FN Thomson Reuters Web of Science™ VR 1.0 PT B AU Ghanayem, BI AF Ghanayem, BI BE Cicolella, A Hardin, B Johanson, G TI An overview of the hematotoxicity of ethylene glycol ethers SO OCCUPATIONAL HYGIENE - RISK MANAGEMENT OF OCCUPATIONAL HAZARDS, VOL 2, ISSUE 1-6, 1996: PROCEEDINGS OF THE INTERNATIONAL SYMPOSIUM ON HEALTH HAZARDS OF GLYCOL ETHERS LA English DT Proceedings Paper CT International Symposium on Health Hazards of Glycol Ethers CY APR 19-21, 1994 CL PONT A MOUSSON, FRANCE SP Natl Inst Safety Res, France, NIOSH, NIOH, WHO, Int Agcy Res Canc Commiss European Communities, Int Commiss Occupat Hlth, Int Occupat Hygiene Assoc, Swedish Work Environm Fund, NIH NIEHS, US EPA, Minist Res & Univ Educ, France, INSERM, France, French Occupat Med, French Comm Hlth Educ, City Nancy, Reg Lorraine DE glycol ethers; hematotoxicity; alkoxyacetic acids C1 NIEHS,BIOCHEM RISK ANAL LAB,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GORDON AND BREACH SCIENCE PUBL PI READING PA P O BOX 90, READING, BERKS, ENGLAND RG1 8JL BN 9-919875-20-5 PY 1996 BP 253 EP & PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BF72T UT WOS:A1996BF72T00022 ER PT S AU Karl, M Chrousos, GP AF Karl, M Chrousos, GP BE Melmed, S TI Experimental and clinical models of CRH-induced pituitary tumors SO ONCOGENESIS AND MOLECULAR BIOLOGY OF PITUITARY TUMORS SE Frontiers of Hormone Research LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; HORMONE-BINDING-PROTEIN; CUSHINGS-SYNDROME; MESSENGER-RNA; TRANSGENIC MICE; HUMAN-PLACENTA; ADRENAL AXIS; HUMAN-PLASMA; RAT-BRAIN; DISEASE RP Karl, M (reprint author), NICHHD, SECT PEDIAT ENDOCRINOL,DEV ENDOCRINOL BRANCH,NIH, 10 CTR DR, MSC 1862, BETHESDA, MD 20892 USA. NR 74 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 BN 3-8055-6254-3 J9 FRONT HORM RES JI Front.Horm.Res. PY 1996 VL 20 BP 54 EP 71 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BF44A UT WOS:A1996BF44A00003 ER PT J AU Cultraro, CM Cogliati, T Hearing, LE Segal, S AF Cultraro, CM Cogliati, T Hearing, LE Segal, S TI Basic mutant Max reverses a c-Myc block to differentiation SO ONCOLOGY REPORTS LA English DT Article DE Myc; Max; differentiation ID MURINE ERYTHROLEUKEMIA-CELLS; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; ORNITHINE DECARBOXYLASE; ERYTHROID DIFFERENTIATION; EXPRESSION; PROTEIN; GENE; COTRANSFORMATION; TRANSFORMATION AB Murine erythroleukemia (MEL) cells overexpressing a transfected c-myc gene are blocked in their ability to undergo inducer-mediated differentiation, whereas overexpression of a transfected max gene mutated within the basic region (bm-max) accelerates differentiation. Based on these findings, we cotransfected MEL cells with plasmids which express human c-Myc constitutively and bm-Max in a zinc-inducible manner. Competition of endogenous proteins for binding to bm-Max can be considered negligible in cells expressing such high constitutive levels of c-Myc. Thus, this system provides a cell culture model for studying Myc:Max complex formation and its effect on erythroid differentiation. Clones expressing high levels of c-Myc and low levels of bm-Max are blocked in their ability to undergo N,N'-hexamethylene bisacetamide (HMBA)-mediated differentiation, presumably due to a preponderance of growth-promoting Myc:Max complexes. However, increased expression of bm-Max, in these clones, allows differentiation to occur by decreasing the levels of functional Myc:Max complexes. Although the exogenously expressed c-Myc and bm-Max associate in vivo, the basic region mutation in bm-Max abolishes the binding of Myc:bm-Max complexes to the specific E-box consensus sequence. We demonstrate that this sequestering of c-Myc by bm-Max reverses the c-Myc block to differentiation. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20889. NR 56 TC 4 Z9 4 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD JAN-FEB PY 1996 VL 3 IS 1 BP 141 EP 146 PG 6 WC Oncology SC Oncology GA TK696 UT WOS:A1996TK69600028 PM 21594332 ER PT J AU Asano, T An, T Zwelling, LA Takano, H Fojo, AT Kleinerman, ES AF Asano, T An, T Zwelling, LA Takano, H Fojo, AT Kleinerman, ES TI Transfection of a human topoisomerase II alpha gene into etoposide-resistant human breast tumor cells sensitizes the cells to etoposide SO ONCOLOGY RESEARCH LA English DT Article DE topoisomerase II; human; promoter; breast cancer; etoposide ID MUTANTS RESISTANT; POINT MUTATION; LINE; EXPRESSION; AMSACRINE; IDENTIFICATION; CLONING; DRUGS; FORM; CDNA AB The etoposide-resistant human breast cancer cell line MDA-VP was derived from MDA-parent cells by sequential selection in increasing concentrations of etoposide. MDA-VP cells express a lower amount of topoisomerase II alpha mRNA than the MDA-parent does, have mutations in topoisomerase II alpha (topo II) cDNA, and show cross-resistance to doxorubicin and amsacrine. We investigated whether transfer of a normal human topoisomerase II alpha (H-topo II) gene into MDA-VP cells could overcome their resistance to etoposide. H-topo II in a mammalian expression vector containing a glucocorticoid-inducible mouse mammary tumor virus (MMTV) promoter (pMAMneo) was transfected into MDA-VP cells (MDA-VP-hTOP2MAM). These H-topo II-transfected cells showed increased H-topo II mRNA expression and protein levels compared with MDA-VP parental cells or with MDA-VP cells transfected with the control pMAM vector (MDA-VP-MAM). Following cell exposure to dexamethasone, DNA-protein cleavable complex formation and cytotoxicity induced by etoposide, doxorubicin, and amsacrine were increased in the MDA-VP-hTOP2MAM cells compared with MDA-VP-MAM cells. However, these changes were short-lived, and by 24 h, cytotoxicity, cleavable DNA-protein complex formation, and H-topo II protein levels returned to baseline values. These results indicate that sensitivity of MDA-VP cells correlated with changes in cellular H-topo II. The gene transfer of a normal H-topo II gene can sensitize MDA-VP cells to the actions of multiple antineoplastic agents that target topo II. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CLIN INVEST,HOUSTON,TX 77030. NCI,MED BRANCH,BETHESDA,MD 20892. RP Asano, T (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CELL BIOL,HOUSTON,TX 77030, USA. FU NCI NIH HHS [CA 42992, CA 40090, CA 16672] NR 21 TC 16 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1996 VL 8 IS 3 BP 101 EP 110 PG 10 WC Oncology SC Oncology GA UX191 UT WOS:A1996UX19100001 PM 8823806 ER PT J AU Fujimori, A Hoki, Y Popescu, NC Pommier, Y AF Fujimori, A Hoki, Y Popescu, NC Pommier, Y TI Silencing and selective methylation of the normal topoisomerase I gene in camptothecin-resistant CEM/C2 human leukemia cells SO ONCOLOGY RESEARCH LA English DT Article DE topoisomerase I; camptothecin; drug resistance; gene regulation; DNA methylation ID SITU HYBRIDIZATION; DNA METHYLATION; LUNG-CANCER; LINE; EXPRESSION; MUTATION; LOCALIZATION; SENSITIVITY; 9-NITRO-CAMPTOTHECIN; IDENTIFICATION AB Camptothecin resistance of the human leukemia CEM/C2 cells is associated with a topoisomerase I (top1) mutation: Asn722Ser (Fujimori, A. et al. Cancer Res. 55:1339-1346; 1995). The corresponding DNA point mutation generates a novel site for the restriction endonuclease DdeL. We found that only the mutated top1 transcript was detectable in CEM/C2 by reverse transcriptase-polymerase chain reaction. Genomic DNA analysis by Southern blotting with DdeI showed that both the mutated and normal top1 genes were present in CEM/C2 cells. The mechanism of normal top1 allele silencing was further investigated. Cytogenetic analysis with a human chromosome 20 specific probe and restriction mapping by Southern blotting showed that both cell lines had a similar copy number of chromosome 20, with the predominant population containing 5-6 copies, and no detectable top1 gene rearrangement. Southern blotting using methylcytosine-sensitive restriction endonuclease (HpaII) indicated differential top1 methylation in CEM/C2 cells. Global cytosine methylation, however, appeared similar in CEM/C2 and wild-type CEM cells. These results indicate that gene-specific DNA methylation can play a role in downregulating top1 gene(s) and in the cellular resistance to camptothecins. Copyright (C) 1996 Elsevier Science Inc. C1 NCI,NIH,MOL PHARMACOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. NCI,NIH,EXPT CARCINOGENESIS LAB,DIV BASIC SCI,BETHESDA,MD 20892. NR 33 TC 24 Z9 24 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1996 VL 8 IS 7-8 BP 295 EP 301 PG 7 WC Oncology SC Oncology GA VU948 UT WOS:A1996VU94800005 PM 8938793 ER PT J AU Wang, M Fudge, K Rhim, JS Stearns, ME AF Wang, M Fudge, K Rhim, JS Stearns, ME TI Cytokine regulation of the matrix metalloproteinases and their inhibitors in human papillomavirus-18 transformed human prostatic tumor cell lines SO ONCOLOGY RESEARCH LA English DT Article DE IL-10; TIMP-1; MMP-2; human prostate cell lines ID HUMAN SYNOVIAL FIBROBLASTS; NECROSIS-FACTOR-ALPHA; TISSUE INHIBITOR; GENE-EXPRESSION; GROWTH-FACTOR; TIMP; COLLAGENASE; IL-10; DEXAMETHASONE; STROMELYSIN AB Cytokines may play a critical role in influencing the invasive and metastatic behavior of advanced cancers. To investigate the influence of cytokines on tissue inhibitor of metalloproteinase (TIMP) and matrix metalloproteinase (MMP) expression we have established cultures from prostate tissues of low Gleason sum 5 and high Gleason sum 10 cancers. We have examined the influence of different cytokines (interleukin [IL]-10, IL-4, IL-6, IL-2, and interferon-gamma) on TIMP-1, TIMP-2, MMP-2, and MMP-9 protein and mRNA expression in human papillomavirus (HPV)-18 immortalized human prostate cell lines derived from the primary cultures. Western blot and northern blot analysis revealed that IL-10, IL-6 and IL-4 all upregulated TIMP-1 expression after 16-36 h. In contrast, IL-10 and IL-4 (but not IL-6) downregulated MMP-2 mRNA and protein levels to different degrees over 24-36 h. The levels of TIMP-2 and MMP-9 protein and mRNA were not influenced substantially by any of the cytokines. Also, IL-2 and interferon-gamma had little or no effect on any of these genes. In sum, the data showed that IL-10 (or IL-4) upregulated TIMP-1 and coordinately downregulated MMP-2 expression. Thus, cytokines might control the molar ratio of TIMP-1 and MMP-2 to influence the level of protease activity and perhaps the invasive behavior of malignant cells in vivo. Copyright (C) 1996 Elsevier Science Inc. C1 ALLEGHENY UNIV HLTH SCI,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19102. NCI,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA57180] NR 29 TC 37 Z9 37 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1996 VL 8 IS 7-8 BP 303 EP 315 PG 13 WC Oncology SC Oncology GA VU948 UT WOS:A1996VU94800006 PM 8938794 ER PT J AU Goldwasser, F Bae, I Fornace, AJ Pommier, Y AF Goldwasser, F Bae, I Fornace, AJ Pommier, Y TI Differential GADD45, p21(C1P/WAF1) MCL-1 and topoisomerase II gene induction and secondary DNA fragmentation after camptothecin-induced DNA damage in two mutant p53 human colon cancer cell lines SO ONCOLOGY RESEARCH LA English DT Article DE apoptosis; p53; camptothecin; DNA topoisomerase I; colon cancer ID HL-60 CELLS; INDUCED APOPTOSIS; BCL-2 FAMILY; P53-INDEPENDENT PATHWAY; EPITHELIAL-CELLS; UP-REGULATION; EXPRESSION; INHIBITORS; DEATH; RNA AB Camptothecin (CPT) traps covalent DNA topoisomerase I-linked DNA single-strand breaks (cleavable complexes). To determine the differences in DNA damage signalling leading to differential sensitivity to CPT, two human colon cancer cell lines, SW620 and KM12, with nonfunctional p53 and the same level of topoisomerase I cleavable complex formation but differential sensitivity to CPT (Cancer Res. 56:4430-7; 1996) were studied. The levels of mRNA expression of DNA damage-inducible or death-related genes were measured at different times after CPT treatment. KM12 cells exhibited 3-fold higher basal levels of BCL-2 mRNA. Consistently, secondary DNA fragmentation, quantitated using a filter elution assay, was detected 24 h later and was 2-4-fold lower in KM12 cells than in SW620 cells. No induction of BAX was detected in either cell line. Consistent with the absence of functional p53, p21(CIP1/WAF1) and GADD45 genes were not induced within the first 24 h. However, in SW620 cells, both mRNA levels were increased more than 10-fold at 48 h. The BCL-2-related gene MCL-1 and topoisomerase II mRNA were induced at 24 h, and topoisomerase I mRNA levels increased 3-fold at 48 h, only in SW620 cells. We conclude that cellular response to CPT-induced DNA damage can involve p53-independent pathways leading to the induction of p53-effector genes. Induction of these genes at the onset of apoptosis is associated with CPT sensitivity. Copyright (C) 1996 Elsevier Science Inc. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. SAMYANG GENEX RES INST,MOL PHARMACOL LAB,TAEJON 305348,SOUTH KOREA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 48 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1996 VL 8 IS 7-8 BP 317 EP 323 PG 7 WC Oncology SC Oncology GA VU948 UT WOS:A1996VU94800007 PM 8938795 ER PT J AU Hess, JL Mitton, KP Bunce, GE AF Hess, JL Mitton, KP Bunce, GE TI Precataractous changes affect lens transparency in the selenite cataract SO OPHTHALMIC RESEARCH LA English DT Article; Proceedings Paper CT 7th Scheimpflug-Club Meeting - International Forum on Advanced Techniques in Lens and Cataract Research CY JUN 06-08, 1995 CL KANAZAWA, JAPAN SP Scheimpflug Club DE cataract model; crystallin; glutathione; lens; phase separation; rat; selenite ID PHASE-SEPARATION; RAT LENS; CRYSTALLIN; TEMPERATURE; CALPAIN AB Selenite treatment of the preweanling rat stabilized the transparency of the lens nucleus to decreasing temperature. Hence, we compared properties of the cortex and nucleus from lenses of selenite-treated and age-matched control rats. A subcutaneous dose of 30 nmol Na2SeO3/g body weight was administered to 10- to 13-day-old Sprague-Dawley rats. Uninjected, age matched littermates served as controls. As required, lenses were frozen in liquid N-2 and separated into nuclear and cortical-epithelial fractions. Transparency of solutions of lens proteins (90-100 mg per mi) was monitored from 30 to 2 degrees C as percent transmittance (%T) at 490 nm. The critical phase separation temperature, T-c, was the temperature at 80%T. Protein associations were monitored with gel filtration chromatography. The nuclear 'cold cataract', in intact lenses, formed at similar temperatures at 14 and 15 days of age, but at a significantly lower temperature when the lenses were from a selenite-treated rat. The T-c, however, was greater by 1.5-2 degrees C for solutions of proteins isolated from whole lenses or lens nuclei from rats 24 and 48 h after treatment with selenite. Further, less gamma-crystallin was associated with the alpha-crystallin fraction in extracts from the nucleus of lenses from treated rats. Altered phase separation properties occurred as an early event in the etiology of selenite cataract. The different in vivo and in vitro responses to temperature indicated that properties of lens crystallins do not solely establish transparency in the intact lens. C1 NEI,NIH,BETHESDA,MD 20892. RP Hess, JL (reprint author), VIRGINIA POLYTECH INST & STATE UNIV,DEPT BIOCHEM & ANAEROB MICROBIOL,BLACKSBURG,VA 24061, USA. FU NEI NIH HHS [EY06123] NR 17 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHALMIC RES JI Ophthalmic Res. PY 1996 VL 28 SU 2 BP 45 EP 53 PG 9 WC Ophthalmology SC Ophthalmology GA VG258 UT WOS:A1996VG25800009 PM 8883089 ER PT J AU Ellwein, LB AF Ellwein, LB TI Improving clinical evaluations of new eye care technologies SO OPHTHALMOLOGY LA English DT Editorial Material RP Ellwein, LB (reprint author), NEI,ECTF EXECUT COMM,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 1996 VL 103 IS 1 BP 3 EP 4 PG 2 WC Ophthalmology SC Ophthalmology GA TT675 UT WOS:A1996TT67500005 PM 8628557 ER PT J AU Ferris, FL Bailey, I AF Ferris, FL Bailey, I TI Standardizing the measurement of visual acuity for clinical research studies - Guidelines from the eye care technology forum SO OPHTHALMOLOGY LA English DT Article ID CHARTS C1 NEI,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD 20892. UNIV CALIF BERKELEY,SCH OPTOMETRY,BERKELEY,CA 94720. NR 8 TC 108 Z9 110 U1 2 U2 19 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 1996 VL 103 IS 1 BP 181 EP 182 PG 2 WC Ophthalmology SC Ophthalmology GA TT675 UT WOS:A1996TT67500029 PM 8628551 ER PT S AU LaMontagne, J AF LaMontagne, J BE Brown, LE Hampson, AW Webster, RG TI Influenza pandemic planning - What should be done? SO OPTIONS FOR THE CONTROL OF INFLUENZA III SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 3rd International Conference on Options for the Control of Influenza CY MAY 04-09, 1996 CL CAIRNS, AUSTRALIA SP WHO, Austr Soc Microbiol, CSL Ltd, Pasteur Merieux Serums & Vaccins, Pasteur Merieux MSD Connaught Labs, SmithKline Beecham, Becton Dickinson, Evans Med, Glaxo Wellcome, Parke Davis, Wyeth Lederle Vaccines & Pediat, Chiron Biocine, Eisai Co Ltd, Nippon Glaxo, Solvay Duphar, Res Fdn Microbial Dis Osaka Univ RP LaMontagne, J (reprint author), NIAID,DHHS,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82461-8 J9 INT CONGR SER PY 1996 VL 1123 BP 43 EP 44 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases; Virology SC Public, Environmental & Occupational Health; Infectious Diseases; Virology GA BG94X UT WOS:A1996BG94X00005 ER PT S AU Deng, YP Bennink, JR Yewdell, JW AF Deng, YP Bennink, JR Yewdell, JW BE Brown, LE Hampson, AW Webster, RG TI Why are so few viral peptides recognized by MHC class I restricted T lymphocytes? SO OPTIONS FOR THE CONTROL OF INFLUENZA III SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 3rd International Conference on Options for the Control of Influenza CY MAY 04-09, 1996 CL CAIRNS, AUSTRALIA SP WHO, Austr Soc Microbiol, CSL Ltd, Pasteur Merieux Serums & Vaccins, Pasteur Merieux MSD Connaught Labs, SmithKline Beecham, Becton Dickinson, Evans Med, Glaxo Wellcome, Parke Davis, Wyeth Lederle Vaccines & Pediat, Chiron Biocine, Eisai Co Ltd, Nippon Glaxo, Solvay Duphar, Res Fdn Microbial Dis Osaka Univ RP Deng, YP (reprint author), NIAID,VIRAL DIS LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82461-8 J9 INT CONGR SER PY 1996 VL 1123 BP 195 EP 202 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases; Virology SC Public, Environmental & Occupational Health; Infectious Diseases; Virology GA BG94X UT WOS:A1996BG94X00029 ER PT S AU Bacik, I Snyder, HL Anton, LC Russ, G Otvos, L Yewdell, JW Bennink, JR AF Bacik, I Snyder, HL Anton, LC Russ, G Otvos, L Yewdell, JW Bennink, JR BE Brown, LE Hampson, AW Webster, RG TI Using N-linked glycosylation to study the generation of MHC class I associated peptides from exported proteins SO OPTIONS FOR THE CONTROL OF INFLUENZA III SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 3rd International Conference on Options for the Control of Influenza CY MAY 04-09, 1996 CL CAIRNS, AUSTRALIA SP WHO, Austr Soc Microbiol, CSL Ltd, Pasteur Merieux Serums & Vaccins, Pasteur Merieux MSD Connaught Labs, SmithKline Beecham, Becton Dickinson, Evans Med, Glaxo Wellcome, Parke Davis, Wyeth Lederle Vaccines & Pediat, Chiron Biocine, Eisai Co Ltd, Nippon Glaxo, Solvay Duphar, Res Fdn Microbial Dis Osaka Univ RP Bacik, I (reprint author), NIAID,VIRAL DIS LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Anton, Luis/C-4740-2013 OI Anton, Luis/0000-0001-9665-011X NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82461-8 J9 INT CONGR SER PY 1996 VL 1123 BP 203 EP 208 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases; Virology SC Public, Environmental & Occupational Health; Infectious Diseases; Virology GA BG94X UT WOS:A1996BG94X00030 ER PT S AU Kelsall, BL Strober, W AF Kelsall, BL Strober, W BE Weiner, HL Mayer, LF TI The role of dendritic cells in antigen processing in the Peyer's patch SO ORAL TOLERANCE: MECHANISMS AND APPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Oral Tolerance - Mechanisms and Applications CY MAR 30-APR 02, 1995 CL MT SINAI HOSP MED CTR, NEW YORK, NY SP New York Acad Sci, Autoimmune Inc, Fdn Neurol Dis, Berlex Labs, Eli Lilly & Co, Glaxo Inc, Glaxo Res Inst, Hoffmann La Roche Inc, Merck Res Labs, NIAID, NIAMSD, NIDDKD, Natl Multiple Sclerosis Soc, Pfizer Inc, Cent Res Div, Solvay Pharm HO MT SINAI HOSP MED CTR ID MONOCLONAL-ANTIBODY; LANGERHANS CELLS; T-CELLS; MOUSE; IDENTIFICATION; MACROPHAGES RP Kelsall, BL (reprint author), NIAID,MUCOSAL IMMUN SECT,CLIN INVEST LAB,NIH,BLDG 10,ROOM 11N238,900 ROCKVILLE PIKE,BETHESDA,MD 20814, USA. NR 22 TC 17 Z9 18 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-996-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 778 BP 47 EP 54 DI 10.1111/j.1749-6632.1996.tb21113.x PG 8 WC Immunology; Multidisciplinary Sciences SC Immunology; Science & Technology - Other Topics GA BF31A UT WOS:A1996BF31A00005 PM 8611015 ER PT S AU Caspi, RR Stiff, LR Morawetz, R MillerRivero, NE Chan, CC Wiggert, B Nussenblatt, RB Morse, HC Rizzo, LV AF Caspi, RR Stiff, LR Morawetz, R MillerRivero, NE Chan, CC Wiggert, B Nussenblatt, RB Morse, HC Rizzo, LV BE Weiner, HL Mayer, LF TI Cytokine-dependent modulation of oral tolerance in a murine model of autoimmune uveitis SO ORAL TOLERANCE: MECHANISMS AND APPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Oral Tolerance - Mechanisms and Applications CY MAR 30-APR 02, 1995 CL MT SINAI HOSP MED CTR, NEW YORK, NY SP New York Acad Sci, Autoimmune Inc, Fdn Neurol Dis, Berlex Labs, Eli Lilly & Co, Glaxo Inc, Glaxo Res Inst, Hoffmann La Roche Inc, Merck Res Labs, NIAID, NIAMSD, NIDDKD, Natl Multiple Sclerosis Soc, Pfizer Inc, Cent Res Div, Solvay Pharm HO MT SINAI HOSP MED CTR ID UVEORETINITIS; MICE; MOUSE C1 NEI,LAB CELL & MOL BIOL,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. RP Caspi, RR (reprint author), NEI,IMMUNOL LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 10N222,10 CTR DR,BETHESDA,MD 20892, USA. RI Rizzo, Luiz Vicente/B-4458-2009; OI Morse, Herbert/0000-0002-9331-3705 NR 14 TC 24 Z9 24 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-996-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 778 BP 315 EP 324 DI 10.1111/j.1749-6632.1996.tb21139.x PG 10 WC Immunology; Multidisciplinary Sciences SC Immunology; Science & Technology - Other Topics GA BF31A UT WOS:A1996BF31A00031 PM 8610985 ER PT S AU Nussenblatt, RB Whitcup, SM deSmet, MD Caspi, RR Kozhich, AT Weiner, HL Vistica, B Gery, I AF Nussenblatt, RB Whitcup, SM deSmet, MD Caspi, RR Kozhich, AT Weiner, HL Vistica, B Gery, I BE Weiner, HL Mayer, LF TI Intraocular inflammatory disease (uveitis) and the use of oral tolerance - A status report SO ORAL TOLERANCE: MECHANISMS AND APPLICATIONS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Oral Tolerance - Mechanisms and Applications CY MAR 30-APR 02, 1995 CL MT SINAI HOSP MED CTR, NEW YORK, NY SP New York Acad Sci, Autoimmune Inc, Fdn Neurol Dis, Berlex Labs, Eli Lilly & Co, Glaxo Inc, Glaxo Res Inst, Hoffmann La Roche Inc, Merck Res Labs, NIAID, NIAMSD, NIDDKD, Natl Multiple Sclerosis Soc, Pfizer Inc, Cent Res Div, Solvay Pharm HO MT SINAI HOSP MED CTR ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; IMMUNE-COMPLEXES; RETINAL ANTIGENS; INHIBITION; INDUCTION; RATS C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP,SCH MED,CTR NEUROL DIS, DEPT NEUROL, BOSTON, MA 02115 USA. RP Nussenblatt, RB (reprint author), NEI, IMMUNOL LAB, BLDG 10, ROOM 10N202, 10 CTR DR, BETHESDA, MD 20892 USA. OI de Smet, Marc/0000-0002-9217-5603 NR 23 TC 36 Z9 36 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 0-89766-996-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 778 BP 325 EP 337 DI 10.1111/j.1749-6632.1996.tb21140.x PG 13 WC Immunology; Multidisciplinary Sciences SC Immunology; Science & Technology - Other Topics GA BF31A UT WOS:A1996BF31A00032 PM 8610986 ER PT S AU Fukushima, A Whitcup, SM Nussenblatt, RB Gery, I AF Fukushima, A Whitcup, SM Nussenblatt, RB Gery, I BE Weiner, HL Mayer, LF TI Effects of cyclosporin A on the induction of oral tolerance SO ORAL TOLERANCE: MECHANISMS AND APPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Oral Tolerance - Mechanisms and Applications CY MAR 30-APR 02, 1995 CL MT SINAI HOSP MED CTR, NEW YORK, NY SP New York Acad Sci, Autoimmune Inc, Fdn Neurol Dis, Berlex Labs, Eli Lilly & Co, Glaxo Inc, Glaxo Res Inst, Hoffmann La Roche Inc, Merck Res Labs, NIAID, NIAMSD, NIDDKD, Natl Multiple Sclerosis Soc, Pfizer Inc, Cent Res Div, Solvay Pharm HO MT SINAI HOSP MED CTR C1 AUTOIMMUNE INC,LEXINGTON,MA 02173. RP Fukushima, A (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N210,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-996-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 778 BP 376 EP 378 DI 10.1111/j.1749-6632.1996.tb21148.x PG 3 WC Immunology; Multidisciplinary Sciences SC Immunology; Science & Technology - Other Topics GA BF31A UT WOS:A1996BF31A00040 PM 8610995 ER PT J AU Bacon, WE Maggi, S Looker, A Harris, T Nair, CR Giaconi, J Honkanen, R Ho, SC Peffers, KA Torring, O Gass, R Gonzalez, N AF Bacon, WE Maggi, S Looker, A Harris, T Nair, CR Giaconi, J Honkanen, R Ho, SC Peffers, KA Torring, O Gass, R Gonzalez, N TI International comparison of hip fracture rates in 1988-89 SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE hip fracture; hospital discharge data; incidence rates; international comparison ID HOSPITAL DISCHARGE DATA; UNITED-STATES; WHITE WOMEN; BONE MASS; DENSITY; RISK AB A comparison of hip fracture rates among nine countries (Canada, Chile, Finland, Hong Kong, Scotland, Sweden, Switzerland, the United States and Venezuela) was made using national hospital discharge data for the same time interval. The rates increased by age and were higher for females than males in all nine countries. When based on overall discharge rates, the incidence of hip fracture appeared high in three European countries (Finland, Scotland and Sweden) relative to the other countries. However, when transfer cases were removed and adjustments made for differences in case definition, the risk of hip fracture for both men and women was much similar among the four European and two North American countries, but higher than in Hong Kong. Rates of fracture were lowest in Venezuela and Chile, varying from three to 11 times less than for residents of the other seven countries. Although there are limitations in using hospital discharge data as a measure of incidence, the wide variation in the risk of hip fracture across the nine countries appears real but differences between North American and north European countries may not be as great as previously reported. Such cross-national comparisons may help clarify different etiologic hypotheses. C1 NIH,WHO,RES PROGRAM AGING,BETHESDA,MD 20892. NIA,BETHESDA,MD 20892. CANC CTR HLTH INFORMAT,OTTAWA,ON,CANADA. CATHOLIC UNIV CHILE,SANTIAGO,CHILE. UNIV KUOPIO,SF-70211 KUOPIO,FINLAND. CHINESE UNIV HONG KONG,HONG KONG,HONG KONG. CITY HOSP NHS TRUST,EDINBURGH,MIDLOTHIAN,SCOTLAND. KAROLINSKA HOSP,S-10401 STOCKHOLM,SWEDEN. UNIV ZURICH,ZURICH,SWITZERLAND. HOP UNIV CARACAS,CARACAS,VENEZUELA. RP Bacon, WE (reprint author), NATL CTR HLTH STAT,6525 BELCREST RD,ROOM 952,HYATTSVILLE,MD 20781, USA. NR 44 TC 112 Z9 116 U1 0 U2 1 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING, SURREY, ENGLAND GU7 3DJ SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 1996 VL 6 IS 1 BP 69 EP 75 DI 10.1007/BF01626541 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TT680 UT WOS:A1996TT68000012 PM 8845603 ER PT B AU Max, MB AF Max, MB BE Cohen, MJM Campbell, JN TI Collecting better data about drug treatments for chronic pain SO PAIN TREATMENT CENTERS AT A CROSSROADS: A PRACTICAL AND CONCEPTUAL REAPPRAISAL SE PROGRESS IN PAIN RESEARCH AND MANAGEMENT LA English DT Proceedings Paper CT Bristol-Myers Squibb Symposium on Pain Research - Pain Treatment Centers at a Crossroads: A Practical and Conceptual Reappraisal CY MAR 03-05, 1995 CL JOHNS HOPKINS HOSP, BALTIMORE, MD SP Bristol Myers Squibb, Johns Hopkins Hosp HO JOHNS HOPKINS HOSP C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT ASSOC STUDY PAIN (IASP) PRESS PI SEATTLE PA 909 NE 43RD ST, SUITE 304, SEATTLE, WA 98105 BN 0-931092-14-0 J9 PROG PAIN RES MANAG PY 1996 VL 7 BP 163 EP 172 PG 10 WC Medicine, General & Internal; Clinical Neurology; Psychiatry; Rehabilitation SC General & Internal Medicine; Neurosciences & Neurology; Psychiatry; Rehabilitation GA BF81Y UT WOS:A1996BF81Y00014 ER PT S AU Landi, MT Ceroni, M Martignoni, E Bertazzi, PA Caporaso, NE Nappi, G AF Landi, MT Ceroni, M Martignoni, E Bertazzi, PA Caporaso, NE Nappi, G BE Battistin, L Scarlato, G Caraceni, T Ruggieri, S TI Gene-environment interaction in Parkinson's disease - The case of CYP2D6 gene polymorphism SO PARKINSON'S DISEASE SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 11th International Symposium on Parkinsons Disease CY MAR 26-30, 1994 CL ROME, ITALY SP World Federat Neurol, Res Comm Extrapyramidal Dis, Italian League Parkinsons Dis & Extrapyramidal Disorders ID DEBRISOQUINE 4-HYDROXYLATION; MONOAMINE-OXIDASE; METABOLISM; HYDROXYLATION; SPARTEINE; PHENOTYPE; OXIDATION; BRAIN; MPTP; PERSONALITY C1 UNIV PAVIA,FDN C MONDINO,NEUROL INST,I-27100 PAVIA,ITALY. NCI,GENET EPIDEMIOL BRANCH,ROCKVILLE,MD 20892. RP Landi, MT (reprint author), UNIV MILAN,EPOCA,EPIDEMIOL RES CTR,I-20122 MILAN,ITALY. RI ceroni, mauro/G-7080-2011; bertazzi, pietro alberto/D-5039-2017 OI ceroni, mauro/0000-0002-8947-5007; bertazzi, pietro alberto/0000-0003-3475-2449 NR 80 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 0091-3952 BN 0-7817-0341-7 J9 ADV NEUROL JI Adv.Neurol. PY 1996 VL 69 BP 61 EP 72 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE52P UT WOS:A1996BE52P00008 PM 8615186 ER PT S AU Appollonio, I Grafman, J Clark, K Kosslyn, SM Frattola, L AF Appollonio, I Grafman, J Clark, K Kosslyn, SM Frattola, L BE Battistin, L Scarlato, G Caraceni, T Ruggieri, S TI Image generation from long-term memory in Parkinson's disease SO PARKINSON'S DISEASE SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 11th International Symposium on Parkinsons Disease CY MAR 26-30, 1994 CL ROME, ITALY SP World Federat Neurol, Res Comm Extrapyramidal Dis, Italian League Parkinsons Dis & Extrapyramidal Disorders ID VISUO-SPATIAL IMPAIRMENT; MENTAL-IMAGERY; VISUOSPATIAL IMPAIRMENT; SELECTIVE DEFICITS; ABILITIES; AGE; ORIENTATION; PERFORMANCE; ALZHEIMERS; DEMENTIA C1 NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. HARVARD UNIV,DEPT PSYCHOL,CAMBRIDGE,MA 02138. RP Appollonio, I (reprint author), UNIV MILAN,SAN GERARDO HOSP,DEPT NEUROL,MILAN,ITALY. OI Grafman, Jordan H./0000-0001-8645-4457 FU NINDS NIH HHS [1P01 NS27950-01A1] NR 69 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 0091-3952 BN 0-7817-0341-7 J9 ADV NEUROL JI Adv.Neurol. PY 1996 VL 69 BP 349 EP 359 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE52P UT WOS:A1996BE52P00043 PM 8615151 ER PT J AU Sidransky, E Fartasch, M Lee, RE Metlay, LA Abella, S Zimran, A Gao, W Elias, PM Ginns, EI Holleran, WM AF Sidransky, E Fartasch, M Lee, RE Metlay, LA Abella, S Zimran, A Gao, W Elias, PM Ginns, EI Holleran, WM TI Epidermal abnormalities may distinguish type 2 from type 1 and type 3 of Gaucher disease SO PEDIATRIC RESEARCH LA English DT Article ID BARRIER FUNCTION; GLUCOCEREBROSIDASE GENE; PERMEABILITY BARRIER; TARGETED DISRUPTION; REPLACEMENT THERAPY; STRATUM-CORNEUM; ICHTHYOSIS; MODEL AB A major clinical challenge in Gaucher disease is the early and presymptomatic discrimination of type 2 (acute neuronopathic) from milder type I and type 3 Gaucher patients to enable appropriate management and counseling, Although most patients with Gaucher disease do not have skin