FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Crawford, NPS Ziogas, A Qian, XL Yang, HY Park, YG Lukes, L Lancaster, M Anton-Culver, H Lowy, D Hunter, KW AF Crawford, Nigel P. S. Ziogas, Al Qian, Xiaolan Yang, Haiyan Park, Yeong-Gwan Lukes, Luanne Lancaster, Mindy Anton-Culver, Hoda Lowy, Doug Hunter, Kent W. TI The role of germline variability in metastatic susceptibility SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract ID BREAST-CANCER; PROGRESSION; CANDIDATE; SIPA1 C1 NCI, Bethesda, MD 20892 USA. Univ Calif Irvine, Irvine, CA 92697 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 7 BP 980 EP 980 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 118VI UT WOS:000242971200025 ER PT J AU Betz, BL Wei, SJ Malarkey, DE Trempus, CS Humble, MM French, JE Tennant, RW AF Betz, Bryan L. Wei, Sung-Jen Malarkey, David E. Trempus, Carol S. Humble, Margaret M. French, John E. Tennant, Raymond W. TI Activated Hras cooperates with disruption of p19(Ar) (f) to induce gastrointestinal stromal tumor (GIST) in mice SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract ID P53-DEPENDENT APOPTOSIS; SUPPRESSOR; MUTATIONS; P53 C1 NIEHS, Natl Ctr Toxicogenom, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 7 BP 1002 EP 1002 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 118VI UT WOS:000242971200047 ER PT J AU Bradsher, J Wang, X Zhang, R Harris, C AF Bradsher, John Wang, Xin Zhang, Ran Harris, Curtis TI A protein complex of CSA, CSB, and p53 is involved in transcription-coupled repair SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 7 BP 1005 EP 1006 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 118VI UT WOS:000242971200050 ER PT J AU Waldmann, TA AF Waldmann, Thomas A. TI Keynote address: Effective cancer therapy through immunomodulation SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract ID T-CELLS; TUMOR IMMUNOSURVEILLANCE; IL-15; BLOCKADE; IMMUNOTHERAPY; ACTIVATION; DACLIZUMAB; IMMUNITY; DEATH; TRANS C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 7 BP 1012 EP 1014 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA 118VI UT WOS:000242971200062 ER PT J AU Wei, SJ Williams, J Dang, H Darden, TA Betz, BL Humble, MM Trempus, CS Johnson, K Cannon, RE Tennant, RW AF Wei, Sung-Jen Williams, Jason Dang, Hong Darden, Thomas A. Betz, Bryan L. Humble, Margaret M. Trempus, Carol S. Johnson, Katina Cannon, Ronald E. Tennant, Raymond W. TI A Glu-Asp acidic motif of the DSS1 binds to human proteasome 19S Rpn3/S3 and is required for the maintenance of proteasome stability and ubiquitin-mediated protein degradation SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract ID SPLIT FOOT MALFORMATION; USTILAGO-MAYDIS; CANDIDATE GENE; YEAST; RECOMBINATION; BRCA2; INVOLVEMENT; HOMOLOG; REPAIR; SEM1 C1 Natl Inst Environm Hlth Sci, Natl Ctr Toxicogenom, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Alpha Gamma Technol Inc, Raleigh, NC 27609 USA. NR 14 TC 0 Z9 0 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 7 BP 1014 EP 1015 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 118VI UT WOS:000242971200063 ER PT J AU Wolf, R Voscopoulos, C Cataisson, C Hennings, H Yuspa, SH AF Wolf, Ronald Voscopoulos, Christopher Cataisson, Christophe Hennings, Henry Yuspa, Stuart H. TI The mouse S100A15 ortholog of the human S100A7/A15 subfamily is a differentiation specific marker that is downregulated with premaligant progression during epidermal carcinogenesis SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract ID PROTEINS; CALCIUM; FAMILY C1 NCI, Lab Carcinogenesis & Tumor Promot, Ctr Canc Res, Bethesda, MD 20814 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 7 BP 1016 EP 1017 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 118VI UT WOS:000242971200065 ER PT J AU Yanaihara, N Caplen, N Bowman, E Seike, M Kumamoto, K Yi, M Stephens, RM Okamoto, A Yokota, J Tanaka, T Calin, GA Liu, CG Croce, CM Harris, CC AF Yanaihara, Nozomu Caplen, Natasha Bowman, Elise Seike, Masahiro Kumamoto, Kensuke Yi, Ming Stephens, Robert M. Okamoto, Aikou Yokota, Jun Tanaka, Tadao Calin, George Adrian Liu, Chang-Gong Croce, Carlo M. Harris, Curtis C. TI Unique MicroRNA molecular profiles in lung cancer diagnosis and prognosis SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract ID GENES C1 NCI, Human Carcinogenesis Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Gene Silencing Sect, Off Sci & Technol Partnership, NIH,Ctr Canc Res, Bethesda, MD 20892 USA. NCI, SAIC Frederick Inc, Adv Biomed Comp Ctr, Ft Detrick, MD 21702 USA. Jikei Univ, Sch Med, Dept Obstet & Gynecol, Tokyo 1058461, Japan. Natl Canc Ctr, Res Inst, Div Biol, Tokyo 1040045, Japan. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NR 2 TC 3 Z9 3 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 7 BP 1017 EP 1018 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 118VI UT WOS:000242971200066 ER PT J AU Haws, LC Su, SH Harris, M DeVito, MJ Walker, NJ Farland, WH Finley, B Birnbaum, LS AF Haws, LC Su, SH Harris, M DeVito, MJ Walker, NJ Farland, WH Finley, B Birnbaum, LS TI Development of a refined database of mammalian relative potency estimates for dioxin-like compounds SO TOXICOLOGICAL SCIENCES LA English DT Review DE dioxin; polychlorinated dibenzo-p-dioxins; polychlorinated dibenzofurans; polychlorinated biphenyls; toxic equivalency factor (TEF); relative potency (REP) ID TOXIC EQUIVALENCY FACTORS; POLYCHLORINATED-BIPHENYLS PCBS; CYP1A2 ENZYME-ACTIVITY; DIBENZO-PARA-DIOXINS; RISK ASSESSMENT; FACTORS TEFS; RECEPTOR; PCDFS; COMPLEX; MIXTURE AB The toxic equivalency factor (TEF) approach has been widely accepted as the most feasible method available at present for evaluating potential health risks associated with exposure to mixtures of dioxin-like compounds (DLCs). The current mammalian TEFs for the DLCs were established by the World Health Organization (WHO) following the meeting of an international expert panel in June of 1997. The TEFs recommended by WHO were determined based on a consensus of scientific judgment and were presented as point estimates. However, the relative potency estimates (REPs) underlying the TEFs were derived from a heterogeneous data set and often span several orders of magnitude. In this article, we present a refined database of mammalian REPs that we believe will facilitate better characterization of the variability and uncertainty inherent in the data. The initial step involved reviewing the REP database used by the WHO panel during its review in 1997. A set of criteria was developed to identify REPs that were determined to be the most representative measure of a biological response and of adequate quality for use in quantitative analyses. REPs were determined to be inappropriate for use in quantitative analyses if any of the established exclusion criteria were met. Comparison of data records to the established exclusion criteria resulted in the identification of a substantial number of REPs believed to be inappropriate for use in quantitative analyses. Next, studies published after 1997 were added to the database. The availability of such a refined database will improve risk assessment for this class of compounds by including additional information from new studies and facilitating the use of quantitative approaches in the further development of TEFs. C1 ChemRisk, Austin, TX 78731 USA. Exponent Inc, New York, NY 10170 USA. ChemRisk, Houston, TX 77042 USA. US EPA, ORD NHEERL ETD, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. US EPA, Off Res & Dev, Washington, DC 20460 USA. ChemRisk, San Francisco, CA 94105 USA. RP Haws, LC (reprint author), ChemRisk, 8024 Mesa Dr,126, Austin, TX 78731 USA. EM lhaws@chemrisk.com RI Walker, Nigel/D-6583-2012; OI Walker, Nigel/0000-0002-9111-6855; harris, mark/0000-0002-9007-1587 NR 42 TC 70 Z9 77 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2006 VL 89 IS 1 BP 4 EP 30 DI 10.1093/toxsci/kfi294 PG 27 WC Toxicology SC Toxicology GA 993XN UT WOS:000233991000002 PM 16120753 ER PT J AU Voss, KA Liu, J Anderson, SP Dunn, C Miller, JD Owen, JR Riley, RT Bacon, CW Corton, JC AF Voss, KA Liu, J Anderson, SP Dunn, C Miller, JD Owen, JR Riley, RT Bacon, CW Corton, JC TI Toxic effects of fumonisin in mouse liver are independent of the peroxisome proliferator-activated receptor alpha SO TOXICOLOGICAL SCIENCES LA English DT Article DE fumonisin; peroxisome proliferator-activated receptor alpha; hepatotoxicity ID NECROSIS-FACTOR-ALPHA; FUSARIUM-MONILIFORME; IN-VIVO; PPAR-ALPHA; RAT-LIVER; SPHINGOLIPID METABOLISM; INCREASED EXPRESSION; NUCLEAR RECEPTORS; RISK-FACTOR; B-1 AB Fumonisin mycotoxins occur worldwide in corn and corn-based foods. Fumonisin B-1 (FB1) is a rodent liver carcinogen and suspected human carcinogen. It inhibits ceramide synthase and increases tissue sphinganine (Sa) and sphingosine (So) concentrations. Events linking disruption of sphingolipid metabolism and fumonisin toxicity are not fully understood; however, Sa and So were shown to bind mouse recombinant peroxisome proliferator-activated receptor alpha (PPAR alpha) in vitro. To investigate the role of PPAR alpha in fumonisin hepatotoxicity in vivo, wild-type (WT) and PPAR alpha-null mice were fed control diets or diets containing 300 ppm FB1, Fusarium verticillioides culture material (CM) providing 300 ppm FB1, or 500 ppm of the peroxisome proliferator WY-14,643 (WY) for 1 week. WY-fed WT mice exhibited hepatomegaly, an effect not found in WY-fed PPAR alpha-null mice, and WY did not change liver sphingoid base concentrations in either strain. Hepatotoxicity found in FB1- and CM-fed WT and PPAR alpha-null mice was similar, qualitatively different from that found in WY-treated animals, and characterized by increased Sa concentration, apoptosis, and cell proliferation. Transcript profiling using oligonucleotide arrays showed that CM and FB1 elicited similar expression patterns of genes involved in cell proliferation, signal transduction, and glutathione metabolism that were different from that altered by WY. Real-time RT-PCR analysis of gene expression demonstrated PPAR alpha-dependence of lipid metabolism gene expression in WY-treated mice, whereas PPAR alpha-independent alterations of genes in lipid metabolism, and other categories, were found in CM- and FB1-fed mice. Together, these findings demonstrate that FB1- and CM-induced hepatotoxicity in mice does not require PPAR alpha. C1 USDA ARS, Toxicol & Mycotoxin Res Unit, Athens, GA 30604 USA. NIEHS, NCI, LCC, Res Triangle Pk, NC 27709 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. CIIT Ctr Hlth Res, Res Triangle Pk, NC 27709 USA. Carleton Univ, Dept Chem, Ottawa, ON K1S 5B6, Canada. ToxicoGenom, Chapel Hill, NC 27514 USA. RP Voss, KA (reprint author), USDA ARS, Toxicol & Mycotoxin Res Unit, POB 5677, Athens, GA 30604 USA. EM kvoss@saa.ars.usda.gov FU Intramural NIH HHS NR 40 TC 9 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2006 VL 89 IS 1 BP 108 EP 119 DI 10.1093/toxsci/kfj019 PG 12 WC Toxicology SC Toxicology GA 993XN UT WOS:000233991000011 PM 16221962 ER PT J AU Burns-Naas, LA Dearman, RJ Germolec, DR Kaminski, NE Kimber, I Ladics, GS Luebke, RW Pfau, JC Pruett, SB AF Burns-Naas, LA Dearman, RJ Germolec, DR Kaminski, NE Kimber, I Ladics, GS Luebke, RW Pfau, JC Pruett, SB TI "Omics" technologies and the immune system SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Review DE omics in immunology; omics in immunotoxicology; immunomics; immunopharmacogenomics immunotoxicogenomics; gene array; allergy; autoimmunity; cytokines; dendritic cells; TCDD; dioxin; ethanol; hypersensitivity; immune-mediated disease; Langerhan's cell; mechanisms of immunotoxicity; sensitization ID INTERLEUKIN-10 PROMOTER POLYMORPHISM; ALLERGIC CONTACT-DERMATITIS; SKIN SENSITIZATION HAZARD; MESSENGER-RNA EXPRESSION; CELLS FOLLOWING EXPOSURE; NECROSIS-FACTOR-ALPHA; HUMAN DENDRITIC CELLS; GENE-EXPRESSION; AUTOIMMUNE-DISEASES; IN-VITRO AB Recent advances in genomics-based identification of gene families and gene polymorphisms associated with immune system dysfunction have answered basic questions in immunology and have begun to move forward our understanding of immune-related disease processes. In toxicology, "omic" technologies have the potential to replace or supplement current immunotoxicological screening procedures, to provide insight into potential mode or mechanisms of action, and to provide data suitable for risk assessment. The application of omic technologies to the study of the immune system also has great potential to appreciably impact the diagnosis and treatment of immune-related diseases. This review focuses on the use of omic technologies in immunopharmacology and immunotoxicology, specifically considering the potential for these technologies to impact chemical hazard identification, risk characterization and risk assessment, and the development and application of novel therapeutics. The state of the science of omics technologies and the immune system is addressed in terms of a continuum of understanding of how omics technologies can and cannot yet be applied in the various aspects of immunopharmacology and immunotoxicology. Additionally, information gaps are identified that, once addressed, will move each area further down the continuum of understanding. C1 Pfizer Global Res & Dev, Worldwide Safety Sci, San Diego, CA 92121 USA. Syngenta Cent Toxicol Lab, Macclesfield SK10 4TJ, Cheshire, England. Natl Inst Environm Hlth Sci, Environm Immunol Lab, Div Intramural Res, Res Triangle Pk, NC 27709 USA. Michigan State Univ, Ctr Integrat Toxicol, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA. DuPont Co Inc, Haskell Lab, Newark, DE 19714 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Expt Toxicol Div, Immunotoxicol Branch, Res Triangle Pk, NC 27711 USA. Univ Montana, Dept Biomed Pharmaceut Sci, Ctr Environm Hlth Sci, Missoula, MT 59812 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Cell Biol & Anat, Shreveport, LA 71130 USA. RP Burns-Naas, LA (reprint author), Pfizer Global Res & Dev, Worldwide Safety Sci, San Diego, CA 92121 USA. EM leighann.buns@pfizer.com FU NIAAA NIH HHS [R01 AA009505] NR 165 TC 2 Z9 2 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PY 2006 VL 16 IS 2-3 BP 101 EP 119 DI 10.1080/15376520600558424 PG 19 WC Toxicology SC Toxicology GA 021BO UT WOS:000235957700007 PM 20021002 ER PT J AU Drecktrah, D Knodler, LA Ireland, R Steele-Mortimer, O AF Drecktrah, D Knodler, LA Ireland, R Steele-Mortimer, O TI The mechanism of Salmonella entry determines the vacuolar environment and intracellular gene expression SO TRAFFIC LA English DT Article DE complement; invasion; macrophage; opsonization; phagocytosis; Salmonella-containing vacuole; Type III secretion ID III SECRETION SYSTEM; PATHOGENICITY ISLAND 2; ENTERICA SEROVAR TYPHIMURIUM; EPITHELIAL-CELLS; BACTERIAL INVASION; VIRULENCE GENES; HOST-CELLS; MEDIATED PHAGOCYTOSIS; NONPHAGOCYTIC CELLS; MURINE MACROPHAGES AB Macrophages are an important intracellular niche for Salmonella particularly for systemic infection. The interaction of Salmonella with these cells is mediated by two type III secretion systems (TTSS), encoded on Salmonella pathogenicity islands 1 and 2 (SPI1, SPI2), which mediate distinct phases of the pathogen-host cell interaction. The SPI1 TTSS mediates invasion whereas the SPI2 TTSS is required for intramacrophage survival. Importantly, however, Salmonella can enter macrophages by either SPI1-dependent invasion or host cell-mediated phagocytosis. Here, we investigated how the mechanism of internalization affects the intracellular environment and TTSS gene expression. Intracellular bacterial survival depended on the method of entry, because complement-opsonized and SPI1-induced Salmonella initiated replication within 8 h whereas immunoglobulin G (IgG)-opsonized and non-opsonized Salmonella were initially killed. Analysis of vacuolar pH showed that acidification of the Salmonella-containing vacuole occurred more rapidly for non-opsonized or SPI1-induced Salmonella compared with IgG-opsonized or complement-opsonized Salmonella. Finally, quantitative polymerase chain reaction was used to compare the transcriptional profiles of selected SPI1 and SPI2 regulon genes. We found that the magnitude of SPI2 gene induction depended on the mechanism of internalization. Unexpectedly, SPI1 genes, which are rapidly downregulated following SPI1-mediated invasion, were induced intracellularly following phagocytic uptake. These results reveal another level of complexity in pathogen-macrophage interactions. C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Hamilton, MT 59840 USA. RP Steele-Mortimer, O (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Hamilton, MT 59840 USA. EM omortimer@niaid.nih.gov FU Intramural NIH HHS NR 63 TC 53 Z9 55 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 JAN PY 2006 VL 7 IS 1 BP 39 EP 51 DI 10.1111/j.1600-0854.2005.00360.x PG 13 WC Cell Biology SC Cell Biology GA 008IX UT WOS:000235035100004 PM 16445685 ER PT J AU de Marco, MC Puertollano, R Martinez-Menarguez, JA Alonso, MA AF de Marco, MC Puertollano, R Martinez-Menarguez, JA Alonso, MA TI Dynamics of MAL2 during glycosylphosphatidylinositol-anchored protein transcytotic transport to the apical surface of hepatoma HepG2 cells SO TRAFFIC LA English DT Article DE apical recycling compartment; epithelial cell; GPI-anchored protein; hepatocyte; lipid rafts; MAL2; subapical compartment; transcytosis ID CANINE KIDNEY-CELLS; POLARIZED MDCK CELLS; EPITHELIAL-CELLS; PLASMA-MEMBRANE; CANALICULAR MEMBRANE; GOLGI; HEPATOCYTES; MACHINERY; COMPONENT; RECEPTOR AB Delivery of glycosylphosphatidylinositol (GPI)-anchored proteins to the apical surface takes place by transcytosis in hepatocytes and also probably in epithelial Madin-Darby canine cells. The integral protein MAL2 was demonstrated to be essential for basolateral-to-apical transcytosis in hepatoma HepG2 cells. Reduction of endogenous MAL2 levels impedes cargo delivery to the apical membrane, but, paradoxically, cargo does not accumulate in the subapical compartment where MAL2 predominantly resides but in distant endosome elements. To understand how transcytosis can be apparently mediated at a distance, we have analyzed the dynamics of machinery and cargo by live-cell imaging of MAL2 and transcytosing CD59, a GPI-anchored protein, in HepG2 cells. MAL2 was revealed as being a highly dynamic protein. Soon after basolateral enclocytosis of CD59, a fraction of MAL2 redistributed into peripheral vesicular clusters that concentrated CD59 and that were accessible to transferrin (Tf) receptor, a basolateral recycling protein. Following Tf receptor segregation, the clusters fused in a MAL2(+) globular structure and moved toward the apical surface for CD59 delivery. All these processes were impaired in cells with reduced MAL2 content. Other GPI-anchored proteins examined behave similarly. As MAL2 is expressed by many types of epithelia, the sorting events described herein are probably of quite general utility. C1 Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. CSIC, E-28049 Madrid, Spain. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Univ Murcia, Fac Med, Dept Biol Celular, E-30071 Murcia, Spain. RP Alonso, MA (reprint author), Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. EM maalonso@cbm.uam.es RI Alonso, Miguel/J-3945-2016 OI Alonso, Miguel/0000-0002-7001-8826 NR 37 TC 15 Z9 15 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 JAN PY 2006 VL 7 IS 1 BP 61 EP 73 DI 10.1111/j.1600-0854.2005.00361.x PG 13 WC Cell Biology SC Cell Biology GA 008IX UT WOS:000235035100006 PM 16445687 ER PT J AU Johnson, DR AF Johnson, DR TI Endothelial cell-mediated antigen presentation SO TRANSFUSION MEDICINE AND HEMOTHERAPY LA English DT Review DE endothelial cells; immune tolerance; transplantation tolerance; transgenes ID CYTOTOXIC T-LYMPHOCYTES; NORMAL HUMAN ORGANS; CLASS-II ANTIGENS; ADHESION MOLECULES; CD40 LIGAND; INTERLEUKIN-2 PRODUCTION; INDUCED ATHEROSCLEROSIS; DETAILED DISTRIBUTION; VASCULAR ENDOTHELIUM; ALLOGRAFT-REJECTION AB Immune recognition of endothelial cells (ECs) has been implicated in a number of vascular diseases. Although ECs have been shown to stimulate T lymphocytes in vitro, these conditions were not physiological, and it remained unclear what occurred in vivo. Antigen presentation by ECs in vivo was tested using transgenic mice that express a protein antigen (beta-galactosidase, beta-gal) exclusively in their ECs. This transgenic approach avoided potentially inflammatory manipulations. Transgenic mice responded to immunization with the antigen ( protein or DNA) with strong B and T cell-mediated immunity. No effects of the immune response on the vessels in vivo could be detected, and ECs continued to express beta-gal. Skin grafts from transgenic mice onto nontransgenic mice suffered a type of vascular rejection, strongly suggesting that specific lymphocytes in hosts recognize and respond against beta-gal+ ECs in the skin grafts. However, heart transplants containing beta-gal+ ECs were accepted indefinitely by nontransgenic hosts. Moreover, skin grafts with beta-gal+ ECs were accepted onto hosts with hearts containing beta-gal+ ECs, suggesting that the immune system had recognized and learned to tolerate the heart ECs. The implications for transplantation and persistent infection are discussed. C1 NIAID, Clin Immunol Branch, DAIT, NIH, Bethesda, MD 20892 USA. RP Johnson, DR (reprint author), NIAID, Clin Immunol Branch, DAIT, NIH, 6610 Rockledge Blvd, Bethesda, MD 20892 USA. EM drjohnson@niaid.nih.gov NR 128 TC 4 Z9 4 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-3796 J9 TRANSFUS MED HEMOTH JI Transfus. Med. Hemother. PY 2006 VL 33 IS 1 BP 58 EP 70 DI 10.1159/000090195 PG 13 WC Hematology; Immunology SC Hematology; Immunology GA 008HV UT WOS:000235031700007 ER PT J AU Anam, K Black, AT Hale, DA AF Anam, K Black, AT Hale, DA TI Low dose busulfan facilitates chimerism and tolerance in a murine model SO TRANSPLANT IMMUNOLOGY LA English DT Article DE chimerism; tolerance; transplantation; sirolimus; bone marrow ID DONOR-SPECIFIC TOLERANCE; NONLETHAL PREPARATIVE REGIMEN; ALLOGENEIC BONE-MARROW; TRANSPLANTATION TOLERANCE; HEMATOPOIETIC CHIMERISM; ALLOGRAFT TOLERANCE; CYNOMOLGUS MONKEYS; MIXED CHIMERISM; SKIN HOMOGRAFTS; MICE AB T cell depletion, sirolimus and "mega" dose donor specific bone marrow (DSBM) infusion promotes stable multilineage chimerism and indefinite survival of skin allografts in completely mismatched mice. The purpose of this study is to determine whether the addition of low dose busulfan can reduce the amount of DSBM required while preserving efficacy. C57BL/6 recipients of BALB/c skin allografts were treated with alpha CD4 and alpha CD8 monoclonal antibodies, DSBM, sirolimus and various doses of busulfan. The kinetics and phenotype of chimerism and the presence of clonal deletion of alloreactive T-cells were defined using flow cytometry. In vitro reactivity was determined using mixed lymphocyte culture. Second skin grafts confirmed the presence of tolerance. All doses of busulfan resulted in engraftment when combined with this regimen using a reduced dose of donor marrow. The level, kinetics and character of chimerism observed were dose related. Chimerism was associated with indefinite allogaft acceptance (> 200 days). Tolerance was documented both in vitro/in vivo and was associated with clonal deletion. Addition of a single low dose of busulfan to an established tolerance protocol reduced the required DSBM dose by over 80% while still promoting comparable levels of donor chimerism and donor-specific tolerance. Published by Elsevier B.V. C1 NIDDK, Transplantat Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Combat Casualty Care Directorate, Dept Defense, Radiat & Combat Injury Dept, Bethesda, MD 20892 USA. RP Hale, DA (reprint author), NIDDK, Transplantat Branch, Dept Hlth & Human Serv, NIH, Room 5-5-750,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM douglash@intra.niddk.nih.gov FU Intramural NIH HHS NR 25 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD JAN PY 2006 VL 15 IS 3 BP 199 EP 204 DI 10.1016/j.trim.2005.09.009 PG 6 WC Immunology; Transplantation SC Immunology; Transplantation GA 011JR UT WOS:000235264900003 PM 16431286 ER PT J AU Grill-Spector, K Henson, R Martin, A AF Grill-Spector, K Henson, R Martin, A TI Repetition and the brain: neural models of stimulus-specific effects SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID SHORT-TERM-MEMORY; LATERAL OCCIPITAL COMPLEX; MONKEY INFEROTEMPORAL CORTEX; INFERIOR TEMPORAL CORTEX; HUMAN VISUAL-CORTEX; CORTICAL ACTIVITY; FACE PERCEPTION; OBJECT RECOGNITION; ADAPTATION; NEURONS AB One of the most robust experience-related cortical dynamics is reduced neural activity when stimuli are repeated. This reduction has been linked to performance improvements due to repetition and also used to probe functional characteristics of neural populations. However, the underlying neural mechanisms are as yet unknown. Here, we consider three models that have been proposed to account for repetition-related reductions in neural activity, and evaluate them in terms of their ability to account for the main properties of this phenomenon as measured with single-cell recordings and neuroimaging techniques. We also discuss future directions for distinguishing between these models, which will be important for understanding the neural consequences of repetition and for interpreting repetition-related effects in neuroirnaging data. C1 Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. Stanford Univ, Neurosci Program, Stanford, CA 94305 USA. MRC, Cognit & Brain Sci Unit, Cambridge, England. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Grill-Spector, K (reprint author), Stanford Univ, Dept Psychol, Bldg 420, Stanford, CA 94305 USA. EM kalanit@psych.stanford.edu RI martin, alex/B-6176-2009; OI Grill-Spector, Kalanit/0000-0002-5404-9606 FU Medical Research Council [MC_U105579226] NR 94 TC 1051 Z9 1069 U1 7 U2 108 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD JAN PY 2006 VL 10 IS 1 BP 14 EP 23 DI 10.1016/j.tics.2005.11.006 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 006PW UT WOS:000234910400007 PM 16321563 ER PT J AU Dean, A AF Dean, A TI On a chromosome far, far away: LCRs and gene expression SO TRENDS IN GENETICS LA English DT Review ID BETA-GLOBIN LOCUS; RNA-POLYMERASE-II; RANGE INTRACHROMOSOMAL INTERACTIONS; HISTONE ACETYLATION PATTERN; CONTROL REGION; CHROMATIN DOMAIN; INTERGENIC TRANSCRIPTION; REGULATORY ELEMENTS; CYTOKINE GENES; ACTIVE GENES AB Transcription activation of a gene involves the ordered recruitment of components of the basal transcription machinery in concert with alterations in chromatin structure, including nucleosome remodeling and posttranslational modification of histones. Enhancers and locus control regions (LCRs) that are remote from the genes they activate, recruit the complexes that carry out these alterations and, sometimes, recruit RNA polymerase II. The question of how these distant activators interact with their target genes has been of long-standing interest. Recent data indicate that LCRs mediate contact with their coordinate genes through the formation of domains of histone modification and of intra- and inter-chromosomal loops and that they might localize genes within nuclear regions that favor transcription. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dean, A (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM anndean@helix.nih.gov FU Intramural NIH HHS NR 69 TC 113 Z9 117 U1 2 U2 12 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JAN PY 2006 VL 22 IS 1 BP 38 EP 45 DI 10.1016/j.tig.2005.11.001 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 006PR UT WOS:000234909900007 PM 16309780 ER PT J AU Aplan, PD AF Aplan, PD TI Causes of oncogenic chromosomal translocation SO TRENDS IN GENETICS LA English DT Review ID DOUBLE-STRAND BREAKS; DNA TOPOISOMERASE-II; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; BREAKPOINT CLUSTER REGION; INTERNATIONAL WORKSHOP; GENE FUSION; ILLEGITIMATE RECOMBINATION; MYELODYSPLASTIC SYNDROMES AB Non-random chromosomal translocations are frequently associated with a variety of cancers, particularly hematologic malignancies and childhood sarcomas. In addition to their diagnostic utility, chromosomal translocations are increasingly being used in the clinic to guide therapeutic decisions. However, the mechanisms that cause these translocations remain poorly understood. Illegitimate V(D)J recombination, class switch recombination, homologous recombination, nonhomologous end-joining and genome fragile sites all have potential roles in the production of non-random chromosomal translocations. In addition, mutations in DNA-repair pathways have been implicated in the production of chromosomal translocations in humans, mice and yeast. Although initially surprising, the identification of these same oncogenic chromosomal translocations in peripheral blood from healthy individuals strongly suggests that the translocation is not sufficient to induce malignant transformation, and that complementary mutations are required to produce a frank malignancy. C1 NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20889 USA. RP Aplan, PD (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM aplanp@mail.nih.gov RI Aplan, Peter/K-9064-2016 FU Intramural NIH HHS NR 86 TC 79 Z9 80 U1 1 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JAN PY 2006 VL 22 IS 1 BP 46 EP 55 DI 10.1016/j.tig.2005.10.002 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 006PR UT WOS:000234909900008 PM 16257470 ER PT J AU Babu, MM Aravind, L AF Babu, MM Aravind, L TI Adaptive evolution by optimizing expression levels in different environments SO TRENDS IN MICROBIOLOGY LA English DT Review ID ESCHERICHIA-COLI; ADAPTATION; GROWTH AB Organisms adapt to environmental changes through the fixation of mutations that enhance reproductive success. A recent study by Dekel and Alon demonstrated that Escherichia coli adapts to different growth conditions by fine-tuning protein levels, as predicted by a simple cost-benefit model. A study by Fong et al. showed that independent evolutionary trajectories lead to similar adaptive endpoints. Initial mutations on the path to adaptation altered the mRNA levels of numerous genes. Subsequent optimization through compensatory mutations restored the expression of most genes to baseline levels, except for a small set that retained differential levels of expression. These studies clarify how adaptation could occur by the alteration of gene expression. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Babu, MM (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM madanm@ncbi.nlm.nih.gov FU Intramural NIH HHS; Medical Research Council [MC_U105185859] NR 9 TC 31 Z9 32 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD JAN PY 2006 VL 14 IS 1 BP 11 EP 14 DI 10.1016/j.tim.2005.11.005 PG 4 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 009PB UT WOS:000235123200005 PM 16356718 ER PT J AU Ambudkar, IS AF Ambudkar, IS TI Ca2+ signaling microdomains: platforms for the assembly and regulation of TRPC channels SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID INOSITOL TRISPHOSPHATE RECEPTOR; CAPACITATIVE CALCIUM-ENTRY; STORE-OPERATED CHANNELS; SALIVARY-GLAND CELLS; PLASMA-MEMBRANE; CATION CHANNEL; ENDOPLASMIC-RETICULUM; POTENTIAL CHANNELS; SURFACE EXPRESSION; INSP(3) RECEPTORS AB The transient receptor potential canonical family (TRPC1-TRPC7) of ion channel proteins, which are activated in response to agonist-stimulated phosphatidylinositol (4,5)-bisphosphate [Ptdlns(4,5)P-2] hydrolysis, are proposed components of the elusive store-operated Ca2+ (SOC) channel. TRPC channels display distinct properties and interact to form homomeric or heteromeric channels that differ in their function and regulation. Although the exact function of TRPC channels and how they are regulated has not been established, increasing data suggest that they are localized and regulated within Ca2+ signaling microdomains. TRPC channels contribute to store-operated and store-independent Ca2+ entry mechanisms, both of which are activated by agonist-stimulated Ptdlns(4,5)P-2 hydrolysis. Elucidation of how cells achieve specificity and precise temporal and spatial coordination of channel activation is crucial for understanding the molecular basis of agonist-mediated stimulation of Ca2+ entry and identifying downstream physiological functions. This review will address the assembly and localization of TRPC channels and how these processes impact their function. C1 NIDCR, Secretory Physiol Sect, GTTB, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), NIDCR, Secretory Physiol Sect, GTTB, NIH, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov NR 86 TC 81 Z9 85 U1 1 U2 3 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 JAN PY 2006 VL 27 IS 1 BP 25 EP 32 DI 10.1016/j.tips.2005.11.008 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 009PE UT WOS:000235123600007 PM 16337693 ER PT J AU Doroshow, J AF Doroshow, James TI Role of the National Cancer Institute in cancer drug development SO TUMOR BIOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PY 2006 VL 27 SU 2 PG 1 WC Oncology SC Oncology GA 120IR UT WOS:000243078700037 ER PT J AU Low, JA AF Low, Jennifer A. TI Novel targets for cancer therapy. SO TUMOR BIOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Bethesda, MD USA. EM lowj@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PY 2006 VL 27 SU 2 PG 1 WC Oncology SC Oncology GA 120IR UT WOS:000243078700038 ER PT J AU Tracey, C Ramirez, J Singh, B Russell, E Stroupe, S Rucker, S Shea, N Russo, P Harvey, L Whiteley, G AF Tracey, Colpitts Ramirez, Javier Singh, Bhawani Russell, Eric Stroupe, Stephen Rucker, Sally Shea, Nancy Russo, Paul Harvey, Linda Whiteley, Gordon TI Proteomic study of lung cancer, benign lung disease, and normals. SO TUMOR BIOLOGY LA English DT Meeting Abstract C1 Clin Proteom, Abbott Labs, Abbott Mol, Chicago, IL USA. NCI Frederick, SAIC Frederick Inc, CPRL, Frederick, MD 21702 USA. EM tracey.colpitts@abbott.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PY 2006 VL 27 SU 2 PG 1 WC Oncology SC Oncology GA 120IR UT WOS:000243078700102 ER PT B AU Hesse, B Rutten, LF Beckjord, E Moser, R AF Hesse, B. Rutten, L. Finney Beckjord, E. Moser, R. GP Medimond TI The Health Information National Trends Survey: Surveillance of cancer prevention and communication constructs in the general US population SO UICC World Cancer Congress, Proceedings LA English DT Proceedings Paper CT World Cancer Congress of the International-Union-Against-Cancer (UICC) CY JUL 08-12, 2006 CL Washington, DC SP Int Union Against Canc C1 NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. RP Hesse, B (reprint author), NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-318-9 PY 2006 BP 301 EP 305 PG 5 WC Oncology SC Oncology GA BGE15 UT WOS:000246257800057 ER PT B AU Kang, SU Shi, ZD Kariki, R Phan, J Worthy, KM Bindu, LK Nicklaus, M Waugh, DS Fisher, RJ Burke, TR AF Kang, Sang-Uk Shi, Zhen-Dan Kariki, Rajeshri Phan, Jason Worthy, Karen M. Bindu, Lakshman K. Nicklaus, Marc Waugh, David S. Fisher, Robert J. Burke, Terrence R., Jr. BE Blondelle, SE TI Application of phenylphosphate mimetics to the design and synthesis of olefin metathesis-derived Grb2 SH2 domain-binding macrocycles SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts ID AFFINITY; LIGANDS C1 [Kang, Sang-Uk; Shi, Zhen-Dan; Kariki, Rajeshri; Nicklaus, Marc; Burke, Terrence R., Jr.] NCI, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. [Phan, Jason; Waugh, David S.] NCI, NIH, Macromol Crystllog Lab, CCR, Frederick, MD 21702 USA. [Worthy, Karen M.; Bindu, Lakshman K.; Fisher, Robert J.] Prot Chem Lab, SAIC Frederick, Frederick, MD 21702 USA. RP Kang, SU (reprint author), NCI, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. RI Burke, Terrence/N-2601-2014 NR 7 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 180 EP + DI 10.1007/978-0-387-26575-9_74 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800074 ER PT B AU Shi, ZD Peruzzi, B Dharmawardana, PG Leech, T Appella, E Worthy, KM Bindu, LK Fisher, RJ Bottaro, DP Burke, TR AF Shi, Zhen-Dan Peruzzi, Benedetta Dharmawardana, Pathirage G. Leech, Tiffany Appella, Ettore Worthy, Karen M. Bindu, Lakshman K. Fisher, Robert J. Bottaro, Donald P. Burke, Terrence R., Jr. BE Blondelle, SE TI Synthesis and use of C-terminally biotinylated peptidomimetics with high Grb2 SH2 domain-binding affinity SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts C1 [Shi, Zhen-Dan; Burke, Terrence R., Jr.] NCI, CCR, Med Chem Lab, NIH, Frederick, MD 21702 USA. [Peruzzi, Benedetta; Dharmawardana, Pathirage G.; Leech, Tiffany] Urol Oncol Branch, Bethesda, MD 20892 USA. [Appella, Ettore] NIH, NCI, CCR, Lab Cell Biol, Bethesda, MD 20892 USA. [Worthy, Karen M.; Bindu, Lakshman K.; Fisher, Robert J.] SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA. RP Shi, ZD (reprint author), NCI, CCR, Med Chem Lab, NIH, Frederick, MD 21702 USA. RI Burke, Terrence/N-2601-2014 NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 208 EP + DI 10.1007/978-0-387-26575-9_88 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800088 ER PT B AU Krajewski, K Marchand, C Pommier, Y Roller, PP AF Krajewski, Krzysztof Marchand, Christophe Pommier, Yves Roller, Peter P. BE Blondelle, SE TI Effect of dimerization and tetramerization on the potency of HIV-1 integrase inhibitory peptides SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts ID VIRUS TYPE-1 INTEGRASE; PROTEIN; CELLS C1 [Krajewski, Krzysztof; Roller, Peter P.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. [Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Krajewski, K (reprint author), NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. RI Marchand, Christophe/D-8559-2016 NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 411 EP + DI 10.1007/978-0-387-26575-9_171 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800171 ER PT B AU Roller, PP Jiang, S Li, P Long, YQ Lee, SL Lin, CY Johnson, M Dickson, RB AF Roller, Peter P. Jiang, Sheng Li, Peng Long, Ya-Qiu Lee, Sheau-Ling Lin, Cheng-Yong Johnson, Michael Dickson, Richard B. BE Blondelle, SE TI Sunflower derived trypsin inhibitors as anti-metastatics SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts ID SERINE-PROTEASE C1 [Roller, Peter P.; Jiang, Sheng; Li, Peng; Long, Ya-Qiu] NCI, Med Chem Lab, NIH, Bldg 376, Frederick, MD 21702 USA. [Lee, Sheau-Ling; Lin, Cheng-Yong; Johnson, Michael; Dickson, Richard B.] Georgetown Univ Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Roller, PP (reprint author), NCI, Med Chem Lab, NIH, Bldg 376, Frederick, MD 21702 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 485 EP + DI 10.1007/978-0-387-26575-9_208 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800208 ER PT B AU Guiotto, A Calderan, A Ruzza, P Osler, A Rubini, C Jo, DG Tang, SC Arumugam, TV Mattson, MP Borin, G AF Guiotto, Andrea Calderan, Andrea Ruzza, Paolo Osler, Alessio Rubini, Chiara Jo, Dong-Gyu Tang, Sung-Chun Arumugam, Thiruma V. Mattson, Mark P. Borin, Gianfranco BE Blondelle, SE TI Synthesis and evaluation of neuroprotective alpha,beta-unsaturated aldehyde scavenger histidyl-containing analogs of carnosine SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts C1 [Guiotto, Andrea; Calderan, Andrea; Ruzza, Paolo; Osler, Alessio; Rubini, Chiara; Borin, Gianfranco] CNR, Inst Biomol Chem, Padova Unit, I-35131 Padua, Italy. [Jo, Dong-Gyu; Tang, Sung-Chun; Arumugam, Thiruma V.; Mattson, Mark P.] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. RP Guiotto, A (reprint author), CNR, Inst Biomol Chem, Padova Unit, I-35131 Padua, Italy. RI Guiotto, Andrea/A-4720-2009; Arumugam, Thiruma/B-4898-2011; Ruzza, Paolo/N-6030-2015 OI Ruzza, Paolo/0000-0002-5596-9295 NR 5 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 491 EP + DI 10.1007/978-0-387-26575-9_211 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800211 ER PT B AU Jiang, S Nikolovska-Coleska, Z Wang, SM Roller, PP AF Jiang, Sheng Nikolovska-Coleska, Zaneta Wang, Shaomeng Roller, Peter P. BE Blondelle, SE TI Synthesis of symmetrical dimeric dicarboxylic acid linked peptides on solid support SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts C1 [Jiang, Sheng; Roller, Peter P.] NIH, NCI, CCR, Med Chem Lab, Frederick, MD 21702 USA. [Nikolovska-Coleska, Zaneta; Wang, Shaomeng] Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. RP Jiang, S (reprint author), NIH, NCI, CCR, Med Chem Lab, Frederick, MD 21702 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 505 EP + DI 10.1007/978-0-387-26575-9_218 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800218 ER PT B AU Shiotani, K Miyazaki, A Li, TY Tsuda, Y Yokoi, T Ambo, A Sasaki, Y Jinsmaa, Y Bryant, SD Lazarus, LH Okada, Y AF Shiotani, Kimitaka Miyazaki, Anna Li, Tingyou Tsuda, Yuko Yokoi, Toshio Ambo, Akihiro Sasaki, Yusuke Jinsmaa, Yunden Bryant, Sharon D. Lazarus, Lawrence H. Okada, Yoshio BE Blondelle, SE TI Systematic study on the structure-activity relationship of pyrazinone ring-containing bioactive opioid ligands SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts ID AMINO-ACIDS; PEPTIDES; AGONISTS C1 [Shiotani, Kimitaka; Li, Tingyou; Tsuda, Yuko; Yokoi, Toshio; Okada, Yoshio] Kobe Gakuin Univ, Grad Sch Food & Med Sci, Kobe, Hyogo 6512180, Japan. [Miyazaki, Anna; Tsuda, Yuko; Yokoi, Toshio; Okada, Yoshio] Kobe Gakuin Univ, Fac Pharmaceut Sci, Kobe, Hyogo 6512180, Japan. [Tsuda, Yuko; Yokoi, Toshio; Okada, Yoshio] Kobe Gakuin Univ, High Technol Res Ctr, Kobe, Hyogo 6512180, Japan. [Ambo, Akihiro; Sasaki, Yusuke] Tohoku Pharmaceut Univ, Sendai, Miyagi 9818558, Japan. [Jinsmaa, Yunden; Bryant, Sharon D.; Lazarus, Lawrence H.] NIEHS, LCBRA, Med Chem Grp, Res Triangle Pk, NC 27709 USA. RP Shiotani, K (reprint author), Kobe Gakuin Univ, Grad Sch Food & Med Sci, Kobe, Hyogo 6512180, Japan. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 507 EP + DI 10.1007/978-0-387-26575-9_219 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800219 ER PT B AU Dyba, M Tarasova, NI Kosakowska-Cholody, T Hamel, E Michejda, CJ AF Dyba, Marcin Tarasova, Nadya I. Kosakowska-Cholody, Teresa Hamel, Ernest Michejda, Christopher J. BE Blondelle, SE TI Tetra and pentapeptide derivatives of hemiasterlin. Synthesis and activity studies SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts ID CYTOTOXIC PEPTIDES C1 [Dyba, Marcin; Tarasova, Nadya I.; Kosakowska-Cholody, Teresa; Michejda, Christopher J.] NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21702 USA. [Hamel, Ernest] NCI, Screening Technol Branch, Frederick, MD 21702 USA. RP Dyba, M (reprint author), NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21702 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 509 EP + DI 10.1007/978-0-387-26575-9_220 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800220 ER PT B AU Lynch, MP Rawale, SV Behery, AA Hudleson, WP Takenouchi, N Yao, K Jacobson, S Kaumaya, PTP AF Lynch, Marcus P. Rawale, Sharad V. Behery, Ahmed A. Hudleson, William P. Takenouchi, Norihiro Yao, Karen Jacobson, Steven Kaumaya, Pravin T. P. BE Blondelle, SE TI Novel retro-inverso envelope peptide mimetic fusion inhibitors as a potential therapy for HTLV-1 infected individuals SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts ID PROTEINS C1 [Lynch, Marcus P.; Behery, Ahmed A.; Hudleson, William P.; Kaumaya, Pravin T. P.] NINDS, NIH, Dept Microbiol, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Lynch, Marcus P.; Rawale, Sharad V.; Kaumaya, Pravin T. P.] NINDS, NIH, Dept Obstet & Gynecol, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Takenouchi, Norihiro; Yao, Karen; Jacobson, Steven] NINDS, NIH, Viral Immunol Sec, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Kaumaya, Pravin T. P.] Ohio State Univ, Arthur G James Comprehensive Cancer Ctr, Columbus, OH 43210 USA. RP Lynch, MP (reprint author), NINDS, NIH, Dept Microbiol, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 527 EP + DI 10.1007/978-0-387-26575-9_229 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800229 ER PT B AU Liu, F Oishi, S Karki, R Shi, ZD Worthy, KM Bindu, LK Maderia, M Nicklaus, M Barchi, JJ Fisher, RJ Burke, TR AF Liu, Fa Oishi, Shinya Karki, Rajeshri Shi, Zhen-Dan Worthy, Karen M. Bindu, Lakshman K. Maderia, Melissa Nicklaus, Marc Barchi, Joseph J., Jr. Fisher, Robert J. Burke, Terrence R., Jr. BE Blondelle, SE TI High affinity Grb2 SH2 domain-binding macrocycles derived from ring-closing methathesis of alkenylglyiene residues with beta-vinyl phosphotyrosyl mimetics SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts C1 [Liu, Fa; Oishi, Shinya; Karki, Rajeshri; Shi, Zhen-Dan; Maderia, Melissa; Nicklaus, Marc; Barchi, Joseph J., Jr.; Burke, Terrence R., Jr.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. [Worthy, Karen M.; Bindu, Lakshman K.; Fisher, Robert J.] SAIC, Chem Lab, Ft Detrick, MD 21702 USA. RP Liu, F (reprint author), NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. RI Barchi Jr., Joseph/N-3784-2014; Burke, Terrence/N-2601-2014 NR 4 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 559 EP + DI 10.1007/978-0-387-26575-9_242 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800242 ER PT B AU Nikiforovich, GV Mihalik, B Catt, KJ Marshall, GR AF Nikiforovich, Gregory V. Mihalik, Balasz Catt, Kevin J. Marshall, Garland R. BE Blondelle, SE TI Molecular mechanisms of constitutive activity: Mutations at position 111 of the angiotensin AT(1) receptor SO UNDERSTANDING BIOLOGY USING PEPTIDES LA English DT Proceedings Paper CT 19th American Peptide Symposium CY JUN 18-23, 2005 CL San Diego, CA SP Amer Peptide Soc, AAPPTEC, Amer Peptide Co, Amer Hlth/GE Healthcare, Amgen, BACHEM, BIOMOL Int, C S Bio Co, Cambridge Res Biochem, Chemico Int, Chem Today, Eli Lilly & Co, ESCOM Sci Fdn, Genentech, Hoffman La Roche, Merck Res Labs, Midwest Bio Tech, NeoMPS Inc, New England BioLabs Inc, Novo Nordisk A S, Peptides Int Inc, PharmaChem Lab, PolyPeptide Labs, RSP Amino Acide LLC, Senn Chem USA, Sinopep Pharmaceut Inc, SynPep Corp, Synthetech, UCB Bioproducts C1 [Nikiforovich, Gregory V.; Marshall, Garland R.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. [Mihalik, Balasz; Catt, Kevin J.] Natl Inst Child Hlth & Human Dev, Endocrinol & Reprod Res Branch, Bethesda, MD USA. RP Nikiforovich, GV (reprint author), Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26569-4 PY 2006 BP 657 EP + DI 10.1007/978-0-387-26575-9_291 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFA80 UT WOS:000240543800291 ER PT J AU Sinha, S AF Sinha, Somdatta BE Wimmer, A Kossler, R TI Multiplicity in Non-Linear Systems SO UNDERSTANDING CHANGE: MODELS, METHODOLOGIES AND METAPHORS LA English DT Article; Book Chapter ID GENE-EXPRESSION; DYNAMICS; COMPLEXITY; MODERNITY; CHAOS C1 [Sinha, Somdatta] Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India. [Sinha, Somdatta] Ctr Adv Studies Berlin, Berlin, Germany. [Sinha, Somdatta] Univ Calif Santa Barbara, Inst Theoret Phys, Santa Barbara, CA 93106 USA. [Sinha, Somdatta] Santa Fe Inst, Santa Fe, NM USA. [Sinha, Somdatta] NIH, Bethesda, MD 20892 USA. [Sinha, Somdatta] Univ Oxford, Ctr Math Biol, Oxford OX1 2JD, England. RP Sinha, S (reprint author), Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India. NR 41 TC 0 Z9 0 U1 0 U2 0 PU PALGRAVE PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, ENGLAND BN 978-0-230-52464-4 PY 2006 BP 222 EP 234 D2 10.1057/9780230524644 PG 13 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BQK32 UT WOS:000281202500016 ER PT S AU Lang, PJ Davis, M AF Lang, Peter J. Davis, Michael BE Anders, S Ende, G Junghoffer, M Kissler, J Wildgruber, D TI Emotion, motivation, and the brain: Reflex foundations in animal and human research SO UNDERSTANDING EMOTIONS SE PROGRESS IN BRAIN RESEARCH LA English DT Review CT Symposium on Understanding Emotions CY SEP, 2004 CL Freudental Castle, Constance, GERMANY SP Heidelberg Acad Sci & Humanities, Unit Konstanz, Ctr Junior Researchers HO Freudental Castle DE fear; startle; amygdala; arousal; conditioning; valence ID FEAR-POTENTIATED STARTLE; AMYGDALOID CENTRAL NUCLEUS; STIMULUS REWARD ASSOCIATIONS; VISUAL CONDITIONED-STIMULI; BASOLATERAL AMYGDALA; PREFRONTAL CORTEX; D-AMPHETAMINE; ORBITOFRONTAL CORTEX; ANTICIPATORY ANXIETY; AFFECTIVE MODULATION AB This review will focus on a motivational circuit in the brain, centered on the amygdala, that underlies human emotion. This neural circuitry of appetitive/approach and defensive/avoidance was laid down early in our evolutionary history in primitive cortex, sub-cortex, and mid-brain, to mediate behaviors basic to the survival of individuals and the propagation of genes to coming generations. Thus, events associated with appetitive rewards, or that threaten danger or pain, engage attention and prompt information gathering more so than other input. Motive cues also occasion metabolic arousal, anticipatory responses, and mobilize the organism to prepare for action. Findings are presented from research with animals, elucidating these psychophysiological (e.g., cardiovascular, neuro-humoral) and behavioral (e.g., startle potentiation, "freezing") patterns in emotion, and defining their mediating brain circuits. Parallel results are described from experiments with humans, showing similar activation patterns in brain and body in response to emotion cues, co-varying with participants' reports of affective valence and increasing emotional arousal. C1 Univ Florida, Dept Clin & Hlth Psychol, NIMH Ctr Study Emot & Attention, Gainesville, FL 32610 USA. RP Lang, PJ (reprint author), Univ Florida, Dept Clin & Hlth Psychol, NIMH Ctr Study Emot & Attention, Gainesville, FL 32610 USA. EM plang@phhp.ufl.edu FU NIMH NIH HHS [MH 47840, MH 58922, MH 57250, MH 37757, MH 59906, MH43975, P50 MH52384] NR 182 TC 181 Z9 191 U1 14 U2 62 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-52182-8 J9 PROG BRAIN RES PY 2006 VL 156 BP 3 EP 29 DI 10.1016/S0079-6123(06)56001-7 PG 27 WC Neurosciences SC Neurosciences & Neurology GA BGH60 UT WOS:000247001200001 PM 17015072 ER PT S AU Sabatinelli, D Lang, PJ Bradley, MM Flaisch, T AF Sabatinelli, Dean Lang, Peter J. Bradley, Margaret M. Flaisch, Tobias BE Anders, S Ende, G Junghoffer, M Kissler, J Wildgruber, D TI The neural basis of narrative imagery: emotion and action SO UNDERSTANDING EMOTIONS SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Understanding Emotions CY SEP, 2004 CL Freudental Castle, Constance, GERMANY SP Heidelberg Acad Sci & Humanities, Unit Konstanz, Ctr Junior Researchers HO Freudental Castle DE emotion; script imagery; fMRI ID POSTTRAUMATIC-STRESS-DISORDER; VISUAL MENTAL-IMAGERY; HUMAN NAVIGATION; MOTOR EXECUTION; FUNCTIONAL MRI; CORTEX; ACTIVATION; BRAIN; FEAR; PERCEPTION AB It has been proposed that narrative emotional imagery activates an associative network of stimulus, semantic, and response (procedural) information. In previous research, predicted response components have been demonstrated through psychophysiological methods in peripheral nervous system. Here we investigate central nervous system concomitants of pleasant, neutral, and unpleasant narrative imagery with functional magnetic resonance imaging. Subjects were presented with brief narrative scripts over headphones, and then imagined themselves engaged in the described events. During script perception, auditory association cortex showed enhanced activation during affectively arousing (pleasant and unpleasant), relative to neutral imagery. Structures involved in language processing (left middle frontal gyrus) and spatial navigation (retrosplenium) were also active during script presentation. At the onset of narrative imagery, supplementary motor area, lateral cerebellum, and left inferior frontal gyrus were initiated, showing enhanced signal change during affectively arousing (pleasant and unpleasant), relative to neutral scripts. These data are consistent with a bioinformational model of emotion that considers response mobilization as the measurable output of narrative imagery. C1 Univ Florida, NIMH, Ctr Study Emot & Attention, Gainesville, FL 32608 USA. RP Sabatinelli, D (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attention, POB 100165 HSC, Gainesville, FL 32608 USA. RI Frank, David/E-8213-2012; OI sabatinelli, dean/0000-0001-7409-8504 FU NIMH NIH HHS [P50 MH072850-01] NR 43 TC 18 Z9 18 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-52182-8 J9 PROG BRAIN RES PY 2006 VL 156 BP 93 EP 103 DI 10.1016/S0079-6123(06)56005-4 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BGH60 UT WOS:000247001200005 PM 17015076 ER PT J AU Propert, KJ Mayer, RD Wang, Y Sant, GR Hanno, PM Peters, KM Kusek, JW AF Propert, KJ Mayer, RD Wang, Y Sant, GR Hanno, PM Peters, KM Kusek, JW CA Interstitial Cystitis Clinical Tri TI Responsiveness of symptom scales for interstitial cystitis SO UROLOGY LA English DT Article ID PENTOSAN POLYSULFATE; CLINICAL-TRIALS; INSTRUMENTS; HEALTH; INDEX AB Objectives. To evaluate the responsiveness of composite scales to change over time in a clinical trial of patients with interstitial cystitis (IC). The measurement of symptoms in IC includes the O'Leary-Sant Symptom and Problem Indexes and the University of Wisconsin Interstitial Cystitis Inventory and scales that measure the individual symptom domains of pain/discomfort, urgency, and voiding frequency. Methods. The data were derived from a randomized clinical trial conducted by the Interstitial Cystitis Clinical Trials Group. Participants met the National Institutes of Health-National Institute for Diabetes, and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency. The primary endpoint was a patient-reported global response assessment (GRA) at 24 weeks. Secondary endpoints included the three composite indexes, pain/discomfort and urgency, and 24-hour frequency. Responsiveness was assessed by comparing symptom score changes against response categories defined by the GRA. Results. Of the 121 subjects in the original trial, 94 with complete data were included. All three composite indexes were sensitive to subject improvement over time as measured by the GRA. A 1.2-point change in the O'Leary-Sant indexes and a 3. 1-point change in the Wisconsin IC inventory corresponded to a one-category change in the GRA. Individual symptoms were also responsive. The correlation was high among the changes in the six outcome measures. Conclusions. The three composite symptom scales are responsive to change over time in patients with IC. These indexes provide important insight into symptom changes and are recommended as secondary endpoints in future clinical trials of IC. Additional endpoints addressing individual symptom domains should also be considered to aid in the evaluation of effect mechanisms. C1 Univ Penn, Sch Med, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Rochester, Rochester, NY USA. Sanofi Synthelabo Inc, New York, NY USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. NIDDK, NIH, Bethesda, MD USA. RP Propert, KJ (reprint author), Univ Penn, Sch Med, Dept Epidemiol & Biostat, Blockley Hall,6th Floor,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kpropert@cceb.upenn.edu FU NIDDK NIH HHS [U01 DK54127, U01 DK54138, U01 DK54133, U01 DK54125, U01 DK54158, U01 DK54108] NR 11 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 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2006 VL 67 IS 1 BP 55 EP 59 DI 10.1016/j.urology.2005.07.014 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 019XA UT WOS:000235870300012 PM 16413332 ER PT S AU Sheets, RL AF Sheets, RL BE Sheets, R Petricciani, J TI Introduction to vaccine cell substrates 2004 SO Vaccine Cell Substrates 2004 SE DEVELOPMENTS IN BIOLOGICALS LA English DT Proceedings Paper CT Vaccine Cell Substrates 2004 Symposium CY JUN 29-JUL 01, 2004 CL Rockville, MD SP NIH, NIAID, Int Assoc Biol C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Sheets, RL (reprint author), NIAID, NIH, 6700B Rockledge Dr,Rm 5145, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1424-6074 BN 3-8055-7999-3 J9 DEV BIOLOGICALS JI Dev. Biols PY 2006 VL 123 BP 3 EP 7 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BEA67 UT WOS:000236477100001 ER PT S AU Sheets, RL AF Sheets, RL BE Sheets, R Petricciani, J TI Adventitious agent test methods SO Vaccine Cell Substrates 2004 SE DEVELOPMENTS IN BIOLOGICALS LA English DT Proceedings Paper CT Vaccine Cell Substrates 2004 Symposium CY JUN 29-JUL 01, 2004 CL Rockville, MD SP NIH, NIAID, Int Assoc Biol ID REVERSE-TRANSCRIPTASE ASSAY; MURINE LEUKEMIA VIRUSES; SIGNALS C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Sheets, RL (reprint author), NIAID, NIH, 6700B Rockledge Dr,Rm 5145, Bethesda, MD 20892 USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1424-6074 BN 3-8055-7999-3 J9 DEV BIOLOGICALS JI Dev. Biols PY 2006 VL 123 BP 135 EP 145 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BEA67 UT WOS:000236477100012 PM 16566441 ER PT S AU Priola, SA AF Priola, SA BE Sheets, R Petricciani, J TI Susceptibility of common laboratory fibroblasts to TSE infection SO Vaccine Cell Substrates 2004 SE DEVELOPMENTS IN BIOLOGICALS LA English DT Meeting Abstract CT Vaccine Cell Substrates 2004 Symposium CY JUN 29-JUL 01, 2004 CL Rockville, MD SP NIH, NIAID, Int Assoc Biol C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1424-6074 BN 3-8055-7999-3 J9 DEV BIOLOGICALS JI Dev. Biols PY 2006 VL 123 BP 311 EP 311 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BEA67 UT WOS:000236477100029 ER PT S AU Moody, TW Jensen, RT AF Moody, Terry W. Jensen, Robert T. BE Vaudry, H Laburthe, M TI Breast cancer VPAC1 receptors SO VIP, PACAP, AND RELATED PEPTIDES: FROM GENE TO THERAPY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on VIP, PACAP and Related Peptides CY SEP 11-14, 2005 CL Rouen, FRANCE SP Conseil Reg Haute-Normandie, Agglomerat Rouen, Inst Fed Rech Multidisciplinaires Peptides, Inst Natl Sante Rech Med, Municipal Rouen, Sci Act Haute-Normandie, Tech Chime-Biol Sante, Univ Paris 7, Univ Rouen DE VIP; chemotherapeutical; conjugate; breast cancer ID TISSUES; TUMORS; VIP AB VIP receptors were investigated in breast cancer biopsy specimens. Twenty biopsy specimens bound I-125-VIP with high affinity. Also, each of the 20 biopsy specimens had high amounts of VPAC1 receptor mRNA. MCF-7 cells have VPAC1 receptors that bound the VIP chemotherapeutic conjugate, (Ala(2,8,9,19,24,25,27) Nle(17), Lys(28))VIP-L2-camptothecin, with high affinity. VIP chemotherapeutic conjugates may be useful agents to inhibit the growth of breast cancer. C1 NCI, Dept Hlth & Human Serv, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Moody, TW (reprint author), NCI, Dept Hlth & Human Serv, Ctr Canc Res, NIH, Bldg 31,Rm 4A48,31 Ctr Dr, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov FU Intramural NIH HHS NR 11 TC 10 Z9 11 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-550-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1070 BP 436 EP 439 DI 10.1196/annals.1317.058 PG 4 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BEZ57 UT WOS:000240364200063 PM 16888206 ER PT S AU Goldberg, ME Bisley, JW Powell, KD Gottlieb, J AF Goldberg, Michael E. Bisley, James W. Powell, Keith D. Gottlieb, Jacqueline BE MartinezConde, S Macknik, SL Martinez, LM Alonso, JM Tse, PU TI Saccades, salience and attention: the role of the lateral intraparietal area in visual behavior SO VISUAL PERCEPTION, PT 2: FUNDAMENTALS OF AWARENESS: MULTI-SENSORY INTEGRATION AND HIGH-ORDER PERCEPTION SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the European Conference on Visual Perception CY AUG, 2005 CL Coruna, SPAIN DE lateral intraparietal area; saccade; attention; contrast sensitivity; monkey ID POSTERIOR PARIETAL CORTEX; SELECTIVE ATTENTION; SUPERIOR COLLICULUS; NEURONAL RESPONSES; SPATIAL ATTENTION; EYE-MOVEMENTS; MONKEY; REPRESENTATION; ENHANCEMENT; PRIMATE AB Neural activity in the lateral intraparietal area (LIP) has been associated with attention to a location in visual space, and with the intention to make saccadic eye movement. In this study we show that neurons in LIP respond to recently flashed task-irrelevant stimuli and saccade targets brought into the receptive field by a saccade, although they respond much to the same stimuli when they are stable in the environment. LIP neurons respond to the appearance of a flashed distractor even when a monkey is planning a memory-guided delayed saccade elsewhere. We then show that a monkey's attention, as defined by an increase in contrast sensitivity, is pinned to the goal of a memory-guided saccade throughout the delay period, unless a distractor appears, in which case attention transiently moves to the site of the distractor and then returns to the goal of the saccade. LIP neurons respond to both the saccade goal and the distractor, and this activity correlates with the monkey's locus of attention. In particular, the activity of LIP neurons predicts when attention migrates from the distractor back to the saccade goal. We suggest that the activity in LIP provides a salience map that is interpreted by the oculomotor system as a saccade goal when a saccade is appropriate, and simultaneously is used by the visual system to determine the locus of attention. C1 Columbia Univ Coll Phys & Surg, Ctr Neurobiol & Behav, Mahoney Ctr Brain & Behav, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Goldberg, ME (reprint author), Columbia Univ Coll Phys & Surg, Ctr Neurobiol & Behav, Mahoney Ctr Brain & Behav, New York, NY 10032 USA. EM meg2008@eolumbia.edu FU NEI NIH HHS [R24 EY015634, R24 EY015634-01, R24 EY015634-02, R24 EY015634-03, R24 EY015634-04] NR 44 TC 121 Z9 121 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-51927-6 J9 PROG BRAIN RES PY 2006 VL 155 BP 157 EP 175 DI 10.1016/S0079-6123(06)55010-1 PG 19 WC Neurosciences SC Neurosciences & Neurology GA BFZ43 UT WOS:000245615200010 PM 17027387 ER PT B AU Pajevic, S Aldroubi, A Basser, PJ AF Pajevic, S Aldroubi, A Basser, PJ BE Weickert, J Hagen, H TI Continuous tensor field approximation of diffusion tensor MRI data SO VISUALIZATION AND PROCESSING OF TENSOR FIELDS LA English DT Proceedings Paper CT Perspective Workshop on Visualization and Processing of Tensor Fields CY APR 18-23, 2004 CL Schloss Dagstuhl, GERMANY ID FEATURES; TRACKING; IMAGES; BRAIN; VISUALIZATION; PROJECTIONS; REDUCTION; PATHWAYS; TISSUES AB Diffusion Tensor MRI (DT-MRI) measurements are a discrete noisy sample of an underlying macroscopic effective diffusion tensor field, D(x), of water. This field is presumed to be piecewise continuous/smooth at a gross anatomical length scale. Here we describe a mathematical framework for obtaining an estimate of this tensor field from the measured DT-MRI data using a spline-based continuous approximation. This methodology facilitates calculation of new structural quantities and provides a framework for applying differential geometric methods to DT-MRI data. A B-spline approximation has already been used to improve robustness of DT-MRI fiber tractography. Here we propose a piecewise continuous approximation based on Non-Uniform Rational B-Splines (NURBS), which addresses some of the shortcomings of the previous implementation. C1 NIH, MSCL, CIT, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Math, Nashville, TN 37240 USA. Natl Inst Hlth, STBB, NICHD, Bethesda, MD 20892 USA. RP NIH, MSCL, CIT, Bethesda, MD 20892 USA. EM pajevic@nih.gov; aldroubi@math.vanderbilt.edu; pjbasser@helix.nih.gov NR 22 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-25032-8 PY 2006 BP 299 EP + DI 10.1007/3-540-31272-2_18 PG 7 WC Mathematics, Applied; Imaging Science & Photographic Technology SC Mathematics; Imaging Science & Photographic Technology GA BDV07 UT WOS:000235580100018 ER PT J AU Edgren, G Hjalgrim, H Tran, TN Rostgaard, K Shanwell, A Titlestad, K Jakobsson, L Gridley, G Wideroff, L Jersild, C Adami, J Melbye, M Reilly, M Nyren, O AF Edgren, G. Hjalgrim, H. Tran, T. N. Rostgaard, K. Shanwell, A. Titlestad, K. Jakobsson, L. Gridley, G. Wideroff, L. Jersild, C. Adami, J. Melbye, M. Reilly, M. Nyren, O. TI A population-based binational register for monitoring long-term outcome and possible disease concordance among blood donors and recipients SO VOX SANGUINIS LA English DT Article DE donation register; epidemiology; haemovigilance; transfusion register; transfusion transmitted disease ID TRANSFUSION; TRANSMISSION; RISKS AB Background and Objectives: Even with appropriate donor deferrals and advanced screening tests, the risk of disease transmission through blood transfusion cannot be completely disregarded. Efficient monitoring of possible disease transmission between blood donors and recipients should be an important component of a comprehensive haemovigilance system. Materials and Methods: We assembled the Scandinavian Donations and Transfusions (SCANDAT) database, with data on virtually all blood donors and recipients who have been registered at least once in any of the computerized local blood bank databases in Sweden and Denmark since the start of computerized registration in 1966. The records of these individuals, with their entire computerized donation and/or transfusion histories and all donor-component-recipient connections, were linked to nationwide population and health registers to attain essentially complete follow-up for up to 36 years regarding reproduction, hospital morbidity, cancer, and death. Results: After data cleaning, the database contained 1 134 290 blood donors who contributed 15 091 280 records of donations and 1 311 079 recipients who received 11 693 844 transfusions. The data quality in the existing data sources was satisfactory. From the data obtained from local blood banks, 4.6%, 1.6%, and 6.4% of the person, donation, and transfusion records, respectively, had to be discarded after review of the legitimacy of recorded values, and comparisons with independent, external databases. Conclusion: It is possible to use existing computerized data, collected in routine health care, in haemovigilance systems for monitoring long-term outcome and disease concordance in blood donors and transfusion recipients. C1 Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark. Merck Res Labs, Dept Epidemiol, Philadelphia, PA USA. Karolinska Univ Hosp, Dept Transfus Med, Stockholm, Sweden. Odense Univ Hosp, Dept Clin Immunol, DK-5000 Odense, Denmark. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Arhus Univ Hosp, Dept Clin Immunol, Aarhus, Denmark. Karolinska Inst, Clin Epidemiol Unit, Dept Med, S-10401 Stockholm, Sweden. RP Nyren, O (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. EM olof.nyren@ki.se RI Hernandez, Jessica/G-6527-2011; Edgren, Gustaf/F-4013-2014; OI Edgren, Gustaf/0000-0002-2198-4745; Rostgaard, Klaus/0000-0001-6220-9414 FU NCI NIH HHS [N01-CP-21175] NR 16 TC 38 Z9 40 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2006 VL 91 IS 4 BP 316 EP 323 DI 10.1111/j.1423-0410.2006.00817.x PG 8 WC Hematology SC Hematology GA 103WD UT WOS:000241917000007 PM 17105607 ER PT J AU Karmaliani, R Bann, CM Mahmood, MA Harris, HS Akhtar, S Goldenberg, RL Moss, N AF Karmaliani, Rozina Bann, Carla M. Mahmood, Mohammad A. Harris, Hillary S. Akhtar, Saeed Goldenberg, Robert L. Moss, Nancy TI Measuring antenatal depression and anxiety: Findings from a community-based study of women in Hyderabad, Pakistan SO WOMEN & HEALTH LA English DT Article DE Aga Khan University anxiety and depression scale; How I Feel scale; item response theory; depression; anxiety; pregnancy; Pakistan ID LOW-INCOME WOMEN; MATERNAL STRESS; SOCIAL SUPPORT; PREGNANCY; HEALTH; POSTPARTUM; PUNJAB; SYMPTOMS; OUTCOMES; COHORT AB This study evaluated the psychometric properties of two possible measures of depression and anxiety among pregnant women in Pakistan for use in the Global Network for Women's and Children's Health Research project, a collaborative, international multi-site research network investigating methods for improving pregnancy and birth outcomes in developing Countries. The first measure, the Aga Khan University Anxiety and Depression Scale (AKUADS), is an Urdu language scale originally developed for the general Pakistani population, whereas the second measure, the How I Feel. scale, was designed for pregnant women in the United States. In an earlier pilot study, we found that the two scales demonstrated similar levels of diagnostic validity. Because neither scale was designed for the specific population of interest, item response theory analyses were conducted to evaluate the psychometric properties of the scales at three levels of measurement: scale, item, and response option. The study results provide insights that may be useful to researchers or clinicians developing or using scales in this population. In particular, our findings suggest that scales designed for populations with lower literacy, such as our target population, may improve data quality by including no more than three response options (e.g., almost always, sometimes, and never) and keeping the direction of item wording consistent throughout the scale. Based on the results from the current study, we recommend a short form of the AKUADS which removes poorly functioning items and reduces respondent burden while retaining the reliability and validity of the longer form. C1 RTI Int, Res Triangle Pk, NC 27709 USA. Aga Khan Univ, Karachi 74800, Pakistan. Univ Adelaide, Adelaide, SA 5005, Australia. Kuwait Univ, Safat 13110, Kuwait. Univ Alabama Birmingham, Birmingham, AL 35294 USA. Natl Inst Child Hlth & Human Dev, Rockville, MD 20852 USA. RP Bann, CM (reprint author), RTI Int, POB 12194, Res Triangle Pk, NC 27709 USA. EM rozina.karmaliani@aku.edu; cmb@rti.org; afzal.mahmood@adelaide.edu.au; hharris@rti.org; saeed.akhtar@hsc.edu.kw; robert.goldenberg@ccc.uab.edu; nm28a@nih.gov NR 53 TC 7 Z9 7 U1 2 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0363-0242 EI 1541-0331 J9 WOMEN HEALTH JI Women Health PY 2006 VL 44 IS 3 BP 79 EP 103 DI 10.1300/J013v44n03_05 PG 25 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 133QL UT WOS:000244027400005 PM 17255067 ER PT J AU Sawyer, KM Wechsberg, WM Myers, BJ AF Sawyer, Kyla Marie Wechsberg, Wendee M. Myers, Bronwyn J. TI Cultural similarities and differences between a sample of Black/African and colored women in South Africa: Convergence of risk related to substance use, sexual behavior, and violence SO WOMEN & HEALTH LA English DT Article DE substance abuse; South Africa; women; violence; HIV; sexual risk behavior ID HIV-INFECTION; ATTRACTIVENESS; POWER AB South Africa is one of the six southern African countries where the HIV levels for childbearing women are 20% or higher. We conducted two focus groups aimed at developing an understanding of the intersections of substance abuse, sexual behavior, and violence affecting the lives of women of color in Cape Town, South Africa. Both Colored and Black/African participants reported using cannabis, methaqualone, and alcohol, although they differed on other drugs used. Black/African women also used heroin, and crack cocaine, whereas Colored women used methamphetamines. For participants in both groups, relationships with men affected sexual and substance use risk behaviors. Although the Black/African women did not trust men to use condoms, the Colored women in the study believed that almost all men use condoms. Both groups of women reported high rates of violence, with Colored participants reporting more gang violence and woman-on-woman violence compared with Black/African participants. The paper discusses these issues, as well as the implications for adapting a culturally specific, brief woman-focused HIV prevention intervention for the South African context. C1 NIDA, Res Triangle Pk, NC 27709 USA. RTI Int, Subst Abuse Treatment Evaluat & Intervent Program, Res Triangle Pk, NC 27709 USA. Med Res Council Cape Town, Alcohol & Drug Abuse Res Unit, ZA-7505 Cape Town, South Africa. RP Sawyer, KM (reprint author), NIDA, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM kms@rti.org; wmw@rti.org; bronwyn.myers@mrc.ac.za OI Myers, Bronwyn/0000-0003-0235-6716 FU NIDA NIH HHS [2R01 DA 11609-S2] NR 29 TC 25 Z9 25 U1 2 U2 3 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2006 VL 43 IS 2 BP 73 EP 92 DI 10.1300/J013v43n02_05 PG 20 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 108SR UT WOS:000242260000005 PM 17000612 ER PT S AU Carpenter, KD Korach, KS AF Carpenter, Karen D. Korach, Kenneth S. BE Creatsas, G Mastorakos, G Chrousos, GP TI Potential biological functions emerging from the different estrogen receptors SO WOMEN'S HEALTH AND DISEASE: GYNECOLOGIC, ENDOCRINE, AND REPRODUCTIVE ISSUES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th Athens Congress on Womens Health and Disease CY SEP 23-25, 2005 CL Athens, GREECE SP Athens Univ, Med Sch, Int Menopause Soc, European Menopause & Andropause Soc, Int Federat Gynecol & Obstet DE estradiol; estrogen receptor; uterus; ovary ID RAT GRANULOSA-CELLS; FOLLICLE-STIMULATING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; ENDOCRINE SEX REVERSAL; ER-BETA; NULL MICE; AROMATASE CYTOCHROME-P450; REPRODUCTIVE PHENOTYPES; OVARIAN-FOLLICLES; KNOCKOUT MOUSE AB Technological advances and new tools have brought about tremendous advances in elucidating the roles of estradiol and the estrogen receptors (ERs) in biological processes, especially within the female reproductive system. Development and analysis of multiple genetic models have provided insight into the particular functions of each of the ERs. This article reviews the insights into ER biology in female reproduction gained from the development and use of new types of experimental models. C1 NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X NR 50 TC 22 Z9 26 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-621-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1092 BP 361 EP 373 DI 10.1196/annals.1365.033 PG 13 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Obstetrics & Gynecology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Obstetrics & Gynecology GA BFZ47 UT WOS:000245624300032 PM 17308161 ER PT J AU Sanders, JM Chen, LJ Lebetkin, EH Burka, LT AF Sanders, JM Chen, LJ Lebetkin, EH Burka, LT TI Metabolism and disposition of 2,2 ',4,4 '-tetrabromodiphenyl ether following administration of single or multiple doses to rats and mice SO XENOBIOTICA LA English DT Article DE polybrominated diphenyl ether (PBDE); metabolism and disposition; persistent organic pollutant ID BROMINATED FLAME RETARDANTS; POLYBROMINATED DIPHENYL ETHERS; 2,2',4,4',5-PENTABROMODIPHENYL ETHER; IN-VITRO; EXPOSURE; TIME; ENVIRONMENT; COMPONENTS; INDUCTION; TISSUE AB The metabolism and disposition of C-14-labelled 2,2',4,4'-tetrabromodiphenyl ether (BDE47) were investigated in F344 rats and B6C3F1 mice. Approximately 75 - 85% of 1 mu mol BDE47 kg(-1) was absorbed following oral administration to either rats or mice. Sex and species differences were observed in tissue distribution and excretion of BDE47-derived radioactivity. Absorption and distribution of 14 C to major tissues were dose-proportional in male rats from 0.1 to 1000 mu mol kg(-1). BDE47-derived radioactivity increased in all rat and mouse tissues examined following repeated daily doses of 1 mu mol kg(-1). Accumulation of C-14 in tissues of mice was less than in corresponding rat tissues. Glutathione conjugates of BDE47 were excreted in rat bile. A glucuronide and a sulfate conjugate of 2,4-dibromophenol were detected in the urine of BDE47-treated rats. BDE47 appears to induce its own metabolism. Increased formation of reactive metabolites over time may correlate with toxicological effects in BDE47-treated rodents. C1 NIEHS, Lab Pharmacol & Chem, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Sanders, JM (reprint author), NIEHS, Lab Pharmacol & Chem, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM sander10@niehs.nih.gov FU Intramural NIH HHS NR 25 TC 32 Z9 34 U1 1 U2 9 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD JAN PY 2006 VL 36 IS 1 BP 103 EP 117 DI 10.1080/00498250500485107 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 016LZ UT WOS:000235623000008 PM 16507516 ER PT J AU Buerger, K Teipel, SJ Zinkowski, R Sunderland, T Andreasen, N Blennow, K Ewers, M DeBernardis, J Shen, Y Kerkman, D Du, YS Hampel, H AF Buerger, K Teipel, SJ Zinkowski, R Sunderland, T Andreasen, N Blennow, K Ewers, M DeBernardis, J Shen, Y Kerkman, D Du, YS Hampel, H TI Increased levels of CSF phosphorylated tau in apolipoprotein E epsilon 4 carriers with mild cognitive impairment SO NEUROSCIENCE LETTERS LA English DT Article DE Alzheimer's disease; mild cognitive impairment; apolipoprotein E; risk factor; phosphorylated tau protein; cerebrospinal fluid ID ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; PROTEIN; THREONINE-231 AB We investigated the correlation between the apolipoprotein E epsilon 4 allele (apoE epsilon 4) carrier status, a major risk factor of Alzheimer's disease (AD), and levels of tau protein phosphorylated at threonine 231 (P-tau(231P)) in cerebrospinal fluid (CSF) in predementia and clinical stages of AD and healthy controls (HC). Thirty-one subjects with mild cognitive impairment (MCI) who had converted to AD during follow-up were included, as well as 71 AD patients, and 29 HC subjects. In MCI, but not in AD and HC, CSF P-tau(231P) levels were significantly higher in apoE epsilon 4 carriers compared to non-carriers (p < 0.001). Controlling for disease duration, the apoE epsilon 4 effect on P-tau(231p) remained significant. Our study indicates that the apoE epsilon 4 carrier status should be considered when CSF P-tau(231P) is evaluated as biomarker candidate of AD in MCI subjects. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Munich, Dementia Res Sect, D-80336 Munich, Germany. Univ Munich, Memory Clin, Alzheimer Mem Ctr, D-80336 Munich, Germany. Univ Munich, Dept Psychiat, Geriatr Psychiat Branch, D-80336 Munich, Germany. Appl NeuroSolut Inc, Vernon Hills, IL 60061 USA. NIMH, NIH, Geriatr Psychiat Branch 10 3D41, Bethesda, MD 20892 USA. Huddinge Univ Hosp, Karolinska Inst, Div Geriatr Med, Neurotec, S-14186 Huddinge, Sweden. Univ Gothenburg, Sahlgrens Univ Hosp, Dept Clin Neurosci, Unit Neurochem, Molndal, Sweden. Sun Hlth Res Inst, Haldeman Lab Mol & Cellular Neurobiol, Sun City, AZ 85351 USA. Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. RP Buerger, K (reprint author), Univ Munich, Dementia Res Sect, Nussbaumstr 7, D-80336 Munich, Germany. EM katharina.buerger@med.uni-muenchen.de; zinkowski@appns.com; trey@helix.nih.gov; niels.andreasen@neurotec.ki.se; kaj.blennow@neuro.gu.se; yong.shen@sunhealth.org; ydu@iupui.edu; harald.hampel@med.uni-muenchen.de NR 13 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 31 PY 2005 VL 391 IS 1-2 BP 48 EP 50 DI 10.1016/j.neulet.2005.08.030 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 993MO UT WOS:000233958400010 PM 16165272 ER PT J AU Guidry, G Willison, BD Blakely, RD Landis, SC Habecker, BA AF Guidry, G Willison, BD Blakely, RD Landis, SC Habecker, BA TI Developmental expression of the high affinity choline transporter in cholinergic sympathetic neurons SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL LA English DT Article DE cholinergic differentiation; sympathetic development; sweat glands ID VESICULAR ACETYLCHOLINE TRANSPORTER; INTESTINAL-PEPTIDE GENE; SWEAT GLAND INNERVATION; NEUROTRANSMITTER PLASTICITY INVIVO; SIGNALING PATHWAYS; MOLECULAR-CLONING; CELL-LINE; RAT; TARGET; PHENOTYPE AB Choline uptake by the high affinity choline transporter (CHT) is the rate-limiting step in acetylcholine synthesis. Induction of CHT is therefore a critical step in cholinergic differentiation, and we examined the developmental expression of CHT in cholinergic sympathetic neurons that innervate rodent sweat glands. During postnatal development the earliest sympathetic axons in the rear footpads are noradrenergic, containing intense tyrosine hydroxylase inummoreactivity and lacking CHT-immunoreactivity (CHT-IR). By postnatal day 7 (P7) in mouse, and P10 in rat, weak CHT-IR appeared in axons associated with the sweat gland anlagen. CHT staining intensity increased during the following weeks in conjunction with plexus arborization and gland maturation. The pattern of CHT-immunoreactivity (CHT-IR) in the sweat gland innervation was similar to staining for the vesicular acetylcholine transporter and vasoactive intestinal peptide. Immunoblots of tissue from sympathectomized rats confirmed that most of the CHT in footpad was contained in sympathetic neurons. Although CHT expression has been reported in noradrenergic sympathetic neurons of the superior cervical ganglion, these data indicate that in the sympathetic neurons projecting to sweat glands CHT is present at detectable levels only after association with the glands. (c) 2005 Elsevier B.V. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. NINDS, Neural Dev Sect, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. RP Habecker, BA (reprint author), Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, L334,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM habecker@ohsu.edu OI Habecker, Beth/0000-0002-4658-8730 FU NHLBI NIH HHS [R01HL68231, R01 HL068231]; NIMH NIH HHS [R37 MH073159, R37MH073159] NR 41 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1566-0702 J9 AUTON NEUROSCI-BASIC JI Auton. Neurosci-Basic Clin. PD DEC 30 PY 2005 VL 123 IS 1-2 BP 54 EP 61 DI 10.1016/j.autneu.2005.10.001 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 996IC UT WOS:000234166600007 PM 16278103 ER PT J AU Le Provost, F Miyoshi, K Vilotte, JL Bierie, B Robinson, GW Hennighausen, L AF Le Provost, F Miyoshi, K Vilotte, JL Bierie, B Robinson, GW Hennighausen, L TI SOCS3 promotes apoptosis of mammary differentiated cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE mammary gland; suppressor of cytokine signalling; differentiation; involution; stromal adipocyte; epithelial cell; gene expression; prolactin; JAK/STAT pathway ID INDUCIBLE SH2-CONTAINING PROTEIN; GLAND DEVELOPMENT; TRANSGENIC MICE; MESSENGER-RNA; EXPRESSION; STAT5B; LIVER; PRL; SUPPRESSORS; INVOLUTION AB Growth and function of the mammary gland is regulated by cytokines and modulated by suppressor of cytokine signalling (SOCS) proteins. In vitro experiments demonstrated that SOCS3 can inhibit PRL induction of milk protein gene expression and STAT5 activation. We explored the SOCS3 expression pattern during mouse mammary development and its regulation by PRL and GH in wild-type and STAT5a-null mammary tissue. Our results suggest that, in vivo, PRL stimulates SOCS3 expression in stromal adipocytes, independently of STAT5a stimulation. In mammary epithelial cells, SOCS3 expression appears to be related to STAT3 activation. Together, our results are consistent with a role of SOCS3 in the mammary gland by promoting apoptosis of differentiated cells (adipocytes during gestation and epithelial cells during involution). (c) 2005 Elsevier Inc. All rights reserved. C1 NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. INRA, Lab Genet Biochim & Cytogenet, F-78350 Jouy En Josas, France. RP Le Provost, F (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. EM Fabienne.LeProvost@jouy.inra.fr RI Robinson, Gertraud/I-2136-2012 FU Intramural NIH HHS NR 23 TC 17 Z9 18 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 30 PY 2005 VL 338 IS 4 BP 1696 EP 1701 DI 10.1016/j.bbrc.2005.10.138 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 991LQ UT WOS:000233815900005 PM 16289036 ER PT J AU Sun, R Jaruga, B Kulkarni, S Sun, HY Gao, B AF Sun, R Jaruga, B Kulkarni, S Sun, HY Gao, B TI IL-6 modulates hepatocyte proliferation via induction of HGF/p21(cip1): Regulation by SOCS3 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE IL-6; liver regeneration; SOCS3; HGF; p21 ID LIVER-REGENERATION; INTERLEUKIN-6-DEFICIENT MICE; PARTIAL-HEPATECTOMY; MOUSE HEPATOCYTES; PRIMARY CULTURE; CELL-LINE; GROWTH; MET; ACTIVATION; EXPRESSION AB The precise role of IL-6 in liver regeneration and hepatocyte proliferation is controversial and the role of SOCS3 in liver regeneration remains unknown. Here we show that in vitro treatment with IL-6 inhibited primary mouse hepatocyte proliferation. IL-6 induced p21(cip1) protein expression in primary mouse hepatocytes. Disruption of the p21(cio1) gene abolished the inhibitory effect of IL-6 on cell proliferation. Co-culture with nonparenchymal liver cells diminished IL-6 inhibition of hepatocyte proliferation, which was likely due to IL-6 stimulation of nonparenchymal cells to produce HGF. Finally, IL-6 induced higher levels of p21(cip1) protein expression and a slightly stronger inhibition of cell proliferation in SOCS3(+/-) mouse hepatocytes compared to wild-type hepatocytes, while liver regeneration was enhanced and prolonged in SOCS3(+/-) mice. Our findings suggest that IL-6 directly inhibits hepatocyte proliferation via a p21(cip1)-dependent mechanism and indirectly enhances hepatocyte proliferation via stimulating nonparenchymal cells to produce HGF. SOCS3 negatively regulates liver regeneration. Published by Elsevier Inc. C1 NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov NR 31 TC 46 Z9 49 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 30 PY 2005 VL 338 IS 4 BP 1943 EP 1949 DI 10.1016/j.bbrc.2005.10.171 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 991LQ UT WOS:000233815900040 PM 16288983 ER PT J AU LaRonde-LeBlanc, N Wlodawer, A AF LaRonde-LeBlanc, N Wlodawer, A TI The RIO kinases: An atypical protein kinase family required for ribosome biogenesis and cell cycle progression SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article; Proceedings Paper CT 4th International Conference on Inhibitors of Protein Kinases (IPK 2005) CY JUN 25-29, 2005 CL Warsaw, POLAND DE atypical protein kinase; structure; ATP binding; enzymatic activity; ribosome biogenesis; Rio1; Rio2 ID RIBONUCLEOTIDE REDUCTASE ICP10; PYRUVATE-DEHYDROGENASE KINASE; CHRONIC MYELOID-LEUKEMIA; SIMPLEX-VIRUS TYPE-2; SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE; WINGED HELIX; CATALYTIC SUBUNIT; STRUCTURAL BASIS; FULGIDUS RIO2 AB Atypical protein kinases (aPKs) include proteins known to be involved in the phosphorylation-mediated regulation of a wide variety of cellular processes, as well as some for which the function is, as yet, unknown. At present, 13 families of aPKs have been identified in the human genome. This review briefly summarizes their known properties, but concentrates in particular on the RIO family of aPKs. Representatives of this family are present in organisms varying from archaea to humans. All these organisms contain at least two RIO proteins, Rio1 and Rio2, but a third Rio3 group is present in multicellular eukaryotes. Crystal structures of A. fulgidus Rio I and Rio2 have shown that whereas the overall fold of these enzymes resembles typical protein kinases, some of the kinase structural domains, particularly those involved in peptide substrate binding, are not present. The mode of binding of nucleotides also differs from other kinases. While the enzymatic activity of Rio I and Rio2 has been demonstrated and both have been shown to be essential in S. cerevisiae and required for proper cell cycle progression and chromosome maintenance, the biological substrates of RIO proteins still remain to be identified. Published by Elsevier B.V. C1 NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, Macromol Crystallog Lab, Bldg 536,Rm 5, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov RI LaRonde-LeBlanc, Nicole/C-3399-2009 OI LaRonde-LeBlanc, Nicole/0000-0002-2778-8358 NR 50 TC 49 Z9 52 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD DEC 30 PY 2005 VL 1754 IS 1-2 SI SI BP 14 EP 24 DI 10.1016/j.bbapap.2005.07.037 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 999AK UT WOS:000234360800003 PM 16182620 ER PT J AU Bailey-Wilson, JE Almasy, L de Andrade, M Bailey, J Bickeboller, H Cordell, HJ Daw, EW Goldin, L Goode, EL Gray-McGuire, C Hening, W Jarvik, G Maher, BS Mendell, N Paterson, AD Rice, J Satten, G Suarez, B Vieland, V Wilcox, M Zhang, HP Ziegler, A MacCluer, JW AF Bailey-Wilson, JE Almasy, L de Andrade, M Bailey, J Bickeboller, H Cordell, HJ Daw, EW Goldin, L Goode, EL Gray-McGuire, C Hening, W Jarvik, G Maher, BS Mendell, N Paterson, AD Rice, J Satten, G Suarez, B Vieland, V Wilcox, M Zhang, HP Ziegler, A MacCluer, JW TI Genetic Analysis Workshop 14: microsatellite and single-nucleotide polymorphism marker loci for genome-wide scans SO BMC GENETICS LA English DT Editorial Material C1 NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Gottingen, D-3400 Gottingen, Germany. Univ Cambridge, Dept Med Genet, Cambridge CB2 1TN, England. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Washington Univ, Sch Med, St Louis, MO USA. Ctr Dis Control, Atlanta, GA 30333 USA. Univ Iowa, Iowa City, IA USA. Boston Univ, Boston, MA 02215 USA. Yale Univ, New Haven, CT USA. Univ Luebeck, Lubeck, Germany. RP Bailey-Wilson, JE (reprint author), NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. EM jebw@mail.nih.gov; almasy@darwin.sfbr.org; mandrade@mayo.edu; jbailey@npih.mednet.ucla.edu; hbickeb@gwdg.de; heather.cordell@cimr.cam.ac.uk; warwick@request.mdacc.tmc.edu; goldinl@mail.nih.gov; egoode@mayo.edu; mcguire@darwin.epbi.cwru.edu; WAHeningMD@aol.com; pair@u.washington.edu; brion@pitt.edu; nmendell@notes.cc.sunysb.edu; andrew.paterson@utoronto.ca; john@zork.wustl.edu; gas0@cdc.gov; bks@themfs.wustl.edu; veronica-vieland@uiowa.edu; mwilcox@bu.edu; heping.zhang@yale.edu; ziegler@imbs.uni-luebeck.de; jean@darwin.sfbr.org RI Maher, Brion/F-9185-2010; Jarvik, Gail/N-6476-2014; Paterson, Andrew/A-4088-2011; OI Jarvik, Gail/0000-0002-6710-8708; Paterson, Andrew/0000-0002-9169-118X; Ziegler, Andreas/0000-0002-8386-5397; Satten, Glen/0000-0001-7275-5371 FU NHGRI NIH HHS [N01HG65403]; NIDDK NIH HHS [R01 DK031775]; NIGMS NIH HHS [R01 GM031575]; NIMH NIH HHS [T32 MH065213]; NINDS NIH HHS [R01 NS027941] NR 2 TC 8 Z9 8 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S1 DI 10.1186/1471-2156-6-S1-S1 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400001 PM 16451554 ER PT J AU Doan, BQ Frangakis, CE Shugart, YY Bailey-Wilson, JE AF Doan, BQ Frangakis, CE Shugart, YY Bailey-Wilson, JE TI Application of the propensity score in a covariate-based linkage analysis of the Collaborative Study on the Genetics of Alcoholism SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID GENOME-WIDE SEARCH; CONSUMPTION; DEPENDENCE; GENES; MODEL AB Background: Covariate-based linkage analyses using a conditional logistic model as implemented in LODPAL can increase the power to detect linkage by minimizing disease heterogeneity. However, each additional covariate analyzed will increase the degrees of freedom for the linkage test, and therefore can also increase the type I error rate. Use of a propensity score (PS) has been shown to improve consistently the statistical power to detect linkage in simulation studies. Defined as the conditional probability of being affected given the observed covariate data, the PS collapses multiple covariates into a single variable. This study evaluates the performance of the PS to detect linkage evidence in a genome-wide linkage analysis of microsatellite marker data from the Collaborative Study on the Genetics of Alcoholism. Analytical methods included nonparametric linkage analysis without covariates, with one covariate at a time including multiple PS definitions, and with multiple covariates simultaneously that corresponded to the PS definitions. Several definitions of the PS were calculated, each with increasing number of covariates up to a maximum of five. To account for the potential inflation in the type 1 error rates, permutation based p-values were calculated. Results: Results suggest that the use of individual covariates may not necessarily increase the power to detect linkage. However the use of a PS can lead to an increase when compared to using all covariates simultaneously. Specifically, PS3, which combines age at interview, sex, and smoking status, resulted in the greatest number of significant markers identified. All methods consistently identified several chromosomal regions as significant, including loci on chromosome 2, 6, 7, and 12. Conclusion: These results suggest that the use of a propensity score can increase the power to detect linkage for a complex disease such as alcoholism, especially when multiple important covariates can be used to predict risk and thereby minimize linkage heterogeneity. However, because the PS is calculated as a conditional probability of being affected, it does require the presence of observed covariate data on both affected and unaffected individuals, which may not always be available in real data sets. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. RP Doan, BQ (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. EM bdoan@jhmi.edu; cfrangak@jhsph.edu; yyao@jhsph.edu; jebw@mail.nih.gov OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCI NIH HHS [R03 CA113240-01, R03 CA113240]; NCRR NIH HHS [P41 RR003655, RR03655] NR 14 TC 5 Z9 5 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S33 DI 10.1186/1471-2156-6-S1-S33 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400033 PM 16451643 ER PT J AU Duggal, P Gillanders, EM Mathias, RA Ibay, GP Klein, AP Baffoe-Bonnie, AG Ou, L Dusenberry, IP Tsai, YY Chines, PS Doan, BQ Bailey-Wilson, JE AF Duggal, P Gillanders, EM Mathias, RA Ibay, GP Klein, AP Baffoe-Bonnie, AG Ou, L Dusenberry, IP Tsai, YY Chines, PS Doan, BQ Bailey-Wilson, JE TI Identification of tag single-nucleotide polymorphisms in regions with varying linkage disequilibrium SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID HAPLOTYPE; ALGORITHM; BLOCKS; GENOME; SNPS AB We compared seven different tagging single-nucleotide polymorphism ( SNP) programs in 10 regions with varied amounts of linkage disequilibrium (LD) and physical distance. We used the Collaborative Studies on the Genetics of Alcoholism dataset, part of the Genetic Analysis Workshop 14. We show that in regions with moderate to strong LD these programs are relatively consistent, despite different parameters and methods. In addition, we compared the selected SNPs in a multipoint linkage analysis for one region with strong LD. As the number of selected SNPs increased, the LOD score, mean information content, and type I error also increased. C1 NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Johns Hopkins Med Sch, CIDR, Baltimore, MD USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Duggal, P (reprint author), NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. EM pduggal@mail.nih.gov; lgilland@mail.nih.gov; rmathias1@mail.nih.gov; ibayg@mail.nih.gov; aklein@mail.nih.gov; A_Bonnie@fccc.edu; Liang.Ou@fccc.edu; idusenbe@gwu.edu; ytsai@cidr.jhmi.edu; pchines@mail.nih.gov; bdoan@mail.nih.gov; jebw@mail.nih.gov OI Bailey-Wilson, Joan/0000-0002-9153-2920 NR 15 TC 4 Z9 4 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S73 DI 10.1186/1471-2156-6-S1-S73 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400073 PM 16451687 ER PT J AU Joo, J Tian, X Zheng, G Lin, JP Geller, NL AF Joo, J Tian, X Zheng, G Lin, JP Geller, NL TI Selection of single-nucleotide polymorphisms in disease association data SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID EFFICIENCY ROBUST-TESTS; MICROARRAY EXPERIMENTS; CANDIDATE GENES; SAMPLE-SIZE; SURVIVAL AB We studied several methods for selecting single-nucleotide polymorphisms ( SNPs) in a disease association study. Two major categories for analytical strategy are the univariate and the set selection approaches. The univariate approach evaluates each SNP marker one at a time, while the set selection approach tests disease association of a set of SNP markers simultaneously. We examined various test statistics that can be utilized in testing disease association and also reviewed several multiple testing procedures that can properly control the family-wise error rates when the univariate approach is applied to multiple markers. The set association methods were then briefly reviewed. Finally, we applied these methods to the data from Collaborative Study on the Genetics of Alcoholism (COGA). C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Joo, J (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr MSC 7938, Bethesda, MD 20892 USA. EM jooj@nhlbi.nih.gov; tianx@nhlbi.nih.gov; zhengg@nhlbi.nih.gov; lingj@nhlbi.nih.gov; gellern@nhlbi.nih.gov NR 17 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S93 DI 10.1186/1471-2156-6-S1-S93 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400093 PM 16451709 ER PT J AU Kerstann, KF Jacobs, K Yang, XH Bergen, AW Goldin, LR Goldstein, AM AF Kerstann, KF Jacobs, K Yang, XH Bergen, AW Goldin, LR Goldstein, AM TI Identification of susceptibility loci for complex diseases in a case-control association study using the Genetic Analysis Workshop 14 dataset SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS AB Although current methods in genetic epidemiology have been extremely successful in identifying genetic loci responsible for Mendelian traits, most common diseases do not follow simple Mendelian modes of inheritance. It is important to consider how our current methodologies function in the realm of complex diseases. The aim of this study was to determine the ability of conventional association methods to fine map a locus of interest. Six study populations were selected from 10 replicates ( New York) from the Genetic Analysis Workshop 14 simulated dataset and analyzed for association between the disease trait and locus D2. Genotypes from 45 single-nucleotide polymorphisms in the telomeric region of chromosome 3 were analyzed by Pearson's chi-square tests for independence to test for association with the disease trait of interest. A significant association was detected within the region; however, it was found 3 cM from the documented location of the D2 disease locus. This result was most likely due to the method used for data simulation. In general, this study showed that conventional case-control association methods could detect disease loci responsible for the development of complex traits. C1 NIH, Div Canc Epidemiol & Genet, NCI, DHHS, Bethesda, MD 20892 USA. BioInformed LLC, Cleveland, OH USA. RP Kerstann, KF (reprint author), NIH, Div Canc Epidemiol & Genet, NCI, DHHS, Bldg 10, Bethesda, MD 20892 USA. EM kkerstan@mail.nih.gov; jacobs@bioinformed.com; royang@mail.nih.gov; bergena@mail.nih.gov; goldinl@mail.nih.gov; goldstea@mail.nih.gov OI Bergen, Andrew/0000-0002-1237-7644 NR 4 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S102 DI 10.1186/1471-2156-6-S1-S102 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400102 PM 16451558 ER PT J AU Klein, AP Tsai, YY Duggal, P Gillanders, EM Barnhart, M Mathias, RA Dusenberry, IP Turiff, A Chines, PS Goldstein, J Wojciechowski, R Hening, W Pugh, EW Bailey-Wilson, JE AF Klein, AP Tsai, YY Duggal, P Gillanders, EM Barnhart, M Mathias, RA Dusenberry, IP Turiff, A Chines, PS Goldstein, J Wojciechowski, R Hening, W Pugh, EW Bailey-Wilson, JE TI Investigation of altering single-nucleotide polymorphism density on the power to detect trait loci and frequency of false positive in nonparametric linkage analyses of qualitative traits SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID MICROSATELLITES; TESTS AB Genome-wide linkage analysis using microsatellite markers has been successful in the identification of numerous Mendelian and complex disease loci. The recent availability of high-density single-nucleotide polymorphism (SNP) maps provides a potentially more powerful option. Using the simulated and Collaborative Study on the Genetics of Alcoholism (COGA) datasets from the Genetics Analysis Workshop 14 (GAW14), we examined how altering the density of SNP marker sets impacted the overall information content, the power to detect trait loci, and the number of false positive results. For the simulated data we used SNP maps with density of 0.3 cM, 1 cM, 2 cM, and 3 cM. For the COGA data we combined the marker sets from Illumina and Affymetrix to create a map with average density of 0.25 cM and then, using a sub-sample of these markers, created maps with density of 0.3 cM, 0.6 cM, 1 cM, 2 cM, and 3 cM. For each marker set, multipoint linkage analysis using MERLIN was performed for both dominant and recessive traits derived from marker loci. Our results showed that information content increased with increased map density. For the homogeneous, completely penetrant traits we created, there was only a modest difference in ability to detect trait loci. Additionally, as map density increased there was only a slight increase in the number of false positive results when there was linkage disequilibrium (LD) between markers. The presence of LD between markers may have led to an increased number of false positive regions but no clear relationship between regions of high LD and locations of false positive linkage signals was observed. C1 NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Johns Hopkins Med Sch, CIDR, Baltimore, MD USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA. RP Klein, AP (reprint author), NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. EM aklein1@jhmi.edu; ytsai@cidr.jhmi.edu; pduggal@mail.nih.gov; lgilland@mail.nih.gov; mbarn@cidr.jhu.edu; rmathias1@mail.nih.gov; idusenbe@gwu.edu; aturiff@gwu.edu; pchines@mail.nih.gov; jgold@cidr.jhmi.edu; kassaq@mail.nih.gov; WAHeningMD@aol.com; ewp@cidr.jhmi.edu; jebw@mail.nih.gov OI Bailey-Wilson, Joan/0000-0002-9153-2920; Wojciechowski, Robert/0000-0002-9593-4652 NR 7 TC 6 Z9 6 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S20 DI 10.1186/1471-2156-6-S1-S20 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400020 PM 16451629 ER PT J AU Lin, JP Wu, C AF Lin, JP Wu, C TI Bivariate genome scans incorporating factor and principal component analyses to identify common genetic components of alcoholism, event-related potential, and electroencephalogram phenotypes SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID TRAIT LINKAGE ANALYSIS; DEPENDENCE AB Genetic components significantly contribute to the susceptibilities of alcoholism and its endophenotypes, such as event-related potential measures and electroencephalogram. An endophenotype is a correlated trait which identifies individuals at risk. Correlated traits could be influenced by shared genes. This study is intended to identify chromosome regions that may harbor common genetic loci contributing to alcoholism, event related potential measures and electroencephalogram. All 143 Collaborative Study on the Genetics of Alcoholism families with 1,614 individuals provided by the Genetic Analysis Workshop 14 were used for the analysis with aldx1 as an alcoholism diagnosis. We carried out factor and principal component analyses on the 12 event-related potentials, then bivariate genome scans on aldx1 and electroencephalogram (ecb21), as well as alcoholism and the principal component scores of the event-related potential measures. A univariate genome scan was also carried out on each trait. Factor and principal component analysis on the event-related potential measures showed that the 4 ttths and 4 ntths belong to one cluster (cluster 1), while the 4 ttdts belonged to another (cluster 2). From each cluster, one principal component was extracted and saved as pc1 (for cluster 1) and pc2 (for cluster 2). The results of genome scans revealed only one chromosome region, chromosome 4 q at about 100 cM, identified by several univariate genome scans including aldx1, ecb21, and pc2, and the evidence of linkage increased significantly in the bivariate genome scans of aldx1 and ecb21 and aldx1 and pc2. Our study suggests that the same quantitative trait locus on the chromosome 4 q region, where ADH3 is located, may influence the risk of alcoholism, variations of electroencephalogram, and the 4 ttdts of the event-related potential measures. C1 NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Lin, JP (reprint author), NHLBI, Off Biostat Res, NIH, 6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. EM linj@nhlbi.nih.gov; wuc@nhlbi.nih.gov NR 8 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S114 DI 10.1186/1471-2156-6-S1-S114 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400114 PM 16451571 ER PT J AU Marroni, F Toni, C Pennato, B Tsai, YY Duggal, P Bailey-Wilson, JE Presciuttini, S AF Marroni, F Toni, C Pennato, B Tsai, YY Duggal, P Bailey-Wilson, JE Presciuttini, S TI Haplotypic structure of the X chromosome in the COGA population sample and the quality of its reconstruction by extant software packages SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID INFERENCE AB Background: The haplotypes of the X chromosome are accessible to direct count in males, whereas the diplotypes of the females may be inferred knowing the haplotype of their sons or fathers. Here, we investigated: 1) the possible large-scale haplotypic structure of the X chromosome in a Caucasian population sample, given the single-nucleotide polymorphism ( SNP) maps and genotypes provided by Illumina and Affimetrix for Genetic Analysis Workshop 14, and, 2) the performances of widely used programs in reconstructing haplotypes from population genotypic data, given their known distribution in a sample of unrelated individuals. Results: All possible unrelated mother-son pairs of Caucasian ancestry ( N = 104) were selected from the 143 families of the Collaborative Study on the Genetics of Alcoholism pedigree files, and the diplotypes of the mothers were inferred from the X chromosomes of their sons. The marker set included 313 SNPs at an average density of 0.47 Mb. Linkage disequilibrium between pairs of markers was computed by the parameter D', whereas for measuring multilocus disequilibrium, we developed here an index called D*, and applied it to all possible sliding windows of 5 markers each. Results showed a complex pattern of haplotypic structure, with regions of low linkage disequilibrium separated by regions of high values of D*. The following programs were evaluated for their accuracy in inferring population haplotype frequencies: 1) ARLEQUIN 2.001; 2) PHASE 2.1.1; 3) SNPHAP 1.1; 4) HAPLOBLOCK 1.2; 5) HAPLOTYPER 1.0. Performances were evaluated by Pearson correlation ( r) coefficient between the true and the inferred distribution of haplotype frequencies. Conclusion: The SNP haplotypic structure of the X chromosome is complex, with regions of high haplotype conservation interspersed among regions of higher haplotype diversity. All the tested programs were accurate ( r = 1) in reconstructing the distribution of haplotype frequencies in case of high D* values. However, only the program PHASE realized a high correlation coefficient ( r > 0.7) in conditions of low linkage disequilibrium. C1 Ctr Retrovirus, Ctr Stat Genet, I-56127 Pisa, Italy. Univ Pisa, Unit Legal Med, Pisa, Italy. NHGRI, Ctr Inherited Dis Res, NIH, Baltimore, MD USA. RP Presciuttini, S (reprint author), Ctr Retrovirus, Ctr Stat Genet, SS Abetone & Brennero 2, I-56127 Pisa, Italy. EM fabio.marroni@biomed.unipi.it; chiara@hint.it; b.pennato@libero.it; ytsai@cidr.jhmi.edu; pduggal@nhgri.nih.gov; jebw@nhgri.nih.gov; sprex@biomed.unipi.it OI Marroni, Fabio/0000-0002-1556-5907; Bailey-Wilson, Joan/0000-0002-9153-2920 NR 10 TC 6 Z9 6 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S77 DI 10.1186/1471-2156-6-S1-S77 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400077 PM 16451691 ER PT J AU Nicodemus, KK Liu, WL Chase, GA Tsai, YY Fallin, MD AF Nicodemus, KK Liu, WL Chase, GA Tsai, YY Fallin, MD TI Comparison of type I error for multiple test corrections in large single-nucleotide polymorphism studies using principal components versus haplotype blocking algorithms SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID RECONSTRUCTION AB Although permutation testing has been the gold standard for assessing significance levels in studies using multiple markers, it is time-consuming. A Bonferroni correction to the nominal p-value that uses the underlying pair-wise linkage disequilibrium (LD) structure among the markers to determine the number of effectively independent tests has recently been proposed. We propose using the number of independent LD blocks plus the number of independent single-nucleotide polymorphisms for correction. Using the Collaborative Study on the Genetics of Alcoholism LD data for chromosome 21, we simulated 1,000 replicates of parent-child trio data under the null hypothesis with two levels of LD: moderate and high. Assuming haplotype blocks were independent, we calculated the number of independent statistical tests using 3 haplotype blocking algorithms. We then compared the type I error rates using a principal components-based method, the three blocking methods, a traditional Bonferroni correction, and the unadjusted p-values obtained from FBAT. Under high LD conditions, the PC method and one of the blocking methods were slightly conservative, whereas the 2 other blocking methods exceeded the target type I error rate. Under conditions of moderate LD, we show that the blocking algorithm corrections are closest to the desired type I error, although still slightly conservative, with the principal components-based method being almost as conservative as the traditional Bonferroni correction. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. Penn State Univ, Coll Med, Dept Hlth Evaluat Sci, Hershey, PA USA. Natl Genome Res Inst, Ctr Inherited Dis Res, NIH, Baltimore, MD USA. RP Fallin, MD (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. EM knicodem@jhsph.edu; wliu@hes.hmc.psu.edu; gchase@hes.hmc.psu.edu; ytsai@cidr.jhmi.edu; dfallin@jhsph.edu NR 9 TC 43 Z9 47 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S78 DI 10.1186/1471-2156-6-S1-S78 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400078 PM 16451692 ER PT J AU Papanicolaou, GJ Justice, CM Kovac, IM Sorant, AJM Wilson, AF AF Papanicolaou, GJ Justice, CM Kovac, IM Sorant, AJM Wilson, AF TI Critical values and variation in type I error along chromosomes in the COGA dataset using the applied pseudo-trait method SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS AB Background: By analyzing a "pseudo-trait," a trait not linked or associated with any of the markers tested, the distribution of the test statistic under the null hypothesis can provide the critical value for the appropriate percentile of the distribution. In addition, the anecdotal observation that p-values tend to be more significant near the telomeres was investigated. Results: The applied pseudo-trait (APT) method was applied to the Affymetrix and Illumina SNPs in the Collaborative Study on the Genetics of Alcoholism dataset to determine appropriate critical values for regression of offspring on mid-parent (ROMP) and Haseman-Elston association and linkage analyses, investigating the occurrence of type I errors in different chromosomal locations, and the extent to which the critical values obtained depend on the type of pseudo-trait used. Conclusion: On average, the 5 percentile critical values obtained for this study were less than the expected 0.05. The distribution of p-values does not seem to depend on chromosomal position for ROMP association analysis methods, but does in some cases for Haseman-Elston linkage analysis. Results vary with different pseudo-traits. C1 NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. RP Papanicolaou, GJ (reprint author), NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. EM gjp@mail.nih.gov; cmj@mail.nih.gov; ikovac@mail.nih.gov; ajms@mail.nih.gov; afw@mail.nih.gov RI Wilson, Alexander/C-2320-2009 FU NCRR NIH HHS [P41 RR003655, RR03655] NR 8 TC 2 Z9 2 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S54 DI 10.1186/1471-2156-6-S1-S54 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400054 PM 16451666 ER PT J AU Roy-Gagnon, MH Mathias, RA Wilson, AF AF Roy-Gagnon, MH Mathias, RA Wilson, AF TI Application of the regression of offspring on mid-parent method to detect associations between single-nucleotide polymorphisms and the beta 2 electroencephalogram phenotype in the COGA data SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID ALCOHOL DEPENDENCE; CANDIDATE GENES; LINKAGE AB The beta 2 electroencephalogram ( EEG) phenotype is used as a quantitative measure related to alcoholism, and evidence of linkage and association has previously been reported in the Collaborative Study on the Genetics of Alcoholism data. In this study, associations between the beta 2 EEG phenotype and single nucleotide polymorphisms from whole-genome Illumina and Affymetrix panels were investigated with the regression of offspring on mid-parent method to identify significant genetic effects and to estimate their heritability. Separate regressions on father and mother were performed to identify parent-specific effects. Estimates of the heritability of the beta 2 EEG phenotype were 0.68 +/- 0.12 and 0.52 +/- 0.07 based on father-offspring and mother-offspring pairs, respectively. Significant associations at the 0.0005 level, some of which were parent-specific, were found on chromosomes 1, 2, 5, 6, 7, 8, 11, 12, 15, 16, 17, 18, and 19 with heritability attributable to each SNP ranging from 0.01 to 8%. C1 NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. RP Roy-Gagnon, MH (reprint author), NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. EM mhrg@mail.nih.gov; rmathias1@mail.nih.gov; afw@mail.nih.gov RI Wilson, Alexander/C-2320-2009 FU NCRR NIH HHS [P41 RR003655, RR03655] NR 11 TC 5 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S56 DI 10.1186/1471-2156-6-S1-S56 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400056 PM 16451668 ER PT J AU Tian, X Joo, J Zheng, G Lin, JP AF Tian, X Joo, J Zheng, G Lin, JP TI Robust trend tests for genetic association in case-control studies using family data SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID SAMPLE-SIZE; SURVIVAL; MARKERS; POWER AB We studied a trend test for genetic association between disease and the number of risk alleles using case-control data. When the data are sampled from families, this trend test can be adjusted to take into account the correlations among family members in complex pedigrees. However, the test depends on the scores based on the underlying genetic model and thus it may have substantial loss of power when the model is misspecified. Since the mode of inheritance will be unknown for complex diseases, we have developed two robust trend tests for case-control studies using family data. These robust tests have relatively good power for a class of possible genetic models. The trend tests and robust trend tests were applied to a dataset of Genetic Analysis Workshop 14 from the Collaborative Study on the Genetics of Alcoholism. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Tian, X (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM tianx@nhlbi.nih.gov; jooj@nhlbi.nih.gov; zhengg@nhlbi.nih.gov; linj@nhlbi.nih.gov NR 13 TC 5 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S107 DI 10.1186/1471-2156-6-S1-S107 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400107 PM 16451563 ER PT J AU Yang, S Joo, J Feng, ZD Lin, JP AF Yang, S Joo, J Feng, ZD Lin, JP TI A new family-based association test via a least-squares method SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID MODEL AB To test the association between a dichotomous phenotype and genetic marker based on family data, we propose a least-squares method using the vector of phenotypes and their cross products within each family. This new approach allows covariate adjustment and is numerically much simpler to implement compared to likelihood-based methods. The new approach is asymptotically equivalent to the generalized estimating equation approach with a diagonal working covariance matrix, thus avoiding some difficulties with the working covariance matrix reported previously in the literature. When applied to the data from Collaborative Study on the Genetics of Alcoholism, this new method shows a significant association between the marker rs1037475 and alcoholism. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98109 USA. RP Yang, S (reprint author), NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. EM yangso@nhlbi.nih.gov; jooj@nhlbi.nih.gov; zfeng@fhcrc.org; linj@nhlbi.nih.gov NR 9 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S110 DI 10.1186/1471-2156-6-S1-S110 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400110 PM 16451567 ER PT J AU Yang, XH Jacobs, K Kerstann, KF Bergen, AW Goldstein, AM Goldin, LR AF Yang, XH Jacobs, K Kerstann, KF Bergen, AW Goldstein, AM Goldin, LR TI Linkage analysis of the GAW14 simulated dataset with microsatellite and single-nucleotide polymorphism markers in large pedigrees SO BMC GENETICS LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS ID LOCI; MAPS AB Recent studies have suggested that a high-density single nucleotide polymorphism (SNP) marker set could provide equivalent or even superior information compared with currently used microsatellite (STR) marker sets for gene mapping by linkage. The focus of this study was to compare results obtained from linkage analyses involving extended pedigrees with STR and single-nucleotide polymorphism (SNP) marker sets. We also wanted to compare the performance of current linkage programs in the presence of high marker density and extended pedigree structures. One replicate of the Genetic Analysis Workshop 14 (GAW14) simulated extended pedigrees (n=50) from New York City was analyzed to identify the major gene D2. Four marker sets with varying information content and density on chromosome 3 (STR [7.5 cM]; SNP [3 cM, 1 cM, 0.3 cM]) were analyzed to detect two traits, the original affection status, and a redefined trait more closely correlated with D2. Multipoint parametric and nonparametric linkage analyses (NPL) were performed using programs GENEHUNTER, MERLIN, SIMWALK2, and S.A.G.E. SIBPAL. Our results suggested that the densest SNP map (0.3 cM) had the greatest power to detect linkage for the original trait (genetic heterogeneity), with the highest LOD score/NPL score and mapping precision. However, no significant improvement in linkage signals was observed with the densest SNP map compared with STR or SNP-1 cM maps for the redefined affection status (genetic homogeneity), possibly due to the extremely high information contents for all maps. Finally, our results suggested that each linkage program had limitations in handling the large, complex pedigrees as well as a high-density SNP marker set. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. BioInformed LLC, Cleveland, OH USA. RP Yang, XH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM royang@mail.nih.gov; jacobs@bioinformed.com; kkerstann@mail.nih.gov; bergena@mail.nih.gov; goldstea@mail.nih.gov; goldin1@mail.nih.gov OI Bergen, Andrew/0000-0002-1237-7644 NR 14 TC 4 Z9 4 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 30 PY 2005 VL 6 SU 1 AR S14 DI 10.1186/1471-2156-6-S1-S14 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 023CR UT WOS:000236103400014 PM 16451599 ER PT J AU Chen, JH Avci, FY Munoz, EM McDowell, LM Chen, M Pedersen, LC Zhang, LJ Linhardt, RJ Liu, J AF Chen, JH Avci, FY Munoz, EM McDowell, LM Chen, M Pedersen, LC Zhang, LJ Linhardt, RJ Liu, J TI Enzymatic redesigning of biologically active heparan sulfate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HERPES-SIMPLEX-VIRUS; FIBROBLAST-GROWTH-FACTOR; 3-O-SULFOTRANSFERASE ISOFORM-5; ANTITHROMBIN-III; SUBSTRATE SPECIFICITIES; ENTRY RECEPTOR; GLYCOPROTEIN-D; BIOSYNTHESIS; BINDING; OLIGOSACCHARIDES AB Heparan sulfate carries a wide range of biological activities, regulating blood coagulation, cell differentiation, and inflammatory responses. The sulfation patterns of the polysaccharide are essential for the biological activities. In this study, we report an enzymatic method for the sulfation of multimilligram amounts of heparan sulfate with specific functions using immobilized sulfotransferases combined with a 3'-phosphoadenosine 5'-phosphosulfate regeneration system. By selecting appropriate enzymatic modification steps, an inactive precursor has been converted to the heparan sulfate having three distinct biological activities, associated with binding to antithrombin, fibroblast growth factor-2, and herpes simplex virus envelope glycoprotein D. Because the recombinant sulfotransferases are expressed in bacteria, and the method uses a low cost sulfo donor, it can be readily utilized to synthesize large quantities of anticoagulant heparin drug or other biologically active heparan sulfates. C1 Univ N Carolina, Div Med Chem & Nat Prod, Sch Pharm, Chapel Hill, NC 27599 USA. Rensselaer Polytech Inst, Dept Chem & Chem Biol, Troy, NY 12180 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Liu, J (reprint author), Univ N Carolina, Div Med Chem & Nat Prod, Sch Pharm, Rm 309,Beard Hall, Chapel Hill, NC 27599 USA. EM jian_liu@unc.edu FU NHLBI NIH HHS [HL52622, R01 HL052622, R01 HL062244, R01 HL062244-05A1]; NIAID NIH HHS [AI50050, R01 AI050050]; NIGMS NIH HHS [R01 GM038060-17, GM069968, GM38060, R01 GM038060, R01 GM038060-16A2, R01 GM069968] NR 46 TC 69 Z9 73 U1 2 U2 22 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 30 PY 2005 VL 280 IS 52 BP 42817 EP 42825 DI 10.1074/jbc.M504338200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 996UO UT WOS:000234200800043 PM 16260789 ER PT J AU Xu, GH Sztalryd, C Lu, XY Tansey, JT Gan, JW Dorward, H Kimmel, AR Londos, C AF Xu, GH Sztalryd, C Lu, XY Tansey, JT Gan, JW Dorward, H Kimmel, AR Londos, C TI Post-translational regulation of adipose differentiation-related protein by the ubiquitin/proteasome pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UBIQUITIN-PROTEASOME PATHWAY; HORMONE-SENSITIVE LIPASE; A-MEDIATED LIPOLYSIS; LIPID DROPLETS; PERILIPIN-A; MESSENGER-RNA; ADIPOCYTE LIPOLYSIS; CELLS; DEGRADATION; EXPRESSION AB Adipose differentiation-related protein ( ADRP) is localized to lipid droplets in most mammalian cells. ADRP, proposed to regulate fatty acid mobilization and lipid droplet formation, is linked to lipid accumulation in foam cells of human atherosclerotic lesions. In this report, we show that ADRP protein accumulates in Chinese hamster ovary fibroblastic cells cultured in the presence of oleic acid but is destabilized when fatty acid sources are removed from culture serum. The latter effect was blocked by the proteasome inhibitor MG132, whereas inhibitors of other proteolytic processes were ineffective. Pulse-chase experiments confirmed that ADRP degradation is inhibited by MG132. Conditions that stimulate ADRP degradation also promoted the covalent modification of ADRP by ubiquitin, whereas the addition of oleic acid to culture media, which promotes triacylglycerol deposition, blunted the appearance of ubiquitinated-ADRP. Treatment with MG132 increased the levels of ADRP associated with lipid droplets, as well as throughout the cytosol. Finally, we demonstrate that the disappearance of ADRP protein after the onset of perilipin expression during adipocyte differentiation is due to degradation by proteasomes Thus, proteolytic degradation of ADRP mediated through the ubiquitin/proteasome pathway appears to be a major mode for the post-translational regulation of ADRP. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100083, Peoples R China. Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100083, Peoples R China. RP Londos, C (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Rm 3140, Bethesda, MD 20892 USA. EM DeanL@intra.niddk.nih.gov FU Intramural NIH HHS NR 48 TC 141 Z9 151 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 30 PY 2005 VL 280 IS 52 BP 42841 EP 42847 DI 10.1074/jbc.M506569200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 996UO UT WOS:000234200800046 PM 16115879 ER PT J AU Hetz, C Vitte, PA Bombrun, A Rostovtseva, TK Montessuit, S Hiver, A Schwarz, MK Church, DJ Korsmeyer, SJ Martinou, JC Antonsson, B AF Hetz, C Vitte, PA Bombrun, A Rostovtseva, TK Montessuit, S Hiver, A Schwarz, MK Church, DJ Korsmeyer, SJ Martinou, JC Antonsson, B TI Bax channel inhibitors prevent mitochondrion-mediated apoptosis and protect neurons in a model of global brain ischemia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; CYTOCHROME-C RELEASE; CELL-DEATH; PROAPOPTOTIC BAX; FORMING ACTIVITY; ION-CHANNEL; BCL-2; MEMBRANES; VDAC; OLIGOMERIZATION AB Ischemic injuries are associated with several pathological conditions, including stroke and myocardial infarction. Several studies have indicated extensive apoptotic cell death in the infarcted area as well as in the penumbra region of the infarcted tissue. Studies with transgenic animals suggest that the mitochondrion-mediated apoptosis pathway is involved in ischemia-related cell death. This pathway is triggered by activation of pro-apoptotic Bcl-2 family members such as Bax. Here, we have identified and synthesized two low molecular weight compounds that block Bax channel activity. The Bax channel inhibitors prevented cytochrome c release from mitochondria, inhibited the decrease in the mitochondrial membrane potential, and protected cells against apoptosis. The Bax channel inhibitors did not affect the conformational activation of Bax or its translocation and insertion into the mitochondrial membrane in cells undergoing apoptosis. Furthermore, the compounds protected neurons in an animal model of global brain ischemia. The protective effect in the animal model correlated with decreased cytochrome c release in the infarcted area. This is the first demonstration that Bax channel activity is required in apoptosis. C1 Serono Pharmaceut Res Inst, CH-1228 Geneva, Switzerland. NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Chile, Inst Ciencias Biomed, Santiago, Chile. RP Antonsson, B (reprint author), Serono Pharmaceut Res Inst, 14 Chem Aulx, CH-1228 Geneva, Switzerland. EM bruno.antonsson@serono.com RI Hetz, Claudio/I-1900-2013 OI Hetz, Claudio/0000-0001-7724-1767 NR 44 TC 91 Z9 98 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 30 PY 2005 VL 280 IS 52 BP 42960 EP 42970 DI 10.1074/jbc.M505843200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 996UO UT WOS:000234200800059 PM 16219766 ER PT J AU Ulmer, TS Bax, A AF Ulmer, TS Bax, A TI Comparison of structure and dynamics of micelle-bound human alpha-synuclein and Parkinson disease variants SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-STRUCTURE DETERMINATION; MOLECULAR FRAGMENT REPLACEMENT; RESIDUAL DIPOLAR COUPLINGS; MODEL-FREE APPROACH; BIOLOGICAL MACROMOLECULES; SECONDARY STRUCTURE; ALZHEIMERS-DISEASE; BACKBONE DYNAMICS; GLOBULAR-PROTEINS; FIBRIL FORMATION AB Three point mutations (A30P, E46K, and A53T) as well as gene triplication genetically link the 140-residue protein alpha-synuclein (aS) to the development of Parkinson disease. Here, the structure and dynamics of micelle-bound aS( A30P) and aS( A53T) are described and compared with wild-type aS, in addition to describing the aS-micelle interaction. A53T is sensed only by directly adjacent residues and leaves the backbone structure and dynamics indistinguishable from the wild type. A30P interrupts one helix turn (Val(26)-Ala(29)) and destabilizes the preceding one. A shift in helix register following A30P disturbs the canonical succession of polar and hydrophobic residues for at least two turns. The shortened helix-N adopts a slightly higher helical content and is less bent, indicating that strain was present in the micelle-bound helix. In the vicinity of the A30P-induced perturbations, the underlying micelle environment has rearranged, but nevertheless all aS variants maintain similar interrelationships with the micelle. Moreover, aS-micelle immersion correlates well with fast and slow aS backbone dynamics, allowing a rare insight into protein-micelle interplay. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room B1-31,5 Mem Dr, Bethesda, MD 20892 USA. EM tulmer@usc.edu; bax@nih.gov FU Intramural NIH HHS NR 78 TC 87 Z9 92 U1 0 U2 21 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 30 PY 2005 VL 280 IS 52 BP 43179 EP 43187 DI 10.1074/jbc.M507624200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 996UO UT WOS:000234200800084 PM 16166095 ER PT J AU Hayes, RB Husgafvel-Pursiainen, K Vainio, H AF Hayes, RB Husgafvel-Pursiainen, K Vainio, H TI Molecular epidemiology: Convergence between toxicology and epidemiology SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Editorial Material ID LUNG-CANCER; PROJECT C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Finnish Inst Occupat Hlth, FIN-00250 Helsinki, Finland. RP Hayes, RB (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8114, Bethesda, MD 20892 USA. EM hayesr@exchange.nih.gov OI Hayes, Richard/0000-0002-0918-661X NR 11 TC 0 Z9 0 U1 0 U2 0 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 DEC 30 PY 2005 VL 592 IS 1-2 BP 1 EP 2 DI 10.1016/j.mrfmmm.2005.05.009 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 996UC UT WOS:000234199400001 PM 15993432 ER PT J AU Raimondi, S Boffetta, P Anttila, S Brockmoller, J Butkiewicz, D Cascorbi, I Clapper, ML Dragani, TA Garte, S Gsur, A Haidinger, G Hirvonen, A Ingelman-Sundberg, M Kalina, I Lan, Q Leoni, VP Le Marchand, L London, SJ Neri, M Povey, AC Rannug, A Reszka, E Ryberg, D Risch, A Romkes, M Ruano-Ravina, A Schoket, B Spinola, M Sugimura, H Wu, XF Taioli, E AF Raimondi, S Boffetta, P Anttila, S Brockmoller, J Butkiewicz, D Cascorbi, I Clapper, ML Dragani, TA Garte, S Gsur, A Haidinger, G Hirvonen, A Ingelman-Sundberg, M Kalina, I Lan, Q Leoni, VP Le Marchand, L London, SJ Neri, M Povey, AC Rannug, A Reszka, E Ryberg, D Risch, A Romkes, M Ruano-Ravina, A Schoket, B Spinola, M Sugimura, H Wu, XF Taioli, E TI Metabolic gene polymorphisms and lung cancer risk in non-smokers - An update of the GSEC study SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT Satellite Meeting on Linking Toxicology to Epidemiology - Biomarkers and New Technologies CY 2004 CL Haikko, FINLAND DE pooled analysis; epidemiology; genetic susceptibility ID S-TRANSFERASE M1; ENVIRONMENTAL TOBACCO-SMOKE; SQUAMOUS-CELL CARCINOMA; LOS-ANGELES-COUNTY; DNA ADDUCT LEVELS; GSTT1 POLYMORPHISMS; AFRICAN-AMERICANS; CLASS-MU; N-ACETYLTRANSFERASE; GSTM1 GENOTYPES AB Background: Since genetic factors may play an important role in lung cancer development at low dose carcinogen exposure, non-smokers are a good model to study genetic susceptibility and its interaction with environmental factors. Materials and methods: We evaluated the role of the metabolic gene polymorphisms CYP1A1MsPI, CYP1A11le(462) Val, GSTM1, and GSTT1 in non-smoker lung cancer patients from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Non-smokers (defined as subjects who never smoked on a regular basis) were selected from the GSEC database. We pooled the raw data from 21 case-control studies for a total of 2764 Caucasians (555 cases and 2209 controls) and 383 Asians (113 cases and 270 controls). Tests of heterogeneity and of inclusion bias were performed. Results: A significant association between lung cancer and CYP1A11le(462)Val polymorphism was observed in Caucasians (adjusted OR= 2.04, 95% Cl 1.17-3.54). GSTT1 deletion seems to be a risk factor for lung cancer in Caucasian non smokers only when the analysis was restricted to studies including healthy controls (adjusted OR= 1.66, 95% Cl 1.12-2.46). A protective effect on lung cancer was observed with the combination of CYP1A1 wild type, GSTM1 null, and GSTT1 non-null genotypes. None of the analysed polymorphisms were associated with lung cancer in Asian non-smokers. Discussion: Our analysis confirms previous findings that CYP1A11le(462) Val polymorphism may play a role in lung carcinogenesis in Caucasian non-smokers. (c) 2005 Elsevier B.V. All rights reserved. C1 IRCCS, Fondaz Policlin, Mol & Genet Epidemiol Unit, I-20122 Milan, Italy. Int Agcy Res Canc, F-69372 Lyon, France. Finnish Inst Occupat Hlth, Helsinki, Finland. Univ Gottingen, Inst Clin Pharmacol, D-3400 Gottingen, Germany. Ctr Oncol, Dept Tumor Biol, Gliwice, Poland. Univ Hosp Schleswig Holstein, Inst Pharmacol, Kiel, Germany. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Ist Nazl Tumori, Dept Expt Oncol, I-20133 Milan, Italy. ONLUS, Genet Res Inst, Milan, Italy. Med Univ Vienna, Canc Res Inst, Vienna, Austria. Karolinska Inst, Dept Physiol Chem, S-10401 Stockholm, Sweden. Safarik Univ, Sch Med, Dept Med Biol, Kosice, Slovakia. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Natl Inst Canc Res, Environm Epidemiol Unit, Genoa, Italy. Univ Manchester, Sch Epidemiol & Hlth Sci, Manchester, Lancs, England. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. Inst Occupat Med, Dept Toxicol & Carcinogenesis, Lodz, Poland. Natl Inst Occupat Hlth, Dept Toxicol, Oslo, Norway. DKFZ, German Canc Res Ctr, Dept Toxicol & Canc Risk Factors, Heidelberg, Germany. Univ Pittsburgh, Pittsburgh, PA USA. Univ Santiago de Compostela, Dept Prevent Med & Publ Hlth, Santiago De Compostela, Spain. Natl Inst Environm Hlth, Jozsef Fodor Natl Ctr Publ Hlth, Budapest, Hungary. Hamamatsu Univ Sch Med, Dept Pathol 1, Hamamatsu, Shizuoka 43131, Japan. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. RP Taioli, E (reprint author), IRCCS, Fondaz Policlin, Mol & Genet Epidemiol Unit, Via Pace 9, I-20122 Milan, Italy. EM epidemiologia@policlinico.mi.it RI Cascorbi, Ingolf/A-4519-2009; Raimondi, Sara/J-5236-2016; Dragani, Tommaso/K-4493-2016; Neri, Monica/J-6308-2012; Risch, Angela/H-2669-2013 OI Raimondi, Sara/0000-0003-4673-9049; London, Stephanie/0000-0003-4911-5290; Dragani, Tommaso/0000-0001-5915-4598; Neri, Monica/0000-0003-4796-3675; Risch, Angela/0000-0002-8026-5505 NR 82 TC 37 Z9 38 U1 0 U2 2 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 DEC 30 PY 2005 VL 592 IS 1-2 BP 45 EP 57 DI 10.1016/j.mrfmmm.2005.06.002 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 996UC UT WOS:000234199400007 PM 16009381 ER PT J AU Hayes, RB Sigurdson, A Moore, L Peters, U Huang, WY Pinsky, P Reding, D Gelmann, EP Rothman, N Pfeiffer, RM Hoover, RN Berg, CD AF Hayes, RB Sigurdson, A Moore, L Peters, U Huang, WY Pinsky, P Reding, D Gelmann, EP Rothman, N Pfeiffer, RM Hoover, RN Berg, CD CA PLCO Trial Team TI Methods for etiologic and early marker investigations in the PLCO trial SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT Satellite Meeting on Linking Toxicology to Epidemiology - Biomarkers and New Technologies CY 2004 CL Haikko, FINLAND DE cohort; molecular epidemiology; cancer ID OVARIAN-CANCER; DIAGNOSTIC PERFORMANCE; CT COLONOGRAPHY; PROTEOMICS; SERUM; CLASSIFICATION AB With the rapid development of biomarkers and new technologies, large-scale biologically-based cohort studies present expanding opportunities for population-based research on disease etiology and early detection markers. The prostate, lung, colorectal and ovarian cancer (PLCO) screening trial is a large randomized trial designed to determine if screening for these cancers leads to mortality reduction for these diseases. Within the Trial, the PLCO etiology and early marker study (EEMS) identifies risk factors for cancer and other diseases and evaluates biologic markers for the early detection of disease. EEMS includes 155,000 volunteers who provide basic risk factor information. Serial blood samples are collected at each of six screening rounds (including one collection for cryopreserved whole blood) from screening arm participants (77,000 subjects) and buccal cells are collected from those in the control arm of the trial. Etiologic studies consider environmental (e.g., diet), biochemical, and genetic factors. Early detection studies focus on blood-based biologic markers of early disease. Clinical epidemiology is also an important component of the PLCO trial. Published by Elsevier B.V. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98109 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RP Hayes, RB (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8114, Bethesda, MD 20892 USA. EM hayesr@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; OI Hayes, Richard/0000-0002-0918-661X NR 34 TC 88 Z9 90 U1 0 U2 2 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 DEC 30 PY 2005 VL 592 IS 1-2 BP 147 EP 154 DI 10.1016/j.mrfmmm.2005.06.013 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 996UC UT WOS:000234199400015 PM 16054167 ER PT J AU Jacobson, KA Gao, ZG Tchilibon, S Duong, HT Joshi, BV Sonin, D Liang, BT AF Jacobson, KA Gao, ZG Tchilibon, S Duong, HT Joshi, BV Sonin, D Liang, BT TI Semirational design of (North)-methanocarba nucleosides as dual acting A(1) and A(3) adenosine receptor agonists: Novel prototypes for cardioprotection SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DERIVATIVES; PROTECTION; SUBTYPES; INJURY; POTENT; PHARMACOLOGY; SELECTIVITY; ACTIVATION; LIGANDS; MOUSE AB Ring-constrained adenosine analogues have been designed to act as dual agonists at tissue-protective A, and A(3) adenosine receptors (ARs). 9-Ribosides transformed into the ring-constrained (N)-methanocarba-2-chloro-5'-uronamides consistently lost affinity at A(1)/A(2A)ARs and gained at A(3)AR. Among 9-riboside derivatives, only N-6-cyclopentyl and 7-norbornyl moieties were extrapolated for mixed A(1)/A(3) selectivity and rat/human A(3)AR equipotency. Consequently, 2 was balanced in affinity and potency at A(1)/A(3)ARs as envisioned and dramatically protected in an intact heart model of global ischemia and reperfusion. C1 NIDDK, Mol Recognit Sect, NIH, LBC, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Dept Cardiol, Farmington, CT 06030 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, NIH, LBC, Bldg 8A,Rm B1A-19, 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 DK031126-01, Z01 DK031115-24, Z01 DK031117-20]; NHLBI NIH HHS [R01 HL482325] NR 28 TC 18 Z9 18 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 29 PY 2005 VL 48 IS 26 BP 8103 EP 8107 DI 10.1021/jm050726b PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 998EQ UT WOS:000234301800001 PM 16366590 ER PT J AU Costanzi, S Joshi, BV Maddileti, S Mamedova, L Gonzalez-Moa, MJ Marquez, VE Harden, TK Jacobson, KA AF Costanzi, S Joshi, BV Maddileti, S Mamedova, L Gonzalez-Moa, MJ Marquez, VE Harden, TK Jacobson, KA TI Human P2Y(6) receptor: Molecular modeling leads to the rational design of a novel agonist based on a unique conformational preference SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID EXTRACELLULAR LOOPS; LIGAND RECOGNITION; NUCLEOSIDES; DYNAMICS; ANALOGS AB Combining molecular dynamics (MD) in a hydrated phospholipid (DOPC) bilayer, a Monte Carlo search, and synthesis of locked nucleotide analogues, we discovered that the Southern conformation of the ribose is preferred for ligand recognition by the P2Y(6) receptor. 2'-Deoxy-(S)-methanocarbaUDP was found to be a full agonist of the receptor and displayed a 10-fold higher potency than that for the corresponding flexible 2'-deoxyUDP. MD results also suggested a conformational change of the second extracellular loop consequent to agonist binding. C1 NIDDK, Computat Chem Core Lab & Mol Recognit Sect, NIH, DHHS, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. NCI, Med Chem Lab, NIH, DHHS, Frederick, MD 21702 USA. RP Costanzi, S (reprint author), NIDDK, Computat Chem Core Lab & Mol Recognit Sect, NIH, DHHS, Bethesda, MD 20892 USA. EM stefanoc@mail.nih.gov RI Jacobson, Kenneth/A-1530-2009; Costanzi, Stefano/G-8990-2013; OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS [Z01 DK031116-20, Z01 DK031126-01] NR 18 TC 57 Z9 57 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 29 PY 2005 VL 48 IS 26 BP 8108 EP 8111 DI 10.1021/jm050911p PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 998EQ UT WOS:000234301800002 PM 16366591 ER PT J AU Balboni, G Guerrini, R Salvadori, S Negri, L Giannini, E Bryant, SD Jinsmaa, Y Lazarus, LH AF Balboni, G Guerrini, R Salvadori, S Negri, L Giannini, E Bryant, SD Jinsmaa, Y Lazarus, LH TI Conversion of the potent delta-opioid agonist H-Dmt-Tic-NH-CH2-Bid into delta-opioid antagonists by N-1-benzimidazole alkylation SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DMT-TIC PHARMACOPHORE; RECEPTOR PROBES; MU; PEPTIDES; LIGANDS; ANALOGS; ENDOMORPHIN-2; DELTORPHINS; SELECTIVITY AB NI-Alkylation of 1H-benzimidizole of the delta agonist H-Dmt-Tic-NH-CH2-Bid with hydrophobic, aromatic, olefinic, acid, ethyl ester, or amide (1-6) became delta antagonists (pA(2) = 8.52-10.14). delta- and mu-Opioid receptor affinities were high (K-i delta = 0.12-0.36 nM and K-i mu = 0.44-1.42 nM). Only delta antagonism (pA(2) = 8.52-10.14) was observed; mu agonism (IC50 = 30-450 nM) was not correlated with changes in alkylating agent or delta antagonism, and some compounds yielded mixed delta antagonism/gamma agonism. C1 Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Univ Roma La Sapienza, Dept Human Physiol & Pharmacol Vittorio Erspamer, I-00185 Rome, Italy. NIEHS, Med Chem Grp, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Lazarus, LH (reprint author), Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. EM lazarus@niehs.nih.gov OI Guerrini, Remo/0000-0002-7619-0918 FU Intramural NIH HHS [Z01 ES090053-20, Z01 ES100472-06, Z99 ES999999] NR 23 TC 12 Z9 12 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 29 PY 2005 VL 48 IS 26 BP 8112 EP 8114 DI 10.1021/jm0582591 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 998EQ UT WOS:000234301800003 PM 16366592 ER PT J AU Miranda, KM Katori, T de Holding, CLT Thomas, L Ridnour, LA MeLendon, WJ Cologna, SM Dutton, AS Champion, HC Mancardi, D Tocchetti, CG Saavedra, JE Keefer, LK Houk, KN Fukuto, JM Kass, DA Paolocci, N Wink, DA AF Miranda, KM Katori, T de Holding, CLT Thomas, L Ridnour, LA MeLendon, WJ Cologna, SM Dutton, AS Champion, HC Mancardi, D Tocchetti, CG Saavedra, JE Keefer, LK Houk, KN Fukuto, JM Kass, DA Paolocci, N Wink, DA TI Comparison of the NO and HNO donating properties of diazeniumdiolates: Primary amine adducts release HNO in vivo SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE; AQUEOUS-SOLUTION; NITROXYL ANION; CARDIOVASCULAR-SYSTEM; NITROGEN(II) OXIDE; NITROSYL HYDRIDE; ANGELIS SALT; CHEMISTRY; TRIOXODINITRATE(II); HEART AB Diazeniumdiolates, more commonly referred to as NONOates, have been extremely useful in the investigation of the biological effects of nitric oxide (NO) and related nitrogen oxides. The NONOate Angell's salt (Na2N2O3) releases nitroxyl (HNO) under physiological conditions and exhibits unique cardiovascular features (i.e., positive inotropy/lusitropy) that may have relevance for pharmacological treatment of heart failure. In the search for new, organic-based compounds that release HNO, we examined isopropylamine NONOate (IPA/NO; Na[(CH3)(2)CHNH(N(O)NO]), which is an adduct of NO and a primary amine. The chemical and pharmacological properties of IPA/NO were compared to those of Angeli's salt and a NO-producing NONOate, DEA/NO (Na[Et2NN(O)NO]), which is a secondary amine adduct. Under physiological conditions IPA/NO exhibited all the markers of HNO production (e.g., reductive nitrosylation, thiol reactivity, positive inotropy). These data suggest that primary amine NONOates may be useful as HNO donors in complement to the existing series of secondary amine NONOates, which are well-characterized NO donors. C1 Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. Johns Hopkins Med Inst, Div Cardiol, Dept Med, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Div Cardiol, Dept Biomed Engn, Baltimore, MD 21287 USA. NCI, Tumor Biol Sect, Radiat Biol Radiat, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Chem & Biochem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Miranda, KM (reprint author), Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. EM kmiranda@email.arizona.edu; wink@mail.nih.gov RI Miranda, Katrina/B-7823-2009; Liu, Peng/D-1233-2013; Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; tocchetti, carlo gabriele/0000-0001-5983-688X; MANCARDI, Daniele/0000-0003-3809-6047; Paolocci, Nazareno/0000-0001-7011-997X FU NCI NIH HHS [N01-CO-12400] NR 57 TC 79 Z9 80 U1 3 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 29 PY 2005 VL 48 IS 26 BP 8220 EP 8228 DI 10.1021/jm050151i PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 998EQ UT WOS:000234301800014 PM 16366603 ER PT J AU Arico, E Wang, E Tornesello, ML Tagliamonte, M Lewis, GK Marincola, FM Buonaguro, FM Buonaguro, L AF Arico, E Wang, E Tornesello, ML Tagliamonte, M Lewis, GK Marincola, FM Buonaguro, FM Buonaguro, L TI Immature monocyte derived dendritic cells gene expression profile in response to Virus-Like Particles stimulation SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID CROSS-PRESENTATION; T-CELLS; NEUTRALIZING ANTIBODIES; RECEPTOR EXPRESSION; HIV-1 ISOLATE; JAK-STAT; IN-VIVO; B-CELLS; CLADE-A; MATURATION AB We have recently developed a candidate HIV-1 vaccine model based on HIV-1 Pr55gag Virus-Like Particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from an Ugandan HIV-1 isolate of the clade A (HIV-VLP(A)s). The HIV-VLP(A)s induce in Balb/c mice systemic and mucosal neutralizing Antibodies as well as cytotoxic T lymphocytes, by intra-peritoneal as well as intra-nasal administration. Moreover, we have recently shown that the baculovirus-expressed HIV-VLPs induce maturation and activation of monocyte-derived dendritic cells (MDDCs) which, in turn, produce Th1- and Th2-specific cytokines and stimulate in vitro a primary and secondary response in autologous CD4+ T cells. In the present manuscript, the effects of the baculovirus-expressed HIV-VLP(A)s on the genomic transcriptional profile of MDDCs obtained from normal healthy donors have been evaluated. The HIV-VLPA stimulation, compared to both PBS and LPS treatment, modulate the expression of genes involved in the morphological and functional changes characterizing the MDDCs activation and maturation. The results of gene profiling analysis here presented are highly informative on the global pattern of gene expression alteration underlying the activation of MDDCs by HIV-VLP(A)s at the early stages of the immune response and may be extremely helpful for the identification of exclusive activation markers. C1 Ist Nazl Tumori, Dept Expt Oncol, Lab Viral Oncogenesis & Immunotherapies & AIDS Re, Fdn G Pascale, I-80131 Naples, Italy. NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. Univ Maryland Baltimore Cty, Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Univ Maryland, Inst Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA. RP Buonaguro, L (reprint author), Ist Nazl Tumori, Dept Expt Oncol, Lab Viral Oncogenesis & Immunotherapies & AIDS Re, Fdn G Pascale, I-80131 Naples, Italy. EM aricoe@cc.nih.gov; EWang@mail.cc.nih.gov; irccsvir@unina.it; irccsvir@unina.it; lewisg@umbi.umd.edu; FMarincola@mail.cc.nih.gov; irccsvir@unina.it; irccsvir@unina.it RI Tornesello, Maria Lina/A-1564-2009 OI Tornesello, Maria Lina/0000-0002-3523-3264 NR 52 TC 31 Z9 31 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD DEC 29 PY 2005 VL 3 AR 45 DI 10.1186/1479-5876-3-45 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 008ZE UT WOS:000235080100001 PM 16384534 ER PT J AU Adams, RJ Brambilla, D AF Adams, RJ Brambilla, D CA STOP 2 Trial Investigators TI Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CLINICAL-TRIALS; CEREBROVASCULAR ACCIDENTS; TRANSCRANIAL DOPPLER; PLASMA HEMOGLOBIN; RECURRENT STROKE; ANEMIA; THERAPY; CHILDREN; RISK; ULTRASONOGRAPHY AB Background Prophylactic transfusion prevents strokes in children with sickle cell anemia who have abnormalities on transcranial Doppler ultrasonographic examination. However, it is not known how long transfusion should be continued in these children. Methods We studied children with sickle cell disease who had a high risk of stroke on the basis of a transcranial Doppler screening examination and who had received transfusions for 30 months or longer, during which time the Doppler readings became normal. The children were randomly assigned to continued transfusion or no continued transfusion. Children with severe stenotic lesions on cerebral magnetic resonance angiography were excluded. The composite primary end point was stroke or reversion to a result on Doppler examination indicative of a high risk of stroke. Results The study was stopped after 79 children of a planned enrollment of 100 underwent randomization. Among the 41 children in the transfusion-halted group, high-risk Doppler results developed in 14 and stroke in 2 others within a mean (+/-SD) of 4.5+/-2.6 months (range, 2.1 to 10.1) of the last transfusion. Neither of these events of the composite end point occurred in the 38 children who continued to receive transfusions. The average of the last two transcranial Doppler results before transfusion was started was the only predictor of the composite end point (P=0.05). Conclusions Discontinuation of transfusion for the prevention of stroke in children with sickle cell disease results in a high rate of reversion to abnormal blood-flow velocities on Doppler studies and stroke. C1 Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Miami, Sch Med, Miami, FL USA. Childrens Hosp Oakland, Oakland, CA USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. E Carolina Univ, Greenville, NC USA. Columbia Univ, New York, NY USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. Emory Univ, Sch Med, Atlanta, GA USA. Grady Hlth Syst, Atlanta, GA USA. Morehouse Sch Med, Atlanta, GA 30310 USA. Childrens Healthcare Atlanta, Atlanta, GA USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Hlth Network, Toronto, ON, Canada. Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. Childrens Mercy Hosp, Kansas City, MO 64108 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Baltimore WAshington Sickle Cell Res Consortium, Baltimore, MD USA. Sinai Hosp, Baltimore, MD 21215 USA. Univ Maryland, Baltimore, MD 21201 USA. Georgetown Univ, Washington, DC USA. Univ Alabama Birmingham, Birmingham, AL USA. Columbus Reg Med Ctr, Columbus, GA USA. Suny Downstate Med Ctr, Kings Cty Hosp Ctr, Brooklyn, NY 11203 USA. Univ So Calif, Los Angeles, CA USA. Louisiana State Univ, New Orleans, LA USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. NHLBI, Bethesda, MD 20892 USA. RP Adams, RJ (reprint author), Med Coll Georgia, Dept Neurol, 1429 Harper St,HF 1154, Augusta, GA 30912 USA. EM rjadams@mcg.edu FU NHLBI NIH HHS [U01 HL 052016, U01 HL 052193] NR 30 TC 237 Z9 244 U1 1 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 29 PY 2005 VL 353 IS 26 BP 2769 EP 2778 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 997LK UT WOS:000234246700008 PM 16382063 ER PT J AU Zarin, DA Tse, T Ide, NC AF Zarin, DA Tse, T Ide, NC TI Trial registration at ClinicalTrials.Gov between May and October 2005 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID REGISTERING CLINICAL-TRIALS; MEDICAL LANGUAGE SYSTEM; INTERNATIONAL COMMITTEE; JOURNAL EDITORS; STATEMENT AB Background Clinical trial registration allows interested parties to obtain information about ongoing and completed trials, but there are few data indicating the quality of the information provided during the registration process. We used information in the publicly available ClinicalTrials.gov database to describe patterns of trial registration before and after the implementation by journal editors of a new policy requiring registration as a prerequisite for publication. Methods We reviewed ClinicalTrials.gov records to determine patterns of completion of the "Intervention Name'' and "Primary Outcome Measure'' data fields for trials registered on May 20 and October 11, 2005, and for trials registered during the interval between these two dates, inclusively. Results During the interval studied, the number of registrations in ClinicalTrials.gov increased by 73 percent from 13,153 to 22,714. The percentage of interventional trials registered by industry with nonspecific Intervention Name entries (attributable to four drug companies) decreased from 10 percent to 2 percent; all other industry and nonindustry records contained specific entries in this field. Of the 2670 studies registered by industry between the two dates, 76 percent provided information in the Primary Outcome Measure field, although these entries varied markedly in their degree of specificity. In the remaining 24 percent of the records, this field was blank. Conclusions During the summer of 2005, there were large increases in the number of clinical trial registrations. Overall, the data contained in records were more complete in October than they were in May, but there still is room for substantial improvement. C1 NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA. RP Zarin, DA (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM dzarin@mail.nih.gov FU Intramural NIH HHS [Z99 LM999999] NR 24 TC 164 Z9 164 U1 1 U2 11 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 DEC 29 PY 2005 VL 353 IS 26 BP 2779 EP 2787 DI 10.1056/NEJMsa053234 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 997LK UT WOS:000234246700009 PM 16382064 ER PT J AU Swain, SM AF Swain, SM TI Aromatase inhibitors - A triumph of translational oncology SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID EARLY BREAST-CANCER; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; ADJUVANT THERAPY; TAMOXIFEN; ANASTROZOLE; RECURRENCE; LETROZOLE; MODEL C1 NCI, Breast Canc Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Swain, SM (reprint author), NCI, Breast Canc Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NR 13 TC 20 Z9 20 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 DEC 29 PY 2005 VL 353 IS 26 BP 2807 EP 2809 DI 10.1056/NEJMe058273 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 997LK UT WOS:000234246700014 PM 16382068 ER PT J AU Donko, A Peterfi, Z Sum, A Leto, T Geiszt, M AF Donko, A Peterfi, Z Sum, A Leto, T Geiszt, M TI Dual oxidases SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT International Conference on Reactive Oxygen Species in Health and Disease CY MAR, 2005 CL Heidelberg, GERMANY SP Acad Europaea, Klaus Tschira Fdn DE dual oxidases; DUOX; NOX; NADPH oxidase; reactive oxygen species; hydrogen peroxide ID RESPIRATORY BURST OXIDASE; AIRWAY EPITHELIAL-CELLS; NADPH OXIDASE; H2O2 GENERATION; ACTIVATION; DUOX; IDENTIFICATION; FERTILIZATION; PROTEINS; CLONING AB Reactive oxygen species (ROS) have an important role in various physiological processes including host defence, mitogenesis, hormone biosynthesis, apoptosis and fertilization. Currently, the most characterized ROS-producing system operates in phagocytic cells, where ROS generated during phagocytosis act in host defence. Recently, several novel homologues of the phagocytic oxidase have been discovered and this protein family is now designated as the NOX/DUOX family of NADPH oxidases. NOX/DUOX enzymes function in a variety of tissues, including colon, kidney, thyroid gland, testis, salivary glands, airways and lymphoid organs. Importantly, members of the enzyme family are also found in non-mammalian species, including Caenorhabditis elegans and sea urchin. The physiological functions of novel NADPH oxidase enzymes are currently largely unknown. This review focuses on our current knowledge about dual oxidases. C1 Semmelweis Univ, Fac Med, Dept Physiol, H-1444 Budapest, Hungary. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Geiszt, M (reprint author), Semmelweis Univ, Fac Med, Dept Physiol, POB 259, H-1444 Budapest, Hungary. EM geiszt@puskin.sote.hu OI Peterfi, Zalan/0000-0002-7432-2438 FU Wellcome Trust NR 26 TC 73 Z9 74 U1 1 U2 7 PU ROYAL SOCIETY PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD DEC 29 PY 2005 VL 360 IS 1464 BP 2301 EP 2308 DI 10.1098/rstb.2005.1767 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 993XT UT WOS:000233992100012 PM 16321800 ER PT J AU Murabito, JM Pencina, MJ Nam, BH D'Agostino, RB Wang, TJ Lloyd-Jones, D Wilson, PWF O'Donnell, CJ AF Murabito, JM Pencina, MJ Nam, BH D'Agostino, RB Wang, TJ Lloyd-Jones, D Wilson, PWF O'Donnell, CJ TI Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; FAMILY-HISTORY; FRAMINGHAM; DEATH; PREVALENCE; TWINS AB Context While parental cardiovascular disease (CVD) doubles the risk for CVD in offspring, the extent of increased risk associated with sibling CVD is unclear. Objective To determine, using validated events, whether sibling CVD predicts outcome in middle-aged adults independent of other risk factors. Design, Setting, and Participants The Framingham Offspring Study, an inception cohort of the Framingham Heart Study, a prospective population-based cohort study initiated in 1948 with the offspring cohort initiated in 1971. Participants (n = 2475) were members of the offspring cohort aged 30 years or older, free of CVD, and with at least I sibling in the study; all were followed up for 8 years. Main Outcome Measures Association of sibling CVD with 8-year personal risk for CVD using pooled logistic regression. A secondary analysis restricted to offspring with both parents in the study assessed the joint impact of parental and sibling CVD occurrence. Results Among 973 person-examinations in the sibling CVD group (mean age, 57 years) and 4506 person-examinations in the no sibling CVD group (mean age, 47 years), 329 CVD events occurred during follow-up. Baseline risk factors were more prevalent in the sibling CVD group compared with the no sibling CVD group. Sibling CVD was associated with a significantly increased risk for incident CVD (age- and sex-adjusted odds ratio [OR], 1.55; 95% confidence interval [CI], 1.19-2.03). Adjustment for risk factors did not substantially attenuate the risk (adjusted OR, 1.45; 95% Cl, 1.10-1.91). In the analysis restricted to persons with both parents in the study, in models adjusting for both sibling and parental CVD, the multivariable-adjusted OR for sibling CVD (1.99; 95% Cl, 1.32-3.00) exceeded that for parental CVD (1.45; 95% Cl, 1.02-2.05). Conclusion Using validated events, sibling CVD conferred increased risk of future CVD events above and beyond established risk factors and parental CVD in middle-aged adults. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA USA. Boston Univ, Stat & Consulting Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. Northwestern Univ, Feinberg Sch Med, Bluhm Cardiovasc Inst, Div Cardiol, Chicago, IL 60611 USA. Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. Med Univ S Carolina, Dept Endocrinol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Diabet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med Genet, Charleston, SC 29425 USA. NHLBI, Bethesda, MD 20892 USA. RP Murabito, JM (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM murabito@bu.edu RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-25195] NR 27 TC 110 Z9 112 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 28 PY 2005 VL 294 IS 24 BP 3117 EP 3123 DI 10.1001/jama.294.24.3117 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 997UL UT WOS:000234274200028 PM 16380592 ER PT J AU Sobolski, GK Barton, JH Emanuel, EJ AF Sobolski, GK Barton, JH Emanuel, EJ TI Technology licensing - Lessons from the US experience SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID INTELLECTUAL PROPERTY; UNIVERSITY C1 NHGRI, Dept Clin Bioeth, NIH, Bethesda, MD 20892 USA. NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Law, Stanford, CA 94305 USA. RP Emanuel, EJ (reprint author), NHGRI, Dept Clin Bioeth, NIH, Bldg 10,Room 1c118,10 Ctr Dr, Bethesda, MD 20892 USA. EM eemanuel@nih.gov NR 16 TC 15 Z9 15 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 DEC 28 PY 2005 VL 294 IS 24 BP 3137 EP 3140 DI 10.1001/jama.294.24.3137 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 997UL UT WOS:000234274200032 PM 16380596 ER PT J AU Yeung, ML Bennasser, Y Myers, TG Jiang, GJ Benkirane, M Jeang, KT AF Yeung, ML Bennasser, Y Myers, TG Jiang, GJ Benkirane, M Jeang, KT TI Changes in microRNA expression profiles in HIV-1-transfected human cells SO RETROVIROLOGY LA English DT Article ID T4 RNA LIGASE; ENCODED MICRORNAS; VIRAL-INFECTIONS; GENE-EXPRESSION; IDENTIFICATION; SUPPRESSION; VIRUSES; SIRNA; MIRNA AB MicroRNAs ( miRNAs) are small RNAs of 18 - 25 nucleotides (nt) in length that play important roles in regulating a variety of biological processes. Recent studies suggest that cellular miRNAs may serve to control the replication of viruses in cells. If such is the case, viruses might be expected to evolve the ability to modulate the expression of cellular miRNAs. To ask if expression of HIV-1 genes changes the miRNA profiles in human cells, we employed a high throughput microarray method, termed the RNA-primed Array-based Klenow Enzyme ( RAKE) assay. Here, we describe the optimization of this assay to quantify the expression of miRNAs in HIV-1 transfected human cells. We report distinct differences in miRNA profiles in mock-transfected HeLa cells versus HeLa cells transfected with an infectious HIV-1 molecular clone, pNL4-3. C1 NIAID, Microarray Res Facil, Res Technol Branch, NIH, Bethesda, MD 20892 USA. CNRS, UPR 1142, Inst Genet Humaine, Mol Virol Lab, Montpellier, France. NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yeungm@niaid.nih.gov; ybennasser@niaid.nih.gov; tmyers@niaid.nih.gov; GJiang@niaid.nih.gov; Monsef.BenKirane@igh.cnrs.fr; kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 27 TC 120 Z9 133 U1 0 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 28 PY 2005 VL 2 AR 81 DI 10.1186/1742-4690-2-81 PG 8 WC Virology SC Virology GA 033OQ UT WOS:000236858800001 PM 16381609 ER PT J AU Catz, P Shinn, W Kapetanovic, IM Kim, H Kim, M Jacobson, EL Jacobson, MK Green, CE AF Catz, P Shinn, W Kapetanovic, IM Kim, H Kim, M Jacobson, EL Jacobson, MK Green, CE TI Simultaneous determination of myristyl nicotinate, nicotinic acid, and nicotinamide in rabbit plasma by liquid chromatography-tandem mass spectrometry using methyl ethyl ketone as a deproteinization solvent SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE myristyl nicotinate; nicotinamide; nicotinic acid; cancer chemoprevention; LC-MS/MS; plasma ID METABOLITES; NIACIN; CARCINOGENESIS; INTEGRITY; FLUORIDE; URINE; SERUM; FLOW AB Myristyl nicotinate (Nia-114) is an ester prodrug being developed for delivery of nicotinic acid (NIC) into the skin for prevention of actinic keratosis and its progression to skin cancer. To facilitate dermal studies of Nia-114, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using methyl ethyl ketone (MEK) as a deproteinization solvent was developed and validated for the simultaneous determination of Nia-114, NIC, and nicotinamide (NAM) in rabbit plasma. NAM is the principal metabolite of NIC, which is also expected to have chemopreventive properties. The analytes were chromatographically separated using a Spherisorb Cyano column under isocratic conditions, and detected by multiple reaction monitoring (MRM) in positive-ion electrospray ionization mode with a run time of 9 min. The method utilized a plasma sample volume of 0.2 ml and isotope-labeled D-4 forms of each analyte as internal standards. The method was linear over the concentration range of 2-1000, 8-1000, and 75-1000 ng/ml, for Nia-114, NIC, and NAM, respectively. The intra- and inter-day assay accuracy and precision were within 15% for all analytes at low, medium, and high quality control standard levels. The relatively high value for the lower limit of quantitation (LLOQ) of NAM was demonstrated to be due to the high level of endogenous NAM in the rabbit plasma (about 350 ng/ml). Endogenous levels of NIC and NAM in human, dog, rat, and mouse plasma were also determined, and mean values ranged from < 2 ng/ml NIC and 38.3 ng/ml NAM in human, to 233 ng/ml NIC and 622 ng/ml NAM in mouse. Nia-114 was generally unstable in rabbit plasma, as evidenced by loss of 44-50% at room temperature by 2 h, and loss of 64-70% upon storage at -20 degrees C for 1 week, whereas it was stable (< 7% loss) upon storage at -80 degrees C for 1 month. Published by Elsevier B,V. C1 SRI Int, Toxicol & Metab Lab, Menlo Pk, CA 94025 USA. NCI, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85724 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. RP Green, CE (reprint author), SRI Int, Toxicol & Metab Lab, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA. EM carol.green@sri.com FU NCI NIH HHS [N01-CN-25137, P01-CA27502]; NIEHS NIH HHS [P30-ES06694] NR 18 TC 25 Z9 27 U1 2 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD DEC 27 PY 2005 VL 829 IS 1-2 BP 123 EP 135 DI 10.1016/j.jchromb.2005.10.003 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 996FC UT WOS:000234158800014 PM 16275131 ER PT J AU McKeith, IG Dickson, DW Lowe, J Emre, M O'Brien, JT Feldman, H Cummings, J Duda, JE Lippa, C Perry, EK Aarsland, D Arai, H Ballard, CG Boeve, B Burn, DJ Costa, D Del Ser, T Dubois, B Galasko, D Gauthier, S Goetz, CG Gomez-Tortosa, E Halliday, G Hansen, LA Hardy, J Iwatsubo, T Kalaria, RN Kaufer, D Kenny, RA Korczyn, A Kosaka, K Lee, VMY Lees, A Litvan, I Londos, E Lopez, OL Minoshima, S Mizuno, Y Molina, JA Mukaetova-Ladinska, EB Pasquier, F Perry, RH Schulz, JB Trojanowski, JQ Yamada, M AF McKeith, IG Dickson, DW Lowe, J Emre, M O'Brien, JT Feldman, H Cummings, J Duda, JE Lippa, C Perry, EK Aarsland, D Arai, H Ballard, CG Boeve, B Burn, DJ Costa, D Del Ser, T Dubois, B Galasko, D Gauthier, S Goetz, CG Gomez-Tortosa, E Halliday, G Hansen, LA Hardy, J Iwatsubo, T Kalaria, RN Kaufer, D Kenny, RA Korczyn, A Kosaka, K Lee, VMY Lees, A Litvan, I Londos, E Lopez, OL Minoshima, S Mizuno, Y Molina, JA Mukaetova-Ladinska, EB Pasquier, F Perry, RH Schulz, JB Trojanowski, JQ Yamada, M CA Consortium DLB TI Diagnosis and management of dementia with Lewy bodies - Third report of the DLB consortium SO NEUROLOGY LA English DT Review ID SLEEP BEHAVIOR DISORDER; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; BODY DISEASE; ALPHA-SYNUCLEIN; NEUROLEPTIC SENSITIVITY; VASCULAR DEMENTIA; NEURODEGENERATIVE DISEASES; INTERNATIONAL WORKSHOP; VISUAL HALLUCINATIONS AB The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in similar to 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors. C1 Newcastle Gen Hosp, Inst Hlth & Aging, Wolfson Res Ctr, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Mayo Clin Jacksonville, Dept Neuropathol, Jacksonville, FL 32224 USA. Univ Nottingham, Sch Mol Med Sci, Div Pathol, Nottingham NG7 2RD, England. Istanbul Univ, Istanbul Fac Med, Dept Neurol, Istanbul, Turkey. Univ British Columbia, Div Neurol, Vancouver, BC V5Z 1M9, Canada. Univ Calif Los Angeles, Alzheimers Dis Ctr, Sch Med, Dept Neurol, Los Angeles, CA USA. VAMC, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. Drexel Univ, Sch Med, Memory Disorders Program, Philadelphia, PA 19104 USA. Stavanger Univ Hosp, Sect Psychiat Psychiat, Stavanger, Norway. Tohoku Univ, Sch Med, Dept Geriatr & Resp Med, Sendai, Miyagi 980, Japan. Wolfson Ctr Age Related Dis, London, England. Mayo Clin, Dept Neurol, Rochester, MN USA. HPP Med Mol, Inst Nucl Med, Oporto, Portugal. Hosp Severo Ochoa, Neurol Sect, Madrid, Spain. Hop La Pitie Salpetriere, Paris, France. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. McGill Ctr Studies Aging, MCSA Alzheimers Dis Res Unit, Quebec City, PQ, Canada. Rush Univ, Ctr Med, Dept Neurol Sci, Chicago, IL 60612 USA. Serv Neurol, Fdn Jimenez Diaz, Madrid, Spain. Prince Wales Med Res Inst, Sydney, NSW, Australia. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Univ Tokyo, Dept Neuropathol & Neurosci, Tokyo, Japan. Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA. Tel Aviv Univ, Dept Neurol, IL-69978 Tel Aviv, Israel. Fukushimera Hosp, Dept Psychiat, Toyohashi, Aichi, Japan. Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. Royal Free & UCL Med Sch, Reta Lila Weston Inst Neurol Studies, London, England. Univ Louisville, Sch Med, Movement Disorder Program, Louisville, KY 40292 USA. Univ Hosp, Dept Clin Sci, Malmo, Sweden. Univ Pittsburgh, Coll Med, Neuropsychol Res Program, Pittsburgh, PA 15260 USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan. Hosp 12 Octubre, Serv Neurol, E-28041 Madrid, Spain. Ctr Hosp, Lille, France. Univ Lille, Lille, France. Univ Gottingen, Dept Neurodegenerat & Restorat Res Ctr Neurol Med, D-3400 Gottingen, Germany. Kanazawa Univ, Grad Sch Med Sci, Dept Neurol & Neurobiol Ageing, Kanazawa, Ishikawa 920, Japan. RP McKeith, IG (reprint author), Newcastle Gen Hosp, Inst Hlth & Aging, Wolfson Res Ctr, Westgate Rd, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. EM i.g.mckeith@ncl.ac.uk RI Hardy, John/C-2451-2009; Lees, Andrew/A-6605-2009; Schulz, Jorg/D-9786-2012; Halliday, Glenda/E-8555-2011; LICEND, CEMND/F-1296-2015; Korczyn, Amos/C-3461-2017; OI Litvan, Irene/0000-0002-3485-3445; Aarsland, Dag/0000-0001-6314-216X; Feldman, Howard/0000-0002-9258-4538; Schulz, Jorg/0000-0002-8903-0593; Halliday, Glenda/0000-0003-0422-8398; Korczyn, Amos/0000-0003-0125-2579; Dickson, Dennis W/0000-0001-7189-7917; O'Brien, John/0000-0002-0837-5080 FU Medical Research Council [G0400074] NR 105 TC 2252 Z9 2302 U1 42 U2 236 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD DEC 27 PY 2005 VL 65 IS 12 BP 1863 EP 1872 DI 10.1212/01.wnl.0000187889.17253.b1 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 997LH UT WOS:000234246400005 PM 16237129 ER PT J AU Peloponese, JM Haller, K Miyazato, A Jeang, KT AF Peloponese, JM Haller, K Miyazato, A Jeang, KT TI Abnormal centrosome amplification in cells through the targeting of Ran-binding protein-1 by the human T cell leukemia virus type-1 Tax oncoprotein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE oncogene; transformation; aneuploidy ID NF-KAPPA-B; HTLV-I TAX; GENOMIC INSTABILITY; MITOTIC SPINDLE; GENETIC INSTABILITY; CANCER PROGRESSION; BREAST-CANCER; EXPRESSION; CYCLE; ABERRATIONS AB Human T cell leukemia virus type-1 (HTLV-1) is an oncogenic retrovirus etiologically causal of adult T cell leukemia. The virus encodes a Tax oncoprotein that functions in transcriptional regulation, cell cycle control, and transformation. Because adult T cell leukemia like many other human cancers is a disease of genomic instability with frequent gains and losses of chromosomes, to understand this disease it is important to comprehend how HTLV-1 engenders aneuploidy in host cells. In this regard, loss of cell cycle checkpoints permits tolerance of aneuploidy but does not explain how aneuploidy is created. We show here that HTLV-1 Tax causes abnormal centrosome fragmentation in the mitotic phase of the cell cycle. We report that Tax directly binds Ran and Ran-binding protein-1, locates to centrosomes/spindle poles, and causes supernumerary centrosomes. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kjeang@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 59 TC 59 Z9 62 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 DEC 27 PY 2005 VL 102 IS 52 BP 18974 EP 18979 DI 10.1073/pnas.0506659103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 998WG UT WOS:000234350000036 PM 16365316 ER PT J AU Cendales, LC Kirk, AD Moresi, JM Ruiz, P Kleiner, DE AF Cendales, LC Kirk, AD Moresi, JM Ruiz, P Kleiner, DE TI Composite tissue allotransplantation: Classification of clinical acute skin rejection SO TRANSPLANTATION LA English DT Article DE composite tissue allotransplantation; acute rejection; scoring system ID ALLOGRAFT; MODEL AB Background. Composite tissue allotransplantation (CTA) is a recently introduced option for limb replacement and reconstruction of other nonreconstructible tissue defects. As with recipients of other allotransplants, CTA recipients can experience rejection episodes that are presumed to be mediated by immune mechanisms similar to those affecting solid organ grafts. However, a systematic examination of this process has not been performed, and there are no standardized criteria for the description of severity or type of rejection Methods. We collected biopsies from human limb allografts and abdominal walls in various stages of rejection for histological and immunohistochernical analysis to formulate a CTA rejection scheme. Biopsies were ranked by severity and reproducibility of the system was tested using a second set of biopsies. Tissue slides were examined blindly by three pathologists and the nonparametric Kendall coefficient of concordance (W) was used to assess the amount of agreement among the pathologists in their classification grades. Results. Rejection initially appeared as a perivascular infiltrate progressing to involve the dermis. Arteritis was observed only in the medium to large size arteries of the subcutis. Myositis was seen occasionally. Perineural involvement without frank neuritis was present in advanced rejection. The infiltrate was predominantly CD4+ in milder cases and CD8+ in advanced cases. HLA-DR was minimally expressed in keratinocytes even in severe rejection. Kendall's W was 0.9375 (p <= 0.0001). Conclusions. Based on this survey, we proposed an initial classification system for acute rejection in the skin of a CTA and demonstrated that this system is easily reproduced by independent pathologists. C1 NIAMSD, Orthoped Sect, Off Clin Director,Dept Hlth & Human Resources, Intramural Res Program,NIH, Bethesda, MD 20892 USA. NIDDK, Transplantat Branch, NIH, Dept Hlth & Human Resources, Bethesda, MD USA. Johns Hopkins Med Inst, Dept Dermatol, Baltimore, MD 21205 USA. Univ Miami, Dept Pathol, Miami, FL 33152 USA. NCI, Pathol Lab, NIH, Dept Hlth & Human Resources, Bethesda, MD 20892 USA. RP Cendales, LC (reprint author), Ctr Dr 10,MSC 1102,CRC Room 1-5140, Bethesda, MD 20892 USA. EM cendalesl@mail.nih.gov RI Kirk, Allan/B-6905-2012; OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 9 TC 24 Z9 26 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 2005 VL 80 IS 12 BP 1676 EP 1680 DI 10.1097/01.tp.0000185304.49987.d8 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 999BR UT WOS:000234364200009 PM 16378060 ER PT J AU Yamamoto, S Lavelle, JM Vagefi, PA Arakawa, H Samelson-Jones, E Moran, S Teranishi, K Kamano, C Fishman, J Awwad, M Neville, DM Shimizu, A Sykes, M Sachs, DH Yamada, K AF Yamamoto, S Lavelle, JM Vagefi, PA Arakawa, H Samelson-Jones, E Moran, S Teranishi, K Kamano, C Fishman, J Awwad, M Neville, DM Shimizu, A Sykes, M Sachs, DH Yamada, K TI Vascularized thymic lobe transplantation in a pig-to-baboon model: A novel strategy for xenogeneic tolerance induction and T-cell reconstitution SO TRANSPLANTATION LA English DT Article DE thymus transplantation; xenotransplantation; pig-to-baboon; tolerance; hDAF pig ID ANTI-GAL ANTIBODY; MINIATURE SWINE; COMPOSITE THYMOKIDNEYS; MISMATCHED BARRIERS; NATURAL ANTIBODIES; NUCLEAR TRANSFER; SELF-TOLERANCE; ADULT THYMUS; IN-VIVO; DONOR AB Background. This laboratory has previously demonstrated the induction of allogeneic tolerance by vascularized thymic lobe (VTL) transplantation in miniature swine. We report here our initial attempt to induce tolerance by VTL transplantation in the clinically relevant, discordant, pig-to-baboon model of xenotransplantation. Methods. Six baboons received xenografts of hDAF VTLs. Four of these baboons also received omental thymic tissue implants. All recipients were treated with an immunosuppressive conditioning regimen that included thymectomy, splenectomy, extracorporeal immunoadsorption of anti-alpha Gal antibodies, and T-cell depletion. Two control baboons received sham operations, of which one also received 5 x 10(8) hDAF porcine thymocytes/kg intravenously. Results. Transplanted VTL grafts supported early thymopoiesis of recipient-type immature thymocytes, and facilitated engraftment of nonvascularized thymic omental implants. Recipients of the VTL grafts demonstrated donor-specific unresponsiveness in MLR assays, development of peripheral CD45RAhigh/CD4 double positive (DP) cells, and positive cytokeratin staining of thymic stroma in the grafts for 2 months following xenotransplantation. The control baboons did not show these markers of thymic reconstitution. The eventual return of Gal natural antibodies led to the destruction of graft epithelial cells and the rejection of all VTL grafts by 3 months posttransplantation. Conclusions. VTL transplantation from hDAF swine to baboons induced early, thymopoiesis in the recipients and donor-specific cellular unresponsiveness in vitro. When coupled with additional strategies aimed at silencing humoral rejection, VTL transplantation may significantly prolong xenograft survival and result in long-term tolerance. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Immerge Biotherapeut, Cambridge, MA USA. NIH, Mol Virol Lab, Bethesda, MD 20892 USA. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,CNY 149,9019 13th St, Boston, MA 02129 USA. EM Kaz.yamada@tbrc.mgh.harvard.edu FU PHS HHS [5PO1-A145897, 5PO1-A139755] NR 42 TC 29 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 2005 VL 80 IS 12 BP 1783 EP 1790 DI 10.1097/01.tp.0000184445.70285.4b PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 999BR UT WOS:000234364200024 PM 16378075 ER PT J AU Mojica, WD Rapkiewicz, AV Liotta, LA Espina, V AF Mojica, WD Rapkiewicz, AV Liotta, LA Espina, V TI Manual exfoliation of fresh tissue obviates the need for frozen sections for molecular profiling SO CANCER CYTOPATHOLOGY LA English DT Article DE cryosection; genomics; laser capture microdissection; molecular profiling; nucleic acid; protein; proteomics; translational research ID PARAFFIN-EMBEDDED TISSUES; POLYMERASE-CHAIN-REACTION; CYTOLOGY AB BACKGROUND. Simple, rapid tissue processing that preserves macromolecules will enhance translational research capabilities. Traditional fixative-based approaches for specimen preservation are ideal for histologic evaluation but are not conducive to molecular studies of nucleic acids and protein. Tissue cryosections preserve macromolecule integrity, but the process is labor intensive and technically challenging. To the authors' knowledge to date, an alternative method capable of retrieving cells while providing adequate histologic detail yet preserving macromolecule integrity has been lacking. In the current study, the authors evaluated the utility of using manual exfoliation of clinical tissue samples as a means of obtaining cells for molecular analysis. This technique possesses the advantages of fixed and frozen tissue sections without their drawbacks. This simple, rapid, nonfixative based technique is capable of preparing cells from human clinical material for further isolation without compromising the preservation of macromolecules in the tissue. METHODS Cells from a variety of clinical resection specimens from solid tumors were directly scraped from the tissue samples using the edge of a glass microscope slide and smeared onto another slide for cytologic evaluation. The manually exfoliated cells were evaluated microscopically for cytologic quality and cellular quantity. Pure cell populations were procured by laser capture microdissection (LCM) with subsequent extraction of nucleic acids and proteins. The integrity and suitability of the recovered nucleic acids and proteins for molecular analysis were evaluated using the polymerase chain reaction (PCR), reverse transcriptase-PCR, and reverse-phase protein microarray, respectively. RESULTS Manual exfoliation permits the selection of homogeneous cell populations by LCM based on well established cytologic characteristics. DNA and mRNA, of comparable quality to frozen sections, can be amplified from the manual exfoliation cells. Proteins of similar quality can be recovered using this technique and quantitated via reverse-phase protein microarray. CONCLUSIONS Molecular macromolecules of high quality and sufficient quantity can be retrieved from human clinical samples using manual exfoliation and LCM to procure specific cell populations. The manual exfoliation technique does not destroy the original tissue source, thereby allowing subsequent formalin tissue fixation. The technique of manual exfoliation in conjunction with LCM can enable the molecular profiling of a sampled selected cell population. Because it does not destroy the original tissue, histologic correlation can be combined with molecular profiling. Cancer (Cancer Cytopathol) 2005;105:483-91. (c) 2005 American Cancer Society. C1 SUNY Buffalo, Dept Pathol, Buffalo, NY 14203 USA. NCI, Pathol Lab, Bethesda, MD USA. George Mason Univ, Ctr Appl Proteom & Mol Med, Manassas, VA USA. RP Mojica, WD (reprint author), SUNY Buffalo, Dept Pathol, 100 High St, Buffalo, NY 14203 USA. EM mojica@buffalo.edu OI Espina, Virginia/0000-0001-5080-5972 NR 20 TC 5 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC 25 PY 2005 VL 105 IS 6 BP 483 EP 491 DI 10.1002/cncr.21347 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 994FF UT WOS:000234015600009 PM 16015639 ER PT J AU Ichijo, T Voutetakis, A Cotrim, AP Bhattachryya, N Fujii, M Chrousos, GP Kino, T AF Ichijo, T Voutetakis, A Cotrim, AP Bhattachryya, N Fujii, M Chrousos, GP Kino, T TI The Smad6-histone deacetylase 3 complex silences the transcriptional activity of the glucocorticoid receptor - Potential clinical implications SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-BETA; ESTROGEN-RECEPTOR; SMAD PROTEINS; STRESS HORMONES; COREPRESSOR; BONE; ACETYLATION; ACTIVATION; PROMOTER; BINDING AB Glucocorticoids play pivotal roles in the maintenance of homeostasis but, when dysregulated, may also have deleterious effects. Smad6, one of the transforming growth factor beta ( TGF beta) family downstream transcription factors, interacts with the N-terminal domain of the glucocorticoid receptor ( GR) through its Mad homology 2 domain and suppresses GR-mediated transcriptional activity in vitro. Adenovirus-mediated Smad6 overexpression inhibits glucocorticoid action in rat liver in vivo, preventing dexamethasone-induced elevation of blood glucose levels and hepatic mRNA expression of phosphoenolpyruvate carboxykinase, a well known rate-limiting enzyme of liver gluconeogenesis. Smad6 suppresses GR-induced transactivation by attracting histone deacetylase 3 to DNA-bound GR and by antagonizing acetylation of histone H3 and H4 induced by p160 histone acetyltransferase. These results indicate that Smad6 regulates glucocorticoid actions as a corepressor of the GR. From our results and known cross-talks between glucocorticoids and TGF beta family molecules, it appears that the anti-glucocorticoid actions of Smad6 may contribute to the neuroprotective, anticatabolic and pro-wound healing properties of the TGF beta family of proteins. C1 NICHD, Reprod Biol & Med Branch, Pediat Endocrinol Sect, NIH,Clin Res Ctr, Bethesda, MD 20892 USA. NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Growth & Dev Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. RP Kino, T (reprint author), NICHD, Reprod Biol & Med Branch, Pediat Endocrinol Sect, NIH,Clin Res Ctr, Bldg 10,Rm 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov NR 61 TC 36 Z9 39 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 23 PY 2005 VL 280 IS 51 BP 42067 EP 42077 DI 10.1074/jbc.M509338200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 993XW UT WOS:000233992700033 PM 16249187 ER PT J AU Bohman, S Matsumoto, T Suh, K Dimberg, A Jakobsson, L Yuspa, S Welsh, LC AF Bohman, S Matsumoto, T Suh, K Dimberg, A Jakobsson, L Yuspa, S Welsh, LC TI Proteomic analysis of vascular endothelial growth factor-induced endothelial cell differentiation reveals a role for chloride intracellular channel 4 (CLIC4) in tubular morphogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-EXPRESSION; ANGIOGENESIS INHIBITORS; COLLAGEN MATRICES; FACTOR RECEPTOR-2; TUBE FORMATION; BLOOD-VESSELS; ANION CHANNEL; PROTEIN; P64H1; FAMILY AB Formation of new vessels from pre-existing capillaries demands extensive reprogramming of endothelial cells through transcriptional and post-transcriptional events. We show that 120 protein spots in a two-dimensional isoelectric focusing/electrophoretic analysis were affected during vascular endothelial growth factor-A-induced endothelial cell tubular morphogenesis in vitro, as a result of changes in charge or expression level of the corresponding proteins. For about 22% of the spots, the protein products could be identified, of which several previously have been implicated in cytoskeletal reorganization and angiogenesis. One such protein was heat shock protein 27, a chaperone involved in beta-actin rearrangement that was identified as regulated in degree of serine phosphorylation. We also identified regulation of chloride intracellular channel 4 (CLIC4), the expression of which decreased during tubular morphogenesis. CLIC4 was expressed at high levels in resting vessels, whereas expression was modulated during pathological angiogenesis such as in tumor vessels. The subcellular localization of CLIC4 in endothelial cells was dependent on whether cells were engaged in proliferation or tube formation. Antisense- and small interfering RNA-mediated suppression of CLIC4 expression led to arrest in tubular morphogenesis. Our data implicate CLIC4 in formation of a vessel lumen. C1 Univ Uppsala, Dept Genet & Pathol, S-75185 Uppsala, Sweden. NCI, Ctr Canc Res, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD 20892 USA. RP Welsh, LC (reprint author), Univ Uppsala, Dept Genet & Pathol, Dag Hammarskjolds Vag 20, S-75185 Uppsala, Sweden. EM Lena.Welsh@genpat.uu.se RI Jakobsson, Lars/B-4200-2011; OI Jakobsson, Lars/0000-0001-7956-587X; Claesson-Welsh, Lena/0000-0003-4275-2000 NR 44 TC 61 Z9 64 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 23 PY 2005 VL 280 IS 51 BP 42397 EP 42404 DI 10.1074/jbc.M506724200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 993XW UT WOS:000233992700070 PM 16239224 ER PT J AU Alder, MN Rogozin, IB Iyer, LM Glazko, GV Cooper, MD Pancer, Z AF Alder, MN Rogozin, IB Iyer, LM Glazko, GV Cooper, MD Pancer, Z TI Diversity and function of adaptive immune receptors in a jawless vertebrate SO SCIENCE LA English DT Article ID AMINO-ACID SITES; VARIABLE LYMPHOCYTE RECEPTORS; SOMATIC DIVERSIFICATION; CRYSTAL-STRUCTURE; PROTEIN; SELECTION; COMPLEX; GENE; SUBSTITUTION; INHIBITION AB Instead of the immunoglobulin-type antigen receptors of jawed vertebrates, jawless fish have variable lymphocyte receptors (VLRs), which consist of leucine-rich repeat (LRR) modules. Somatic diversification of the VLR gene is shown here to occur through a multistep assembly of LRR modules randomly selected from a large bank of flanking cassettes. The predicted concave surface of the VLR is lined with hypervariable positively selected residues, and computational analysis suggests a repertoire of about 1014 unique receptors. Lamprey immunized with anthrax spores responded with the production of soluble antigen-specific VLRs. These findings reveal that two strikingly different modes of antigen recognition through rearranged lymphocyte receptors have evolved in the jawless and jawed vertebrates. C1 Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, Baltimore, MD 21202 USA. Univ Alabama, Howard Hughes Med Inst, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Howard Hughes Med Inst, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Howard Hughes Med Inst, Dept Pediat, Birmingham, AL 35294 USA. Univ Alabama, Howard Hughes Med Inst, Dept Pathol, Birmingham, AL 35294 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Stowers Inst Med Res, Kansas City, MO 64110 USA. RP Pancer, Z (reprint author), Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, 600 E Lombard St, Baltimore, MD 21202 USA. EM pancer@comb.umbi.umd.edu FU Intramural NIH HHS NR 23 TC 162 Z9 170 U1 0 U2 18 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 23 PY 2005 VL 310 IS 5756 BP 1970 EP 1973 DI 10.1126/science.1119420 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 997UX UT WOS:000234275400047 PM 16373579 ER PT J AU Rapaka, RS AF Rapaka, RS TI Natureceuticals (natural products), herbal botanicals, psychoactives, hallucinogenics and related products SO LIFE SCIENCES LA English DT Editorial Material C1 NIDA, Chem & Physiol Syst Res Branch, DBNBR, NIH, Bethesda, MD 20892 USA. RP Rapaka, RS (reprint author), NIDA, Chem & Physiol Syst Res Branch, DBNBR, NIH, Bethesda, MD 20892 USA. EM rr82u@nih.gon NR 0 TC 0 Z9 0 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD DEC 22 PY 2005 VL 78 IS 5 BP 429 EP 430 DI 10.1016/j.lfs.2005.09.010 PG 2 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 990VQ UT WOS:000233771700001 PM 16289239 ER PT J AU Rothman, RB Baumann, MH AF Rothman, RB Baumann, MH TI Targeted screening for biogenic amine transporters: Potential applications for natural products SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT Workshop on Natureceuticals, Nutraceuticals, Herbal Botanicals, and Psychoactives - Drug Discovery and Drug-Drug Interactions CY NOV 05-07, 2004 CL Baltimore, MD SP Natl Inst Drug Abuse, Amer Assoc Pharmaceut Sci DE cocaine; amphetamine; ephedrine; transporter; dopamine ID PUTATIVE COCAINE ANTAGONISTS; CENTRAL-NERVOUS-SYSTEM; RAT CAUDATE MEMBRANES; NEUROTRANSMITTER TRANSPORTERS; DOPAMINE TRANSPORTER; NEUROCHEMICAL NEUTRALIZATION; MONOAMINE TRANSPORTERS; BINDING-SITES; I-125 RTI-55; SEROTONIN AB The biogenic amine transporters (BATs) are integral membrane proteins that terminate the actions of dopamine (DA), serotonin (5-HT) and norepinephrine (NE) by pumping these substrates from the extracellular space back into the nerve terminal. Numerous drugs and medications target BATs, acting as inhibitors or substrates. This paper will review some of the methods used to measure the activity of test drugs at the BATs. These methods include traditional uptake inhibition assays and transporter binding assays, as well as methods developed in our lab to determine if a test agent is a BAT substrate or inhibitor. Newer methods, developed in our lab, are used to determine the potency of test drugs as BAT substrates in a relatively high throughput manner. The potential application of these methods to characterizing natural products will be discussed in reference to results obtained with "purified" natural products, such as ephedrine stereoisomers. (c) 2005 Elsevier Inc. All rights reserved. C1 NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rrothman@intra.nida.nih.gov NR 39 TC 4 Z9 4 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD DEC 22 PY 2005 VL 78 IS 5 BP 512 EP 518 DI 10.1016/j.lfs.2005.09.001 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 990VQ UT WOS:000233771700010 PM 16202429 ER PT J AU Yang, JK Wang, LW Zheng, LX Wan, FY Ahmed, M Lenardo, MJ Wu, H AF Yang, JK Wang, LW Zheng, LX Wan, FY Ahmed, M Lenardo, MJ Wu, H TI Crystal structure of MC159 reveals molecular mechanism of DISC assembly and FLIP inhibition SO MOLECULAR CELL LA English DT Article ID DEATH-EFFECTOR DOMAIN; INDUCED-PROXIMITY MODEL; SIGNALING COMPLEX DISC; CELL-DEATH; CASPASE ACTIVATION; CONTAINING PROTEIN; NMR STRUCTURE; RECEPTOR SIGNALS; PYRIN DOMAIN; APOPTOSIS AB The death-inducing signaling complex (DISC) comprising Fas, Fas-associated death domain (FADD), and caspase-8/10 is assembled via homotypic associations between death domains (DDs) of Fas and FADD and between death effector domains (DEDs) of FADD and caspase-8/10. Caspase-8/10 and FLICE/caspase-8 inhibitory proteins (FLIPs) that inhibit caspase activation at the DISC level contain tandem DEDs. Here, we report the crystal structure of a viral FLIP, MC159, at 1.2 angstrom resolution. It reveals a noncanonical fold of DED1, a dumbbell-shaped structure with rigidly associated DEDs and a different mode of interaction in the DD superfamily. Whereas the conserved hydrophobic patch of DED1 interacts with DED2, the corresponding region of DED2 mediates caspase-8 recruitment and contributes to DISC assembly. In contrast, MC159 cooperatively assembles with Fas and FADD via an extensive surface that encompasses the conserved charge triad. This interaction apparently competes with FADD self-association and disrupts higher-orderoligomerization required for caspase activation in the DISC. C1 Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Wu, H (reprint author), Cornell Univ, Weill Med Coll, Dept Biochem, 1300 York Ave, New York, NY 10021 USA. EM haowu@med.cornell.edu FU Intramural NIH HHS; NIAID NIH HHS [R01 AI-50872, R01 AI050872, R01 AI050872-06A1] NR 59 TC 83 Z9 84 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 22 PY 2005 VL 20 IS 6 BP 939 EP 949 DI 10.1016/j.molcel.2005.10.023 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 998NS UT WOS:000234326300012 PM 16364918 ER PT J AU Cookson, MR Clarimon, J AF Cookson, MR Clarimon, J TI Dystonia and the nuclear envelope SO NEURON LA English DT Editorial Material ID TORSINA; MOVEMENT; PROTEIN AB Mutations in torsinA cause dominantly inherited early-onset torsion dystonia in humans. In this issue of Neuron, Goodchild et al. show that torsinA knockout and knockin mice have similar phenotypes, which suggests that the mutant torsinA allele causes disease because it has decreased function. The experiments also highlight the possible role of nuclear envelope dynamics in maintaining normal neuronal function. C1 NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. OI Clarimon, Jordi/0000-0002-6824-6942 FU Intramural NIH HHS NR 13 TC 8 Z9 8 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 22 PY 2005 VL 48 IS 6 BP 875 EP 877 DI 10.1016/j.neuron.2005.12.006 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 998EP UT WOS:000234301700002 PM 16364891 ER PT J AU Brody, H Miller, FG AF Brody, H Miller, FG TI Academic-industrial relationships SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Michigan State Univ, E Lansing, MI 48824 USA. NIH, Bethesda, MD 20892 USA. RP Brody, H (reprint author), Michigan State Univ, E Lansing, MI 48824 USA. EM brody@msu.edu NR 5 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 DEC 22 PY 2005 VL 353 IS 25 BP 2721 EP 2721 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 995IQ UT WOS:000234094400031 ER PT J AU Oken, MM Marcus, PM Hu, P Beck, TM Hocking, W Kvale, PA Cordes, J Riley, TL Winslow, SD Peace, S Levin, DL Prorok, PC Gohagan, JK AF Oken, MM Marcus, PM Hu, P Beck, TM Hocking, W Kvale, PA Cordes, J Riley, TL Winslow, SD Peace, S Levin, DL Prorok, PC Gohagan, JK CA PLCO Project Team TI Baseline chest radiograph for lung cancer detection in the randomized prostate, lung, colorectal and ovarian cancer screening trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FOLLOW-UP; CARCINOMA; PREVALENCE; STATISTICS; SURVIVAL; PROJECT; PROGRAM; SYSTEM; TREND AB Background. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was initiated in 1992 to examine cause-specific mortality reduction from screening for these four cancers in men and women. We report lung cancer detection results of the baseline screening round. Methods: Of the 154 942 participants enrolled, who were aged 55-74 years with no history of PLCO cancers, 77465 were randomly assigned to the intervention arm. Current or former smokers and never smokers in this arm received an initial single-view posterior-anterior chest radiograph. Results: In the initial screen, 5991 (8.9%, 95% confidence interval [CI] = 8.7% to 9.2%) of radiographs were suspicious for lung cancer: 8.2% (95% CI = 7.9% to 8.5%) for women and 9.6% (95% CI = 9.3% to 10.0%) for men. Rates were highest for older age groups and for smokers. Among those 5991 participants with a positive screen, 206 (3.4%, 95% CI = 3.0% to 3.9%) underwent biopsy examination, 126 (61.2%,95% CI = 54.5% to 67.8%) of whom were diagnosed with lung cancer within 12 months of the screen (59 in women and 67 in men). The positive predictive value was 2.1% (95% CI = 1.7% to 2.5%), and 1.9 lung cancers were detected per 1000 screens. Among these cancers, 44% (95% CI = 35% to 52%) were stage I non-small-cell lung cancer. High rates of lung cancer were found in current smokers (6.3 per 1000 screens) and in former smokers who had smoked within the past 15 years (4.9 per 1000 screens). The lung cancer detection rate among never smokers was 0.4 per 1000 screens; this group accounted for 11% (95% CI = 5.6% to 16.6%) of the cancers identified. Conclusions: In the baseline screen, nearly half the cancers were stage I. Whether this experience results in a reduction in lung cancer mortality is yet to be seen. C1 N Mem Med Ctr, Hubert H HUmphrey Canc Ctr, Robbinsdale, MN 55422 USA. NCI, Biometry Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Early Detect Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. St Lukes Reg Med Ctr, Mt States Tumor Inst, Boise, ID USA. Marshfield Clin Res Fdn, Marshfield, WI USA. Henry Ford Hlth Syst, Detroit, MI USA. Univ Minnesota, Environm & Occupat Hlth Studies Sect, Minneapolis, MN USA. Informat Management Syst Inc, Rockville, MD USA. WESTAT Corp, Rockville, MD 20850 USA. RP Oken, MM (reprint author), N Mem Med Ctr, Hubert H HUmphrey Canc Ctr, 3300 Oakdale Ave N,Plaza 100, Robbinsdale, MN 55422 USA. EM martin.oken@northmemorial.com OI Broski, Karen/0000-0003-1503-8768; Hocking, William/0000-0002-0690-3759; Johnson, Christine Cole/0000-0002-6864-6604; Church, Timothy R./0000-0003-3292-5035 NR 34 TC 63 Z9 64 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 21 PY 2005 VL 97 IS 24 BP 1832 EP 1839 DI 10.1093/jnci/dji430 PG 8 WC Oncology SC Oncology GA 000TO UT WOS:000234485500010 PM 16368945 ER PT J AU McShane, LM Altman, DG Sauerbrei, W Taube, SE Gion, M Clark, GM AF McShane, LM Altman, DG Sauerbrei, W Taube, SE Gion, M Clark, GM TI Re: Reporting recommendations for tumor marker prognostic studies (REMARK) - Reply SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Biometr Res Branch, DCTD, Bethesda, MD 20892 USA. NCI, Canc Diagn Program, DCTD, Bethesda, MD 20892 USA. Univ Oxford Wolfson Coll, Ctr Stat Med, Oxford OX2 6UD, England. Univ Freiburg Klinikum, Inst Med Biometrie & Med Informat, Freiburg, Germany. Osped Civile, Ctr Reg Indicatori Biochim Tumore, Venice, Italy. OSI Pharmaceut Inc, Boulder, CO USA. RP McShane, LM (reprint author), NCI, Biometr Res Branch, DCTD, Room 8126,Execut Plaza N,6130 Execut Blvd, Bethesda, MD 20892 USA. EM lm5h@nih.gov NR 1 TC 2 Z9 2 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 21 PY 2005 VL 97 IS 24 BP 1855 EP 1856 DI 10.1093/jnci/dji446 PG 2 WC Oncology SC Oncology GA 000TO UT WOS:000234485500018 ER PT J AU Ye, ZP Harmison, GG Ragheb, JA Schubert, M AF Ye, ZP Harmison, GG Ragheb, JA Schubert, M TI Targeted infection of HIV-1 Env expressing cells by HIV(CD4/CXCR4) vectors reveals a potential new rationale for HIV-1 mediated down-modulation of CD4 SO RETROVIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEIN; VESICULAR STOMATITIS-VIRUS; PROTEIN INDUCES DEGRADATION; RECOMBINANT VACCINIA VIRUS; SURFACE CD4; VPU PROTEIN; T-CELLS; CYTOPLASMIC DOMAIN; CELLULAR-PROTEINS AB Background: Efficient targeted gene transfer and cell type specific transgene expression are important for the safe and effective expression of transgenes in vivo. Enveloped viral vectors allow insertion of exogenous membrane proteins into their envelopes, which could potentially aid in the targeted transduction of specific cell types. Our goal was to specifically target cells that express the T cell tropic HIV-1 envelope protein (Env) using the highly specific interaction of Env with its cellular receptor (CD4) inserted into the envelope of an HIV-1-based viral vector. Results: To generate HIV-1-based vectors carrying the CD4 molecule in their envelope, the CD4 ectodomain was fused to diverse membrane anchors and inserted together with the HIV-1 coreceptor CXCR4 into the envelopes of HIV-1 vector particles. Independent of the type of CD4 anchor, all chimeric CD4 proteins inserted into HIV-1 vector envelopes and the resultant HIV(CD4/CXCR4) particles were able to selectively confer neomycin resistance to cells expressing the fusogenic T cell tropic HIV-1 Env protein. Unexpectedly, in the absence of Env on the target cells, all vector particles carrying the CD4 ectodomain anchored in their envelope adhered to various cell types without infecting these cells. This cell adhesion was very avid. It was independent of the presence of Env on the target cell, the type of CD4 anchor or the presence of CXCR4 on the particle. In mixed cell populations with defined ratios of Env(+)/Env(-) cells, the targeted transduction of Env(+) cells by HIV(CD4/CXCR4) particles was diminished in proportion to the number of Env- cells. Conclusion: Vector diversion caused by a strong, non-selective cell binding of CD4(+)-vector particles effectively prevents the targeted transduction of HIV-1 Env expressing cells in mixed cell populations. This Env- independent cell adhesion severely limits the effective use of targeted HIV( CD4/CXCR4) vectors designed to interfere with HIV-1 replication in vivo. Importantly, the existence of this newly described and remarkably strong CD4-dependent cell adhesion suggests that the multiple viral efforts to reduce CD4 cell surface expression may, in part, be to prevent cell adhesion to non-target cells and thereby to increase the infectivity of viral progeny. Preventing CD4 down-modulation by HIV-1 might be an effective component of a multi-faceted antiviral strategy. C1 Natl Inst Neurol Disorders & Stroke, Mol Virol & Neurogenet Sect, NIH, Bethesda, MD 20892 USA. US FDA, Lab Pediat & Resp Viral Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NEI, Clin & Mol Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Schubert, M (reprint author), Natl Inst Neurol Disorders & Stroke, Mol Virol & Neurogenet Sect, NIH, Rm 4S-18,5625 Fishers Lane, Bethesda, MD 20892 USA. EM yez@cber.FDA.gov; HarmisoG@ninds.nih.gov; jr50b@nih.gov; schuberm@ninds.nih.gov FU Intramural NIH HHS NR 66 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 21 PY 2005 VL 2 AR 80 DI 10.1186/1742-4690-2-80 PG 15 WC Virology SC Virology GA 033OP UT WOS:000236858700001 PM 16371160 ER PT J AU Otsuka, T Horiguchi, N Kanda, D Kosone, T Yamazaki, Y Yuasa, K Sohara, N Kakizaki, S Sato, K Takagi, H Merlino, G Mori, M AF Otsuka, Toshiyuki Horiguchi, Norio Kanda, Daisuke Kosone, Takashi Yamazaki, Yuichi Yuasa, Kazuhisa Sohara, Naondo Kakizaki, Satoru Sato, Ken Takagi, Hitoshi Merlino, Glenn Mori, Masatomo TI Overexpression of NK2 inhibits liver regeneration after partial hepatectomy in mice SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Hepatocyte growth factor; NK2; Transgenic mice; Partial hepatectomy; Liver regeneration AB AIM: To investigate the in vivo effects of NK2 on liver regeneration after partial hepatectomy (PH). METHODS: Survival after PH was observed with 21 NK2 transgenic mice and 23 wild-type (WT) mice over 10 d. Liver regeneration was analyzed using histology and immunohistochemistry. Expressions of genes were analyzed using Northern blot analysis, immunoprecipitation and immunoblotting, and reverse transcriptase polymerase chain reaction assay. Kaplan-Meier method and the log-rank test were used for analyzing the survival after PH. Differences in the results of immunohistochemistry and percentage of liver regeneration was determined by the Student's t-test. RESULTS: More than half of NK2 transgenic mice died within 48 h after PH. After PH, increased deposition of small lipid droplets in hepatocytes was evident and hepatic proliferation was inhibited in NK2 transgenic mice. The hepatic expression and kinase activity of HGF receptor, c-Met, were unchanged among WT mice and NK2 transgenic mice after PH. The expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in liver tissues were prolonged in NK2 transgenic mice that died after PH. CONCLUSION: Our findings indicate that overexpression of NK2 inhibits liver regeneration after PH. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved. C1 [Otsuka, Toshiyuki; Horiguchi, Norio; Kanda, Daisuke; Kosone, Takashi; Yamazaki, Yuichi; Yuasa, Kazuhisa; Sohara, Naondo; Kakizaki, Satoru; Sato, Ken; Takagi, Hitoshi; Mori, Masatomo] Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, Maebashi, Gumma 3718511, Japan. [Merlino, Glenn] NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Takagi, H (reprint author), Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, 3-39-15 Showa, Maebashi, Gumma 3718511, Japan. EM htakagi@med.gunma-u.ac.jp NR 30 TC 6 Z9 7 U1 0 U2 1 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD DEC 21 PY 2005 VL 11 IS 47 BP 7444 EP 7449 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V20RS UT WOS:000208157700008 PM 16437714 ER PT J AU Lu, ZB Feng, XH Song, L Han, Y Kim, A Herzberg, O Woodson, WR Martin, BM Mariano, PS Dunaway-Mariano, D AF Lu, ZB Feng, XH Song, L Han, Y Kim, A Herzberg, O Woodson, WR Martin, BM Mariano, PS Dunaway-Mariano, D TI Diversity of function in the isocitrate lyase enzyme superfamily: The Dianthus caryophyllus petal death protein cleaves alpha-keto and alpha-hydroxycarboxylic acids SO BIOCHEMISTRY LA English DT Article ID FUNGUS ASPERGILLUS-NIDULANS; CARBON-PHOSPHORUS BOND; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; 2-METHYLISOCITRATE LYASE; KETOPANTOATE HYDROXYMETHYLTRANSFERASE; MYCOBACTERIUM-TUBERCULOSIS; PHOSPHOENOLPYRUVATE MUTASE; 2,3-DIMETHYLMALATE LYASE; RHODOSPIRILLUM-RUBRUM AB The work described in this paper was carried Out to define the chemical function a new member of the isocitrate lyase enzyme family derived from the flowering plant Dianthus caryophyllus. This protein (Swiss-Prot entry Q05957) is synthesized in the senescent flower petals and is named the "petal death protein" or "PDP". On the basis of an analysis of the structural contexts of sequence markers common to the C-C bond lyases of the isocitrate lyase/phosphoenolpyruvate mutase superfamily, a substrate screen that employed a (2R)-malate core Structure was designed. Accordingly, stereochemically defined C(2)and C(3)-substituted malates were synthesized and tested as Substrates for PDP-catalyzed cleavage of the C(2)-C(3) bond. The screen identified (2R)-ethyl, (3S)-methylmalate, and oxaloacetate [likely to bind as the hydrate, C(2)(OH)(2) gem-diol] as the most active Substrates (for each, k(cat)/K-m = 2 x 10(4) M-1 s(-1)). In contrast to the stringent substrate specificities previously observed for the Escherichia coli isocitrate and 2-methylisocitrate lyases, the PDP tolerated hydrogen, methyl, and to a much lesser extent acetate substituents at the C(3) position (S configuration only) and hydoxyl, methyl, ethyl, propyl, and to a much lesser extent isobutyl substituents at C(2) (R configuration only). It is hypothesized that PDP functions in oxalate production in Ca2+ sequestering and/or in carbon scavenging from alpha-hydroxycarboxylate catabolites during the biochemical transition accompanying petal senescence. C1 Univ New Mexico, Dept Chem, Albuquerque, NM 87131 USA. Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. Purdue Univ, Dept Hort, W Lafayette, IN 47907 USA. NIMH, Mol Struct Unit Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. RP Dunaway-Mariano, D (reprint author), Univ New Mexico, Dept Chem, Albuquerque, NM 87131 USA. EM dd39@unm.edu RI Han, Ying/G-3278-2012 FU Intramural NIH HHS; NIGMS NIH HHS [GM28688] NR 59 TC 13 Z9 15 U1 3 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 20 PY 2005 VL 44 IS 50 BP 16365 EP 16376 DI 10.1021/bi0517761 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 994MQ UT WOS:000234036300001 PM 16342929 ER PT J AU Boja, ES Hoodbhoy, T Garfield, M Fales, HM AF Boja, ES Hoodbhoy, T Garfield, M Fales, HM TI Structural conservation of mouse and rat zona pellucida glycoproteins. Probing the native rat zona pellucida proteome by mass spectrometry SO BIOCHEMISTRY LA English DT Article ID ENDOPLASMIC-RETICULUM; SPERM RECEPTORS; ZP3; PROTEINS; MICE; FERTILIZATION; GLYCANS; MAMMALS; GLYCOSYLATION; EXPRESSION AB The mammalian zona pellucida is an egg extracellular matrix to which sperm bind. Mouse zonae are composed of three glycoproteins (ZP1, ZP2, and ZP3), while rat zonae contain four (ZP1, ZP2, ZP3, and ZP4/ZPB). Mouse sperm bind to zonae comprised solely of mouse ZP2 and ZP3. In this report, we show that rat sperm also bind to these zonae, indicating that ZP2 and ZP3 contain a "minimum structure(s)" to which rodent sperm can bind, and ZP1 and ZP4/ZPB are dispensable in these two rodents. These data are consistent with our mass spectrometric analysis of the native rat zona pellucida proteome (defined as the fraction of the total rat proteome to which the zonae glycoproteins contribute) demonstrating that the rat zonae glycoproteins share a high degree of conservation of structural features with respect to their mouse counterparts. The primary sequences of the rat zonae proteins have been deduced from cDNA. Each zona protein undergoes extensive co- and post-translational modification prior to its secretion and incorporation into an extracellular zona matrix. Each has a predicted N-terminal signal peptide that is cleaved off once protein translation begins and an anchoring C-terminal transmembrane domain from which the mature protein is released. Mass spectrometric analysis with a limited amount of native material allowed determination of the mature N-termini of rat ZP1 and ZP3, both of which are characterized by cyclization of glutamine to pyroglutamate; the N-terminus of ZP2 was identified by Edman degradation. The mature C-termini of ZP1 and ZP3 end two amino acids upstream of a conserved dibasic residue that is part of, but distinct from, the consensus furin cleavage sequence, while the C-terminus of ZP2 was not determined. Each zona protein contains a "zona domain" with eight conserved cysteine residues that is thought to play a role in the polymerization of the zona proteins into matrix filaments. Partial disulfide bond assignment indicates that the intramolecular disulfide patterns in rat ZP1, ZP2, and ZP3 are identical to those of their corresponding mouse counterparts. Last, nearly all potential N-glycosylation sites are occupied in the rat zonae glycoproteins (three of three for ZP1, six or seven of seven for ZP2, and four or five of six for ZP3). In comparison, potential O-glycosylation sites are numerous (59-83 Ser/Thr residues), but only two regions were observed to carry O-glycans in rat ZP3. C1 NHLBI, Lab Appl Mass Spectrometry, Cellular & Dev Biol Lab, NIDDK,NIH, Bethesda, MD 20892 USA. NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Fales, HM (reprint author), NHLBI, Lab Appl Mass Spectrometry, Cellular & Dev Biol Lab, NIDDK,NIH, 50 S Dr,Rm 3120, Bethesda, MD 20892 USA. EM hmfales@helix.nih.gov FU Intramural NIH HHS NR 31 TC 24 Z9 30 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 20 PY 2005 VL 44 IS 50 BP 16445 EP 16460 DI 10.1021/bi051883f PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 994MQ UT WOS:000234036300009 PM 16342937 ER PT J AU Roberts, WC Ko, JM Hamilton, C AF Roberts, WC Ko, JM Hamilton, C TI Comparison of valve structure, valve weight, and severity of the valve obstruction in 1849 patients having isolated aortic valve replacement for aortic valve stenosis (with or without associated aortic regurgitation) studied at 3 different medical centers in 2 different time periods SO CIRCULATION LA English DT Article DE aortic valve stenosis; bypass; coronary disease; surgery; valvuloplasty ID ADULTS; AGE AB Background - Aortic valve replacement (AVR) for patients with aortic stenosis ( AS) has now been available for 45 years. During this period, indications for the procedure have changed. Methods and Results - Operatively excised stenotic aortic valves ( with or without associated aortic regurgitation and without associated mitral valve disease) from 3 different medical centers ( National Institutes of Health, Georgetown University Medical Center, and Baylor University Medical Center) were examined during 2 different time periods by the same physician to compare aortic valve structure, valve weight, age at operation, preoperative transvalvular peak pressure gradient, calculated aortic valve area, and whether simultaneous coronary artery bypass grafting (CABG) was performed. Compared with the first 3 decades ( 1961 - 1990) of AVR, patients having this operation during the fourth and fifth decades ( 1991 - 2004) had a lower frequency of congenitally malformed aortic valves, a higher frequency of tricuspid aortic valves, an older age, valves of lighter weight and lower transvalvular peak pressure gradients, and more often simultaneous CABG. Conclusions - Although patients having isolated AVR for AS in the present and last decade were older than in the first 3 decades of valve replacement surgery, congenitally malformed aortic valves continue to be more common than tricuspid aortic valves, but the degree of AS and therefore, valve weight was significantly lower than in the earlier decades. C1 Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Dallas, TX 75246 USA. Baylor Univ, Med Ctr, Dept Pathol, Dallas, TX 75246 USA. Baylor Univ, Med Ctr, Dept Med, Dallas, TX 75246 USA. NHLBI, Pathol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. Baylor Hlth Care Syst, Inst hlth Care Res & Improvement, Dallas, TX USA. RP Roberts, WC (reprint author), Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, 3500 Gaston Ave, Dallas, TX 75246 USA. EM wc.roberts@baylorhealth.edu NR 3 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 20 PY 2005 VL 112 IS 25 BP 3919 EP 3929 DI 10.1161/CIRCULATIONAHA.105.543280 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 994VB UT WOS:000234058200015 PM 16365211 ER PT J AU Gheorghiade, M Zannad, F Sopko, G Klein, L Pina, IL Konstam, MA Massie, BM Roland, E Targum, S Collins, SP Filippatos, G Tavazzi, L AF Gheorghiade, M Zannad, F Sopko, G Klein, L Pina, IL Konstam, MA Massie, BM Roland, E Targum, S Collins, SP Filippatos, G Tavazzi, L CA Int Working Grp Acute Heart Failur TI Acute heart failure syndromes - Current state and framework for future research SO CIRCULATION LA English DT Article DE heart failure; coronary disease; morbidity; mortality ID RANDOMIZED CONTROLLED-TRIAL; NATIONAL REGISTRY ADHERE; IN-HOSPITAL MORTALITY; QUALITY-OF-CARE; INTRAVENOUS MILRINONE; RECEPTOR ANTAGONIST; RISK STRATIFICATION; SURVEY PROGRAM; RENAL-FUNCTION; OPTIME-CHF C1 Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. CHu Nancy, INSERM, Dommartin Les Toul, France. NHLBI, Bethesda, MD 20892 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Agence Francaise Secur Sanitaire Prod Sante, Paris, France. US FDA, Rockville, MD 20857 USA. Univ Cincinnati, Cincinnati, OH USA. Univ Athens Hosp Attikon, Athens, Greece. IRCCS Policlin San Matteo, Pavia, Italy. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol, Galter 10-240,201 E Huron St, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu RI Lainscak, Mitja/F-3237-2015 NR 38 TC 347 Z9 372 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 20 PY 2005 VL 112 IS 25 BP 3958 EP 3968 DI 10.1161/CIRCULATIONAHA.105.590091 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 994VB UT WOS:000234058200019 PM 16365214 ER PT J AU Stopfer, M AF Stopfer, M TI Olfactory coding: Inhibition reshapes odor responses SO CURRENT BIOLOGY LA English DT Editorial Material ID ENCODING NEURAL ASSEMBLIES; DROSOPHILA ANTENNAL LOBE; FLY BRAIN; REPRESENTATIONS; MAP; DISCRIMINATION; MECHANISMS; NETWORK AB Olfactory information is dramatically restructured as it makes its way through the brain. Recent work using a remarkable experimental preparation has revealed how this transformation is achieved. C1 NICHD, Lab Cellular & Synap Neurophysiol, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Stopfer, M (reprint author), NICHD, Lab Cellular & Synap Neurophysiol, Porter Neurosci Res Ctr, Bldg 35,Room 3A-102,35 Convent Dr,MSC 3712, Bethesda, MD 20892 USA. NR 17 TC 6 Z9 6 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 20 PY 2005 VL 15 IS 24 BP R996 EP R998 DI 10.1016/j.cub.2005.11.052 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 998PD UT WOS:000234330300012 PM 16360679 ER PT J AU Castle, PE Walker, JL Schiffman, M Wheeler, CM AF Castle, PE Walker, JL Schiffman, M Wheeler, CM TI Hormonal contraceptive use, pregnancy and parity, and the risk of cervical intraepithelial neoplasia 3 among oncogenic HPV DNA-positive women with equivocal or mildly abnormal cytology SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cervical intraepithelial neoplasia; human papillomavirus (HPV); triage; cofactors; hormonal contraceptive use; pregnancy; parity ID HUMAN-PAPILLOMAVIRUS TYPES; MULTICENTRIC CASE-CONTROL; ATYPICAL SQUAMOUS-CELLS; ASCUS-LSIL TRIAGE; UNDETERMINED SIGNIFICANCE; ORAL-CONTRACEPTIVES; RANDOMIZED-TRIAL; CANCER; MANAGEMENT; WORLDWIDE AB Oral contraceptive (OC) use, hormonal contraceptive use and multiparity are potential risk factors for cervical precancer, cervical intraepithelial neoplasia 3 (CIN3), but a limited number of studies have adequately accounted for possible confounding effect of oncogenic human papillomavirus (HPV) infection. To examine the relationships of these factors with CIN3, we conducted an analysis of women (n = 5,060) with minimally abnormal Pap smears who were enrolled in the ASCUS and LSIL Triage Study (ALTS), a clinical trial to evaluate management strategies. Cervical specimens collected at enrollment were tested for HPV DNA using 2 methods. Multivariate logistics regression models were used to assess associations (odds ratio [OR] with 95% confidence intervals [Cl]) of the potential risk factors (e.g., OC use and parity) with testing oncogenic HPV positive among controls (SEC; MAMMALIAN-CELLS; TRANSFER-RNA; INTERFERING RNAS; PROTEIN; EUKARYOTES; COMPONENT; SELENIUM; AUTOANTIBODIES; IDENTIFICATION AB Selenocysteine (Sec) is inserted into selenoproteins co-translationally with the help of various cis- and trans-acting factors. The specific mechanisms of Sec biosynthesis and insertion into protein in eukaryotic cells, however, are not known. Two proteins, SECp43 and the soluble liver antigen (SLA), were previously reported to interact with tRNA([Ser]Sec), but their functions remained elusive. Herein, we report that knockdown of SECp43 in NIH3T3 or TCMK-1 cells using RNA interference technology resulted in a reduction in the level of methylation at the 2'-hydroxylribosyl moiety in the wobble position (Um34) of Sec tRNA([Ser]Sec), and consequently reduced glutathione peroxidase 1 expression. Double knockdown of SECp43 and SLA resulted in decreased selenoprotein expression. SECp43 formed a complex with Sec tRNA([Ser]Sec) and SLA, and the targeted removal of one of these proteins affected the binding of the other to Sec tRNA([Ser]Sec). SECp43 was located primarily in the nucleus, whereas SLA was found in the cytoplasm. Co-transfection of both proteins resulted in the nuclear translocation of SLA suggesting that SECp43 may also promote shuttling of SLA and Sec tRNA([Ser]Sec) between different cellular compartments. Taken together, these data establish the role of SECp43 and SLA in selenoprotein biosynthesis through interaction with tRNA([Ser]Sec) in a multiprotein complex. The data also reveal a role of SECp43 in regulation of selenoprotein expression by affecting the synthesis of Um34 on tRNA([Ser]Sec) and the intracellular location of SLA. C1 NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. Univ Hawaii Manoa, Dept Cell & Mol Biol, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bldg 37,Rm 6032A, Bethesda, MD 20892 USA. EM hatfield@dc37a.nci.nih.gov RI Gladyshev, Vadim/A-9894-2013 FU Intramural NIH HHS; NIGMS NIH HHS [GM061603] NR 28 TC 57 Z9 61 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 16 PY 2005 VL 280 IS 50 BP 41568 EP 41575 DI 10.1074/jbc.M506696200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 992EJ UT WOS:000233866900057 PM 16230358 ER PT J AU Tanaka, Y Tachiwana, H Yoda, K Masumoto, H Okazaki, T Kurumizaka, H Yokoyama, S AF Tanaka, Y Tachiwana, H Yoda, K Masumoto, H Okazaki, T Kurumizaka, H Yokoyama, S TI Human centromere protein B induces translational positioning of nucleosomes on alpha-satellite sequences SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INNER KINETOCHORE PLATE; CENP-B; CRYSTAL-STRUCTURE; CELL-CYCLE; NULL MICE; ANGSTROM RESOLUTION; BINDING PROTEIN; CORE PARTICLE; HISTONE H3; IN-VITRO AB The human centromere proteins A (CENP-A) and B (CENP-B) are the fundamental centromere components of chromosomes. CENP-A is the centromere-specific histone H3 variant, and CENP-B specifically binds a 17-base pair sequence (the CENP-B box), which appears within every other alpha-satellite DNA repeat. In the present study, we demonstrated centromere-specific nucleosome formation in vitro with recombinant proteins, including histones H2A, H2B, H4, CENP-A, and the DNA-binding domain of CENP-B. The CENP-A nucleosome wraps 147 base pairs of the alpha-satellite sequence within its nucleosome core particle, like the canonical H3 nucleosome. Surprisingly, CENP-B binds to nucleosomal DNA when the CENP-B box is wrapped within the nucleosome core particle and induces translational positioning of the nucleosome without affecting its rotational setting. This CENP-B-induced translational positioning only occurs when the CENP-B box sequence is settled in the proper rotational setting with respect to the histone octamer surface. Therefore, CENP-B may be a determinant for translational positioning of the centromere-specific nucleosomes through its binding to the nucleosomal CENP-B box. C1 Waseda Univ, Grad Sch Sci & Engn, Dept Elect Engn & Biosci, Shinjuku Ku, Tokyo 1698555, Japan. RIKEN, Genom Sci Ctr, Prot Res Grp, Yokohama, Kanagawa 2300045, Japan. Univ Tokyo, Grad Sch Sci, Dept Biochem & Biophys, Bunkyo Ku, Tokyo 1130033, Japan. Nagoya Univ, Biosci Ctr, Chikusa Ku, Nagoya, Aichi 4648601, Japan. NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. Fujita Hlth Univ, Inst Comprehens Med Sci, Toyoake, Aichi 4701192, Japan. RIKEN, Harima Inst, SPring 8, Sayo, Hyogo 6795148, Japan. RP Kurumizaka, H (reprint author), Waseda Univ, Grad Sch Sci & Engn, Dept Elect Engn & Biosci, Shinjuku Ku, 3-4-1 Okubo, Tokyo 1698555, Japan. EM kurumizaka@waseda.jp; yokoyama@biochem.s.u-tokyo.ac.jp RI Yokoyama, Shigeyuki/N-6911-2015 OI Yokoyama, Shigeyuki/0000-0003-3133-7338 NR 57 TC 34 Z9 35 U1 4 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 16 PY 2005 VL 280 IS 50 BP 41609 EP 41618 DI 10.1074/jbc.M509666200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 992EJ UT WOS:000233866900061 PM 16183641 ER PT J AU Zubkov, S Gronenborn, AM Byeon, IJL Mohanty, S AF Zubkov, S Gronenborn, AM Byeon, IJL Mohanty, S TI Structural consequences of the pH-induced conformational switch in A. polyphemus pheromone-binding protein: Mechanisms of ligand release SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Antheraea polyphemus; pheromone-binding protein; olfaction; NMR structure; signal transduction ID NMR STRUCTURE CALCULATION; OLFACTORY RECEPTOR-CELLS; AMINO-ACID-SEQUENCE; ANTHERAEA-POLYPHEMUS; SECONDARY STRUCTURE; MAMESTRA-BRASSICAE; SEXUAL ATTRACTION; CRYSTAL-STRUCTURE; MOTH PHEROMONE; CHEMICAL-SHIFT AB Olfaction in moths is one of the most impressive examples of chemical communication found in nature for its exquisite sensitivity and selectivity. Pheromone-binding proteins (PBPs), present in the antennae of male moth and other insect species, bind the hydrophobic pheromone molecules and transport them to the G protein-coupled olfactory receptor proteins. The targeted delivery of these non-polar ligands to membrane-bound receptors involves ligand release on or near the target cell membranes, the molecular details of which are still not well understood. The PBP from the giant silk moth Antheraea polyphemus (ApolPBP) binds acetate pheromone only at pH above 6.0, and its structure at pH 6.3 has been determined previously. Here we report the solution NMR structure of ApolPBP at the acidic pH 5.2. Comparison of the present structure to that at neutral pH reveals the details of the pH-induced conformational changes and provides mechanistic clues for ligand release at acidic pH. The ApolPBP pH-induced structural change is quite different from that observed for alcohol binding Bombyx mori PBP (BmorPBP), where the C-terminal segment folds into a helix and occupies the ligand binding cavity. We observe a reorientation of helices alpha 1, beta 3, and alpha 4 at acidic pH caused by protonation of His69, His70 and His95 in the interior. This provides the driving force behind the opening of the ligand binding cavity and the release of the pheromone molecule from its carrier protein near the membrane. (c) 2005 Elsevier Ltd. All rights reserved. C1 SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. Auburn Univ, Dept Chem & Biochem, Auburn, AL 36849 USA. NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Mohanty, S (reprint author), SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. EM smita.mohanty@stonybrook.edu OI Gronenborn, Angela M/0000-0001-9072-3525 FU Intramural NIH HHS NR 54 TC 33 Z9 36 U1 0 U2 8 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 16 PY 2005 VL 354 IS 5 BP 1081 EP 1090 DI 10.1016/j.jmb.2005.10.015 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 995GW UT WOS:000234089800007 PM 16289114 ER PT J AU Mejia, R Olivero, O Rivera-Goba, M Anders, A Caban, C Leon-Monzon, M Marquez, E AF Mejia, R Olivero, O Rivera-Goba, M Anders, A Caban, C Leon-Monzon, M Marquez, E TI Asian scientists and the "glass ceiling" SO SCIENCE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Mejia, R (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. OI Mejia, Raymond/0000-0001-6237-5893 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 16 PY 2005 VL 310 IS 5755 BP 1767 EP 1767 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 995II UT WOS:000234093600017 PM 16363026 ER PT J AU Engels, EA Cerhan, JR Linet, MS Cozen, W Colt, JS Davis, S Gridley, G Severson, RK Hartge, P AF Engels, EA Cerhan, JR Linet, MS Cozen, W Colt, JS Davis, S Gridley, G Severson, RK Hartge, P TI Immune-related conditions and immune-modulating medications as risk factors for non-Hodgkin's lymphoma: A case-control study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE autoimmune diseases; case-control studies; immunosuppression; lymphoma; non-Hodgkin; methotrexate; organ transplantation; risk factors; Sjogren's syndrome ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; EPSTEIN-BARR-VIRUS; RHEUMATOID-ARTHRITIS; UNITED-STATES; AUTOIMMUNE-DISEASES; MALIGNANT-LYMPHOMAS; CANCER-RISK; COHORT; HISTORY AB In immunosuppressed or autoimmune disease states, disordered immune responses may lead to non-Hodgkin's lymphoma (NHL). In a US population-based case-control study of NHL (1998-2000), the authors collected personal histories of immune-related conditions and use of immune-modulating therapies as well as family histories of autoimmune conditions. The study included 1,321 NHL cases and 1,057 controls; only half received some questionnaire components. NHL was associated with Sjogren's syndrome (odds ratio (OR) = 13, 95% confidence interval (CI): 1.7, 100) and lupus (OR = 4.2, 95% CI: 1.2, 15). Two specific NHL subtypes were strongly associated with Sjogren's syndrome: salivary gland (OR = 290, 95% CI: 33, 2600) and marginal zone (OR = 75, 95% CI: 9.1, 610). NHL was less convincingly associated with receipt of an organ transplant (OR = 2.0, 95% CI: 0.4, 11). Other autoimmune conditions were too rare to evaluate or not associated with NHL. Corticosteroid use was unrelated to NHL (OR = 1.0, 95% CI: 0.8, 1.2), but methotrexate use was marginally associated (OR = 2.3, 95% CI: 0.7, 7.5). Family history of dermatomyositis was associated with NHL (7 cases vs. 0 controls, OR = infinite; two-sided p = 0.02), but dermatomyositis was absent in cases themselves. Family history of remaining conditions was unrelated to NHL. Results suggest that disordered immunity in some immune-related conditions can lead to NHL. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS, Rockville, MD 20852 USA. Mayo Clin & Mayo Fdn, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. Univ So Calif, Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Wayne State Univ, Dept Family Med, Detroit, MI 48202 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. RP Engels, EA (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS, 6120 Execut Blvd,EPS 8010, Rockville, MD 20852 USA. EM engelse@exchange.nih.gov OI Cerhan, James/0000-0002-7482-178X FU NCI NIH HHS [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105] NR 43 TC 59 Z9 68 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2005 VL 162 IS 12 BP 1153 EP 1161 DI 10.1093/aje/kwi341 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 991YI UT WOS:000233850400003 PM 16251389 ER PT J AU Smith, I Nathan, C Peavy, HH AF Smith, I Nathan, C Peavy, HH TI Progress and new directions in genetics of tuberculosis - An NHLBI working group report SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE bacterial virulence factors; genetics; host immunologic response; Mycobacterium tuberculosis; tuberculosis ID NITRIC-OXIDE SYNTHASE; VIRULENT MYCOBACTERIUM-TUBERCULOSIS; INTERSTITIAL LUNG-DISEASE; T-CELLS; PULMONARY TUBERCULOSIS; MURINE TUBERCULOSIS; INNATE IMMUNITY; SOCIAL-ISSUES; INFECTION; MACROPHAGES AB Tuberculosis (TB), along with AIDS and malaria, is one of the three major killers among infectious diseases. New approaches to preventing, diagnosing, and curing TB are needed, which depend on a better understanding of Mycobacterium tuberculosis and the host. The National Heart, Lung, and Blood Institute convened a working group to develop recommendations for future TB research, including genetic aspects of the disease. The following areas were identified: (7) animal model research to improve understanding of persistence, reactivation, and granulomatous reactions; (2) preclinical studies aimed at shortening treatment of TB; (3) new resources for manipulating and characterizing the M. tuberculosis genome, proteome chips for more specific diagnoses, and studies of genes that appear to be essential but whose functions are not known; (4) prospective studies associated with clinical trials in populations with or at risk of TB to advance development of diagnostics and prognostics; (5) new quantitative and bioinformatic approaches to study the interaction between M. tuberculosis and the infected host and how this influences the infection process; (6) molecular characterization of M. tuberculosis genome diversity and phylogenetic analysis; (7) coordinated studies of human genome scans; (8) genetic epidemiology studies; (9) activities to foster knowledge dissemination, education, and training; and (10) coordination between the National Institutes of Health, the Gates Foundation, the Global Alliance for Tuberculosis Drug Development, and other organizations C1 TB Ctr, Publ Hlth Res Inst, Newark, NJ 07103 USA. Cornell Univ, Dept Microbiol & Immunol, Weill Med Coll, New York, NY USA. NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. RP Smith, I (reprint author), TB Ctr, Publ Hlth Res Inst, 225 Warren St, Newark, NJ 07103 USA. EM smitty@phri.org NR 65 TC 8 Z9 9 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 15 PY 2005 VL 172 IS 12 BP 1491 EP 1496 DI 10.1164/rccm.200506-997WS PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 994GK UT WOS:000234019000006 PM 16192449 ER PT J AU Smith, JA Whitcup, SM Suhler, EB Levy-Clarke, G Robinson, M Thompson, DJS Kim, J Barron, KS AF Smith, JA Whitcup, SM Suhler, EB Levy-Clarke, G Robinson, M Thompson, DJS Kim, J Barron, KS TI Assessment of inflammatory response in a study of uveitis associated with juvenile idiopathic arthritis: Comment on the article by Smith et al - Reply SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Letter ID LASER FLARE PHOTOMETRY; CELL PHOTOMETRY; COMPLICATIONS C1 NEI, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. NIAID, Bethesda, MD 20892 USA. RP Smith, JA (reprint author), NEI, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD DEC 15 PY 2005 VL 53 IS 6 BP 986 EP 987 DI 10.1002/art.21598 PG 2 WC Rheumatology SC Rheumatology GA 995FL UT WOS:000234086100028 ER PT J AU Hasler, G Neumeister, A van der Veen, JW Tumonis, T Bain, EE Shen, J Drevets, WC Charney, DS AF Hasler, G Neumeister, A van der Veen, JW Tumonis, T Bain, EE Shen, J Drevets, WC Charney, DS TI Normal prefrontal gamma-aminobutyric acid levels in remitted depressed subjects determined by proton magnetic resonance spectroscopy SO BIOLOGICAL PSYCHIATRY LA English DT Article DE euthymic subjects; gamma-aminobutyric acid; magnetic resonance spectroscopy; major depression; prefrontal cortex; psychiatric genetics ID PLASMA GABA LEVELS; MAJOR DEPRESSION; MOOD DISORDERS; QUANTUM FILTER; HUMAN BRAIN; RECEPTORS; ASSOCIATION; INHIBITOR; GLUTAMATE; DECREASE AB Background: There is growing evidence that the brain gamma-aminobutyric acid (GABA) system is involved in depression. Lowered plasma GABA levels were identified as a traitlike abnormality found in patients with remitted unipolar depression and in healthy first-degree relatives of patients with unipolar depression. Major depressive disorder has been associated with neuroimaging and neuropathological abnormalities in the prefrontal cortex by various types of evidence. As a result, the current study investigates whether GABA levels in the prefrontal cortex differ between unmedicated subjects with remitted major depressive disorder (rMDD) and healthy control subjects. Methods: Sixteen rMDD subjects and 15 healthy control subjects underwent magnetic resonance spectroscopy. We used a 3 Tesla GE whole body scanner with a homogeneous resonator coil providing a homogenous radiofrequency field and capability of obtaining measurement from the prefrontal cortex. Gamma-aminobutyric acid levels were measured in the ventromedial prefrontal cortex and dorsolateral/anterior medial prefrontal cortex. Results: There was no difference in GABA concentrations between rMDD subjects and bealthy control subjects in the ventromedial prefrontal cortex and dorsolateral/anterior medial prefrontal cortex. Secondary analyses provided preliminary evidence for a negative relationship between the glutamate/glutamine (Glx)/GABA ratio and age of onset of major depression in the ventromedial prefrontal cortex. Conclusions: This result suggests that GABA levels in the prefrontal cortex, if found to be reduced in symptomatic depression, do not represent a persistent characteristic of major depression. Further research is needed to determine brain GABA levels in different brain regions, in different stages of depressive illness, and in different depressive subtypes. C1 NIMH, NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, NIH, Sect Expt Therapeut, Magnet Resonance Spect Core, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Clin Neurosci Div, Dept Psychiat, New Haven, CT 06520 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Pharmacol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Biol Chem, New York, NY 10029 USA. RP Hasler, G (reprint author), NIMH, NIH, Mood & Anxiety Disorders Program, 15K N Dr,Room 300C,MSC 2670, Bethesda, MD 20892 USA. EM g.hasler@bluewin.ch RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 NR 37 TC 65 Z9 68 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2005 VL 58 IS 12 BP 969 EP 973 DI 10.1016/j.biopsych.2005.05.017 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 996TQ UT WOS:000234198100007 PM 16043137 ER PT J AU Li, PK Xiao, ZL Hu, ZG Pandit, B Sun, YJ Sackett, DL Werbovetz, K Lewis, A Johnsamuel, J AF Li, PK Xiao, ZL Hu, ZG Pandit, B Sun, YJ Sackett, DL Werbovetz, K Lewis, A Johnsamuel, J TI Conformationally restricted analogs of Combretastatin A-4 derived from SU5416 SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID AGENTS; TUBULIN; APOPTOSIS; TAXOL AB A series of compounds originally derived from the vascular endothelial growth factor receptor tyrosine kinase inhibitor, SU5416, was synthesized and evaluated. The most potent compound in this series, compound 7, structurally resembles the potent anti -microtubule agent Combretastatin A-4, inhibited tubulin polymerization, and showed potent growth inhibitory activities on both prostate and breast cancer lines with IC50 values in low to subnanomolar range. (c) 2005 Elsevier Ltd. All rights reserved. C1 Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Li, PK (reprint author), Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, 500 W 12Th Ave, Columbus, OH 43210 USA. EM li.27@osu.edu RI Werbovetz, Karl/E-4290-2011 NR 10 TC 27 Z9 27 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 15 PY 2005 VL 15 IS 24 BP 5382 EP 5385 DI 10.1016/j.bmcl.2005.09.001 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 983BO UT WOS:000233206300005 PM 16213720 ER PT J AU Grundt, P Kopajtic, TA Katz, JL Newman, AH AF Grundt, P Kopajtic, TA Katz, JL Newman, AH TI N-8-substituted benztropinamine analogs as selective dopamine transporter ligands SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE monoamine transporters; dopamine transporters; cocaine; muscarinic M1 receptor; benztropine; benztropinamine; ligand binding ID MOLECULAR-FIELD ANALYSIS; MONOAMINE TRANSPORTERS; UPTAKE INHIBITORS; BINDING-AFFINITY; COCAINE REWARD; DISCOVERY; MECHANISMS; RECEPTORS AB A series of N-8-substituted benztropinamines was synthesized and evaluated for binding at the dopamine (DAT), serotonin (SERT), norepinephrine (NET) transporters, and muscarinic M1 receptors. In general, the isosteric replacement of the C-3 benzhydrol ether of benztropine by a benzhydryl amino group was well tolerated at the DAT. However, for certain N-8 substituted derivatives, selectivity over muscarinic M1 receptor affinity was reduced. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Newman, AH (reprint author), NIDA, Med Chem Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov OI Katz, Jonathan/0000-0002-1068-1159 FU Intramural NIH HHS NR 22 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 15 PY 2005 VL 15 IS 24 BP 5419 EP 5423 DI 10.1016/j.bmcl.2005.08.111 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 983BO UT WOS:000233206300013 PM 16213721 ER PT J AU Li, TY Shiotani, K Miyazaki, A Fujita, Y Tsuda, Y Ambo, A Sasaki, Y Jinsmaa, Y Marczak, E Bryant, SD Lazarus, LH Okada, Y AF Li, TY Shiotani, K Miyazaki, A Fujita, Y Tsuda, Y Ambo, A Sasaki, Y Jinsmaa, Y Marczak, E Bryant, SD Lazarus, LH Okada, Y TI New series of potent delta-opioid antagonists containing the H-Dmt-Tic-NH-hexyl-NH-R motif SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE opioid; delta-opioid receptor antagonist ID MOUSE VAS-DEFERENS; RECEPTOR ANTAGONIST; RAT-BRAIN; MEDIATED ANALGESIA; DIPEPTIDE ANALOGS; ACID; PEPTIDES; PHARMACOPHORE; ENDOMORPHIN-2; DERIVATIVES AB Heterodimeric compounds H-Dmt-Tic-NH-hexyl-NH-R (R = Dmt, Tic, and Phe) exhibited high affinity to delta-(K(i)delta = 0.13-0.89 nM) and p-opioid receptors (K(i)mu = 0.38-2.81 nM) with extraordinary potent delta antagonism (pA(2) = 10.2-10.4). These compounds represent the prototype for a new class of structural homologues lacking mu-opioid receptor-associated agonism IC50 = 1.6-5.8 mu M) based on the framework of bis-[H-Dmt-NH]-alkyl (Okada, Y.; Tsuda, Y.; Fujita, Y.; YDkoi, T.; Sasaki, Y.; Ambo, A.; Konishi, R.; Nagata, M.; Salvadori, S.; Jinsmaa, Y.; Bryant, S. D.; Lazarus, L. H. J. Med. Chem. 2003, 46, 3201), which exhibited both high p affinity and bioactivity. (c) 2005 Elsevier Ltd. All rights reserved. C1 Kobe Gakuin Univ, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Tohoku Pharmaceut Univ, Dept Biochem, Aoba Ku, Sendai, Miyagi 9818558, Japan. NIEHS, Med Chem Grp, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Lazarus, LH (reprint author), Kobe Gakuin Univ, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. EM lazarus@niehs.nih.gov; okada@pharm.kobegakuin.ac.jp FU Intramural NIH HHS NR 34 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 15 PY 2005 VL 15 IS 24 BP 5517 EP 5520 DI 10.1016/j.bmcl.2005.08.073 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 983BO UT WOS:000233206300034 PM 16183273 ER PT J AU Fu, K Weisenburger, DD Greiner, TC Dave, S Wright, G Rosenwald, A Chiorazzi, M Iqbal, J Gesk, S Siebert, R De Jong, D Jaffe, ES Wilson, WH Delabie, J Ott, G Dave, BJ Sanger, WG Smith, LM Rimsza, L Braziel, RM Muller-Hermelink, HK Campo, E Gascoyne, RD Staudt, LM Chan, WC AF Fu, K Weisenburger, DD Greiner, TC Dave, S Wright, G Rosenwald, A Chiorazzi, M Iqbal, J Gesk, S Siebert, R De Jong, D Jaffe, ES Wilson, WH Delabie, J Ott, G Dave, BJ Sanger, WG Smith, LM Rimsza, L Braziel, RM Muller-Hermelink, HK Campo, E Gascoyne, RD Staudt, LM Chan, WC CA Lymphoma Leukemia Mol Profiling Pr TI Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling SO BLOOD LA English DT Article ID DEPENDENT KINASE INHIBITOR; CYCLIN D1 EXPRESSION; PROLIFERATIVE ACTIVITY; D3; P27(KIP1); PROTEIN; GRADE; T(6/14)(P21.1,Q32.3); OVEREXPRESSION; REARRANGEMENTS AB Cyclin D1 overexpression is believed to be essential in the pathogenesis of mantle cell lymphoma (MCL). Hence, the existence of cyclin D1-negative MCL has been controversial and difficult to substantiate. Our previous gene expression profiling study identified several cases that lacked cyclin D1 expression, but had a gene expression signature typical of MCL. Herein, we report the clinical, pathologic, and genetic features of 6 cases of cyclin D1-negative MCL. All 6 cases exhibited the characteristic morphologic features and the unique gene expression signature of MCL but lacked the t(11;14)(q13; q32) by fluorescence in situ hybridization (FISH) analysis. The tumor cells also failed to express cyclin D1 protein, but instead expressed either cyclin D2 (2 cases) or cyclin D3 (4 cases). There was good correlation between cyclin D protein expression and the corresponding mRNA expression levels by gene expression analysis. Using interphase FISH, we did not detect chromosomal translocations or amplifications involving CCND2 and CCND3 loci in these cases. Patients with cyclin D1-negative MCL were similar clinically to those with cyclin D1-positive MCL. In conclusion, cases of cyclin D1-negative MCL do exist and are part of the spectrum of MCL. Up-regulation of cyclin D2 or D3 may substitute for cyclin D1 in the pathogenesis of MCL. C1 Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Nebraska Med Ctr 983135, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Human Genet Lab, Omaha, NE 68198 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Sect Lymphoma Clin Res, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel, Germany. Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Pathol, Amsterdam, Netherlands. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. Univ Arizona, Hlth Sci Ctr, Dept Pathol, Tucson, AZ USA. Univ Oregon, Hlth Sci Ctr, Dept Pathol, Portland, OR USA. Univ Barcelona, Hosp Clin, Dept Pathol, Barcelona, Spain. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. RP Fu, K (reprint author), Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Nebraska Med Ctr 983135, Omaha, NE 68198 USA. EM kfu@unmc.edu RI Siebert, Reiner/A-8049-2010; OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 FU NCI NIH HHS [CA36727, CA84967] NR 48 TC 182 Z9 191 U1 1 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2005 VL 106 IS 13 BP 4315 EP 4321 DI 10.1182/blood-2005-04-1753 PG 7 WC Hematology SC Hematology GA 993AU UT WOS:000233925900049 PM 16123218 ER PT J AU von Eschenbach, AC AF von Eschenbach, AC TI Keynote speech: Progress with a purpose SO CANCER LA English DT Editorial Material C1 NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP von Eschenbach, AC (reprint author), NCI, NIH, Dept Hlth & Human Serv, Bldg 31,Room 10A19,31 Ctr Dr,MSC 258, Bethesda, MD 20892 USA. EM ncipressofficers@mail.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2005 VL 104 IS 12 SU S BP 2903 EP 2904 DI 10.1002/cncr.21513 PG 2 WC Oncology SC Oncology GA 993SD UT WOS:000233974300004 PM 16247778 ER PT J AU Chu, KC Chu, KT AF Chu, KC Chu, KT TI 1999-2001 cancer mortality rates for Asian and Pacific Islander ethnic groups with comparisons to their 1988-1992 rates SO CANCER LA English DT Article; Proceedings Paper CT AANCART 5th Asian-American-Cancer-Control-Academy Conference CY OCT 22-23, 2004 CL Sacramento, CA SP Asian Amer Network Canc Awareness , Res & Training, Asian Amer Canc Control Acad DE AANCART; Asian American; cancer; Pacific Islander; cancer mortality AB We report upper and lower boundary estimates of the 1999-2001 site-specific cancer mortality rates for Asian Indians, Chinese, Filipinos, Koreans, Vietnamese, Native Hawaiians, and Samoans. These rates are for the seven states (California, Hawaii, Illinois, New Jersey, New York, Texas, and Washington) that officially record mortality data for these ethnicities. The rates are based on the 2000 Census, which reports two population counts as follows: persons who identify themselves as belonging to a single ethnic group (which forms the basis for an upper boundary estimate of the rates) and persons who identify themselves as belonging to a single ethnic group or to multiple groups that include the single ethnic group (which forms the basis for a lower boundary estimate for the rates). The top five cancers for each Asian and Pacific Islander ethnic group by gender are reported. In addition, the 1988-1992 cancer mortality rates based on the 1990 Census for Chinese, Filipino, Japanese, and Native Hawaiians are determined. Their 1999-2001 and 1988-1992 rates are compared. C1 NCI, Disparities Res Branch, Ctr Reduce Canc Hlth Disparities, Bethesda, MD 20892 USA. United Hlth Consultants, Gaithersburg, MD USA. RP Chu, KC (reprint author), NCI, Disparities Res Branch, Ctr Reduce Canc Hlth Disparities, 6116 Execut Blvd,Room 602, Bethesda, MD 20892 USA. EM kc10d@nih.gov FU NCI NIH HHS [U01 CA086322] NR 7 TC 9 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2005 VL 104 IS 12 SU S BP 2989 EP 2998 DI 10.1002/cncr.21509 PG 10 WC Oncology SC Oncology GA 993SD UT WOS:000233974300021 PM 16270326 ER PT J AU Karadag, A Fedarko, NS Fisher, LW AF Karadag, A Fedarko, NS Fisher, LW TI Dentin matrix protein 1 enhances invasion potential of colon cancer cells by bridging matrix metalloproteinase-9 to integrins and CD44 SO CANCER RESEARCH LA English DT Article ID COMPLEMENT-MEDIATED ATTACK; BONE SIALOPROTEIN; METALLOPROTEINASE EXPRESSION; ALPHA(V)BETA(3) INTEGRIN; ACIDIC PHOSPHOPROTEIN; COLORECTAL-CANCER; LIVER METASTASIS; SIBLING PROTEINS; BINDING LIGAND; TUMOR-CELLS AB The up-regulation of various matrix metalloproteinases (MMP), certain cell receptors such as integrins and CD44, and the SIBLING family of integrin-binding glycophosphoproteins have been reported separately and in various combinations for many types of tumors. The mechanisms by which these different proteins may be interacting and enhancing the ability of a cancer cell to survive and metastasize have become an interesting issue in cancer biology. Dentin matrix protein I (DMP1) has been known for a number of years to bind to CD44 and ArgGlyAsp sequence-dependent integrins. This SIBLING was recently shown to be able to specifically bind and activate proMMP-9 and to make MMP-9 much less sensitive to inhibition by tissue inhibitors of metalloproteinases and synthetic inhibitors. In this study, we used a modified Boyden chamber assay to show that. DMP1 enhanced the invasiveness of the MMP-9 expressing colon cancer cell line, SW480, through Matrigel in a dose-dependant manner. DMPI (100 nmol/L) increased invasion 4-fold over controls (86.1 +/- 13.9 versus 22.3 +/- 9.8, P < 0.001).The enhanced invasive potential required the presence of MMP-9 and at. least one of Lite cell surface receptors, CD44, alpha(v)beta(3), or alpha(v)beta(5) integrin. The bridging of MMP-9 to the cell surface receptors was shown by both pull-down and fluorescence activated cell sorting experiments. Because all of these proteins were also shown by immunohistochemistry to be expressed in serial sections of a colon adenocarcinoma, we have hypothesized that the MMP-9/DMP1/cell surface complexes observed to enhance cell invasion in. vitro may be aiding metastatic events in vivo. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr, Baltimore, MD 21218 USA. RP Fisher, LW (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Room 228,Bldg 30,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lfisher@dir.nidcr.nih.gov FU Intramural NIH HHS; NIDCR NIH HHS [Z01 DE000074-33] NR 30 TC 40 Z9 41 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2005 VL 65 IS 24 BP 11545 EP 11552 DI 10.1158/0008-5472.CAN-05-2861 PG 8 WC Oncology SC Oncology GA 996FF UT WOS:000234159100041 PM 16357164 ER PT J AU Huff, LM Wang, Z Iglesias, A Fojo, T Lee, JS AF Huff, LM Wang, Z Iglesias, A Fojo, T Lee, JS TI Aberrant transcription from an unrelated promoter can result in MDR-1 expression following drug selection in vitro and in relapsed lymphoma samples SO CANCER RESEARCH LA English DT Article ID MULTIDRUG-RESISTANCE GENE; POLYMERASE CHAIN-REACTION; ENDOGENOUS RETROVIRAL PROMOTER; ENDOTHELIN-B RECEPTOR; P-GLYCOPROTEIN GENE; KB CARCINOMA-CELLS; HUMAN-TUMORS; ACTIVATION; LINES; RNA AB The development of drug resistance in the treatment of cancer remains a major problem. The hallmark of multidrug resistance is cross-resistance to multiple structurally unrelated compounds. The MDR-1 gene encoding P-glycoprotein mediates one of the most extensively studied mechanisms of drug resistance. Previous studies led to the proposal that two promoters control expression of the MDR-1 gene, and these were designated the upstream and downstream promoters. In the present article, we provide evidence that transcripts originating from the putative upstream promoter of MDR-1 are in fact aberrant transcripts whose expression is regulated by nearby genomic sequences that include a human endogenous retroviral long terminal repeat (LTR). Expression of this 1:17 R occurs in all cells. We show that following drug selection, especially in cases where gene amplification has occurred, MDR-1 transcripts can begin near this retroviral LTR with transcription proceeding in the direction opposite of the usual LTR transcription. Because expression of these aberrant MDR-1 transcripts (AMT) is found primarily in drug-resistant cell lines, we conclude that the development of drug resistance or the attendant drug exposure might have a role in the activation of this phenomenon or the selection of cells expressing AMTs. Demonstration of similar aberrant transcripts in tumor samples obtained from patients with relapsed lymphoma suggests that this phenomenon may also occur clinically. C1 NCI, Med Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Emory Univ, Atlanta, GA 30322 USA. Gyeongsang Natl Univ, Coll Med, Chinju, South Korea. RP Fojo, T (reprint author), NCI, Med Oncol Branch, Canc Res Ctr, NIH, 10 Ctr Dr,Bldg 10,Rm 13N 240 MSC 1903, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 42 TC 11 Z9 11 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2005 VL 65 IS 24 BP 11694 EP 11703 PG 10 WC Oncology SC Oncology GA 996FF UT WOS:000234159100058 PM 16357181 ER PT J AU Cross, AJ Peters, U Kirsh, VA Andriole, GL Reding, D Hayes, RB Sinha, R AF Cross, AJ Peters, U Kirsh, VA Andriole, GL Reding, D Hayes, RB Sinha, R TI A prospective study of meat and meat mutagens and prostate cancer risk SO CANCER RESEARCH LA English DT Article ID HETEROCYCLIC AMINE CONTENT; PAN-FRIED MEAT; VARYING DEGREES; FOOD MUTAGENS; COOKED FOODS; DIETARY-FAT; CARCINOGEN; EXPRESSION; PHIP; COOKING AB High-temperature cooked meat contains heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP). In rodents, a high intake of PhIP induces prostate tumors. We prospectively investigated the association between meat and meat mutagens, specifically PhIP, and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Diet was assessed using a 137-item food frequency questionnaire and a detailed meat-cooking questionnaire linked to a database for BaP and the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (DiMeIQx), and PhIP. During follow-up, we ascertained a total of 1,338 prostate cancer cases among 29,361 men; of these, 868 were incident cases (diagnosed after the first year of follow-up) and 520 were advanced cases (stage III or IV or a Gleason score of >= 7). Total, red, or white meat intake was not associated with prostate cancer risk. More than 10 g/d of very well done meat, compared with no consumption, was associated with a 1.4-fold increased risk of prostate cancer [95% confidence interval (95% CI), 1.05-1.92] and a 1.7-fold increased risk (95% CI, 1.19-2.40) of incident disease. Although there was no association with MeIQx and DiMeIQx, the highest quintile of PhIP was associated with a 1.2-fold increased risk of prostate cancer (95% CL 1.01-1.48) and a 1.3-fold increased risk of incident disease (95% CI, 1.01-1.61). In conclusion, very well done meat was positively associated with prostate cancer risk. lit addition, this study lends epidemiologic support to the animal studies, which have implicated PIAP as a prostate carcinogen. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Canc Care Ontario, Div Prevent Oncol, Toronto, ON, Canada. Washington Univ, St Louis, MO USA. Marshfield Clin Res Fdn, Marshfield, WI USA. RP Cross, AJ (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. EM crossa@mail.nih.gov RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU Intramural NIH HHS NR 41 TC 100 Z9 101 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2005 VL 65 IS 24 BP 11779 EP 11784 DI 10.1158/0008-5472CAN-05-2191 PG 6 WC Oncology SC Oncology GA 996FF UT WOS:000234159100068 PM 16357191 ER PT J AU Cerasoli, DM Griffiths, EM Doctor, BP Saxena, A Fedorko, JM Greig, NH Yu, QS Huang, Y Wilgus, H Karatzas, CN Koplovitz, I Lenz, DE AF Cerasoli, DM Griffiths, EM Doctor, BP Saxena, A Fedorko, JM Greig, NH Yu, QS Huang, Y Wilgus, H Karatzas, CN Koplovitz, I Lenz, DE TI In vitro and in vivo characterization of recombinant human butyrylcholinesterase (Protexia (TM)) as a potential nerve agent bioscavenger SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Meeting Abstract CT 8th International Meeting on Cholinesterases CY SEP 26-30, 2004 CL Univ Perugia, Perugia, ITALY HO Univ Perugia DE organophosphorus nerve agent; butyrylcholinesterase; bioscavenger; recombinant ID TOXICITY; SOMAN C1 USAMRICD, Div Pharmacol, Aberdeen Proving Ground, MD 21010 USA. WRAIR, Div Biochem, Silver Spring, MD 20910 USA. NIA, Drug Design & Dev Sect, Baltimore, MD 21224 USA. Nexia Biotechnol Inc, Vaudreuil Dorion, PQ J7V 8P5, Canada. NR 4 TC 56 Z9 59 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD DEC 15 PY 2005 VL 157 SI SI MA 07 BP 363 EP 365 DI 10.1016/j.cbi.2005.10.052 PG 3 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 998RN UT WOS:000234337000057 PM 16429486 ER PT J AU Matrisian, LM Barker, AD Eggermont, AMM AF Matrisian, LM Barker, AD Eggermont, AMM TI AACR-NCI-HORTC International Conference - Molecular Targets and Cancer Therapeutics - Discovery, Biology, and Clinical Applications - The premier international meeting featuring novel cancer therapeutics - November 14-18, 2005 - Pennsylvania Convention Center - Philadelphia, Pennsylvania - Welcome SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP II EP II PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700001 ER PT J AU Rezvani, K Brenchley, JM Price, DA Kilical, Y Gostick, E Sewell, AK Li, JM Mielke, S Douek, DC Barrett, AJ AF Rezvani, K Brenchley, JM Price, DA Kilical, Y Gostick, E Sewell, AK Li, JM Mielke, S Douek, DC Barrett, AJ TI T-cell responses directed against multiple HLA-A*0201-restricted epitopes derived from Wilms' tumor 1 protein in patients with leukemia and healthy donors: Identification, quantification, and characterization SO CLINICAL CANCER RESEARCH LA English DT Article ID WILMS-TUMOR GENE; ACUTE MYELOID-LEUKEMIA; VERSUS-HOST-DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; GLUTAMIC-ACID DECARBOXYLASE; WT1 PRODUCT; ADOPTIVE IMMUNOTHERAPY; LYMPHOCYTES; ANTIGEN; PEPTIDE AB Purpose: Antigens derived from the Wilms' tumor (WT1) protein, which is overexpressed in leukemias, are attractive targets for immunotherapy. Four HLA-A*0201-restricted WT1-derived epitopes have been identified: WT37,WT126, WT187, and WT235. We determined the natural immunogenecity of these antigens in patients with hematologic malignancies and healthy donor. Experimental Design: To detect very low frequencies of WT1-specific CD8(+) T cells, we used quantitative reverse transcription-PCR to measure IFN-gamma mRNA production by WT1 peptide pulsed CD8(+) T cells from 12 healthy donors, 8 patients with chronic myelogenous leukemia, 6 patients with acute myelogenous leukemia, and 8 patients with acute lymphoblastic leukemia. Results: Responses were detected in 5 of 8 chronic myelogenous leukemia patients, 4 of 6 patients with acute myelogenous leukemia, and 7 of 12 healthy donors. No responses were detected in patients with acute lymphoblastic leukemia. The magnitude and extent of these CD8(+) T-cell responses was greater in patients with myeloid leukemias than in healthy donors. Clonotypic analysis of WT1-specific CD8(+) T cells directly ex vivo in one case showed that this naturally occurring population was oligoclonal. Using fluorescent peptide-MHC class I tetramers incorporating mutations in the 0 domain (D227K/T228A) that abrogate binding to the CD8 coreceptor, we were able to confirm the presence of high-avidity T-cell clones within the antigen-specific repertoire. Conclusion: The natural occurrence of high-avidity WT1-specific CD8(+) T cells in the periphery could facilitate vaccination strategies to expand immune responses against myeloid leukemias. C1 NHLBI, NIH, Stem Cell Allotransplantat Sect, Hematol Branch, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Oxford, Nuffield Dept Med, Oxford, England. RP Rezvani, K (reprint author), NHLBI, NIH, Stem Cell Allotransplantat Sect, Hematol Branch, Room 3E-5288,Bldg 10,900 Rockville Pike, Bethesda, MD 20892 USA. EM rezvanik@nhlbi.nih.gov RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Sewell, Andrew/0000-0003-3194-3135 FU Medical Research Council [G108/441] NR 45 TC 80 Z9 80 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 BP 8799 EP 8807 DI 10.1158/1078-0432.CCR-05-1314 PN 1 PG 9 WC Oncology SC Oncology GA 998YR UT WOS:000234356300037 PM 16361568 ER PT J AU Sridhar, SS Canil, CM Hotte, SJ Chi, KN Ernst, S Pond, GR Dick, C Zwiebel, JA Moore, MJ AF Sridhar, SS Canil, CM Hotte, SJ Chi, KN Ernst, S Pond, GR Dick, C Zwiebel, JA Moore, MJ TI A phase 2 study of GTI-2040 plus docetaxel and prednisone as 1st line treatment in hormone-refractory prostate cancer (HRPC). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Juravinski Canc Ctr, Hamilton, ON, Canada. Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 8974S EP 8974S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700038 ER PT J AU Fracasso, PM Rudek, MA Ellis, MJ Goodner, SA Dancey, J McLeod, HL AF Fracasso, PM Rudek, MA Ellis, MJ Goodner, SA Dancey, J McLeod, HL TI A pharmacokinetic and pharmacodynamic Phase 1 study of UCN-01 and irinotecan in resistant solid tumors. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Washington Univ, Sch Med, St Louis, MO USA. Johns Hopkins Univ, Sidney Kimmell Comprehens Canc Ctr, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 8985S EP 8985S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700087 ER PT J AU Houghton, PJ Maris, JM Friedman, HS Keir, ST Lock, RB Gorlick, R Kolb, EA Reynolds, CP Morton, C Smith, MA AF Houghton, PJ Maris, JM Friedman, HS Keir, ST Lock, RB Gorlick, R Kolb, EA Reynolds, CP Morton, C Smith, MA TI Evaluation of bortezomib against childhood tumor models by the pediatric preclinical testing program (PPTP) SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT 17th EORTC/AACR/NCI International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP European Soc Comparat Endocrinol, City Manchester, Univ Manchester, AstraZeneca, Bristol Myers Squibb, Pfizer, Sanofi Aventis, Bayer Healthcare Pharmaceut, Lilly, Genentech, GlaxoSmithKline, Johnson & Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Duke Univ, Durham, NC 27706 USA. Childrens Canc Inst Australia, Randwick, NSW, Australia. Albert Einstein Coll Med, New York, NY USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 8987S EP 8988S PN 2 PG 2 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700098 ER PT J AU Shoemaker, RH Scudiero, D Currens, M Akee, R McCloud, T Cardellina, J Sausville, EA Radomska, H Tenen, DG AF Shoemaker, RH Scudiero, D Currens, M Akee, R McCloud, T Cardellina, J Sausville, EA Radomska, H Tenen, DG TI A novel small molecule activator of CEBPa signaling with anti-leukemic potential identified in a high-throughput screen. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Frederick, MD 21701 USA. SAIC Frederick, Frederick, MD 21701 USA. Univ Maryland, Baltimore, MD 21201 USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 8989S EP 8989S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700102 ER PT J AU Chen, EX Zhang, WJ Pond, GR Dancey, J Oza, A Siu, LL Moore, M AF Chen, EX Zhang, WJ Pond, GR Dancey, J Oza, A Siu, LL Moore, M TI Correlation between erlotinib concentrations and severity of skin rash. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 PMH Phase II Consortium, Toronto, ON, Canada. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 8993S EP 8993S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700121 ER PT J AU Bergen, AW Baccarelli, A McDaniel, TK Kuhn, K Chudin, E Bender, P Pfeiffer, R Packer, B Yeager, M Chanock, S AF Bergen, AW Baccarelli, A McDaniel, TK Kuhn, K Chudin, E Bender, P Pfeiffer, R Packer, B Yeager, M Chanock, S TI Cancer gene sequence variation, lymphoblast transcript levels and association analysis. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Bethesda, MD 20892 USA. Univ Milan, I-20122 Milan, Italy. Illumina, San Diego, CA USA. Coriell Inst, Camden, NJ USA. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9000S EP 9000S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700153 ER PT J AU Zibert, JR Eriksen, J Svane, IM Skovsgaard, T Axelsson, C Flyger, H Balslev, E Bates, SE Litman, T AF Zibert, JR Eriksen, J Svane, IM Skovsgaard, T Axelsson, C Flyger, H Balslev, E Bates, SE Litman, T TI Gene expression pattern of primary breast tumors among Danish women with focus on apoptotic and multidrug resistance genes. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Univ Hosp Herlev, Herlev, Denmark. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. Ctr Bioinformat, E Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9002S EP 9002S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700158 ER PT J AU Kosakowska-Cholody, T Monks, AP Cholody, WM Hariprakasha, HK Kar, S Carr, BI Michejda, CJ AF Kosakowska-Cholody, T Monks, AP Cholody, WM Hariprakasha, HK Kar, S Carr, BI Michejda, CJ TI Ribonucleotide reductase and Cdc7 are important targets of HKH40A, a potent agent against gastrointestinal cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Frederick, MD 21701 USA. SAIC, Frederick, MD USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9016S EP 9016S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700208 ER PT J AU Agama, KK Antony, S Nagarajan, M Cushman, M Pommier, Y AF Agama, KK Antony, S Nagarajan, M Cushman, M Pommier, Y TI Bisindenoisoquinoline (NSC 727357): A novel inhibitor of topoisomerases. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, NIH, Bethesda, MD 20892 USA. Dept Med Chem & Mol Pharmacol, W Lafayette, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9019S EP 9019S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700223 ER PT J AU Antony, S Agarra, KK Nagarajan, M Cushman, M Pommier, Y AF Antony, S Agarra, KK Nagarajan, M Cushman, M Pommier, Y TI Cellular topoisomerase I inhibition and antiproliferative activity of indenoisoquinolines selected for preclinical development. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, NIH, Bethesda, MD 20892 USA. Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9019S EP 9019S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700221 ER PT J AU Rapisarda, A Uranchimeg, B Hollingshead, M Borgel, S Carter, J Shoemaker, RH Melillo, G AF Rapisarda, A Uranchimeg, B Hollingshead, M Borgel, S Carter, J Shoemaker, RH Melillo, G TI Topotecan inhibits HIF-1 alpha, but not HIF-2 alpha, protein accumulation and tumor growth in human renal cancer cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 SAIC Frederick Inc, Frederick, MD USA. Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9019S EP 9019S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700220 ER PT J AU Miao, ZH Rao, VA Agama, K Antony, S Pommier, Y AF Miao, ZH Rao, VA Agama, K Antony, S Pommier, Y TI 4-nitroquinoline-1-oxide induces the formation of cellular topoisomerase I-DNA cleavage complexes. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9020S EP 9020S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700227 ER PT J AU Li, J Sparreboom, A Zhao, M Robey, R Bates, S Baker, SD AF Li, J Sparreboom, A Zhao, M Robey, R Bates, S Baker, SD TI Gefitinib and erlotinil epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, are substrates for the breast cancer resistance protein (BCRP)/ABCG2 transporter. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Johns Hopkins Univ, Baltimore, MD USA. Natl Canc Inst, Bethesda, MD USA. RI Sparreboom, Alex/B-3247-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9027S EP 9027S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700253 ER PT J AU Liu, YM Borchert, G Surazynski, A Hu, CAA Phang, JM AF Liu, YM Borchert, G Surazynski, A Hu, CAA Phang, JM TI Proline oxidase, a p53-induced gene, metabolically activates both intrinsic and extrinsic pathways for apoptosis: The role of superoxide radicals, NFAT and MEK/ERK signaling. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Natl Canc Inst, Frederick, MD USA. SAIC, Basic Res Program, Frederick, MD USA. Univ New Mexico, Albuquerque, NM 87131 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9038S EP 9038S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700297 ER PT J AU Grubbs, CJ Bode, AM Dong, ZG Steele, VE Juliana, MM Lubet, RA AF Grubbs, CJ Bode, AM Dong, ZG Steele, VE Juliana, MM Lubet, RA TI Chemopreventive and therapeutic effects of the EGFr inhibitor Iressa in the methylnitrosourea (MNU)-induced model of mammary carcinogenesis. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Univ Alabama, Birmingham, AL USA. Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9041S EP 9041S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700311 ER PT J AU Nolan, KA Chinje, E Wind, N Zhao, H Burke, T Stratford, I Bryce, R AF Nolan, KA Chinje, E Wind, N Zhao, H Burke, T Stratford, I Bryce, R TI In silico identification, biochemical and cell-based characterization of novel inhibitors of NQO1. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Univ Manchester, Sch Pharm, Manchester, Lancs, England. NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9051S EP 9052S PN 2 PG 2 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700356 ER PT J AU Tarasova, NI Henrich, CJ Amadei, G Bokesch, HR Dyba, MA Tarasov, SG McMahon, JB Michejda, CJ AF Tarasova, NI Henrich, CJ Amadei, G Bokesch, HR Dyba, MA Tarasov, SG McMahon, JB Michejda, CJ TI Transmembrane inhibitors of ABCG2, an ABC transporter that confers chemoresistance in cancer stem cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Frederick, MD 21701 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9052S EP 9052S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700357 ER PT J AU Lubet, RA Grubbs, CJ Christov, K Brouillette, W Muccio, DD AF Lubet, RA Grubbs, CJ Christov, K Brouillette, W Muccio, DD TI Therapy and prevention of methylnitrosourea (MNU)-induced mammary cancers with new retinoids and correlations with short-term biomarkers. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. Univ Illinois, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9053S EP 9053S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700361 ER PT J AU Puzanov, I Lee, W Berlin, JD Calcutt, MW Hachey, DL Vermeulen, W Low, J Rothenberg, ML AF Puzanov, I Lee, W Berlin, JD Calcutt, MW Hachey, DL Vermeulen, W Low, J Rothenberg, ML TI Phase I and pharmacokinetic trial of SJG-136 administered on a daily x 5 schedule. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. NCI, Bethesda, MD 20892 USA. RI Puzanov, Igor/A-7179-2009 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9061S EP 9061S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700390 ER PT J AU Giubellino, A Dharmawardana, PG Coleman, JA Sun, JL Burgess, TL Bottaro, DP AF Giubellino, A Dharmawardana, PG Coleman, JA Sun, JL Burgess, TL Bottaro, DP TI c-Met ectodomain shedding as a potential tumor biomarker in vivo. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Bethesda, MD 20892 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9065S EP 9065S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700404 ER PT J AU Huan, R Wallqvist, A Thanki, N Covell, D AF Huan, R Wallqvist, A Thanki, N Covell, D TI Linking pathway gene expressions to the growth inhibition response from the National Cancer Institute's anticancer screen and drug mechanism of action. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, NIH, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9069S EP 9069S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701004 ER PT J AU Agulnik, M da Cunha-Santos, G Hedley, D Nicklee, T dos Reis, PP Ho, J Pond, GR Winquist, E Soulieres, D Chen, EX Squire, JA Marano, P Kamel-Reid, S Dancey, J Siu, LL Tsao, MS AF Agulnik, M da Cunha-Santos, G Hedley, D Nicklee, T dos Reis, PP Ho, J Pond, GR Winquist, E Soulieres, D Chen, EX Squire, JA Marano, P Kamel-Reid, S Dancey, J Siu, LL Tsao, MS TI Pharmacodynamic studies of erlotinib in tumor and skin tissue samples of patients (Pts) with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Princess Margaret Hosp Phase II Consortium, Toronto, ON, Canada. Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. Natl Canc Inst, Kingston, ON, Canada. NCI, Bethesda, MD 20892 USA. RI Reis, Patricia/F-4701-2012 OI Reis, Patricia/0000-0003-3775-3797 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9071S EP 9071S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701011 ER PT J AU Jia, L Noker, P Coward, L Gorman, G Kitada, S Reed, JC AF Jia, L Noker, P Coward, L Gorman, G Kitada, S Reed, JC TI In vitro and in vivo bioconversion of apogossypol hexaacetate to apogossypol: Implication for chemotherapy development. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, DTP, DCTD, NIH, Rockville, MD USA. So Res Inst, Birmingham, AL 35255 USA. Burnham Inst, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9073S EP 9073S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701018 ER PT J AU Smith, NF Baker, SD Zhao, M Harris, JW Figg, WD Sparreboom, A AF Smith, NF Baker, SD Zhao, M Harris, JW Figg, WD Sparreboom, A TI Modulation of erlotinib (OSI-774, Tarceva (R)) pharmacokinetics in mice by a novel cytochrome P450 3A4 (CYP3A4) inhibitor, BAS 100. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Bioavailabil Syst LLC, Cocoa Beach, FL USA. RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9076S EP 9076S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701029 ER PT J AU Sissung, TM Piekarz, RL Bates, SE Price, DK Hwang, K Figg, WD Sparreboom, A AF Sissung, TM Piekarz, RL Bates, SE Price, DK Hwang, K Figg, WD Sparreboom, A TI ABCB1 variants and QTc interval prolongation associated with the cyclic depsipeptide FK228. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Bethesda, MD 20892 USA. RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9078S EP 9078S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701036 ER PT J AU Gregorc, V Hidalgo, M Spreafico, A Aondio, G Cusatis, G Marsh, S Steinberg, SM Ludovini, V Villa, E Sparreboom, A Baker, SD AF Gregorc, V Hidalgo, M Spreafico, A Aondio, G Cusatis, G Marsh, S Steinberg, SM Ludovini, V Villa, E Sparreboom, A Baker, SD TI Inherited EGFR variants and survival in patients with non-small cell lung cancer (NSCLC) treated with gefitinib. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Sci Inst Univ Hosp San Rafaelle, Milan, Italy. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Washington Univ, Sch Med, St Louis, MO USA. NCI, Bethesda, MD 20892 USA. Policlin Monteluce Hosp, Perugia, Italy. RI Sparreboom, Alex/B-3247-2008; Cusatis, Gianluca/G-2539-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9079S EP 9079S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701040 ER PT J AU Koga, F Tsutsumi, S Neckers, L AF Koga, F Tsutsumi, S Neckers, L TI Geldanamycin effectively inhibits in vitro invasion and VEGF secretion mediated cooperatively by Met and HIF-1 alpha signaling pathways in aggressive bladder cancer cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Urol Oncol Branch, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9084S EP 9084S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701062 ER PT J AU Meng, LH Shankavaram, U Chen, C Ganzalez, F Weinstein, J Pommier, Y AF Meng, LH Shankavaram, U Chen, C Ganzalez, F Weinstein, J Pommier, Y TI Selective activity of aminoflavone (NSC 626288), a novel drug in phase I clinical trials is determined by cellular expression of sulfotransferase. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9086S EP 9087S PN 2 PG 2 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701073 ER PT J AU Marks, CL AF Marks, CL TI The NCI-Mouse models of human cancers consortium and experimental therapeutics. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9097S EP 9097S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701113 ER PT J AU Oza, AM Elit, L Biagi, J Gotlieb, W Tonkin, KS Tsao, M Hedley, D Hansen, C Dancey, J Eisenhauer, E Seymour, L AF Oza, AM Elit, L Biagi, J Gotlieb, W Tonkin, KS Tsao, M Hedley, D Hansen, C Dancey, J Eisenhauer, E Seymour, L TI A phase II study of temsirolimus (CCI-779) in patients with metastatic and/or locally recurrent endometrial cancer - NCICCTG IND 160. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. NCI, Bethesda, MD 20892 USA. NR 0 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9099S EP 9099S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701121 ER PT J AU Nguyen, DM Reddy, RM Tsai, W Yeows, WS Ziauddin, MF Zuo, JT Schrump, DS AF Nguyen, DM Reddy, RM Tsai, W Yeows, WS Ziauddin, MF Zuo, JT Schrump, DS TI The essential role of the mitochondria-dependent death signaling cascade in chemotherapy-induced potentiation of Apo2L/TRAIL cytotoxicity in cultured thoracic cancer cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9104S EP 9104S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701141 ER PT J AU Kreitman, RJ Wilson, WH Stetler-Stevenson, M FitzGerald, DJ Pastan, I AF Kreitman, RJ Wilson, WH Stetler-Stevenson, M FitzGerald, DJ Pastan, I TI Recombinant anti-CD22 immunotoxin BL22 induces durable complete remissions in phase I and II trials of patients with chemoresistant hairy cell leukemia. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9120S EP 9121S PN 2 PG 2 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701208 ER PT J AU Rao, VA Fan, A Meng, LH North, P Hickson, I Pommier, Y AF Rao, VA Fan, A Meng, LH North, P Hickson, I Pommier, Y TI Phosphorylation of Bloom's syndrome protein (BLM), dissociation from topoisomerase III alpha and colocalization with gamma-H2AX after topoisomerase I-induced replication damage by camptothecin. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Natl Canc Inst, Bethesda, MD USA. Univ Oxford, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9125S EP 9125S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701226 ER PT J AU Seamon, JA Rugg, CA Emanuel, S Calcagno, AM Ambudkar, SV Middleton, SA Greenberger, LM AF Seamon, JA Rugg, CA Emanuel, S Calcagno, AM Ambudkar, SV Middleton, SA Greenberger, LM TI The ABCG2 transporter mediates resistance to the CDK1/aurora inhibitor, JNJ-7706621. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Johnson & Johnson Consumer Prod Inc, Raritan, NJ USA. NCI, NIH, Bethesda, MD 20892 USA. RI Calcagno, Anna Maria/A-5617-2012 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9127S EP 9127S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701233 ER PT J AU Duran, I Nicklee, T Siu, LL Birle, D Pond, GR Kortmansky, J Singh, D Hirte, H Goss, G Le, L Dancey, J Hedley, D AF Duran, I Nicklee, T Siu, LL Birle, D Pond, GR Kortmansky, J Singh, D Hirte, H Goss, G Le, L Dancey, J Hedley, D TI Pharmacodynamic evaluations of paired tumor biopsies in advanced neuroendocrine carcinomas (NECs) treated with the mTOR inhibitor temsirolimus. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Princess Margaret Hosp, Phase Consortium 2, Toronto, ON, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Chicago, Chicago, IL 60637 USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9131S EP 9131S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701248 ER PT J AU Przytycki, P Przytycka, T Capala, J AF Przytycki, P Przytycka, T Capala, J TI In silico optimization of multi-target, selective blockage of EGF, IGF, and insulin signaling pathways. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Montgomery Blair High Sch, Math Sci Comp Sci Magnet Program, Silver Spring, MD USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9132S EP 9132S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701252 ER PT J AU Gills, JJ Hollbeck, S Hollingshead, M Hewitt, S Kozikowski, AP Dennis, PA AF Gills, JJ Hollbeck, S Hollingshead, M Hewitt, S Kozikowski, AP Dennis, PA TI Spectrum of anti-tumor activity and molecular correlates of response to phosphatidylinositol ether lipid analogues, novel lipid-based inhibitors of Akt. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Natl Canc Inst, Bethesda, MD USA. Univ Illinois, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9136S EP 9136S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701270 ER PT J AU Hassan, R Remaley, AT Sampson, M Zhang, JL Cox, DD Pingpank, J Alexander, R Willingham, M Pastan, I Onda, M AF Hassan, R Remaley, AT Sampson, M Zhang, JL Cox, DD Pingpank, J Alexander, R Willingham, M Pastan, I Onda, M TI Detection and quantitation of serum mesothelin, a tumor marker for patients with mesothelioma and ovarian cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Natl Canc Inst, Bethesda, MD USA. Natl Inst Hlth, Bethesda, MD USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9137S EP 9137S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701273 ER PT J AU Lee, MJ Chung, EJ Lee, S Brady, JN Trepel, JB AF Lee, MJ Chung, EJ Lee, S Brady, JN Trepel, JB TI Requirement for nuclear beta-catenin in HTLV-1 tax-induced transactivation: Identification of a new molecular target for the treatment of adult T-cell leukemia. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9142S EP 9142S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701292 ER PT J AU Tsutsumi, S Scroggins, B Tian, ZQ Santi, D Neckers, L AF Tsutsumi, S Scroggins, B Tian, ZQ Santi, D Neckers, L TI Cell-impermeable derivatives of the heat shock protein 90 inhibitor geldanamycin display low cytotoxicity but strongly inhibit tumor cell invasion in vitro SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Kosan Biosci, Hayward, CA USA. NCI, NIH, Rockville, MD USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9149S EP 9149S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701321 ER PT J AU Hose, C Shoemaker, R Monks, A AF Hose, C Shoemaker, R Monks, A TI Gene profiling of PXD-101, a novel hydroxamate type inhibitor of histone deacetylase, leads to identification of aurora kinase inhibition. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 SAIC Frederick, Frederick, MD USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9152S EP 9152S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701334 ER PT J AU Alley, MC Smith, AC Donohue, SJ Schweikart, KM Newman, DJ Tomaszewski, JE AF Alley, MC Smith, AC Donohue, SJ Schweikart, KM Newman, DJ Tomaszewski, JE TI Comparison of the relative efficacies and toxicities of halichondrin B analogues. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Dev Therapeut Program, DCTD, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, DCTD, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9156S EP 9156S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701350 ER PT J AU Kondapaka, SB Sarangan, R Burke, JR Mesner, KK Shoemaker, RH AF Kondapaka, SB Sarangan, R Burke, JR Mesner, KK Shoemaker, RH TI Adaphostin targets Src and Zap-70 in addition to Bcr/abl kinase. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9162S EP 9162S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701374 ER PT J AU Linhares, Y Gavard, J Basile, JR Gutkind, JS AF Linhares, Y Gavard, J Basile, JR Gutkind, JS TI Semaphorin 3E/plexin-D1 signaling induces focal adhesion disassembly, inactivates Rho, and inhibits endothelial cell motility. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NIDCR, NIH, Bethesda, MD USA. RI Gutkind, J. Silvio/A-1053-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9165S EP 9166S PN 2 PG 2 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701390 ER PT J AU Michejda, CJ Hunt, JT AF Michejda, CJ Hunt, JT TI Overview. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Frederick, MD 21701 USA. Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9168S EP 9168S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701395 ER PT J AU Newman, DJ AF Newman, DJ TI Preclinical development of halichondrin B and its derivative Eisai E7389. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9168S EP 9168S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701396 ER PT J AU Szabo, E AF Szabo, E TI Identifying molecular targets for cancer prevention: Overview. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9171S EP 9171S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701407 ER PT J AU Melillo, G AF Melillo, G TI Targeting topoisomerases to inhibit hypoxia inducible factor 1 (HIF-1): Mechanism and clinical implications. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9174S EP 9175S PN 2 PG 2 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701422 ER PT J AU Pommier, Y AF Pommier, Y TI Interfacial inhibition of protein-nucleic acid interactions: One of nature's paradigms for drug discovery. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9177S EP 9177S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701431 ER PT J AU Coleman, CN AF Coleman, CN TI Molecular targets for radiation modification. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 9179S EP 9180S PN 2 PG 2 WC Oncology SC Oncology GA 999IJ UT WOS:000234382701441 ER PT J AU Sostaric, JZ Miyoshi, N Riesz, P DeGraff, WG Mitchell, JB AF Sostaric, JZ Miyoshi, N Riesz, P DeGraff, WG Mitchell, JB TI n-Alkyl glucopyranosides completely inhibit ultrasound-induced cytolysis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE free radicals; EPR; ESR; sonoporation; sonophoresis; sonochemistry; radiolysis; HIFU; ultrasound; surfactants; HL-60; protection; sonoprotection; cytolysis; sonolysis; sonication; glucopyranoside; sugars; bioreactors ID CELLS-IN-VITRO; SUPEROXIDE-DISMUTASE; SURFACTANT SOLUTIONS; ACOUSTIC CAVITATION; HYDROGEN-PEROXIDE; SONOCHEMISTRY; BUBBLES; DAMAGE; CYSTEAMINE; FREQUENCY AB The mechanism(s) responsible for sudden cytolysis observed when cells are exposed to ultrasound could be mechanical and/or free radical in nature. Free radical reactions are initiated in the core and in the interfacial regions of collapsing acoustic cavitation bubbles. Because cyclic sugars are known to inhibit free radical chain reactions, we investigated the effects of n-alkyl-beta-D-glucopyranosides of varying hydrophobicity on ultrasound (1.057 MHz)-induced cytolysis of HL-60 cells in vitro. n-Alkyl glucopyranosides with hexyl-(5 mM), heptyl-(3 mM), or octyl-(2 mM) n-alkyl chains protected 100% of the cell population frorn ultrasound-induced cytolysis under a range of conditions that resulted in 35 to 100% cytolysis in the absence of glucopyranos ides. The protected cell populations also possessed long-term reproductive viability. However, the hydrophilic methyl-beta-D-glucopyranoside could not protect cells, even up to a concentration of 30 mM. Furthermore, none of the glucopyranosides could prevent cytolysis of cells frorn a mechanically induced shear stress. Spin trapping and electron spin resonance experiments confirmed the presence of inertial cavitation in cell suspensions both in the presence and in the absence of the surfactants. It is concluded that surface-active glucopyranosides efficiently quench cytotoxic radicals and/or their precursors at the gas/solution interface of collapsing cavitation bubbles. Published by Elsevier Inc. C1 NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Fukui, Fac Med, Dept Pathol Sci, Div Tumor Pathol, Fukui 9101193, Japan. RP Sostaric, JZ (reprint author), Ohio State Univ, Ctr Biomed EPR Imaging, Daivs Heart & Lung Res Inst, 420 W 12th Ave,TMRF 184, Columbus, OH 43210 USA. EM sostaric.2@osu.edu; jbm@helix.nih.gov RI Sostaric, Joe/A-6033-2008 FU Intramural NIH HHS NR 54 TC 14 Z9 14 U1 1 U2 1 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 DEC 15 PY 2005 VL 39 IS 12 BP 1539 EP 1548 DI 10.1016/j.freeradbiomed.2005.07.020 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 991XJ UT WOS:000233847700001 PM 16298679 ER PT J AU Grice, EA Rochelle, ES Green, ED Chakravarti, A McCallion, AS AF Grice, EA Rochelle, ES Green, ED Chakravarti, A McCallion, AS TI Evaluation of the RET regulatory landscape reveals the biological relevance of a HSCR-implicated enhancer SO HUMAN MOLECULAR GENETICS LA English DT Article ID HIRSCHSPRUNG-DISEASE; MAMMALIAN GENOMES; C-RET; SEQUENCES; MOUSE; EXPRESSION; ELEMENTS; IDENTIFICATION; PROTOONCOGENE; MUTATION AB Evolutionary sequence conservation is now a relatively common approach for the prediction of functional DNA sequences. However, the fraction of conserved non-coding sequences with regulatory potential is still unknown. In this study, we focus on elucidating the regulatory landscape of RET, a crucial developmental gene within which we have recently identified a regulatory Hirschsprung disease (HSCR) susceptibility variant. We report a systematic examination of conserved non-coding sequences (n=45) identified in a 220 kb interval encompassing RET. We demonstrate that most of these conserved elements are capable of enhancer or suppressor activity in vitro, and the majority of the elements exert cell type-dependent control. We show that discrete sequences within regulatory elements can bind nuclear protein in a cell type-dependent manner that is consistent with their identified in vitro regulatory control. Finally, we focused our attention on the enhancer implicated in HSCR to demonstrate that this element drives reporter expression in cell populations of the excretory system and central nervous system (CNS) and peripheral nervous system (PNS), consistent with expression of the endogenous RET protein. Importantly, this sequence also modulates expression in the enteric nervous system consistent with its proposed role in HSCR. C1 Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Comparat Med, Baltimore, MD 21205 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP McCallion, AS (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, BRB Room 449,733 N Broadway, Baltimore, MD 21205 USA. EM amccalli@jhmi.edu OI Grice, Elizabeth/0000-0003-3939-2200 NR 37 TC 53 Z9 56 U1 0 U2 2 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 DEC 15 PY 2005 VL 14 IS 24 BP 3837 EP 3845 DI 10.1093/hmg/ddi408 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 997BB UT WOS:000234218900006 PM 16269442 ER PT J AU Thompson, DA Janecke, AR Lange, J Feathers, KL Hubner, CA McHenry, CL Stockton, DW Rammesmayer, G Lupski, JR Antinolo, G Ayuso, C Baiget, M Gouras, P Heckenlively, JR den Hollander, A Jacobson, SG Lewis, RA Sieving, PA Wissinger, B Yzer, S Zrenner, E Utermann, G Gal, A AF Thompson, DA Janecke, AR Lange, J Feathers, KL Hubner, CA McHenry, CL Stockton, DW Rammesmayer, G Lupski, JR Antinolo, G Ayuso, C Baiget, M Gouras, P Heckenlively, JR den Hollander, A Jacobson, SG Lewis, RA Sieving, PA Wissinger, B Yzer, S Zrenner, E Utermann, G Gal, A TI Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle SO HUMAN MOLECULAR GENETICS LA English DT Article ID SHORT-CHAIN DEHYDROGENASE/REDUCTASE; PROTEIN-STRUCTURE PREDICTION; LEBER CONGENITAL AMAUROSIS; DELAYED DARK-ADAPTATION; ALL-TRANS-RETINOL; BINDING-PROTEIN; FUNDUS-ALBIPUNCTATUS; RETINITIS-PIGMENTOSA; CHILDHOOD BLINDNESS; IN-VIVO AB Retinoid dehydrogenases/reductases catalyze key oxidation-reduction reactions in the visual cycle that converts vitamin A to 11-cis retinal, the chromophore of the rod and cone photoreceptors. It has recently been shown that mutations in RDH12, encoding a retinol dehydrogenase, result in severe and early-onset autosomal recessive retinal dystrophy (arRD). In a cohort of 1011 individuals diagnosed with arRD, we have now identified 20 different disease-associated RDH12 mutations, of which 16 are novel, in a total of 22 individuals (2.2%). Haplotype analysis suggested a founder mutation for each of the three common mutations: p.L99I, p.T155I and c.806_810delCCCTG. Patients typically presented with early disease that affected the function of both rods and cones and progressed to legal blindness in early adulthood. Eleven of the missense variants identified in our study exhibited profound loss of catalytic activity when expressed in transiently transfected COS-7 cells and assayed for ability to convert all-trans retinal to all-trans retinol. Loss-of-function appeared to result from decreased protein stability, as expression levels were significantly reduced. For the p.T49M variant, differing activity profiles were associated with each of the alleles of the common p.R161Q RDH12 polymorphism, suggesting that genetic background may act as a modifier of mutation effect. A locus (LCA3) for Leber congenital amaurosis, a severe, early-onset form of arRD, maps close to RDH12 on chromosome 14q24. Haplotype analysis in the family in which LCA3 was mapped excluded RDH12 as the LCA3 gene and thus suggests the presence of a novel arRD gene in this region. C1 Univ Michigan, WK Kellogg Eye Ctr, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48105 USA. Med Univ Innsbruck, Dept Med Genet Mol & Klin Pharmakol, Innsbruck, Austria. Univ Klinikum Hamburg Eppendorf, Inst Humangenet, Hamburg, Germany. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Hosp Univ Virgen Rocio, Unidad Genet Med & Diagnost Prenatal, Seville, Spain. Fdn Jimenez Diaz, E-28040 Madrid, Spain. Hosp San Pau, Barcelona, Spain. Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. Radboud Univ Nijmegen Med Ctr, Dept Human Genet, Nijmegen, Netherlands. Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Tubingen, Klin Augenheilkunde, Tubingen, Germany. Rotterdam Eye Hosp, Rotterdam, Netherlands. McGill Univ, Ctr Hlth, McGill Ocular Genet Lab, Montreal, PQ, Canada. RP Thompson, DA (reprint author), Univ Michigan, WK Kellogg Eye Ctr, Sch Med, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA. EM dathom@umich.edu RI Hollander, Anneke/N-4911-2014; IBIS, REPRODUCCION/P-3399-2015; Hubner, Christian/A-2950-2017; OI Hubner, Christian/0000-0002-1030-4943; Janecke, Andreas/0000-0001-7155-0315; Ayuso, Carmen/0000-0002-9242-7065 FU NCRR NIH HHS [M01-RR00042]; NEI NIH HHS [P30-EY07003, R01-EY12298, R01-EY13385] NR 40 TC 49 Z9 51 U1 0 U2 0 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 DEC 15 PY 2005 VL 14 IS 24 BP 3865 EP 3875 DI 10.1093/hmg/ddi411 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 997BB UT WOS:000234218900009 PM 16269441 ER PT J AU Petersen, DC Glashoff, RH Shrestha, S Bergeron, J Laten, A Gold, B van Rensburg, EJ Dean, M Hayes, VM AF Petersen, DC Glashoff, RH Shrestha, S Bergeron, J Laten, A Gold, B van Rensburg, EJ Dean, M Hayes, VM TI Risk for HIV-1 infection associated with a common CXCL12 (SDF1) polymorphism and CXCR4 variation in an African population SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CXC chemokine ligand 12 (CXCL 12); CXC chemokine receptor 4 (CXCR4); SDFI-3 ' A single-nucleotide polymorphism; HIV-1 infection risk; African population ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR CXCR4; GRADIENT GEL-ELECTROPHORESIS; GENETIC POLYMORPHISMS; DISEASE PROGRESSION; MOLECULAR-CLONING; CHROMOSOMAL LOCALIZATION; GENOMIC ORGANIZATION; I INFECTION; CCR5 AB CXC chemokine ligand 12 (CXCL 12), or stromal cell-derived factor 1 (SDF1), is file only known natural ligand for the HIV-1 coreceptor, CXC chemokine receptor 4 (CXCR4). A single nucleotide polymorphism (SNP) in the CXCL12 gene (SDF1-3'A) has been associated with disease progression to AIDS in sonic studies, but not others. Mutations in the CXCR4 gene are generally rare and have not been implicated in HIV-1/AIDS pathogenesis. This Study analyzed the SDF1-3'A SNP and performed mutation screening for polymorphic markers in the CXCR4 gene to determine the presence or absence of significant associations with susceptibility to HIV-1 infection. The study consisted of 257 HIV-1-seropositive patients and 113 HIV-1-seronegative controls representing a sub-Saharan African population belonging to the Xhosa ethnic group of south Africa. The SDF1-3'A SNP was associated with ail increased risk for HIV-1 infection (P = 0.0319) whereas no significant association was observed between the Occurrence of the SDF1-3'A SNP and increased or decreased plasma levels of CXCL12. Comprehensive Mutation analysis of the CXCR4 gene confirmed a high degree of genetic conservation within the coding region of this ancient Population. C1 St Vincents Hosp, Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW 2010, Australia. Univ Stellenbosch, Tygerberg Med Sch, Dept Med Virol, ZA-7600 Stellenbosch, South Africa. Univ Stellenbosch, Tygerberg Med Sch, Dept Urol, ZA-7600 Stellenbosch, South Africa. Natl Canc Inst, Lab Genom Divers, Frederick, MD USA. Sci Applicat Int Corp, Basic Res Program, Frederick, MD USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. Univ Pretoria, Dept Med Virol, ZA-0002 Pretoria, South Africa. RP Hayes, VM (reprint author), St Vincents Hosp, Garvan Inst Med Res, Canc Res Program, 384 Victoria St, Darlinghurst, NSW 2010, Australia. EM v.hayes@garvan.org.au RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400, Z01 BC005652-15] NR 49 TC 37 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2005 VL 40 IS 5 BP 521 EP 526 DI 10.1097/01.qai.0000186360.42834.28 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 989SR UT WOS:000233694600003 PM 16284526 ER PT J AU Penzak, SR Fomnentini, E Alfaro, RM Long, M Natarajan, V Kovacs, J AF Penzak, SR Fomnentini, E Alfaro, RM Long, M Natarajan, V Kovacs, J TI Prednisolone pharmacokinetics in the presence and absence of Ritonavir after oral prednisone administration to healthy volunteers SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE protease inhibitor; drug interaction; cytochrome P450; corticosteroid ID HUMAN-IMMUNODEFICIENCY-VIRUS; RENAL-TRANSPLANT RECIPIENTS; P-GLYCOPROTEIN; HIV; OSTEONECROSIS; THERAPY; PATIENT; KETOCONAZOLE; FLUTICASONE; METABOLISM AB Corticosteroid therapy has been associated with bone toxicities (eg, osteonecrosis) and Cushing syndrome in HIV-infected patients; this may be partially attributable to a pharmacokinetic drug interaction between HIV protease inhibitors and corticosteroids. The purpose of this study was to characterize the influence of low-dose ritonavir on prednisolone pharmacokinetics in healthy subjects. Ten HIV-seronegative volunteers were given single oral doses of prednisone, 20 mg, before (baseline) and after receiving ritonavir, 200 mg, twice daily for 4 and 14 days. After each prednisone close, serial blood samples were collected and prednisolone concentrations were determined; pharmacokinetic parameter values were compared between the groups. Geometric mean ratios (GMRs, 90% confidence interval [Cl]) of the prednisolone area under the plasma concentration versus time Curve (AUC(0-infinity)) after 4 and 14 days of ritonavir versus baseline were 1.41 (90% Cl: 1.08 to 1.74) and 1.30 (90% Cl: 1.09 to 1.49), respectively (P = 0.002 and P = 0.004, respectively). GMRs of prednisolone apparent oral clearance (Cl/F) were 0.71 (09% Cl: 0.57 to 0.93) and 0.77 (90%, Cl: 0.67 to 0.92) after 4 and 14 days of ritonavir versus baseline, respectively (P = 0.0004 and P = 0.0003, respectively). Ritonavir significantly increased the systemic exposure of prednisolone in healthy subjects. Results from this investigation suggest that corticosteroid exposure is likely elevated in HIV-infected patients receiving protease inhibitors. C1 NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA. NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Penzak, SR (reprint author), NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bldg 10,Room 1N 257, Bethesda, MD 20892 USA. EM Spenzak@mail.cc.nih.gov NR 40 TC 23 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2005 VL 40 IS 5 BP 573 EP 580 DI 10.1097/01.qai.0000187444.38461.70 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 989SR UT WOS:000233694600011 PM 16284534 ER PT J AU Allen, MA Liang, TS La Salvia, T Tjugum, B Gulakowski, RJ Murguia, M AF Allen, MA Liang, TS La Salvia, T Tjugum, B Gulakowski, RJ Murguia, M TI Assessing the attitudes, knowledge, and awareness of HIV vaccine research among adults in the United States SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; vaccine; survey; attitudes; racial and ethnic minorities ID TRIALS; PARTICIPATION; WILLINGNESS; RECRUITMENT AB Objectives: To assess HIV vaccine research attitudes, awareness, and knowledge among adults in the general US population, African Americans, Hispanics, and men who have sex with men (MSM). Methods: Applying results of focus groups and a media content analysis, a survey was designed and conducted to validate key HIV vaccine research themes and messages identified by focus groups and a media content analysis. Between December 2002 and February 2003, 3509 telephone interviews were conducted, including 2008 randomly selected from the general population, and 501 population-specific samples of African Americans and Hispanics, and 500 from MSM. Results: Although the majority of each Population believes that an HIV preventive vaccine is the best way to control and end the global AIDS epidemic, only 34.9% of African Americans and 28.8% of the general Population are supportive of someone they know volunteering for ail HIV vaccine trial. The Study also found that 47.1% of African Americans, 26.5% of Hispanics, and 13.4% of MSM believed air HIV vaccine already exists and is being kept secret, and 78.0% of African Americans, 57.5% of Hispanics, and 68.0%, of MSM did not know or incorrectly believed that the vaccines being tested could cause HIV infection. A subanalysis of the general Population also found that women generally had less knowledge of or a decreased awareness about HIV vaccine research. Conclusions: Awareness, knowledge, and attitudes toward HIV vaccine research vary by Population and these issues must be addressed to ensure an adequate number of volunteers for future domestic HIV preventive vaccine clinical trials. In some Populations, barriers Such as misinformation and distrust must be targeted to increase support for HIV vaccine research. C1 NIAID, NIH, Div Aids, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. Ogilvy Publ Relat Worldwide Inc, New York, NY USA. RP Murguia, M (reprint author), NIAID, NIH, Div Aids, 6700-B Rockledge Dr, Bethesda, MD 20892 USA. EM mmurguia@niaid.nih.gov OI Allen, Mary/0000-0001-8163-0714 NR 15 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2005 VL 40 IS 5 BP 617 EP 624 DI 10.1097/01.qai.0000174655.63653.38 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 989SR UT WOS:000233694600017 PM 16284540 ER PT J AU Sailer, MHM Hazel, TG Panchision, DM Hoeppner, DJ Schwab, ME McKay, RDG AF Sailer, MHM Hazel, TG Panchision, DM Hoeppner, DJ Schwab, ME McKay, RDG TI BMP2 and FGF2 cooperate to induce neural-crest-like fates from fetal and adult CNS stem cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE forebrain; neural stem cell; cranial neural crest; choroid plexus mesenchyme (CPm); epithelial-mesenchymal transition (EMT); Snai1; Snai2 ID CENTRAL-NERVOUS-SYSTEM; FIBROBLAST-GROWTH-FACTOR; TRANSCRIPTION FACTORS; NEURONAL DIFFERENTIATION; DEVELOPMENTAL-CHANGES; SELF-RENEWAL; SPECIFICATION; WNT; SIGNALS; SNAIL AB CNS stem cells are best characterized by their ability to self-renew and to generate multiple differentiated derivatives, but the effect of mitogenic signals, such as fibroblast growth factor 2 (FGF2), on the positional identity of these cells is not well understood. Here, we report that bone morphogenetic protein 2 (BMP2) induces telencephalic CNS stem cells to fates characteristic of neural crest and choroid plexus mesenchyme, a cell type of undetermined lineage in rodents. This induction occurs both in dissociated cell culture and cortical explants of embryonic day 14.5 (E14.5) embryos, but only when cells have been exposed to FGF2. Neither EGF nor IGF1 can substitute for FGF2. An early step in this response is activation of beta-catenin, a mediator of Wnt activity. The CNS stem cells first undergo an epithelial-to-mesenchymal transition and subsequently differentiate to smooth-muscle and non-CNS glia cells. Similar responses are seen with stem cells from E14.5 cortex, E18.5 cortex and adult subventricular zone, but with a progressive shift toward gliogenesis that is characteristic of normal development. These data indicate that FGF2 confers competence for dorsalization independently of its mitogenic action. This rapid and efficient induction of dorsal fates may allow identification of positional identity effectors that are coregulated by FGF2 and BMP2. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Zurich, Brain Res Inst, CH-8057 Zurich, Switzerland. Swiss Fed Inst Technol, Dept Biol, CH-8057 Zurich, Switzerland. Childrens Natl Med Ctr, Childrens Res Inst, Ctr Res Neurosci, Washington, DC 20010 USA. RP McKay, RDG (reprint author), NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM mckay@codon.nih.gov RI Schwab, Martin/B-6818-2016 FU Intramural NIH HHS NR 79 TC 46 Z9 50 U1 1 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD DEC 15 PY 2005 VL 118 IS 24 BP 5849 EP 5860 DI 10.1242/jcs.02708 PG 12 WC Cell Biology SC Cell Biology GA 005GW UT WOS:000234811600019 PM 16339968 ER PT J AU Nakashima, H Nakano, M Ohnishi, R Hiraoka, Y Kaneda, Y Sugino, A Masumoto, H AF Nakashima, H Nakano, M Ohnishi, R Hiraoka, Y Kaneda, Y Sugino, A Masumoto, H TI Assembly of additional heterochromatin distinct from centromere-kinetochore chromatin is required for de novo formation of human artificial chromosome SO JOURNAL OF CELL SCIENCE LA English DT Article DE centromere; heterochromatin; HAC; transcription; epigenetics ID ALPHA-SATELLITE DNA; CENP-B; TRANSGENE EXPRESSION; MODIFICATION PATTERN; HISTONE MODIFICATION; OUTER KINETOCHORE; VERTEBRATE CELLS; COMPLEX; METHYLATION; COHESION AB Alpha-satellite (alphoid) DNA is necessary for de novo formation of human artificial chromosomes (HACs) in human cultured cells. To investigate the relationship among centromeric, transcriptionally permissive and nonpermissive chromatin assemblies on de novo HAC formation, we constructed bacterial artificial chromosome (BAC)-based linear HAC vectors whose left vector arms are occupied by beta geo coding genes with or without a functional promoter in addition to a common marker gene on the right arm. Although HACs were successfully generated from the vectors with promoter-less constructs on the left arm in HT1080 cells, we failed to generate a stable HAC from the vectors with a functional promoter on the left arm. Despite this failure in HAC formation, centromere components (CENP-A, CENP-B and CENP-C) assembled at the integration sites correlating with a transcriptionally active state of both marker genes on the vector arms. However, on the stable HAC, chromatin immunoprecipitation analysis showed that HP1 alpha and trimethyl histone H3-K9 were enriched at the nontranscribing left vector arm. A transcriptionally active state on both vector arms is not compatible with heterochromatin formation on the introduced BAC DNA, suggesting that epigenetic assembly of heterochromatin is distinct from centromere chromatin assembly and is required for the establishment of a stable artificial chromosome. C1 Nagoya Univ, Div Biol Sci, Grad Sch Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan. Osaka Univ, Grad Sch Med, Div Gene Therapy Sci, Suita, Osaka 5650871, Japan. Osaka Univ, Grad Sch Frontier Biosci, Labs Biomol Networks, Suita, Osaka 5650871, Japan. Natl Inst Informat & Commun Technol, Kansai Adv Res Ctr, Nishi Ku, Kobe, Hyogo 6512492, Japan. RP Masumoto, H (reprint author), NCI, Lab Siosyst & Canc, NIH, Bldg 37,Rm 5040,900 Rockville Pike, Bethesda, MD 20892 USA. EM masumoth@mail.nih.gov RI Hiraoka, Yasushi/B-5111-2009 OI Hiraoka, Yasushi/0000-0001-9407-8228 FU Intramural NIH HHS NR 68 TC 33 Z9 35 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD DEC 15 PY 2005 VL 118 IS 24 BP 5885 EP 5898 DI 10.1242/jcs.02702 PG 14 WC Cell Biology SC Cell Biology GA 005GW UT WOS:000234811600022 PM 16339970 ER PT J AU Ettinger, R Sims, GP Fairhurst, AM Robbins, R da Silva, YS Spolski, R Leonard, WJ Lipsky, PE AF Ettinger, R Sims, GP Fairhurst, AM Robbins, R da Silva, YS Spolski, R Leonard, WJ Lipsky, PE TI IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED CYTIDINE DEAMINASE; COMMON GAMMA-CHAIN; SOMATIC HYPERMUTATION; MONOCLONAL-ANTIBODY; GENE-EXPRESSION; CD40 LIGATION; CUTTING EDGE; T-CELLS; GENERATION; RECEPTOR AB IL-21 is a type I cytokine that influences the function or T cells, NK cells, and B cells. In this study, we report that IL-21 plays a major role in stimulating the differentiation of human B cells. When human B cells were stimulated through the BCR, IL-21 induced minimal proliferation, IgD down-modulation, and small numbers of plasma cells. In contrast, after CD40 engagement, IL-21 induced extensive proliferation, class switch recombination (CSR), and plasma cell differentiation. Upon cross-linking both BCR and CD40, IL-21 induced the largest numbers of plasma cells. IL-21 drove both postswitch memory cells as well as poorly responsive naive cord blood B cells to differentiate into plasma cells. The effect of IL-21 was more potent than the combination of IL-2 and IL-10, especially when responsiveness of cord blood B cells was examined. IL-21 costimulation potently induced the expression of both B lymphocyte-induced maturation protein-1 (BLIMP-1) and activation-induced cytidine deaminase as well as the production of large amounts of IgG from B cells. Despite the induction of activation-induced cytidine deaminase and CSR, IL-21 did not induce somatic hypermutation. Finally, IL-2 enhanced the effects of IL-21, whereas IL-4 inhibited IL-21-induced plasma cell differentiation. Taken together, our data show that IL-21 plays a central role in CSR and plasma cell differentiation during T cell-dependent B cell responses. C1 NIAMSD, NIH, Autoimmun Branch, Bethesda, MD 20892 USA. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Ettinger, R (reprint author), NIAMSD, NIH, Autoimmun Branch, Bldg 10,Room 6D-47B, Bethesda, MD 20892 USA. EM ettingerr@mail.nih.gov FU Intramural NIH HHS NR 57 TC 341 Z9 357 U1 1 U2 17 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2005 VL 175 IS 12 BP 7867 EP 7879 PG 13 WC Immunology SC Immunology GA 994KJ UT WOS:000234030400013 PM 16339522 ER PT J AU Abrahams, VM Visintin, I Aldo, PB Guller, S Romero, R Mor, G AF Abrahams, VM Visintin, I Aldo, PB Guller, S Romero, R Mor, G TI A role for TLRs in the regulation of immune cell migration by first trimester trophoblast cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; TOLL-LIKE RECEPTOR-4; INTRAUTERINE INFECTION; PRETERM DELIVERY; HUMAN-NEUTROPHILS; HUMAN MONOCYTES; HUMAN PLACENTA; HUMAN DECIDUA; PREGNANCY; EXPRESSION AB Normal pregnancy is characterized by the presence of innate immune cells at the maternal-fetal interface. Originally, it was postulated that the presence of these leukocytes was due to an immune response toward paternal Ags expressed by the invading trophoblasts. Instead, we and others postulate that these innate immune cells are necessary for successful implantation and pregnancy. However, elevated leukocyte infiltration may be an underlying cause of pregnancy complications, such as preterm labor or preeclampsia. Furthermore, such conditions have been attributed to an intrauterine infection. Therefore, we hypothesize that first trimester trophoblast cells, upon recognition of microbes through TLRs, may coordinate an immune response by recruiting cells of the innate immune system to the maternal-fetal interface. In this study, we have demonstrated that human first trimester trophoblast cells constitutively secrete the chemokines growth-related oncogene, growth-related oncogene alpha, IL-8, and MCP-1 and are able to recruit monocytes and NK cells, and to a lesser degree, neutrophils. Following the ligation of TLR-3 by the viral ligand, poly(I:C), or TLR-4 by bacterial LPS, trophoblast secretion of chemokines is significantly increased and this in turn results in elevated monocyte and neutrophil chemotaxis. In addition, TLR-3 stimulation also induces trophoblast cells to secrete RANTES. These result., suggest a novel mechanism by which first trimester trophoblast cells may differentially modulate the maternal immune system during normal pregnancy and in the presence of an intrauterine infection. Such altered trophoblast cell responses might contribute to the pathogenesis of certain pregnancy complications. C1 Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Reprod Immunol Unit, New Haven, CT 06520 USA. NICHHD, Perinatol Res Branch, Detroit, MI 48202 USA. RP Mor, G (reprint author), Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Reprod Immunol Unit, New Haven, CT 06520 USA. EM gil.mor@yale.edu FU Intramural NIH HHS; NICHD NIH HHS [R01HD049446-01] NR 57 TC 113 Z9 124 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2005 VL 175 IS 12 BP 8096 EP 8104 PG 9 WC Immunology SC Immunology GA 994KJ UT WOS:000234030400038 PM 16339547 ER PT J AU Santiago, HC Feng, CG Bafica, A Roffe, E Arantes, RM Cheever, A Taylor, G Vierira, LQ Aliberti, J Gazzinelli, RT Sher, A AF Santiago, HC Feng, CG Bafica, A Roffe, E Arantes, RM Cheever, A Taylor, G Vierira, LQ Aliberti, J Gazzinelli, RT Sher, A TI Mice deficient in LRG-47 display enhanced snsceptibility to Trypanosoma cruzi infection associated with defective hemopoiesis and intracellular control of parasite growth SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW HYPOPLASIA; NITRIC-OXIDE SYNTHASE; INDUCIBLE GENE IGTP; INTERFERON-GAMMA; HOST-RESISTANCE; P47 GTPASES; MYCOBACTERIUM-TUBERCULOSIS; INCREASED SUSCEPTIBILITY; TOXOPLASMA-GONDII; CHAGAS-DISEASE AB IFN-gamma is known to be required for host control of intracellular Trypanosoma cruzi infection in mice, although the basis of its protective function is poorly understood. LRG-47 is an IFN-inducible p47GTPase that has been shown to regulate host resistance to intracellular pathogens. To investigate the possible role of LRG-47 in IFN-gamma-dependent control of T. cruzi infection, LRG-47 knockout (KO) and wild-type (WT) mice were infected with the Y strain of this parasite, and host responses were analyzed. When assayed on day 12 after parasite inoculation, LRG-47 KO mice, in contrast to IFN gamma/KO mice, controlled early parasitemia almost as effectively as WT animals. However, the infected LRG-47 KO mice displayed a rebound in parasite growth on day 15, and all succumbed to the infection by day 19. Additional analysis indicated that LRG-47-deficient mice exhibit unimpaired proinflammatory responses throughout the infection. Instead, reactivated disease in the KO animals was associated with severe splenic and thymic atrophy, anemia, and thrombocytopenia not observed in their WT counterparts. In addition, in vitro studies revealed that IFN-gamma-stimulated LRG-47 KO macrophages display defective intracellular killing of amastigotes despite normal expression of TNF and NO synthetase type 2 and that both NO synthetase type 2 and LRG-47 are required for optimum WN-gamma-dependent restriction of parasite growth. Together, these data establish that LRG-47 can influence pathogen control by simultaneously regulating macrophage-microbicidal activity and hemopoietic function. C1 Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, BR-31270901 Belo Horizonte, MG, Brazil. Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Pathol, BR-31270901 Belo Horizonte, MG, Brazil. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Fundacao Oswaldo Cruz, Lab Imunorregulacao & Microbiol, Salvador, BA, Brazil. Biomed Res Inst, Rockville, MD 20852 USA. VA Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA. Duke Univ, Ctr Study Aging, Durham, NC 27710 USA. Duke Univ, Dept Med, Durham, NC 27710 USA. Duke Univ, Dept Immunol, Med Ctr, Durham, NC 27710 USA. Duke Univ, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil. RP Santiago, HC (reprint author), Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Avenida Antonio Carlos,6627 Pampulha, BR-31270901 Belo Horizonte, MG, Brazil. EM santiago@icb.ufmg.br; asher@maid.nih.gov RI Santiago, Helton/F-8704-2012; Aliberti, Julio/I-7354-2013; Arantes, Rosa /C-5749-2013; Aliberti, Julio/G-4565-2012; Roffe, Ester/H-4688-2012 OI Santiago, Helton/0000-0002-5695-8256; Aliberti, Julio/0000-0003-3420-8478; Arantes, Rosa /0000-0003-1428-9717; FU NIAID NIH HHS [R01 AI057831] NR 40 TC 64 Z9 68 U1 0 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2005 VL 175 IS 12 BP 8165 EP 8172 PG 8 WC Immunology SC Immunology GA 994KJ UT WOS:000234030400046 PM 16339555 ER PT J AU Peebles, RS Hashimoto, K Sheller, JR Moore, ML Morrow, JD Ji, SQ Elias, JA Goleniewska, K O'Neal, J Mitchell, DB Graham, BS Zhou, WS AF Peebles, RS Hashimoto, K Sheller, JR Moore, ML Morrow, JD Ji, SQ Elias, JA Goleniewska, K O'Neal, J Mitchell, DB Graham, BS Zhou, WS TI Allergen-induced airway hyperresponsiveness mediated by cyclooxygenase inhibition is not dependent on 5-lipoxygenase or IL-5, but is IL-13 dependent SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-5; TRANSGENIC MICE; MURINE MODEL; DEFICIENT MICE; BALB/C MICE; ASTHMA; HYPERREACTIVITY; INFLAMMATION; LUNG; EOSINOPHILIA AB Cyclooxygenase (COX) inhibition during allergic sensitization and allergen airway challenge results in augmented allergic inflammation. We hypothesized that this increase in allergic inflammation was dependent on increased generation of leukotrienes that results from COX inhibition, as leukotrienes are important proinflammatory mediators of allergic disease. To test this hypothesis, we allergically sensitized and challenged mice deficient in 5-lipoxygenase (5-LO). We found that 5-LO knockout mice that were treated with a COX inhibitor during allergic sensitization and challenge had significantly increased airway hyperresponsiveness (AHR) (p < 0.01) and airway eosinophilia (p < 0.01) compared with 5-LO knockout mice that were treated with vehicle. The proinflammatory cytokines have also been hypothesized to be critical regulators of airway inflammation and AHR. We found that the increase in airway eosinophilia seen with COX inhibition is dependent on IL-5, whereas the increase in AHR is not dependent on this cytokine. In contrast, the COX inhibition-mediated increase in AHR is dependent on IL-13, but airway eosinophilia is not. These results elucidate the pathways by which COX inhibition exerts a critical effect of the pulmonary allergen-induced inflammatory response and confirm that COX products are important regulators of allergic inflammation. C1 Vanderbilt Univ, Med Ctr N T 1217, Ctr Lung Res, Dept Med,Sch Med, Nashville, TN 37232 USA. LINCO Res, St Charles, MO 63304 USA. Yale Univ, Dept Med, New Haven, CT 06520 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Peebles, RS (reprint author), Vanderbilt Univ, Med Ctr N T 1217, Ctr Lung Res, Dept Med,Sch Med, Nashville, TN 37232 USA. EM stokes.peebles@vanderbilt.edu FU NCI NIH HHS [CA77839]; NHLBI NIH HHS [HL-069949]; NIAID NIH HHS [AI 054660]; NIDDK NIH HHS [DK48831]; NIGMS NIH HHS [GM 15431] NR 52 TC 15 Z9 15 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 DEC 15 PY 2005 VL 175 IS 12 BP 8253 EP 8259 PG 7 WC Immunology SC Immunology GA 994KJ UT WOS:000234030400056 PM 16339565 ER PT J AU Nemeth, ZH Lutz, CS Csoka, B Deitch, EA Leibovich, SJ Gause, WC Tone, M Pacher, P Vizi, ES Hasko, G AF Nemeth, ZH Lutz, CS Csoka, B Deitch, EA Leibovich, SJ Gause, WC Tone, M Pacher, P Vizi, ES Hasko, G TI Adenosine augments IL-10 production by macrophages through an A(2B) receptor-mediated posttranscriptional mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; INTESTINAL EPITHELIAL-CELLS; AU-RICH ELEMENTS; GENE-EXPRESSION; MESSENGER-RNA; TNF-ALPHA; INTERLEUKIN-10 PROMOTER; 3'-UNTRANSLATED REGION; TRANSCRIPTION FACTOR; HUMAN MONOCYTES AB Adenosine receptor ligands have anti-inflammatory effects and modulate immune responses by up-regulating IL-10 production by immunostimulated macrophages. The adenosine receptor family comprises G protein-coupled heptahelical transmembrane receptors classified into four types: A(1), A(2A), A(2B), and A(3). Our understanding of the signaling mechanisms leading to enhanced IL-10 production following adenosine receptor occupancy on macrophages is limited. In this study, we demonstrate that adenosine receptor occupancy increases IL-10 production by LPS-stimulated macrophages without affecting IL-10 promoter activity and IL-10 mRNA levels, indicating a posttranscriptional mechanism. Transfection experiments with reporter constructs containing sequences corresponding to the AU-rich Y-untranslated region (UTR) of IL-10 mRNA confirmed that adenosine receptor activation acts by relieving the translational repressive effect of the IL-10 3'-UTR. By contrast, adenosine receptor activation failed to liberate the translational arrest conferred by the 3'-UTR of TNF-alpha mRNA. The IL-10 3'-UTR formed specific complexes with proteins present in cytoplasmic extracts of RAW 264.7 cells. Adenosine enhanced binding of proteins to a region of the IL-10 3'-UTR containing the GUAUUUAUU nonamer. The stimulatory effect of adenosine on IL-10 production was mediated through the A(2B) receptor, because the order of potency of selective agonists was 5'-N-ethylcarboxamidoadenosine (NECA) > N-6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) > 2-chloro-N-6-cyclopentyladenosine (CCPA) = 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethyl-carboxamidoadenosine (CGS-21680). Also, the selective A(2B) antagonist, alloxazine, prevented the effect of adenosine. Collectively, these studies identify a novel pathway in which activation of a G protein-coupled receptor augments translation of an anti-inflammatory gene. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Mol Biol, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Cell Biol, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Mol Med, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NIAAA, NIH, Bethesda, MD 20892 USA. Inst Expt Med, Dept Pharmacol, Budapest, Hungary. RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, 185 S Orange Ave, Newark, NJ 07103 USA. EM haskoge@umdnj.edu RI Pacher, Pal/B-6378-2008; OI Pacher, Pal/0000-0001-7036-8108; Csoka, Balazs/0000-0002-7562-1130 FU Intramural NIH HHS [Z01 AA000375-02]; NIAID NIH HHS [R01 AI031678-11, R01 AI031678, R01 AI031678-06, R01 AI031678-07, R01 AI031678-08, R01 AI031678-09, R01 AI031678-10, R01 AI031678-12]; NIAMS NIH HHS [R03 AR052038, R03AR052038-01]; NIGMS NIH HHS [R01 GM066189, R01 GM066189-01, R01 GM66189, R01-GM57982] NR 51 TC 129 Z9 133 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2005 VL 175 IS 12 BP 8260 EP 8270 PG 11 WC Immunology SC Immunology GA 994KJ UT WOS:000234030400057 PM 16339566 ER PT J AU Niland, B Banki, K Biddison, WE Perl, A AF Niland, B Banki, K Biddison, WE Perl, A TI CD8(+) T cell-mediated HLA-A*0201-restricted cytotoxicity to transaldolase peptide 168-176 in patients with multiple sclerosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; CLONAL EXPANSIONS; TRANSALDOLASE; BRAIN; OLIGODENDROCYTES; EXPRESSION; LESIONS; AUTOIMMUNITY; METABOLISM; ACTIVATION AB Transaldolase (TAL) is expressed at selectively high levels in oligodendrocytes and targeted by autoreactive T cells of patients with multiple sclerosis (MS). Among 14 TAL peptides with predicted RLA-A2 binding, TAL 168-176 (LLFSFAQAV, TALpep) exhibited high affinity for HLA-A2. Prevalence of HLA -A2- restricted CD8(+) T cells specific for TALpep was increased in PBMC of HLA-A(2+) MS patients, as compared with HLA-A(2-) MS patients, HLA-A2+ other neurological disease patients, and HLA-A2+ healthy donors. HLA-A*0201/TALpep tetramers detected increased frequency of TAL-specific CD8+ T cells, and precursor frequency of TAL-specific IFN-gamma-producing T cells was increased in each of seven HLA-A2+ MS patients tested. Stimulation by TALpep or rTAL of PBMC from HLA-A(2+) MS patients elicited killing of TALpep-pulsed HLA-42-transfected HmyA2.1 lymphoma cells, but not HLA-A3-transfected control HmyA3.1 targets. Without peptide pulsing of targets, HLA-A2-transfected, but not control MO3.13 oligodendroglial cells, expressing high levels of endogenous TAL, were also killed by CD8+ CTL of MS patients, indicating recognition of endogenously processed TAL. TCR V beta repertoire analysis revealed use of the TCR V beta 14 gene by T cell lines (TCL) of MS patients generated via stimulation by TAL- or TALpep-pulsed APCs. All TAL-specific TCL-binding HLA-A*0201/TALpep tetramers expressed TCR V beta 14 on the cell surface. Moreover, Ab to TCR V beta 14 abrogated cytotoxicity by HLA-A2-restricted TAL-specific TCL. Therefore, TAL-specific CTL may serve as a novel target for therapeutic intervention in patients with MS. C1 SUNY Syracuse, Dept Med, Coll Med, Syracuse, NY 13210 USA. SUNY Syracuse, Dept Pathol, Coll Med, Syracuse, NY 13210 USA. SUNY Syracuse, Dept Microbiol & Immunol, Coll Med, Syracuse, NY 13210 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Perl, A (reprint author), SUNY Syracuse, Dept Med, Coll Med, 750 E Adams St, Syracuse, NY 13210 USA. EM perla@upstate.edu OI Perl, Andras/0000-0002-5017-1348 FU NIDDK NIH HHS [R01 DK 49221] NR 60 TC 23 Z9 24 U1 1 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 DEC 15 PY 2005 VL 175 IS 12 BP 8365 EP 8378 PG 14 WC Immunology SC Immunology GA 994KJ UT WOS:000234030400069 PM 16339578 ER PT J AU Johnson, DC McFarland, EJ Muresan, P Fenton, T McNamara, J Read, JS Hawkins, E Bouquin, PL Estep, SG Tomaras, GD Vincent, CA Rathore, M Melvin, AJ Gurunathan, S Lambert, J AF Johnson, DC McFarland, EJ Muresan, P Fenton, T McNamara, J Read, JS Hawkins, E Bouquin, PL Estep, SG Tomaras, GD Vincent, CA Rathore, M Melvin, AJ Gurunathan, S Lambert, J TI Safety and immunogenicity of an HIV-1 recombinant canarypox vaccine in newborns and infants of HIV-1 infected women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 10th Conference on Retroviruses and Opportunistic Infections CY FEB 10-14, 2003 CL BOSTON, MA ID IMMUNE-RESPONSES; VIRUS; CHILDREN AB Pediatric AIDS Clinical Trials Group protocol 326 is a study of 2 formulations of recombinant canarypox ALVAC vaccine (vCP205) against human immunodeficiency virus type 1 (HIV-1). HIV-1-exposed infants were randomized to receive 1 of 2 formulations of vCP205 or placebo at birth and 4, 8, and 12 weeks. The vaccines were safe. Lymphoproliferative responses were detected at >= 2 time points in 44%-56% of vaccinees and none of the placebo recipients. A cytotoxic T lymphocyte response on at least 1 occasion was detected in 62.5% of infants in cohort 1 (10(6.08) median tissue culture dose [TCID50] vaccine formulation) and 44% of infants in cohort 2 (10(6.33) TCID50 vaccine formulation). Rare mucosal immunoglobulin A responses and no measurable vaccine-elicited serum antibodies were detected. In children, vCP205 appeared to be safe and immunogenic. C1 Sinai Childrens Hosp, Dept Pediat, Chicago, IL 60608 USA. Rosalind Franklin Univ Med & Sci, N Chicago, IL USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat Infect Dis, Denver, CO 80202 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. NIAID, Clin Immunol Branch, Div Allergy & Immunol Transplantat, NIH, Bethesda, MD 20892 USA. NIAID, Div Aids, Pharmaceut Affairs Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. Social & Sci Syst Inc, Silver Spring, MD USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr Virol, Durham, NC 27710 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Sanofi Pasteur, Swiftwater, PA USA. Univ Florida, Hlth Sci Ctr, Jacksonville, FL 32209 USA. Univ Washington, Seattle, WA 98195 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. Inst Child Hlth, London, England. RP Johnson, DC (reprint author), Sinai Childrens Hosp, Dept Pediat, F444,15th St & Calif Ave, Chicago, IL 60608 USA. EM johda@sinai.org RI Tomaras, Georgia/J-5041-2016 FU NCRR NIH HHS [RR-000240, RR-00069]; NIAID NIH HHS [AI-41089, AI-46725]; NICHD NIH HHS [HD-33162, HD-33345] NR 15 TC 32 Z9 32 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 DEC 15 PY 2005 VL 192 IS 12 BP 2129 EP 2133 DI 10.1086/498163 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 984QK UT WOS:000233319200016 PM 16288378 ER PT J AU Regino, CAS Torti, SV Ma, R Yap, GPA Kreisel, KA Torti, FM Planalp, RP Brechbiel, MW AF Regino, CAS Torti, SV Ma, R Yap, GPA Kreisel, KA Torti, FM Planalp, RP Brechbiel, MW TI N-picolyl derivatives of Kemp's triamine as potential antitumor agents: A preliminary investigation SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CELL-CYCLE PROGRESSION; IRON-DEFICIENCY; ADVANCED NEUROBLASTOMA; CRYSTAL-STRUCTURES; LIGAND OXIDATION; DNA-SYNTHESIS; DEFEROXAMINE; PROLIFERATION; COMPLEXES; CHELATORS AB Preorganized tripodal ligands such as the N-picolyl derivatives of cis,cis-1,3,5-triamino-cis,cis-1,3,5-trimethylcyclohexane (Kemp's triamine) were prepared as analogues to N,N',N"-tris(2pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (tachpyr) in hopes of enhancing the rate of formation and stability of the metal complexes. A tricyclic bisaminal was formed via the reduction of the Schiff base, while the tri(picolyl) derivative was synthesized via reductive amination of pyridine carboxaldehyde. Their cytotoxicities to the HeLa cell line were evaluated and directly compared to tachpyr and N,N'N''-tris(2-pyridylmethyl)tris(2-aminoethyl)amine (trenpyr). Results indicate that N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triamino-cis,cis-1,3,5trimethylcyclohexane (Kemp's pyr) exhibits cytotoxic activity against the HeLa cancer cell line comparable to tachpyr (IC50 approximate to 8.0 mu M). Both Kemp's pyr and tachpyr show higher cytotoxic activity over the aliphatic analogue of trenpyr (IC50 approximate to 14 mu M), suggesting that the major contributor to the activity is the ligand's ability to form a stable and tight complex and that the equatorial/axial equilibrium impacting the complex formation for the cyclohexane-based ligands is not significant. C1 NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Wake Forest Sch Med, Dept Biochem, Winston Salem, NC 27157 USA. Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA. RP Brechbiel, MW (reprint author), NCI, Radiat Oncol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov FU Intramural NIH HHS [Z01 SC006353-25, Z01 SC010051-12]; NIDDK NIH HHS [R01 DK057781, DK 57781] NR 52 TC 6 Z9 8 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 15 PY 2005 VL 48 IS 25 BP 7993 EP 7999 DI 10.1021/jm050724r PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 992ZR UT WOS:000233923000009 PM 16335923 ER PT J AU Li, TY Fujita, Y Shiotani, K Miyazaki, A Tsuda, Y Ambo, A Sasaki, Y Jinsmaa, Y Marczak, E Bryant, SD Salvadori, S Lazarus, LH Okada, Y AF Li, TY Fujita, Y Shiotani, K Miyazaki, A Tsuda, Y Ambo, A Sasaki, Y Jinsmaa, Y Marczak, E Bryant, SD Salvadori, S Lazarus, LH Okada, Y TI Potent Dmt-Tic pharmacophoric delta- and mu-opioid receptor antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MOUSE VAS-DEFERENS; RAT-BRAIN; ENDOMORPHIN-2 ANALOGS; BETA-FUNALTREXAMINE; MEDIATED ANALGESIA; HIGH-AFFINITY; PEPTIDE; BIPHALIN; AGONIST; DERIVATIVES AB A series of dimeric Dmt-Tic (2',6'-dimethyl-L-tyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) analogues (8-14, 18-22) were covalently linked through diaminoalkane and symmetric or asymmetric 3,6-diaminoalkyl-2(1H)-pyrazinone moieties. All the compounds exhibited high affinity for both 6-opioid receptors K(6) = 0.06-1.53 nM] andy-opioid receptors [K-i(mu) = 1.375.72 nM], resulting in moderate delta-receptor selectivity [K-i(mu)/K-i(delta) = 3-46]. Regardless of the type of linker between the Dmt-Tic pharmacophores, delta-opioid-mediated antagonism was extraordinarily high in all analogues (pA(2) = 10.42-11.28), while in vitro agonism (MVD and GPI bioassays) was essentially absent (ca. 3 to > 10 mu M). While an unmodified N-terminus (9, 13, 18) revealed weaku-opioid antagonism (pA(2) = 6.78-6.99), N,N'-dimethylation (21, 22), which negatively impacts on mu-opioid-associated agonism (Balboni et al., Bioorg. Med. Chem. 2003, 11, 5435-5441), markedly enhanced mu-opioid antagonism (pA(2) = 8.34 and 7.71 for 21 and 22, respectively) without affecting 6-opioid activity. These data are the first evidence that a single dimeric opioid ligand containing the Dmt-Tic pharmacophore exhibits highly potent 6- andy-opioid antagonist activities. C1 NIEHS, Med Chem Grp, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Tohoku Pharmaceut Univ, Dept Biochem, Aoba Ku, Sendai, Miyagi 9818558, Japan. Kobe Gakuin Univ, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. RP Lazarus, LH (reprint author), NIEHS, Med Chem Grp, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. EM lazarus@niehs.nih.gov; okada@pharm.kobegakuin.ac.jp FU Intramural NIH HHS NR 52 TC 16 Z9 17 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 15 PY 2005 VL 48 IS 25 BP 8035 EP 8044 DI 10.1021/jm050377l PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 992ZR UT WOS:000233923000013 PM 16335927 ER PT J AU Bohle, DS Ivanic, J Saavedra, JE Smith, KN Wang, YN AF Bohle, DS Ivanic, J Saavedra, JE Smith, KN Wang, YN TI E/Z conformation and the vibrational spectroscopy of Me(2)NN(O)=NOMe SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID DENSITY-FUNCTIONAL THEORY; NITRIC-OXIDE; CHEMISTRY; NO; DECOMPOSITION; SYSTEMS; ION AB The simple neutral diazenium diolate, O(2)-methyl-1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate, [Me(2)NN(O)= NOMe], was experimentally examined by vibrational spectroscopy and the results compared to the theoretically calculated values in an effort to detect both Z and E conformers which result from the stereochemistry of the N=N multiple bond. Room-temperature Raman and infrared spectra were measured and the results compared with the values calculated theoretically with MP2 and density functional techniques (B3LYP). An analysis of the observed frequencies suggests that, down to a detection limit of about (1)/(1000), only a small quantity of trans (E) diazeniumdiolate, < 0.05%, may be present at room temperature. C1 McGill Univ, Dept Chem, Montreal, PQ H3A 2K6, Canada. NCI, SAIC Frederick, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. NCI, SAIC Frederick, Basic Res Program, Chem Sect, Frederick, MD 21702 USA. RP Bohle, DS (reprint author), McGill Univ, Dept Chem, Montreal, PQ H3A 2K6, Canada. EM scott.bohle@mcgill.ca FU NCI NIH HHS [N01-CO-12400] NR 31 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD DEC 15 PY 2005 VL 109 IS 49 BP 11317 EP 11321 DI 10.1021/jp054730a PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 991YN UT WOS:000233850900028 PM 16331917 ER PT J AU Small, A Hong, S Pine, D AF Small, A Hong, S Pine, D TI Scattering properties of core-shell particles in plastic matrices SO JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS LA English DT Article DE blends; core-shell polymers; light scattering; optics; transparency ID RHEOLOGICAL PROPERTIES; MODIFIER BLENDS; INTERFACE; SPHERES; LAYER AB Blending submicron rubber particles with plastics can enhance the mechanical strength of the composite material. However, the difference in refractive index between the particle and matrix scatters light, making the material more opaque. We consider the possibility of reducing a particle's scattering cross section by adding coatings. We find that adding coatings can reduce the amount of scattering by changing the effective dielectric contrast between the particle and the matrix. We also found that, when the refractive index of the particle is very close to that of the matrix the order of the layers can have significant effects on the transmitted light. Such effects may be useful for engineering the optical properties of particle-doped plastics. Resonant effects akin to those found in antireflection coatings on planar surfaces are difficult to obtain and rarely provide a significant reduction in scattering. We discuss theoretical models that can qualitatively explain some of our results. (c) 2005 Wiley Periodicals, Inc. C1 Natl Inst Child Hlth & Human Dev, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Arkema Inc, King Of Prussia, PA 19406 USA. NYU, Dept Phys, New York, NY 10003 USA. RP Natl Inst Child Hlth & Human Dev, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM smallalex@mail.nih.gov RI Pine, David/B-7740-2016 OI Pine, David/0000-0002-3304-6684 NR 25 TC 13 Z9 13 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-6266 EI 1099-0488 J9 J POLYM SCI POL PHYS JI J. Polym. Sci. Pt. B-Polym. Phys. PD DEC 15 PY 2005 VL 43 IS 24 BP 3534 EP 3548 DI 10.1002/polb.20624 PG 15 WC Polymer Science SC Polymer Science GA 989MP UT WOS:000233678400003 ER PT J AU Humble, MC Trempus, CS Spalding, JW Cannon, RE Tennant, RW AF Humble, MC Trempus, CS Spalding, JW Cannon, RE Tennant, RW TI Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review SO ONCOGENE LA English DT Review DE ras; epidermal; carcinogenesis; Tg.AC; carcinogen assay; transgenic mouse model ID V-HA-RAS; TG.AC MOUSE SKIN; CENTER-DOT-AC; VASCULAR-PERMEABILITY FACTOR; LOCUS-CONTROL REGIONS; EPIDERMAL STEM-CELLS; GLOBIN GENE; ORNITHINE-DECARBOXYLASE; PAPILLOMA DEVELOPMENT; CARCINOGENICITY BIOASSAYS AB The genetically initiated Tg.AC transgenic mouse carries a transgene consisting of an oncogenic v-Ha-ras coding region flanked 50 by a mouse zeta-globin promoter and 30 by an SV-40 polyadenylation sequence. Located on chromosome 11, the transgene is transcriptionally silent until activated by chemical carcinogens, UV light, or full-thickness wounding. Expression of the transgene is an early event that drives cellular proliferation resulting in clonal expansion and tumor formation, the unique characteristics now associated with the Tg.AC mouse. This ras-dependent phenotype has resulted in the widespread interest and use of the Tg.AC mouse in experimental skin carcinogenesis and as an alternative carcinogenesis assay. This review examines the general biology of the tumorigenic responses observed in Tg.AC mice, the genetic interactions of the ras transgene, and explores the cellular and molecular regulation of zeta-globin promoted transgene expression. As a prototype alternative model to the current long-term rodent bioassays, the Tg.AC has generated a healthy discussion on the future of transgenic bioassays, and opened the doors for subsequent models for toxicity testing. The further exploration and elucidation of the molecular controls of transgene expression will enhance the usefulness of this mouse and enable a better understanding of the Tg.AC's discriminate response to chemical carcinogens. C1 NIEHS, Natl ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27514 USA. RP Cannon, RE (reprint author), NIEHS, Natl ctr Toxicogenom, POB 12233,MD FI-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cannon1@niehs.nih.gov FU NIEHS NIH HHS [T32 ES07126] NR 94 TC 18 Z9 19 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 15 PY 2005 VL 24 IS 56 BP 8217 EP 8228 DI 10.1038/sj.onc.1209000 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 993LV UT WOS:000233956500001 PM 16355251 ER PT J AU Bi, XL Jones, T Abbasi, F Lee, H Stultz, B Hursh, DA Mortin, MA AF Bi, XL Jones, T Abbasi, F Lee, H Stultz, B Hursh, DA Mortin, MA TI Drosophila caliban, a nuclear export mediator, can function as a tumor suppressor in human lung cancer cells SO ONCOGENE LA English DT Article DE caliban; Sdccag1; tumor suppressor; nuclear export; lung cancer; interference RNA ID PROSPERO GENE; CRM1; LOCALIZATION; HOMOLOG; REVEALS; ENCODES; SIGNALS; PROTEIN; SYSTEM; DOMAIN AB We previously showed that the Drosophila DNA binding homeodomain of Prospero included a 28 amino-acid sequence (HDA) that functions as a nuclear export signal. We describe here the identification of a protein we named Caliban, which can directly interact with the HDA. Caliban is homologous to human Sdccag1, which has been implicated in colon and lung cancer. Here we show that Caliban and Sdccag1 are mediators of nuclear export in fly and human cells, as interference RNA abrogates export of EYFP-HDA in normal fly and human lung cells. Caliban functions as a bipartite mediator nuclear export as the carboxy terminus binds HDA and the amino terminus itself functions as an NES, which directly binds the NES receptor Exportin. Finally, while non-cancerous lung cells have functional Sdccag1, five human lung carcinoma cell lines do not, even though Exportin still functions in these cells. Expression of fly Caliban in these human lung cancer cells restores EYFP-HDA nuclear export, reduces a cell's ability to form colonies on soft agar and reduces cell invasiveness. We suggest that Sdccag1 inactivation contributes to the transformed state of human lung cancer cells and that Caliban should be considered a candidate for use in lung cancer gene therapy. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Mortin, MA (reprint author), NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. EM mortinm@mail.nih.gov RI Bi, Xiaolin/E-7469-2010; Mortin, Mark/B-4251-2008; Bi, Xiaolin/C-7038-2014 OI Bi, Xiaolin/0000-0002-7172-7851; Bi, Xiaolin/0000-0003-2837-9457 NR 21 TC 12 Z9 16 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 15 PY 2005 VL 24 IS 56 BP 8229 EP 8239 DI 10.1038/sj.onc.1208962 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 993LV UT WOS:000233956500002 PM 16103875 ER PT J AU Troendle, JF AF Troendle, JF TI Multiple comparisons between two groups on multiple Bernoulli outcomes while accounting for covariates SO STATISTICS IN MEDICINE LA English DT Article DE bootstrap; discrete; familywise error; logistic model; permutation AB The problem of adjusting for multiplicity when one has multiple outcome variables can be handled quite nicely by step-down permutation tests. More difficult is the problem when one wants an analysis of each outcome variable to be adjusted for some covariates and the outcome variables are Bernoulli. Special permutations can be used where the outcome vectors are permuted within each strata of the data defined by the levels of the (made discrete) covariates. This method is described and shown to control the familywise error rate at any prespecified level. The method is compared through simulation to a vector bootstrap approach, also using a step-down testing procedure. It is seen that the method using permutations within strata is superior to the vector bootstrap in terms of error control and power. The method is illustrated on a data set of 55 minor malformations of babies of diabetic and non-diabetic mothers. Published in 2005 by John Wiley & Sons, Ltd. C1 NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH,US Dept DHHS, Bethesda, MD 20892 USA. RP Troendle, JF (reprint author), NICHD, BMSB, DESPR, US Dept DHHS,NIH, 6100 Execut Blvd,Room 7B05, Bethesda, MD 20892 USA. EM jt3t@nih.gov NR 10 TC 6 Z9 6 U1 0 U2 0 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 DEC 15 PY 2005 VL 24 IS 23 BP 3581 EP 3591 DI 10.1002/sim.2202 PG 11 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 984YQ UT WOS:000233343700004 PM 15977268 ER PT J AU Aoyama, H Couse, JF Hewitt, SC Haseman, JK He, H Zheng, XL Majstoravich, S Korach, KS Dixon, D AF Aoyama, H Couse, JF Hewitt, SC Haseman, JK He, H Zheng, XL Majstoravich, S Korach, KS Dixon, D TI Upregulation of estrogen receptor expression in the uterus of ovariectomized B6C3F1 mice and Ishikawa cells treated with bromoethane SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE bromoethane; mouse; uterus; ishikawa; estrogen receptor alpha ID MESSENGER-RIBONUCLEIC-ACID; RAT UTEROTROPHIC BIOASSAY; TRANSGENIC MICE; BREAST-CANCER; OECD PROGRAM; IN-VITRO; CHEMICALS; EXPOSURE; ALPHA; DIETHYLSTILBESTROL AB In a 2-year NTP bioassay, Bromoethane (BE) was found to induce endometrial neoplasms in the uterus of B6C3F1 mice [National Toxicology Program, 1989. Toxicology and Carcinogenesis Studies of Bromoethane (Ethyl Bromide) in F344/N Rats and B6C3F1 Mice. TR No. 363, U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC; Picut, C.A., Aoyama, H., Holder, J.W., Gold, L.S., Maronpot, R.R., Dixon, D., 2003. Bromoethane, chloroethane and ethylene oxide induced uterine neoplasms in B6C3F1 mice from 2-year NTP inhalation bioassays: pathology and incidence data revisited. Exp. Toxicol. Pathol. 55, 1-9]. In women, hormonal influences, such as "unopposed" estrogenic stimulus, have been implicated as important etiologic factors in uterine cancer. BE, however, does not affect the serum concentrations of sex hormones in female B6C3F1 mice [Bucher, J.R., Morgan, D.L., Adkins Jr., B. Travlos, G.S., Davis, B.J., Morris, R., Elwell, M.R., 1995. Early changes in sex hormones are not evident in mice exposed to the uterine carcinogens chloroethane or bromoethane. Toxicol. Appl. Pharmacol. 130, 169-173] and the mechanism of BE-induced uterine carcinogenesis still remains unclear. In the present study, we examined the estrogenic effects of BE on the uterus of ovariectomized B6C3F1 mice and on Ishikawa cells. Groups of 6 mice were given daily s.c. injections of 0, 100, 500 or 1000 mg BE/kg for 3 consecutive days. Mice treated with 17 beta-estradiol served as positive controls. Mice were necropsied 24 h after the final injection, and uteri were weighed and examined histologically and immunohistochemically along with the vagina. Changes observed in the estrogen-treated mice included increased uterine weights, edema and inflammation of the endometrium, increased epithelial layers of the uterine and vaginal lumens and keratinization of the vaginal epithelium. In the BE-treated mice, no such changes occurred; however, immunohistochemical staining of the uterus revealed a significant increase in immunoexpression of the estrogen receptor alpha (ER alpha) in the two higher dose groups. Analysis of mRNA also showed slightly increased uterine ER alpha expression in these groups. Upregulated expression of ER alpha was confirmed in BE-treated Ishikawa cells, in which Western blotting analyses identified an intense signal at approximately 66 kDa, which is consistent with ER alpha. These data suggest that upregulated expression of ER alpha may be important in the induction of endometrial neoplasms in BE-treated mice. Published by Elsevier Inc. C1 Natl Inst Environm Hlth Sci, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dixon, D (reprint author), Inst Environm Toxicol, Lab Reprod Toxicol, 4321 Uchimoriya Machi, Ibaraki 3030043, Japan. EM dixon@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X NR 37 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 15 PY 2005 VL 209 IS 3 BP 226 EP 235 DI 10.1016/j.taap.2005.04.012 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 995SV UT WOS:000234125100004 PM 15922381 ER PT J AU Guo, TL Chi, RP Karrow, NA Zhang, LX Pruett, SB Germolec, DR White, KL AF Guo, TL Chi, RP Karrow, NA Zhang, LX Pruett, SB Germolec, DR White, KL TI Thalidomide enhances both primary and secondary host resistances to Listeria monocytogenes infection by a neutrophil-related mechanism in female B6C3F1 mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE thalidomide; neutrophils; rodent; Listeria ID TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; LOW-DOSE THALIDOMIDE; POLYMORPHONUCLEAR LEUKOCYTES; CELLS; RESPONSES; LYMPHOCYTES; MODULATION; ACTIVATION; INHIBITORS AB Previously, we have reported that thalidomide can modulate the immune responses in female B6C3F1 mice. Furthermore, thalidomide immunomodulation increased primary host resistance to intravenously infected Listeria monocytogenes. The present study was intended to evaluate the mechanisms underlying the enhanced host resistance to L. monocytogenes by focusing on the neutrophils. Female B6C3F1 mice were treated intraperitoneally with thalidomide (100 mg/kg) for 15 days. Exposure to thalidomide increased the numbers of neutrophils in the spleens and livers of L. monocytogenes-infected mice when compared to the L. monocytogenes-infected control mice. Additionally, the percentage of neutrophils was also significantly increased after Thd treatment in L. monocytogenes-infected mice. Further studies using antibodies to deplete corresponding cells indicated that thalidomide-mediated increase in primary host resistance (both the moribundity and colony counts in the liver and spleen) to L. monocytogenes infection was due to its effect on neutrophils but not CD8(+) T cells or NK cells. Finally, Thd exposure also increased host resistance to secondary host resistance to L. monocytogenes infection, and depletion of neutrophils abolished the protective effect. In conclusion, thalidomide enhanced host resistance to both primary and secondary L. monocytogenes infections by a neutrophil-related mechanism in female B6C3F1 mice. (c) 2005 Elsevier Inc. All rights reserved. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. LSU, Hlth Sci Ctr, Dept Cellular Biol & Anat, Shreveport, LA 71130 USA. Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Guo, TL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980316, Richmond, VA 23298 USA. EM tlguo@hsc.vcu.edu FU NIEHS NIH HHS [ES 55387, R21ES 012286] NR 42 TC 4 Z9 4 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 15 PY 2005 VL 209 IS 3 BP 244 EP 254 DI 10.1016/j.taap.2005.04.014 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 995SV UT WOS:000234125100006 PM 15921716 ER PT J AU Powell, JD Fitzhugh, C Kang, EM Hsieh, M Schwartz, RH Tisdale, JF AF Powell, JD Fitzhugh, C Kang, EM Hsieh, M Schwartz, RH Tisdale, JF TI Low-dose radiation plus rapamycin promotes long-term bone marrow chimerism SO TRANSPLANTATION LA English DT Article DE hematopoietic; rapamycin; chimerisin ID SICKLE-CELL-ANEMIA; ANTITHYMOCYTE GLOBULIN INDUCTION; SIROLIMUS MONOTHERAPY; TRANSPLANTATION; TOLERANCE; EXPERIENCE; DISEASE; TRANSFUSIONS; MECHANISMS; LEUKEMIA AB Background. The ability to achieve significant donor engraftment without fully myeloablative conditioning has revolutionized allogeneic stem cell transplantation. These nonmyeloablative approaches may allow extension of this potentially curative modality to an increasing number of patients including those with non-malignant diseases. Although a number of regimens have been explored, the optimal means of conditioning has not been determined. Methods. We previously demonstrated that rapamycin (RAPA) has the ability to promote T-cell tolerance even in the presence of costimulation. in the current study, we examine the ability of rapamycin or the calcineurin inhibitor cyclosporine A (CSA) to promote chimerism in a murine haploidentical bone marrow transplantation model. Mice were conditioned with 300 cGy and received either RAPA at 3 mg/kg/day IP, CSA at 20 mg/kg/day IP, or no immunosuppression starting on the day before the transplant and continued for 4 weeks. Results. There was no apparent toxicity, and animals maintained normal blood counts throughout. More importantly, long-term macrochimerism was observed only in the RAPA-treated group. Conclusions. These results establish a simple, nontoxic, irradiation-based regimen that facilitates engraftment without ablation. This strategy may prove useful in nonmalignant disorders such as hemoglobinopathies in which moderate levels of donor chimerism could prove curative. C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Tisdale, JF (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N116,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Johntis@intra.niddk.nih.gov FU Intramural NIH HHS NR 23 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2005 VL 80 IS 11 BP 1541 EP 1545 DI 10.1097/01.tp.0000185299.72295.90 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 999BP UT WOS:000234364000003 PM 16371922 ER PT J AU Kobayashi, H Brechbiel, MW AF Kobayashi, H Brechbiel, MW TI Nano-sized MRI contrast agents with dendrimer cores SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE dendrimer; magnetic resonance imaging; contrast agent; paramagnetic; polymer; nano size ID MAGNETIC-RESONANCE LYMPHOGRAPHY; IRON-OXIDE PARTICLES; AFFINITY FOLATE RECEPTOR; NEUTRON-CAPTURE THERAPY; BREAST-CANCER XENOGRAFT; NON-HODGKINS-LYMPHOMA; GD-DTPA-POLYLYSINE; MONOCLONAL-ANTIBODY; POLYAMIDOAMINE DENDRIMER; IN-VIVO AB Gadolinium-based MRI contrast agents (CAs) can be effective at a similar to 100-fold lower concentration of Gadolinium ions in comparison to the concentration of Iodine atoms required for CT imaging. Therefore, a number of dendrimer based macromolecular MRI CAs of various sizes and properties prepared employing relatively simple chemistry are readily available that can provide sufficient contrast enhancement for various applications. Molecules up to 20 nm in diameter behave differently in the body depending on their size. Even if these molecules possess similar chemical properties, small changes in size can greatly impact their pharmacokinetics. Changes in molecular size up to 15 nm in diameter altered permeability across the vascular wall, excretion route, and recognition by the reticuloenclothelial system. Smaller sized polyamidoamine (PAMAM) dendrimer-based contrast agents, i.e., less than 3 nm in diameter, easily "leak" across the vascular wall resulting in rapid perfusion throughout the body. Contrast agents 3-6 nm in diameter were quickly excreted through the kidney indicating these agents to be potentially suitable as functional renal contrast agents. Contrast agents 7-12 out in diameter were retained in circulation and were better suited for use as blood pool contrast agents. Hydrophobic variants of CAs formed with polyropylenimine diaminobutane (DAB) dendrimer cores quickly accumulated in the liver and potentially have use as liver contrast agents. Larger hydrophilic agents have suitable characteristics for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents and might also be employed as either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy. (c) 2005 Elsevier B.V. All rights reserved. C1 NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,10 Ctr Dr, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov NR 87 TC 300 Z9 308 U1 21 U2 174 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD DEC 14 PY 2005 VL 57 IS 15 BP 2271 EP 2286 DI 10.1016/j.addr.2005.09.016 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 998ES UT WOS:000234302000011 PM 16290152 ER PT J AU Dietrich, MO Mantese, CE Porciuncula, LO Ghisleni, G Vinade, L Souza, DO Portela, LV AF Dietrich, MO Mantese, CE Porciuncula, LO Ghisleni, G Vinade, L Souza, DO Portela, LV TI Exercise affects glutamate receptors in postsynaptic densities from cortical mice brain SO BRAIN RESEARCH LA English DT Article DE voluntary exercise; brain; glutamate receptor; NMDA; phosphorylation ID D-ASPARTATE RECEPTORS; NEUROTROPHIC FACTOR; EXCITATORY SYNAPSES; KAINATE RECEPTORS; SYNAPTIC-PLASTICITY; MOLECULAR-MECHANISMS; HIPPOCAMPAL-NEURONS; PHYSICAL-EXERCISE; RUNNING WHEEL; AMPA AB Physical activity has been proposed as a behavior intervention that promotes mental health and some of the benefits induced by exercise have been related to the glutamatergic system. Indeed, glutamate is the most abundant excitatory neurotransmitter in brain. Thus, we evaluated if voluntary exercise in mice could modulate glutamatergic synapses at level of postsynaptic density (PSD). Through Western blot, we found that exercise during 1 month increased glutamatergic-related protein content in PSD from cortex of mice. Exercise increased the immunocontent of GluR1 (129%), SAP-97 (179%), GRIP-1 (129%), and in less extent, GluR2/3 (118%) and PSD-95 (112%) proteins. The overall content of NMDA subunits R1, R2A and P2B were not altered in mice that had exercised, however, the phosphorylated NMDA subunits, phospho-NMDAR1 (150%), and phospho-NMDAR2B (183%) showed a strong increase. Because exercise increased the content of phosphorylated forms of NMDA receptors, we evaluated the binding of MK-801, a specific ligand that binds to open NMDA channel. Exercise increased the binding of MK-801 in cortical cellular membranes in 51%. Altogether, our results point to a modulation of glutamatergic synapses by exercise with likely implications in the exercise-induced mental health. (C) 2005 Elsevier B.V. All rights reserved. C1 Univ Fed Rio Grande Sul, Inst Ciencias Basicas Saude, Dept Bioquim, BR-90035003 Porto Alegre, RS, Brazil. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Portela, LV (reprint author), Univ Fed Rio Grande Sul, Inst Ciencias Basicas Saude, Dept Bioquim, Rua Ramiro Barcelos,2600 Anexo, BR-90035003 Porto Alegre, RS, Brazil. EM roskaportela@gmail.com RI Ghisleni, Gabriele/D-5032-2013; Souza, Diogo/J-8894-2014; Dietrich, Marcelo/A-9928-2009 OI Souza, Diogo/0000-0002-4322-0404; Dietrich, Marcelo/0000-0001-9781-2221 FU Intramural NIH HHS NR 53 TC 37 Z9 44 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 14 PY 2005 VL 1065 IS 1-2 BP 20 EP 25 DI 10.1016/j.brainres.2005.09.038 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 997FA UT WOS:000234229200003 PM 16298350 ER PT J AU Park, Y Hunter, DJ Spiegelman, D Bergkvist, L Berrino, F van den Brandt, PA Buring, JE Colditz, GA Freudenheim, JL Fuchs, CS Giovannucci, E Goldbohm, RA Graham, S Harnack, L Hartman, AM Jacobs, DR Kato, I Krogh, V Leitzmann, MF McCullough, ML Miller, AB Pietinen, P Rohan, TE Schatzkin, A Willett, WC Wolk, A Zeleniuch-Jacquotte, A Zhang, SMM Smith-Warner, SA AF Park, Y Hunter, DJ Spiegelman, D Bergkvist, L Berrino, F van den Brandt, PA Buring, JE Colditz, GA Freudenheim, JL Fuchs, CS Giovannucci, E Goldbohm, RA Graham, S Harnack, L Hartman, AM Jacobs, DR Kato, I Krogh, V Leitzmann, MF McCullough, ML Miller, AB Pietinen, P Rohan, TE Schatzkin, A Willett, WC Wolk, A Zeleniuch-Jacquotte, A Zhang, SMM Smith-Warner, SA TI Dietary fiber intake and risk of colorectal cancer - A pooled analysis of prospective cohort studies SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; SCALE PROSPECTIVE COHORT; WOMENS HEALTH; COLON-CANCER; REGRESSION-MODELS; RANDOMIZED TRIAL; LOW-FAT; REPRODUCIBILITY; RECURRENCE; ADENOMA AB Context Inconsistent findings from observational studies have continued the controversy over the effects of dietary fiber on colorectal cancer. Objective To evaluate the association between dietary fiber intake and risk of colorectal cancer. Design, Setting, and Participants From 13 prospective cohort studies included in the Pooling Project of Prospective Studies of Diet and Cancer, 725 628 men and women were followed up for 6 to 20 years across studies. Study- and sex-specific relative risks (RRs) were estimated with the Cox proportional hazards model and were subsequently pooled using a random-effects model. Main Outcome Measure Incident colorectal cancer. Results During 6 to 20 years of follow-up across studies, 8081 colorectal cancer cases were identified. For comparison of the highest vs lowest study- and sex-specific quintile of dietary fiber intake, a significant inverse association was found in the age-adjusted model (pooled RR=0.84; 95% confidence interval [CI], 0.77-0.92). However, the association was attenuated and no longer statistically significant after adjusting for other risk factors (pooled multivariate RR=0.94; 95% Cl, 0.86-1.03). In categorical analyses compared with dietary fiber intake of 10 to <15 g/d, the pooled multivariate RR was 1.18 (95% Cl, 1.05-1.31) for less than 10 g/d (11% of the overall study population); and RR, 1.00 (95% Cl, 0.85-1.17) for 30 or more g/d. Fiber intake from cereals, fruits, and vegetables was not associated with risk of colorectal cancer. The pooled multivariate RRs comparing the highest vs lowest study- and sex-specific quintile of dietary fiber intake were 1.00 (95% Cl, 0.90-1.11) for colon cancer and 0.85 (95% Cl, 0.72-1.01) for rectal cancer (P for common effects by tumor site=.07). Conclusions In this large pooled analysis, dietary fiber intake was inversely associated with risk of colorectal cancer in age-adjusted analyses. However, after accounting for other dietary risk factors, high dietary fiber intake was not associated with a reduced risk of colorectal cancer. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Cent Hosp Vasteras, Dept Surg, Vasteras, Sweden. Cent Hosp Vasteras, Clin Res Ctr, Vasteras, Sweden. Natl Canc Inst, Epidemiol Unit, I-20133 Milan, Italy. Maastricht Univ, Dept Epidemiol, Maastricht, Netherlands. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. TNO, Nutr & Food Res Inst, Dept Epidemiol, NL-3700 AJ Zeist, Netherlands. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Wayne State Univ, Dept Pathol, Karmanos Canc Inst, Detroit, MI 48202 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Amer Canc Soc, Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Univ Toronto, Dept Publ Hlth Sci, Toronto, ON, Canada. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. NYU, Dept Environm Med, New York, NY 10016 USA. RP Smith-Warner, SA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM pooling@hsphsun2.harvard.edu RI Krogh, Vittorio/K-2628-2016; Colditz, Graham/A-3963-2009; OI Krogh, Vittorio/0000-0003-0122-8624; Colditz, Graham/0000-0002-7307-0291; Park, Yikyung/0000-0002-6281-489X FU NCI NIH HHS [CA55075, CA78548] NR 51 TC 223 Z9 238 U1 5 U2 32 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 DEC 14 PY 2005 VL 294 IS 22 BP 2849 EP 2857 DI 10.1001/jama.294.22.2849 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 991PU UT WOS:000233826700025 PM 16352792 ER PT J AU Stolzenberg-Solomon, RZ Graubard, BI Chari, S Limburg, P Taylor, PR Virtamo, J Albanes, D AF Stolzenberg-Solomon, RZ Graubard, BI Chari, S Limburg, P Taylor, PR Virtamo, J Albanes, D TI Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GROWTH-FACTOR-I; C-PEPTIDE; COLORECTAL-CANCER; EXOGENOUS INSULIN; PHYSICAL-ACTIVITY; PLASMA-GLUCOSE; HAMSTER MODEL; RISK; MORTALITY; COHORT AB Context Obesity, diabetes mellitus, and glucose intolerance have been associated with increased pancreatic cancer risk; however, prediagnostic serum insulin concentration has not been evaluated as a predictor of this malignancy. Objective To investigate whether prediagnostic fasting glucose and insulin concentrations and insulin resistance are associated with subsequent incidence of exocrine pancreatic cancer in a cohort of male smokers. Design, Setting, and Participants A case-cohort prospective study within,the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985-1988) cohort of 29 133 male Finnish smokers ages 50 to 69 years. The study included 400 randomly sampled subcohort control participants and 169 incident pancreatic cancer cases that occurred after the fifth year of follow-up. All participants were followed up through December 2001 (up to 16.7 years of follow-up). Main Outcome Measures Incident exocrine pancreatic cancer identified from the Finnish Cancer Registry. Results After adjusting forage, smoking, and body mass index, higher baseline fasting serum concentrations of glucose, insulin, and insulin resistance were positively associated with pancreatic cancer. The presence of biochemically defined diabetes mellitus (glucose, >= 126 mg/dL [>= 6.99 mmo/L]) and insulin concentration in the highest vs lowest quartile both showed a significant 2-fold increased risk (hazard ratio [HRI], 2.13; 95% confidence interval [CI], 1.04-4.35; and HR, 2.01; 95% Cl, 1.03-3.93; respectively). There were significant interactions for all the biomarker exposures by follow-up time, such that the positive associations were stronger among the cases that occurred more than 10 years after baseline (highest vs lowest quartile: glucose, HR, 2.16; 95% Cl, 1.05-4.42; P for trend=.02; insulin, HR, 2.90; 95% Cl, 1.22-6.92; P for trend=.005; and insulin resistance, HR, 2.71; 95% Cl, 1.19-6.18; P for trend =.006). Conclusions These results support the hypothesis that exposure to higher insulin concentrations and insulin resistance predicts the risk of exocrine pancreatic cancer. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Stolzenberg-Solomon, RZ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA. EM rs221z@nih.gov RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; Intramural NIH HHS; NCI NIH HHS [N01-CN-45165] NR 33 TC 195 Z9 201 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 14 PY 2005 VL 294 IS 22 BP 2872 EP 2878 DI 10.1001/jama.294.22.2872 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 991PU UT WOS:000233826700028 PM 16352795 ER PT J AU Wu, W Xu, JH Wu, XS Wu, LG AF Wu, W Xu, JH Wu, XS Wu, LG TI Activity-dependent acceleration of endocytosis at a central synapse SO JOURNAL OF NEUROSCIENCE LA English DT Article DE synapse; calcium; plasticity; endocytosis; short-term facilitation; exocytosis ID RETINAL BIPOLAR CELLS; HIPPOCAMPAL SYNAPSES; SUSTAINED STIMULATION; VESICLE ENDOCYTOSIS; RAPID ENDOCYTOSIS; CHROMAFFIN CELLS; MEDIAL NUCLEUS; TRAPEZOID BODY; EXOCYTOSIS; KINETICS AB Accumulated evidence indicates the existence of rapid and slow endocytosis at many synapses. It has been proposed that rapid endocytosis is activated by intense stimulation when vesicle recycling needs to be speeded up to supply vesicles at hippocampal synapses. However, the evidence, as obtained with imaging techniques, which are somewhat indirect in indicating rapid endocytosis, is controversial. Furthermore, a slower time course of endocytosis is often found after more intense nerve activity, casting doubt on the role of rapid endocytosis at synapses. Here, we addressed this issue at a mammalian central synapse, the calyx of Held, using a capacitance measurement technique that provides a higher time resolution than imaging techniques. We found that rapid endocytosis with a time constant of similar to 1-2 s was activated during intense nerve activity. Reducing the presynaptic calcium current or buffering the intracellular calcium with EGTA significantly inhibited rapid endocytosis, suggesting that calcium triggers rapid endocytosis. During intense stimulation, rapid endocytosis retrieved up to approximately eight vesicles per second per active zone, approximately eightfold larger than reported in the hippocampus, and thus played a dominant role during and within 3 s after intense stimulation. Slow endocytosis became dominant 3 s after intense stimulation likely because of the fall of the intracellular calcium level that deactivated rapid endocytosis. These results underscore the importance of calcium-triggered rapid endocytosis, which offers the nerve terminal the plasticity to speed up vesicle cycling during intense nerve activity. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Wu, LG (reprint author), NINDS, NIH, 36 Convent Dr,Bldg 36,Room 1C12, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov OI Xu, Jianhua/0000-0003-0084-8856 FU Intramural NIH HHS; NINDS NIH HHS [Z01 NS003009-02] NR 28 TC 82 Z9 83 U1 0 U2 8 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 DEC 14 PY 2005 VL 25 IS 50 BP 11676 EP 11683 DI 10.1523/JNEUROSCI.2972-05.2005 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 993GI UT WOS:000233942200022 PM 16354926 ER PT J AU Laird, FM Cai, HB Savonenko, AV Farah, MH He, KW Melnikova, T Wen, HJ Chiang, HC Xu, GL Koliatsos, VE Borchelt, DR Price, DL Lee, HK Wong, PC AF Laird, FM Cai, HB Savonenko, AV Farah, MH He, KW Melnikova, T Wen, HJ Chiang, HC Xu, GL Koliatsos, VE Borchelt, DR Price, DL Lee, HK Wong, PC TI BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BACE1 null mice; selective vulnerability; A beta amyloidosis; Alzheimer's; cognition; synaptic plasticity; RNAi ID LONG-TERM POTENTIATION; FAMILIAL ALZHEIMERS-DISEASE; PROTEIN-CLEAVING ENZYME; GAMMA-SECRETASE COMPLEX; TRANSGENIC MOUSE MODEL; NF-KAPPA-B; PRECURSOR PROTEIN; A-BETA; IN-VIVO; APOLIPOPROTEIN-E AB A transmembrane aspartyl protease termed beta-site APP cleavage enzyme 1 (BACE1) that cleaves the amyloid-beta precursor protein (APP), which is abundant in neurons, is required for the generation of amyloid-beta(A beta) peptides implicated in the pathogenesis of Alzheimer's disease (AD). We now demonstrate that BACE1, enriched in neurons of the CNS, is a major determinant that predisposes the brain to A beta amyloidogenesis. The physiologically high levels of BACE1 activity coupled with low levels of BACE2 and alpha-secretase anti-amyloidogenic activities in neurons is a major contributor to the accumulation of A beta in the CNS, whereas other organs are spared. Significantly, deletion of BACE1 in APPswe;PS1 Delta E9 mice prevents both A beta deposition and age-associated cognitive abnormalities that occur in this model of A beta amyloidosis. Moreover, A beta deposits are sensitive to BACE1 dosage and can be efficiently cleared from the CNS when BACE1 is silenced. However, BACE1 null mice manifest alterations in hippocampal synaptic plasticity as well as in performance on tests of cognition and emotion. Importantly, memory deficits but not emotional alterations in BACE1(-/-) mice are prevented by coexpressing APPswe;PS1 Delta E9 transgenes, indicating that other potential substrates of BACE1 may affect neural circuits related to emotion. Our results establish BACE1 and APP processing pathways as critical for cognitive, emotional, and synaptic functions, and future studies should be alert to potential mechanism-based side effects that may occur with BACE1 inhibitors designed to ameliorate A beta amyloidosis in AD. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. NIH, Neurogenet Lab, Bethesda, MD 20892 USA. RP Wong, PC (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 558 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM wong@jhmi.edu RI Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 FU Intramural NIH HHS [Z01 AG000959-04, Z99 AG999999]; NIA NIH HHS [AG02556, P50 AG005146, P50 AG05146]; NINDS NIH HHS [R01 NS041438, P01 NS047308, R01 NS045150, R01 NS41438, R01 NS45150] NR 94 TC 289 Z9 297 U1 2 U2 19 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 DEC 14 PY 2005 VL 25 IS 50 BP 11693 EP 11709 DI 10.1523/JNEUROSCI.2766-05.2005 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 993GI UT WOS:000233942200024 PM 16354928 ER PT J AU Je, HS Zhou, JZ Yang, F Lu, B AF Je, HS Zhou, JZ Yang, F Lu, B TI Distinct mechanisms for neurotrophin-3-induced acute and long-term synaptic potentiation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE synaptogenesis; Xenopus; TrkC; internalization; synaptic plasticity; FM dye; synaptic varicosity ID NERVE GROWTH-FACTOR; DEVELOPING NEUROMUSCULAR SYNAPSES; REGULATED KINASE ACTIVATION; GREEN FLUORESCENT PROTEIN; RETROGRADE SIGNAL; MAMMALIAN TARGET; TRK RECEPTORS; NEUROTROPHIC FACTOR; CELL-CULTURE; BDNF AB Although neurotrophins elicit both acute and long-term effects, it is unclear whether the two modes of action are mediated by the same or different mechanisms. Using neuromuscular junction (NMJ) as a model system, we identified three characteristic features required for long-term, but not acute, forms of synaptic modulation by neurotrophin-3 (NT-3): endocytosis of NT-3-receptor complex, activation of the PI3 kinase substrate Akt, and new protein synthesis. Long-term effects were eliminated when NT-3 was conjugated to a bead that was too large to be endocytosed or when dominant-negative dynamin was expressed in presynaptic neurons. Presynaptic inhibition of Akt also selectively prevented NT-3-mediated long-term effects. Blockade of protein translation by the mammalian target of rapamycin inhibitor rapamycin prevented the long-term structural and functional changes at the NMJ, without affecting the acute potentiation of synaptic transmission by NT-3. These results reveal fundamental differences between acute and long-term modulation by neurotrophins. C1 NICHHD, Sect Neural Dev & Plast, Porter Neurosci Res Ctr,NIH, Lab Cellular & Synapt Neurophysiol,Gene Cognit, Bethesda, MD 20892 USA. George Washington Univ, Grad Program Genet, Washington, DC 20052 USA. RP Lu, B (reprint author), NICHHD, Sect Neural Dev & Plast, Porter Neurosci Res Ctr,NIH, Lab Cellular & Synapt Neurophysiol,Gene Cognit, Bldg 35,Room 1C1004 Off,MSC 3714,35 Lincoln Dr, Bethesda, MD 20892 USA. EM bailu@mail.nih.gov RI Yang, Feng/C-9530-2011; Lu, Bai/A-4018-2012; OI Je, hyunsoo/0000-0002-2924-5621 NR 54 TC 18 Z9 18 U1 0 U2 4 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 DEC 14 PY 2005 VL 25 IS 50 BP 11719 EP 11729 DI 10.1523/JNEUROSCI.4087-05.2005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 993GI UT WOS:000233942200026 PM 16354930 ER PT J AU Shen, Y Leatherbury, L Rosenthal, J Yu, Q Pappas, MA Wessels, A Lucas, J Siegfried, B Chatterjee, B Svenson, K Lo, CW AF Shen, Y Leatherbury, L Rosenthal, J Yu, Q Pappas, MA Wessels, A Lucas, J Siegfried, B Chatterjee, B Svenson, K Lo, CW TI Cardiovascular phenotyping of fetal mice by noninvasive high-frequency ultrasound facilitates recovery of ENU-induced mutations causing congenital cardiac and extracardiac defects SO PHYSIOLOGICAL GENOMICS LA English DT Article DE echocardiography; congenital heart defects; mouse mutagenesis; ethylnitrosourea ID INTRAUTERINE GROWTH-RETARDATION; INTACT VENTRICULAR SEPTUM; HEART DEVELOPMENT; IN-UTERO; DOPPLER-ECHOCARDIOGRAPHY; PRENATAL-DIAGNOSIS; DUCTUS-ARTERIOSUS; PULMONARY REGURGITATION; GENE; DISEASE AB As part of a large-scale noninvasive fetal ultrasound screen to recover ethylnitrosourea (ENU)-induced mutations causing congenital heart defects in mice, we established a high-throughput ultrasound scanning strategy for interrogating fetal mice in utero utilizing three orthogonal imaging planes defined by the fetus' vertebral column and body axes, structures readily seen by ultrasound. This contrasts with the difficulty of acquiring clinical ultrasound imaging planes which are defined by the fetal heart. By use of the three orthogonal imaging planes for two-dimensional (2D) imaging together with color flow, spectral Doppler, and M-mode imaging, all of the major elements of the heart can be evaluated. In this manner, 10,091 ENU-mutagenized mouse fetuses were ultrasound scanned between embryonic days 12.5 and 19.5, with 324 fetuses found to die prenatally and 425 exhibiting cardiovascular defects. Further analysis by necropsy and histology showed heart defects that included conotruncal anomalies, obstructive lesions, and shunt lesions as well as other complex heart diseases. Ultrasound imaging also identified craniofacial/ head defects and body wall closure defects, which necropsy revealed as encephalocele, holoprosencephaly, omphalocele, or gastroschisis. Genome scanning mapped one ENU- induced mutation associated with persistence truncus arteriosus and holoprosencephaly to mouse chromosome 2, while another mutation associated with cardiac defects and omphalocele was mapped to mouse chromosome 17. These studies show the efficacy of this novel ultrasound scanning strategy for noninvasive ultrasound phenotyping to facilitate the recovery of ENU-induced mutations causing congenital heart defects and other extracardiac anomalies. C1 NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Med Univ S Carolina, Dept Anat & Cell Biol, Charleston, SC 29425 USA. Jackson Lab, Bar Harbor, ME USA. RP Lo, CW (reprint author), NHLBI, Dev Biol Lab, NIH, Bldg 50,Rm 4537,9000 Rockville Pike, Bethesda, MD 20892 USA. EM loc@nhlbi.nih.gov FU Intramural NIH HHS NR 56 TC 37 Z9 39 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD DEC 14 PY 2005 VL 24 IS 1 BP 23 EP 36 DI 10.1152/physiolgenomics.00129.2005 PG 14 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 995FO UT WOS:000234086400004 PM 16174781 ER PT J AU Jaroniec, CP Kaufman, JD Stahl, SJ Viard, M Blumenthal, R Wingfield, PT Bax, A AF Jaroniec, CP Kaufman, JD Stahl, SJ Viard, M Blumenthal, R Wingfield, PT Bax, A TI Structure and dynamics of micelle-associated human immunodeficiency virus gp41 fusion domain SO BIOCHEMISTRY LA English DT Review ID NUCLEAR-MAGNETIC-RESONANCE; RESIDUAL DIPOLAR COUPLINGS; MODEL-FREE APPROACH; 3-DIMENSIONAL SOLUTION STRUCTURE; MEDIATED MEMBRANE-FUSION; A TRANSMEMBRANE DOMAIN; HIV-1 GP41; ENVELOPE GLYCOPROTEIN; NMR-SPECTROSCOPY; INFLUENZA HEMAGGLUTININ AB The N-terminal fusion domain of the HIV-1 gp4l envelope glycoprotein is responsible for initiating the fusion of viral and cellular membranes, leading to the subsequent infection of the host cell by HIV-1. We have investigated the backbone structure and dynamics of the 30 N-terminal residues of HIV-1 gp4l in membrane-mimicking environments using NMR spectroscopy and N-15- and N-15,C-13,H-2-labeled peptides. Similar N-15-H-1 HSQC spectra were obtained in a variety of detergents, including SDS, DPC, mixed DPC/SDS, and LPPG micelles, indicating that the peptide structure is not strongly influenced by the type of detergent used. Detailed characterization was carried out in SDS micelles, where the longterm sample stability was found to be optimal. In addition to J-coupling and NOE restraints, a nearly complete set of backbone residual dipolar coupling restraints was recorded for the fusion domain-micelle complex aligned with respect to the magnetic field using a stretched polyacrylamide gel. Backbone amide 15N spin relaxation and amide hydrogen exchange rates with the solvent were also measured. The ensemble of NMR structures reveals an uninterrupted alpha-helix for the least mobile residues (S-2 > 0.65), lle-4 to Met- 19, with transient helical character extending up to Ala-22. A 12-residue (Ile-4 to Ala-15) segment is fully shielded from solvent, with Gly-3 and Gly-16 found at micelle-solvent interfaces. Res dues external to the micelle exhibit enhanced picosecond to nanosecond time scale dynamics relative to the residues buried in the micelle, and their mobility increases with the distance from the micelle. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21702 USA. RP Jaroniec, CP (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM jaroniec@speck.niddk.nih.gov; bax@nih.gov RI Jaroniec, Christopher/A-4948-2008; OI Jaroniec, Christopher/0000-0003-0364-2888 FU Intramural NIH HHS NR 111 TC 97 Z9 99 U1 3 U2 25 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 13 PY 2005 VL 44 IS 49 BP 16167 EP 16180 DI 10.1021/bi051672a PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 992QH UT WOS:000233898400023 PM 16331977 ER PT J AU Sakamoto, T Yildez, A Selvin, PR Sellers, JR AF Sakamoto, T Yildez, A Selvin, PR Sellers, JR TI Step-size is determined by neck length in myosin V SO BIOCHEMISTRY LA English DT Article ID 2-HEADED BINDING; MOTOR; ACTIN; LEVER; PROCESSIVITY; MOVEMENT; DOMAIN; ROD; HMM AB The highly processive motor, myosin V, has an extremely long neck containing six calmodulin-binding IQ motifs that allows it to take multiple 36 nm steps corresponding to the pseudo-repeat of actin. To further investigate how myosin V moves processively on actin filaments, we altered the length of the neck by adding or deleting IQ motifs in myosin constructs lacking the globular tail domain. These myosin V IQ mutants were fluorescently labeled by exchange of a single Cy3-labeled calmodulin into the neck region of one head. We measured the step-size of these individual IQ mutants with nanometer precision and subsecond resolution using FIONA. The step-size was proportional to neck length for constructs containing 2, 4, 6, and 8 IQ motifs, providing strong support for the swinging lever-arm model of myosin motility. In addition, the kinetics of stepping provided additional support for the hand-over-hand model whereby the two heads alternately assume the leading position. Interestingly, the 8 IQ myosin V mutant Gave a broad distribution of step-sizes with multiple peaks, suggesting that this mutant has many choices of binding sites on an actin filament. These data demonstrate that the step-size of myosin V is affected by the length of its neck and is not solely determined by the pseudo-repeat of the actin filament. C1 NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. Univ Illinois, Dept Phys, Urbana, IL 61801 USA. Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA. RP Sellers, JR (reprint author), NHLBI, Lab Mol Physiol, NIH, Bldg 10,Room 8N202, Bethesda, MD 20892 USA. EM sellersj@nhlbi.nih.gov FU Intramural NIH HHS NR 26 TC 58 Z9 59 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 13 PY 2005 VL 44 IS 49 BP 16203 EP 16210 DI 10.1021/bi0512086 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 992QH UT WOS:000233898400026 PM 16331980 ER PT J AU Mitchell, GF Vita, JA Larson, MG Parise, H Keyes, MJ Warner, E Vasan, RS Levy, D Benjamin, EJ AF Mitchell, GF Vita, JA Larson, MG Parise, H Keyes, MJ Warner, E Vasan, RS Levy, D Benjamin, EJ TI Cross-sectional relations of peripheral microvascular function, cardiovascular disease risk factors, and aortic stiffness - The Framingham Heart Study SO CIRCULATION LA English DT Article DE endothelium; microcirculation; risk factors; epidemiology ID DEPENDENT DIABETES-MELLITUS; INCREASED PULSE PRESSURE; FLOW-MEDIATED DILATION; MIDLIFE BLOOD-PRESSURE; WHITE-MATTER LESIONS; ARTERIAL STIFFNESS; CEREBRAL ARTERIOLES; HYPERCHOLESTEROLEMIC PATIENTS; ENDOTHELIAL DYSFUNCTION; SYSTOLIC HYPERTENSION AB Background-Aortic stiffness and small-artery structure and function share various risk factors; however, relations between these 2 measures of vascular function are complex and incompletely understood. Methods and Results-We examined hyperemic forearm blood flow, an indicator of microvascular structure and function, and aortic stiffness in 2045 participants (1107 women, mean age 61 +/- 9 years) in the Framingham Heart Study offspring cohort. Using arterial tonometry, we evaluated 3 measures of aortic stiffness: brachial pulse pressure; carotid-femoral pulse wave velocity (CFPWV), which is related directly to aortic wall stiffness; and forward pressure wave amplitude (P-f), which is related directly to aortic wall stiffness and inversely to aortic diameter. Using high-resolution ultrasound and Doppler, we evaluated brachial artery diameter, blood flow, and forearm vascular resistance (FVR) at baseline and during reactive hyperemia after 5 minutes of forearm ischemia. In multivariable models that adjusted for cardiovascular disease risk factors, local brachial pulse pressure, CFPWV, and P-f, considered separately, were associated with increased baseline and hyperemic FVR (P < 0.001). In models that further adjusted for mean arterial pressure, each measure of aortic stiffness was associated with reduced hyperemic flow (P < 0.001). In risk factor-adjusted models that simultaneously considered CFPWV and P-f, both were associated with increased FVR at baseline (P < 0.01) and during hyperemia (P < 0.001). Conclusions-Our findings indicate that abnormal aortic stiffness and increased pressure pulsatility are associated with blunted microvascular reactivity to ischemic stress that is in excess of changes attributable to conventional cardiovascular disease risk factors alone, including mean arterial pressure. C1 Cardiovasc Engn Inc, Waltham, MA 02453 USA. Boston Univ, Sch Med, Dept Math & Stat, Evans Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. NHLBIs Framingham Study, Framingham, MA USA. RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, Univ Off Pk,Bldg 2,51 Sawyer Rd,Suite 100, Waltham, MA 02453 USA. EM GaryFMitchell@mindspring.com OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K24-HL-04334, N01-HC-25195, R01-HL60040, R01-HL70100] NR 59 TC 148 Z9 152 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 13 PY 2005 VL 112 IS 24 BP 3722 EP 3728 DI 10.1161/CIRCULATIONAHA.105.551168 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 992RM UT WOS:000233901500010 PM 16330686 ER PT J AU Vihtelic, TS Fadool, JM Gao, J Thornton, KA Hyde, DR Wistow, G AF Vihtelic, TS Fadool, JM Gao, J Thornton, KA Hyde, DR Wistow, G TI Expressed sequence tag analysis of zebrafish eye tissues for NEIBank SO MOLECULAR VISION LA English DT Review ID 6000 NONREDUNDANT TRANSCRIPTS; PERIPHERAL MYELIN PROTEIN-22; RETINAL-PIGMENT EPITHELIUM; TARGETED GENE KNOCKDOWN; TIGHT JUNCTION STRANDS; VISUAL-SYSTEM DEFECTS; INNER NUCLEAR LAYER; ADULT GOLDFISH EYE; ROD PHOTORECEPTORS; DANIO-RERIO AB Purpose: To characterize gene expression patterns in various tissues of the zebrafish (Danio rerio) eye and identify zebrafish orthologs of human genes by expressed sequence tag (EST) analysis for NEIBank. Methods: mRNA was extracted from adult zebrafish eye tissues, including lenses, anterior segments (minus lens), retinas, posterior segments lacking retinas, and whole eyes. Five different cDNA libraries were constructed in the pCMVSport6 vector. Approximately 4,000 clones from each library were sequenced and analyzed using various bioinformatics programs. Results: The analysis yielded approximately 2,500 different gene clusters for each library. Combining data from the five libraries produced 10,392 unique gene clusters. GenBank accession numbers were identified for 37.6% (3,906) of the total gene clusters in the combined libraries and approximately 50% were linked to Unigene clusters in the current database. Several new crystallin genes, including two gamma N-crystallins, and a second major intrinsic protein (MIP) were identified in the lens library. In addition, a zebrafish homolog of cochlin (COCH), a gene that may play a role in the pathogenesis of human glaucoma, was identified in the anterior segment library. Surprisingly, no clear ortholog of the major retinal transcription factor Nrl was identified. Conclusions: The zebrafish eye tissue cDNA libraries are a useful resource for comparative gene expression analysis. These libraries will complement the cDNA libraries made for the Zebrafish Gene Collection (ZGC) and provide an additional source for gene identification and characterization in the vertebrate eye. C1 Univ Notre Dame, Dept Biol Sci, Ctr Zebrafish Res, Notre Dame, IN 46556 USA. Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Vihtelic, TS (reprint author), Univ Notre Dame, Dept Biol Sci, Ctr Zebrafish Res, Galvin Life Sci Bldg, Notre Dame, IN 46556 USA. EM tvihteli@nd.edu FU NEI NIH HHS [R01 EY014455] NR 127 TC 36 Z9 37 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 DEC 13 PY 2005 VL 11 IS 127 BP 1083 EP 1100 PG 18 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 996JS UT WOS:000234170800001 PM 16379021 ER PT J AU Gupta, A Sumner, CJ Castor, M Maslanka, S Sobel, J AF Gupta, A Sumner, CJ Castor, M Maslanka, S Sobel, J TI Adult botulism type F in the United States, 1981-2002 SO NEUROLOGY LA English DT Article; Proceedings Paper CT 4th International Conference on Emerging Infectious Diseases CY FEB 29-MAR 03, 2004 CL Atlanta, GA SP Ctr Dis Control & Prevent, Amer Soc Microbiol, Assoc Public Hlth Labs, Council State & Territorial Epidemiologists, WHO ID CLOSTRIDIUM-BOTULINUM; INFANT BOTULISM; FOODBORNE BOTULISM; TOXIN; NEUROTOXIN; BARATII; IDENTIFICATION AB Background: Clostridium botulinum neurotoxin types A, B, and E cause most cases of the paralytic disease botulism. Little is known about the epidemiology, clinical features, or microbiology of botulism type F. Methods: Cases of adult type F botulism were identified by review of data collected by CDC's National Botulism Surveillance System between 1981 and 2002. A case was either an individual whose serum or stool demonstrated type F toxin or whose stool culture yielded an organism producing toxin type F. A detailed review of cases' medical charts and laboratory data from CDC and local health departments was performed. Results: Between 1981 and 2002, 1,269 cases of botulism among adults and infants were reported to CDC; 13 (1%) were adult type F. The median age of type F cases was 54 years; 7 (54%) were female. None were part of outbreaks. A toxigenic Clostridium baratii was identified in 9 (69%) of 13 cases. Among 11 cases for which clinical data were available, all required mechanical ventilation for a median duration of 17 days ( range, 10 to 84); 8 (73%) were intubated within 24 hours of symptom onset. All patients had nearly complete or complete quadriplegia at the nadir of neurologic dysfunction, which occurred on average on day 5. On average by day 8, improvement in neuromuscular function was noted. The median duration of acute hospitalization was 31 days ( range, 20 to 60). No deaths were reported. In only one case was a possible foodborne etiology identified. Conclusions: Toxigenic C baratii are the sole documented causes of type F botulism in the United States since 1981. These cases are characterized by a fulminant course with rapid progression to respiratory failure and paralysis, making early recognition and intervention critical to appropriate management. C1 Ctr Dis Control & Prevent, Foodborne & Diarrheal Res Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Div Appl Publ Hlth Training, Epidem Intelligence Serv, Atlanta, GA USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Gupta, A (reprint author), Ctr Dis Control & Prevent, Foodborne & Diarrheal Res Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, 1600 Clifton Rd,MS-A-38, Atlanta, GA 30333 USA. EM agupta25@jhmi.edu NR 33 TC 30 Z9 32 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 13 PY 2005 VL 65 IS 11 BP 1694 EP 1700 DI 10.1212/01.wnl.0000187127.92446.4c PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 992QG UT WOS:000233898300004 PM 16344510 ER PT J AU Clancy, L Mruk, K Archer, K Woelfel, M Mongkolsapaya, J Screaton, G Lenardo, MJ Chan, FKM AF Clancy, L Mruk, K Archer, K Woelfel, M Mongkolsapaya, J Screaton, G Lenardo, MJ Chan, FKM TI Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE decoy receptors ID CELL-DEATH; IN-VIVO; TUMORICIDAL ACTIVITY; ANTITUMOR-ACTIVITY; CRYSTAL-STRUCTURE; DECOY RECEPTORS; CANCER-THERAPY; TNF RECEPTOR; COMPLEX; SPECIFICITY AB Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a cytokine with potential therapeutic value against cancers because of its selective cytotoxicity to many transformed, but not normal, cells. The "decoy receptors" TRAIL-R3 (TR3) and TRAIL-R4 (TR4) were believed to negatively regulate TRAIL-induced cytotoxicity by competing for ligand binding with TRAIL-R1 (TR1) and TRAIL-R2 (TR2). Here, we show that inhibition of TRAIL-induced apoptosis by TR4 critically depends on its association with TR2 via the NH2-terminal preligand assembly domain overlapping the first partial cysteine-rich domain of both receptors. By contrast, ligand binding by TR4 is dispensable for its apoptosis inhibitory function, thereby excluding the possibility that TR4 was a "decoy" to inhibit apoptosis by binding up TRAIL. In primary CD8(+) T cells, which express only TR2 and TR4 and are resistant to TRAIL-induced apoptosis, stimulation with phorbol myristate acetate abrogated the ligand-independent interaction between TR2 and TR4 and enhanced their sensitivity to TRAIL-induced apoptosis. Hence, whereas most TNF receptors normally form only homotrimeric complexes, the preligand assembly domains in TR2 and TR4 permit mixed complex formation as a means to regulate apoptosis induction. We propose that TR4 is a "regulatory" rather than "decoy" receptor that inhibits apoptosis signaling by TRAIL through this previously uncharacterized ligand-independent mechanism. C1 Univ Massachusetts, Sch Med, Dept Pathol, Immunol & Virol Program, Worcester, MA 01655 USA. NIAID, Immunol Lab, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Div Med, London W12 0NN, England. RP Chan, FKM (reprint author), Univ Massachusetts, Sch Med, Dept Pathol, Immunol & Virol Program, 55 Lake Ave N, Worcester, MA 01655 USA. EM francis.chan@umassmed.edu RI Chan, Francis/E-9647-2014; Chan, Francis K. L./F-4851-2010; OI Chan, Francis/0000-0002-4803-8353; Chan, Francis K. L./0000-0001-7388-2436; Screaton, Gavin/0000-0002-3549-4309; Mruk, Karen/0000-0003-4560-4951 FU NIAID NIH HHS [AI065877, R21 AI065877]; NIDDK NIH HHS [DK32520, P30 DK032520] NR 31 TC 133 Z9 139 U1 0 U2 8 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 DEC 13 PY 2005 VL 102 IS 50 BP 18099 EP 18104 DI 10.1073/pnas.0507329102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 994DL UT WOS:000234010500040 PM 16319225 ER PT J AU Hesse, BW Nelson, DE Kreps, GL Croyle, RT Arora, NK Rimer, BK Viswanath, K AF Hesse, BW Nelson, DE Kreps, GL Croyle, RT Arora, NK Rimer, BK Viswanath, K TI Trust and sources of health information - The impact of the Internet and its implications for health care providers: Findings from the first Health Information National Trends Survey SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MEDICAL INFORMATION; CANCER-PATIENTS; COMMUNICATION; QUALITY; TELEMEDICINE; COMMUNITIES; PHYSICIANS; SUPPORT; SYSTEMS; CANADA AB Background: The context in which patients consume health information has changed dramatically with diffusion of the Internet, advances in telemedicine, and changes in media health coverage. The objective of this study was to provide nationally representative estimates for health-related uses of the Internet, level of trust in health information sources, and preferences for cancer information sources. Methods: Data from the Health Information National Trends Survey were used. A total of 6369 persons 18 years or older were studied. The main outcome measures were online health activities, levels of trust, and source preference. Results: Analyses indicated that 63.0% (95% confidence interval [CI], 61.7%-64.3%) of the US adult population in 2003 reported ever going online, with 63.7% (95% Cl, 61.7%-65.8%) of the online population having looked for health information for themselves or others at least once in the previous 12 months. Despite newly available communication channels, physicians remained the most highly trusted information source to patients, with 62.4% (95% Cl, 60.8%-64.0%) of adults expressing a lot of trust in their physicians. When asked where they preferred going for specific health information, 49.5% (95% Cl, 48.1%-50.8%) reported wanting to go to their physicians first. When asked where they actually went, 48.6% (95% Cl, 46.1%-5 1.0%) reported going online first, with only 10.9% (95% Cl, 9.5%-12.3%) going to their physicians first. Conclusion: The Health Information National Trends Survey data portray a tectonic shift in the ways in which patients consume health and medical information, with more patients looking for information online before talking with their physicians. C1 NCI, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. George Mason Univ, Dept Commun, Fairfax, VA 22030 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Harvard Univ, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hesse, BW (reprint author), NCI, 6130 Execut Blvd,Mail Stop Code 7365, Bethesda, MD 20892 USA. EM hesseb@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 56 TC 532 Z9 536 U1 7 U2 102 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 12 PY 2005 VL 165 IS 22 BP 2618 EP 2624 DI 10.1001/archinte.165.22.2618 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 992KW UT WOS:000233883800013 PM 16344419 ER PT J AU Endoh, M Tamura, G Honda, T Homma, N Terashima, M Nishizuka, S Motoyama, T AF Endoh, M Tamura, G Honda, T Homma, N Terashima, M Nishizuka, S Motoyama, T TI RASSF2, a potential tumour suppressor, is silenced by CpG island hypermethylation in gastric cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE RASSF2; hypermethylation; gastric cancer ID PROMOTER METHYLATION STATUS; K-RAS; MICROSATELLITE INSTABILITY; DAP-KINASE; EFFECTOR; GENE; CARCINOMA; EPITHELIA; MUTATIONS; NORE1 AB RASSF2, a member of the RASSF1 family, has recently been identified as a potential tumour suppressor. We examined methylation status in multiple regions which included the CpG island and spanned the transcription start site of RASSF2 in 10 gastric cancer cell lines, as well as 78 primary gastric cancers and corresponding non-neoplastic gastric epithelia. Hypermethylation of RASSF2 in at least one of the regions examined was detected in seven (70%) of the 10 cell lines; two (20%) exhibited hypermethylation in all the regions examined including the transcription start site and lost expression of RASSF2 mRNA, which could, however, be restored by 5-aza-2' deoxycytidine treatment, while the other five (50%) cell lines exhibited hypermethylation at the 5'- and/or 3'- edge, with four of them expressing RASSF2 mRNA. In primary gastric cancers and corresponding non-neoplastic gastric epithelia, frequencies of RASSF2 methylation ranged from 29% (23 out of 78) to 79% (62 out of 78) and 3% (two out of 78) to 60% (47 out of 78), respectively, at different CpG sites examined. Methylation was frequently observed at the 5'- and 3'- edges, and became less frequent near the transcription start site in both the primary gastric cancers and corresponding non- neoplastic gastric epithelia. Hypermethylation near the transcription start site was mostly cancer-specific. We thus showed that RASSF2 is silenced by hypermethylation near the transcription start site in gastric cancer. Hypermethylation was found initially to occur at the 5'- and 3'-furthest regions of the CpG island in non-neoplastic gastric epithelia, to gradually spreads near the transcription start site to shut down RASSF2 expression, and ultimately to constitute a field-defect placing tissue increased risk for development of gastric cancer. C1 Yamagata Univ, Sch Med, Dept Pathol, Yamagata 9909585, Japan. Fukushima Med Univ, Dept Surg, Fukushima 9601295, Japan. NCI, Mol Therapeut Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Tamura, G (reprint author), Yamagata Univ, Sch Med, Dept Pathol, 2-2-2 Iida Nishi, Yamagata 9909585, Japan. EM gtamura@med.id.yamagata-u.ac.jp NR 22 TC 47 Z9 47 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD DEC 12 PY 2005 VL 93 IS 12 BP 1395 EP 1399 DI 10.1038/sj.bjc.6602854 PG 5 WC Oncology SC Oncology GA 990WV UT WOS:000233774800012 PM 16265349 ER PT J AU Adamo, R Saksena, R Kovac, P AF Adamo, R Saksena, R Kovac, P TI Synthesis of the beta anomer of the spacer-equipped tetrasaccharide side chain of the major glycoprotein of the Bacillus anthracis exosporium SO CARBOHYDRATE RESEARCH LA English DT Article DE anthrax; anthrose; exosporium glycoprotein; thioglycoside; oligosaccharide ID STEREOSPECIFIC SYNTHESIS; RHAMNOPYRANOSYL LINKAGE; OLIGOSACCHARIDES; MANNOPYRANOSYL; GLYCOSIDES AB The glycoside of the tetrasaccharide sequence beta-Ant-(1 -> 3)-alpha-L-Rhap-(1 -> 3)-alpha-L-Rhap-(1 -> 2)-L-Rhap, whose aglycon allows conjugation to proteins, was synthesized for the first time. A stepwise synthetic approach was applied with thioglycosides as glycosyl donors, and the beta anomer of the compound was obtained equipped with a spacer group whose further transformation allows conjugation to suitable carriers. To synthesize the beta-anthrosyl linkage with high stereoselectivity, a linker-equipped rhamnotriose derivative was glycosylated with ethyl 4-azido-3-O-benzyl-2-O-bromoacetyl-4,6-dideoxy-1-thio-beta-D-glucopyranoside. Further functionalization of the tetrasaccharide thus obtained, followed by deprotection, gave the target Substance. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIDDK, LMC, NIH, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, LMC, NIH, Bethesda, MD 20892 USA. EM kpn@helix.nih.gov FU Intramural NIH HHS NR 13 TC 33 Z9 33 U1 1 U2 8 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 DEC 12 PY 2005 VL 340 IS 17 BP 2579 EP 2582 DI 10.1016/j.carres.2005.09.015 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 987GK UT WOS:000233506200001 PM 16216230 ER PT J AU Steele, VE Kelloff, GJ AF Steele, VE Kelloff, GJ TI Development of cancer chemopreventive drugs based on mechanistic approaches SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE chemoprevention; drug development; anticancer; antimutagenesis; chemoprotection ID PROSTAGLANDIN-H SYNTHASE-2; SURROGATE END-POINTS; INTRAEPITHELIAL NEOPLASIA; BREAST-CANCER; AROMATASE INHIBITORS; THERAPEUTIC ACTIVITY; MESSENGER-RNA; COLON-CANCER; TUMOR-CELLS; CELECOXIB AB One of the most important medical practices of the 21st century is the chemoprevention of cancer, Much progress has been made in this new emerging field, but much work remains before widespread use and practice of cancer prevention becomes commonplace. Cancer chemoprevention includes the concepts of inhibition, reversal, and retardation of the cancer process, The process of carcinogenesis requires 20-40 years to reach invasive cancer, This process follows multiple, diverse. and complex pathways in a stochastic process, called clonal evolution. Many of these pathways appear amenable to inhibition. reversal, or retardation at various points. It is urgent that we identify key pathways in the evolution of the cancer cell. which can be exploited to prevent this carcinogenesis process. Basic researchers are identifying many genetic lesions and epigenetic processes associated with the progression of precancer to invasive disease, These precancer lesions are also called intraepithelial neoplasia (IEN). Many of these early precancerous lesions favor cell division over quiescence and protect cells against apoptosis when signals are present. Many oncogenes, which are active during early development, are reactivated in adulthood by aberrant gene promoting errors. Normal regulatory genes can become mutated, making them insensitive to normal regulatory signals. Tumor suppressor genes are deleted or mutated rendering them inactive, These are several of a wide range of defects in cellular machinery, which can lead to evolution of the cancer phenotype. Errors may not have to appear in a defined order for cells to progress along the cancer pathway. To conquer this diverse disease, it is necessary to attack multiple key pathways at once for a predetermined period of time. Agent combination prevention strategies are. therefore, essential to decrease cancer morbidity. Each cancer type, organ location, or individual genetic background may require a custom combination of prevention strategies to be successful. Published by Elsevier B.V. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Steele, VE (reprint author), NCI, NIH, EPN 2108,MSC 7322,9000 Rockville Pike, Bethesda, MD 20892 USA. EM vsly@nih.gov NR 49 TC 25 Z9 26 U1 0 U2 0 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 DEC 11 PY 2005 VL 591 IS 1-2 BP 16 EP 23 DI 10.1016/j.mrfmmm.2005.04.018 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 993OK UT WOS:000233963200004 PM 16083917 ER PT J AU Izzotti, A Bagnasco, M Cartiglia, C Longobardi, M Camoirano, A Tampa, E Lubet, RA De Flora, S AF Izzotti, A Bagnasco, M Cartiglia, C Longobardi, M Camoirano, A Tampa, E Lubet, RA De Flora, S TI Modulation of multigene expression and proteome profiles by chemopreventive agents SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE cancer chemoprevention; cDNA array; proteome; DNA adducts; environmental cigarette smoke; 5.6-benzoflavone; indole 3-carbinol; N-acetylcysteine; oltipraz; phenethyl isothiocyanate ID N-ACETYLCYSTEINE; CANCER; ISOTHIOCYANATES; RATS; INDOLE-3-CARBINOL; PREVENTION; EFFICACY; INDUCERS; ENZYMES; POINTS AB Analysis of transcriptome and proteome profiles by microarray technologies provides a formidable. new tool in cancer chemoprevention research. An ideal chemopreventive agent should not excessively alter per se the basal make-up of multigene expression and protein synthesis and should at the same time be able to attenuate alterations induced by risk factors, In order to validate this working hypothesis, we previously performed a series of studies in animal models using the thiol N-acetyl-L-cysteine (NAC) and the nonsteroidal antiinflammatory drug sulindac. We report herein the results of new studies evaluating modulation of DNA adduct levels and expression of 4858 genes in lung and liver of Sprague-Dawley rats. either unexposed or exposed to environmental cigarette smoke (ECS). The tested chemopreventive agents included NAC oltipraz (OPZ). 5,6-benzoflavone (5,6-BF), phenethyl isothiocyanate (PEITC), and indole 3-carbinol (13C). Combinations of OPZ with NAC and of PEITC with 13C were also assayed. Excepting OPZ, all treatments inhibited by at least 50% the formation of bulky DNA adducts in the lung of ECS-exposed rats. Hierarchical cluster analysis and principal component analysis allowed us to classify the agents according to their influence on basal gene expression and their ability to attenuate ECS-induced transcriptome alterations. PEITC and 13C were the most effective but the least safe agents. 5,6-BF displayed intermediate patterns, OPZ wits poorly effective in lung and considerably altered the basal gene expression in liver. NAC had a medium efficacy and was the safest agent, as also supported by the analysis of 518 proteins in rat lung. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. NCI, Bethesda, MD 20892 USA. RP Izzotti, A (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy. EM izzotti@unige.it OI izzotti, alberto/0000-0002-8588-0347 FU NCI NIH HHS [N01-CN-752008] NR 26 TC 34 Z9 35 U1 1 U2 1 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 DEC 11 PY 2005 VL 591 IS 1-2 BP 212 EP 223 DI 10.1016/j.mrfmmm.2005.03.032 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 993OK UT WOS:000233963200019 PM 16083920 ER PT J AU Shebzukhov, YV Koroleva, EP Khlgatian, SV Belousov, PV Kuz'mina, KE Radko, BV Longpre, F Lagarkova, MA Kadachigova, TS Gurova, OV Meshcheryakov, AA Lichinitser, MR Knuth, A Jager, E Kuprash, DV Nedospasov, SA AF Shebzukhov, YV Koroleva, EP Khlgatian, SV Belousov, PV Kuz'mina, KE Radko, BV Longpre, F Lagarkova, MA Kadachigova, TS Gurova, OV Meshcheryakov, AA Lichinitser, MR Knuth, A Jager, E Kuprash, DV Nedospasov, SA TI Antibody response to a non-conserved C-terminal part of human histone deacetylase 3 in colon cancer patients SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE antibodies; epitopes; HDAC3; serology ID ESTROGEN-RECEPTOR-ALPHA; NEGATIVE REGULATION; GROWTH-INHIBITION; HUMAN NEOPLASMS; EXPRESSION; CELLS; GENE; ACETYLATION; ACTIVATION; CARCINOMA AB Antibodies to cancer antigens can often be detected in the sera of patients, although the mechanism of the underlying humoral immune response is poorly understood. Using immunoscreening of tumor-derived cDNA expression libraries (SEREX), we identified human histone deacetylase 3 (HDAC3) as serologically defined antigen in colon cancer. Closely related HDAC1 and HDAC2 do not elicit humoral response in colon cancer patients. We show that the C-terminal region of HDAC3 protein lacking the homology to other Class I HDAC contains at least 3 distinct B-cell epitopes that are recognized by the serum antibodies. HDAC3 in combination with other SEREX antigens may become a useful molecular biomarker with diagnostic or prognostic value for a subset of colon cancer patients. (Supplementary material for this article can be found on the International Journal of Cancer website at http://www. interscience.wiley.com/jpages/0020-7136/suppmat/index.html). (c) 2005 Wiley-Liss, Inc. C1 Russian Acad Sci, Engelhardt Inst Mol Biol, Lab Mol Immunol, Moscow 119991, Russia. NCI, Basic Res Program, SAIC Frederick, Canc Res Ctr, Frederick, MD 21701 USA. NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21701 USA. Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Dept Mol Immunol, Moscow, Russia. Municipal Hosp 24, Dept Coloproctol 1, Moscow, Russia. Russian Acad Med Sci, NN Blokhin Canc Res Ctr, Moscow, Russia. Univ Zurich Hosp, Dept Oncol, CH-8091 Zurich, Switzerland. Krankenhaus NW Frankfurt, Med Klin 2, Frankfurt, Germany. RP Nedospasov, SA (reprint author), Russian Acad Sci, Engelhardt Inst Mol Biol, Lab Mol Immunol, Vavilov St 32, Moscow 119991, Russia. EM snedos@online.ru RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; FU NCI NIH HHS [N01-CO-12400] NR 29 TC 13 Z9 14 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 DEC 10 PY 2005 VL 117 IS 5 BP 800 EP 806 DI 10.1002/ijc.21240 PG 7 WC Oncology SC Oncology GA 980PT UT WOS:000233031200014 PM 15981215 ER PT J AU Correale, P Cusi, MG Tsang, KY Del Vecchio, MT Marsili, S La Placa, M Intrivici, C Aquino, A Micheli, L Nencini, C Ferrari, F Giorgi, G Bonmassar, E Francini, G AF Correale, P Cusi, MG Tsang, KY Del Vecchio, MT Marsili, S La Placa, M Intrivici, C Aquino, A Micheli, L Nencini, C Ferrari, F Giorgi, G Bonmassar, E Francini, G TI Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong immunologic and antitumor activity in metastatic colon cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; HEAT-SHOCK PROTEINS; CARCINOEMBRYONIC ANTIGEN; IMMUNE-RESPONSES; DENDRITIC CELLS; T-CELLS; CROSS-PRESENTATION; IN-VITRO; MULTIDRUG REGIMEN; TUMOR-ANTIGENS AB Purpose Tumor cell killing by anticancer drugs may be supported by their immuno- and pharmacologic effects. Chemotherapy is in fact able to (A) upregulate tumor-associated antigen expression, including carcinoembryonic antigen (CEA) or other target molecules such as thymidylate synthase (TS); and (B) downregulate tumor cell resistance to the death signals induced by tumor antigen-specific cytotoxic T lymphocytes. This provides the rationale for combining chemo- and immunotherapy. Materials and Methods We describe the results of a translational phase II trial designed to evaluate the toxicity, antitumor activity and immunologic effects of gemcitabine + FOLFOX-4 (oxaliplatin, fluorouracil, and folinic acid) polychemotherapy followed by the subcutaneous administration of granulocyte macrophage colony-stimulating factor and low-dose interleukin-2 in colorectal carcinoma patients. The study involved 29 patients (16 men and 13 women with a mean age of 69 years), 21 of whom had received a previous line of treatment, and 19 had liver involvement. Results The treatment was well tolerated and induced very high objective response (68.9%) and disease control rates (96.5%), with an average time to progression of 12.5 months. An immunologic study of peripheral blood mononuclear cells (PBMC) taken from 20 patients showed an enhanced proliferative response to colon carcinoma antigen and a significant reduction in suppressive regulatory T lymphocytes (CD4(+)CD25(T-reg)(+)). A cytofluorimetric study of the PBMCs of five HLA-A((star))02.01(+) patients who achieved an objective response showed an increased frequency of cytolytic T lymphocyte precursors specific for known CEA- and TS-derived epitopes. Conclusion The results show that our regimen has strong immunologic and antitumor activity in colorectal cancer patients and deserves to be investigated in phase III trials. C1 Univ Siena, Sch Med, Sect Med Oncol, I-53100 Siena, Italy. Univ Siena, Sch Med, Sect Pathol, Dept Human Pathol & Oncol, I-53100 Siena, Italy. Univ Siena, Sch Med, Sect Virol, Dept Mol Biol, I-53100 Siena, Italy. Univ Siena, Sch Med, Giorgio Segre Dept Pharmacol, I-53100 Siena, Italy. Univ Siena, Sch Med, Dept Imaging & Radiol, I-53100 Siena, Italy. Univ Siena, Sch Med, Interdept Oncopharmacol Ctr, I-53100 Siena, Italy. Univ Roma Tor Vergata, Dept Neurosci, Med Oncol & Pharmacol Sect, Rome, Italy. NCI, Expt Oncol Sect, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Francini, G (reprint author), Univ Siena, Sch Med, Dept Human Pathol & Oncol, Oncol Sect, Via Bracci 11, I-53100 Siena, Italy. EM francini@unisi.it RI Correale, Pierpaolo/K-1640-2016 OI Correale, Pierpaolo/0000-0003-2154-6734 NR 59 TC 114 Z9 122 U1 1 U2 9 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 DEC 10 PY 2005 VL 23 IS 35 BP 8950 EP 8958 DI 10.1200/JCO.2005.12.147 PG 9 WC Oncology SC Oncology GA 994JA UT WOS:000234026500006 PM 16061910 ER PT J AU O'Mahony, D Kummar, S Gutierrez, ME AF O'Mahony, D Kummar, S Gutierrez, ME TI Non-small-cell lung cancer vaccine therapy: A concise review SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID COLONY-STIMULATING FACTOR; TUMOR-INFILTRATING LYMPHOCYTES; PEPTIDE-BASED VACCINES; DENDRITIC CELLS; AUTOLOGOUS TUMOR; CARCINOEMBRYONIC ANTIGEN; ANTITUMOR IMMUNITY; MYCOBACTERIUM-VACCAE; COLORECTAL-CANCER; RANDOMIZED TRIAL AB Lung cancer is the leading cause of cancer deaths in the United States and throughout the world; globally, there are more than 1.1 million deaths each year. Treatment modalities currently employed are significantly limited; 50% of patients experience disease recurrence after surgery, and less than a quarter of patients respond to systemic chemotherapy. These statistics have fueled the search for a safer, more effective treatment modality. Despite significant advances in our understanding of the molecular basis of cancer immunology, many obstacles remain. However, encouraging clinical results in patients immunized with autologous tumor cell vaccines expressing granulocyte macrophage colony-stimulating factor strongly advocate further investigation of immunotherapy in non-small-cell lung cancer (NSCLC). Further studies are needed to demonstrate whether these novel therapies can potentially complement or even replace current therapeutic approaches. We present a review of the various vaccine-based strategies employed to target and treat NSCLC. C1 NCI, Med Oncol Clin Res Unit, NIH, Bethesda, MD 20892 USA. RP O'Mahony, D (reprint author), Ctr Canc Res, Med Oncol Res Unit, 10 Ctr Dr,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM omahonyd@mail.nih.gov NR 65 TC 35 Z9 35 U1 1 U2 4 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 DEC 10 PY 2005 VL 23 IS 35 BP 9022 EP 9028 DI 10.1200/JCO.2005.02.3101 PG 7 WC Oncology SC Oncology GA 994JA UT WOS:000234026500013 PM 16219932 ER PT J AU Yoon, JW Kang, JK Lee, KR Lee, HW Han, JW Seo, DW Kim, YK AF Yoon, JW Kang, JK Lee, KR Lee, HW Han, JW Seo, DW Kim, YK TI beta-carboline alkaloid suppresses NF-kappa B transcriptional activity through inhibition of IKK signaling pathway SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID NITRIC-OXIDE SYNTHASE; SESQUITERPENE LACTONE; KINASE IKK; ACTIVATION; EXPRESSION; BINDING; PHOSPHORYLATION; INFLAMMATION; MACROPHAGES; PROTEINS AB Nuclear factor (NF)-kappa B transcription factors play an evolutionarily conserved and critical role in the triggering and coordination of both innate and adaptive immune responses. Therefore, there is intense interest in understanding the regulation of this transcription factor in the context of various diseases. Studies investigated the suppression mechanism of NF-kappa B signaling pathways by a beta-carboline alkaloid (C-1) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. beta-Carboline alkaloid decreased the level of inducible nitric oxide sythase (iNOS) protein and NOS promoter activities in a concentration-dependent manner. This effect was accompanied by the reduction of NF-kappa B DNA binding activity as well as NF-kappa B nuclear translocation. In addition, beta-carboline alkaloid reduced the degradation and phosphorylation of I kappa B, and attenuated IKK activity in LPS-stimulated RAW 264.7 cells. Taken together, these results indicate that beta-carboline alkaloid has the capability to suppress NF-kappa B signaling pathway through inhibition of IKK activity in LPS-stimulated RAW 264.7 cells. C1 Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea. NCI, Extracellular Matrix Pathol Sect, Pathol Lab, NIH, Bethesda, MD USA. Kwandong Univ, Coll Med, Dept Pharmacol, Gangneung, South Korea. RP Han, JW (reprint author), Sungkyunkwan Univ, Coll Pharm, 300 Chonchon Dong, Suwon 440746, South Korea. EM jhhan551@skku.edu RI Kang, Jaeku/D-4933-2011 OI Kang, Jaeku/0000-0002-8660-7940 NR 25 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD DEC 10 PY 2005 VL 68 IS 23-24 BP 2005 EP 2017 DI 10.1080/15287390491009110 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 983PO UT WOS:000233244800002 PM 16326420 ER PT J AU Kimm, SYS Glynn, NW Obarzanek, E Kriska, AM Liu, K AF Kimm, SYS Glynn, NW Obarzanek, E Kriska, AM Liu, K TI Physical activity and BMI in adolescence - Authors' reply SO LANCET LA English DT Letter C1 Univ New Mexico, Hlth Sci Ctr, Dept Internal Med Epidemiol, Albuquerque, NM 87131 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. NHLBI, Behav Med & Prevent Sci Res Grp, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. RP Kimm, SYS (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Internal Med Epidemiol, Albuquerque, NM 87131 USA. EM kimm+@pitt.edu NR 4 TC 0 Z9 0 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 10 PY 2005 VL 366 IS 9502 BP 2003 EP 2004 DI 10.1016/S0140-6736(05)67811-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 991PW UT WOS:000233826900017 ER PT J AU Stadtman, ER Arai, H Berlett, BS AF Stadtman, ER Arai, H Berlett, BS TI Protein oxidation by the cytochrome P450 mixed-function oxidation system SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Review DE cytochrome P450; mixed-function oxidation; low-density lipoprotein oxidation ID LOW-DENSITY-LIPOPROTEIN; MICROSOMAL LIPID-PEROXIDATION; METAL-CATALYZED OXIDATION; GLUTAMINE-SYNTHETASE; OXIDIZED PROTEINS; ESCHERICHIA-COLI; PROTEOLYSIS; INACTIVATION; DEGRADATION; ACID AB This mini-review summarizes results of studies on the oxidation of proteins and low-density lipoprotein (LDL) by various mixed-function oxidation (MFO) systems. Oxidation of LDL by the O-2/FeCl3/H2O2/ascorbate MFO system is dependent on all four components and is much greater when reactions are carried out in the presence of a physiological bicarbonate/CO2 buffer system as compared to phosphate buffer. However, FeCl3 in this system could be replaced by hemin or the heme-containing protein, hemoglobin, or cytochrome c. Oxidation of LDL by the O-2/cytochrome P450 cytochrome c reductase/NADPH/FeCl3 MFO system is only slightly higher (25%) in the bicarbonate/CO2 buffer as compared to phosphate buffer, but is dependent on all components except FeCl3. Omission of FeCl3 led to a 60% loss of activity. These results suggest that peroxymonobicarbonate and/or free radical derivatives of bicarbonate ion and/or CO2 might contribute to LDL oxidation by these MFO systems. Published by Elsevier Inc. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM erstadtman@nih.gov NR 49 TC 8 Z9 8 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 9 PY 2005 VL 338 IS 1 BP 432 EP 436 DI 10.1016/j.bbrc.2005.07.203 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 984IO UT WOS:000233296700061 PM 16140263 ER PT J AU Wang, Q Song, CC Irizarry, L Dai, RM Zhang, XD Li, CCH AF Wang, Q Song, CC Irizarry, L Dai, RM Zhang, XD Li, CCH TI Multifunctional roles of the conserved arg residues in the second region of homology of p97/valosin-containing protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VALOSIN-CONTAINING PROTEIN; ATPASE ACTIVITY; AAA-ATPASE; MEMBRANE-FUSION; COMPLEX; P97; HYDROLYSIS; UBIQUITIN; SUBUNIT; P97-VCP AB The 97-kDa molecular chaperone valosin-containing protein (VCP) belongs to a highly conserved AAA family and forms a hexameric structure that is essential for its biological functions. The AAA domain contains highly conserved motifs, the Walker A, Walker B, and the second region of homology (SRH). Although Walker A and B motifs mediate ATP binding and hydrolysis, respectively, the function of the SRH in VCP is not clear. We examined the significance of the SRH in VCP, especially the conserved Arg(359) and Arg(362) in the first AAA domain, D1 and Arg(635) and Arg(638) in the second AAA domain, D2. We show that Arg359 and Arg362 in D1 are critical for maintaining the hexameric structure and the ability to bind the polyubiquitin chains. Although the rest of the tested SRH mutants retain the hexameric structure, all of them exhibit severely reduced ATPase activity. Tryptophan fluorescence analysis showed that all of the tested mutants can bind to ATP or ADP. Thus, the reduced ATPase activity likely results from the hampered communications among protomers during hydrolysis. Moreover, when the ATPase-defective mutant R635A or R638A is mixed with the Walker A mutant of D2, the ATPase activity is partially restored, suggesting that Arg635 and Arg638 can stimulate the ATPase activity of the neighboring protomer. Interestingly, mutation of Arg359 and Arg362 uncouples the inhibitory effect of p47, a VCP co-factor, on the ATPase activity of VCP. Therefore, the Arg residues allow D1 to take on a specific conformation that is required for substrate binding and co-factor communications. Taken together, these results demonstrate that the conserved Arg residues in the SRH of both D1 and D2 play critical roles in communicating the conformational changes required for ATP hydrolysis, and SRH in D1 also contributes to substrate binding and co-factor communications. C1 NCI, Lab Canc Prevent, NIH, Frederick, MD 21702 USA. NCI, Basic Res Program, Sci Applicat Int Corp, Canc Res Ctr,NIH, Frederick, MD 21702 USA. Univ London Imperial Coll Sci Technol & Med, Ctr Struct Biol, Dept Biol Sci, London SW7 2AZ, England. RP Wang, Q (reprint author), NCI, Lab Canc Prevent, NIH, Frederick, MD 21702 USA. EM qwang@ncifcrf.gov; licc@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 35 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 9 PY 2005 VL 280 IS 49 BP 40515 EP 40523 DI 10.1074/jbc.M509636200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 989IR UT WOS:000233666600018 PM 16216872 ER PT J AU Hu, JP de Souza-Pinto, NC Haraguchi, K Hogue, BA Jaruga, P Greenberg, MM Dizdaroglu, M Bohr, VA AF Hu, JP de Souza-Pinto, NC Haraguchi, K Hogue, BA Jaruga, P Greenberg, MM Dizdaroglu, M Bohr, VA TI Repair of formamidopyrimidines in DNA involves different glycosylases - Role of the OGG1, NTH1, and NEIL1 enzymes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OXIDATIVELY DAMAGED DNA; BASE DAMAGE; ENDONUCLEASE-VIII; ESCHERICHIA-COLI; CENTER-DOT; IN-VIVO; LESIONS; EXCISION; IDENTIFICATION; CHROMATIN AB The oxidatively induced DNA lesions 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 4,6-diamino-5-formamidopyrimidine (FapyA) are formed abundantly in DNA of cultured cells or tissues exposed to ionizing radiation or to other free radical-generating systems. In vitro studies indicate that these lesions are miscoding, can block the progression of DNA polymerases, and are substrates for base excision repair. However, no study has yet addressed how these lesions are metabolized in cellular extracts. The synthesis of oligonucleotides containing FapyG and FapyA at defined positions was recently reported. These constructs allowed us to investigate the repair of Fapy lesions in nuclear and mitochondrial extracts from wild type and knock-out mice lacking the two major DNA glycosylases for repair of oxidative DNA damage, OGG1and NTH1. The background level of FapyG/FapyA in DNA from these mice was also determined. Endogenous FapyG levels in liver DNA from wild type mice were significantly higher than 8-hydroxyguanine levels. FapyG and FapyA were efficiently repaired in nuclear and mitochondrial extracts from wild type animals but not in the glycosylase-deficient mice. Our results indicated that OGG1 and NTH1 are the major DNA glycosylases for the removal of FapyG and FapyA, respectively. Tissue-specific analysis suggested that other DNA glycosylases may contribute to FapyA repair when NTH1 is poorly expressed. We identified NEIL1 in liver mitochondria, which could account for the residual incision activity in the absence of OGG1 and NTH1. FapyG and FapyA levels were significantly elevated in DNA from the knock-out mice, underscoring the biological role of OGG1 and NTH1 in the repair of these lesions. C1 NIA, Lab Mol Gerontol, IRP, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA. Natl Inst Stand & Technol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, IRP, NIH, Box1,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov RI Souza-Pinto, Nadja/C-3462-2013; Jaruga, Pawel/M-4378-2015 OI Souza-Pinto, Nadja/0000-0003-4206-964X; FU NCI NIH HHS [CA-074954] NR 43 TC 117 Z9 121 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 9 PY 2005 VL 280 IS 49 BP 40544 EP 40551 DI 10.1074/jbc.M508772200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 989IR UT WOS:000233666600021 PM 16221681 ER PT J AU Piknova, B Gladwin, MT Schechter, AN Hogg, N AF Piknova, B Gladwin, MT Schechter, AN Hogg, N TI Electron paramagnetic resonance analysis of nitrosylhemoglobin in humans during NO inhalation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RED-BLOOD-CELLS; NITRIC-OXIDE; S-NITROSOHEMOGLOBIN; PHYSIOLOGICAL CONDITIONS; NITROSYL HEMOGLOBIN; EPR SPECTROSCOPY; LIGAND-BINDING; OXYHEMOGLOBIN; OXIDATION; DEOXYHEMOGLOBIN AB The reactions of nitric oxide with hemoglobin play an important role in explaining the vascular biology of this free radical. It is perhaps surprising that the level of nitrosylhemoglobin (HbNO) in which NO is bound to the ferrous hemoglobin heme in whole human blood under basal and stimulated conditions is a matter of some controversy, with measurements ranging from< 1 nM to close to 10 mu M. In order to examine HbNO levels in human blood by using EPR spectroscopy, we have developed a regression-based spectral analysis technique that has a detection level of about 200 nM HbNO. We have utilized this methodology to detect the level of HbNO under basal conditions and during NO inhalation. The major findings of this study are as follows. (i) HbNO can be accurately detected and quantified in whole blood with a detection limit of similar to 200 nM. (ii) By using regression analysis, levels of HbNO as low as 0.5 - 1 mu M can be deconvoluted into component species. (iii) HbNO is present at less than 200 nM at basal conditions in both arterial and venous blood and is formed at a level of 0.5 - 2.5 mu M upon inhalation of 80 ppm NO. (iv) The levels of HbNO detected by EPR are remarkably close (within a factor of 2) to those detected by tri-iodide-based chemiluminescence and much smaller than those detected by photolysis chemiluminescence. (v) The half-time of HbNO in vivo is similar to 40 min. C1 Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Free Radical Res Ctr, Milwaukee, WI 53226 USA. NIDDK, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Hogg, N (reprint author), Med Coll Wisconsin, Dept Biophys, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM nhogg@mcw.edu FU NIBIB NIH HHS [EB001980]; NIGMS NIH HHS [GM55792] NR 42 TC 30 Z9 32 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 9 PY 2005 VL 280 IS 49 BP 40583 EP 40588 DI 10.1074/jbc.M506292200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 989IR UT WOS:000233666600026 PM 16183646 ER PT J AU Liu, FL Boross, PI Wang, YF Tozser, J Louis, JM Harrison, RW Weber, IT AF Liu, FL Boross, PI Wang, YF Tozser, J Louis, JM Harrison, RW Weber, IT TI Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L241, 150V, and G73S SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE aspartic protease; catalysis; non-active site mutants; indinavir; substrate analog ID ELECTRON-DENSITY MAPS; VIRUS TYPE-1 PROTEASE; HUMAN-IMMUNODEFICIENCY; SUBSTRATE-ANALOGS; CROSS-RESISTANCE; DIMER STABILITY; SITE MUTATIONS; BINDING-SITE; ACTIVE-SITE; MUTANTS AB The crystal structures, dimer stabilities, and kinetics have been analyzed for wild-type human immunodeficiency virus type 1 (HIV-1) protease (PR) and resistant mutants PRL241, PR150 nu, and PRG73S to gain insight into the molecular basis of drug resistance. The mutations lie in different structural regions. Mutation 150V alters a residue in the flexible flap that interacts with the inhibitor, L24I alters a residue adjacent to the catalytic Asp25, and G73S lies at the protein surface far from the inhibitor-binding site. PRL241 and PRI50V, showed a 4% and 18% lower k(cat)/K-m, respectively, relative to PR. The relative k(cat)/K-m of PRG73S varied from 14% to 400% when assayed using different substrates. Inhibition constants (K-i) of the antiviral drug indinavir for the reaction catalyzed by the mutant enzymes were about threefold and 50-fold higher for PRL24I and PRI50 nu, respectively, relative to PR and PRG73S. The dimer dissociation constant (K-d) was estimated to be approximately 20 nM for both PRL24I and PRI50 nu, and below 5 nM for PRG73S and PR. Crystal structures of the mutants PRL24I, PRI50 nu and PRG73S were determined in complexes with indinavir, or the p2/NC substrate analog at resolutions of 1.10-1.50 angstrom. Each mutant revealed distinct structural changes relative to PR. The mutated residues in PRL241 and PRI50V had reduced intersubunit contacts, consistent with the increased Kd for dimer dissociation. Relative to PR, PRI50V had fewer interactions of Va150 with inhibitors, in agreement with the dramatically increased Ki. The distal mutation G73S introduced new hydrogen bond interactions that can transmit changes to the substrate-binding site and alter catalytic activity. Therefore, the structural alterations observed for drug-resistant mutations were in agreement with kinetic and stability changes. (c) 2005 Elsevier Ltd. All rights reserved. C1 Georgia State Univ, Dept Biol, Mol Basis Dis Program, Atlanta, GA 30303 USA. Univ Debrecen, Res Ctr Mol Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Georgia State Univ, Dept Comp Sci, Mol Basis Dis Program, Atlanta, GA 30303 USA. Georgia State Univ, Dept Chem, Mol Basis Dis Program, Atlanta, GA 30303 USA. RP Weber, IT (reprint author), Georgia State Univ, Dept Biol, Mol Basis Dis Program, POB 4010, Atlanta, GA 30303 USA. EM iweber@gsu.edu RI Tozser, Jozsef/A-7840-2008 OI Tozser, Jozsef/0000-0003-0274-0056 FU FIC NIH HHS [R03 TW001001, TW01001]; NIGMS NIH HHS [GM62920, R01 GM062920, U01 GM062920] NR 33 TC 41 Z9 41 U1 2 U2 7 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 9 PY 2005 VL 354 IS 4 BP 789 EP 800 DI 10.1016/j.jmb.2005.09.095 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 995GU UT WOS:000234089600005 PM 16277992 ER PT J AU Rattray, AJ Strathern, JN AF Rattray, AJ Strathern, JN TI Homologous recombination is promoted by translesion polymerase Pol eta SO MOLECULAR CELL LA English DT Editorial Material ID CELLS; DNA AB Two new studies provide in vivo (Kawamoto et al., 2005 [this issue of Molecular Cell]) and in vitro (Mcllwraith et al., 2005 [this issue of Molecular Cell]) evidence that pol eta functions to extend 3' strands exchanged during homologous recombination and raise the issue of how TLS polymerases are selected onto different substrates. C1 NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Rattray, AJ (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, POB B, Frederick, MD 21702 USA. RI Rattray, Alison/A-4847-2008 NR 7 TC 18 Z9 18 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 9 PY 2005 VL 20 IS 5 BP 658 EP 659 DI 10.1016/j.molcel.2005.11.018 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 994LN UT WOS:000234033400004 PM 16337590 ER PT J AU McIlwraith, MJ Vaisman, A Liu, YL Fanning, E Woodgate, R West, SC AF McIlwraith, MJ Vaisman, A Liu, YL Fanning, E Woodgate, R West, SC TI Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombination SO MOLECULAR CELL LA English DT Article ID PIGMENTOSUM VARIANT CELLS; ESCHERICHIA-COLI DINB; TRANSLESION SYNTHESIS; SACCHAROMYCES-CEREVISIAE; XERODERMA-PIGMENTOSUM; REPLICATION FORKS; NUCLEAR ANTIGEN; LESION-BYPASS; BREAK REPAIR; PCNA AB Stalled replication forks pose a serious threat to genome integrity. To overcome the catastrophic consequences associated with fork demise, translesion synthesis (TLS) polymerases such as pol eta promote DNA synthesis past lesions. Alternatively, a stalled fork may collapse and undergo repair by homologous recombination. By using fractionated cell extracts and purified recombinant proteins, we show that pol eta extends DNA synthesis from D loop recombination intermediates in which an invading strand serves as the primer. Extracts from XP-V cells, which are defective in pol eta, exhibit severely reduced D loop extension activity. The D loop extension activity of pol eta is unusual, as this reaction cannot be promoted by the replicative DNA polymerase alpha or by other TLS polymerases such as pol iota. Moreover, we find that pol eta interacts with RAD51 recombinase and RAD51 stimulates pol eta-mediated D loop extension. Our results indicate a dual function for pol eta at stalled replication forks: the promotion of translesion synthesis and the reinitiation of DNA synthesis by homologous recombination repair. C1 Canc Res UK, London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37232 USA. RP West, SC (reprint author), Canc Res UK, London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. EM stephen.west@cancer.org.uk RI Vaisman, Alexandra/C-3766-2013; OI Vaisman, Alexandra/0000-0002-2521-1467; Mcilwraith, Michael/0000-0003-1559-4369; West, Stephen/0000-0001-8848-9418 FU Intramural NIH HHS; NIGMS NIH HHS [GM52948] NR 56 TC 141 Z9 142 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 9 PY 2005 VL 20 IS 5 BP 783 EP 792 DI 10.1016/j.molcel.2005.10.001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 994LN UT WOS:000234033400015 PM 16337601 ER PT J AU Hernandez, D Ruiz, CP Crawley, A Malkani, R Werner, J Gwinn-Hardy, K Dickson, D DeVrieze, FW Hardy, J Singleton, A AF Hernandez, D Ruiz, CP Crawley, A Malkani, R Werner, J Gwinn-Hardy, K Dickson, D DeVrieze, FW Hardy, J Singleton, A TI The dardarin G2019S mutation is a common cause of Parkinson's disease but not other neurodegenerative diseases SO NEUROSCIENCE LETTERS LA English DT Article DE Parkinson's disease; parkinsonism; dementia; LRRK2; dardarin genetics ID AUTOSOMAL-DOMINANT PARKINSONISM; LRRK2 MUTATION; GENE AB Mutations in the leucine-rich kinase 2 gene (LRRK2) encoding dardarin, on chromosome 12, are a common cause of familial and sporadic Parkinson's disease. The most common mutation, a heterozygous 6055G> A transition (G2019S) accounts for approximately 3-10% of familial Parkinson's disease and 1-8% sporadic Parkinson's disease in several European-derived populations. Some families with disease caused by LRRK2 mutations have been reported to include patients with highly variable clinical and pathological features. We screened for the most common LRRK2 mutation in a series of patients with Parkinson's Disease, Alzheimer's disease, Progressive Supranuclear Palsy, Multiple System Atrophy and frontotemporal dementia, as well as in neurologically normal controls. The mutation was found only in Parkinson's disease patients or their relatives and not in those with other neurodegenerative disease. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Natl Inst Aging & Neurol Dis & Stroke, Neurogenet Lab, Bethesda, MD 20892 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. RP Hardy, J (reprint author), Natl Inst Aging & Neurol Dis & Stroke, Neurogenet Lab, Porter Neurosci Bldg,Bldg 10,Room 6C103,35 Conven, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Gwinn, Katrina/C-2508-2009; Paisan-Ruiz, Coro/C-2912-2009; Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; OI Dickson, Dennis W/0000-0001-7189-7917; Gwinn, Katrina/0000-0002-8277-651X NR 19 TC 67 Z9 70 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 9 PY 2005 VL 389 IS 3 BP 137 EP 139 DI 10.1016/j.neulet.2005.07.044 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 969SF UT WOS:000232254300005 PM 16102903 ER PT J AU Zimmerberg, J Chernomordik, LV AF Zimmerberg, J Chernomordik, LV TI Synaptic membranes bend to the wilt of a neurotoxin SO SCIENCE LA English DT Editorial Material ID INFLUENZA HEMAGGLUTININ; BIOLOGICAL-MEMBRANES; FUSION; HEMIFUSION; EXOCYTOSIS C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov; chernoml@mail.nih.gov NR 19 TC 28 Z9 30 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 9 PY 2005 VL 310 IS 5754 BP 1626 EP 1627 DI 10.1126/science.1122439 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 993NV UT WOS:000233961700031 PM 16339436 ER PT J AU Goodman, MF Kunkel, TA AF Goodman, MF Kunkel, TA TI Dale Mosbaugh Commemorative DNA Repair - Introduction SO DNA REPAIR LA English DT Editorial Material C1 NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Struct Biol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 8 PY 2005 VL 4 IS 12 BP 1345 EP 1345 DI 10.1016/j.dnarep.2005.09.012 PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 994NP UT WOS:000234038800001 ER PT J AU Prasad, R Batra, VK Yang, XP Krahn, JM Pedersen, LC Beard, WA Wilson, SH AF Prasad, R Batra, VK Yang, XP Krahn, JM Pedersen, LC Beard, WA Wilson, SH TI Structural insight into the DNA polymerase beta deoxyribose phosphate lyase mechanism SO DNA REPAIR LA English DT Article; Proceedings Paper CT Dale W Mosbaugh Memorial Symposium on Genetic Toxicology and DNA Repair CY OCT 11-12, 2004 CL Oregon State Univ, Corvallis, OR HO Oregon State Univ DE DNA polymerase beta; DNA repair; base excision repair; dRP lyase; beta-elimination; Schiff base nucleophile ID BASE-EXCISION-REPAIR; N-TERMINAL DOMAIN; SITE-DIRECTED MUTAGENESIS; POLY(ADP-RIBOSE) POLYMERASE-1; CATALYTIC MECHANISM; ESCHERICHIA-COLI; ENDONUCLEASE-III; ABASIC SITES; SUBSTRATE-SPECIFICITY; IMINO INTERMEDIATE AB A large number of biochemical and genetic studies have demonstrated the involvement of DNA polymerase beta (Pol beta) in mammalian base excision repair (BER). Pot beta participates in BER sub-pathways by contributing gap filling DNA synthesis and lyase removal of the 5'-deoxyribose phosphate (dRP) group from the cleaved abasic site. To better understand the mechanism of the dRP lyase reaction at an atomic level, we determined a crystal structure of Pot beta complexed with 5'-phosphorylated abasic sugar analogs in nicked DNA. This DNA ligand represents a potential BER intermediate. The crystal structure reveals that the dRP group is bound in a non-catalytic binding site. The catalytic nucleophile in the dRP lyase reaction, Lys72, and all other potential secondary nucleophiles, are too far away to participate in nucleophilic attack on the C1' of the sugar. An approximate model of the dRP group in the expected catalytic binding site suggests that a rotation of 120 degrees about the dRP 3'-phosphate is required to position the epsilon-amino Lys72 close to the dRPC1'. This model also suggests that several other side chains are in position to facilitate the beta-elimination reaction. From results of mutational analysis of key residues in the dRP lyase active site, it appears that the substrate dRP can be stabilized in the observed non-catalytic binding conformation, hindering dRP lyase activity. Published by Elsevier B.V. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov NR 80 TC 41 Z9 43 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 8 PY 2005 VL 4 IS 12 BP 1347 EP 1357 DI 10.1016/j.dnarep.2005.08.009 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 994NP UT WOS:000234038800003 PM 16172026 ER PT J AU Garcia-Diaz, M Bebenek, K Gao, GH Pedersen, LC London, RE Kunkel, TA AF Garcia-Diaz, M Bebenek, K Gao, GH Pedersen, LC London, RE Kunkel, TA TI Structure-function studies of DNA polymerase lambda SO DNA REPAIR LA English DT Article; Proceedings Paper CT Dale W Mosbaugh Memorial Symposium on Genetic Toxicology and DNA Repair CY OCT 11-12, 2004 CL Oregon State Univ, Corvallis, OR HO Oregon State Univ DE DNA polymerase lambda; family X; non-homologous DNA end-joining; DNA repair; dRP lyase; enzyme mechanism ID BASE-EXCISION-REPAIR; DEOXYRIBONUCLEIC-ACID POLYMERASE; STRAND BREAK REPAIR; YEAST SACCHAROMYCES-CEREVISIAE; CELL NUCLEAR ANTIGEN; N-TERMINAL DOMAIN; MU POL-MU; BETA-POLYMERASE; NOVIKOFF HEPATOMA; NONHOMOLOGOUS DNA AB DNA polymerase lambda is a member of the X family of polymerases that is implicated in non-homologous end-joining of double-strand breaks in DNA and in base excision repair of DNA damage. To better understand the roles of DNA polymerase lambda in these repair pathways, here we review its structure and biochemical properties, with emphasis on its gap-tilling polymerization activity, its dRP lyase activity and its unusual DNA synthetic (in)fidelity. Published by Elsevier B.V. C1 NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Struct Biol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Intramural NIH HHS NR 91 TC 50 Z9 50 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 8 PY 2005 VL 4 IS 12 BP 1358 EP 1367 DI 10.1016/j.dnarep.2005.09.001 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 994NP UT WOS:000234038800004 PM 16213194 ER PT J AU Shen, X Woodgate, R Goodman, MF AF Shen, X Woodgate, R Goodman, MF TI Lyase activities intrinsic to Escherichia coli polymerases IV and V SO DNA REPAIR LA English DT Article; Proceedings Paper CT Dale W Mosbaugh Memorial Symposium on Genetic Toxicology and DNA Repair CY OCT 11-12, 2004 CL Oregon State Univ, Corvallis, OR HO Oregon State Univ DE AP lyase; 5'-dRP lyase; DNA polymerase V; DNA polymerase IV; base excision repair ID BASE EXCISION-REPAIR; DNA-POLYMERASE; PHOSPHATE LYASE; IN-VITRO; INDUCED MUTAGENESIS; ADAPTIVE MUTATION; RECA PROTEIN; POL-IV; BETA; IDENTIFICATION AB Escherichia coli DNA polymerase IV and V (pol IV and pol V) are error-prone DNA polymerases that are induced as part of the SOS regulon in response to DNA damage. Both are members of the Y-family of DNA polymerases. Their principal biological roles appear to involve translesion synthesis (TLS) and the generation of mutational diversity to cope with stress. Although neither enzyme is known to be involved in base excision repair (BER), we have nevertheless observed apurinic/apyrimidinic 5-deoxyribose phosphate (AP/5'-dRP) lyase activities intrinsic to each polymerase. Pols IV and V catalyze cleavage of the phosphodiester backbone at the 3'-side of an apurinic/apyrimidinic (AP) site as well as the removal of a 5'-deoxyribose phosphate (dRP) at a preincised AP site. The specific activities of the two error-prone polymerase-associated lyases are approximately 80-fold less than the associated lyase activity of human DNA polymerase beta, which is a key enzyme used in short patch BER. Pol IV forms a covalent Schiff's base intermediate with substrate DNA that is trapped by sodium borohydride, as proscribed by a beta-elimination mechanism. In contrast, a NaBH4 trapped intermediate is not observed for pol V, even though the lyase specific activity of pol V is slightly higher than that of pol IV Incubation of pol V (UmuD'C-2)with a molar excess of UmuD drives an exchange of subunits to form UmuD'D + insoluble UmuC causing inactivation of polymerase and lyase activities. The concomitant loss of both activities is strong evidence that pol V contains a bona fide lyase activity. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ So Calif, Hedco Mol Biol Labs, Dept Chem & Biol Sci, Los Angeles, CA 90089 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Goodman, MF (reprint author), Univ So Calif, Hedco Mol Biol Labs, Dept Chem & Biol Sci, SHS Room 172,Univ Pk, Los Angeles, CA 90089 USA. EM mgoodman@usc.edu FU Intramural NIH HHS; NIEHS NIH HHS [ES012259]; NIGMS NIH HHS [GM21422] NR 32 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 8 PY 2005 VL 4 IS 12 BP 1368 EP 1373 DI 10.1016/j.dnarep.2005.08.005 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 994NP UT WOS:000234038800005 PM 16202661 ER PT J AU Chan, SSL Longley, MJ Naviaux, RK Copeland, WC AF Chan, SSL Longley, MJ Naviaux, RK Copeland, WC TI Mono-allelic POLG expression resulting from nonsense-mediated decay and alternative splicing in a patient with Alpers syndrome SO DNA REPAIR LA English DT Article; Proceedings Paper CT Dale W Mosbaugh Memorial Symposium on Genetic Toxicology and DNA Repair CY OCT 11-12, 2004 CL Oregon State Univ, Corvallis, OR HO Oregon State Univ DE nonsense-mediated mRNA decay; exon skipping; Alpers syndrome; DNA polymerase gamma; premature termination codon; nonsense-associated alternative splicing ID MITOCHONDRIAL-DNA POLYMERASE; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; MESSENGER-RNA DECAY; GAMMA MUTATIONS; TRANSLATION; DEPLETION; DEGENERATION; SUBUNIT; DISEASE; CELLS AB Alpers syndrome is an autosomal recessive mitochondrial DNA depletion disorder that affects children and young adults. It is characterized by a progressive, fatal brain and liver disease. This syndrome has been associated with mutations in POLG, the gene encoding the mitochondrial DNA polymerase (pol gamma). Most patients with Alpers syndrome have been found to be compound heterozygotes, carrying two pathogenic mutations in trans at the POLG locus. POLG is a nuclear-encoded gene whose protein product is imported into mitochondria, where it is essential for mtDNA replication and repair. We studied the skin fibroblasts of a patient with Alpers syndrome having the genotype E873stop/A467T. The E873stop mutation produces a premature termination codon (TAG) in exon 17. The A467T mutation produces a threonine to alanine substitution at a highly conserved site in exon 7. The allele bearing the stop codon (E873-TAG) is predicted to produce a truncated, catalytically inactive polymerase. However, only full-length pol gamma protein was detected by Western blot analysis. Here, we show that transcripts containing this stop codon undergo nonsense-associated alternative splicing and nonsense-mediated decay. More than 95% of the functional POLG mRNA was derived from the allele bearing the A467T mutation and less than 5% contained the E873stop mutation. These events ensured that virtually all POLG protein in the cell was expressed from the A467T allele. Therefore, the Alpers phenotype in this patient was a consequence of a single-copy gene dose of the A467T allele, and selective elimination of transcripts bearing the E873stop mutation. Published by Elsevier B.V. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Calif San Diego, Dept Med, Mitochondrial & Metab Dis Ctr, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Pediat, Mitochondrial & Metab Dis Ctr, San Diego, CA 92103 USA. RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, NIH, 111 TW Alexander Dr,Bldg 101,Rm E316, Res Triangle Pk, NC 27709 USA. EM copelan1@niehs.nih.gov FU Intramural NIH HHS NR 30 TC 33 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 8 PY 2005 VL 4 IS 12 BP 1381 EP 1389 DI 10.1016/j.dnarep.2005.08.010 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 994NP UT WOS:000234038800007 PM 16181814 ER PT J AU Steeg, PS AF Steeg, PS TI Cancer biology - Emissaries set up new sites SO NATURE LA English DT Editorial Material ID METASTASIS; CELLS C1 NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM steegp@mail.nih.gov NR 7 TC 18 Z9 21 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 8 PY 2005 VL 438 IS 7069 BP 750 EP 751 DI 10.1038/438750b PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 990XX UT WOS:000233777800028 PM 16341000 ER PT J AU Lindblad-Toh, K Wade, CM Mikkelsen, TS Karlsson, EK Jaffe, DB Kamal, M Clamp, M Chang, JL Kulbokas, EJ Zody, MC Mauceli, E Xie, XH Breen, M Wayne, RK Ostrander, EA Ponting, CP Galibert, F Smith, DR deJong, PJ Kirkness, E Alvarez, P Biagi, T Brockman, W Butler, J Chin, CW Cook, A Cuff, J Daly, MJ DeCaprio, D Gnerre, S Grabherr, M Kellis, M Kleber, M Bardeleben, C Goodstadt, L Heger, A Hitte, C Kim, L Koepfli, KP Parker, HG Pollinger, JP Searle, SMJ Sutter, NB Thomas, R Webber, C Lander, ES AF Lindblad-Toh, K Wade, CM Mikkelsen, TS Karlsson, EK Jaffe, DB Kamal, M Clamp, M Chang, JL Kulbokas, EJ Zody, MC Mauceli, E Xie, XH Breen, M Wayne, RK Ostrander, EA Ponting, CP Galibert, F Smith, DR deJong, PJ Kirkness, E Alvarez, P Biagi, T Brockman, W Butler, J Chin, CW Cook, A Cuff, J Daly, MJ DeCaprio, D Gnerre, S Grabherr, M Kellis, M Kleber, M Bardeleben, C Goodstadt, L Heger, A Hitte, C Kim, L Koepfli, KP Parker, HG Pollinger, JP Searle, SMJ Sutter, NB Thomas, R Webber, C Lander, ES CA Broad Inst Genome Sequencing Plat TI Genome sequence, comparative analysis and haplotype structure of the domestic dog SO NATURE LA English DT Review ID SINGLE NUCLEOTIDE POLYMORPHISMS; MOLECULAR EVOLUTION; LINKAGE DISEQUILIBRIUM; GENE DESERTS; BODY-SIZE; ACCELERATED EVOLUTION; MAMMALIAN EVOLUTION; NONCODING SEQUENCES; CANIS-FAMILIARIS; DNA-SEQUENCES AB Here we report a high-quality draft genome sequence of the domestic dog ( Canis familiaris), together with a dense map of single nucleotide polymorphisms ( SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health. C1 Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Boston Univ, Program Bioinformat, Boston, MA 02215 USA. N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Oxford, Dept Human Anat & Genet, MRC Funct Genet, Oxford OX1 3QX, England. Univ Rennes 1, Fac Med, CNRS, UMR Genet & Dev 6061, F-35043 Rennes, France. Agencourt Biosci Corp, Beverly, MA 01915 USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Inst Genom Res, Rockville, MD 20850 USA. Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Lindblad-Toh, K (reprint author), Harvard Univ, Broad Inst, 320 Charles St, Cambridge, MA 02141 USA. EM lander@broad.mit.edu RI Mikkelsen, Tarjei/A-1306-2007; Parker, Heidi/C-6954-2008; OI Mikkelsen, Tarjei/0000-0002-8133-3135; Karlsson, Elinor/0000-0002-4343-3776; Wade, Claire/0000-0003-3413-4771; Ponting, Chris/0000-0003-0202-7816; Heger, Andreas/0000-0001-7720-0447; Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS NR 119 TC 1221 Z9 1318 U1 42 U2 313 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 8 PY 2005 VL 438 IS 7069 BP 803 EP 819 DI 10.1038/nature04338 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 990XX UT WOS:000233777800043 PM 16341006 ER PT J AU Zhou, ZF Peters, EJ Hamilton, SP McMahon, F Thomas, C McGrath, PJ Rush, J Trivedi, MH Charney, DS Roy, A Wisniewski, S Lipsky, R Goldman, D AF Zhou, ZF Peters, EJ Hamilton, SP McMahon, F Thomas, C McGrath, PJ Rush, J Trivedi, MH Charney, DS Roy, A Wisniewski, S Lipsky, R Goldman, D TI Response to Zhang et al. (2005) - Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron 45, 11-16 SO NEURON LA English DT Letter ID TPH2 C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Human Genet, San Francisco, CA 94143 USA. NIMH, NIH, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, New York, NY 10027 USA. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. Mt Sinai Sch Med, New York, NY 10029 USA. DVA New Jersey Hlth Care Syst, Mental Hlth & Behav Sci 116A, E Orange, NJ 07018 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM dgneuro@mail.nih.gov RI McGrath, Patrick/I-6410-2013; Goldman, David/F-9772-2010; OI McGrath, Patrick/0000-0001-7217-7321; Goldman, David/0000-0002-1724-5405; Hamilton, Steven/0000-0001-8106-6260 NR 8 TC 30 Z9 30 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 8 PY 2005 VL 48 IS 5 BP 702 EP 703 DI 10.1016/j.neuron.2005.11.018 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 993BI UT WOS:000233927300002 PM 16337901 ER PT J AU Fischer, A Sananbenesi, F Pang, PT Lu, B Tsai, LH AF Fischer, A Sananbenesi, F Pang, PT Lu, B Tsai, LH TI Opposing roles of transient and prolonged expression of p25 in synaptic plasticity and hippocampus-dependent memory SO NEURON LA English DT Article ID CDK5 ACTIVATOR P35; ALZHEIMERS-DISEASE; TRANSGENIC MICE; NEUROFIBRILLARY TANGLES; DENDRITIC SPINES; CONDITIONED FEAR; KINASE-ACTIVITY; NMDA RECEPTORS; HUMAN BRAIN; NEURODEGENERATION AB While deregulation of cyclin-dependent kinase 5 (Cdk5) has been implicated in neurodegenerative diseases, its precise role in synaptic plasticity and memory remains elusive. Proteolytic cleavage of p35, a regulatory subunit of Cdk5, by calpain results in the generation of the truncated p25 protein, which causes hyperactivation of Cdk5. Using region-specific and inducible transgenic mice, we show that transiently increased p25 expression in the hippocampus enhanced long-term potentiation (LTP) and facilitated hippocampus-dependent memory. Moreover, p25 expression increased the number of dendritic spines and synapses. Importantly, enhanced memory achieved by a transient expression of p25 followed by its repression did not cause neurodegeneration. In contrast, prolonged p25 production caused severe cognitive deficits, which were accompanied by synaptic and neuronal loss and impaired LTP. Our data suggest a role for p25 in synaptic plasticity, synaptogenesis, learning, and memory and provide a model whereby deregulation of a plasticity factor can contribute to neurodegeneration. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. NIMH, Gene Cognit & Psychosis Program, Bethesda, MD 20892 USA. RP Tsai, LH (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM li-huei_tsai@hms.harvard.edu RI Lu, Bai/A-4018-2012 FU Intramural NIH HHS; NINDS NIH HHS [NS051874] NR 58 TC 158 Z9 175 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 8 PY 2005 VL 48 IS 5 BP 825 EP 838 DI 10.1016/j.neuron.2005.10.033 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 993BI UT WOS:000233927300020 PM 16337919 ER PT J AU Einat, H Yuan, P Manji, HK AF Einat, H Yuan, P Manji, HK TI Increased anxiety-like behaviors and mitochondrial dysfunction in mice with targeted mutation of the Bcl-2 gene: Further support for the involvement of mitochondrial function in anxiety disorders SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE animal models; knockout; affective disorders; plasticity ID CELL-DEATH; BCL-2-DEFICIENT MICE; TRANSGENIC MICE; PERMEABILITY TRANSITION; BIPOLAR DISORDER; RAT HIPPOCAMPUS; CALCIUM-UPTAKE; L-DEPRENYL; EXPRESSION; NEURONS AB There is growing evidence that anxiety disorders are associated with impairments of cellular plasticity and resilience. Paralleling these advances in our understanding of the neurobiologic underpinnings of anxiety disorders is the growing appreciation of the diverse functions that mitochondria play in regulating integrated CNS function. The emerging data suggest that mitochondrial Ca2+ sequestration has a key role in modulating the tone of synaptic plasticity in a variety of neuroanatomical regions, including those implicated in the pathophysiology of anxiety disorders. Furthermore, activation of peripheral mitochondrial benzodiazepine receptors resulted in reduced anxiety in rats. One of the major modulators of mitochondrial function is Bcl-2 proteins imbedded in the inner mitochondrial membrane. Bcl-2 overexpression increases mitochondria Ca2+ uptake capacity and resistance to Ca2+-inhibition of respiration and upregulation of Bcl-2 increases maximal uptake capacity of mitochondria. We have, therefore, explored the significance of Bcl-2 in the association between mitochondrial function and affective disorders testing Bcl-2 heterozygote mice in models of affective and anxiety disorders. Mutant mice have reduced mitochondrial Bcl-2 levels, and although they have no gross behavioral abnormalities, they demonstrate a significant increase of anxiety-like behaviors. Bcl-2 heterozygote mice spent less time in the center of an open field, spent less time outside an enclosure in the "emergence test", were less likely to explore the transparent part of a black/white box or the open arms of an elevated plus maze compared with WT controls. Mutant mice did not differ from WT in measures of locomotion or in the forced swim test for depression-like behavior suggesting a specific effect on anxiety-like behaviors. Our study, therefore demonstrates that Bcl-2 may be a key factor in anxiety disorders and that its effects may possibly originate from its role in the mitochondria. (c) 2005 Published by Elsevier B.V. C1 Univ Minnesota, Coll Pharm, Duluth, MN 55812 USA. NIMH, Mol Pathophysiol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Einat, H (reprint author), Univ Minnesota, Coll Pharm, 376 Kirby Plaza,1208 Kirby Dr, Duluth, MN 55812 USA. EM heinat@d.umn.edu; yuanp@mail.nih.gov; manjih@mail.nih.gov RI Einat, Haim/A-7203-2009 NR 70 TC 63 Z9 64 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD DEC 7 PY 2005 VL 165 IS 2 BP 172 EP 180 DI 10.1016/j.bbr.2005.06.012 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 986LD UT WOS:000233450200003 PM 16095731 ER PT J AU Berezhkovskii, AM Bezrukov, SM AF Berezhkovskii, AM Bezrukov, SM TI Channel-facilitated membrane transport: Constructive role of particle attraction to the channel pore SO CHEMICAL PHYSICS LA English DT Article DE diffusion in channels; Smoluchowski equation; efficient sieving ID ESCHERICHIA-COLI; SUGAR-TRANSPORT; OUTER-MEMBRANE; VDAC CHANNELS; ION CHANNELS; MALTOPORIN; BINDING; ATP; MOLECULES; MECHANISM AB We approach channel-facilitated membrane transport using a stochastic model based on considerations of particle diffusion inside the channel pore. This model allows us to rationalize the experimental observation that metabolite-specific biological channels exhibit affinities to their metabolites. We demonstrate that there is an optimal attractive interaction between the channel and the particle that maximizes the particle flux through the channel. A model in which the translocating solute jumps between neighboring binding sites is also analyzed. It is shown that the results predicted by the diffusion model can be recovered from the analysis of the binding-site model in a special limiting case. The binding-site model also describes the flux through a narrow channel where molecules cannot jump one over the other, and the regime of single-file diffusion is realized. Published by Elsevier B.V. C1 NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. EM bezrukos@mail.nih.gov NR 25 TC 35 Z9 35 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 J9 CHEM PHYS JI Chem. Phys. PD DEC 7 PY 2005 VL 319 IS 1-3 SI SI BP 342 EP 349 DI 10.1016/j.chemphys.2005.04.021 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 993LL UT WOS:000233955500034 ER PT J AU Yang, JS Lee, SY Spano, S Gad, H Zhang, LL Nie, ZZ Bonazzi, M Corda, D Luini, A Hsu, VW AF Yang, JS Lee, SY Spano, S Gad, H Zhang, LL Nie, ZZ Bonazzi, M Corda, D Luini, A Hsu, VW TI A role for BARS at the fission step of COPI vesicle formation from Golgi membrane SO EMBO JOURNAL LA English DT Article DE ARFGAP1; BARS; COPI; membrane fission; vesicle formation ID ADP-RIBOSYLATION FACTOR; RETROGRADE TRANSPORT; LYSOPHOSPHATIDIC ACID; COATED VESICLES; PROTEIN; ER; COMPLEX; CTBP3/BARS; CTBP/BARS; COATOMER AB The core complex of Coat Protein I (COPI), known as coatomer, is sufficient to induce coated vesicular-like structures from liposomal membrane. In the context of biological Golgi membrane, both palmitoyl-coenzyme A (p-coA) and ARFGAP1, a GTPase-activating protein (GAP) for ADP-Ribosylation Factor 1, also participate in vesicle formation, but how their roles may be linked remains unknown. Moreover, whether COPI vesicle formation from Golgi membrane requires additional factors also remains unclear. We now show that Brefeldin-A ADP-Ribosylated Substrate (BARS) plays a critical role in the fission step of COPI vesicle formation from Golgi membrane. This role of BARS requires its interaction with ARFGAP1, which is in turn regulated oppositely by p-coA and nicotinamide adenine dinucleotide, which act as cofactors of BARS. Our findings not only identify a new factor needed for COPI vesicle formation from Golgi membrane but also reveal a surprising mechanism by which the roles of p-coA and GAP are linked in this process. C1 Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, Chieti, Italy. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Hsu, VW (reprint author), Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, 1 Jimmy Fund Way,Smith 538, Boston, MA 02115 USA. EM vhsu@rics.bwh.harvard.edu RI Spano, Stefania/F-4951-2011; Bonazzi, Matteo/G-1623-2011; Corda, Daniela/K-6385-2016 OI Bonazzi, Matteo/0000-0001-5499-8759; Corda, Daniela/0000-0002-3614-751X FU Telethon [GGP04235] NR 30 TC 61 Z9 64 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 7 PY 2005 VL 24 IS 23 BP 4133 EP 4143 DI 10.1038/sj.emboj.7600873 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 998RI UT WOS:000234336400015 PM 16292346 ER PT J AU Jessup, JM Stewart, A Greene, FL Minsky, BD AF Jessup, JM Stewart, A Greene, FL Minsky, BD TI Adjuvant chemotherapy for stage III colon cancer - Implications of race/ethnicity, age, and differentiation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DATA-BASE REPORT; COLORECTAL-CANCER; BOWEL PROJECT; AFRICAN-AMERICANS; RANDOMIZED-TRIAL; ELDERLY-PATIENTS; POOLED ANALYSIS; BREAST-CANCER; THERAPY; FLUOROURACIL AB Context A 1990 National Institutes of Health Consensus Conference recommended that patients with stage III colon cancer receive adjuvant chemotherapy because survival was improved in clinical trials in patients who received a 5-fluorouracil-based regimen. Objective To determine whether adjuvant chemotherapy is used in the community as a standard of practice that improves outcome and whether it failed to benefit any specific sets of patients. Design, Setting, and Participants Prospective data from 85 934 patients with stage III colon cancer from 560 hospital cancer registries were entered into the National Cancer Data Base between 1990 and 2002 and included standard clinical, pathological, and first course of treatment variables. Main Outcome Measures Prevalence of adjuvant chemotherapy usage and 5-year survival in patients treated in US hospitals. Results Adjuvant chemotherapy use increased from 39% in 1991 to 64% in 2002 but was lower in black, female, and elderly patients. It improved 5-year survival from almost 8% in 1991 to more than 16% in 1997 compared with surgery alone. Adjuvant chemotherapy increases survival in elderly patients as much as it does in younger patients. However, the benefit of adjuvant chemotherapy in blacks and, those with high-grade cancers is not as great. Conclusions Adjuvant chemotherapy use has increased from 1990 to 2002 for patients with stage III colon cancer with an associated increase in 5-year survival of 16%. The benefit of adjuvant chemotherapy seems to be lower in black patients and high-grade cancers. Women have the same benefit but are less often treated. Elderly patients have the same benefit as younger patients but are less frequently treated. New options for adjuvant therapy in 2004-2005 may further improve the outcome of patients with stage III colon cancer. C1 NCI, Canc Diag Program, Div Canc Treatment & Diag, Rockville, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. Amer Coll Surg, Canc Dept, Chicago, IL USA. Carolinas Med Ctr, Dept Surg, Charlotte, NC 28203 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Jessup, JM (reprint author), NCI, Canc Diag Program, Div Canc Treatment & Diag, Execut Plaza N 6040,6130 Execut Blvd, Rockville, MD 20892 USA. EM jessupj@mail.nih.gov NR 43 TC 187 Z9 192 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 7 PY 2005 VL 294 IS 21 BP 2703 EP 2711 DI 10.1001/jama.294.21.2703 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 990EV UT WOS:000233726900018 PM 16333005 ER PT J AU Fera, F Weickert, TW Goldberg, TE Tessitore, A Hariri, A Das, S Lee, S Zoltick, B Meeter, M Myers, CE Gluck, MA Weinberger, DR Mattay, VS AF Fera, F Weickert, TW Goldberg, TE Tessitore, A Hariri, A Das, S Lee, S Zoltick, B Meeter, M Myers, CE Gluck, MA Weinberger, DR Mattay, VS TI Neural mechanisms underlying probabilistic category learning in normal aging SO JOURNAL OF NEUROSCIENCE LA English DT Article DE prefrontal cortex; parietal cortex; caudate nucleus; aging; category learning; compensation ID ADULT AGE-DIFFERENCES; CEREBRAL-BLOOD-FLOW; RHESUS-MONKEY; OLDER-ADULTS; RECOGNITION MEMORY; NONDECLARATIVE MEMORY; CORTICAL ACTIVITY; SERIAL PATTERNS; WORKING-MEMORY; FRONTAL-CORTEX AB Probabilistic category learning engages neural circuitry that includes the prefrontal cortex and caudate nucleus, two regions that show prominent changes with normal aging. However, the specific contributions of these brain regions are uncertain, and the effects of normal aging have not been examined previously in probabilistic category learning. In the present study, using a blood oxygenation level-dependent functional magnetic resonance imaging block design, 18 healthy young adults (mean age, 25.5 +/- 2.6 years) and 15 older adults (mean age, 67.1 +/- 5.3 years) were assessed on the probabilistic category learning "weather prediction" test. Whole-brain functional images acquired using a 1.5T scanner (General Electric, Milwaukee, WI) with gradient echo, echo planar imaging (3/1 mm; repetition time, 3000 ms; echo time, 50 ms) were analyzed using second-level random- effects procedures [SPM99 (Statistical Parametric Mapping)]. Young and older adults displayed equivalent probabilistic category learning curves, used similar strategies, and activated analogous neural networks, including the prefrontal and parietal cortices and the caudate nucleus. However, the extent of caudate and prefrontal activation was less and parietal activation was greater in older participants. The percentage correct and reaction time were mainly positively correlated with caudate and prefrontal activation in young individuals but positively correlated with prefrontal and parietal cortices in older individuals. Differential activation within a circumscribed neural network in the context of equivalent learning suggests that some brain regions, such as the parietal cortices, may provide a compensatory mechanism for healthy older adults in the context of deficient prefrontal cortex and caudate nuclei responses. C1 NIMH, Clin Brain Disorders Branch, NIMH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Inst Neurol Sci, Neuroimaging Lab, Natl Res Council, I-87050 Cosenza, Italy. Univ Naples 2, Dept Neurosci, Div Neurol 2, I-80131 Naples, Italy. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. Vrije Univ Amsterdam, Dept Cognit Psychol, NL-1081 BT Amsterdam, Netherlands. Rutgers State Univ, Dept Psychol, Newark, NJ 07102 USA. Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA. RP Mattay, VS (reprint author), NIMH, Clin Brain Disorders Branch, NIMH, Dept Hlth & Human Serv, Bldg 10,Room 3C108, Bethesda, MD 20892 USA. EM vsm@mail.nih.gov RI Meeter, Martijn/A-2926-2009; OI Meeter, Martijn/0000-0002-5112-6717; Myers, Catherine/0000-0002-2776-4823 FU Intramural NIH HHS NR 60 TC 64 Z9 65 U1 1 U2 10 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 DEC 7 PY 2005 VL 25 IS 49 BP 11340 EP 11348 DI 10.1523/JNEUROSCI.2736-05.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 993GF UT WOS:000233941900013 PM 16339029 ER PT J AU Kirsch, P Esslinger, C Chen, Q Mier, D Lis, S Siddhanti, S Gruppe, H Mattay, VS Gallhofer, B Meyer-Lindenberg, A AF Kirsch, P Esslinger, C Chen, Q Mier, D Lis, S Siddhanti, S Gruppe, H Mattay, VS Gallhofer, B Meyer-Lindenberg, A TI Oxytocin modulates neural circuitry for social cognition and fear in humans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amygdala; social cognition; human; fMRI; oxytocin; fear ID HUMAN BRAIN; AMYGDALA; VASOPRESSIN; FACES; RECOGNITION; BEHAVIOR; STRESS; MECHANISM; RESPONSES; DISORDER AB In non-human mammals, the neuropeptide oxytocin is a key mediator of complex emotional and social behaviors, including attachment, social recognition, and aggression. Oxytocin reduces anxiety and impacts on fear conditioning and extinction. Recently, oxytocin administration in humans was shown to increase trust, suggesting involvement of the amygdala, a central component of the neurocircuitry of fear and social cognition that has been linked to trust and highly expresses oxytocin receptors in many mammals. However, no human data on the effects of this peptide on brain function were available. Here, we show that human amygdala function is strongly modulated by oxytocin. We used functional magnetic resonance imaging to image amygdala activation by fear-inducing visual stimuli in 15 healthy males after double-blind crossover intranasal application of placebo or oxytocin. Compared with placebo, oxytocin potently reduced activation of the amygdala and reduced coupling of the amygdala to brainstem regions implicated in autonomic and behavioral manifestations of fear. Our results indicate a neural mechanism for the effects of oxytocin in social cognition in the human brain and provide a methodology and rationale for exploring therapeutic strategies in disorders in which abnormal amygdala function has been implicated, such as social phobia or autism. C1 NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Giessen, Ctr Psychiat & Psychotherapy, Cognit Neurosci Grp, D-35385 Giessen, Germany. NIMH, Neuroimaging Core Facil, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIMH, Unit Syst Neurosci Psychiat, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Meyer-Lindenberg, A (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, 10-3C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM andreasml@nih.gov OI Mier, Daniela/0000-0003-2518-7492; Kirsch, Peter/0000-0002-0817-1248; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Lis, Stefanie/0000-0002-8051-2756 FU Intramural NIH HHS NR 39 TC 753 Z9 764 U1 36 U2 211 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 DEC 7 PY 2005 VL 25 IS 49 BP 11489 EP 11493 DI 10.1523/JNEUROSCI.3984-05.2005 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 993GF UT WOS:000233941900026 PM 16339042 ER PT J AU Bauer, AK Dixon, D DeGraff, LM Cho, HY Walker, CR Malkinson, AM Kleeberger, SR AF Bauer, AK Dixon, D DeGraff, LM Cho, HY Walker, CR Malkinson, AM Kleeberger, SR TI Toll-like receptor 4 in butylated hydroxytoluene-induced mouse pulmonary inflammation and tumorigenesis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LUNG-TUMORS; CANCER; MICE; SUSCEPTIBILITY; GENE; 3-METHYLCHOLANTHRENE; ENHANCEMENT; RECEPTORS; PROMOTION; DISEASE AB Because chronic pulmonary diseases predispose to lung neoplasia, the identification of the molecular mechanisms involved could provide novel preventive, diagnostic, and therapeutic strategies. Toll-like receptors (TLRs) transduce exogenous and endogenous signals into the production of inflammatory cytokines to coordinate adaptive immune responses. To determine the role of Tlr4 in chronic lung inflammation, we compared lung permeability, leukocyte infiltration, and nuclear factor kappa B (NF kappa B) and activator protein 1 (AP-1) DNA binding in butylated hydroxytoluene (BHT)-treated (four weekly injections of 125-200 mg/kg each) inbred mouse strains with functional Tlr4 (OuJ and BALB) and mutated Tlr4 (HeJ and BALB(Lps-d)). We also measured primary tumor formation in these mice after single-carcinogen injection (3-methylcholanthrene; 10 mu g/kg), followed by BHT treatment (six weekly injections of 125-200 mg/kg each). Mice with functional Tlr4 had reduced lung permeability, leukocyte inflammation, and primary tumor formation (BALB(Lps-d), mean = 22.3 tumors/mouse, versus BALB, mean = 13.9 tumors/mouse, difference = 8.4 tumors/mouse, 95% confidence interval = 4.6 to 12.1 tumors/mouse; P =.025) compared with mice with mutated Tlr4. NF kappa B DNA binding activity was higher in 00 than in HeJ mice; however, AP-1 activity was elevated in HeJ mice. To our knowledge, this is the first model to demonstrate a modulatory role for Tlr4 in chronic lung inflammation and tumorigenesis. C1 NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Denver, CO USA. RP Bauer, AK (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr,Bldg 101,Rm E214, Res Triangle Pk, NC 27709 USA. EM bauer1@niehs.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA33497, CA96133] NR 25 TC 51 Z9 57 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 7 PY 2005 VL 97 IS 23 BP 1778 EP 1781 DI 10.1093/jnci/dji403 PG 4 WC Oncology SC Oncology GA 993AL UT WOS:000233925000013 PM 16333033 ER PT J AU Fears, TR Tucker, MA AF Fears, TR Tucker, MA TI Re: Sun exposure and mortality from melanoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Fears, TR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Rm 8040, Bethesda, MD 20892 USA. EM fearst@epndce.nci.nih.gov RI Tucker, Margaret/B-4297-2015 NR 7 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 7 PY 2005 VL 97 IS 23 BP 1789 EP 1790 DI 10.1093/jnci/dji410 PG 2 WC Oncology SC Oncology GA 993AL UT WOS:000233925000020 PM 16333038 ER PT J AU Dagdug, L Chernomordik, V Weiss, GH Gandjbakhche, AH AF Dagdug, L Chernomordik, V Weiss, GH Gandjbakhche, AH TI Monte Carlo simulations of increased/decreased scattering inclusions inside a turbid slab SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DOMAIN OPTICAL MAMMOGRAPHY; BREAST-TUMORS; BOUNDARY-CONDITIONS; DIFFUSION; MODEL AB We analyse the effect on scattered photons of anomalous optical inclusions in a turbid slab with otherwise uniform properties. Our motivation for doing so is that inclusions affect scattering contrast used to quantify optical properties found from transmitted light intensity measured in transillumination experiments. The analysis is based on a lattice random walk formalism which takes into account effects of both positive and negative deviations of the scattering coefficient from that of the bulk. Our simulations indicate the existence of a qualitative difference between the effects of these two types of perturbations. In the case of positive perturbations the time delay is found to be proportional to the square of the size of the inclusion while for negative perturbations the time delay is a linear function of its volume. C1 Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Dagdug, L (reprint author), Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Apartado Postal 55-534, Mexico City 09340, DF, Mexico. FU Intramural NIH HHS NR 17 TC 2 Z9 2 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD DEC 7 PY 2005 VL 50 IS 23 BP 5573 EP 5581 DI 10.1088/0031-9155/50/23/011 PG 9 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 994UE UT WOS:000234055900012 PM 16306653 ER PT J AU Jeang, KT AF Jeang, KT TI The value of Institute of Human Virology meeting abstracts and beyond SO RETROVIROLOGY LA English DT Editorial Material ID ACCESS AB This month Retrovirology publishes the meeting abstracts from the 10th annual Institute of Human Virology conference held August 29(th) to September 2(nd), 2005 in Baltimore, Maryland, USA. In this editorial, the rationale for publishing meeting abstracts is discussed. C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 8 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 7 PY 2005 VL 2 AR 74 DI 10.1186/1742-4690-2-74 PG 2 WC Virology SC Virology GA 033OI UT WOS:000236858000001 ER PT J AU Arnoult, D Rismanchi, N Grodet, A Roberts, RG Seeburg, DP Estaquier, J Sheng, M Blackstone, C AF Arnoult, D Rismanchi, N Grodet, A Roberts, RG Seeburg, DP Estaquier, J Sheng, M Blackstone, C TI Bax/Bak-dependent release promotes of DDP/TIMM8a promotes Drp1-mediated mitochondrial fission and mitoptosis during programmed cell death SO CURRENT BIOLOGY LA English DT Article ID GTPASE EFFECTOR DOMAIN; CYTOCHROME-C RELEASE; SMALL TIM PROTEINS; APOPTOSIS; IMPORT; BAX; AUTOPHAGY; FUSION; MORPHOLOGY; DYNAMICS AB Mitochondrial morphology within cells is controlled by precisely regulated rates of fusion and fission [14]. During programmed cell death (PCD), mitochondria undergo extensive fragmentation [5-7] and ultimately caspase-independent elimination through a process known as mitoptosis [8]. Though this increased fragmentation is due to increased fission through the recruitment of the dynamin-like GTPase Drp1 to mitochondria [9, 10], as well as to a block in mitochondrial fusion [11, 12], cellular mechanisms underlying these processes remain unclear. Here, we describe a mechanism for the increased mitochondrial Drp1 levels and subsequent stimulation of mitochondrial fission seen during PCD. We observed Bax/Bak-mediated release of DDP/TIMM8a, a mitochondrial intermembrane space (IMS) protein [13, 14], into the cytoplasm, where it binds to and promotes the mitochondrial redistribution of Drp1, a mediator of mitochondrial fission. Using both loss- and gain-of-function assays, we also demonstrate that the Drp1- and DDP/TIMM8a-dependent mitochondrial fragmentation observed during PCD is an important step in mitoptosis, which in turn is involved in caspase-independent cell death. Thus, following Bax/Bak-mediated mitochondrial outer membrane permeabilization (MOMP), IMS proteins released comprise not only apoptogenic factors such as cytochrome c involved in caspase activation [15, 16] but also DDP/TIMM8a, which activates Drp1-mediated fission to promote mitochondrial fragmentation and subsequently elimination during PCD. C1 MIT, Picower Inst Learning & Memory, RIKEN, Ctr Res Neurosci,Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. NINDS, Cellular Neurol Unit, NIH, Bethesda, MD 20892 USA. NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Unite Physiopathol Infect Lentivirales, F-75724 Paris, France. Univ Paris 07, INSERM U327, IFR02, F-75018 Paris, France. Kings Coll London, Div Med & Mol Genet, GKT Med Sch, London SE1 9RT, England. RP Sheng, M (reprint author), MIT, Picower Inst Learning & Memory, RIKEN, Ctr Res Neurosci,Dept Brain & Cognit Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM msheng@mit.edu; blackstc@ninds.nih.gov RI Roberts, Roland/C-3596-2009; OI Roberts, Roland/0000-0001-6636-1579 FU Intramural NIH HHS; Wellcome Trust NR 42 TC 123 Z9 129 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 6 PY 2005 VL 15 IS 23 BP 2112 EP 2118 DI 10.1016/j.cub.2005.10.041 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 994EM UT WOS:000234013400024 PM 16332536 ER PT J AU Luo, RB Jacques, K Ahvazi, B Stauffer, S Premont, RT Randazzo, PA AF Luo, RB Jacques, K Ahvazi, B Stauffer, S Premont, RT Randazzo, PA TI Mutational analysis of the Arf1 center dot GTP/Arf GAP interface reveals an Arf1 mutant that selectively affects the Arf GAP ASAP1 SO CURRENT BIOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; ADP-RIBOSYLATION FACTORS; GOLGI MEMBRANES; ASAP1; COATOMER; AGAP1; GAP; GGA; RECRUITMENT; CLATHRIN AB Arf1 is a GTP binding protein that functions at a number of cellular sites to control membrane traffic and actin remodeling. Arf1 is regulated by site-specific GTPase-activating proteins (GAPs). The combined results of crystallographic and biochemical studies [13] have led to the proposal that Arf1 GAPs differ in the specific interface formed with Arf1. To test this hypothesis, we have used mutagenesis to examine the interaction of three Arf GAPs (ASAP1, AGAP1, and ArfGAP1) with switch 1, switch 2, and alpha helix3 of Arf1. The GAPs were similar in being affected by mutations in switch 1 and 2. However, effects of a mutation within a helix3 and specific mutations within switch 1 and 2 differed among the GAPs. The largest differences were observed with a change of isoleucine 46 to aspartate ([146D]Arf1), which reduced ASAP1-induced catalysis by similar to 10,000-fold but had a 3-fold effect on AGAP1. The reduction was due to an isolated effect on the catalytic rate, k(cat). In vivo [146D]Arf1 had no detectable effect on the Golgi apparatus but, instead, functioned as a constitutively active mutant in the cell periphery, affecting the localization of ASAP1 and paxillin. Based on our results, we conclude that the contribution of specific residues within switch 1 of Arf to binding and achieving a transition state toward GTP hydrolysis differs among Arf GAPs. C1 NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIAMSD, Xray Crystallog Facil, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Med, Div Gastroenterol, Durham, NC 27710 USA. RP Randazzo, PA (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM randazzo@helix.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [GM 59989] NR 24 TC 16 Z9 16 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 6 PY 2005 VL 15 IS 23 BP 2164 EP 2169 DI 10.1016/j.cub.2005.10.065 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 994EM UT WOS:000234013400032 PM 16332543 ER PT J AU Koh, KK Han, SH Quon, MJ AF Koh, KK Han, SH Quon, MJ TI Inflammatory markers and the metabolic syndrome - Insights from therapeutic interventions SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERCELLULAR-ADHESION MOLECULE-1; FUTURE MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK-FACTORS; COA REDUCTASE INHIBITORS; STABLE ANGINA-PECTORIS; VASCULAR SMOOTH-MUSCLE; APPARENTLY HEALTHY-MEN AB Inflammation in the vasculature might be an important pathogenic link between cardiovascular diseases and the metabolic syndrome. Inflammation can be reduced by a variety of approaches including diet, exercise, cardiovascular drugs, and insulin sensitizers. Importantly, these different measures improve vascular function and reduce inflammation by distinct mechanisms. Therefore, combination therapy including lifestyle modifications and multiple drugs from separate classes might produce additive beneficial outcomes. We review plausible mechanisms for effects of combination therapy to reduce inflammation, improve endothelial dysfunction, and decrease insulin resistance in atherosclerosis, coronary heart disease, and hypertension in the context of insulin-resistant states including diabetes, obesity, and the metabolic syndrome. C1 Gachon Med Sch, Div Cardiol, Vasc Med & Atherosclerosis Unit, Gil Heart Ctr, Inchon 405760, South Korea. Natl Ctr Complementary & Alternat Med, Diabet Unit, Clin Invest Lab, NIH, Bethesda, MD USA. RP Koh, KK (reprint author), Gachon Med Sch, Div Cardiol, Vasc Med & Atherosclerosis Unit, Gil Heart Ctr, 1198 Kuwoldong, Inchon 405760, South Korea. EM kwangk@ghil.com RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 84 TC 213 Z9 221 U1 1 U2 9 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 DEC 6 PY 2005 VL 46 IS 11 BP 1978 EP 1985 DI 10.1016/j.jacc.2005.06.082 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 990PM UT WOS:000233755700002 PM 16325028 ER PT J AU Freundt, EC Lenardo, MJ AF Freundt, EC Lenardo, MJ TI Interfering with interferons: Hepatitis C virus counters innate immunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; NF-KAPPA-B; RIG-I; ADAPTER; ACTIVATION; INFECTION; CULTURE; EVASION; PROTEIN C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC,Human Immunol Unit, Oxford OX3 9DS, England. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM lenardo@nih.gov NR 22 TC 15 Z9 20 U1 1 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 DEC 6 PY 2005 VL 102 IS 49 BP 17539 EP 17540 DI 10.1073/pnas.0509221102 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 991XU UT WOS:000233849000001 PM 16314558 ER PT J AU Bradley, CM Craigie, R AF Bradley, CM Craigie, R TI Seeing is believing: Structure of the catalytic domain of HIV-1 integrase in complex with human LEDGF/p75 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; PREINTEGRATION COMPLEXES; DNA INTEGRATION; HUMAN GENOME; HUMAN-CELLS; PROTEINS; NUCLEAR; IDENTIFICATION; REPLICATION; TRAFFICKING C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), NIDDK, Mol Biol Lab, NIH, 5 Ctr Dr, Bethesda, MD 20892 USA. EM bobc@helix.nih.gov NR 23 TC 10 Z9 11 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 6 PY 2005 VL 102 IS 49 BP 17543 EP 17544 DI 10.1073/pnas.0509078102 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 991XU UT WOS:000233849000003 PM 16314581 ER PT J AU Murray, JM Wieland, SF Purcell, RH Chisari, FV AF Murray, JM Wieland, SF Purcell, RH Chisari, FV TI Dynamics of hepatitis B virus clearance in chimpanzees SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mathematical modeling; pathogenesis; covalently closed circular DNA ID CYTOTOXIC T-LYMPHOCYTES; ACUTE VIRAL-HEPATITIS; NUCLEOCAPSID ANTIGEN; HEPATOCYTE TURNOVER; TRANSGENIC MICE; INFECTION; RESPONSES; EPITOPES; CELLS; REPLICATION AB Mathematical modeling was performed to test the extent to which cytopathic and noncytopathic T cell effector functions contribute to resolution of hepatitis B virus (HBV) infection in three acutely infected chimpanzees. Simulations based exclusively on cytopathic functions show a poor fit to the data and would require the destruction and regeneration of approximate to 11 livers for clearance to occur. In contrast, a simulation based on a combination of cytopathic and noncytopathic functions provided a significantly better fit to the data (P < 0.001) and required as much as 5-fold less destruction to clear the virus from the liver. The best fit simulation supports the notion that during the early phase of HBV clearance, noncytopathic T cell effector mechanisms inhibit viral replication and greatly shorten the half-life of the long lived covalently closed circular viral DNA transcriptional template, thereby limiting the extent to which cytopathic T cell effector functions and tissue destruction are required to terminate acute HBV infection. C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. NIAID, NIH, Bethesda, MD 20892 USA. Natl Ctr HIV Epidemiol & Clin Res, Darlinghurst, NSW 2010, Australia. Univ New S Wales, Sch Math, Sydney, NSW 2052, Australia. RP Chisari, FV (reprint author), Scripps Res Inst, Dept Mol & Expt Med, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM fchisari@scripps.edu RI Murray, John/B-5481-2009; Chisari, Francis/A-3086-2008; OI Murray, John/0000-0001-9314-2283; Chisari, Francis/0000-0002-4832-1044 FU NIAID NIH HHS [AI20001, R01 AI020001] NR 23 TC 75 Z9 81 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 DEC 6 PY 2005 VL 102 IS 49 BP 17780 EP 17785 DI 10.1073/pnas.0508913102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 991XU UT WOS:000233849000044 PM 16306261 ER PT J AU Rajaram, S Scott, RL Nash, HA AF Rajaram, S Scott, RL Nash, HA TI Retrograde signaling from the brain to the retina modulates the termination of the light response in Drosaphila SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE acetylcholine; electroretinogram; general anesthetics; photoreceptor ID VOLATILE GENERAL-ANESTHETICS; NINAC MYOSIN-III; DROSOPHILA-MELANOGASTER; PRESYNAPTIC INHIBITION; SYNAPTIC TRANSMISSION; VISUAL TRANSDUCTION; PHOTORECEPTORS; MUTANTS; DEACTIVATION; HISTAMINE AB A critical factor in visual function is the speed with which photoreceptors (PRs) return to the resting state when light intensity dims. Several elements subserve this process, many of which promote the termination of the phototransduction cascade. Although the known elements are intrinsic to PRs, we have found that prompt restoration to the resting state of the Drosophila electroretinogram can require effective communication between the retina and the underlying brain. The requirement is seen more dramatically with long than with short light pulses, distinguishing the phenomenon from gross disruption of the termination machinery. The speed of recovery is affected by mutations (in the Hdc and ort genes) that prevent PRs from transmitting visual information to the brain. It is also affected by manipulation (using either drugs like neostigmine or genetic tools to inactivate neurotransmitter release) of cholinergic signals that arise in the brain. Intracellular recordings support the hypothesis that PRs are the target of this communication. We infer that signaling from the retina to the optic lobe prompts a feedback signal to retinal PRs. Although the mechanism of this retrograde signaling remains to be discerned, the phenomenon establishes a previously unappreciated mode of control of the temporal responsiveness of a primary sensory neuron. C1 NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Nash, HA (reprint author), NIMH, Mol Biol Lab, NIH, Bldg 35,Room 1B-1002,9000 Rockville Pike, Bethesda, MD 20892 USA. EM howardnash@mail.nih.gov RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 FU Intramural NIH HHS NR 31 TC 10 Z9 10 U1 1 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 DEC 6 PY 2005 VL 102 IS 49 BP 17840 EP 17845 DI 10.1073/pnas.0508858102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 991XU UT WOS:000233849000054 PM 16314566 ER PT J AU Vallon, V Grahammer, F Volkl, H Sandu, CD Richter, K Rexhepaj, R Gerlach, U Rong, Q Pfeifer, K Lang, F AF Vallon, V Grahammer, F Volkl, H Sandu, CD Richter, K Rexhepaj, R Gerlach, U Rong, Q Pfeifer, K Lang, F TI KCNQ1-dependent transport in renal and gastrointestinal epithelia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE K+ channels; H+ secretion; Cl- secretion; glucose transport; amino acid transport ID POTASSIUM CHANNEL; TARGETED DISRUPTION; INTRINSIC-FACTOR; CYSTIC-FIBROSIS; PARIETAL-CELLS; K+ CONDUCTANCE; MOUSE MODEL; KCNQ1; RAT; EXPRESSION AB Mutations in the gene encoding for the K+ channel a-subunit KCNQ1 have been associated with long QT syndrome and deafness. Besides heart and inner ear epithelial cells, KCNQ1 is expressed in a variety of epithelial cells including renal proximal tubule and gastrointestinal tract epithelial cells. At these sites, cellular K+ ions exit through KCNQ1 channel complexes, which may serve to recycle K+ or to maintain cell membrane potential and thus the driving force for electrogenic transepithelial transport, e.g., Na+/glucose cotransport. Employing pharmacologic inhibition and gene knockout, the present study, demonstrates the importance of KCNQ1 K+ channel complexes for the maintenance of the driving force for proximal tubular and intestinal Na+ absorption, gastric acid secretion, and cAMP-induced jejunal Cl- secretion. In the kidney, KCNQ1 appears dispensable under basal conditions because of limited substrate delivery for electrogenic Na+ reabsorption to KCNQ1-expressing mid to late proximal tubule. During conditions of increased substrate load, however, luminal KCNQ1 serves to repolarize the proximal tubule and stabilize the driving force for Na+ reabsorption. In mice lacking functional KCNQ1, impaired intestinal absorption is associated with reduced serum vitamin B12 concentrations, mild macrocytic anemia, and fecal loss of Na+ and K+, the latter affecting K+ homeostasis. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92161 USA. Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92161 USA. Vet Affairs San Diego Hlth Care Syst, La Jolla, CA 92161 USA. Univ Tubingen, Dept Physiol 1, D-72076 Tubingen, Germany. Innsbruck Med Univ, Dept Physiol & Med Phys, A-6020 Innsbruck, Austria. Aventis Pharma Deutsch GmbH, D-65926 Frankfurt, Germany. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20982 USA. RP Vallon, V (reprint author), Univ Calif San Diego, Dept Med, 3350 La Jolla Village Dr 9151, La Jolla, CA 92161 USA. EM vvallon@ucsd.edu OI Pfeifer, Karl/0000-0002-0254-682X FU NIDDK NIH HHS [DK28602, R01 DK056248, DK56248, R01 DK028602] NR 28 TC 124 Z9 127 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 DEC 6 PY 2005 VL 102 IS 49 BP 17864 EP 17869 DI 10.1073/pnas.0505860102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 991XU UT WOS:000233849000058 PM 16314573 ER PT J AU Bossert, JM Ghitza, UE Lu, L Epstein, DH Shaham, Y AF Bossert, JM Ghitza, UE Lu, L Epstein, DH Shaham, Y TI Neurobiology of relapse to heroin and cocaine seeking: An update and clinical implications SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article; Proceedings Paper CT 4th Spring Meeting of the European Journal of Pharmacology CY JUN 10-12, 2005 CL Zeist, NETHERLANDS DE cocaine; conditioned drug cues; extinction; heroin; incubation; reinstatement; relapse; review; stress ID STRESS-INDUCED REINSTATEMENT; CORTICOTROPIN-RELEASING-FACTOR; CONDITIONED PLACE PREFERENCE; VENTRAL TEGMENTAL AREA; CUE-INDUCED REINSTATEMENT; SELF-ADMINISTRATION BEHAVIOR; MEDIAL PREFRONTAL CORTEX; EXTRACELLULAR DOPAMINE LEVELS; DRUG-INDUCED REINSTATEMENT; TIME-DEPENDENT CHANGES AB The central problem in the treatment of cocaine and heroin addiction is high rates of relapse to drug use after periods of forced or self-imposed abstinence. Relapse can be modeled in laboratory animals a reinstatement procedure in which responding for drug is extinguished and then reinstated by acute exposure to the drug, drug cues, or stress. In this review, we first summarize data from recent (2003-2005) studies on the neural substrates involved in reinstatement of heroin and cocaine seeking. We also discuss the neural mechanisms underlying the progressive increase in cocaine seeking after withdrawal (incubation of cocaine craving). Finally, we provide an update on several novel candidate medications for relapse prevention suggested by recent preclinical studies, and we discuss the translation of findings from nonhuman laboratory studies to the clinical phenomenon of relapse. (c) 2005 Elsevier B.V. All rights reserved. C1 NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. NIDA, Clin Pharmacol & Therapeut Res Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI shaham, yavin/G-1306-2014 NR 167 TC 183 Z9 194 U1 2 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 EI 1879-0712 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD DEC 5 PY 2005 VL 526 IS 1-3 BP 36 EP 50 DI 10.1016/j.ejphar.2005.09.030 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993MR UT WOS:000233958700005 PM 16289451 ER PT J AU Nallamshetty, S Crook, M Boehm, M Yoshimoto, T Olive, M Nabel, EG AF Nallamshetty, S Crook, M Boehm, M Yoshimoto, T Olive, M Nabel, EG TI The cell cycle regulator p27(Kip1) interacts with MCM7, a DNA replication licensing factor, to inhibit initiation of DNA replication SO FEBS LETTERS LA English DT Article DE cell cycle; cyclin-dependent kinase inhibitor; p27(Kip1); DNA replication; MCM ID XENOPUS EGG EXTRACTS; CDK INHIBITOR; RETINOBLASTOMA PROTEIN; HELICASE ACTIVITY; S-PHASE; COMPLEX; KINASE; P27; PROGRESSION; ORIGINS AB The G1/S phase restriction point is a critical checkpoint that interfaces between the cell cycle regulatory machinery and DNA replicator proteins. Here, we report a novel function for the cyclin-dependent kinase inhibitor p27(Kip1) in inhibiting DNA replication through its interaction with MCM7, a DNA replication protein that is essential for initiation of DNA replication and maintenance of genomic integrity. We find that p27(Kip1) binds the conserved minichromosome maintenance (MCM) domain of MCM7. The proteins interact endogenously in vivo in a growth factor-dependent manner, such that the carboxyl terminal domain of p27(Kip1) inhibits DNA replication independent of its function as a cyclin-dependent kinase inhibitor. This novel function of P27(Kip1) may prevent inappropriate initiation of DNA replication prior to S phase. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, NIH, Bldg 50,Room 4523,50 Ctr Dr, Bethesda, MD 20892 USA. EM nabele@nih.gov FU Intramural NIH HHS NR 34 TC 15 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 5 PY 2005 VL 579 IS 29 BP 6529 EP 6536 DI 10.1016/j.febslet.2005.10.028 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 991UL UT WOS:000233839500002 PM 16289477 ER PT J AU Wise, RA AF Wise, RA TI Forebrain substrates of reward and motivation SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article; Proceedings Paper CT Neuroscience Conference on Anatomy of the Soul CY MAY 19-24, 2005 CL Ameland, NETHERLANDS DE reward; reinforcement; motivation; medial forebrain bundle; dopamine ID VENTRAL TEGMENTAL AREA; BRAIN-STIMULATION REWARD; MEDIAL PREFRONTAL CORTEX; HYPOTHALAMIC SELF-STIMULATION; PIMOZIDE-INDUCED EXTINCTION; LATERAL PREOPTIC AREA; FREELY MOVING RATS; NUCLEUS-ACCUMBENS; ELECTRICAL-STIMULATION; SUBSTANTIA-NIGRA AB Electrical stimulation of the medial forebrain bundle can reward arbitrary acts or motivate biologically primitive, species-typical behaviors like feeding or copulation. The subsystems involved in these behaviors are only partially characterized, but they appear to transsynaptically activate the mesocorticolimbic dopamine system. Basal function of the dopamine system is essential for arousal and motor function; phasic activation of this system is rewarding and can potentiate the effectiveness of reward-predictors that guide learned behaviors. This system is phasically activated by most drugs of abuse and such activation contributes to the habit-forming actions of these drugs. C1 NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Wise, RA (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rwise@intra.nida.nih.gov RI Wise, Roy/A-6465-2012 FU Intramural NIH HHS [Z99 DA999999] NR 128 TC 150 Z9 155 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 5 PY 2005 VL 493 IS 1 BP 115 EP 121 DI 10.1002/cne.20689 PG 7 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 984IL UT WOS:000233296400018 PM 16254990 ER PT J AU Berman, J Chesney, MA AF Berman, J Chesney, MA TI Complementary and alternative medicine in 2006: optimising the dose of the intervention SO MEDICAL JOURNAL OF AUSTRALIA LA English DT Editorial Material ID CONTROLLED TRIAL C1 Natl Ctr Complementary & Alternat Med, Off Clin & Regulatory Affairs, NIH, Bethesda, MD 20892 USA. Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA. RP Berman, J (reprint author), Natl Ctr Complementary & Alternat Med, Off Clin & Regulatory Affairs, NIH, Bethesda, MD 20892 USA. EM bermanjo@mail.nih.gov NR 8 TC 5 Z9 5 U1 0 U2 0 PU AUSTRALASIAN MED PUBL CO LTD PI SYDNEY PA LEVEL 1, 76 BERRY ST, SYDNEY, NSW 2060, AUSTRALIA SN 0025-729X J9 MED J AUSTRALIA JI Med. J. Aust. PD DEC 5 PY 2005 VL 183 IS 11-12 BP 574 EP 575 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 999OE UT WOS:000234398200007 PM 16336133 ER PT J AU Ho, NCY Tran, JR Bektas, A AF Ho, NCY Tran, JR Bektas, A TI Marfan's syndrome SO LANCET LA English DT Editorial Material ID MUTATIONS C1 Johns Hopkins Med Inst, Dept Pediat, Bethesda, MD 20814 USA. NIH, Baltimore, MD USA. RP Ho, NCY (reprint author), Johns Hopkins Med Inst, Dept Pediat, 8315 N Brook Lane, Bethesda, MD 20814 USA. EM nho1@jhmi.edu NR 14 TC 22 Z9 24 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 3 PY 2005 VL 366 IS 9501 BP 1978 EP 1981 DI 10.1016/S0140-6736(05)66995-4 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 990XY UT WOS:000233777900028 PM 16325702 ER PT J AU Wawer, MJ Reynolds, SJ Serwadda, D Kigozi, G Kiwanuka, N Gray, RH AF Wawer, MJ Reynolds, SJ Serwadda, D Kigozi, G Kiwanuka, N Gray, RH TI Might male circumcision be more protective against HIV in the highly exposed? An immunological hypothesis SO AIDS LA English DT Letter ID FEMALE SEX WORKERS; INFECTION; RESPONSES; MUCOSAL; NAIROBI; COHORT; PROSTITUTES; INDIVIDUALS; RISK; IGA C1 Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. NIAID, NIH, Bethesda, MD 20892 USA. Makerere Univ, Inst Publ Hlth, Kampala, Uganda. Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Wawer, MJ (reprint author), Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. NR 20 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0269-9370 J9 AIDS JI Aids PD DEC 2 PY 2005 VL 19 IS 18 BP 2181 EP 2182 DI 10.1097/01.aids.0000194132.51006.4f PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 987BK UT WOS:000233493200022 PM 16284475 ER PT J AU Guo, DH Han, JY Adam, BL Colburn, NH Wang, MH Dong, Z Eizirik, DL She, JX Wang, CY AF Guo, DH Han, JY Adam, BL Colburn, NH Wang, MH Dong, Z Eizirik, DL She, JX Wang, CY TI Proteomic analysis of SUM04 substrates in HEK293 cells under serum starvation-induced stress SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE SUMO; sumoylation; ubiquitylation; substrate; stress; ROS; H2O2; 2D PAGE; MALDI-TOF ID TRANSCRIPTION FACTOR AP-2; PROTEIN MODIFICATION; OXIDATIVE STRESS; KAPPA-B; SUMOYLATION; MODIFIER; ACTIVATION; CHAPERONES; EXPRESSION; INDUCTION AB The substrates of SUMO4, a novel member for the SUMO gene family, were characterized in HEK293 cells cultured under serum starvation by proteomic analysis. We identified 90 SUMO4 substrates including anti-stress proteins such as antioxidant enzymes and molecular chaperones or co-chaperones. The substrates also include proteins involved in the regulation of DNA repair and synthesis, RNA processing, protein degradation, and glucose metabolism. Several SUMO4-associated transcription factors were characterized by Western blot analyses. AP-1 was selected for in vitro conjugation assays to confirm SUMO4 sumoylation of these transcription factors. Further functional analyses of the transcription factors suggested that SUMO4 sumoylation represses AP-1 and AP-2 alpha transcriptional activity, but enhances GR DNA binding capacity. These results demonstrate that SUMO4 sumoylation may play an important role in the regulation of intracellular stress. (c) 2005 Elsevier Inc. All rights reserved. C1 Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA 30912 USA. NCI, Lab Canc Prevent, Ft Detrick, MD 21702 USA. Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA. Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA. Univ Libre Bruxelles, Expt Med Lab, B-1070 Brussels, Belgium. RP Wang, CY (reprint author), Med Coll Georgia, Ctr Biotechnol & Genom Med, 1120 15th St, Augusta, GA 30912 USA. EM cwang@mcg.edu NR 41 TC 58 Z9 64 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 2 PY 2005 VL 337 IS 4 BP 1308 EP 1318 DI 10.1016/j.bbrc.2005.09.191 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 981XF UT WOS:000233120600041 PM 16236267 ER PT J AU Chiapperino, D Cai, MM Sayer, JM Yagi, H Kroth, H Masutani, C Hanaoka, F Jerina, DM Cheh, AM AF Chiapperino, D Cai, MM Sayer, JM Yagi, H Kroth, H Masutani, C Hanaoka, F Jerina, DM Cheh, AM TI Error-prone translesion synthesis by human DNA polymerase eta on DNA-containing deoxyadenosine adducts of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE PHOSPHORIBOSYLTRANSFERASE GENE; DOSE-DEPENDENT DIFFERENCES; TEMPLATE-PRIMER JUNCTION; NMR SOLUTION STRUCTURE; THYMINE DIMER BYPASS; DG MISMATCH OPPOSITE; CODON 61 SEQUENCE; XERODERMA-PIGMENTOSUM; CRYSTAL-STRUCTURE; Y-FAMILY AB When human DNA polymerase eta(pol eta) encounters N(6)-deoxyadenosine adducts formed by trans epoxide ring opening of the 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ( BaP DE) isomer with ( +)-7R,8S,9S,10R configuration (( +)-BaP DE-2), misincorporation of A or G and incorporation of the correct T are equally likely to occur. On the other hand, the enzyme exhibits a 3-fold preference for correct T incorporation opposite adducts formed by trans ring opening of the ( -)-(7S,8R,9R,10S)- DE-2 enantiomer. Adducts at dA formed by cis ring opening of these two BaP DE-2 isomers exhibit a 3-fold preference for A over T incorporation, with G intermediate between the two. Extension one nucleotide beyond these adducts is generally weaker than incorporation across from them, but among mismatches the ( adducted A*)(.)A mispair is the most favored for extension. Because mutations can only occur if mispairs are extended, this observation is consistent with the occurrence of A(.)T to T(.)A transversions as common mutations in animal cells treated with BaP DE-2 isomers. Adducts with S absolute configuration at the point of attachment of the hydrocarbon to the base inhibit incorporation and extension by pol eta to a lesser extent than their R counterparts. Template-primers containing each of the four isomeric dA adducts derived from BaP DE-2 and two adducts derived from 9,10-epoxy-7,8,9,10-tetrahydrobenzo[ a] pyrene in which the 7- and 8-hydroxyl groups of the DEs are replaced with hydrogens exhibit reduced electrophoretic mobilities relative to the unadducted oligonucleotides. This effect is largely independent of DNA sequence. Decreased mobility correlates with an increased rate of incorporation by pol eta, suggesting a systematic relationship between the overall DNA structure and efficiency of the enzyme. C1 NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. American Univ, Dept Chem, Washington, DC 20016 USA. Japan Sci & Technol Corp, RIKEN, Wako, Saitama 3510198, Japan. Japan Sci & Technol Corp, Solut Oriented Res Sci & Technol, Wako, Saitama 3510198, Japan. Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan. RP Cheh, AM (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM acheh@american.edu RI Masutani, Chikahide/I-6160-2014 FU Intramural NIH HHS NR 61 TC 14 Z9 15 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 2 PY 2005 VL 280 IS 48 BP 39684 EP 39692 DI 10.1074/jbc.M508008200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 986PD UT WOS:000233461300004 PM 16188888 ER PT J AU Di Noto, L Whitson, LJ Cao, XH Hart, PJ Levine, RL AF Di Noto, L Whitson, LJ Cao, XH Hart, PJ Levine, RL TI Proteasomal degradation of mutant superoxide dismutases linked to amyotrophic lateral sclerosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTICATALYTIC PROTEINASE COMPLEX; MOLECULAR-WEIGHT COMPLEXES; MOTOR-NEURON DEGENERATION; CU,ZN-SUPEROXIDE DISMUTASE; SELECTIVE DEGRADATION; GLUTAMINE-SYNTHETASE; MODIFIED HEMOGLOBIN; 20S PROTEASOME; STABILITY; SOD1 AB Mutations in copper-zinc superoxide dismutase cause the neurodegenerative disease amyotrophic lateral sclerosis. Many of the mutant proteins have increased turnover in vivo and decreased thermal stability. Here we show that purified, metal-free superoxide dismutases are degraded in vitro by purified 20 S proteasome in the absence of ATP and without ubiquitinylation, whereas their metal-bound counterparts are not. The rate of degradation by the proteasome varied among the mutants studied, and the rate correlated with the in vivo half-life. The monomeric forms of both mutant and wild-type superoxide dismutase are particularly susceptible to degradation by the proteasome. Exposure of hydrophobic regions as a consequence of decreased thermal stability may allow the proteasome to recognize these molecules as non-native. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. RP Levine, RL (reprint author), Bldg 50 Rm 2351, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Levine, Rodney/D-9885-2011 FU Intramural NIH HHS; NINDS NIH HHS [NS39112, R01 NS039112] NR 55 TC 31 Z9 31 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 2 PY 2005 VL 280 IS 48 BP 39907 EP 39913 DI 10.1074/jbc.M506247200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 986PD UT WOS:000233461300029 PM 16195234 ER PT J AU Iwaki, S Tkaczyk, C Satterthwaite, AB Halcomb, K Beaven, MA Metcalfe, DD Gilfillan, AM AF Iwaki, S Tkaczyk, C Satterthwaite, AB Halcomb, K Beaven, MA Metcalfe, DD Gilfillan, AM TI Btk plays a crucial role in the amplification of Fc epsilon RI-mediated mast cell activation by Kit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; BRUTONS TYROSINE KINASE; ALPHA GENE-EXPRESSION; AFFINITY IGE RECEPTOR; PROTEIN-KINASE; NUCLEAR-FACTOR; C-KIT; CYTOKINE PRODUCTION; TERMINAL KINASE; T-CELLS AB Stem cell factor (SCF) acts in synergy with antigen to enhance the calcium signal, degranulation, activation of transcription factors, and cytokine production in human mast cells. However, the underlying mechanisms for this synergy remain unclear. Here we show, utilizing bone marrow-derived mast cells (BMMCs) from Btk and Lyn knock-out mice, that activation of Btk via Lyn plays a key role in promoting synergy. As in human mast cells, SCF enhanced degranulation and cytokine production in BMMCs. In Btk(-/-) BMMCs, in which there was a partial reduction in the capacity to degranulate in response to antigen, SCF was unable to enhance the residual antigen-mediated degranulation. Furthermore, as with antigen, the ability of SCF to promote cytokine production was abrogated in the Btk(-/-) BMMCs. The impairment of responses in Btk(-/-) cells correlated with an inability of SCF to augment phospholipase C gamma(1) activation and calcium mobilization, and to phosphorylate NF kappa B and NFAT for cytokine gene transcription in these cells. Similar studies with Lyn(-/-) and Btk(-/-)/ Lyn(-/-) BMMCs indicated that Lyn was a regulator of Btk for these responses. These data demonstrate, for the first time, that Btk is a key regulator of a Kit-mediated amplification pathway that augments Fc epsilon RI-mediated mast cell activation. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Rm 11C206,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM agilfillan@niaid.nih.gov FU Intramural NIH HHS NR 49 TC 65 Z9 67 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 2 PY 2005 VL 280 IS 48 BP 40261 EP 40270 DI 10.1074/jbc.M506063200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 986PD UT WOS:000233461300068 PM 16176929 ER PT J AU Holmes, JB Tsai, J AF Holmes, JB Tsai, J TI Characterizing conserved structural contacts by pair-wise relative contacts and relative packing groups SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE structural alignment; fold classification; globin family; conserved structural contacts; protein side-chain packing ID PROTEIN STRUCTURES; SIDE-CHAIN; CORE STRUCTURES; STRUCTURE ALIGNMENTS; PHYLOGENETIC TREES; SEQUENCE ALIGNMENT; DATABASE; HEMOGLOBIN; RESOLUTION; FAMILIES AB To adequately deal with the inherent complexity of interactions between protein side-chains, we develop and describe here a novel method for characterizing protein packing within a fold family Instead of approaching side-chain interactions absolutely from one residue to another, we instead consider the relative interactions of contacting residue pairs. The basic element, the pair-wise relative contact, is constructed from a sequence 11 alignment and contact analysis of a set of structures and consists of a cluster of similarly oriented, interacting, side-chain pairs. To demonstrate this usefulness in analyzing protein structure, we used the pair-wise construct's relative contacts to analyze two sets of protein structures as defined by SCOP: the diverse globin-like superfamily (126 structures) and the more uniform heme binding globin family (a 94 structure subset of the globin-like superfamily). The superfamily structure set produced 1.266 unique pair-wise relative contacts, whereas the family structure subset gave 1001 unique pair-wise relative contacts. For both sets, we show that these constructs can be used to accurately and automatically differentiate between fold classes. Furthermore, these pair-wise relative contacts correlate well with sequence identity and thus provide a direct relationship between changes in sequence and changes in structure. To capture the complexity of protein packing, these pair-wise relative contacts can be superimposed around a single residue to create a multi-body construct called a relative packing group. Construction of convex hulls around the individual packing groups provides a measure of the variation in packing around a residue and defines an approximate volume of space occupied by the groups interacting with a residue. We find that these relative packing groups are useful in understanding the structural quality of sequence or structure alignments. Moreover, they provide context to calculate a value for structural randomness, which is important in properly assessing the quality of a structural alignment. The results of this study provide the framework for future analysis for correlating sequence changes to specific structure changes. (c) 2005 Elsevier Ltd. All rights reserved. C1 Texas A&M Univ, Dept Biochem & Biophys, Ctr Struct Biol, College Stn, TX 77843 USA. NICHD, Mol Genet Lab, NIH, Bethesda, MD 20952 USA. RP Tsai, J (reprint author), Texas A&M Univ, Dept Biochem & Biophys, Ctr Struct Biol, College Stn, TX 77843 USA. EM jerrytsai@tamu.edu FU NCI NIH HHS [CA90301] NR 51 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 2 PY 2005 VL 354 IS 3 BP 706 EP 721 DI 10.1016/j.jmb.2005.09.081 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 989LB UT WOS:000233674100018 PM 16269154 ER PT J AU Chen, J Errico, SL Freed, WJ AF Chen, J Errico, SL Freed, WJ TI Reactive oxygen species and p38 phosphorylation regulate the protective effect of Delta(9)-tetrahydrocannabinol in the apoptotic response to NMDA SO NEUROSCIENCE LETTERS LA English DT Article DE THC; NMDA; reactiveoxygenspecies; apoptosis; MAP kinase; neuroprotection ID ACTIVATED PROTEIN-KINASE; N-TERMINAL KINASE; OXIDATIVE STRESS; CANNABINOID RECEPTOR; PC12 CELLS; DEATH; CB1; NEUROTOXICITY; ANTIOXIDANTS; INVOLVEMENT AB NMDA causes oxidative stress in neurons, and produces cell death involving elements of both necrosis and apoptosis. To examine the neuroprotective mechanism of Delta(9)-tetrahydrocannabinol (THC) in NMDA-induced death of AF5 cells, we measured reactive oxygen species (ROS) formation after exposure to NMDA. ROS generation was increased by NMDA, and NMDA-induced ROS generation was significantly decreased by THC. Western blotting revealed an increase in phosphorylated p38 MAPK after NMDA treatment, which was also blocked by pretreatment with THC. The time course of ROS generation and activation of MAPK signaling pathways were similar. SB203580, a p38 inhibitor, partially blocked glutamate excitotoxicity in AF5 cells. The present data suggest that THC protects against NMDA-induced apoptosis in AF5 cells by blocking ROS generation and inhibiting the activation of p38-MAPK. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 NIDA, Dev & Plast Sect, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Chen, J (reprint author), NIDA, Dev & Plast Sect, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 333 Cassell Dr,Triad Bldg,Room 3505, Baltimore, MD 21224 USA. EM jchen@intra.nida.nih.gov FU NIDA NIH HHS [Z01 DA000411-08] NR 24 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 2 PY 2005 VL 389 IS 2 BP 99 EP 103 DI 10.1016/j.neulet.2005.07.028 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 968UH UT WOS:000232187500008 PM 16098661 ER PT J AU Castellone, MD Teramoto, H Williams, BO Druey, KM Gutkind, JS AF Castellone, MD Teramoto, H Williams, BO Druey, KM Gutkind, JS TI Prostaglandin E-2 promotes colon cancer cell growth through a G(s)-axin-beta-catenin signaling axis SO SCIENCE LA English DT Article ID ACTIVATED PROTEIN-KINASE; BETA-CATENIN; ALPHA-SUBUNITS; PHOSPHORYLATION; RECEPTOR; MECHANISM; COMPLEX; INACTIVATION; CARCINOMA; TRANSCRIPTION AB How cyclooxygenase-2 (COX-2) and its proinflammatory metabolite prostaglandin E2 (PGE2) enhance colon cancer progression remains poorly understood. We show that PGE2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor, EP2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase Akt by free G protein beta gamma subunits and the direct association of the G protein a. subunit with the regulator of G protein signaling (RGS) domain of axin. This leads to the inactivation and release of glycogen synthase kinase 3 beta from its complex with axin, thereby relieving the inhibitory phosphorytation of beta-catenin and activating its signaling pathway. These findings may provide a molecular framework for the future evaluation of chemopreventive strategies for colorectal cancer. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Kojin Hosp, Nagoya, Aichi 4638530, Japan. Van Andel Res Inst, Lab Cell Signaling & Carcinogenesis, Grand Rapids, MI 49503 USA. NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Williams, Bart/A-3539-2013; OI Williams, Bart/0000-0002-5261-5301; CASTELLONE, MARIADOMENICA/0000-0003-0507-8037 FU Intramural NIH HHS NR 40 TC 542 Z9 567 U1 7 U2 34 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 2 PY 2005 VL 310 IS 5753 BP 1504 EP 1510 DI 10.1126/science.1116221 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 990PU UT WOS:000233756500047 PM 16293724 ER PT J AU Fauci, AS AF Fauci, AS TI Emerging and reemerging infectious diseases: The perpetual challenge SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT Spring Meeting of the Association-of-American-Medical-Colleges-Council-of-Deans CY APR 09, 2005 CL Santa Fe, NM SP Assoc Amer Med Coll Council Deans ID PLASMODIUM-FALCIPARUM; GENOME SEQUENCE; EMERGENCE AB Public health officials once suggested that it might someday be possible to "close the book" on the study and treatment of infectious diseases. However, it is now clear that endemic diseases as well as newly emerging ones (e.g., severe acute respiratory syndrome [SARS]), reemerging ones (e.g., West Nile virus), and even deliberately disseminated infectious diseases (e.g., anthrax from bioterrorism) continue to pose a substantial threat throughout the world. Over the past several decades, the global effort to identify and characterize infectious agents, decipher the underlying pathways by which they cause disease, and develop preventive measures and treatments for many of the world's most dangerous pathogens has helped control many endemic diseases. But despite considerable progress, infectious diseases continue to present significant challenges as new microbial threats emerge and reemerge. HIV/AIDS, malaria, tuberculosis, influenza, SARS, West Nile virus, Marburg virus, and bioterrorism are examples of some of the emerging and reemerging threats. in responding to these ongoing challenges, a new paradigm in countermeasure development is needed. In the past, U.S. government-sponsored biomedical researchers have focused on basic research and concept development, leaving product development to the pharmaceutical industry. Increasingly, however, the government has become involved in more targeted countermeasure development efforts. in this regard, partnerships between government, industry, and academia are necessary as we struggle to maintain and update our armamentarium in the struggle to outwit the microbes that pose a never-ending threat to mankind. C1 NIAID, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Dept Hlth & Human Serv, Bldg 31,Room 7A03,MSC 2520,9000 Rockville Pike, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 42 TC 32 Z9 35 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD DEC PY 2005 VL 80 IS 12 BP 1079 EP 1085 DI 10.1097/00001888-200512000-00002 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 987MJ UT WOS:000233521700002 PM 16306276 ER PT J AU Spanagel, R Heilig, M AF Spanagel, R Heilig, M TI Addiction and its brain science SO ADDICTION LA English DT Article DE animal models of addictive behavior; association studies; conditional mutants; gene expression profiling; neuroimaging; QTL-analysis ID ALCOHOL DEPENDENCE; DRUG-ADDICTION; ETHANOL-CONSUMPTION; SEEKING BEHAVIOR; RAT; ACAMPROSATE; REINSTATEMENT; RECEPTORS; REWARD; GENES AB Aims To illustrate how modern neurobiological approaches will help to identify the neurocircuits and genes involved in addictive behavior. Background The current disorder concept of addiction includes neurobiological foundations and neurobiological research assuming irreversible molecular and structural changes within the brain dopamine reinforcement system, constituting the 'molecular and structural switch' from controlled drug intake to compulsive drug abuse. However, those irreversible changes have not so far been identified and it is suggested that in addition to the mesolimbic dopamine system, other brain systems including the mesocortical and nigrostriatal pathways as well as their non-dopaminergic feedback-loops might be involved in addictive behavior. Neurobiological approach A three-step neurobiological approach is described that allows in a first step via novel animal models and imaging techniques to identify the neuroanatomical sites mediating voluntary drug intake, reinstatement of drug-seeking behavior, relapse, loss of control and drug intake despite negative consequences. In a subsequent step, forward genetic approaches including quantitative trait loci (QTL)-analysis and gene expression profiling are helpful in identifying so-called candidate genes. In a final step, conditional animal mutants and selective pharmacological tools are used to functionally validate candidate genes. Following this validation process, the transfer to the human situation has to be made and candidate genes have to be verified further in well-phenotyped cohorts of addicted patients. Conclusion This three-step neurobiological approach, that must involve an interdisciplinary team including experimental psychologists, geneticists, molecular biologists and finally clinical addiction researchers, will allow us to understand where and how the addicted brain goes awry. C1 Univ Heidelberg, CIMH, Dept Psychopharmacol, D-68159 Mannheim, Germany. NIAAA, Div Intramural Clin & Biol Res, Bethesda, MD USA. RP Spanagel, R (reprint author), Univ Heidelberg, CIMH, Dept Psychopharmacol, D-68159 Mannheim, Germany. EM spanagel@zl-mannheim.de OI Heilig, Markus/0000-0003-2706-2482 NR 45 TC 48 Z9 51 U1 3 U2 14 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 2005 VL 100 IS 12 BP 1813 EP 1822 DI 10.1111/j.1360-0443.2005.01260.x PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 987EJ UT WOS:000233500900012 PM 16367982 ER PT J AU Egli, M AF Egli, M TI Can experimental paradigms and animal models be used to discover clinically effective medications for alcoholism? SO ADDICTION BIOLOGY LA English DT Review ID CONDITIONED PLACE PREFERENCE; ETHANOL-SEEKING BEHAVIOR; CORTICOTROPIN-RELEASING FACTOR; 5-HT2 RECEPTOR ANTAGONIST; FOOD-MAINTAINED BEHAVIOR; LIMITED-ACCESS PROCEDURE; RHESUS-MONKEYS; REDUCES ETHANOL; PREFERRING RATS; C57BL/6 MICE AB Evaluating medications in animal laboratory paradigms can reveal whether the compound is effective in an established alcoholism model, at clinically relevant doses and exposure conditions, when administered orally (or transdermally) and without serious limiting side effects. Positive outcomes constitute a possible discovery for relevance to alcoholism and, under favorable marketing conditions, encourage further development. Medication testing using animal models of alcoholism might also guide clinical testing by discriminating clinically effective front clinically ineffective compounds. This ability rests on whether there are tests or, more reasonably, batteries of tests having this discriminative ability. The present paper examines this possibility. Effects of naltrexone and acamprosate in animal paradigms which model behavioral aspects of alcoholism are reviewed and compared with the effects of compounds which have limited effects in alcoholics. It is not clear at present whether any single paradigm or combination of paradigms differentiates clinically effective from clinically limited compounds. Steps are suggested to improve the use of preclinical laboratory tests to predict which compounds are likely to be effective medications for reducing drinking and sustaining abstinence in human alcoholics. C1 NIAAA, Div Neurosci & Behav, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Egli, M (reprint author), NIAAA, Div Neurosci & Behav, NIH, Dept Hlth & Human Serv, 5635 Fishers Lane,Room 2050,MSC 9304, Bethesda, MD 20892 USA. EM megli@mail.nih.gov NR 119 TC 52 Z9 52 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD DEC PY 2005 VL 10 IS 4 BP 309 EP 319 DI 10.1080/13556210500314550 PG 11 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 992GQ UT WOS:000233872800002 PM 16318951 ER PT J AU Warner, HR AF Warner, Huber R. TI Twenty years of progress in biogerontology research SO AGE LA English DT Review ID GILFORD-PROGERIA-SYNDROME; EXTENDS LIFE-SPAN; CAENORHABDITIS-ELEGANS; CELL-DEATH; DROSOPHILA-MELANOGASTER; CALORIE RESTRICTION; HUMAN-FIBROBLASTS; OXIDATIVE DAMAGE; BONE-MARROW; STEM-CELL AB The first 10 years of NIA's existence were characterized by funding for descriptive and discovery research, as the field had not yet come of age. As Couzin expressed it in the July 1, 2005 issue of Science, "Just 2 or 3 decades ago, research on aging was a backwater" (Couzin J 2005 How much can human life span be extended. Science 309: 83). With the isolation of long-lived animal mutants and the application of the tools of molecular biology and transgenic technology to biogerontology research, the situation has changed dramatically since then, and aging research has become increasingly mechanistic and respectable. This transition has been aided by some well-thought out research initiatives by the NIA, and the purpose of this article is to provide a brief summary of the progress made in the past 20 years, and describe the part that NIA initiatives and funding have played in this transition. C1 NIA, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Coll Biol Sci, St Paul, MN 55108 USA. RP Warner, HR (reprint author), NIA, NIH, Bethesda, MD 20892 USA. EM warne033@umn.edu NR 68 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD DEC PY 2005 VL 27 IS 4 BP 321 EP 328 DI 10.1007/s11357-005-4556-8 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 121PP UT WOS:000243169800009 PM 23598666 ER PT J AU Landi, F Russo, A Cesari, M Barillaro, C Onder, G Zamboni, V De Santis, A Pahor, M Ferrucci, L Bernabei, R AF Landi, F Russo, A Cesari, M Barillaro, C Onder, G Zamboni, V De Santis, A Pahor, M Ferrucci, L Bernabei, R TI The ilSIRENTE study: a prospective cohort study on persons aged 80 years and older living in a mountain community of Central Italy SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE aging; disability; ilSIRENTE study; mobility; physical performance ID MINIMUM DATA SET; PHYSICAL PERFORMANCE; MAINTAINING MOBILITY; INFLAMMATORY MARKERS; EXTREME LONGEVITY; WOMENS HEALTH; LATE-LIFE; DISABILITY; CARE; INCHIANTI AB Background and aims: "Invecchiamento e Longevita nel Sirente" (Aging and Longevity in the Sirente geographic area, ilSIRENTE) aims at investigating the socio-demographic, functional, clinical and biological characteristics of all subjects aged 80 years and older residing in a well-defined mountain area of Central Italy. Methods: Data are from the baseline evaluation of the ilSIRENTE prospective cohort study. A list of all persons living in the Sirente area was obtained from the Registry Offices of the 13 municipalities involved in the study. Data collection started in December 2003 and was completed in September 2004. Among the 429 residents older than 80 years eligible for the study, 364 accepted to participate (response rate 84%). Participants were assessed by trained staff who collected information on socio-demographic factors, clinical conditions, medication use, physical performance and muscle strength. All participants were also evaluated using the Minimum Data Set for Home Care (MDS-HC) form and a slightly modified version of the "Invecchiare in CHIANTI" study. Results: The mean age of participants was 85.6 +/- 4.8 years (range 80-102 years), with over 20% of participants aged 90 years or older. More than 65% of participants were women. Most participants (70%) were independent or required limited assistance in performing basic activities of daily living (ADL), whereas 30% of participants were independent in instrumental activities of daily living (IADL). Cognitive function (assessed by the Cognitive Performance Score) was normal in 80% of the sample. Higher degrees of disabilities (defined as the sum of dependencies in ADLs and IADLs) were associated with worse physical performance and lower muscle strength. Conclusions: Data on the socio-demographic characteristics and health status of very old people living in the Sirente mountain community are discussed and compared with findings from other epidemiological studies. C1 Univ Sacred Heart, Dept Gerontol Geriatr & Physiat, I-00168 Rome, Italy. Univ Florida, Coll Med, Dept Aging & Geriatr Res, Gainesville, FL USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Landi, F (reprint author), Univ Cattolica Sacro Cuore, Ist Med Interna & Geriatr, CEMI, Largo Agostino Gemelli 8, I-00168 Rome, Italy. EM francesco-landi@rm.unicatt.it RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 34 TC 40 Z9 40 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD DEC PY 2005 VL 17 IS 6 BP 486 EP 493 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 006CL UT WOS:000234872600008 PM 16485867 ER PT J AU Han, Y Oota, H Osier, MV Pakstis, AJ Speed, WC Odunsi, A Okonofua, F Kajuna, SLB Karoma, NJ Kungulilo, S Grigorenko, E Zhukova, OV Bonne-Tamir, B Lu, RB Parnas, J Schulz, LO Kidd, JR Kidd, KK AF Han, Y Oota, H Osier, MV Pakstis, AJ Speed, WC Odunsi, A Okonofua, F Kajuna, SLB Karoma, NJ Kungulilo, S Grigorenko, E Zhukova, OV Bonne-Tamir, B Lu, RB Parnas, J Schulz, LO Kidd, JR Kidd, KK TI Considerable haplotype diversity within the 23kb encompassing the ADH7 gene SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol dehydrogenase; ADH7; linkage disequilibrium; haplotype; evolution ID ALDEHYDE DEHYDROGENASE GENOTYPES; STOMACH ALCOHOL-DEHYDROGENASE; LINKAGE DISEQUILIBRIUM; ADH2-ASTERISK-2 ALLELE; CLASS-IV; RISK; MEN; ETHANOL; LOCUS; POLYMORPHISM AB Background: Of the seven known human alcohol dehydrogenase (ADH) genes, the nonliver expressed ADH7 gene codes for the enzyme with the highest maximal activity for ethanol. Previous study from our laboratory has suggested that ADH7 has an epistatic role for protection against alcoholism based on a single ADH7 SNP. Methods: We have now studied seven SNPs, additional populations for the SNP previously examined, and six more new SNPs, across 23 kb of ADH7 in 38 population samples originating from different geographical regions of the world. Results: The overall linkage disequilibrium is moderate to strong across this region even though considerable 7-SNP haplotype diversity is observed. This uncommonly high haplotype diversity is explained by high LD within each "half," the three upstream SNPs and the four downstream SNPs, but near randomization between the "halves." This division significantly simplified the haplotype pattern: only four major haplotypes account for almost all chromosomes in all populations in each "half." Conclusions: The low linkage disequilibrium between these two "halves" suggests multiple recombination(s) have occurred in this region, specifically, within intron 7. The absence of strong LD between the functional variation in ADH1B that is strongly associated with alcoholism and any of the variation in ADH7 supports the genetic independence of ADH7 in association studies. Thus, the previously observed epistatic effect of ADH7 cannot be explained by its linkage disequilibrium with a causative factor in ADH1B. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Psychol, New Haven, CT 06520 USA. Rochester Inst Technol, Coll Sci, Rochester, NY 14623 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. Univ Benin, Fac Med, Dept Obstet & Gynecol, Benin, Nigeria. Muhimbili Univ, Coll Hlth Sci, Dar Es Salaam, Tanzania. Hubert Kairuki Mem Univ, Dar Es Salaam, Tanzania. NI Vavilov Inst Gen Genet, Moscow, Russia. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. TriServ Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan. Univ Copenhagen, Ctr Subject Res, Danish Natl Res Fdn, DK-1168 Copenhagen, Denmark. Univ Texas, Coll Hlth Sci, El Paso, TX 79968 USA. RP Kidd, KK (reprint author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St,SHM I-353, New Haven, CT 06520 USA. FU NIAAA NIH HHS [AA09379]; NIGMS NIH HHS [GM57672] NR 41 TC 16 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2005 VL 29 IS 12 BP 2091 EP 2100 DI 10.1097/01.alc.0000191769.92667.04 PG 10 WC Substance Abuse SC Substance Abuse GA 999KV UT WOS:000234389100002 PM 16385178 ER PT J AU Wattendorf, DJ Muenke, M AF Wattendorf, DJ Muenke, M TI Klinefelter syndrome SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID MALES; XXY AB To complement the 2005 Annual Clinical Focus on medical genomics, AFP is publishing a series of short reviews on genetic syndromes. This series was designed to increase awareness of these diseases so that family physicians can recognize and diagnose children with these disorders and understand the kind of care they might require in the future. This review discusses Klinefelter syndrome. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, F Edward Herbert Sch Med, Dept Family Med, Bethesda, MD 20814 USA. NIH, Med Genet Residency Program, Bethesda, MD 20892 USA. NIH, Fellowship Training Program, Bethesda, MD 20892 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov NR 13 TC 18 Z9 18 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD DEC 1 PY 2005 VL 72 IS 11 BP 2259 EP 2262 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 990ZC UT WOS:000233780900012 PM 16342850 ER PT J AU Velie, EM Schairer, C Flood, A He, JP Khattree, R Schatzkin, A AF Velie, EM Schairer, C Flood, A He, JP Khattree, R Schatzkin, A TI Empirically derived dietary patterns and risk of postmenopausal breast cancer in a large prospective cohort study(1-3) SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE breast cancer; dietary patterns; nutrition; factor analysis; cohort study ID FOOD-FREQUENCY QUESTIONNAIRE; PROGESTERONE-RECEPTOR STATUS; EATING PATTERNS; NUTRITIONAL EPIDEMIOLOGY; ESTROGEN-RECEPTOR; CLUSTER-ANALYSIS; BLOOD-PRESSURE; WOMEN; HEALTH; FAT AB Background: Inconsistent associations have been reported between diet and breast cancer. Objective: We prospectively examined the association between dietary patterns and postmenopausal breast cancer risk in a US-wide cohort study. Design: Data were analyzed from 40 559 women who completed a self-administered 61-item Block food-frequency questionnaire in the Breast Cancer Detection Demonstration Project, 1987-1998; 1868 of those women developed breast cancer. Dietary patterns were defined by using principal components factor analysis. Cox proportional hazard regression was used to assess breast cancer risk. Results: Three major dietary patterns emerged: vegetable-fish/ poultry-fruit, beef/pork-starch, and traditional southern. The vegetable-fish/poultry-fruit pattern was associated with higher education than were the other patterns, but was similar in nutrient intake to the traditional southern pattern. After adjustment for con-founders, there was no significant association between the vegetable-fish/poultry-fruit and beef/pork-starch patterns and breast cancer. The traditional southern pattern, however, was associated with a nonsignificantly reduced breast cancer risk among all cases (in situ and invasive) that was significant for invasive breast cancer (relative hazard = 0.78; 95% CI = 0.65, 0.95; P for trend = 0.003). This diet was also associated with a reduced risk in women without a family history of breast cancer (P = 0.05), who were underweight or normal weight [body mass index (in kg/m(2)) < 25; P = 0.02], or who had tumors positive for estrogen receptor (P = 0.01) or progesterone receptor (P = 0.003). Foods in the traditional southern pattern associated with reduced breast cancer risk were legumes, low mayonnaise-salad dressing intake, and possibly cabbage. Conclusions: The traditional southern diet or its components are associated with a reduced risk of invasive breast cancer in postmenopausal women. C1 Michigan State Univ, Coll Human Med, Dept Epidemiol, E Lansing, MI 48824 USA. Michigan State Univ, Data Coordinating Ctr, E Lansing, MI 48824 USA. Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA. Oakland Univ, Dept Math & Stat, Rochester, MI 48063 USA. RP Velie, EM (reprint author), Michigan State Univ, Coll Human Med, Dept Epidemiol, B601 W Fee Hall, E Lansing, MI 48824 USA. EM velie@msu.edu FU NCI NIH HHS [K07CA094984] NR 65 TC 71 Z9 71 U1 1 U2 6 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 2005 VL 82 IS 6 BP 1308 EP 1319 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 993BC UT WOS:000233926700022 PM 16332665 ER PT J AU Hassan, R Laszik, ZG Lerner, M Raffeld, M Postier, R Brackett, D AF Hassan, R Laszik, ZG Lerner, M Raffeld, M Postier, R Brackett, D TI Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE mesothelin; pancreatic, ampullar, and common bile duct cancer; chronic pancreatitis; immunohistochemistry ID GENE-EXPRESSION; MONOCLONAL-ANTIBODY; AMPULLARY CARCINOMA; MOLECULAR-CLONING; OVARIAN CANCERS; SERIAL ANALYSIS; TUMOR-MARKERS; CHOLANGIOCARCINOMA; DIAGNOSIS; SURVIVAL AB Mesothelin, a cell surface glycoprotein present on normal mesothelial cells, has been reported to be expressed in pancreatic adenocarcinomas. We conducted this study to fully characterize mesothelin expression in surgically resected, formalin-fixed, paraffin-embedded tissue specimens of 18 pancreatic adenocarcinomas, 9 adenocarcinomas of the ampulla of Vater 12 adenocarcinomas of the common bile duct, and 17 cases of chronic pancreatitis. Mesothelin immunostaining was performed using the antimesothelin monoclonal antibody 5B2. All 18 cases (100%) of pancreatic adenocarcinomas showed mesothelin expression, as did 8 (89%) of 9 cases of ampullar adenocarcinoma and all 12 cases (100%) of common bile duct adenocarcinoma. In all cases of pancreaticobiliary adenocarcinoma, the adjacent normal pancreas did not stain for mesothelin. Of 17 specimens of chronic pancreatitis, 16 were negative for mesothelin expression, and 1 case showed weak mesothelin staining of fewer that 5% of normal pancreatic ducts. Our results demonstrated mesothelin expression in the majority of pancreaticobiliary adenocarcinomas and no expression in normal pancreatic tissues and in chronic pancreatitis. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Surg, Oklahoma City, OK USA. Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA. RP Hassan, R (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Room 5116, Bethesda, MD 20892 USA. NR 24 TC 116 Z9 118 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 2005 VL 124 IS 6 BP 838 EP 845 DI 10.1309/F1B64CL7H8VJKEAF PG 8 WC Pathology SC Pathology GA 985ZA UT WOS:000233416400003 PM 16416732 ER PT J AU Freeman, LEB Bonner, MR Blair, A Hoppin, JA Sandler, DP Lubin, JH Dosemeci, M Lynch, CF Knott, C Alavanja, MCR AF Freeman, LEB Bonner, MR Blair, A Hoppin, JA Sandler, DP Lubin, JH Dosemeci, M Lynch, CF Knott, C Alavanja, MCR TI Cancer incidence among male pesticide applicators in the agricultural health study cohort exposed to diazinon SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; diazinon; insecticides; neoplasms; pesticides ID NON-HODGKINS-LYMPHOMA; SISTER-CHROMATID EXCHANGES; UNITED-STATES; RISK-FACTORS; LUNG-CANCER; CELLS; IMMUNOTOXICITY; GENOTOXICITY; INDUCTION; CHEMICALS AB Little is known about the potential carcinogenicity associated with routine application of diazinon, a common organophosphate insecticide. The authors explored a possible association of diazinon exposure with cancer risk in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina enrolled in 1993-1997. A total of 23,106 male applicators provided information in a self-administered questionnaire. Among 4,961 applicators who reported using diazinon, 301 incident cancer cases were diagnosed during the follow-up period ending December 2002 compared with 968 cases among 18,145 participants who reported no use. Poisson regression was used to calculate rate ratios and 95% confidence intervals. Two quantitative exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days, a measure that incorporates probability of pesticide exposure with lifetime pesticide application frequency. When lifetime exposure days were used, increased risks for the highest tertile of exposure and significant tests for trend for lung cancer and leukemia were observed. No other cancer site showed an association with diazinon for the highest tertile of exposure. Because these results were based on small numbers, additional analyses are necessary as more cases accrue to clarify whether diazinon is associated with cancer risk in humans. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Dept Hlth & Human Serv, NIH, Rockville, MD USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC USA. Univ Iowa, Dept Epidemiol, Iowa City, IA USA. Ctr Publ Hlth Res & Evaluat, Durham, NC USA. RP Alavanja, MCR (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, EPS 8000,6120 Execut Blvd, Bethesda, MD 20892 USA. EM alavanjm@mail.nih.gov RI Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS NR 31 TC 51 Z9 52 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2005 VL 162 IS 11 BP 1070 EP 1079 DI 10.1093/aje/kwi321 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 986ZT UT WOS:000233488900004 PM 16236997 ER PT J AU Zheng, W Chow, WH Yang, G Jin, F Rothman, N Blair, A Li, HL Wen, WQ Ji, BT Li, Q Shu, XO Gao, YT AF Zheng, W Chow, WH Yang, G Jin, F Rothman, N Blair, A Li, HL Wen, WQ Ji, BT Li, Q Shu, XO Gao, YT TI The Shanghai Women's Health Study: Rationale, study design, and baseline characteristics SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; diet; neoplasms; nutrition; occupations ID BREAST-CANCER RISK; GREEN TEA CONSUMPTION; CORONARY-HEART-DISEASE; BODY-FAT DISTRIBUTION; SOY FOOD-CONSUMPTION; CHINESE-WOMEN; REPRODUCTIVE FACTORS; ENDOMETRIAL CANCER; PANCREATIC-CANCER; PHYSICAL-ACTIVITY AB Although cancer is a major cause of morbidity and mortality in most nations, the spectrum of cancer occurrence varies substantially worldwide. Most previous epidemiologic studies investigating cancer etiology were conducted in North American and western European countries that are relatively homogenous in terms of cancer spectrums and many lifestyle exposures. These limitations may have hindered these studies from evaluating some important etiologic hypotheses. From 1996 to 2000, the Shanghai Women's Health Study recruited 74,942 adult Chinese women from selected urban communities, with a 92% response rate. All participants completed a detailed baseline survey and anthropometrics. Approximately 88% of cohort members donated a urine sample (n = 65,755) and a blood (n = 56,832) or exfoliated buccal cell (n = 8,934) sample. Noteworthy characteristics of this cohort include low consumption of alcohol (1.9%) and use of tobacco (2.4%); high intake of fish (mean, 50.8 g/day), soy foods (mean, 142.3 g/day), and certain vegetables; low prevalence of obesity (5.1%); and nearly 100% employment outside the home. Currently, this cohort of women is being followed via biennial in-person recontact and periodic linkage to cancer and vital statistics registries. The resources from the cohort will be valuable in future studies of environmental exposures and biomarkers for the risk of cancer and other chronic diseases. C1 Vanderbilt Univ, Dept Med, Ctr Hlth Serv Res, Nashville, TN 37232 USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Zheng, W (reprint author), Vanderbilt Univ, Dept Med, Ctr Hlth Serv Res, Med Ctr E,6000, Nashville, TN 37232 USA. EM wei.zheng@vanderbilt.edu FU Intramural NIH HHS; NCI NIH HHS [N02 CP1101066, R01 CA70867] NR 67 TC 227 Z9 229 U1 2 U2 19 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2005 VL 162 IS 11 BP 1123 EP 1131 DI 10.1093/aje/kwi322 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 986ZT UT WOS:000233488900010 PM 16236996 ER PT J AU Jones, DK Catani, M Pierpaoli, C Reeves, SJ Shergill, SS O'Sullivan, M Maguire, P Horsfield, MA Simmons, A Williams, SCR Howard, RJ AF Jones, DK Catani, M Pierpaoli, C Reeves, SJ Shergill, SS O'Sullivan, M Maguire, P Horsfield, MA Simmons, A Williams, SCR Howard, RJ TI A diffusion tensor magnetic resonance imaging study of frontal cortex connections in very-late-onset schizophrenia-like psychosis SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID WHITE-MATTER ANISOTROPY; LATE PARAPHRENIA; HUMAN BRAIN; SIGNAL HYPERINTENSITIES; PARANOID PSYCHOSIS; ABNORMALITIES; MRI; LIFE; SYMPTOMS; PATHWAYS AB Objective: Onset of psychosis after the age of 60 may be associated with structural abnormalities within cerebral white matter. The authors looked within white-matter tracts, which mediate connectivity of the frontal lobes, in psychotic patients for evidence of loss of fiber integrity consistent with degenerative damage. Methods: Fourteen patients with very-late-onset schizophrenia-like psychosis and an age-matched control group underwent diffusion tensor magnetic resonance imaging. Tract maps were constructed for each subject from the imaging data, and measurements of fractional anisotropy and mean diffusivity were made within the uncinate, superior longitudinal, and inferior occipito-frontal fasciculi, and the cingulum. Results: There were no significant differences in fractional anisotropy, a measure of the ordering of axons within fiber tracts, nor in mean diffusivity, an orientationally-averaged measure of the bulk diffusivity within each voxel, between patients and control subjects. Conclusion: The lack of difference in fractional anisotropy and mean diffusivity measures between patients and controls argues against the presence of structural abnormalities within these tracts and the notion that a focal white-matter abnormality within the tracts investigated underpins the onset of psychosis. C1 Inst Psychiat, Old Age Psychiat Sect, London SE5 8AF, England. NICHHD, Sect Tissue Biophys & Biomimet, LIMB, NIH, Bethesda, MD 20892 USA. Maudsley Hosp & Inst Psychiat, London SE5 8AZ, England. Inst Psychiat, Sect Neuroimaging, Div Psychol Med, London SE5 8AF, England. St George Hosp, Sch Med, Div Clin Neurosci, London, England. Leicester Royal Infirm, Div Med Phys, Leicester, Leics, England. Inst Psychiat, Dept Neurol, London SE5 8AF, England. RP Howard, RJ (reprint author), Inst Psychiat, Old Age Psychiat Sect, De Crespigny Pk, London SE5 8AF, England. EM r.howard@iop.kcl.ac.uk RI Reeves, Suzanne/B-3539-2011; Pierpaoli, Carlo/E-1672-2011; turton, miranda/F-4682-2011; Jones, Derek/D-1460-2009; Shergill, Sukhi/G-7725-2011; Williams, Steve/D-6979-2011; Simmons, Andrew/B-8848-2008; Catani, Marco/H-7801-2012; Horsfield, Mark/C-6569-2013; O'Sullivan, Michael/A-1796-2010 OI Jones, Derek/0000-0003-4409-8049; Williams, Steve/0000-0003-4299-1941; Simmons, Andrew/0000-0003-2306-5811; Catani, Marco/0000-0002-5488-6463; Horsfield, Mark/0000-0002-0815-6697; FU Medical Research Council [G9810900]; Wellcome Trust NR 56 TC 48 Z9 48 U1 2 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD DEC PY 2005 VL 13 IS 12 BP 1092 EP 1099 DI 10.1176/appi.ajgp.13.12.1092 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 988QA UT WOS:000233614500009 PM 16319302 ER PT J AU Hammond, P Hutton, TJ Allanson, JE Buxton, B Campbell, LE Smith, JC Donnai, D Smith, AK Metcalfe, K Murphy, KC Patton, M Pober, B Prescott, K Scambler, P Shaw, A Smith, ACM Stevens, AF Temple, IK Hennekam, R Tassabehji, M AF Hammond, P Hutton, TJ Allanson, JE Buxton, B Campbell, LE Smith, JC Donnai, D Smith, AK Metcalfe, K Murphy, KC Patton, M Pober, B Prescott, K Scambler, P Shaw, A Smith, ACM Stevens, AF Temple, IK Hennekam, R Tassabehji, M TI Discriminating power of localized three-dimensional facial morphology SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SMITH-MAGENIS-SYNDROME; BARDET-BIEDL-SYNDROME; NOONAN-SYNDROME; PHENOTYPE; FACE; GENE; MUTATIONS; GROWTH; TBX1 AB Many genetic syndromes involve a facial gestalt that suggests a preliminary diagnosis to an experienced clinical geneticist even before a clinical examination and genotyping are undertaken. Previously, using visualization and pattern recognition, we showed that dense surface models (DSMs) of full face shape characterize facial dysmorphology in Noonan and in 22q11 deletion syndromes. In this much larger study of 696 individuals, we extend the use of DSMs of the full face to establish accurate discrimination between controls and individuals with Williams, Smith-Magenis, 22q11 deletion, or Noonan syndromes and between individuals with different syndromes in these groups. However, the full power of the DSM approach is demonstrated by the comparable discriminating abilities of localized facial features, such as periorbital, perinasal, and perioral patches, and the correlation of DSM-based predictions and molecular findings. This study demonstrates the potential of face shape models to assist clinical training through visualization, to support clinical diagnosis of affected individuals through pattern recognition, and to enable the objective comparison of individuals sharing other phenotypic or genotypic properties. C1 UCL, Eastman Dent Inst, Biomed Informat Inst, London WC1X 8LD, England. UCL, Dept Comp Sci, London WC1X 8LD, England. UCL, Inst Child Hlth, London WC1X 8LD, England. Kings Coll London, Inst Psychiat, London WC2R 2LS, England. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Royal Coll Surgeons Ireland, Dublin 2, Ireland. Univ Manchester, St Marys Hosp, Acad Unit Med Genet, Manchester M13 0JH, Lancs, England. Univ Manchester, St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. Eastern Reg Genet Program, Ottawa, ON, Canada. Childrens Hosp, Boston, MA 02115 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ Southampton, Wessex Clin Genet Serv, Southampton, Hants, England. Univ Southampton, Div Human Genet, Southampton, Hants, England. Hosp Trust, Southampton, Hants, England. RP Hammond, P (reprint author), UCL, Eastman Dent Inst, Biomed Informat Inst, 256 Grays Inn Rd, London WC1X 8LD, England. EM p.hammond@eastman.ucl.ac.uk RI Scambler, Peter/C-4998-2008; Murphy, Kieran/D-3577-2012; campbell, linda/C-6231-2013; Karmiloff-Smith, Annette/N-4535-2014; temple, isabel/K-2391-2015; OI Scambler, Peter/0000-0002-1487-4628; campbell, linda/0000-0002-8872-9626; Karmiloff-Smith, Annette/0000-0002-2470-5609; Murphy, Kieran/0000-0003-2930-4465 FU FIC NIH HHS [R21 TW006761, R21TW06761-01]; NHGRI NIH HHS [01-HG-0109]; Wellcome Trust NR 25 TC 82 Z9 87 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2005 VL 77 IS 6 BP 999 EP 1010 DI 10.1086/498396 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 983OE UT WOS:000233241200009 PM 16380911 ER PT J AU Nishimura, DY Swiderski, RE Searby, CC Berg, EM Ferguson, AL Hennekam, R Merin, S Weleber, RG Biesecker, LG Stone, EM Sheffield, VC AF Nishimura, DY Swiderski, RE Searby, CC Berg, EM Ferguson, AL Hennekam, R Merin, S Weleber, RG Biesecker, LG Stone, EM Sheffield, VC TI Comparative genomics and gene expression analysis identifies BBS9, a new Bardet-Biedl syndrome gene SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HUMAN OBESITY SYNDROME; CHROMOSOME 16Q; SYNDROME LOCUS; MUTATIONS; DISEASE; PROTEIN AB Bardet-Biedl syndrome (BBS) is an autosomal recessive, genetically heterogeneous, pleiotropic human disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Eight BBS genes representing all known mapped loci have been identified. Mutation analysis of the known BBS genes in BBS patients indicate that additional BBS genes exist and/or that unidentified mutations exist in the known genes. To identify new BBS genes, we performed homozygosity mapping of small, consanguineous BBS pedigrees, using moderately dense SNP arrays. A bioinformatics approach combining comparative genomic analysis and gene expression studies of a BBS-knockout mouse model was used to prioritize BBS candidate genes within the newly identified loci for mutation screening. By use of this strategy, parathyroid hormone-responsive gene B1 (B1) was found to be a novel BBS gene (BBS9), supported by the identification of homozygous mutations in BBS patients. The identification of BBS9 illustrates the power of using a combination of comparative genomic analysis, gene expression studies, and homozygosity mapping with SNP arrays in small, consanguineous families for the identification of rare autosomal recessive disorders. We also demonstrate that small, consanguineous families are useful in identifying intragenic deletions. This type of mutation is likely to be underreported because of the difficulty of deletion detection in the heterozygous state by the mutation screening methods that are used in many studies. C1 Univ Iowa, Dept Pediat, Div Med Genet, Howard Hughes Med Inst, Iowa City, IA 52242 USA. Univ Iowa, Dept Ophthalmol, Iowa City, IA 52242 USA. Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA. UCL, Inst Child Hlth, London, England. Great Ormond St Hosp Sick Children, London WC1N 3JH, England. Hadassah Med Org, Dept Ophthalmol, Jerusalem, Israel. Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Sheffield, VC (reprint author), Univ Iowa, Dept Pediat, Div Med Genet, Howard Hughes Med Inst, Iowa City, IA 52242 USA. EM val-sheffield@uiowa.edu OI Searby, Charles/0000-0002-8108-8782 FU NEI NIH HHS [R01-EY-11298, R01 EY011298]; NHLBI NIH HHS [P50-HL-55006, P50 HL055006] NR 35 TC 122 Z9 125 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2005 VL 77 IS 6 BP 1021 EP 1033 DI 10.1086/498323 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 983OE UT WOS:000233241200011 PM 16380913 ER PT J AU Nathanson, KL Kanetsky, PA Hawes, R Vaughn, DJ Letrero, R Tucker, K Friedlander, M Phillips, KA Hogg, D Jewett, MAS Lohynska, R Daugaard, G Richard, S Chompret, A Bonati-Pellie, C Heidenreich, A Olah, E Geczi, L Bodrogi, I Ormiston, WJ Daly, PA Oosterhuis, JW Gillis, AJM Looijenga, LHJ Guilford, P Fossa, SD Heimdal, K Tjulandin, SA Liubchenko, L Stoll, H Weber, W Huddart, R Crockford, GP Forman, D Oliver, DT Einhorn, L Weber, BL Kramer, J McMaster, M Greene, MH Pike, M Cortessis, V Chen, C Schwartz, SM Bishop, DT Easton, DF Stratton, MR Rapley, EA AF Nathanson, KL Kanetsky, PA Hawes, R Vaughn, DJ Letrero, R Tucker, K Friedlander, M Phillips, KA Hogg, D Jewett, MAS Lohynska, R Daugaard, G Richard, S Chompret, A Bonati-Pellie, C Heidenreich, A Olah, E Geczi, L Bodrogi, I Ormiston, WJ Daly, PA Oosterhuis, JW Gillis, AJM Looijenga, LHJ Guilford, P Fossa, SD Heimdal, K Tjulandin, SA Liubchenko, L Stoll, H Weber, W Huddart, R Crockford, GP Forman, D Oliver, DT Einhorn, L Weber, BL Kramer, J McMaster, M Greene, MH Pike, M Cortessis, V Chen, C Schwartz, SM Bishop, DT Easton, DF Stratton, MR Rapley, EA TI The Y deletion gr/gr and susceptibility to testicular germ cell tumor SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MALE-SPECIFIC REGION; MALE-INFERTILITY; EUROPEAN COUNTRIES; GONADAL-FUNCTION; CANCER; CHROMOSOME; FAMILY; RISK; GENE; MEN AB Testicular germ cell tumor (TGCT) is the most common cancer in young men. Despite a considerable familial component to TGCT risk, no genetic change that confers increased risk has been substantiated to date. The human Y chromosome carries a number of genes specifically involved in male germ cell development, and deletion of the AZFc region at Yq11 is the most common known genetic cause of infertility. Recently, a 1.6-Mb deletion of the Y chromosome that removes part of the AZFc region-known as the "gr/gr" deletion-has been associated with infertility. In epidemiological studies, male infertility has shown an association with TGCT that is out of proportion with what can be explained by tumor effects. Thus, we hypothesized that the gr/gr deletion may be associated with TGCT. Using logistic modeling, we analyzed this deletion in a large series of TGCT cases with and without a family history of TGCT. The gr/gr deletion was present in 3.0% (13/431) of TGCT cases with a family history, 2% (28/1,376) of TGCT cases without a family history, and 1.3% (33/2,599) of unaffected males. Presence of the gr/gr deletion was associated with a twofold increased risk of TGCT (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.3-3.6; P = .005) and a threefold increased risk of TGCT among patients with a positive family history (aOR 3.2; 95% CI 1.5-6.7; P = .0027). The gr/gr deletion was more strongly associated with seminoma (aOR 3.0; 95% CI 1.6-5.4; P = .0004) than with nonseminoma TGCT (aOR 1.5; 95% CI 0.72-3.0; P = .29). These data indicate that the Y microdeletion gr/gr is a rare, low-penetrance allele that confers susceptibility to TGCT. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England. Univ New S Wales, Dept Med Oncol, Div Med, Sydney, NSW, Australia. Prince Wales Hosp Randwick, Sydney, NSW, Australia. Peter MacCallum Canc Ctr, Dept Haematol & Med Oncol, Melbourne, Vic, Australia. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Univ Toronto, Toronto, ON, Canada. Univ Hosp Prague, Dept Radiotherapy & Oncol, Prague, Czech Republic. Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark. CHU Bicetre, EPHE, UMR 8125, Fac Med Paris Sud, Le Kremlin Bicetre, France. CHU Bicetre, Serv Urol, Le Kremlin Bicetre, France. Inst Gustave Roussy, Villejuif, France. Hop Paul Brousse, INSERM U535, Villejuif, France. Univ Marburg, Dept Urol Oncol, Marburg, Germany. Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary. Natl Inst Oncol, Dept Chemotherapy, Budapest, Hungary. St James Hosp, Dept Med Oncol, Dublin 8, Ireland. Erasmus Univ, Med Ctr, Dept Pathol, Rotterdam, Netherlands. Dr Daniel Den Hoed Canc Ctr, Josphine Nefkens Inst, NL-3008 AE Rotterdam, Netherlands. Univ Otago, Canc Genet Lab, Dunedin, New Zealand. Natl Hosp Norway, Radiumhosp Trust, Dept Clin Canc Res & Genet, Oslo, Norway. NN Blokhin Russian Canc Res Ctr, Lab Clin Genet, Inst Clin Oncol, Moscow, Russia. Univ Basel Hosp, Familial Canc Clin, CH-4031 Basel, Switzerland. St Jamess Univ Hosp, Genet Epidemiol Div, Canc Res UK Clin Ctr, Leeds, W Yorkshire, England. Barts & London Queen Marys Sch Med, Dept Med Oncol, London, England. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46204 USA. NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. Univ So Calif, Dept Preventat Med, Keck Sch Med, Los Angeles, CA USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Univ Cambridge, Canc Res UK, Genet Epidemiol Unit, Cambridge, England. RP Nathanson, KL (reprint author), Univ Penn, Sch Med, Dept Med, 513 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM knathans@mail.med.upenn.edu RI friedlander, michael/G-3490-2013; OI friedlander, michael/0000-0002-6488-0604; Daugaard, Gedske/0000-0002-9618-9180; Phillips, Kelly-Anne/0000-0002-0475-1771; Bishop, Tim/0000-0002-8752-8785 FU NCI NIH HHS [R01 CA085914, R01 CA085914-01, R01 CA085914-02, R01 CA085914-03, R01 CA085914-04, R01 CA085914-05, R01 CA085914-06, R01 CA085914-07, R01 CA085914-08, R01 CA085914-09, R01 CA085914-10, R01 CA10204, R01CA085914]; NIDCD NIH HHS [R01 DC010204] NR 45 TC 104 Z9 110 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2005 VL 77 IS 6 BP 1034 EP 1043 DI 10.1086/498455 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 983OE UT WOS:000233241200012 PM 16380914 ER PT J AU Plenge, RM Padyukov, L Remmers, EF Purcell, S Lee, AT Karlson, EW Wolfe, F Kastner, DL Alfredsson, L Altshuler, D Gregersen, PK Klareskog, L Rioux, JD AF Plenge, RM Padyukov, L Remmers, EF Purcell, S Lee, AT Karlson, EW Wolfe, F Kastner, DL Alfredsson, L Altshuler, D Gregersen, PK Klareskog, L Rioux, JD TI Replication of putative candidate-gene associations with rheumatoid arthritis in > 4,000 samples from North America and Sweden: Association of susceptibility with PTPN22, CTLA4, and PADI4 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISM; JUVENILE IDIOPATHIC ARTHRITIS; CYCLIC CITRULLINATED PEPTIDE; GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAIT LOCI; FACTOR RECEPTOR-II; CROHNS-DISEASE; AUTOIMMUNE-DISEASES; SHARED EPITOPE; FUNCTIONAL VARIANT AB Candidate-gene association studies in rheumatoid arthritis (RA) have lead to encouraging yet apparently inconsistent results. One explanation for the inconsistency is insufficient power to detect modest effects in the context of a low prior probability of a true effect. To overcome this limitation, we selected alleles with an increased probability of a disease association, on the basis of a review of the literature on RA and other autoimmune diseases, and tested them for association with RA susceptibility in a sample collection powered to detect modest genetic effects. We tested 17 alleles from 14 genes in 2,370 RA cases and 1,757 controls from the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) collections. We found strong evidence of an association of PTPN22 with the development of anti-citrulline antibody positive RA (odds ratio [OR] 1.49; P = .001), using previously untested EIRA samples. We provide support for an association of CTLA4 (CT60 allele, OR 1.23; P = .001) and PADI4 (PADI4_94, OR 1.24; P = .001) with the development of RA, but only in the NARAC cohort. The CTLA4 association is stronger in patients with RA from both cohorts who are seropositive for anti-citrulline antibodies (P = .006). Exploration of our data set with clinically relevant subsets of RA reveals that PTPN22 is associated with an earlier age at disease onset (P = .004) and that PTPN22 has a stronger effect in males than in females (P = .03). A meta-analysis failed to demonstrate an association of the remaining alleles with RA susceptibility, suggesting that the previously published associations may represent false-positive results. Given the strong statistical power to replicate a true-positive association in this study, our results provide support for PTPN22, CTLA4, and PADI4 as RA susceptibility genes and demonstrate novel associations with clinically relevant subsets of RA. C1 Univ Montreal, Broad Inst MIT & Harvard, Montreal, PQ H1T 1C8, Canada. Montreal Heart Inst, Inst Cardiol Montreal, Montreal, PQ H1T 1C8, Canada. Program Med & Populat Genet, Cambridge, MA USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, England. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Karolinska Inst, Rheumatol Unit, Stockholm, Sweden. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. N Shore LIJ Inst Med Res, Robert S Boas Ctr Genom & Human Genet, Manhasset, NY USA. Natl Data Bank Rheumat Dis, Wichita, KS USA. RP Rioux, JD (reprint author), Univ Montreal, Broad Inst MIT & Harvard, 5000 Belanger, Montreal, PQ H1T 1C8, Canada. EM rioux@broad.mit.edu RI Padyukov, Leonid/A-4890-2009; Altshuler, David/A-4476-2009; Rioux, John/A-9599-2015; OI Padyukov, Leonid/0000-0003-2950-5670; Altshuler, David/0000-0002-7250-4107; Rioux, John/0000-0001-7560-8326; Klareskog, Lars/0000-0001-9601-6186; Alfredsson, Lars/0000-0003-1688-6697 FU Intramural NIH HHS; NIAID NIH HHS [K08 AI 55314, K08 AI055314]; NIAMS NIH HHS [K24 AR0524-01, N01-AR-2-2263, P60 AR047782, P60 AR47782-05, R01 AR049880, R01 AR49880-01, R01-AR44222] NR 92 TC 334 Z9 349 U1 6 U2 15 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2005 VL 77 IS 6 BP 1044 EP 1060 DI 10.1086/498651 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 983OE UT WOS:000233241200013 PM 16380915 ER PT J AU Sutton, EJ McInerney-Leo, A Bondy, CA Gollust, SE King, D Biesecker, B AF Sutton, EJ McInerney-Leo, A Bondy, CA Gollust, SE King, D Biesecker, B TI Turner syndrome: Four challenges across the lifespan SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Turner syndrome; infertility; short stature; sexual development; health care providers ID PSYCHOLOGICAL CONSEQUENCES; WOMEN; WEIGHT; HEIGHT; PARENTS; ACHONDROPLASIA; PERCEPTION; THERAPY; STATURE; ILLNESS AB Turner syndrome (TS) is a sex chromosome condition that occurs in approximately 1/2,500 live female births. Despite the prevalence of this chromosomal condition, the challenges these women face throughout their lives are not fully understood. This qualitative research study aimed to characterize the subjective experiences of individuals with TS throughout their lifespan, to investigate their concerns and obstacles, and to offer insight into the strengths and weaknesses of health care delivery, as they perceived them. Ninety-seven girls and women with TS and 21 parents consented to participate in this interview study. Interviews were semi-structured and openended in design. Questions sought to elicit responses relating to existing concerns associated with their condition and positive and negative health care experiences. Participants were divided into four age categories (childhood, adolescence, adulthood, and mature adulthood) to facilitate a comparative analysis across the age spectrum. Regardless of age, infertility was the most frequently cited concern followed closely by short stature. Sexual development and function and general health were also viewed as challenges by a number of participants in each age group. Although the relative weight of these four concerns tended to shift based upon the individual's age and life experiences, all four issues remained significant throughout the lifespan. Enhanced awareness of the evolving physical and psychological challenges faced by girls and women with TS may help health care providers (HCPs) improve the quality of life for these individuals. Published 2005 Wiley-Liss, Ine.(dagger) C1 NHGRI, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Biesecker, B (reprint author), NHGRI, NIH, 10 Ctr Dr 10-10C101, Bethesda, MD 20892 USA. EM barbarab@mail.nih.gov FU Intramural NIH HHS [Z01 HG200317-04] NR 41 TC 25 Z9 27 U1 3 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 1 PY 2005 VL 139A IS 2 BP 57 EP 66 DI 10.1002/ajmg.a.30911 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 989TJ UT WOS:000233696500001 PM 16252273 ER PT J AU Grange, DK Kaler, SG Albers, GM Petterchak, JA Thorpe, CM deMello, DE AF Grange, DK Kaler, SG Albers, GM Petterchak, JA Thorpe, CM deMello, DE TI Severe bilateral panlobular emphysema and pulmonary arterial hypoplasia: Unusual manifestations of Menkes disease SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Menkes disease; emphysema; venous aneurysm; arterial aneurysm; pulmonary arterial hypoplasia; arterial tortuosity ID COPPER; PATIENT; THERAPY; DEFECT AB Menkes disease is an X-linked recessive disorder of copper transport characterized by neurological deterioration, connective tissue, and vascular defects, abnormal hair, and death in early childhood. We report on a patient with Menkes disease in whom severe diffuse emphysema caused respiratory failure and death at 14 months of age. He had severe growth and developmental delays and other typical clinical manifestations of Menkes disease. He developed respiratory problems requiring continuous supplemental oxygen and a progressively enlarging soft tissue mass appeared on the neck. Imaging studies revealed cystic spaces in multiple lobes of the lung consistent with bullous emphysema. The neck mass was determined to be an internal jugular venous aneurysm. At autopsy, extensive emphysematous change was evident. Post-mortem. barium injections of the pulmonary arterial system revealed marked dilatation and tortuosity of the preacinar pulmonary arteries and reduced numbers of intra-acinar arteries. Severe emphysema, presumably caused by abnormal elastin due to deficiency of the copper-dependent enzyme lysyl oxidase, may represent an underestimated clinical complication of Menkes disease and should be considered in the differential diagnosis of chronic respiratory disease in these patients. (c) 2005 Wiley-Liss, Inc. C1 Washington Univ, Dept Pediat, Sch Med, St Louis, MO 63130 USA. NICHHD, Unit Pediat Genet, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63103 USA. St Louis Univ, Sch Med, Dept Pathol, St Louis, MO 63103 USA. Cardinal Glennon Childrens Hosp, St Louis, MO USA. RP Grange, DK (reprint author), St Louis Childrens Hosp, Dept Pediat, Div Genet & Genom Med, 1 Childrens Pl, St Louis, MO 63110 USA. EM grange_d@kids.wustl.edu NR 15 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 1 PY 2005 VL 139A IS 2 BP 151 EP 155 DI 10.1002/ajmg.a.31001 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 989TJ UT WOS:000233696500016 PM 16278898 ER PT J AU Nieman, LK Ilias, I AF Nieman, LK Ilias, I TI Evaluation and treatment of Cushing's syndrome SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE pituitary neoplasms; adrenal gland neoplasms; Cushing's syndrome ID CORTICOTROPIN-RELEASING-HORMONE; DEXAMETHASONE-SUPPRESSION TEST; INFERIOR PETROSAL SINUS; ECTOPIC ADRENOCORTICOTROPIN SYNDROME; MIDNIGHT SERUM CORTISOL; URINARY FREE CORTISOL; LONG-TERM FOLLOW; DIFFERENTIAL-DIAGNOSIS; TRANSSPHENOIDAL SURGERY; SALIVARY CORTISOL AB Cushing's syndrome results from sustained pathologic hypercortisolism caused by excessive corticotropin (ACTH) secretion by tumors in the pituitary gland (Cushing's disease, 70%) or elsewhere (15%), or by ACTH-independent cortisol secretion from adrenal tumors (15%). The clinical features are variable, and no single pattern is seen in all patients. Those features most specific for Cushing's syndrome include abnormal fat distribution, particularly in the supraclavicular and temporal fossae, proximal muscle weakness, wide purple striae, and decreased linear growth with continued weight gain in a child. Patients with characteristics Of glucocorticoid excess should be screened with measurements of saliva or urine cortisol or dexamethasone Suppression testing. The diagnosis of Cushing's syndrome should be followed by the measurement of plasma ACTH concentration to determine whether the hypercortisolism is ACTH-independent. In ACTH-dependent patients, bilateral inferior petrosal sinus sampling with measurement of ACTH before and after administration of ACTH-releasing hormone most accurately distinguishes pituitary from ectopic ACTH secretion. Surgical resection Of tumor is the optimal treatment for all forms Of Cushing's syndrome; bilateral adrenalectomy, medical treatment, or radiotherapy are sought in inoperable or recurrent cases. The medical treatment of choice is ketoconazole. The prognosis is better for Cushing's disease and benign adrenal causes Of Cushing's syndrome than adrenocortical cancer and malignant ACTH-producing tumors. (c) 2005 Elsevier Inc. All rights reserved. C1 NICHHD, CRC, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), NICHHD, CRC, Reprod Biol & Med Branch, NIH, Bldg 10,1 E,Rm 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM NiemanL@nih.gov NR 100 TC 71 Z9 78 U1 0 U2 15 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2005 VL 118 IS 12 BP 1340 EP 1346 DI 10.1016/j.amjmed.2005.01.059 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 996ER UT WOS:000234157700006 PM 16378774 ER PT J AU Sherman, S Miller, H AF Sherman, S Miller, H TI The NIH State-of-the-Science Conference on Management of Menopause-Related Symptoms March 21-23, 2005 - Introduction SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIA, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Sherman, S (reprint author), NIA, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2005 VL 118 IS 12 BP 1404 EP 1405 DI 10.1016/j.amjmed.2005.10.030 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 996ER UT WOS:000234157700017 ER PT J AU Sherman, S AF Sherman, S TI Defining the menopausal transition SO AMERICAN JOURNAL OF MEDICINE LA English DT Meeting Abstract CT NIH Scientific Workshop on Menopausal Hormone Therapy CY OCT, 2002 CL Bethesda, MD SP Natl Inst Hlth C1 NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2005 VL 118 IS 12 BP 1405 EP 1405 DI 10.1016/j.amjmed.2005.10.006 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 996ER UT WOS:000234157700019 ER PT J AU Schmidt, PJ AF Schmidt, PJ TI Mood, depression, and reproductive hormones in the menopausal transition SO AMERICAN JOURNAL OF MEDICINE LA English DT Meeting Abstract CT NIH Scientific Workshop on Menopausal Hormone Therapy CY OCT, 2002 CL Bethesda, MD SP Natl Inst Hlth C1 NIMH, Behav Endocrinol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2005 VL 118 IS 12 BP 1407 EP 1407 DI 10.1016/j.amjmed.2005.10.012 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 996ER UT WOS:000234157700025 ER PT J AU Sherman, S Nerurkar, L Miller, H Schiff, I AF Sherman, S Nerurkar, L Miller, H Schiff, I TI Research opportunities for reducing the burden of menopause-related symptoms SO AMERICAN JOURNAL OF MEDICINE LA English DT Meeting Abstract CT NIH Scientific Workshop on Menopausal Hormone Therapy CY OCT, 2002 CL Bethesda, MD SP Natl Inst Hlth C1 NIA, NIH, Bethesda, MD 20892 USA. NIH, Off Med Applicat Res, Off Director, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2005 VL 118 IS 12 BP 1411 EP 1412 DI 10.1016/j.amjmed.2005.10.029 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 996ER UT WOS:000234157700042 ER PT J AU Hendler, I McPherson, CA Goldenberg, RL AF Hendler, I McPherson, CA Goldenberg, RL TI Preterm predictors: Constipation, childbirth, and cervical surgery? Reply SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 NICHHD, Maternal Fetal Med Unit Network, NIH, Bethesda, MD 20892 USA. RP Hendler, I (reprint author), NICHHD, Maternal Fetal Med Unit Network, NIH, Bethesda, MD 20892 USA. EM ihendler@med.wayne.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 BP 2179 EP 2180 DI 10.1016/j.ajog.2005.05.029 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IL UT WOS:000233947700054 ER PT J AU Andrews, W Jeffcoat, M Schwebke, J Klebanoff, M Zhang, J Cliver, S AF Andrews, W Jeffcoat, M Schwebke, J Klebanoff, M Zhang, J Cliver, S TI Longitudinal study of vaginal flora: Increasing periodontal disease (PD) burden is associated with increased risk for bacterial vaginosis (BV) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Univ Alabama, Birmingham, AL USA. Univ Penn, Philadelphia, PA 19104 USA. NIH, Epidemiol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 657 BP S186 EP S186 DI 10.1016/j.ajog.2005.10.750 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800653 ER PT J AU Bailit, J AF Bailit, J CA NICHD MFMU Network TI The MFMU Cesarean Registry: Impact of time of day on cesarean complications SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, MFMU, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 414 BP S122 EP S122 DI 10.1016/j.ajog.2005.10.435 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800412 ER PT J AU Bloom, SL AF Bloom, SL TI The MFMU network randomized trial of fetal pulse oximetry SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 MFMU Network, NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 1 BP S2 EP S2 DI 10.1016/j.ajog.2005.10.002 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800002 ER PT J AU Chatworapongsa, T Espinoza, J Nien, JK Goncalves, L Edwin, S Richani, K Soto, E Santolaya, J Kim, CJ Kim, YM Romero, R AF Chatworapongsa, T Espinoza, J Nien, JK Goncalves, L Edwin, S Richani, K Soto, E Santolaya, J Kim, CJ Kim, YM Romero, R TI Preeclampsia and SGA are characterized by low concentrations of a novel factor involved in angiogenesis and endothelial cell function: SVEGFR-2 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 213 BP S71 EP S71 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800213 ER PT J AU Dizon-Townson, D AF Dizon-Townson, D TI Impact of smoking during pregnancy and functional coagulation testing SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, MFMU, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S BP S81 EP S81 DI 10.1016/j.ajog.2005.10.553 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800256 ER PT J AU Durnwald, C AF Durnwald, C CA NICHD-MFMU Network TI The MFMU cesarean registry: Safety and efficacy of VBAC in preterm trial of labor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 MFMU Network, NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 45 BP S20 EP S20 DI 10.1016/j.ajog.2005.10.050 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800046 ER PT J AU Erez, O Hoppensteadt, D Espinoza, J Goncalves, L Nien, JK Fareed, J Romero, R AF Erez, O Hoppensteadt, D Espinoza, J Goncalves, L Nien, JK Fareed, J Romero, R TI Preeclampsia 15 associated with low concentrations of the novel regulatory factor of coagulation: Protein Z SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 218 BP S72 EP S72 DI 10.1016/j.ajog.2005.10.258 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800218 ER PT J AU Espinoza, J Nien, JK Kusanovic, JP Richani, K Gomez, R Kim, CJ Mittal, P Chaiworapongsa, T Romero, R AF Espinoza, J Nien, JK Kusanovic, JP Richani, K Gomez, R Kim, CJ Mittal, P Chaiworapongsa, T Romero, R TI A role for the anti-angiogenic factor sVEGFR-1 in the "Mirror Syndrome" (Ballantine Syndrome) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Hosp Dr Sotero del Rio, Ctr Perinatal Diagnosis & Res, Santiago, Chile. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 457 BP S134 EP S134 DI 10.1016/j.ajog.2005.10.481 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800455 ER PT J AU Friel, L Kuivaniemi, H Gomez, R Goddard, K Nien, JK Tromp, G Lu, Q Xu, ZY Behnke, E Solari, M Espinoza, J Kim, CJ Chaiworapongsa, T Kim, YM Lenk, G Volkenant, K Romero, R AF Friel, L Kuivaniemi, H Gomez, R Goddard, K Nien, JK Tromp, G Lu, Q Xu, ZY Behnke, E Solari, M Espinoza, J Kim, CJ Chaiworapongsa, T Kim, YM Lenk, G Volkenant, K Romero, R TI Genetic predisposition for preterm PROM: Results of a large candidate-gene association study of mothers and their offspring SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 48202 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. Hosp Dr Sotero del Rio, Ctr Perinatal Diag & Res, Santiago, 44106, Chile. Case Western Reserve Univ, Sch Med, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 37 BP S17 EP S17 DI 10.1016/j.ajog.2005.10.040 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800038 ER PT J AU Goncalves, L Nien, JK Espinoza, J Kusanovic, JP Lee, W Swope, B Soto, E AF Goncalves, L Nien, JK Espinoza, J Kusanovic, JP Lee, W Swope, B Soto, E TI Two-dimensional (2D) ultrasound (US) versus three- and four-dimensional (3D/4D) us in obstetrical practice: Does the new technology add anything? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. William Beaumont Hosp, Dept Obstet & Gynecol, Royal Oak, MI 48072 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 521 BP S150 EP S150 DI 10.1016/j.ajog.2005.10.600 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800518 ER PT J AU Grobman, W AF Grobman, W TI The MFMU Cesarean Registry: Induction of labor following one prior cesarean SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD MFMU, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 422 BP S124 EP S124 DI 10.1016/j.ajog.2005.10.445 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800420 ER PT J AU Grobman, W AF Grobman, W TI The MFMU Cesarean Registry: Does an unfavorable cervix at induction of labor in women with one prior cesarean affect maternal morbidity? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD MFMU, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 423 BP S125 EP S125 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800421 ER PT J AU Grobman, W AF Grobman, W TI The MFMU Cesarean Registry: Development of a clinically-useful prediction model for VBAC success SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD MFMU, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 424 BP S125 EP S125 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800422 ER PT J AU Haddad, R Gould, B Tromp, G Romero, R Zingg, H AF Haddad, R Gould, B Tromp, G Romero, R Zingg, H TI Functional genomics reveals fundamental differences in the gene expression profile of infection-induced and progesterone withdrawal-induced preterm labor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 17 BP S7 EP S7 DI 10.1016/j.ajog.2005.10.207 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800018 ER PT J AU Hassan, S Haddad, R Hendler, I Khalek, N Tromp, G Diamond, M Sorokin, Y Malone, J Romero, R AF Hassan, S Haddad, R Hendler, I Khalek, N Tromp, G Diamond, M Sorokin, Y Malone, J Romero, R TI A comprehensive, unbiased and systematic description of the biological processes involved in cervical ripening/dilatation using functional genomics SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48202 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 26 BP S11 EP S11 DI 10.1016/j.ajog.2005.10.209 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800027 ER PT J AU Hendler, I AF Hendler, I TI The MFMU Cesarean Registry: Changing patterns of VBAC attempts and success rates SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD MFMU Network, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 426 BP S125 EP S125 DI 10.1016/j.ajog.2005.10.449 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800424 ER PT J AU Hendler, I AF Hendler, I TI The impact of high body mass index on the prediction of spontaneous preterm birth by ultrasonographic cervical length SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 MFMU, NICHD, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 154 BP S54 EP S54 DI 10.1016/j.ajog.2005.10.169 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800155 ER PT J AU Kim, CJ Kim, JS Lee, SD Kim, YM Richani, K Espinoza, J Romero, R AF Kim, CJ Kim, JS Lee, SD Kim, YM Richani, K Espinoza, J Romero, R TI Fetal macrophages are not present in the myometrium of women who undergo labor at term SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Seoul Natl Univ, Coll Med, Dept Forens Med, Seoul, South Korea. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 596 BP S170 EP S170 DI 10.1016/j.ajog.2005.10.682 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800592 ER PT J AU Kusanovic, JP Espinoza, J Hoppensteadt, D Nien, JK Kim, CJ Erez, O Soto, E Fareed, J Romero, R AF Kusanovic, JP Espinoza, J Hoppensteadt, D Nien, JK Kim, CJ Erez, O Soto, E Fareed, J Romero, R TI Preterm labor leading to preterm delivery in the absence of inflammation/infection is associated with low maternal plasma protein Z concentrations SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 15 BP S6 EP S6 DI 10.1016/j.ajog.2005.10.205 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800016 ER PT J AU Levine, R Lam, C Qian, C Yu, K Maynard, S Sibai, B Epstein, F Karumanchi, A AF Levine, R Lam, C Qian, C Yu, K Maynard, S Sibai, B Epstein, F Karumanchi, A TI Circulating angiogenic factors in gestational hypertension SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, NIH, DHHS, Epidemiol Branch, Bethesda, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NICHD, NIH, DHHS, Stat Branch, Bethesda, MD USA. Allied Technol Grp, Rockville, MD USA. George Washington Univ, Sch Med, Washington, DC USA. Univ Cincinnati, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 228 BP S74 EP S74 DI 10.1016/j.ajog.2005.10.269 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800228 ER PT J AU Levine, R Lam, C Qian, C Yu, K Maynard, S Sibai, B Romero, R Epstein, F Karumanchi, A AF Levine, R Lam, C Qian, C Yu, K Maynard, S Sibai, B Romero, R Epstein, F Karumanchi, A TI Soluble endoglin, a novel circulating anti-angiogenic factor in preeclampsia (PE) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, NIH, DHHS, Epidemiol Branch, Bethesda, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Allied Technol Grp, Rockville, MD USA. NICHD, NIH, DHHS, Stat Branch, Bethesda, MD USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 31 BP S14 EP S14 DI 10.1016/j.ajog.2005.10.032 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800032 ER PT J AU Levine, R Lam, C Qian, C Yu, K Maynard, S Sibai, B Epstein, F Karumanchi, A AF Levine, R Lam, C Qian, C Yu, K Maynard, S Sibai, B Epstein, F Karumanchi, A TI Soluble endoglin and other circulating angiogenic factors in normotensive pregnancy with fetal growth restriction SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, NIH, DHHS, Epidemiol Branch, Bethesda, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Allied Technol Grp, Rockville, MD USA. NICHD, NIH, DHHS, Stat Branch, Bethesda, MD USA. George Washington Univ, Sch Med, Washington, DC USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 229 BP S75 EP S75 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800229 ER PT J AU Levine, R Lam, C Qian, C Yu, K Maynard, S Sibai, B Epstein, F Karumanchi, A AF Levine, R Lam, C Qian, C Yu, K Maynard, S Sibai, B Epstein, F Karumanchi, A TI Circulating angiogenic factors in smokers and non-smokers during normal pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, NIH, DHHS, Epidemiol Branch, Bethesda, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Allied Technol Grp, Rockville, MD USA. NICHD, NIH, DHHS, Stat Branch, Bethesda, MD USA. George Washington Univ, Sch Med, Washington, DC USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 230 BP S75 EP S75 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800230 ER PT J AU Lin, M AF Lin, M CA NICHD MFMU Network TI Impact of quantitative fetal fibronectin (FFN) change on efficacy of antibiotic vs. placebo treatment of asymptomatic FFN positive women to prevent subsequent preterm birth (PB) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 MFMU, NICHD, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 159 BP S56 EP S56 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800160 ER PT J AU Lin, M AF Lin, M TI The MFMU Cesarean Registry: Complications of primary prelabor cesarean in obese gravidas SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 430 BP S126 EP S126 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800428 ER PT J AU Lin, M AF Lin, M TI The MFMU Cesarean Registry: Complications of primary cesarean section in multiple gestations SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 429 BP S126 EP S126 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800427 ER PT J AU Louis, J AF Louis, J CA NICHD MFMU Network TI The MFMU cesarean registry: Perioperative morbidity among HIV infected women undergoing cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 679 BP S191 EP S191 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800675 ER PT J AU Mari, G Balasubramaniam, M Soto, E Espinoza, J Nien, JK Richani, K Treadwell, M AF Mari, G Balasubramaniam, M Soto, E Espinoza, J Nien, JK Richani, K Treadwell, M TI Middle cerebral artery peak systolic velocity and ductus venosus pulsatility index - Which is best in predicting perinatal mortality of SGA fetuses with abnormal umbilical artery? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Detroit, MI USA. Beaumont Hosp, Royal Oak, MI USA. NICHD, Perinatal Res Branch, NIH, DHHS, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 577 BP S165 EP S166 DI 10.1016/j.ajog.2005.10.662 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800573 ER PT J AU Mari, G Erez, O Richani, K Goncalves, L Kusanovic, JP Soto, E Balasubramaniam, M Nien, JK AF Mari, G Erez, O Richani, K Goncalves, L Kusanovic, JP Soto, E Balasubramaniam, M Nien, JK TI Middle cerebral artery peak systolic velocity and ductus venosus reversed flow in the prediction of acid-base status of IUGR fetuses delivered at 30 weeks gestation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Detroit, MI USA. Beaumont Hosp, Royal Oak, MI USA. NICHD, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 197 BP S65 EP S65 DI 10.1016/j.ajog.2005.10.520 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800197 ER PT J AU Mittal, P Nien, JK Lee, W Goncalves, L Espinoza, J Swope, B Treadwell, M Romero, R AF Mittal, P Nien, JK Lee, W Goncalves, L Espinoza, J Swope, B Treadwell, M Romero, R TI Fetal insula to parietal bone distance in the assessment of ventriculomegaly SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 536 BP S154 EP S154 DI 10.1016/j.ajog.2005.10.617 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800532 ER PT J AU Nien, JK Yoon, BH Espinoza, J Kusanovic, JP Erez, O Soto, E Richani, K Gomez, R Romero, R AF Nien, JK Yoon, BH Espinoza, J Kusanovic, JP Erez, O Soto, E Richani, K Gomez, R Romero, R TI MMP-8 PLT: A rapid bedside test for the detection of intra-amniotic inflammation can identify patients at risk for preterm delivery within 7 days SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 48202 USA. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. Hosp Dr Sotero del Rio, Ctr Perinatal Diag & Res, Santiago, Chile. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 71 BP S32 EP S32 DI 10.1016/j.ajog.2005.10.080 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800072 ER PT J AU Nien, JK Hoppensteadt, D Erez, O Espinoza, J Soto, E Kusanovic, JP Kim, CJ Mittal, P Fareed, J Santolaya, J Romero, R AF Nien, JK Hoppensteadt, D Erez, O Espinoza, J Soto, E Kusanovic, JP Kim, CJ Mittal, P Fareed, J Santolaya, J Romero, R TI Pyelonephritis during pregnancy: A cause for an acquired deficiency of protein Z SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 666 BP S188 EP S188 DI 10.1016/j.ajog.2005.10.759 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800662 ER PT J AU Reddy, L Ko, CW Willinger, M AF Reddy, L Ko, CW Willinger, M TI Maternal age and the risk of stillbirth during pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 645 BP S182 EP S183 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800641 ER PT J AU Richani, K Romero, R Soto, E Nien, JK Espinoza, J Cushenberry, E Kim, CJ AF Richani, K Romero, R Soto, E Nien, JK Espinoza, J Cushenberry, E Kim, CJ TI Genetic origin and proportion of basal plate surface cells in normal and abnormal pregnancies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 614 BP S175 EP S175 DI 10.1016/j.ajog.2005.10.701 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800610 ER PT J AU Richani, K Romero, R Cushenberry, E Soto, E Espinoza, J Kim, CJ AF Richani, K Romero, R Cushenberry, E Soto, E Espinoza, J Kim, CJ TI Tissue microarray technology: A high throughput method for molecular analysis of the human placenta SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 613 BP S174 EP S174 DI 10.1016/j.ajog.2005.10.700 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800609 ER PT J AU Roberson, R Woodard, J Toso, L Abebe, D Poggi, S Spong, C AF Roberson, R Woodard, J Toso, L Abebe, D Poggi, S Spong, C TI Postnatal inflammatory rat model for cerebral palsy: Too different from human SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NIAAA, NIH, NICHD, Unite Perinatal Dev Neurobiol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 201 BP S66 EP S66 DI 10.1016/j.ajog.2005.10.524 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800201 ER PT J AU Sciscione, A AF Sciscione, A TI The MFMU cesarean registry: Previous preterm low transverse cesarean delivery and risk of subsequent uterine rupture SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 MFMU Network, NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 44 BP S20 EP S20 DI 10.1016/j.ajog.2005.10.049 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800045 ER PT J AU Sibai, B AF Sibai, B CA NICHD MFMU Network TI Maternal thrombophilias are not associated with adverse pregnancy outcome (APO): A prospective observational study SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 240 BP S77 EP S77 DI 10.1016/j.ajog.2005.10.281 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800240 ER PT J AU Sorokin, Y Romer, R AF Sorokin, Y Romer, R CA NICHD MFMU Network TI Elevated maternal serum IL-6 and CRP are associated with preterm delivery < 32 weeks and subsequent neonatal intraventricular hemorrhage SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Perinatol Res Branch, Detroit, MI USA. NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 186 BP S62 EP S62 DI 10.1016/j.ajog.2005.10.528 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800186 ER PT J AU Soto, E Espinoza, J Nien, JK Kusanovic, JP Erez, O Richani, K Santolaya, J Romero, R AF Soto, E Espinoza, J Nien, JK Kusanovic, JP Erez, O Richani, K Santolaya, J Romero, R TI Human-defensin 2: A natural anti-microbial agent present in normal amniotic fluid participates in the host response to intra-amniotic infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 592 BP S169 EP S169 DI 10.1016/j.ajog.2005.10.678 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800588 ER PT J AU Toso, L Roberson, R Woodard, J Abebe, D Spong, C AF Toso, L Roberson, R Woodard, J Abebe, D Spong, C TI Prenatal alcohol exposure alters GABAA5 expression: A mechanism of alcohol-induced learning dysfunction SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NIAAA, NICHD, NIH, UPDN, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 203 BP S67 EP S67 DI 10.1016/j.ajog.2005.10.526 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800203 ER PT J AU Toso, L Roberson, R Woodard, J Abebe, D Poggi, S Spong, C AF Toso, L Roberson, R Woodard, J Abebe, D Poggi, S Spong, C TI NMDA in adult mouse brain: Mechanism of learning deficits prevention after prenatal alcohol exposure SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 UPDN, NICHD, NIAAA, NIH, Bethesda, MD USA. INOVA Hosp, Alexandria, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 54 BP S24 EP S24 DI 10.1016/j.ajog.2005.10.060 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800055 ER PT J AU Toso, L Woodard, J Roberson, R Abebe, D Spong, C AF Toso, L Woodard, J Roberson, R Abebe, D Spong, C TI Fetal alcohol syndrome: Prevention of learning deficits is mediated through NMDA and GABA expression SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 UPDN, NICHD, NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 19 BP S9 EP S9 DI 10.1016/j.ajog.2005.10.020 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800020 ER PT J AU Varner, M AF Varner, M TI The MFMU Cesarean Registry: VBAC success and complication rates following one previous cesarean for multifetal gestation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 444 BP S130 EP S130 DI 10.1016/j.ajog.2005.10.468 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800442 ER PT J AU Wang, XY Romer, R Mallard, C Arvidsson, P Gustavsson, M Hagberg, H AF Wang, XY Romer, R Mallard, C Arvidsson, P Gustavsson, M Hagberg, H TI Melatonin and N-acetylcysteine reduce brain injury in response to lipopolysaccharide-sensitized hypoxia-ischemia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Sahlgrenska Acad, Dept Physiol, Perinatal Ctr, Gothenburg, Sweden. NICHHD, Perinatol Res Branch, NIH, Dept H&H, Detroit, MI USA. Sahlgrenska Acad, Dept Obstet & Gynecol, Gothenburg, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 62 BP S28 EP S28 DI 10.1016/j.ajog.2005.10.070 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800063 ER PT J AU Wapner, RJ AF Wapner, RJ TI Maternal and fetal adrenal function following single and repeat courses of antenatal corticosteroids (ACS) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 MFMU Network, NICHD, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 10 BP S5 EP S5 DI 10.1016/j.ajog.2005.10.011 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800011 ER PT J AU Tsai, JH Freeman, JM Chan, CC Schwartz, GS Derby, EA Petersen, MR Holland, EJ AF Tsai, JH Freeman, JM Chan, CC Schwartz, GS Derby, EA Petersen, MR Holland, EJ TI A progressive anterior fibrosis syndrome in patients with postsurgical congenital aniridia SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID IMPLANTATION; IRIS; KERATOPATHY AB PURPOSE: To report the characteristics of a newly recognized clinical entity in congential aniridia that we have termed aniridic fibrosis syndrome. DESIGN: Interventional case series. METHODS: Retrospective chart review of 155 eyes in 80 patients with congenital aniridia was carried out to identify and characterize eyes that had anterior chamber fibrosis. Histopathologic evaluation was performed in three eyes. RESULTS: Seven eyes in six patients were identified to have aniridic fibrosis syndrome. All eyes had undergone previous intraocular anterior segment surgery, some eyes with multiple procedures. Seven eyes had undergone cataract surgery with posterior chamber intraocular lens; six eyes had undergone previous implantation of tube shunt devices, and four eyes had undergone previous penetrating keratoplasty. Clinically, the syndrome was characterized by a progressive retrolenticular and retrocorneal membrane that caused forward displacement of intraocular lenses. Surgical findings indicated that the fibrotic membrane also can involve the ciliary body and anterior retina. Histopathologic evidence from three eyes indicated that the extensive fibrotic tissue originated from the root of the rudimentary iris and entrapped the intraocular lens haptics. Endothelial decompensation that was subsequent to the formation of the aniridic fibrosis syndrome was seen in all eyes. CONCLUSION: Aniridic fibrosis syndrome is characterized by the development of a progressive anterior chamber fibrosis. A possible mechanism that promotes the formation of this fibrotic material may be the proximity or touching of intraocular devices on immature vessels in the rudimentary iris found in aniridia. Patients with aniridia with a history of penetrating keratoplasty, intraocular lenses, and tube shunts should be monitored for aniridic fibrosis syndrome; early surgical intervention is recommended. C1 Univ Cincinnati, Cincinnati, OH USA. Cincinnati Eye Inst, Cincinnati, OH USA. NEI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. RP Holland, EJ (reprint author), 580 S Loop Rd,Suite 200, Edgewood, KY 41017 USA. EM eholland@fuse.net NR 15 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2005 VL 140 IS 6 BP 1075 EP 1079 DI 10.1016/j.ajo.2005.07.035 PG 5 WC Ophthalmology SC Ophthalmology GA 000QA UT WOS:000234475900017 PM 16376654 ER PT J AU Musser, JM DeLeo, FR AF Musser, JM DeLeo, FR TI Toward a genome-wide systems biology analysis of host-pathogen interactions in group A Streptococcus SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Review ID ACUTE RHEUMATIC-FEVER; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; APOPTOSIS DIFFERENTIATION PROGRAM; HYALURONIC-ACID CAPSULE; GENE-EXPRESSION; VIRULENCE FACTOR; HAEMOPHILUS-INFLUENZAE; NONINVASIVE INFECTIONS; NEUTROPHIL APOPTOSIS; MACROLIDE RESISTANCE AB Genome-wide analysis of microbial pathogens and molecular pathogenesis processes has become an area of considerable activity in the last 5 years. These studies have been made possible by several advances, including completion of the human genome sequence, publication of genome sequences for many human pathogens, development of microarray technology and high throughput proteomics, and maturation of bioinformatics. Despite these advances, relatively little effort has been expended in the bacterial pathogenesis arena to develop and use integrated research platforms in a systems biology approach to enhance our understanding of disease processes. This review discusses progress made in exploiting an integrated genome-wide research platform to gain new knowledge about how the human bacterial pathogen group A Streptococcus causes disease. Results of these studies have provided many new avenues for basic pathogenesis research and translational research focused on development of an efficacious human vaccine and novel therapeutics. one goal in summarizing this line of study is to bring exciting new findings to the attention of the investigative pathology community. In addition, we hope the review will stimulate investigators to consider using analogous approaches for analysis of the molecular pathogenesis of other microbes. C1 Methodist Hosp, Ctr Mol & Translat Human Infect Dis Res, Res Inst, Houston, TX 77030 USA. Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Musser, JM (reprint author), Methodist Hosp, Ctr Mol & Translat Human Infect Dis Res, Res Inst, 6565 Fannin St,F816, Houston, TX 77030 USA. EM jmmusser@tmh.tmc.edu OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS; NIAID NIH HHS [U01 AI060595, U01 AI60595] NR 78 TC 71 Z9 74 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2005 VL 167 IS 6 BP 1461 EP 1472 DI 10.1016/S0002-9440(10)61232-1 PG 12 WC Pathology SC Pathology GA 988EE UT WOS:000233573600001 PM 16314461 ER PT J AU Wagner, AK McElligott, J Wagner, EP Gerber, LH AF Wagner, AK McElligott, J Wagner, EP Gerber, LH TI Measuring rehabilitation research capacity - Report from the AAPM&R Research Advisory Committee SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE rehabilitation; research capacity; metrics; taxonomy; researchers; research environment ID ACADEMIC MEDICINE; FACULTY; SURGERY; HEALTH; WOMEN AB There is considerable concern regarding the paucity of individuals pursuing biomedical research in general and rehabilitation research in particular. The Research Advisory Committee (RAC) of the American Academy of Physical Medicine and Rehabilitation (AAPM&R) accepted the task to explore the barriers to biomedical research careers for physicians and rehabilitation scientists and, in particular, those factors pertaining to successfully conducting rehabilitation research. Concurrently, the Foundation for PM&R was also exploring the related issue of building capacity for rehabilitation research and planning a Rehabilitation Research Summit to address this issue for the spring of 2005. The goals of the Research Summit included the identification of barriers to rehabilitation research and development of an active agenda to enhance research capacity. As such, AAPM&R and the Foundation for PM&R worked through the RAC survey to provide some key information that would help the summit leaders achieve their goals. This report presents portions of the survey related to research capacity and outlines the methodology of the data collection and analysis within the context of the capacity taxonomy framework as presented at the Research Summit, "Building Research Capacity," held in the spring of 2005. This survey report provides quantitative information about researchers and academicians, their research environment, as well as their barriers and incentives for conducting rehabilitation research. Observations here provide a platform for future work in understanding the adequacy of the rehabilitation research enterprise, its appropriateness, and ability to meet societal needs for those with disabilities C1 NIH, Warren G Magnuson Clin Ctr, Rehabil Med Dept, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Natl Rehabil Hosp, Dublin, Ireland. RP Gerber, LH (reprint author), NIH, Warren G Magnuson Clin Ctr, Rehabil Med Dept, Bldg 10 6s235, Bethesda, MD 20892 USA. NR 25 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD DEC PY 2005 VL 84 IS 12 BP 955 EP 968 DI 10.1097/01.phm.0000187860.11221.8c PG 14 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 991QI UT WOS:000233828200006 PM 16327412 ER PT J AU Yamamura, K Steenbergen, C Murphy, E AF Yamamura, K Steenbergen, C Murphy, E TI Protein kinase C and preconditioning: Role of the sarcoplasmic reticulum SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE calcium; protein kinase C-epsilon; 1,2-dioctanoyl-sn glycerol; protein phosphatase 1 ID ISOLATED RAT-HEART; CARDIAC MYOCYTES; INDUCED CARDIOPROTECTION; RABBIT CARDIOMYOCYTES; SIGNALING MODULES; PHORBOL ESTER; PKC-EPSILON; TROPONIN-I; PHOSPHOLAMBAN; TRANSLOCATION AB Activation of protein kinase C (PKC) is cardioprotective, but the mechanism(s) by which PKC mediates protection is not fully understood. Inasmuch as PKC has been well documented to modulate sarcoplasmic reticulum (SR) Ca2+ and because altered SR Ca2+ handling during ischemia is involved in cardioprotection, we examined the role of PKC-mediated alterations of SR Ca2+ in cardioprotection. Using isolated adult rat ventricular myocytes, we found that addition of 1,2-dioctanoyl-sn-glycerol (DOG), to activate PKC under conditions that reduced myocyte death associated with simulated ischemia and reperfusion, also reduced SR Ca-2+. Cell death was 57.9 +/- 2.9% and 47.3 +/- 1.8% in untreated and DOG-treated myocytes, respectively (P < 0.05). Using fura 2 fluorescence to monitor Ca2+ transients and caffeine-releasable SR Ca2+, we examined the effect of DOG on SR Ca2+. Caffeine-releasable SR Ca2+ was significantly reduced (by similar to 65%) after 10 min of DOG treatment compared with untreated myocytes (P < 0.05). From our examination of the mechanism by which PKC alters SR Ca2+, we present the novel finding that DOG treatment reduced the phosphorylation of phospholamban (PLB) at Ser(16). This effect is mediated by PKC-epsilon, because a PKC-epsilon-selective inhibitory peptide blocked the DOG-mediated decrease in phosphorylation of PLB and abolished the DOG-induced reduction in caffeine-releasable SR Ca2+. Using immunoprecipitation, we further demonstrated that DOG increased the association between protein phosphatase 1 and PLB. These data suggest that activated PKC-epsilon reduces SR Ca2+ content through PLB dephosphorylation and that reduced SR Ca2+ may be important in cardioprotection. C1 Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RP Murphy, E (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, 111 TW Alexander Dr,Bldg 10,F2-07, Res Triangle Pk, NC 27709 USA. EM murphy1@niehs.nih.gov FU NHLBI NIH HHS [R01 HL039752] NR 42 TC 18 Z9 18 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC PY 2005 VL 289 IS 6 BP H2484 EP H2490 DI 10.1152/ajpheart.00590.2005 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 982QL UT WOS:000233176600029 PM 16055516 ER PT J AU Castrop, H Lorenz, JN Hansen, PB Friis, U Mizel, D Oppermann, M Jensen, BL Briggs, J Skott, O Schnermann, J AF Castrop, H Lorenz, JN Hansen, PB Friis, U Mizel, D Oppermann, M Jensen, BL Briggs, J Skott, O Schnermann, J TI Contribution of the basolateral isoform of the Na-K-2Cl(-) cotransporter (NKCC1/BSC2) to renin secretion SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE NKCC1 knockout mice; plasma renin; renin mRNA; patch clamp; juxtaglomerular granular cells ID RAT JUXTAGLOMERULAR CELLS; THICK ASCENDING LIMB; MACULA DENSA CELLS; NA+-K+-2CL(-) COTRANSPORTER; MICE LACKING; KIDNEY; EXPRESSION; FUROSEMIDE; CHANNELS; STIMULATION AB Acute administration of loop diuretics like furosemide leads to a stimulation of renin secretion, an effect thought to result from inhibition of Na-K-2Cl cotransporter (NKCC2)-mediated salt transport at the luminal surface of the macula densa ( MD). However, loop diuretics also inhibit NKCC1, the second isoform of the Na-K-2Cl cotransporter, with similar potency. In the present study, we examined the influence of furosemide on renin secretion in NKCC1-deficient mice to distinguish between effects of the loop diuretic involving NKCC2 and, by implication, the MD pathway, and effects that might occur via inhibition of NKCC1. Baseline plasma renin concentration (PRC) was 1,212 +/- 211 in NKCC1 +/+ (n = 13) and 3,851 +/- 579 ng ANG I (.) ml(-1) (.) h(-1) in NKCC1 -/- mice ( n = 14; P = 0.00024). Acute administration of furosemide ( 50 mg/kg i.p.) increased PRC significantly to 9,324 +/- 1,018 ng ANG I (.) ml(-1) (.) h(-1) in NKCC1 +/+ ( n = 13; P < 0.0001 compared with basal) and to 14,188 +/- 2,274 ng ANG I (.) ml(-1) (.) h(-1) in NKCC1 -/- mice [n = 14; P = 0.0002 compared with basal; P = 0.034 compared with wild-type (WT) plus furosemide]. Renin mRNA expression was about threefold higher in NKCC1 -/- compared with WT mice. There was considerable recruitment of granular cells to upstream regions of afferent arterioles in NKCC1 -/- mice. Patch-clamp studies in single juxtaglomerular granular (JG) cells from WT mice showed an similar to 10% increase in membrane capacitance during incubation with furosemide (10(-4) M), indicating a direct effect of the loop diuretic on renin secretion. No effect of furosemide on membrane capacitance was observed in JG cells from NKCC1-deficient mice. Furosemide (10(-3) M) significantly stimulated renin release from primary cultures of JG cells from WT mice, whereas no response was observed in NKCC1-/- mice. Our data suggest that a functional NKCC1 suppresses basal renin release, at least in part, through a direct effect on JG cells. C1 NIDDK, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Univ So Denmark, Dept Physiol, Odense, Denmark. RP Schnermann, J (reprint author), NIDDK, NIH, Bldg 10,Rm 4 D51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov RI Briggs, Josephine/B-9394-2009; OI Briggs, Josephine/0000-0003-0798-1190; Skott, Ole/0000-0002-1684-6655 FU Intramural NIH HHS [Z01 DK043408-06]; NIDDK NIH HHS [DK-057552, R01 DK057552] NR 35 TC 42 Z9 42 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2005 VL 289 IS 6 BP F1185 EP F1192 DI 10.1152/ajprenal.00455.2004 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 981RA UT WOS:000233104500004 PM 16106034 ER PT J AU Kim, YH Verlander, JW Matthews, SW Kurtz, I Shin, W Weiner, ID Everett, LA Green, ED Nielsen, S Wall, SM AF Kim, YH Verlander, JW Matthews, SW Kurtz, I Shin, W Weiner, ID Everett, LA Green, ED Nielsen, S Wall, SM TI Intercalated cell H+/OH- transporter expression is reduced in Slc26a4 null mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE NBC3; AE1; acid-base balance ID VACUOLAR H+-ATPASE; CORTICAL COLLECTING DUCT; RENAL TUBULAR-ACIDOSIS; PENDRED-SYNDROME GENE; RAT-KIDNEY; MOUSE KIDNEY; METABOLIC-ACIDOSIS; LOCALIZATION; SUBTYPES; SECRETION AB Slc26a4 ( Pds) encodes pendrin, a Cl-/HCO3- exchanger expressed in the apical region of type B and non-A, non-B cells, which mediates secretion of OH- equivalents. Thus genetic disruption of Slc26a4 leads to systemic alkalosis in some treatment models. However, humans and mice with genetic disruption of Slc26a4 have normal acid-base balance under basal conditions. Thus we asked: 1) Is net acid excretion altered in Slc26a4 (-/-) mice under basal conditions? 2) In the absence of pendrin-mediated OH- secretion, are increases in intracellular and systemic pH minimized through changes in intercalated cell subtype abundance or intercalated cell H+/OH- transporter expression? To answer these questions, net acid excretion and H+/OH- transporter expression were examined in Slc26a4 (-/-) and Slc26a4 (-/-) mice using balance studies, immunolocalization, and immunoblotting. Excretion of ammonium, titratable acid, and citrate were the same in Slc26a4 null and wild-type mice. However, urinary pH and P-CO2 were much lower in Slc26a4 null relative to wild-type mice due to reduced urinary buffering of secreted H+ by HCO3- . Abundance of non-A, but not type A intercalated cells, was reduced within the cortical collecting ducts of Slc26a4 null mice. Moreover, kidneys from Slc26a4 null mice had reduced H+-ATPase, NBC3 and RhBG total protein expression, particularly within type B and non-A, non-B intercalated cells, although RhCG protein expression was unchanged. Reduced intercalated cell H+/OH- transporter expression is observed in Slc26a4 null mice, which likely attenuates the rise in intracellular and systemic pH expected with genetic disruption of Slc26a4. C1 Emory Univ, Dept Med, Atlanta, GA 30322 USA. Univ Florida, Coll Med, Dept Med, Gainesville, FL 32611 USA. Wellcome Trust Sanger Inst, Cambridge, England. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. Univ Aarhus, Water & Salt Res Ctr, DK-8000 Aarhus, Denmark. Univ Calif Los Angeles, Sch Med, Div Nephrol, Los Angeles, CA 90024 USA. N Florida S Georgia Vet Hlth Syst, Nephrol & Hypertens Sect, Gainesville, FL USA. RP Wall, SM (reprint author), Div Renal, WMB Rm 338,1639 Pierce Dr,NE, Atlanta, GA 30322 USA. EM smwall@emory.edu RI Verlander, Jill/I-5991-2015; Weiner, Irving/G-6333-2016 OI Weiner, Irving/0000-0002-0046-0600 FU NIDDK NIH HHS [R01 DK045788, DK-52935] NR 39 TC 28 Z9 29 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2005 VL 289 IS 6 BP F1262 EP F1272 DI 10.1152/ajprenal.00206.2005 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 981RA UT WOS:000233104500013 PM 16144965 ER PT J AU Muthappan, P Forster, H Wendler, D AF Muthappan, P Forster, H Wendler, D TI Research advance directives: Protection or obstacle? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CLINICAL RESEARCH; ADULTS AB Objective: This study assessed how many adults completed a research advance directive and the preferences indicated on the completed forms. Method: The authors analyzed all 2,371 adults admitted as inpatients to the NIH Clinical Center from March 14 to Sept. 13, 2000. Results: Overall, 11% of adult inpatients completed a research advance directive. Of those who specified preferences, 13% were not willing to participate in future research should they become unable to consent, 76% were willing to participate in research that might help them, 49% were willing to participate in research that would not help them and posed minimal risk, and 9% were willing to participate in research that would not help them and posed greater than minimal risk. Conclusions: Proposals to allow cognitively impaired adults to participate in research only with a formal advance directive could block important research. More flexible approaches should be considered to protect these individuals. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 4 TC 18 Z9 18 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2005 VL 162 IS 12 BP 2389 EP 2391 DI 10.1176/appi.ajp.162.12.2389 PG 3 WC Psychiatry SC Psychiatry GA 990OX UT WOS:000233754200028 PM 16330609 ER PT J AU Burchard, EG Borrell, LN Choudhry, S Naqvi, M Tsai, HJ Rodriguez-Santana, JR Chapela, R Rogers, SD Mei, R Rodriguez-Cintron, W Arena, JF Kittles, R Perez-Stable, EJ Ziv, E Risch, N AF Burchard, EG Borrell, LN Choudhry, S Naqvi, M Tsai, HJ Rodriguez-Santana, JR Chapela, R Rogers, SD Mei, R Rodriguez-Cintron, W Arena, JF Kittles, R Perez-Stable, EJ Ziv, E Risch, N TI Latino populations: A unique opportunity for the study of race, genetics, and social environment in epidemiological research SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PUERTO-RICAN; MEXICAN-AMERICANS; HISPANIC PARADOX; RISK-FACTOR; ASTHMA; HEALTH; MORTALITY; ADMIXTURE; ASSOCIATION; LOCI AB Latinos are the largest minority population in the United States. Although usually classified as a single ethnic group by researchers, Latinos are heterogeneous from cultural, socioeconomic, and genetic perspectives. From a cultural and social perspective, Latinos represent a wide variety of national origins and ethnic and cultural groups, with a full spectrum of social class. From a genetic perspective, Latinos are descended from indigenous American, European, and African populations. We review the historical events that led to the formation of contemporary Latino populations and use results from recent genetic and clinical studies to illustrate the unique opportunity Latino groups offer for studying the interaction between racial, genetic, and environmental contributions to disease occurrence and drug response. C1 Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Div Clin Pharmacol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biopharmaceut Sci, Div Pharmaceut Sci & Pharmacogenet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Human Genet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Med Effectiveness Res Ctr Dis Populat, San Francisco, CA 94143 USA. Columbia Univ, Sch Dent & Oral Surg, New York, NY USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. Pediat Pulm Program San Juan, San Juan, PR USA. Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Affymetrix Inc, Santa Clara, CA USA. Univ Puerto Rico, Sch Med, Vet Affairs Med Ctr, San Juan, PR 00936 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Kaiser Permanente Med Ctr, Div Res, Oakland, CA 94611 USA. RP Burchard, EG (reprint author), Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care, San Francisco, CA 94143 USA. EM esteban@sfgh.ucs.edu RI Tsai, Hui-Ju /E-3937-2010 FU NCI NIH HHS [U01 CA086117, U01CA86117]; NHLBI NIH HHS [HL07185, K23 HL004464, K23 HL04464, T32 HL007185]; NIGMS NIH HHS [GM61390, U01 GM061390, U19 GM061390] NR 57 TC 118 Z9 119 U1 0 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2005 VL 95 IS 12 BP 2161 EP 2168 DI 10.2105/AJPH.2005.068668 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 989EP UT WOS:000233656000016 PM 16257940 ER PT J AU Thorne, PS Kulhankova, K Yin, M Cohn, R Arbes, SJ Zeldin, DC AF Thorne, PS Kulhankova, K Yin, M Cohn, R Arbes, SJ Zeldin, DC TI Endotoxin exposure is a risk factor for asthma - The National Survey of Endotoxin in United States Housing SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE airway inflammation; house dust; lipopolysaccharide; wheeze ID LOWER RESPIRATORY-TRACT; DUST-INDUCED INFLAMMATION; GRAIN DUST; COTTON DUST; AIRBORNE ENDOTOXIN; ALLERGIC DISEASES; BIRTH COHORT; CHILDREN; FARM; LIPOPOLYSACCHARIDE AB Background: Although research has shown that early life exposure to household endotoxin protects against development of allergies, studies are less clear on the relationship between household endotoxin exposure and prevalence of wheezing and asthma. We assayed 2,552 house dust samples in a representative nationwide sample to explore relationships between endotoxin exposures and risk factors for asthma, asthma symptoms, and medication use. Methods: House dust was vacuum-sampled from five locations within homes and assayed for endotoxin. Health, demographic, and housing information was assessed through questionnaire and on-site evaluation of 2,456 residents of 831 homes selected to represent the demographics of the United States. Results: Endotoxin concentration (EU/mg) and load (EU/m(2)) were highly correlated (r = 0.73-0.79). Geometric mean endotoxin concentrations were as follows (in EU/mg): bedroom floors, 35.3 (5th-95th percentile, 5.0-260); bedding, 18.7 (2.0-142); family room floors, 63.9 (11.5-331); sofas, 44.8 (6.4-240); and kitchen floors, 80.5 (9.8-512). Multivariate analysis demonstrated significant relationships between increasing endotoxin levels and diagnosed asthma, asthma symptoms in the past year, current use of asthma medications, and wheezing among residents of the homes. These relationships were strongest for bedroom floor and bedding dust and were observed in adults only. Modeling the joint effect of bedding and bedroom floor endotoxin on recent asthma symptoms yielded an adjusted odds ratio of 2.83 (95% confidence interval, 1.01-7.87). When stratified by allergy status, allergic subjects with higher endotoxin exposure were no more likely to have diagnosed asthma or asthma symptoms than nonallergic subjects. Conclusion: This study demonstrates that household endotoxin exposure is a significant risk factor for increased asthma prevalence. C1 Univ Iowa, Coll Publ Hlth, Dept Environm & Occupat Hlth, Environm Hlth Sci Res Ctr, Iowa City, IA 52242 USA. Constella Grp Inc, Durham, NC USA. NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. RP Thorne, PS (reprint author), Univ Iowa, Coll Publ Hlth, Dept Environm & Occupat Hlth, Environm Hlth Sci Res Ctr, 100 Oakdale Campus,176 IREH, Iowa City, IA 52242 USA. EM peter-thorne@uiowa.edu FU Intramural NIH HHS; NIEHS NIH HHS [P30 ES05605, Z01 ES025041-08] NR 41 TC 184 Z9 189 U1 1 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2005 VL 172 IS 11 BP 1371 EP 1377 DI 10.1164/rccm.200505-758OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 989TR UT WOS:000233697300006 PM 16141442 ER PT J AU Yende, S Tuomanen, EI Wunderink, R Kanaya, A Newman, AB Harris, T Rekeneire, NC Kritchevsky, SB AF Yende, S Tuomanen, EI Wunderink, R Kanaya, A Newman, AB Harris, T Rekeneire, NC Kritchevsky, SB CA Hlth ABC Study TI Preinfection systemic inflammatory markers and risk of hospitalization due to pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 101st International Conference of the American-Thoracic-Society CY MAY 20-25, 2005 CL San Diego, CA SP Amer Thorac Soc, Fogarty AIDS Int Training & Res Program DE inflammatory markers; interleukin 6; tumor necrosis factor; pneumonia ID TUMOR-NECROSIS-FACTOR; COMMUNITY-ACQUIRED PNEUMONIA; ANTIBACTERIAL DEFENSE-MECHANISMS; ESCHERICHIA-COLI PNEUMONIA; FACTOR-ALPHA; PNEUMOCOCCAL PNEUMONIA; HOST-DEFENSE; IN-VITRO; MICE; RECEPTOR AB Rationale: Elevated proinflammatory cytokines are associated with severity of pneumonia, but the role of preinfection cytokine levels in the predisposition to pneumonia in humans is less clear. Objective: To ascertain role of preinfection inflammatory markers on susceptibility to community-acquired pneumonia (CAP). Methods: Longitudinal analysis over 6.5 yr of a cohort that consisted of 70- to 79-yr-old well-functioning elderly individuals. Measurements: Association between preinfection tumor necrosis factor (TNF), interleukin 6 (IL-6), and C-reactive protein (CIRP) levels and CAP requiring hospitalization. Results: Of the 3,075 participants, 161 (5.2%) developed at least one episode of CAP requiring hospitalization over a median duration of 3.3 yr. The highest tertiles of TNF (> 3.7 pg/ml) and IL-6 (> 2.4 pg/ml) were associated with increased risk of CAP, and the adjusted odds ratios were 1.6 (95% confidence interval [CI], 1.02-2.7) and 1.7 (95% CI, 1.1-2.8), respectively. The adjusted risk of CAP with at least one of these markers in the highest tertile was 1.6 (95% CI, 1.1-2.3). TNF and IL-6 levels in the highest tertile had a synergistic effect (p = 0.01 for interaction), and risk of CAP for both markers in the highest tertile was 2.8 (95% CI, 1.8-4.3). An FEV1 of 50% or less of predicted was associated with the highest risk of CAP (adjusted odds ratio, 3.6; 95% CI, 2.3-5.6). Furthermore, TNF and IL-6 levels modified risk of CAP in participants with coexisting medical conditions and history of smoking. Conclusion: In the well-functioning elderly subjects, preinfection systemic levels of TNF and IL-6 were associated with higher risk of CAP requiring hospitalization in smokers and those with coexisting medical conditions. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Northwestern Univ, Feinberg Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. RP Yende, S (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Crit Care Med, CRISMA Lab, 3550 Terrace St, Pittsburgh, PA 15261 USA. EM yendes@upmc.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781; Tuomanen, Elaine/0000-0003-0349-8716; Wunderink, Richard/0000-0002-8527-4195 FU NHLBI NIH HHS [NHLBI-RO1HL74104]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIAID NIH HHS [NIAID 27913, NIAID 39482] NR 35 TC 66 Z9 68 U1 2 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2005 VL 172 IS 11 BP 1440 EP 1446 DI 10.1164/rccm.200506-888OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 989TR UT WOS:000233697300015 PM 16166617 ER PT J AU Yu, VL Klugman, KP Wagener, MM Chiou, CC Baddour, LM AF Yu, VL Klugman, KP Wagener, MM Chiou, CC Baddour, LM TI Is combination the only issue? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID COMMUNITY-ACQUIRED PNEUMONIA; THERAPY C1 VA Med Ctr, Pittsburgh, PA USA. Emory Univ, Atlanta, GA 30322 USA. NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Yu, VL (reprint author), VA Med Ctr, Pittsburgh, PA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2005 VL 172 IS 11 BP 1474 EP 1474 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 989TR UT WOS:000233697300023 ER PT J AU Russo, P Catassi, A Cesario, A Imperatori, A Rotolo, N Fini, M Granone, P Dominioni, L AF Russo, P Catassi, A Cesario, A Imperatori, A Rotolo, N Fini, M Granone, P Dominioni, L TI Molecular mechanisms of hexavalent chromium-induced apoptosis in human bronchoalveolar cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE apoptosis; bronchial epithelial cells; hexavalent chromium; p53; PUMA ID COLORECTAL-CANCER CELLS; LUNG-CANCER; MESOTHELIOMA CELLS; EXCISION-REPAIR; DNA LESIONS; P53; ACTIVATION; PATHWAY; GENE; CARCINOGENICITY AB Hexavalent chromium (Cr[VI]) is classified by the International Agency for Research on Cancer as a group I carcinogen. Although the U.S. Occupational Safety and Health Administration was obliged to reduce the permissible exposure limit (PEL), it was reported that U.S. workers continue to be exposed to dangerously high Cr(VI) levels. In this study, we examined the role of p53 and target genes in a bronchoalveolar carcinoma isogenic cell line system and in primary human bronchial epithelial cells. p53-Negative parental H358 cell line, the same line in which the wild-type p53 expression vector (pC53-SN3) was introduced, and cells obtained from biopsies of human bronchus were exposed to chromate. Induction of DNA strand breaks were evaluated by alkaline elution assay, and apoptosis was analyzed by gel ladder, annexin V-PI staining, and ELISA, whereas p53 and target genes were evaluated by Western blots. Although Cr(VI) induced DNA strand breaks in both H358 cell clones, apoptosis was present only in the p53-transfected cells (H358p53(+/+)). In these cells, Cr(Vi)-induced apoptosis is mediated by p53 upregulation of p53-upregulated modulator of apoptosis (PUMA), BAX translocation to mitochondria, cytochrome c release, and caspase-3 activation. In primary human bronchial epithelial cells expressing functional pS3, Cr(VI) induced expression of PUMA and Noxa, which promote apoptosis through BAX. This result establishes p53 as the "necessary" player in Cr(Vi)-induced apoptosis. To the best of our knowledge, this is the first report indicating strict correlation of Cr(VI) apoptosis to PUMA induction on primary human bronchoalveolar cells in short-term cultures. C1 Natl Canc Inst, Lab Transpat Res B Lung Canc, Dept Integrated Med Oncol, I-16132 Genoa, Italy. Univ Genoa, Dept Biol, I-16126 Genoa, Italy. Univ Sacred Heart, Div Gen Thorac Surg, Dept Surg Sci, I-00168 Rome, Italy. Ist Ric Cura Carattere Sci San Raffaele, Clin Resp & Pathol Translat Lab, Rome, Italy. Ist Ric Cura Carattere Sci San Raffaele, Dept Internal Med Sci, Rome, Italy. Univ Insubria, Ctr Thorac Surg, Varese, Italy. RP Russo, P (reprint author), Natl Canc Inst, Lab Transpat Res B Lung Canc, Dept Integrated Med Oncol, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. EM patrizia.russo@istge.it RI CESARIO, Alfredo/O-4215-2015 OI CESARIO, Alfredo/0000-0003-4687-0709 NR 46 TC 38 Z9 39 U1 0 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2005 VL 33 IS 6 BP 589 EP 600 DI 10.1165/rcmb.2005-0213OC PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 990FG UT WOS:000233728000009 PM 16166740 ER PT J AU Mannon, RB Hoffmann, SC Kampen, RL Cheng, OC Kleiner, DE Ryschkewitsch, C Curfman, B Major, E Hale, DA Kirk, AD AF Mannon, RB Hoffmann, SC Kampen, RL Cheng, OC Kleiner, DE Ryschkewitsch, C Curfman, B Major, E Hale, DA Kirk, AD TI Molecular evaluation of BK polyomavirus nephropathy SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article; Proceedings Paper CT American Transplant Congress 2004 CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat DE fibrosis; inflammation; kidney; polyomavirus; rejection; transplant ID RENAL-ALLOGRAFT REJECTION; VIRUS-INFECTION; MESENCHYMAL TRANSITION; INTERSTITIAL NEPHRITIS; TRANSPLANT RECIPIENTS; MESSENGER-RNA; KIDNEY; URINE; TIME; INJURY AB Understanding at a molecular level, the immunologic response of polyomavirus nephropathy (PVN), a critical cause of kidney graft loss, could lead to new targets for treatment and diagnosis. We undertook a transcriptional evaluation of kidney allograft biopsies from recipients with PVN or acute rejection (AR), as well as from recipients with stable allograft function (SF). In both the PVN and AR groups, Banff histologic scores and immunohistochemical analysis of inflammatory infiltrates were similar. Despite their different etiologies, the transcriptional profiles of PVN and AR were remarkably similar. However, transcription of genes previously linked to AR including CD8 (65.9 +/- 18.8) and related molecules IFN-gamma(55.1 +/- 17.0), CXCR3 (49.9 +/- 12.8) and perforin (153.8 +/- 50.4) were significantly higher in PVN compared to AR (30.9 +/- 2.0, 14.0 +/- 7.3, 12.1 +/- 7.3 and 15.6 +/- 3.8-fold, respectively; p < 0.01). Importantly, transcription of molecules associated with graft fibrosis including matrix collagens, TGF beta, MMP2 and 9, as well as markers of epithelial-mesenchymal transformation (EMT) were significantly higher in PVN than AR. Thus, renal allografts with PVN transcribe proinflammatory genes equal in character and larger in magnitude to that seen during acute cellular rejection. BK infection creates a transcriptional microenvironment that promotes graft fibrosis. These findings provide new insights into the intrarenal inflammation of BK infection that promotes graft loss. C1 NIDDKD, Transplantat Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NINDS, Lab Mol Med & Neorosci, NIH, Bethesda, MD 20892 USA. RP Mannon, RB (reprint author), NIDDKD, Transplantat Branch, Bethesda, MD 20892 USA. EM rozm@mail.nih.gov RI Kirk, Allan/B-6905-2012; OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 35 TC 60 Z9 61 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2005 VL 5 IS 12 BP 2883 EP 2893 DI 10.1111/j.1600-6143.2005.01096.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 985WW UT WOS:000233410400010 PM 16303001 ER PT J AU Barillas-Mury, C Kumar, S AF Barillas-Mury, Carolina Kumar, Sanjeev TI Peroxidases mediate refractoriness to Plasmodium infection in Anopheles gambiae SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Barillas-Mury, Carolina; Kumar, Sanjeev] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 6 BP 2 EP 2 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000007 ER PT J AU Lehmann, T Marcet, PL Graham, DH Dahl, ER Dubey, JP AF Lehmann, Tovi Marcet, Paula L. Graham, Douglas H. Dahl, Erica R. Dubey, J. P. TI Worldwide population structure of Toxoplasma gondii SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Lehmann, Tovi] NIAID, NIH, Rockville, MD USA. [Marcet, Paula L.; Graham, Douglas H.; Dahl, Erica R.] Ctr Dis Control & Prevent, DPD, Chamblee, GA USA. [Dubey, J. P.] USDA ARS, Anim & Nat Resources Inst, Anim Parasit Dis Lab, Beltsville, MD USA. RI marcet, Paula/B-1758-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 25 BP 9 EP 9 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000026 ER PT J AU Kamda, JD Tako, EA Goldszmid, R Singer, SM AF Kamda, Joel D. Tako, Ernest A. Goldszmid, Romina Singer, Steven M. TI Dendritic cells, regulatory T-cells and Giardia lamblia infection SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Kamda, Joel D.; Tako, Ernest A.; Singer, Steven M.] Georgetown Univ, Washington, DC USA. [Goldszmid, Romina] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 30 BP 10 EP 10 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000031 ER PT J AU Morens, D AF Morens, David TI Albert Sabin, the armed forces epidemiology board, and epidemic dengue in Hawai'i: A crash program to find the cause of dengue fever during World War II, based on new data from the Albert B. Sabin archives, University of Cincinnati SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Morens, David] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 38 BP 13 EP 13 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000039 ER PT J AU Oliveira, F Kamhawi, S Seitz, AE Pham, VM Fischer, L Ward, J Valenzuela, JG AF Oliveira, Fablano Kamhawi, Shaden Seitz, Amy E. Pham, Van My Fischer, Laurent Ward, Jerrold Valenzuela, Jesus G. TI From transcriptome to immunome: Identification of DTH inducing proteins from a Phlebotomus ariasi salivary gland cDNA library SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Oliveira, Fablano; Kamhawi, Shaden; Seitz, Amy E.; Pham, Van My; Fischer, Laurent; Ward, Jerrold; Valenzuela, Jesus G.] NIH, Rockville, MD USA. RI Oliveira, Fabiano/B-4251-2009 OI Oliveira, Fabiano/0000-0002-7924-8038 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 48 BP 17 EP 17 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000049 ER PT J AU Bergmann-Leitner, ES Duncan, EH Leitner, WW Williams, JL Lyon, JA AF Bergmann-Leitner, Elke S. Duncan, Elizabeth H. Leitner, Wolfgang W. Williams, Jackie L. Lyon, Jeffrey A. TI Gene gun immunization against circumsporozoite protein of Plasmodium berghei induces protective immunity independent of effector T cells SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Bergmann-Leitner, Elke S.; Duncan, Elizabeth H.; Williams, Jackie L.; Lyon, Jeffrey A.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Leitner, Wolfgang W.] Natl Inst Hlth, Bethesda, MD USA. RI Bergmann-Leitner, Elke/B-3548-2011; Leitner, Wolfgang/F-5741-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Leitner, Wolfgang/0000-0003-3125-5922 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 60 BP 21 EP 21 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000061 ER PT J AU Fouda, GGA Leke, RGF Mu, JB Su, XZ Long, C Diouf, A Sama, G Johnson, A Taylor, DW AF Fouda, Genevieve G. A. Leke, Rose G. F. Mu, Jianbing Su, Xiazhuan Long, Carole Diouf, Ababacar Sama, Grace Johnson, Armead Taylor, Diane W. TI Multiplicity of MSP-119 variants among Cameroonian women during pregnancy SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Fouda, Genevieve G. A.; Diouf, Ababacar; Johnson, Armead; Taylor, Diane W.] Georgetown Univ, Washington, DC USA. [Leke, Rose G. F.; Sama, Grace] Univ Yaounde, Ctr Biotechnol, Yaounde, Cameroon. [Mu, Jianbing; Su, Xiazhuan; Long, Carole] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 104 BP 35 EP 35 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000105 ER PT J AU Nylen, S Maurya, R Eidsmo, L Sundar, S Sacks, D AF Nylen, Susanne Maurya, Radeshyam Eidsmo, Liv Sundar, Shyam Sacks, David TI Are regulatory T cells important in the pathology of human visceral leishmaniasis? SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Nylen, Susanne; Sacks, David] NIH, Bethesda, MD 20892 USA. [Maurya, Radeshyam; Sundar, Shyam] Banaras Hindu Univ, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India. [Eidsmo, Liv] Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 111 BP 37 EP 38 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000112 ER PT J AU Nash, TE Talaat, KR Mitre, EE AF Nash, Theodore E. Talaat, Kawsar R. Mitre, Edward E. TI Beneficial use of methotrexate in neurocysticercosis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Nash, Theodore E.; Talaat, Kawsar R.; Mitre, Edward E.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 121 BP 41 EP 41 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000122 ER PT J AU Davis, CW Nguyen, HY Hanna, SL Sanchez, MD Doms, RW Pierson, TC AF Davis, Carl W. Nguyen, Hai-Yen Hanna, Sheri L. Sanchez, Melissa D. Doms, Robert W. Pierson, Theodore C. TI West Nile virus produced in human cells selectively infects cells expressing DC-SIGNR, but not cells expressing DC-SIGN SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Davis, Carl W.; Nguyen, Hai-Yen; Hanna, Sheri L.; Sanchez, Melissa D.; Doms, Robert W.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Pierson, Theodore C.] NIH, Viral Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 278 BP 92 EP 93 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000278 ER PT J AU Coulibaly, YI Dembele, B Diallo, AA Diallo, D Sissoko, M Yalcoue, D Lipner, E Fay, M Doumbo, O Nutman, TB Traore, SF Klion, AD AF Coulibaly, Yaya I. Dembele, Benoit Diallo, Abdallah A. Diallo, Dapa Sissoko, Mady Yalcoue, Daniel Lipner, Ettie Fay, Michael Doumbo, Ogobara Nutman, Thomas B. Traore, Sekou F. Klion, Amy D. TI Safety and efficacy of doxycycline for the treatment of Mansonella perstans infection in an area coendemic for Wuchereria bancrofti SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Coulibaly, Yaya I.; Dembele, Benoit; Diallo, Abdallah A.; Diallo, Dapa; Sissoko, Mady; Yalcoue, Daniel; Doumbo, Ogobara; Traore, Sekou F.] Univ Mali, Sch Med Pharm & Dent, Bamako, Mali. [Lipner, Ettie; Fay, Michael; Nutman, Thomas B.; Klion, Amy D.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 281 BP 93 EP 94 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000281 ER PT J AU Sharma, I Fang, J McCutchan, TF AF Sharma, Indu Fang, Jun McCutchan, Thomas F. TI Dissecting: The translational machinery of plasmodium falciparum SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Sharma, Indu; Fang, Jun; McCutchan, Thomas F.] Natl Inst Hlth, NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S BP 132 EP 132 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000396 ER PT J AU Takala, SL Smith, DL Coulibaly, D Thera, MA Ouattara, A Stine, C Doumbo, O Plowe, C AF Takala, Shannon L. Smith, David L. Coulibaly, Drissa Thera, Mahamadou A. Ouattara, Amed Stine, Colin Doumbo, Ogobara Plowe, Christopher TI A high-throughput method for genotyping the 19kda region of plasmodium falciparum merozoite surface protein 1 (MSP-1) using allele frequency determination and haplotype estimation SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Takala, Shannon L.; Ouattara, Amed; Stine, Colin; Plowe, Christopher] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Smith, David L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Coulibaly, Drissa; Thera, Mahamadou A.; Doumbo, Ogobara] Univ Bamako, Bamako, Mali. RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 398 BP 132 EP 133 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000397 ER PT J AU Aebig, JA Mullen, GE Dobrescu, G Rausch, K Lambert, L Long, CA Saul, A Miles, AP AF Aebig, Joan A. Mullen, Gregory E. Dobrescu, Gelu Rausch, Kelly Lambert, Lynn Long, Carole A. Saul, Allan Miles, Aaron P. TI CPG binding to malaria vaccine candidates: Interactions and immune responses SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Aebig, Joan A.; Mullen, Gregory E.; Dobrescu, Gelu; Rausch, Kelly; Lambert, Lynn; Long, Carole A.; Saul, Allan; Miles, Aaron P.] NIAID, Malaria Vaccine Dev Branch, Natl Inst Hlth, Rockville, MD USA. OI Saul, Allan/0000-0003-0665-4091 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 411 BP 136 EP 137 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000410 ER PT J AU Stockelman, MG Jones, TR Lucas, C Tsai, CW Salas, C Salazar, M Utz, GC Martin, LB Narum, DL AF Stockelman, Michael G. Jones, Trevor R. Lucas, Carmen Tsai, Chia-Wen Salas, Carola Salazar, Milagros Utz, Gregory C. Martin, Laura B. Narum, David L. TI Immunogenicity and protective efficacy in Aotus monkeys of recombinant Plasmodium falciparum MSP142 and EBP2/BAEBL RII protein vaccines SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Stockelman, Michael G.] USN, Med Res Ctr, Silver Spring, MD USA. [Jones, Trevor R.] USN, Med Res Unit 2, Jakarta, Indonesia. [Lucas, Carmen; Salas, Carola; Salazar, Milagros] USN, Med Res Ctr Detachment, Lima, Peru. [Utz, Gregory C.] USN, San Diego Med Ctr, San Diego, CA USA. [Tsai, Chia-Wen; Martin, Laura B.; Narum, David L.] NIAID, Rockville, MD USA. RI Martin, Laura/N-1789-2013 OI Martin, Laura/0000-0002-4431-4381 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 410 BP 136 EP 136 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000409 ER PT J AU Rausch, KM Dobrescu, G McClellan, HA Tsai, CW Long, CA Saul, A Miles, AP AF Rausch, Kelly M. Dobrescu, Gelu McClellan, Holly A. Tsai, Chiawei W. Long, Carole A. Saul, Allan Miles, Aaron P. TI MONTANIDE ISA 51 vaccines: Protecting antigens from modification, quality control of emulsions, and comparative immunogenicity of vaccine formulations SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Rausch, Kelly M.; Dobrescu, Gelu; McClellan, Holly A.; Tsai, Chiawei W.; Long, Carole A.; Saul, Allan] NIAID, NIH, Malaria Vaccine Dev Branch, Rockville, MD USA. [Miles, Aaron P.] George Washington Univ, Dept Microbiol Immunol & Trop Med, Human Hookworm Vaccine Initiat, Washington, DC USA. OI Saul, Allan/0000-0003-0665-4091 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 414 BP 137 EP 138 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000413 ER PT J AU Zhu, D Saul, A Miles, A AF Zhu, Daming Saul, Allan Miles, Aaron TI A quantitative slot blot assay for bacterial host cell protein impurities in recombinant proteins expressed in E. coli SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Zhu, Daming; Saul, Allan] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Miles, Aaron] NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD USA. OI Saul, Allan/0000-0003-0665-4091 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 419 BP 139 EP 139 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000418 ER PT J AU Molina-Cruz, A Kumar, S Gupta, L DeJong, R Barillas-Mury, C AF Molina-Cruz, Alvaro Kumar, Sanjeev Gupta, Lalita DeJong, Randall Barillas-Mury, Carolina TI Effect of Plasmodium berghi infection on Anopheles gambiae midgut responses to oxidative stress SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Molina-Cruz, Alvaro; Kumar, Sanjeev; Gupta, Lalita; DeJong, Randall; Barillas-Mury, Carolina] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 431 BP 143 EP 143 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000430 ER PT J AU Yaro, AS Dao, A Adamou, A Toure, AM Traore, SF Lehmann, T AF Yaro, Alpha S. Dao, Adama Adamou, Abdoulaye Toure, Abdoulaye M. Traore, Sekou F. Lehmann, Tovi TI The relationship between female size and egg batch size does not vary between the molecular forms of Anopheles gambiae sl in Mali SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Yaro, Alpha S.; Dao, Adama; Adamou, Abdoulaye; Toure, Abdoulaye M.; Traore, Sekou F.] MRTC, Bamako, Mali. [Lehmann, Tovi] NIH, LMVR, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 451 BP 149 EP 149 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000450 ER PT J AU Diabate, A Dabire, R Millogo, N Gimnig, J Hawley, WA Lehmann, T AF Diabate, Abdoulaye Dabire, Rock Millogo, Niama Gimnig, John Hawley, William A. Lehmann, Tovi TI Can predator avoidance behavior explain the spatial segregation between the molecular forms of Anopheles gambiae? SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Diabate, Abdoulaye; Lehmann, Tovi] NIAID, NIH, Rockville, MD USA. [Dabire, Rock; Millogo, Niama] IRSS Ctr Muraz Lab Parasitol Entomol, Bobo Dioulasso, Burkina Faso. [Hawley, William A.] Ctr Dis Control & Prevent, DPD, Chamblee, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 462 BP 152 EP 153 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000461 ER PT J AU Kumar, S Barillas-Mury, C AF Kumar, Sanjeev Barillas-Mury, Carolina TI Cell biology of Plasmodium falciparum midgut invasion of Anopheline mosquitoes SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Kumar, Sanjeev; Barillas-Mury, Carolina] NIAID, NIH, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 463 BP 153 EP 153 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000462 ER PT J AU Doumbia, S Sogoba, N Baber, I Keita, M Manko, A Toure, MB Traore, SF Ribeiro, J AF Doumbia, Seydou Sogoba, Nofomon Baber, Ibrahima Keita, Moussa Manko, A. Toure, Mahamadou B. Traore, Sekou F. Ribeiro, Jose TI Monitoring larval habitats and malaria transmission in areas of seasonal transmission: Significance for a dry season vector control strategy SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Doumbia, Seydou; Sogoba, Nofomon; Baber, Ibrahima; Keita, Moussa; Manko, A.; Toure, Mahamadou B.; Traore, Sekou F.] Malaria Res & Training Ctr, Bamako, Mali. [Ribeiro, Jose] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 483 BP 159 EP 159 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000482 ER PT J AU Thompson, RW Cheever, AW Ellies, LG Mentink-Kane, M Wynn, TA AF Thompson, Robert W. Cheever, Allen W. Ellies, Lesley G. Mentink-Kane, Margaret Wynn, Thomas A. TI Cationic amino acid transporter-2 negatively regulates hepatic pathology during murine schistosomiasis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Thompson, Robert W.; Cheever, Allen W.; Mentink-Kane, Margaret; Wynn, Thomas A.] NIAID, NIH, LPD, Bethesda, MD 20892 USA. [Ellies, Lesley G.] Univ Calif San Diego, Sch Med, UCSD Canc Ctr, Dept Med, La Jolla, CA 92093 USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 496 BP 163 EP 163 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000495 ER PT J AU Hanley, KA Schirtzinger, EE Hanson, CT Whitehead, SS AF Hanley, Kathryn A. Schirtzinger, Erin E. Hanson, Christopher T. Whitehead, Stephen S. TI In vitro and in vivo phenotypes of dengue virus serotype 3, subtype III lineages associated with mild or severe disease outbreaks SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Hanley, Kathryn A.; Schirtzinger, Erin E.] New Mexico State Univ, Las Cruces, NM 88003 USA. [Hanson, Christopher T.; Whitehead, Stephen S.] NIH, Lab Infect Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 518 BP 169 EP 170 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000517 ER PT J AU Kotsyfakis, M Andersen, JF Francischetti, IM Ribeiro, JM AF Kotsyfakis, Michaill Andersen, John F. Francischetti, Ivo M. Ribeiro, Jose M. TI Ixodes scapularis can suppress host cysteine protease activity in the sites of blood feeding SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Kotsyfakis, Michaill; Andersen, John F.; Francischetti, Ivo M.; Ribeiro, Jose M.] NIAID, NIH, Rockville, MD USA. RI Kotsyfakis, Michail/G-9525-2014 OI Kotsyfakis, Michail/0000-0002-7526-1876 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 547 BP 180 EP 180 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000546 ER PT J AU Blaney, JE Hanson, CT Firestone, CY Durbin, AP Murphy, BR Whitehead, SS AF Blaney, Joseph E. Hanson, Christopher T. Firestone, Cai-Yen Durbin, Anna P. Murphy, Brian R. Whitehead, Stephen S. TI Progress on live-attenuated dengue virus vaccines containing a tetravalent formulation of recombinant viruses SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Blaney, Joseph E.; Hanson, Christopher T.; Firestone, Cai-Yen; Murphy, Brian R.; Whitehead, Stephen S.] NIAID, NIH, Bethesda, MD 20892 USA. [Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 551 BP 181 EP 181 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000550 ER PT J AU McArthur, JH Marron, JA Thumar, B Wanionek, K Lovchik, J Karron, RA Murphy, BR Blaney, JE Whitehead, SS Durbin, AP AF McArthur, Julie H. Marron, Jennifer A. Thumar, Bhavin Wanionek, Kimberli Lovchik, Janece Karron, Ruth A. Murphy, Brian R. Blaney, Joseph E. Whitehead, Stephen S. Durbin, Anna P. TI The live attenuated dengue serotype 1 vaccine RDEN4 Delta 30 is safe and immunogenic in healthy volunteers SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [McArthur, Julie H.; Marron, Jennifer A.; Thumar, Bhavin; Wanionek, Kimberli; Lovchik, Janece; Karron, Ruth A.; Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Murphy, Brian R.; Whitehead, Stephen S.] NIAID, NIH, Bethesda, MD 20892 USA. [Blaney, Joseph E.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 550 BP 181 EP 181 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000549 ER PT J AU Takala, SL Coulibaly, D Thera, MA Dicko, A Smith, DL Guindo, AB Kone, AK Ouattara, A Djjmde, A Sehdev, P Lyke, K Diallo, D Plowe, CV Doumbo, OK AF Takala, Shannon L. Coulibaly, Drissa Thera, Mahamadou A. Dicko, Alassane Smith, David L. Guindo, Ando B. Kone, Abdoulaye K. Ouattara, Amed Djjmde, Abdoulaye Sehdev, Paul Lyke, Kirsten Diallo, Dapa Plowe, Christopher V. Doumbo, Ogobara K. TI Prevalence of merozoite surface protein-1 19kda haplotypes at a malaria vaccine testing site in Bandiagara, Mali SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Takala, Shannon L.; Ouattara, Amed; Sehdev, Paul; Lyke, Kirsten; Plowe, Christopher V.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Coulibaly, Drissa; Thera, Mahamadou A.; Dicko, Alassane; Guindo, Ando B.; Kone, Abdoulaye K.; Djjmde, Abdoulaye; Diallo, Dapa; Doumbo, Ogobara K.] Univ Bamako, Bamako, Mali. [Smith, David L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 556 BP 183 EP 183 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000555 ER PT J AU Bergmann-Leitner, ES Duncan, EH Khan, F Williams, JL Leitner, WW Angov, E Tsokos, GC Lyon, JA AF Bergmann-Leitner, Elike S. Duncan, Elizabeth H. Khan, Farhat Williams, Jackie L. Leitner, Wolfgang W. Angov, Evelina Tsokos, George C. Lyon, Jeffrey A. TI C3d binding to the circumsporozoite protein carboxy-terminus deviates immunity against malaria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Bergmann-Leitner, Elike S.; Duncan, Elizabeth H.; Khan, Farhat; Williams, Jackie L.; Angov, Evelina; Tsokos, George C.; Lyon, Jeffrey A.] Walter Reed Army Inst, Silver Spring, MD USA. [Leitner, Wolfgang W.] NIH, Bethesda, MD 20892 USA. RI Bergmann-Leitner, Elke/B-3548-2011; Leitner, Wolfgang/F-5741-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Leitner, Wolfgang/0000-0003-3125-5922 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 560 BP 185 EP 185 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000559 ER PT J AU Nkrumah, L Moura, P Yu, M Patel, J Ferdig, MT Wellems, TE Fidock, DA AF Nkrumah, Louis Moura, Pedro Yu, Min Patel, Jigar Ferdig, Michael T. Wellems, Thomas E. Fidock, David A. TI Genetic analysis of the Plasmodium falciparum sodium-proton exchanger (pfnhe) and its contribution to quinine resistance SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Nkrumah, Louis; Moura, Pedro; Yu, Min; Fidock, David A.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Patel, Jigar; Ferdig, Michael T.] Univ Notre Dame, Notre Dame, IN 46556 USA. [Wellems, Thomas E.] NIAID, NIH, Bethesda, MD 20892 USA. RI Ferdig, Michael/C-6627-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 598 BP 197 EP 198 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001021 ER PT J AU Kone, A Mu, J Sagara, I Plowe, CV Doumbo, OK Wellems, TE Djimde, AA AF Kone, Aminatou Mu, Jianbing Sagara, Issaka Plowe, Christopher V. Doumbo, Ogobara K. Wellems, Thomas E. Djimde, Abdoulaye A. TI PfNHE polymorphisms are associated with quinine usage in Mali SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Kone, Aminatou; Sagara, Issaka; Doumbo, Ogobara K.; Djimde, Abdoulaye A.] Univ Bamako, Bamako, Mali. [Mu, Jianbing; Wellems, Thomas E.] Natl Inst Hlth, Rockville, MD USA. [Plowe, Christopher V.] Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 599 BP 198 EP 198 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001022 ER PT J AU Chretien, JP Prudhomme, W Awuondo, K Tang, D Remich, S Ogutu, B Nanakorn, A Ohrt, C AF Chretien, Jean-Paul Prudhomme, Wendy Awuondo, Ken Tang, Doug Remich, Shon Ogutu, Bernard Nanakorn, Ampon Ohrt, Colin TI Quality assurance for malaria clinical trial microscopy based on theoretical and empirical evidence SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Chretien, Jean-Paul] DoD Global Emerging Infect Surveillance & Respose, Silver Spring, MD USA. [Prudhomme, Wendy] Natl Inst Hlth, Bethesda, MD USA. [Awuondo, Ken; Remich, Shon; Ogutu, Bernard; Nanakorn, Ampon] USA, Med Res Unit Kenya, Kisumu, Kenya. [Ohrt, Colin] Walter Reed Army Inst Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 604 BP 200 EP 200 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001027 ER PT J AU Kim, YJ Law, M Nutman, TB AF Kim, Yae-Jean Law, Melissa Nutman, Thomas B. TI Brugia malayi L3 larvae secrete a chemotactic factor for human eosinophils that mimics a CCR3 ligand SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Kim, Yae-Jean; Law, Melissa; Nutman, Thomas B.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 608 BP 201 EP 201 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001031 ER PT J AU Mitre, E Nutman, TB AF Mitre, Edward Nutman, Thomas B. TI CD4+T-cells are the predominant IL-10 producing cells in the circulation of filarial-infected patients SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Mitre, Edward; Nutman, Thomas B.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 612 BP 202 EP 202 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001035 ER PT J AU Taylor, MD Wilson, MS Finney, CA Harris, A Allen, JE Maizels, RM AF Taylor, Matthew D. Wilson, Mark S. Finney, Constance A. Harris, Anjanette Allen, Judith E. Maizels, Rick M. TI Helminth induced regulatory T cells: Their role in the establishment and persistence of infection, and control of allergy SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Taylor, Matthew D.; Finney, Constance A.; Harris, Anjanette; Allen, Judith E.; Maizels, Rick M.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Wilson, Mark S.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 613 BP 202 EP 203 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001036 ER PT J AU Tallaat, KR Nutman, TB AF Tallaat, Kawsar R. Nutman, Thomas B. TI Brugia malayi microfilariae inhibit Mycobacterium tuberculosis-induced IFN Gamma production by CD4+ T cells in a human coinfection model SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Tallaat, Kawsar R.; Nutman, Thomas B.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 614 BP 203 EP 203 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001037 ER PT J AU O'Meara, WP McKenzie, FE AF O'Meara, Wendy Prudhomme McKenzie, F. Ellis TI The impact of diagnostic technique on vaccine efficacy measurements in clinical trials SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [O'Meara, Wendy Prudhomme; McKenzie, F. Ellis] Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 631 BP 208 EP 208 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001054 ER PT J AU Anderson, JM Miller, NJ Reynoso, D Mather, TN Valenzuela, JG AF Anderson, Jennifer M. Miller, Nathan J. Reynoso, David Mather, Thomas N. Valenzuela, Jesus G. TI A high throughput screening method to identify tick salivary antigens eliciting a cellular immune response in tick sensitized hosts SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Anderson, Jennifer M.; Reynoso, David; Valenzuela, Jesus G.] NIH, Rockville, MD USA. [Miller, Nathan J.; Mather, Thomas N.] Univ Rhode Isl, Kingston, RI 02881 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 643 BP 212 EP 212 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001066 ER PT J AU Sun, PF Stuelten, C Arany, P Porter, K Roberts, A Burgess, T AF Sun, Peifang Stuelten, Christina Arany, Praveen Porter, Kevin Roberts, Anita Burgess, Timothy TI Dengue virus induces production of transforming growth factor B1 - A potential mechanism for immune regulation SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Sun, Peifang; Porter, Kevin; Burgess, Timothy] USN, Med Res Ctr, Silver Spring, MD USA. [Stuelten, Christina; Arany, Praveen; Roberts, Anita] NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 731 BP 241 EP 242 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001154 ER PT J AU Lipner, EM Weill, GJ Dembele, N Suliman, S Alley, WS Toe, L Boatin, B Nutman, TB AF Lipner, Ettie M. Weill, Gary J. Dembele, Noumouza Suliman, S. Alley, William Soumbey Toe, Laurent Boatin, Boayke Nutman, Thomas B. TI Field applicability of an ICT rapid-format Ov16 antibody test to assess onchocerciasis control efforts in endemic regions SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Lipner, Ettie M.; Nutman, Thomas B.] NIAID, NIH, Bethesda, MD 20892 USA. [Weill, Gary J.] Washington Univ, Sch Med, St Louis, MO USA. [Dembele, Noumouza; Suliman, S.; Alley, William Soumbey; Toe, Laurent; Boatin, Boayke] Onchocerciasis Control Program, Ouagadougou, Burkina Faso. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 763 BP 251 EP 252 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001186 ER PT J AU DeLong, CR Kim, YJ Nutman, TB AF DeLong, Christine R. Kim, Yae-Jean Nutman, Thomas B. TI Quantification of number of somatic cells in Brugia malayi microfilariae SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [DeLong, Christine R.; Kim, Yae-Jean; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 766 BP 252 EP 253 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001189 ER PT J AU Michelin, R Oladeinde, F Williams, A Frederick, L Kinyua, A Shaw, R Lobban, K Leitner, W Stewart, J AF Michelin, Ruel Oladeinde, Frederick Williams, Arthur Frederick, Laafayette Kinyua, Anthony Shaw, Roosevelt Lobban, Kathleen Leitner, Wolfgang Stewart, Juarine TI Nematicidal activity of compounds from new strain of Bacillus mojavensis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Michelin, Ruel; Oladeinde, Frederick; Williams, Arthur; Kinyua, Anthony; Shaw, Roosevelt; Stewart, Juarine] Morgan State Univ, Baltimore, MD 21239 USA. [Frederick, Laafayette] Howard Univ, Washington, DC 20059 USA. [Lobban, Kathleen] Univ W Indies, Kingston 7, Jamaica. [Leitner, Wolfgang] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 769 BP 253 EP 254 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001192 ER PT J AU Gerena, L Dow, GS Ellis, WY Caridha, D Heady, TN Coyne, PE Magill, AJ Kyle, DE Milhous, WK AF Gerena, Lucia Dow, Geoffrey S. Ellis, William Y. Caridha, Diana Heady, Tiffany N. Coyne, Phillip E. Magill, Alan J. Kyle, Dennis E. Milhous, Wilbur K. TI Development of stereoselective lariam analogs would have no advantage over lariam against emerging resistance in West Africa SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Gerena, Lucia; Dow, Geoffrey S.; Ellis, William Y.; Caridha, Diana; Heady, Tiffany N.; Magill, Alan J.; Kyle, Dennis E.; Milhous, Wilbur K.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Coyne, Phillip E.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 818 BP 269 EP 269 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001241 ER PT J AU Sa, JM Yamamoto, MM Fernadez-Becerra, C Wellems, TE del Portillo, HA AF Sa, Juliana M. Yamamoto, Marcio M. Fernadez-Becerra, Carmen Wellems, Thomas E. del Portillo, Hernando A. TI Modulation of chloroquine sensitivity in Plasmodium falciparum by over-expression of a P-vivax ortholog of the chloroquine resistance transporter gene, PfCRT SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Sa, Juliana M.; Wellems, Thomas E.] NIH, Rockville, MD USA. [Yamamoto, Marcio M.; Fernadez-Becerra, Carmen; del Portillo, Hernando A.] Univ Sao Paulo, Sao Paulo, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 835 BP 274 EP 275 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001258 ER PT J AU O'Meara, WP Smith, D McKenzie, FE AF O'Meara, Wendy Prudhomme Smith, David McKenzie, F. Ellis TI Potential impact of intermittent preventive treatment for infants on the spread of drug resistant malaria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [O'Meara, Wendy Prudhomme; Smith, David; McKenzie, F. Ellis] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 836 BP 275 EP 275 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001259 ER PT J AU Koilta, OA Bagayoko, MW Sissako, A Coulibaly, A Sangare, L Mahamadou, I Colborn, J Janka, J Wellems, TE Krogstad, DJ AF Koilta, Ousmane A. Bagayoko, Mamadou W. Sissako, Aliou Coulibaly, Aliou Sangare, Lansana Mahamadou, Ibrah Colborn, James Janka, Jacqueline Wellems, Thomas E. Krogstad, Donald J. TI Incidence of malarial infection and disease among children with hemoglobin S in the malaria-endemic village of Missira in Kolokani, Mali SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Colborn, James; Krogstad, Donald J.] Tulane Univ, New Orleans, LA USA. [Koilta, Ousmane A.; Bagayoko, Mamadou W.; Sissako, Aliou; Coulibaly, Aliou; Sangare, Lansana; Mahamadou, Ibrah] Univ Bamako, Fac Sci, Bamako, Mali. [Janka, Jacqueline; Wellems, Thomas E.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 858 BP 283 EP 283 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001281 ER PT J AU Quakyi, IA Leke, R Zhou, A Befidi-Mengue, R Lohoue, J Thuita, L Christenson, K Tchinda, V Kouontchou, S Nyonglema, P Meli, J Stowers, A Kaslow, D Taylor, DW Johnson, AH AF Quakyi, Isabella A. Leke, Rose Zhou, Ainong Befidi-Mengue, Rosa Lohoue, Julienne Thuita, Lucy Christenson, Kit Tchinda, Viviane Kouontchou, Samuel Nyonglema, Philomena Meli, Jean Stowers, Anthony Kaslow, David Taylor, Diane Wallace Johnson, Armead H. TI Naturally acquired antibodies to seven variants of the recombinant Plasmodium falciparum merozoite surface protein 1 19-kilodalton domain provide protection against asymptomatic parasitemia SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Quakyi, Isabella A.] Univ Ghana, Coll Hlth Sci, Legon, Accra, Ghana. [Leke, Rose; Befidi-Mengue, Rosa; Lohoue, Julienne; Tchinda, Viviane; Kouontchou, Samuel; Nyonglema, Philomena; Meli, Jean] Univ Yaounde 1, Fac Med& Biomed Sci, Yaounde, Cameroon. [Zhou, Ainong; Thuita, Lucy; Christenson, Kit; Taylor, Diane Wallace; Johnson, Armead H.] Georgetown Univ, Dept Biol, Washington, DC 20057 USA. [Zhou, Ainong; Thuita, Lucy; Christenson, Kit; Taylor, Diane Wallace; Johnson, Armead H.] Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. [Stowers, Anthony; Kaslow, David] NIAID, Malaria Vaccine Dev Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 860 BP 284 EP 284 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001283 ER PT J AU Dent, AE Chelimo, K Sumba, PO Tisch, D McHugh, MM John, CC Singh, S Long, C Kazura, JW Moormann, AM AF Dent, Arlene E. Chelimo, Kiprotich Sumba, Peter Odada Tisch, Daniel McHugh, Marilyn M. John, Chandy C. Singh, Sanjay Long, Carole Kazura, James W. Moormann, Ann M. TI Antibodies to CSP and MSP-1(42KDA) correlate with protection from Plasmodium falciparum infection in both adults and children while antibodies to MSP-1(19kDa) are protective only for children SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Dent, Arlene E.; McHugh, Marilyn M.; Kazura, James W.; Moormann, Ann M.] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA. [Chelimo, Kiprotich; Sumba, Peter Odada] Kenya Govt Med Res Ctr, Ctr Vector Biol & Control Res, Kisumu, Kenya. [John, Chandy C.] Case Western Reserve Univ, Rainbow Ctr Int Hlth, Cleveland, OH 44106 USA. [Singh, Sanjay; Long, Carole] NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 864 BP 285 EP 285 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001287 ER PT J AU Iriko, H Takeo, S Jin, L Kaneko, O Torii, M Sattabongkot, J Singh, S Sawasaki, T Endo, Y Tsuboi, T AF Iriko, Hideyuki Takeo, Satoru Jin, Ling Kaneko, Osamu Torii, Motomi Sattabongkot, Jetsumon Singh, Sanjay Sawasaki, Tatsuya Endo, Yaeta Tsuboi, Takafumi TI Screening of novel malaria transmission-blocking vaccine candidates using wheat germ cell-free protein synthesis system SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Iriko, Hideyuki; Takeo, Satoru; Jin, Ling; Torii, Motomi; Sawasaki, Tatsuya; Endo, Yaeta; Tsuboi, Takafumi] Ehime Univ, Cell Free Sci & Technol Res Ctr, Matsuyama, Ehime, Japan. [Kaneko, Osamu] Ehime Univ, Sch Med, Dept Mol Parasitol, Toon, Japan. [Sattabongkot, Jetsumon] USAMC AFRIMS, Dept Entomol, Bangkok, Thailand. [Singh, Sanjay] NIAID, Malaria Vaccine Dev Branch, Natl Inst Hlth, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 885 BP 292 EP 292 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001308 ER PT J AU Narum, DL Ogun, SA Batchelor, A Holder, AA AF Narum, David L. Ogun, Solabomi A. Batchelor, Adrian Holder, Anthony A. TI Studies with the rodent malaria Plasmodium yoelii support development of a multicomponent blood stage malaria vaccine SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Narum, David L.] Natl Inst Hlth, Rockville, MD USA. [Ogun, Solabomi A.; Holder, Anthony A.] Natl Inst Med Res, London NW7 1AA, England. [Batchelor, Adrian] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. RI Holder, Anthony/A-7554-2013 OI Holder, Anthony/0000-0002-8490-6058 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 888 BP 293 EP 293 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001311 ER PT J AU Jimenez, AJ Calvo, E James, A AF Jimenez, Alyssa J. Calvo, Eric James, Anthony TI Nanos (NOS) gene of the vector mosquito, Anopheles stephensi: A potential use for a developmentally regulated gene in a gene drive system SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Jimenez, Alyssa J.; James, Anthony] Univ Calif Irvine, Irvine, CA USA. [Calvo, Eric] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 894 BP 294 EP 294 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001317 ER PT J AU de Merida, AM Morales-Betoulle, ME Lopez, MR Molina, E Rosales, S Molina-Cruz, A Black, WC AF de Merida, Ana Maria Morales-Betoulle, Maria Eugenia Lopez, Maria Rene Molina, Eduviges Rosales, Sandra Molina-Cruz, Alvaro Black, William C. TI Population structure of Aedes aegypti in Central America and the Caribbean SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [de Merida, Ana Maria; Morales-Betoulle, Maria Eugenia; Lopez, Maria Rene; Molina, Eduviges; Rosales, Sandra] Univ Valle Guatemala MERTU, Ctr Dis Control & Prevent, Guatemala City, Guatemala. [Molina-Cruz, Alvaro] Natl Inst Hlth, Bethesda, MD USA. [Black, William C.] Colorado State Univ, Ft Collins, CO 80523 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 908 BP 298 EP 298 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001331 ER PT J AU DeJong, RJ Miller, LM Barillas-Mury, C AF DeJong, Randall J. Miller, Lisa M. Barillas-Mury, Carolina TI Catalase alleles and fecundity in Anopheles gambiae SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [DeJong, Randall J.; Barillas-Mury, Carolina] NIH, Rockville, MD USA. [Miller, Lisa M.] Colorado State Univ, Ft Collins, CO 80523 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 931 BP 305 EP 305 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001354 ER PT J AU Baber, I Nafomon, S Doumbia, S Keita, M Sacko, A Maiga, M Diallo, B Koumare, S Dolo, G Traore, SF Ribeiro, J AF Baber, Ibrahima Nafomon, Sogoba Doumbia, Seydou Keita, Moussa Sacko, Adama Maiga, Mamoudou Diallo, Brehima Koumare, Sekou Dolo, Guimoko Traore, Sekou F. Ribeiro, Jose TI Survival of Anopheles gambiae S. L. larvae during the dry season along the niger river bed in Mali SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Baber, Ibrahima; Nafomon, Sogoba; Doumbia, Seydou; Keita, Moussa; Sacko, Adama; Maiga, Mamoudou; Diallo, Brehima; Koumare, Sekou; Dolo, Guimoko; Traore, Sekou F.] Malaria Res & Training Ctr, Bamako, Mali. [Ribeiro, Jose] NIAID, LMVR, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 943 BP 309 EP 309 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001366 ER PT J AU Babu, S Blauvelt, CP Kumaraswami, V Nutman, TB AF Babu, Subash Blauvelt, Carla P. Kumaraswami, V. Nutman, Thomas B. TI Impairment of both Th1 and Th2 responses in lymphatic filariasis: A role for T cell extrinsic (TGF beta, IDO, CTLA-4, PD-1) and intrinsic (FOXP3 and E3 ubiquitin ligases) factors SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Babu, Subash; Blauvelt, Carla P.; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA. [Kumaraswami, V.] TRC, Madras, Tamil Nadu, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 997 BP 327 EP 327 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001420 ER PT J AU Pesce, JT Kaviratne, MK Cheever, AW Young, DA Collins, M Grusby, MJ Urban, JF Wynn, TA AF Pesce, John T. Kaviratne, Mallika Kaviratne Cheever, Allen W. Young, Deborah A. Collins, Mary Grusby, Michael J. Urban, Joseph F. Wynn, Thomas A. TI IL-21 receptor deficiency decreases Th2 responses following helminth infection SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Pesce, John T.; Kaviratne, Mallika Kaviratne; Wynn, Thomas A.] NIAID, NIH, LPD, Bethesda, MD 20892 USA. [Cheever, Allen W.] Biomed Res Inst, Rockville, MD 20852 USA. [Young, Deborah A.; Collins, Mary] Wyeth Ayerst Res, Cambridge, MA USA. [Grusby, Michael J.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Urban, Joseph F.] USDA, Beltsville Human Nutr Res Ctr, Nutr Requirements & Funct Lab, Beltsville, MD 20705 USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 999 BP 328 EP 328 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001422 ER PT J AU Gilden, K Kubofcik, J Siegel, R Nutman, TB AF Gilden, K. Kubofcik, Joseph Siegel, Richard Nutman, Thomas B. TI Live microfilariae of Brugia Malayi induce cell death in dendritic cells through a trail-dependent mechanism SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Gilden, K.; Kubofcik, Joseph; Nutman, Thomas B.] NIAID, NIH, Bethesda, MD 20892 USA. [Siegel, Richard] NIAMS, NIH, Bethesda, MD USA. RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1009 BP 331 EP 332 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001432 ER PT J AU Anderson, C Beverley, SM Sacks, DL AF Anderson, Charles Beverley, Steve M. Sacks, David L. TI A naturally occuring strain of Leishmania Major which is lacking side chain galactose residues on phosphoglycans reveals a role for the immune response to the presence of sugars SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Anderson, Charles; Sacks, David L.] NIAID, NIH, Bethesda, MD 20892 USA. [Beverley, Steve M.] Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1010 BP 332 EP 332 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001433 ER PT J AU Oliphant, T Nybakken, G Nelson, C Chen, B Engle, M Pierson, T Fremont, D Diamond, M AF Oliphant, Theodore Nybakken, Grant Nelson, Christopher Chen, Beverley Engle, Michael Pierson, Theodore Fremont, Daved Diamond, Michael TI The molecular basis of neutralization by antibodies that recognize domains I and II of west Nile virus envelope protein SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Oliphant, Theodore; Nybakken, Grant; Nelson, Christopher; Chen, Beverley; Engle, Michael; Fremont, Daved; Diamond, Michael] Washington Univ, Sch Med, St Louis, MO USA. [Pierson, Theodore] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1019 BP 334 EP 335 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001442 ER PT J AU Ess, JL Oliphant, TL Xu, Q Freemont, DH Diamond, MS Pierson, TC AF Ess, Jessica L. Oliphant, Theodore L. Xu, Qing Freemont, Daved H. Diamond, Michael S. Pierson, Ted C. TI The development of rapid and quantitative methods for measuring anti body-mediated neutralization and enhancement of West Nile virus infection SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Ess, Jessica L.; Xu, Qing; Pierson, Ted C.] NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA. [Oliphant, Theodore L.; Diamond, Michael S.] Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USA. [Freemont, Daved H.; Diamond, Michael S.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Dept Med, Sch Med, St Louis, MO 63110 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1020 BP 335 EP 335 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001443 ER PT J AU Keane-Myers, AM Urban, J Norris, H Bundoc, V Boesen, A Wetzel, B AF Keane-Myers, Andrea M. Urban, Joseph Norris, Hillary Bundoc, Virgilio Boesen, Agnieszka Wetzel, Brittany TI Abrogation of allergic inflammation by Ascaris Suum pseudoceolomic fluid (pcf) SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Keane-Myers, Andrea M.; Norris, Hillary; Bundoc, Virgilio; Boesen, Agnieszka; Wetzel, Brittany] NIH, Rockville, MD USA. [Urban, Joseph] USDA, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1027 BP 337 EP 337 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001450 ER PT J AU Heinrichs, V Mundorff, E Lohre, JA West, LL Kuznetsova, MA Howard, TA Kortok, MM Marsh, K Makobongo, MO Liu, X LaClair, TA Long, CA Whalen, RG Locher, CP AF Heinrichs, Volker Mundorff, Emily Lohre, Jack A. West, Leslie L. Kuznetsova, Maria A. Howard, Tevis A. Kortok, Moses M. Marsh, Kevin Makobongo, Morris O. Liu, Xia LaClair, Tracy A. Long, Carole A. Whalen, Robert G. Locher, Christopher P. TI Improvement of Plasmodium Falciparum erythrocyte membrane protein-1 (PfEMP-1) vaccine antigens using directed molecular evolution SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Heinrichs, Volker; Mundorff, Emily; Lohre, Jack A.; West, Leslie L.; Kuznetsova, Maria A.; Whalen, Robert G.; Locher, Christopher P.] Maxygen Inc, Redwood City, CA USA. [Howard, Tevis A.; Kortok, Moses M.; Marsh, Kevin] Kenya Govt Med Res Ctr, Kilifi, Kenya. [Makobongo, Morris O.; Liu, Xia; LaClair, Tracy A.; Long, Carole A.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1031 BP 339 EP 339 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001454 ER PT J AU Medina, S Long, CA Dobrescu, G Aebig, JA Orcutt, A Zhou, H Moretz, SE Miller, LH Saul, A Martin, LB AF Medina, Sarimar Long, Carole A. Dobrescu, Gelu Aebig, Joan A. Orcutt, Andrew Zhou, Hong Moretz, Samuel E. Miller, Louis H. Saul, Allan Martin, Laura B. TI Msp1(42) based vaccines: Improving the immunogenicity of alhydrogel formulations by the addition of CPG 7909 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Medina, Sarimar; Long, Carole A.; Dobrescu, Gelu; Aebig, Joan A.; Orcutt, Andrew; Zhou, Hong; Moretz, Samuel E.; Miller, Louis H.; Saul, Allan; Martin, Laura B.] NIAID, MVDB, NIH, Rockville, MD USA. RI Martin, Laura/N-1789-2013; OI Martin, Laura/0000-0002-4431-4381; Saul, Allan/0000-0003-0665-4091 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1033 BP 339 EP 340 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001456 ER PT J AU Wu, Y Miles, AP Lambert, L Muratova, O Orcutt, A Keister, D Bello, S Sattabongkot, J Miller, L Long, C Saul, A AF Wu, Yimin Miles, Aaron P. Lambert, Lynn Muratova, Olga Orcutt, Andrew Keister, David Bello, Sheila Sattabongkot, Jetsumon Miller, Louis Long, Carole Saul, Allan TI Aiming for sustained high-level antibody responses: formulation of PFS25 and PVS25 transmission blocking vaccines SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Wu, Yimin; Miles, Aaron P.; Lambert, Lynn; Muratova, Olga; Orcutt, Andrew; Keister, David; Bello, Sheila; Miller, Louis; Long, Carole; Saul, Allan] NIAID, Malaria Vaccine Dev Branch, Rockville, MD USA. [Sattabongkot, Jetsumon] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. OI Saul, Allan/0000-0003-0665-4091 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1035 BP 340 EP 340 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001458 ER PT J AU Bafica, A Scanga, C Feng, C Sher, A AF Bafica, Andre Scanga, Charles Feng, Carl Sher, Alan TI Toll-like receptor (TLR)9 regulates TH1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium Tuberculosis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Bafica, Andre; Scanga, Charles; Feng, Carl; Sher, Alan] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1047 BP 344 EP 344 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001470 ER PT J AU Goodwin, KB Simonsen, L AF Goodwin, Katherine B. Simonsen, Lone TI Effectiveness of insecticide treated nets in reducing all-cause mortality among children in sub-saharan Africa: A quantitative review of four large clinical trials SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Goodwin, Katherine B.; Simonsen, Lone] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1049 BP 345 EP 345 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001472 ER PT J AU Ostera, G Fairhurst, R Brittain, N Wellems, T AF Ostera, Graciella Fairhurst, Rick Brittain, Nathaniel Wellems, Thomas TI Hemoglobin C phenotype on a normal erythrocyte background SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Ostera, Graciella; Fairhurst, Rick; Brittain, Nathaniel; Wellems, Thomas] Natl Inst Hlth, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1063 BP 350 EP 350 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001486 ER PT J AU Dicko, A Diemert, DJ Sagara, I Sogoba, M Niambele, MB Assadou, MH Guindo, O Kamate, B Baby, M Sissoko, M Mullen, G Sissoko, M Mahant, S Thera, MA Dolo, A Long, C Diallo, DA Miller, LH Saul, A Doumbo, OK AF Dicko, Alassane Diemert, David J. Sagara, Issaka Sogoba, Moussa Niambele, Mohamed B. Assadou, Mahamadoun H. Guindo, Ousmane Kamate, Beh Baby, Mounirou Sissoko, Mady Mullen, Gregory Sissoko, Mahamadou Mahant, Siddhartha Thera, Mahamadou A. Dolo, Amagana Long, Carole Diallo, Dapa A. Miller, Louis H. Saul, Allan Doumbo, Ogobara K. TI Double-blind, randomized, controlled, phase 1 study of the AMA1-C1/alhydrogel (R) vaccine for Plasmodium falciparum malaria, in semi-immune malian adults SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Dicko, Alassane; Sagara, Issaka; Sogoba, Moussa; Niambele, Mohamed B.; Assadou, Mahamadoun H.; Guindo, Ousmane; Kamate, Beh; Baby, Mounirou; Sissoko, Mady; Sissoko, Mahamadou; Thera, Mahamadou A.; Dolo, Amagana; Diallo, Dapa A.; Doumbo, Ogobara K.] Malaria Res & Training Ctr, Bamako, Mali. [Diemert, David J.; Mullen, Gregory; Mahant, Siddhartha; Long, Carole; Miller, Louis H.; Saul, Allan] NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1084 BP 357 EP 357 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001507 ER PT J AU Dilemert, DJ Dicko, A Dolo, A Sogoba, M Sagara, I Orcutt, A Diallo, DA Mahanty, S Miller, LH Long, C Saul, A Doumbo, OK Mullen, G AF Dilemert, David J. Dicko, Alassane Dolo, Amagana Sogoba, Moussa Sagara, Issaka Orcutt, Andrew Diallo, Dapa A. Mahanty, Siddhartha Miller, Louis H. Long, Carole Saul, Allan Doumbo, Ogobara K. Mullen, Gregory TI AMA1-C1/alhydrogel (R) vaccine for Plasmodium falciparum malaria induces cross-reactive antibodies to a non-vaccine AMA1 allele in malian adults SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Dilemert, David J.; Orcutt, Andrew; Mahanty, Siddhartha; Miller, Louis H.; Long, Carole; Saul, Allan; Mullen, Gregory] NIAID, Rockville, MD USA. [Dicko, Alassane; Dolo, Amagana; Sogoba, Moussa; Sagara, Issaka; Diallo, Dapa A.; Doumbo, Ogobara K.] Malaria Rs & Training Ctr, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1085 BP 357 EP 358 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001508 ER PT J AU Patterson, NB Campo, JJ Stefaniak, ME Bruder, J Limbach, K Mullen, G King, CR Miles, AP Miller, LH Long, C Saul, A Doolan, DL AF Patterson, Noelle B. Campo, Joseph J. Stefaniak, Maureen E. Bruder, Joseph Limbach, Keith Mullen, Greg King, C. Richter Miles, Aaron P. Miller, Louis H. Long, Carole Saul, Allan Doolan, Denise L. TI Plasmodium falciparum multi-antigen adenvirus vectored-vaccine is immunogenic in both homolgous and heterologous boost regimens in a Yucatan swine model of malaria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Patterson, Noelle B.; Campo, Joseph J.; Stefaniak, Maureen E.; Limbach, Keith; Doolan, Denise L.] USN, Med Res Ctr, Silver Spring, MD USA. [Bruder, Joseph; King, C. Richter] GenVec Inc, Gaithersburg, MD USA. [Mullen, Greg; Miles, Aaron P.; Miller, Louis H.; Long, Carole; Saul, Allan] Natl Inst Hlth, Malaria Vaccine Dev Branch, Rockville, MD USA. RI Doolan, Denise/F-1969-2015; OI Saul, Allan/0000-0003-0665-4091 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1087 BP 358 EP 358 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001510 ER PT J AU Walsh, DS Gettayacamin, M Lyon, JA Leitner, WW Stewart, A Pichyangkul, S Gosi, P Tongtawe, P Holland, CA Kolodny, N Cohen, J Voss, G Ballou, R Heppner, DG Heppner, DG AF Walsh, Douglas S. Gettayacamin, Montip Lyon, Jeffrey A. Leitner, Wolfgang W. Stewart, Ann Pichyangkul, Sathit Gosi, Panita Tongtawe, Pongsri Holland, Carolyn A. Kolodny, Nelly Cohen, Joe Voss, Gerald Ballou, Ripley Heppner, D. Gray, Jr. Heppner, D. Gray TI Heterologous prime-boost immunization with epidermal gene gun administered Plasmodium falciparum circumsporozoite protein (CSP) encoding DNA and intramuscular RTS,S/ASO2A in rhesus monkeys generates robust cutaneous delayed-type hypersensitivity responses against CSPC terminus SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Walsh, Douglas S.; Lyon, Jeffrey A.; Stewart, Ann; Holland, Carolyn A.; Kolodny, Nelly; Heppner, D. Gray, Jr.; Heppner, D. Gray] Walter Reed Army Inst Res, Silver Spring, MD USA. [Gettayacamin, Montip; Pichyangkul, Sathit; Gosi, Panita; Tongtawe, Pongsri] Armed Forces Res Inst Med Sci, US Army Med Component, Bangkok 10400, Thailand. [Leitner, Wolfgang W.] Natl Inst Hlth, Dermatol Branch, Bethesda, MD USA. [Cohen, Joe; Voss, Gerald; Ballou, Ripley] GlaxoSmithKline Biol, Rixensart, Belgium. RI Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1089 BP 359 EP 359 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001512 ER PT J AU Weiss, WR Jiang, G Conteh, S Parra, N Richie, NO Valencia, A Singh, P Limbach, K Carucci, DJ Seclegah, M Brice, GT Doolan, DL Richie, TL AF Weiss, Walter R. Jiang, George Conteh, Solomon Parra, Nannette Richie, Nancy O. Valencia, Anais Singh, Priti Limbach, Keith Carucci, Daniel J. Seclegah, Martha Brice, Gary T. Doolan, Denise L. Richie, Thomas L. TI The effect of immunization interval on the immunogenicity and protective efficacy of a multistage Plasmodium knowlesi DNA prime/poxvirus boost vaccine in cynomolgus monkeys SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Weiss, Walter R.; Jiang, George; Conteh, Solomon; Richie, Nancy O.; Valencia, Anais; Singh, Priti; Limbach, Keith; Seclegah, Martha; Doolan, Denise L.; Richie, Thomas L.] USN, Med Res Ctr, Malaria Program, Silver Spring, MD USA. [Parra, Nannette] Armed Forces Radiobiol Res Inst, Bethesda, MD USA. [Carucci, Daniel J.] Fdn Natl Inst Hlth, Bethesda, MD USA. [Brice, Gary T.] Naval Med Res Unit 2, Jakarta, Indonesia. RI Doolan, Denise/F-1969-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2005 VL 73 IS 6 SU S MA 1088 BP 359 EP 359 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990001511 ER PT J AU Dean, J AF Dean, J TI Molecular biology of sperm-egg interactions SO ANDROLOGIA LA English DT Article; Proceedings Paper CT 4th International Workshop on Molecular Andrology CY OCT 07-09, 2005 CL Giessen, GERMANY SP Deutsch Forsch Gemeinsch, Fonds Chemischen Ind, European Acad Androl, German Soc Androl, German Soc Reproduct Med, Justus Liebig Univ, Dean Fac Med, Giessener Hochschul Gesell e V, Hessian Ctr Reproduct Med, Schering AG, Ferring Arzneimittel GmbH, Organon GmbH, Jenapharm GmbH & Co KG, Miletnyi Biotech GmbH, DPC Biermann GmbH ID MASS-SPECTROMETRY C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD USA. RP Dean, J (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-4569 J9 ANDROLOGIA JI Andrologia PD DEC PY 2005 VL 37 IS 6 BP 198 EP 199 DI 10.1111/j.1439-0272.2005.00686.x PG 2 WC Andrology SC Endocrinology & Metabolism GA 991IL UT WOS:000233806400002 PM 16336245 ER PT J AU Stinstra, JG Hopenfeld, B MacLeod, RS AF Stinstra, JG Hopenfeld, B MacLeod, RS TI On the passive cardiac conductivity SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article; Proceedings Paper CT International Biofluids Mechanics Symposium CY DEC 12-14, 2003 CL Pasadena, CA SP US Natl Comm Biomech, Biomed Engn Soc, Int Federat Med & Biol Engn DE conductivity; cardiac tissue; bidomain; cardiac modeling ID ELECTRICAL-CONDUCTIVITY; SUBENDOCARDIAL ISCHEMIA; DIELECTRIC-PROPERTIES; VOLTAGE CLAMP; MUSCLE CELLS; MYOCYTES; TISSUES; HEART; RESISTIVITY; MYOCARDIUM AB In order to relate the structure of cardiac tissue to its passive electrical conductivity, we created a geometrical model of cardiac tissue on a cellular scale that encompassed myocytes, capillaries, and the interstitial space that surrounds them. A special mesh generator was developed for this model to create realistically shaped myocytes and interstitial space with a controled degree of variation included in each model. In order to derive the effective conductivities, we used a finite element model to compute the currents flowing through the intracellular and extracellular space due to an externally applied electrical field. The product of these computations were the effective conductivity tensors for the intracellular and extracellular spaces. The simulations of bidomain conductivities for healthy tissue resulted in an effective intracellular conductivity of 0.16 S/m (longitudinal) and 0.005 S/m (transverse) and an effective extracellular conductivity of 0.21 S/m (longitudinal) and 0.06 S/m (transverse). The latter values are within the range of measured values reported in literature. Furthermore, we anticipate that this method can be used to simulate pathological conditions for which measured data is far more sparse. C1 Univ Utah, Nora Eccles Harrison CardioVasc Res & Training In, Salt Lake City, UT 84112 USA. Univ Utah, Sci Comp & Imaging Inst, Salt Lake City, UT 84112 USA. Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Stinstra, JG (reprint author), Univ Utah, Nora Eccles Harrison CardioVasc Res & Training In, Room 207,95 South 2000 East, Salt Lake City, UT 84112 USA. EM jeroen@cvrti.utah.edu NR 36 TC 34 Z9 35 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD DEC PY 2005 VL 33 IS 12 BP 1743 EP 1751 DI 10.1007/s10439-005-7257-7 PG 9 WC Engineering, Biomedical SC Engineering GA 999NC UT WOS:000234395300013 PM 16389523 ER PT J AU Leviton, A Dammann, O Durum, SK AF Leviton, A Dammann, O Durum, SK TI The adaptive immune response in neonatal cerebral white matter damage SO ANNALS OF NEUROLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; T-CELL-ACTIVATION; CENTRAL-NERVOUS-SYSTEM; NATURAL-KILLER-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TUMOR-NECROSIS-FACTOR; BIRTH-WEIGHT INFANTS; DENDRITIC CELLS; MULTIPLE-SCLEROSIS; INNATE IMMUNITY AB Hypotheses that inflammation contributes to neonatal cerebral white matter damage have evolved over the last three decades. The latest, expanded here, suggests that the adaptive immune system contributes to the intensity and duration of the processes that result in damage to cerebral white matter in the fetus and newborn. We propose several mechanisms by which fetal T lymphocytes could be activated during fetal exposure to infection. These include specific recognition of bacterial antigens, specific recognition of autoantigens, polyclonal activation by Toll-like receptors, and bystander activation by cytokines. C1 Childrens Hosp, Neuroepidemiol Unit, Boston, MA 02215 USA. Hannover Med Sch, Dept Obstet, Perinatal Infect Dis Epidemiol Unit, D-3000 Hannover, Germany. Hannover Med Sch, Dept Pediat, Perinatal Infect Dis Epidemiol Unit, D-3000 Hannover, Germany. NCI, Immunol Cytokine Grp, Frederick, MD 21701 USA. RP Leviton, A (reprint author), Childrens Hosp, Neuroepidemiol Unit, 1 Autumn St,720, Boston, MA 02215 USA. EM alan.leviton@childrens.harvard.edu FU NINDS NIH HHS [1U01 NS 40069-01A2] NR 87 TC 45 Z9 46 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2005 VL 58 IS 6 BP 821 EP 828 DI 10.1002/ana.20662 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989WE UT WOS:000233703900002 PM 16250014 ER PT J AU Polman, CH Reingold, SC Edan, G Filippi, M Hartung, HP Kappos, L Lublin, FD Metz, LM McFarland, HF O'Connor, PW Sandberg-Wollheim, M Thompson, AJ Weinshenker, BG Wolinsky, JS AF Polman, CH Reingold, SC Edan, G Filippi, M Hartung, HP Kappos, L Lublin, FD Metz, LM McFarland, HF O'Connor, PW Sandberg-Wollheim, M Thompson, AJ Weinshenker, BG Wolinsky, JS TI Diagnostic criteria for multiple sclerosis: 2005 Revisions to the "McDonald Criteria" SO ANNALS OF NEUROLOGY LA English DT Article ID CLINICALLY ISOLATED SYNDROMES; SPINAL-CORD MRI; TECHNOLOGY-ASSESSMENT SUBCOMMITTEE; NEUROMYELITIS-OPTICA; PREDICT CONVERSION; IMAGING CRITERIA; NATURAL-HISTORY; WHITE-MATTER; SUSPECTED MS; THERAPEUTICS AB New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The "McDonald Criteria" have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity. C1 Free Univ Amsterdam, Amsterdam, Netherlands. Natl Multiple Sclerosis Soc, New York, NY USA. Sci & Clin Review Associates LLC, New York, NY USA. Ctr Hosp Reg Univ Rennes, Rennes, France. Univ Hosp San Raffaele, Dept Neurol, Neuroimaging Res Unit, Milan, Italy. Univ Dusseldorf, Dept Neurol, D-4000 Dusseldorf, Germany. Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland. Univ Basel Hosp, Dept Res, CH-4031 Basel, Switzerland. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Foothills Med Ctr, Calgary, AB, Canada. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Lund Hosp, S-22185 Lund, Sweden. UCL Inst Neurol, London WC1N 3BG, England. Mayo Clin, Coll Med, Rochester, MN USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. RP Polman, CH (reprint author), VU Med Ctr Amsterdam, Dept Neurol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM ch.polman@vumc.nl RI Thompson, Alan/C-2654-2008 OI Thompson, Alan/0000-0002-4333-8496 FU Multiple Sclerosis Society [748] NR 40 TC 2882 Z9 2993 U1 29 U2 171 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2005 VL 58 IS 6 BP 840 EP 846 DI 10.1002/ana.206703 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989WE UT WOS:000233703900004 PM 16283615 ER PT J AU Chen, HL Jacobs, E Schwarzschild, MA McCullough, ML Calle, EE Thun, MJ Ascherio, A AF Chen, HL Jacobs, E Schwarzschild, MA McCullough, ML Calle, EE Thun, MJ Ascherio, A TI Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID SODIUM-SALICYLATE; NEUROPROTECTION; ACTIVATION; ASPIRIN; MODEL AB We investigated whether nonsteroidal antiinflammatory drug use was associated with a lower risk for Parkinson's disease (PD) in a large cohort of US men and women. PD risk was lower among ibuprofen users than nonusers. Compared with nonusers, the relative risks were 0.73 for users of fewer than 2 tablets/week, 0.72 for 2 to 6.9 tablets/week, and 0.62 for 1 or more tablets/day (p trend=0.03). No association was found between the use of aspirin, other nonsteroidal and inflammatory drugs, or acetaminophen and PD risk. The results suggest that ibuprofen use may delay or prevent the onset of PD. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC USA. Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM aascheri@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU NINDS NIH HHS [NS 48468] NR 18 TC 239 Z9 248 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2005 VL 58 IS 6 BP 963 EP 967 DI 10.1002/ana.20682 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989WE UT WOS:000233703900021 PM 16240369 ER PT J AU Hartman, AL Gasior, M Rogawski, MA AF Hartman, AL Gasior, M Rogawski, MA TI Evidence for neurosteroids as mediators of seizure protection in the ketogenic diet SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 130th Annual Meeting of the American-Neurological-Association CY SEP 25-28, 2005 CL San Diego, CA SP Amer Neurol Assoc, AstraZeneca C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Natl Inst Neurol Disorders & Stroke, Epilepsy Res Sect, NIH, Bethesda, MD USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2005 VL 58 IS 6 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989WE UT WOS:000233703900037 ER PT J AU Myers, AJ Pittman, A Fung, HC Kaleem, M Marlowe, L Pittman, A Duckworth, J Evans, J Evans, J Gibson, A Morris, CM Lees, A de Silva, R Hardy, JA AF Myers, AJ Pittman, A Fung, HC Kaleem, M Marlowe, L Pittman, A Duckworth, J Evans, J Evans, J Gibson, A Morris, CM Lees, A de Silva, R Hardy, JA TI The H1c haplotype of the MAPT locus is associated with autopsy confirmed late onset Alzheimer's disease SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 130th Annual Meeting of the American-Neurological-Association CY SEP 25-28, 2005 CL San Diego, CA SP Amer Neurol Assoc, AstraZeneca C1 NIH, Bethesda, MD 20892 USA. UCL, Reta Lila Weston Inst Neurol Studies, London, England. Newcastle Gen Hosp, Inst Hlth & Aging, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. RI de Silva, Rohan/C-1734-2008; Myers, Amanda/B-1796-2010; Pittman, Alan/D-6231-2012; Lees, Andrew/A-6605-2009 OI de Silva, Rohan/0000-0002-5052-5775; Myers, Amanda/0000-0002-3100-9396; NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2005 VL 58 IS 6 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989WE UT WOS:000233703900034 ER PT J AU Olivieri, A Santini, G Patti, C Chisesi, T De Souza, C Rubagotti, A Aversa, S Billio, A Porcellini, A Candela, M Centurioni, R Congiu, AM Brunori, M Nati, S Spriano, M Vimercati, R Marino, G Contu, A Tedeschi, L Majolino, I Crugnola, M Sertoli, MR AF Olivieri, A Santini, G Patti, C Chisesi, T De Souza, C Rubagotti, A Aversa, S Billio, A Porcellini, A Candela, M Centurioni, R Congiu, AM Brunori, M Nati, S Spriano, M Vimercati, R Marino, G Contu, A Tedeschi, L Majolino, I Crugnola, M Sertoli, MR TI Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG SO ANNALS OF ONCOLOGY LA English DT Article DE autologous stem cell transplantation; high-dose sequential therapy; high-grade NHL; VACOP-B ID BONE-MARROW-TRANSPLANTATION; PROSPECTIVE RANDOMIZED-TRIAL; COOPERATIVE-STUDY-GROUP; STANDARD REGIMEN CHOP; MACOP-B; CONVENTIONAL CHEMOTHERAPY; ITALIAN MULTICENTER; INTERMEDIATE-GRADE; CELL LYMPHOMA; COMBINATION AB Background: There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL. Patients and methods: Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B). Results: According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement. Conclusions: Aggressive NHL patients do not benefit from upfront HDS/HDT. C1 Univ Ancona, Dept Hematol, I-60020 Ancona, Italy. San Martino Hosp, Dept Hematol, Genoa, Italy. Cervello Hosp, Dept Hematol, Palermo, Italy. San Giovanni Hosp, Div Hematol, Venice, Italy. Univ Campinas, Dept Hematol, Campinas, Brazil. Univ Genoa, Dept Med Oncol, Biostat Unit, Genoa, Italy. Natl Canc Inst, Genoa, Italy. Gen Hosp, Div Oncol, Padua, Italy. San Maurizio Hosp, Div Hematol, Bolzano, Italy. Gen Hosp, Div Hematol, Noale, Italy. Univ Ancona, Inst Med, I-60020 Ancona, Italy. Gen Hosp, Div Med, Civitanova Marche, Italy. Gen Hosp, Div Oncol, Sassari, Italy. San Carlo Borromeo Hosp, Div Oncol, Milan, Italy. San Camillo Hosp, Div Hematol, Rome, Italy. Univ Parma, Inst Hematol, I-43100 Parma, Italy. RP Olivieri, A (reprint author), Univ Ancona, Dept Hematol, Via Conca N1, I-60020 Ancona, Italy. EM a.olivieri@ao-umbertoprimo.marche.iy NR 30 TC 28 Z9 32 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2005 VL 16 IS 12 BP 1941 EP 1948 DI 10.1093/annonc/mdi399 PG 8 WC Oncology SC Oncology GA 987AA UT WOS:000233489600014 PM 16157621 ER PT J AU McGriff-Lee, NJ Csako, G Chen, JT Dang, DK Rosenfeld, KG AF McGriff-Lee, NJ Csako, G Chen, JT Dang, DK Rosenfeld, KG TI Search for predictors of nontherapeutic INR results with warfarin therapy SO ANNALS OF PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Midyear Clinical Meeting of the American-Society-of-Health-System-Pharmacists CY DEC 10, 2002 CL ATLANTA, GA SP Amer Soc Hlth Syst Pharmacists DE warfarin monitoring, predictors; atrial fibrillation, mechanical heart valve replacement ID ATRIAL-FIBRILLATION; ANTITHROMBOTIC THERAPY; ORAL ANTICOAGULATION; STROKE PREVENTION; SELF-MANAGEMENT; DRUG-THERAPY; METABOLISM; FREQUENCY; PATTERNS; STANDARD AB BACKGROUND: The effectiveness and safety of warfarin require maintaining an international normalized ratio (INR) within the therapeutic range. OBJECTIVE: To identify predictors of nontherapeutic INR results in patients receiving warfarin. METHODS: A retrospective study was conducted using 350 ambulatory care patients from a broad geographic region, all receiving long-term warfarin therapy and followed in a tertiary-care cardiology clinic. Possible predictors of nontherapeutic INR results (gender, age, body weight, body mass index, height, race, tobacco use, alcohol use, warfarin dose, therapeutic indication, regimen intensity, INR monitoring frequency/category, interacting medications, adverse events) were assessed with logistic regression models. Subset analysis involved 146 patients concurrently monitored with capillary whole blood INR (CoaguChek). RESULTS: As measured on venous specimens, 52% (182/350) of the patients had subtherapeutic INR results and 13% (44/350) had supratherapeutic INR results despite frequent (<= 4 wk) monitoring in 75% of the patients. Due to the small sample size, supratherapeutic INR results could not be further analyzed. Of 19 predictors tested, only daily warfarin dose (p < 0.02) and regimen intensity (p < 0.03) were significant independent and additive predictors of subtherapeutic results. Patients on the high-intensity regimen (INR 2.5-3.5) and receiving warfarin <= 6 mg/day had >50% risk of having subtherapeutic INR results. Subtherapeutic CoaguChek results were independent predictors of subtherapeutic venipuncture INR results in the subset (p = 0.001). CONCLUSIONS: In the absence of readily identifiable predictors, only higher warfarin dosing and/or more frequent monitoring (possibly with point-of-care/home monitoring devices) may minimize the time that INRs are subtherapeutic, especially in patients receiving low-dose and/or high-intensity anticoagulation therapy. C1 NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Hematol Serv, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Chen, JT (reprint author), Purdue Univ, Dept Pharm Practice, R Heine Pharm Bldg,Rm 502D,575 Stadium Mall Dr, W Lafayette, IN 47907 USA. EM jtchen@pharmacy.purdue.edu NR 28 TC 6 Z9 6 U1 0 U2 2 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD DEC PY 2005 VL 39 IS 12 BP 1996 EP 2002 DI 10.1345/aph.1E381 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 988ZW UT WOS:000233643700004 PM 16288081 ER PT J AU Maker, AV Phan, GQ Attia, P Yang, JC Sherry, RM Topalian, SL Kammula, US Royal, RE Haworth, LR Levy, C Kleiner, D Mavroukakis, SA Yellin, M Rosenberg, SA AF Maker, AV Phan, GQ Attia, P Yang, JC Sherry, RM Topalian, SL Kammula, US Royal, RE Haworth, LR Levy, C Kleiner, D Mavroukakis, SA Yellin, M Rosenberg, SA TI Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: A phase I/II study SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE cytotoxic T lymphocyte-associated antigen 4; Interleukin 2; melanoma; autoimmunity ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; METASTATIC MELANOMA; CTLA-4 BLOCKADE; COMBINATION IMMUNOTHERAPY; CELL-ACTIVATION; CANCER; MODEL; IDENTIFICATION; EXPRESSION; RECEPTOR AB Background: Cytotoxic T lymphocyte-associated antigen (CTLA)-4 can inhibit T-cell responses and is involved in tolerance against self antigens. We previously reported autoimmune manifestations and objective cancer regressions in patients with metastatic melanoma treated with CTLA-4 blockade. The possibility of activating tumor-reactive T cells while removing inhibitory activity with CTLA-4 blockade has stimulated interest in using anti-CTLA-4 antibodies in combination with other cancer immunotherapies to improve clinical outcomes. In this study, we assessed the antitumor activity and autoimmune toxicity of CTLA-4 blockade in combination with an immune-activating stimulus, interleukin (IL)-2, in patients with metastatic melanoma. Methods: Thirty-six patients received anti-CTLA-4 antibody every 3 weeks. Three patients per cohort received doses of .1, .3, 1.0, and 2.0 mg/kg. Twenty-four patients received 3.0 mg/kg. All patients received IL-2 therapy (720,000 IU/kg every 8 hours to a maximum of 15 doses). Results: Eight patients (22%) experienced objective tumor responses (three complete and five partial), including metastases in the lungs, lymph nodes, mediastinum, and subcutaneous tissues. Six of the eight patients have ongoing objective responses at 11 to 19 months. Five patients (14%) developed grade III/IV autoimmune toxicities secondary to anti-CTLA-4 administration, including four patients with enterocolitis and one with arthritis and uveitis. Conclusions: There is not evidence to support a synergistic effect of CTLA-4 blockade plus IL-2 administration, because the 22% objective response rate is that expected from the sum of these two agents administered alone. Durable cancer regressions were seen in patients treated with this combination. C1 NCI, Surg Branch, NIH, Bethesda, MD 20814 USA. Medarex Inc, Bloomsbury, NJ 08804 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC Room 3-3940,10 Ctr Dr, Bethesda, MD 20814 USA. EM sar@nih.gov OI Kleiner, David/0000-0003-3442-4453 FU NCI NIH HHS [Z01 SC003811-31] NR 26 TC 288 Z9 305 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2005 VL 12 IS 12 BP 1005 EP 1016 DI 10.1245/ASO.2005.03.536 PG 12 WC Oncology; Surgery SC Oncology; Surgery GA 986KK UT WOS:000233448300008 PM 16283570 ER PT J AU Horvath, KA Ferguson, TB Guyton, RA Edwards, FH AF Horvath, KA Ferguson, TB Guyton, RA Edwards, FH TI Impact of unstable angina on outcomes of transmyocardial laser revascularization combined with coronary artery bypass grafting SO ANNALS OF THORACIC SURGERY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; REFRACTORY ANGINA; FOLLOW-UP; MEDICAL THERAPY; PECTORIS; MULTICENTER; CO2-LASER; SURGERY; DISEASE AB Background. For sole therapy transmyocardial laser revascularization (TMR), unstable angina has been demonstrated to be a significant independent predictor of operative mortality. The objective of this study was to investigate the preoperative risk profile of patients undergoing TMR plus coronary artery bypass graft surgery (CABG) and to determine the impact of unstable angina on outcomes. Methods. Using The Society of Thoracic Surgeons National Cardiac Database from 1998 to 2003, 5,618 patients underwent TMR plus CABG. These patients were compared with 932,715 patients who underwent CABG only operations. Results. The TMR plus CABG patients had a significantly higher incidence of diabetes (50% versus 34%), renal failure (7% versus 5%), peripheral vascular disease (20% versus 16%), reoperative surgery (26% versus 9%), three-vessel coronary artery disease (80% versus 71%), hyperlipidemia (73% versus 62%; p < 0.001 for all comparisons). The incidence of preoperative unstable angina was similar (46% versus 47%). The unadjusted perioperative mortality was 3.8% for TMR plus CABG patients. When unstable angina patients were removed, the observed mortality for TMR plus CABG was decreased to 2.7%. Conclusions. It is likely that patients who undergo TMR plus CABG have a higher prevalence of diffuse coronary disease based on their preoperative demographics. Despite the increased risk associated with such anatomy, the mortality rate was not significantly increased when TMR was added to CABG in an effort to provide a more complete revascularization. As was noted from the outcomes of sole therapy TMR, in unstable angina patients, TMR plus CABG carries a higher risk, but this risk is not significantly different from that of such patients treated with CABG alone. C1 NHLBI, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Emory Univ, Sch Med, Div Cardiothorac Surg, Atlanta, GA USA. Univ Florida, Div Cardiothorac Surg, Jacksonville, FL USA. RP Horvath, KA (reprint author), NHLBI, NIH, 10 Ctr Dr,Bldg 10CRC,Room 6-5140,MSC 1454, Bethesda, MD 20892 USA. EM khorvath@nih.gov NR 19 TC 3 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2005 VL 80 IS 6 BP 2082 EP 2085 DI 10.1016/j.athoracsur.2005.06.020 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 993BD UT WOS:000233926800017 PM 16305849 ER PT J AU Zhu, WM Burnette, A Dorjsuren, D Roberts, PE Huleihel, M Shoemaker, RH Marquez, VE Agbaria, R Sei, S AF Zhu, WM Burnette, A Dorjsuren, D Roberts, PE Huleihel, M Shoemaker, RH Marquez, VE Agbaria, R Sei, S TI Potent antiviral activity of North-methanocarbathymidine against Kaposi's sarcoma-associated herpesvirus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SIMPLEX-VIRUS TYPE-1; NARROW SUBSTRATE-SPECIFICITY; THYMIDINE KINASE; DNA-POLYMERASE; HIV-INFECTION; ANTIRETROVIRAL THERAPY; DEOXYRIBONUCLEIC ACID; THYMIDYLATE SYNTHASE; ENZYMATIC-SYNTHESIS; PERIPHERAL-BLOOD AB Kaposi's sarcoma-associated herpesvirus (KSHV) infection is a prerequisite for the development of Kaposi's sarcoma (KS). Blocking lytic KSHV replication may hinder KS tumorigenesis. Here, we report potent in vitro anti-KSHV activity of 2'-exo-methanocarbathymidine [North-methanocarbathymidine (N-MCT)], a thymidine analog with a pseudosugar ring locked in the northern conformation, which has previously been shown to block the replication of herpes simplex virus types 1 and 2. N-MCT inhibited KSHV virion production in lytically induced KSHV-infected BCBL-1 cells with a substantially lower 50% inhibitory concentration (IC50) than those of cidofovir (CDV) and ganciclovir (GCV) (IC50, mean standard deviation: 0.08 +/- 0.03, 0.42 +/- 0.07, and 0.96 +/- 0.49 mu M for N-MCT, CDV, and GCV, respectively). The reduction in KSHV virion production was accompanied by a corresponding decrease in KSHV DNA levels in the N-MCT-treated BCBL-1 cells, indicating that the compound blocked lytic KSHV DNA replication. A time- and dose-dependent accumulation of N-MCT-triphosphate (TP) was demonstrated in lytically induced BCBL-1 cells, while uninfected cells showed virtually no accumulation. The levels of N-MCT-TP were significantly decreased in the presence of 5'-ethynylthymidine, a potent inhibitor of herpesvirus thymidine kinase, resulting in the abrogation of anti-KSHV activity of N-MCT. N-MCT-TP more effectively blocked in vitro DNA synthesis by KSHV DNA polymerase with an IC50 of 6.24 +/- 0.08 mu M (mean standard deviation) compared to CDV-diphosphate (14.70 +/- 2.47 mu M) or GCV-TP (24.59 +/- 5.60 mu M). Taken together, N-MCT is a highly potent and target-specific anti-KSHV agent which inhibits lytic KSHV DNA synthesis through its triphosphate metabolite produced in KSHV-infected cells expressing a virally encoded thymidine kinase. C1 SAIC Frederick, Lab Antiviral Drug Mechanisms, Frederick, MD USA. Ben Gurion Univ Negev, Natl Inst Biotechnol, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Virol, IL-84105 Beer Sheva, Israel. NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA. NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21702 USA. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. RP Sei, S (reprint author), NCI, SAIC Frederick, Dev Therapeut Program, Lab Human Toxicol & Pharmacol, Bldg 439,POB B, Frederick, MD 21702 USA. EM sei@ncifcrf.gov RI HULEIHEL, MAHMOUD/F-1837-2012 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 64 TC 15 Z9 15 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2005 VL 49 IS 12 BP 4965 EP 4973 DI 10.1128/AAC.49.12.4965-4973.2005 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 989RS UT WOS:000233692100018 PM 16304159 ER PT J AU Wurthwein, G Groll, AH Hempel, G Adler-Shohet, FC Lieberman, JM Walsh, TJ AF Wurthwein, G Groll, AH Hempel, G Adler-Shohet, FC Lieberman, JM Walsh, TJ TI Population pharmacokinetics of amphotericin B lipid complex in neonates SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BIRTH-WEIGHT INFANTS; INVASIVE FUNGAL-INFECTIONS; CLINICAL PHARMACOKINETICS; TISSUE DISTRIBUTION; PEDIATRIC-PATIENTS; CANDIDIASIS; FORMULATIONS; FLUCONAZOLE; AMBISOME; PLASMA AB The pharmacokinetics of amphotericin B lipid complex (ABLC) were investigated in neonates with invasive candidiasis enrolled in a phase 11 multicenter trial. Sparse blood (153 samples; I to 9 per patient, I to 254 h after the dose) and random urine and cerebrospinal fluid (CSF) samples of 28 neonates (median weight [WT], 1.06 kg; range, 0.48 to 4.9 kg; median gestational age, 27 weeks; range, 24 to 41 weeks) were analyzed. Patients received intravenous ABLC at 2.5 (n = 15) or 5 (n = 13) mg/kg of body weight once a day over 1 or 2 h, respectively, for a median of 21 days (range, 4 to 47 days). Concentrations of amphotericin B were quantified as total drug by high-performance liquid chromatography. Blood data for time after dose (TAD) of < 24 h fitted best to a one-compartment model with an additive-error model for residual variability, WT0.75 (where 0.75 is an exponent) as a covariate of clearance (CL), and WT as a covariate of volume of distribution (P). Prior amphotericin B, postnatal age, and gestational age did not further improve the model. The final model equations were CL (liters/h) = 0.399 X WT0.75 (interindividual variability, 35%) and V (liters) = 10.5 X WT (interindividual variability, 43%). Noncompartmental analysis of pooled data with a TAD of >24 III revealed a terminal half-life of 395 h. Mean concentrations in the urine after 1, 2, and 3 weeks ranged from 0.082 to 0.430 mu g/ml, and those in CSF ranged from undetectable to 0.074 mu g/ml. The disposition of ABLC in neonates was similar to that observed in other age groups: weight was the only factor that influenced clearance. Based on these results and previously published safety and efficacy data, we recommend a daily dosage between 2.5 and 5.0 mg/kg for treatment of invasive Candida infections in neonates. C1 NCI, Immunocompromised Host Sect, NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. Childrens Univ Hosp, Ctr Bone Marrow Transplantat, Infect Dis Res Program, Munster, Germany. Childrens Univ Hosp, Dept Pediat Hematol Oncol, Munster, Germany. Univ Hosp, Clin Pharmacokinet Sect, Coordinating Ctr Clin Trials, Munster, Germany. Millers Childrens Hosp, Long Beach, CA USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, NIH, Pediat Oncol Branch, CRC-1-5750,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 48 TC 55 Z9 59 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2005 VL 49 IS 12 BP 5092 EP 5098 DI 10.1128/AAC.49.12.5092-5098.2005 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 989RS UT WOS:000233692100036 PM 16304177 ER PT J AU Irigoyen, P Lee, AT Wener, MH Li, WT Kern, M Batliwalla, F Lum, RF Massarotti, E Weisman, M Bombardier, C Remmers, EF Kastner, DL Seldin, MF Criswell, LA Gregersen, PK AF Irigoyen, P Lee, AT Wener, MH Li, WT Kern, M Batliwalla, F Lum, RF Massarotti, E Weisman, M Bombardier, C Remmers, EF Kastner, DL Seldin, MF Criswell, LA Gregersen, PK TI Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis - Contrasting effects of HLA-DR3 and the shared epitope alleles SO ARTHRITIS AND RHEUMATISM LA English DT Article ID HLA CLASS-II; RECENT-ONSET; ASSOCIATION; DISEASE; AUTOANTIBODIES; PREDICTION; SUSCEPTIBILITY; HETEROGENEITY; HYPOTHESIS; HEPATITIS AB Objective. To examine the association between HLA-DRB1 alleles and the production of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) autoantibodies in patients with rheumatoid arthritis (RA). Methods. We studied 1,723 Caucasian RA patients enrolled in the North American Rheumatoid Arthritis Consortium (NARAC) family cohort and the Study of New Onset Rheumatoid Arthritis (SONORA) cohort. All patients were tested for anti-CCP antibodies (by enzyme-linked immunosorbent assay), RF (by nephelometry), and HLA-DR genotype (by polymerase chain reaction and sequence-specific oligonucleotide hybridization). Results. When controlled for the presence of RF, anti-CCP positivity was strongly associated with the HLA-DRB1 shared epitope (SE). In RF+ patients, the presence of the SE was very significantly associated with anti-CCP positivity, with an odds ratio (OR) of 5.8 and a 95% confidence interval (95% CI) of 4.1-8.3. This relationship was also seen in RF- patients (OR 3.1 [95% CI 1.8-5.3]). In contrast, RF positivity was not significantly associated with presence of the SE independently of anti-CCP antibodies. Strikingly, HLA-DRB1*03 was strongly associated with reduced anti-CCP titers, even after controlling for the presence of the SE and restricting the analysis to anti-CCP+ patients. HLA-DR3 was also associated with anti-CCP- RA in our population. Conclusion. The HLA-DRB1 SE is strongly associated with the production of anti-CCP antibodies, but not RE In contrast, HLA-DR3 alleles are associated with anti-CCP- disease and with lower levels of anti-CCP antibodies, even when controlling for the SE. These data emphasize the complexity of the genetic effects of the major histocompatibility complex on the RA phenotype. C1 N Shore Long Isl Jewish Inst Med Res, Robert S Boas Ctr Genom & Human Genet, Manhasset, NY 11030 USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Tufts New England Med Ctr, Boston, MA USA. Cedars Sinai Med Ctr, Los Angeles, CA USA. Univ Toronto, Toronto, ON, Canada. NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Davis, CA 95616 USA. RP Gregersen, PK (reprint author), N Shore Long Isl Jewish Inst Med Res, Robert S Boas Ctr Genom & Human Genet, 350 Community Dr, Manhasset, NY 11030 USA. EM peterg@nshs.edu OI Li, Wentian/0000-0003-1155-110X FU NCRR NIH HHS [5-M01-RR0079]; NIAMS NIH HHS [N01-AR-42232, R01-AR-44222] NR 33 TC 122 Z9 132 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 3813 EP 3818 DI 10.1002/art.21419 PG 6 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500018 PM 16320316 ER PT J AU Smolen, JS Maini, RN Han, CL Baker, D Lipsky, PL AF Smolen, JS Maini, RN Han, CL Baker, D Lipsky, PL CA ATTRACT Study Grp TI Radiographic benefit without clinical improvement in infliximab-treated patients with rheumatoid arthritis: comment on the article by Smolen et al - Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID ANTITUMOR NECROSIS FACTOR; FACTOR-ALPHA; FUNCTIONAL-CAPACITY; DISEASE-ACTIVITY; METHOTREXATE; DESTRUCTION; INFLAMMATION; COMBINATION; CARE C1 Med Univ Vienna, Vienna, Austria. Kennedy Inst, London, England. Centocor Inc, Malvern, PA USA. NIH, Bethesda, MD 20892 USA. RP Smolen, JS (reprint author), Med Univ Vienna, Vienna, Austria. NR 21 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4045 EP 4047 DI 10.1002/art.21608 PG 3 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500045 ER PT J AU Irigoyen, P Lee, AT Wener, M Li, WT Kern, L Batliwalla, F Lum, RF Massarotti, E Weisman, M Bombardier, C Remmers, EF Kastner, DL Seldin, MF Criswell, LA Gregersen, PK AF Irigoyen, P Lee, AT Wener, M Li, WT Kern, L Batliwalla, F Lum, RF Massarotti, E Weisman, M Bombardier, C Remmers, EF Kastner, DL Seldin, MF Criswell, LA Gregersen, PK TI Regulation of anti-CCP antibodies in rheumatoid arthritis: contrasting effects of HLA-DR3 and the shared epitope alleles. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 N Shore LIJ Med Ctr, New Hyde Pk, NY USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Tufts New England Med Ctr, Boston, MA USA. Cedars Sinai Med Ctr, Los Angeles, CA USA. Univ Toronto, Toronto, ON, Canada. NIAMSD, Bethesda, MD 20892 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4053 EP 4054 PG 2 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500055 ER PT J AU Skapenko, A Kalden, JR Lipsky, PE Schulze-Koops, H AF Skapenko, A Kalden, JR Lipsky, PE Schulze-Koops, H TI The IL-4Ralpha chain-binding cytokines, IL-4 and IL-13, induce Foxp3 expressing CD25+CD4+regulatory T cells from CD25-CD4+precursors. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Erlangen Nurnberg, Erlangen, Germany. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4063 EP 4063 PG 1 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500076 ER PT J AU Colburn, NT Mogul, D Chae, JJ Balow, J Richard, K Wood, G Barham, B Haverkamp, M Park, G Sun, HW Aksentijevich, I Kastner, D AF Colburn, NT Mogul, D Chae, JJ Balow, J Richard, K Wood, G Barham, B Haverkamp, M Park, G Sun, HW Aksentijevich, I Kastner, D TI Early innate inflammatory changes in familial Mediterranean fever patients undergoing structured treatment interruption of colchicine. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4068 EP 4069 PG 2 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500088 ER PT J AU Albuquerque, SM Zhang, G Zhou, XD Weisman, M Ward, MM Bruckel, J Davis, JC Inman, R Maksymowych, WP Martin, TM Rosenbaum, JT Khan, MA Schumacher, HR Yu, DY Xiong, M Jin, L Reveille, JD AF Albuquerque, SM Zhang, G Zhou, XD Weisman, M Ward, MM Bruckel, J Davis, JC Inman, R Maksymowych, WP Martin, TM Rosenbaum, JT Khan, MA Schumacher, HR Yu, DY Xiong, M Jin, L Reveille, JD TI Association of IL-1 genes with anhylosing spondylitis susceptibility. Evidence from family-based analyses. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Texas, Houston, TX USA. Univ Cincinnati, Cincinnati, OH USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NIAMS, Bethesda, MD USA. Spondylitis Assoc Amer, Sherman Oaks, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Toronto, Toronto, ON, Canada. Univ Alberta, Edmonton, AB, Canada. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Penn, Philadelphia, PA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4077 EP 4077 PG 1 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500110 ER PT J AU Hazel, EM Bernatsky, S Clarke, AE Cooper, GS Joseph, L Pineau, CA AF Hazel, EM Bernatsky, S Clarke, AE Cooper, GS Joseph, L Pineau, CA TI Low rates of influenza vaccinations in a cohort of SLE patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 McGill Univ, Montreal, PQ, Canada. Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4082 EP 4082 PG 1 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500122 ER PT J AU Bouali, H Nowling, T Cooper, GS Dooley, MA Nietert, PJ Gilkeson, G AF Bouali, H Nowling, T Cooper, GS Dooley, MA Nietert, PJ Gilkeson, G TI Peroxisome proliferator-activated receptor gamma (PPAR?) polymorphisms and demographic factors: Their association with lupus nephritis in the CLU cohort. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Med Univ S Carolina, Charleston, SC USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4084 EP 4085 PG 2 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500128 ER PT J AU McCrae, RR Martin, TA Costa, PT AF McCrae, RR Martin, TA Costa, PT TI Age trends and age norms for the NEO Personality Inventory-3 in adolescents and adults SO ASSESSMENT LA English DT Article DE personality; age norms; development; adolescents; test revision ID YOUNG ADULTHOOD; TRAITS; CULTURES AB The NEO Personality Inventory-3 (NEO-PI-3) is a modification of the Revised NEO Personality Inventory (NEO-PI-R) designed to be more understandable to adolescents. Data from adults aged 21 to 91 showed that the NEO-PI-3 also functions as well or better than the NEO-PI-R in adults. Age trends from combined adolescent (n = 500) and adult (n = 635) samples confirmed previous cross-sectional findings and demonstrated the importance of studying age changes especially at the facet level and during the decade of the 20s. Normative data for self-report and observer rating forms for adolescents, younger and older adults, and all adults are discussed, as well as for a combined-age group. It is argued that combined-age norms may be most appropriate for depicting the personality scores of individuals, but the utility for some purposes of within-age group scores is also acknowledged. C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Susquehanna Univ, Selinsgrove, PA 17870 USA. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mccraej@grc.nia.nih.gov OI Costa, Paul/0000-0003-4375-1712 NR 30 TC 47 Z9 49 U1 2 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD DEC PY 2005 VL 12 IS 4 BP 363 EP 373 DI 10.1177/1073191105279724 PG 11 WC Psychology, Clinical SC Psychology GA 984AM UT WOS:000233274800001 PM 16244117 ER PT J AU Bekris, LM Shephard, C Peterson, M Hoehna, J Yserloo, BV Rutledge, E Farin, F Kavanagh, TJ Lernmark, A AF Bekris, LM Shephard, C Peterson, M Hoehna, J Yserloo, BV Rutledge, E Farin, F Kavanagh, TJ Lernmark, A TI Glutathione-s-transferase M1 and T1 polymorphisms and associations with type 1 diabetes age-at-onset SO AUTOIMMUNITY LA English DT Article DE type 1 diabetes; glutathione-s-transferase; age-at-onset; GSTM1; GSTT1; polymorphism ID GLUTAMIC-ACID DECARBOXYLASE; ISLET-CELL ANTIBODIES; COWS MILK CONSUMPTION; KAPPA-B ACTIVATION; OXIDATIVE STRESS; RHEUMATOID-ARTHRITIS; ANTIOXIDANT ENZYMES; RINM5F CELLS; CHRONIC-PANCREATITIS; GENE POLYMORPHISMS AB Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta cell destruction involving auto-reactive T-cells, pro-inflammatory cytokines, reactive oxygen species (ROS) and loss of insulin. Monozygotic twin studies show a 20-60% concordance with T1D indicating there may be an environmental component to the disease. Glutathione (GSH) is the major endogenous antioxidant produced by the cell. GSH participates directly in the neutralization of free radicals and plays a role in the immune response. Glutathione-s-transferases (GSTs) conjugate GSH to free-radicals or xenobiotics. GST activity depletes GSH levels and may either detoxify or enhance the toxicity of a compound. Glutathione-s-transferase mu 1 (GSTM1) and glutathione-s-transferase theta 1 (GSTT1) have polymorphic homozygous deletion (null) genotypes resulting in complete absence of enzyme activity. GSTM1 and GSTT1 null genotypes in Caucasian populations have frequencies of approximately 40-60% and 15-20%, respectively. GST null genotypes have been associated with susceptibility to cancer and protection against chronic pancreatitis. The aim of this study was to investigate associations with GSTM1 and GSTT1 polymorphisms in a group T1D patients and control subjects 0-35 years old who participated in the Combined Swedish Childhood Diabetes Registry and Diabetes Incidence Study (1986-1988). Results show that the presence of the GSTM1 and not the null genotype (OR, 2.13 95% CI, 1.23-3.70, p -value, 0.007, Bonferroni corrected p -value, 0.035) may be a susceptibility factor in T1D 14-20 years old. These results suggest that the GSTM1 null genotype is associated with T1D protection and T1D age-at-onset and that susceptibility to T1D may involve GST conjugation. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. Univ Washington, UW NIEHS Ctr Ecogenet & Environm Hlth, Seattle, WA 98195 USA. RP Bekris, LM (reprint author), Univ Washington, Dept Med, Box 357710, Seattle, WA 98195 USA. EM lbekris@u.washington.edu NR 96 TC 29 Z9 33 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PD DEC PY 2005 VL 38 IS 8 BP 567 EP 575 DI 10.1080/08916930500407238 PG 9 WC Immunology SC Immunology GA 997NH UT WOS:000234251800002 PM 16390810 ER PT J AU Donaldson, JG AF Donaldson, JG TI Arfs, phosphoinositides and membrane traffic SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT BioScience 2005 Conference CY JUL 17-21, 2005 CL Glasgow, SCOTLAND DE ADP-ribosylation factor (Arf); clathrin-independent endocytosis; endocytosis; Golgi; membrane traffic; phosphoinositide ID ADP-RIBOSYLATION FACTOR; PLASMA-MEMBRANE; PHOSPHOLIPASE-D; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; REGULATED EXOCYTOSIS; DOWNSTREAM EFFECTOR; NUCLEOTIDE-EXCHANGE; PROTEINS; VESICLES; PATHWAY AB Arf (ADP-ribosylation factor) GTP-binding proteins function in cells to regulate membrane traffic and structure. Arfs accomplish this task through modification of membrane lipids and the recruitment of proteins, including coat proteins and actin, to membrane surfaces. Arf1 and Arf6 are the most divergent and most studied human Arf proteins that localize predominantly to the Golgi complex and plasma membrane respectively. We have been studying the targeting of Arf1 and Arf6 to these specific compartments and the common and divergent activities that they exert on these membranes. We have found that Arf6 acts through activation of type I phosphaticlylincisitol 4-phosphate S-kinases to generate phosphaticlylinositol 4,5-bisphosphate and that this activity is instrumental in facilitating the actin cytoskeletal rearrangements and alterations in endosomal membrane trafficking observed with increased Arf6 activation. Arf1 can also stimulate the activity of phosphatidylinositol kinases and recruit coat proteins and actin cytoskeletal elements to the Golgi complex. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Donaldson, JG (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Rm 2503, Bethesda, MD 20892 USA. EM jdonalds@helix.nih.gov NR 18 TC 28 Z9 28 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD DEC PY 2005 VL 33 BP 1276 EP 1278 PN 6 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 993CR UT WOS:000233930800012 PM 16246097 ER PT J AU Spiegel, S Milstien, S AF Spiegel, S Milstien, S TI Critical role of acylglycerol kinase in epidermal growth factor-induced mitogenesis of prostate cancer cells SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT BioScience 2005 Conference CY JUL 17-21, 2005 CL Glasgow, SCOTLAND DE acylglycerol kinase; epidermal growth factor (EGF); G-protein-coupled receptor (GPCR); lysophosphatidic acid (LPA); phosphatidic acid (PA); prostate cancer ID PROTEIN-COUPLED RECEPTORS; LYSOPHOSPHATIDIC ACID RECEPTOR; OVARIAN-CANCER; PHOSPHATIDIC-ACID; PHOSPHOLIPASE-D; EDG FAMILY; EGF RECEPTOR; HUMAN BREAST; PROLIFERATION; TRANSACTIVATION AB The bioactive phospholipids, LPA (lysophosphaticlic acid) and PA (phosphatidic acid), regulate pivotal processes related to the pathogenesis of cancer. Recently, we cloned a novel type of lipid kinase that phosphorylates monciacylglycerols (such as 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand) and diacylglycerols, to form LPA and PA, respectively. This AGK (acylglycerol kinase) is highly expressed in prostate cancer cell lines and the results reviewed here suggest that AGK might be a critical player in the initiation and progression of prostate cancer. Intriguingly, down-regulation of endogenous AGK inhibited EGF (epidermal growth factor), but not LPA-induced ERK1/2 (extracellular-signal-regulated kinase 1/2) activation and progression through the S-phase of the cell cycle. in this review, we will summarize the evidence demonstrating that AGK amplifies EGF growth signalling pathways that play an important role in the pathophysiology of prostate cancer. Because LPA has long been implicated as an autocrine and paracrine growth stimulatory factor for prostate cancer cells, the identification of this novel lipid kinase that regulates its production could provide new and useful targets for preventive or therapeutic measures. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Massey Canc Ctr, Dept Biochem, Richmond, VA 23298 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. EM sspiegel@vcu.edu FU NCI NIH HHS [CA61774]; NIAID NIH HHS [AI50094]; NIGMS NIH HHS [GM43880] NR 54 TC 15 Z9 15 U1 0 U2 3 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD DEC PY 2005 VL 33 BP 1362 EP 1365 PN 6 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 993CR UT WOS:000233930800034 PM 16246119 ER PT J AU Frank, GK Bailer, UF Henry, SE Drevets, W Meltzer, CC Price, JC Mathis, CA Wagner, A Hoge, J Ziolko, S Barbarich-Marsteller, N Weissfeld, L Kaye, WH AF Frank, GK Bailer, UF Henry, SE Drevets, W Meltzer, CC Price, JC Mathis, CA Wagner, A Hoge, J Ziolko, S Barbarich-Marsteller, N Weissfeld, L Kaye, WH TI Increased dopamine D2/D3 receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [C-11]raclopride SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anorexia nervosa; dopamine; positron emission tomography; [C-11]raclopride; eating disorders; brain imaging ID EATING-DISORDERS; PERSONALITY-TRAITS; ADDICTION; RATS; HYPERACTIVITY; AMPHETAMINE; RELEASE; HUMANS; MODEL; PET AB Backgound: Several lines of evidence support the possibility that disturbances of dopamine (DA) function could contribute to alterations of weight, feeding, motor activity, and reward in anorexia nervosa (AN). Methods: To assess possibly trait-related disturbances but avoid confounding effects of malnutrition, 10 women who were recovered from AN (REC AN) were compared with 12 healthy control women (CW). Positron emission tomography with [C-11]raclopride was used to assess DA D2/D3 receptor binding. Results: The women who were recovered from AN had significantly higher [C-11]raclopride binding potential in the antero-ventral striatum than CW. For REC AN, [C-11]raclopride binding potential was positively related to harm avoidance in the dorsal caudate and dorsal putamen. Conclusions: These data lend support for the possibility that decreased intrasynaptic DA concentration or increased D2/D3 receptor density or affinity is associated with AN and mighty contribute to the characteristic harm avoidance or increased physical activity found in AN. Most intriguing is the possibility that individuals with AN might have a DA related disturbance of reward mechanisms contributing to altered hedonics of feeding behaviour and theirascetic, anhedonic temperament. C1 Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15213 USA. Presbyterian Univ Hosp, Dept Radiol, Pittsburgh, PA USA. Presbyterian Univ Hosp, Dept Neurol, Pittsburgh, PA USA. Univ Calif San Diego, Sch Med, Dept Child & Adolescent Psychiat, San Diego, CA 92103 USA. Med Univ Vienna, Dept Gen Psychiat, Univ Hosp Psychiat, Vienna, Austria. NIMH, Neuroimaging Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Dept Neurobiol & Behav, Grad Program Neurosci, Stony Brook, NY 11794 USA. RP Kaye, WH (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, 3811 Ohara St,Iroquois Bldg,Suite 600, Pittsburgh, PA 15213 USA. EM kayewh@upmc.edu RI Mathis, Chester/A-8607-2009; OI Frank, Guido/0000-0002-6590-3441 FU NIMH NIH HHS [MH46001, T32-MH18399, MH42984]; NIMHD NIH HHS [K05-MD01894] NR 39 TC 176 Z9 179 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2005 VL 58 IS 11 BP 908 EP 912 DI 10.1016/j.biopsych.2005.05.003 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 994MM UT WOS:000234035900010 PM 15992780 ER PT J AU Swedo, SE Snider, LA AF Swedo, SE Snider, LA TI Regarding "Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders" - Reply SO BIOLOGICAL PSYCHIATRY LA English DT Letter C1 NIMH, Sect Behav Pediat, Pediat & Dev Neuropsychiat Branch, NIH,DHHS, Bethesda, MD 20892 USA. RP Swedo, SE (reprint author), NIMH, Sect Behav Pediat, Pediat & Dev Neuropsychiat Branch, NIH,DHHS, Bldg 10,Room 4N208,10 Ctr Dr,MSC 1225, Bethesda, MD 20892 USA. EM sniderl@mail.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2005 VL 58 IS 11 BP 918 EP 919 DI 10.1016/j.biopsych.2005.08.006 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 994MM UT WOS:000234035900014 ER PT J AU Pavletic, S Vogelsang, G AF Pavletic, S Vogelsang, G TI National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: Preface to the series SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Pavletic, S (reprint author), NCI, Bethesda, MD 20892 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2005 VL 11 IS 12 BP 943 EP 944 DI 10.1016/j.bbmt.2005.10.001 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 995JC UT WOS:000234095600001 ER PT J AU Filipovich, AH Weisdorf, D Pavletic, S Socie, G Wingard, JR Lee, SJ Martin, P Chien, J Przepiorka, D Couriel, D Cowen, EW Dinndorf, P Farrell, A Hartzman, R Henslee-Downey, J Jacobsohn, D McDonald, G Mittleman, B Rizzo, JD Robinson, M Schubert, M Schultz, K Shulman, H Turner, M Vogelsang, G Flowers, MED AF Filipovich, AH Weisdorf, D Pavletic, S Socie, G Wingard, JR Lee, SJ Martin, P Chien, J Przepiorka, D Couriel, D Cowen, EW Dinndorf, P Farrell, A Hartzman, R Henslee-Downey, J Jacobsohn, D McDonald, G Mittleman, B Rizzo, JD Robinson, M Schubert, M Schultz, K Shulman, H Turner, M Vogelsang, G Flowers, MED TI National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; allogeneic hematopoietic cell transplantation; consensus; diagnosis; staging ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; RISK-FACTORS; PREDICTIVE FACTORS; RECIPIENTS; BLOOD; DONORS; MULTICENTER; MORTALITY; CHILDREN AB This consensus document is intended to serve 3 functions. First, it standardizes the criteria for diagnosis of chronic graft-versus-host disease (GVHD). Second, it proposes a new clinical scoring system (0-3) that describes the extent and severity of chronic GVHD for each organ or site at any given time, taking functional impact into account. Third, it proposes new guidelines for global assessment of chronic GVHD severity that are based on the number of organs or sites involved and the degree of involvement in affected organs (mild, moderate, or severe). Diagnosis of chronic GVHD requires the presence of at least 1 diagnostic clinical sign of chronic GVHD (e.g., poikiloderma or esophageal web) or the presence of at least I distinctive manifestation (e.g., keratoconjunctivitis sicca) confirmed by pertinent biopsy or other relevant tests (e.g., Schirmer test) in the same or another organ. Furthermore, other possible diagnoses for clinical symptoms must be excluded. No time limit is set for the diagnosis of chronic GVHD. The Working Group recognized 2 main categories of GVHD, each with 2 subcategories. The acute GVHD category is defined in the absence of diagnostic or distinctive features of chronic GVHD and includes (1) classic acute GVHD occurring within 100 days after transplantation and (2) persistent, recurrent, or late acute GVHD (features of acute GVHD occurring beyond 100 days, often during withdrawal of immune suppression). The broad category of chronic GVHD includes (1) classic chronic GVHD (without features or characteristics of acute GVHD) and (2) an overlap syndrome in which diagnostic or distinctive features of chronic GVHD and acute GVHD appear together. It is currently recommended that systemic therapy he considered for patients who meet criteria for chronic GVHD of moderate to severe global severity. (c) 2005 American Society for Blood and Marrow Transplantation. C1 Univ Cincinnati, Childrens Hosp, Div Hematol Oncol, Cincinnati, OH 45229 USA. Univ Minnesota, Minneapolis, MN USA. Natl Canc Inst, NIH, Bethesda, MD USA. Hop St Louis, Paris, France. Univ Florida, Shands Cans Ctr, Gainesville, FL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. US FDA, Rockville, MD 20857 USA. Naval Med Res Ctr, CW Bill Young Dept Def Marrow Donor Recruitment &, Silver Spring, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Childrens Mem Hosp, Sch Med, Chicago, IL 60614 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Filipovich, AH (reprint author), Univ Cincinnati, Childrens Hosp, Div Hematol Oncol, 333 Burnet Ave,MLC 7015, Cincinnati, OH 45229 USA. EM lisa.filipovich@cchmc.org FU Intramural NIH HHS NR 29 TC 1471 Z9 1526 U1 9 U2 35 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2005 VL 11 IS 12 BP 945 EP 956 DI 10.1016/j.bbmt.2005.09.004 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 995JC UT WOS:000234095600002 PM 16338616 ER PT J AU Seebach, JD Stussi, G Passweg, JR Loberiza, FR Gajewski, JL Keating, A Goerner, M Rowlings, PA Tiberghien, P Elfenbein, GJ Gale, RP van Rood, JJ Reddy, V Gluckman, E Bolwell, BJ Klumpp, TR Horowitz, MM Ringden, O Barrett, AJ AF Seebach, JD Stussi, G Passweg, JR Loberiza, FR Gajewski, JL Keating, A Goerner, M Rowlings, PA Tiberghien, P Elfenbein, GJ Gale, RP van Rood, JJ Reddy, V Gluckman, E Bolwell, BJ Klumpp, TR Horowitz, MM Ringden, O Barrett, AJ CA GVHD Working Comm Ctr Int Blood Ma TI ABO blood group barrier in allogeneic bone marrow transplantation revisited SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE bone marrow transplantation; ABO blood groups; GVHD; survival; engraftment ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; COLONY-STIMULATING FACTOR; RISK-FACTORS; INCOMPATIBILITY; DONOR; APLASIA; ENGRAFTMENT; MORBIDITY; REMISSION AB Reports have shown a worse outcome for donor-recipient pairs mismatched for ABO blood groups in bone marrow transplantation (BMT). These studies, however, included small and heterogenous study populations, and not all considered bidirectional ABO incompatibility separately. Because the issue remains controversial, we analyzed the effect of ABO mismatch on the overall survival, transplant-related mortality, and occurrence of acute and chronic graft-versus-host disease (GVHD) in a large homogenous group of patients undergoing allogeneic BMT. A total of 3103 patients with early-stage leukemia who underwent transplantation between 1990 and 1998 with bone marrow from an HIA-identical sibling and who were reported to the Center for International Blood and Marrow Transplant Research were studied. The median follow-up was 54 months. A total of 2108 (67.9%) donor-recipient pairs were ABO identical, 451 (14.5%) had a minor mismatch, 430 (13.9%) had a major mismatch, and 114 (3.7%) had a bidirectional ABO mismatch. The groups did not differ significantly in patient or donor characteristics except for more female-to-male sex mismatch in the bidirectional ABO mismatch group (P=.017). In multivariate models of overall survival, transplant-related mortality, and grade H to IV acute GVHD, there were no significant differences among the 4 groups. Bidirectional ABO mismatch was associated with a significantly higher risk of grade III or IV acute GVHD (hazard ratio, 1.869; 95% confidence interval, 1.192-2.93; P=.006). Patients with major ABO mismatch received red blood cell transfusions (P=.001) for a longer timer after transplantation and had a slightly slower neutrophil recovery (P <.001). There was no evidence of a substantial effect of ABO blood group incompatibility on the outcome of conventional BMT among patients with leukemia. (c) 2005 American Society for Blood and Marrow Transplantation. C1 Med Coll Wisconsin, Hlth Policy Inst, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. Univ Zurich Hosp, Dept Internal Med, CH-8091 Zurich, Switzerland. Univ Basel Hosp, Dept Internal Med, CH-4031 Basel, Switzerland. Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. Heidelberg Univ, Heidelberg, Germany. Univ Newcastle, Newcastle Mater Hosp, Hunter Area Pathol Serv, Newcastle, NSW 2308, Australia. Etab Francais Sang Bourgogne Franche Comte, INSERM, Besancon, France. Roger Williams Canc Med Ctr, Providence, RI USA. Ctr Adv Studies Leukemia, Los Angeles, CA USA. Leiden Univ, Med Ctr, Europdonor Fdn, Leiden, Netherlands. Univ Florida, Coll Med, Gainesville, FL USA. Hop St Louis, Hematol Serv, Paris, France. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Temple Univ, Fox Chase BMT Program, Philadelphia, PA 19122 USA. Huddinge Univ Hosp, Dept Clin Immunol, S-14186 Huddinge, Sweden. NHLBI, NIH, Bethesda, MD 20892 USA. RP Horowitz, MM (reprint author), Med Coll Wisconsin, Hlth Policy Inst, Ctr Int Blood & Marrow Transplant Res, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM marymh@mcw.edu FU NCI NIH HHS [U24-CA76518] NR 26 TC 54 Z9 57 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2005 VL 11 IS 12 BP 1006 EP 1013 DI 10.1016/j.bbmt.2005.07.015 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 995JC UT WOS:000234095600009 PM 16338623 ER PT J AU Pfeiffer, RM Ryan, L Litonjua, A Pee, D AF Pfeiffer, RM Ryan, L Litonjua, A Pee, D TI A case-cohort design for assessing covariate effects in longitudinal studies SO BIOMETRICS LA English DT Article DE biased sampling; cohort study; correlated binary data; nested random-effects model ID HOSPITAL ADMISSIONS; NUISANCE PARAMETER; EFFECTS MODELS; AIR-POLLUTION; BINARY DATA; RISK; HOMOGENEITY; INFERENCE; LIFE AB The case-cohort design for longitudinal data consists of a subcohort sampled at the beginning of the study that is followed repeatedly over time, and a case sample that is ascertained through the course of the study. Although some members in the subcohort may experience events over the study period, we refer to it as the "control-cohort." The case sample is a random sample of subjects not in the control-cohort, who have experienced at least one event during the study period. Different correlations among repeated observations on the same individual are accommodated by a two-level random-effects model. This design allows consistent estimation of all parameters estimable in a cohort design and is a cost-effective way to study the effects of covariates on repeated observations of relatively rare binary outcomes when exposure assessment is expensive. It is an extension of the case-cohort design (Prentice, 1986, Biornetrika 73, 1-11) and the bidirectional case-crossover design (Navidi, 1998, Biometrics 54, 596-605). A simulation study compares the efficiency of the longitudinal case-cohort design to a full cohort analysis, and we find that in certain situations up to 90% efficiency can be obtained with half the sample size required for a full cohort analysis. A bootstrap method is presented that permits testing for intra-subject homogeneity in the presence of unidentifiable nuisance parameters in the two-level random-effects model. As an illustration we apply the design to data from an ongoing study of childhood asthma. C1 NCI, Biostat Branch, DCEG, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Informat Management Serv Inc, Rockville, MD 20852 USA. RP Pfeiffer, RM (reprint author), NCI, Biostat Branch, DCEG, EPS-8030, Bethesda, MD 20892 USA. EM pfeiffer@amail.nih.gov RI Ryan, Louise/A-4562-2009; Pfeiffer, Ruth /F-4748-2011; OI Ryan, Louise/0000-0001-5957-2490; Litonjua, Augusto/0000-0003-0422-5875 NR 27 TC 3 Z9 3 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2005 VL 61 IS 4 BP 982 EP 991 DI 10.1111/j.1541-0420.2005.00364.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 994WP UT WOS:000234062200015 PM 16401271 ER PT J AU Hans, C Dunson, DB AF Hans, C Dunson, DB TI Bayesian inferences on umbrella orderings SO BIOMETRICS LA English DT Article DE bathtub shapes; downturn order; gibbs sampler; mixture prior; order constraint; probit model; shape restriction; variable selection ID ISOTONIC REGRESSION; RESTRICTIONS; SELECTION; BIOASSAY; SUBJECT; POINTS; BINARY; TESTS AB In regression applications with categorical predictors, interest often focuses on comparing the null hypothesis of homogeneity to an ordered alternative. This article proposes a Bayesian approach for addressing this problem in the setting of normal linear and probit regression models. The regression coefficients are assigned a conditionally conjugate prior density consisting of mixtures of point masses at 0 and truncated normal densities, with a (possibly unknown) changepoint parameter included to accommodate umbrella ordering. Two strategies of prior elicitation are considered: (1) a Bayesian Bonferroni approach in which the probability of the global null hypothesis is specified and local hypotheses are considered independent; and (2) an approach which treats these probabilities as random. A single Gibbs sampling chain can be used to obtain posterior probabilities for the different hypotheses and to estimate regression coefficients and predictive quantities either by model averaging or under the preferred hypothesis. The methods are applied to data from a carcinogenesis study. C1 Duke Univ, Inst Stat & Decis Sci, Durham, NC 27708 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Hans, C (reprint author), Duke Univ, Inst Stat & Decis Sci, Durham, NC 27708 USA. EM hans@stat.duke.edu NR 28 TC 8 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2005 VL 61 IS 4 BP 1018 EP 1026 DI 10.1111/j.1541-0420.2005.00373.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 994WP UT WOS:000234062200019 PM 16401275 ER PT J AU Harezlak, J Ryan, LM Giedd, JN Lange, N AF Harezlak, J Ryan, LM Giedd, JN Lange, N TI Individual and population penalized regression splines for accelerated longitudinal designs SO BIOMETRICS LA English DT Article DE brain volume; growth curves; magnetic resonance imaging; mixed effects; pediatric development; smooth regression ID BRAIN-DEVELOPMENT; EFFECTS MODELS; CURVES; VARIANCE; MRI AB In an accelerated longitudinal design (ALD), individuals enter the study at different points of their growth trajectory and are observed over a short time span relative to the entire time span of interest. ALD data are combined across independent units to provide an estimate of an overall population curve and predictions of individual patterns of change. As a modest extension of the work of Ruppert et al. (2003, Semiparametric Regression, Cambridge University Press), we develop a computationally efficient procedure for the application of longitudinal serniparametric methods under ALD sampling schemes. We compare balanced and complete longitudinal designs to ALDs using the Berkeley Growth Study data and apply our method to longitudinal magnetic resonance imaging (MRI) brain structure size (volume) measurements from an ongoing developmental study. Potential applications extend beyond growth studies to many other fields in which cost and feasibility constraints impose restrictions on sample size and on the numbers and timings of repeated measurements across subjects. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Stat Neuroimaging Lab, Belmont, MA 02478 USA. RP Harezlak, J (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM jharezla@hsph.harvard.edu RI Giedd, Jay/A-3080-2008; Ryan, Louise/A-4562-2009; Giedd, Jay/B-7302-2012; Harezlak, Jaroslaw/P-8557-2014; Giedd, Jay/J-9644-2015 OI Ryan, Louise/0000-0001-5957-2490; Giedd, Jay/0000-0003-0827-3460; Harezlak, Jaroslaw/0000-0002-3070-7686; Giedd, Jay/0000-0003-2002-8978 FU NCI NIH HHS [CA48061]; NIEHS NIH HHS [ES07142]; NIGMS NIH HHS [GM29745]; NIMH NIH HHS [MH60450]; NINDS NIH HHS [NS37483] NR 36 TC 12 Z9 13 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2005 VL 61 IS 4 BP 1037 EP 1048 DI 10.1111/j.1541-0420.2005.00376.x PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 994WP UT WOS:000234062200021 PM 16401277 ER PT J AU Albert, PS Hunsberger, S AF Albert, PS Hunsberger, S TI On analyzing circadian rhythms data using nonlinear mixed models with harmonic terms SO BIOMETRICS LA English DT Article DE harmonic models; nonlinear models; periodic data; seasonal data; smoothing ID ERRORS AB Wang, Ke, and Brown (2003, Biometrics 59, 804-812) developed a smoothing-based approach for modeling circadian rhythms with random effects. Their approach is flexible in that fixed and random covariates can affect both the amplitude and phase shift of a nonparametrically smoothed periodic function. In motivating their approach, Wang et al. stated that a simple sinusoidal function is too restrictive. In addition, they stated that "although adding harmonics can improve the fit, it is difficult to decide how many harmonics to include in the model, and the results are difficult to interpret." We disagree with the notion that harmonic models cannot be a useful tool in modeling longitudinal circadian rhythm data. In this note, we show how nonlinear mixed models with harmonic terms allow for a simple and flexible alternative to Wang et al.'s approach. We show how to choose the number of harmonics using penalized likelihood to flexibly model circadian rhythms and to estimate the effect of covariates on the rhythms. We fit harmonic models to the cortisol circadian rhythm data presented by Wang et al. to illustrate our approach. Furthermore, we evaluate the properties of our procedure with a small simulation study. The proposed parametric approach provides an alternative to Wang et al.'s semiparametric approach and has the added advantage of being easy to implement in most statistical software packages. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), NCI, Biometr Res Branch, Execut Plaza N,Room 8136, Bethesda, MD 20892 USA. EM albertp@ctep.nci.nih.gov NR 12 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2005 VL 61 IS 4 BP 1115 EP 1120 DI 10.1111/j.0006-341X.2005.464_1.x PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 994WP UT WOS:000234062200030 PM 16401286 ER PT J AU Sen, S Paraggio, NA Gearheart, LA Connor, EE Issa, A Coleman, RS Wilson, DM Wyatt, MD Berg, MA AF Sen, S Paraggio, NA Gearheart, LA Connor, EE Issa, A Coleman, RS Wilson, DM Wyatt, MD Berg, MA TI Effect of protein binding on ultrafast DNA dynamics: Characterization of a DNA : APE1 complex SO BIOPHYSICAL JOURNAL LA English DT Article ID HUMAN ABASIC ENDONUCLEASE; SOLVATION DYNAMICS; SOLVENT POLARITY; NUCLEIC-ACIDS; SITE ANALOGS; AMINO-ACID; REPAIR; FEMTOSECOND; BASE; PICOSECOND AB Synthetic oligonucleotides with a fluorescent coumarin group replacing a basepair have been used in recent time-resolved Stokes-shift experiments to measure DNA dynamics on the femtosecond to nanosecond timescales. Here, we show that the APE1 endonuclease cleaves such a modified oligonucleotide at the abasic site opposite the coumarin with only a fourfold reduction in rate. In addition, a noncatalytic mutant (D210N) binds tightly to the same oligonucleotide, albeit with an 85-fold reduction in binding constant relative to a native oligonucleotide containing a guanine opposite the abasic site. Thus, the modified oligonucleotide retains substantial biological activity and serves as a useful model of native DNA. In the complex of the coumarin-containing oligonucleotide and the noncatalytic APE1, the dye's absorption spectrum is shifted relative to its spectrum in either water or within the unbound oligonucleotide. Thus the dye occupies a site within the DNA: protein complex. This result is consistent with modeling, which shows that the complex accommodates coumarin at the site of the orphaned base with little distortion of the native structure. Stokes-shift measurements of the complex show surprisingly little change in the dynamics within the 40 ps - 40 ns time range. C1 Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. Univ S Carolina, Dept Basic Pharmaceut Sci, Columbia, SC 29208 USA. Presbyterian Coll, Dept Chem, Clinton, SC USA. Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Berg, MA (reprint author), Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. EM berg@mail.chem.sc.edu OI Berg, Mark/0000-0002-9063-4810; Wyatt, Michael/0000-0003-1815-9565 FU NIEHS NIH HHS [ES-00333]; NIGMS NIH HHS [GM-61292, R01 GM061292] NR 53 TC 22 Z9 24 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 2005 VL 89 IS 6 BP 4129 EP 4138 DI 10.1529/biophysj.105.062695 PG 10 WC Biophysics SC Biophysics GA 988JO UT WOS:000233590800050 PM 16199493 ER PT J AU Rich, BA Bhangoo, RK Vinton, DT Berghorst, LH Dickstein, DP Grillon, C Davidson, RJ Leibenluft, E AF Rich, BA Bhangoo, RK Vinton, DT Berghorst, LH Dickstein, DP Grillon, C Davidson, RJ Leibenluft, E TI Using affect-modulated startle to study phenotypes of pediatric bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; children; mood dysregulation; phenotypes; reward; startle ID POSTTRAUMATIC-STRESS-DISORDER; FEAR-POTENTIATED STARTLE; PREPULSE INHIBITION; ACOUSTIC STARTLE; REFLEX MODULATION; DECISION-MAKING; SPIDER PHOBICS; RATING-SCALE; MANIA; EMOTION AB Objectives: Affective neuroscience research that investigates core symptoms of pediatric bipolar disorder (PBD) may be effective in differentiating PBD phenotypes. The current study used affect-modulated startle to examine potential differences in reactivity to emotional stimuli (reward and punishment) in narrow and broad phenotype PBD and controls. Methods: Thirty children meeting DSM-IV bipolar disorder criteria (i.e. narrow phenotype PBD with defined manic episodes with elevated/ expansive mood), 19 children meeting criteria for severe mood dysregulation (i.e. broad phenotype with chronic irritability, hyper-reactivity, and hyperarousal), and 19 controls completed a lottery startle paradigm involving reward (money) and punishment (loud noise). Startle probes were presented during anticipation of the emotional stimulus, immediately following the presentation of the stimulus, or during return to baseline following the stimulus. Results: By self-report, patients and controls found the putative punishment to be preferable to the neutral condition. In the reward condition, patient samples reported greater arousal than did controls, but no between-group differences were found on the magnitude of startle response during the reward, punishment, or neutral conditions. Conclusions: The failure to find differences in affect-modulated startle between control children and those with narrow or broad PBD phenotypes speaks to the methodological challenges associated with studying reward mechanisms in PBD. Alternative paradigms that focus on different aspects of reward mechanisms are discussed. C1 NIH, Pediat & Dev Neuropsychiat Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Psychiat, Davis, CA 95616 USA. NIMH, Mood & Anxiety Program, Unit Affect Psychophysiol, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. RP Rich, BA (reprint author), NIH, Pediat & Dev Neuropsychiat Branch, Dept Hlth & Human Serv, 10 Ctr Dr MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA. EM brendanrich@mail.nih.gov RI Dickstein, Daniel/L-3210-2016 OI Dickstein, Daniel/0000-0003-1647-5329 NR 47 TC 17 Z9 17 U1 7 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2005 VL 7 IS 6 BP 536 EP 545 DI 10.1111/j.1399-5618.2005.00265.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 991MO UT WOS:000233818300007 PM 16403179 ER PT J AU Muraoka, N Shum, L Fukumoto, S Nomura, T Ohishi, M Nonaka, K AF Muraoka, N Shum, L Fukumoto, S Nomura, T Ohishi, M Nonaka, K TI Transforming growth factor-beta 3 promotes mesenchymal cell proliferation and angiogenesis mediated by the enhancement of Cyclin D1, Flk-1, and CD31 gene expression during CL/Fr mouse lip fusion SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Japanese-Society-of-Pediatric-Dentistry CY 2004 CL Fukuoka, JAPAN SP Japanese Soc Pediatr Dentistry DE cleft lip; CL/Fraser mouse; mesenchymal cells; TGF-beta 3; Flk-1; CD31; cychn D1; serum-free organ culture ID CLEFT-LIP; TGF-BETA; TRANSCRIPTION FACTOR; PALATAL FUSION; MICE; TGF-BETA-3; KINASE; PALATOGENESIS; INHIBITION; FREQUENCY AB BACKGROUND: Cleft lip with or without cleft palate is the most common congenital anomaly in the craniofacial region. Knowledge of the molecular mechanisms behind normal lip fusion can contribute to better intervention and improved functional clinical outcome. Transforming growth factor-beta 3 (TGF-beta 3) has been implicated in lip morphogenesis. Therefore, we hypothesized that TGF-beta 3 functions during lip fusion through regulation of angiogenesis and mesenchymal cell cycle progression during early developmental stages. METHODS: To test this hypothesis we used the CL/Fraser mouse model, which has a high incidence of cleft lip. Lips isolated from embryonic day (ED) 11.5 mouse embryos were allowed to develop in serum-free organ cultures in the presence or absence of TGF-beta 3. The lips that developed in these cultures fused in 2 days. RESULTS: During normal development, we detected positive immunoreactions for TGF-beta 3 at the site of fusion. We also detected mesenchymal cells that were immunopositive for Flk-1 and CD31, which are markers for endothelial cell precursors. Exogenous TGF-beta 3 accelerated lip fusion in culture. This enhancement was associated with an increase in the number of capillary blood vessels in the lips cultured in the presence of TGF-beta 3, in comparison with controls. In tandem, TGF-beta 3 increased the level of expression of both Flk-1 and CD31. Our data suggest that an elevated level of TGF-beta 3 may promote angiogenesis in developing lips that is mediated by increased Flk-1 and CD31 expression. We also detected increased cyclin D1 expression (a marker for cell proliferation) in the presence of TGF-beta 3, which suggests that TGF-beta 3 promoted cell proliferation. CONCLUSIONS: TGF-beta 3 promoted cell proliferation and angiogenesis in lip mesenchymal tissues. These events led to enhanced lip fusion in the presence of TGF-beta 3. C1 Kyushu Univ, Div Oral Hlth Growth & Dev, Sect Pediat Dent, Fukuoka 812, Japan. Kyushu Univ, Grad Sch Dent Sci, Fukuoka 812, Japan. Natl Inst Dent & Craniofacial Res, Div Basic & Translat Sci, NIH, Bethesda, MD USA. Osaka Univ, Grad Sch Med, Dept Radiat Biol & Med Genet, Osaka, Japan. Kyushu Univ, Div Maxillofacial Diagnost & Surg Sci, Fukuoka 8128582, Japan. RP Nonaka, K (reprint author), Kyushu Univ, Fac Dent Sci, Div Pediat Dent, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan. EM nonaka@dent.kyushu-u.ac.jp NR 37 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD DEC PY 2005 VL 73 IS 12 BP 956 EP 965 DI 10.1002/bdra.20191 PG 10 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 000LR UT WOS:000234464000002 PM 16323168 ER PT J AU Golub, M Costa, L Crofton, K Frank, D Fried, P Gladen, B Henderson, R Liebelt, E Lusskin, S Marty, S Rowland, A Scialli, J Vore, M AF Golub, M Costa, L Crofton, K Frank, D Fried, P Gladen, B Henderson, R Liebelt, E Lusskin, S Marty, S Rowland, A Scialli, J Vore, M TI NTP-CERHR expert panel report on the reproductive and developmental toxicity of amphetamine and methamphetamine SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review ID COLLABORATIVE BEHAVIORAL TERATOLOGY; DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; KINASE-A ACTIVITY; EARLY POSTNATAL-DEVELOPMENT; REAGGREGATE TISSUE-CULTURE; NERVOUS-SYSTEM STIMULANTS; STRIATAL DOPAMINE RELEASE; D-2-LIKE BINDING-SITES; PRENATAL D-AMPHETAMINE C1 Calif Environm Protect Agcy, Sacramento, CA USA. Univ Washington, Seattle, WA 98195 USA. US EPA, Res Triangle Pk, NC 27711 USA. Boston Med Ctr, Boston, MA USA. Carleton Univ, Ottawa, ON K1S 5B6, Canada. NIEHS, Res Triangle Pk, NC 27709 USA. Lovelace Resp Res Inst, Albuquerque, NM USA. Univ Alabama, Sch Med, Birmingham, AL USA. NYU, Sch Med, New York, NY USA. Dow Chem Co USA, Midland, MI 48674 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Kentucky, Lexington, KY USA. RP Golub, M (reprint author), Care of Shelby MD, NIEHS, EC-32,POB 12233, Res Triangle Pk, NC 27709 USA. RI Crofton, Kevin/J-4798-2015 OI Crofton, Kevin/0000-0003-1749-9971 NR 258 TC 20 Z9 22 U1 0 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD DEC PY 2005 VL 74 IS 6 BP 471 EP 584 DI 10.1002/bdrb.20048 PG 114 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 999MX UT WOS:000234394800001 PM 16167346 ER PT J AU Wilson, WH AF Wilson, WH TI R-CHOP strikes again with survival benefit in follicular lymphoma SO BLOOD LA English DT Editorial Material ID LOW-GRADE; CHEMOTHERAPY; RITUXIMAB AB Hiddemann and colleagues demonstrate improved response duration and overall survival with the addition of rituximab to CHOP, compared with CHOP alone, in symptomatic patients with untreated advanced-stage follicular lymphoma. C1 NCI, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2005 VL 106 IS 12 BP 3678 EP 3679 DI 10.1182/blood-2005-09-3701 PG 2 WC Hematology SC Hematology GA 989HB UT WOS:000233662400002 ER PT J AU Trinchieri, G AF Trinchieri, G TI Cytokine receptor gene plays antioncogene SO BLOOD LA English DT Editorial Material ID IL-12 AB The opportunity to study the dynamics of thrombopoeisis in real time has long been awaited. C1 NIAID, Bethesda, MD 20892 USA. RP Trinchieri, G (reprint author), NIAID, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2005 VL 106 IS 12 BP 3684 EP 3685 DI 10.1182/blood-2005-09-3678 PG 2 WC Hematology SC Hematology GA 989HB UT WOS:000233662400009 ER PT J AU Parker, C Omine, M Richards, S Nishimura, J Bessler, M Ware, R Hillmen, P Luzzatto, L Young, N Kinoshita, T Rosse, W Socie, G AF Parker, C Omine, M Richards, S Nishimura, J Bessler, M Ware, R Hillmen, P Luzzatto, L Young, N Kinoshita, T Rosse, W Socie, G CA Int PNH Interest Grp TI Diagnosis and management of paroxysmal nocturnal hemoglobinuria SO BLOOD LA English DT Review ID BONE-MARROW-TRANSPLANTATION; HEMATOPOIETIC-CELL TRANSPLANTATION; AMPLICON MELTING ANALYSIS; ESOPHAGEAL MOTOR FUNCTION; BUDD-CHIARI-SYNDROME; IN-VIVO EVIDENCE; APLASTIC-ANEMIA; IDENTICAL TWIN; FLOW-CYTOMETRY; VENOUS THROMBOSIS C1 George E Whalen VA Med Ctr, Hematol Oncol Sect, Salt Lake City, UT 84148 USA. Univ Utah, Sch Med, Div Hematol, Salt Lake City, UT USA. Showa Univ, Fujigaoka Hosp, Dept Med, Div Hematol, Kanagawa, Japan. Govt Japan, Minist Hlth Labor & Welf, Res Committee Idiopath Hematopoiet Disorders, Leeds, W Yorkshire, England. HMDS, Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England. Duke Univ, Med Ctr, Dept Med, Div Cellular Therapy, Durham, NC USA. Duke Univ, Sch Med, Durham, NC USA. Washington Univ, Sch Med, Div Hematol, St Louis, MO USA. St Jude Childrens Res Hosp, Div Hematol, Memphis, TN USA. Ist Nazl Ric Canc, Genoa, Italy. Hematol Branch, NIH, Bethesda, MD USA. Osaka Univ, Res Inst Microbial Dis, Osaka, Japan. Hop St Louis, Serv Hematol Greffe Moelle, Paris, France. RP Parker, C (reprint author), George E Whalen VA Med Ctr, Hematol Oncol Sect, Salt Lake City, UT 84148 USA. EM charles.parker@hsc.utah.edu RI Kinoshita, Taroh/C-7353-2009 FU NCI NIH HHS [R01-CA89 091] NR 90 TC 298 Z9 316 U1 0 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2005 VL 106 IS 12 BP 3699 EP 3709 DI 10.1182/blood-2005-04-1717 PG 11 WC Hematology SC Hematology GA 989HB UT WOS:000233662400014 PM 16051736 ER PT J AU Economopoulou, M Bdeir, K Cines, DB Fogt, F Bdeir, Y Lubkowski, J Lu, WY Preissner, KT Hammes, HP Chavakis, T AF Economopoulou, M Bdeir, K Cines, DB Fogt, F Bdeir, Y Lubkowski, J Lu, WY Preissner, KT Hammes, HP Chavakis, T TI Inhibition of pathologic retinal neovascularization by alpha-defensins SO BLOOD LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NEUTROPHIL DEFENSINS; IN-VIVO; FIBRONECTIN; ANGIOGENESIS; RETINOPATHY; RECEPTOR; INTEGRIN; BINDING; DYSFUNCTION AB Proliferative retinopathies, such as those complicating prematurity and diabetes, are major causes of blindness. A prominent feature of these retinopathies is excessive neovascularization, which is orchestrated by the hypoxia-induced vascular endothelial growth factor (VEGF) stimulating endothelial cells and the integrin-mediated adhesive interactions of endothelial cells with extracellular matrix components such as fibronectin (FN). Recently, we demonstrated that alpha-defensins interfere with alpha 5 beta 1-FN interactions and dependent endothelial cell functions. Here, alpha-defensins were studied in hypoxia-induced proliferative retinopathy. In vitro, alpha-defensins specifically inhibited alpha 5 beta 1-integrin-dependent migration of bovine retinal endothelial cells (BRECs) to FN, attenuated the VEGF-stimulated increase in endothelial permeability, and blocked BREC proliferation and capillary sprout formation in 3-dimensional fibrin-matrices. An up-regulation of beta 1-integrin and FN was observed in the retinal vessels in the mouse model of hypoxia-induced retinal angiogenesis. Systemic and local administration of a-defensins reduced retinal neovascularization by 45% and 60%, respectively, and this effect was comparable to the inhibitory effect of alpha 5 beta 1-blocking antibody. alpha-Defensins were detected in human diabetic retinas associated with normal retinal vessels but were absent from proliferative lesions. Together, these data show that a-defensins inhibit pathologic retinal neovascularization in vivo and may provide a clinically efficient strategy against proliferative retinopathies. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Clin Mannheim, Dept Internal Med 5, Mannheim, Germany. Univ Giessen, Dept Ophthalmol, Giessen, Germany. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NCI, Macromol Assembly Struct & Cell Signaling Sect, Frederick, MD 21701 USA. Univ Maryland, Inst Human Virol, Inst Biotechnol, Baltimore, MD 21201 USA. Univ Giessen, Inst Biochem, Giessen, Germany. RP Chavakis, T (reprint author), NCI, Expt Immunol Branch, NIH, Rm 4B17,10 Ctr Dr, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov RI Lu, Wuyuan/B-2268-2010 FU NHLBI NIH HHS [P01 HL076406] NR 48 TC 43 Z9 47 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2005 VL 106 IS 12 BP 3831 EP 3838 DI 10.1182/blood-2005-03-0889 PG 8 WC Hematology SC Hematology GA 989HB UT WOS:000233662400032 PM 16123222 ER PT J AU Wada, T Schurman, SH Garabedian, EK Yachie, A Candotti, F AF Wada, T Schurman, SH Garabedian, EK Yachie, A Candotti, F TI Analysis of T-cell repertoire diversity in Wiskott-Aldrich syndrome SO BLOOD LA English DT Article ID SYNDROME PROTEIN; IN-VIVO; LYMPHOCYTES; EXPRESSION; WASP; ACTIVATION; APOPTOSIS AB Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by thrombocytopenia, eczema, and variable degrees of impaired cellular and humoral immunity. Age-dependent T-cell lymphopenia has been described in WAS, however, the diversity of the T-cell compartment over time in these patients has not been characterized. We have used complementarity-determining region 3 (CDR3) size distribution analysis to assess T-cell receptor (TCR) V beta repertoire in 13 patients with WAS. Diverse CDR3 size pattern was demonstrated in patients under 15 years of age regardless of the levels of WAS protein (WASP) expression. in contrast, older patients showed significantly higher skewing of TCRV beta repertoire as compared with healthy adults. We did not find correlation between clinical score and complexity of TCRV beta repertoire. These findings suggest that WASP deficiency does not limit thymic generation of a normal TCR and indicate that T-cell oligoclonality may contribute to the immunodeficiency in older patients with WAS. C1 NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. Kanazawa Univ, Fac Med, Sch Hlth Sci, Dept Lab Sci, Kanazawa, Ishikawa 920, Japan. RP Candotti, F (reprint author), NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Bldg 49,Rm 3A20,MSC 4442, Bethesda, MD 20892 USA. EM fabio@nhgri.nih.gov RI Yachie, Akihiro/C-4660-2015; OI Schurman, Shepherd/0000-0002-9133-7906 NR 21 TC 24 Z9 26 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2005 VL 106 IS 12 BP 3895 EP 3897 DI 10.1182/blood-2005-06-2336 PG 3 WC Hematology SC Hematology GA 989HB UT WOS:000233662400041 PM 16091449 ER PT J AU Du, Y Jenkins, NA Copeland, NG AF Du, Y Jenkins, NA Copeland, NG TI Insertional mutagenesis identifies genes that promote the immortalization of primary bone marrow progenitor cells SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIAS; CHRONIC MYELOID-LEUKEMIA; PR-DOMAIN; MYELODYSPLASTIC SYNDROMES; BLAST-CRISIS; EV11 GENE; EXPRESSION AB Retroviruses can induce hematopoietic disease via insertional mutagenesis of cancer genes and provide valuable molecular tags for cancer gene discovery. Here we show that insertional mutagenesis can also identify genes that promote the immortalization of hematopoietic cells, which normally have only limited self-renewal. Transduction of mouse bone marrow cells with replication-incompetent murine stem cell virus (MSCV) expressing only neo, followed by serial passage in liquid culture containing stem cell factor (SCIF) and interleukin-3 (IL-3), produced immortalized immature myeloid cell lines with neutrophil and macrophage differentiation potential in about 50% of the infected cultures. More than half of the lines have MSCV insertions at Evil or Prdm16. These loci encode transcription factor homologs and are validated human myeloid leukemia genes. Integrations are located in intron 1 or 2, where they promote expression of truncated proteins lacking the PRDI-BF1-RIZ1 homologous (PR) domain, similar to what is observed in human leukemias with EVI1 or PRDM16 mutations. Evi1 overexpression alone appears sufficient to immortalize immature myeloid cells and does not seem to require any other cooperating mutations. Genes identified by insertional mutagenesis by their nature could also be involved in immortalization of leukemic stem cells, and thus represent attractive drug targets for treating cancer. C1 NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Copeland, NG (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. EM copeland@ncifcrf.gov FU Intramural NIH HHS NR 53 TC 130 Z9 135 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2005 VL 106 IS 12 BP 3932 EP 3939 DI 10.1182/blood-2005-03-1113 PG 8 WC Hematology SC Hematology GA 989HB UT WOS:000233662400046 PM 16109773 ER PT J AU Baraniuk, JN Casado, B Maibach, H Clauw, DJ Pannell, LK Hess, S AF Baraniuk, JN Casado, B Maibach, H Clauw, DJ Pannell, LK Hess, S TI A chronic fatigue syndrome - related proteome in human cerebrospinal fluid SO BMC NEUROLOGY LA English DT Review ID CEREBRAL AMYLOID ANGIOPATHY; HUMAN ALPHA(1)-ACID GLYCOPROTEIN; HUMAN CYSTATIN-C; ALZHEIMERS-DISEASE; CHOROID-PLEXUS; LYSOPHOSPHOLIPASE-D; MULTIPLE-SCLEROSIS; MASS-SPECTROMETRY; OVARIAN-CANCER; CDNA CLONING AB Background: Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and fibromyalgia are overlapping symptom complexes without objective markers or known pathophysiology. Neurological dysfunction is common. We assessed cerebrospinal fluid to find proteins that were differentially expressed in this CFS-spectrum of illnesses compared to control subjects. Methods: Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control subjects (50 mu l/subject) were pooled into one sample per group (cohort 1). Cohort 2 of 12 control and 9 CFS subjects had their fluids (200 mu/subject) assessed individually. After trypsin digestion, peptides were analyzed by capillary chromatography, quadrupole-time-of-flight mass spectrometry, peptide sequencing, bioinformatic protein identification, and statistical analysis. Results: Pooled CFS and PGI samples shared 20 proteins that were not detectable in the pooled control sample (cohort 1 CFS-related proteome). Multilogistic regression analysis (GLM) of cohort 2 detected 10 proteins that were shared by CFS individuals and the cohort 1 CFS-related proteome, but were not detected in control samples. Detection of >= 1 of a select set of 5 CFS-related proteins predicted CFS status with 80% concordance ( logistic model). The proteins were alpha-1-macroglobulin, amyloid precursor-like protein 1, keratin 16, orosomucoid 2 and pigment epithelium-derived factor. Overall, 62 of 115 proteins were newly described. Conclusion: This pilot study detected an identical set of central nervous system, innate immune and amyloidogenic proteins in cerebrospinal fluids from two independent cohorts of subjects with overlapping CFS, PGI and fibromyalgia. Although syndrome names and definitions were different, the proteome and presumed pathological mechanism(s) may be shared. C1 Georgetown Univ, Georgetown Proteom Lab, Div Rheumatol Immunol & Allergy, Washington, DC 20007 USA. Univ Pavia, Dept Biochim A Castellani, Pavia, Italy. Univ Michigan, Ctr Advancement Clin Res, Ann Arbor, MI USA. Univ Alabama, Canc Res Inst, Mobile, AL USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Baraniuk, JN (reprint author), Georgetown Univ, Georgetown Proteom Lab, Div Rheumatol Immunol & Allergy, Room B-105,Lower Level Kober Cogan Bldg,3800 Rese, Washington, DC 20007 USA. EM baraniuj@georgetown.edu; bc48@georgetown.edu; hildamaibach@comcast.net; dclauw@med.umich.edu; lpannell@usouthal.edu; Sonja_Hess@nih.gov RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 FU NCRR NIH HHS [M01 RR023942-025281, 1 M01-RR13297-01A1, M01 RR013297, M01 RR023942]; NIAID NIH HHS [R01 AI042403, R01 AI42403]; NIEHS NIH HHS [R01 ES015382, R01 ES015382-01] NR 103 TC 32 Z9 32 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD DEC 1 PY 2005 VL 5 AR 22 DI 10.1186/1471-2377-5-22 PG 19 WC Clinical Neurology SC Neurosciences & Neurology GA 024SW UT WOS:000236217500001 PM 16321154 ER PT J AU Savani, BN Montero, A Kurlander, R Childs, R Hensel, N Barrett, AJ AF Savani, BN Montero, A Kurlander, R Childs, R Hensel, N Barrett, AJ TI Imatinib synergizes with donor lymphocyte infusions to achieve rapid molecular remission of CML relapsing after allogeneic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE CML; allogeneic stem cell transplantation; DLI; imatinib ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; VERSUS-HOST-DISEASE; FOLLOW-UP; PROLIFERATION; IMMUNOTHERAPY; TRANSFUSIONS; ACTIVATION; RESPONSES AB Donor lymphocyte infusions (DLI) have been the mainstay of treatment for chronic myeloid leukemia (CML) relapsing after allogeneic stem cell transplantation (alloSCT). Imatinib mesylate (IM) is also effective in these patients. However, advanced phase relapse (APRel) responds poorly with either treatment. To test the possibility that combinations of DLI and IM might be more effective, 37 patients with CML relapsing after alloSCT between August 1994 and May 2004 were studied. Ten had molecular relapse (MRel), 14 hematological relapse (HRel) and 13 APRel. Thirteen received DLI, 9 IM and 11 DLI+IM. Four patients received DLI+IM but not concurrently. Thirty (81%) patients responded ( actuarial survival and current leukemia-free survival of 80.6 +/- 6.7% and 69.1 +/- 7.7%). Of 30 patients, 26 are in molecular remission (MR), median follow-up of 1226 days ( range 249 - 3257) since relapse. Ten of 11 patients ( including four with APRel) treated with DLI+IM achieved MR in 3 months and all are alive in MR. In contrast, only two of 22 treated with either modality (1/13 DLI and 1/9 IM) achieved MR at 3 months, 15 are alive, 11 in MR. Four patients receiving nonconcurrent DLI+IM are also alive in MR. In conclusion, DLI appears to synergize with IM to induce rapid and durable MR. C1 NHLBI, Stem Cell Allogeneic Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogeneic Transplantat Sect, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Room 3-5320,10 Ctr Dr,MSC 12, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov NR 31 TC 62 Z9 69 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD DEC PY 2005 VL 36 IS 11 BP 1009 EP 1015 DI 10.1038/sj.bmt.1705167 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 983ZR UT WOS:000233271400012 PM 16205732 ER PT J AU Khan, NL Jain, S Lynch, JM Pavese, N Abou-Sleiman, P Holton, JL Healy, DG Gilks, WP Sweeney, MG Ganguly, M Gibbons, V Gandhi, S Vaughan, J Eunson, LH Katzenschlager, R Gayton, J Lennox, G Revesz, T Nicholl, D Bhatia, KP Quinn, N Brooks, D Lees, AJ Davis, MB Piccini, P Singleton, AB Wood, NW AF Khan, NL Jain, S Lynch, JM Pavese, N Abou-Sleiman, P Holton, JL Healy, DG Gilks, WP Sweeney, MG Ganguly, M Gibbons, V Gandhi, S Vaughan, J Eunson, LH Katzenschlager, R Gayton, J Lennox, G Revesz, T Nicholl, D Bhatia, KP Quinn, N Brooks, D Lees, AJ Davis, MB Piccini, P Singleton, AB Wood, NW TI Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data SO BRAIN LA English DT Article DE LRRK2; dardarin; Lewy bodies ID AUTOSOMAL-DOMINANT PARKINSONISM; DIAGNOSIS; SYNUCLEIN; LOCUS; IDENTIFICATION; DYSFUNCTION; FREQUENT; PET AB We have established that the frequency of LRRK2 mutations in a series of 118 cases of familial Parkinson's disease is 5.1%. In the largest family with autosomal dominant, late-onset Parkinson's disease where affected subjects share a Y1699C missense mutation we provide a detailed clinical, pathological and imaging report. The phenotype in this large British kindred included asymmetrical, levodopa-responsive parkinsonism where unilateral leg tremor at onset and foot dystonia were prominent features. There was no significant abnormality of cognition but there was prominent behavioural disorder. We observed a lower age of onset in successive generations. Histopathology in one patient showed substantia nigra cell loss and Lewy body formation, with small numbers of cortical Lewy bodies. (18)F-dopa positron emission tomography (PET) in another patient showed a pattern of nigrostriatal dysfunction typical of idiopathic Parkinson's disease. (18)F-dopa-PET scans in unaffected family members prior to identifying the disease locus did not detect subclinical nigrostriatal dysfunction. Olfaction was assessed in affected subjects and Lewy bodies were identified in the olfactory bulb as well as cortex and brainstem of one deceased patient. In order to assess the role of mutations in this gene in other familial cases we undertook a mutation screen of all 51 exons of LRRK2 in 117 other smaller British kindreds with familial Parkinson's disease. The commonest mutation was G2019S and we also identified two novel mutations, R1941H and T2356I, in the coding sequence. These data suggest that parkinsonism caused by mutations in LRRK2 is likely to represent the commonest locus for autosomal dominant Parkinson's disease with a phenotype, pathology and in vivo imaging similar to idiopathic, late-onset Parkinson's disease. C1 Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England. Inst Neurol, Queen Sq Brain Bank, London WC1N 3BG, England. Royal Free Hosp, Reta Lila Weston Unit Neurol Studies, London NW3 2QG, England. UCL, Sch Med, London W1N 8AA, England. MRC, Ctr Clin Sci, London, England. Hammersmith Hosp, Imperial Coll, Fac Med, Div Neurosci, London, England. Univ Exeter, Exeter, Devon, England. Addenbrookes Hosp, Dept Neurol, Cambridge, England. Queen Elizabeth Hosp, Dept Neurol, Birmingham B15 2TH, W Midlands, England. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Wood, NW (reprint author), Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England. EM n.wood@ion.ucl.ac.uk RI Singleton, Andrew/C-3010-2009; Lees, Andrew/A-6605-2009; Wood, Nicholas/C-2505-2009; Gilks, William/P-9137-2015; Holton, Janice/F-6831-2011; Revesz, Tamas/A-8732-2010; OI Wood, Nicholas/0000-0002-9500-3348; Gilks, William/0000-0001-7814-3173; Holton, Janice/0000-0002-3882-5249; Revesz, Tamas/0000-0003-2501-0259; Brooks, David/0000-0003-2602-2518 FU Medical Research Council [MC_U120036861]; Parkinson's UK [G-4029, G-4062] NR 30 TC 190 Z9 197 U1 1 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD DEC PY 2005 VL 128 BP 2786 EP 2796 DI 10.1093/brain/awh667 PN 12 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989JA UT WOS:000233667500006 PM 16272164 ER EF