter was inserted, also in reverse orientation, at the R-U5 border of the viral 5'LTR. Upon transduction of target cells, the inserted promoter is copied to the 3'LTR during reverse transcription of the vector genomic RNA, where it then drives transgene expression. We tested this system using a green fluorescent protein (GFP) gene and the SV40 promoter. Reverse transcription-activated retroviral vectors may allow for the generation of stable retroviral VPC lines encoding cytotoxic or inhibitory genes. C1 NCI, Metab Branch, Ctr Canc Res, Mark O Hatfield Clin Res Ctr,NIH, Bethesda, MD 20892 USA. RP Morris, JC (reprint author), NCI, Metab Branch, Ctr Canc Res, Mark O Hatfield Clin Res Ctr,NIH, Rm 4-5330, Bethesda, MD 20892 USA. EM jmorris@mail.nih.gov NR 40 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAR PY 2007 VL 15 IS 3 BP 552 EP 559 DI 10.1038/sj.mt.6300062 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 139AZ UT WOS:000244405700019 PM 17191073 ER PT J AU Liang, SB Yoshimitsu, M Poeppl, A Rasaiah, VI Cai, JH Fowler, DH Medin, JA AF Liang, Sheng-Ben Yoshimitsu, Makoto Poeppl, Armando Rasaiah, Vanessa I. Cai, Jianhui Fowler, Daniel H. Medin, Jeffrey A. TI Multiple reduced-intensity conditioning regimens facilitate correction of Fabry mice after transplantation of transduced cells SO MOLECULAR THERAPY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; SEVERE COMBINED IMMUNODEFICIENCY; GENE-THERAPY; ALPHA-GALACTOSIDASE; REPLACEMENT THERAPY; RETROVIRAL VECTOR; FOLLOW-UP; DISEASE; EXPRESSION; ENGRAFTMENT AB Hematopoietic cell transplantation can impact lysosomal storage disorders (LSDs) and will be enhanced by gene therapy. Transduced cells in LSDs often secrete the therapeutic hydrolase, which can be used by bystander cells. However, toxicity associated with myeloablative transplant preparative regimens limits many applications of this approach in gene therapy. We hypothesized that reduced-intensity ( RI) conditioning regimens would allow stable engraftment of therapeutically transduced cells and allow correction of Fabry disease. We transplanted transduced cells into Fabry mice receiving eight different clinically relevant chemotherapy- and/or radiotherapy-based RI conditioning regimens generating modest and transient lymphoid/myeloid cell depletion. Two comprehensive transplantation Protocols were performed. Firstly, transplantation of 0.38 x 10(6) gene-modified stem/progenitor cells was nominally effective; none of the RI regimens led to stable alpha-galactosidase A (alpha-gal A) correction. Secondly, transduced cells were preselected for functional transgene expression and transplanted at a higher dose (0.72 x 10(6) cells). Each RI regimen yielded engraftment of functional transgene-positive cells through 180 days along with increased plasma alpha-gal A activity. Importantly, the RI regimens mediated broad organ enzyme correction and were not associated with immune responses against alpha-gal A. RI conditioning thus has an important role in gene therapy for LSDs; a variety of regimens can be effective in this context. C1 Univ Hlth Network, Div Stem Cell & Dev Biol, Ontario Canc Inst, Toronto, ON, Canada. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. RP Medin, JA (reprint author), Univ Hlth Network, Div Stem Cell & Dev Biol, Ontario Canc Inst, Toronto, ON, Canada. EM jmedin@uhnres.utoronto.ca FU NHLBI NIH HHS [HL70569] NR 31 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAR PY 2007 VL 15 IS 3 BP 618 EP 627 DI 10.1038/sj.mt.6300075 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 139AZ UT WOS:000244405700027 PM 17228315 ER PT J AU Zhang, QJ Xiao, XS Li, SQ Jia, XY Yang, ZK Huang, SZ Caruso, RC Guan, TQ Sergeev, Y Guo, XM Hejtmancik, JF AF Zhang, Qingjiong Xiao, Xueshan Li, Shiqiang Jia, Xiaoyun Yang, Zhikuan Huang, Shizhou Caruso, Rafael C. Guan, Tianqin Sergeev, Yuri Guo, Xiangming Hejtmancik, J. Fielding TI Mutations in NYX of individuals with high myopia, but without night blindness SO MOLECULAR VISION LA English DT Article ID RICH REPEAT PROTEIN; GENE; LOCUS; MAPS; NYCTALOPIN; FAMILIES; ELECTRORETINOGRAM; EXPRESSION; RESPONSES; COLLAGEN AB PURPOSE: High myopia is a common genetic variant that severely affects vision. Genes responsible for myopia without linked additional functional defects have not been identified. Mutations in the nyctalopin gene (NYX) located at Xp11.4 are responsible for a complete form of congenital stationary night blindness (CSNB1). High myopia is usually observed in patients with CSNB1. This study was designed to test the possibility that mutations in the NYX gene might cause high myopia without congenital stationary night blindness (CSNB). METHODS: The genomic sequence of NYX in 52 male probands with high myopia but without CSNB was analyzed through direct DNA sequencing. Variations in the NYX were verified by analyzing available family members and 232 controls. RESULTS: Two unrelated male individuals with high myopia but without night blindness were found to have novel Cys48Trp and Arg191Gln mutations in NYX. The mutations were found to be located in distinct regions, different from the locations of mutations known to cause congenital stationary night blindness with myopia (CSNB1). CONCLUSIONS: Mutations in NYX may cause high myopia without CSNB. The observations suggest that NYX may have independent effects on myopia and night blindness. C1 Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Peoples R China. NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, QJ (reprint author), Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Peoples R China. EM qingjiongzhang@yahoo.com NR 43 TC 24 Z9 24 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 MAR 1 PY 2007 VL 13 IS 35-37 BP 330 EP 336 PG 7 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 151BN UT WOS:000245263400002 PM 17392683 ER PT J AU McCrae, RR AF McCrae, Robert R. TI Aesthetic chills as a universal marker of openness to experience SO MOTIVATION AND EMOTION LA English DT Article DE personality; openness to experience; music chills ID PERSONALITY-TRAITS; EMOTION; CULTURES; MUSIC; BRAIN AB Aesthetic chills are transient emotional responses to music or other experiences of beauty. Item 188 of the Revised NEO Personality Inventory (NEO-PI-R) asks respondents if they have experienced these chills, and in American samples it is one of the best definers of Openness to Experience, one of the five basic personality factors. As part of the NEO-PI-R, the item has been translated into over 40 languages, and an examination of back-translations suggests that the phenomenon can be expressed in all the languages examined. Data from the Personality Profiles of Cultures Project show that Item 188 is one of the best definers of Openness in most of the 51 cultures examined. Aesthetic chills appear to be a universal emotional experience, although the functions they serve and the mechanisms that account for them remain to be discovered. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, Baltimore, MD 21224 USA. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mccraej@grc.nia.nih.gov NR 34 TC 56 Z9 57 U1 3 U2 14 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0146-7239 J9 MOTIV EMOTION JI Motiv. Emot. PD MAR PY 2007 VL 31 IS 1 BP 5 EP 11 DI 10.1007/s11031-007-9053-1 PG 7 WC Psychology, Experimental; Psychology, Social SC Psychology GA 153LW UT WOS:000245438000002 ER PT J AU McFarland, HR AF McFarland, H. R. TI MRI as a therapeutic marker: What we're learning from clinical trials SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 11th Annual Meeting of the Americas-Committee-for-Treatment-and-Research-in- Multiple-Sclerosis CY OCT 08, 2006 CL Chicago, IL SP Amer Comm Treatment & Res Multiple Scleros ID MULTIPLE-SCLEROSIS C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NR 4 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 MAR PY 2007 VL 13 IS 2 BP 281 EP 282 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 158LK UT WOS:000245792800026 ER PT J AU Raju, R Dalakas, MC AF Raju, Raghavan Dalakas, Marinos C. TI Absence of upregulated genes associated with protein accumulations in desmin myopathy SO MUSCLE & NERVE LA English DT Article DE desmin myopathy; inclusion-body myopathy; microarray; protein accumulation; protein-surplus myopathy ID MYOFIBRILLAR MYOPATHY; MUTATIONS; DISEASES AB In desmin myopathy but not hereditary inclusion-body myopathy (hIBM), there is accumulation of myofibrillar proteins including desmin, myotilin, dystrophin, gelsolin, actin, and CDC kinase. To assess the cause of protein excess, we studied the genes coding the accumulated proteins in desmin myopathy, hIBM, and controls. No differences were found among them. In desmin myopathy, protein accumulation is not due to upregulation of genes triggered by mutant desmin, but rather to posttranslational disassembly of intermediate filaments. C1 Natl Inst Neurol Disorders & Stroke, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), Natl Inst Neurol Disorders & Stroke, Neuromuscular Dis Sect, 10 Ctr Dr,Room 10-4N248, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov RI Raju, Raghavan/E-9219-2011 FU Intramural NIH HHS NR 15 TC 4 Z9 4 U1 0 U2 0 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 MAR PY 2007 VL 35 IS 3 BP 386 EP 388 DI 10.1002/mus.20680 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 143LN UT WOS:000244723600015 PM 17068785 ER PT J AU Wilson, DM Thompson, LH AF Wilson, David M., III Thompson, Laity H. TI Molecular mechanisms of sister-chromatid exchange SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE sister-chromatid exchange; single-strand break DNA repair; CHO EM9; XRCC1; bloom syndrome; homologous recombination; DNA replication forks ID STRAND-BREAK REPAIR; BLOOMS-SYNDROME HELICASE; BASE EXCISION-REPAIR; DNA-LIGASE-III; CHINESE-HAMSTER CELLS; POLYMERASE-BETA INTERACTION; GENE TARGETING EFFICIENCY; FANCONI-ANEMIA PATHWAY; HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS AB Sister-chromatid exchange (SCE) is the process whereby, during DNA replication, two sister chromatids break and rejoin with one another, physically exchanging regions of the parental strands in the duplicated chromosomes. This process is considered to be conservative and error-free, since no information is generally altered during reciprocal interchange by homologous recombination. Upon the advent of non-radiolabel detection methods for SCE, such events were used as genetic indicators for potential genotoxins/mutagens in laboratory toxicology tests, since, as we now know, most forms of DNA damage induce chromatid exchange upon replication fork collapse. Much of our present understanding of the mechanisms of SCE stems from studies involving nonhuman vertebrate cell lines that are defective in processes of DNA repair and/or recombination. In this article, we present a historical perspective of studies spearheaded by Dr. Anthony V. Carrano and colleagues focusing on SCE as a genetic outcome, and the role of the single-strand break DNA repair protein XRCC1 in suppressing SCE. A more general overview of the cellular processes and key protein "effectors" that regulate the manifestation of SCE is also presented. (c) 2006 Elsevier B.V All rights reserved. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Lawrence Livermore Natl Lab, Livermore, CA 94551 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wilsonda@grc.nia.nih.gov FU NCI NIH HHS [CA11256] NR 125 TC 137 Z9 140 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAR 1 PY 2007 VL 616 IS 1-2 BP 11 EP 23 DI 10.1016/j.mrfmmm.2006.11.017 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 143YC UT WOS:000244761300004 PM 17157333 ER PT J AU King, AA Shaughnessy, DT Mure, K Leszczynska, J Ward, WO Umbach, DM Xu, ZL Ducharme, D Taylor, JA DeMarini, DM Klein, CB AF King, Audrey A. Shaughnessy, Daniel T. Mure, Kanae Leszczynska, Joanna Ward, William O. Umbach, David M. Xu, Zongli Ducharme, Danica Taylor, Jack A. DeMarini, David M. Klein, Catherine B. TI Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE cinnamaldehyde; vanillin; spontaneous mutagenesis; microarray; comet assay; human cells; HPRT ID CHINESE-HAMSTER-CELLS; CHROMOSOME-ABERRATIONS; ESCHERICHIA-COLI; DROSOPHILA-MELANOGASTER; MITOMYCIN-C; SPONTANEOUS MUTAGENESIS; SPONTANEOUS MUTATION; OXIDATIVE STRESS; MAMMALIAN-CELLS; SOMATIC-CELLS AB Vanillin (VAN) and cinnamaldehyde (CIN) are dietary flavorings that exhibit antimmagenic activity against mutagen-induced and spontaneous mutations in bacteria. Although these compounds were antimutagenic against chromosomal mutations in mammalian cells, they have not been studied for antimutagenesis against spontaneous gene mutations in mammalian cells. Thus, we initiated studies with VAN and CIN in human mismatch repair-deficient (hMLH1(-)) HCT 116 colon cancer cells, which exhibit high spontaneous mutation rates (mutations/cell/generation) at the HPRT locus, permitting analysis of antimutagenic effects of agents against spontaneous mutation. Long-term (1-3 weeks) treatment of HCT1 16 cells with VAN at minimally toxic concentralions (0.5-2.5 mM) reduced the spontaneous HPRT mutant fraction (MR, mutants/10(6) survivors) in a concentration-related manner by 19-73%. A similar treatment with CIN at 2.5-7.5 mu M yielded a 13-56% reduction of the spontaneous MR Short-term (4-h) treatments also reduced the spontaneous MF by 64% (VAN) and 31% (CIN). To investigate the mechanisms of antimmagenesis, we evaluated the ability of VAN and CIN to induce DNA damage (comet assay) and to alter global gene expression (Affymetrix GeneChip((R))) after 4-h treatments. Both VAN and CIN induced DNA damage in both mismatch repair-proficient (HCT116 + chr3) and deficient (HCT 116) cells at concentrations that were antimutagenic in HCT 116 cells. There were 64 genes whose expression was changed similarly by both VAN and CIN; these included genes related to DNA damage, stress responses, oxidative damage, apoptosis, and cell growth. RT-PCR results paralleled the Affymetrix results for four selected genes (HMOX1, DDIT4, GCLM, and CLK4). Our results show for the first time that VAN and CIN are antimutagenic against spontaneous mutations in mammalian (human) cells. These and other data lead us to propose that VAN and CIN may induce DNA damage that elicits recombinational DNA repair, which reduces spontaneous mutations. (c) 2006 Elsevier B.V. All rights reserved. C1 NYU, Sch Med, Nelson Inst Environm Med, Tuxedo Pk, NY 10988 USA. DHHS, Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. Wakayama Med Coll, Sch Med, Dept Publ Hlth, Wakayama 6418509, Japan. US Environm Protect Agcy, Environm Carcinogenesis Div, Res Triangle Pk, NC 27711 USA. RP Klein, CB (reprint author), NYU, Sch Med, Nelson Inst Environm Med, 57 Old Forge Rd, Tuxedo Pk, NY 10988 USA. EM kleinc@env.med.nyu.edu OI xu, zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398 FU Intramural NIH HHS [Z99 ES999999]; NCI NIH HHS [CA016087, P30 CA016087, R03 CA089732-02, R03 CA89732]; NIEHS NIH HHS [ES000260, P30 ES000260, P30 ES000260-40, P30 ES000260-409021, P30 ES000260-41, P30 ES000260-419021, P30 ES000260-42, P30 ES000260-429021, T32 ES007324, T32 ES007324-05] NR 48 TC 39 Z9 43 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAR 1 PY 2007 VL 616 IS 1-2 BP 60 EP 69 DI 10.1016/j.mrfmmm.2006.11.022 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 143YC UT WOS:000244761300008 PM 17178418 ER PT J AU Torres, MS White, JF Bischoff, JF AF Torres, Monica S. White, James F., Jr. Bischoff, Joseph F. TI Hypocrella panamensis sp nov (Clavicipitaceae, Hypocreales): a new species infecting scale insects on Piper carrilloanum in Panama SO MYCOLOGICAL RESEARCH LA English DT Article DE ascomycota; Clavicipitaceae; molecular systematics; morphology ID LARGE STROMATA; GENUS; ASCHERSONIA; ANAMORPH; MODEL; DNA AB A new species, Hypocrella panamensis, is described from collections and cultures obtained on Barro Colorado island, Panama. In order to aid in placement of this fungus, phylogenetic analyses were conducted using LSU (rDNA) sequences. Hypocrella panamensis is characterized by possessing pulvinate stromata with a Lecanicillium-like anamorphic state and superficial perithecia. Hypocrella panamensis consistently grouped in a clade containing Hypocrella nectrioides, H. phyllogena, and H. africana (100% PP). Most species of Hypocrella possess Aschersonia or Hirsutella anamorphs. Hypocrella panamensis is unique in the genus Hypocrella in possession of a Lecanicillium-like anamorphic state. In its biological habit Hypocrella panamensis is similar to other species in Hypocrella in that it infects and degrades the scale insect, then grows superficially on nutrients that emerge to the plant surface through the stylet wound. (c) 2007 The British Mycological Society. Published by Elsevier Ltd. All rights reserved. C1 Rutgers State Univ, Dept Plant Biol & Pathol, New Brunswick, NJ 08901 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Torres, MS (reprint author), Rutgers State Univ, Dept Plant Biol & Pathol, 59 Dudley Rd, New Brunswick, NJ 08901 USA. EM mstorres@eden.rutgers.edu RI White, James/C-2280-2009 NR 22 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0953-7562 J9 MYCOL RES JI Mycol. Res. PD MAR PY 2007 VL 111 BP 317 EP 323 DI 10.1016/j.mycres.2007.01.005 PN 3 PG 7 WC Mycology SC Mycology GA 167NJ UT WOS:000246458100007 PM 17368009 ER PT J AU Mannes, A Iadarola, M AF Mannes, Andrew Iadarola, Michael TI Potential downsides of perfect pain relief SO NATURE LA English DT Letter C1 NIH, Dept Anesthesia & Surg Serv, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Bethesda, MD 20892 USA. RP Mannes, A (reprint author), NIH, Dept Anesthesia & Surg Serv, Warren Grant Magnuson Clin Ctr, 10 Ctr Dr, Bethesda, MD 20892 USA. OI Mannes, Andrew/0000-0001-5834-5667 NR 1 TC 3 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 1 PY 2007 VL 446 IS 7131 BP 24 EP 24 DI 10.1038/446024a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 140RY UT WOS:000244525600016 PM 17330023 ER PT J AU Even-Ram, S Doyle, AD Conti, MA Matsumoto, K Adelstein, RS Yamada, KM AF Even-Ram, Sharona Doyle, Andrew D. Conti, Mary Anne Matsumoto, Kazue Adelstein, Robert S. Yamada, Kenneth M. TI Myosin IIA regulates cell motility and actomyosin microtubule crosstalk SO NATURE CELL BIOLOGY LA English DT Article ID MITOTIC KINESIN EG5; MIGRATING CELLS; INHIBITORS; DYNAMICS; ADHESION; RAC; CONTRACTILITY; TRANSLOCATION; ORGANIZATION; CYTOSKELETON AB Non-muscle myosin II has diverse functions in cell contractility, cytokinesis and locomotion, but the specific contributions of its different isoforms have yet to be clarified. Here, we report that ablation of the myosin IIA isoform results in pronounced defects in cellular contractility, focal adhesions, actin stress fibre organization and tail retraction. Nevertheless, myosin IIA-deficient cells display substantially increased cell migration and exaggerated membrane ruffling, which was dependent on the small G-protein Rac1, its activator Tiam1 and the microtubule moter kinesin Eg5. Myosin IIA deficiency stabilized microtubules, shifting the balance between actomyosin and microtubules with increased microtubules in active membrane ruffles. When microtubule polymerization was suppressed, myosin IIB could partially compensate for the absence of the IIA isoform in cellular contractility, but not in cell migration. We conclude that myosin IIA negatively regulates cell migration and suggest that it maintains a balance between the actomyosin and microtubule systems by regulating microtubule dynamics. C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Yamada, KM (reprint author), NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. EM ky4w@nih.gov OI Even-Ram, Sharona/0000-0002-5540-3822; Yamada, Kenneth/0000-0003-1512-6805; Adelstein, Robert/0000-0002-8683-2144 FU Intramural NIH HHS NR 37 TC 266 Z9 271 U1 4 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAR PY 2007 VL 9 IS 3 BP 299 EP U104 DI 10.1038/ncb1540 PG 17 WC Cell Biology SC Cell Biology GA 141DT UT WOS:000244558600014 PM 17310241 ER PT J AU Launer, LJ AF Launer, Lenore J. TI Is migraine with aura associated with increased risk of cardiovascular disease? SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Editorial Material DE aura; cardiovascular disease; migraine; stroke; women ID PATHOPHYSIOLOGY C1 NIA, Neuroepidemiol Sect, NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Launer, LJ (reprint author), NIA, Neuroepidemiol Sect, NIH, Lab Epidemiol Demog & Biometry, Room 3C309,Gateway Bldg,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1743-4297 J9 NAT CLIN PRACT CARD JI Nat. Clin. Pract. Cardiovasc. Med. PD MAR PY 2007 VL 4 IS 3 BP 126 EP 127 DI 10.1038/ncpcardio0795 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 138QT UT WOS:000244378000004 PM 17245321 ER PT J AU Voon, V Lang, AE Hallett, M AF Voon, V. Lang, A. E. Hallett, M. TI Diagnosing psychogenic movement disorders - which criteria should be used in clinical practice? SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Editorial Material DE conversion disorder; diagnosis; psychogenic movement disorder ID CONVERSION SYMPTOMS C1 NINDS, NIH, Med Neurol Branch, Bethesda, MD 20892 USA. Univ Toronto, Div Neurol, Toronto, ON, Canada. Toronto Western Hosp, Movement Disorders Unit, Toronto, ON M5T 2S8, Canada. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Voon, V (reprint author), NINDS, NIH, Med Neurol Branch, 10 Ctr Dr,Bldg 10,Room 5S213, Bethesda, MD 20892 USA. EM voonv@ninds.nih.gov NR 6 TC 13 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD MAR PY 2007 VL 3 IS 3 BP 134 EP 135 DI 10.1038/ncpneuro0408 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 143KA UT WOS:000244718900006 PM 17262077 ER PT J AU Gulley, JL Dahut, WL AF Gulley, James L. Dahut, William L. TI Future directions in tumor immunotherapy: CTLA4 blockade SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material ID AVIDITY C1 NCI, Med Oncol Branch, GU GYN Clin Res Sect, Bethesda, MD 20892 USA. NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Dahut, WL (reprint author), NCI, Med Oncol Branch, GU GYN Clin Res Sect, Room 12N226,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dahutw@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 10 TC 13 Z9 13 U1 0 U2 0 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 MAR PY 2007 VL 4 IS 3 BP 136 EP 137 DI 10.1038/ncponc0749 PG 2 WC Oncology SC Oncology GA 141MC UT WOS:000244581700002 PM 17327854 ER PT J AU Gourley, M Miller, FW AF Gourley, Mark Miller, Frederick W. TI Mechanisms of Disease: environmental factors in the pathogenesis of rheumatic disease SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Review DE environment; exposures; occupation; rheumatic disease; risk factors ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; EPSTEIN-BARR-VIRUS; OCCUPATIONAL RISK-FACTORS; PARVOVIRUS B19 INFECTION; ORAL-CONTRACEPTIVES; SILICA EXPOSURE; ARTHRITIS; ASSOCIATION; AUTOIMMUNITY; ANTIBODIES AB Most rheumatic diseases are complex disorders for which pathogenetic mechanisms are poorly understood. Nonetheless, increasing evidence suggests that many of these illnesses result from one or more specific environmental exposures in genetically susceptible individuals. Although much progress has been made over the past few decades in advancing our knowledge of the genetics of rheumatic diseases, few studies have assessed environmental features and understanding of which exposures are important in pathogenesis remains limited. In this article, we review the difficulties inherent in deciphering the interacting environmental and genetic risk factors for rheumatic diseases, the current state of knowledge of infectious and noninfectious risk factors, possible mechanisms by which environmental exposures might induce pathologic processes and future directions. The advances in technologies and statistical approaches, development of collaborating consortia and focused resources that have resulted in the explosion of genetic information must now be applied to environmental studies so we can eventually interrupt pathogenesis before the onset of disease and transform the practice of medicine from curative to pre-emptive paradigms. C1 NIEHS, Environm Autoimmun Grp, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. NIH, Environm Autoimmun Grp, Clin Res Ctr, Bethesda, MD USA. RP Gourley, M (reprint author), NIEHS, Environm Autoimmun Grp, NIH, Bldg 10,CRC,Room 4-2340, Bethesda, MD 20892 USA. EM gourleym@mail.nih.gov OI Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS NR 58 TC 38 Z9 38 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD MAR PY 2007 VL 3 IS 3 BP 172 EP 180 DI 10.1038/ncprheum0435 PG 9 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 141MD UT WOS:000244581900013 PM 17334340 ER PT J AU Chanock, SJ Thomas, G AF Chanock, Stephen J. Thomas, Gilles TI The devil is in the DNA SO NATURE GENETICS LA English DT Editorial Material ID COLORECTAL CANCERS; HUMAN BREAST; MUTATIONAL ANALYSIS; GENE AB In the current era of large-scale cancer genome sequencing, the interpretation of somatic sequence alterations is a formidable challenge. A new study of known mutations represents an important step in cataloging somatic mutations in individual tumors. C1 NCI, Pediat Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Pediat Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov NR 15 TC 13 Z9 13 U1 0 U2 0 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 MAR PY 2007 VL 39 IS 3 BP 283 EP 284 DI 10.1038/ng0307-283 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 140CK UT WOS:000244480000005 PM 17325673 ER PT J AU Thomas, RK Baker, AC DeBiasi, RM Winckler, W LaFramboise, T Lin, WM Wang, M Feng, W Zander, T MacConnaill, LE Lee, JC Nicoletti, R Hatton, C Goyette, M Girard, L Majmudar, K Ziaugra, L Wong, KK Gabriel, S Beroukhim, R Peyton, M Barretina, J Dutt, A Emery, C Greulich, H Shah, K Sasaki, H Gazdar, A Minna, J Armstrong, SA Mellinghoff, IK Hodi, FS Dranoff, G Mischel, PS Cloughesy, TF Nelson, SF Liau, LM Mertz, K Rubin, MA Moch, H Loda, M Catalona, W Fletcher, J Signoretti, S Kaye, F Anderson, KC Demetri, GD Dummer, R Wagner, S Herlyn, M Sellers, WR Meyerson, M Garraway, LA AF Thomas, Roman K. Baker, Alissa C. DeBiasi, Ralph M. Winckler, Wendy LaFramboise, Thomas Lin, William M. Wang, Meng Feng, Whei Zander, Thomas MacConnaill, Laura E. Lee, Jeffrey C. Nicoletti, Rick Hatton, Charlie Goyette, Mary Girard, Luc Majmudar, Kuntal Ziaugra, Liuda Wong, Kwok-Kin Gabriel, Stacey Beroukhim, Rameen Peyton, Michael Barretina, Jordi Dutt, Amit Emery, Caroline Greulich, Heidi Shah, Kinjal Sasaki, Hidefumi Gazdar, Adi Minna, John Armstrong, Scott A. Mellinghoff, Ingo K. Hodi, F. Stephen Dranoff, Glenn Mischel, Paul S. Cloughesy, Tim F. Nelson, Stan F. Liau, Linda M. Mertz, Kirsten Rubin, Mark A. Moch, Holger Loda, Massimo Catalona, William Fletcher, Jonathan Signoretti, Sabina Kaye, Frederic Anderson, Kenneth C. Demetri, George D. Dummer, Reinhard Wagner, Stephan Herlyn, Meenhard Sellers, William R. Meyerson, Matthew Garraway, Levi A. TI High-throughput oncogene mutation profiling in human cancer SO NATURE GENETICS LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE JAK2; OF-FUNCTION MUTATION; MYELOPROLIFERATIVE DISORDERS; ACTIVATING MUTATIONS; LUNG ADENOCARCINOMA; POLYCYTHEMIA-VERA; GENE; SENSITIVITY; GEFITINIB AB Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression(1,2). However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. Nagoya City Univ, Sch Med, Dept Surg 2, Nagoya, Aichi 4678601, Japan. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol & Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60637 USA. NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. USN, Natl Med Ctr, Bethesda, MD 20084 USA. Dana Farber Canc Inst, Ludwig Ctr Canc Res, Boston, MA 02115 USA. Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. Med Univ Vienna, Austrian Acad Sci, Dept Dermatol, Div Immunol Allergy & Infect Dis, A-1090 Vienna, Austria. Austrian Acad Sci, Ctr Mol Med, A-1090 Vienna, Austria. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Novartis Inst BioMed Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Program Med Oncol, Boston, MA 02115 USA. Max Planck Soc, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, D-50931 Cologne, Germany. Univ Cologne, Fac Med, D-50931 Cologne, Germany. Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany. RP Garraway, LA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM levi_garraway@dfci.harvard.edu RI Peyton, Michael/A-8728-2008; Nelson, Stanley/D-4771-2009; kaye, frederic/E-2437-2011; Meyerson, Matthew/E-7123-2012; Dutt, Amit/I-1911-2013; OI Dutt, Amit/0000-0002-1119-4774; Wagner, Stephan/0000-0003-4941-7029; Rubin, Mark/0000-0002-8321-9950; wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [P50 CA070907, P50CA70907] NR 27 TC 616 Z9 633 U1 7 U2 25 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 MAR PY 2007 VL 39 IS 3 BP 347 EP 351 DI 10.1038/ng1975 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 140CK UT WOS:000244480000016 PM 17293865 ER PT J AU Cox, A Dunning, AM Garcia-Closas, M Balasubramanian, S Reed, MWR Pooley, KA Scollen, S Baynes, C Ponder, BAJ Chanock, S Lissowska, J Brinton, L Peplonska, B Southey, MC Hopper, JL McCredie, MRE Giles, GG Fletcher, O Johnson, N Silva, ID Gibson, L Bojesen, SE Nordestgaard, BG Axelsson, CK Torres, D Hamann, U Justenhoven, C Brauch, H Chang-Claude, J Kropp, S Risch, A Wang-Gohrke, S Schurmann, P Bogdanova, N Dork, T Fagerholm, R Aaltonen, K Blomqvist, C Nevanlinna, H Seal, S Renwick, A Stratton, MR Rahman, N Sangrajrang, S Hughes, D Odefrey, F Brennan, P Spurdle, AB Chenevix-Trench, G Beesley, J Mannermaa, A Hartikainen, J Kataja, V Kosma, VM Couch, FJ Olson, JE Goode, EL Broeks, A Schmidt, MK Hogervorst, FBL Van't Veer, LJ Kang, D Yoo, KY Noh, DY Ahn, SH Wedren, S Hall, P Low, YL Liu, JJ Milne, RL Ribas, G Gonzalez-Neira, A Benitez, J Sigurdson, AJ Stredrick, DL Alexander, BH Struewing, JP Pharoah, PDP Easton, DF AF Cox, Angela Dunning, Alison M. Garcia-Closas, Montserrat Balasubramanian, Sabapathy Reed, Malcolm W. R. Pooley, Karen A. Scollen, Serena Baynes, Caroline Ponder, Bruce A. J. Chanock, Stephen Lissowska, Jolanta Brinton, Louise Peplonska, Beata Southey, Melissa C. Hopper, John L. McCredie, Margaret R. E. Giles, Graham G. Fletcher, Olivia Johnson, Nichola dos Santos Silva, Isabel Gibson, Lorna Bojesen, Stig E. Nordestgaard, Borge G. Axelsson, Christen K. Torres, Diana Hamann, Ute Justenhoven, Christina Brauch, Hiltrud Chang-Claude, Jenny Kropp, Silke Risch, Angela Wang-Gohrke, Shan Schuermann, Peter Bogdanova, Natalia Doerk, Thilo Fagerholm, Rainer Aaltonen, Kirsimari Blomqvist, Carl Nevanlinna, Heli Seal, Sheila Renwick, Anthony Stratton, Michael R. Rahman, Nazneen Sangrajrang, Suleeporn Hughes, David Odefrey, Fabrice Brennan, Paul Spurdle, Amanda B. Chenevix-Trench, Georgia Beesley, Jonathan Mannermaa, Arto Hartikainen, Jaana Kataja, Vesa Kosma, Veli-Matti Couch, Fergus J. Olson, Janet E. Goode, Ellen L. Broeks, Annegien Schmidt, Marjanka K. Hogervorst, Frans B. L. Van't Veer, Laura J. Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Ahn, Sei-Hyun Wedren, Sara Hall, Per Low, Yen-Ling Liu, Jianjun Milne, Roger L. Ribas, Gloria Gonzalez-Neira, Anna Benitez, Javier Sigurdson, Alice J. Stredrick, Denise L. Alexander, Bruce H. Struewing, Jeffery P. Pharoah, Paul D. P. Easton, Douglas F. CA Kathleen Cunningham Fdn Consortium Breast Canc Assoc Consortium TI A common coding variant in CASP8 is associated with breast cancer risk SO NATURE GENETICS LA English DT Article ID TRANSFORMING-GROWTH-FACTOR-BETA-1 GENE; ATAXIA-TELANGIECTASIA; REDUCED RISK; TGF-BETA; SUSCEPTIBILITY; POLYMORPHISMS; WOMEN; IGFBP3; REGION; LOCUS AB The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3-202 C -> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A -> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies. C1 Univ Sheffield, Sch Med, Sheffield S10 2RX, S Yorkshire, England. Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England. Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Core Genotyping Facil, Ctr Adv Technol, Bethesda, MD 20892 USA. Ctr Canc, PL-02781 Warsaw, Poland. M Sklodowska Curie Inst Oncol, PL-02781 Warsaw, Poland. Nofer Inst Occupat Med, PL-90950 Lodz, Poland. Univ Melbourne, Melbourne, Vic 3010, Australia. Univ Otago, Dunedin, New Zealand. Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3053, Australia. Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. Univ Copenhagen, Herlev Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark. Univ Copenhagen, Herlev Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark. Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany. Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. Univ Tubingen, D-72074 Tubingen, Germany. German Canc Res Ctr, D-69120 Heidelberg, Germany. Univ Ulm, D-89069 Ulm, Germany. Hannover Med Sch, Dept Gynecol & Obstet, D-30625 Hannover, Germany. Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany. Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00290 Helsinki, Finland. Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England. Natl Canc Inst, Bangkok 10400, Thailand. Int Agcy Res Canc, F-69372 Lyon, France. Queensland Inst Med Res, Brisbane, Qld 4029, Australia. Univ Kuopio, Inst Clin Med Pathol & Forens Med, FI-70211 Kuopio, Finland. Kuopio Univ Hosp, Dept Oncol, FI-70211 Kuopio, Finland. Kuopio Univ Hosp, Dept Pathol, FI-70211 Kuopio, Finland. Mayo Clin Coll Med, Rochester, MN 55905 USA. Netherlands Canc Inst, Dept Expt Therapy, NL-1066 CX Amsterdam, Netherlands. Netherlands Canc Inst, Dept Epidemiol & Mol Pathol, NL-1066 CX Amsterdam, Netherlands. Seoul Natl Univ, Coll Med, Seoul 151742, South Korea. Univ Ulsan, Coll Med, Dept Surg, Ulsan 680749, South Korea. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Genome Inst Singapore, Singapore 138672, Singapore. CNIO, Spanish Natl Canc Res Ctr, E-28049 Madrid, Spain. NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN 55455 USA. RP Cox, A (reprint author), Univ Sheffield, Sch Med, Sheffield S10 2RX, S Yorkshire, England. EM a.cox@shef.ac.uk RI Rahman, Nazneen/D-2802-2013; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Hartikainen, Jaana/E-6256-2015; Struewing, Jeffery/I-7502-2013; Dork, Thilo/J-8620-2012; Risch, Angela/H-2669-2013; Spurdle, Amanda/A-4978-2011; Noh, Dong-Young/G-5531-2011; Peplonska, Beata/F-6004-2010; Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Rahman, Nazneen/B-8890-2012; Gonzalez-Neira, Anna/C-5791-2015 OI Rahman, Nazneen/0000-0003-4376-0440; Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison Margaret/0000-0001-6651-7166; Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Struewing, Jeffery/0000-0002-4848-3334; Risch, Angela/0000-0002-8026-5505; Spurdle, Amanda/0000-0003-1337-7897; FU Intramural NIH HHS; NCI NIH HHS [CA-95-003, CA82267, P50 CA116201]; Wellcome Trust [068545/Z/02] NR 30 TC 367 Z9 375 U1 5 U2 41 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2007 VL 39 IS 3 BP 352 EP 358 DI 10.1038/ng1981 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 140CK UT WOS:000244480000017 PM 17293864 ER PT J AU Cabral, WA Chang, W Barnes, AM Weis, M Scott, MA Leikin, S Makareeva, E Kuznetsova, NV Rosenbaum, KN Tifft, CJ Bulas, DI Kozma, C Smith, PA Eyre, DR Marini, JC AF Cabral, Wayne A. Chang, Weizhong Barnes, Aileen M. Weis, MaryAnn Scott, Melissa A. Leikin, Sergey Makareeva, Elena Kuznetsova, Natalia V. Rosenbaum, Kenneth N. Tifft, Cynthia J. Bulas, Dorothy I. Kozma, Chahira Smith, Peter A. Eyre, David R. Marini, Joan C. TI Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta SO NATURE GENETICS LA English DT Article ID MEMBRANE-ASSOCIATED PROTEOGLYCAN; CARTILAGE-ASSOCIATED PROTEIN; COLLAGEN TRIPLE-HELIX; I COLLAGEN; RESIDUES; MUTATIONS; LEPRECAN; IDENTIFICATION; FIBRILS; DISEASE AB A recessive form of severe osteogenesis imperfecta that is not caused by mutations in type I collagen has long been suspected. Mutations in human CRTAP (cartilage-associated protein) causing recessive bone disease have been reported. CRTAP forms a complex with cyclophilin B and prolyl 3-hydroxylase 1, which is encoded by LEPRE1 and hydroxylates one residue in type I collagen, alpha 1(I) Pro986. We present the first five cases of a new recessive bone disorder resulting from null LEPRE1 alleles; its phenotype overlaps with lethal/severe osteogenesis imperfecta but has distinctive features. Furthermore, a mutant allele from West Africa, also found in African Americans, occurs in four of five cases. All proband LEPRE1 mutations led to premature termination codons and minimal mRNA and protein. Proband collagen had minimal 3-hydroxylation of alpha 1(I) Pro986 but excess lysyl hydroxylation and glycosylation along the collagen helix. Proband collagen secretion was moderately delayed, but total collagen secretion was increased. Prolyl 3-hydroxylase 1 is therefore crucial for bone development and collagen helix formation. C1 NICHHD, Bione & Extracellular Matrix Branach, NIH, Bethesda, MD 20892 USA. Univ Washington, Orthopaed Res Labs, Seattle, WA 98195 USA. NICHHD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Diagnost Imaging & Radiol, Washington, DC 20010 USA. Georgetown Univ Hosp, Dept Pediat, Washington, DC 20007 USA. Shriners Hosp Children, Chicago, IL 60707 USA. RP Marini, JC (reprint author), NICHHD, Bione & Extracellular Matrix Branach, NIH, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov RI Leikin, Sergey/A-5518-2008; Makareeva, Elena/F-5183-2011 OI Leikin, Sergey/0000-0001-7095-0739; FU NIAMS NIH HHS [AR37318, R01 AR036794, R37 AR037318]; NICHD NIH HHS [HD22657] NR 30 TC 213 Z9 228 U1 1 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 MAR PY 2007 VL 39 IS 3 BP 359 EP 365 DI 10.1038/ng1968 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 140CK UT WOS:000244480000018 PM 17277775 ER PT J AU Berner, V Liu, H Zhou, Q Alderson, KL Sun, K Weiss, JM Back, TC Longo, DL Blazar, BR Wiltrout, RH Welniak, LA Redelman, D Murphy, WJ AF Berner, Vanessa Liu, Haiyan Zhou, Qing Alderson, Kory L. Sun, Kai Weiss, Jonathan M. Back, Timothy C. Longo, Dan L. Blazar, Bruce R. Wiltrout, Robert H. Welniak, Lisbeth A. Redelman, Doug Murphy, William J. TI IFN-gamma mediates CD4(+) T-cell loss and impairs secondary antitumor responses after successful initial immunotherapy SO NATURE MEDICINE LA English DT Article ID HOMEOSTATIC PROLIFERATION; CD8-T-CELL MEMORY; INTERFERON-GAMMA; CD4-T-CELL HELP; ACUTE INFECTION; LYMPHOCYTES; EXPRESSION; GENERATION; DEATH; MICE AB Protective cell-mediated immune responses in cancer are critically dependent on T-helper type 1 (T(H)1) cytokines such as interferon-gamma (IFN-gamma). We have previously shown that the combination of CD40 stimulation and interleukin- 2 (IL-2) leads to synergistic antitumor responses in several models of advanced metastatic disease. We now report that after this treatment and other immunotherapy regimens, the CD4(+)T- cell population, in contrast to CD8(+)T cells, did not significantly increase but rather exhibited a substantial level of apoptosis that was dependent on IFN-gamma. Mice immunized with tumor cells and treated with an immunotherapy regimen that was initially protective were later unable to mount effective memory responses compared with immunized mice not receiving immunotherapy. Immunotherapy given to tumor-bearing Ifngr(-/-) mice resulted in restoration of secondary responses. Thus, although immunotherapeutic regimens inducing strong IFN-gamma responses can lead to successful early antitumor efficacy, they may also impair the development of durable antitumor responses. C1 Univ Nevada, Dept Microbiol & Immunol, Reno, NV 89557 USA. Univ Nevada, Dept Physiol & Cell Biol, Reno, NV 89557 USA. Natl Canc Inst, Ctr Canc Res, Expt Immunol Lab, Frederick, MD 21702 USA. NIA, Baltimore, MD 21224 USA. Univ Minnesota, Div Bone Marrow Transplantat, Ctr Canc, Minneapolis, MN 55455 USA. Univ Minnesota, Div Bone Marrow Transplantat, Dept Pediat, Minneapolis, MN 55455 USA. RP Murphy, WJ (reprint author), Univ Nevada, Dept Microbiol & Immunol, Reno, NV 89557 USA. EM wmurphy@medicine.nevada.edu FU NCI NIH HHS [N01-CO-12400, R01 CA095572, R01 CA095572-04A1, R01 CA72669, R01 CA95572]; NCRR NIH HHS [P20 RR16464] NR 25 TC 91 Z9 93 U1 0 U2 1 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 MAR PY 2007 VL 13 IS 3 BP 354 EP 360 DI 10.1038/nm1554 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 143JC UT WOS:000244715700049 PM 17334371 ER PT J AU Ikeda, SR Dunlap, K AF Ikeda, Stephen R. Dunlap, Kathleen TI Calcium channels diversify their signaling portfolio SO NATURE NEUROSCIENCE LA English DT Editorial Material ID G-PROTEIN; CA2+ CHANNELS; BETA-GAMMA; MODULATION; NEURONS; PATHWAY; FORM C1 NIAAA, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. Tufts Univ, Dept Neurosci, Boston, MA 02111 USA. RP Ikeda, SR (reprint author), NIAAA, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. EM sikeda@mail.nih.gov; kathleen.dunlap@tufts.edu OI Ikeda, Stephen/0000-0002-4088-9508 NR 15 TC 4 Z9 4 U1 1 U2 2 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 MAR PY 2007 VL 10 IS 3 BP 269 EP 271 DI 10.1038/nn0307-269 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 140CM UT WOS:000244480300003 PM 17318216 ER PT J AU Nelson, MI Holmes, EC AF Nelson, Martha I. Holmes, Edward C. TI The evolution of epidemic influenza SO NATURE REVIEWS GENETICS LA English DT Review ID A-VIRUS; HEMAGGLUTININ GENE; AVIAN INFLUENZA; RNA VIRUSES; PHYLOGENETIC ANALYSIS; COCIRCULATING LINEAGES; MOLECULAR EVOLUTION; ANTIGENIC EVOLUTION; POSITIVE SELECTION; NUCLEOPROTEIN GENE AB Recent developments in complete- genome sequencing, antigenic mapping and epidemiological modelling are greatly improving our knowledge of the evolution of human influenza virus at the epidemiological scale. In particular, recent studies have revealed a more complex relationship between antigenic evolution, natural selection and reassortment than previously realized. Despite these advances, there is much that remains to be understood about the epidemiology of influenza virus, particularly the processes that determine the virus's strong seasonality. We argue that a complete understanding of the evolutionary biology of this important human pathogen will require a genomic view of genetic diversity, including the acquisition of polymorphism data from within individual hosts and from geographical regions, particularly the tropics, which have been poorly surveyed to date. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. RP Holmes, EC (reprint author), NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. EM ech15@psu.edu OI Holmes, Edward/0000-0001-9596-3552 NR 88 TC 233 Z9 249 U1 13 U2 87 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 MAR PY 2007 VL 8 IS 3 BP 196 EP 205 DI 10.1038/nrg2053 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 137DY UT WOS:000244274400013 PM 17262054 ER PT J AU Trinchieri, G Sher, A AF Trinchieri, Giorgio Sher, Alan TI Cooperation of Toll-like receptor signals in innate immune defence SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID INTERFERON REGULATORY FACTOR; DENDRITIC CELL SUBSETS; DOUBLE-STRANDED-RNA; RESPONSES IN-VIVO; C-TYPE LECTINS; CUTTING EDGE; MYCOBACTERIUM-TUBERCULOSIS; SYNERGISTIC ACTIVATION; ADAPTIVE IMMUNITY; TRYPANOSOMA-CRUZI AB The mechanisms by which the recognition of Toll-like receptor (TLR) ligands leads to host immunity remain poorly defined. It is now thought that to induce an effective immune response, microorganisms must stimulate complex sets of pattern-recognition receptors, both within and outside of the TLR family. The combined activation of these different receptors can result in complementary, synergistic or antagonistic effects that modulate innate and adaptive immunity. Therefore, a complete understanding of the role of TLRs in host resistance to infection requires 'decoding' of these multiple receptor interactions. This Review highlights recent advances in the newly emerging field of TLR cooperation and discusses their implications for the development of adjuvants and immunotherapies. C1 NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Bldg 560,Room 31-93, Frederick, MD 21702 USA. EM trinchig@mail.nih.gov; asher@niaid.nih.gov FU Intramural NIH HHS NR 105 TC 794 Z9 855 U1 15 U2 98 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD MAR PY 2007 VL 7 IS 3 BP 179 EP 190 DI 10.1038/nri2038 PG 12 WC Immunology SC Immunology GA 140CN UT WOS:000244480400011 PM 17318230 ER PT J AU Suzuki, Y Craigie, R AF Suzuki, Youichi Craigie, Robert TI The road to chromatin - nuclear entry of retroviruses SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; CENTRAL DNA FLAP; REVERSE TRANSCRIPTION COMPLEXES; ROUS-SARCOMA VIRUS; TYPE-1 PREINTEGRATION COMPLEXES; VIRAL PROTEIN-R; TO-AUTOINTEGRATION FACTOR; NONDIVIDING HUMAN-CELLS; HIV-1 MATRIX PROTEIN AB Human immunodeficiency virus 1 (HIV-1) and other retroviruses synthesize a DNA copy of their genome after entry into the host cell. Integration of this DNA into the host cell's genome is an essential step in the viral replication cycle. The viral DNA is synthesized in the cytoplasm and is associated with viral and cellular proteins in a large nucleoprotein complex. Before integration into the host genome can occur, this complex must be transported to the nucleus and must cross the nuclear envelope. This Review summarizes our current knowledge of how this journey is accomplished. C1 NIDDKD, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Lab Host Factors, Ctr Emerging Virus Res, Inst Virus Res,Sakyo Ku, Kyoto 6068507, Japan. RP Craigie, R (reprint author), NIDDKD, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. EM bobc@helix.nih.gov FU Intramural NIH HHS NR 163 TC 144 Z9 149 U1 3 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD MAR PY 2007 VL 5 IS 3 BP 187 EP 196 DI 10.1038/nrmicro1579 PG 10 WC Microbiology SC Microbiology GA 137EE UT WOS:000244275000011 PM 17304248 ER PT J AU Voeltz, GK Prinz, WA AF Voeltz, Gia K. Prinz, William A. TI Sheets, ribbons and tubules - how organelles get their shape SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID TRANSITIONAL ENDOPLASMIC-RETICULUM; MITOCHONDRIAL CRISTAE MORPHOLOGY; ATP SYNTHASE; SACCHAROMYCES-CEREVISIAE; MICROTUBULE DISRUPTION; MEMBRANE CURVATURE; NUCLEAR-ENVELOPE; GOLGI STRUCTURE; SUBUNIT-E; IN-VIVO AB Most membrane-bound organelles have elaborate, dynamic shapes and often include regions with distinct morphologies. These complex structures are relatively conserved throughout evolution, which indicates that they are important for optimal organelle function. Various mechanisms of determining organelle shape have been proposed-proteins that stabilize highly curved membranes, the tethering of organelles to other cellular components and the regulation of membrane fission and fusion might all contribute. C1 NIDDK, Lab Cell Biochem & Biol, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Voeltz, GK (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM gia.voeltz@colorado.edu; wprinz@helix.nih.gov FU Intramural NIH HHS NR 54 TC 81 Z9 82 U1 3 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD MAR PY 2007 VL 8 IS 3 BP 258 EP 264 DI 10.1038/nrm2119 PG 7 WC Cell Biology SC Cell Biology GA 140CJ UT WOS:000244479900020 PM 17287811 ER PT J AU Lee, S Joshi, A Nagashima, K Freed, EO Hurley, JH AF Lee, Sangho Joshi, Anjali Nagashima, Kunio Freed, Eric O. Hurley, James H. TI Structural basis for viral late-domain binding to Alix SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID PROTEIN-SORTING PATHWAY; VIRUS LIFE-CYCLE; TSG101; APOPTOSIS; ESCRT; AIP1/ALIX; MOTIFS; OVEREXPRESSION; RELEASE; NETWORK AB The modular protein Alix is a central node in endosomal-lysosomal trafficking and the budding of human immunodeficiency virus (HIV)-1. The Gag p6 protein of HIV-1 contains a LYPx(n)LxxL motif that is required for Alix-mediated budding and binds a region of Alix spanning residues 360-702. The structure of this fragment of Alix has the shape of the letter 'V' and is termed the V domain. The V domain has a topologically complex arrangement of 11 alpha-helices, with connecting loops that cross three times between the two arms of the V. The conserved residue Phe676 is at the center of a large hydrophobic pocket and is crucial for binding to a peptide model of HIV-1 p6. Overexpression of the V domain inhibits HIV-1 release from cells. This inhibition of release is reversed by mutations that block binding of the Alix V domain to p6. C1 NIDDK, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, NIH,US Dept Hlth & Human Serv, Frederick, MD 21702 USA. NCI, Image Anal Lab, Res Technol Program, SAIC Frederick,NIH,US Dept Hlth & Human Serv, Frederick, MD 21702 USA. RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov FU Intramural NIH HHS [Z01 DK036118-14]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 45 TC 91 Z9 93 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAR PY 2007 VL 14 IS 3 BP 194 EP 199 DI 10.1038/nsmb1203 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 143IX UT WOS:000244715200007 PM 17277784 ER PT J AU Pekcec, A Bauer, B Hartz, AM Winter, J Tollner, K Miller, DS Potschka, H AF Pekcec, A. Bauer, B. Hartz, A. M. Winter, J. Toellner, K. Miller, D. S. Potschka, H. TI Regulation and prevention of seizure-induceo up-regulation of P-glycoprotein in rat brain capillaries SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 48th Spring Meeting of the Deutsche-Gesellschaft-fur Experimentelle-ung-Klinische-Pharmakologie-und-Toxikologie CY MAR 13-15, 2007 CL Mainz, GERMANY SP Deutsch Gesell Experimentelle & Klinische Pharmakol & Toxikol C1 Univ Munich, Dept Pharmacol Toxicol & Pharm, Munich, Germany. NIEHS, NIH, Chem Pharmacol Lab, Res Triangle Pk, NC 27709 USA. Univ Vet Med, Inst Pharmacol & Toxicol, Hannover, Germany. RI Toellner, Kai-Michael/F-1519-2011 OI Toellner, Kai-Michael/0000-0001-8404-645X 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 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2007 VL 375 SU 1 MA 248 BP 54 EP 54 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 161EK UT WOS:000245997000249 ER PT J AU Saur, O Shih, M Elsken, CS Forster, MJ Stark, H AF Saur, O. Shih, M. Elsken, C. S. Forster, M. J. Stark, H. TI The dopamine D-3 receptor antagonist ST 198 as a potential cocaine abuse therapeutic agent SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 48th Spring Meeting of the Deutsche-Gesellschaft-fur Experimentelle-ung-Klinische-Pharmakologie-und-Toxikologie CY MAR 13-15, 2007 CL Mainz, GERMANY SP Deutsch Gesell Experimentelle & Klinische Pharmakol & Toxikol C1 Univ Frankfurt, Inst Pharmazeut Chem, D-60438 Frankfurt, Germany. NIH, Natl Inst Drug Abuse, Bethesda, MD 20892 USA. Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. RI Stark, Holger/A-4235-2009; Fachbereich14, Dekanat/C-8553-2015 OI Stark, Holger/0000-0003-0642-0180; 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 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2007 VL 375 SU 1 MA 257 BP 56 EP 56 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 161EK UT WOS:000245997000258 ER PT J AU Klein, C Matthes, J Piekorz, R Koch, WJ Bimbaumer, L Numberg, B Herzig, S AF Klein, C. Matthes, J. Piekorz, R. Koch, W. J. Bimbaumer, L. Nuemberg, B. Herzig, S. TI Role of inhibitory proteins G(i alpha 2) and G(i alpha 3) for cardiac L-type calcium channel gating and survival of transgenic mice SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 48th Spring Meeting of the Deutsche-Gesellschaft-fur Experimentelle-ung-Klinische-Pharmakologie-und-Toxikologie CY MAR 13-15, 2007 CL Mainz, GERMANY SP Deutsch Gesell Experimentelle & Klinische Pharmakol & Toxikol C1 Univ Cologne, Dept Pharmacol, Cologne, Germany. Univ Dusseldorf, Dept Biochem & Mol Biol 2, D-4000 Dusseldorf, Germany. Univ Philadelphia, Ctr Translat Med, Philadelphia, PA USA. NIH, Res Triangle Pk, NC 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 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2007 VL 375 SU 1 MA 274 BP 59 EP 59 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 161EK UT WOS:000245997000274 ER PT J AU Westermann, D Mersmann Melchior, A Freudenberper, T Petrik, C Lullmann-Rauch, R Rauch, R Ung, MF Levkau, B Baba, H Unger, TH Zacharowski, K Tschbpe, C Fischer, JW AF Westermann, D. Mersmann Melchior, A. Freudenberper, T. Petrik, C. Luellmann-Rauch, R. Rauch, R. Ung, M. F. Levkau, B. Baba, H. Unger, T. H. Zacharowski, K. Tschbpe, C. Fischer, J. W. TI Cardiac dysfunction and decreased survival of biglycan-deficient mice after myocardial infarction SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 48th Spring Meeting of the Deutsche-Gesellschaft-fur Experimentelle-ung-Klinische-Pharmakologie-und-Toxikologie CY MAR 13-15, 2007 CL Mainz, GERMANY SP Deutsch Gesell Experimentelle & Klinische Pharmakol & Toxikol C1 Charite Univ Klinikum, Abt Kardiol & Pneumol, Berlin, Germany. Univ Dusseldorf, Abt Anasthesie, Mol Kardioprotekt & Entzundung, D-4000 Dusseldorf, Germany. Univ Dusseldorf, Inst Pharmakol & Klin Pharmakol, D-4000 Dusseldorf, Germany. Charite Univ Med Berlin, Inst Pharmakol & Toxikol, Cardiovasc Res Ctr, Berlin, Germany. Univ Kiel, Inst Anat, D-2300 Kiel, Germany. NIH, Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. Univ Klinikum Essen, Inst Pathophysiol, Essen, Germany. Univ Klinikum Essen, Inst Pathol, Essen, Germany. 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 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2007 VL 375 SU 1 MA 295 BP 63 EP 63 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 161EK UT WOS:000245997000295 ER PT J AU Lukasova, M Wirth, A Wettschureck, N Gutkind, S Offermanns, S AF Lukasova, M. Wirth, A. Wettschureck, N. Gutkind, S. Offermanns, S. TI Role of RhoGEF proteins in DOCA-salt induced hypertension SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 48th Spring Meeting of the Deutsche-Gesellschaft-fur Experimentelle-ung-Klinische-Pharmakologie-und-Toxikologie CY MAR 13-15, 2007 CL Mainz, GERMANY SP Deutsch Gesell Experimentelle & Klinische Pharmakol & Toxikol C1 Univ Heidelberg, Inst Pharmakol, D-69120 Heidelberg, Germany. NIH, NIDCR, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 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 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2007 VL 375 SU 1 BP 64 EP 65 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 161EK UT WOS:000245997000303 ER PT J AU Ruwiedel, K Schieke, SM Brenden, H Bruhnke, S Schafer, C Schroeder, P Fritsche, E Abel, J Krutmann, J Grether-Beck, S AF Ruwiedel, K. Schieke, S. M. Brenden, H. Bruhnke, S. Schaefer, C. Schroeder, P. Fritsche, E. Abel, J. Krutmann, J. Grether-Beck, S. TI Expression of matrix metalloprotease 1 (MMP1) in human skin is depending on a molecular crosstalk of ultraviolet (UV) A- and UVB-induced signaling SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 48th Spring Meeting of the Deutsche-Gesellschaft-fur Experimentelle-ung-Klinische-Pharmakologie-und-Toxikologie CY MAR 13-15, 2007 CL Mainz, GERMANY SP Deutsch Gesell Experimentelle & Klinische Pharmakol & Toxikol C1 Univ Dusseldorf, Inst Environm Hlth Res, IUF gGmbH, D-40225 Dusseldorf, Germany. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2007 VL 375 SU 1 MA 363 BP 75 EP 75 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 161EK UT WOS:000245997000362 ER PT J AU Yao, RS Yi, YJ Grubbs, CJ Lubet, RA You, M AF Yao, Ruisheng Yi, Yijun Grubbs, Clinton J. Lubet, Ronald A. You, Ming TI Gene expression profiling of chemically induced rat bladder tumors SO NEOPLASIA LA English DT Article DE rat bladder tumors; expression profile; microarray; chemical carcinogen; pathways ID TRANSITIONAL-CELL-CARCINOMA; URINARY-BLADDER; ANNEXIN A1; P53 MUTATIONS; EXCHANGE FACTORS; LIPOCORTIN 1; HA-RAS; CANCER; PROGRESSION; ACTIVATION AB A variety of genetic alterations and gene expression changes are involved in the pathogenesis of bladder tumors. To explore expression changes in 4-hydroxybuty-( butyl) nitrosamine-induced rat bladder tumors, microarray analysis was performed. Analysis yielded 1,138 known genes and 867 expressed sequence tags that were changed when comparing tumors to normal rat epithelia. Altered genes included cell cycle-related genes, EGFR-Ras signaling genes, apoptosis genes, growth factors, and oncogenes. Using the pathway visualization tool GenMAPP, we found that these genes can be grouped along several pathways that control apoptosis, cell cycle, and integrin-mediated cell adhesion. When comparing current data with previous mouse bladder tumor data, we found that > 280 of the same known genes were differentially expressed in both mouse and rat bladder tumors, including cell cycle-related genes, small G proteins, apoptosis genes, oncogenes, tumor-suppressor genes, and growth factors. These results suggest that multiple pathways are involved in rat bladder tumorigenesis, and a common molecular mechanism was found in both rat and mouse bladder tumors. C1 Washington Univ, Dept Surg, Sch Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP You, M (reprint author), Washington Univ, Dept Surg, Sch Med, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA. EM youm@msnotes.wustl.edu NR 64 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1476-5586 J9 NEOPLASIA JI Neoplasia PD MAR PY 2007 VL 9 IS 3 BP 207 EP 221 DI 10.1593/neo.06814 PG 15 WC Oncology SC Oncology GA 149AP UT WOS:000245119000005 PM 17401461 ER PT J AU Perlman, WR Webster, MJ Herman, MM Kleinman, JE Weickert, CS AF Perlman, William R. Webster, Maree J. Herman, Mary M. Kleinman, Joel E. Weickert, Cynthia Shannon TI Age-related differences in glucocorticoid receptor mRNA levels in the human brain SO NEUROBIOLOGY OF AGING LA English DT Article DE glucocorticoid receptor; human; prefrontal cortex; hippocampus; primary visual cortex; visual association cortex; in situ hybridization; development; age; neuroendocrinology; stress ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DEXAMETHASONE-SUPPRESSION TEST; POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSIVE DISORDER; HUMAN LIFE-SPAN; MINERALOCORTICOID-RECEPTOR; HIPPOCAMPAL VOLUME; GENE-EXPRESSION; PREFRONTAL CORTEX; RIBONUCLEIC-ACID AB Glucocorticoids and their receptors (GRs) are implicated in dynamic cognitive and neuroendocrine processes mediated by the prefrontal cortex and hippocampus. Additionally, a primary defect in forebrain GR levels can mimic symptoms of depression. We hypothesized that changes in GR mRNA levels may occur in the human brain across the life span thus positioning GR to differentially influence behavior and disease susceptibility. Following in situ hybridization with a riboprobe for human GR mRNA, we employed quantitative film autoradiography to measure expression levels in the prefrontal cortex and hippocampus in five age groups (infants, adolescents, young adults, adults, and aged) and in primary visual and visual association cortices for comparison. We detected a main effect of age group on cortical, but not hippocampal GR mRNA, with greater cortical expression in adolescents and adults than in infants or the aged. Increased GR mRNA in prefrontal cortex during adolescence and adulthood suggests that human GR-mediated forebrain regulation of cognition and the neuroendocrine stress response may be more salient during late maturation and at maturity. Published by Elsevier Inc. C1 NIMH, Clin Brain Disorders Branch, MINDS Unit, NIH, Bethesda, MD 20892 USA. US Dept Hlth & Human Serv, MINDS Unit, Intramural Res Program, NIMH,NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Fdn Lab Brain Res, Bethesda, MD 20814 USA. RP Weickert, CS (reprint author), NIMH, Clin Brain Disorders Branch, MINDS Unit, NIH, 10 Ctr Dr,Room 4D18, Bethesda, MD 20892 USA. EM perlmanw@intra.nimh.nih.gov; websterm@stanleyresearch.org; hermanm@intra.nimh.nih.gov; kleinmaj@intra.nimh.nih.gov; shannowc@intra.nimh.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011 FU Intramural NIH HHS NR 84 TC 68 Z9 68 U1 0 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 MAR PY 2007 VL 28 IS 3 BP 447 EP 458 DI 10.1016/j.neurobiolaging.2006.01.010 PG 12 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 137CG UT WOS:000244269800014 PM 16540204 ER PT J AU Myers, AJ Pittman, AM Zhao, AS Rohrer, K Kaleem, M Marlowe, L Lees, A Leung, D McKeith, IG Perry, RH Morris, CM Trojanowski, JQ Clark, C Karlawish, J Arnold, S Forman, MS Van Deerlin, V de Silva, R Hardy, J AF Myers, Amanda J. Pittman, Alan M. Zhao, Alice S. Rohrer, Kristen Kaleem, Mona Marlowe, Lauren Lees, Andrew Leung, Doris McKeith, Ian G. Perry, Robert H. Morris, Chris M. Trojanowski, John Q. Clark, Christopher Karlawish, Jason Arnold, Steve Forman, Mark S. Van Deerlin, Vivianna de Silva, Rohan Hardy, John TI The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts SO NEUROBIOLOGY OF DISEASE LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; CORTICOBASAL DEGENERATION; FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; PROMOTER REGION; GENE; FTDP-17 AB Previously we have shown that the H1c haplotype on the background of the HI clade of haplotypes at the MAPT locus is associated with increased risk for progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Alzheimer's disease (AD). Here we replicated the association with AD in an additional autopsy confirmed series. We show that this haplotype increases both the expression of total MAPT transcript as well as specifically increasing the proportion of 4 microtubule binding repeat containing transcripts. We discuss these findings both in terms of the problems facing the dissection of the etiologies of complex traits and the pathogenesis of the tauopathies. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. UCL, Reta Lila Weston Inst Neurol Studies, London WC1N 1PJ, England. Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. Inst Neurol, Sara Koe PSP Res Ctr, London WC1N 1PJ, England. Newcastle Gen Hosp, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Porter Neurosci Bldg,35 Convent Dr, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI de Silva, Rohan/C-1734-2008; Myers, Amanda/B-1796-2010; Hardy, John/C-2451-2009; Pittman, Alan/D-6231-2012; Lees, Andrew/A-6605-2009; Leung, Doris/R-5447-2016 OI de Silva, Rohan/0000-0002-5052-5775; Myers, Amanda/0000-0002-3100-9396; Leung, Doris/0000-0002-2558-7798 FU Intramural NIH HHS; Medical Research Council [G0501560, G0501560(76517), G0701075]; NIA NIH HHS [AG 05146, AG-10124, AG-17586, AG05128, P30-AG13846, P50 AG16570, P50-AG08671]; NIMH NIH HHS [MH60451]; NINDS NIH HHS [NS39764] NR 19 TC 134 Z9 138 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAR PY 2007 VL 25 IS 3 BP 561 EP 570 DI 10.1016/j.nbd.2006.10.018 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 145NQ UT WOS:000244872200012 PM 17174556 ER PT J AU Schmitt, JE Wallace, GL Rosenthal, MA Molloy, EA Ordaz, S Lenroot, R Clasen, LS Blumenthal, JD Kendler, KS Neale, MC Giedd, JN AF Schmitt, J. Eric Wallace, Gregory L. Rosenthal, Michael A. Molloy, Elizabeth A. Ordaz, Sarah Lenroot, Rhoshel Clasen, Liv S. Blumenthal, Jonathan D. Kendler, Kenneth S. Neale, Michael C. Giedd, Jay N. TI A multivariate analysis of neuroanatomic relationships in a genetically informative pediatric sample SO NEUROIMAGE LA English DT Article ID BRAIN STRUCTURE; MONOZYGOTIC TWINS; CORTICAL DEVELOPMENT; CEREBRAL-CORTEX; MRI DATA; SCHIZOPHRENIA; SIZE; VOLUMES; GENES; REGIONALIZATION AB An important component of brain mapping is an understanding of the relationships between neuroanatomic structures, as well as the nature of shared causal factors. Prior twin studies have demonstrated that much of individual differences in human anatomy are caused by genetic differences, but information is limited on whether different structures share common genetic factors. We performed a multivariate statistical genetic analysis on volumetric MRI measures (cerebrum cerebellum, lateral ventricles, corpus callosum, thalamus, and basai ganglia) from a pediatric sample of 326 twins and 158 singletons. Our results suggest that the great majority of variability in cerebrum, cerebellum, thalamus and basal ganglia is determined by a single genetic factor. Though most (75%) of the variability in corpus callosum was explained by additive genetic effects these were largely independent of other structures. We also observed relatively small but significant environmental effects common to multiple neuroanatomic regions, particularly between thalamus, basal ganglia, and lateral ventricles. These findings are concordant with prior volumetric twin studies and support radial models of brain evolution. (c) 2006 Published by Elsevier Inc. C1 NIMH, NIH, Dept Hlth & Human Serv, Clin Psychiat Branch, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23298 USA. RP Giedd, JN (reprint author), NIMH, NIH, Dept Hlth & Human Serv, Clin Psychiat Branch, Room 4C110,10 Ctr Dr,MSC 1367, Bethesda, MD 20892 USA. EM jg@nih.gov RI Giedd, Jay/A-3080-2008; Wallace, Gregory/A-4789-2008; 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; Wallace, Gregory/0000-0003-0329-5054 FU NIDA NIH HHS [DA-18673]; NIMH NIH HHS [MH-20030, MH-65322] NR 64 TC 43 Z9 44 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 MAR PY 2007 VL 35 IS 1 BP 70 EP 82 DI 10.1016/j.neuroimage.2006.04.232 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 145VN UT WOS:000244894000008 PM 17208460 ER PT J AU Goldstein, RZ Tomasi, D Alia-Klein, N Zhang, L Telang, F Volkow, ND AF Goldstein, Rita Z. Tomasi, Dardo Alia-Klein, Nelly Zhang, Lei Telang, Frank Volkow, Nora D. TI The effect of practice on a sustained attention task in cocaine abusers SO NEUROIMAGE LA English DT Article DE fMRI BOLD; adaptation; practice effects; prefrontal cortex; alertness; drug abuse; drug addiction; salience; reward ID MEDIAL PREFRONTAL CORTEX; WORKING-MEMORY; ANTERIOR CINGULATE; FUNCTIONAL-ANATOMY; VISUAL-ATTENTION; DRUG-ADDICTION; FRONTAL-CORTEX; ACTIVATION; BRAIN; HABITUATION AB Habituation enables the organism to attend selectively to novel stimuli by diminishing no-longer necessary responses to repeated stimuli. Because the prefrontal cortex (PFC) has a core role in monitoring attention and behavioral control especially under novelty, neural habituation responses may be modified in drug addiction, a psychopathology that entails PFC abnormalities in both structure and function. Sixteen cocaine abusers and 12 gender-, race-, education-, and intelligence-matched healthy control subjects performed an incentive sustained attention task twice, under novelty and after practice, during functional magnetic resonance imaging. For cocaine abusers practice effects were noted in the PFC (including anterior cingulate cortex/ventromedial rostral PFC, dorsolateral PFC, and medial frontal gyrus) and cerebellum (signal attenuations/decreases: return to baseline); activations in these regions were associated with craving, frequency of use, and length of abstinence. In the control subjects practice effects were instead restricted to posterior brain regions (precuneus and cuneus) (signal amplifications/increases: deactivation away from baseline). Also, only in the cocaine abusers, increased speed of behavioral performance between novelty to practice was associated with a respective attenuation of activation in the thalamus. Overall, we report for the first time a differential pattern of neural responses to repeated presentation of an incentive sustained attention task in cocaine addiction. Our results suggest a disruption in drug addiction of neural habituation to practice that possibly encompasses opponent anterior vs. posterior brain adaptation to the novelty of the experience: overly expeditious for the former but overly protracted for the latter. Overall, cocaine addicted individuals may be predisposed to an increased challenge when required to maintain alertness as a task progresses, not able to optimally utilize a prematurely habituating PFC to compensate with an increased attribution of salience to a desired reward. (c) 2006 Elsevier Inc. All rights reserved. C1 Brookhaven Natl Lab, Dept Med Res, Ctr Translat NeuroImaging, Upton, NY 11973 USA. SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11794 USA. NIDA, Bethesda, MD 20892 USA. NIAAA, Rockville, MD 20857 USA. RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, Dept Med Res, Ctr Translat NeuroImaging, POB 5000, Upton, NY 11973 USA. EM rgoldstein@bnl.gov RI Tomasi, Dardo/J-2127-2015 FU NCRR NIH HHS [5-MO1-RR-10710, M01 RR010710]; NIAAA NIH HHS [AA/ODO9481-04]; NIDA NIH HHS [1K23 DA15517-01, K23 DA015517, R03 DA 017070-01, R03 DA017070] NR 56 TC 31 Z9 32 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2007 VL 35 IS 1 BP 194 EP 206 DI 10.1016/j.neuroimage.2006.12.004 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 145VN UT WOS:000244894000019 PM 17236790 ER PT J AU Blair, KS Smith, BW Mitchell, DGV Morton, J Vythilingam, M Pessoa, L Fridberg, D Zametkin, A Nelson, EE Drevets, WC Pine, DS Martin, A Blair, RJR AF Blair, K. S. Smith, B. W. Mitchell, D. G. V. Morton, J. Vythilingam, M. Pessoa, L. Fridberg, D. Zametkin, A. Nelson, E. E. Drevets, W. C. Pine, D. S. Martin, A. Blair, R. J. R. TI Modulation of emotion by cognition and cognition by emotion SO NEUROIMAGE LA English DT Article DE fMRI; emotion; attention; stroop interference; emotional interference ID EVENT-RELATED FMRI; NEGATIVE AFFECT; VOLUNTARY SUPPRESSION; ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX; NEURAL CIRCUITRY; HUMAN AMYGDALA; ATTENTION; RESPONSES; FACES AB In this study, we examined the impact of goal-directed processing on the response to emotional pictures and the impact of emotional pictures on goal-directed processing. Subjects (N = 22) viewed neutral or emotional pictures in the presence or absence of a demanding cognitive task. Goal-directed processing disrupted the BOLD response to emotional pictures. In particular, the BOLD response within bilateral amygdala and inferior frontal gyrus decreased during concurrent task performance. Moreover, the presence of both positive and negative distractors disrupted task performance, with reaction times increasing for emotional relative to neutral distractors. Moreover, in line with the suggestion of the importance of lateral frontal regions in emotional regulation [Ochsner, K. N., Ray, R. D., Cooper, J. C., Robertson, E. R., Chopra, S., Gabrieli, J. D., et al. (2004). For better or for worse: neural systems supporting the cognitive down-and up-regulation of negative emotion. Neurolmage, 23(2), 483-499], connectivity analysis revealed positive connectivity between lateral superior frontal cortex and regions of middle frontal cortex previously implicated in emotional suppression [Beauregard, M., Levesque, J., and Bourgouin, P. (2001). Neural correlates of conscious self-regulation of emotion. J. Neurosci., 21 (18), RC165.; Levesque, J., Eugene, F., Joanette, Y., Paquette, V., Mensour, B., Beaudoin, G., et al. (2003). Neural circuitry underlying voluntary suppression of sadness. Biol. Psychiatry, 53 (6)9 502-510.; Ohira, H., Nomura, M., Ichikawa, N., Isowa, T., lidaka, T., Sato, A., et al. (2006). Association of neural and physiological responses during voluntary emotion suppression. Neuro-Image, 29 (3), 721-733] and negative connectivity with bilateral amygdala. These data suggest that processes involved in emotional regulation are recruited during task performance in the context of emotional distractors. (c) 2006 Elsevier Inc. All rights reserved. C1 NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Univ New Mexico, Dept Psychol, Albuquerque, NM 87505 USA. UCL, Inst Cognit Neurosci, London WC1E 6BT, England. Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. NIMH, Lab Brain & Cognit, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Blair, KS (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. EM peschark@mail.nih.gov RI Nelson, Eric/B-8980-2008; martin, alex/B-6176-2009; Frank, David/E-8213-2012 OI Nelson, Eric/0000-0002-3376-2453; FU Intramural NIH HHS [Z99 MH999999] NR 46 TC 182 Z9 194 U1 8 U2 48 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 MAR PY 2007 VL 35 IS 1 BP 430 EP 440 DI 10.1016/j.neuroimage.2006.11.048 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 145VN UT WOS:000244894000041 PM 17239620 ER PT J AU Peineau, S Taghibiglou, C Bradley, C Wong, TP Liu, LD Lu, J Lo, E Wu, DC Saule, E Bouschet, T Matthews, P Isaac, JTR Bortolotto, ZA Wang, YT Collingridge, GL AF Peineau, Stephane Taghibiglou, Changiz Bradley, Clarrisa Wong, Tak Pan Liu, Lidong Lu, Jie Lo, Edmond Wu, Dongchuan Saule, Emilia Bouschet, Tristan Matthews, Paul Isaac, John T. R. Bortolotto, Zuner A. Wang, Yu Tian Collingridge, Graham L. TI UP inhibits LTD in the hippocampus via regulation of GSK3 beta SO NEURON LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; LONG-TERM DEPRESSION; PROTEIN-KINASE; SYNAPTIC PLASTICITY; TAU-PROTEIN; RAT-BRAIN; RECEPTOR TRAFFICKING; ALZHEIMERS-DISEASE; NEURONAL POLARITY; NMDA RECEPTORS AB Glycogen synthase kinase-3 (GSK3) has been implicated in major neurological disorders, but its role in normal neuronal function is largely unknown. Here we show that GSK3 beta mediates an interaction between two major forms of synaptic plasticity in the brain, N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) and NMDA receptor-dependent long-term depression (LTD). In rat hippocampal slices, GSK3 beta inhibitors block the induction of LTD. Furthermore, the activity of GSK3 beta is enhanced during LTD via activation of PP1. Conversely, following the induction of LTP, there is inhibition of GSK3 beta activity. This regulation of GSK3 beta during LTP involves activation of NMDA receptors and the PI3K-Akt pathway and disrupts the ability of synapses to undergo LTD for up to 1 hr. We conclude that the regulation of GSK3 beta activity provides a powerful mechanism to preserve information encoded during LTP from erasure by subsequent LTD, perhaps thereby permitting the initial consolidation of learnt information. C1 MRC, Ctr Synapt Plast, Dept Anat, Sch Med Sci, Bristol BS8 1TD, Avon, England. Univ British Columbia, Brain Res Ctr, UBC Hosp, Vancouver, BC V6T 1Z3, Canada. Univ British Columbia, Dept Med, UBC Hosp, Vancouver, BC V6T 1Z3, Canada. NINDS, NIH, Bethesda, MD 20892 USA. RP Collingridge, GL (reprint author), MRC, Ctr Synapt Plast, Dept Anat, Sch Med Sci, Univ Walk, Bristol BS8 1TD, Avon, England. EM g.l.collingridge@bristol.ac.uk RI Wang, Yu Tian/A-4729-2008; Collingridge, Graham/C-4605-2015; Wang, Yu Tian/J-8255-2015; Wu, Dong Chuan/O-3909-2015 OI Collingridge, Graham/0000-0002-9572-5359; Wang, Yu Tian/0000-0001-8592-0698; FU Medical Research Council [G9532377] NR 65 TC 343 Z9 355 U1 1 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 1 PY 2007 VL 53 IS 5 BP 703 EP 717 DI 10.1016/j.neuron.2007.01.029 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 149DL UT WOS:000245127100011 PM 17329210 ER PT J AU Kaminski, RM Witkin, JM Shippenberg, TS AF Kaminski, Rafal M. Witkin, Jeffrey M. Shippenberg, Toni S. TI Pharmacological and genetic manipulation of kappa opioid receptors: Effects on cocaine- and pentylenetetrazol-induced convulsions and seizure kindling SO NEUROPHARMACOLOGY LA English DT Article DE kappa opioid receptor; cocaine; pentylenctetrazol; convulsions; kindling; knock-out mice; seizure ID PILOCARPINE-INDUCED SEIZURES; BEHAVIORAL SENSITIZATION; NEUROACTIVE STEROIDS; STATUS EPILEPTICUS; AGONISTS; ANTICONVULSANT; DYNORPHIN; MODULATION; EPILEPSY; MOUSE AB The present study used pharmacological and gene ablation techniques to examine the involvement of kappa opioid receptors (KOPr) in modulating the convulsant effects of two mechanistically different drugs: cocaine and pentylenetetrazol (PTZ; GABA-A receptor antagonist) in mice. Systemic administration of the selective KOPr-1 agonist, U69593 (0.16-0.6 mg/kg; s.c.), failed to modify cocaine-evoked convulsions or cocaine kindling. Similarly, no alteration in responsiveness to cocaine was observed in wild-type mice that received the selective KOPr-1 antagonist, nor-binaltorphimine (nor-BNI; 5 mg/kg) or in mice lacking the gene encoding KOPr-1. In contrast to cocaine, U69593 attenuated the seizures induced by acute or repeated PTZ administration. Nor-BNI decreased the threshold for PTZ-evoked seizures and increased seizure incidence during the initial induction of kindling relative to controls. Decreased thresholds for PTZ-induced seizures were also observed in KOPr-1 knock out mice. Together, these data demonstrate an involvement of endogenous KOPr systems in modulating vulnerability to the convulsant effects of PTZ but not cocaine. Furthermore, they demonstrate that KOPr-1 activation protects against acute and kindled seizure, induced by this convulsant. Finally, the results of our study suggest that KOPr-1 antagonists will not have therapeutic utility against cocaine-induced seizures, while they may prove beneficial in attenuating several actions of cocaine that have been linked to its abuse. (c) 2006 Published by Elsevier Ltd. C1 NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, NIH,Intramural Res Program, Baltimore, MD 21224 USA. NIDA, Drug Dev Grp, Behav Neurosci Branch, NIH,Intramural Res Program, Baltimore, MD 21224 USA. RP Kaminski, RM (reprint author), NINDS, Epilepsy Res Sect, NIH, 35 Lincoln Dr,MSC 3702,Bldg 35,Room 1C1000, Bethesda, MD 20892 USA. EM kaminskr@mail.nih.gov FU Intramural NIH HHS NR 66 TC 8 Z9 9 U1 0 U2 0 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 MAR PY 2007 VL 52 IS 3 BP 895 EP 903 DI 10.1016/j.neuropharm.2006.10.007 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 146VK UT WOS:000244962600022 PM 17126860 ER PT J AU Swanson, JM Kinsbourne, M Nigg, J Lanphear, B Stefanatos, GA Volkow, N Taylor, E Casey, BJ Castellanos, FX Wadhwa, PD AF Swanson, James M. Kinsbourne, Marcel Nigg, Joel Lanphear, Bruce Stefanatos, Gerry A. Volkow, Nora Taylor, Eric Casey, B. J. Castellanos, F. Xavier Wadhwa, Pathik D. TI Etiologic subtypes of attention-deficit/hyperactivity disorder: Brain imaging, molecular genetic and environmental factors and the dopamine hypothesis SO NEUROPSYCHOLOGY REVIEW LA English DT Review DE ADHD (or Attention-Deficit/Hyperactivity disorder); dopamine; molecular genetics; brain imaging; environmental risk; minimal brain dysfunction ID DEFICIT-HYPERACTIVITY DISORDER; ANALOG CLASSROOM ASSESSMENT; D-4 RECEPTOR GENE; ORAL METHYLPHENIDATE; EXTRACELLULAR DOPAMINE; PSYCHIATRIC-DISORDERS; TRANSPORTER GENE; 7-REPEAT ALLELE; GENOMEWIDE SCAN; FETAL-GROWTH AB Multiple theories of Attention-Deficit/Hyperactivity Disorder (ADHD) have been proposed, but one that has stood the test of time is the dopamine deficit theory. We review the narrow literature from recent brain imaging and molecular genetic studies that has improved our understanding of the role of dopamine in manifestation of symptoms of ADHD, performance deficits on neuropsychological tasks, and response to stimulant medication that constitutes the most common treatment of this disorder. First, we consider evidence of the presence of dopamine deficits based on the recent literature that (1) confinns abnormalities in dopamine-modulated frontal-striatal circuits, reflected by size (smaller-than-average components) and function (hypoactivation); (2) clarifies the agonist effects of stimulant medication on dopaminergic mechanisms at the synaptic and circuit level of analysis; and (3) challenges the most-widely accepted ADHD-related neural abnormality in the dopamine system (higher-than-normal dopamine transporter [DAT] density). Second, we discuss possible genetic etiologies of dopamine deficits based on recent molecular genetic literature, including (1) multiple replications that confirm the association of ADHD with candidate genes related to the dopamine receptor D4 (DRD4) and the DAT; (2) replication of differences in performance of neuropsychological tasks as a function of the DRD4 genotype; and (3) multiple genome-wide linkage scans that demonstrate the limitations of this method when applied to complex disorders but implicate additional genes that may contribute to the genetic basis of ADHD. Third, we review possible environmental etiologies of dopamine deficits based on recent studies of (1) toxic substances that may affect the dopamine system in early development and contribute substantially to the etiology of ADHD; (2) fetal adaptations in dopamine systems in response to stress that may alter early development with lasting effects, as proposed by the developmental origins of health and disease hypothesis; and (3) gene-environment interactions that may moderate selective damage or adaptation of dopamine neurons. Based on these reviews, we identify critical issues about etiologic subtypes of ADHD that may involve dopamine, discuss methods that could be used to address these issues, and review old and new theories that may direct research in this area in the future. C1 Univ Calif Irvine, Dept Pediat, Irvine, CA 92612 USA. New Sch Social Res, Dept Psychol, New York, NY 10011 USA. Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. Childrens Hosp, Dept Pediat, Cincinnati, OH 45229 USA. Albert Einstein Med Ctr, Cognit Neurophysiol Lab, Philadelphia, PA 19141 USA. Natl Inst Drug Abuse, Rockville, MD USA. Brookhaven Natl Lab, Rockville, MD USA. Inst Psychiat, Dept Child Psychiat, London, England. Cornell Univ, Weill Coll Med, Sackler Inst, New York, NY USA. NYU, Dept Child Psychiat & Adolescent, New York, NY USA. Univ Calif Irvine, Dept Psychiat & OB GYN, Irvine, CA 92612 USA. RP Swanson, JM (reprint author), Univ Calif Irvine, Dept Pediat, 19722 MacArthur Blvd, Irvine, CA 92612 USA. EM jmswanso@uci.edu OI Castellanos, Francisco/0000-0001-9192-9437 NR 147 TC 263 Z9 274 U1 10 U2 67 PU CONSULTANTS BUREAU/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1040-7308 J9 NEUROPSYCHOL REV JI Neuropsychol. Rev. PD MAR PY 2007 VL 17 IS 1 BP 39 EP 59 DI 10.1007/s11065-007-9019-9 PG 21 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA 147PH UT WOS:000245014400003 PM 17318414 ER PT J AU Panlilio, LV Solinas, M Matthews, SA Goldberg, SR AF Panlilio, Leigh V. Solinas, Marcello Matthews, Stephanie A. Goldberg, Steven R. TI Previous exposure to THC alters the reinforcing efficacy and anxiety-related effects of cocaine in rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE self-administration; gateway drug hypothesis; progressive-ratio schedule; open field; light-dark test; heroin ID CORTICOTROPIN-RELEASING-FACTOR; RECEPTOR AGONIST CP-55,940; SELF-ADMINISTERED COCAINE; SOCIAL-INTERACTION TEST; LONG-TERM DEPRESSION; BEHAVIORAL SENSITIZATION; DRUG-USE; INTRAVENOUS COCAINE; NUCLEUS-ACCUMBENS; DELTA(9)-TETRAHYDROCANNABINOL EXPOSURE AB The hypothesis that prior cannabis exposure increases the likelihood of becoming addicted to other drugs can be evaluated by giving rats a history of tetrahydrocannabinol ( THC) exposure, then allowing them to self- administer other drugs. In Experiment 1, THC pre-exposure did not alter the acquisition of cocaine self- administration or the amount of cocaine taken under a fixed-ratio 1 ( FR1) schedule, with one response required for each injection. Under a progressive-ratio schedule, with the response requirement increasing exponentially with each injection, cocaine- seeking was significantly reduced in THC- exposed rats, suggesting that the regimen of THC exposure used in the present study caused cocaine to be devalued as a reinforcer. In contrast, in an earlier study that used the same regimen, a history of THC exposure did not alter the value of heroin as a reinforcer under the progressive- ratio schedule, but it increased heroin self- administration under the FR1 schedule. Experiment 2 examined how this regimen of THC pre-exposure alters the locomotor effects of cocaine and heroin. THC pre-exposure produced cross-tolerance to the motor-depressant effects of heroin; this may explain the shortened post-injection pauses exhibited by THC- exposed rats under FR1 heroin self- administration. When given cocaine, THC-exposed rats exhibited normal increases in locomotion, but they avoided the center of the open field, suggesting that this THC pre-exposure regimen enhances the anxiogenic effects of cocaine. This enhanced anxiogenic effect-which was verified in Experiment 3 using another model of anxiety, the light - dark test-may explain the reduced reinforcing value of cocaine observed in THC- exposed rats in Experiment 1. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. Univ Poitiers, Lab Biol Physiol Cellulaire, CNRS 6187, Poitiers, France. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov RI Solinas, Marcello/M-3500-2016 OI Solinas, Marcello/0000-0002-0664-5964 FU Intramural NIH HHS NR 76 TC 33 Z9 33 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2007 VL 32 IS 3 BP 646 EP 657 DI 10.1038/sj.npp.1301109 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 137EA UT WOS:000244274600015 PM 16738542 ER PT J AU Miller, FG AF Miller, Franklin G. TI Financial relationships of institutional review board members SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID INDUSTRY C1 NIH, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 3 TC 1 Z9 1 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 MAR 1 PY 2007 VL 356 IS 9 BP 965 EP 965 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 140HV UT WOS:000244496400032 PM 17329710 ER PT J AU Stratakis, CA AF Stratakis, Constantine A. TI Case 36-2006: A pregnant woman with new hypertension SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CORTICOSTEROIDS C1 NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 4 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 MAR 1 PY 2007 VL 356 IS 9 BP 967 EP 967 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 140HV UT WOS:000244496400038 PM 17338056 ER PT J AU Maderia, M Shenoy, S Van, QN Marquez, VE Barchi, JJ AF Maderia, Melissa Shenoy, Shilpa Van, Que N. Marquez, Victor E. Barchi, Joseph J., Jr. TI Biophysical studies of DNA modified with conformationally constrained nucleotides: comparison of 2 '-exo (north) and 3 '-exo (south) 'locked' templates SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEIC-ACID RECOGNITION; (CYTOSINE C5)-METHYLTRANSFERASE; BICYCLO<3.1.0>HEXANE TEMPLATE; ANTIGENE TECHNOLOGY; BIOLOGICAL-ACTIVITY; NEPLANOCIN-C; SUGAR RING; NUCLEOSIDES; LNA; ANALOGS AB The biophysical properties of oligodeoxyribonucleotides (ODNs) selectively modified with conformationally 'locked' bicyclo[3.1.0]hexane pseudosugars (Maier,M.A., Choi,Y., Gaus,H., Barchi,J.J. Jr, Marquez,V.E., Manoharan,M. (2004) Synthesis and characterization of oligonucleotides containing conformationally constrained bicyclo[3.1.0]hexane pseudosugar analogs Nucleic Acids Res., 32, 3642-3650) have been studied by various techniques. Six separate synthetic ODNs based on the Dickerson Drew dodecamer sequence (CGCGAAT*T*CGCG) were examined where each one (or both) of the thymidines (T*) were substituted with a bicyclic pseudosugar locked in either a North (2'-exo) or South (3'-exo) ring pucker. Circular dichroism spectroscopy, differential scanning calorimetry and H-1 NMR spectroscopy were used to examine the duplex stability and conformational properties of the ODNs. Replacement of one or both thymidines with North-locked sugars (RNA-like) into the dodecamer did not greatly affect duplex formation or melt temperatures but distinct differences in thermodynamic parameters were observed. In contrast, incorporation of South-locked sugar derivatives that were predicted to stabilize this standard B-DNA, had the unexpected effect of causing a conformational equilibrium between different duplex forms at specific strand and salt concentrations. Our data and those of others suggest that although DNA can tolerate modifications with RNA-like (North) nucleotides, a more complicated spectrum of changes emerges with modifications restricted to South (DNA-like) puckers. C1 NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21702 USA. SAIC Frederick Inc, Mol Targets Dev Program, Frederick, MD 21702 USA. SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Barchi, JJ (reprint author), NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21702 USA. EM barchi@helix.nih.gov RI Barchi Jr., Joseph/N-3784-2014 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 51 TC 8 Z9 8 U1 0 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 MAR PY 2007 VL 35 IS 6 BP 1978 EP 1991 DI 10.1093/nar/gkm025 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 162XU UT WOS:000246123600030 PM 17341464 ER PT J AU Gardner, DB AF Gardner, Deborah B. TI Advancing national health care: Do we dare consider comprehensive reform again? SO NURSING ECONOMICS LA English DT Article AB Educating ourselves on various strategies that could improve the health care system is a useful first step to better participate in the health care reform debate. The primary issue is that most people believe building on the current system is the only politically viable course. Others maintain the opposite view, that only comprehensive change can provide sustainable universal health care. C1 NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Gardner, DB (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 2 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD MAR-APR PY 2007 VL 25 IS 2 BP 124 EP 126 PG 3 WC Nursing SC Nursing GA 159ET UT WOS:000245848900011 PM 17500500 ER PT J AU Pannacciulli, N Ortega, E Koska, J Salbe, AD Bunt, JC Krakoff, J AF Pannacciulli, Nicola Ortega, Emilio Koska, Juraj Salbe, Arline D. Bunt, Joy C. Krakoff, Jonathan TI Glucose response to an oral glucose tolerance test predicts weight change in non-diabetic subjects SO OBESITY LA English DT Article DE post-load glucose response; weight regulation; predictors; Pima Indians ID DIET-INDUCED THERMOGENESIS; DEPENDENT DIABETES-MELLITUS; BLOOD-GLUCOSE; PIMA-INDIANS; BODY-WEIGHT; FOOD-INTAKE; INSULIN-RESISTANCE; INTRAVENOUS GLUCOSE; NONOBESE WOMEN; OBESE SUBJECTS AB Objective: Glucose exerts a dual action in the regulation of energy balance, consisting of inhibition of energy intake and stimulation of energy expenditure. Whether blood glucose affects long-term regulation of body weight in humans remains to be established. We sought to test the hypothesis that the post-challenge glucose response is a predictor of weight change. Research Methods and Procedures: We performed a prospective analysis of the impact of glucose response to an oral glucose tolerance test (OGTT) and a mixed-meal test (MT) on subsequent changes in body weight (BW) on 253 Pima Indians (166 men and 87 women) with normal glucose regulation at baseline and follow-up (follow-up: 7 4 years). Main outcome measures included BW change (total, percent, and annual), plasma glucose and insulin concentrations during OGTT and MT [total and incremental areas under the curve (AUCs)], resting metabolic rate (RMR; indirect calorimetry), and insulin action (euglycemic-hyper-insulinemic clamp). Results: Total and incremental glucose AUCs during the OGTT (but not the MT) were negatively associated with BW change (total, percent, and annual), both before and after adjusting for sex, age, initial BW, follow-up time, insulin action, RMR, fasting plasma glucose and insulin concentrations, and insulin response. Total and incremental glucose AUCs during the OGTT were independent determinants of final BW with age, initial BW, follow-up time, fasting plasma insulin concentrations, and RMR. Discussion: Higher post-challenge glucose response protects against BW gain in subjects with normal glucose regulation. We propose that this action may be because of the effect of glucose on food intake and/or thermogenesis. C1 NIDDKD, NIH, DHHS, ODCRS,PECRB, Phoenix, AZ 85016 USA. RP Pannacciulli, N (reprint author), NIDDKD, NIH, DHHS, ODCRS,PECRB, 4212 N 16Th St, Phoenix, AZ 85016 USA. EM nicolap@mail.nih.gov FU Intramural NIH HHS [Z99 DK999999, 001-0059-954] NR 45 TC 8 Z9 9 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1930-7381 J9 OBESITY JI Obesity PD MAR PY 2007 VL 15 IS 3 BP 632 EP 639 DI 10.1038/oby.2007.572 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 212OD UT WOS:000249605800013 PM 17372313 ER PT J AU Gunderson, EP Lewis, CE Wei, GS Whitmer, RA Quesenberry, CP Sidney, S AF Gunderson, Erica P. Lewis, Cora E. Wei, Gina S. Whitmer, Rachel A. Quesenberry, Charles P. Sidney, Steve TI Lactation and changes in maternal metabolic risk factors SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN-CHOLESTEROL; DEPENDENT DIABETES-MELLITUS; YOUNG-ADULTS; GLUCOSE-TOLERANCE; WEIGHT-GAIN; POSTPARTUM LACTATION; REPRODUCTIVE HISTORY; INSULIN-RESISTANCE; LIPID-METABOLISM AB OBJECTIVE: To examine the relationship between duration of lactation and changes in maternal metabolic risk factors. METHODS: This 3-year prospective study examined changes in metabolic risk factors among lactating women from preconception to postweaning and among nonlactating women from preconception to postdelivery, in comparison with nongravid women. Of 1,051 (490 black, 561 white) women who attended two consecutive study visits in years 7 (1992-1993) and 10 (1995-1996), 942 were nongravid and 109 had one interim birth. Of parous women, 48 (45%) did not lactate, and 61 (55%) lactated and weaned before year 10. The lactated and weaned women were subdivided by duration of lactation into less than 3 months and 3 months or more. Multiple linear regression models estimated mean 3-year changes in metabolic risk factors adjusted for age, race, parity, education, and behavioral covariates. RESULTS: Both parous women who did not lactate and parous women who lactated and weaned gained more weight (+5.6, +4.4 kg) and waist girth (+5.3, +4.9 cm) than nongravid women over the 3-year interval; P<.001. Low-density lipoprotein cholesterol (+6.7 mg/dL, P<.05) and fasting insulin (+2.6 microunits, P=.06) increased more for parous women who did not lactate than for nongravid and parous women who lactated and weaned. High-density lipoprotein cholesterol decrements for both parous women who did not lactate and parous women who lactated and weaned were 4.0 mg/dL greater than for nongravid women (P<.001). Among parous, lactated and weaned women, lactation for 3 months or longer was associated with a smaller decrement in high-density lipoprotein cholesterol (-1.3 mg/dL versus -7.3 mg/dL for less than 3 months; P<.01). CONCLUSION: Lactation may attenuate unfavorable metabolic risk factor changes that occur with pregnancy, with effects apparent after weaning. As a modifiable behavior, lactation may affect women's future risk of cardiovascular and metabolic diseases. C1 Kaiser Permanente, Div Res, Epidemiol & Prevent Sect, Oakland, CA 94612 USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Gunderson, EP (reprint author), Kaiser Permanente, Div Res, Epidemiol & Prevent Sect, 2000 Broadway, Oakland, CA 94612 USA. EM epg@dor.kaiser.org FU NHLBI NIH HHS [N01 HC048047, N01 HC048048, N01 HC048049, N01 HC048050, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095, N01HC48047, N01HC48048, N01HC48049, N01HC48050, N01HC95095]; NIDDK NIH HHS [1 K01 DK059944, K01 DK059944, K01 DK059944-04A1] NR 59 TC 47 Z9 48 U1 0 U2 5 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 MAR PY 2007 VL 109 IS 3 BP 729 EP 738 DI 10.1097/01.AOG.0000252831.06695.03 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171YL UT WOS:000246771200021 PM 17329527 ER PT J AU Buggage, RR Levy-Clarke, G Sen, HN Ursea, R Srivastava, SK Suhler, EB Altemare, C Velez, G Ragheb, J Chan, CC Nussenblatt, RB Bamji, AT Sran, P Waldmann, T Thompson, DJS AF Buggage, Ronald R. Levy-Clarke, Grace Sen, Hatice N. Ursea, Roxana Srivastava, Sumil K. Suhler, Eric B. Altemare, Chandra Velez, Gisela Ragheb, Jack Chan, Chi-Chao Nussenblatt, Robert B. Bamji, Alison T. Sran, Puspha Waldmann, Thomas Thompson, Darby J. S. TI A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behet's disease SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Behcet's disease; uveitis; daclizumab; clinical trial ID POSTERIOR UVEITIS; IL-2 RECEPTOR; INTERMEDIATE AB Purpose: To investigate the safety and efficacy of daclizumab (Zenapax, humanized anti-Tac, HAT) in controlling the ocular manifestations of Beh et's disease. Design: Randomized, placebo-controlled, double-masked clinical trial. Participants: Seventeen participants with Behcet's disease experiencing at least two prior ocular attacks and requiring treatment with immunosuppressive agents for the ocular complications of Behcet's disease. Methods: Participants received either intravenous placebo or daclizumab (1 mg/kg) infusions every two weeks for six weeks, then every four weeks while continuing their standard immunosuppressive regimens. If clinically indicated, tapering of the standard immunosuppressive medications was allowed after six months of study enrollment. Complete ocular and physical examinations and an adverse event assessment were performed at baseline and prior to each study infusion. Main Outcome Measures: Primary safety endpoints were the development of a life-threatening complication or a severe opportunistic infection. Primary efficacy outcomes were the number of ocular attacks and an assessment of systemic immunosuppressive medications required during the study, including the ability to taper concomitant immunosuppressive therapy. Results: Nine participants randomized to daclizumab and eight to placebo were followed monthly. Follow-up ranged from one to 34 months, with a median follow-up of 15 months. Two participants randomized to daclizumab discontinued study therapy prior to the end of the study for personal reasons. No participant experienced a safety endpoint, and visual acuity remained stable in all participants during the course of the study. Ten participants (six daclizumab, four placebo) experienced ocular attacks requiring therapy. The median ocular attack rate during the study was greater in the daclizumab arm than the placebo arm (median 1.27 vs. 0.17 attacks/year, respectively). Participants in the placebo arm also experienced a greater reduction in the immunosuppressive medication score compared to participants receiving daclizumab (median -4.0 vs. -1.0, respectively). Conclusions: The observed results in the placebo group demonstrate that careful follow-up and treatment with standard combination immunosupprcssive therapy can be effective for the management of the ocular complications of Behcet's disease. In our small study, there was no suggestion that daclizumab was beneficial in comparison with placebo. However, the low observed attack rate limited our ability to make a definitive treatment group comparison. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. RP Levy-Clarke, G (reprint author), NEI, Immunol Lab, NIH, Bldg 10,10 Ctr Dr,Room 10N112, Bethesda, MD 20892 USA. EM Clarkeg@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22] NR 14 TC 43 Z9 46 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD MAR-APR PY 2007 VL 15 IS 2 BP 63 EP 70 DI 10.1080/09273940701299370 PG 8 WC Ophthalmology SC Ophthalmology GA 174UC UT WOS:000246967300002 PM 17558830 ER PT J AU Whitley, S Reeves, DM AF Whitley, Stephanie Reeves, Dianne M. TI Formbuilder: A tool for promoting data sharing and reuse within the cancer community. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 TerpSys, Rockville, MD USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2007 VL 34 IS 2 MA 2067 BP 502 EP 502 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 146QP UT WOS:000244949700122 ER PT J AU Parchen, D Castro, K Herringa, C Ness, E Bevans, M AF Parchen, Debbie Castro, Kathleen Herringa, Cynthia Ness, Elizabeth Bevans, Margaret TI Development of outcomes for an oncology nurse internship program. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2007 VL 34 IS 2 MA 2240 BP 536 EP 537 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 146QP UT WOS:000244949700223 ER PT J AU Castro, K Sampl, K Grasmeder, S Miller, B Mitchell, S Singer, S Soho, C AF Castro, Kathleen Sampl, Katherina Grasmeder, Sophia Miller, Beatrice Mitchell, Sandra Singer, Sarah Soho, Claudia TI Supporting community education: A collaborative effort between volunteer organizations to develop a hematopoietic stem cell transplant patient and caregiver educational symposium. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. Arlington Fairfax Hematol Oncol, Arlington, VA USA. Holy Cross Hosp, Silver Spring, MD USA. Leukemia & Lymphoma Soc, Natl Capital Area Chapter, Alexandria, VA USA. WESTAT Corp, Rockville, MD 20850 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2007 VL 34 IS 2 MA 2270 BP 544 EP 544 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 146QP UT WOS:000244949700245 ER PT J AU Ness, E Reeves, D AF Ness, Elizabeth Reeves, Dianne TI Developing electronic case report forms while establishing standards. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2007 VL 34 IS 2 MA 2337 BP 556 EP 556 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 146QP UT WOS:000244949700281 ER PT J AU Levy, C Allen, T AF Levy, Catherine Allen, Tamika TI Early detection and management of adverse events associated with ipilimumab: How the research nurse plays a vital role. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2007 VL 34 IS 2 MA 2375 BP 563 EP 564 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 146QP UT WOS:000244949700302 ER PT J AU Carroll, E Woolery, M AF Carroll, Ellen Woolery, Myra TI Making changes: Meeting knowledge and competency needs of pediatric nurses. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2007 VL 34 IS 2 MA 2426 BP 573 EP 573 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 146QP UT WOS:000244949700328 ER PT J AU Baccaglini, L Atkinson, JC Patton, LL Glick, M Ficarra, G Peterson, DE AF Baccaglini, Lorena Atkinson, Jane C. Patton, Lauren L. Glick, Michael Ficarra, Giuseppe Peterson, Douglas E. TI Management of oral lesions in HIV-positive patients SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article; Proceedings Paper CT 4th World Workshop on Oral Medicine CY APR 30-MAY 03, 2006 CL San Juan, PR SP Amer Acad Oral Med ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HAIRY LEUKOPLAKIA; DOUBLE-BLIND; OROPHARYNGEAL CANDIDIASIS; INTRALESIONAL VINBLASTINE; OPPORTUNISTIC INFECTIONS; IMMUNE SUPPRESSION; ACYCLOVIR THERAPY; APHTHOUS ULCERS AB We conducted a systematic review of treatments for 8 HIV-associated oral lesions. Most trials have focused on treatment of oral candidiasis. There were no double-blind, placebo-controlled randomized trials (RCT) for topical treatment of oral hairy leukoplakia, and only 1 RCT of systemic desciclovir. Only thalidomide was tested by RCT for recurrent aphthous-like lesions. One double-blind RCT compared vinblastine and sodium tetradecyl sulfate for localized treatment of oral Kaposi's sarcoma. Famciclovir, acyclovir, and valaciclovir were effective for mucocutaneous herpes simplex (HSV) lesions, but orolabial lesions were not reported separately. There were no RCT for topical treatments of HSV lesions, herpes zoster, warts, or periodontal diseases. In conclusion, there is a need for well-designed RCTs for treatment of most oral/perioral lesions in HIV patients. Standardized outcome measures should be developed to allow comparisons across trials. The reader is referred to the full online version for additional information. C1 Univ Florida, Coll Dent, Dept Community Dent & Behav Sci, Gainesville, FL 32610 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Univ N Carolina, Sch Dent, Dept Dent Ecol, Chapel Hill, NC USA. Univ Med & Dent New Jersey, Dept Diagnost Sci, Newark, NJ 07103 USA. Univ Florence, Reference Ctr Study Oral Dis, Florence, Italy. Univ Connecticut, Ctr Hlth, Dept Oral Hlth & Diagnost Sci, Sch Dent Med, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Neck Oral Oncol Program, Neag Comprehens Canc Ctr, Farmington, CT USA. RP Baccaglini, L (reprint author), Univ Florida, Coll Dent, Dept Community Dent & Behav Sci, 1329 SW 16th St,Suite 5182 POB 103628, Gainesville, FL 32610 USA. EM lbaccaglini@dental.ufl.edu OI Patton, Lauren/0000-0002-8253-4588 NR 42 TC 10 Z9 12 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD MAR PY 2007 VL 103 IS 3 SU 1 BP S50 EP S56 DI 10.1016/j.tripleo.2006.11.002 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 155VO UT WOS:000245606800010 ER PT J AU Saleh, AS Najjar, SS Muller, DC Shetty, V Ferrucci, L Gelber, AC Ling, SM AF Saleh, A. S. Najjar, S. S. Muller, D. C. Shetty, V. Ferrucci, L. Gelber, A. C. Ling, S. M. TI Arterial stiffness and hand osteoarthritis: a novel relationship? SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE aging; osteoarthritis; vascular stiffness; pulse wave velocity ID PULSE-WAVE VELOCITY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; VASCULAR-DISEASE; RISK-FACTOR; CROSS-LINK; PREVALENCE; WOMEN; ARTHRITIS; AGE; DISTENSIBILITY AB Objective: Osteoarthritis (OA) and vascular stiffening may share elements of common pathogenesis, but their potential relatedness has been the focus of little prior inquiry. We tested the hypothesis that these two aging-associated conditions are related to each other. Method We analyzed cross-sectional data from 256 participants of the Baltimore Longitudinal Study of Aging (BLSA), a study of normative aging. All underwent measurement of arterial pulse wave velocity (PWV), an index of vascular stiffness, as well as hand radiographs that were graded for evidence of OA. Twenty total joints across three joint groups (distal interphalangeal [DIP], proximal interphalangeal [PIP], carpal-metacarpal [CMC]) were each assigned a Kellgren-Lawrence grade (K-L) of 0 (normal) through 4 (severe), with K-L grades >= 2 considered evidence of definite CA. Radiographic hand OA was defined as definite CA changes in at least two of the three anatomic hand sites (DIP, PIP, CMC). CA burden was represented by the total number of affected CA joints, and a cumulative K-L grade was aggregated across all hand joint groups. The relationship of PWV with these three measures of hand CA was assessed by linear regression. Results: Upon univariate analysis, the presence of radiographic hand CA (beta = 218.1, P < 0.01), the total number of CA joints (beta = 32.9, P < 0.01), and the cumulative K-L grade across all joint groups (beta = 12.2, P < 0.01) were each associated with increased PWV. These associations, however, were no longer significant in age-adjusted models. Conclusion: Although significant individual relationships between PWV and several measures of hand OA were observed, these associations were largely attributable to the confounding effect of age. (C) 2006 Published by Elsevier Ltd on behalf of OsteoArthritis Research Society International. C1 NIA, Lab Cardiovasc Sci, IRP, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA. NIA, Clin Res Branch, IRP, Baltimore, MD 21224 USA. RP Ling, SM (reprint author), Harbor Hosp, NIA, IRP, Clin Res Branch, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM lingsh@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000015-49] NR 29 TC 10 Z9 13 U1 0 U2 1 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 MAR PY 2007 VL 15 IS 3 BP 357 EP 361 DI 10.1016/j.joca.2006.09.008 PG 5 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 147NH UT WOS:000245009200017 PM 17097316 ER PT J AU Tolea, MI Black, SA Carter-Pokras, OD Kling, MA AF Tolea, M. I. Black, S. A. Carter-Pokras, O. D. Kling, M. A. TI Depressive symptoms as a risk factor for osteoporosis and fractures in older Mexican American women SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE depression; elderly; fractures; Mexican Americans; osteoporosis; women ID BONE-MINERAL DENSITY; HORMONE REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; HIP FRACTURE; MAJOR DEPRESSION; CHRONIC DISEASES; SELF-REPORT; FOLLOW-UP; MENOPAUSE; FALLS AB Introduction and hypothesis Despite higher rates of depression, lower hormone replacement therapy (HRT) use, and inadequate knowledge of factors associated with osteoporosis, Mexican Americans have been understudied with regards to the association between depression, osteoporosis, and fractures. We hypothesized that depression increases the risk for osteoporosis and fractures among older Mexican American women. Methods Seven years of prospective data (1993-2001) from the Hispanic Established Populations for Epidemiologic Studies of the Elderly were analyzed for 1,350 women in the Southwest United States who had complete data for at least the first follow-up interview. Results Respondents (mean age:75) were generally poorly educated, had low income, and reported poor or fair health. High levels of depressive symptoms were reported by 31%, while new diagnosis of osteoporosis and new fractures were reported by 18 and 13%, respectively. Logistic regression analyses showed that predictors of newly diagnosed osteoporosis included age, high school (HS) education, ever having been an alcoholic, early menopause, hormone replacement therapy, and high levels of depressive symptoms. Factors predictive of new fractures included age, HS education, diabetes, early menopause, and high levels of depressive symptoms. Conclusions Depressive symptoms were associated with increased risk of osteoporosis and new fractures, even after controlling for other predictive factors. C1 Univ Maryland, Dept Epidemiol & Prevent Med, Sch Med, Baltimore, MD 21201 USA. NIMH, Clin Neuroendocrinol Branch, Intramural Res Programs, Baltimore, MD USA. RP Tolea, MI (reprint author), Univ Maryland, Dept Epidemiol & Prevent Med, Sch Med, Howard Hall Room 140C,660 W Redwood St, Baltimore, MD 21201 USA. EM mtolea@epi.umaryland.edu; opokras@epi.umaryland.edu RI Kling, Mitchel/F-4152-2010; Carter-Pokras, Olivia/B-1652-2012 OI Kling, Mitchel/0000-0002-2232-1409; Carter-Pokras, Olivia/0000-0002-6310-6932 FU NIA NIH HHS [T32 AG00262]; NIDDK NIH HHS [R01 DK51261] NR 46 TC 13 Z9 17 U1 0 U2 5 PU SPRINGER LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2007 VL 18 IS 3 BP 315 EP 322 DI 10.1007/s00198-006-0242-7 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 134PJ UT WOS:000244095000008 PM 17053870 ER PT J AU Cepollaro, C Lauretani, F Gozzini, A Masi, L Falchetti, A Amedei, A Carbonell-Sala, S Tanini, A Corsi, AM Bandinelli, S Ferrucci, L Brandi, ML AF Cepollaro, C. Lauretani, F. Gozzini, A. Masi, L. Falchetti, A. Amedei, A. Carbonell-Sala, S. Tanini, A. Corsi, A. M. Bandinelli, S. Ferrucci, L. Brandi, M. L. TI Relationship of volumetric BMD and structural parameters with ER alpha polymorphisms in men SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT 7th International Symposium on Osteoporosis CY APR 18-22, 2007 CL Washington, DC SP Natl Osteoporosis Fdn C1 Univ Florence, Dept Internal Med, Florence, Italy. Tuscany Hlth Reg Agcy, Florence, Italy. Azienda Sanitaria Firenze, Rehabil Unit, Florence, Italy. NIA, NIH, Clin Res Branch, Longitudinal Studies Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2007 VL 18 SU 1 BP S165 EP S165 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 160YP UT WOS:000245980900335 ER PT J AU Linet, MS Byrne, J Willis, GB Wacholder, S Forman, MR AF Linet, Martha S. Byrne, Julianne Willis, Gordon B. Wacholder, Sholom Forman, Michele R. TI Maternal sensitivity concerning aetiological research into childhood cancer: results of preliminary focus groups SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE questionnaire administration; medical records; bias; childhood cancer; qualitative study ID ELECTROMAGNETIC-FIELDS; MAGNETIC-FIELDS; ACUTE-LEUKEMIA; RISK-FACTORS; RECALL BIAS; X-RAY; EXPOSURE; CHILDREN; PARENTS; PREGNANCY AB We and others have postulated that modifications to epidemiological methods and tools could improve understanding of childhood cancer aetiology. We describe features of paediatric cancer that influence study design and data collection strategies, and examine determinants of the reproducibility and accuracy of mothers' responses to questionnaires, which are the primary source of risk factor information. Two focus group sessions with mothers of children with acute lymphoblastic leukaemia (ALL) and two with mothers of children with brain tumours were conducted to explore: the optimal time of day, method of administration, and location for the interview; the availability of alternative data sources; the interval between paediatric cancer diagnosis and epidemiological interview; and other features which may affect maternal interview responses. Mothers of children with both types of cancer preferred being interviewed at home during the evening and were willing to provide complete access to their offsprings' medical records. Emotional, socio-economic and perhaps cultural differences between the groups of mothers were exemplified by the willingness of mothers of children with ALL to participate in epidemiological interviews earlier in their child's treatment course and to provide greater access to maternal reproductive history records compared with mothers of children with brain tumours. Parental concerns about the difficult disease and treatment course of children with brain tumours were a key element in their decision to defer participating in epidemiological interviews for many months after their child's cancer diagnosis. We conclude that the focus group approach can contribute to a broad strategy for improving questionnaires and methods for conducting paediatric cancer epidemiological research. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Westat Corp, Rockville, MD USA. RP Linet, MS (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7048, Bethesda, MD 20892 USA. EM linetm@mail.nih.gov NR 61 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAR PY 2007 VL 21 IS 2 BP 169 EP 178 DI 10.1111/j.1365-3016.2007.00792.x PG 10 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 134WV UT WOS:000244116000008 PM 17302647 ER PT J AU Leveille, SG Bean, J Ngo, L McMullen, W Guralnik, JM AF Leveille, Suzanne G. Bean, Jonathan Ngo, Long McMullen, William Guralnik, Jack M. TI The pathway from musculoskeletal pain to mobility difficulty in older disabled women SO PAIN LA English DT Article DE pain; mobility; disability; osteoarthritis; fibromyalgia; aging; musculoskeletal; women ID NUTRITION EXAMINATION SURVEY; DEPRESSIVE SYMPTOMS; PHYSICAL-DISABILITY; NATIONAL-HEALTH; COMMUNITY; ADULTS; IMPACT; KNEE; PROGRESSION; PEOPLE AB Little is known about the pathway from musculoskeletal pain to mobility difficulty among older persons. We examined potential physical and psychological mediators of the pain-disability relationship in the Women's Health and Aging Study (WHAS), a cohort of women aged >= 65 who had at least mild disability at baseline. Pain was classified according to location and severity (widespread pain; lower extremity pain; other pain; none or mild pain in only one site). Among women without a lot of difficulty in stair climbing (n = 676) or walking (n = 510) at baseline, those who reported widespread pain were more likely than those with none or mild pain to develop a lot of difficulty with mobility during the 3 year follow-up. The likelihood for mobility difficulty was unchanged after adjusting for physical impairments and symptoms of depression and anxiety (walking aOR = 1.85, 95%CI, 1.08-3.17; stair climbing, aOR = 2.68, 95%CI, 1.56-4.62). Lower extremity pain was associated with increased likelihood for difficulty with climbing stairs but not with walking. However, this association was attenuated after adjusting for physical impairments and psychological symptoms (aOR = 1.66, 95%CI, 0.99-2.77). Pain was not associated with increased risk for becoming unable to walk or climb stairs. The findings suggest that pain is a unique domain as a cause of disablement, independent of the usual pathway to disability via physical impairments. Research is needed to better understand the development of pain-related disability in order to determine optimum approaches to prevent and treat mobility disability in older persons with persistent pain. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Div Gen Med & Primary Care, Beth Israel Deaconess Med Ctr,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. NIA, Lab Epidemiol, Demog & Biometry Program, Bethesda, MD 20892 USA. RP Leveille, SG (reprint author), Harvard Univ, Sch Med, Div Gen Med & Primary Care, Beth Israel Deaconess Med Ctr,Dept Med, Boston, MA 02215 USA. EM sleveill@bidmc.harvard.edu RI Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 FU Intramural NIH HHS; NIA NIH HHS [N01 AG012112, N01-AG12112, P01 AG004390, P01 AG004390-21A10016] NR 37 TC 65 Z9 67 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 2007 VL 128 IS 1-2 BP 69 EP 77 DI 10.1016/j.pain.2006.08.031 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 147BM UT WOS:000244978400011 PM 17055167 ER PT J AU Wang, XM Wu, TX Hamza, M Ramsay, ES Wahl, SM Dionne, RA AF Wang, Xiao-Min Wu, Tian-Xia Hamza, May Ramsay, Edward S. Wahl, Sharon M. Dionne, Raymond A. TI Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain SO PAIN LA English DT Article DE acute inflammation; pain; COX-2 inhibition; gene/protein expression ID CYTOKINE SIGNALING SOCS; INDUCIBLE CYCLOOXYGENASE; ANTIINFLAMMATORY DRUGS; RHEUMATOID-ARTHRITIS; SUPEROXIDE-DISMUTASE; IL-6 PRODUCTION; TISSUE-INJURY; INHIBITORS; INDUCTION; SUPPRESSORS AB New insights into the biological properties of cyclooxygenase-2 (COX-2) and its response pathway challenge the hypothesis that COX-2 is simply pro-inflammatory and inhibition of COX-2 solely prevents the development of inflammation and ameliorates inflammatory pain. The present study performed a comprehensive analysis of gene/protein expression induced by a selective inhibitor of COX-2, rofecoxib, compared with a non-selective COX inhibitor, ibuprofen, and placebo in a clinical model of acute inflammatory pain (the surgical extraction of impacted third molars) using microarray analysis followed by quantitative RT-PCR verification and Western blotting. Inhibition of COX-2 modulated gene expression related to inflammation and pain, the arachidonic acid pathway, apoptosis/angiogenesis, cell adhesion and signal transduction. Compared to placebo, rofecoxib treatment increased the gene expression of ANXA3 (annexin 3), SOD2 (superoxide dismutase 2), SOCS3 (suppressor of cytokine signaling 3) and IL1RN (IL1 receptor antagonist) which are associated with inhibition of phospholipase A, and suppression of cytokine signaling cascades, respectively. Both rofecoxib and ibuprofen treatment increased the gene expression of the pro-inflammatory mediators, IL6 and CCL2 (chemokine C-C motif ligand 2), following tissue injury compared to the placebo treatment. These results indicate a complex role for COX-2 in the inflammatory cascade in addition to the well-characterized COX-dependent pathway, as multiple pathways are also involved in rofecoxib-induced anti-inflammatory and analgesic effects at the gene expression level. These findings may also suggest an alternative hypothesis for the adverse effects attributed to selective inhibition of COX-2. Published by Elsevier B.V. on behalf of International Association for the Study of Pain. C1 NINR, NIH, Bethesda, MD 20892 USA. NIDCR, NIH, Bethesda, MD 20892 USA. RP Dionne, RA (reprint author), NINR, NIH, Bethesda, MD 20892 USA. EM dionner@mail.nih.gov RI Hamza, May/A-5053-2010 OI Hamza, May/0000-0002-7637-3060 FU Intramural NIH HHS; NIDCR NIH HHS [Z01 DE000286-26] NR 47 TC 27 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 2007 VL 128 IS 1-2 BP 136 EP 147 DI 10.1016/j.pain.2006.09.011 PG 12 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 147BM UT WOS:000244978400017 PM 17070997 ER PT J AU Uhlmann, EJ Seed, PC Schwan, TG Storch, GA AF Uhlmann, Erik J. Seed, Patrick C. Schwan, Tom G. Storch, Gregory A. TI Polymerase chain reaction of tick-borne relapsing fever caused by Borrelia hermsii SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Borrelia hermsii; tick-borne relapsing fever; PCR ID DIAGNOSIS AB A patient presented to our hospital with symptoms consistent with relapsing fever. A blood specimen was positive by genus-specific polymerase chain reaction, and sequencing revealed Borrelia hermsii. We propose the polymerase chain reaction as a possible alternative for currently used tests for the diagnosis of tick-bome relapsing fever. C1 Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, NIH, Hamilton, MT 59840 USA. RP Storch, GA (reprint author), Washington Univ, Sch Med, Dept Pediat, Box 8116,1 Childrens Pl, St Louis, MO 63110 USA. EM storch@kids.wustl.edu NR 6 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAR PY 2007 VL 26 IS 3 BP 267 EP 269 DI 10.1097/01.inf.0000254392.99545.69 PG 3 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 148QO UT WOS:000245089900017 PM 17484230 ER PT J AU Chen, AM Cai, B Dietrich, KN Radcliffe, J Rogan, WJ AF Chen, Aimin Cai, Bo Dietrich, Kim N. Radcliffe, Jerilynn Rogan, Walter J. TI Lead exposure, IQ, and behavior in urban 5- to 7-year-olds: Does lead affect Behavior only by lowering IQ? SO PEDIATRICS LA English DT Article; Proceedings Paper CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA DE lead; cognition; behavior; child; longitudinal studies ID PORT-PIRIE COHORT; 6-YEAR-OLD CHILDREN; BLOOD LEAD; ENVIRONMENTAL LEAD; CHELATION-THERAPY; SCHOOL ENTRY; LEVEL; INTELLIGENCE; DEFICITS; AGE AB BACKGROUND. Lead exposure in childhood lowers IQ scores, but its effect on children's behavior is less clear. Because IQ, per se, affects behavior, measuring the direct effect of lead requires measuring and then adjusting for IQ. In addition, either peak blood lead concentration, usually at 2 years old, or the lower blood lead level measured at school age may be the most relevant. Few studies have all of this information. OBJECTIVES. The purpose of this work was to differentiate the direct effect of lead on behavior and the indirect effect through IQ and to examine the strength of the association for peak and concurrent blood lead concentration. METHODS. Data come from a clinical trial of the chelating drug succimer to prevent cognitive impairment in 780 urban 12- to 33- month- olds with blood lead concentrations of 20 to 44 mu g/ dL. The children were followed from ages 2 to 7 years. The trial data were analyzed as a prospective observational study. RESULTS. Blood lead concentration at 2 years old was not associated with Conners' Parent Rating Scale- Revised scores at 5 years of age or Behavioral Assessment Systems for Children scores at 7 years of age. Blood lead level at 7 years of age had direct effects on the Behavioral Assessment Systems for Children behavioral symptoms index, externalizing, and school problems at age 7. CONCLUSIONS. Concurrent blood lead concentration was associated with externalizing and school problems scales at 7 years of age, and the effect was not entirely mediated through the effect of lead on IQ. C1 NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. Childrens Hosp Philadelphia, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, MD 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 ES043011-13] NR 49 TC 54 Z9 57 U1 1 U2 12 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 MAR PY 2007 VL 119 IS 3 BP E650 EP E658 DI 10.1542/peds.2006-1973 PG 9 WC Pediatrics SC Pediatrics GA 141LK UT WOS:000244579800062 PM 17332184 ER PT J AU Lindsey, JC Malee, KM Brouwers, P Hughes, MD AF Lindsey, Jane C. Malee, Kathleen M. Brouwers, Pim Hughes, Michael D. CA PACTG 219C Study Team TI Neurodevelopmental functioning in HIV-infected infants and young children before and after the introduction of protease inhibitor-based highly active antiretroviral therapy SO PEDIATRICS LA English DT Article DE HIV; neurodevelopmental functioning; cohort study ID IMMUNODEFICIENCY-VIRUS DISEASE; AIDS DEMENTIA COMPLEX; MONONUCLEAR PHAGOCYTES; COGNITIVE-DEVELOPMENT; COMBINATION THERAPY; CEREBROSPINAL-FLUID; ENCEPHALOPATHY; ZIDOVUDINE; MORTALITY; REPLICATION AB OBJECTIVES. The purpose of this work was to examine the effects of HIV infection and the impact of highly active antiretroviral treatment with protease inhibitors on neurodevelopmental functioning during the first 3 years of life. PATIENTS AND METHODS. Pediatric AIDS Clinical Trials Group 219/219C is a longitudinal cohort study that has enrolled HIV- infected ( HIV+) and HIV-exposed but uninfected (HIV-) infants and children since 1993. Longitudinal profiles of neurodevelopmental functioning as measured by the Bayley Scales of Infant Development were compared by HIV- infection status before and after the availability of highly active antiretroviral therapy with a protease inhibitor and within infants with Bayley tests available before and after initiating protease inhibitor therapy. RESULTS. In the pre-protease inhibitor era, mean mental and motor scores in HIV+ ( n = 54) infants < 1 year of age were significantly lower than those among HIV- infants ( n = 221) and remained lower up to 2 years of age. After protease inhibitors became available, mean mental and motor functioning of HIV+ infants ( n = 91) < 1 year of age were still significantly lower than those of HIV- infants ( n = 838). However, against a background of declining scores among the HIV- infants, there was evidence of limited improvement in the HIV+ infants relative to their uninfected peers. Among infants who had Bayley II evaluations before and after starting a protease inhibitor, there was a trend to improved mental and motor scores after initiation of protease inhibitor therapy. CONCLUSIONS. The suppression of systemic viral replication and subsequent substantial improvements in survival and immunologic status brought about by highly active antiretroviral therapy have been followed by limited improvements in neurodevelopmental functioning in young children. Additional longitudinal research is needed to better understand the role of antiretroviral therapy as well as the impact of genetic and environmental factors on neurodevelopmental functioning in children affected by HIV. C1 Northwestern Univ, Chicago Childrens Mem Hosp, Chicago, IL 60614 USA. Harvard Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA. NIMH, Ctr Mental Hlth Res AIDS, NIH, Rockville, MD 20857 USA. RP Malee, KM (reprint author), Northwestern Univ, Chicago Childrens Mem Hosp, 2300 Childrens Pl,Box 155, Chicago, IL 60614 USA. EM kmalee@childrensmemorial.org FU NIAID NIH HHS [5U01 AI41110] NR 44 TC 41 Z9 41 U1 1 U2 1 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 MAR PY 2007 VL 119 IS 3 BP E681 EP E693 DI 10.1542/peds.2006-1145 PG 13 WC Pediatrics SC Pediatrics GA 141LK UT WOS:000244579800066 PM 17296781 ER PT J AU Mussi-Pinhata, MM Freimanis, L Yamamoto, AY Korelitz, J Pinto, JA Cruz, MLS Losso, MH Read, JS AF Mussi-Pinhata, Marisa M. Freimanis, Laura Yamamoto, Aparecida Y. Korelitz, James Pinto, Jorge A. Cruz, Maria L. S. Losso, Marcelo H. Read, Jennifer S. CA Natl Inst Child Hlth Human Dev Int TI Infectious disease morbidity among young HIV-1 exposed but uninfected infants in Latin American and Caribbean countries: The National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study SO PEDIATRICS LA English DT Article DE HIV-1; infancy; infections; Latin America; Caribbean ID SYNCYTIAL VIRUS-INFECTION; COTRIMOXAZOLE PROPHYLAXIS; NATURAL-HISTORY; BORN; HOSPITALIZATION; BRONCHIOLITIS; MORTALITY; WOMEN; EPIDEMIOLOGY; MOTHERS AB OBJECTIVE. The goal was to describe the frequency, characteristics, and correlates of infectious disease morbidity during the first 6 months of life among HIV-1 exposed but uninfected infants. METHODS. The study population consisted of infants enrolled in the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study who were HIV-1 uninfected and had follow- up data through the 6- month study visit. Definitive and presumed infections were recorded at study visits ( birth, 6 - 12 weeks, and 6 months). RESULTS. Of 462 HIV-1-uninfected infants with 11 644 child- weeks of observation, 283 experienced >= 1 infection. These 283 infants experienced 522 infections ( 1.8 infections per infant). The overall incidence rate of infections was 4.5 cases per 100 child- weeks of observation. Overall, the most common infections were skin or mucous membrane infections ( 1.9 cases per 100 child- weeks) and respiratory tract infections ( 1.7 cases per 100 child- weeks). Thirty-six percent of infants had > 1 respiratory tract infection ( 1.8 cases per 100 child- weeks). Incidence rates of upper and lower respiratory tract infections were similar ( 0.89 cases per 100 child- weeks and 0.9 cases per 100 child- weeks, respectively). Cutaneous and/ or oral candidiasis occurred in 48 neonates ( 10.3%) and 92 older infants ( 19.3%). Early neonatal sepsis was diagnosed in 12 infants ( 26.0 cases per 1000 infants). Overall, 81 of 462 ( 17.5%) infants were hospitalized with an infection. Infants with lower respiratory tract infections were hospitalized frequently ( 40.7%). The occurrence of >= 1 neonatal infection was associated with more- advanced maternal HIV-1 disease, tobacco use during pregnancy, infant anemia, and crowding. Lower maternal CD4(+) cell counts, receipt of intrapartum antibiotic treatment, and country of residence were associated with postneonatal infections. CONCLUSIONS. Close monitoring of HIV-1-exposed infants, especially those who are anemic at birth or whose mothers have more- advanced HIV-1 disease or who smoked during pregnancy, remains important. C1 USP, FMPR, Dept Pucricultura & Pediat, BR-14049900 Ribeirao Preto, SP, Brazil. Westat Corp, Rockville, MD USA. Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. Hosp Servidores Estado, Rio De Janeiro, Brazil. Hosp Gen Agudos, Buenos Aires, DF, Argentina. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, Bethesda, MD 20892 USA. RP Mussi-Pinhata, MM (reprint author), USP, FMPR, Dept Pucricultura & Pediat, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil. EM mmmpinha@fmrp.usp.br RI Mussi-Pinhata, Marisa/G-6568-2012 FU NICHD NIH HHS [N01-HD-3-3345] NR 40 TC 46 Z9 47 U1 0 U2 7 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 MAR PY 2007 VL 119 IS 3 BP E694 EP E704 DI 10.1542/peds.2006-1856 PG 11 WC Pediatrics SC Pediatrics GA 141LK UT WOS:000244579800067 PM 17296782 ER PT J AU Gafni, RI Baron, J AF Gafni, Rachel I. Baron, Jeffrey TI Childhood bone mass acquisition and peak bone mass may not be important determinants of bone mass in late adulthood SO PEDIATRICS LA English DT Article; Proceedings Paper CT Workshop on Skeletal Effects of Pharmacologic Agents in Children CY APR 14, 2005 CL Natl Inst Hlth, Bethesda, MD SP Amer Soc Bone & Mineral Res, Natl Inst Child Hlth & Human Dev HO Natl Inst Hlth DE bone mass acquisition; childhood; adolescence; peak bone mass ID GROWTH-PLATE SENESCENCE; CATCH-UP GROWTH; CALCIUM SUPPLEMENTATION; GENETIC-DETERMINANTS; PREPUBERTAL GIRLS; MINERAL DENSITY; OSTEOPOROSIS; CHILDREN; GAIN; TWIN AB During childhood and adolescence, bone mass acquisition occurs primarily through skeletal growth. It is widely assumed that bone mass acquisition throughout childhood is an important determinant of the risk of osteoporosis in late adulthood; bone mass is thought to resemble a bank account in which deposits persist indefinitely. However, several well- controlled clinical studies suggest that increasing bone mass acquisition during childhood will have only transient effects. A likely explanation is that bone mass is governed by a homeostatic system that tends to return to a set point after any perturbation and, therefore, bone mass depends primarily on recent conditions, not those in the distant past. Indeed, in an animal model, we have shown evidence that bone mass acquisition in early life has no effect on bone mass in adulthood, in part because many areas of the juvenile skeleton are replaced in toto through skeletal growth. Therefore, it should not be assumed that alterations in childhood bone mass acquisition will affect bone mass many decades later in late adulthood. This issue remains open and the solution may depend on the type of childhood condition (for example calcium intake versus exercise) and its magnitude, timing, and duration. To date, both animal studies and clinical studies suggest that much of the effect of early bone mass acquisition does not persist. C1 NICHHD, Sect Growth & Dev, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. RP Baron, J (reprint author), NICHHD, Sect Growth & Dev, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM jeffrey.baron@nih.gov FU Intramural NIH HHS NR 26 TC 48 Z9 48 U1 3 U2 8 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 MAR PY 2007 VL 119 SU S BP S131 EP S136 DI 10.1542/peds.2006-2023D PG 6 WC Pediatrics SC Pediatrics GA 186DS UT WOS:000247759900002 PM 17332232 ER PT J AU Devadas, K Boykins, RA Hewlett, IK Wood, OL Clouse, KA Yamada, KM Dhawan, S AF Devadas, Krishnakumar Boykins, Robert A. Hewlett, Indira K. Wood, Owen L. Clouse, Kathleen A. Yamada, Kenneth M. Dhawan, Subhash TI Antibodies against a multiple-peptide conjugate comprising chemically modified human immunodeficiency virus type-1 functional Tat peptides inhibit infection SO PEPTIDES LA English DT Article DE HIV-Tat; peptides; AIDS; vaccination ID NF-KAPPA-B; RHESUS MACAQUES; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSES; T-CELLS; PROTEIN; HIV-1; MONOCYTES; ACTIVATION; IDENTIFICATION AB We demonstrated recently that selective side-chain modification of functional cysteine-rich (Tat(21-40)) and arginine-rich (Tat(53-68)) domains of the HIV-1 Tat protein blocks pathogenic activities of these peptides while retaining their immunological characteristics. In the present study, we have synthesized a multiple-peptide conjugate system comprising modified Tat(21-40) and Tat(53-68) peptides (HIV-1-Tat-MPC). Immunization of mice with this highly homogeneous 10.7 kDa HIV-1-Tat-MPC synthetic construct induced an effective immune response in mice. The antibodies generated against HIV-1-Tat-MPC efficiently suppressed Tat-induced viral replication and significantly reduced HIV-associated cytopathic effects in human monocytes. These results indicate that epitope-specific antibodies directed against functional sites of Tat protein using non-pathogenic peptides inhibit HIV pathogenesis. The HIV-1-Tat-MPC, therefore, has potential for the development of a safe, effective, and economical therapeutic vaccine to reduce the progression of HIV infection. (c) 2006 Elsevier Inc. All rights reserved. C1 US FDA, Immunopathogenesis Sect, Mol Virol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA. Cell Biol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Dhawan, S (reprint author), US FDA, Immunopathogenesis Sect, Mol Virol Lab, Ctr Biol Evaluat & Res, 140 Rockville Pike,HFM 315, Rockville, MD 20852 USA. EM subhash.dhawan@fda.hhs.gov OI Yamada, Kenneth/0000-0003-1512-6805 NR 42 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAR PY 2007 VL 28 IS 3 BP 496 EP 504 DI 10.1016/j.peptides.2006.11.007 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 141XG UT WOS:000244611700002 PM 17188401 ER PT J AU Schooler, C AF Schooler, Carmi TI Use It-and Keep It, Longer, Probably A Reply to Salthouse (2006) SO PERSPECTIVES ON PSYCHOLOGICAL SCIENCE LA English DT Editorial Material AB In this article, I call into serious question Salthouse's (2006) conclusions evaluating and disparaging the validity of the "use it or lose it" hypothesis regarding mental exercise and mental aging. I do so, in some part, by using data not discussed by Salthouse. The core of my argument relies heavily on a critical assessment of the conclusions that Salthouse derived from both his theoretical reasoning and his review of the literature. The more judicious conclusion I reach is that, although the whole story regarding cognitive function and aging is not known, at some level and to some degree, "using" it often delays the eventuality of "losing" it. C1 [Schooler, Carmi] NIMH, SSES, IRP, NIH,DHHS, Bethesda, MD 20892 USA. RP Schooler, C (reprint author), NIMH, SSES, IRP, NIH,DHHS, 6101 Execut Blvd,Room 362,MSC 8408, Bethesda, MD 20892 USA. EM carmi.schooler@nih.gov NR 26 TC 25 Z9 25 U1 3 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1745-6916 J9 PERSPECT PSYCHOL SCI JI Perspect. Psychol. Sci. PD MAR PY 2007 VL 2 IS 1 BP 24 EP 29 DI 10.1111/j.1745-6916.2007.00026.x PG 6 WC Psychology, Multidisciplinary SC Psychology GA V10FQ UT WOS:000207450300002 PM 26151916 ER PT J AU Ong, HL Liu, XB Sharma, A Hegde, RS Ambudkar, IS AF Ong, Hwei L. Liu, Xibao Sharma, Ajay Hegde, Ramanujan S. Ambudkar, Indu S. TI Intracellular Ca2+ release via the ER translocon activates store-operated calcium entry SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE store-operated Ca2+ entry; endoplasmic reticulum; Ca2+; pactamycin; thapsigargin; translocons ID PROTEIN-CONDUCTING CHANNEL; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; ACINAR-CELLS; THAPSIGARGIN; INHIBITION; INFLUX; COMPLEX; STIM1; PORE AB Store-operated Ca2+ entry (SOCE) is activated in response to depletion of intracellular Ca2+ from the endoplasmic reticulum (ER). A variety of agonists stimulate SOCE via IP3-dependent Ca2+ depletion. SOCE is also activated by thapsigargin, an inhibitor of Ca2+ reuptake into the ER that induces a net Ca2+ loss from the ER by unmasking a Ca2+ "leak" pathway. The molecular identity of this Ca2+ leak channel and the physiological conditions under which such agonist-independent Ca2+ depletion might occur remain poorly characterized. In this study, we report that inhibition of the initiation step of protein synthesis (with pactamycin) resulted in detectable Ca2+ depletion in ER and activation of SOCE. This was completely prevented if the ribosome-nascent chain complexes were first stabilized with an irreversible inhibitor of translational elongation (emetine), suggesting that ER Ca2+ depletion had occurred through open translocons at the ER. Notably, emetine pretreatment also attenuated thapsigargin-mediated Ca2+ release and SOCE. Furthermore, both pactamycin and thapsigargin stimulated translocation of STIM1, a protein required for activation of SOCE, to the subplasma membrane region and activated the SOCE-associated current, I-SOC. In aggregate, these data reveal an agonist-independent mechanism for internal Ca2+ store depletion and activation of SOCE. We suggest that the functional coupling between SOCE and protein synthesis is likely to be critical for maintaining [Ca2+](ER) within a range that is required to prevent ER stress during changes in cellular translational activity. C1 Natl Inst Dent & Craniofacial Res, Secret Physiol Sect, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), Natl Inst Dent & Craniofacial Res, Secret Physiol Sect, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov OI Hegde, Ramanujan/0000-0001-8338-852X NR 36 TC 30 Z9 30 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD MAR PY 2007 VL 453 IS 6 BP 797 EP 808 DI 10.1007/s00424-006-0163-5 PG 12 WC Physiology SC Physiology GA 137PC UT WOS:000244303500006 PM 17171366 ER PT J AU Lee, SJ Perera, L Coulter, SJ Mohrenweiser, HW Jetten, A Goldstein, JA AF Lee, Su-Jun Perera, Lalith Coulter, Sherry J. Mohrenweiser, Harvey W. Jetten, Anton Goldstein, Joyce A. TI The discovery of new coding alleles of human CYP26A1 that are potentially defective in the metabolism of all-trans retinoic acid and their assessment in a recombinant cDNA expression system SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE CYP26A1; P450; polymorphisms; retinoic acid; retinoic acid metabolism ID PROMYELOCYTIC LEUKEMIA-CELLS; MULTIPLE SEQUENCE ALIGNMENT; CAUDAL REGRESSION SYNDROME; HUMAN CYTOCHROME-P450; ESCHERICHIA-COLI; MOUSE EMBRYO; ENZYME; IDENTIFICATION; GENE; PHARMACOGENOMICS AB Objectives Retinoic acid (RA) is a critical regulator of gene expression during embryonic development and in the maintenance of adult epithelial tissues. This study was undertaken to identify genetic polymorphisms of CYP26A1 which might affect these processes. We sequenced CYP26A1 in racially diverse individuals and assessed the metabolism of retinoic acid by newly identified coding alleles of CYP26A1 in a recombinant system. Methods CYP26A1 was sequenced in 24 Caucasians, 24 African-Americans, 24 Asians, and 20 individuals of unknown racial origin. cDNA constructs for wild-type and coding alleles of CYP26A1 were constructed in a pcDNA3.1 expression vector and expressed in Cos-1 cells. A FLAG tag at the C-terminal end of the cDNA was used to quantitate the recombinant CYP26A1 proteins. Results A total of 13 single nucleotide polymorphisms (SNPs) were identified in CYP26A1. Three SNPs produced coding changes: R173S, F186L, and C358R. These alleles were termed as CYP26A1*2, CYP26A1*3, and CYP26A1*4, respectively, by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee at hftp://www.cypalleles.ki.se/. Wild type CYP26A1 protein metabolized all-trans-retinoic acid (at-RA) to 4-oxo-RA, 4-OH-RA as well as water-soluble metabolites. CYP26A1.3 (F186L and CYP26A1.4 (C358R) allelic proteins exhibited significantly lower metabolism (40-80%) of at-RA than wild-type CYP26A1.1 protein. Conclusion This is the first study to identify coding alleles of CYP26A1. Two coding alleles, CYP26A1*3 and CYP26A1*4, are predicted to be defective based on the metabolism of at-RA by the recombinant proteins. These studies suggest the need for future clinical studies of polymorphisms of CYP26A1 in embryonic development. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. Lawrence Livermore Natl Lab, Livermore, CA USA. RP Goldstein, JA (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov RI Goldstein, Joyce/A-6681-2012; perera, Lalith/B-6879-2012; OI perera, Lalith/0000-0003-0823-1631; Coulter, Sherry/0000-0002-2732-3470; Jetten, Anton/0000-0003-0954-4445 FU Intramural NIH HHS [Z01 ES021024-26]; NIEHS NIH HHS [Y1-ES-8054-05] NR 47 TC 13 Z9 14 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 MAR PY 2007 VL 17 IS 3 BP 169 EP 180 DI 10.1097/FPC.0b013e32801152d6 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 147EW UT WOS:000244987200001 PM 17460545 ER PT J AU Hortin, GL Sviridov, D AF Hortin, Glen L. Sviridov, Denis TI Diagnostic potential for urinary proteomics SO PHARMACOGENOMICS LA English DT Review DE kidney disease; microalbumin; microglobulins; nephrotoxins; urinary peptidomics; urinary proteomics ID CHROMATOGRAPHY-MASS-SPECTROMETRY; TRANSITIONAL-CELL CARCINOMA; RENAL-ALLOGRAFT REJECTION; PROSTAGLANDIN-D SYNTHASE; CHRONIC KIDNEY-DISEASE; LIQUID-CHROMATOGRAPHY; PROSTATE-CANCER; 2-DIMENSIONAL ELECTROPHORESIS; BIOMARKER DISCOVERY; FANCONI-SYNDROME AB Urine represents a modified ultrafiltrate of plasma, with protein concentrations typically approximately 1000-fold lower than plasma. Urine's low protein concentration might suggest it to be a less promising diagnostic specimen than plasma. However, urine can be obtained noninvasively and tests of many urinary proteins are well-established in clinical practice. Proteomic technologies expand opportunities to analyze urinary proteins, identifying more than 1000 proteins and peptides in urine. Urine offers a sampling of most plasma proteins, with increased proportions of low-molecular-weight protein and peptide components. Urine also offers enriched sampling of proteins released along the urinary tract. Although urine presents some challenges as a diagnostic specimen, its diverse range of potential markers offers great potential for diagnosis of both systemic and kidney diseases. Examples of clinical situations where this may be of value are for more sensitive detection of kidney transplant rejection or of renal toxicity of medications. C1 NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov FU Intramural NIH HHS NR 168 TC 36 Z9 36 U1 1 U2 9 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD MAR PY 2007 VL 8 IS 3 BP 237 EP 255 DI 10.2217/14622416.8.3.237 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 145OS UT WOS:000244875000008 PM 17324112 ER PT J AU Yu, J Zhang, S Epstein, DH Fang, YX Shi, J Qin, HF Yao, SJ Le Foll, B Lu, L AF Yu, Jiang Zhang, Shun Epstein, David H. Fang, Yuxia Shi, Jie Qin, Hufu Yao, Shujun Le Foll, Bernard Lu, Lin TI Gender and stimulus difference in cue-induced responses in abstinent heroin users SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE heroin abuse; cue reactivity; craving; gender difference; cue paradigm ID COCAINE-DEPENDENT INDIVIDUALS; CONDITIONED PLACE PREFERENCE; SEX-DIFFERENCES; ABUSE PATIENTS; DRUG-ABUSE; REACTIVITY; ADDICTION; RELAPSE; STRESS; EXPOSURE AB Background: Environmental stimuli associated with drug taking have been known to elicit drug craving and increase the likelihood of relapse, and sex differences have been observed in the development of drug addiction and relapse to drug taking. Differential cue paradigms (drug-related imagery scripts and drug-related paraphernalia) have been used to investigate cue-induced drug craving. However, there is little research on the possible gender differences in responses to drug cues in heroin-dependent individuals. This study examined whether two different stimuli, drugrelated imagery scripts and drug-related paraphernalia, produce similar or different patterns of cue reactivity in heroin-dependent men and women. Methods: In the laboratory sessions, 26 male and 23 female heroin-dependent subjects were exposed to script-guided imagery of heroin-related cue situations and to heroin-related paraphernalia (e.g., needles, syringes, spoons, cigarette filters, and aluminum foil). Heroin craving, subjective anxiety, emotion state ratings, and cardiovascular changes were assessed. Results: Significant increases in heroin craving were seen with drug-imagery scripts or drug paraphernalia but not with neutral-relaxing imagery or neutral-item handling. In addition, drug imagery and paraphernalia produced significant increases in subjective anxiety, negative emotions, systolic and diastolic blood pressure, and heart rate, as well as decreases in positive emotion. Paraphernalia exposure was somewhat more effective than imagery scripts in inducing heroin craving, primarily reflecting a lower response to imagery scripts among men. Most other dependent measures also differed by gender, and each gender difference occurred with imagery scripts only or with paraphernalia only. Conclusions: The present results indicate that heroin-imagery scripts and heroin paraphernalia each induce heroin craving and emotional and cardiovascular changes, but that the changes show a complex pattern of gender differences that may need to be taken into account in future laboratory studies. (c) 2007 Elsevier Inc. All rights reserved. C1 Peking Univ, Natl Inst Drug Dependence, Beijing 640041, Peoples R China. Tangshan Mental Hlth Hosp, Tangshan 063004, Peoples R China. Tangshan Ankan Hosp, Tangshan 063000, Peoples R China. NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Ctr Addict & Mental Hlth, Translat Addict Res Lab, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, 38 Xueyuan Rd, Beijing 640041, Peoples R China. EM linlu@bjmu.edu.cn RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 FU Intramural NIH HHS NR 64 TC 30 Z9 34 U1 1 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 MAR PY 2007 VL 86 IS 3 BP 485 EP 492 DI 10.1016/j.pbb.2007.01.008 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 160SD UT WOS:000245961700008 PM 17306353 ER PT J AU Doyle, ME Egan, JM AF Doyle, Maire E. Egan, Josephine M. TI Mechanisms of action of glucagon-like peptide 1 in the pancreas SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE GLP-1 receptor; exendin 4; insulin synthesis and secretion; exendin (9-39); beta cell; Islet of Langerhans; proliferation; differentiation; cAMP; PKA; Epac; PI3 kinase; FoxO1; IRS2; PDX-1 ID PROTEIN-KINASE-A; BETA-CELL MASS; STIMULATED INSULIN-SECRETION; K-ATP CHANNEL; GASTRIC-INHIBITORY POLYPEPTIDE; TRANSCRIPTION FACTOR PDX-1; CYTOKINE-INDUCED APOPTOSIS; CA2+-INDUCED CA2+ RELEASE; CAMP-RESPONSIVE ELEMENT; GENE PROMOTER ACTIVITY AB Glucagon-like peptide 1 (GLP-1) is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate, and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past 20 years culminating in a naturally occurring GLP-1 receptor (GLP-1R) agonist, exendin 4 (Ex-4), now being used to treat type 2 diabetes trellitus (TMM). GLP-1 engages a specific guanine nucleotide-binding protein (G-protein) coupled receptor (GPCR) that is present in tissues other than the pancreas (brain, kidney, lung, heart, and major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1R activation, adenylyl cyclase (AC) is activated and cAMP is generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the protein kinase A (PKA) and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1R activation also increases insulin synthesis, beta cell proliferation, and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in T2DM patients treated with Ex-4. This review will focus on the effects resulting from GLP-1R activation in the pancreas. (c) 2007 Elsevier Inc. All rights reserved. C1 NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32611 USA. Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL 32610 USA. RP Egan, JM (reprint author), NIA, Diabet Sect, NIH, Box 23,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM eganj@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000906-09, Z01 AG000214-14, Z01 AG000905-09] NR 421 TC 273 Z9 306 U1 7 U2 70 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAR PY 2007 VL 113 IS 3 BP 546 EP 593 DI 10.1016/j.pharmthera.2006.11.007 PG 48 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 154DY UT WOS:000245488200006 PM 17306374 ER PT J AU Manna, F Lorman, V Podgornik, R Zeks, B AF Manna, F. Lorman, V. Podgornik, R. Zeks, B. TI Screwlike order, macroscopic chirality, and elastic distortions in high-density DNA mesophases SO PHYSICAL REVIEW E LA English DT Article ID LIQUID-CRYSTALS; PHASES; DIFFRACTION; TWIST AB We investigate a new screwlike liquid-crystalline ordering in solutions of helical biopolymers and its influence on the state of individual molecules. In the resulting mesophase translational and rotational motions of molecules are coupled in screw fluctuations. We show that in contrast to the case of conventional chiral liquid crystals the elastic distortion does not twist the screw order but leads to overwinding of individual helical molecules. This explains the peculiarities of high-density DNA mesophases. C1 Univ Montpellier 2, Lab Phys Math & Theor, F-34095 Montpellier, France. Univ Ljubljana, Fac Math & Phys, Dept Phys, SI-1000 Ljubljana, Slovenia. J Stefan Inst, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia. NICHHD, LPSB, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Ljubljana, Fac Med, Inst Biophys, SI-1000 Ljubljana, Slovenia. RP Manna, F (reprint author), Univ Montpellier 2, Lab Phys Math & Theor, F-34095 Montpellier, France. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 23 TC 12 Z9 12 U1 0 U2 1 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD MAR PY 2007 VL 75 IS 3 AR 030901 DI 10.1103/PhysRevE.75.030901 PN 1 PG 4 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 151XL UT WOS:000245324300006 PM 17500660 ER PT J AU Brinker, AM Ma, J Lipsky, PE Raskin, I AF Brinker, Anita M. Ma, Jun Lipsky, Peter E. Raskin, Ilya TI Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae) SO PHYTOCHEMISTRY LA English DT Review DE Tripterygium; Celastraceae; thunder god vine; terpenoids; triptolide; inflammation; antiinflammatory drugs; immunosuppression ID WILFORDII HOOK-F; NF-KAPPA-B; DNA-POLYMERASE-BETA; NITRIC-OXIDE SYNTHASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLLAGEN-INDUCED ARTHRITIS; BARR-VIRUS-ACTIVATION; CHINESE HERBAL PLANT; SKIN-TUMOR PROMOTION; SESQUITERPENE PYRIDINE ALKALOIDS AB Plants in the genus Tripterygium, such as Tripterygium wifordii Hook.f., have a long history of use in traditional Chinese medicine. In recent years there has been considerable interest in the use of Tripterygium extracts and of the main bioactive constituent, the diterpene triepoxide triptolide (1), to treat a variety of autoimmune and inflammation-related conditions. The main mode of action of the Tripterygium extracts,and triptolide (1) is the inhibition of expression of proinflammatory genes such as those for interleukin-2 (IL-2), inducible nitric oxide synthase (NOS), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-gamma). The efficacy and safety of certain types of Tripterygium extracts were confirmed in human clinical trials in the US and abroad. Over 300 compounds have been identified in the genus Tripterygium, and many of these have been evaluated for biological activity. The overall activity of the extract is based on the interaction between its components. Therefore, the safety and efficacy of the extract cannot be fully mimicked by any individual constituent. This review discusses the biochemical composition and biological and pharmacological activities of Tripterygium extracts, and their main bioactive components. (c) 2006 Elsevier Ltd. All rights reserved. C1 Rutgers State Univ, Cook Coll, Biotechnol Ctr Agr & Environm, New Brunswick, NJ 08901 USA. NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Raskin, I (reprint author), Rutgers State Univ, Cook Coll, Biotechnol Ctr Agr & Environm, Foran Hall,59 Dudley Rd, New Brunswick, NJ 08901 USA. EM raskin@aesop.rutgers.edu FU FIC NIH HHS [U01 TW006674]; NCCIH NIH HHS [1-P50 AT002776-01, P50 AT002776] NR 399 TC 195 Z9 230 U1 2 U2 55 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD MAR PY 2007 VL 68 IS 6 BP 732 EP 766 DI 10.1016/j.phytochem.2006.11.029 PG 35 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 152CQ UT WOS:000245338800002 PM 17250858 ER PT J AU Venkova-Canova, T Srivastava, P Chattoraj, DK AF Venkova-Canova, Tatiana Srivastava, Preeti Chattoraj, Dhruba K. TI Transcriptional inactivation of a regulatory site for replication of Vibrio cholerae chromosome II. SO PLASMID LA English DT Meeting Abstract ID INITIATOR; RCTB C1 NIH, NCI, Biochem Lab, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0147-619X J9 PLASMID JI Plasmid PD MAR PY 2007 VL 57 IS 2 BP 189 EP 190 PG 2 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 152PM UT WOS:000245374100024 ER PT J AU Srivastava, P Chattoraj, DK AF Srivastava, Preeti Chattoraj, Dhruba K. TI Role of MreB in chromosome segregation in Vibrio cholerae. SO PLASMID LA English DT Meeting Abstract C1 NIH, NCI, Biochem Lab, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0147-619X J9 PLASMID JI Plasmid PD MAR PY 2007 VL 57 IS 2 BP 190 EP 190 PG 1 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 152PM UT WOS:000245374100025 ER PT J AU Austin, S AF Austin, Stuart TI Partition and stability - Summary SO PLASMID LA English DT Editorial Material C1 NCI, Genet Recombinat & Chromosome Biol Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0147-619X J9 PLASMID JI Plasmid PD MAR PY 2007 VL 57 IS 2 BP 198 EP 199 PG 2 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 152PM UT WOS:000245374100044 ER PT J AU Sengupta, M Neilsen, H Austin, S AF Sengupta, Manjistha Neilsen, Henrik Austin, Stuart TI A fresh look at P1 plasmid segregation. SO PLASMID LA English DT Meeting Abstract C1 NCI, Genet Recombinat & Chromosome Biol Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0147-619X J9 PLASMID JI Plasmid PD MAR PY 2007 VL 57 IS 2 BP 199 EP 199 PG 1 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 152PM UT WOS:000245374100045 ER PT J AU Srivastava, P Chattoraj, DK AF Srivastava, Preeti Chattoraj, Dhruba K. TI Segregation of Vibrio cholerae chromosomes at different cell growth rates. SO PLASMID LA English DT Meeting Abstract ID PARTITION C1 NIH, NCI, Biochem Lab, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0147-619X J9 PLASMID JI Plasmid PD MAR PY 2007 VL 57 IS 2 BP 200 EP 201 PG 2 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 152PM UT WOS:000245374100050 ER PT J AU Klimke, W Ciufo, S Fedorov, B Kapustin, Y Kiryutin, B Kochergin, A O'Neilll, K Resenchuk, S Tolstoy, I Tatusova, T AF Klimke, William Ciufo, Stacy Fedorov, Boris Kapustin, Yuri Kiryutin, Boris Kochergin, Andrey O'Neilll, Kathlenn Resenchuk, Sergei Tolstoy, Igor Tatusova, Tatiana TI NCBI entrez resourcesfor genomes and plasmids. SO PLASMID LA English DT Meeting Abstract C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 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 0147-619X J9 PLASMID JI Plasmid PD MAR PY 2007 VL 57 IS 2 BP 242 EP 243 PG 2 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 152PM UT WOS:000245374100140 ER PT J AU Huizing, M Parkes, JM Helip-Wooley, A White, JG Gahl, WA AF Huizing, Marjan Parkes, Jennifer M. Helip-Wooley, Amanda White, James G. Gahl, William A. TI Platelet alpha granules in BLOC-2 and BLOC-3 subtypes of Hermansky-Pudlak syndrome SO PLATELETS LA English DT Article DE Hermansky-Pudlak syndrome; delta granule; alpha granule; BLOC; lysosome-related organelle ID MULTIVESICULAR BODIES; PULMONARY-FIBROSIS; SYNDROME TYPE-5; DENSE GRANULES; MEGAKARYOCYTE; TRAFFICKING; DEFECTS; MELANOCYTES; BIOGENESIS; ORGANELLES AB Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelle biogenesis that displays genetic locus heterogeneity. The eight known HPS proteins combine in functional complexes, two of which are called BLOC-2 and BLOC-3; a BLOC is a Biogenesis of Lysosome-related Organelles Complex. Organelles affected in HPS include the melanosome, resulting in hypopigmentation, and the platelet delta (dense) granule, resulting in prolonged bleeding times. Whole mount electron microscopy (EM) detects the absence of platelet delta granules and confirms the diagnosis of HPS. To date, the status of other organelles and granules in HPS platelets has not been documented. We performed ultrastructural studies on platelets of patients with different genetic forms of HPS, specifically those comprising the BLOC-2 and BLOC-3 subtypes. No differences in distribution, size or quantity of other platelet organelles and membrane structures could be detected in our patients. Since alpha and delta granules are formed from multivesicular bodies in the megakaryocyte, and since only delta granules are defective in HPS, we conclude that HPS genes function within the portion of delta granule biogenesis that has diverged from that of alpha granules. Thus, it is unlikely that the generalized bleeding diathesis of HPS is attributed to a deficiency of alpha granules. C1 NHGRI, NIH, Med Genet Branch, Sect Human Biochem Genet, Bethesda, MD 20892 USA. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. NIH, Off Rare Dis, Intramural Program, Bethesda, MD USA. RP Huizing, M (reprint author), NHGRI, NIH, Med Genet Branch, Sect Human Biochem Genet, 10 Ctr Dr,Bld 10,Rm 10C103, Bethesda, MD 20892 USA. EM mhuizing@mail.nih.gov FU Intramural NIH HHS NR 38 TC 14 Z9 14 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0953-7104 J9 PLATELETS JI Platelets PD MAR PY 2007 VL 18 IS 2 BP 150 EP 157 DI 10.1080/13576500600936039 PG 8 WC Cell Biology; Hematology SC Cell Biology; Hematology GA 144ID UT WOS:000244788800007 PM 17365864 ER PT J AU Smith, DL McKenzie, FE Snow, RW Hay, SI AF Smith, David L. McKenzie, F. Ellis Snow, Robert W. Hay, Simon I. TI Revisiting the basic reproductive number for malaria and its implications for malaria control SO PLOS BIOLOGY LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; VECTOR-CONTROL; TRANSMISSION DYNAMICS; ANOPHELES MOSQUITOS; INOCULATION RATES; WESTERN KENYA; BORNE DISEASE; AFRICA; INFECTION; CONSEQUENCES AB The prospects for the success of malaria control depend, in part, on the basic reproductive number for malaria, R(0). Here, we estimate Ro in a novel way for 121 African populations, and thereby increase the number of R(0) estimates for malaria by an order of magnitude. The estimates range from around one to more than 3,000. We also consider malaria transmission and control in finite human populations, of size H. We show that classic formulas approximate the expected number of mosquitoes that could trace infection back to one mosquito after one parasite generation, Z(0)(H), but they overestimate the expected number of infected humans per infected human, R(0)(M. Heterogeneous biting increases Ro and, as we show, Z(0)(H) but we also show that it sometimes reduces R(0)(H) those who are bitten most both infect many vectors and absorb infectious bites. The large range of R(0) estimates strongly supports the long-held notion that malaria control presents variable challenges across its transmission spectrum. In populations where Ro is highest, malaria control will require multiple, integrated methods that target those who are bitten most. Therefore, strategic planning for malaria control should consider R(0), the spatial scale of transmission, human population density, and heterogeneous biting. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Kenya Govt Med Res Ctr, Ctr Geog Med, Malaria Publ Hlth & Epidemiol Grp, Nairobi, Kenya. Univ Oxford, John Radcliffe Hosp, Ctr Trop Med, Oxford OX3 9DU, England. Univ Oxford, Dept Zool, Spatial Epidemiol & Ecol Grp, Oxford OX1 3PS, England. RP Smith, DL (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM smitdave@helix.nih.gov 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 Intramural NIH HHS [Z99 TW999999]; Wellcome Trust [079080, 079091] NR 57 TC 198 Z9 199 U1 6 U2 44 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 MAR PY 2007 VL 5 IS 3 BP 531 EP 542 AR e42 DI 10.1371/journal.pbio.0050042 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 150TW UT WOS:000245243500013 PM 17311470 ER PT J AU Tsang, KY Chan, D Cheslett, D Chan, WCW So, CL Melhado, IG Chan, TWY Kwan, KM Hunziker, EB Yamada, Y Bateman, JF Cheung, KMC Cheah, KSE AF Tsang, Kwok Yeung Chan, Danny Cheslett, Deborah Chan, Wilson C. W. So, Chi Leong Melhado, Ian G. Chan, Tori W. Y. Kwan, Kin Ming Hunziker, Ernst B. Yamada, Yoshihiko Bateman, John F. Cheung, Kenneth M. C. Cheah, Kathryn S. E. TI Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function SO PLOS BIOLOGY LA English DT Article ID UNFOLDED-PROTEIN RESPONSE; SCHMID METAPHYSEAL CHONDRODYSPLASIA; BECKWITH-WIEDEMANN-SYNDROME; X COLLAGEN; GROWTH-PLATE; IN-VITRO; MESSENGER-RNA; ER STRESS; INTRACELLULAR RETENTION; CELL-DIFFERENTIATION AB In protein folding and secretion disorders, activation of endoplasmic reticulum (ER) stress signaling (ERSS) protects cells, alleviating stress that would otherwise trigger apoptosis. Whether the stress-surviving cells resume normal function is not known. We studied the in vivo impact of ER stress in terminally differentiating hypertrophic chondrocytes (HCs) during endochondral bone formation. In transgenic mice expressing mutant Collagen X as a consequence of a 13-base pair deletion in Col10a1 (13del), misfolded od(X) chains accumulate in HCs and elicit ERSS. Histological and gene expression analyses showed that these chondrocytes survived ER stress, but terminal differentiation is interrupted, and endochondral bone formation is delayed, producing a chondrodysplasia phenotype. This altered differentiation involves cell-cycle re-entry, the re-expression of genes characteristic of a prehypertrophiclike state, and is cell-autonomous. Concomitantly, expression of Col10a1 and 13del mRNAs are reduced, and ER stress is alleviated. ERSS, abnormal chondrocyte differentiation, and altered growth plate architecture also occur in mice expressing mutant Collagen 11 and aggrecan. Alteration of the differentiation program in chondrocytes expressing unfolded or misfolded proteins may be part of an adaptive response that facilitates survival and recovery from the ensuing ER stress. However, the altered differentiation disrupts the highly coordinated events of endochondral ossification culminating in chondrodysplasia. C1 Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Dept Orthopaed & Traumatol, Hong Kong, Hong Kong, Peoples R China. Univ Bern, ITI Res Inst Dent & Skeletal Biol, Bern, Switzerland. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD USA. Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia. Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. RP Cheah, KSE (reprint author), Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. EM hrmbdkc@hkusua.hku.hk RI Chan, Danny/C-4203-2009; Cheah, Kathryn/C-4222-2009; OI Cheslett, Deborah/0000-0002-4084-1467; Bateman, John/0000-0001-8542-0730 NR 70 TC 99 Z9 106 U1 1 U2 8 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 MAR PY 2007 VL 5 IS 3 BP 568 EP 585 AR e44 DI 10.1371/journal.pbio.0050044 PG 18 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 150TW UT WOS:000245243500016 PM 17298185 ER PT J AU Shoemaker, BA Panchenko, AR AF Shoemaker, Benjamin A. Panchenko, Anna R. TI Deciphering protein-protein interactions. Part I. Experimental techniques and databases SO PLOS COMPUTATIONAL BIOLOGY LA English DT Review ID YEAST SACCHAROMYCES-CEREVISIAE; SIMPLE PHYSICAL MODEL; POST-GENOMIC ERA; MASS-SPECTROMETRY; GENE-EXPRESSION; INTERACTION NETWORKS; HOT-SPOTS; 3-DIMENSIONAL STRUCTURE; DOMAIN INTERACTIONS; INTEGRATED ANALYSIS AB Proteins interact with each other in a highly specific manner, and protein interactions play a key role in many cellular processes; in particular, the distortion of protein interfaces may lead to the development of many diseases. To understand the mechanisms of protein recognition at the molecular level and to unravel the global picture of protein interactions in the cell, different experimental techniques have been developed. Some methods characterize individual protein interactions while others are advanced for screening interactions on a genome-wide scale. In this review we describe different experimental techniques of protein interaction identification together with various databases which attempt to classify the large array of experimental data. We discuss the main promises and pitfalls of different methods and present several approaches to verify and validate the diverse experimental data produced by high-throughput techniques. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA. RP Panchenko, AR (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA. EM panch@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 130 TC 165 Z9 171 U1 2 U2 27 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAR PY 2007 VL 3 IS 3 BP 337 EP 344 AR e42 DI 10.1371/journal.pcbi.0030042 PG 8 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 163VJ UT WOS:000246191000002 PM 17397251 ER PT J AU Shalowitz, DI Garrett-Mayer, E Wendler, D AF Shalowitz, David I. Garrett-Mayer, Elizabeth Wendler, David TI How should treatment decisions be made for incapacitated patients, and why? SO PLOS MEDICINE LA English DT Editorial Material ID LIFE-SUSTAINING TREATMENT; ADVANCE DIRECTIVES; TREATMENT CHOICES; CARE; END; PREFERENCES; SURROGATES; INTERVENTIONS; ATTITUDES; OUTCOMES C1 Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Johns Hopkins Univ, Div Biostat, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. EM dwendler@nih.gov RI Shalowitz, David/A-7432-2009; OI Shalowitz, David/0000-0002-5189-4687 NR 35 TC 14 Z9 14 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD MAR PY 2007 VL 4 IS 3 BP 423 EP 428 AR e35 DI 10.1371/journal.pmed.0040035 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 150TY UT WOS:000245243700008 PM 17388655 ER PT J AU Mohiuddin, MM AF Mohiuddin, Muhammad M. TI Clinical xenotransplantation of organs: Why aren't we there yet? SO PLOS MEDICINE LA English DT Article ID INCOMPATIBLE CARBOHYDRATE ANTIGEN; PORCINE ENDOGENOUS RETROVIRUSES; TO-PRIMATE XENOTRANSPLANTATION; CARDIAC XENOGRAFT SURVIVAL; LIVING PIG-TISSUE; HYPERACUTE REJECTION; TRANSGENIC PIG; MONOCLONAL-ANTIBODY; ENDOTHELIAL-CELLS; NONHUMAN-PRIMATES C1 NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA. RP Mohiuddin, MM (reprint author), NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA. EM mohiuddinm@mail.nih.gov RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 75 TC 5 Z9 5 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD MAR PY 2007 VL 4 IS 3 BP 429 EP 434 AR e75 DI 10.1371/journal.pmed.0040075 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 150TY UT WOS:000245243700009 PM 17388658 ER PT J AU Guindo, A Fairhurst, RM Doumbo, OK Wellems, TE Diallo, DA AF Guindo, Aldiouma Fairhurst, Rick M. Doumbo, Ogobara K. Wellems, Thomas E. Diallo, Dapa A. TI X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria SO PLOS MEDICINE LA English DT Article ID GLUCOSE-6-PHOSPHATE DEHYDROGENASE; PLASMODIUM-FALCIPARUM; HEMOGLOBIN-C; AFRICAN CHILDREN; RESISTANCE; POPULATION; MORTALITY; VARIANT; ENZYME; CELLS AB Background Glucose-6-phosphate dehydrogenase (G6PD) is important in the control of oxidant stress in erythrocytes, the host cells for Plasmodium falciparum. Mutations in this enzyme produce X-linked deficiency states associated with protection against malaria, notably in Africa where the A-form of G6PD deficiency is widespread. Some reports have proposed that heterozygous females with mosaic populations of normal and deficient erythrocytes (due to random X chromosome inactivation) have malaria resistance similar to or greater than hemizygous males with populations of uniformly deficient erythrocytes. These proposals are paradoxical, and they are not consistent with currently hypothesized mechanisms of protection. Methods and Findings We conducted large case-control studies of the A-form of G6PD deficiency in cases of severe or uncomplicated malaria among two ethnic populations of rural Mali, West Africa, where malaria is hyperendemic. Our results indicate that the uniform state of G6PD deficiency in hemizygous male children conferred significant protection against severe, life-threatening malaria, and that it may have likewise protected homozygous female children. No such protection was evident from the mosaic state of G6PD deficiency in heterozygous females. We also found no significant differences in the parasite densities of males and females with differences in G6PD status. Pooled odds ratios from meta-analysis of our data and data from a previous study confirmed highly significant protection against severe malaria in hemizygous males but not in heterozygous females. Among the different forms of severe malaria, protection was principally evident against cerebral malaria, the most frequent form of life-threatening malaria in these studies. Conclusions The A-form of G6PD deficiency in Africa is under strong natural selection from the preferential protection it provides to hemizygous males against life-threatening malaria. Little or no such protection is present among heterozygous females. Although these conclusions are consistent with data from at least one previous study, they have not heretofore been realized to our knowledge, and they therefore give fresh perspectives on malaria protection by G6PD deficiency as an X-linked trait. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Univ Bamako, Fac MEd Pharm & Odontostomatol, Malaria Res & Training Ctr, Bamako, Mali. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM twellems@niaid.nih.gov FU Intramural NIH HHS NR 24 TC 107 Z9 110 U1 4 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD MAR PY 2007 VL 4 IS 3 BP 516 EP 522 AR e66 DI 10.1371/journal.pmed.0040066 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 150TY UT WOS:000245243700019 PM 17355169 ER PT J AU Takala, SL Coulibaly, D Thera, MA Dicko, A Smith, DL Guindo, AB Kone, AK Traore, K Ouattara, A Djimde, AA Sehdev, PS Lyke, KE Diallo, DA Doumbo, OK Plowe, CV AF Takala, Shannon L. Coulibaly, Drissa Thera, Mahamadou A. Dicko, Alassane Smith, David L. Guindo, Ando B. Kone, Abdoulaye K. Traore, Karim Ouattara, Amed Djimde, Abdoulaye A. Sehdev, Paul S. Lyke, Kirsten E. Diallo, Dapa A. Doumbo, Ogobara K. Plowe, Christopher V. TI Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali SO PLOS MEDICINE LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; PLASMODIUM-FALCIPARUM MALARIA; BAY COHORT PROJECT; SEQUENCE DIVERSITY; SERUM ANTIBODIES; LINKAGE DISEQUILIBRIUM; 19-KILODALTON DOMAIN; TERMINAL FRAGMENT; CONJUGATE VACCINE; IMMUNE-RESPONSE AB Background Malaria vaccines based on the 19-kDa region of merozoite surface protein 1 (MSP-1(19)) derived from the 3D7 strain of Plasmodium falciparum are being tested in clinical trials in Africa. Knowledge of the distribution and natural dynamics of vaccine antigen polymorphisms in populations in which malaria vaccines will be tested will guide vaccine design and permit distinction between natural fluctuations in genetic diversity and vaccine-induced selection. Methods and Findings Using pyrosequencing, six single-nucleotide polymorphisms in the nucleotide sequence encoding MSP-1(19) were genotyped from 1,363 malaria infections experienced by 100 children who participated in a prospective cohort study in Mali from 1999 to 2001. The frequencies of 14 MSP-1(19) haplotypes were compared over the course of the malaria transmission season for all three years, in three age groups, and in consecutive infections within individuals. While the frequency of individual MSP-1(19) haplotypes fluctuated, haplotypes corresponding to FVO and FUP strains of P. falciparum (MSP-1(19) haplotypes QKSNGL and EKSNGL, respectively) were most prevalent during three consecutive years and in all age groups with overall prevalences of 46% (95% confidence interval [CI] 44%-49%) and 36% (95% CI 34%-39%), respectively. The 3D7 haplotype had a lower overall prevalence of 16% (95% CI 14%-18%). Multiplicity of infection based on MSP-1(19) was higher at the beginning of the transmission season and in the oldest individuals (aged >= 11 y). Three MSP-119 haplotypes had a reduced frequency in symptomatic infections compared to asymptomatic infections. Analyses of the dynamics of MSP-1(19) polymorphisms in consecutive infections implicate three polymorphisms (at positions 1691, 1700, and 1701) as being particularly important in determining allele specificity of anti-MSP-1(19) immunity. Conclusions Parasites with MSP-1(19) haplotypes different from that of the leading vaccine strain were consistently the most prevalent at a vaccine trial site. If immunity elicited by an MSP-1-based vaccine is allele-specific, a vaccine based on either the FVO or FUP strain might have better initial efficacy at this site. This study, to our knowledge the largest of its kind to date, provides molecular information needed to interpret population responses to MSP-1-based vaccines and suggests that certain MSP-1(19) polymorphisms may be relevant to cross-protective immunity. C1 Univ Maryland, Sch Med, Ctr Vacc Dev, Baltimore, MD 21201 USA. Univ Bamako, Malaria Res & Training Ctr, Bamako, Mali. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Plowe, CV (reprint author), Univ Maryland, Sch Med, Ctr Vacc Dev, Baltimore, MD 21201 USA. EM cplowe@medicine.umaryland.edu RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU FIC NIH HHS [D43 TW001589, D43TW001589]; NIAID NIH HHS [N01AI85346, U19 AI065683, U19AI065683] NR 46 TC 61 Z9 61 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD MAR PY 2007 VL 4 IS 3 BP 523 EP 534 AR e93 DI 10.1371/journal.pmed.0040093 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 150TY UT WOS:000245243700020 PM 17355170 ER PT J AU Subbarao, K Luke, C AF Subbarao, Kanta Luke, Catherine TI H5N1 viruses and vaccines SO PLOS PATHOGENS LA English DT Editorial Material ID INFLUENZA-A H5N1; AVIAN-INFLUENZA; REVERSE-GENETICS; MF59-ADJUVANTED INFLUENZA; INACTIVATED VACCINES; PROTECTIVE IMMUNITY; NEWCASTLE-DISEASE; RANDOMIZED-TRIAL; LETHAL CHALLENGE; MOUSE MODEL C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU Intramural NIH HHS NR 36 TC 55 Z9 63 U1 0 U2 7 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 MAR PY 2007 VL 3 IS 3 AR e40 DI 10.1371/journal.ppat.0030040 PG 3 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 196PT UT WOS:000248495200002 PM 17335350 ER PT J AU Wexler, HK Fletcher, BW AF Wexler, Harry K. Fletcher, Bennett W. TI National Criminal Justice Drug Abuse Treatment Studies (CJ-DATS) overview SO PRISON JOURNAL LA English DT Article DE offenders; drug treatment; reentry AB In 2002, the National Institute on Drug Abuse (NIDA) launched the National Criminal Justice Drug Abuse Treatment Studies (CJ-DATS), a major research initiative. Researchers from 9 research centers and a coordinating center and NIDA work together with federal, state, and local criminal justice partners to develop and test integrated approaches to the treatment of offenders with drug use disorders. There are 13 major studies within CJ-DATS that cover 8 study areas, including screening and referral, modifying treatment programs and interventions for reentering offenders, improving engagement and retention, linking services in the community, improving coordination with criminal justice reentry processes, addressing the needs of special populations, understanding the general organizational and contextual factors in treating offenders, and understanding current treatment practices for the drug-involved offender. C1 Natl Dev & Res Inst Inc, New York, NY 10048 USA. Natl Inst Drug Abuse, Bethesda, MD USA. RP Wexler, HK (reprint author), Natl Dev & Res Inst Inc, New York, NY 10048 USA. NR 13 TC 18 Z9 18 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0032-8855 J9 PRISON J JI Prison J. PD MAR PY 2007 VL 87 IS 1 BP 9 EP 24 DI 10.1177/0032885506299036 PG 16 WC Criminology & Penology SC Criminology & Penology GA 153CC UT WOS:000245408300002 ER PT J AU Fletcher, BW Lehman, WEK Wexler, HK Melnick, G AF Fletcher, Bennett W. Lehman, Wayne E. K. Wexler, Harry K. Melnick, Gerald TI Who participates in the Criminal Justice Drug Abuse Treatment Studies (CJ-DATS)? SO PRISON JOURNAL LA English DT Article DE racial/ethnic differences; gender diffetences; mental health problems; HIV-risk behaviors; substance use; criminal behavior ID VIOLENCE RISK-ASSESSMENT; MENTAL-DISORDERS; SUBSTANCE-ABUSE; HIV RISK; CORRECTIONAL FACILITIES; PSYCHIATRIC-DISORDERS; INCARCERATED WOMEN; GENDER DIFFERENCES; CLUSTER-ANALYSIS; PRISON-INMATES AB The national Criminal Justice Drug Abuse Treatment Studies (CJ-DATS) is a multisite research program to improve outcomes for offenders with drug problems who are reentering the community after incarceration. Baseline data from three ongoing CJ-DATS studies were pooled to examine the characteristics of study participants. These analyses suggest that CJ-DATS study participants have serious drug problems, criminal, histories, and mental health problems that can decrease the likelihood of successful community reentry unless addressed. HIV-risk behavior was associated with several categories of criminal acts, suggesting that the relationship between sexual risk behaviors and crime may need further investigation. C1 NIDA, Bethesda, MD 20892 USA. Natl Dev & Res Inst Inc, New York, NY USA. RP Fletcher, BW (reprint author), NIDA, Bethesda, MD 20892 USA. NR 48 TC 5 Z9 5 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0032-8855 J9 PRISON J JI Prison J. PD MAR PY 2007 VL 87 IS 1 BP 25 EP 57 DI 10.1177/0032885506299037 PG 33 WC Criminology & Penology SC Criminology & Penology GA 153CC UT WOS:000245408300003 ER PT J AU Pierce, BL Adi, DMFK McIntosh, L Deutsch, K Hood, L Ostrander, EA Austin, MA Stanford, JL AF Pierce, Brandon L. Adi, Danielle M. Friedrichsen-Kar McIntosh, Laura Deutsch, Kerry Hood, Lee Ostrander, Elaine A. Austin, Melissa A. Stanford, Janet L. TI Genomic scan of 12 hereditary prostate cancer families having an occurrence of pancreas cancer SO PROSTATE LA English DT Article DE Prostate Cancer Genetic Research Study (PROGRESS); heterogeneity; pancreatic cancer; genetic susceptibility; linkage analysis ID MALE BREAST-CANCER; SUSCEPTIBILITY GENES; LINKAGE ANALYSIS; WIDE SCAN; GENETICS; IDENTIFICATION; REPLICATION; CONSORTIUM; REGION; LOCUS AB BACKGROUND. Prostate cancer is a genetically heterogeneous disease. Using the occurrence of other cancers in hereditary prostate cancer (HPC) families is a promising strategy for developing genetically homogeneous data sets that can enhance the ability to identify susceptibility loci using linkage analysis. METHODS. Twelve HPC families with the co-occurrence of adenocarcinoma of the pancreas were selected from the Prostate Cancer Genetic Research Study (PROGRESS). Non-parametric linkage analysis for a prostate/pancreas cancer susceptibility phenotype was performed using 441 genome-wide microsatellite markers. RESULTS. No statistically significant linkage signal was detected in this analysis. The strongest linkage signals, as measured by Kong and Cox LOD score (KC LOD), were observed on chromosomes 2q37.2-q37.3 (KC LOD = 1.01; P = 0.02) and 16q23.2 (KC LOC = 1.05; P = 0.01). CONCLUSIONS. Despite the lack of statistically significant findings, four chromosomal regions, three of which (2q, 16q, 17q) were previously noted as harboring potential susceptibility loci, showed suggestive linkage results in this scan. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Univ Washington, Inst Publ Hlth Genet, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Sch Publ Hlth & Commun Med, Seattle, WA 98195 USA. Inst Syst Biol, Seattle, WA USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, M4-B874,Box 19024, Seattle, WA 98109 USA. EM jstanfor@fhcrc.org OI Pierce, Brandon/0000-0002-7829-952X; Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS NR 29 TC 6 Z9 6 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 MAR 1 PY 2007 VL 67 IS 4 BP 410 EP 415 DI 10.1002/pros.20527 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 140MS UT WOS:000244510000009 PM 17192958 ER PT J AU Xiang, ZX Steinbach, PJ Jacobson, MP Friesner, RA Honig, B AF Xiang, Zhexin Steinbach, Peter J. Jacobson, Matthew P. Friesner, Richard A. Honig, Barry TI Prediction of side-chain conformations on protein surfaces SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE side-chain prediction; entropy; conformational mobility; colony energy; protein structure ID SOLVENT ACCESSIBILITY; X-RAY; ENTROPY; BINDING; ENERGY; RECOGNITION; SPECIFICITY; RESOLUTION; ALGORITHM; ACCURACY AB An approach is described that improves the prediction of the conformations of surface side chains in crystal structures, given the main-chain conformation of a protein. A key element of the methodology involves the use of the colony energy. This phenomenological term favors conformations found in frequently sampled regions, thereby approximating entropic effects and serving to smooth the potential energy surface. Use of the colony energy significantly improves prediction accuracy for surface side chains with little additional computational cost. Prediction accuracy was quantified as the percentage of side-chain dihedral angles predicted to be within 40 degrees of the angles measured by X-ray diffraction. Use of the colony energy in predictions for single side chains improved the prediction accuracy for X, and chi(1+2) from 65 and 40% to 74 and 59%, respectively. Several other factors that affect prediction of surface side-chain conformations were also analyzed, including the extent of conformational sampling, details of the rotamer library employed, and accounting for the crystallographic environment. The prediction of conformations for polar residues on the surface was generally found to be more difficult than those for hydrophobic residues, except for polar residues participating in hydrogen bonds with other protein groups. For surface residues with hydrogen-bonded side chains, the prediction accuracy of chi(1) and chi(1+2) was 79 and 63%, respectively. For surface polar residues, in general (all side-chain prediction), the accuracy of X, and chi(1+2) was only 73 and 561%, respectively. The most accurate results were obtained using the colony energy and an all-atom description that includes neighboring molecules in the crystal (protein chains and hetero atoms). Here, the accuracy of chi(1) and chi(1+2) predictions for surface side chains was 82 and 73%, respectively. The root mean square deviations obtained for hydrogen-bonding surface side chains were 1.64 and 1.81 angstrom, with and without consideration of crystal packing effects, respectively. C1 NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Columbia Univ, Dept Chem, New York, NY 10027 USA. Columbia Univ, Ctr Computat Biol & Bioinformat, Howard Hughes Med Inst, New York, NY 10032 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. RP Xiang, ZX (reprint author), NIH, Ctr Mol Modeling, Ctr Informat Technol, Bldg 12A Room 2051,12 S Dr, Bethesda, MD 20892 USA. EM xiangz@mail.nih.gov OI Jacobson, Matthew/0000-0001-6262-655X FU NIGMS NIH HHS [R01 GM052018, GM-30518, R01 GM030518, R01 GM052018-12, R37 GM030518] NR 33 TC 23 Z9 23 U1 0 U2 2 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 MAR PY 2007 VL 66 IS 4 BP 814 EP 823 DI 10.1002/prot.21099 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 137MG UT WOS:000244296100006 PM 17206724 ER PT J AU Braunschweig, T Kaserer, K Chung, JY Bilke, S Krizman, D Knezevic, V Hewitt, SM AF Braunschweig, Till Kaserer, Klaus Chung, Joon-Yong Bilke, Sven Krizman, David Knezevic, Vladimir Hewitt, Stephen M. TI Proteomic expression profiling of thyroid neoplasms SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE antibody array; biomarker; immunohistochemistry; thyroid neoplasm; tissue microarray ID FINE-NEEDLE ASPIRATION; CARCINOMA CELL-LINES; C-MYC; FOLLICULAR NEOPLASMS; ANTIBODY MICROARRAY; PROSTATE-CANCER; PROTEIN; RECEPTOR; ONCOGENES; TUMORS AB Thyroid cancer is the most common endocrine neoplasm with multiple histologic subtypes, each associated with different treatments and outcomes. Differentiating benign neoplasms such as follicular adenomas from malignant entities such as follicular carcinomas and papillary carcinoma can be challenging. To define the proteomic profile of different thyroid tumors, we screened an antibody array of 330 features against five thyroid neoplasms: follicular adenoma, follicular carcinoma, papillary carcinoma, anaplastic carcinoma, and medullary carcinoma as well as normal thyroid epithelium. Eight candidate biomarkers; c-erbB-2, Stat5a, Annexin IV, IL-11, RAR alpha, FGF7, Caspase 9, and phospho-c-myc were idenfified as differentially expressed on the antibody array, and validated with immunohistochemistry on tissue microarrays, with a total of 144 samples of the same variety of thyroid neoplasms. Analysis revealed c-erbB-2, Annexin IV, and Stat5a have potential clinical utility to differentiate follicular adenoma, follicular carcinoma, and papillary carcinoma from each other. By using an antibody array as a discovery platform and a tissue microarray as a first step in validation on a large number of specimens, we have identified new markers that have potential utility in the diagnosis of thyroid neoplasms. C1 NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Canc Genome Anat Project, NIH, Bethesda, MD 20892 USA. NCI, Oncogenom Sect, Pediat Oncol Branch, Ctr Adv Technol,NIH, Bethesda, MD 20892 USA. RP Hewitt, SM (reprint author), Ctr Adv Technol, TARP Lab, MSC 4605, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 NR 45 TC 11 Z9 12 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1862-8346 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD MAR PY 2007 VL 1 IS 3 BP 264 EP 271 DI 10.1002/prca.200600381 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 169TU UT WOS:000246615500002 PM 21136677 ER PT J AU Insel, TR AF Insel, Thomas R. TI Devising prevention and treatment strategies for the nation's diverse populations with mental illness - Commentary SO PSYCHIATRIC SERVICES LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, Room 8235,MSC 9669,6001 Execut Blvd, Bethesda, MD 20892 USA. EM insel@mail.nih.gov NR 1 TC 4 Z9 4 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2007 VL 58 IS 3 BP 395 EP 395 DI 10.1176/appi.ps.58.3.395 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 140EM UT WOS:000244487000016 PM 17325114 ER PT J AU Nishikawa, T Hayashi, T Koga, I Uchida, Y AF Nishikawa, Tadashi Hayashi, Teruo Koga, Itsuyuki Uchida, Yasunori TI Neuroleptic withdrawal with remitted schizophrenics: A naturalistic follow-up study SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; MAINTENANCE THERAPY; NORTHWICK PARK; RELAPSE; INTERMITTENT; PREDICTORS; OUTPATIENTS; SULPIRIDE; FLUPHENAZINE; HALOPERIDOL AB Despite proven efficacy of maintenance pharmacotherapy in schizophrenia, indefinite neuroleptic treatment may not be optimal for all patients. It is uncertain how long maintenance therapy should be continued and how to identify those patients who can withdraw eventually from neuroleptics. Prospective randomized controlled studies are the ideal approach for evaluation of medication, however they are inevitably for the short term and may not be suitable for addressing the above-mentioned issue. In this study, we naturalistically followed up 30 remitted schizophrenics for 10.7 years on average and examined factors that might affect the outcomes. Of 30 remitted patients, 8 cases (26.7%) ceased neuroleptic use completely for more than 2 years. The details of clinical courses of those 8 cases were described as case reports in this report. Importantly, 4 of 8 withdrawal cases required 2 or more trials in order for neuroleptic withdrawal to reach a drug-free state. Factors which significantly affected successful withdrawal involved the mode of onset and the ages at first neuroleptic withdrawal trial. Our results suggest that approximately one-fourth of completely remitted patients could withdraw neuroleptics, but certain cases may need withdrawal trials at least a few times to accomplish the drug-free state. C1 Seiwakai Nishikawa Hosp, Hamada 6970052, Japan. NIH, NIDA, Dept Hlth & Human Serv, Baltimore, MD USA. RP Nishikawa, T (reprint author), Seiwakai Nishikawa Hosp, Hamada 6970052, Japan. EM mnishikawa@s7.dion.ne.jp NR 35 TC 1 Z9 1 U1 1 U2 2 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD SPR PY 2007 VL 70 IS 1 BP 68 EP 79 DI 10.1521/psyc.2007.70.1.68 PG 12 WC Psychiatry SC Psychiatry GA 157SH UT WOS:000245740700007 PM 17492913 ER PT J AU Arora, N AF Arora, N. TI Are cancer survivors receiving adequate communication about medical tests and symptom management from their follow-up care physicians? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, DCCPS, ARP, Outcomes Res Branch, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2007 VL 16 IS 3 SU S BP S23 EP S23 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 147ZS UT WOS:000245044900041 ER PT J AU Beckjord, E Arora, N AF Beckjord, E. Arora, N. TI Risk perception, self-efficacy and cancer survivorship: Testing the risk perception attitude framework in adult cancer survivors SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Canc Prevent Fellowship Program, Bethesda, MD USA. Natl Canc Inst, Outcomes Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2007 VL 16 IS 3 SU S BP S31 EP S31 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 147ZS UT WOS:000245044900056 ER PT J AU Bellizzi, K Rowland, J Miller, M Hamilton, A Aziz, N Arora, N AF Bellizzi, K. Rowland, J. Miller, M. Hamilton, A. Aziz, N. Arora, N. TI Health behaviors and health-related quality of life of adult non-Hodgkin's lymphoma survivors: Results from the ECHOS-NHL study SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Ctr, Div Canc Control & Populat Sci, Bethesda, MD USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2007 VL 16 IS 3 SU S BP S14 EP S14 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 147ZS UT WOS:000245044900025 ER PT J AU Bevans, M Leidy, NK Childs, R Friedmann, E AF Bevans, M. Leidy, N. K. Childs, R. Friedmann, E. TI The influence of baseline psychosocial wellbeing on hospitalization and survival following allogeneic hematopoietic stem cell transplantation SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Inst Hlth, Dept Nursing, Bethesda, MD USA. United Biosource Corp, Ctr Hlth Outcomes Res, Bethesda, MD USA. NHLBI, Hematol Branch, Stem Cell Transplantat Sect, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2007 VL 16 IS 3 SU S BP S14 EP S15 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 147ZS UT WOS:000245044900026 ER PT J AU Hadley, J AF Hadley, J. TI National cancer institute director's consumer liaison group: Patient cancer advocacy summit-listening and learning together: Building a bridge of trust SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Off Liaison Activ, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2007 VL 16 IS 3 SU S BP S45 EP S46 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 147ZS UT WOS:000245044900084 ER PT J AU McLaughlin, W Kudela, M Arora, N Rowland, J AF McLaughlin, W. Kudela, M. Arora, N. Rowland, J. TI Factors influencing cancer survivorship: Understanding survivors' perspectives SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. Westat Corp, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2007 VL 16 IS 3 SU S BP S98 EP S99 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 147ZS UT WOS:000245044900190 ER PT J AU Prince, P Bevans, MF Mitchell, SA Barrett, AJ Childs, R Fowler, D Krumlauf, M Savani, B Soeken, K AF Prince, P. Bevans, M. F. Mitchell, S. A. Barrett, A. J. Childs, R. Fowler, D. Krumlauf, M. Savani, B. Soeken, K. TI Spiritual well-being in Hispanic and non-hispanic survivors of allogeneic hematopoietic stem cell transplantation SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Ctr Canc, NIH, Bethesda, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2007 VL 16 IS 3 SU S BP S57 EP S57 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 147ZS UT WOS:000245044900107 ER PT J AU Snyder, DJ AF Snyder, D. J. TI Neuropsychiatric toxicity in cancer clinical research: A cautionary tale for the psycho-oncologist SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 NIMH, Div Intramural Res, Off Clin Director, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2007 VL 16 IS 3 SU S BP S86 EP S87 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 147ZS UT WOS:000245044900166 ER PT J AU Wiener, L Pao, M Wendler, D Grady, C Battles, H Steffen-Smith, E Ballard, E Steinberg, S Brennan, T AF Wiener, L. Pao, M. Wendler, D. Grady, C. Battles, H. Steffen-Smith, E. Ballard, E. Steinberg, S. Brennan, T. TI An exploratory study of the use of five wishes as a tool for advanced care planning in young adults with high-risk cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. NIMH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2007 VL 16 IS 3 SU S BP S67 EP S68 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 147ZS UT WOS:000245044900129 ER PT J AU Lockenhoff, CE Carstensen, LL AF Lockenhoff, Corinna E. Carstensen, Laura L. TI Aging, emotion, and health-related decision strategies: Motivational manipulations can reduce age differences SO PSYCHOLOGY AND AGING LA English DT Article DE socioemotional selectivity theory; time perspective; positivity effect; age differences; health care decisions ID ADULT LIFE-SPAN; OLDER-ADULTS; INDIVIDUAL-DIFFERENCES; MAKING COMPETENCE; NEGATIVE IMAGES; MEMORY; CHOICE; INFORMATION; COMPLEXITY; COGNITION AB According to socioemotional selectivity theory, age-related constraints on time horizons are associated with motivational changes that increasingly favor goals related to emotional well-being. Such changes have implications for emotionally taxing tasks such as making decisions, especially when decisions require consideration of unpleasant information. This study examined age differences in information acquisition and recall in the health care realm. Using computer-based decision scenarios, 60 older and 60 young adults reviewed choice criteria that contained positive, negative, and neutral information about different physicians and health care plans. As predicted, older adults reviewed and recalled a greater proportion of positive than of negative information compared with young adults. Age differences were eliminated when motivational manipulations elicited information-gathering goals or when time perspective was controlled statistically. Implications for improving decision strategies in older adults are discussed. C1 Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. RP Lockenhoff, CE (reprint author), NIA, Ctr Gerontol Res, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LoeckenhoffC@grc.nia.nih.gov OI Loeckenhoff, Corinna/0000-0003-1605-1323 FU Intramural NIH HHS; PHS HHS [R01-8816] NR 58 TC 125 Z9 128 U1 3 U2 45 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD MAR PY 2007 VL 22 IS 1 BP 134 EP 146 DI 10.1037/0882-7974.22.1.134 PG 13 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 148FP UT WOS:000245060300015 PM 17385990 ER PT J AU Isaacowitz, DM Lockenhoff, CE Lane, RD Wright, R Sechrest, L Riedel, R Costa, PT AF Isaacowitz, Derek M. Lockenhoff, Corinna E. Lane, Richard D. Wright, Ron Sechrest, Lee Riedel, Robert Costa, Paul T. TI Age differences in recognition of emotion in lexical stimuli and facial expressions SO PSYCHOLOGY AND AGING LA English DT Article DE emotion recognition; facial expressions; lexical stimuli; aging ID ADULT LIFE-SPAN; ALEXITHYMIA; PICTURES; WORDS; SCALE; PERCEPTION; ACTIVATION; ATTENTION; COGNITION; AMYGDALA AB Age differences in emotion recognition from lexical stimuli and facial expressions were examined in a cross-sectional sample of adults aged 18 to 85 (N = 357). Emotion-specific response biases differed by age: Older adults were disproportionately more likely to incorrectly label lexical stimuli as happiness, sadness, and surprise and to incorrectly label facial stimuli as disgust and fear. After these biases were controlled, findings suggested that older adults were less accurate at identifying emotions than were young adults, but the pattern differed across emotions and task types. The lexical task showed stronger age differences than the facial task, and for lexical stimuli, age groups differed in accuracy for all emotional states except fear. For facial stimuli, in contrast, age groups differed only in accuracy for anger, disgust, fear, and happiness. Implications for age-related changes in different types of emotional processing are discussed. C1 NIA, Lab Personal & Cognit, Triad Technol Ctr, Baltimore, MD 21224 USA. Brandeis Univ, Dept Psychol, Waltham, MA 02254 USA. Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. RP Isaacowitz, DM (reprint author), NIA, Lab Personal & Cognit, Triad Technol Ctr, 4th Floor,333 Cassell Dr, Baltimore, MD 21224 USA. EM dmi@brandeis.edu; costap@grc.nia.nih.gov OI Loeckenhoff, Corinna/0000-0003-1605-1323; Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS; NCRR NIH HHS [2S07 RR05675-23] NR 59 TC 113 Z9 117 U1 2 U2 16 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD MAR PY 2007 VL 22 IS 1 BP 147 EP 159 DI 10.1037/0882-7974.22.1.147 PG 13 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 148FP UT WOS:000245060300016 PM 17385991 ER PT J AU Vitiello, B AF Vitiello, Benedetto TI Research in child and adolescent psychopharmacology: recent accomplishments and new challenges SO PSYCHOPHARMACOLOGY LA English DT Review DE psychopharmacology; children; adolescents; research ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; STIMULANT MEDICATION USE; PEDIATRIC PSYCHOPHARMACOLOGY; SUDDEN-DEATH; ANTIDEPRESSANT DRUGS; MULTIMODAL-TREATMENT AB Rationale Research in pediatric psychopharmacology has expanded considerably in the last 10 years. Still, controversy remains about the effectiveness and safety of commonly used psychotropics and their role in child treatment, thus pointing to the need for more in-depth and targeted investigations. Objectives To review recent accomplishments and current limitations of pediatric psychopharmacology, and discuss approaches to further research. Methods Selective review of the relevant literature and research in progress. Results Controlled clinical trials have been conducted in many common psychiatric disorders in children and adolescents, thus providing a basis on which evidence-based treatment guidelines can be constructed. Little innovation has, however, occurred in treatment development and testing. Safety concerns are prominent and have a major influence on clinical practice and drug utilization. Conclusions While a research infrastructure has been successfully built for conducting pediatric clinical trials, important aspects such as long-term treatment effects, optimal sequencing and individualization of interventions, and integration of neuroscience findings into innovative, theory-driven treatment development remain to be addressed. C1 NIMH, Chief Child & Adolescent Treatment & Prevent Inte, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Chief Child & Adolescent Treatment & Prevent Inte, Room 7147,6001 Execut Blvd,MSC 9633, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov NR 86 TC 35 Z9 35 U1 5 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 2007 VL 191 IS 1 BP 5 EP 13 DI 10.1007/s00213-006-0414-3 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 137PH UT WOS:000244304000002 PM 16718480 ER PT J AU McClure, EB Adler, A Monk, CS Cameron, J Smith, S Nelson, EE Leibenluft, E Ernst, M Pine, DS AF McClure, Erin B. Adler, Abby Monk, Christopher S. Cameron, Jennifer Smith, Samantha Nelson, Eric E. Leibenluft, Ellen Ernst, Monique Pine, Daniel S. TI fMRI predictors of treatment outcome in pediatric anxiety disorders SO PSYCHOPHARMACOLOGY LA English DT Article DE amygdala; fMRI; anxiety ID COGNITIVE-BEHAVIORAL THERAPY; EMOTIONAL FACIAL EXPRESSIONS; GENERALIZED SOCIAL PHOBIA; CEREBRAL-BLOOD-FLOW; AMYGDALA RESPONSE; FEARFUL FACES; ANTIDEPRESSANT TREATMENT; ADOLESCENT DEPRESSION; MAJOR DEPRESSION; BRAIN ENGAGEMENT AB Introduction A growing number of studies have found evidence that anxiety and depressive disorders are associated with atypical amygdala hyperactivation, which decreases with effective treatment. Interest has emerged in this phenomenon as a possible biological marker for individuals who are likely to benefit from tailored treatment approaches. Objective The present study was designed to examine relationships between pretreatment amygdala activity and treatment response in a sample of anxious children and adolescents. Materials and methods Participants, who were diagnosed predominantly with generalized anxiety disorder (GAD), underwent functional magnetic resonance imaging (fMRI) scanning before treatment with fluoxetine or cognitive behavioral therapy (CBT). Results Results indicated significant negative associations between degree of left amygdala activation and measures of posttreatment symptom improvement in the group, as a whole. Discussion Taken together with research on associations between adult amygdala activation and treatment response, these findings suggest that patients whose pretreatment amygdala activity is the strongest may be particularly likely to respond well to such widely used treatments as selective serotonin reuptake inhibitor (SSRI) medications and CBT. C1 Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. NIMH, Emot Dev & Affect Neurosci Branch, Mood & Anxiety Disorders Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Human Growth & Dev, Ann Arbor, MI 48109 USA. NIMH, Unit Affect Disorders,Dept Human & Hlth Serv, Pediat & Dev Neuropsychiat Branch, Mood & Anxiety Disorders Program,NIH, Bethesda, MD 20892 USA. RP McClure, EB (reprint author), Georgia State Univ, Dept Psychol, POB 5010, Atlanta, GA 30302 USA. EM emcclure@gsu.edu RI Nelson, Eric/B-8980-2008; Monk, Christopher/J-1805-2014 OI Nelson, Eric/0000-0002-3376-2453; NR 45 TC 74 Z9 76 U1 3 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 2007 VL 191 IS 1 BP 97 EP 105 DI 10.1007/s00213-006-0542-9 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 137PH UT WOS:000244304000009 PM 16972100 ER PT J AU Tierney, E Aman, M Stout, D Pappas, K Arnold, LE Vitiello, B Scahill, L McDougle, C McCracken, J Wheeler, C Martin, A Posey, D Shah, B AF Tierney, Elaine Aman, Michael Stout, David Pappas, Krista Arnold, L. Eugene Vitiello, Benedetto Scahill, Lawrence McDougle, Christopher McCracken, James Wheeler, Courtney Martin, Andres Posey, David Shah, Bhavik TI Parent satisfaction in a multi-site acute trial of risperidone in children with autism: a social validity study SO PSYCHOPHARMACOLOGY LA English DT Article DE autism; consumer satisfaction; parent satisfaction; clinical trial; child; risperidone ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; RANDOMIZED CLINICAL-TRIAL; PERVASIVE DEVELOPMENTAL DISORDERS; OBSESSIVE-COMPULSIVE SCALE; APPLIED BEHAVIOR ANALYSIS; ONCE-A-DAY; OROS METHYLPHENIDATE; ABERRANT BEHAVIOR; ETHICAL-ISSUES; PLACEBO AB Rationale Subjects who view experimental procedures as worthwhile are more likely to participate in clinical trials and comply with study procedures. Designing studies that consider the consumer's perspective will help to forge a better alliance between participants and researchers. Objective Participant satisfaction is seldom assessed in pharmacological research. In this paper, we report on parent satisfaction in a randomized clinical trial in children with autistic disorder and severely disruptive behavior. Method Parents of 101 children with autism who had participated in a multi-site 8-week double-blind clinical trial of risperidone were given a questionnaire at the end to elicit their perceptions of the appropriateness and acceptability of clinical trial procedures. Results Ninety-six (95.0%) parents returned the questionnaire. Of these, 80.0 to 96.8%, depending on the question, expressed satisfaction with their child's research participation regardless of treatment outcome or assignment to active drug or placebo. In all, 90.5% of parents indicated that they would "definitely" recommend the clinical trial to other families with similar children. A total of 92.7% indicated that they would rejoin the clinical trial if they had to do it all over again. Ethnic minority subjects were more satisfied than white participants with the use of "learning tests". Conclusions Parents of children participating in this trial were highly satisfied and supportive of the clinical trial procedures. Random assignment to drug or placebo and the clinical response of their children did not appear to influence their views. Further satisfaction studies of this sort are encouraged. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA. Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. NIMH, NIH, Bethesda, MD 20892 USA. Yale Univ, Ctr Child Study, New Haven, CT USA. Indiana Univ, James Whitcomb Riley Hosp Children, Indianapolis, IN 46204 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Tierney, E (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. EM Tierney@kennedykrieger.org OI Scahill, Lawrence/0000-0001-5073-1707 FU NCRR NIH HHS [M01 RR00034, M01 RR00052, M01 RR00750, M01 RR06022]; NIMH NIH HHS [N01MH80011, N01MH70010, N01MH70001, N01MH70009] NR 31 TC 10 Z9 10 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 2007 VL 191 IS 1 BP 149 EP 157 DI 10.1007/s00213-006-0604-z PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 137PH UT WOS:000244304000014 PM 17123125 ER PT J AU Brenner, AV AF Brenner, Alina V. TI Autoimmune thyroiditis after the Chernobyl accident SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association-Conference on Radiation and Health CY JUN 18-21, 2006 CL Pacific Grove, CA SP Amer Stat Assoc ID CANCER C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD USA. NR 5 TC 0 Z9 0 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 MAR PY 2007 VL 167 IS 3 BP 341 EP 342 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 145PI UT WOS:000244876600014 ER PT J AU Bouville, A AF Bouville, Andre TI Dosimetry in Chernobyl studies SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association-Conference on Radiation and Health CY JUN 18-21, 2006 CL Pacific Grove, CA SP Amer Stat Assoc ID THYROID-CANCER C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. NR 6 TC 0 Z9 0 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 MAR PY 2007 VL 167 IS 3 BP 342 EP 343 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 145PI UT WOS:000244876600015 ER PT J AU Mabuchi, K AF Mabuchi, Kiyohiko TI Overview of studies of long-term cardiovascular effects in humans SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association-Conference on Radiation and Health CY JUN 18-21, 2006 CL Pacific Grove, CA SP Amer Stat Assoc ID HEART-DISEASE; MORTALITY; RADIOTHERAPY; CANCER C1 NCI, Radiat Epidemiol Branch, NIH, Rockville, MD USA. NR 5 TC 1 Z9 1 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 MAR PY 2007 VL 167 IS 3 BP 348 EP 349 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 145PI UT WOS:000244876600021 ER PT J AU Shilnikova, N Preston, D Okatenko, P Gilbert, E Ron, E Sokolnikov, M Kuznetsova, I Khokhryakov, V Vassilenko, E Koshurnikova, N AF Shilnikova, Natalia Preston, Dale Okatenko, Pavel Gilbert, Ethel Ron, Elaine Sokolnikov, Mikhail Kuznetsova, Irina Khokhryakov, Valentin Vassilenko, Eugeny Koshurnikova, Nina TI Mayak worker mortality: Overview and site-specific risks SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association-Conference on Radiation and Health CY JUN 18-21, 2006 CL Pacific Grove, CA SP Amer Stat Assoc ID CANCER-MORTALITY; LUNG-CANCER C1 So Ural Biophys Inst, Ozyorsk, Russia. Hirosoft Int Corp, Seattle, WA USA. NCI, NIH, Rockville, MD USA. Mayak Prod Assoc, Ozyorsk, Russia. NR 5 TC 0 Z9 0 U1 0 U2 1 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 MAR PY 2007 VL 167 IS 3 BP 352 EP 353 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 145PI UT WOS:000244876600025 ER PT J AU Gilbert, ES Sokolnikov, ME Shilnikova, NS Preston, DL Ron, E Okatenko, PV Khokhryakov, VF Vassilenko, EK Koshurnikova, NA AF Gilbert, E. S. Sokolnikov, M. E. Shilnikova, N. S. Preston, D. L. Ron, E. Okatenko, P. V. Khokhryakov, V. F. Vassilenko, E. K. Koshurnikova, N. A. TI Mayak worker study: Risks of lung, liver and bone cancer from plutonium SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association-Conference on Radiation and Health CY JUN 18-21, 2006 CL Pacific Grove, CA SP Amer Stat Assoc C1 NCI, NIH, Rockville, MD USA. So Ural Biophys Inst, Ozyorsk, Russia. Hirosoft Int Corp, Seattle, WA USA. Mayak Prod Assoc, Ozyorsk, Russia. NR 4 TC 0 Z9 0 U1 0 U2 1 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 MAR PY 2007 VL 167 IS 3 BP 353 EP 354 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 145PI UT WOS:000244876600026 ER PT J AU Land, CE Zhumadilov, Z Gusev, BI Hartshorne, MH Wiest, PW Woodward, PW Crooks, LA Luckyanov, NK Fillmore, CM Carr, Z Abisheva, G Sigurdson, AS Beck, HL Bouville, A Langer, J Weinstock, R Gordeev, KI Simon, SL AF Land, C. E. Zhumadilov, Z. Gusev, B. I. Hartshorne, M. H. Wiest, P. W. Woodward, P. W. Crooks, L. A. Luckyanov, N. K. Fillmore, C. M. Carr, Z. Abisheva, G. Sigurdson, A. S. Beck, H. L. Bouville, A. Langer, J. Weinstock, R. Gordeev, K. I. Simon, S. L. TI Radiation dose and thyroid disease prevalence near the semipalatinsk nuclear test site in Kazakhstan SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association-Conference on Radiation and Health CY JUN 18-21, 2006 CL Pacific Grove, CA SP Amer Stat Assoc ID FALLOUT C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. VA Med Ctr, Albuquerque, NM USA. Univ New Mexico, Sch Med, Dept Radiol, Albuquerque, NM 87131 USA. Univ Wisconsin, Armed Forces Inst Pathol, Madison, WI 53706 USA. Res Triangle Inst, Moscow, Russia. Inst Biophys, Moscow, Russia. NR 4 TC 0 Z9 0 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 MAR PY 2007 VL 167 IS 3 BP 354 EP 355 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 145PI UT WOS:000244876600027 ER PT J AU O'Connor, SD Yao, JH Summers, RM AF O'Connor, Stacy D. Yao, Jianhua Summers, Ronald M. TI Lytic metastases in thoracolumbar spine: Computer-aided detection at CT - Preliminary study SO RADIOLOGY LA English DT Article ID BONE METASTASES; BREAST-CANCER; DIAGNOSIS; TOMOGRAPHY; RADIOLOGISTS; NODULES; MRI AB Purpose: To evaluate the sensitivity of a computer-aided detection ( CAD) system for detection of lytic thoracolumbar spinal lesions at body CT, with results of manual lesion segmentation as the reference standard. Materials and Methods: The study was HIPAA compliant and institutional review board approved; the institutional review board waived the need for informed consent. The CAD system segments the spine on CT images and searches for detections that match size, shape, location, and attenuation criteria. To reduce false-positive findings, 16 features for each detection were computed and fed to a classifier trained with manually segmented lesions. The data set consisted of CT studies of 50 patients ( 30 men, 20 women; range, 18-82 years; mean, 54.8 years) with 28 lesions. Studies were assigned to either a training ( 29 studies) or testing ( 21 studies) set. Sensitivities and false-positive rates ( FPRs) for training and testing sets were calculated for these lesions, which were probable lytic metastases with areas 0.8 cm(2) or greater. Results: Training set sensitivity was 0.83 ( 10 of 12; 95% confidence interval: 0.51, 0.97), with an FPR of 7.4 per patient. Test set sensitivity was 0.94 ( 15 of 16; 95% confidence interval: 0.68, 1.00), with an FPR of 4.5 per patient. There was no significant difference between the CAD sensitivities of the training and test sets ( P = .56). Of three false-negative findings, two were due to incomplete segmentation of the vertebral pedicle, and the third was rejected by the classifier. False-positive detections were most often attributable to veins that connect the basivertebral vein with the anterior venous plexus ( 106 [ 34%] of 310) and to low-attenuating disks ( 83 [ 27%] of 310). Conclusion: This CAD system successfully identified probable lytic metastases in the thoracolumbar spine and generalized well to an independent testing set. C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Room 1C351,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS NR 29 TC 18 Z9 22 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2007 VL 242 IS 3 BP 811 EP 816 DI 10.1148/radiol.2423060260 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 142VR UT WOS:000244679200020 PM 17325068 ER PT J AU Seam, N Finkelstein, SE Gonzales, DA Schrump, DS Gladwin, MT AF Seam, Nitin Finkelstein, Steven E. Gonzales, Denise A. Schrump, David S. Gladwin, Mark T. TI The workup of stridor: Virtual bronchoscopy as a complementary technique in the diagnosis of subglottic stenosis SO RESPIRATORY CARE LA English DT Editorial Material ID FIBEROPTIC BRONCHOSCOPY C1 Washington Sch Med, Dept Gen Surg, St Louis, MO USA. NCI, Sect Thorac Oncol, Surg Branch, Bethesda, MD 20892 USA. RP Seam, N (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 2C145,10 Ctr Dr, Bethesda, MD 20892 USA. EM nseam@cc.nih.gov NR 6 TC 2 Z9 2 U1 0 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD MAR PY 2007 VL 52 IS 3 BP 337 EP 339 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 146FN UT WOS:000244920000008 PM 17375441 ER PT J AU Hansman, GS Oka, T Katayama, K Takeda, N AF Hansman, Grant S. Oka, Tomoichiro Katayama, Kazuhiko Takeda, Naokazu TI Human sapoviruses: genetic diversity, recombination, and classification SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID VIRUS-LIKE PARTICLES; BLOOD GROUP ANTIGENS; SAPPORO-LIKE VIRUSES; POLYMERASE CHAIN-REACTION; DAY-CARE-CENTER; HUMAN CALICIVIRUS; NORWALK-VIRUS; MOLECULAR CHARACTERIZATION; ACUTE GASTROENTERITIS; VIRAL GASTROENTERITIS AB The family Caliciviridae contains four genera Sapovirus, Norovirus, Lagovirus and Vesivirus, which include Sapporo virus (SaV), Norwalk virus (NoV), Rabbit hemorrhagic disease virus (RHDV) and Feline calicivirus (FCV), respectively. SaV is a causative agent of gastroenteritis in children and adults. SaV can be divided into five genogroups (GI-GV), among which GI, GII, GIV and GV are known to infect humans, whereas SaV GIII infects porcine species. Detection methods include ELISA, RT-PCR and real-time RT-PCR. Since few SaV studies have been conducted, it is difficult to draw correlations between or conclusions about rates of incidence, detection and overall prevalence. Nevertheless, most studies agree that SaV infection is more frequent in young children than adults and that infection in children almost always occurs by 5 years of age. In addition, children at day-care centres and institutions are at greatest risk of SaV-associated infection and transmission. Recently, a number of important findings concerning human SaV were discovered. SaV strains were detected in water samples, which included untreated wastewater specimens, treated wastewater samples and river samples. SaV strains were also detected in shellfish samples destined for human consumption, and recombinant SaV strains were identified in a number of different countries. The purpose of this review was to highlight the current knowledge of human SaV, which appears to be an increasingly important virus causing gastroenteritis in humans. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 NIAID, Dept Virol 2, Tokyo 2080011, Japan. RP Hansman, GS (reprint author), NIAID, Dept Virol 2, 4-7-1 Gakuen, Tokyo 2080011, Japan. EM ghansman@nih.go.jp OI Hansman, Grant/0000-0001-8735-4618 NR 59 TC 81 Z9 91 U1 3 U2 13 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD MAR-APR PY 2007 VL 17 IS 2 BP 133 EP 141 DI 10.1002/rmv.533 PG 9 WC Virology SC Virology GA 152RH UT WOS:000245379000005 PM 17340567 ER PT J AU Santos, MCL Pagliuca, LMF Fernandes, AFC AF Lavinas Santos, Miria Conceicao Freitag Pagliuca, Lorita Marlena Carvalho Fernandes, Ana Fatima TI Palliative care to the cancer patient: Reflections according to Paterson and Zderads view SO REVISTA LATINO-AMERICANA DE ENFERMAGEM LA English DT Article DE neoplasms; hospice care AB This reflective study presents the approach of the Nursing Palliative Care to the cancer patient without therapeutic possibility according to the Paterson and Zderad's Humanistic Nursing Theory. The palliative care aims to provide the patient without therapeutic possibility and his family better quality of life. When the nurse, in addition to delivering palliative care to the cancer patient, uses the Humanistic Theory, (s)he starts to recognize each person as a singular existence. This recognition permits one to understand the person's meaning in the process of his(er) disease. C1 [Lavinas Santos, Miria Conceicao] Natl Canc Inst, Bethesda, MD USA. RP Santos, MCL (reprint author), Natl Canc Inst, Bethesda, MD USA. EM mlavinas@fortainet.com.br; pagliuca@ufc.br; afcana@ufc.br NR 13 TC 2 Z9 5 U1 1 U2 10 PU UNIV SAO PAOLO PI PIRACICABA PA AV PADUA DIAS 11, C P 9, PIRACICABA, SP 13418-900, BRAZIL SN 0104-1169 J9 REV LAT-AM ENFERM JI Rev. Latino-Am. Enfermagem PD MAR-APR PY 2007 VL 15 IS 2 BP 350 EP 354 DI 10.1590/S0104-11692007000200024 PG 5 WC Nursing SC Nursing GA 272GE UT WOS:000253847100024 ER PT J AU Carroll, KL Ghirlando, R Ames, JM Corden, JL AF Carroll, Kristina L. Ghirlando, Rodolfo Ames, Jessica M. Corden, Jeffry L. TI Interaction of yeast RNA-binding proteins Nrd1 and Nab3 with RNA polymerase II terminator elements SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE snoRNA; RNA-binding domain; transcription termination ID CRYPTIC UNSTABLE TRANSCRIPTS; 3'-END FORMATION; GENE-EXPRESSION; COMPLEX; EXOSOME; SNORNA; ULTRACENTRIFUGATION; POLYADENYLATION; ACCUMULATION; RECOGNITION AB Yeast RNA-binding proteins Nrd1 and Nab3 direct transcription termination of sn/snoRNA transcripts, some mRNA transcripts, and a class of intergenic and anti-sense transcripts. Recognition of Nrd1- and Nab3-binding sites is a critical first step in the termination and subsequent processing or degradation of these transcripts. In this article, we describe the purification and characterization of an Nrd1-Nab3 heterodimer. This Nrd1-Nab3 complex binds specifically to RNA sequences derived from a snoRNA terminator. The relative binding to mutant terminators correlates with the in vivo termination efficiency of these mutations, indicating that the primary specificity determinant in nonpoly(A) termination is Nrd1-Nab3 binding. In addition, several snoRNA terminators contain multiple Nrd1- and Nab3-binding sites and we show that multiple heterodimers bind cooperatively to one of these terminators in vitro. C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Corden, JL (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, 725 N Wolfe St, Baltimore, MD 21205 USA. EM jcorden@jhmi.edu RI Ghirlando, Rodolfo/A-8880-2009 FU Intramural NIH HHS; NIGMS NIH HHS [GM66108, R01 GM066108] NR 38 TC 78 Z9 78 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD MAR PY 2007 VL 13 IS 3 BP 361 EP 373 DI 10.1261/rna.338407 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139MH UT WOS:000244435400007 PM 17237360 ER PT J AU O'Brien, TR Kachapati, K Zhang, MD Bergeron, J Edlin, BR Dean, M AF O'Brien, Thomas R. Kachapati, Kritika Zhang, Mingdong Bergeron, Julie Edlin, Brian R. Dean, Michael TI HCV infection clearance with functional or non-functional caspase-12 SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Ctr Adv Technol, NIH,Dept Hlth & Human Serv, Gaithersburg, MD 20877 USA. NCI, Ctr Canc Res, NIH, Dept Hlth & Human Serv, Gaithersburg, MD 20877 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. Univ Calif San Francisco, Urban Hlth Study, San Francisco, CA 94143 USA. Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. RP O'Brien, TR (reprint author), NCI, Div Canc Epidemiol & Genet, Ctr Adv Technol, NIH,Dept Hlth & Human Serv, Room 225A,MSC 4605,8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM obrient@mail.nih.gov RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 4 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PD MAR PY 2007 VL 42 IS 3 BP 416 EP 417 DI 10.1080/00365520601076074 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 148KX UT WOS:000245074500021 PM 17354126 ER PT J AU Weinberger, DR Barenboim, M Lipska, B Nicodemus, K Straub, R Egan, M Meyer-Lindenberg, A Kleinman, J AF Weinberger, D. R. Barenboim, M. Lipska, B. Nicodemus, K. Straub, R. Egan, M. Meyer-Lindenberg, A. Kleinman, J. TI Complex genetics in human brain: Lessons from COMT and schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 10th International Congress on Schizophrenia Research CY APR 02-06, 2005 CL Savannah, GA C1 NIH, NIMH, Cognit & Psychosis Program, Bethesda, MD 20892 USA. RI Sambataro, Fabio/E-3426-2010 OI Sambataro, Fabio/0000-0003-2102-416X NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2007 VL 33 IS 2 BP 292 EP 292 PG 1 WC Psychiatry SC Psychiatry GA 140LL UT WOS:000244506600258 ER PT J AU Weinberger, DR Sambataro, F Nicodemus, K Mattay, V Lipska, B Vakkalanka, K Lieberman, R Rujescu, D Egan, M Goldberg, T Chen, J Kleinman, J Huffaker, S AF Weinberger, D. R. Sambataro, F. Nicodemus, K. Mattay, V. Lipska, B. Vakkalanka, K. Lieberman, R. Rujescu, D. Egan, M. Goldberg, T. Chen, J. Kleinman, J. Huffaker, S. TI Novel schizophrenia susceptibility genes from brain expression profiles SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 10th International Congress on Schizophrenia Research CY APR 02-06, 2005 CL Savannah, GA C1 NIH, NIMH, Bethesda, MD 20892 USA. RI Sambataro, Fabio/E-3426-2010 OI Sambataro, Fabio/0000-0003-2102-416X NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2007 VL 33 IS 2 BP 292 EP 292 PG 1 WC Psychiatry SC Psychiatry GA 140LL UT WOS:000244506600259 ER PT J AU Chen, J Lipska, BK Weinberger, DR AF Chen, J. Lipska, B. K. Weinberger, D. R. TI New genetic mouse models of schizophrenia: Mimicking cognitive dysfunction by altering susceptibility gene expression SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 10th International Congress on Schizophrenia Research CY APR 02-06, 2005 CL Savannah, GA C1 NIH, NIMH, Cognit & Psychosis Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2007 VL 33 IS 2 BP 296 EP 296 PG 1 WC Psychiatry SC Psychiatry GA 140LL UT WOS:000244506600270 ER PT J AU Goldberg, T AF Goldberg, T. TI Genotypic effects on episodic memory: Experience from bdnf, G72, and GRM3 SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 10th International Congress on Schizophrenia Research CY APR 02-06, 2005 CL Savannah, GA C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2007 VL 33 IS 2 BP 298 EP 298 PG 1 WC Psychiatry SC Psychiatry GA 140LL UT WOS:000244506600278 ER PT J AU Lipska, BK Mitkus, S Hyde, TM Weinberger, DR Kleinman, JE AF Lipska, B. K. Mitkus, S. Hyde, T. M. Weinberger, D. R. Kleinman, J. E. TI Abnormalities in the DISC1 pathway in schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 10th International Congress on Schizophrenia Research CY APR 02-06, 2005 CL Savannah, GA C1 NIMH, CBDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2007 VL 33 IS 2 BP 310 EP 311 PG 2 WC Psychiatry SC Psychiatry GA 140LL UT WOS:000244506600314 ER PT J AU Weickert, T Goldberg, TE Chen, Q Callicott, JH Apud, A Das, S Zoltick, B Egan, MF Weinberger, DR Mattay, VS AF Weickert, T. Goldberg, T. E. Chen, Q. Callicott, J. H. Apud, A. Das, S. Zoltick, B. Egan, M. F. Weinberger, D. R. Mattay, V. S. TI Neural mechanisms underlying probabilistic category learning in patients with schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 10th International Congress on Schizophrenia Research CY APR 02-06, 2005 CL Savannah, GA C1 NIH, NIMH, Bethesda, MD 20892 USA. RI Callicott, Joseph/C-9102-2009 OI Callicott, Joseph/0000-0003-1298-3334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2007 VL 33 IS 2 BP 387 EP 388 PG 2 WC Psychiatry SC Psychiatry GA 140LL UT WOS:000244506600533 ER PT J AU Shapiro, DI Marenco, S Goldberg, TE Cannon-Spoor, EH Egan, MF Weinberger, DR AF Shapiro, D. I. Marenco, S. Goldberg, T. E. Cannon-Spoor, E. H. Egan, M. F. Weinberger, D. R. TI Is premorbid adjustment a predictor of cognition in schizophrenia and discordant siblings? SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 10th International Congress on Schizophrenia Research CY APR 02-06, 2005 CL Savannah, GA C1 NIMH, NIH, CBDB, Washington, DC USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2007 VL 33 IS 2 BP 576 EP 576 PG 1 WC Psychiatry SC Psychiatry GA 140LL UT WOS:000244506601463 ER PT J AU Jones, NL AF Jones, Nancy L. TI A code of ethics for the life sciences SO SCIENCE AND ENGINEERING ETHICS LA English DT Article DE professionalism; ethics; code; research integrity; life sciences; norms; social contract ID SCIENTIFIC SOCIETIES; RESEARCH INTEGRITY; NORMS; RESEARCHERS; VALUES AB The activities of the life sciences are essential to provide solutions for the future, for both individuals and society. Society has demanded growing accountability from the scientific community as implications of life science research rise in influence and there are concerns about the credibility, integrity and motives of science. While the scientific community has responded to concerns about its integrity in part by initiating training in research integrity and the responsible conduct of research, this approach is minimal. The scientific community justifies itself by appealing to the ethos of science, claiming academic freedom, self-direction, and self-regulation, but no comprehensive codification of this foundational ethos has been forthcoming. A review of the professional norms of science and a prototype code of ethics for the life sciences provide a framework to spur discussions within the scientific community to define scientific professionalism. A formalization of implicit principles can provide guidance for recognizing divergence from the norms, place these norms within a context that would enhance education of trainees, and provide a framework for discussing externally and internally applied pressures that are influencing the practice of science. The prototype code articulates the goal for life sciences research and the responsibilities associated with the freedom of exploration, the principles for the practice of science, and the virtues of the scientists themselves. The time is ripe for scientific communities to reinvigorate professionalism and define the basis of their social contract. Codifying the basis of the social contract between science and society will sustain public trust in the scientific enterprise. C1 NIAID, NIH, DHHS, SPEB,OSPFM, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. RP Jones, NL (reprint author), NIAID, NIH, DHHS, SPEB,OSPFM, Bldg 31 7A30A, Bethesda, MD 20892 USA. EM jonesna@niaid.nih.gov NR 28 TC 21 Z9 21 U1 8 U2 19 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1353-3452 J9 SCI ENG ETHICS JI Sci. Eng. Ethics PD MAR PY 2007 VL 13 IS 1 BP 25 EP 43 DI 10.1007/s11948-006-0007-x PG 19 WC Ethics; Engineering, Multidisciplinary; History & Philosophy Of Science; Multidisciplinary Sciences; Philosophy SC Social Sciences - Other Topics; Engineering; History & Philosophy of Science; Science & Technology - Other Topics; Philosophy GA 211VK UT WOS:000249551200003 PM 17703607 ER PT J AU Collins, FS Barker, AD AF Collins, Francis S. Barker, Anna D. TI Mapping the cancer genome - Pinpointing the genes involved in cancer will help chart a new course across the complex landscape of human malignancies SO SCIENTIFIC AMERICAN LA English DT Article AB Pinpointing the genes involved in cancer will help chart a new course across the complex landscape of human malignancies. Changes in the structure or activity of genes underlie the malignant behavior of many cancer cells. The Cancer Genome Atlas is a monumental initiative to eventually identify all the genetic alterations in different forms of cancer so that gene changes driving disease can be targeted directly. Identification of the genes involved is already advancing diagnosis and treatment. C1 NCI, Adv Technol & Strateg Partnerships, Bethesda, MD 20892 USA. NR 2 TC 115 Z9 118 U1 1 U2 15 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 0036-8733 J9 SCI AM JI Sci.Am. PD MAR PY 2007 VL 296 IS 3 BP 50 EP 57 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 135OX UT WOS:000244164000027 PM 17348159 ER PT J AU Caplan, LJ Schooler, C AF Caplan, Leslie J. Schooler, Carmi TI Socioeconomic status and financial coping strategies: The mediating role of perceived control SO SOCIAL PSYCHOLOGY QUARTERLY LA English DT Article ID DEPRESSIVE SYMPTOMS; PERSONAL CONTROL; FIT HYPOTHESIS; SOCIAL SUPPORT; SELF-ESTEEM; COMMUNITY SAMPLE; OLDER-ADULTS; STRESS; HEALTH; SENSE AB We examine the relations among socioeconomic status, control beliefs, and two coping styles (problem-focused vs. emotion-focused) in the context of financial stress. Findings indicate that low socioeconomic status (SES) is linked to greater use of emotion-focused financial coping and lesser use of problem-focused financial coping. The effects of SES on the use of problem-focused financial coping appear to be entirely mediated by two measures of perceived control: self-confidence and fatalism. In contrast, the effects of SES on emotion focused financial coping are not mediated in this way. Results also indicated that problem-focused and emotion-focused financial coping are differentially related to financial stress and to general psychosocial distress. These results suggest that low SES may decrease one control beliefs, which in turn decrease the likelihood of choosing effective financial coping processes, resulting in double disadvantage. C1 NIMH, Sect Socio Environm Studies, Bethesda, MD 20892 USA. RP Caplan, LJ (reprint author), NIMH, Sect Socio Environm Studies, 6101 Execut Blvd,Room 364, Bethesda, MD 20892 USA. EM leslie.caplan@nih.gov NR 60 TC 19 Z9 19 U1 7 U2 14 PU AMER SOCIOLOGICAL ASSOC PI WASHINGTON PA 1307 NEW YORK AVE NW #700, WASHINGTON, DC 20005-4712 USA SN 0190-2725 J9 SOC PSYCHOL QUART JI Soc. Psychol. Q. PD MAR PY 2007 VL 70 IS 1 BP 43 EP 58 PG 16 WC Psychology, Social SC Psychology GA 152ML UT WOS:000245366000006 ER PT J AU King, RB Bratter, JL AF King, Rosalind Berkowitz Bratter, Jenifer L. TI A path toward interracial marriage: Women's first partners and husbands across racial lines SO SOCIOLOGICAL QUARTERLY LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the American-Sociological-Association CY AUG 17-21, 2001 CL ANAHEIM, CA SP Amer Sociol Assoc ID ASIAN-AMERICAN INTERMARRIAGE; UNITED-STATES; RESIDENTIAL SEGREGATION; FRIENDSHIP SEGREGATION; MEXICAN-AMERICANS; RACE; BLACK; PATTERNS; TRENDS; WHITE AB We examine interracial marriage as a culminating event in a sequence of intimate relationships across the life course. Using data from the 1995 National Survey of Family Growth, we analyze the background characteristics associated with selecting a first sex partner and first husband who differ in race/ethnicity from the respondent as well as the continuity across both outcomes. Our results show that respondents' race/ethnicity, parents' education, and region of birth are significant predictors of both choices. Selecting partners across racial lines for first sex is significantly associated with the selection of a first husband across race; the association between both outcomes is particularly strong for non-Hispanic black women, implying that social integration across race may be a life course phenomenon. C1 NICHHD, Demog & Behav Sci Branch, Populat Res Ctr, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Rice Univ, Dept Sociol, Houston, TX 77005 USA. RP King, RB (reprint author), NICHHD, Demog & Behav Sci Branch, Populat Res Ctr, NIH,US Dept Hlth & Human Serv, 6100 Execut Blvd,Room 8B07, Bethesda, MD 20892 USA. EM jlb1@rice.edu NR 90 TC 16 Z9 16 U1 3 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0038-0253 J9 SOCIOL QUART JI Sociol. Q. PD SPR PY 2007 VL 48 IS 2 BP 343 EP 369 DI 10.1111/j.1533-8525.2007.00081.x PG 27 WC Sociology SC Sociology GA 161CW UT WOS:000245992900007 ER PT J AU Fawcett, JW Curt, A Steeves, JD Coleman, WP Tuszynski, MH Lammertse, D Bartlett, PF Blight, AR Dietz, V Ditunno, J Dobkin, BH Havton, LA Ellaway, PH Fehlings, MG Privat, A Grossman, R Guest, JD Kleitman, N Nakamura, M Gaviria, M Short, D AF Fawcett, J. W. Curt, A. Steeves, J. D. Coleman, W. P. Tuszynski, M. H. Lammertse, D. Bartlett, P. F. Blight, A. R. Dietz, V. Ditunno, J. Dobkin, B. H. Havton, L. A. Ellaway, P. H. Fehlings, M. G. Privat, A. Grossman, R. Guest, J. D. Kleitman, N. Nakamura, M. Gaviria, M. Short, D. TI Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials SO SPINAL CORD LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; NEUROLOGIC RECOVERY; TIRILAZAD MESYLATE; MOTOR RECOVERY; METHYLPREDNISOLONE; MULTICENTER; QUADRIPLEGIA; TETRAPLEGIA; NALOXONE AB The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients ( American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions ( AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to 18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods. C1 Univ Cambridge, Ctr Brain Repair, Cambridge CB2 2PY, England. Univ British Columbia, ICORD, Vancouver, BC V5Z 1M9, Canada. Vancouver Coastal Hlth Res Inst, Vancouver, BC, Canada. WPCMath, Buffalo, NY USA. Univ Calif San Diego, Ctr Neural Repair, La Jolla, CA 92093 USA. Craig Hosp, Englewood, CO USA. Univ Queensland, Queensland Brain Inst, St Lucia, Qld, Australia. Acorda Therapeut, Hawthorne, NY USA. Balgrist Univ Hosp, Spinal Cord Injury Ctr, Zurich, Switzerland. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Univ Calif Los Angeles, Dept Neurol, Geffen Sch Med, Neurol Rehabil & Res Program, Los Angeles, CA 90024 USA. Univ London Imperial Coll Sci & Technol, Dept Movement & Balance, Div Neurosci & Mental Hlth, London, England. Univ Toronto, Toronto Western Hosp, Krembil Neurosci Ctr, Head Spine & Spinal Cord Injury Program, Toronto, ON M5T 2S8, Canada. CHU St Eloi, Inst Neurosci, INSERM U583, Montpellier, France. Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. Lois Pope LIFE Ctr, Dept Neurol Surg, Miami, FL USA. NINDS, NIH, Bethesda, MD 20892 USA. Keio Univ, Sch Med, Dept Orthopaed Surg, Tokyo, Japan. Robert Jones & Agnes Hunt Orthopaed & Dis Hosp, NHS Trust, Midlands Ctr Spinal Injuries, Oswestry, Shrops, England. RP Fawcett, JW (reprint author), Univ Cambridge, Ctr Brain Repair, Robinson Way, Cambridge CB2 2PY, England. RI Bartlett, Perry/F-3813-2012; Nakamura, Masaya/K-4111-2013; OI Kleitman, Naomi/0000-0003-1089-0257; Lammertse, Daniel/0000-0003-4590-2481; Fawcett, James/0000-0002-7990-4568 FU Medical Research Council [G9828345] NR 20 TC 326 Z9 337 U1 2 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD MAR PY 2007 VL 45 IS 3 BP 190 EP 205 DI 10.1038/sj.sc.3102007 PG 16 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 141IA UT WOS:000244570800002 PM 17179973 ER PT J AU Steeves, JD Lammertse, D Curt, A Fawcett, JW Tuszynski, MH Ditunno, JF Ellaway, PH Fehlings, MG Guest, JD Kleitman, N Bartlett, PF Blight, AR Blight, AR Dietz, V Dobkin, BH Grossman, R Short, D Nakamura, M Coleman, WP Gaviria, M Privat, A AF Steeves, J. D. Lammertse, D. Curt, A. Fawcett, J. W. Tuszynski, M. H. Ditunno, J. F. Ellaway, P. H. Fehlings, M. G. Guest, J. D. Kleitman, N. Bartlett, P. F. Blight, A. R. Blight, A. R. Dietz, V. Dobkin, B. H. Grossman, R. Short, D. Nakamura, M. Coleman, W. P. Gaviria, M. Privat, A. TI Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures SO SPINAL CORD LA English DT Article DE spinal cord injury; clinical trial; neurologic assessment; outcome measures; functional recovery ID RANDOMIZED CONTROLLED-TRIAL; MOTOR-EVOKED-POTENTIALS; CUTANEOUS ELECTRICAL-STIMULATION; FUNCTIONAL INDEPENDENCE MEASURE; SYMPATHETIC SKIN-RESPONSE; PHYSIOLOGICAL STIMULI; PERCEPTUAL THRESHOLD; QUADRIPLEGIA INDEX; TIRILAZAD MESYLATE; RECOVERY AB An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: ( 1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, ( 2) those that categorize a subject's functional ability to engage in activities of daily living, and ( 3) those that measure an individual's quality of life ( QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures. C1 Univ British Columbia, ICORD, Vancouver, BC V6T 1Z4, Canada. Vancouver Coastal Hlth Res Inst, Vancouver, BC V6T 1Z4, Canada. Craig Hosp, Englewood, CO USA. Univ Cambridge, Ctr Brain Repair, Cambridge, England. Univ Calif San Diego, Ctr Neural Repair, La Jolla, CA 92093 USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Imperial Coll London, Dept Movement & Balance, Div Neurosci & Mental Hlth, London, England. Univ Toronto, Toronto Gen Hosp, Krembil Neurosci Ctr, Head Spine & Spinal Cord Injury Program, Toronto, ON M5G 1L7, Canada. Lois Pope LIFE Ctr, Dept Neurol Surg, Miami, FL USA. Lois Pope LIFE Ctr, Miami Project Cure Paralysis, Miami, FL USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Queensland, Queensland Brain Inst, St Lucia, Qld, Australia. Acorda Therapeut, Hawthorne, NY USA. Balgrist Univ Hosp, Spinal Cord Injury Ctr, Zurich, Switzerland. Univ Calif Los Angeles, Dept Neurol, Geffen Sch Med, Neurol Rehabil & Res Program, Los Angeles, CA 90024 USA. Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. Robert Jones & Agnes Hunt Orthopaed & Dist Hosp, NHS Trust, Midlands Ctr Spinal Injuries, Oswestry, Shrops, England. Keio Univ, Sch Med, Dept Orthopaed Surg, Tokyo, Japan. WPCMath, Buffalo, NY USA. CHU St Eloi, INSERM U583, Inst Neurosci, Montpellier, France. RP Steeves, JD (reprint author), Univ British Columbia, ICORD, C-O 2469-6270 Univ Blvd, Vancouver, BC V6T 1Z4, Canada. RI Bartlett, Perry/F-3813-2012; Nakamura, Masaya/K-4111-2013; OI Kleitman, Naomi/0000-0003-1089-0257; Lammertse, Daniel/0000-0003-4590-2481; Fawcett, James/0000-0002-7990-4568 NR 75 TC 226 Z9 233 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD MAR PY 2007 VL 45 IS 3 BP 206 EP 221 DI 10.1038/sj.sc.3102008 PG 16 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 141IA UT WOS:000244570800003 PM 17179972 ER PT J AU Tuszynski, MH Steeves, JD Fawcett, JW Lammertse, D Kalichman, M Rask, C Curt, A Ditunno, JF Fehlings, MG Guest, JD Ellaway, PH Kleitman, N Bartlett, PF Blight, AR Dietz, V Dobkin, BH Grosman, R Privat, A AF Tuszynski, M. H. Steeves, J. D. Fawcett, J. W. Lammertse, D. Kalichman, M. Rask, C. Curt, A. Ditunno, J. F. Fehlings, M. G. Guest, J. D. Ellaway, P. H. Kleitman, N. Bartlett, P. F. Blight, A. R. Dietz, V. Dobkin, B. H. Grosman, R. Privat, A. TI Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP Panel: clinical trial inclusion exclusion criteria and ethics SO SPINAL CORD LA English DT Article DE spinal cord injury; clinical trial; clinical assessment; confounding variables; inclusion criteria; exclusion criteria; ethics; informed consent ID PARKINSONS-DISEASE; PLACEBO SURGERY; TRANSPLANTATION; RISK AB The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the third of four papers. It examines inclusion and exclusion criteria that can influence the design and analysis of clinical trials in SCI, together with confounding variables and ethical considerations. Inclusion and exclusion criteria for clinical trials should consider several factors. Among these are ( 1) the enrollment of subjects at appropriate stages after SCI, where there is supporting data from animal models or previous human studies; ( 2) the severity, level, type, or size of the cord injury, which can influence spontaneous recovery rate and likelihood that an experimental treatment will clinically benefit the subject; and ( 3) the confounding effects of various independent variables such as pre-existing or concomitant medical conditions, other medications, surgical interventions, and rehabilitation regimens. An issue of substantial importance in the design of clinical trials for SCI is the inclusion of blinded assessments and sham surgery controls: every effort should be made to address these major issues prospectively and carefully, if clear and objective information is to be gained from a clinical trial. The highest ethical standards must be respected in the performance of clinical trials, including the adequacy and clarity of informed consent. C1 Univ Calif San Diego, Dept Neurosci, Ctr Neural Repair, La Jolla, CA 92093 USA. Vet Adm Med Ctr, Dept Neurol, La Jolla, CA 90034 USA. Univ British Columbia, ICORD, Vancouver, BC V5Z 1M9, Canada. Vancouver Coastal Hlth Res Inst, Vancouver, BC, Canada. Univ Cambridge, Ctr Brain Repair, Cambridge, England. Craig Hosp, Englewood, CO USA. Univ Colorado, Dept Phys Med & Rehabil, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Calif San Diego, Res Eth Program, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. Inst OneWorld Hlth, San Francisco, CA USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Rehabil Med, Philadelphia, PA 19107 USA. Univ Toronto, Dept Surg, Div Neurosurg, Toronto, ON, Canada. Univ Miami, Dept Neurosurg, Miami, FL 33152 USA. Univ London Imperial Coll Sci & Technol, Dept Movement & Balance, Div Neurosci & Mental Hlth, London, England. NINDS, NIH, Bethesda, MD 20892 USA. Acorda Therapeut Inc, Hawthorne, NY USA. Balgrist Univ Hosp, Spinal Cord Injury Ctr, Zurich, Switzerland. Univ Calif Los Angeles, Dept Neurol, Geffen Sch Med, Neurol Rehabil & Res Program, Los Angeles, CA 90024 USA. Methodist Neurol Inst, Houston, TX USA. CHU St Eloi, Inst Neurosci, INSERM U583, Montpellier, France. RP Tuszynski, MH (reprint author), Univ Calif San Diego, Dept Neurosci, Ctr Neural Repair, La Jolla, CA 92093 USA. RI Bartlett, Perry/F-3813-2012; OI Kleitman, Naomi/0000-0003-1089-0257; Fawcett, James/0000-0002-7990-4568 NR 12 TC 101 Z9 103 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD MAR PY 2007 VL 45 IS 3 BP 222 EP 231 DI 10.1038/sj.sc.3102009 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 141IA UT WOS:000244570800004 PM 17179971 ER PT J AU Lammertse, D Tuszynski, MH Steeves, JD Steeves, JD Fawcett, JW Rask, C Ditunno, JF Fehlings, MG Guest, JD Ellaway, PH Kleitman, N Blight, AR Dobkin, BH Grossman, R Katoh, H Privat, A Kalichman, M AF Lammertse, D. Tuszynski, M. H. Steeves, J. D. Steeves, J. D. Fawcett, J. W. Rask, C. Ditunno, J. F. Fehlings, M. G. Guest, J. D. Ellaway, P. H. Kleitman, N. Blight, A. R. Dobkin, B. H. Grossman, R. Katoh, H. Privat, A. Kalichman, M. TI Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design SO SPINAL CORD LA English DT Article DE spinal cord injury; clinical trial; clinical trial design; clinical trial protocols; trial assessment; trial oversight; ASIA; motor system; sensory system ID SUSTAINED-RELEASE 4-AMINOPYRIDINE; PARKINSONS-DISEASE; FAMPRIDINE-SR; METHYLPREDNISOLONE; TRANSPLANTATION AB The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the fourth of four papers. Here, we examine the phases of a clinical trial program, the elements, types, and protocols for valid clinical trial design. The most rigorous and valid SCI clinical trial would be a prospective double-blind randomized control trial utilizing appropriate placebo control subjects. However, in specific situations, it is recognized that other trial procedures may have to be considered. We review the strengths and limitations of the various types of clinical trials with specific reference to SCI. It is imperative that the design and conduct of SCI clinical trials should meet appropriate standards of scientific inquiry to insure that meaningful conclusions about efficacy and safety can be achieved and that the interests of trial subjects are protected. We propose these clinical trials guidelines for use by the SCI clinical research community. C1 Craig Hosp, Englewood, CO 80113 USA. Univ Colorado, Dept Phys Med & Rehabil, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Calif San Diego, Ctr Neural Repair, Dept Neurosci, La Jolla, CA 92093 USA. Vet Adm Med Ctr, Dept Neurol, La Jolla, CA 90034 USA. Univ British Columbia, ICORD, Vancouver, BC V5Z 1M9, Canada. Vancouver Coastal Hlth Res Inst, Vancouver, BC, Canada. Univ Cambridge, Ctr Brain Repair, Cambridge, England. Inst OneWorld Hlth, San Francisco, CA USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Rehabil Med, Philadelphia, PA 19107 USA. Univ Toronto, Dept Surg, Div Neurosurg, Toronto, ON, Canada. Univ Miami, Dept Neurosurg, Miami, FL 33152 USA. Univ London Imperial Coll Sci & Technol, Dept Movement & Balance, Div Neurosci & Mental Hlth, London, England. NINDS, NIH, Bethesda, MD 20892 USA. Acorda Therapeut Inc, Hawthorne, NY USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Methodist Neurol Inst, Houston, TX USA. Keio Univ, Sch Med, Tokyo, Japan. CHU St Eloi, Inst Neurosci, INSERM U583, Montpellier, France. Univ Calif San Diego, Res Eth Program, Dept Pathol, La Jolla, CA 92093 USA. RP Lammertse, D (reprint author), Craig Hosp, 3425 S Clarkson St, Englewood, CO 80113 USA. OI Kleitman, Naomi/0000-0003-1089-0257; Lammertse, Daniel/0000-0003-4590-2481; Fawcett, James/0000-0002-7990-4568 FU NICHD NIH HHS [U01 HD037439] NR 20 TC 100 Z9 105 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD MAR PY 2007 VL 45 IS 3 BP 232 EP 242 DI 10.1038/sj.sc.3102010 PG 11 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 141IA UT WOS:000244570800005 PM 17179970 ER PT J AU Chen, SS Fitzgerald, W Zimmerberg, J Kleinman, HK Margolis, L AF Chen, Silvia S. Fitzgerald, Wendy Zimmerberg, Joshua Kleinman, Hynda K. Margolis, Leonid TI Cell-cell and cell-extracellular matrix interactions regulate embryonic stem cell differentiation SO STEM CELLS LA English DT Article DE embryonic stem cell biology; rhesus; real-time reverse transcription-polymerase chain reaction; lineage analysis ID TERATOCARCINOMA CELLS; IN-VITRO; COLLAGEN; LAMININ; GROWTH; CARDIOMYOCYTES; PROLIFERATION; EXPRESSION; LIVER; SHAPE AB Cell interactions with the extracellular matrix (ECM) play a critical role in their physiology. Here, we sought to determine the role of exogenous and endogenous ECM in the differentiation of nonhuman primate ESCs. We evaluated cell differentiation from expression of lineage gene mRNA and proteins using real-time polymerase chain reaction and immunohistochemistry. We found that ESCs that attached to and spread upon highly adhesive collagen do not differentiate efficiently, whereas on the less adhesive Matrigel, ESCs form aggregates and differentiate along mesoderm and especially endoderm. lineages. To further decrease ESC attachment to the substrate, we cultured them either on nonadhesive agarose or in suspension. In both cases, ESCs formed aggregates and efficiently differentiated along endoderm and mesoderm lineages, most strikingly into cardiomyocytes. Aggregates formed by thus-differentiated ESCs started to beat with a frequency of 50-100 beats per minute and continued to beat for approximately a month. In spite of the presence of exogenous ECM, ESCs were dependent on endogenous ECM for their survival and differentiation, as the inhibition of endogenous collagen induced a gradual loss of ESCs and neither a simple matrix, such as type I collagen, nor the complex matrix Matrigel was able to rescue these cells. In conclusion, adhesiveness to various ECM and nonbiological substrates determines the differentiation of ESCs in such a way that efficient cell-cell aggregation, together with less efficient cell attachment and spreading, results in more efficient cell differentiation. C1 NIDCR, NIH, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. NIDCR, NIH, NASA, NICHHD,Ctr Tissue Culture Dimens 3, Bethesda, MD 20892 USA. NIDCR, NIH, Cell Biol Sect, Bethesda, MD 20892 USA. RP Kleinman, HK (reprint author), NIDCR, NIH, Lab Cellular & Mol Biophys, 30 Convent Dr,Bldg 30,Room 407, Bethesda, MD 20892 USA. EM hkleinman@dir.nidcr.nih.gov; margolil@mail.nih.gov FU Intramural NIH HHS NR 29 TC 100 Z9 107 U1 1 U2 11 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAR PY 2007 VL 25 IS 3 BP 553 EP 561 DI 10.1634/stemcells.2006-0419 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 145EC UT WOS:000244847100002 PM 17332514 ER PT J AU Terunuma, A Kapoor, V Yee, C Telford, WG Udey, MC Vogel, JC AF Terunuma, Atsushi Kapoor, Veena Yee, Carole Telford, William G. Udey, Mark C. Vogel, Jonathan C. TI Stem cell activity of human side population and alpha 6 integrin-bright keratinocytes defined by a quantitative in vivo assay SO STEM CELLS LA English DT Article DE xenotransplantation; tissue engineering; MHC class I genes; flow cytometry; nude mice ID MULTIDRUG-RESISTANCE GENE; LONG-TERM; TRANSGENE EXPRESSION; EPIDERMIS; VITRO; IDENTIFICATION; REPOPULATION; EPITHELIUM; PHENOTYPE; SELECTION AB The isolation and characterization of living human epithelial stem cells is difficult because distinguishing cell surface markers have not been identified with certainty. Side population keratinocytes (SP-KCs) that efflux Hoechst 33342 fluorescent dye, analogous to bone marrow-derived side population (SP) hematopoietic stem cells, have been identified in human skin, but their potential to function as keratinocyte stem cells (KSCs) in vivo is not known. On the other hand, human keratinocyte populations that express elevated levels of beta 1 and alpha 6 integrins and are distinct from SP-KCs, which express low levels of integrins, may be enriched for KSCs based on reported results of in vitro cell culture assays. When in vitro assays were used to measure total cell output of human SP-KCs and integrin-bright keratinocytes, we could not document their superior long-term proliferative activity versus unfractionated keratinocytes. To further assess the KSC characteristics in SP-KCs and integrin-bright keratinocytes, we used an in vivo competitive repopulation assay in which bioengineered human epidermis containing competing keratinocyte populations with different human major histocompatibility (MHC) class I antigens were grafted onto immunocompromised mice, and the intrinsic MHC class I antigens are used to quantify expansion of competing populations. In these in vivo studies, human SP-KCs showed little competitive expansion in vivo and were not enriched for KSCs. In contrast, keratinocytes expressing elevated levels of a6 integrin and low levels of CD71 (alpha 6-bright/CD71-dim) expanded over 200-fold during the 33-week in vivo study. These results definitively demonstrate that human alpha 6-bright/CD71-dim keratinocytes are enriched with KSCs, whereas SP-KCs are not. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Vogel, JC (reprint author), NCI, Dermatol Branch, NIH, Bldg 10-Room 12N260,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. EM jonvogel@mail.nih.gov FU Intramural NIH HHS NR 30 TC 43 Z9 51 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAR PY 2007 VL 25 IS 3 BP 664 EP 669 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 145EC UT WOS:000244847100014 PM 17332515 ER PT J AU Zhou, BY Ye, ZH Chen, GB Gao, ZGP Zhang, YA Cheng, LZ AF Zhou, Betty Ying Ye, Zhahui Chen, Guibin Gao, Zhigang Peter Zhang, Yu A. Cheng, Linzhao TI Inducible and reversible transgene expression in human stem cells after efficient and stable gene transfer SO STEM CELLS LA English DT Article DE human embryonic stem cells; human hematopoietic progenitor cells; gene transfer; lentiviral vectors; inducible gene expression ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; INACTIVATING LENTIVIRUS VECTOR; IN-VIVO; RNA INTERFERENCE; BETA-GLOBIN; THERAPY; ESTABLISHMENT; PROMOTERS; TRANSCRIPTION; TRANSMISSION AB We report here a lentiviral vector system for regulated transgene expression. We used the tetracycline repressor fused with a transcriptional suppression domain (tTS) to specifically suppress transgene expression. Human cells were first transduced with a tTS-expressing vector and subsequently transduced with a second lentiviral vector-containing transgene controlled by a regular promoter adjacent to a high-affinity tTS-binding site (tetO). After optimizing the location of the tetO site in the latter vector, we achieved a better inducible transgene expression than the previous lentiviral vectors using the tetracycline repressor systems. In this new system, the transgene transcription from a cellular promoter such as EF1 alpha or ubiquitin-C promoter is suppressed by the tTS bound to the nearby tetO site. In the presence of the tetracycline analog doxycycline (Dox), however, the tTS binding is released from the transgene vector and transcription from the promoter is restored. Thus, this system simply adds an extra level of regulation, suitable for any types of promoters (ubiquitous or cell-specific). We tested this tTSsuppressive, Dox-inducible system in 293T cells, human multipotent hematopoietic progenitor cells, and three human embryonic stem cell lines, using a dual-gene vector containing the green fluorescent protein reporter or a cellular gene. We observed a tight suppression in the uninduced state. However, the suppression is reversible, and transgene expression was restored at 5 ng/ml Dox. The lentiviral vectors containing the tTS-suppressive, Dox-inducible system offer a universal, inducible, and reversible transgene expression system in essentially any mammalian cell types, including human embryonic stem cells. C1 Johns Hopkins Univ, Sch Med, Stem Cell Program, Inst Cell Engn, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Grad Program Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA. Capital Univ Med Sci, Xuanwu Hosp, Beijing, Peoples R China. RP Cheng, LZ (reprint author), Johns Hopkins Univ, Sch Med, Stem Cell Program, Inst Cell Engn, Broadway Res Bldg,Room 747,733 N Broadway, Baltimore, MD 21205 USA. EM lcheng@welch.jhu.edu OI Ye, Zhaohui/0000-0001-5272-9168 FU NHLBI NIH HHS [HL 74781] NR 47 TC 45 Z9 50 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAR PY 2007 VL 25 IS 3 BP 779 EP 789 DI 10.1634/stemcells.2006-0128 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 145EC UT WOS:000244847100028 PM 17158240 ER PT J AU Timsit, YE Negishi, M AF Timsit, Yoav E. Negishi, Masahiko TI CAR and PXR: The xenobiotic-sensing receptors SO STEROIDS LA English DT Review DE constitutive androstane receptor; pregnane X receptor; estrogen receptor; glucocorticoid receptor; structure-function relationship; physiology ID PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; RAT HEPATOCYTE CULTURES; INDEPENDENT NUCLEAR TRANSLOCATION; THYROID-HORMONE METABOLISM; HUMAN ESTROGEN-RECEPTOR; EPIDERMAL-GROWTH-FACTOR; INHIBITORY CROSS-TALK; GLUCOCORTICOID-RECEPTOR; GENE-EXPRESSION AB The xenobiotic receptors CAR and PXR constitute two important members of the NR1I nuclear receptor family They function as sensors of toxic byproducts derived from endogenous metabolism and of exogenous chemicals, in order to enhance their elimination. This unique function of CAR and PXR sets them apart from the steroid hormone receptors. In contrast, the steroid receptors, exemplified by the estrogen receptor (ER) and glucocorticoid receptor (GR), are the sensors that tightly monitor and respond to changes in circulating steroid hormone levels to maintain body homeostasis. This divergence of the chemical-and steroid-sensing functions has evolved to ensure the fidelity of the steroid hormone endocrine regulation while allowing development of metabolic elimination pathways for xenobiotics. The development of the xenobiotic receptors CAR and PXR also reflect the increasing complexity of metabolism in higher organisms, which necessitate novel mechanisms for handling and eliminating metabolic by-products and foreign compounds from the body. The purpose of this review is to discuss similarities and differences between the xenobiotic receptors CAR and PXR with the prototypical steroid hormone receptors ER and GR. Interesting differences in structure explain in part the divergence in function and activation mechanisms of CAR/PXR from ER/GR. In addition, the physiological roles of CAR and PXR will be reviewed, with discussion of interactions of CAR and PXR with endocrine signaling pathways. (c) 2006 Elsevier Inc. All rights reserved. C1 NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU Intramural NIH HHS [Z01 ES071005-09, Z01 ES080040-22, Z99 ES999999] NR 121 TC 220 Z9 228 U1 0 U2 22 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 MAR PY 2007 VL 72 IS 3 BP 231 EP 246 DI 10.1016/j.steroids.2006.12.006 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 149OD UT WOS:000245155400001 PM 17284330 ER PT J AU Keskin, O Nussinov, R AF Keskin, Ozlem Nussinov, Ruth TI Similar binding sites and different partners: Implications to shared proteins in cellular pathways SO STRUCTURE LA English DT Article ID INTERACTION NETWORK; EVOLUTIONARY RATE; YEAST PROTEOME; COMPLEXES; INTERFACES; SEQUENCE; RESIDUES; ORGANIZATION; CONSERVATION; ALIGNMENT AB We studied a data set of structurally similar interfaces that bind to proteins with different binding-site structures and different functions. Our multipartner protein interface clusters enable us to address questions like: What makes a given site bind different proteins? How similar/different are the interactions? And, what drives the apparently less-specific association? We find that proteins with common binding-site motifs preferentially use conserved interactions at similar interface locations, despite the different partners. Helices are major vehicles for binding different partners, allowing alternate ways to achieve favorable association. The binding sites are characterized by imperfect packing, planar architectures, bridging water molecules, and, on average, smaller size. Interestingly, analysis of the connectivity of these proteins illustrates that they have more interactions with other proteins. These findings are important in predicting "date hubs," if we assume that "date hubs" are shared proteins with binding sites capable of transient binding to multipartners, linking higher-order networks. C1 Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Sariyer, Turkey. Coll Engn, Rumelifeneri Yolu, TR-34450 Sariyer, Turkey. NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Keskin, O (reprint author), Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Sariyer, Turkey. EM okeskin@ku.edu.tr; ruthn@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 50 TC 87 Z9 89 U1 2 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAR PY 2007 VL 15 IS 3 BP 341 EP 354 DI 10.1016/j.str.2007.01.007 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 155ZK UT WOS:000245617400010 PM 17355869 ER PT J AU Belle, SH Berk, PD Courcoulas, AP Flum, DR Miles, CW Mitchell, JE Pories, WJ Wolfe, BM Yanovski, SZ AF Belle, Steven H. Berk, Paul D. Courcoulas, Anita P. Flum, David R. Miles, Carolyn W. Mitchell, James E. Pories, Walter J. Wolfe, Bruce M. Yanovski, Susan Z. CA Longitudinal Assessment Bariatric TI Safety and efficacy of bariatric surgery: Longitudinal Assessment of Bariatric Surgery SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Bariatric surgery; Obesity ID Y GASTRIC BYPASS; VERTICAL BANDED GASTROPLASTY; CHRONIC KIDNEY-DISEASE; FATTY LIVER-DISEASE; WEIGHT-LOSS; MORBID-OBESITY; SLEEP-APNEA; IMPACT; RISK; OUTCOMES AB Background: Obesity is a leading health concern in the United States. Because traditional treatment approaches for weight loss are generally unsuccessful in the long term, bariatric surgical procedures are increasingly being performed to treat extreme obesity. To facilitate research in this field, the National Institute of Diabetes and Digestive and Kidney Diseases responded to this knowledge gap by establishing the Longitudinal Assessment of Bariatric Surgery (LABS) consortium. Methods: A competitive National Institute of Diabetes and Digestive and Kidney Diseases grant process resulted in the creation of a group of investigators with expertise in bariatric surgery, internal medicine, endocrinology, behavioral science, outcomes research, epidemiology, biostatistics, and other relevant fields. These investigators have worked closely to plan, develop, and conduct the LABS study. The LABS consortium protocol is a prospective, multicenter observational cohort study of consecutive patients undergoing bariatric surgery at 6 clinical centers. LABS includes an extensive database of information systematically collected preoperatively, at surgery, perioperatively during the 30-day postoperative period, and longer term. Results: The LABS study has been organized into 3 phases. LABS-1 will include all patients >= 18 years of age who have undergone bariatric surgery by LABS-certified surgeons with the goal to evaluate the short-term safety of bariatric surgery. LABS-2, a subset of approximately 2400 LABS-1 patients, will evaluate the relationship of patient and surgical characteristics to the longer term safety and efficacy of bariatric surgery. LABS-3 will involve a subset of LABS-2 subjects who will undergo detailed studies of mechanisms involved in weight change. The rationale, goals, and approach to study bariatric surgery are detailed in this report, along with a description of the outcomes, measures, and hypotheses used in LABS-1 and -2. Conclusion: The goal of the LABS consortium is to accelerate clinical research and understanding of extreme obesity and its complications by evaluating the risks and benefits of bariatric surgery. LABS investigators use standardized definitions, high-fidelity data collection, and validated instruments to enhance the ability of clinicians to provide meaningful evidence-based recommendations for patient evaluation, selection for surgery, and follow-up care. (Surg Obes Relat Dis 2007;3:116-126.) (C) 2007 American Society for Bariatric Surgery. All rights reserved. C1 [Belle, Steven H.] Univ Pittsburgh, Grad Sch Publ Hlth, Data Coordinating Ctr, Pittsburgh, PA USA. [Berk, Paul D.] Columbia Presbyterian Med Ctr, New York, NY 10032 USA. [Courcoulas, Anita P.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Flum, David R.] Univ Washington, Seattle, WA 98195 USA. [Miles, Carolyn W.; Yanovski, Susan Z.] NIDDK, Bethesda, MD USA. [Mitchell, James E.] Neuropsychiat Res Inst, Fargo, ND USA. [Pories, Walter J.] E Carolina Med Ctr, Greenville, NC USA. [Wolfe, Bruce M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Courcoulas, AP (reprint author), Minimally Invas Bariatr & Gen Surg, 3380 Blvd Allies,Suite 390, Pittsburgh, PA 15213 USA. EM courcoulasap@upmc.edu FU Ethicon Endosurgery (Johnson Johnson, Inc.) FX Dr. Courcoulas is a consultant for KCI, Inc., Stryker, U.S. Surgical, Inc. (Tyco Health), and GNC (General Nutrition Corporation)-paid consultant. Dr. Pories is a member of the speakers' bureau, a consultant for, and is a recipient of a research grant and meeting expenses reimbursement from Ethicon Endosurgery (Johnson & Johnson, Inc.), receives meeting expense reimbursement from U.S. Surgical, Inc. (Tyco Health, Inc.), and is the Chairman of the Board of Directors (of and receives meeting expense reimbursement from the Surgical Review Corporation. NR 55 TC 133 Z9 134 U1 5 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD MAR-APR PY 2007 VL 3 IS 2 BP 116 EP 126 DI 10.1016/j.soard.2007.01.006 PG 11 WC Surgery SC Surgery GA 375EO UT WOS:000261097100002 PM 17386392 ER PT J AU Xu, H Partilla, JS Wang, XY Rutherford, JM Tidgewell, K Prisinzano, TE Bohn, LM Rothman, RB AF Xu, Heng Partilla, John S. Wang, Xiaoying Rutherford, John M. Tidgewell, Kevin Prisinzano, Thomas E. Bohn, Laura M. Rothman, Richard B. TI A comparison of noninternalizing (Herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence SO SYNAPSE LA English DT Article DE DAMGO; herkinorin; tolerance; dependence; G proteins ID ADENYLYL-CYCLASE SUPERACTIVATION; MORPHINE-TOLERANCE; PEPTIDE RECEPTOR; NEUTRAL ANTAGONISTS; PHYSICAL-DEPENDENCE; BINDING-SITES; PROTEIN; DESENSITIZATION; RAT; HYPERALGESIA AB Previous studies established that Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO) and (2S,4aR,6aR,7R,9S,10aS,10bR)-9-(Benzoyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester (herkinorin) are fully efficacious mu-agonists. Herkinorin (HERK), unlike DAMGO, does not recruit beta-arrestin and promote mu-receptor internalization, even in cells that over express beta-arrestin. We hypothesized that chronic HERK and DAMGO treatment will differentially affect cellular markers of tolerance and dependence. CHO cells expressing the cloned human mu-receptor were treated for 20 h with 10 mu M DAMGO, HERK, morphine, or medium. Both DAMGO and HERK acted as full agonists in the [S-35]-GTP-gamma-S binding assay with E-MAX values of 230% and EC50 values of 12.8 and 92.5 nM, respectively. In the cAMP assay, DAMGO and HERK had similar EMAX values of similar to 80% and EC50 values of 3.23 and 48.7 nM, respectively. Chronic exposure to both drugs produced moderate tolerance to both drugs (similar to 2 to 5 fold) in the [S-35]GTP-gamma-S binding assay. In the cAMP assay, chronic DAMGO produced tolerance to both drugs (similar to 3 to 4 fold). Chronic HERK eliminated the ability of either drug to inhibit forskolin-stimulated cAMP accumulation. Chronic DAMGO increased, and chronic HERK decreased, forskolin-stimulated cAMP accumulation. Naloxone, after chronic HERK (but not DAMGO) induced a large increase in forskolin-stimulated cAMP accumulation. Viewed collectively with published data, the current data indicate that both internalizing and noninternalizing mu-agonists produce cellular signs of tolerance and dependence. C1 NIDA, Clin Psychopharmacol Sect, IRP, NIH,DHHS, Baltimore, MD 21224 USA. Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. Ohio State Univ, Coll Med & Publ Hlth, Dept Pharmacol, Columbus, OH 43210 USA. Ohio State Univ, Coll Med & Publ Hlth, Dept Psychiat, Columbus, OH 43210 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, IRP, NIH,DHHS, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rrothman@mail.nih.gov RI Bohn, Laura/A-4412-2008; Prisinzano, Thomas/B-7877-2010; Bohn, Laura/A-7483-2014 OI Bohn, Laura/0000-0002-6474-8179 FU Intramural NIH HHS; NIDA NIH HHS [R01 DA12970, R01 DA018151, R01 DA018151-01A2] NR 36 TC 35 Z9 35 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR PY 2007 VL 61 IS 3 BP 166 EP 175 DI 10.1002/syn.20356 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 125RA UT WOS:000243458700006 PM 17152090 ER PT J AU Phillips, JM Yamamoto, Y Negishi, M Maronpot, RR Goodman, JI AF Phillips, Jennifer M. Yamamoto, Yukio Negishi, Masahiko Maronpot, Robert R. Goodman, Jay I. TI Orphan nuclear receptor constitutive active/androstane receptor-mediated alterations in DNA methylation during phenobarbital promotion of liver tumorigenesis SO TOXICOLOGICAL SCIENCES LA English DT Article DE CAR; DNA methylation; mouse liver; phenobarbital; tumors ID PREGNANE X RECEPTOR; GC-RICH REGIONS; ANDROSTANE RECEPTOR; HUMAN CANCER; CPG ISLANDS; CAR; MOUSE; GENE; 5-METHYLCYTOSINE; TUMORS AB Altered DNA methylation is an epigenetic mechanism that plays a key role in the carcinogenesis process, and the nongenotoxic rodent hepatocarcinogen phenobarbital (PB) alters the methylation status of DNA in mouse liver. The constitutive active/androstane nuclear receptor (CAR) mediates half of the PB-induced hepatic gene expression changes and it is essential for liver tumor promotion in PB-treated mice. Here, a technique involving methylation-sensitive restriction digestion, arbitrarily primed PCR, and capillary electrophoresis was utilized to detect PB-induced regions of altered DNA methylation (RAMs) in CAR wildtype (WT) mice that are sensitive to promotion by PB and resistant CAR knockout (KO) mice. The CAR WT mice developed preneoplastic lesions after 23 weeks of PB treatment (precancerous) and liver tumors after 32 weeks, while the CAR KO mice did not develop tumors (Y. Yamamoto, et al., 2004, Cancer Res. 64, 7197-7200). Our goal was to discern those RAMs which are playing important roles in tumor formation by comparing the RAMs that form in sensitive and resistant groups of mice. Using this novel approach, 42 unique RAMs were identified in the precancerous as compared to the CAR KO, 23-week PB-treated tissue. Of these 42 RAMs, 14 carried forward to the tumor tissue, and additionally, 104 total unique RAMs were observed in the tumor tissue. These results indicate that there are unique RAMs occurring in the sensitive CAR WT mice and that a portion of these are seen in both the precancerous and tumor tissue. We hypothesize that these unique RAMs may be facilitating the tumorigenesis process, and these data support the view that DNA methylation plays a causative role in PB-induced tumorigenesis. C1 Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA. Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Goodman, JI (reprint author), Michigan State Univ, Dept Pharmacol & Toxicol, B-440 Life Sci Bldg, E Lansing, MI 48824 USA. EM goodman3@msu.edu FU NIEHS NIH HHS [T32-ES-7255] NR 49 TC 29 Z9 33 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 MAR PY 2007 VL 96 IS 1 BP 72 EP 82 DI 10.1093/toxsci/kfl188 PG 11 WC Toxicology SC Toxicology GA 136ZP UT WOS:000244262900009 PM 17172636 ER PT J AU Kaminski, RM Blaszczak, P Dekundy, A Parada-Turska, J Calderazzo, L Cavalheiro, EA Turski, WA AF Kaminski, Rafal M. Blaszczak, Piotr Dekundy, Andrzej Parada-Turska, Jolanta Calderazzo, Lineu Cavalheiro, Esper A. Turski, Waldemar A. TI Lithium-methomyl induced seizures in rats: A new model of status epilepticus? SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE methomyl; lithium; seizures; EEG; neurodegeneration; rats ID ANTICHOLINESTERASE-TREATED MICE; PILOCARPINE MODEL; ADULT RATS; SIGNAL-TRANSDUCTION; BRAIN-DAMAGE; EPILEPSY; DRUGS; ANTAGONISTS; IMMATURE; STRESS AB Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithium pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality. (c) 2006 Elsevier Inc. All rights reserved. C1 Inst Agr Med, Dept Toxicol, PL-20950 Lublin, Poland. Med Univ, Dept Rheumatol & Connect Tissue Dis, PL-20090 Lublin, Poland. Escola Paulista Med, Lab Expt Neurol, Dept Neurol & Neurosurg, BR-04023 Sao Paulo, Brazil. Med Univ, Dept Expt & Clin Pharmacol, PL-20090 Lublin, Poland. RP Kaminski, RM (reprint author), NINDS, NIH, 35 Convent Dr,MSC 3702,Bldg 35,Rm 1C1000, Bethesda, MD 20892 USA. EM kaminskr@mail.nih.gov NR 41 TC 1 Z9 1 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR PY 2007 VL 219 IS 2-3 BP 122 EP 127 DI 10.1016/j.taap.2006.09.017 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 145VF UT WOS:000244893200005 PM 17092527 ER PT J AU Drecktrah, D Knodler, LA Howe, D Steele-Mortimer, O AF Drecktrah, Dan Knodler, Leigh A. Howe, Dale Steele-Mortimer, Olivia TI Salmonella trafficking is defined by continuous dynamic interactions with the endolysosomal system SO TRAFFIC LA English DT Article DE acidification; confocal; Coxiella; endosome; lysosome; microtubules; phagosome; SCV; type III secretion; V-ATPase ID III SECRETION SYSTEM; LYSOSOMAL MEMBRANE-GLYCOPROTEINS; TYPHIMURIUM-CONTAINING VACUOLES; PATHOGENICITY ISLAND 2; ENTERICA SEROVAR TYPHIMURIUM; HAMSTER OVARY CELLS; COXIELLA-BURNETII; EPITHELIAL-CELLS; HOST-CELLS; LEISHMANIA-AMAZONENSIS AB Following invasion of non-phagocytic host cells, Salmonella enterica survives and replicates within a phagosome-like compartment known as the Salmonella-containing vacuole (SCV). It is now well established that SCV biogenesis, like phagosome biogenesis, involves sequential interactions with the endocytic pathway. However, Salmonella is believed to limit these interactions and, in particular, to avoid fusion of terminal lysosomes with the SCV. In this study, we reassessed this process using a high-resolution live-cell imaging approach and found an unanticipated level of interaction between the SCV and the endocytic pathway. Direct interactions, in which late endosomal/lysosomal content was transferred to SCVs, were detected within 30 min of invasion and continued for several hours. Mechanistically, these interactions were very similar to phagosome-lysosome fusion because they were accompanied by rapid acidification of the SCV, could be blocked by chemical perturbation of microtubules or vacuolar acidification and involved the small GTPase Rab7. In comparison with vacuoles containing internalized Escherichia coli or heat-killed Salmonella, SCVs did show some delay of fusion and acidification, although, this appeared to be independent of either type III secretion system. These results provide compelling evidence that inhibition of SCV-lysosome fusion is not the major determinant in establishment of the Salmonella replicative niche in epithelial cells. C1 NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Steele-Mortimer, O (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM omortimer@niaid.nih.gov NR 69 TC 87 Z9 88 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 MAR PY 2007 VL 8 IS 3 BP 212 EP 225 DI 10.1111/j.1600-0854.2006.00529.x PG 14 WC Cell Biology SC Cell Biology GA 134WY UT WOS:000244116300004 PM 17233756 ER PT J AU Sullivan, MT Cotten, R Read, EJ Wallace, EL AF Sullivan, Marian T. Cotten, Russell Read, Elizabeth J. Wallace, Edward L. TI Blood collection and transfusion in the United States in 2001 SO TRANSFUSION LA English DT Article ID COMPONENTS AB BACKGROUND: Collection, processing, and transfusion of blood and blood components in the United States in 2001 were measured and compared with prior years. STUDY DESIGN AND METHODS: The survey was completed by 1443 blood centers and hospitals. Statistical procedures were used to verity the representativeness of the sample and to estimate national totals. RESULTS: The total US blood supply in 2001 was 15,320,000 units (before testing), 10.4 percent greater than in 1999. It included 14,259,000 allogeneic units, 619,000 autologous units, and 273,000 red cell (RBC) units collected by apheresis. Transfusion of whole blood (WB) and RBCs increased by 12.2 percent to 13,898,000 units. Platelet (PLT) transfusions totaled 10,196,000 units, an increase of 12.6 percent in comparison with 1999. The use of single-donor apheresis PLTs increased by 26.0 percent to 7,582,000 PLT concentrate equivalent units. The use of PLTs from WB (PLT concentrates) continued a downtrend, declining 13.9 percent to 2,614,000. CONCLUSIONS: The margin between transfusion demand and the total allogeneic supply in 2001 was 1,162,000 units, 7.9 percent of supply. By comparison, the 1999 margin was 9.1 percent. The rate of blood collection per 1,000 donor-eligible population in 2001 was 8.9 percent higher than in 1999, due largely to additional donations following the September terrorist attacks. During the same period, however, the rate of transfusion per 1,000 total US population increased by 9.9 percent to 50.0 units, the highest in 15 years of measurement. The steady increase in demand continues to challenge the US blood community. C1 NIH, Natl Blood Data Resource Ctr, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Ctr Management Syst, Naples, Italy. RP Sullivan, MT (reprint author), Res Triangle Int, 6110 Execut Blvs,Suite 905, Rockville, MD 20852 USA. EM msullivan@rti.org NR 10 TC 115 Z9 121 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 2007 VL 47 IS 3 BP 385 EP 394 DI 10.1111/j.1537-2995.2007.01128.x PG 10 WC Hematology SC Hematology GA 145LJ UT WOS:000244866300008 PM 17319817 ER PT J AU Sverdlov, AV Csuros, M Rogozin, IB Koonin, EV AF Sverdlov, Alexander V. Csuros, Miklos Rogozin, Igor B. Koonin, Eugene V. TI A glimpse of a putative pre-intron phase of eukaryotic evolution SO TRENDS IN GENETICS LA English DT Article ID SPLICEOSOMAL INTRONS; GENES; CONSERVATION; PIECES; ORIGIN; GAIN AB Comparison of the exon-intron structures of ancient eukaryotic paralogs reveals the absence of conserved intron positions in these genes. This is in contrast to the conservation of intron positions in orthologous genes from even the most evolutionarily distant eukaryotes and in more recent paralogs. The lack of conserved intron positions in ancient paralogs probably reflects the origination of these genes during the earliest phase of eukaryotic evolution, which was characterized by concomitant invasion of genes by group II self-splicing elements (which were to become introns in the future) and extensive duplication of genes. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Montreal, Dept Comp Sci & Operat Res, Montreal, PQ H3C 3J7, Canada. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 21 TC 13 Z9 14 U1 0 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAR PY 2007 VL 23 IS 3 BP 105 EP 108 DI 10.1016/j.tig.2007.01.001 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 147JW UT WOS:000245000300002 PM 17239982 ER PT J AU Guan, RJ Mariuzza, RA AF Guan, Rongjin Mariuzza, Roy A. TI Peptidoglycan recognition proteins of the innate immune system SO TRENDS IN MICROBIOLOGY LA English DT Review ID GRAM-POSITIVE BACTERIA; L-ALANINE AMIDASE; DROSOPHILA-IMD-PATHWAY; PATTERN-RECOGNITION; CRYSTAL-STRUCTURE; PGRP-LC; ANGSTROM RESOLUTION; STRUCTURAL BASIS; I-ALPHA; RECEPTOR AB Peptidoglycan (PGN) is the major component of bacterial cell walls and one of the main microbial products recognized by the innate immune system. PGN recognition is mediated by several families of pattern recognition molecules, including Toll-like receptors, nucleotide-binding oligomerization domain-containing proteins, and peptidoglycan recognition proteins (PGRPs). However, only the interaction of PGN with PGRPs, which are highly conserved from insects to mammals, has so far been characterized at the molecular level. Here, we describe recent structural studies of PGRPs that reveal the basis for PGN recognition and provide insights into the signal transduction and antibacterial activities of these innate immune proteins. C1 Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, WM Keck Lab Struct Biol, Rockville, MD 20850 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mariuzza, RA (reprint author), Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, WM Keck Lab Struct Biol, Rockville, MD 20850 USA. EM mariuzza@carb.nist.gov NR 64 TC 59 Z9 69 U1 4 U2 21 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAR PY 2007 VL 15 IS 3 BP 127 EP 134 DI 10.1016/j.tim.2007.01.006 PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 153WA UT WOS:000245465700006 PM 17275309 ER PT J AU Scheschonka, A Tang, ZS Betz, H AF Scheschonka, Astrid Tang, Zhongshu Betz, Heinrich TI Sumoylation in neurons: nuclear and synaptic roles? SO TRENDS IN NEUROSCIENCES LA English DT Review ID METABOTROPIC GLUTAMATE RECEPTORS; MEF2 TRANSCRIPTION FACTORS; SUMO-BINDING MOTIF; FILAMIN-A; UBIQUITIN; PROTEINS; DIFFERENTIATION; IDENTIFICATION; INTERACTS; MODIFIER AB Sumoylation is a post-translational modification that was originally thought to only target nuclear proteins. Evidence has emerged, however, that the role of sumoylation is much more diverse: three plasma membrane proteins belonging to different protein families (glucose transporters, K+ channels and metabotropic glutamate receptors) have been shown to be sumoylated. In addition, sumoylation of transcription factors, such as myocyte enhancer factor 2 (MEF2), was found to regulate synapse formation., A major role of sumoylation in other systems is to modify protein-protein interactions, and because protein interactions are particularly elaborate in the nervous system and crucial for synapse formation and function, sumoylation could constitute a major regulatory mechanism in neurons. In this review, we evaluate the available data and discuss possible roles for sumoylation in the regulation of crucial neurobiological processes, such as neuronal development and synaptic transmission. C1 Max Planck Inst Brain Res, Dept Neurochem, D-60528 Frankfurt, Germany. RP Scheschonka, A (reprint author), NEI, NIH, 35 Lincoln Dr,MSC 3731, Bethesda, MD 20892 USA. EM scheschonka@mpih-frankfurt.mpg.de; neurochemie@mpih-frankfurt.mpg.de NR 52 TC 37 Z9 38 U1 1 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 2007 VL 30 IS 3 BP 85 EP 91 DI 10.1016/j.tins.2007.01.003 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 149SK UT WOS:000245166700001 PM 17241677 ER PT J AU Plenz, D Thiagarajan, TC AF Plenz, Dietmar Thiagarajan, Tara C. TI The organizing principles of neuronal avalanches: cell assemblies in the cortex? SO TRENDS IN NEUROSCIENCES LA English DT Review ID EPILEPTIFORM ACTIVITY; NEOCORTICAL SLICE; ACTIVITY PATTERNS; NETWORKS; OSCILLATIONS; CRITICALITY; SYNCHRONIZATION; PROPAGATION; ORGANIZATION; HIPPOCAMPUS AB Neuronal avalanches are spatiotemporal patterns of neuronal activity that occur spontaneously in superficial layers of the mammalian cortex under various experimental conditions. These patterns reflect fast propagation of local synchrony, display a rich spatiotemporal diversity and recur over several hours. The statistical organization of pattern sizes is invariant to the choice of spatial scale, demonstrating that the functional linking of cortical sites into avalanches occurs on all spatial scales with a fractal organization. These features suggest an underlying network of neuronal interactions that balances diverse representations with predictable recurrence, similar to what has been theorized for cell assembly formation. We propose that avalanches reflect the transient formation of cell assemblies in the cortex and discuss various models that provide mechanistic insights into the underlying dynamics, suggesting that they arise in a critical regime. C1 Natl Inst Mental Hlth, Porter Neurosci Res Ctr, Sect Neural Network Physiol, Bethesda, MD 20892 USA. RP Plenz, D (reprint author), Natl Inst Mental Hlth, Porter Neurosci Res Ctr, Sect Neural Network Physiol, Bldg 35 Room 3A-100,35 Convent Dr, Bethesda, MD 20892 USA. EM plenzd@mail.nih.gov FU Intramural NIH HHS NR 60 TC 187 Z9 189 U1 2 U2 16 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 2007 VL 30 IS 3 BP 101 EP 110 DI 10.1016/j.tins.2007.01.005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 149SK UT WOS:000245166700003 PM 17275102 ER PT J AU Jacobson, KA Gao, ZG Liang, BT AF Jacobson, Kenneth A. Gao, Zhan-Guo Liang, Bruce T. TI Neoceptors: reengineering GPCRs to recognize tailored ligands SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID A(2A) ADENOSINE RECEPTOR; ACTIVATION; INFLAMMATION; AGONISTS; SITE; REPERFUSION; MUTAGENESIS; PROTECTION; BINDING; INJURY AB Efforts to model and reengineer the putative binding sites of G-protein-coupled receptors (GPCRs) have led to an approach that combines small-molecule 'classical' medicinal chemistry and gene therapy. In this approach, complementary structural changes (e.g. based on novel ionic or H-bonds) are made in the receptor and ligand for the selective enhancement of affinity. Thus, a modified receptor (neoceptor) is designed for activation by tailor-made agonists that do not interact with the native receptor. The neoceptor is no longer activated by the native agonist, but rather functions as a scaffold for the docking of novel small molecules (neoligands). In theory, the approach could verify the accuracy of GPCR molecular modeling, the investigation of signaling, the design of small molecules to rescue disease-related mutations, and small-molecule-directed gene therapy. The neoceptor-neoligand pairing could offer spatial specificity by delivering the neoceptor to a target site, and temporal specificity by administering neolligand when needed. C1 NIDDK, Mol Recognit Sect, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, Farmington, CT 06030 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031115-24] NR 40 TC 20 Z9 20 U1 1 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAR PY 2007 VL 28 IS 3 BP 111 EP 116 DI 10.1016/j.tips.2007.01.006 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 150YG UT WOS:000245254900003 PM 17280720 ER PT J AU Kalueff, AV Ren-Patterson, RF Murphy, DL AF Kalueff, Allan V. Ren-Patterson, Renee F. Murphy, Dennis L. TI The developing use of heterozygous mutant mouse models in brain monoamine transporter research SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID SEROTONIN-TRANSPORTER; KNOCKOUT MICE; 5-HT TRANSPORTER; PLACE PREFERENCE; COCAINE REWARD; GENE; ANXIETY; DOPAMINE; BEHAVIOR; DISORDERS AB 5-Hydroxytryptamine (5-HT), dopamine and norepinephrine are important monoamine neurotransmitters implicated in multiple brain mechanisms and regulated by high-affinity transmembrane monoamine transporters. Although knockout mice lacking 5-HT, dopamine or norepinephrine transporters are widely used to assess brain monoamine processes, these models have several methodological limitations. There is mounting evidence that heterozygous mutant mice with reduced (but not abolished) monoamine transporter functions could provide models with greater relevance to the genetics of human disorders, which only rarely involve complete loss-of-function mutations. Here, we discuss why heterozygous mouse models, in addition to knockout mice, might be useful for brain monoamine transporter research. C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, Bldg 10,Room 3D41,10 Ctr Dr,1264, Bethesda, MD 20892 USA. EM kalueva@mail.nih.gov FU Intramural NIH HHS NR 39 TC 35 Z9 37 U1 1 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAR PY 2007 VL 28 IS 3 BP 122 EP 127 DI 10.1016/j.tips.2007.01.002 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 150YG UT WOS:000245254900005 PM 17275930 ER PT J AU Lemiale, F Haddada, H Nabel, GJ Brough, DE King, CR Gall, JGD AF Lemiale, Franck Haddada, Hedi Nabel, Gary J. Brough, Douglas E. King, C. Richter Gall, Jason G. D. TI Novel adenovirus vaccine vectors based on the enteric-tropic serotype 41 SO VACCINE LA English DT Article DE adenovirus; vaccine vector; human immunodeficiency virus ID REPLICATION-DEFECTIVE ADENOVIRUS; IN-VIVO; GENE DELIVERY; VIRUS; DNA; IMMUNOGENICITY; TYPE-41; IMMUNITY; PROTEIN; SYSTEM AB Replication-defective adenovirus vectors, primarily developed from serotype 5 (Ad5) viruses, have been widely used for gene transfer and vaccination approaches. Vectors based on other serotypes of adenovirus could be used in conjunction with, or in place of, Ad5 vectors. In this study, Ad41, an enteric adenovirus usually described as 'non-cultivable' or 'fastidious,' has been successfully cloned, rescued and propagated on 293-ORF6 cells. The complementation capabilities of this cell line allow generation of Ad41 vectors at titers comparable to those obtained for Ad5 vectors. Mice immunized with an Ad41 vector containing an HIV envelope (Env) gene mounted anti-Env cellular and humoral immune responses. Ad41-Env vectors appear to be particularly attractive when used in heterologous prime-boost regimens, where they induce significantly higher cellular immune responses to HIV-Env than Ad5-based regimens. Ad41-based constructs are attractive vaccine vectors alone or in combination with Ad5 adenovectors, since each vector type can provide circumvention of pre-existing immunity to the other. (c) 2006 Elsevier Ltd. All rights reserved. C1 GenVec Inc, Gaithersburg, MD 20878 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Gall, JGD (reprint author), GenVec Inc, 65 W Watkins Mill Rd, Gaithersburg, MD 20878 USA. EM jgall@genvec.com FU Intramural NIH HHS [Z99 AI999999] NR 52 TC 39 Z9 45 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 1 PY 2007 VL 25 IS 11 BP 2074 EP 2084 DI 10.1016/j.vaccine.2006.11.025 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 146PZ UT WOS:000244948100017 PM 17250935 ER PT J AU Zaharoff, DA Rogers, CJ Hance, KW Schlom, J Greiner, JW AF Zaharoff, David A. Rogers, Connie J. Hance, Kenneth W. Schlom, Jeffrey Greiner, John W. TI Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination SO VACCINE LA English DT Article DE adjuvant; depot; vaccination ID ADSORBED VACCINES; INTRANASAL IMMUNIZATION; DEACETYLATED CHITIN; ITCHING NODULES; ADJUVANTS; ALUMINUM; MICE; OIL; HYPERSENSITIVITY; STIMULATION AB The development of safe, novel adjuvants is necessary to maximize the efficacy of new and/or available vaccines. Chitosan is a non-toxic, biocompatible, biodegradable, natural polysaccharide derived from the exoskeletons of crustaceans and insects. Chitosan's biodegradability, immunological activity and high viscosity make it an excellent candidate as a depot/adjuvant for parenteral vaccination. To this end, we explored chitosan solution as an adjuvant for subcutaneous vaccination of mice with a model protein antigen. We found that chitosan enhanced antigen-specific antibody titers over five-fold and antigen-specific splenic CD4(+) proliferation over six-fold. Strong increases in antibody titers together with robust delayed-type hypersensitivity (DTH) responses revealed that chitosan induced both Immoral and cell-mediated immune responses. When compared with traditional vaccine adjuvants, chitosan was equipotent to incomplete Freund's adjuvant (IFA) and superior to aluminum hydroxide. Mechanistic studies revealed that chitosan exhibited at least two characteristics that may allow it to function as an immune adjuvant. First, the viscous chitosan solution created an antigen depot. More specifically, less than 9% of a protein antigen, when delivered in saline, remained at the injection site after 8 h. However, more than 60% of a protein antigen delivered in chitosan remained at the injection site for 7 days. Second, chitosan induced a transient 67% cellular expansion in draining lymph nodes. The expansion peaked between 14 and 21 days after chitosan injection and diminished as the polysaccharide was degraded. These mechanistic studies, taken together with the enhancement of a vaccine response, demonstrate that chitosan is a promising and safe platform for parenteral vaccine delivery. Published by Elsevier Ltd. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Greiner, JW (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM jg117s@nih.gov OI Zaharoff, David/0000-0001-6885-6727 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010426-06] NR 46 TC 134 Z9 143 U1 3 U2 26 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 MAR 1 PY 2007 VL 25 IS 11 BP 2085 EP 2094 DI 10.1016/j.vaccine.2006.11.034 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 146PZ UT WOS:000244948100018 PM 17258843 ER PT J AU Hazra, R Jankelevich, S Mackall, CL Avila, NA Wolters, P Civitello, L Christensen, B Jacobsen, F Steinberg, SM Yarchoan, R AF Hazra, Rohan Jankelevich, Shirley Mackall, Crystal L. Avila, Nilo A. Wolters, Pamela Civitello, Lucy Christensen, Barbara Jacobsen, Freda Steinberg, Seth M. Yarchoan, Robert TI Immunologic, virologic, and neuropsychologic responses in human immunodeficiency virus-infected children receiving their first highly active antiretroviral therapy regimen SO VIRAL IMMUNOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; HIV-1-INFECTED CHILDREN; IMMUNE RECONSTITUTION; T-CELLS; COMBINATION THERAPY; 1-INFECTED CHILDREN; HIV-INFECTION; THYMIC VOLUME; DISEASE; ZIDOVUDINE AB Our objective was to measure the early dynamics, evolution, and durability over 96 wk of immunologic responses in children receiving their first highly active antiretroviral therapy (HAART) regimen. The study was designed as a prospective, single-arm study. Twelve human immunodeficiency virus (HIV)-infected children (median age, 11.8 yr) were enrolled. All subjects received stavudine, nevirapine, and ritonavir. Serial measurements included HIV viral load, lymphocyte subsets, thymic volume by computed tomography (CT), neurocognitive testing, and brain CT. Baseline median CD4(+) T cell count was 589 cells/mm(3), viral load was 3.9. log(10) HIV RNA copies/mL, and thymic volume was 16.3 cm(3). Ten children had an undetectable viral load at week 48. Eight maintained an undetectable viral load at 96 wk. The median increase in absolute CD4(+) T cell count was 225 cells/mm(3) by week 48, and 307 cells/mm(3) by week 96. The median increase in naive (CD45RA(+)CD62L(+)) CD4(+) T cells was 133 cells/mm(3) by week 48, and 147 cells/mm(3) by week 96. The median number of naive CD8(+) T cells increased from 205 to 284 cells/mm3 by week 24; this increase was sustained to week 96. The number of B cells increased and was associated with a decrease in immunoglobulin levels. The number of natural killer cells was stable. There were no significant changes in thymic volume. Most children exhibited stable cognitive function over the course of the study. We conclude that, in this cohort of relatively immunocompetent HIV-infected children, an initial HAART regimen was associated with rapid and sustained increases in total CD4(+) T cells, in naive CD4(+) and CD8(+) T cells, and in B cells through 96 wk. C1 NCI, HIV & AIDS Malignancy Branch, Bethesda, MD USA. NCI, Pediat Oncol Branch, Bethesda, MD USA. NIH, Clin Ctr Diagnost Radiol Dept, Bethesda, MD USA. Med Illness Counseling Ctr, Chevy Chase, MD USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Hazra, R (reprint author), 10 Ctr Dr,MSC 1868, Bethesda, MD 20892 USA. EM hazrar@mail.nih.gov FU Intramural NIH HHS NR 38 TC 2 Z9 3 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PD SPR PY 2007 VL 20 IS 1 BP 131 EP 141 DI 10.1089/vim.2006.0079 PG 11 WC Immunology; Virology SC Immunology; Virology GA 157HU UT WOS:000245710300013 PM 17425427 ER PT J AU Tang, SX Ablan, S Dueck, M Ayala-Lopez, W Soto, B Caplan, M Nagashima, K Hewlett, IK Freed, EO Levin, JG AF Tang, Shixing Ablan, Sherimay Dueck, Megan Ayala-Lopez, Wilfredo Soto, Brenda Caplan, Margaret Nagashima, Kunio Hewlett, Indira K. Freed, Eric O. Levin, Judith G. TI A second-site suppressor significantly improves the defective phenotype impolsed by mutation of an aromatic residue in the N-terminal domain of the HIV-1 capsid protein SO VIROLOGY LA English DT Article DE HIV-1 capsid protein; second-site suppressors; HIV-1 viral cores; dominant-negative inhibition; HIV-1 assembly; structural models; reverse transcriptase; transmission electron microscopy ID HUMAN-IMMUNODEFICIENCY-VIRUS; ROUS-SARCOMA-VIRUS; FUSION INHIBITOR T-20; WILD-TYPE VIRUS; IN-VITRO; GAG PROTEINS; TYPE-1 GAG; 3-DIMENSIONAL STRUCTURE; REVERSE-TRANSCRIPTASE; VIRION MORPHOGENESIS AB The HIV-1 capsid (CA) protein plays an important role in virus assembly and infectivity. Previously, we showed that Ala substitutions in the N-terminal residues Trp23 and Phe40 cause a severely defective phenotype. In searching for mutations at these positions that result in a non-lethal phenotype, we identified one candidate, W23F. Mutant virions contained aberrant cores, but unlike W23A, also displayed some infectivity in a single-round replication assay and delayed replication kinetics in MT-4 cells. Following long-term passage in MT-4 cells, two second-site mutations were isolated. In particular, the W23F/V261 mutation partially restored the wild-type phenotype, including production of particles with conical cores and wild-type replication kinetics in MT-4 cells. A structural model is proposed to explain the suppressor phenotype. These findings describe a novel occurrence, namely suppression of a mutation in a hydrophobic residue that is critical for maintaining the structural integrity of CA and proper core assembly. Published by Elsevier Inc. C1 NICHHD, Mol Genet Lab, Viral Gene Regulat Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Image Anal Lab, Frederick, MD 21702 USA. RP Levin, JG (reprint author), NICHHD, Mol Genet Lab, Viral Gene Regulat Sect, NIH, Bldg 6B,Room 216, Bethesda, MD 20892 USA. EM levinju@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NICHD NIH HHS [Z01 HD000069-33] NR 68 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 1 PY 2007 VL 359 IS 1 BP 105 EP 115 DI 10.1016/j.virol.2006.09.027 PG 11 WC Virology SC Virology GA 143PT UT WOS:000244735700012 PM 17055023 ER PT J AU Charity, JC Katz, E Moss, B AF Charity, James C. Katz, Ehud Moss, Bernard TI Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin SO VIROLOGY LA English DT Article DE poxvirus; drug-resistant mutants; rifampicin ID GENE; POXVIRUS; POLYPEPTIDE; ENVELOPES; MUTATIONS; STAGE AB D13 protein trimers, which form an external lattice providing curvature to the membrane of vaccinia virus immature virions, are the target of the drug rifampicin. We obtained 63 rifampicin-resistant mutants following random PCR mutagenesis of the D13L gene and 5 that arose spontaneously. Sequencing indicated that 26 mutants contained a single, unique, amino acid substitution whereas others contained 2 or more. The single mutations, including 6 previously identified, mapped to 24 different amino acids that were distributed over the length of the protein with the majority clustered between amino acids 17 to 33, 222 to 243 and 480 to 488. Two or three different substitutions occurred in six of the 24 amino acids. Representative mutant viruses of each cluster replicated to wild-type levels in the absence of rifampicin and nearly two logs higher than wild-type in the presence of drug. The large number and fitness of the mutations are remarkable in view of the extreme sequence conservation (99-100% amino acid identity amongst all orthopoxviruses). Clustering of mutations could suggest the presence of a rifampicin-bin ding pocket comprised of discontinuous regions of D13. Published by Elsevier Inc. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS; NIAID NIH HHS [Z01 AI000539-18] NR 17 TC 14 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 1 PY 2007 VL 359 IS 1 BP 227 EP 232 DI 10.1016/j.virol.2006.09.031 PG 6 WC Virology SC Virology GA 143PT UT WOS:000244735700025 PM 17055024 ER PT J AU Chin, S Popat, V Boyne, MS Cochran, C Tulloch-Reid, M AF Chin, S. Popat, V. Boyne, M. S. Cochran, C. Tulloch-Reid, M. TI Insulinoma induced hypoglycaemia in a Jamaican patient SO WEST INDIAN MEDICAL JOURNAL LA English DT Article ID PREOPERATIVE LOCALIZATION; STIMULATION; CALCIUM AB Herein reported is the case of a young woman who had hyperinsulinaemic hypoglycaemia which was biochemically consistent with an insulinoma. Initial imaging was negative and definitive treatment was delayed until repeat imaging localized the tumour several years later This case demonstrates the importance of clinical judgment and biochemical testing in the diagnosis of insulinoma despite negative imaging. C1 Univ Hosp W Indies, Dept Med, Kingston 7, Jamaica. NICHHD, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ W Indies, Res Inst Trop Med, Kingston 7, Jamaica. RP Chin, S (reprint author), Univ W Indies, Dept Med, Kingston 7, Jamaica. EM swardchin@yahoo.com RI Tulloch-Reid, Marshall/E-4383-2012; Boyne, Michael/I-2242-2013 OI Boyne, Michael/0000-0002-5227-2492 FU Intramural NIH HHS NR 15 TC 2 Z9 2 U1 0 U2 0 PU UNIV WEST INDIES FACULTY MEDICAL SCIENCES PI KINGSTON PA MONA CAMPUS, KINGSTON 7, JAMAICA SN 0043-3144 J9 W INDIAN MED J JI West Ind. Med. J. PD MAR PY 2007 VL 56 IS 2 BP 182 EP 186 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 202ML UT WOS:000248905700015 PM 17910152 ER PT J AU Lee, J Choi, Y Lee, PC Kang, S Bok, J Cho, J AF Lee, Jaecheon Choi, Yunjaie Lee, Peter-Changwhan Kang, Seungha Bok, Jinduck Cho, Jaiesoon TI Recombinant production of Penicillium oxalicum PJ3 phytase in Pichia Pastoris SO WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE Penicillium oxalicum; phytase; phytate; Pichia pastoris; recombinant ID GLYCOSYLATION; PURIFICATION; EXPRESSION; FUNGI AB The 1,332 bp phytase gene of Penicillium oxalicum PJ3 was inserted into the expression vector, pPICZ alpha A and expressed in the methylotrophic yeast, Pichia pastoris as an active, extracellular phytase. The recombinant phytase reached a maximum yield of 12 U/ml of medium at 120 h of cultivation after methanol induction under shake-flask conditions. The enzyme was glycosylated, with a molecular mass of about 62.5 kDa. The Michaelis constant (K (m)) and maximum reaction rate (V (max)) for sodium phytate was 0.37 mM and 526.3 U/mg of protein, respectively. The optimal activity occurred at pH 4.5 and 55 degrees C. C1 NIEHS, Insoitol Signaling Grp, LST, NIH,DHSS, Res Triangle Pk, NC 27709 USA. Seoul Natl Univ, Sch Agr Biotechnol, Coll Agr & Life Sci, Seoul 151742, South Korea. Choong Ang Biotech Co Ltd, Ansan, South Korea. RP Cho, J (reprint author), NIEHS, Insoitol Signaling Grp, LST, NIH,DHSS, Res Triangle Pk, NC 27709 USA. EM cho3@niehs.nih.gov NR 18 TC 13 Z9 15 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0959-3993 J9 WORLD J MICROB BIOT JI World J. Microbiol. Biotechnol. PD MAR PY 2007 VL 23 IS 3 BP 443 EP 446 DI 10.1007/s11274-006-9236-z PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 137WK UT WOS:000244323200019 ER PT J AU Arany, PR Sato, M Shomolo, S Roberts, AB AF Arany, Praveen R. Sato, Misako Shomolo, Shawheen Roberts, Anita B. TI Healing wound as a tumor microenvironment niche SO WOUND REPAIR AND REGENERATION LA English DT Meeting Abstract C1 NIH, NCI, LCRC, Bethesda, MD 20892 USA. Harvard Dent Sch, BSDM, Boston, MA USA. NR 0 TC 6 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2007 VL 15 IS 2 MA 31 BP A22 EP A22 PG 1 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 143RM UT WOS:000244741900047 ER PT J AU Chigurupati, S Arumugam, TV Jameel, S Mughal, MR Mattson, MP Poosala, S AF Chigurupati, Srinivasulu Arumugam, Tiruma V. Jameel, Shafaq Mughal, Mohamed R. Mattson, Mark P. Poosala, Suresh TI Impaired notch signaling significantly delays wound healing SO WOUND REPAIR AND REGENERATION LA English DT Meeting Abstract C1 Natl Inst Aging Intramural Res Program, Comparat Med Sect, Baltimore, MD 21224 USA. Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD USA. RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012 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 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2007 VL 15 IS 2 MA 106 BP A43 EP A43 PG 1 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 143RM UT WOS:000244741900122 ER PT J AU Patel, AA Gupta, D Seligson, D Hattab, EM Balis, UJ Ulbright, TM Kohane, IS Berman, JJ Gilbertson, JR Dry, S Schirripa, O Yu, H Becich, MJ Parwani, AV AF Patel, Ashokkumar A. Gupta, Dilipkumar Seligson, David Hattab, Eyas M. Balis, Ulysses J. Ulbright, Thomas M. Kohane, Isaac S. Berman, Jules J. Gilbertson, John R. Dry, Sarah Schirripa, Osvaldo Yu, Hong Becich, Michael J. Parwani, Anil V. CA Shared Pathology Informatics TI Availability and quality of paraffin blocks identified in pathology archives: A multi-institutional study by the Shared Pathology Informatics Network (SPIN) SO BMC CANCER LA English DT Article ID CANCER TISSUE RESOURCE; PROSTATE-CANCER; CAPSURE; LESSONS; BANK AB Background: Shared Pathology Informatics Network (SPIN) is a tissue resource initiative that utilizes clinical reports of the vast amount of paraffin-embedded tissues routinely stored by medical centers. SPIN has an informatics component (sending tissue-related queries to multiple institutions via the internet) and a service component (providing histopathologically annotated tissue specimens for medical research). This paper examines if tissue blocks, identified by localized computer searches at participating institutions, can be retrieved in adequate quantity and quality to support medical researchers. Methods: Four centers evaluated pathology reports (1990-2005) for common and rare tumors to determine the percentage of cases where suitable tissue blocks with tumor were available. Each site generated a list of 100 common tumor cases (25 cases each of breast adenocarcinoma, colonic adenocarcinoma, lung squamous carcinoma, and prostate adenocarcinoma) and 100 rare tumor cases (25 cases each of adrenal cortical carcinoma, gastro-intestinal stromal tumor [ GIST], adenoid cystic carcinoma, and mycosis fungoides) using a combination of Tumor Registry, laboratory information system (LIS) and/or SPIN-related tools. Pathologists identified the slides/blocks with tumor and noted first 3 slides with largest tumor and availability of the corresponding block. Results: Common tumors cases (n = 400), the institutional retrieval rates (all blocks) were 83% (A), 95% (B), 80% (C), and 98% (D). Retrieval rate (tumor blocks) from all centers for common tumors was 73% with mean largest tumor size of 1.49 cm; retrieval (tumor blocks) was highest-lung (84%) and lowest-prostate (54%). Rare tumors cases (n = 400), each institution's retrieval rates (all blocks) were 78% (A), 73% (B), 67% (C), and 84% (D). Retrieval rate (tumor blocks) from all centers for rare tumors was 66% with mean largest tumor size of 1.56 cm; retrieval (tumor blocks) was highest for GIST (72%) and lowest for adenoid cystic carcinoma (58%). Conclusion: Assessment shows availability and quality of archival tissue blocks that are retrievable and associated electronic data that can be of value for researchers. This study serves to compliment the data from which uniform use of the SPIN query tools by all four centers will be measured to assure and highlight the usefulness of archival material for obtaining tumor tissues for research. C1 Univ Pittsburgh, Dept Pathol, Ctr Pathol Informat, Benedum Oncol Informat Ctr, Pittsburgh, PA 15260 USA. Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. Indiana Univ, Dept Pathol, Indianapolis, IN 46204 USA. Harvard Univ, Dept Pathol, Boston, MA 02115 USA. NCI, Canc Diag Program, NIH, Bethesda, MD 20892 USA. RP Patel, AA (reprint author), Univ Pittsburgh, Dept Pathol, Ctr Pathol Informat, Benedum Oncol Informat Ctr, Pittsburgh, PA 15260 USA. EM patelaa@upmc.edu; dkgupta10@hotmail.com; dseligson@mednet.ucla.edu; ehattab@iupui.edu; ulysses@umich.edu; tulbrigh@iupui.edu; isaac_kohane@harvard.edu; jjberman@alum.mit.edu; jgi@alum.mit.edu; sdry@mednet.ucla.edu; oschirripa@mednet.ucla.edu; hyu@mednet.ucla.edu; becich@pitt.edu; parwaniav@upmc.edu RI Kohane, Isaac Kohane/K-3716-2012; Hattab, Eyas/E-9342-2016; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Hattab, Eyas/0000-0002-3660-6261; parwani, anil/0000-0002-7616-1666 FU NCI NIH HHS [U01CA091429, P30 CA016042, U01 CA091343, U01 CA091429, U01CA091343, UO1CA91338-01] NR 26 TC 11 Z9 11 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD FEB 28 PY 2007 VL 7 AR 37 DI 10.1186/1471-2407-7-37 PG 14 WC Oncology SC Oncology GA 144EP UT WOS:000244779100001 PM 17386082 ER PT J AU Bierut, LJ Cubells, JF Iacono, WG Li, MD Madden, PAF Nelson, EC Pollock, JD Swan, GE Vanyukov, M AF Bierut, Laura Jean Cubells, Joseph F. Iacono, William G. Li, Ming D. Madden, Pamela A. F. Nelson, Elliot C. Pollock, Jonathan D. Swan, Gary E. Vanyukov, Michael TI Genetic research and smoking behavior SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID NICOTINE DEPENDENCE C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. Univ Virginia, Dept Psychiat, Charlottesville, VA USA. NIDA, Div Basic Neurosci & Behav Res, Bethesda, MD 20892 USA. SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA. Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA. RP Bierut, LJ (reprint author), Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. EM gary.swan@sri.com RI Pollock, Jonathan/B-1554-2009 NR 6 TC 13 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 28 PY 2007 VL 297 IS 8 BP 809 EP 809 DI 10.1001/jama.297.8.809 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 140DS UT WOS:000244485000019 PM 17327520 ER PT J AU Ade, KK Lovinger, DM AF Ade, Kristen K. Lovinger, David M. TI Anandamide regulates postnatal development of long-term synaptic plasticity in the rat dorsolateral striatum SO JOURNAL OF NEUROSCIENCE LA English DT Article DE endocannabinoid; basal ganglia; long-term depression; LTD; long-term potentiation; LTP; glutamate; development ID CANNABINOID RECEPTOR; ENDOCANNABINOID RELEASE; CORTICOSTRIATAL SYNAPSES; DORSAL STRIATUM; IN-VITRO; DEPRESSION; NEURONS; INACTIVATION; POTENTIATION; NEOSTRIATUM AB Long-term changes in synaptic efficacy produced by high-frequency stimulation (HFS) of glutamatergic afferents to the rat dorsolateral striatum exhibit heterogeneity during early stages of postnatal development. Whereas HFS most often induces striatal long-term potentiation (LTP) in rats postnatal day 12 (P12)-P14, the same stimulation tends to induce long-term depression (LTD) at ages P16-P34. Previous studies have shown that striatal LTD induction depends on retrograde endocannabinoid signaling and activation of the CB1 cannabinoid receptor. It is also known that levels of one of the primary endogenous CB1 receptor agonists, anandamide (AEA), increases during development in whole-brain samples. In the present study, we sought to determine whether this developmental increase in AEA also takes place in striatal tissue and whether increased AEA levels contribute to the postnatal switch in the response to HFS. We observed a pronounced increase in striatal levels of AEA, but not the other major endogenous cannabinoid 2-arachidonoylglycerol (2-AG), during the postnatal period characterized by the switch from LTP to LTD. Furthermore, application of synthetic AEA during HFS in field recordings of slices from P12-P14 rats allowed for induction of LTD whereas blocking the CB1 receptor during HFS in animals P16-P34 resulted in expression of LTP. However, blocking 2-AG synthesis with the DAG-lipase inhibitor tetrahydrolipstatin did not alter HFS-induced striatal LTD. In addition, synaptic depression produced by a synthetic CB1 agonist was similar across development. Together, these findings suggest that the robust developmental increase in striatal AEA may be the key factor in the emergence of HFS-induced striatal LTD. C1 NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,TS-13, Bethesda, MD 20892 USA. NR 48 TC 43 Z9 45 U1 0 U2 2 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 FEB 28 PY 2007 VL 27 IS 9 BP 2403 EP 2409 DI 10.1523/JNEUROSCI.2916-06.2007 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 143XA UT WOS:000244758500029 PM 17329438 ER PT J AU Altamura, M Elvevag, B Blasi, G Bertolino, A Callicott, JH Weinberger, DR Mattay, VS Goldberg, TE AF Altamura, Mario Elvevag, Brita Blasi, Giuseppe Bertolino, Alessandro Callicott, Joseph H. Weinberger, Daniel R. Mattay, Venkata S. Goldberg, Terry E. TI Dissociating the effects of Sternberg working memory demands in prefrontal cortex SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE functional magnetic resonance imaging; load; maintenance; healthy adults ID EVENT-RELATED FMRI; POSITRON-EMISSION-TOMOGRAPHY; AGE-RELATED-CHANGES; FUNCTIONAL MRI; SUSTAINED ACTIVITY; BRAIN ACTIVATION; NEURAL SYSTEMS; MAINTENANCE; TASK; LOAD AB Earlier neuroimaging studies of working memory (WM) have demonstrated that dorsolateral prefrontal cortex (DLPFC) activity increases as maintenance and load demand increases. However, few studies have carefully disambiguated these two WM processes at the behavioral and physiological levels. The objective of the present functional resonance imaging (fMRI) study was to map within prefrontal cortex locales that are selectively load sensitive, delay sensitive, or both. We studied 18 right-handed normal subjects with fMRI at 3 Tesla during a block design version of the Sternberg task. WM load was manipulated by varying the memory set size (3, 5, or 8 letters). The effect of memory maintenance was examined by employing two time delays (I s and 6 s) between the letter set and probe stimuli. The DLPFC was strongly activated in load manipulation, whereas activation as a function of delay was restricted to the left premotor regions and Broca's areas. Moreover, regions of prefrontal cortex on the right (BA 46) were found to be exclusively affected by load. These results suggest the possibility that top-down modulation of attention or cognitive control at encoding and/or decisionmaking may be mediated by these areas. Published by Elsevier Ireland Ltd. C1 Univ Foggia, Dept Biomed Sci, Psychiat Unit, Foggia, Italy. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Univ Bari, Dept Neurol & Psychiat, I-70121 Bari, Italy. IRCCSS Casa Sollievo Sofferenza, Dept Neuroradiol, San Giovanni Rotondo, Italy. RP Altamura, M (reprint author), Univ Foggia, Dept Biomed Sci, Psychiat Unit, Foggia, Italy. EM m_altamura@virgilio.it RI Callicott, Joseph/C-9102-2009 OI Callicott, Joseph/0000-0003-1298-3334 NR 53 TC 34 Z9 34 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD FEB 28 PY 2007 VL 154 IS 2 BP 103 EP 114 DI 10.1016/j.pscychresns.2006.08.002 PG 12 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 148FQ UT WOS:000245060400001 PM 17292590 ER PT J AU Lusa, L McShane, LM Radmacher, MD Shih, JH Wright, GW Simon, R AF Lusa, Lara McShane, Lisa M. Radmacher, Michael D. Shih, Joanna H. Wright, George W. Simon, Richard TI Appropriateness of some resampling-based inference procedures for assessing performance of prognostic classifiers derived from microarray data SO STATISTICS IN MEDICINE LA English DT Article DE cross-validation; microarray; gene-expression; classification; resampling; molecular profiling ID GENE-EXPRESSION PROFILES; ACUTE MYELOID-LEUKEMIA; B-CELL LYMPHOMA; BREAST-CANCER; OUTCOME PREDICTION; CROSS-VALIDATION; SURVIVAL; CLASSIFICATION; SIGNATURE; BOOTSTRAP AB The goal of many gene-expression microarray profiling clinical, studies is to develop a multivariate classifier to predict patient disease outcome from a gene-expression profile measured on some biological specimen from the patient. Often some preliminary validation of the predictive power of a profile-based classifier is carried out using the same data set that was used to derive the classifier. Techniques such as cross-validation or bootstrapping can be used in this setting to assess predictive power, and if applied correctly, can result in a less biased estimate of predictive accuracy of a classifier. However, some investigators have attempted to apply standard statistical inference procedures to assess the statistical significance of associations between true and cross-validated predicted outcomes. We demonstrate in this paper that naive application of standard statistical inference procedures to these measures of association under null situations can result in greatly inflated testing type I error rates. Under alternatives of small to moderate associations, confidence interval coverage probabilities may be too low, although for very large associations coverage probabilities approach their intended values. Our results suggest that caution should be exercised in interpreting some of the claims of exceptional prognostic classifier performance that have been reported in prominent biomedical journals in the past few years. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA. Ist Nazl Studio & Cura Tumori, Dept Expt Oncol, I-20133 Milan, Italy. IFOM, Mol Genet Canc Grp, Fdn Ist FIRC Oncol Mol, Milan, Italy. RP McShane, LM (reprint author), NCI, Biometr Res Branch, EPN 8126,6130 Execut Blvd, Bethesda, MD 20892 USA. EM lara.lusa@ifom-ieo-campus.it; Lm5h@nih.gov; radmacher.2@osu.edu; jshih@mail.nih.gov; wrightge@mail.nih.gov; rsimon@mail.nih.gov RI Lusa, Lara/C-6692-2015 OI Lusa, Lara/0000-0002-8981-2421 NR 26 TC 8 Z9 8 U1 0 U2 1 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 FEB 28 PY 2007 VL 26 IS 5 BP 1102 EP 1113 DI 10.1002/sim.2598 PG 12 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 139HE UT WOS:000244422100012 PM 16755534 ER PT J AU Blaney, JE Sathe, NS Hanson, CT Firestone, CY Murphy, BR Whitehead, SS AF Blaney, Joseph E., Jr. Sathe, Neeraj S. Hanson, Christopher T. Firestone, Cai Yen Murphy, Brian R. Whitehead, Stephen S. TI Vaccine candidates for dengue virus type 1 (DEN1) generated by replacement of the structural genes of rDEN4 and rDEN4 Delta 30 with those of DEN1 SO VIROLOGY JOURNAL LA English DT Article ID RHESUS-MONKEYS; HUMAN VOLUNTEERS; LIVE; IMMUNOGENICITY; RECOMBINANT; SAFETY; FEVER; MICE; ENCEPHALITIS; REPLICATION AB Background: Antigenic chimeric viruses have previously been generated in which the structural genes of recombinant dengue virus type 4 (rDEN4) have been replaced with those derived from DEN2 or DEN3. Two vaccine candidates were identified, rDEN2/4 Delta 30(ME) and rDEN3/4 Delta 30(ME), which contain the membrane (M) precursor and envelope (E) genes of DEN2 and DEN3, respectively, and a 30 nucleotide deletion (Delta 30) in the 3' untranslated region of the DEN4 backbone. Based on the promising preclinical phenotypes of these viruses and the safety and immunogenicity of rDEN2/4 Delta 30(ME) in humans, we now describe the generation of a panel of four antigenic chimeric DEN4 viruses using either the capsid (C), M, and E (CME) or ME structural genes of DENI Puerto Rico/94 strain. Results: Four antigenic chimeric viruses were generated and found to replicate efficiently in Vero cells: rDENI/4(CME), rDENI/4 Delta 30(CME), rDENI/4(ME), and rDENI/4 Delta 30(ME). With the exception of rDENI/4(ME), each chimeric virus was significantly attenuated in a SCID- HuH-7 mouse xenograft model with a 25-fold or greater reduction in replication compared to wild type DENI. In rhesus monkeys, only chimeric viruses with the Delta 30 mutation appeared to be attenuated as measured by duration and magnitude of viremia. rDENI/4 Delta 30(CME) appeared over- attenuated since it failed to induce detectable neutralizing antibody and did not confer protection from wild type DENI challenge. In contrast, rDENI/4 Delta 30(ME) induced 66% seroconversion and protection from DENI challenge. Presence of the Delta 30 mutation conferred a significant restriction in mosquito infectivity upon rDENI/4 Delta 30(ME) which was shown to be non- infectious for Aedes aegypti fed an infectious bloodmeal. Conclusion: The attenuation phenotype in SCID-HuH-7 mice, rhesus monkeys, and mosquitoes and the protective immunity observed in rhesus monkeys suggest that rDENI/4 Delta 30(ME) should be considered for evaluation in a clinical trial. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Blaney, JE (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM jblaney@niaid.nih.gov; sathen@niaid.nih.gov; chanson@niaid.nih.gov; cfirestone@niaid.nih.gov; bmurphy@niaid.nih.gov; swhitehead@niaid.nih.gov NR 33 TC 23 Z9 23 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD FEB 28 PY 2007 VL 4 AR 23 DI 10.1186/1743-422-4-23 PG 11 WC Virology SC Virology GA 182PW UT WOS:000247517500001 PM 17328799 ER PT J AU Klarmann, GJ Eisenhauer, BM Zhang, Y Gotte, M Pata, JD Chatterjee, DK Hecht, SM Le Grice, SFJ AF Klarmann, George J. Eisenhauer, Brian M. Zhang, Yi Gotte, Matthias Pata, Janice D. Chatterjee, Deb K. Hecht, Sidney M. Le Grice, Stuart F. J. TI Investigating the "steric gate" of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase by targeted insertion of unnatural amino acids SO BIOCHEMISTRY LA English DT Article ID DNA-POLYMERASE-I; CRYSTAL-STRUCTURE; NUCLEOTIDE INCORPORATION; ANGSTROM RESOLUTION; PROTEIN-STRUCTURE; ESCHERICHIA-COLI; PRIMER TERMINUS; MINOR-GROOVE; ACTIVE-SITE; REPLICATION AB To investigate how structural changes in the amino acid side chain affect nucleotide substrate selection in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), a variety of non-natural tyrosine analogues were substituted for Tyr115 of p66 RT. RT variants containing meta-Tyr, nor-Tyr, aminomethyl-Phe, and 1- and 2-naphthyl-Tyr were produced in an Escherichia coli coupled transcription/translation system. Mutant p66 subunits were reconstituted with wild-type (WT) p51 RT and purified by affinity chromatography. Each modified enzyme retained DNA polymerase activity following this procedure. Aminomethyl-Phe115 RT incorporated dCTP more efficiently than the WT and was resistant to the chain terminator (-)-beta-2',3'- dideoxy-3'-thiacytidine triphosphate (3TCTP) when examined in a steady-state fidelity assay. However, 2-naphthyl-Tyr115 RT inefficiently incorporated dCTP at low concentrations and was kinetically slower with all dCTP analogues tested. Models of RT containing these side chains suggest that the aminomethyl-Phe115 substitution provides new hydrogen bonds through the minor groove to the incoming dNTP and the template residue of the terminal base pair. These hydrogen bonds likely contribute to the increased efficiency of dCTP incorporation. In contrast, models of HIV-1 RT containing 2-naphthyl-Tyr115 reveal significant steric clashes with Pro157 of the p66 palm subdomain, necessitating rearrangement of the active site. C1 Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD 21702 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. Univ Virginia, Dept Biol, Charlottesville, VA 22904 USA. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. SUNY Albany, Div Mol Med, Wadsworth Ctr, Albany, NY 12201 USA. SAIC Frederick Inc, Prot Express Lab, Frederick, MD 21702 USA. RP Le Grice, SFJ (reprint author), Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM slegrice@ncifcrf.gov OI Pata, Janice/0000-0001-5999-5442 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 39 TC 6 Z9 6 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 27 PY 2007 VL 46 IS 8 BP 2118 EP 2126 DI 10.1021/bi061772w PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 136TX UT WOS:000244248100007 PM 17274599 ER PT J AU Schneeweiss, S Setoguchi, S Brookhart, A Dormuth, C Wang, PS AF Schneeweiss, Sebastian Setoguchi, Soko Brookhart, Alan Dormuth, Colin Wang, Philip S. TI Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Article ID INSTRUMENTAL VARIABLES; PROPENSITY SCORE; TERM; THERAPEUTICS; TOLERABILITY; CONFOUNDERS; DEMENTIA; EFFICACY; TRIALS; AGENTS AB Background: Public health advisories have warned that the use of atypical antipsychotic medications increases the risk of death among elderly patients. We assessed the short-term mortality in a population-based cohort of elderly people in British Columbia who were prescribed conventional and atypical antipsychotic medications. Methods: We used linked health care utilization data of all BC residents to identify a cohort of people aged 65 years and older who began taking antipsychotic medications between January 1996 and December 2004 and were free of cancer. We compared the 180-day all-cause mortality between residents taking conventional antipsychotic medications and those taking atypical antipsychotic medications. Results: Of 37 241 elderly people in the study cohort, 12 882 were prescribed a conventional antipsychotic medication and 24 359 an atypical formulation. Within the first 180 days of use, 1822 patients (14.1%) in the conventional drug group died, compared with 2337 (9.6%) in the atypical drug group (mortality ratio 1.47, 95% confidence interval [CI] 1.39-1.56). Multi-variable adjustment resulted in a 180-day mortality ratio of 1.32 (1.23-1.42). In comparison with risperidone, haloperidol was associated with the greatest increase in mortality (mortality ratio 2.14, 95% CI 1.86-2.45) and loxapine the lowest (mortality ratio 1.29, 95% CI 1.19-1.40). The greatest increase in mortality occurred among people taking higher (above median) doses of conventional antipsychotic medications (mortality ratio 1.67, 95% CI 1.50-1.86) and during the first 40 days after the start of drug therapy (mortality ratio 1.60, 95% CI 1.42-1.80). Results were confirmed in propensity score analyses and instrumental variable estimation, minimizing residual confounding. Interpretation: Among elderly patients, the risk of death associated with conventional antipsychotic medications is comparable to and possibly greater than the risk of death associated with atypical antipsychotic medications. Until further evidence is available, physicians should consider all antipsychotic medications to be equally risky in elderly patients. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Pharmacoepidemiol & Pharmacoecon, Dept Med, Boston, MA 02125 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ British Columbia, Dept Anesthesia Pharmacol & Therapeut, Vancouver, BC V5Z 1M9, Canada. NIMH, Dv Serv & Intervent Res, Bethesda, MD 20892 USA. RP Schneeweiss, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Pharmacoepidemiol & Pharmacoecon, Dept Med, 1620 Tremont St, Boston, MA 02125 USA. EM schneeweiss@post.harvard.edu RI Schneeweiss, Sebastian/C-2125-2013; OI Dormuth, Colin/0000-0001-8577-8783 FU NIA NIH HHS [R01 AG021950, R01-AG021950]; PHS HHS [29020050016I] NR 35 TC 187 Z9 189 U1 0 U2 8 PU CMA MEDIA INC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD FEB 27 PY 2007 VL 176 IS 5 BP 627 EP 632 DI 10.1503/cmaj.061250 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 136LQ UT WOS:000244224800013 PM 17325327 ER PT J AU Lloyd-Jones, DM Liu, K Colangelo, LA Yan, LL Klein, L Loria, CM Lewis, CE Savage, P AF Lloyd-Jones, Donald M. Liu, Kiang Colangelo, Laura A. Yan, Lijing L. Klein, Liviu Loria, Catherine M. Lewis, Cora E. Savage, Peter TI Consistently stable or decreased body mass index in young adulthood and longitudinal changes in metabolic syndrome components - The coronary artery risk development in young adults study SO CIRCULATION LA English DT Article DE diabetes mellitus; metabolism; obesity; prevention; risk factors ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; MIDDLE-AGED MEN; CARDIOVASCULAR-DISEASE; HEART-DISEASE; US ADULTS; MEDICARE COSTS; FACTOR PROFILE; OLDER AGE; ALL-CAUSE AB Background - Data are sparse regarding the association of stable body mass index (BMI) over the long term with metabolic syndrome components in young adults. Methods and Results - Participants in the Coronary Artery Risk Development in Young Adults Study, including white and black adults 18 to 30 years of age at the initial examination in 1985 to 1986, were stratified into groups by baseline BMI and change in BMI (stable/decreased, increased > 2 kg/m(2), or fluctuating) across all 6 examinations between years 0 and 15 of the study. Changes in metabolic syndrome components were compared between groups. Among 1358 men and 1321 women, 16.3% maintained a stable BMI, 73.9% had an increased BMI, and 9.8% had a fluctuating BMI. Over 15 years, participants with stable BMI had essentially unchanged levels of metabolic syndrome components, regardless of baseline BMI, whereas those with increased BMI had progressively worsening levels. For example, men with a baseline BMI of 20.0 to 24.9 kg/m(2) and stable BMI during follow-up had a mean increase of only 15 mg/dL in fasting triglycerides over 15 years compared with 65 mg/dL (P < 0.001) in those whose BMI increased. Incidence of metabolic syndrome at year 15 was lower in the stable BMI group (2.2%) compared with the increased BMI group (18.8%; P < 0.001). Conclusions - Adverse progression of metabolic syndrome components with advancing age may not be inevitable. Young adults who maintained stable BMI over time had minimal progression of risk factors and lower incidence of metabolic syndrome regardless of baseline BMI. Greater public health efforts should be aimed at long-term weight stabilization. C1 Northwestern Univ, Feineberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Peking Univ, Guanghua Sch Management, Dept Hlth Econ & Management, Beijing, Peoples R China. NHLBI, Bethesda, MD 20892 USA. Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Feineberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Ste 1102, Chicago, IL 60611 USA. EM dlj@northwestern.edu RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-48049] NR 39 TC 74 Z9 76 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP 1004 EP 1011 DI 10.1161/CIRCULATIONAHA.106.648642 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200012 PM 17283263 ER PT J AU Allison, MA Manson, J Langer, R Carr, JJ Rossouw, J Cochrane, B Eaton, C Greenland, P Hendrix, S Hsia, J Hunt, J Jackson, R Johnson, K Kuller, L Phillips, L Robinson, J AF Allison, Matthew A. Manson, JoAnn Langer, Robert Carr, J. Jeffrey Rossouw, Jacques Cochrane, Barbara Eaton, Charles Greenland, Philip Hendrix, Susan Hsia, Judith Hunt, Julie Jackson, Rebecca Johnson, Karen Kuller, Lewis Phillips, Lawrence Robinson, Jennifer TI History of oophorectomy is associated with higher risk of subclinical coronary artery disease in women with hysterectomy SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Harvard Univ, Boston, MA 02115 USA. Geisinger Hlth Syst, Danville, PA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NHLBI, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Mem Hosp Rhode Isl, Pawtucket, RI USA. Northwestern Univ, Chicago, IL 60611 USA. Wayne State Univ, Detroit, MI USA. George Washington Univ, Washington, DC USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Tennessee, Memphis, TN USA. Univ Pittsburgh, Pittsburgh, PA USA. Emory Univ, Atlanta, GA 30322 USA. Univ Iowa, Iowa City, IA USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E283 EP E283 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200346 ER PT J AU Belin, RJ Psaty, BM Manolio, TA Newman, AB Heckbert, SR Lloyd-Jones, DM AF Belin, Rashad J. Psaty, Bruce M. Manolio, Teri A. Newman, Anne B. Heckbert, Susan R. Lloyd-Jones, Donald M. TI Impact of subclinical CVD and inflammation on the occurrence of CVD events and mortality in elderly subjects with incident atrial fibrillation within the cardiovascular health study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Northwestern Univ, Chicago, IL 60611 USA. Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. RI Lloyd-Jones, Donald/C-5899-2009; Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E272 EP E272 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200292 ER PT J AU Carr, JJ Person, S Sidney, S Evans, G Colangelo, L Jacobs, D Liu, KA Lewis, CE Schreiner, P Loria, C Wei, G Hulley, S Williams, OD AF Carr, John J. Person, Sharina Sidney, Stephen Evans, Gregory Colangelo, Laura Jacobs, David Liu, Kiang Lewis, Cora E. Schreiner, Pamela Loria, Catherine Wei, Gina Hulley, Stephan Williams, O. D. TI Coronary artery calcified plaque in individuals 38 to 50 years old and cardiovascular risk factors measured 5 years earlier: The coronary artery risk development in young adults (CARDIA) study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Alabama, Birmingham, AL USA. Kaiser Permanente, Oakland, CA USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Minnesota, Minneapolis, MN USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E217 EP E217 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200033 ER PT J AU Chu, AY Astor, BC Coresh, J Berthier-Schaad, Y Smith, MW Shuldiner, AR Kao, WHL AF Chu, Audrey Y. Astor, Brad C. Coresh, Josef Berthier-Schaad, Yvette Smith, Michael W. Shuldiner, Alan R. Kao, W. H. Linda TI Association of apolipoprotein e e4 polymorphism with age: The third national health and nutrition examination survey genetic study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Natl Canc Inst, Lab Genom Diversity & Bas Rsch Program, SAIC Frederick, Frederick, MD USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RI Smith, Michael/B-5341-2012 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E295 EP E295 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200401 ER PT J AU Colangelo, L Liu, KA Daviglus, ML Loria, C Sidney, S AF Colangelo, Laura Liu, Kiang Daviglus, Martha L. Loria, Catherine Sidney, Steve TI Risk factors for hypertension in lean and overweight/obese individuals: The CARDIA study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Northwestern Univ, Chicago, IL 60611 USA. NIH, NHLBI, Bethesda, MD 20892 USA. Kaiser Permanente, Oakland, CA 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E255 EP E255 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200210 ER PT J AU Daviglus, ML Liu, K Van Horn, L Colangelo, L Schreiner, PJ Lewis, CE Gross, M Loria, C AF Daviglus, Martha L. Liu, Kiang Van Horn, Linda Colangelo, Laura Schreiner, Pamela J. Lewis, Cora E. Gross, Myron Loria, Catherine TI Healthy lifestyle in young adulthood and markers of inflammation in middle age: The coronary artery risk development in young adults (CARDIA) study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Northwestern Univ, Chicago, IL 60611 USA. Univ Minnesota, Minneapolis, MN USA. Univ Alabama, Birmingham, AL USA. 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E222 EP E222 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200055 ER PT J AU Fornage, M Carr, JJ Jacobs, DR Loria, CM Steffen, LM Williams, OD AF Fornage, Myriam Carr, Jeffrey J. Jacobs, David R. Loria, Catherine M. Steffen, Lyn M. Williams, O. Dale TI Association of alox15 gene polymorphisms with prevalence and progression of coronary artery calcification: The CARDIA study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 Univ Texas, Houston, TX USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Minnesota, Minneapolis, MN USA. NIH, NHLBI, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E295 EP E296 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200403 ER PT J AU Fox, CS Heard-Costa, N Cupples, LA Dupuis, J Vasan, RS Atwood, LD AF Fox, Caroline S. Heard-Costa, Nancy Cupples, L. Adrienne Dupuis, Josee Vasan, Ramachandran S. Atwood, Larry D. TI Genome-wide association with adiposity-related traits: The Framingham heart study 100K project SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E241 EP E241 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200144 ER PT J AU Fox, CS Hwang, SJ Massaro, JM Pou, KM Larson, MG Hoffmann, U O'Donnell, CJ AF Fox, Caroline S. Hwang, Shih-Jen Massaro, Joseph M. Pou, Karla M. Larson, Martin G. Hoffmann, Udo O'Donnell, Christopher J. TI Subcutaneous and visceral adipose tissue and their association with coronary and aortic artery calcification: The Framingham heart study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E241 EP E241 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200143 ER PT J AU Godreau, A Liu, K Daviglus, ML Colangelo, L Loria, C Greenland, P AF Godreau, Ayleen Liu, Kiang Daviglus, Martha L. Colangelo, Laura Loria, Catherine Greenland, Philip TI Cross-sectional association of fasting glucose levels with coronary artery calcium: The coronary artery risk development in youth adults (CARDIA) study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 Northwestern Univ, Chicago, IL 60611 USA. NHLBI, 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E286 EP E286 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200359 ER PT J AU Gu, D Rice, T He, J Jaquish, CE Hixson, JE Gu, CC Yang, W Yao, Z Liu, D Rao, DC AF Gu, Dongfeng Rice, Treva He, Jiang Jaquish, Cashell E. Hixson, James E. Gu, C. C. Yang, Wenjie Yao, Zhijian Liu, Depei Rao, D. C. TI Heritability of blood pressure responses to low and high dietary sodium intervention in the GenSalt study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 Chinese Acad Med Sci, Beijing 100037, Peoples R China. Washington Univ, St Louis, MO USA. Tulane Univ, New Orleans, LA 70118 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Chinese Natl Human Genome Ctr, Beijing, Peoples R China. RI Rice, Treva/D-1385-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E223 EP E223 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200059 ER PT J AU He, JA Gu, DF Jaquish, CE Rao, DC Hixson, JE Chen, CS Gu, CC Liu, D Whelton, PK AF He, Jiang Gu, Dongfeng Jaquish, Cashell E. Rao, D. C. Hixson, James E. Chen, Chung-Shiuan Gu, C. C. Liu, Depei Whelton, Paul K. TI Gender difference in blood pressure responses to low and high dietary sodium intervention in the GenSalt study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Tulane Univ, New Orleans, LA 70118 USA. Chinese Acad Med Sci, Beijing 100037, Peoples R China. NIH, NHLBI, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. Univ Texas, Hlth Sci Ctr, Houston, TX 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E254 EP E254 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200207 ER PT J AU Hwang, SJ Yang, Q Larson, MG Benjamin, EJ Vasan, RS Meigs, JB Parikh, NI O'Donnell, CJ Levy, D Fox, CS AF Hwang, Shih-Jen Yang, Qiong Larson, Martin G. Benjamin, Emelia J. Vasan, Ramachandran S. Meigs, James B. Parikh, Nisha I. O'Donnell, Christopher J. Levy, Daniel Fox, Caroline S. TI Genome-wide association with renal function traits in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RI Yang, Qiong/G-5438-2014 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E223 EP E223 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200061 ER PT J AU Lewis, CE Loria, C Person, SD Iribarren, C Kiefe, CI Jacobs, DR Carr, JJ AF Lewis, Cora E. Loria, Catherine Person, Sharina D. Iribarren, Carlos Kiefe, Catarina I. Jacobs, David R. Carr, J. J. TI 20-Year weight change patterns, obesity, and subclinical CVD in young adults: CARDIA SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Univ Alabama, Birmingham, AL USA. NHLBI, Bethesda, MD 20892 USA. Kaiser Permanente, Oakland, CA USA. Univ Minnesota, Minneapolis, MN USA. Wake Forest Univ, Winston Salem, NC 27109 USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E220 EP E221 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200048 ER PT J AU Liu, K Loria, C Daviglus, M Colangelo, L Carnethon, M Savage, P AF Liu, Kiang Loria, Catherine Daviglus, Martha Colangelo, Laura Carnethon, Mercedes Savage, Peter TI Metabolic syndrome (MetS) in young adulthood and incident diabetes in middle age: The coronary artery risk development in young adults (CARDIA) study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 Northwestern Univ, Sch Med, Chicago, IL USA. NHLBI, Natl Inst Hlth, 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E215 EP E215 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200024 ER PT J AU Loria, C Liu, K Colangelo, L Lloyd-Jones, D Daviglus, M Savage, P Lewis, CE AF Loria, Catherine Liu, Kiang Colangelo, Laura Lloyd-Jones, Donald Daviglus, Martha Savage, Peter Lewis, Cora E. TI Initial body mass index in young adults predicts 20-year risk of incident diabetes: The coronary artery risk development in young adults (CARDIA) study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 NHLBI, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Alabama, Birmingham, AL USA. RI Lloyd-Jones, Donald/C-5899-2009 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E215 EP E216 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200027 ER PT J AU North, KE Franceschini, N Chung, J Baird, L Avery, C Freedman, BI Kraja, AT Arnett, D Miller, MB Pankow, JS Lewis, CE Myers, RH Leppert, M Hunt, SC AF North, Kari E. Franceschini, Nora Chung, Jay Baird, Lisa Avery, Christy Freedman, Barry I. Kraja, Aldi T. Arnett, Donna Miller, Michael B. Pankow, James S. Lewis, Cora E. Myers, Richard H. Leppert, Mark Hunt, Steve C. TI Evidence for association between CHEK2 variants and type 2 diabetes: The HyperGEN study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 Univ N Carolina, Chapel Hill, NC USA. NHLBI, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Alabama, Birmingham, AL USA. Univ Minnesota, Minneapolis, MN USA. Univ Alabama, Sch Med, Birmingham, AL USA. Boston Univ, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E293 EP E294 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200394 ER PT J AU O'Donnell, CJ Demissie, S Murabito, JM Fox, CS Hwang, SJ Wang, TJ Cupples, LA AF O'Donnell, Christopher J. Demissie, Serkalem Murabito, Joanne M. Fox, Caroline S. Hwang, Shih-Jen Wang, Thomas J. Cupples, L. Adrienne TI Deciphering genetic determinants for subclinical atherosclerosis in multiple arterial beds: Genome-wide association study in the NHLBI framingham heart study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 NHLBI Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E294 EP E294 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200397 ER PT J AU Parikh, NI Keyes, MJ Pou, KM Hamburg, N Larson, MG Vita, JA O'Donnell, CJ Vasan, RS Mitchell, GF Hoffmann, U Fox, CS Benjamin, EJ AF Parikh, Nisha I. Keyes, Michelle J. Pou, Karla M. Hamburg, Naomi Larson, Martin G. Vita, Joseph A. O'Donnell, Christopher J. Vasan, Ramachandran S. Mitchell, Gary F. Hoffmann, Udo Fox, Caroline S. Benjamin, Emelia J. TI Adiposity-related traits and endothelial function in the framingham offspring cohort SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Boston Univ, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E219 EP E219 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200040 ER PT J AU Parikh, NI Hwang, SJ Larson, MG Fox, CS Manders, ES Murabito, J Massaro, JM Hoffmann, U O'Donnell, CJ AF Parikh, Nisha I. Hwang, Shih-Jen Larson, Martin G. Fox, Caroline S. Manders, Emily S. Murabito, Joanne Massaro, Joseph M. Hoffmann, Udo O'Donnell, Christopher J. TI Validated parental history of premature cardiovascular disease as a risk factor for coronary artery calcification in the framingham third-generation cohort SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 Boston Univ, Sch Med, NHLBI, Framingham Heart Study, Framingham, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, NHLBI, Framingham Heart Study, Framingham, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E217 EP E217 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200034 ER PT J AU Pletcher, MJ Bibbons-Domingo, K Vittinghoff, E Lewis, CE Wei, GS Sidney, S McCulloch, CE Hulley, SB AF Pletcher, Mark J. Bibbons-Domingo, Kirsten Vittinghoff, Eric Lewis, Cora E. Wei, Gina S. Sidney, Stephen McCulloch, Charles E. Hulley, Stephen B. TI Increases in systolic blood pressure appear atherogenic at any level and any age in CARDIA SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Alabama, Birmingham, AL USA. NHLBI, Bethesda, MD 20892 USA. Kaiser Permanente, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E224 EP E224 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200062 ER PT J AU Scherer, ML Sigurdsson, S Detrano, R Garcia, M Eiriksdottir, G Launer, L Karlsdottir, G Thorgeirsson, G Gudnason, V Harris, TB AF Scherer, Matthew L. Sigurdsson, Sigudur Detrano, Robert Garcia, Melissa Eiriksdottir, Gudny Launer, Lenore Karlsdottir, Gyda Thorgeirsson, Gudmundur Gudnason, Vilmundur Harris, Tamara B. TI T-wave axis is associated with coronary artery calcium score in an asymptomatic elderly population SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 NIA, Howard Hughes Med Inst, Bethesda, MD 20892 USA. Icelandic Heart Assoc, Reykjavik, Iceland. Univ Calif Los Angeles, Los Angeles, CA USA. NIA, Bethesda, MD 20892 USA. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E284 EP E284 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200352 ER PT J AU Walker, ER Wyatt, SB Wofford, M Nelson, C Akylbekova, E Wilson, G Keahy, W Taylor, HA Jones, D AF Walker, Evelyn R. Wyatt, Sharon B. Wofford, Marion Nelson, Cheryl Akylbekova, Ermekgul Wilson, Gregory Keahy, Wanda Taylor, Herman A. Jones, Dan TI Patterns of antihypertensive therapy in the Jackson heart study cohort SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 NHLBI, Jackson Field Site, Jackson, MS USA. Univ Mississippi, Sch Nursing, Jackson, MS 39216 USA. Univ Mississippi, Jackson, MS 39216 USA. NHLBI, Bethesda, MD 20892 USA. Jackson State Univ, Coordinating Ctr, Jackson, MS USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E256 EP E256 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200215 ER PT J AU Webber, LS Catellier, DJ Lytle, LA Murray, DM Pratt, CA Young, DR Elder, JP Lohman, TG Stevens, J Pate, RR AF Webber, Larry S. Catellier, Diane J. Lytle, Leslie A. Murray, David M. Pratt, Charlotte A. Young, Deborah R. Elder, John P. Lohman, Timothy G. Stevens, June Pate, Russell R. TI Outcomes of a randomized controlled field trial to promote physical activity in middle-school girls: Trial of activity for adolescent girls SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 Tulane Univ, New Orleans, LA 70118 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Minnesota, Minneapolis, MN USA. Ohio State Univ, Columbus, OH 43210 USA. NHLBI, Div Prevent Populat Sci, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. Univ Arizona, Tucson, AZ USA. Univ S Carolina, Columbia, SC 29208 USA. NR 0 TC 1 Z9 1 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E221 EP E221 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200049 ER PT J AU Ashikaga, H Coppola, BA Hopenfeld, B Leifer, ES McVeigh, ER Omens, JH AF Ashikaga, Hiroshi Coppola, Benjamin A. Hopenfeld, Bruce Leifer, Eric S. McVeigh, Elliot R. Omens, Jeffrey H. TI Transmural dispersion of myofiber mechanics - Implications for electrical heterogeneity in vivo SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CANINE LEFT-VENTRICLE; ACTIVATION-RECOVERY INTERVALS; OVINE LEFT-VENTRICLE; LONG-QT SYNDROME; T-WAVE; M-CELL; ELECTROPHYSIOLOGICAL PROPERTIES; MYOCARDIAL BAND; LATERAL WALL; DOG HEART AB Objectives. We investigated whether transmural mechanics could yield insight into the transmural electrical sequence. Background. Although the concept of transmural dispersion of repolarization has helped explain a variety of arrhythmias, its presence in vivo is still disputable. Methods. We studied the time course of transmural myofiber mechanics in the anterior left ventricle of normal canines in vivo (n = 14) using transmural bead markers under biplane cineradiography. In 4 of these animals, plunge electrodes were placed in the myocardial tissue within the bead set to measure transmural electrical sequence. Results. The onset of myofiber shortening was earliest at endocardial layers and progressively delayed toward epicardial layers (p < 0.001), resulting in transmural dispersion of myofiber shortening of 39 ms. The onset of myofiber relaxation was earliest at epicardial layers and most delayed at subendocardial layers (p = 0.004), resulting in transmural dispersion of myofiber relaxation of 83 ms. There was no significant transmural gradient in electrical repolarization (p = NS). Conclusions. Despite lack of evidence of significant transmural gradient in electrical repolarization in vivo, there is transmural dispersion of myofiber relaxation as well as shortening. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Med & Bioengn, La Jolla, CA 92093 USA. RP Ashikaga, H (reprint author), NHLBI, Cardiac Energet Lab, NIH, 9000 Rockville Pike,Bldg 10-B1D416, Bethesda, MD 20892 USA. EM ha8000@gmail.com OI Ashikaga, Hiroshi/0000-0003-3689-6892 FU Intramural NIH HHS [Z01 HL004609-08]; NHLBI NIH HHS [R01-HL32583, Z01-HL4004609, R01 HL032583] NR 52 TC 80 Z9 85 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 27 PY 2007 VL 49 IS 8 BP 909 EP 916 DI 10.1016/j.jacc.2006.07.074 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 141YU UT WOS:000244615900010 PM 17320750 ER PT J AU Hardy, J Myers, A AF Hardy, John Myers, Amanda TI Genetic variability in expression of proteins and the risk of sporadic neurologic diseases SO NEUROLOGY LA English DT Editorial Material ID ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASE; LOCUS C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Univ Miami, Miller Sch Med, Dept Psychiat, Miami, FL 33152 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Porter Neurosci Bldg,NIH Main Campus, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Myers, Amanda/B-1796-2010; Hardy, John/C-2451-2009 OI Myers, Amanda/0000-0002-3100-9396; FU Medical Research Council [G0701075] NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 27 PY 2007 VL 68 IS 9 BP 632 EP 633 DI 10.1212/01.wnl.0000256793.58438.c4 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 140DA UT WOS:000244482400002 PM 17325268 ER PT J AU Dombi, E Solomon, J Gillespie, AJ Fox, E Balis, FM Patronas, N Korf, BR Babovic-Vuksanovic, D Packer, RJ Belasco, J Goldman, S Jakacki, R Kieran, M Steinberg, SM Widemann, BC AF Dombi, E. Solomon, J. Gillespie, A. J. Fox, E. Balis, F. M. Patronas, N. Korf, B. R. Babovic-Vuksanovic, D. Packer, R. J. Belasco, J. Goldman, S. Jakacki, R. Kieran, M. Steinberg, S. M. Widemann, B. C. TI NF1 plexiform neurofibroma growth rate by volumetric MRI - Relationship to age and body weight SO NEUROLOGY LA English DT Article ID SOLID TUMORS; PHASE-I AB Objective: To longitudinally analyze changes in plexiform neurofibroma (PN) volume in relation to age and body growth in children and young adults with neurofibromatosis type 1 and inoperable, symptomatic, or progressive PNs, using a sensitive, automated method of volumetric MRI analysis. Methods: We included patients 25 years of age and younger with PNs entered in a natural history study or in treatment trials who had volumetric MRI over >= 16 months. Results: We studied 49 patients (median age 8.3 years) with 61 PNs and a median evaluation period of 34 months (range 18 to 70). The PN growth rates varied among patients, but were constant within patients. Thirty-four patients (69%) experienced >= 20% increase in PN volume during the observation period. PN volume increased more rapidly than body weight over time (p = 0.026). Younger patients had the most rapid PN growth rate. Conclusions: Volume increase of plexiform neurofibromas is a realistic and meaningful trial endpoint. In most patients plexiform neurofibroma growth rate exceeded body growth rate. The youngest patients had the fastest plexiform neurofibroma growth rate, and clinical drug development should be directed toward this population. Age stratification for clinical trials for plexiform neurofibromas should be considered. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Med Numer Inc, Sterling, VA USA. NIH, Diagnost Radiol Dept, Ctr Clin, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Mayo Clin, Rochester, MN USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Biostat & Data Management Sect, CCR, Bethesda, MD 20892 USA. RP Dombi, E (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10 CRC,Room 1-5750,MSC 1101, Bethesda, MD 20892 USA. EM dombie@mail.nih.gov OI Kieran, Mark/0000-0003-2184-7692 FU Intramural NIH HHS NR 13 TC 54 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 27 PY 2007 VL 68 IS 9 BP 643 EP 647 DI 10.1212/01.wnl.0000250332.89420.e6 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 140DA UT WOS:000244482400004 PM 17215493 ER PT J AU Gaillard, WD Weinstein, S Conry, J Pearl, PL Fazilat, S Fazilat, S Vezina, LG Reeves-Tyer, P Theodore, WH AF Gaillard, W. D. Weinstein, S. Conry, J. Pearl, P. L. Fazilat, S. Fazilat, S. Vezina, L. G. Reeves-Tyer, P. Theodore, W. H. TI Prognosis of children with partial epilepsy - MRI and serial (18)FDG-PET SO NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; POSITRON EMISSION TOMOGRAPHY; DIAGNOSED PARTIAL SEIZURES; 1ST UNPROVOKED SEIZURE; FEBRILE SEIZURES; HIPPOCAMPAL SCLEROSIS; MAGNETIC-RESONANCE; RECURRENT SEIZURES; VOLUMETRIC MRI; BLOOD-FLOW AB Objective: To study the evolution of cerebral glucose metabolism after partial seizure onset in children, and its relation to clinical variables. Methods: Thirty-eight children had 3.4 +/- .8 (18)FDG-PET scans over 3.0 +/- 1.3 years starting within a year after their third unprovoked partial seizure. (18)FDG-PET was analyzed with a region of interest template to measure normalized metabolism in 12 paired anatomic areas. Scans with absolute asymmetry index, vertical bar AI vertical bar, greater than 0.13 in at least one cortical region other than the cerebellum were considered abnormal. Standard clinical T1- and T2-weighted MRI (1.5 T) scans were obtained. Results: Patients with initial normal PET (n = 28) were significantly more likely to remain in good seizure control than those with abnormal initial PET. Patients with initially normal PET scans that became abnormal had longer epilepsy duration before the first PET scan, but not greater seizure frequency, than those with PET always normal. There was no evidence for progression of hypometabolism. Patients with shorter time since last seizure and higher seizure frequency were more likely to have abnormal PET scans. Six of the seven patients whose PET scans were always abnormal had poor seizure control. Febrile seizure history did not affect PET findings. MRI was strongly predictive of initial PET results (chi(2) = 13.1; p < 0.02) but did not predict fluctuation hypometabolism. A model combining MRI and initial PET was strongly predictive of clinical course. Conclusions: Initial imaging studies can help predict clinical course for children who have had at least three partial seizures. Serial FDG-PET is affected by seizure frequency and time since last seizure. C1 Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. NINDS, Clin Epilepsy Sect, Div Intramural Res, Washington, DC USA. RP Gaillard, WD (reprint author), Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM wgaillar@cnmc.org FU NINDS NIH HHS [K08 NS01663] NR 42 TC 12 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 27 PY 2007 VL 68 IS 9 BP 655 EP 659 DI 10.1212/01.wnl.0000255942.25101.8d PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 140DA UT WOS:000244482400006 PM 17325271 ER PT J AU Grundy, GJ Hesse, JE Gellert, M AF Grundy, Gabrielle J. Hesse, Joanne E. Gellert, Martin TI Requirements for DNA hairpin formation by RAG1/2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunoglobulin gene; recombination; transposase ID CODING END SEQUENCE; V(D)J RECOMBINATION; SYNAPTIC COMPLEX; ACTIVE-SITE; MUTATIONAL ANALYSIS; RAG2 PROTEINS; TN10 TRANSPOSITION; SIGNAL SEQUENCES; AMINO-ACIDS; 12/23 RULE AB The rearrangement of antigen receptor genes is initiated by doublestrand breaks catalyzed by the RAG1/2 complex at the junctions of recombination signal sequences and coding segments. As with some "cut-and-paste" transposases, such as Tn5 and Hermes, a DNA hairpin is formed at one end of the break via a nicked intermediate. By using abasic DNA substrates, we show that different base positions are important for the two steps of cleavage. Removal of one base in the coding flank enhances hairpin formation, bypassing a requirement for a paired complex of two signal sequences. Rescue by abasic substrates is consistent with a base-flip mechanism seen in the crystal structure of the Tn5 postcleavage complex and may mimic the DNA changes on paired complex formation. We have searched for a tryptophan residue in RAG1 that would be the functional equivalent of W298 in Tn5, which stabilizes the DNA interaction by stacking the flipped base on the indole ring. A W956A mutation in RAG1 had an inhibitory effect on both nicking and hairpin stages that could be rescued by abasic substrates. W956 is therefore a likely candidate for interacting with this base during hairpin formation. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gellert, M (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Room 241, Bethesda, MD 20892 USA. EM gellert@helix.nih.gov FU Intramural NIH HHS NR 44 TC 19 Z9 22 U1 0 U2 1 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 FEB 27 PY 2007 VL 104 IS 9 BP 3078 EP 3083 DI 10.1073/pnas.0611293104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142PG UT WOS:000244661400013 PM 17307873 ER PT J AU Suh, JY Iwahara, J Clore, GM AF Suh, Jeong-Yong Iwahara, Junji Clore, G. Marius TI Intramolecular domain-domain association/dissociation and phosphoryl transfer in the mannitol transporter of Escherichia coli are not coupled SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE domain motion; NMR; protein dynamics; relaxation dispersion; phosphotransferase system ID GLYCOSE PHOSPHOTRANSFERASE SYSTEM; RESIDUAL DIPOLAR COUPLINGS; TRANSFER COMPLEX; BACTERIAL PHOSPHOENOLPYRUVATE; CARBOHYDRATE TRANSPORTERS; PROTEIN ASSOCIATION; TIME SCALES; ENZYME-I; NMR; RELAXATION AB The Escherichia coli mannitol transporter (ll(Mtl)) comprises three domains connected by flexible linkers:a transmembrane domain (C) and two cytoplasmic domains (A and B). ll(Mtl) catalyzes three successive phosphoryl-transfer reactions: one intermolecular (from histidine phosphocarrier protein to the A domain) and two intramolecular (from the A to the B domain and from the B domain to the incoming sugar bound to the C domain). A key functional requirement of ll(Mtl) is that the A and B cytoplasmic domains be able to rapidly associate and dissociate while maintaining reasonably high occupancy of an active stereospecific AB complex to ensure effective phosphoryl transfer along the pathway. We have investigated the rate of intramolecular domain-domain association and dissociation in llBA(Mtl) by using 111 relaxation dispersion spectroscopy in the rotating frame. The open, dissociated state (comprising an ensemble of states) and the closed, associated state (comprising the stereospecific complex) are approximately equally populated. The first-order rate constants for intramolecular association and dissociation are 1.7 (+/- 0.3) x 10(4) and 1.8 (+/- 0.4) x 10(4) s(-1), respectively. These values compare to rate constants of approximate to 500 s(-1) for A -> B and B A phosphoryl transfer, derived from qualitative lineshape analysis of H-1-N-15 correlation spectra taken during the course of active catalysis. Thus, on average, approximate to 80 association/ dissociation events are required to effect a single phosphoryltransfer reaction. We conclude that intramolecular phosphoryl transfer between the A and B domains of ll(Mtl) is rate-limited by chemistry and not by the rate of formation or dissociation of a stereospecific complex in which the active sites are optimally apposed. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008; OI Clore, G. Marius/0000-0003-3809-1027; Iwahara, Junji/0000-0003-4732-2173 NR 38 TC 16 Z9 16 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 FEB 27 PY 2007 VL 104 IS 9 BP 3153 EP 3158 DI 10.1073/pnas.0609103104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142PG UT WOS:000244661400026 PM 17360622 ER PT J AU Kuroda, F Moss, J Vaughan, M AF Kuroda, Fuminobu Moss, Joel Vaughan, Martha TI Regulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) and BIG2 activity via PKA and protein phosphatase 1 gamma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ADP-ribosylation factor; phosphorylation; siRNA; cyclic AMP ID ADP-RIBOSYLATION FACTORS; KINASE-A; RI-ALPHA; ARF; DOMAIN; SUBUNITS; COMPLEX; SEC7; SPECIFICITY; CONTAINS AB Brefeldin A-inhibited guanine nucleotide-exchange proteins (GEPs) BIG1 and BIG2 activate ADP-ribosylation factor (ARF) GTPases, which are required for vesicular trafficking. Both molecules contain one or more sites for binding protein kinase A, i.e., A kinase-anchoring protein (AKAP) sequences. Elevation of cell cAMP caused PKA-catalyzed phosphorylation and nuclear accumulation of BIG1 but not BIG2. We then asked whether BIG1 phosphorylation altered its GEP activity. Incubation of BIG1 or BiG2 with PKA catalytic subunits and ATP resulted in retardation of their electrophoretic migration, consistent with PKA phosphorylation. Okadaic acid inhibits many protein phosphatases, including protein phosphatase 1 (PP1) and PP2A, that can reverse PKA-catalyzed phosphorylation. Incubation of HepG2 cells with okadaic acid caused concentration-dependent accumulation of presumably phosphorylated BIG1 and BIG2 with decreased mobility, which was increased by subsequent incubation in vitro with specific recombinant phosphatases, PP1 gamma > PP2A >> PP1 alpha. For assays of GEP activity, BIG1 and BIG2 were immunoprecipitated from cells that had been depleted, respectively, of BIG2 and BIG1 by using specific siRNA. GEP activity of each was significantly decreased after incubation with recombinant PKA plus ATP and restored by incubation with PP1 gamma. In agreement with a role for PP1 gamma in regulation of BIG, endogenous PP1 gamma, but not PP1 alpha or beta, was immunoprecipitated with BIG1 or BIG2 from microsomal fractions. All observations are consistent with the effects of BIG1 and BIG2 phosphorylation on vesicular trafficking, via alterations in ARF activation and regulatory roles for cAMP, PKA, and PIP1 gamma in ARF activation by BIG1 and BIG2. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Vaughan, M (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. EM vaughanm@nhibi.nih.gov FU Intramural NIH HHS NR 29 TC 26 Z9 30 U1 0 U2 1 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 FEB 27 PY 2007 VL 104 IS 9 BP 3201 EP 3206 DI 10.1073/pnas.0611696104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142PG UT WOS:000244661400034 PM 17360629 ER PT J AU Kinter, A McNally, J Riggin, L Jackson, R Roby, G Fauci, AS AF Kinter, Audrey McNally, Jonathan Riggin, Lindsey Jackson, Robert Roby, Gregg Fauci, Anthony S. TI Suppression of HIV-specific T cell activity by lymph node CD25(+) regulatory T cells from HIV-infected individuals SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytolytic T lymphocyte; cytokine; proliferation ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERIPHERAL-BLOOD; IMMUNE-RESPONSES; DENDRITIC CELLS; HELPER-CELLS; IN-VIVO; CD4(+); PATHOGENESIS; INDUCTION; TOLERANCE AB CD25(+) CD4(+) FoxP3(+) regulatory T (Treg) cells isolated from the peripheral blood of asymptomatic HIV-infected individuals have been demonstrated to significantly suppress HIV-specific immune responses in vitro. CD25(+) Treg cell suppressor activity in the peripheral blood seems to diminish with progression of HIV disease, and it has been suggested that loss of Treg cells contributes to aberrant immune activation and disease progression. However, phenotypic studies suggest that Treg cells may migrate to, and be maintained or even expanded in, tissue sites of HIV replication. Currently, it is not known whether tissue-associated Treg cells maintain suppressive activity in the context of HIV infection, particularly in individuals with advanced disease. The present study demonstrates that CD25(+) Treg cells isolated from lymph nodes and peripheral blood of HIV+ subjects, even those with high viral loads and/or low CD4(+) T cell counts, maintain potent suppressive activity against HIV-specif ic cytolytic T cell function. This activity was better in lymph node as compared with peripheral blood, particularly in patients with high levels of plasma viremia. In addition, the expression of certain CD25(+) Treg-associated markers on CD4(+) T cells isolated from lymph nodes differed significantly from those on CD4(+) T cell subsets isolated from the peripheral blood. These data suggest that CD25(+) Treg cell-mediated suppression of HIV-specific responses continues throughout the course of HIV disease and, because of their particularly potent suppression of HIV-specific CTL activity in lymphoid tissue, may considerably impact the ability to control HIV replication in vivo. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kinter, A (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A33,10 Ctr Dr,9000 Rockville Pike, Bethesda, MD 20892 USA. EM akinter@niaid.nih.gov; afauci@niaid.nih.gov NR 56 TC 130 Z9 137 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 FEB 27 PY 2007 VL 104 IS 9 BP 3390 EP 3395 DI 10.1073/pnas.06114234104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142PG UT WOS:000244661400066 PM 17360656 ER PT J AU Martinelli, E Cicala, C Van Ryk, D Goode, DJ Macleod, K Arthos, J Fauci, AS AF Martinelli, Elena Cicala, Claudia Van Ryk, Donald Goode, Diana J. Macleod, Katilyn Arthos, James Fauci, Arthony S. TI HIV-1 gp120 inhibits TLR9-mediated activation and IFN-alpha secretion in plasmacytoid dendritic cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cpG; interferon alpha ID INTERFERON-PRODUCING CELLS; NATURAL-KILLER-CELLS; TOLL-LIKE RECEPTOR-7; VIRUS TYPE-1 GP120; IMMUNODEFICIENCY-VIRUS; CHEMOKINE PRODUCTION; T-LYMPHOCYTES; NK-CELLS; INFECTION; PROTEIN AB Plasmacytoid dendritic cells (pDCs) play a central role in innate and adaptive immune responses against viral infections. pDCs secrete type I IFNs and proinflarnmatory cytokines upon stimulation by either TLR7 or TLR9. Throughout the course of HIV infection, the production of type-I IFINs is profoundly impaired, and total pDC cell counts in peripheral blood correlates inversely with viral load and positively with CD4(+) T cell count. The origin of these defects is unclear. pIDCs express C1134, CCR5, and CXCR4, the primary receptor and coreceptors, respectively, for the HIV envelope; yet little is known concerning the effects of the viral envelope on these cells. Here, we show that exposure of pDCs to gp120 results in the suppression of activation of these cells. This suppression is specific for TLR9-mediated responses, because TLR7-mediated responses are unaffected by gp120. gp120 also suppressed TI-1119-mediated induction of proinflarnmatory cytokines and expression of CD83, a marker of DC activation. Finally, gp120 suppressed pDC-induced cytolytic activity of natural killer cells. Taken together, these data demonstrate that the direct interaction of HIV-1 gp120 with pIDCs interferes with TLR9 activation resulting in a decreased ability of pDCs to secrete antiviral and inflammatory factors that play a central role in initiating host immune responses against invading pathogens. C1 NIAID, Immunogenet Lab, Bethesda, MD 20892 USA. RP Martinelli, E (reprint author), NIH, 10-11N120,9000 Rockville Pike, Bethesda, MD 20892 USA. EM martinee1@niaid.nih.gov NR 48 TC 129 Z9 135 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 27 PY 2007 VL 104 IS 9 BP 3396 EP 3401 DI 10.1073/pnas.0611353104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142PG UT WOS:000244661400067 PM 17360657 ER PT J AU Pozsgay, V Kubler-Kielb, J AF Pozsgay, Vince Kubler-Kielb, Joanna TI Synthesis of an experimental glycolipoprotein vaccine against Lyme disease SO CARBOHYDRATE RESEARCH LA English DT Article DE aminooxy; Borrelia burgdorferi; conjugation; glycolipid; glycolipoprotein; Lyme disease; oxime; vaccine ID REVERSED MICELLAR MEDIUM AB A novel glycolipid was synthesized that corresponds to cholesteryl palmitoyl-galactopyranoside 1 found in the spirochete Borrelia burgdorferi, the causative agent of Lyme disease. In order to fashion I in a conjugatable form, the palmitoyl residue was modified to include a terminal aldehydo, moiety that anchored the glycolipid to aminooxypropylated serum albumin using oxime chemistry. The glycolipoprotein so obtained incorporates an average of 18 glycolipid moieties per albumin molecule. The novel glycolipoprotein constructs are soluble in water and are candidates toward developing a semisynthetic vaccine against Lyme disease. (c) 2006 Elsevier Ltd. All rights reserved. C1 NICHHD, Lab Dev & Mol Immun, NIH, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), NICHHD, Lab Dev & Mol Immun, NIH, Bethesda, MD 20892 USA. EM pozsgayv@mail.nih.gov FU Intramural NIH HHS [Z01 HD001313-13] NR 12 TC 14 Z9 15 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD FEB 26 PY 2007 VL 342 IS 3-4 BP 621 EP 626 DI 10.1016/j.carres.2006.11.014 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 141AP UT WOS:000244548700026 PM 17182019 ER PT J AU Kubler-Kielb, J Vinogradov, E Chu, CY Schneerson, R AF Kubler-Kielb, Joanna Vinogradov, Evgeny Chu, Chiayung Schneerson, Rachel TI O-Acetylation in the O-specific polysaccharide isolated from Shigella flexneri serotype 2a SO CARBOHYDRATE RESEARCH LA English DT Article DE Shigella; Flexneri; LPS; O-acetylation; O-specific chain ID CAPSULAR POLYSACCHARIDE; CONJUGATE VACCINES; NEISSERIA-MENINGITIDIS; IMMUNOGENICITY; ANTIGEN; TYPE-2A; SAFETY AB Shigella flexneri causes diarrheal diseases especially in infants and children in developing countries. Modifications of the lipopolysaccharide (LPS) molecule, like bacteriophage-mediated glucosylation and acetylation of the O-specific chain (O-SP), are important for the LPS antigenicity and consequently for the immunogenicity of the polysaccharide-based vaccines against shigellosis. Here, we report the degree of O-acetylation and the localisation of O-acetyl groups and side-chain glucose substitution in the O-SP (scheme) in different preparations of S. flexneri type 2a LPS. [GRAPHICS] (c) 2006 Elsevier Ltd. All rights reserved. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. RP Kubler-Kielb, J (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kielbj@mail.nih.gov OI Vinogradov, Evgeny/0000-0002-5364-1376 FU Intramural NIH HHS [Z99 HD999999] NR 19 TC 25 Z9 26 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD FEB 26 PY 2007 VL 342 IS 3-4 BP 643 EP 647 DI 10.1016/j.carres.2006.09.017 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 141AP UT WOS:000244548700030 PM 17087926 ER PT J AU Berg, JM AF Berg, Jeremy M. TI NIH and chemistry SO CHEMICAL & ENGINEERING NEWS LA English DT Letter C1 NIGMS, Bethesda, MD USA. RP Berg, JM (reprint author), NIGMS, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2347 J9 CHEM ENG NEWS JI Chem. Eng. News PD FEB 26 PY 2007 VL 85 IS 9 BP 6 EP 6 PG 1 WC Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA 140PU UT WOS:000244518800006 ER PT J AU Lou, H Dean, M AF Lou, H. Dean, M. TI Targeted therapy for cancer stem cells: the patched pathway and ABC transporters SO ONCOGENE LA English DT Review DE cancer stem cell; hedgehog/patched pathway; smoothened; ABC transporters; ABCG2; cyclopamine ID HUMAN HOMOLOG; TERATOCARCINOMA CELLS; MULTIDRUG-RESISTANCE; CARCINOMA SYNDROME; SIDE-POPULATION; HEDGEHOG; DROSOPHILA; INHIBITION; MUTATIONS; GENE AB Data from certain leukemias as well as brain and breast cancer indicate that there is a small population of tumor cells with 'stem cell' characteristics and the capacity for self-renewal. The self-renewing cells have many of the properties of normal stem cells and have been termed 'cancer stem cells'. These cancer stem cells make up as few as 1% of the cells in a tumor, making them difficult to detect and study. Like normal stem cells, cancer stem cells have a number of properties permitting them to survive traditional cancer chemotherapy and radiation therapy. These cells express high levels of ATP-binding cassette (ABC) drug transporters, providing for a level of resistance; are relatively quiescent; have higher levels of DNA repair and a lowered ability to enter apoptosis. Combined cancer therapy approaches targeting the cancer stem cells and the non-stem cells may be developed with increased efficacy. Efforts to target the Hedgehog/Patched pathway, critical to embryonic growth and differentiation, and the ABCG2 drug efflux transporter will be presented. C1 NCI, Frederick, MD 21702 USA. RP Dean, M (reprint author), NCI, Frederick, MD 21702 USA. EM dean@ncifcrf.gov OI Dean, Michael/0000-0003-2234-0631 FU Intramural NIH HHS NR 37 TC 128 Z9 146 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 26 PY 2007 VL 26 IS 9 BP 1357 EP 1360 DI 10.1038/sj.onc.1210200 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 141DU UT WOS:000244558700014 PM 17322922 ER PT J AU Sherman, ME Dasgupta, A Schiffman, M Nayar, R Solomon, D AF Sherman, Mark E. Dasgupta, Abhijit Schiffman, Mark Nayar, Ritu Solomon, Diane TI The Bethesda interobserver reproducibility study (BIRST) - A web-based assessment of the Bethesda 2001 System for classifying cervical cytology SO CANCER CYTOPATHOLOGY LA English DT Article DE Bethesda System; cytology; cervix; screening; Internet; reproducibility ID ATYPICAL SQUAMOUS-CELLS; PAPANICOLAOU TEST; CERVICOVAGINAL CYTOLOGY; COMPARISON PROGRAM; QUALITY ASSURANCE; DIAGNOSES; ACCURACY; TRIAGE; SMEAR AB BACKGROUND. The Bethesda System (TBS) along with its companion atlas was updated in 2001 to improve standardization, clarity, and reproducibility of cervical cytology reporting. METHODS. The authors used a novel web-based format to compare assessments of 77 images demonstrating a range of classical and borderline cytologic changes by a self-selected group of United States cytotechnologists (n = 216) and pathologists (n = 185). RESULTS. Participants were highly experienced, with 71.2% of cytotechnologists and 53.0% of pathologists reporting > 10 years of practice. The mean percentage of exact agreement with the panel was slightly though significantly higher for cytotechnologists (57.0%) compared with pathologists (53.4%), adjusted for experience (P=.004); cervical cytology percentage effort (P=.0005); or cervical accession volume (P=.0002). Compared with the TBS panel, exact agreement was achieved for 55.1% of image ratings compared with 82.3% agreement at the level of Negative vs non-Negative for images with a single-panel interpretation. Agreement with the panel was highest for images classified as Low-Grade Squamous Intraepithelial Lesion and lowest for Atypical Squamous Cells qualified as either of Undetermined Significance or Cannot Exclude a High-Grade Squamous Intraepithelial Lesion. Reviewers were less sensitive in identifying high-grade glandular lesions than they were in identifying high-grade squamous lesions at any threshold (P <.001). CONCLUSIONS. Morphologic appearances of images were more important determinants than participants' academic or professional degrees with regard to inter-observer reproducibility in classifying cervical cytology images. Experienced cytotechnologists and pathologists performed similarly Participants achieved higher sensitivity for identifying high-grade squamous lesions than they did for high-grade glandular lesions. These findings demonstrated that web-based studies may be useful in assessing interobserver agreement in classifying images. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD USA. Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. Natl Canc Inst, Div Canc Prevent, Breast & Gynecol Canc Res Grp, Bethesda, MD USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Bethesda, MD USA. RP Sherman, ME (reprint author), Natl Canc Inst, 6120 Execut Blvd, Rockville, MD 20852 USA. EM shermanm@mail.nih.gov NR 19 TC 27 Z9 29 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD FEB 25 PY 2007 VL 111 IS 1 BP 15 EP 25 DI 10.1002/cncr.22423 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA 138BX UT WOS:000244338700002 PM 17186503 ER EF