abnormalities, a subset of patients with severe type 2 Gaucher disease display ichthyosiform skin. Analogous findings occur in the skin of type 2 (null allele) Gaucher mice. Ultrastructural and functional studies of epidermis from these mice reveal that glucocerebrosidase is required to generate functionally competent membranes for normal epidermal barrier function, We have extended our studies by examining the epidermal lipid content and ultrastructure in all three types of Gaucher patients. Only the type 2 Gaucher patients, some of whom had clinical ichthyosis, demonstrated an increased ratio of epidermal glucosylceramide to ceramide as well as extensive ultrastructural abnormalities, including the persistence of incompletely processed lamellar body-derived contents throughout the stratum corneum interstices. These epidermal alterations may provide a means for early differentiation of type 2 Gaucher disease. C1 UNIV ERLANGEN NURNBERG,DEPT DERMATOL,W-8520 ERLANGEN,GERMANY. UNIV PITTSBURGH,SCH MED,DEPT PATHOL,PITTSBURGH,PA 15261. UNIV ROCHESTER,SCH MED,DEPT PATHOL,ROCHESTER,NY 14642. WAYNE STATE UNIV,CHILDRENS HOSP MICHIGAN,SCH MED,DEPT PEDIAT,DIV HEMATOL ONCOL,DETROIT,MI 48201. SHAARE ZEDEK MED CTR,DEPT MED,GAUCHER CLIN,IL-91000 JERUSALEM,ISRAEL. UNIV CALIF SAN FRANCISCO,SCH MED,VET ADM MED CTR,DEPT DERMATOL,DERMATOL SERV,SAN FRANCISCO,CA 94143. RP Sidransky, E (reprint author), NIMH,CLIN NEUROSCI BRANCH,SECT MOLEC NEUROGENET,BLDG 49,ROOM B1EE16,49 CONVENT DR,MSC 4405,BETHESDA,MD 20892, USA. FU NIAMS NIH HHS [AR 19098]; PHS HHS [39448] NR 28 TC 56 Z9 58 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 1996 VL 39 IS 1 BP 134 EP 141 DI 10.1203/00006450-199601000-00020 PG 8 WC Pediatrics SC Pediatrics GA TM658 UT WOS:A1996TM65800020 PM 8825398 ER PT B AU Akamatsu, M Ye, B Yan, XJ Kole, HK Burke, TR Roller, PP AF Akamatsu, M Ye, B Yan, XJ Kole, HK Burke, TR Roller, PP BE Nishi, N TI Characterization of tyrosine-phosphate mimick containing tyrosine phosphatase inhibitory peptides SO PEPTIDE CHEMISTRY 1995 LA English DT Proceedings Paper CT 33rd Symposium on Peptide Chemistry CY OCT 04-06, 1995 CL SAPPORO, JAPAN SP Japanese Peptide Soc, Chem Soc Japan, Japan Soc Biosci Biotechnol & Agrochem, Pharm Soc Japan C1 NCI,MED CHEM LAB,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,NIH,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU PROTEIN RESEARCH FOUNDATION PI OSAKA PA 476 INA , MINOH-SHI, OSAKA 562, JAPAN BN 4-88667-133-0 PY 1996 BP 369 EP 372 PG 4 WC Chemistry, Medicinal; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA BF27H UT WOS:A1996BF27H00093 ER PT J AU Malin, DH Lake, JR McDermitt, LS Smith, DA Witherspoon, WE Jones, JA Schumann, MD Payza, K Ho, KK Burgess, K AF Malin, DH Lake, JR McDermitt, LS Smith, DA Witherspoon, WE Jones, JA Schumann, MD Payza, K Ho, KK Burgess, K TI Enhanced antiopiate activity and enzyme resistance in a peptidomimetic of FMRFamide containing E-2,3-methanomethionine and E-2,3-methanophenylalanine SO PEPTIDES LA English DT Article DE FMRFamide; NPFF; NPFF receptors; neuropeptide FF; F8Famide; antiopiate peptides; cyclopropylogs; rat; opiate dependence; opiate abstinence syndrome ID NEUROPEPTIDE; MORPHINE; RAT; PHE-MET-ARG-PHE-NH2; INHIBITION; ABSTINENCE; PEPTIDE AB FMRFamide is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. Peptidomimetics of FMRFamide substituted with conformationally constrained stereoisomers of Z-2,3-methanomethionine or E-2,3-methanomethionine precipitated abstinence syndrome far more potently than FMRFamide itself. The current study determined the effect on antiopiate potency of an additional rigid substitution. A peptidomimetic containing a stereoisomer of E-2,3-methanomethionine was compared with a peptidomimetic additionally substituted at the C-terminal with E-2,3-methanophenylalanine. Morphine abstinence signs were observed after varying doses (0.125-25.0 mu g) of these two peptidomimetics were injected into the third ventricle of morphine-dependent rats. The peptidomimetic containing both rigid substitutions was far more potent than the peptidomimetic of FMRFamide containing methanomethionine alone. The increased potency appears to be related to enzyme resistance rather than receptor affinity. C1 TEXAS A&M UNIV, COLLEGE STN, TX 77843 USA. NIH, WASHINGTON, DC 20032 USA. RP Malin, DH (reprint author), UNIV HOUSTON CLEAR LAKE, BOX 237, HOUSTON, TX 77058 USA. RI Burgess, Kevin/B-5372-2015 OI Burgess, Kevin/0000-0001-6597-1842 FU NIDA NIH HHS [DAO6554] NR 20 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 1 BP 83 EP 86 DI 10.1016/0196-9781(95)02062-4 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA TT027 UT WOS:A1996TT02700013 PM 8822514 ER PT J AU Goodman, CB Emilien, B Becketts, K Cadet, JL Rothman, RB AF Goodman, CB Emilien, B Becketts, K Cadet, JL Rothman, RB TI Downregulation of Mu-opioid binding sites following chronic administration of neuropeptide FF (NPFF) and morphine SO PEPTIDES LA English DT Article DE NPFF; opioid mu receptor; [I-125]DAMGO; opiate; receptor autoradiography; morphine ID RECEPTOR DOWN-REGULATION; RAT SPINAL-CORD; UP-REGULATION; MODULATING PEPTIDES; INDUCED ANALGESIA; OPIATE RECEPTORS; DEPENDENT RATS; BRAIN; TOLERANCE; FLFQPQRFAMIDE AB The effect of continuous ICV infusion of NPFF (10 mu g/mu l) and morphine (40 mu g/mu l) on mu-opioid binding sites was examined in rats using the in vitro radiolabeled techniques of whole-brain homogenate receptor binding and quantitative autoradiography. Mu receptors were labeled with [H-3] [D-Ala(2)-MePhe(4),Glyol(5)] enkephalin in the homogenate binding experiments and with [I-125][D-Ala(2)-MePhe(4),Gly-ol(5)] enkephalin in autoradiographic studies. In homogenate binding studies, chronic administration of NPFF or morphine significantly downregulated mu receptors by 20% and 44%, respectively. Quantitative autoradiographic experiments demonstrated downregulation of mu opioid receptors in specific brain nuclei for both NPFF- and morphine-treated animals. Within the striatum and several nuclei of the thalamus, the mu receptors of the NPFF- and morphine-treated animals were decreased by 20-30% and 38-73%, respectively. These results suggest that NPFF may modulate opioid-mediated responses in part by altering the density of mu-opioid receptors. C1 NIDA,NIH,MOLEC NEUROPSYCHIAT SECT,DIV IRP,BALTIMORE,MD 21224. RP Goodman, CB (reprint author), NIDA,NIH,CLIN PSYCHOPHARMACOL SECT,DIV IRP,4940 EASTERN AVE,POB 5180,BALTIMORE,MD 21224, USA. NR 54 TC 28 Z9 28 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 3 BP 389 EP 397 DI 10.1016/0196-9781(96)00002-2 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA UN154 UT WOS:A1996UN15400006 PM 8735964 ER PT J AU Xiao, Q Challis, JRG Fraser, M Wlodek, ME Thorburn, GD Cuttita, F Hill, DJ StPierre, S Spindel, ER McDonald, TJ AF Xiao, Q Challis, JRG Fraser, M Wlodek, ME Thorburn, GD Cuttita, F Hill, DJ StPierre, S Spindel, ER McDonald, TJ TI Locations and molecular forms of gastrin-releasing peptide-like immunoreactive entities in ovine pregnancy SO PEPTIDES LA English DT Article DE gastrin-releasing peptide; bombesin; reverse-phase HPLC; gel filtration; ovine pregnancy uterus ID BOMBESIN; CLONING; GROWTH; TISSUE; CELLS; FETAL AB Large quantities of gastrin-releasing peptide-like immunoreactivity (GRP-LI) are present in ovine pregnancy fluids (allantoic fluid > fetal plasma > esophageal fluid = amniotic fluid = urine > maternal plasma) and in term endometrium (60 +/- 29 pmol . g(-1)) and myometrium (4.5 +/- 1.2 pmol . g(-1)). The larger molecular size [greater than GRP(1-27)] of this GRP-LI entity is not due to a GRP binding protein nor to a C-terminal extension of GRP. In contrast, ovine fetal colon extracts appear to contain the usual GRP(1-27) and GRP(18-27) forms. Hence, the uterus, not the fetus, is the probable source of this novel GRP-like peptide. It apparently acts as a hormone in ovine pregnancy and may play an important role in fetal-placental development. C1 UNIV WESTERN ONTARIO,DEPT MED,LONDON,ON,CANADA. UNIV WESTERN ONTARIO,DEPT BIOCHEM,LONDON,ON,CANADA. UNIV WESTERN ONTARIO,DEPT OBSTET & GYNECOL,LONDON,ON,CANADA. UNIV WESTERN ONTARIO,DEPT PHYSIOL,LONDON,ON,CANADA. UNIV WESTERN ONTARIO,DEPT PAEDIAT,LONDON,ON,CANADA. UNIV WESTERN ONTARIO,ROBARTS RES INST,LONDON,ON,CANADA. UNIV WESTERN ONTARIO,LAWSON RES INST,LONDON,ON,CANADA. MONASH UNIV,DEPT PHYSIOL,MELBOURNE,VIC 3168,AUSTRALIA. NCI,BETHESDA,MD 20892. UNIV QUEBEC,INST RES NATL SANTE,CLAIRE,PQ,CANADA. OREGON REG PRIMATE RES CTR,DIV NEUROSCI,BEAVERTON,OR 97006. RI Challis, John/E-7419-2014 NR 20 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 3 BP 489 EP 495 DI 10.1016/0196-9781(96)00003-4 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA UN154 UT WOS:A1996UN15400019 PM 8735977 ER PT J AU Moody, TW AF Moody, TW TI Peptides and growth factors in non-small cell lung cancer SO PEPTIDES LA English DT Review DE non-small cell lung cancer; VIP; PACAP; EGF receptor; transforming growth factor alpha; Her2/neu; thymosin-alpha 1 ID VASOACTIVE-INTESTINAL-PEPTIDE; CYCLASE-ACTIVATING POLYPEPTIDE; BOMBESIN-LIKE PEPTIDES; HIGH-AFFINITY BINDING; NEURO-BLASTOMA CELLS; ELEVATES CYTOSOLIC CALCIUM; RECEPTOR TYROSINE KINASES; ADENYLATE-CYCLASE; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING AB Numerous growth factors and receptors that alter proliferation have been identified in lung cancer. In non-small cell lung cancer (NSCLC) cell lines, high levels of vasoactive intestinal peptide (VIP) mRNA have been detected by Northern analysis, and immunoreactive VIP is present. VIP elevates intracellular cAMP and stimulates the clonal growth of NSCLC cells. Also, transforming growth factor alpha (TGF-alpha) mRNA is present in NSCLC cells and TGF-alpha is present in conditioned media exposed to NSCLC cells. TGF-alpha binds with high affinity to epidermal growth factor (EGF) receptors present on NSCLC cells. EGF stimulates tyrosine kinase activity and growth in NSCLC cells. Synthetic peptide antagonists and monoclonal antibodies have been identified that disrupt autocrine growth pathways and inhibit NSCLC growth. These data suggest that VIP and TGF-alpha are important autocrine growth factors for NSCLC. RP Moody, TW (reprint author), NCI, BIOMARKERS & PREVENT RES BRANCH, BLDG C, RM 300, 9610 MED CTR DR, ROCKVILLE, MD 20850 USA. NR 150 TC 35 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 3 BP 545 EP 555 DI 10.1016/0196-9781(95)02148-5 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA UN154 UT WOS:A1996UN15400028 PM 8735986 ER PT J AU Sills, TL Vaccarino, FJ AF Sills, TL Vaccarino, FJ TI Individual differences in the feeding response to CCKB antagonists: Role of the nucleus accumbens SO PEPTIDES LA English DT Article DE cholecystokinin; L-365,260; devazepide; receptors; CCKA; CCKB; individual differences; feeding; nucleus accumbens; rat ID INDUCED LOCOMOTOR-ACTIVITY; INCREASES FOOD-INTAKE; RECEPTOR ANTAGONIST; ADMINISTERED CHOLECYSTOKININ; CEREBRAL-VENTRICLES; DOPAMINE NEURONS; RATS; SATIETY; BRAIN; AMPHETAMINE AB Cholecystokinin (CCK) decreases food intake in a variety of species when administered systemically or centrally. Moreover, both CCKA and CCKB receptor mechanisms have been implicated in CCK's effects on feeding. Previous work done in our laboratory has shown that rats exhibit significant individual differences in the consumption of sugar. Moreover, intra-nucleus accumbens (Acc) administration of CCK reduced sugar consumption in rats with high baseline sugar intake (High) but did not affect sugar consumption in rats with low baseline sugar intake (Low). Thus, CCK mechanisms may contribute to individual differences in sugar intake observed in rats. The present study examined the involvement of endogenous CCK mechanisms in the regulation of sugar intake in Low and High rats. In Experiment 1, male Wistar rats were administered either the CCKA antagonist devazepide (0.001, 0.01, 0.1 mg/kg) or the CCK, antagonist L,365-260 (0.01, 0.1, 0.5 mg/kg) IP, and their intake of sugar and powdered lab chow recorded for 1 h. Experiment 2 was identical to Experiment 1 with the exception that rats received intra-Acc administrations of the selective CCKB antagonist PD-135158 (3, 10, 30 mu g). Results showed that blockade of CCKB, but not CCKA, receptors produced an increase in sugar consumption in Low rats and a decrease in sugar consumption in High rats. These effects were obtained with both systemic and intra-Acc administrations of a selective CCKB antagonist. These results suggest that endogenous CCK contributes to the mechanism regulating sugar consumption in Low and High rats through its actions on CCKB receptors in the Acc. C1 UNIV TORONTO,DEPT PSYCHOL,TORONTO,ON M5S 1A1,CANADA. UNIV TORONTO,DEPT PSYCHIAT,TORONTO,ON M5S 1A1,CANADA. NIMH,SECT BEHAV NEUROPHARMACOL,BETHESDA,MD 20892. CLARKE INST PSYCHIAT,TORONTO,ON M5T 1R8,CANADA. NR 48 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 4 BP 593 EP 599 DI 10.1016/0196-9781(96)00032-0 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA UU136 UT WOS:A1996UU13600006 PM 8804067 ER PT J AU Viswanathan, M Johren, O deOliveira, AM Saavedra, JM AF Viswanathan, M Johren, O deOliveira, AM Saavedra, JM TI Increased non-angiotensin II [I-125]CGP 42112 binding in rat carotid artery after balloon injury SO PEPTIDES LA English DT Article DE injury; arteries; macrophages; CGP 42112; binding sites; inflammation ID NEOINTIMA FORMATION; RECEPTOR SUBTYPES; VASA VASORUM; ATHEROSCLEROSIS; CGP-42112A; EXPRESSION; AORTA AB In this study, [I-125]CGP 42112, a ligand of high affinity and selectivity for the angiotensin II AT(2) receptor, was used to detect and quantify a non-angiotensin II binding site in the balloon-injured carotid artery of the rat. The amount of [I-125]CGP 42112 binding was significantly enhanced in the adventitia of the injured arteries. Localization of the binding site using emulsion autoradiography and immunocytochemistry suggests that the binding sites may be expressed by macrophages in the inflamed tissue surrounding the injured artery. RP Viswanathan, M (reprint author), NIMH,PHARMACOL SECT,CLIN SCI LAB,NATL INST HLTH,BLDG 10,ROOM 2D-45,10 CTR DR,MSC 1514,BETHESDA,MD 20892, USA. RI Johren, Olaf/G-6967-2011 NR 23 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 4 BP 695 EP 699 DI 10.1016/0196-9781(96)00064-2 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA UU136 UT WOS:A1996UU13600021 PM 8804082 ER PT J AU MacArthur, L Eiden, L AF MacArthur, L Eiden, L TI Neuropeptide genes: Targets of activity-dependent signal transduction SO PEPTIDES LA English DT Review DE neuropeptide gene regulation; signaling pathways; adrenal medulla; central nervous system ID BOVINE CHROMAFFIN CELLS; RAT ADRENAL-MEDULLA; VASOACTIVE INTESTINAL POLYPEPTIDE; PREPROENKEPHALIN MESSENGER-RNA; C-FOS EXPRESSION; PROTEIN-KINASE-C; DOPAMINE RECEPTOR GENE; SUBSTANCE-P; PHORBOL ESTER; CYCLIC-AMP AB Neuroendocrine cells respond to hormones and synaptic input by increasing or decreasing their own electrical activity and secretory output, and by changes in the repertoire of expression of neuronal genes. Neuropeptide genes are among those whose transcription rates can be dramatically up- and downregulated when neuronal activity is altered. In the last decade or so, our understanding of neuropeptide gene regulation has evolved from the concept of calcium-dependent coupling of neuropeptide secretion and biosynthesis to the current perspective of neuropeptide genes as the targets of multiple intracellular signaling pathways, entrained by intrinsic electrical activity and by transsynaptic influences. This review describes our current understanding of neuropeptide gene regulation in the adrenal gland as well as in the peripheral and central nervous systems. Particular emphasis is placed on the molecular mechanisms that allow unique patterns of expression of neuropeptide genes within specific types of neuroendocrine cells that contribute to the remarkable anatomical specificity of neuropeptide gene expression. C1 NIMH, MOLEC NEUROSCI SECT, CELL BIOL LAB, BETHESDA, MD 20892 USA. RP MacArthur, L (reprint author), NIDR, NEUROBIOL ANESTHESIOL BRANCH, CELLULAR & MOL MECH SECT, BLDG 49, ROOM 1A-11, BETHESDA, MD 20892 USA. OI Eiden, Lee/0000-0001-7524-944X NR 109 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 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 4 BP 721 EP 728 DI 10.1016/0196-9781(95)02100-0 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA UU136 UT WOS:A1996UU13600024 PM 8804085 ER PT J AU Quinn, KA Unsworth, EJ Miller, MJ Mulshine, JL Cuttitta, F AF Quinn, KA Unsworth, EJ Miller, MJ Mulshine, JL Cuttitta, F TI Biochemical characterization of mouse liver IBE(1)-amide immunoreactivity: Limitations of antibody-based approaches for verification of peptide expression SO PEPTIDES LA English DT Article DE insulin-like growth factor-I; hemoglobin; peptide analysis; immunoblotting; mouse AB A high titer, specific antiserum, raised against a synthetic analogue of a unique peptide region within the human IGF-IB prohormone, detected specific immunoreactivity in extracts of mouse, chicken, sheep, and human liver. Specificity was confirmed by the ablation of immunoreactivity in the presence of excess synthetic immunogen. Here we report the isolation and characterization of one of the immunoreactive species from an extract of mouse liver: amino acid sequencing revealed that the purified product was 78% identical to the NH2-terminus of the alpha-subunit of mouse hemoglobin. Immunoblot analysis of a commercial preparation of mouse hemoglobin confirmed that the antiserum recognized hemoglobin. Addition of excess synthetic peptide to the antiserum eliminated the immunobinding to hemoglobin. The apparent ''specificity'' of even affinity-purified antiserum for hemoglobin provides a cautionary note for the interpretation of studies concluding antigen expression based solely on the presence of positive immunoreactivity. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,DIV CLIN SCI,ROCKVILLE,MD 20850. NR 6 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 5 BP 881 EP 883 DI 10.1016/0196-9781(96)00103-9 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA VA137 UT WOS:A1996VA13700021 PM 8844781 ER PT J AU Feigenbaum, JJ Choubal, MD Payza, K Kanofsky, JR Crumrine, DS AF Feigenbaum, JJ Choubal, MD Payza, K Kanofsky, JR Crumrine, DS TI Receptor inactivation by dye-neuropeptide conjugates .1. The synthesis of cys-containing dye-neuropeptide conjugates SO PEPTIDES LA English DT Article DE dye; azure-B; FMRFamide; FMRFamide analogue; cys-containing neuropeptide; receptor inactivation; dye-neuropeptide conjugate ID INVIVO AB In an attempt to attenuate specifically identified receptors through photolysis, a four-step synthesis of a useful tethered derivative of Azure-B (Az) was developed. After characterization, this derivative was covalently attached to CFMRFamide, CFMRF, and CLRFamide (i.e., three different neuropeptide analogues of the putative neurotransmitter FMRFamide. This resulted in the formation of three dye-neuropeptide conjugates: Az-CFMRFamide, Az-CFMRF, and Az-CLRFamide. C1 LOYOLA UNIV,DEPT CHEM,CHICAGO,IL 60626. NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,BETHESDA,MD 20032. LOYOLA UNIV,STRITCH SCH MED,DEPT MED,MAYWOOD,IL 60153. LOYOLA UNIV,STRITCH SCH MED,DEPT BIOCHEM,MAYWOOD,IL 60153. EDWARD HINES JR VET ADM HOSP,MED SERV,HINES,IL 60153. RP Feigenbaum, JJ (reprint author), AMER INST BIOTECHNOL,DEPT RES & DEV,EXECUT HOUSE,500 E HIGGINS RD,ELK GROVE VILLAGE,IL 60007, USA. NR 13 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 6 BP 991 EP 994 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA VL919 UT WOS:A1996VL91900014 PM 8899818 ER PT J AU Feigenbaum, JJ Choubal, MD Crumrine, DS Kanofsky, JR Payza, K AF Feigenbaum, JJ Choubal, MD Crumrine, DS Kanofsky, JR Payza, K TI Receptor inactivation by dye-neuropeptide conjugates .3. Comparative binding of dye-neuropeptide conjugates to FMRFamide receptors of Helix aspersa and Loligo pealei SO PEPTIDES LA English DT Article DE dye; FMRFamide; analogues; neuropeptide; dye-neuropeptide conjugates; specific binding to FMRFamide receptors; Helix aspersa; Loligo pealei ID SINGLET OXYGEN; KINETICS; WATER AB Three neuropeptide analogues of FMRFamide (FMRFa) were covalently attached to a tethered derivative of methylene blue to form dye-neuropeptide conjugates. The comparative binding of the latter to FMRFa receptors was subsequently examined in both Helix aspersa (circumesophageal ganglia) and squid (optic lobe membrane). In Helix, the FMRFa analogue CFMRFamide (CFMRFa) inhibited the specific binding of the FMRFa ligand [I-125]daYFnLRFa in a dose-dependent manner. Az-CFMRFa, one of the dye-neuropeptide conjugates, also dose-dependently inhibited the specific binding of [I-125] daYFnLRFa. Moreover, their potencies equaled or exceeded that of FMRFamide. In squid, the binding of CFMRFa and FMRFa was similar. However, the dye-neuropeptide conjugate (IC50 of 14 nM) was about 44-fold less potent than FMRFa. The conjugates were synthesized as part of a study seeking to target and inactivate preselected receptors with heretofore unattainable selectivity and permanence. Copyright (C) 1996 Elsevier Science Inc. C1 LOYOLA UNIV,DEPT CHEM,CHICAGO,IL 60626. LOYOLA UNIV,STRITCH SCH MED,DEPT MED,MAYWOOD,IL 60153. LOYOLA UNIV,STRITCH SCH MED,DEPT BIOCHEM,MAYWOOD,IL 60153. EDWARD HINES VET ADM MED CTR,MED SERV,HINES,IL 60141. NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,BETHESDA,MD 20892. RP Feigenbaum, JJ (reprint author), AMER INST BIOTECHNOL,DEPT RES & DEV,EXECUT HOUSE,500 E HIGGINS RD,ELK GROVE VILLAGE,IL 60007, USA. NR 13 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 8 BP 1279 EP 1284 DI 10.1016/S0196-9781(96)00192-1 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA VY302 UT WOS:A1996VY30200003 PM 8971919 ER PT J AU Moody, TW Venugopal, R Hu, V Gozes, Y McDermed, J Leban, JJ AF Moody, TW Venugopal, R Hu, V Gozes, Y McDermed, J Leban, JJ TI BW1023U90: A new GRP receptor antagonist for small-cell lung cancer cells SO PEPTIDES LA English DT Article DE GRP receptors; antagonists; small-cell lung cancer; calcium; growth ID GASTRIN-RELEASING PEPTIDE; BOMBESIN-LIKE PEPTIDES; CYTOSOLIC CALCIUM; ANALOGS FUNCTION; HIGH-AFFINITY; GROWTH; CARCINOMA; CLONING; INHIBIT; SOMATOSTATIN AB Gastrin-releasing peptide (GRP) receptor antagonists were synthesized and their ability to interact with small-cell lung cancer (SCLC) cells determined. [I-125]BW1023U90, bound with high affinity (K-d = 2 nM) to a single class of sites (Bmax = 55 fmol/mg protein) using SCLC cell line NCI-H345. [I-125]BW1023U90 binding was time dependent and reversible even at 37 degrees C as the ligand was minimally internalized. Specific [I-125]BW1023U90 binding was inhibited with high affinity by GRP as well as bombesin (BB) but not neuromedin B (NMB). BW1023U90 inhibited the ability of BB to elevate cytosolic Ca2+ and increase the growth of SCLC cells. A BW1023U90 analogue, BW2258U89 10 mu g/day, SC) slowed SCLC xenograft formation in nude mice and [I-125]BW1023U90 localized to SCLC tumors 1 h after injection into nude mice. BW2258U89 (4% by weight) was placed in microspheres and slowly released over a 3-week period in nude mice bearing SCLC xenografts. The microspheres containing BW2258U89 strongly inhibited SCLC growth in vivo. A radioimmunoassay was developed for the GRP receptor antagonists and the rabbit antiserum cross-reacted totally with BW2258U89 or BW1023U90. BW2258U89 immunoreactivity (5 nM) was detected in the plasma of nude mice containing the microspheres after 1 week. These data suggest that GRP receptor antagonists bind to receptors on SCLC tumors. Copyright (C) 1996 Elsevier Science Inc. C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20037. ISRAEL INST BIOL RES,IL-70450 NESS ZIONA,ISRAEL. BURROUGHS WELLCOME CO,DIV ORGAN CHEM,RES TRIANGLE PK,NC 27709. RP Moody, TW (reprint author), NCI,BIOMARKERS & PREVENT RES BRANCH,9610 MED CTR DR,BLDG C,ROOM 300,ROCKVILLE,MD 20850, USA. OI Hu, Valerie/0000-0002-3357-0777 NR 33 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 8 BP 1337 EP 1343 DI 10.1016/S0196-9781(96)00195-7 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA VY302 UT WOS:A1996VY30200013 PM 8971929 ER PT S AU Lee, SST Gonzalez, FJ AF Lee, SST Gonzalez, FJ BE Reddy, JK Suga, T Mannaerts, GP Lazarow, PB Subrammani, S TI Targeted disruption of the peroxisome proliferator-activated receptor alpha gene, PPAR alpha SO PEROXISOMES: BIOLOGY AND ROLE IN TOXICOLOGY AND DISEASE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT International Symposium on Peroxisomes - Biology and Role in Toxicology and Disease CY JUN 28-JUL 02, 1995 CL ASPEN, CO SP New York Acad Sci, Int Human Frontiers Sci Program, Ono Pharm Co Ltd, Dow Chem Co, NIH, Sankyo Co Ltd, Bayer Yakuhin Ltd, Daiichi Pharm Co Ltd, Fujisawa Pharm Co Ltd, ICI, Kissei Pharm Co Ltd, Parke Davis Pharm Res, Shionogi & Co Ltd, Taisho Pharm Co Ltd, Teijin Ltd, Yamanouchi Pharm Co Ltd, Beckman Instruments, Chugai Pharm Co Ltd, Ciba Geigy, Dainippon Pharm Co Ltd, Eli Lilly & Co, Fdn Belge Rech, Fujirebio Inc, Fuji yakuhin Co Ltd, GD Searle Res & Dev, Hoechst Japan Ltd, Kabi Pharmacia K K, Kirin Brewery Co Ltd, Lederle Japan Ltd, Meiji Seika Kaisha Ltd Natl Ltd, Merck & Co, Mitsubishi Chem Corp, Nemoto & Co Ltd, New Drug Dev Res Ctr Inc, Nippon Boehringer Ingelheim Co Ltd, Nippon Chemiphar Co Ltd, Nippon Kayaku Co Ltd, Pfizer Inc, Sandoz Pharm Ltd, Shiseido Co Ltd, Soc Gen, Taiho Pharm Co Ltd, Coca Cola Co, Green Cross Corp, Tsumura & Co, Warner Lambert K K, Zeneca, Amer Express, Oce ID FATTY-ACIDS; EXPRESSION; INDUCTION; RAT; SUPERFAMILY; RISK; DNA C1 NCI, LAB METAB, NIH, BETHESDA, MD 20892 USA. NR 25 TC 23 Z9 23 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 0-89766-968-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 804 BP 524 EP 529 DI 10.1111/j.1749-6632.1996.tb18642.x PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine; Science & Technology - Other Topics GA BH28R UT WOS:A1996BH28R00040 PM 8993570 ER PT S AU Youssef, JA Cunningham, ML Song, WO Badr, MZ AF Youssef, JA Cunningham, ML Song, WO Badr, MZ BE Reddy, JK Suga, T Mannaerts, GP Lazarow, PB Subrammani, S TI Metabolic requirements for the hepatocellular proliferation induced by peroxisome proliferators - Role of coenzyme A SO PEROXISOMES: BIOLOGY AND ROLE IN TOXICOLOGY AND DISEASE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT International Symposium on Peroxisomes - Biology and Role in Toxicology and Disease CY JUN 28-JUL 02, 1995 CL ASPEN, CO SP New York Acad Sci, Int Human Frontiers Sci Program, Ono Pharm Co Ltd, Dow Chem Co, NIH, Sankyo Co Ltd, Bayer Yakuhin Ltd, Daiichi Pharm Co Ltd, Fujisawa Pharm Co Ltd, ICI, Kissei Pharm Co Ltd, Parke Davis Pharm Res, Shionogi & Co Ltd, Taisho Pharm Co Ltd, Teijin Ltd, Yamanouchi Pharm Co Ltd, Beckman Instruments, Chugai Pharm Co Ltd, Ciba Geigy, Dainippon Pharm Co Ltd, Eli Lilly & Co, Fdn Belge Rech, Fujirebio Inc, Fuji yakuhin Co Ltd, GD Searle Res & Dev, Hoechst Japan Ltd, Kabi Pharmacia K K, Kirin Brewery Co Ltd, Lederle Japan Ltd, Meiji Seika Kaisha Ltd Natl Ltd, Merck & Co, Mitsubishi Chem Corp, Nemoto & Co Ltd, New Drug Dev Res Ctr Inc, Nippon Boehringer Ingelheim Co Ltd, Nippon Chemiphar Co Ltd, Nippon Kayaku Co Ltd, Pfizer Inc, Sandoz Pharm Ltd, Shiseido Co Ltd, Soc Gen, Taiho Pharm Co Ltd, Coca Cola Co, Green Cross Corp, Tsumura & Co, Warner Lambert K K, Zeneca, Amer Express, Oce C1 UNIV MISSOURI, DIV PHARMACOL, KANSAS CITY, MO 64108 USA. NIEHS, CHEM BRANCH, RES TRIANGLE PK, NC 27709 USA. MICHIGAN STATE UNIV, E LANSING, MI 48824 USA. NR 8 TC 2 Z9 2 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 0-89766-968-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 804 BP 725 EP 727 DI 10.1111/j.1749-6632.1996.tb18681.x PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine; Science & Technology - Other Topics GA BH28R UT WOS:A1996BH28R00079 PM 8993605 ER PT S AU Dadras, SS Thorgeirsson, SS Reddy, JK AF Dadras, SS Thorgeirsson, SS Reddy, JK BE Reddy, JK Suga, T Mannaerts, GP Lazarow, PB Subrammani, S TI Stable expression of peroxisomal fatty acyl-CoA oxidase in vitro SO PEROXISOMES: BIOLOGY AND ROLE IN TOXICOLOGY AND DISEASE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT International Symposium on Peroxisomes - Biology and Role in Toxicology and Disease CY JUN 28-JUL 02, 1995 CL ASPEN, CO SP New York Acad Sci, Int Human Frontiers Sci Program, Ono Pharm Co Ltd, Dow Chem Co, NIH, Sankyo Co Ltd, Bayer Yakuhin Ltd, Daiichi Pharm Co Ltd, Fujisawa Pharm Co Ltd, ICI, Kissei Pharm Co Ltd, Parke Davis Pharm Res, Shionogi & Co Ltd, Taisho Pharm Co Ltd, Teijin Ltd, Yamanouchi Pharm Co Ltd, Beckman Instruments, Chugai Pharm Co Ltd, Ciba Geigy, Dainippon Pharm Co Ltd, Eli Lilly & Co, Fdn Belge Rech, Fujirebio Inc, Fuji yakuhin Co Ltd, GD Searle Res & Dev, Hoechst Japan Ltd, Kabi Pharmacia K K, Kirin Brewery Co Ltd, Lederle Japan Ltd, Meiji Seika Kaisha Ltd Natl Ltd, Merck & Co, Mitsubishi Chem Corp, Nemoto & Co Ltd, New Drug Dev Res Ctr Inc, Nippon Boehringer Ingelheim Co Ltd, Nippon Chemiphar Co Ltd, Nippon Kayaku Co Ltd, Pfizer Inc, Sandoz Pharm Ltd, Shiseido Co Ltd, Soc Gen, Taiho Pharm Co Ltd, Coca Cola Co, Green Cross Corp, Tsumura & Co, Warner Lambert K K, Zeneca, Amer Express, Oce ID LIVER; RAT C1 NORTHWESTERN UNIV, SCH MED, DEPT PATHOL, CHICAGO, IL 60611 USA. NCI, NIH, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [R37 GM23750] NR 6 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 0-89766-968-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 804 BP 787 EP 791 DI 10.1111/j.1749-6632.1996.tb18702.x PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine; Science & Technology - Other Topics GA BH28R UT WOS:A1996BH28R00100 PM 8993624 ER PT S AU Ingram, DK Shimada, A Spangler, EL Ikari, H Hengemihle, J Kuo, H Greig, N AF Ingram, DK Shimada, A Spangler, EL Ikari, H Hengemihle, J Kuo, H Greig, N BE Kitani, K Aoba, A Goto, S TI Cognitive enhancement - New strategies for stimulating cholinergic, glutamatergic, and nitric oxide systems SO PHARMACOLOGICAL INTERVENTION IN AGING AND AGE-ASSOCIATED DISORDERS: PROCEEDINGS OF THE SIXTH CONGRESS OF THE INTERNATIONAL ASSOCIATION OF BIOMEDICAL GERONTOLOGY SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th Congress for the International-Association-of-Biomedical-Gerontology CY AUG 20-23, 1995 CL TOKYO, JAPAN SP Int Assoc Biomed Gerontol ID D-ASPARTATE RECEPTOR; INDUCED LEARNING IMPAIRMENT; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; 14-UNIT T-MAZE; ALZHEIMERS-DISEASE; D-CYCLOSERINE; AGED RATS; MEMORY IMPAIRMENT; GLYCINE PRODRUG C1 NAGOYA UNIV, SCH MED, DEPT GERIATR, SHOWA KU, NAGOYA, AICHI 466, JAPAN. RP Ingram, DK (reprint author), NIA, MOLEC PHYSIOL & GENET SECT, NATHAN W SHOCK LABS, GERONTOL RES CTR, NIH, BALTIMORE, MD 21224 USA. NR 80 TC 34 Z9 34 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-031-X; 1-57331-030-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 786 BP 348 EP 361 DI 10.1111/j.1749-6632.1996.tb39076.x PG 14 WC Geriatrics & Gerontology; Multidisciplinary Sciences; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Science & Technology - Other Topics; Pharmacology & Pharmacy GA BF92J UT WOS:A1996BF92J00030 PM 8687034 ER PT S AU Wu, RM Murphy, DL Chiueh, CC AF Wu, RM Murphy, DL Chiueh, CC BE Kitani, K Aoba, A Goto, S TI Suppression of hydroxyl radical formation and protection of nigral neurons by l-deprenyl (selegiline) SO PHARMACOLOGICAL INTERVENTION IN AGING AND AGE-ASSOCIATED DISORDERS: PROCEEDINGS OF THE SIXTH CONGRESS OF THE INTERNATIONAL ASSOCIATION OF BIOMEDICAL GERONTOLOGY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th Congress for the International-Association-of-Biomedical-Gerontology CY AUG 20-23, 1995 CL TOKYO, JAPAN SP Int Assoc Biomed Gerontol ID MAO-B; INTRACRANIAL MICRODIALYSIS; PARKINSONS-DISEASE; MONOAMINE-OXIDASE; IN-VIVO; (-)DEPRENYL; DOPAMINE; MPTP; INJURY; RATS C1 NATL TAIWAN UNIV HOSP,COLL MED,DEPT NEUROL,TAIPEI 10016,TAIWAN. RP Wu, RM (reprint author), NIMH,CLIN SCI LAB,NIH,CLIN CTR 103D41,BETHESDA,MD 20892, USA. OI Wu, Ruey-Meei/0000-0002-4947-5467 NR 39 TC 32 Z9 32 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 1-57331-030-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 786 BP 379 EP 390 DI 10.1111/j.1749-6632.1996.tb39078.x PG 12 WC Geriatrics & Gerontology; Multidisciplinary Sciences; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Science & Technology - Other Topics; Pharmacology & Pharmacy GA BF92J UT WOS:A1996BF92J00032 PM 8687036 ER PT J AU Altemus, M Glowa, JR Galliven, E Leong, YM Murphy, DL AF Altemus, M Glowa, JR Galliven, E Leong, YM Murphy, DL TI Effects of serotonergic agents on food-restriction-induced hyperactivity SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE serotonin; obsessive-compulsive disorder; anorexia nervosa; animal model; stress; adjunctive behavior; serotonin reuptake inhibitor ID OBSESSIVE-COMPULSIVE DISORDER; CORTICOTROPIN-RELEASING HORMONE; SEMISTARVATION-INDUCED HYPERACTIVITY; SCHEDULE-INDUCED-POLYDIPSIA; ACTIVITY-WHEEL STRESS; ADULT MALE-RATS; ANOREXIA-NERVOSA; TYROSINE-HYDROXYLASE; FEMALE RATS; THERAPEUTIC IMPLICATIONS AB Rats that are fed for 90 min per day can stabilize their weight after an initial drop; however, if rats on this feeding schedule are also given access to a running wheel, they run excessively, eat less, lose weight, and often die. To investigate this phenomenon as a possible animal model of obsessive-compulsive disorder (OCD), rats were treated for 5 weeks with fluoxetine, an antidepressant that relieves OCD symptoms in humans (5 mg/kg, 2.5 mg/kg), or imipramine, an antidepressant that does not affect OCD symptoms (5 mg/kg), or saline prior to exposure to food restriction and the running wheel. In addition, because chronic fluoxetine treatment is thought to enhance serotonergic neurotransmission, for contrast an additional group of rats were treated with parachlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor that depletes serotonin. Rats treated with fluoxetine lost significantly less weight, ran significantly less, and increased food intake more rapidly during restriction of food availability than saline-treated rats. Rats treated with imipramine did not differ from those treated with saline on these parameters. Compared to saline-treated rats, rats treated with PCPA lost more weight, ate less food, and increased running more rapidly. These effects of pharmacological treatment indicate an inverse relationhip between central serotonergic activity and vulnerability to develop food-restriction-induced anorexia and compulsive running. In addition, like OCD in humans, this phenomenon in rats seems to be blocked by chronic treatment with a serotonin selective reuptake inhibitor but not a less selective monoamine reuptake inhibitor. C1 NIMH, CLIN SCI LAB, DIV INTRAMURAL RES PROGRAMS, BETHESDA, MD 20892 USA. NIDDKD, MED CHEM LAB, DIV INTRAMURAL RES PROGRAMS, BETHESDA, MD 20892 USA. NR 83 TC 58 Z9 61 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 1996 VL 53 IS 1 BP 123 EP 131 DI 10.1016/0091-3057(95)02003-9 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA TL889 UT WOS:A1996TL88900016 PM 8848441 ER PT B AU Bialy, G AF Bialy, G BE Bhasin, S Gabelnick, HL Spieler, JM Swerdloff, RS Wang, C Kelly, C TI Hormonal methods of male contraception are flawed and impractical SO PHARMACOLOGY, BIOLOGY, AND CLINICAL APPLICATIONS OF ANDROGENS: CURRENT STATUS AND FUTURE PROSPECTS LA English DT Proceedings Paper CT 2nd International Androgen Workshop on Pharmacology, Biology, and Clinical Applications of Androgens - Current Status and Future Prospects CY FEB 17-20, 1995 CL LONG BEACH, CA SP Contracept Res & Dev Program, US AID C1 NICHHD,POPULAT RES CTR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS, INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 BN 0-471-13320-5 PY 1996 BP 387 EP 393 PG 7 WC Andrology; Endocrinology & Metabolism SC Endocrinology & Metabolism GA BG18U UT WOS:A1996BG18U00038 ER PT B AU Sokoloff, L Gotoh, J Law, MJ Takahashi, S AF Sokoloff, L Gotoh, J Law, MJ Takahashi, S BE Krieglstein, J TI Functional activation of energy metabolism in nervous tissue: Roles of neurons and astroglia SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1996 LA English DT Proceedings Paper CT 6th International Symposium on Pharmacology of Cerebral Ischemia CY JUL, 1996 CL MARBURG, GERMANY SP Dtsche Forschungsgemeinsch, Bonn, Philipps Univ, Marburg, Asta Medica AG, Frankfurt am Main, Bayer AG, Leverkusen, Behringwerke AG, Marburg, Biotrend Chemikalien GmbH, Koln, Boehringer Ingelheim GmbH, Ingelheim, Byk Gulden Lomberg Chem Fabrik GmbH, Konstanz, Dr Willmar Schwabe Arzneimittel GmbH, Karlsruhe, Hoechst AG, Frankfurt am Main, Image Proc & Vis Co Ltd, Coventry, UK, Janssen Gmbh, Neuss, Knoll AG, Ludwigshafen, Lichtwer Pharma Gmbh, Berlin, Luitpold Pharma, Munchen, Merz + Co GmbH & Co, Frankfurt am Main, Oxford Optr Ltd, Oxford, UK, Sandoz Pharma Ltd, Basel, Schweiz, Schering AG, Berlin, Schwarz Pharma AG, Monheim, Smithkline Beecham Pharma GmbH, Munchen, Smithkline Beecham Pharma, Harlow, UK, Upjohn GmbH, Heppenheim AB Metabolic mapping of local functional activity in nervous tissues with the 2-deoxyglucose (DG) method has shown that functional activation of metabolism occurs mainly in neuropil. Local glucose utilization (ICMRglc) increases quantitatively in proportion to the degree of functional activation and linearly with spike frequency in synapse-rich terminal projection zones of activated pathways; perikarya do not appear to be affected. Membrane depolarization by electrical stimulation, elevated extracellular K+ concentration ([K+](o)), or opening of voltage-dependent Naf channels with veratridine stimulates ICMRglc, in neural tissues, and this increase is blocked by ouabain, a specific inhibitor of Na+,K+-ATPase. Activation of this enzyme to restore the ionic gradients that were partially degraded by the enhanced spike activity appears to mediate the function-related increases in energy metabolism. Because the DG method lacks the spatial resolution needed to identify the cellular and subcellular elements in neuropil (e.g., axon terminals, dendrites, or astrocytic processes enveloping synapses) that contribute to the increased ICMRglc, we have simulated in vitro conditions to be expected from increased spike activity in vivo (e.g., increases in [K+](o) and intracellular Na+ and extracellular neurotransmitter concentrations) and examined their effects on [C-14]DG phosphorylation in cultured rat brain neurons and astroglia. Increased timulated [C-14]DG phosphorylation in neuronal and mixed neuronal-astroglial but not in astroglial cultures, and veratridine (75 mu M) stimulated [C-14]DG phosphorylation in both neuronal and astroglial cultures. These stimulations were blocked by 1 mM ouabain or 10 mu M tetrodotoxin (TTX), which blocks voltage-dependent Naf channels. Monensin (10 mu M), a Naf ionophore and Na+/H+ exchanger, doubled the rate of [C-14]DG phosphorylation, and this increase was only partially blocked by ouabain and unaffected by TTX. L-Clutamate (500 mu M) stimulated [C-14]DG phosphorylation in astroglia, and this stimulation was unaffected by inhibitors of NMDA or non-NMDA receptors but completely blocked by ouabain and absent in Na+-free medium. Competitive inhibitors of glutamate reuptake, such as threo-hydroxyaspartate (THA), which themselves are also transported like glutamate into cells together with Na+ by the glutamate/Na+ cotransporter, also stimulated phosphoryIation of [C-14]DC but not in Na+-free medium. These results suggest that astroglia do indeed contribute to the increases in energy metabolism associated with functional activation by the following mechanisms: spike activity in axonal terminals releases glutamater the glutamate is taken up together with Na+ by the astroglia via the glutamate/Na+ cotransporter; and the increase in intracellular Na+ results in stimulation of astroglial Na+,K+-ATPase activity. RP Sokoloff, L (reprint author), NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WISSENSCHAFTLICHE verlagsgesellschaft mbh PI STUTTGART PA POSTFACH 40, BIRKENWALDSTRASSE 44, 70191 STUTTGART, GERMANY BN 3-88763-053-X PY 1996 BP 259 EP 270 PG 12 WC Cardiac & Cardiovascular Systems; Neurosciences; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BH54J UT WOS:A1996BH54J00027 ER PT B AU Kennedy, C Horinaka, N Artz, N Jehle, J Takahashi, S Sokoloff, L AF Kennedy, C Horinaka, N Artz, N Jehle, J Takahashi, S Sokoloff, L BE Krieglstein, J TI Examination of the cerebrovascular response to glucose deprivation SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1996 LA English DT Proceedings Paper CT 6th International Symposium on Pharmacology of Cerebral Ischemia CY JUL, 1996 CL MARBURG, GERMANY SP Dtsche Forschungsgemeinsch, Bonn, Philipps Univ, Marburg, Asta Medica AG, Frankfurt am Main, Bayer AG, Leverkusen, Behringwerke AG, Marburg, Biotrend Chemikalien GmbH, Koln, Boehringer Ingelheim GmbH, Ingelheim, Byk Gulden Lomberg Chem Fabrik GmbH, Konstanz, Dr Willmar Schwabe Arzneimittel GmbH, Karlsruhe, Hoechst AG, Frankfurt am Main, Image Proc & Vis Co Ltd, Coventry, UK, Janssen Gmbh, Neuss, Knoll AG, Ludwigshafen, Lichtwer Pharma Gmbh, Berlin, Luitpold Pharma, Munchen, Merz + Co GmbH & Co, Frankfurt am Main, Oxford Optr Ltd, Oxford, UK, Sandoz Pharma Ltd, Basel, Schweiz, Schering AG, Berlin, Schwarz Pharma AG, Monheim, Smithkline Beecham Pharma GmbH, Munchen, Smithkline Beecham Pharma, Harlow, UK, Upjohn GmbH, Heppenheim AB When the supply of glucose to the brain is limited by hypoglycemia or by blocking its metabolism with 2-deoxyglucose (DG) cerebral blood flow increases. The present studies in unanesthetized rats made hypoglycemic with insulin show that the increases in CBF, measured with the [C-14]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5-3.0 mM at which point CBF rises sharply. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3- concentrations and arterial pH. However, none of these changes nor insulin itself could be responsible for the increase in CBF because insulin under euglycemic conditions had similar effects on plasma constituents without affecting CBF. Furthermore, inhibition of brain glucose metabolism with pharmacological doses of DG increased CBF in a manner similar to that resulting from insulin-induced hypoglycemia without altering plasma lactate and Kf levels, and with only a slight increase in arterial pH. A role for nitric oxide as mediator of the increases in CBF was also excluded. Acute and chronic blockade of nitric oxide synthase activity with N-G-nitro-L-arginine raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia or blockade of glucose metabolism with pharmacological doses of deoxyglucose. Studies on the effects of insulin-induced hypoglycemia on cerebral blood flow (CBF) have prodced inconsistent results. Some have reported little or no change (Kety et al., 1948; Eisenberg and Seltzer 1962; Hernandez et al., 1980; Ghajar et al., 1982), but most have found significant increases (Della Porta et al., 1964; Norberg and Siesjo 1976; Abdul-Rahman et al., 1980; Hollinger and Bryan, 1987; Bryan et al., 1987; Ichord et al., 1994). The differences may be accounted for by the presence or absence of anesthesia, variability in the nutritional state, level and duration of hypoglycemia, or the method used to determine CBF. In all studies in which it was determined, cerebral energy metabolism, measured as either cerebral oxygen consumption (CMRO2) and/or glucose utilization (CMRglc), was reduced during insulin-induced hypoglycemia, the number of regions affected and the extent of reductions in metabolism varying with the severity of the hypoglycemia (Kety et al., 1948; Eisenberg and Seltzer 1964: Norberg and Siesjo 1976; Ratcheson et al.. 1981; Ghajar et al., 1982; Suda et al., 1990). The mechanism responsible for the increased blood flow is unknown, but some clue may be in the observation that deoxyglucose (in pharmaculogical doses), also causes marked increases in CBF throughout the brain (Breieret al., 1993). Deoxyglucose blocks the metabolism of glucose early in the glycolytic pathway and, like hypoglycemia, deprives the tissue of its essen tial substrate. Its administration has clinical effects that closely resemble those of insulin-induced hypoglycemia in spite of there being an elevation in the concentration of blood glucose (Landau et al., 1958). This mode of producing glucoprivation suggest that neither direct action of insulin nor the blood glucose level in itself is responsible for the vascular response. The Endothelium-Derived Relaxing Factor (EDRF) of Furchgott and Zawadzki (1980), later identified as nitric oxide (Palmer et al., 1987; Ignarro et al., 1987) is enzymatically produced in brain tissue and vascular endothelium and mediates the effects of a number of vasodilator drugs. It also plays a role in the regulation of systemic blood pressure and vasculartone (Ignarro, 1989; Monicada et al., 1991). When its synthesis is blocked with N-G-nitro-L-arginine (L-NAME) cerebral blood flow is reduced throughout the brain despite an elevation in mean arterial blood pressure (MABP) (Sokoloff et al., 1992; Adachi et al., 1994). Inhibition of nitric oxide synthase activity has also been reported to attenuate the increases in CBF during insulin-induced hypoglycemia in anesthetized, mechanically ventilated piglets, suggesting that nitric oxide plays a role in mediating the cerebrovascular response to hypoglycemia (Ichord et al., 1994). In the studies reported here in unanesthetized rats we confirm previous observations that depriving the brain of its essential substrate results in increases in CBF. The findings eliminate insulin as well as insulin-induced changes in blood constituents as mediators of the cerebral vasodilator effects. We have also examined the possibility that nitric oxide may play a role in the vascular response but found no evidence in support of this consideration. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RP Sokoloff, L (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WISSENSCHAFTLICHE verlagsgesellschaft mbh PI STUTTGART PA POSTFACH 40, BIRKENWALDSTRASSE 44, 70191 STUTTGART, GERMANY BN 3-88763-053-X PY 1996 BP 271 EP 284 PG 14 WC Cardiac & Cardiovascular Systems; Neurosciences; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BH54J UT WOS:A1996BH54J00028 ER PT B AU Yasuma, Y McCarron, RM Ruetzler, C Strasser, A Spatz, M AF Yasuma, Y McCarron, RM Ruetzler, C Strasser, A Spatz, M BE Krieglstein, J TI ETA receptor-mediated postischemic: Cerebral hypoperfusion SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1996 LA English DT Proceedings Paper CT 6th International Symposium on Pharmacology of Cerebral Ischemia CY JUL, 1996 CL MARBURG, GERMANY SP Dtsche Forschungsgemeinsch, Bonn, Philipps Univ, Marburg, Asta Medica AG, Frankfurt am Main, Bayer AG, Leverkusen, Behringwerke AG, Marburg, Biotrend Chemikalien GmbH, Koln, Boehringer Ingelheim GmbH, Ingelheim, Byk Gulden Lomberg Chem Fabrik GmbH, Konstanz, Dr Willmar Schwabe Arzneimittel GmbH, Karlsruhe, Hoechst AG, Frankfurt am Main, Image Proc & Vis Co Ltd, Coventry, UK, Janssen Gmbh, Neuss, Knoll AG, Ludwigshafen, Lichtwer Pharma Gmbh, Berlin, Luitpold Pharma, Munchen, Merz + Co GmbH & Co, Frankfurt am Main, Oxford Optr Ltd, Oxford, UK, Sandoz Pharma Ltd, Basel, Schweiz, Schering AG, Berlin, Schwarz Pharma AG, Monheim, Smithkline Beecham Pharma GmbH, Munchen, Smithkline Beecham Pharma, Harlow, UK, Upjohn GmbH, Heppenheim C1 NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892. RP Spatz, M (reprint author), NINCDS,STROKE BRANCH,NIH,36 CONVENT DR,MSC 4128,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WISSENSCHAFTLICHE verlagsgesellschaft mbh PI STUTTGART PA POSTFACH 40, BIRKENWALDSTRASSE 44, 70191 STUTTGART, GERMANY BN 3-88763-053-X PY 1996 BP 291 EP 298 PG 8 WC Cardiac & Cardiovascular Systems; Neurosciences; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BH54J UT WOS:A1996BH54J00030 ER PT B AU Tasaki, K Nawashiro, H Ohtsuki, T Ruetzler, C Martin, D Hallenbeck, J AF Tasaki, K Nawashiro, H Ohtsuki, T Ruetzler, C Martin, D Hallenbeck, J BE Krieglstein, J TI Cytokines in the induction of tolerance to ischemia SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1996 LA English DT Proceedings Paper CT 6th International Symposium on Pharmacology of Cerebral Ischemia CY JUL, 1996 CL MARBURG, GERMANY SP Dtsche Forschungsgemeinsch, Bonn, Philipps Univ, Marburg, Asta Medica AG, Frankfurt am Main, Bayer AG, Leverkusen, Behringwerke AG, Marburg, Biotrend Chemikalien GmbH, Koln, Boehringer Ingelheim GmbH, Ingelheim, Byk Gulden Lomberg Chem Fabrik GmbH, Konstanz, Dr Willmar Schwabe Arzneimittel GmbH, Karlsruhe, Hoechst AG, Frankfurt am Main, Image Proc & Vis Co Ltd, Coventry, UK, Janssen Gmbh, Neuss, Knoll AG, Ludwigshafen, Lichtwer Pharma Gmbh, Berlin, Luitpold Pharma, Munchen, Merz + Co GmbH & Co, Frankfurt am Main, Oxford Optr Ltd, Oxford, UK, Sandoz Pharma Ltd, Basel, Schweiz, Schering AG, Berlin, Schwarz Pharma AG, Monheim, Smithkline Beecham Pharma GmbH, Munchen, Smithkline Beecham Pharma, Harlow, UK, Upjohn GmbH, Heppenheim AB A series of studies have been conducted that implicate the cytokines, TNF-alpha and IL-1, in the induction of tolerance to ischemia in several animal species and in both focal and global models of ischemia. In a focal model of ischemia in the rat, intravenous lipopolysaccharide between 48 and 96 h before occluding the middle cerebral artery reduced infarct size measured 24 h later. Tumor necrosis factor binding protein nullified this protective effect. In a focal model of ischemia in the mouse, intracisternal TNF-alpha 48 h before occlusion of the middle cerebral artery reduced infarct size measured 24 h later. In a global model of ischemia in the gerbil, IL-1 was implicated in the induction of tolerance by ''preconditioning'' ischemia and also shown to be a direct mediator of tolerance to ischemia. C1 NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892. RP Hallenbeck, J (reprint author), NINCDS,STROKE BRANCH,NIH,BLDG 36,ROOM 4A03,36 CONVENT DR,MSC 4128,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WISSENSCHAFTLICHE verlagsgesellschaft mbh PI STUTTGART PA POSTFACH 40, BIRKENWALDSTRASSE 44, 70191 STUTTGART, GERMANY BN 3-88763-053-X PY 1996 BP 421 EP 428 PG 8 WC Cardiac & Cardiovascular Systems; Neurosciences; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BH54J UT WOS:A1996BH54J00042 ER PT J AU Williams, GM Whysner, J Ames, B Boyle, P Doull, J Greim, H Hayashi, Y Hill, RN Kimbrough, RD Krewski, D Kroes, R Monson, R Munro, IC Rajewsky, MF Scheuplein, RJ Sugimura, T Swenberg, JA Travis, CC Sieber, S AF Williams, GM Whysner, J Ames, B Boyle, P Doull, J Greim, H Hayashi, Y Hill, RN Kimbrough, RD Krewski, D Kroes, R Monson, R Munro, IC Rajewsky, MF Scheuplein, RJ Sugimura, T Swenberg, JA Travis, CC Sieber, S TI The use of mechanistic data in the risk assessments of ten chemicals: An introduction to the chemical-specific reviews SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE DNA reactivity; epigenetic effects; risk assessment; cancer mechanism; threshold AB The International Expert Panel on Carcinogen Risk Assessment of the American Health Foundation has planned, directed and reviewed in depth analyses of mechanistic data for 10 rodent carcinogens. The purpose of this review was to illustrate the use of mechanistic data in carcinogen risk assessment. The mechanisms by which a chemical produces cancer in rodents provided important information for determining whether or not humans would be at risk at low exposure levels. For epigenetic (non-DNA-reactive) carcinogens, current exposure levels for these chemicals below a threshold do not pose a risk. For DNA-reactive agents at sufficient exposures, humans would be expected to be at risk. However, protective mechanisms may lower the expected risk, especially at low-level exposures. C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. EUROPEAN INST ONCOL,MILAN,ITALY. UNIV KANSAS,MED CTR,KANSAS CITY,KS 66103. UNIV MILAN,MILAN,ITALY. SOC RADIAT & ENVIRONM RES,MUNICH,GERMANY. NATL INST HLTH SCI,TOKYO,JAPAN. US EPA,WASHINGTON,DC 20460. INST EVALUATING HLTH RISKS,WASHINGTON,DC. HLTH & WELF CANADA,OTTAWA,ON,CANADA. UNIV UTRECHT,NL-3508 TC UTRECHT,NETHERLANDS. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. CANTOX INC,MISSISSAUGA,ON,CANADA. UNIV ESSEN GESAMTHSCH,SCH MED,ESSEN,GERMANY. WEINBERG CONSULTING GRP,WASHINGTON,DC. NATL CANC CTR,TOKYO 104,JAPAN. UNIV N CAROLINA,CHAPEL HILL,NC. OAK RIDGE NATL LAB,OAK RIDGE,TN. NATL CANC INST,BETHESDA,MD. US EPA,WASHINGTON,DC 20460. NATL INST PUBL HLTH & ENVIRONM PROTECT,NL-3720 BA BILTHOVEN,NETHERLANDS. US FDA,WASHINGTON,DC 20204. RP Williams, GM (reprint author), AMER HLTH FDN,TOXICOL & RISK ASSESSMENT PROGRAM,1 DANA RD,VALHALLA,NY 10595, USA. NR 7 TC 25 Z9 25 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PY 1996 VL 71 IS 1-2 BP 1 EP 5 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VH867 UT WOS:A1996VH86700002 ER PT J AU Duncan, WC AF Duncan, WC TI Circadian rhythms and the pharmacology of affective illness SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE depression; sleep; body temperature; serotonin; melatonin; cortisol ID SLOW-WAVE SLEEP; MONOAMINE-OXIDASE INHIBITORS; MAJOR DEPRESSIVE DISORDER; SEASONAL AFFECTIVE-DISORDER; PHASE RESPONSE CURVE; CORE BODY-TEMPERATURE; NON-REM SLEEP; DEXAMETHASONE SUPPRESSION TEST; NOCTURNAL MELATONIN SECRETION; N-ACETYLTRANSFERASE ACTIVITY AB The chronic effects of antidepressant drugs (ADs) on circadian rhythms of behavior, physiology and endocrinology are reviewed. The timekeeping properties of several classes of ADs, including tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, serotonin agonists and antagonists, benzodiazepines, and melatonin are reviewed. Pharmacological effects on the circadian amplitude and phase, as well as effects on day-night measurements of motor activity, sleep-wake, body temperature (Tb), 3-methoxy-4-hydroxyphenylglycol, cortisol, thyroid hormone, prolactin, growth hormone and melatonin are examined. ADs often lower nocturnal Tb and affect the homeostatic regulation of sleep. ADs often advance the timing and decrease the amount of slow wave sleep, reduce rapid eye movement sleep and increase or decrease arousal. Together, AD effects on nocturnal Tb and sleep may be related to their therapeutic properties. ADs sometimes delay nocturnal cortisol timing and increase nocturnal melatonin, thyroid hormone and prolactin levels; these effects often vary with diagnosis, and clinical state. The effects of ADs on the coupling of the central circadian pacemaker to photic and nonphotic zeitgebers are discussed. Copyright (C) 1996 Elsevier Science Inc. RP Duncan, WC (reprint author), NIMH, CLIN PSYCHOBIOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 534 TC 99 Z9 103 U1 5 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PY 1996 VL 71 IS 3 BP 253 EP 312 DI 10.1016/S0163-7258(96)00092-7 PG 60 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VP191 UT WOS:A1996VP19100001 PM 8940745 ER PT J AU Skolnick, P Layer, RT Popik, P Nowak, G Paul, IA Trullas, R AF Skolnick, P Layer, RT Popik, P Nowak, G Paul, IA Trullas, R TI Adaptation of N-methyl-D-aspartate (NMDA) receptors following antidepressant treatment: Implications for the pharmacotherapy of depression SO PHARMACOPSYCHIATRY LA English DT Article ID STRESS-INDUCED ANHEDONIA; ANTAGONISTS; IMIPRAMINE; COMPLEX; CORTEX; ACID AB NMDA antagonists mimic the effects of clinically effective antidepressants in both preclinical tests predictive of antidepressant action and procedures designed to model aspects of depressive symptomatology. These findings led to experiments demonstrating that chronic administration of NMDA antagonists to rodents results in a downregulation of cortical beta-adrenoceptors, a phenomenon also observed following chronic treatment with many antidepressants. These neurochemical and behavioral similarities between antidepressants and NMDA antagonists prompted us to examine the impact of chronic antidepressant treatment on NMDA receptors. Chronic (14 days) but not acute (1 day) administration of seventeen different antidepressants to mice produced adaptive changes in radioligand binding to NMDA receptors. Detailed studies with three antidepressants (imipramine, citalopram, and electroconvulsive shock) show that these changes develop slowly, persist for some time after cessation of treatment, and (for imipramine and citalopram) are dose dependent. Moreover, following chronic treatment with imipramine, these changes in radioligand binding to NMDA receptors appear restricted to the cerebral cortex, Based on the consistency of these effects across antidepressant treatments, we propose that adaptive changes in NMDA receptors may be the final common pathway for antidepressant action. The recent demonstration (Nowak et al., 1995) that radioligand binding to NMDA receptors is altered in frontal cortex of suicide victims (compared to age and post-mortem interval matched controls) is consistent with the hypothesis (Trullas and Skolnick, 1990) that this family of ligand gated ion channels is involved in the pathophysiology of depression. C1 POLISH ACAD SCI,INST PHARMACOL,KRAKOW,POLAND. UNIV MISSISSIPPI,MED CTR,DEPT PSYCHIAT & HUMAN BEHAV,JACKSON,MS. CSIC,DEPT BIOANALYT MED,NEUROBIOL UNIT,BARCELONA,SPAIN. RP Skolnick, P (reprint author), NIDDK,NIH,NEUROSCI LAB,BLDG 8,ROOM 11,BETHESDA,MD 20892, USA. RI Popik, Piotr/R-5383-2016; Trullas, Ramon/D-2197-2016 OI Popik, Piotr/0000-0003-0722-1263; Trullas, Ramon/0000-0001-7951-9881 NR 28 TC 229 Z9 235 U1 3 U2 14 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD JAN PY 1996 VL 29 IS 1 BP 23 EP 26 DI 10.1055/s-2007-979537 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA TX827 UT WOS:A1996TX82700004 PM 8852530 ER PT J AU Deutsch, J Rapoport, SI Purdon, D AF Deutsch, J Rapoport, SI Purdon, D TI Isolation and HPLC separation of polyunsaturated species of rat brain acyl-CoA produced during decapitation - Ischemia SO PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS LA English DT Article ID ESTERS AB Acyl-CoA is a crucial metabolic intermediate for the incorporation of fatty acid into membrane phospholipid. The rat brain long chain acyl-CoAs were isolated and quantitated with a procedure involving solid phase extraction with an oligonucleotide purification cartridge, followed by separation and quantitation by HPLC with special emphasis on resolution of the polyunsaturate acyl-CoAs. This procedure is uniquely suited to the rapid analysis of all molecular species of brain acyl-CoA including the polyunsaturate molecular species which are affected by ischemia. A selective 3-4 fold increase in arachidonoyl-CoA was found in rat brain after 3 min of ischemia when compared with microwaved brain. In contrast, the concentration of all other molecular species of acyl-CoA did not change over the time course of the ischemia. C1 NIA, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. RP Deutsch, J (reprint author), HEBREW UNIV JERUSALEM, SCH PHARM, DEPT PHARMACEUT CHEM, IL-91120 JERUSALEM, ISRAEL. NR 7 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-6507 J9 PHOSPHORUS SULFUR JI Phosphorus Sulfur Silicon Relat. Elem. PY 1996 VL 109 IS 1-4 BP 389 EP 392 PG 4 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA VQ054 UT WOS:A1996VQ05400089 ER PT J AU DasSarma, S Lanczycki, CJ Kotlyar, R Ghaisas, SV AF DasSarma, S Lanczycki, CJ Kotlyar, R Ghaisas, SV TI Scale invariance and dynamical correlations in growth models of molecular beam epitaxy SO PHYSICAL REVIEW E LA English DT Article ID SCANNING TUNNELING MICROSCOPY; ON-SOLID RULES; SURFACE-DIFFUSION; KINETIC-GROWTH; NONEQUILIBRIUM GROWTH; GROWING INTERFACES; CRYSTAL-GROWTH; 2+1 DIMENSIONS; CONTINUUM; SIMULATION AB Dynamical scaling behavior of the kinetic roughening phenomena in (1+1)- and (2+1)-dimensional models of molecular beam epitaxy (MBE) is studied using kinetic Monte Carlo simulations mostly within the solid-on-solid lattice gas approximation. We relate the simulation results of our finite temperature stochastic Monte Carlo algorithm, which employs local-configuration-dependent thermally activated Arrhenius diffusion, to those obtained from simpler manifestly nonequilibrium dynamical growth models involving instantaneous relaxation. The extracted critical exponents for kinetic roughening are found to be temperature dependent due to finite size and crossover effects, and in particular, the growth (beta) and roughness (alpha) exponents decrease with increasing temperature as diffusion noise becomes stronger relative to the deposition noise. We find strong evidence for anomalous dynamic scaling, with global and local scaling behaviors being substantially different in 1+1 dimensions. Remarkably, the anomalous roughness exponent alpha' (= alpha in the usual dynamic scaling situation) defining the spatial scaling in the height-height correlation function is found to be approximately a temperature-independent constant (approximate to 0.6-0.7 in 1+1 dimensions) in all our models, including the Arrhenius-activated diffusion model. An associated significant result is the marked up-down (h --> -h) asymmetry in our simulated growth morphologies, clearly indicating the presence of nonlinear microscopically irreversible processes dominating local growth features. We study in some detail the recently suggested connection between height fluctuations in MBE growth models and intermittent fluctuations in fluid turbulence by numerically calculating the multiaffine dynamic scaling behavior of higher moments of the height correlation functions and by obtaining the stretched exponential behavior of the step-height distribution functions in our growth models. We critically analyze our growth rules to comment on possible coarse-grained continuum descriptions that could qualitatively account for our MBE simulation results. C1 NIH,DIV COMP RES & TECHNOL,COMPUTAT BIOSCI & ENGN LAB,BETHESDA,MD 20892. UNIV POONA,DEPT ELECTR SCI,POONA 411007,MAHARASHTRA,INDIA. RP DasSarma, S (reprint author), UNIV MARYLAND,DEPT PHYS,COLLEGE PK,MD 20742, USA. RI Das Sarma, Sankar/B-2400-2009 OI Das Sarma, Sankar/0000-0002-0439-986X NR 80 TC 125 Z9 126 U1 1 U2 10 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD JAN PY 1996 VL 53 IS 1 BP 359 EP 388 DI 10.1103/PhysRevE.53.359 PN A PG 30 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA TR117 UT WOS:A1996TR11700049 ER PT B AU Christian, MC AF Christian, MC BE Pinedo, HM Schornagel, JH TI Phase I trials of ormaplatin (NSC 363812) SO PLATINUM AND OTHER METAL COORDINATION COMPOUNDS IN CANCER CHEMOTHERAPY 2 LA English DT Proceedings Paper CT 7th International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy (ISPCC 95) CY MAR 01-04, 1995 CL AMSTERDAM, NETHERLANDS SP European Canc Ctr C1 NCI,INVEST DRUG BRANCH,CANC THERAPY EVALUAT PROGRAM,DIV CANC TREATMENT,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45287-1 PY 1996 BP 187 EP 192 PG 6 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA BF46P UT WOS:A1996BF46P00017 ER PT B AU OConnor, PM Fan, SJ AF OConnor, PM Fan, SJ BE Pinedo, HM Schornagel, JH TI Cell cycle checkpoints and cancer chemotherapy SO PLATINUM AND OTHER METAL COORDINATION COMPOUNDS IN CANCER CHEMOTHERAPY 2 LA English DT Proceedings Paper CT 7th International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy (ISPCC 95) CY MAR 01-04, 1995 CL AMSTERDAM, NETHERLANDS SP European Canc Ctr C1 NCI,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45287-1 PY 1996 BP 293 EP 301 PG 9 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA BF46P UT WOS:A1996BF46P00027 ER PT J AU Jerina, DM Sayer, JM Yeh, HJC Liu, XH Yagi, H Schurter, E Gorenstein, D AF Jerina, DM Sayer, JM Yeh, HJC Liu, XH Yagi, H Schurter, E Gorenstein, D TI NMR conformational analysis of DNA duplexes containing diol epoxide adducts of polycyclic aromatic hydrocarbons SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article; Proceedings Paper CT 15th International Symposium on Polycyclic Aromatic Compounds / 2nd Biennial Meeting of International-Society-for-Polycyclic-Aromatic-Compounds CY SEP 19-22, 1995 CL BELGIRATE, NOVARA, ITALY SP Int Soc Polycycl Aromat Compounds DE NMR conformational analysis; bay-region diol epoxides; modified oligonucleotides; DNA adducts; deoxyadenosine adducts; intercalation; minor groove; benzo[a]pyrene ID DEOXYADENOSINE N-6-AMINO GROUP; COVALENTLY ATTACHED BENZOPYRENE; DG MISMATCH OPPOSITE; MODIFIED DEOXYGUANOSINE; TRANS ADDITION; (+)-CIS-ANTI-DG ADDUCT; NONANUCLEOTIDE DUPLEX; BASE DISPLACEMENT; DELETION SITE; INTERCALATION AB The principal adducts formed between DNA and polycyclic aromatic hydrocarbon diol epoxides result from N-alkylation of the exocyclic amino groups of the purine bases by the benzylic carbon atom of the epoxide. To date, the solution conformations of mon than a dozen alkylated DNA duplexes have been examined by 2D NMR spectroscopy. For trans opened diol epoxides, oligomer duplexes containing N-2-adducts at deoxyguanosine have the hydrocarbon residue lying in the minor groove whereas those containing N-6-adducts at deoxyadenosine have the hydrocarbon intercalated within the DNA helix. Absolute configuration at the site of attachment appears to be a major determinant in establishing whether the hydrocarbon lies to the 3'- or the 5'-side of the adducted base. For trans opened deoxyadenosine adducts with R-absolute configuration, the hydrocarbon residue is positioned toward the 5'-end of the adducted strand whereas trans opened deoxyguanosine adducts with R-absolute configuration have the hydrocarbon located toward the 3'-end of the adducted strand. C1 NIDDKD,LABS BIOORGAN & ANALYT CHEM,NIH,BETHESDA,MD 20982. PURDUE UNIV,DEPT CHEM,W LAFAYETTE,IN 47901. UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET,GALVESTON,TX 77555. NR 25 TC 18 Z9 18 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1996 VL 10 IS 1-4 BP 145 EP 152 DI 10.1080/10406639608034691 PG 8 WC Chemistry, Organic SC Chemistry GA WD676 UT WOS:A1996WD67600020 ER PT J AU Page, JE Christner, DF Lakshman, MK Zajc, B OhHara, T Lipinski, LJ Ross, HL Agarwal, R Szeliga, J Yagi, H Sayer, JM Jerina, DM Dipple, A AF Page, JE Christner, DF Lakshman, MK Zajc, B OhHara, T Lipinski, LJ Ross, HL Agarwal, R Szeliga, J Yagi, H Sayer, JM Jerina, DM Dipple, A TI Effects of polycyclic aromatic hydrocarbon adducts with deoxyguanosine and deoxyadenosine in vivo and in vitro SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article; Proceedings Paper CT 15th International Symposium on Polycyclic Aromatic Compounds / 2nd Biennial Meeting of International-Society-for-Polycyclic-Aromatic-Compounds CY SEP 19-22, 1995 CL BELGIRATE, NOVARA, ITALY SP Int Soc Polycycl Aromat Compounds ID SHUTTLE VECTOR PLASMID; MUTAGENIC SPECIFICITY; SOLUTION CONFORMATION; DIOL EPOXIDES; OPPOSITE DT; MOUSE SKIN; DNA DUPLEX; BENZOPYRENE; BENZOPHENANTHRENE; CELLS AB Reactive metabolites from non-planar polycyclic aromatic hydrocarbon carcinogens react extensively with both deoxyadenosine and deoxyguanosine in DNA whereas those from planar molecules react predominantly only with deoxyguanosine. In vitro studies with single adducts in oligonucleotides showed that both types of adduct blocked primer extension and that the limited amount of nucleotide addition opposite the adduct varied with the polymerase, the sequence context of the adduct and the chemical structure of the adduct. When these same single adduct containing-oligonucleotides were introduced into a single-stranded vector that was allowed to replicate in Escherichia coli, the major events observed were blockage of replication, insertion of the correct nucleotide (i.e. T opposite an A adduct and C opposite a G adduct), and insertion of A opposite the adduct. Ln mouse skin, benzo[c]phenanthrene 4S,3R-dihydrodiol 2S,1R-epoxide initiated substantially more tumors per DNA adduct formed than did the other three isomers. This isomer generates mostly adenine adducts in DNA, suggesting that, in this case, adenine adducts are intrinsically more tumorigenic than guanine adducts. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. NIDDKD,NIH,BETHESDA,MD 20892. NR 34 TC 0 Z9 0 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1996 VL 10 IS 1-4 BP 171 EP 178 DI 10.1080/10406639608034694 PG 8 WC Chemistry, Organic SC Chemistry GA WD676 UT WOS:A1996WD67600023 ER PT J AU Harris, CC AF Harris, CC TI Tumor suppressor genes: At the crossroads of molecular carcinogenesis, molecular epidemiology, and human risk assessment SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT 25th Anniversary Symposium of the American-Health-Foundation - Toward Optimal Health: Examining Goals for Nutrition and the Environment CY NOV 16-17, 1994 CL TARRYTOWN, NY SP Amer Hlth Fdn ID HEPATITIS-B VIRUS; HUMAN HEPATOCELLULAR-CARCINOMA; P53 MUTATIONS; X-PROTEIN; LUNG; DNA; CANCER; EXPRESSION; INVITRO; LESIONS RP Harris, CC (reprint author), NCI,NIH,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2001,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 33 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN-FEB PY 1996 VL 25 IS 1 BP 10 EP 12 DI 10.1006/pmed.1996.0005 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA UD442 UT WOS:A1996UD44200004 PM 8778751 ER PT J AU Greenwald, P AF Greenwald, P TI The potential of dietary modification to prevent cancer SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT 25th Anniversary Symposium of the American-Health-Foundation - Toward Optimal Health: Examining Goals for Nutrition and the Environment CY NOV 16-17, 1994 CL TARRYTOWN, NY SP Amer Hlth Fdn RP Greenwald, P (reprint author), NCI,NIH,DIV CANC PREVENT & CONTROL,BLDG 31,ROOM 10A52,BETHESDA,MD 20892, USA. NR 10 TC 6 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN-FEB PY 1996 VL 25 IS 1 BP 41 EP 43 DI 10.1006/pmed.1996.0014 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA UD442 UT WOS:A1996UD44200013 PM 8778761 ER PT J AU Stone, EJ AF Stone, EJ TI Can school health education programs make a difference? SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT 25th Anniversary Symposium of the American-Health-Foundation - Toward Optimal Health: Examining Goals for Nutrition and the Environment CY NOV 16-17, 1994 CL TARRYTOWN, NY SP Amer Hlth Fdn RP Stone, EJ (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,2 ROCKLEDGE CTR,ROOM 8134,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN-FEB PY 1996 VL 25 IS 1 BP 54 EP 55 DI 10.1006/pmed.1996.0019 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA UD442 UT WOS:A1996UD44200018 PM 8778766 ER PT S AU Greenwald, P Kelloff, GJ AF Greenwald, P Kelloff, GJ BE Stewart, BW McGregor, D Kleihues, P TI The role of chemoprevention in cancer control SO PRINCIPLES OF CHEMOPREVENTION SE IARC SCIENTIFIC PUBLICATIONS LA English DT Proceedings Paper CT IARC Conference on Principles of Chemoprevention CY NOV 10-16, 1995 CL LYON, FRANCE SP Int Agcy Res Canc AB Chemoprevention is a promising strategy for cancer prevention that is international in application and may be more immediate in worldwide impact than either dietary modification or prevention of exposure to carcinogens. Precedent for a chemopreventive approach is found in cardiology, where cholesterol-lowering, antihypertensive and antiplatelet agents are administered to prevent heart disease progression in high-risk individuals. The multistep nature of carcinogenesis provides many opportunities for chemopreventive interventions with agents targeted to specific mechanisms involved in cancer initiation, promotion and progression. The well-defined strategy for development of chemopreventive agents includes evaluation of leads from epidemiological and experimental research; preclinical efficacy testing of candidate agents; and assessments of the preclinical and clinical safety, toxicity, bioavailability and pharmacokinetics of those that are the most promising. Short-term clinical trials then determine optimal dosing and characterize the efficacy of the best agents against intermediate biomarkers of cancer. Large-scale randomized trials, the final stage of this strategy, evaluate whether the chemopreventive agents actually do reduce cancer risk. The systematic development of agents is coupled with basic research into mechanisms of action and subsequent application of the findings to agent design and discovery. Major objectives of chemopreventive drug development include identification and validation of intermediate biomarkers that are accurate predictors of future cancer incidence and that can serve as surrogate end points for clinical disease. Complementary international efforts to standardize chemopreventive trial designs and protocols among communities worldwide would help ensure a valid comparison of results across countries and more efficient and effective cancer-preventive regimens. RP Greenwald, P (reprint author), NCI,CHEMOPREVENT BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU INT AGENCY RESEARCH CANCER PI LYONS PA 150, COURS ALBERT THOMAS, 69372 LYONS, FRANCE SN 0300-5038 BN 92-832-2139-7 J9 IARC SCI PUBL PY 1996 IS 139 BP 13 EP 22 PG 10 WC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics SC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics GA BJ53S UT WOS:A1996BJ53S00002 PM 8923016 ER PT S AU Kelloff, GJ Boone, CW Steele, VE Crowell, JA Lubet, RA Greenwald, P Hawk, ET Fay, JR Sigman, CC AF Kelloff, GJ Boone, CW Steele, VE Crowell, JA Lubet, RA Greenwald, P Hawk, ET Fay, JR Sigman, CC BE Stewart, BW McGregor, D Kleihues, P TI Mechanistic considerations in the evaluation of chemopreventive data SO PRINCIPLES OF CHEMOPREVENTION SE IARC SCIENTIFIC PUBLICATIONS LA English DT Proceedings Paper CT IARC Conference on Principles of Chemoprevention CY NOV 10-16, 1995 CL LYON, FRANCE SP Int Agcy Res Canc AB Possible chemopreventive mechanisms include carcinogen-blocking activities, antioxidant/antiinflammatory activities and antiproliferation/antiprogression activities. Carcinogen-blocking activities encompass inhibition of carcinogen uptake, inhibition of carcinogen formation or activation, deactivation or detoxification of carcinogens, prevention of carcinogen binding to DNA, and enhancement of the level or fidelity of DNA repair. Antioxidant/anti-inflammatory activities include scavenging of reactive electrophiles and oxygen radicals, and inhibition of arachidonic acid metabolism. Antiproliferation/antiprogression activities comprise modulation of signal transduction, modulation of hormonal and growth factor activity, inhibition of aberrant oncogene activity, inhibition of polyamine metabolism, induction of terminal differentiation. restoration of immune responses, enhancement of intercellular communication, restoration of tumour suppressor function, induction of apoptosis, telomerase inhibition. correction of DNA methylation imbalances, inhibition of angiogenesis, inhibition of basement membrane degradation, and activation of antimetastasis genes. In evaluating the potential efficacy of chemopreventive agents several mechanistic parameters are weighed: (1) the number of chemoprevention-related pharmacological activities, (2) the impact of the agent on likely carcinogenesis pathways to the targeted cancer, (3) pharmacodynamics, and (4) specificity for chemopreventive activity compared with interference with normal cellular function. Mechanistic data are important throughout the development process for chemopreventive drugs, and they are particularly important in the earlier phases of identifying promising candidate agents and characterizing efficacy. In vitro mechanistic assays are a first step in evaluating chemopreventive potential. Mechanistic considerations are also useful in defining animal efficacy models and in interpreting the results of assays in these models. Mechanistic data are also applied in designing short-term Phase II clinical chemoprevention trials that use reductions in intermediate biomarkers of cancer rather than cancer incidence as end points. The basis for identifying and evaluating these biomarkers is in understanding carcinogenesis and chemopreventive mechanisms. RP Kelloff, GJ (reprint author), NCI,DIV CANC PREVENT & CONTROL,NIH,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 5 U1 0 U2 0 PU INT AGENCY RESEARCH CANCER PI LYONS PA 150, COURS ALBERT THOMAS, 69372 LYONS, FRANCE SN 0300-5038 BN 92-832-2139-7 J9 IARC SCI PUBL PY 1996 IS 139 BP 203 EP 219 PG 17 WC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics SC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics GA BJ53S UT WOS:A1996BJ53S00018 PM 8923032 ER PT J AU Safar, J AF Safar, J TI The folding intermediate concept of prion protein formation and conformational links to infectivity SO PRIONS PRIONS PRIONS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID DISEASES RP Safar, J (reprint author), NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BETHESDA,MD 20892, USA. RI Safar, Jiri/G-6512-2013 NR 14 TC 8 Z9 8 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 207 BP 69 EP 76 PG 8 WC Immunology; Microbiology SC Immunology; Microbiology GA BF03T UT WOS:A1996BF03T00006 PM 8575207 ER PT J AU Wickner, RB Masison, DC AF Wickner, RB Masison, DC TI Evidence for two prions in yeast: [URE3] and [PSI] SO PRIONS PRIONS PRIONS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID SACCHAROMYCES-CEREVISIAE; GENE; SCRAPIE; PRP; MITOCHONDRIAL; MUTATION; PROTEIN RP Wickner, RB (reprint author), NIDDKD,SECT GENET SIMPLE EUKARYOTES,NIH,BLDG 8,ROOM 207,BETHESDA,MD 20892, USA. NR 39 TC 21 Z9 22 U1 2 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 207 BP 147 EP 160 PG 14 WC Immunology; Microbiology SC Immunology; Microbiology GA BF03T UT WOS:A1996BF03T00010 PM 8575202 ER PT B AU McQueen, PG Jin, AJ Pierpaoli, C Basser, PJ AF McQueen, PG Jin, AJ Pierpaoli, C Basser, PJ BE Bajpai, PK TI Development of a finite element model of molecular diffusion in living brain from in vivo magnetic resonance SO PROCEEDINGS OF THE 1996 FIFTEENTH SOUTHERN BIOMEDICAL ENGINEERING CONFERENCE LA English DT Meeting Abstract CT 15th Southern Biomedical Engineering Conference CY MAR 29-31, 1996 CL DAYTON, OH SP Univ Dayton, Dayton, Wright State Univ, Dayton, Wright Patterson Air Force Base, Armstrong Lab, Dayton, IEEE, Engn Med & Biol Soc, Soc Biomat C1 NIH,DCRR,PSL,BETHESDA,MD 20892. OI Jin, Albert/0000-0003-3826-1081 NR 0 TC 0 Z9 0 U1 0 U2 0 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 BN 0-7803-3131-1 PY 1996 BP 289 EP 292 DI 10.1109/SBEC.1996.493206 PG 4 WC Engineering, Aerospace; Computer Science, Artificial Intelligence; Engineering, Biomedical; Engineering, Electrical & Electronic; Ergonomics; Instruments & Instrumentation; Materials Science, Biomaterials; Radiology, Nuclear Medicine & Medical Imaging; Rehabilitation SC Engineering; Computer Science; Instruments & Instrumentation; Materials Science; Radiology, Nuclear Medicine & Medical Imaging; Rehabilitation GA BF41T UT WOS:A1996BF41T00074 ER PT J AU Fauci, AS AF Fauci, AS TI An HIV vaccine: Breaking the paradigms SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article; Proceedings Paper CT 108th Annual Meeting of the Tri-Societies CY MAY 05-08, 1995 CL SAN DIEGO, CA SP Tri Soc ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; PROTECTION; PATHOGENESIS; CHIMPANZEES; PLASMA RP Fauci, AS (reprint author), NIAID,NIH,BLDG 31,ROOM 7A03,31 CTR DR,MSC 2520,BETHESDA,MD 20892, USA. NR 47 TC 10 Z9 11 U1 0 U2 5 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD JAN PY 1996 VL 108 IS 1 BP 6 EP 13 PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA TU697 UT WOS:A1996TU69700002 PM 8834058 ER PT J AU Boirivant, M Fuss, I Fiocchi, C Klein, JS Strong, SA Strober, W AF Boirivant, M Fuss, I Fiocchi, C Klein, JS Strong, SA Strober, W TI Hypoproliferative human lamina propria T cells retain the capacity to secrete lymphokines when stimulated via CD2/CD28 pathways SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article ID MONOCLONAL-ANTIBODY; CLONAL ANERGY; LYMPHOCYTE-T; FUNCTIONAL-CHARACTERIZATION; RECEPTOR OCCUPANCY; ANTIGEN; ACTIVATION; PROLIFERATION; INHIBITION; INDUCTION AB Human lamina propria (LP)T cells exhibit a reduced proliferative capacity in response to antigen-specific stimulation. To investigate the functional state of such hypoproliferative T cells, we determined the capacity of LP T cells to produce lymphokines when stimulated by monoclonal antibodies that crosslink either the TCR/CD3 complex or accessory pathway molecules (CD2,CD28). We found that TCR/CD3-mediated proliferative responses of LP T cells were greatly diminished when compared to peripheral blood (PB)T cells, but were largely restored when cells were preincubated in IL-2. Despite their proliferative hyporesponsiveness, LP T cells (as compared to PB T cells) secreted equal amounts of IL-2 and increased amounts of IFN-gamma, IL-4 and IL-5; these increased cytokine responses were most evident when cells were stimulated via the accessory pathways. In further studies, purified CD4+ LP T cells were compared with purified CD4+/CD45RO + PB T cells (i.e., the PB T cell subset they most resemble). LP T cells produced significantly more IFN-gamma and IL-5 but less IL-4 than their CD45RO+ PB counterparts. Overall, LP T cells are unresponsive T cells following stimulation via the TCR/CD3 pathway but nevertheless retain the capacity to produce increased levels of TH1 and TH2-type lymphokines following stimulation via the CD2/CD28 accessory pathway; thus, they are best classified as modified ''anergic'' T cells. C1 NIAID,NIH,MUCOSAL IMMUN SECT,CLIN INVEST LAB,BETHESDA,MD 20892. CLEVELAND CLIN FDN,DEPT COLORECTAL SURG,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,RES INST,CLEVELAND,OH 44195. RI BOIRIVANT, MONICA/B-9977-2016 NR 35 TC 40 Z9 40 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD JAN PY 1996 VL 108 IS 1 BP 55 EP 67 PG 13 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA TU697 UT WOS:A1996TU69700009 PM 8834065 ER PT B AU Fozard, JL AF Fozard, JL GP HUMAN FACTORS & ERGON SOC TI Aging and technology: A developmental view SO PROCEEDINGS OF THE HUMAN FACTORS AND ERGONOMICS SOCIETY - 40TH ANNUAL MEETING, VOLS 1 AND 2: HUMAN CENTERED TECHNOLOGY - KEY TO THE FUTURE LA English DT Proceedings Paper CT Human-Factors-and-Ergonomics-Society 40th Annual Meeting on Human Centered Technology - Key to the Future CY 1996 CL PHILADELPHIA, PA SP Human Factors & Ergon Soc C1 NIA,CTR GERONTOL RES,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMAN FACTORS AND ERGONOMICS SOC PI SANTA MONICA PA PO BOX 1369, SANTA MONICA, CA 90406-1369 BN 0-945289-06-5 PY 1996 BP 138 EP 140 PG 3 WC Ergonomics SC Engineering GA BG25A UT WOS:A1996BG25A00027 ER PT B AU Long, LR Gill, MJ Thoma, GR AF Long, LR Gill, MJ Thoma, GR GP IEEE COMP SOC TI High speed satellite access to biomedical text/image databases SO PROCEEDINGS OF THE THIRD FORUM ON RESEARCH AND TECHNOLOGY ADVANCES IN DIGITAL LIBRARIES (ADL '96) LA English DT Proceedings Paper CT 3rd Forum on Research and Technology Advances in Digital Libraries (ADL 96) CY MAY 13-15, 1996 CL WASHINGTON, DC SP NASA Goddard Space Flight Ctr, Natl Lib Med, IEEE, Comp Soc, Tech Comm Data Engn & Task Force Digital Libs, Lib Congress, Brown Univ, Columbia Univ, Cornell Univ, George Washington Univ, Natl Inst Stand & Technol, Rutgers Ctr Informat Management Integrat & Connectiv, Univ Milan, Univ Maryland, Univ Baltimore Cty, Univ Texas Austin C1 NATL LIB MED,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I E E E, COMPUTER SOC PRESS PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, LOS ALAMITOS, CA 90720 BN 0-8186-7402-4 PY 1996 BP 35 EP 44 DI 10.1109/ADL.1996.502514 PG 10 WC Computer Science, Information Systems SC Computer Science GA BF68X UT WOS:A1996BF68X00004 ER PT J AU Bhaumik, SR Chary, KVR Govil, G Liu, K Miles, HT AF Bhaumik, SR Chary, KVR Govil, G Liu, K Miles, HT TI NMR characterisation of a DNA triplex formed by homo-purine and homo-pyrimidine strands at 1:1 molar ratio and acidic pH SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 TATA INST FUNDAMENTAL RES,MUMBAI,INDIA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP PB124 EP PB124 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300276 ER PT J AU CasasFinet, JR Urbaneja, MA Arthur, LO Henderson, LE AF CasasFinet, JR Urbaneja, MA Arthur, LO Henderson, LE TI Structural determinants of RNA binding affinity in HIV-1 nucleocapsid protein (NCP) p7 SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP PB217 EP PB217 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300313 ER PT J AU Chary, KVR Bhaumik, SR Govil, G Liu, K Miles, HT AF Chary, KVR Bhaumik, SR Govil, G Liu, K Miles, HT TI DNA strands complementary in parallel orientation, form an antiparallel duplex at neutral pH with A-C, G-T and T-C mismatched base pairs. SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 TATA INST FUNDAMENTAL RES,MUMBAI,INDIA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP PB123 EP PB123 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300274 ER PT J AU Feigin, AM Schagina, LC Bezrukov, SM Kaulin, YA Takemoto, JY Teeter, JH Brand, JG AF Feigin, AM Schagina, LC Bezrukov, SM Kaulin, YA Takemoto, JY Teeter, JH Brand, JG TI Functioning of syringomycin E channels: Effect of ionic strength SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 MONELL CHEM SENSES CTR,PHILADELPHIA,PA 19104. RUSSIAN ACAD SCI,INST CYTOL,ST PETERSBURG 194064,RUSSIA. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. UTAH STATE UNIV,LOGAN,UT 84322. RI Takemoto, Jon/A-5309-2011 OI Takemoto, Jon/0000-0001-9919-9168 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP PC321 EP PC321 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300411 ER PT J AU Kempner, E Bernstein, S AF Kempner, E Bernstein, S TI Radiobiological implications of RNA target analysis SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD. NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP PB302 EP PB302 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300316 ER PT J AU Maraboeuf, F Morimatsu, K Voloshin, O Horii, T CameriniOtero, D Takahashi, M AF Maraboeuf, F Morimatsu, K Voloshin, O Horii, T CameriniOtero, D Takahashi, M TI DNA-binding sites of RecA protein SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 INST CURIE,F-91405 ORSAY,FRANCE. BIKEN INST,OSAKA,JAPAN. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP PB202 EP PB202 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300299 ER PT J AU Trus, BL Greenstone, HL Roden, RBS Schiller, JT Booy, FP AF Trus, BL Greenstone, HL Roden, RBS Schiller, JT Booy, FP TI 3D reconstruction of bovine papillomavirus visualized at 9 angstrom SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 NIH,DCRT,CBEL,BETHESDA,MD 20892. NCI,LCO,NIH,BETHESDA,MD 20892. NIAMS,LSB,NIH,BETHESDA,MD 20892. NR 7 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP PA105 EP PA105 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300101 ER PT J AU Gronenborn, AM AF Gronenborn, AM TI Intercalation, DNA kinking and transcription control: Structures of protein/DNA complexes SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP SA102 EP SA102 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300008 ER PT J AU Parry, DAD Jones, LN Booy, FP Cheng, N Watts, NR Steven, AC AF Parry, DAD Jones, LN Booy, FP Cheng, N Watts, NR Steven, AC TI Intermediate filament structure: Hard alpha-keratin SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 MASSEY UNIV,DEPT PHYS,PALMERSTON NORTH,NEW ZEALAND. CSIRO,DIV WOOL TECHNOL,GEELONG,VIC,AUSTRALIA. NIAMS,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP SF201 EP SF201 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300062 ER PT J AU Tjandra, N Grzesiek, S Pastor, RW Bax, A AF Tjandra, N Grzesiek, S Pastor, RW Bax, A TI Anisotropic diffusion and orientation of proteins in solution studied by heteronuclear NMR. SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP SH402 EP SH402 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300085 ER PT J AU Natsukari, N Kulaga, H Baker, I Wyatt, RJ Masserano, JM AF Natsukari, N Kulaga, H Baker, I Wyatt, RJ Masserano, JM TI Evaluation of cyclic AMP accumulation in EBV-transformed human B-lymphocytes: Effects of dopamine agonists, isoproterenol, prostaglandin E(1), cholera toxin, forskolin, and phorbol 12-myristate-13-acetate SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE cyclic AMP; dopamine; protein kinase C; transformed human lymphocytes ID PROTEIN-KINASE-C; PERIPHERAL-BLOOD LYMPHOCYTES; BETA-ADRENERGIC AGONISTS; HIGH-AFFINITY BINDING; ADENYLATE-CYCLASE; SCHIZOPHRENIC-PATIENTS; H-3 SPIPERONE; CELLS; CALMODULIN; RAT AB 1. Phorbol 12-myristate-13-acetate (PMA), a protein kinase C activator, elevated cyclic AMP accumulation in EBV-transformed human B-lymphocytes, and potentiated isoproterenol-, prostaglandin- (PGE(1)), cholera toxin-, and forskolin-stimulated cyclic AMP accumulation. 2. The dopamine D-1 receptor agonist, SXF38393 (10(-7) to 10(-5) M), had no effect on cyclic AMP accumulation in transformed human B-lymphocytes. 3. The dopamine D-2 receptor agonist, quinpirole (10(-7) to 10(-4) M) did not inhibit cyclic AMP accumulation even when cyclic AMP accumulation was maximized by the addition of PMA and forskolin. 4. These data suggest that dopamine D-1- and D-2-receptor coupling to a cyclic AMP generating system is not present at detectable levels in transformed human B-lymphocytes. C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 31 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JAN PY 1996 VL 20 IS 1 BP 99 EP 108 DI 10.1016/0278-5846(95)00295-2 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UC928 UT WOS:A1996UC92800006 PM 8861180 ER PT J AU Bustin, M Reeves, R AF Bustin, M Reeves, R TI High-mobility-group chromosomal proteins: Architectural components that facilitate chromatin function SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 54 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY LA English DT Review ID DNA-BINDING PROTEIN; NEGATIVELY SUPERCOILED DNA; BOVINE INTERLEUKIN-2 CDNA; NUCLEOSOME CORE PARTICLES; SEQUENCE-SPECIFIC BINDING; TRANSCRIPTION FACTOR-I; SEX-DETERMINING REGION; AMINO-ACID SEQUENCE; C-TERMINAL DOMAINS; HMG-I C1 WASHINGTON STATE UNIV,DEPT BIOCHEM & BIOPHYS,PULLMAN,WA 99164. WASHINGTON STATE UNIV,DEPT GENET & CELL BIOL,PULLMAN,WA 99164. RP Bustin, M (reprint author), NCI,NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. RI Bustin, Michael/G-6155-2015 NR 297 TC 626 Z9 645 U1 1 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0278-5846 J9 PROG NUCLEIC ACID RE PY 1996 VL 54 BP 35 EP 100 DI 10.1016/S0079-6603(08)60360-8 PG 68 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF80W UT WOS:A1996BF80W00002 PM 8768072 ER PT J AU Osborne, N Chader, J AF Osborne, N Chader, J TI Untitled SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Editorial Material C1 NEI,VIS RES LAB,NIH,BETHESDA,MD 20892. RP Osborne, N (reprint author), UNIV OXFORD,NUFFIELD LAB OPHTHALMOL,WALTON ST,OXFORD OX2 6AW,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PY 1996 VL 15 IS 2 BP R7 EP R7 DI 10.1016/S1350-9462(96)90000-2 PG 1 WC Ophthalmology SC Ophthalmology GA VK290 UT WOS:A1996VK29000001 ER PT S AU Esposito, C Patel, A Liu, ZH Striker, GE Striker, LJ AF Esposito, C Patel, A Liu, ZH Striker, GE Striker, LJ BE Koide, H Ichikawa, I TI Involvement of synthesis and degradation pathways of collagen type IV in human glomerulosclerosis: Molecular analysis by in situ reverse transcription and competitive polymerase chain reaction SO PROGRESSION OF CHRONIC RENAL DISEASES SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Proceedings Paper CT International Symposium on Progression of Chronic Renal Diseases CY MAY 20-23, 1995 CL SHIZUOKA, JAPAN ID MESSENGER-RNA; GROWTH-HORMONE; TRANSGENIC MICE; EXPRESSION; GLOMERULONEPHRITIS; GLOMERULI; TIMP-2 RP Esposito, C (reprint author), NIDDK,MDB,RENAL CELL BIOL SECT,NIH,BLDG 10,ROOM 3N110,10 CTR DR MSC 1268,BETHESDA,MD 20892, USA. NR 18 TC 9 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 BN 3-8055-6243-8 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 1996 VL 118 BP 12 EP 16 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA BF56G UT WOS:A1996BF56G00003 PM 8744034 ER PT J AU Reich, R Martin, GR AF Reich, R Martin, GR TI Identification of arachidonic acid pathways required for the invasive and metastatic activity of malignant tumor cells SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Article DE collagenase; arachidonic acid; lipoxygenase; cyclooxygenase; metastasis; invasion ID BASEMENT-MEMBRANE COLLAGEN; RHEUMATOID SYNOVIAL-CELLS; CANCER METASTASIS; MACROPHAGE COLLAGENASE; PLASMINOGEN-ACTIVATOR; BREAST-CANCER; PROTEINASES; PROSTAGLANDIN; INDOMETHACIN; DEGRADATION AB Metastasis is a complex process, almost a cascade, involving multiple steps and activities. However, an important factor is that malignant cells are able to penetrate through the multiple basement membrane barriers surrounding tissues, blood vessels, nerves and muscle that would otherwise block their dissemination. Penetration of malignant tumor cells through basement membrane is an active process requiring proteolysis. We report here that inhibitors of both the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism convert mouse melanoma and human fibrosarcoma cells to a non invasive stare by reducing the production of MMP-2, an enzyme required for the degradation of basement membranes. Specific metabolites of each pathway, i.e. PGF(2 alpha) and 5-HPETE, are able to transcend the block and restore collagenase production, invasiveness in vitro and metastatic activity in vivo. These studies indicate a key role for arachidonic acid metabolites in metastasis and suggest novel therapeutic approaches for inhibiting the spread of cancer. C1 NIA, NIH, BALTIMORE, MD 21224 USA. RP Reich, R (reprint author), HEBREW UNIV JERUSALEM, DEPT PHARMACOL, IL-91120 JERUSALEM, ISRAEL. NR 67 TC 76 Z9 78 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-6980 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD JAN PY 1996 VL 51 IS 1 BP 1 EP 17 DI 10.1016/0090-6980(95)00154-9 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UB393 UT WOS:A1996UB39300001 PM 8900440 ER PT J AU Ichikawa, T Nihei, N Kuramochi, J Kawana, Y Killary, AM RinkerSchaeffer, CW Barrett, JC Isaacs, JT Kugoh, H Oshimura, M Shimazaki, J AF Ichikawa, T Nihei, N Kuramochi, J Kawana, Y Killary, AM RinkerSchaeffer, CW Barrett, JC Isaacs, JT Kugoh, H Oshimura, M Shimazaki, J TI Metastasis suppressor genes for prostate cancer SO PROSTATE LA English DT Article; Proceedings Paper CT International Conference on Androgenic Hormones, Prostate Cancer, and Benign Prostatic Hyperplasia CY MAR 13-15, 1995 CL NEW ORLEANS, LA SP Wayne State Univ, Dept Med & Urol DE prostate cancer; metastasis; metastasis suppressor genes ID HUMAN CHROMOSOME-11; DELETION AB To examine the role of human chromosomes in the development of metastatic prostate cancer, we introduced a copy of human chromosomes into highly metastatic Dunning R-3327 rat prostatic cancer cells by microcell-mediated chromosome transfer. Each microcell hybrid clones containing human chromosomes 8, 10, 11, and 17, respectively, showed decreased ability to metastasize to the lung, without any loss of tumorigenicity. This finding demonstrates that these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions of human chromosomes was observed in human chromosome 10, 11, and 17 studies. In the human chromosome 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletions of human chromosome 8. Relationships between the size of human chromosomes introduced into microcell hybrid clones and the number of lung metastases produced by the clones were analyzed to determine which part of human chromosomes contained metastasis suppressor gene(s) for prostate cancer. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasis suppressor genes on human chromosomes 8, 10, and 11 were located on 8p23-q12, 10q, 11p13-11.2, respectively. Further analyses are proposed to confirm the potentially useful advantage of this assay system to identify metastasis suppressor gene(s) for prostate cancer. (C) 1996 Wiley-Liss, Inc. C1 TOTTORI UNIV,SCH MED,DEPT MOLEC & CELL GENET,YONAGO,TOTTORI 683,JAPAN. UNIV TEXAS,MD ANDERSON CANC CTR,DIV LAB MED,HEMATOPATHOL LAB,HOUSTON,TX 77030. UNIV CHICAGO,DEPT UROL,CHICAGO,IL 60637. JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. NIEHS,NIH,ENVIRONM CARCINOGENESIS PROGRAM,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RP Ichikawa, T (reprint author), CHIBA UNIV,SCH MED,DEPT UROL,CHUO KU,1-8-1 INOHANA,CHIBA 260,JAPAN. NR 10 TC 6 Z9 7 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0270-4137 J9 PROSTATE JI Prostate PY 1996 SU 6 BP 31 EP 35 PG 5 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA UB911 UT WOS:A1996UB91100007 ER PT J AU DiFrancesco, V Garnier, J Munson, PJ AF DiFrancesco, V Garnier, J Munson, PJ TI Improving protein secondary structure prediction with aligned homologous sequences SO PROTEIN SCIENCE LA English DT Article DE prediction; protein secondary structure; sequence alignments AB Most recent protein secondary structure prediction methods use sequence alignments to improve the prediction quality. We investigate the relationship between the location of secondary structural elements, gaps, and variable residue positions in multiple sequence alignments. We further investigate how these relationships compare with those found in structurally aligned protein families. We show how such associations may be used to improve the quality of prediction of the secondary structure elements, using the Quadratic-Logistic method with profiles. Furthermore, we analyze the extent to which the number of homologous sequences influences the quality of prediction. The analysis of variable residue positions shows that surprisingly, helical regions exhibit greater variability than do coil regions, which are generally thought to be the most common secondary structure elements in loops. However, the correlation between variability and the presence of helices does not significantly improve prediction quality. Gaps are a distinct signal for coil regions. Increasing the coil propensity for those residues occurring in gap regions enhances the overall prediction quality. Prediction accuracy increases initially with the number of homologues, but changes negligibly as the number of homologues exceeds about 14. The alignment quality affects the prediction more than other factors, hence a careful selection and alignment of even a small number of homologues can lead to significant improvements in prediction accuracy. C1 NIH, DIV COMP RES & TECHNOL,STRUCT BIOL LAB, ANALYT BIOSTAT SECT,12 S MSC 5626, BETHESDA, MD 20892 USA. NIH, FOGARTY INT CTR, BETHESDA, MD 20892 USA. RP DiFrancesco, V (reprint author), NIH, DIV COMP RES & TECHNOL,STRUCT BIOL LAB, ANALYT BIOSTAT SECT,12 S MSC 5626, BLDG 12A-ROOM 2041, BETHESDA, MD 20892 USA. NR 33 TC 39 Z9 39 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 1996 VL 5 IS 1 BP 106 EP 113 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TN944 UT WOS:A1996TN94400013 PM 8771202 ER PT J AU Gronenborn, AM Clore, GM AF Gronenborn, AM Clore, GM TI Rapid screening for structural integrity of expressed proteins by heteronuclear NMR spectroscopy SO PROTEIN SCIENCE LA English DT Article DE H-1-N-15 HSQC spectroscopy; interleukin-1 beta; protein GB1 domain; structural screening AB A simple and rapid method based on N-15 labeling and H-1-N-15 heteronuclear single quantum coherence spectroscopy is presented to directly assess the structural integrity of overexpressed proteins in crude Escherichia coli extracts without the need for any purification. The method is demonstrated using two different expression systems and two different proteins, the B1 immunoglobulin-binding domain of streptococcal protein G (56 residues) and human interleukin-1 beta (153 residues). It is shown that high quality H-1-N-15 correlation spectra, recorded in as little as 15 min and displaying only cross-peaks arising from the overexpressed protein of interest, can be obtained from crude E. coli extracts. RP Gronenborn, AM (reprint author), NIDDKD,NIH,PHYS CHEM LAB,BLDG 5,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 8 TC 42 Z9 42 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 1996 VL 5 IS 1 BP 174 EP 177 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TN944 UT WOS:A1996TN94400023 PM 8771212 ER PT J AU Koonin, EV Rudd, KE AF Koonin, EV Rudd, KE TI Two domains of superfamily I helicases may exist as separate proteins SO PROTEIN SCIENCE LA English DT Article DE ATPases; conserved amino acid motifs; domain evolution; helicases ID PUTATIVE HELICASES; SEQUENCE; ALIGNMENT; MOTIF; GENE; DNA; REPLICATION AB DNA and RNA helicases of superfamily I are characterized by seven conserved motifs. The five N-terminal motifs are separated from the two C-terminal ones by a spacer that is highly variable in both sequence and length, suggesting the existence of two distinct domains. Using computer methods for protein sequence analysis, we show that PhoH, an ATP-binding protein that is conserved in Escherichia coli and Mycobacterium leprae, is homologous to the putative N-terminal domain of the helicases, whereas the putative E. coli protein YjhR is homologous to the C-terminal domain. These findings suggest that the N- and C-terminal domains of superfamily I helicases have distinct activities, with only the N-terminal domain having the ATPase activity. It is speculated that PhoH and YjhR have evolved from helicases through deletion of the portions of the helicase genes coding for the C- and N-terminal domain, respectively. RP Koonin, EV (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,BETHESDA,MD 20894, USA. NR 31 TC 24 Z9 24 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 1996 VL 5 IS 1 BP 178 EP 180 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TN944 UT WOS:A1996TN94400024 PM 8771213 ER PT J AU McCrae, RR AF McCrae, RR TI Integrating the levels of personality SO PSYCHOLOGICAL INQUIRY LA English DT Article RP McCrae, RR (reprint author), NIA, STRESS & COPING SECT, CTR GERONTOL RES, NIH, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 21 TC 14 Z9 14 U1 0 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1047-840X J9 PSYCHOL INQ JI Psychol. Inq. PY 1996 VL 7 IS 4 BP 353 EP 356 DI 10.1207/s15327965pli0704_10 PG 4 WC Psychology, Multidisciplinary SC Psychology GA VH613 UT WOS:A1996VH61300010 ER PT J AU Preston, KL Sullivan, JT Strain, EC Bigelow, GE AF Preston, KL Sullivan, JT Strain, EC Bigelow, GE TI Enhancement of cocaine's abuse liability in methadone maintenance patients SO PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 20-25, 1992 CL KEYSTONE, CO SP Coll Problems Drug Dependence DE cocaine; methadone; opiates; humans; cocaine abuse; drug abuse; abuse liability; drug interactions ID BETA-ENDORPHIN LEVELS; RHESUS-MONKEYS; MORPHINE; BUPRENORPHINE; CLIENTS; AMPHETAMINE; COMBINATION; NALTREXONE; DEPENDENCE; ADDICTION AB The present study was conducted to determine whether methadone maintenance alters the pharmacodynamic effects of single doses of cocaine. Twenty-two current users of IV cocaine who were not seeking treatment for their illicit cocaine use participated while living on a research unit. Eleven were maintained on methadone 50 mg PO daily as treatment for their opioid abuse; 11 were opioid abusers who were not physically dependent on opioids and who provided opioid-free urines throughout the study. Each subject received acute cocaine challenge doses of 0, 12.5, 25, and 50 mg intravenously in random order under double-blind conditions in separate test sessions. Physiologic and subject-rated responses were measured before injection and for 2 h after. In the methadone maintenance group, cocaine challenge sessions occur-red 15.5 h after the daily methadone dose. There were significant differences between the methadone-dependent and nondependent groups: 1) baseline differences related to chronic methadone administration and not associated with cocaine administration (lower respiration rates and pupil diameter; higher skin temperature) and 2) differences in response tc, cocaine administration; cocaine-induced increases in subject ratings of Drug Effect, Rush, Good Effects, Liking, and Desire for Cocaine and in heart rate were greater in the methadone maintenance patients compared to the non-dependent group, These results indicate that the positive subjective effects and some physiological effects of cocaine are enhanced in methadone-maintained individuals, suggesting a pharmacological basis for the high rates of cocaine abuse among methadone maintenance patients. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD. RP Preston, KL (reprint author), NIDA,DIV INTRAMURAL RES,CLIN TRIALS SECT,POB 5180,BALTIMORE,MD 21224, USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NIDA NIH HHS [R01DA-05196, K05 DA-00050, R18DA-96120] NR 46 TC 44 Z9 44 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 1996 VL 123 IS 1 BP 15 EP 25 DI 10.1007/BF02246276 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TR772 UT WOS:A1996TR77200003 PM 8741950 ER PT J AU Wojnicki, FHE Glowa, JR AF Wojnicki, FHE Glowa, JR TI Effects of drug history on the acquisition of responding maintained by GBR 12909 in rhesus monkeys SO PSYCHOPHARMACOLOGY LA English DT Article DE self-administration; GBR 12909; behavioral history; reinforcement; cocaine; DA reuptake inhibitors; rhesus monkeys ID DOPAMINE UPTAKE INHIBITOR; PHARMACOLOGICAL CHARACTERIZATION; FIXED-RATIO; NONHUMAN-PRIMATES; SQUIRREL-MONKEYS; SENSITIZES RATS; COCAINE; GBR-12909; BEHAVIOR; SCHEDULE AB The reinforcing effects of cocaine have been associated with its actions at the dopamine reuptake site. Previous studies have shown that selective dopamine reuptake inhibitors can attenuate cocaine self-administration in animals, suggesting that they may serve as pharmacotherapeutic agents. In order to assess the potential reinforcing effects of one of these agents, the acquisition and maintenance of GBR 12909 self-administration were studied in different groups of rhesus monkeys (Macaca mulatta) that were either experimentally naive or experienced with respect to the self-administration of cocaine or GBR 12909. Lever-pressing was maintained under a multiple FR30 schedule with alternating components of either food or drug presentation, Experimentally naive monkeys failed to self-administer low doses of GBR 12909 (3-30 mu g/kg per injection). However, after a history of cocaine self-administration, GBR 12909 (56 mu g/kg per injection and then 30 mu g/kg per injection) maintained numbers of drug deliveries similar to those maintained by cocaine. When another group of experimentally-naive monkeys was initially exposed to GBR 12909 self-ad ministration, 56 mu g/kg per injection failed to maintain responding. However, subsequent exposure to 100 mu g/kg per injection established GBR 12909 self-administration, and high levels of responding were sustained later when the unit dose was decreased to 30 mu g/kg per injection. In monkeys with prior experience with cocaine self-administration (similar to 75 sessions) unit doses of either 30 mu g/kg per injection or 56 mu g/kg per injection GBR 12909 maintained responding. In another group of monkeys with a more extensive history of cocaine self-administration (similar to 320 sessions), unit doses of either 10 mu g/kg per injection or 30 mu g/kg per injection GBR 12909 maintained responding. These results show that drug-maintained responding can be established with higher unit doses of GBR 12909. After exposure to these higher, more effective doses of GBR 12909, or effective doses of cocaine, lower doses of GBR 12909 are more likely to support drug-maintained responding. C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 37 TC 27 Z9 27 U1 4 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 1996 VL 123 IS 1 BP 34 EP 41 DI 10.1007/BF02246278 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TR772 UT WOS:A1996TR77200005 PM 8741952 ER PT J AU Rudorfer, MV AF Rudorfer, MV TI Untitled SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Editorial Material RP Rudorfer, MV (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 1 BP 1 EP 2 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA UQ557 UT WOS:A1996UQ55700001 ER PT J AU Cowdry, R AF Cowdry, R TI Ethical dilemmas in clinical research - Introductory remarks SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Editorial Material RP Cowdry, R (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 1 BP 5 EP 6 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA UQ557 UT WOS:A1996UQ55700002 ER PT J AU Shore, D AF Shore, D TI Ethical principles and informed consent: An NIMH perspective SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article; Proceedings Paper CT 35th Annual New-Clinical-Drug-Evaluation-Unit Meeting, of the National-Institute-of-Mental-Health CY MAY 30-JUN 03, 1995 CL ORLANDO, FL SP New Clin Drug Evaluat Unit, NIMH RP Shore, D (reprint author), NIMH,DIV CLIN & TREATMENT RES,ROOM 18C-26,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 4 TC 12 Z9 12 U1 1 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 1 BP 7 EP 10 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA UQ557 UT WOS:A1996UQ55700003 PM 8927678 ER PT J AU Rudorfer, MV AF Rudorfer, MV TI Editor's note SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Editorial Material RP Rudorfer, MV (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 291 EP 292 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300001 ER PT J AU Vitiello, B Stover, ES AF Vitiello, B Stover, ES TI Psychopharmacology in HIV-positive patients: Research perspectives SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE HIV-positive; psychopharmacology ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; IMMUNE STATUS; DEPRESSED-PATIENTS; INFECTION; ILLNESS; MOOD; DISORDERS; TRIAL; MEN AB Psychotropic medications play an important role in the treatment of human immunodeficiency virus (HIV)-positive subjects suffering from neuropsychiatric disorders or other acquired immunodeficiency syndrome (AIDS)-related symptomatology, The quality of life of these patients can be significantly improved by the appropriate use of these agents. Various aspects of psychopharmacology that are relevant to HIV-positive patients include assessment of efficacy, tolerability, drug-drug interactions, end effects on cognition. These topics need further investigation and require focused research efforts. This report highlights current research needs and presents specific recommendations that emerged at a recent meeting on psychopharmacology for HIV-positive patients organized by the National Institute of Mental Health (NIMH). RP Vitiello, B (reprint author), NIMH,OFF AIDS,ROOM 10-75,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 20 TC 9 Z9 9 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 293 EP 297 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300002 PM 8961771 ER PT J AU Rush, AJ Gullion, CM Prien, RF AF Rush, AJ Gullion, CM Prien, RF TI A curbstone consult to applicants for National Institute of Mental Health grant support SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE grant-writing strategies; funding applications; NIMH grant support AB With research budgets tight and review procedures being streamlined, applicants for research funds, especially newer investigators, may become disheartened. This article provides advice that we believe improves the quality of a written application, We detail ideas for how to develop applications that are complete and most easily understood by reviewers, Important elements include: a focus on selected, specific critical hypotheses that have both clinical and theoretical significance, documenting feasibility, establishing reliable effect sizes, providing specific analyses for each hypothesis, and writing a clear, well-articulated, ''reader-friendly'' application, In addition, we emphasize the value of collegial review and critique of the application prior to submission, We believe this ''curbstone'' advice will facilitate a well-reasoned review and if funds are available, eventual funding. C1 UNIV TEXAS,SW MED CTR,DEPT PSYCHIAT,DALLAS,TX. NIMH,CLIN TREATMENT RES BRANCH,ROCKVILLE,MD 20857. OI Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [MH-41115] NR 3 TC 2 Z9 2 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 311 EP 320 PG 10 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300004 PM 8961773 ER PT J AU Ernst, N Liebenauer, LL Jons, PH Tebeka, D Cohen, RM Zametkin, AJ AF Ernst, N Liebenauer, LL Jons, PH Tebeka, D Cohen, RM Zametkin, AJ TI Selegiline in adults with attention deficit hyperactivity disorder: Clinical efficacy and safety SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE selegiline; MAOI-B; ADHD; adults; placebo ID MINIMAL BRAIN-DYSFUNCTION; MONOAMINE-OXIDASE INHIBITORS; RESIDUAL TYPE; L-DEPRENYL; AMPHETAMINE; CHILDREN AB Clinical effects of high-dose and low-dose selegiline treatment were examined in 24 adults with attention deficit hyperactivity disorder (ADHD). The study used a double-blind randomized three-arm parallel-groups design with a 2-week placebo baseline followed by 6 weeks of treatment (placebo, 20 mg/day, or 60 mg/day selegiline) and then by 2 weeks of placebo posttreatment. A two-way repeated measures analysis of variance (ANOVA) showed no Drug x Time interaction and no main effect of Drug on severity of ADHD symptoms as self-rated by the subjects on the Conners Abbreviated Teacher Rating Scale (Conners ATRS), There was a significant effect of Time, indicating decreased ADHD symptom severity scores in all three groups, Selegiline treatment was not more effective than placebo, Side effects were more severe in the high-dose selegiline group than in either of the other groups, These preliminary results must be interpreted with caution because of methodological limitations in terms of sample size, patient population selection, and measurement tools. C1 NIMH, BETHESDA, MD 20892 USA. NR 28 TC 16 Z9 16 U1 1 U2 2 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 327 EP 334 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300006 ER PT J AU Cott, J AF Cott, J TI The NIMH pharmacologic treatment research program SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 NIMH,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 426 EP 426 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300046 ER PT J AU Kumra, S Jacobsen, L Frazier, J Rapoport, JL AF Kumra, S Jacobsen, L Frazier, J Rapoport, JL TI Clozapine for treatment-resistant childhood-onset schizophrenia: A double-blind comparison with haloperidol SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 469 EP 469 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300089 ER PT J AU Little, JT Ketter, TA Kimbrell, TA Stein, R Danielson, A Benson, B Willis, MW Post, RM AF Little, JT Ketter, TA Kimbrell, TA Stein, R Danielson, A Benson, B Willis, MW Post, RM TI Venlafaxine and bupropion responders in contrast to nonresponders have baseline prefrontal and paralimbic hypometabolism SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,STANFORD,CA 94305. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 478 EP 478 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300098 ER PT J AU Rudorfer, MV AF Rudorfer, MV TI Editor's note SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Editorial Material RP Rudorfer, MV (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 4 BP 541 EP 543 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA WA890 UT WOS:A1996WA89000001 ER PT J AU Little, JT Ketter, TA Kimbrell, TA Danielson, A Benson, B Willis, MW Post, RM AF Little, JT Ketter, TA Kimbrell, TA Danielson, A Benson, B Willis, MW Post, RM TI Venlafaxine or bupropion responders but not nonresponders show baseline prefrontal and paralimbic hypometabolism compared with controls SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY MAY 28-31, 1996 CL BOCA RATON, FL SP NIMH, New Clin Drug Evaluat Unit DE depression; venlafaxine; bupropion; positron emission tomography; cerebral glucose metabolism ID UNIPOLAR DEPRESSION; AFFECTIVE-DISORDERS; SLEEP-DEPRIVATION; METABOLISM; SYSTEM; MOOD AB In this study, 11 unipolar depressed outpatients received baseline (medication-free) fluorine-18 deoxyglucose positron emission tomography scans prior to randomization to double-blind venlafaxine or bupropion monotherapy, with the option of a subsequent medication crossover. Based on Clinical Global Impressions ratings, 6 of 11 responded to at least one medication. Regional cerebral glucose metabolic rate (rCMRglu) for these 6 responders was compared with 18 age- and gender-matched healthy controls; the 5 nonresponders were compared with 15 matched healthy controls. Compared with healthy controls, responders showed decreased (normalized > absolute) left middle frontal gyral, bilateral medial prefrontal, and bilateral temporal rCMRglu. In contrast, nonrespenders showed decreased (normalized > absolute) cerebellar rCMRglu. These preliminary data suggest that among never-hospitalized unipolar depressed outpatients, those showing baseline prefrontal and paralimbic hypometabolism may be more likely to show a positive response to standard antidepressant treatments such as venlafaxine or bupropion. C1 STANFORD UNIV,SCH MED,STANFORD,CA 94305. RP Little, JT (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N212,BETHESDA,MD 20892, USA. NR 23 TC 42 Z9 42 U1 2 U2 4 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 4 BP 629 EP 635 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA WA890 UT WOS:A1996WA89000013 PM 8993084 ER PT J AU Lenfant, C AF Lenfant, C TI Papers from the National Heart, Lung, and Blood Institute Workshop on Hypertension in Selected US Minority Populations - Foreword SO PUBLIC HEALTH REPORTS LA English DT Editorial Material RP Lenfant, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PY 1996 VL 111 SU 2 BP 1 EP 1 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VW307 UT WOS:A1996VW30700001 ER PT J AU Crespo, CJ Loria, CM Burt, VL AF Crespo, CJ Loria, CM Burt, VL TI Hypertension and other cardiovascular disease risk factors among Mexican Americans, Cuban Americans, and Puerto Ricans from the Hispanic Health and Nutrition Examination Survey SO PUBLIC HEALTH REPORTS LA English DT Article ID PREVALENCE AB DESPITE THEIR HIGHER PREVALENCE of obesity and diabetes, Hispanics have lower or equal rates of hypertension than non-Hispanic whites (1-4). Healthy People 2000 objectives call for increasing the proportion of hypertensive men whose blood pressure is under control to at least 40%. In addition, the objectives recommend reducing the prevalence of overweight to 41% among hypertensive women, and to 35% among hypertensive men (5). The Hispanic Health and Nutrition Examination Survey (HHANES) collected data on Mexican Americans (MA), Cuban Americans (CA), and Puerto Ricans (PR) living in the continental United States. A trained physician measured systolic (SEP) and diastolic (DBP) blood pressure twice in one visit. Our findings provide data to assess baseline estimates for several Healthy People 2000 objectives among Hispanics. Based on criteria from The Fifth Report of the Joint Notional Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V), we found Hispanic women to have higher rates of awareness, treatment, and control of hypertension than men. Only 8% of MA and PR men and 9% of CA men who were hypertensive had their high blood pressure under control. The prevalence of overweight among hypertensive men ranged from 39% to 60%; and among hypertensive women, from 44% to 74%. Hispanic women with six or fewer years of education had higher prevalence of hypertension and other cardiovascular disease (CVD) risk factors. Future research should investigate the socioeconomic factors associated with the presence of these risk factors. C1 CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,SURVEY PLANNING & DEV BRANCH,ATLANTA,GA 30333. RP Crespo, CJ (reprint author), NHLBI,OFF PREVENT EDUC & CONTROL,BLDG 31,ROOM 4A18,BETHESDA,MD 20892, USA. NR 9 TC 43 Z9 45 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PY 1996 VL 111 SU 2 BP 7 EP 10 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VW307 UT WOS:A1996VW30700003 PM 8898761 ER PT J AU Loria, CM Crespo, CJ Burt, V AF Loria, CM Crespo, CJ Burt, V TI Blood pressure among Mexican-American, Cuban-American, and mainland Puerto Rican children SO PUBLIC HEALTH REPORTS LA English DT Article ID BOGALUSA HEART; WHITE AB LITTLE IS KNOWN ABOUT BLOOD PRESSURE LEVELS and the extent of high blood pressure in Hispanic children and adolescents, especially in groups other than Mexican Americans. The authors of this study investigated the levels of systolic blood pressure (SEP) and diastolic brood pressure (DBP) and the extent of high blood pressure among Mexican-American, Cuban-American, and mainland Puerto Rican children and adolescents who participated in the Hispanic Health and Nutrition Examination Survey (HHANES). Very few children and adolescents in these three Hispanic groups had high normal or high blood pressure. Puerto Rican children had significantly lower DBP than Mexican-American (2.4 mmHg) and Cuban-American (1.8 mmHg) children. Their SEP was also lower (1.7 mmHg) than that of Cuban-American children. These findings should be interpreted cautiously, however, since a significant observer effect was also found in this study. Correlates of blood pressure in children in all three Hispanic groups were consistent with those found in studies of other ethnic groups. Age, body mass index, and pulse rate were significant predictors of both SEP and DBP (P less than 0.05). Gender was an important predictor of SEP but not DBP Socioeconomic and cultural factors were not significant predictors of blood pressure in these Hispanic groups. C1 NHLBI,BETHESDA,MD 20892. RP Loria, CM (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,HYATTSVILLE,MD 20782, USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PY 1996 VL 111 SU 2 BP 22 EP 24 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VW307 UT WOS:A1996VW30700007 PM 8898765 ER PT J AU deCourten, MP Pettitt, DJ Knowler, WC AF deCourten, MP Pettitt, DJ Knowler, WC TI Hypertension in Pima Indians: Prevalence and predictors SO PUBLIC HEALTH REPORTS LA English DT Article ID DIABETES-MELLITUS; INSULIN AB THE PIMA INDIANS HAVE THE WORLD'S HIGHEST reported incidence of diabetes. Since 1965, this population has participated in a longitudinal epidemiological study of diabetes and its complications. The examinations have included a medical history for diabetes and other major health problems. The focus of this study is the correlation between the prevalence of hypertension and glucose tolerance in this population. Of the 4315 adults ages 18 and older, 50% had normal glucose tolerance; 12%, impaired glucose tolerance (IGT); 8%, newly diagnosed diabetes; and 31%, previously diagnosed diabetes of a mean duration of 11 years. Age-sex adjusted prevalence of hypertension was 24% in those with normal glucose tolerance, 34% in those with IGT, and 40% in those with diabetes. Hypertension was more common in men than in women and was positively related to obesity. Of the 2667 children ages 6 to 17 years, 4% had IGT, and 1% had diabetes. Blood pressure was higher in boys than girls and was associated with older age and worse glucose tolerance. Longitudinal analyses of data from 188 children ages 5 to 9 years who had their follow-up exam at ages 18 to 24 revealed no relationship between insulin concentration and blood pressure in either sex. In this group mean blood pressure at followup was positively correlated with relative weight, mean blood pressure, and 2-hour post-load plasma glucose concentration at baseline. In a multiple regression model, relative weight was the strongest predictor of mean brood pressure at the follow-up exam. C1 NIDDK,DAES,PHOENIX EPIDEMIOL & CLIN RES BRANCH,NIH,PHOENIX,AZ 85014. RI de Courten, Maximilian/B-3300-2012 OI de Courten, Maximilian/0000-0001-9997-9359 NR 8 TC 9 Z9 9 U1 0 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PY 1996 VL 111 SU 2 BP 40 EP 43 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VW307 UT WOS:A1996VW30700013 PM 8898771 ER PT J AU Curb, JD Aluli, NE Huang, BJ Sharp, DS Rodriguez, BL Burchfiel, CM Chiu, D AF Curb, JD Aluli, NE Huang, BJ Sharp, DS Rodriguez, BL Burchfiel, CM Chiu, D TI Hypertension in elderly Japanese Americans and adult native Hawaiians SO PUBLIC HEALTH REPORTS LA English DT Article ID CORONARY HEART-DISEASE; STROKE; RISK; MEN AB POPULATION-BASED DATA ON HYPERTENSION IN HAWAII are limited. Two groups for which data from the 1980s exist are Japanese-American men ages 60 to 81 in the Honolulu Heart Program (HHP) and native Hawaiians ages 20 to 59 in the Molokai Heart Study (MHS). In the elderly HHP men, the mean systolic blood pressure (SEP) was higher and the mean diastolic blood pressure (DBP) was lower in the older age groups. In the MHS, both the mean SEP and the mean DBP were higher with increasing age in both sexes. Among Japanese-American men, 53% of those ages 60 to 64 were hypertensive (SEP greater than or equal to 140 mmHg or DBP greater than or equal to 90 mmHg, or taking antihypertensive medications), as were 59% of those ages 65 to 74, and 67% of those ages 75 to 81. Among native Hawaiians, 6% of men and 8% of women ages 20 to 24 were hypertensive, as were 37% of men and 41% of women ages 45 to 54. At ages 55 to 59 the prevalence for men was 31%; and for women, 33%. These data indicate that hypertension is relatively common in both ethnic groups; however, native Hawaiians appear to be at greater risk of cardiovascular disease overall. C1 NHLBI,HONOLULU HEART PROGRAM,HONOLULU,HI. RP Curb, JD (reprint author), UNIV HAWAII,JOHN A BURNS SCH MED,KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-05102] NR 10 TC 2 Z9 2 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PY 1996 VL 111 SU 2 BP 53 EP 55 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VW307 UT WOS:A1996VW30700018 PM 8898776 ER PT J AU Keller, JB Higgins, M Fujimoto, W Hanis, C Havas, S Hazuda, H Howard, BV Ramirez, AG Rhoades, E Sherwin, R Yu, E AF Keller, JB Higgins, M Fujimoto, W Hanis, C Havas, S Hazuda, H Howard, BV Ramirez, AG Rhoades, E Sherwin, R Yu, E TI NHLBI workshop panel discussion: A scientific perspective SO PUBLIC HEALTH REPORTS LA English DT Editorial Material AB THE WORKSHOP ON THE EPIDEMIOLOGY OF HYPERTENSION in Hispanic Americans, Native Americans, and Asian/Pacific Islander Americans concluded with a panel discussion of the findings from a scientific perspective. Panel members presented their ideas for research direction on measuring and identifying more accurately the frequency, distribution, and determinants of hypertension in minority populations, evaluating mechanisms leading to hypertension, and identifying the implications for public health and medical practice. Several members stressed the need for additional data collections, using standardized methods. They stated that future studies, including longitudinal ones, should target specific ethnic populations and subpopulations and address the role of acculturation, assimilation, modernization, and socioeconomic status. They also recommended comparative and collaborative studies among groups. They emphasized the importance of obesity and diabetes or impaired glucose tolerance as determinants of hypertension in all three populations, and suggested that there may be differences in the etiology and pathophysiology of hypertension among the groups, with visceral adiposity or insulin resistance syndrome being more important in Asian populations. The potential for identification of genes involved in blood pressure variation and hypertension risk may help understand the interaction of genes with the environment. Minority groups in the United States share the problem of high prevalence of high blood pressure and low rates of control. For this reason, the panel urged a new era of community-based, culturally sensitive prevention and control projects. RP Keller, JB (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,6701 ROCKLEDGE DR,MSC 7934,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PY 1996 VL 111 SU 2 BP 71 EP 73 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VW307 UT WOS:A1996VW30700024 PM 8898782 ER PT J AU Alvarado, M Smolenski, MC Balcazar, H OrtegaHarrison, Z Della, D Tam, T Poolaw, L Lewis, R Jacobs, J AF Alvarado, M Smolenski, MC Balcazar, H OrtegaHarrison, Z Della, D Tam, T Poolaw, L Lewis, R Jacobs, J TI Community panel discussions: From research to community action SO PUBLIC HEALTH REPORTS LA English DT Editorial Material AB HYPERTENSION AND CARDIOVASCULAR DISEASE are increasing among minorities. Participants at the workshop on the Epidemiology of Hypertension in Hispanic Americans, Native Americans, and Asian/Pacific islander Americans voiced a need to intensify a systemic approach for community-based strategies to guide prevention, treatment, and control. To answer this need, a panel addressed recommended community-based strategies from inclusion of community members in the research process to implementation and application of findings for community action. Recommended strategies include encouraging close cooperation and data sharing between investigators and community groups; including differences in culture, heritage, and local influences in hypertension research; training and working with minority researchers and health care professionals; and intensifying comprehensive and culturally appropriate education programs that focus on prevention, treatment, and control of hypertension. This article contains a summary of key areas of emphasis, as well as implementation strategies to decrease hypertension and other cardiovascular diseases in specific ethnic groups. C1 ARIZONA STATE UNIV,TEMPE,AZ 85287. FAIRFIELD UNIV,FAIRFIELD,CT 06430. UNIV OKLAHOMA,HLTH SERV,NORMAN,OK 73019. UNIV OKLAHOMA,INDIAN HLTH CLIN,NORMAN,OK 73019. NIH,OFF ALTENAT MED,BETHESDA,MD 20892. RP Alvarado, M (reprint author), NHLBI,OFF PREVENT EDUC & CONTROL,NIH,BLDG 31,ROOM 4A18,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PY 1996 VL 111 SU 2 BP 74 EP 76 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VW307 UT WOS:A1996VW30700025 PM 8898783 ER PT J AU NowjackRaymer, RE Gift, HC AF NowjackRaymer, RE Gift, HC TI Use of mouthguards and headgear in organized sports by school-aged children SO PUBLIC HEALTH REPORTS LA English DT Article ID FOOTBALL AB SPORTS-RELATED OROFACIAL trauma is a serious problem that can be prevented by wearing protective mouthguards and headgear. While this equipment is available, few studies have been done of wearing practices. This study assesses the wearing practices using data from the Child Health Supplement of the 1991 National Health interview Survey. Results indicate that football was the only sport in which the majority of children used mouthguards and headgear. While statistically significant differences (p less than or equal to .05) were found in use of the equipment in ail sports by grade level, gender, parent's education, ethnicity, and by region of the country, these differences were not consistent across sports. Healthy People 2000 calls for extending requirements for use of orofacial protective devices to ail organizations sponsoring sports that pose risk to injury. Given the complex nature of the findings, multifaceted initiatives that include the promulgation of rules must be developed and tested to determine what approaches are effective in ensuring consistent use. RP NowjackRaymer, RE (reprint author), NIDR,NIH,DIS PREVENT & HLTH PROMOT BRANCH,DIV EPIDEMIOL & ORAL DIS PREVENT,NATCHER BLDG,BETHESDA,MD 20892, USA. NR 27 TC 29 Z9 30 U1 2 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 1996 VL 111 IS 1 BP 82 EP 86 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TW900 UT WOS:A1996TW90000029 PM 8610199 ER PT J AU Hall, P Mattsson, A Boice, JD AF Hall, P Mattsson, A Boice, JD TI Thyroid cancer after diagnostic administration of iodine-131 SO RADIATION RESEARCH LA English DT Article ID RETROSPECTIVE COHORT; RADIATION; CHERNOBYL; I-131; HYPERTHYROIDISM; IRRADIATION; CHILDHOOD; LEUKEMIA; NODULES; DISEASE AB To provide quantitative data on the risk of thyroid cancer after exposure to I-131, 34,104 patients administered I-131 for diagnostic purposes were followed for up to 40 years, The mean thyroid dose was estimated as 1.1 Gy, and 67 thyroid cancers occurred in contrast to 49.7 expected (standardized incidence ratio = 1.35; 95% confidence interval 1.05-1.71). Excess cancers were apparent only among patients referred because of a suspected thyroid tumor, and no increased risk was seen among those referred for other reasons. Further, risk was not related to radiation dose to the thyroid gland, time since exposure or age at exposure. The slight excess of thyroid cancer thus appeared to be due to the underlying thyroid condition and not radiation exposure. Among those under age 20 years when I-131 was administered, a small excess risk (3 cancers compared to 1.8 expected) was about 2-10 times lower than that predicted from data for the A-bomb survivors. These data suggest that protraction of dose may result in a lower risk than an acute X-ray exposure of the same total dose. (C) 1996 by Radiation Research Safety C1 NCI, DIV CANC ETIOL, EPIDEMIOL & BIOSTAT PROGRAM, BETHESDA, MD 20892 USA. RP KAROLINSKA HOSP, RADIUMHEMMET, DEPT GEN ONCOL, S-17176 STOCKHOLM, SWEDEN. FU NCI NIH HHS [N01-CP-51034] NR 34 TC 58 Z9 64 U1 0 U2 1 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD JAN PY 1996 VL 145 IS 1 BP 86 EP 92 DI 10.2307/3579200 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA TM491 UT WOS:A1996TM49100013 PM 8532842 ER PT J AU Gibril, F Doppman, JL Chang, R Weber, HC Termanini, B Jensen, RT AF Gibril, F Doppman, JL Chang, R Weber, HC Termanini, B Jensen, RT TI Metastatic gastrinomas: Localization with selective arterial injection of secretin SO RADIOLOGY LA English DT Article DE endocrine glands, neoplasms; hormones; liver neoplasms, metastases; pancreas, neoplasms ID ZOLLINGER-ELLISON SYNDROME; PANCREATIC VEIN CATHETERIZATION; ISLET-CELL TUMORS; ENDOCRINE TUMORS; INTRAARTERIAL INJECTION; AGGRESSIVE RESECTION; CURATIVE RESECTION; MANAGEMENT; CALCIUM; ASSAY AB PURPOSE: To evaluate localization of hepatic metastases with the intraarterial secretin injection test in Zollinger-Ellison syndrome (ZES). MATERIALS AND METHODS: Results in 74 patients with ZES (aged 15-70 years) were retrospectively studied. All patients had undergone computed tomography (CT), magnetic resonance (MR) imaging, ultrasound, abdominal angiography, and an intraarterial secretin test, in which venous blood is sampled periodically after injection of secretin. RESULTS: Twenty-two patients had liver metastases. An increase in venous gastrin concentration of at least 25% at 20 seconds or 50% at 30 seconds after injection indicated a positive result. Results were positive in 41% of patients with and 2% without liver metastases (P < .0001). Sensitivity of the intraarterial secretin test was 41%; of CT and ultrasound, 64%; and of MR imaging and angiography, 77%. Intraarterial secretin test results assisted in clinical management in 22% of patients. CONCLUSION: With the criteria developed, the intraarterial secretin test had high specificity but low sensitivity. It should be used when imaging results are unclear. C1 NATL INST HLTH,NIDDK,DIGEST DIS BRANCH,BETHESDA,MD 20892. NATL INST HLTH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NR 46 TC 37 Z9 37 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 1996 VL 198 IS 1 BP 77 EP 84 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TM680 UT WOS:A1996TM68000020 PM 8539410 ER PT J AU Avila, NA Premkumar, A Shawker, TH Jones, JV Laue, L Cutler, GB AF Avila, NA Premkumar, A Shawker, TH Jones, JV Laue, L Cutler, GB TI Testicular adrenal rest tissue in congenital adrenal hyperplasia: Findings at gray-scale and color Doppler US SO RADIOLOGY LA English DT Article DE adrenal gland, abnormalities; testis, abnormalities; testis, US ID ADRENOGENITAL SYNDROME; MASSES AB PURPOSE: To study the ultrasound (US) features of scrotal adrenal rest tissue in congenital adrenal hyperplasia (CAH). MATERIALS AND METHODS: Gray-scale and color Doppler US examinations were performed of scrotal masses in eight patients. The masses were evaluated for size, location, echogenicity, sound attenuation, and vascularity. RESULTS: Seventeen intratesticular masses and one extratesticular mass were examined. All were hypoechoic except for one intratesticular mass that contained hyperechoic areas. Six masses demonstrated sound attenuation. The mediastinum testis was found in the center of 11 of the 17 intratesticular masses. At color Doppler US, six masses were hypervascular, seven were isovascular, and five were hypovascular relative to the normal testicle. All intratesticular masses contained vascular structures that entered them from the normal testis without change in course or caliber. Eleven masses showed a spokelike pattern of converging vessels. CONCLUSION: The US features of scrotal adrenal rests assist diagnosis of CAH. C1 NATL INST HLTH,NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. RP Avila, NA (reprint author), NATL INST HLTH,HENRY M JACKSON FDN,DEPT DIAGNOST RADIOL,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,BETHESDA,MD 20892, USA. NR 16 TC 51 Z9 55 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 1996 VL 198 IS 1 BP 99 EP 104 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TM680 UT WOS:A1996TM68000024 PM 8539414 ER PT J AU Deterding, LJ Khaledi, M Tomer, KB AF Deterding, LJ Khaledi, M Tomer, KB TI Coaxial continuous-flow fast-atom bombardment vs electrospray ionization: A sensitivity comparison on a magnetic sector instrument SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ACCURATE MASS MEASUREMENT; SPECTROMETRY; PROTEINS; PEPTIDES; GLYCOPROTEINS; BIOMOLECULES; SPECTRA; IONS AB The performance of an electrospray (ESI) source was evaluated and compared to that of a coaxial continuous-flow fast-atom bombardment source on a magnetic mass spectrometer using ten different peptides over the mass range of 400 to 3500 Da and using a variety of scanning modes. Results show that sensitivities using the two ionization techniques are similar, with limits-of-detection in the attomole to low femtomole range. In addition, proteins fan be routinely detected using ESI at femtomole levels. The observance of the noncovalent complex of RNase A and cytidine 2'-monophosphate yields evidence that these complexes can be studied using instruments that operate at high accelerating voltages. C1 N CAROLINA STATE UNIV,DEPT CHEM,RALEIGH,NC 27695. RP Deterding, LJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Tomer, Kenneth/E-8018-2013 NR 34 TC 1 Z9 1 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 1996 VL 10 IS 1 BP 60 EP 64 DI 10.1002/(SICI)1097-0231(19960115)10:1<60::AID-RCM446>3.0.CO;2-3 PG 5 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA TQ173 UT WOS:A1996TQ17300012 PM 8563017 ER PT S AU Aguilera, G Kiss, A AF Aguilera, G Kiss, A BE Raizada, MK Phillips, MI Sumners, C TI Regulation of the hypothalmic-pituitary-adrenal axis and vasopressin secretion - Role of angiotensin II SO RECENT ADVANCES IN CELLULAR AND MOLECULAR ASPECTS OF ANGIOTENSIN RECEPTORS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 1st International Symposium on the Cellular and Molecular Aspects of Angiotensin Receptors CY DEC 09-11, 1994 CL GAINESVILLE, FL SP ICBR, Hypertens Ctr, Univ Florida, Dept Pharm & Physiol, Bristol Myers Squibb Co, Ciba-Geigy Ltd, Basel, Dupont Merck Pharm Co, Cadus Pharm Corp, Upjohn Co, Glaxo Res ID CORTICOTROPIN-RELEASING FACTOR; PARAVENTRICULAR NUCLEUS; RAT-BRAIN; ACTH-SECRETION; LOCALIZATION; RECEPTORS; STRESS; CELLS RP Aguilera, G (reprint author), NICHHD,SECT ENDOCRINE PHYSIOL,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 28 TC 13 Z9 15 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45209-X J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 396 BP 105 EP 112 PG 8 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BF60P UT WOS:A1996BF60P00011 PM 8726690 ER PT S AU Ciuffo, GM Johren, O Egidy, G Heemskerk, FMJ Saavedra, JM AF Ciuffo, GM Johren, O Egidy, G Heemskerk, FMJ Saavedra, JM BE Raizada, MK Phillips, MI Sumners, C TI Heterogeneity of rat angiotensin II AT(2) receptor SO RECENT ADVANCES IN CELLULAR AND MOLECULAR ASPECTS OF ANGIOTENSIN RECEPTORS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 1st International Symposium on the Cellular and Molecular Aspects of Angiotensin Receptors CY DEC 09-11, 1994 CL GAINESVILLE, FL SP ICBR, Hypertens Ctr, Univ Florida, Dept Pharm & Physiol, Bristol Myers Squibb Co, Ciba-Geigy Ltd, Basel, Dupont Merck Pharm Co, Cadus Pharm Corp, Upjohn Co, Glaxo Res ID HUMAN KIDNEY; SUBTYPES; BRAIN; EXPRESSION; REVEALS; CLONING; FETAL RP Ciuffo, GM (reprint author), NIMH,PHARMACOL SECT,NIH,BLDG 10,ROOM 2D45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 31 TC 5 Z9 6 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45209-X J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 396 BP 189 EP 197 PG 9 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BF60P UT WOS:A1996BF60P00020 PM 8726699 ER PT S AU Saavedra, JM deOliveira, AM Johren, O Viswanathan, M AF Saavedra, JM deOliveira, AM Johren, O Viswanathan, M BE Raizada, MK Phillips, MI Sumners, C TI Brain antgiotensin II and related receptors: New developments SO RECENT ADVANCES IN CELLULAR AND MOLECULAR ASPECTS OF ANGIOTENSIN RECEPTORS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 1st International Symposium on the Cellular and Molecular Aspects of Angiotensin Receptors CY DEC 09-11, 1994 CL GAINESVILLE, FL SP ICBR, Hypertens Ctr, Univ Florida, Dept Pharm & Physiol, Bristol Myers Squibb Co, Ciba-Geigy Ltd, Basel, Dupont Merck Pharm Co, Cadus Pharm Corp, Upjohn Co, Glaxo Res ID ANGIOTENSIN-II; RAT-BRAIN; BINDING-SITES; IDENTIFICATION; SUBTYPES; ISCHEMIA; GERBIL; MOUSE RP Saavedra, JM (reprint author), NIMH,PHARMACOL SECT,CLIN SCI LAB,10 CTR DR,MSC 1514,BLDG 10,ROOM 2D-45,BETHESDA,MD 20892, USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45209-X J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 396 BP 247 EP 252 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BF60P UT WOS:A1996BF60P00026 PM 8726705 ER PT B AU Robbins, JB Schneerson, R Szu, SC AF Robbins, JB Schneerson, R Szu, SC BE Lim, DJ Bluestone, CD Casselbrant, M Klein, JO Ogra, PL TI New ideas about vaccine-induced immunity to otitis media SO RECENT ADVANCES IN OTITIS MEDIA LA English DT Proceedings Paper CT 6th International Symposium on Recent Advances in Otitis Media CY JUN 04-08, 1995 CL FT LAUDERDALE, FL SP Childrens Hosp Pittsburgh, Dept Pediat Otolaryngol, Univ Pittsburgh Med Ctr, Ctr Continuing Educ Hlth Sci, Int Symp Otitis Media Inc, Deafness Res Fdn, NIH, Natl Inst Deafness & Other Commun Disorders C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC (CANADA) PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 621, L C D 1, HAMILTON, ON L8N 3K7, CANADA BN 1-55009-028-3 PY 1996 BP 8 EP 9 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA BK06P UT WOS:000071026900003 ER PT B AU Hoffman, HJ Overpeck, MD Hildesheim, ME AF Hoffman, HJ Overpeck, MD Hildesheim, ME BE Lim, DJ Bluestone, CD Casselbrant, M Klein, JO Ogra, PL TI Factors in the United States affecting risk of frequent ear infections, deafness or trouble hearing and related conditions SO RECENT ADVANCES IN OTITIS MEDIA LA English DT Proceedings Paper CT 6th International Symposium on Recent Advances in Otitis Media CY JUN 04-08, 1995 CL FT LAUDERDALE, FL SP Childrens Hosp Pittsburgh, Dept Pediat Otolaryngol, Univ Pittsburgh Med Ctr, Ctr Continuing Educ Hlth Sci, Int Symp Otitis Media Inc, Deafness Res Fdn, NIH, Natl Inst Deafness & Other Commun Disorders C1 Natl Inst Deafness & Other Commun Disorders, Stat & Data Syst Branch, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU B C DECKER INC (CANADA) PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 621, L C D 1, HAMILTON, ON L8N 3K7, CANADA BN 1-55009-028-3 PY 1996 BP 71 EP 75 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA BK06P UT WOS:000071026900028 ER PT B AU Gu, XX Tsai, CM Apicella, MA Lim, DJ AF Gu, XX Tsai, CM Apicella, MA Lim, DJ BE Lim, DJ Bluestone, CD Casselbrant, M Klein, JO Ogra, PL TI Biologic properties of released and cell-bound endotoxin from nontypeable Haemophilus influenzae SO RECENT ADVANCES IN OTITIS MEDIA LA English DT Proceedings Paper CT 6th International Symposium on Recent Advances in Otitis Media CY JUN 04-08, 1995 CL FT LAUDERDALE, FL SP Childrens Hosp Pittsburgh, Dept Pediat Otolaryngol, Univ Pittsburgh Med Ctr, Ctr Continuing Educ Hlth Sci, Int Symp Otitis Media Inc, Deafness Res Fdn, NIH, Natl Inst Deafness & Other Commun Disorders C1 NIDOCD, NIH, Rockville, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU B C DECKER INC (CANADA) PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 621, L C D 1, HAMILTON, ON L8N 3K7, CANADA BN 1-55009-028-3 PY 1996 BP 476 EP 479 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA BK06P UT WOS:000071026900197 ER PT B AU Gu, XX Tsai, CM Ueyama, T Lim, DJ AF Gu, XX Tsai, CM Ueyama, T Lim, DJ BE Lim, DJ Bluestone, CD Casselbrant, M Klein, JO Ogra, PL TI Characterization of detoxified nontypeable Haemophilus influenzae lipooligosaccharide conjugated to tetanus toxoid SO RECENT ADVANCES IN OTITIS MEDIA LA English DT Proceedings Paper CT 6th International Symposium on Recent Advances in Otitis Media CY JUN 04-08, 1995 CL FT LAUDERDALE, FL SP Childrens Hosp Pittsburgh, Dept Pediat Otolaryngol, Univ Pittsburgh Med Ctr, Ctr Continuing Educ Hlth Sci, Int Symp Otitis Media Inc, Deafness Res Fdn, NIH, Natl Inst Deafness & Other Commun Disorders C1 NIDOCD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC (CANADA) PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 621, L C D 1, HAMILTON, ON L8N 3K7, CANADA BN 1-55009-028-3 PY 1996 BP 505 EP 507 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA BK06P UT WOS:000071026900209 ER PT B AU Gu, XX Ueyama, T Tsai, CM Karpas, AB Lim, DJ AF Gu, XX Ueyama, T Tsai, CM Karpas, AB Lim, DJ BE Lim, DJ Bluestone, CD Casselbrant, M Klein, JO Ogra, PL TI Characterization of monoclonal antibodies to nontypeable Haemophilus influenzae lipooligosaccharides SO RECENT ADVANCES IN OTITIS MEDIA LA English DT Proceedings Paper CT 6th International Symposium on Recent Advances in Otitis Media CY JUN 04-08, 1995 CL FT LAUDERDALE, FL SP Childrens Hosp Pittsburgh, Dept Pediat Otolaryngol, Univ Pittsburgh Med Ctr, Ctr Continuing Educ Hlth Sci, Int Symp Otitis Media Inc, Deafness Res Fdn, NIH, Natl Inst Deafness & Other Commun Disorders C1 NIDOCD, NIH, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU B C DECKER INC (CANADA) PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 621, L C D 1, HAMILTON, ON L8N 3K7, CANADA BN 1-55009-028-3 PY 1996 BP 511 EP 513 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA BK06P UT WOS:000071026900211 ER PT S AU Heyes, MP AF Heyes, MP BE Filippini, GA Costa, CVL Bertazzo, A TI The kynurenine pathway and neurologic disease - Therapeutic strategies SO RECENT ADVANCES IN TRYPTOPHAN RESEARCH: TRYPTOPHAN AND SEROTONIN PATHWAYS SE Advances in Experimental Medicine and Biology LA English DT Proceedings Paper CT 8th International Meeting on Tryptophan Research CY JUN 25-29, 1995 CL PADUA, ITALY SP Univ Padova, Natl Res Council, Italian Chem Soc, Div Pharm Sci, Reg Veneto, City Padova ID QUINOLINIC ACID FORMATION; SPINAL-CORD INJURY; CEREBROSPINAL-FLUID; DELAYED INCREASES; IMMUNE ACTIVATION; BRAIN; 4-CHLORO-3-HYDROXYANTHRANILATE; 6-CHLOROTRYPTOPHAN; METABOLISM; MECHANISM RP Heyes, MP (reprint author), NIMH, CLIN SCI LAB, ANALYT BIOCHEM SECT, BLDG 10, ROOM 3D40, BETHESDA, MD 20892 USA. NR 23 TC 32 Z9 33 U1 0 U2 2 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45309-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 398 BP 125 EP 129 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BG56D UT WOS:A1996BG56D00020 PM 8906254 ER PT S AU Melillo, G Bosco, MC Musso, T Varesio, L AF Melillo, G Bosco, MC Musso, T Varesio, L BE Filippini, GA Costa, CVL Bertazzo, A TI Immunobiology of picolinic acid SO RECENT ADVANCES IN TRYPTOPHAN RESEARCH: TRYPTOPHAN AND SEROTONIN PATHWAYS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 8th International Meeting on Tryptophan Research CY JUN 25-29, 1995 CL PADUA, ITALY SP Univ Padova, Natl Res Council, Italian Chem Soc, Div Pharm Sci, Region Veneto, City Padova ID NITRIC-OXIDE SYNTHASE; INDOLEAMINE 2,3-DIOXYGENASE; ERYTHROPOIETIN GENE; INTERFERON-GAMMA; MOUSE MACROPHAGES; IFN-GAMMA; INDUCTION; EXPRESSION; CELLS; INTERLEUKIN-2 RP Melillo, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MACROPHAGE CELL BIOL SECT,LAB EXP IMMUNOL,BRMO,NIH,FREDERICK,MD 21702, USA. RI Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 NR 44 TC 18 Z9 18 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45309-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 398 BP 135 EP 141 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BG56D UT WOS:A1996BG56D00022 PM 8906256 ER PT S AU Sternberg, EM AF Sternberg, EM BE Filippini, GA Costa, CVL Bertazzo, A TI Pathogenesis of L-tryptophan eosinophilia myalgia syndrome SO RECENT ADVANCES IN TRYPTOPHAN RESEARCH: TRYPTOPHAN AND SEROTONIN PATHWAYS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 8th International Meeting on Tryptophan Research CY JUN 25-29, 1995 CL PADUA, ITALY SP Univ Padova, Natl Res Council, Italian Chem Soc, Div Pharm Sci, Region Veneto, City Padova ID LEWIS RATS; CONTAMINANT; 1,1'-ETHYLIDENEBIS(L-TRYPTOPHAN); DISEASE; L-5-HYDROXYTRYPTOPHAN; SCLERODERMA; FASCIITIS; INGESTION; BLOOD; EMS RP Sternberg, EM (reprint author), NIMH,NIH,BLDG 10,RM 3S-23110 CTR DR,MSC 1284,BETHESDA,MD 20892, USA. NR 25 TC 13 Z9 13 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45309-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 398 BP 325 EP 330 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BG56D UT WOS:A1996BG56D00050 PM 8906284 ER PT S AU Korach, KS Couse, JF Curtis, SW Washburn, TF Lindzey, J Kimbro, KS Eddy, EM Migliaccio, S Snedeker, SM Lubahn, DB Schomberg, DW Smith, EP AF Korach, KS Couse, JF Curtis, SW Washburn, TF Lindzey, J Kimbro, KS Eddy, EM Migliaccio, S Snedeker, SM Lubahn, DB Schomberg, DW Smith, EP BE Conn, PM TI Estrogen receptor gene disruption: Molecular characterization and experimental and clinical phenotypes SO RECENT PROGRESS IN HORMONE RESEARCH, VOL 51: PROCEEDINGS OF THE 1995 CONFERENCE SE RECENT PROGRESS IN HORMONE RESEARCH LA English DT Review CT 1995 Conference on Recent Progress in Hormone Research CY 1995 CL WA SP Endocrine Soc, MERCK ID PROGESTERONE-RECEPTOR; DIETHYLSTILBESTROL METABOLITES; MOUSE; HORMONE; TRANSCRIPTION; ANTIESTROGEN; EXPRESSION; ANALOGS; INSENSITIVITY; MUTATIONS AB The estrogen receptor (ER) is thought to play a crucial role in the regulation of many life processes, including development, reproduction and normal physiology. Because there have been no known mutations of the estrogen receptor in normal tissue of humans and animals, its presence and tissue distribution is thought to be essential for survival. Using the techniques of homologous recombination, we have disrupted the ER gene and have produced a line of transgenic mice possessing the altered ER gene (ERKO). The mouse ER gene was disrupted by inserting a 1.8 kb PGK-Neomycin sequence into exon 2, approximately 280 bp downstream of the transcription start codon. The corner targeting of the disruption was demonstrated by Southern blot analysis and PCR. Western blot analysis of uterine preparations from ERKO females showed no detectable ER protein. Heterozygotes had one half the level of ER protein compared to wild-type animals. Estrogen insensitivity was confirmed using estrogen agonists, estradiol, hydroxy tamoxifen, diethylstilbestrol treatment for 3 days which resulted in a 3-4-fold increase in uterine wet weight and vaginal cornification in wild-type females, while ERKO mice were totally unresponsive. These data were further supported by the failure of estrogen or EGF treatment to induce DNA synthesis in uterine tissue of similarly treated mice. Lactoferrin, an estrogen-responsive gene in the uterus, was also assayed by Northern blot. Wild-type mice treated with a single estradiol injection showed a 350-fold induction in lactoferrin mRNA, while ERKO females showed no detectable response. Both male and female animals survive to adulthood with normal gross external phenotypes. As expected, females are infertile and demonstrate hypoplastic uteri and hyperemic ovaries with no apparent corpora lutea. Males are also infertile, with atrophy of the testes and seminiferous tubule dysmorphogenesis. Although the reproductive capabilities have been altered with a dramatic effect on the gonads, prenatal development of the reproductive tracts of both sexes appear to be independent of an ER-mediated response. Analysis of the mammary glands of the ERKO females at 4 months of age showed a primitive ductal rudiment rather than the fully developed ductal tree seen in wild-type siblings. Also absent were the terminal end buds seen during normal ductal morphogenesis. Both sexes show a decrease in skeletal bone density, supporting a direct role for ER action in bone. A single patient is described who is homozygous for a point mutation in the human ER gene at codon 157. The mutation produces a truncation of the ER protein and results in estrogen insensitivity syndrome, Most significant of the clinical findings are effects on skeletal bone density and retarded bone age. Findings from the patient and mice suggest that the absence of functional ER is net lethal. Mutation in the ER gene is present in the human population. Further characterization of the mice and identification of additional patients will be required to more fully understand the consequences of ER gene mutations. C1 NIEHS, GAMETE BIOL SECT, REPROD & DEV TOXICOL LAB, RES TRIANGLE PK, NC 27709 USA. NIEHS, REPROD TOXICOL GRP, RES TRIANGLE PK, NC 27709 USA. UNIV MISSOURI, SCH MED, DEPT HUMAN GENET, COLUMBIA, MO USA. DUKE UNIV, MED CTR, DEPT PHYSIOL & CELL BIOL, DURHAM, NC USA. UNIV CINCINNATI, CHILDRENS HOSP, SCH MED, DEPT PEDIAT, CINCINNATI, OH USA. RP Korach, KS (reprint author), NIEHS, RECEPTOR BIOL SECT, POB 12233, RES TRIANGLE PK, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 50 TC 280 Z9 289 U1 1 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0079-9963 BN 0-879225-22-0 J9 RECENT PROG HORM RES PY 1996 VL 51 BP 159 EP 188 PG 30 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJ31P UT WOS:A1996BJ31P00006 PM 8701078 ER PT S AU Cidlowski, JA King, KL EvansStorms, RB Montague, JW Bortner, CD Hughes, FM AF Cidlowski, JA King, KL EvansStorms, RB Montague, JW Bortner, CD Hughes, FM BE Conn, PM TI The biochemistry and molecular biology of glucocorticoid-induced apoptosis in the immune system SO RECENT PROGRESS IN HORMONE RESEARCH, VOL 51: PROCEEDINGS OF THE 1995 CONFERENCE SE RECENT PROGRESS IN HORMONE RESEARCH LA English DT Review CT 1995 Conference on Recent Progress in Hormone Research CY 1995 CL WA SP Endocrine Soc, MERCK ID PROGRAMMED CELL-DEATH; CIS-TRANS-ISOMERASE; BINDING-PROTEIN CYCLOPHILIN; 28S RIBOSOMAL-RNA; RAT-LIVER NUCLEI; INTERNUCLEOSOMAL DNA FRAGMENTATION; POLYACRYLAMIDE GEL-ELECTROPHORESIS; CALCIUM-DEPENDENT ENDONUCLEASE; RADIATION-INDUCED APOPTOSIS; KILOBASE PAIR FRAGMENTS AB Apoptosis is a form of programmed cell death that occurs under numerous developmental and physiological conditions that require the selective elimination of cells from tissues and organs without the production of an inflammatory response. The initiation of apoptosis is controlled by a regulation of the balance between death and life signals perceived by the cell. A typical response of cells to an apoptotic stimulus includes a reduction in cell volume, compaction of intracellular organelles, chromatin condensation, and the generation of apoptotic bodies which contain degraded cellular components. Apoptotic bodies are often engulfed by neighboring cells or macrophages, preventing the occurrence of an inflammatory response in the region of the dying cells. Although the molecular basis for this cellular suicide is poorly understood, evidence indicates that apoptosis is an active process, requiring energy for its effective completion. We have sought to define the catabolic ''effector'' molecules that carry out the apoptotic process using glucocorticoid-induced apoptosis in rodent and human lymphocytes as model systems. These cells respond to dexamethasone with an arrest of cell growth, chromatin condensation, cell shrinkage, and the selective degradation of DNA, RNA, and protein. These effects are dependent on the presence of functional glucocorticoid receptors and require gene expression. The fragmentation of DNA and its associated cell shrinkage has been a focus of our efforts, because these effects reflect an irreversible commitment to death. Accordingly, we have developed assays to study apoptosis at the single cell level and to identify, purify, and clone the nuclease(s) that cause DNA damage in apoptotic cells. Using these approaches, we have identified and characterized a novel low molecular weight nuclease (NUC18) whose activity correlates with the DNA degradation occurring during apoptosis. NUC18 requires calcium for optimal activity in vitro and is inhibited by zinc and aurintricarboxylic acid, two known inhibitors of apoptosis. The amino acid sequence of pure NUC18 reveals a surprising homology to the cyclophilin family of proteins. Furthermore, recombinant cyclophilins have biochemical and pharmacological properties identical to those of NUC18. We have also studied the molecular basis for the catabolism of RNA and proteins that occurs during lymphocyte apoptosis. Recent experiments have identified selective cleavage of 28S ribosomal RNA and a novel nonlysosomal protease, both of which contribute to the demise of the cell. In summary, we present an evolving model that unifies the activation of apoptosis in lymphocytes by glucocorticoids with the counter-balancing effect of inhibitors such as Bcl-2. RP Cidlowski, JA (reprint author), NIEHS, MOL ENDOCRINOL GRP, LAB INTEGRAT BIOL, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 161 TC 109 Z9 114 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0079-9963 BN 0-879225-22-0 J9 RECENT PROG HORM RES PY 1996 VL 51 BP 457 EP 491 PG 35 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJ31P UT WOS:A1996BJ31P00018 PM 8701091 ER PT J AU Reid, JD Lukas, W Shafaatian, R Bertl, A ScheurmannKettner, C Guy, HR North, RA AF Reid, JD Lukas, W Shafaatian, R Bertl, A ScheurmannKettner, C Guy, HR North, RA TI The S-cerevisiae outwardly-rectifying potassium channel (DUK1) identifies a new family of channels with duplicated pore domains. SO RECEPTORS & CHANNELS LA English DT Article DE DUK1; ion channel; pore domain; potassium channel; Saccharomyces cerevisiae; yeast ID SACCHAROMYCES-CEREVISIAE; PLASMA-MEMBRANE; K+ CHANNELS; YEAST; GENE; PROTEIN; TETRAETHYLAMMONIUM AB Potassium channel subunits have six or two transmembrane segments in addition to a conserved pore-forming (P) domain; four subunits come together to form a channel. A gene was identified in S. cerevisiae (J0911) encoding a protein with eight probable membrane-spanning segments and two such P regions. This protein (Duk1p) is a potassium channel because Xenopus oocytes injected with the corresponding RNA express potassium currents activated by depolarization that are not seen in control oocytes. Similar potassium currents were recorded from wildtype S. cerevisiae spheroplasts, but not from those in which the DUK1 locus had been disrupted. Cells carrying the duk1 Delta 1::HIS disruption in addition to a chimeric gene comprising DUK1 behind the GAL1 promoter showed outward currents when grown in galactose, but not when grown in glucose. Additional sequences with the duplicate pore motif were found in C. elegans, suggesting that these proteins represent a novel structural family of potassium channel proteins. C1 UNIV KARLSRUHE, INST BOT, D-76128 KARLSRUHE, GERMANY. UNIV GOTTINGEN, INST PLANZENPHYSIOL, D-37073 GOTTINGEN, GERMANY. NCI, MATH BIOL LAB, BETHESDA, MD 20892 USA. RP GLAXO INST MOLEC BIOL SA, 14 CHEMIN AULX, CH-1228 GENEVA, SWITZERLAND. NR 39 TC 45 Z9 47 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1060-6823 J9 RECEPTOR CHANNEL JI Recept. Channels PY 1996 VL 4 IS 1 BP 51 EP 62 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UH958 UT WOS:A1996UH95800005 PM 8723646 ER PT S AU Wang, MY Kaslow, DC Shiloach, J AF Wang, MY Kaslow, DC Shiloach, J BE Asenjo, JA Andrews, BA TI Production of a malaria transmission-blocking protein from recombinant yeast SO RECOMBINANT DNA BIOTECHNOLOGY III: THE INTEGRATION OF BIOLOGICAL AND ENGINEERING SCIENCES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Recombinant DNA Biotechnology III - The Integration of Biological and Engineering Sciences CY OCT 16-21, 1994 CL DEAUVILLE, FRANCE SP Engn Fdn, European Sci Fdn, Amgen Inc, Boehringer Mannheim Diagnost, European Community, Genentech Inc, Glaxo Res & Dev Ltd, Inual Santiago, Chile, Lilly Res Labs, Merck Res Labs, Miles Inc, Novo Nordisk, Pharmacia Biotechnol, Phyton Catalyt Inc, Schering Plough, Xoma Corp ID SACCHAROMYCES-CEREVISIAE; EXPRESSION; PURIFICATION C1 NIDDK,BIOTHECHNOL UNIT,NIH,BETHESDA,MD 20892. NIAID,MOL VACCINE SECT,NIH,BETHESDA,MD 20892. NR 16 TC 3 Z9 3 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-962-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 782 BP 123 EP 132 DI 10.1111/j.1749-6632.1996.tb40554.x PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA BF66V UT WOS:A1996BF66V00013 PM 8659889 ER PT J AU Wolffe, AP AF Wolffe, AP TI Chromatin and gene regulation at the onset of embryonic development SO REPRODUCTION NUTRITION DEVELOPMENT LA English DT Article; Proceedings Paper CT IETS Satellite Symposium on Nuclear Information in Early Embryonic Development - Perspectives and Applications to Reproductive Biotechnology CY JAN 15, 1997 CL NICE, FRANCE SP INRA DE chromatin; nuclear organization; embryo; Xenopus ID POSITION-EFFECT VARIEGATION; 5S RNA GENE; METAPHASE CHROMOSOME STRUCTURE; EARLY XENOPUS EMBRYOGENESIS; EARLY AMPHIBIAN DEVELOPMENT; DOSAGE-DEPENDENT MODIFIERS; DROSOPHILA HOMEOTIC GENES; TRANSCRIPTION IN-VIVO; CPG BINDING-PROTEIN; SOMATIC HISTONE H1 AB Major transitions in chromosome and chromatin structure occur during development. Recent genetic and biochemical experiments demonstrate that these alterations in genome organization make significant contributions to establishing and maintaining states of differential transcriptional activity. Developmentally regulated changes in histone variants have a causal role in determining patterns of gene activity, directing the repression of specific eukaryotic genes. Chromosomal proteins such as Polycomb stabilize and maintain transcriptionally repressed states. Proteins regulating mitotic chromosome condensation have a role in determining the overall transcriptional activity of a chromosome. In this review, I place the developmental roles of these chromosomal constituents in a structural and functional context. Considerable insight now exists into the molecular mechanisms regulating chromosomal activity during development. Chromosomal architecture is emerging as a key controlling influence in the developmental regulation of gene expression. Recent genetic experiments using Caenorhabditis elegans, Drosophila melanogaster and the mouse have provided clear evidence for the functional differentiation of chromosomal structures during development. Chromosomes are visualized as highly specialized entities, within which the activity of particular domains is largely determined by defined structural proteins. At a more local level, the mechanisms regulating gene transcription during early embryogenesis in Xenopus and the mouse have been found to be dependent on the biochemical composition of individual nucleosomes. Thus, variation in the type and modification of chromosomal and chromatin structural proteins provides a dominant means of controlling the transcriptional activity of individual genes, individual chromosomal domains and of entire chromosomes. The focus of this review is to summarize these recent advances and to discuss their implications for developmental biology. RP Wolffe, AP (reprint author), NICHHD,MOL EMBRYOL LAB,NIH,BLDG 18 T,ROOM 106,BETHESDA,MD 20892, USA. NR 235 TC 18 Z9 19 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0926-5287 J9 REPROD NUTR DEV JI Reprod. Nutr. Dev. PY 1996 VL 36 IS 6 BP 581 EP 606 PG 26 WC Developmental Biology; Nutrition & Dietetics; Reproductive Biology; Zoology SC Developmental Biology; Nutrition & Dietetics; Reproductive Biology; Zoology GA WD239 UT WOS:A1996WD23900002 PM 9021871 ER PT J AU Garcia, RMG Atwater, I Lelkes, P Mathias, PCDF AF Garcia, RMG Atwater, I Lelkes, P Mathias, PCDF TI The inhibition of K+-secretory response by caffeine in bovine chromaffin cells is time dependent SO RESEARCH COMMUNICATIONS IN ALCOHOL AND SUBSTANCES OF ABUSE LA English DT Article ID ADRENAL-MEDULLARY CELLS; INDUCED CALCIUM RELEASE; CATECHOLAMINE SECRETION; SARCOPLASMIC-RETICULUM; STIMULATION; AGONIST; MUSCLE AB Catecholamine secretion was studied using cultures of bovine chromaffin cells. Secretory response induced by K+ (50 mM) was inhibited 62% by 50 mM caffeine, when both stimulators were added together. Preincubation with caffeine, 50 mM, decreased the catecholamines release stimulated by potassium. The effect was time-dependent and reached 90% of inhibition when the cells were exposed previously to caffeine for more than 5 min. Ca-45 uptake was not affected by the simultaneous challenge with potassium and caffeine. However 5 min of preincubation with caffeine decreased 50% of radioactive uptake in chromaffin cells stimulated by potassium. These results indicate that caffeine inhibits the K+-secretory response in bovine chromaffin cells through a time-dependent mechanism which blocks the Ca2+ influx. This may be due to interaction with the intracellular calcium buffer system. C1 NIDDK,CELL BIOL & GENET LAB,NIH,BETHESDA,MD 20892. UNIV WISCONSIN,SCH MED,DEPT MED,CELL BIOL LAB,MILWAUKEE,WI 53201. RP Garcia, RMG (reprint author), UNIV ESTADUAL MARINGA,LAB SECRET CELL BIOL,BR-87020900 MARINGA,PARANA,BRAZIL. NR 15 TC 1 Z9 1 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 SN 1080-8388 J9 RES COMMUN ALCOHOL S JI Res. Commun. Alcohol Subst. Abus. PY 1996 VL 17 IS 1-2 BP 15 EP 21 PG 7 WC Substance Abuse SC Substance Abuse GA VY398 UT WOS:A1996VY39800002 ER PT J AU Liu, KJ Jiang, JJ Ji, LL Shi, XL Schwartz, HM AF Liu, KJ Jiang, JJ Ji, LL Shi, XL Schwartz, HM TI An HPLC and EPR investigation on the stability of DMPO and DMPO spin adducts in vivo SO RESEARCH ON CHEMICAL INTERMEDIATES LA English DT Article; Proceedings Paper CT IV GIRSE National Congress/II International Workshop on In Vivo ESR and ESR Imaging CY 1995 CL LAQUILA, ITALY SP Italian Grp Electron Spin Resonance ID HYDROXYL-RADICAL GENERATION; ACTIVE OXYGEN; SUPEROXIDE; IRON; REDUCTION; SYSTEMS; CELLS; RATS; ESR AB Application of the spin trapping technique in intact animals requires an understanding of the stability and distribution of the spin traps and their spin adducts in vivo. We studied the stability of DMPO in vivo in mice using HPLC and the stability of spin adducts of DMPO by EPR in plasma, whole blood, peritoneal fluid, and homogenized heart tissue of the rat. At 15 minutes after intraperitoneal injection DMPO had similar concentrations in the liver, heart, and blood of the mice and 40% remained in the organs 2 hours after the injection. In contrast, the spin adduct DMPO-OH was short lived, with a half-life of 3.0 minutes in plasma, and was not detectable 1 minute after formation in whole blood and homogenized heart tissue. The carbon centered spin adduct DMPO-CH(OH)CH3 was more stable, having half-lives of 16, 11, 3.6, and 0.79 minutes in plasma, peritoneal fluid, whole blood, and homogenized heart tissue, respectively. The spin adduct DMPO-SO3 was sufficiently stable for the adduct to be observed directly from living mice. C1 DARTMOUTH COLL,SCH MED,DEPT RADIOL,HANOVER,NH 03755. UNIV WISCONSIN,BIODYNAM LABS,MADISON,WI 53706. NCI,LAB EXPTL PATHOL,BETHESDA,MD 20892. RI Shi, Xianglin/B-8588-2012 NR 30 TC 10 Z9 10 U1 0 U2 3 PU VSP BV PI ZEIST PA PO BOX 346, 3700 AH ZEIST, NETHERLANDS SN 0922-6168 J9 RES CHEM INTERMEDIAT JI Res. Chem. Intermed. PY 1996 VL 22 IS 5 BP 499 EP 509 PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA UQ622 UT WOS:A1996UQ62200010 ER PT B AU Lyon, GR AF Lyon, GR BE Speece, DL Keogh, BK TI Methodological issues and strategies for assessing developmental change and evaluating response to intervention SO RESEARCH ON CLASSROOM ECOLOGIES: IMPLICATIONS FOR INCLUSION OF CHILDREN WITH LEARNING DISABILITIES LA English DT Proceedings Paper CT Symposium on Research on Classroom Ecologies - Implications for Inclusion of Children with Learning Disabilities CY OCT, 1994 CL BANDERA, TX SP Council Except Children, Illinois State Board Educ, Texas State Educ Agcy, Great Lakes Reg Resource Ctr, S Atlantic Reg Resource Ctr C1 NICHHD,NIH,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 BN 0-8058-1896-0 PY 1996 BP 213 EP 227 PG 15 WC Education, Special SC Education & Educational Research GA BF53L UT WOS:A1996BF53L00014 ER PT J AU Walton, RC Byrnes, GA Chan, CC Nussenblatt, RB AF Walton, RC Byrnes, GA Chan, CC Nussenblatt, RB TI Fluorescein angiography in the progressive outer retinal necrosis syndrome SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE acquired immune deficiency syndrome; fluorescein angiography; progressive outer retinal necrosis; varicella-zoster virus ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; VARICELLA-ZOSTER VIRUS; RETINITIS; RETINOPATHY AB Purpose: Progressive outer retinal necrosis syndrome is a devastating retinopathy seen primarily in patients with acquired immune deficiency syndrome. To provide additional details of the pathogenesis of this disease, the authors describe the evolution of clinical and fluorescein angiographic changes during the course of progressive outer retinal necrosis syndrome. Methods: The authors performed serial clinical examinations, fundus photography, and fluorescein angiography in a patient with acquired immune deficiency syndrome with progressive outer retinal necrosis syndrome, Clinical and fluorescein angiographic findings were correlated to provide detailed sequential analysis of the pathologic changes occurring during the course of this disorder. Results: The angiographic changes seen during the various stages of the disease consisted of zonal microvascular alterations, retinal pigment epithelium (RPE) destruction, and choroidal leakage. Retinal damage was correlated closely with regions of choroidal leakage and was clinically evident as outer retinal whitening. Disease reactivation occurred as a prominent brush-fire border of intense leakage involving the retina, RPE, and choroid. Extensive damage to the retinal vasculature and RPE was noted in the wake of clinical infection. Conclusions: The angiographic findings in our patient demonstrate that the progressive outer retinal necrosis syndrome is a retinochoroiditis that involves the full thickness of retina as well as the RPE and choroid. The inflammatory changes seen throughout the course of this disease correlate with the histopathologic patterns reported to date. C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 7 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1996 VL 16 IS 5 BP 393 EP 398 DI 10.1097/00006982-199616050-00005 PG 6 WC Ophthalmology SC Ophthalmology GA VP395 UT WOS:A1996VP39500005 PM 8912965 ER PT B AU Pantaleo, G AF Pantaleo, G BE Girard, M Dodet, B TI Virologic and immunologic events associated with primary HIV infection in peripheral blood and lymph nodes SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 10th Anniversary of the Cent Gardes Meeting - Retroviruses of Human AIDS and Related Animal Diseases CY OCT 23-25, 1995 CL PARIS, FRANCE SP Cent Gardes C1 NIAID,NIH,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RI Pantaleo, Giuseppe/K-6163-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 2-906077-75-5 PY 1996 BP 13 EP 16 PG 4 WC Immunology; Virology SC Immunology; Virology GA BF35V UT WOS:A1996BF35V00003 ER PT B AU Bradac, J AF Bradac, J BE Girard, M Dodet, B TI Inter- and intra-subtype neutralization of human immunodeficiency virus type-1 SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 10th Anniversary of the Cent Gardes Meeting - Retroviruses of Human AIDS and Related Animal Diseases CY OCT 23-25, 1995 CL PARIS, FRANCE SP Cent Gardes C1 NIAID,NIH,DIV AIDS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 2-906077-75-5 PY 1996 BP 87 EP 95 PG 9 WC Immunology; Virology SC Immunology; Virology GA BF35V UT WOS:A1996BF35V00017 ER PT B AU Freed, EO AF Freed, EO BE Girard, M Dodet, B TI Characterization of HIV-1 matrix and gp41 domains involved in Env incorporation into virions SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 10th Anniversary of the Cent Gardes Meeting - Retroviruses of Human AIDS and Related Animal Diseases CY OCT 23-25, 1995 CL PARIS, FRANCE SP Cent Gardes C1 NIAID,NIH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 2-906077-75-5 PY 1996 BP 111 EP 116 PG 6 WC Immunology; Virology SC Immunology; Virology GA BF35V UT WOS:A1996BF35V00020 ER PT B AU Nara, PL AF Nara, PL BE Girard, M Dodet, B TI Physiologic concentrations of human plasma alters the immunochemistry and increases the neutralization resistant fraction of HIV-1 SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 10th Anniversary of the Cent Gardes Meeting - Retroviruses of Human AIDS and Related Animal Diseases CY OCT 23-25, 1995 CL PARIS, FRANCE SP Cent Gardes C1 NCI,NIH,FREDERICK CANC RES & DEV CTR,VIRUS BIOL SECT,LAB TUMOR CELL BIOL,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 2-906077-75-5 PY 1996 BP 117 EP 125 PG 9 WC Immunology; Virology SC Immunology; Virology GA BF35V UT WOS:A1996BF35V00021 ER PT B AU Fauci, AS AF Fauci, AS BE Girard, M Dodet, B TI Host factors in the pathogenesis of human immunodeficiency virus disease SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 10th Anniversary of the Cent Gardes Meeting - Retroviruses of Human AIDS and Related Animal Diseases CY OCT 23-25, 1995 CL PARIS, FRANCE SP Cent Gardes C1 NIAID,NATL INST HLTH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 2-906077-75-5 PY 1996 BP 237 EP 241 PG 5 WC Immunology; Virology SC Immunology; Virology GA BF35V UT WOS:A1996BF35V00040 ER PT B AU Fast, PE AF Fast, PE BE Girard, M Dodet, B TI HIV vaccine clinical trials: Experience of the NIAID AIDS vaccine evaluation group SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 10th Anniversary of the Cent Gardes Meeting - Retroviruses of Human AIDS and Related Animal Diseases CY OCT 23-25, 1995 CL PARIS, FRANCE SP Cent Gardes C1 NIAID,DIV AIDS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 2-906077-75-5 PY 1996 BP 283 EP 290 PG 8 WC Immunology; Virology SC Immunology; Virology GA BF35V UT WOS:A1996BF35V00048 ER PT B AU Lane, HC AF Lane, HC BE Girard, M Dodet, B TI The role of interleukin-2 in the management of patients with HIV infection SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 10th Anniversary of the Cent Gardes Meeting - Retroviruses of Human AIDS and Related Animal Diseases CY OCT 23-25, 1995 CL PARIS, FRANCE SP Cent Gardes C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 2-906077-75-5 PY 1996 BP 317 EP 320 PG 4 WC Immunology; Virology SC Immunology; Virology GA BF35V UT WOS:A1996BF35V00053 ER PT S AU Okazaki, IJ Moss, J AF Okazaki, IJ Moss, J BE Blaustein, MP Pette, D Schultz, G Schweiger, M Habermann, E Grunicke, H TI Structure and function of eukaryotic mono-ADP-ribosyltransferases SO REVIEWS OF PHYSIOLOGY, BIOCHEMISTRY AND PHARMACOLOGY SE Reviews of Physiology Biochemistry and Pharmacology LA English DT Review ID HEAT-LABILE ENTEROTOXIN; ACTIVE-SITE MUTATIONS; AERUGINOSA EXOTOXIN-A; NAD-BINDING-SITE; DIFFERENTIATION MARKER RT6; AMINO-ACID-SEQUENCE; RHO-GENE-PRODUCT; ESCHERICHIA-COLI ENTEROTOXIN; OUTER SEGMENT PROTEINS; PERFRINGENS IOTA TOXIN RP NHLBI, PULM CRIT CARE MED BRANCH, NIH, BETHESDA, MD 20892 USA. NR 208 TC 18 Z9 19 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0303-4240 BN 3-540-61435-4 J9 REV PHYSIOL BIOCH P JI Rev. Physiol. Biochem. Pharmacol. PY 1996 VL 129 BP 51 EP 104 PG 54 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Physiology GA BG91S UT WOS:A1996BG91S00002 PM 8898563 ER PT J AU Jin, DJ Zhou, YN AF Jin, DJ Zhou, YN TI Mutational analysis of structure-function relationship of RNA polymerase in Escherichia coli SO RNA POLYMERASE AND ASSOCIATED FACTORS, PT A SE METHODS IN ENZYMOLOGY LA English DT Review ID STREPTOLYDIGIN-RESISTANT MUTANTS; BETA-SUBUNIT GENE; RIFAMPICIN-RESISTANT; TRANSCRIPTION TERMINATION; BACILLUS-SUBTILIS; RPOB GENE; CHAIN ELONGATION; ACTIVE-CENTER; REGION; RHO RP Jin, DJ (reprint author), NCI,DEV GENET SECT,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892, USA. NR 77 TC 25 Z9 25 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 273 BP 300 EP 319 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG51M UT WOS:A1996BG51M00025 PM 8791620 ER PT J AU Hinton, DM MarchAmegadzie, R Gerber, JS Sharma, M AF Hinton, DM MarchAmegadzie, R Gerber, JS Sharma, M TI Bacteriophage T4 middle transcription system: T4-modified RNA polymerase; AsiA, a sigma(70) binding protein; and transcriptional activator MotA SO RNA POLYMERASE AND ASSOCIATED FACTORS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID ESCHERICHIA-COLI; ALPHA-SUBUNIT; GENE-PRODUCT; INVITRO; PROMOTER; IDENTIFICATION; PURIFICATION; EXPRESSION; INHIBITION RP Hinton, DM (reprint author), NIDDK,MOL & CELLULAR BIOL LAB,BETHESDA,MD 20892, USA. NR 37 TC 35 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 274 BP 43 EP 57 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG79B UT WOS:A1996BG79B00005 PM 8902795 ER PT J AU Ge, H Martinez, E Chiang, CM Roeder, RG AF Ge, H Martinez, E Chiang, CM Roeder, RG TI Activator-dependent transcription by mammalian RNA polymerase II: In vitro reconstitution with general transcription factors and cofactors SO RNA POLYMERASE AND ASSOCIATED FACTORS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID INITIATION; PURIFICATION; COACTIVATOR; PROMOTER; PC4 RP Ge, H (reprint author), NICHHD,LAB MOL EMBRYOL,NIH,BETHESDA,MD 20892, USA. NR 18 TC 49 Z9 49 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 274 BP 57 EP 71 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG79B UT WOS:A1996BG79B00006 PM 8902796 ER PT J AU Zhong, M Wisniewski, J Fritsch, M Mizuguchi, G Orosz, A Jedlicka, P Wu, C AF Zhong, M Wisniewski, J Fritsch, M Mizuguchi, G Orosz, A Jedlicka, P Wu, C TI Purification of heat shock transcription factor of Drosophila SO RNA POLYMERASE AND ASSOCIATED FACTORS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review RP Zhong, M (reprint author), NCI,NIH,BIOCHEM LAB,BETHESDA,MD 20892, USA. RI yu, yan/C-2322-2012 NR 7 TC 6 Z9 6 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 274 BP 113 EP 119 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG79B UT WOS:A1996BG79B00009 PM 8902799 ER PT J AU Studitsky, VM Clark, DJ Felsenfeld, G AF Studitsky, VM Clark, DJ Felsenfeld, G TI Preparation of nucleosomal templates for transcription in vitro SO RNA POLYMERASE AND ASSOCIATED FACTORS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID COLI RNA-POLYMERASE; TRANSCRIBING POLYMERASE; CHROMATIN; HISTONES; INVITRO; DNA; DISPLACEMENT; ELONGATION; INITIATION; INHIBIT C1 NIDDKD,CELLULAR & DEV BIOL LAB,NIH,BETHESDA,MD 20892. RP Studitsky, VM (reprint author), NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892, USA. RI Studitsky, Vasily/A-9382-2014 NR 18 TC 8 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 274 BP 246 EP 256 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG79B UT WOS:A1996BG79B00019 PM 8902809 ER PT J AU Ura, K Wolffe, AP AF Ura, K Wolffe, AP TI Reconstruction of transcriptionally active and silent chromatin SO RNA POLYMERASE AND ASSOCIATED FACTORS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID LINKER HISTONES; NUCLEOSOMAL TEMPLATES; RNA GENES; DNA; H1; PROMOTER; FILAMENT; H5 RP Ura, K (reprint author), NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892, USA. NR 22 TC 9 Z9 9 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 274 BP 257 EP 271 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG79B UT WOS:A1996BG79B00020 PM 8902810 ER PT J AU Tsukiyama, T Wu, C AF Tsukiyama, T Wu, C TI Purification of GAGA factor of Drosophila and its role in nucleosome disruption SO RNA POLYMERASE AND ASSOCIATED FACTORS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID TRANSCRIPTION FACTOR; GENE; CHROMATIN; PROMOTER; EXTRACTS RP Tsukiyama, T (reprint author), NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892, USA. NR 10 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 274 BP 291 EP 299 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG79B UT WOS:A1996BG79B00023 PM 8902813 ER PT J AU Das, A Barik, S Ghosh, B Whalen, W AF Das, A Barik, S Ghosh, B Whalen, W TI Immunoprinting: A technique used to study dynamic protein-nucleic acid interactions within transcription elongation complex SO RNA POLYMERASE AND ASSOCIATED FACTORS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID N-GENE-PRODUCT; PHAGE-LAMBDA; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; ANTITERMINATION; TERMINATION; RNA; SITE; RECOGNITION; NUSA C1 UNIV S ALABAMA,COLL MED,DEPT BIOCHEM & MOL BIOL,MOBILE,AL 36688. COUNCIL & IND RES,CTR BIOCHEM TECHNOL,DELHI 110007,INDIA. NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. RP Das, A (reprint author), UNIV CONNECTICUT,SCH MED,DEPT MICROBIOL,FARMINGTON,CT 06030, USA. RI Ghosh, Balaram/G-1248-2010 FU NIGMS NIH HHS [GM28946] NR 32 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 274 BP 363 EP 374 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG79B UT WOS:A1996BG79B00029 PM 8902819 ER PT J AU Das, A Pal, M Mena, JG Whalen, W Wolska, K Crossley, R Rees, W vonHippel, PH Costantino, N Court, D Mazzulla, M Altieri, AS Byrd, RA Chattopadhyay, S DeVito, J Ghosh, B AF Das, A Pal, M Mena, JG Whalen, W Wolska, K Crossley, R Rees, W vonHippel, PH Costantino, N Court, D Mazzulla, M Altieri, AS Byrd, RA Chattopadhyay, S DeVito, J Ghosh, B TI Components of multiprotein-RNA complex that controls transcription elongation in Escherichia coli phage lambda SO RNA POLYMERASE AND ASSOCIATED FACTORS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID N-GENE-PRODUCT; BACTERIOPHAGE-LAMBDA; ANTITERMINATION PROTEIN; CHAIN ELONGATION; NUSA PROTEIN; HOST FACTOR; TERMINATION; POLYMERASE; INVITRO; CLEAVAGE C1 NCI,MOL VIROL LAB,NIH,BETHESDA,MD 20892. WARSAW UNIV,INST MICROBIOL,WARSAW 64,POLAND. NATL JEWISH CTR IMMUNOL & RESP MED,HOWARD HUGHES MED INST,DENVER,CO 80206. UNIV OREGON,DEPT CHEM,INST MOL BIOL,EUGENE,OR 97403. NCI,FREDERICK CANC RES & DEV CTR,LAB CHROMOSOME BIOL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOL NMR SECT,FREDERICK,MD 21702. MIT,DEPT BIOL,CTR CANC RES,CAMBRIDGE,MA 02138. US FDA,CTR BIOL EVALUAT & RES,LAB MYCOBACTERIA,BETHESDA,MD 20892. CSIR,CTR BIOCHEM TECHNOL,DELHI 110007,INDIA. RP Das, A (reprint author), UNIV CONNECTICUT,SCH MED,DEPT MICROBIOL,FARMINGTON,CT 06030, USA. RI Ghosh, Balaram/G-1248-2010; Garcia-Mena, Jaime/B-1625-2008; Byrd, R. Andrew/F-8042-2015 OI Garcia-Mena, Jaime/0000-0002-0595-3711; Byrd, R. Andrew/0000-0003-3625-4232 FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [GM15792, GM28946] NR 53 TC 18 Z9 18 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 274 BP 374 EP 402 PG 29 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG79B UT WOS:A1996BG79B00030 PM 8902820 ER PT J AU Pause, A Aso, T Linehan, WM Conaway, JW Conaway, RC Klausner, RD AF Pause, A Aso, T Linehan, WM Conaway, JW Conaway, RC Klausner, RD TI Interaction of von Hippel-Lindau tumor suppressor gene product with elongin SO RNA POLYMERASE AND ASSOCIATED FACTORS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID RNA-POLYMERASE-II; TRANSCRIPTION FACTOR; FACTOR-SIII; RAT-LIVER; ELONGATION; INITIATION; PROMOTERS C1 OKLAHOMA MED RES FDN,PROGRAM MOL & CELL BIOL,OKLAHOMA CITY,OK 73104. NCI,UROL ONCOL SECT,SURG BRANCH,NIH,BETHESDA,MD 20892. RP Pause, A (reprint author), NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892, USA. OI Conaway, Joan/0000-0002-2786-0663 NR 15 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 274 BP 436 EP 441 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG79B UT WOS:A1996BG79B00033 PM 8902823 ER PT J AU Schneider, TD AF Schneider, TD TI Reading of DNA sequence logos: Prediction of major groove binding by information theory SO RNA POLYMERASE AND ASSOCIATED FACTORS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID GENE ACTIVATOR PROTEIN; AMP RECEPTOR PROTEIN; ESCHERICHIA-COLI; B-DNA; SITES; RECOGNITION; COMPLEX; OXYR; SPECIFICITY; POLYMERASE RP Schneider, TD (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,FREDERICK,MD 21702, USA. OI Schneider, Thomas/0000-0002-9841-1531 NR 37 TC 58 Z9 59 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 274 BP 445 EP 455 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG79B UT WOS:A1996BG79B00034 PM 8902824 ER PT J AU Koivisto, P Visakorpi, T Kallioniemi, OP AF Koivisto, P Visakorpi, T Kallioniemi, OP TI Androgen receptor gene amplification: A novel molecular mechanism for endocrine therapy resistance in human prostate cancer SO SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION LA English DT Article DE androgen receptor gene; gene amplification; hormone refractory; molecular genetics; prostate cancer ID COMPARATIVE GENOMIC HYBRIDIZATION; MUTATIONS; TUMORS AB Since the development and growth of the prostate cancer is highly dependent on androgens, androgen deprivation therapy continues to be the treatment of choice for patients with advanced prostate cancer. The therapy is very effective, but responses are often short-lived. We describe here a novel molecular mechanism that may explain why prostate cancer cells become resistant to hormonal therapy. Amplification of the androgen receptor (AR) gene was found to be selected for during androgen deprivation therapy in 23% of prostate cancer patients who experienced local tumor recurrence. Amplification leads to increased expression of the AR gene, which enables the cancer cells to more effectively utilize the residual low levels of androgens for sustaining cell growth. Discovery of AR amplification as a possible molecular mechanism of therapy resistance in prostate cancer should prove useful for development of more effective endocrine therapy regimens as well as diagnostic and predictive tests for therapy failure. C1 TAMPERE UNIV, INST MED TECHNOL, CANC GENET LAB, FIN-33101 TAMPERE, FINLAND. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. RP TAMPERE UNIV HOSP, CANC GENET LAB, DEPT CLIN CHEM, POB 2000, FIN-33521 TAMPERE, FINLAND. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 19 TC 46 Z9 47 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0036-5513 EI 1502-7686 J9 SCAND J CLIN LAB INV JI Scand. J. Clin. Lab. Invest. PY 1996 VL 56 SU 226 BP 57 EP 63 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VW127 UT WOS:A1996VW12700006 PM 8981668 ER PT J AU Elin, RJ Hristova, EN Cecco, SA Niemela, TE Rehak, NN AF Elin, RJ Hristova, EN Cecco, SA Niemela, TE Rehak, NN TI Comparison of precision and effect of pH and calcium on the AVL and NOVA magnesium ion-selective electrodes SO SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION LA English DT Article; Proceedings Paper CT 15th International Symposium on Blood Gases and Electrolytes CY MAY 20-23, 1994 CL EKOXEN CTR, LINKOPING, SWEDEN SP Int Federat Clin Chem, Amer Assoc Clin Chem, Electrolyte & Blood Gas Div, Japanese Soc Clin Chem, Comm Blood Gases & Electrolytes HO EKOXEN CTR DE ionized calcium; ionized magnesium; serum AB We compared the precision of the AVL 988-4 and NOVA CRT instruments for determining ionized magnesium (iMg) and assessed the effect of pH and ionized calcium (iCa) concentration on the results. Within-run and day-to-day precision for the iMg electrodes were determined using three levels of control material supplied by each manufacturer. The effect of pH on iMg results was assessed by analyzing anaerobic serum samples from patients, reanalyzing those same samples after pH was increased by in vitro loss of CO2 and comparing the results. To assess the effect of iCa concentration on the iMg results, we added CaCl2 to aqueous standards from both manufacturers and to a normal serum pool. The results show comparable coefficients of variation for the two iMg electrodes both within-run (0.68 - 2.05 for NOVA; 0.77 - 2.60 for AVL) and day-to-day (2.90 - 6.48 for NOVA; 1.71 - 4.93 for AVL). The AVL results were not affected by the increase in serum pH and agreed with the NOVA results that were adjusted to a pH of 7.4 (paired t-test; p > 0.2). There was a significant direct relationship between the iCa and iMg results for both analyzers, but the AVL slopes were smaller (0.026, 0.083) than the NOVA slopes (0.129, 0.165). Thus, these two iMg electrodes have comparable precision but differ in response to an increase in pH and iCa. RP Elin, RJ (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,CLIN CHEM SERV,BLDG 10,ROOM 2C-306,BETHESDA,MD 20892, USA. OI Niemela, Julie/0000-0003-4197-3792 NR 6 TC 8 Z9 8 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0036-5513 J9 SCAND J CLIN LAB INV JI Scand. J. Clin. Lab. Invest. PY 1996 VL 56 SU 224 BP 203 EP 210 DI 10.3109/00365519609088641 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VB798 UT WOS:A1996VB79800022 PM 8865437 ER PT J AU Weiss, HA Forman, D AF Weiss, HA Forman, D TI Aspirin, non-steroidal anti-inflammatory drugs and protection from colorectal cancer: A review of the epidemiological evidence SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE aspirin; colorectal cancer; epidemiology; NSAID ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FAMILIAL ADENOMATOUS POLYPOSIS; FECAL OCCULT BLOOD; 18 MAJOR CANCERS; COLON-CANCER; LARGE-BOWEL; REDUCED RISK; MORTALITY; DISEASES AB There is substantial experimental, clinical and epidemiological evidence that regular use of non-steroid anti-inflammatory drugs (NSAIDs), particularly aspirin, is associated with a reduced risk of colorectal cancer. The protective effect is thought to arise from inhibition of prostaglandin synthesis, although the precise mechanism remains unclear. Of the epidemiological studies carried out, all but one have found that regular use of NSAIDs reduces the risk of colorectal cancer by 30-50%. The consistency of this finding across studies and the magnitude of the reduced risk tend to support a causal association between NSAID use and reduced risk of colorectal cancer. Further, the protective effect increases with longer duration of use, and persists after controlling for other colorectal cancer risk factors. However, these observational studies are limited by inherent biases, potential confounding with other lifestyle factors, and sparse information on dose and duration of use. Only one randomized controlled trial has been carried out, and no reduction in risk was associated with intake of one aspirin per day, though this may be due to the short follow-up period and the low dose of aspirin taken. Further observational studies and randomized controlled trials are needed to confirm the association, to quantify the dosage required for a protective effect, and to identify those patients most likely to benefit. C1 UNIV LEEDS,CTR CANC RES,COOKRIDGE HOSP,LEEDS,W YORKSHIRE,ENGLAND. RP Weiss, HA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N RM 443,6130 EXEC BLVD,BETHESDA,MD 20892, USA. NR 29 TC 10 Z9 10 U1 2 U2 5 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 1996 VL 31 SU 220 BP 137 EP 141 DI 10.3109/00365529609094766 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL284 UT WOS:A1996VL28400025 ER PT B AU Ralston, E Ploug, T AF Ralston, E Ploug, T BE Malecki, M Roomans, GM TI Pre-embedding staining of single muscle fibers for light and electron microscopy studies of subcellular organization SO SCANNING MICROSCOPY SUPPLEMENT 10, 1996: THE SCIENCE OF BIOLOGICAL SPECIMEN PREPARATION FOR MICROSCOPY LA English DT Proceedings Paper CT 14th Pfefferkorn Conference on the Science of Biological Specimen Preparation for Microscopy CY AUG 06-11, 1995 CL BELLEVILLE, IL SP Scanning Microscopy Int DE skeletal muscle; soleus; immunocytochemistry; immunogold; nanogold; permeabilization; pre-embedding; glucose transport; GLUT4; trafficking ID GLUCOSE-TRANSPORTER; LOCALIZATION; GLUT4; CELLS; RAT; IMMUNOCYTOCHEMISTRY; ARCHITECTURE; ANTIBODIES; LABEL AB Skeletal muscle fibers are large, multinucleated cells which pose a challenge to the morphologist. In the course of studies of the distribution of the glucose transporter GLUT4, in muscle, we have compared different preparative procedures, for both light (LM) and electron microscopy (EM) immunocytochemistry. Here we show that pre-embedding staining of single teased fibers, or of single enzymatically dissociated fibers, has several advantages over the use of sections for observing discrete patterns that extend over long distances in the cells. We report on an optimization study carried out to establish fixation and permeabilization conditions for EM immunogold labeling of the fibers. We find that a simple fixation with depolymerized paraformaldehyde alone, followed by permeabilization with 0.01 % saponin, offers the best compromise between the conflicting demands of unhindered tissue penetration and morphology preservation. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Ralston, E (reprint author), NINDS, Neurobiol Lab, NIH, Bldg 36,Rm 2A-21, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU SCANNING MICROSCOPY INTERNATIONAL PI CHICAGO PA PO BOX 66507, AMF O'HARE, CHICAGO, IL 60666 USA BN 0-931288-49-5 PY 1996 BP 249 EP 260 PG 12 WC Biochemical Research Methods; Microscopy SC Biochemistry & Molecular Biology; Microscopy GA BM31Y UT WOS:000078376200020 ER PT J AU Muntaner, C AF Muntaner, C TI Occupations, factors, and schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Letter RP Muntaner, C (reprint author), NIMH,LAB SOCIOENVIRONM STUDIES,INTRAMURAL RES PROGRAM,7550 WISCONSIN AVE,B1A14,BETHESDA,MD 20892, USA. RI Muntaner, C/A-5043-2010 NR 8 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1996 VL 22 IS 1 BP 11 EP 12 PG 2 WC Psychiatry SC Psychiatry GA TZ303 UT WOS:A1996TZ30300004 PM 8685654 ER PT J AU McCarley, RW Hsiao, JK Freedman, R Pfefferbaum, A Donchin, E AF McCarley, RW Hsiao, JK Freedman, R Pfefferbaum, A Donchin, E TI Neuroimaging and the cognitive neuroscience of schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material ID MAGNETIC-RESONANCE SPECTROSCOPY; POSITRON EMISSION TOMOGRAPHY; MONOZYGOTIC TWINS DISCORDANT; CEREBRAL BLOOD-FLOW; NEUROLEPTIC-NAIVE PATIENTS; GLUCOSE METABOLIC-RATE; HIGH-ENERGY PHOSPHATE; TEMPORAL-LOBE; PREFRONTAL CORTEX; FIRST-EPISODE AB The Carmel Workshop on Cognitive Psychophysiology began in 1980, and the focus of the 1996 workshop was on schizophrenia. Research into schizophrenia is in the midst of a period of unparalleled advance, driven in large part, by improvements in neuroimaging technology that make detailed examination of in vivo brain structure and function possible. Neuroimaging studies may help provide a bridge between investigations demonstrating molecular and cellular abnormalities in schizophrenia and those demonstrating cognitive dysfunction. The workshop brought together experts in different neuroimaging modalities to present the strengths and advantages of each, as well as the insights each modality might bring into normal and schizophrenic cognition. It began with a series of tutorials to inform participants of the state of the art in various disciplines. It then broke into four panels, each given a very specific topic assignment related to neuroimaging and/or the cognitive neuroscience of schizophrenia. After 1 1/2 days of discussion, each panel reported its conclusions to the workshop. Group I presented cellular models of the pathophysiology of schizophrenia. Group II examined experimental paradigms for studying cognitive function and schizophrenia. Group III examined technical issues in image processing and combining data across different modalities. Group IV sought to survey the current state of knowledge about the pathophysiology of schizophrenia. The conclusions of each of the groups are presented in this report. C1 NIMH,DIV CLIN & TREATMENT RES,SCHIZOPHRENIA RES BRANCH,ROCKVILLE,MD 20857. NIMH,DIV CLIN & TREATMENT RES,NEUROIMAGING PROGRAM,ROCKVILLE,MD 20857. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. STANFORD UNIV,SCH MED,STANFORD,CA 94305. VET AFFAIRS MED CTR,PALO ALTO,CA 94304. UNIV ILLINOIS,CHAMPAIGN,IL 61820. RP McCarley, RW (reprint author), HARVARD UNIV,VET AFFAIRS MED CTR,SCH MED,940 BELMONT ST,BROCKTON,MA 02401, USA. NR 122 TC 34 Z9 34 U1 5 U2 5 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1996 VL 22 IS 4 BP 703 EP 725 PG 23 WC Psychiatry SC Psychiatry GA VT404 UT WOS:A1996VT40400013 PM 8938923 ER PT S AU Devereux, TR Malarkey, DE Maronpot, RR AF Devereux, TR Malarkey, DE Maronpot, RR BE Maltoni, C Soffritti, M Davis, W TI The contribution of rodent liver and lung carcinogenesis models to our knowledge of the cancer latent period SO SCIENTIFIC BASES OF CANCER CHEMOPREVENTION SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT International Forum on the Scientific Bases of Cancer Chemoprevention CY MAR 31-APR 02, 1996 CL BOLOGNA, ITALY SP European Commiss, Europe Against Canc Programme, Zeneca, Italian League Fight Against Canc, Bologna Sect, Ciba Geigy, Coca Cola, Fdn Casa Risparmio Bologna, Leica, Manutencoop, Redwall, Takeda Italia Famaceutici DE cancer latency; experimental carcinogenesis; rodent carcinogenesis models RP Devereux, TR (reprint author), NIEHS,MOL TOXICOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82453-7 J9 INT CONGR SER PY 1996 VL 1120 BP 45 EP 59 PG 15 WC Oncology SC Oncology GA BG95Q UT WOS:A1996BG95Q00006 ER PT S AU Kelloff, GJ Boone, CW Malone, WF Nayfield, SG Hawk, ET Crowell, JA Lubet, RA Steele, VE Sigman, CC AF Kelloff, GJ Boone, CW Malone, WF Nayfield, SG Hawk, ET Crowell, JA Lubet, RA Steele, VE Sigman, CC BE Maltoni, C Soffritti, M Davis, W TI The contribution of epidemiology and molecular biology for identifying population groups eligible for cancer chemoprevention SO SCIENTIFIC BASES OF CANCER CHEMOPREVENTION SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT International Forum on the Scientific Bases of Cancer Chemoprevention CY MAR 31-APR 02, 1996 CL BOLOGNA, ITALY SP European Commiss, Europe Against Canc Programme, Zeneca, Italian League Fight Against Canc, Bologna Sect, Ciba Geigy, Coca Cola, Fdn Casa Risparmio Bologna, Leica, Manutencoop, Redwall, Takeda Italia Famaceutici DE intraepithelial neoplasia; phase II/III clinical trials; risk biomarkers RP Kelloff, GJ (reprint author), NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,EXECUT PLAZA N,SUITE 201,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82453-7 J9 INT CONGR SER PY 1996 VL 1120 BP 75 EP 92 PG 18 WC Oncology SC Oncology GA BG95Q UT WOS:A1996BG95Q00009 ER PT J AU Masoliver, J Weiss, GH AF Masoliver, J Weiss, GH TI Resolution in time of two electrophoretic peaks SO SEPARATION SCIENCE AND TECHNOLOGY LA English DT Article AB The question of whether a gel gradient can improve the resolvability of two peaks by means of gel electrophoresis is studied. The criterion used is the time to a specific resolution, defined as the time to the appearance of a minimum in the concentration profile between the peaks. Although the analysis is phrased in terms of gel electrophoresis, it is more generally applicable to other separation techniques. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP Masoliver, J (reprint author), UNIV BARCELONA,DEPT FIS FONAMENTAL,DIAGONAL 647,E-08028 BARCELONA,SPAIN. RI Masoliver, Jaume/F-7198-2016 OI Masoliver, Jaume/0000-0002-5810-879X NR 6 TC 2 Z9 2 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0149-6395 J9 SEPAR SCI TECHNOL JI Sep. Sci. Technol. PY 1996 VL 31 IS 3 BP 319 EP 326 DI 10.1080/01496399608000698 PG 8 WC Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA TY651 UT WOS:A1996TY65100002 ER PT J AU Jones, DH Griffith, JC Maddox, JW Willmering, B AF Jones, DH Griffith, JC Maddox, JW Willmering, B TI Using the RFP process to select a serials vendor: A work in progress SO SERIALS LIBRARIAN LA English DT Proceedings Paper CT Proceedings of the 10th Anniversary Conference of the North-American-Serials-Interest-Group CY JUN 01-04, 1996 CL DUKE UNIVERSITY, DURHAM, NC SP N Amer Serials Interest Grp HO DUKE UNIVERSITY AB In this workshop, two librarians and a vendor described, and discussed the Request for Proposal (RFP) process to serials acquisitions librarians and vendor representatives. The format of the workshop followed the process of an actual RFP,beginning with the planning stage, the drafting of the request document, the submission to sources, the receipt by the solicited vendors, the preparation of a response, the evaluation, and the actual award. The central theme of the workshop was the contrast between the formal Request for Proposal (RFP) and the informal RFP. The formal RFP is usually mandated by law or by institutional regulations and always involves a Purchasing Department or Contracting Office outside the library, The informal RFP is not required by institutional or governmental regulations and is administered totally within the library. C1 NATL LIB MED,SERIALS RECORD SECT,BETHESDA,MD. RP Willmering, B (reprint author), NATL LIB MED,SERIALS RECORD SECT,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 SN 0361-526X J9 SERIALS LIBR JI Ser. Libr. PY 1996 VL 28 IS 3-4 BP 325 EP 329 DI 10.1300/J123v28n03_18 PG 5 WC Information Science & Library Science SC Information Science & Library Science GA WK640 UT WOS:A1996WK64000018 ER PT J AU Kaufman, D AF Kaufman, D TI Introduction - A tribute to Bruce Chabner SO STEM CELLS LA English DT Item About an Individual C1 NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. RP Kaufman, D (reprint author), JACKSON CLIN,JACKSON,TN, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JAN PY 1996 VL 14 IS 1 BP 3 EP 4 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA TR729 UT WOS:A1996TR72900002 ER PT J AU Chu, E Grem, JL Johnston, PG Allegra, CJ AF Chu, E Grem, JL Johnston, PG Allegra, CJ TI New concepts for the development and use of antifolates SO STEM CELLS LA English DT Article; Proceedings Paper CT Chabner Symposium CY APR 07, 1995 CL NCI, BETHESDA, MD SP NCI HO NCI DE antifolates; thymidylate synthase; enzyme regulation; monoclonal antibodies; immunohistochemistry; interferon; biochemical modulation ID HUMAN THYMIDYLATE SYNTHASE; HIGH-DOSE LEUCOVORIN; INTERFERON ALFA-2A; COLON-CANCER; FLUOROURACIL; CELLS; 5-FLUOROURACIL; CARCINOMA; SYNTHETASE; INHIBITION AB Approximately one-third of all cases of colorectal carcinoma present in an advanced and, therefore, incurable stage, For these patients, the development of new chemotherapeutic strategies is of central importance. Biochemical modulation of 5-fluorouracil (5-FU) has resulted in approximately a two-fold increase in activity of 5-FU, Recent preclinical investigations suggest that interferon can also modulate the activity of 5-FU and may result in enhanced response rates in patients, One of the critical mechanisms of resistance to 5-FU appears to be the acute induction in thymidylate synthase (TS) levels following therapy with inhibitors of this enzyme, This mechanism is based on a novel autoregulatory feedback pathway wherein the TS protein regulates its own translational efficiency. Regulatory function of the enzyme is dependent on its state of occupancy by either the physiologic ligands or inhibitors, including fluoropyrimidines and antifolates. Ongoing efforts are directed towards utilizing knowledge of this protein/messenger RNA interaction for therapeutic benefit, Given the importance of TS, our laboratory has developed antibodies capable of quantitating the levels of this enzyme in fresh or paraffin-embedded tissues, preliminary investigations suggest that the level of TS has prognostic importance in patients with rectal carcinoma and may be used to predict responsiveness to fluoropyrimidine agents, Novel strategies utilizing dual modulation of 5-FU with leucovorin and interferon are under investigation in both the advanced and adjuvant disease settings. Emerging mechanistic concepts regarding TS, along with the development of new, more potent inhibitors will hopefully result in future therapeutic gains. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. NR 20 TC 19 Z9 19 U1 0 U2 1 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JAN PY 1996 VL 14 IS 1 BP 41 EP 46 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA TR729 UT WOS:A1996TR72900010 PM 8820950 ER PT J AU Bates, SE Wilson, WH Fojo, AT Alvarez, M Zhan, Z Regis, J Robey, R Hose, C Monks, A Kang, YK Chabner, B AF Bates, SE Wilson, WH Fojo, AT Alvarez, M Zhan, Z Regis, J Robey, R Hose, C Monks, A Kang, YK Chabner, B TI Clinical reversal of multidrug resistance SO STEM CELLS LA English DT Article; Proceedings Paper CT Chabner Symposium CY APR 07, 1995 CL NCI, BETHESDA, MD SP NCI HO NCI DE multidrug resistance; P-glycoprotein; lymphoma; chemotherapy; antagonist; verapamil ID P-GLYCOPROTEIN EXPRESSION; TUMOR-CELL LINES; PHASE-I TRIAL; DRUG-RESISTANCE; ACUTE-LEUKEMIA; HUMAN CANCER; CYCLOSPORINE; VERAPAMIL; ETOPOSIDE; CHEMOTHERAPY AB Reversal of drug resistance offers the hope of increasing the efficacy of conventional chemotherapy, We tested dexverapamil as a P-glgcoprotein antagonist in combination with EPOCH chemotherapy in refractory non-Hodgkin's lymphoma, In a cross-over design, dexverapamil was added to EPOCH after disease stabilization or progression occurred, Objective responses were observed in 10 of 11 assessable patients, Biopsies for mdr-1 were obtained before EPOCH treatment and at the time of cross-over to dexverapamil, Levels of mdr-1 were low before EPOCH, but increased four-fold or more in 42% of patients in whom serial samples were obtained, Pharmacokinetic analysis revealed median peak concentrations of dexverapamil and its metabolite, nor-dexverapamil, of 1.65 mu mol/l and 1.58 mu mol/l, respectively, Since both are comparable antagonists, a median peak total reversing concentration of 3.24 mu mol/l was achieved, Pharmacokinetic analysis of doxorubicin and etoposide levels confirmed a delay in the clearance of doxoruhicin ranging from 5% to 24%; no change in the pharmacokinetics of etoposide was observed, This study provides sufficient rationale for testing dexverapamil in a randomized clinical trial. RP Bates, SE (reprint author), NCI,MED BRANCH,DIV CANC TREATMENT,BLDG 10,12N226,BETHESDA,MD 20892, USA. RI Scala, Stefania/K-1380-2016 OI Scala, Stefania/0000-0001-9524-2616 NR 31 TC 32 Z9 33 U1 0 U2 1 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JAN PY 1996 VL 14 IS 1 BP 56 EP 63 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA TR729 UT WOS:A1996TR72900012 PM 8820952 ER PT J AU Reed, E AF Reed, E TI Closing remarks SO STEM CELLS LA English DT Editorial Material DE cancer treatment; drug development RP Reed, E (reprint author), NCI,CLIN PHARMACOL BRANCH,MED OVARIAN CANC SECT,BLDG 10,ROOM 12C103,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JAN PY 1996 VL 14 IS 1 BP 64 EP 65 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA TR729 UT WOS:A1996TR72900013 ER PT B AU Thoma, GR AF Thoma, GR BE Sethi, IK Jain, RC TI Virtual digital library SO STORAGE AND RETRIEVAL FOR STILL IMAGE AND VIDEO DATABASES IV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Storage and Retrieval for Still Image and Video Databases IV CY FEB 01-02, 1996 CL SAN JOSE, CA SP Soc Imaging Sci & Technol, Soc Photo Opt Instrumentat Engineers DE virtual library; document image transmission; way image archive; mixed text/image database; multisocket transmission C1 NATL LIB MED,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2044-1 J9 P SOC PHOTO-OPT INS PY 1996 VL 2670 BP 88 EP 93 DI 10.1117/12.234786 PG 6 WC Computer Science, Information Systems; Optics SC Computer Science; Optics GA BF18L UT WOS:A1996BF18L00009 ER PT B AU Long, LR Berman, LE Thoma, GR AF Long, LR Berman, LE Thoma, GR BE Sethi, IK Jain, RC TI A prototype client/server application for biomedical text/image retrieval on the Internet SO STORAGE AND RETRIEVAL FOR STILL IMAGE AND VIDEO DATABASES IV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Storage and Retrieval for Still Image and Video Databases IV CY FEB 01-02, 1996 CL SAN JOSE, CA SP Soc Imaging Sci & Technol, Soc Photo Opt Instrumentat Engineers DE medical; database; client/server; Internet; information; informatics C1 NATL LIB MED,BETHESDA,MD 20894. NR 0 TC 2 Z9 2 U1 0 U2 1 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2044-1 J9 P SOC PHOTO-OPT INS PY 1996 VL 2670 BP 362 EP 372 DI 10.1117/12.234775 PG 11 WC Computer Science, Information Systems; Optics SC Computer Science; Optics GA BF18L UT WOS:A1996BF18L00033 ER PT B AU Goldstein, DS Pacak, K Kopin, IJ AF Goldstein, DS Pacak, K Kopin, IJ BE McCarty, R Aguilera, G Sabban, EL Kvetnansky, R TI Nonspecificity versus primitive specificity of stress responses SO STRESS - MOLECULAR GENETIC AND NEUROBIOLOGICAL ADVANCES, VOLS 1 AMD 2 LA English DT Proceedings Paper CT 6th International Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 19-24, 1995 CL SMOLENICE CASTLE, SMOLENICE, SLOVAKIA SP Boehringer Mannheim GmbH, NICHHD, Nippon Zoki Pharm Co Ltd, Slovak Acad Sci, Solvay Duphar B V, Wakunaga Pharm Co Ltd HO SMOLENICE CASTLE RP Goldstein, DS (reprint author), NINCDS,NATL INST HLTH,BLDG 10,ROOM 6N252,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 11 Z9 12 U1 0 U2 0 PU HARWOOD ACADEMIC PUBL GMBH PI CHUR PA POSTSTRASSE 22, 7000 CHUR, SWITZERLAND BN 90-5702-520-5 PY 1996 BP 3 EP 20 PG 18 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences & Neurology GA BH67T UT WOS:A1996BH67T00001 ER PT B AU Pacak, K Makino, S Palkovits, M Kvetnansky, R Kopin, IJ Goldstein, DS AF Pacak, K Makino, S Palkovits, M Kvetnansky, R Kopin, IJ Goldstein, DS BE McCarty, R Aguilera, G Sabban, EL Kvetnansky, R TI Immobilization-induced norepinephrine release in the paraventricular nucleus and the central nucleus of the amygdala: Association with corticotropin-releasing hormone gene expression SO STRESS - MOLECULAR GENETIC AND NEUROBIOLOGICAL ADVANCES, VOLS 1 AMD 2 LA English DT Proceedings Paper CT 6th International Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 19-24, 1995 CL SMOLENICE CASTLE, SMOLENICE, SLOVAKIA SP Boehringer Mannheim GmbH, NICHHD, Nippon Zoki Pharm Co Ltd, Slovak Acad Sci, Solvay Duphar B V, Wakunaga Pharm Co Ltd HO SMOLENICE CASTLE RP Pacak, K (reprint author), NINCDS,NATL INST HLTH,BLDG 10,ROOM 5N214,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HARWOOD ACADEMIC PUBL GMBH PI CHUR PA POSTSTRASSE 22, 7000 CHUR, SWITZERLAND BN 90-5702-520-5 PY 1996 BP 49 EP 66 PG 18 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences & Neurology GA BH67T UT WOS:A1996BH67T00003 ER PT B AU Smith, MA Makino, S Michelson, D Altemus, M Kvetnansky, R Post, RM AF Smith, MA Makino, S Michelson, D Altemus, M Kvetnansky, R Post, RM BE McCarty, R Aguilera, G Sabban, EL Kvetnansky, R TI Neurotrophin-3 and brain-derived neurotrophic factor expression in the locus coeruleus: Differential regulation by stress, antidepressants and electroconvulsive seizures SO STRESS - MOLECULAR GENETIC AND NEUROBIOLOGICAL ADVANCES, VOLS 1 AMD 2 LA English DT Proceedings Paper CT 6th International Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 19-24, 1995 CL SMOLENICE CASTLE, SMOLENICE, SLOVAKIA SP Boehringer Mannheim GmbH, NICHHD, Nippon Zoki Pharm Co Ltd, Slovak Acad Sci, Solvay Duphar B V, Wakunaga Pharm Co Ltd HO SMOLENICE CASTLE RP Smith, MA (reprint author), NIMH,BIOL PSYCHOL BRANCH,BLDG 10,ROOM 3N212,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HARWOOD ACADEMIC PUBL GMBH PI CHUR PA POSTSTRASSE 22, 7000 CHUR, SWITZERLAND BN 90-5702-520-5 PY 1996 BP 121 EP 134 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences & Neurology GA BH67T UT WOS:A1996BH67T00007 ER PT B AU Aguilera, G RabadanDiehl, C Luo, X Kiss, A AF Aguilera, G RabadanDiehl, C Luo, X Kiss, A BE McCarty, R Aguilera, G Sabban, EL Kvetnansky, R TI Regulation of pituitary ACTH secretion during stress: Role of corticotropin releasing hormone and vasopressin SO STRESS - MOLECULAR GENETIC AND NEUROBIOLOGICAL ADVANCES, VOLS 1 AMD 2 LA English DT Proceedings Paper CT 6th International Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 19-24, 1995 CL SMOLENICE CASTLE, SMOLENICE, SLOVAKIA SP Boehringer Mannheim GmbH, NICHHD, Nippon Zoki Pharm Co Ltd, Slovak Acad Sci, Solvay Duphar B V, Wakunaga Pharm Co Ltd HO SMOLENICE CASTLE RP Aguilera, G (reprint author), NICHHD,SECT ENDOCRINE PHYSIOL,DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262,10 CTR DR MSC1862,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU HARWOOD ACADEMIC PUBL GMBH PI CHUR PA POSTSTRASSE 22, 7000 CHUR, SWITZERLAND BN 90-5702-520-5 PY 1996 BP 385 EP 399 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences & Neurology GA BH67T UT WOS:A1996BH67T00030 ER PT B AU Nielsen, DA Schuebel, KE Nakhai, B Hall, FS Raskin, JS Giblin, B Ellison, J Jenkins, GL Akhtar, L Virkkunen, M Linnoila, M Goldman, D AF Nielsen, DA Schuebel, KE Nakhai, B Hall, FS Raskin, JS Giblin, B Ellison, J Jenkins, GL Akhtar, L Virkkunen, M Linnoila, M Goldman, D BE McCarty, R Aguilera, G Sabban, EL Kvetnansky, R TI Behavioral and genetic studies on tryptophan hydroxylase and the serotonin receptor 5-HT1A genes SO STRESS - MOLECULAR GENETIC AND NEUROBIOLOGICAL ADVANCES, VOLS 1 AMD 2 LA English DT Proceedings Paper CT 6th International Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 19-24, 1995 CL SMOLENICE CASTLE, SMOLENICE, SLOVAKIA SP Boehringer Mannheim GmbH, NICHHD, Nippon Zoki Pharm Co Ltd, Slovak Acad Sci, Solvay Duphar B V, Wakunaga Pharm Co Ltd HO SMOLENICE CASTLE RP Nielsen, DA (reprint author), NIAAA,MOL GENET SECT,NIH,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. RI Nielsen, David/B-4655-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HARWOOD ACADEMIC PUBL GMBH PI CHUR PA POSTSTRASSE 22, 7000 CHUR, SWITZERLAND BN 90-5702-520-5 PY 1996 BP 695 EP 709 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences & Neurology GA BH67T UT WOS:A1996BH67T00054 ER PT B AU Goldstein, DS AF Goldstein, DS BE McCarty, R Aguilera, G Sabban, EL Kvetnansky, R TI Stress, catecholamines, and cardiovascular disease SO STRESS - MOLECULAR GENETIC AND NEUROBIOLOGICAL ADVANCES, VOLS 1 AMD 2 LA English DT Proceedings Paper CT 6th International Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 19-24, 1995 CL SMOLENICE CASTLE, SMOLENICE, SLOVAKIA SP Boehringer Mannheim GmbH, NICHHD, Nippon Zoki Pharm Co Ltd, Slovak Acad Sci, Solvay Duphar B V, Wakunaga Pharm Co Ltd HO SMOLENICE CASTLE RP Goldstein, DS (reprint author), NINCDS,NIH,BLDG 10,ROOM 6N252,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU HARWOOD ACADEMIC PUBL GMBH PI CHUR PA POSTSTRASSE 22, 7000 CHUR, SWITZERLAND BN 90-5702-520-5 PY 1996 BP 833 EP 862 PG 30 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences & Neurology GA BH67T UT WOS:A1996BH67T00067 ER PT B AU Eisenhofer, G Pacak, K Goldstein, DS McCarty, R AF Eisenhofer, G Pacak, K Goldstein, DS McCarty, R BE McCarty, R Aguilera, G Sabban, EL Kvetnansky, R TI Neuronal uptake and sympathoadrenal release of catecholamines in aged rats SO STRESS - MOLECULAR GENETIC AND NEUROBIOLOGICAL ADVANCES, VOLS 1 AMD 2 LA English DT Proceedings Paper CT 6th International Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 19-24, 1995 CL SMOLENICE CASTLE, SMOLENICE, SLOVAKIA SP Boehringer Mannheim GmbH, NICHHD, Nippon Zoki Pharm Co Ltd, Slovak Acad Sci, Solvay Duphar B V, Wakunaga Pharm Co Ltd HO SMOLENICE CASTLE RP Eisenhofer, G (reprint author), NINCDS,CLIN NEUROSCI BRANCH,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU HARWOOD ACADEMIC PUBL GMBH PI CHUR PA POSTSTRASSE 22, 7000 CHUR, SWITZERLAND BN 90-5702-520-5 PY 1996 BP 949 EP 965 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Neurosciences & Neurology GA BH67T UT WOS:A1996BH67T00074 ER PT J AU Crouse, JR Goldbourt, U Evans, G Pinsky, J Sharrett, AR Sorlie, P Riley, W Heiss, G AF Crouse, JR Goldbourt, U Evans, G Pinsky, J Sharrett, AR Sorlie, P Riley, W Heiss, G TI Risk factors and segment-specific carotid arterial enlargement in the atherosclerosis risk in communities (ARIC) cohort SO STROKE LA English DT Article DE arteriosclerosis; carotid arteries; risk factors; ultrasonics ID CIGARETTE SMOKERS; CORONARY ATHEROSCLEROSIS; DISEASE; ULTRASOUND; POPULATION; STENOSIS; ASSOCIATIONS; DETERMINANTS; CHOLESTEROL; PROGRESSION AB Background and Purpose B-mode ultrasound imaging affords the opportunity to quantify both intimal-medial thickness (IMT) and lumen diameter of extracranial carotid arteries in ambulatory populations. Since the relation of IMT to lumen diameter may be complex, we asked whether cardiovascular disease risk factors (previously shown to be associated with greater arterial IMT) are related to smaller lumen diameters. Methods We used B-mode ultrasound to quantify lumen diameter, interadventitial diameter, and IMT of the extracranial carotid arteries and assessed the relationship of these measures to body mass index, smoking, low-density lipoprotein (LDL) and high-density lipoprotein cholesterol, hypertension, and diabetes in 6088 male and 7493 female participants in the Atherosclerosis Risk in Communities (ARIC) cohort. Results Smoking, hypertension, and LDL cholesterol were consistently related to greater IMT in the common and internal carotid arteries of men and women, as has been previously reported. In the internal carotid artery: smoking, hypertension, and LDL cholesterol were consistently related to smaller lumens. In the common carotid artery, body mass index, smoking, and hypertension were related to significantly larger, and LDL cholesterol to smaller, lumens. Thus, only LDL cholesterol was consistently associated with smaller lumens in both the common and internal carotid arteries. Conclusions Risk factors relate positively to IMT in both the common and internal carotid arteries and inversely with lumen diameter in the internal carotid artery, in parallel with their relation to clinical events. However. their association with lumen diameters of the common carotid artery in population-based samples is more complex, and in some cases adverse levels of risk factors map be associated with larger lumens. C1 NHLBI,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC. RP Crouse, JR (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55018, N01-HC-55016] NR 42 TC 142 Z9 142 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1996 VL 27 IS 1 BP 69 EP 75 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TN254 UT WOS:A1996TN25400014 PM 8553406 ER PT J AU Takahashi, H Kirsch, JR Hashimoto, K London, ED Traystman, RJ AF Takahashi, H Kirsch, JR Hashimoto, K London, ED Traystman, RJ TI The sigma ligand (+)-pentazocine decreases brain injury following transient focal ischemia in rat. SO STROKE LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. NIDA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1996 VL 27 IS 1 BP 140 EP 140 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TN254 UT WOS:A1996TN25400184 ER PT J AU Wasserman, E AF Wasserman, E TI AHA affiliates fund 1166 new research awards SO STROKE LA English DT News Item RP Wasserman, E (reprint author), NINDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,BLDG 10,ROOM 5N226,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1996 VL 27 IS 1 BP A18 EP A18 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TN254 UT WOS:A1996TN25400211 ER PT S AU Wess, J Blin, N Yun, J Schoneberg, T Liu, J AF Wess, J Blin, N Yun, J Schoneberg, T Liu, J BE Schwartz, TW Hjorth, SA Kastrup, JS TI G protein-coupled receptors: Structural basis of receptor assembly and G protein recognition SO STRUCTURE AND FUNCTION OF 7TM RECEPTORS SE ALFRED BENZON SYMPOSIUM SERIES LA English DT Proceedings Paper CT Symposium on Structure and Function of 7TM Receptors CY JUN 11-15, 1995 CL ROYAL DANISH ACAD SCI & LETT, COPENHAGEN, DENMARK SP Alfred Benzon Fdn HO ROYAL DANISH ACAD SCI & LETT C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD PI COPENHAGEN K PA 35 NORRE SOGADE POSTBOX 2148, DK-1016 COPENHAGEN K, DENMARK SN 0105-3639 BN 87-16-11603-8 J9 ALFRED BENZON SYMP S PY 1996 VL 39 BP 43 EP 56 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BF83Y UT WOS:A1996BF83Y00003 ER PT S AU Devane, WA AF Devane, WA BE Schwartz, TW Hjorth, SA Kastrup, JS TI Cannabinoid receptors and anandamide - An endogenous cannabimimetic ligand SO STRUCTURE AND FUNCTION OF 7TM RECEPTORS SE ALFRED BENZON SYMPOSIUM SERIES LA English DT Proceedings Paper CT Symposium on Structure and Function of 7TM Receptors CY JUN 11-15, 1995 CL ROYAL DANISH ACAD SCI & LETT, COPENHAGEN, DENMARK SP Alfred Benzon Fdn HO ROYAL DANISH ACAD SCI & LETT C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MUNKSGAARD PI COPENHAGEN K PA 35 NORRE SOGADE POSTBOX 2148, DK-1016 COPENHAGEN K, DENMARK SN 0105-3639 BN 87-16-11603-8 J9 ALFRED BENZON SYMP S PY 1996 VL 39 BP 317 EP 325 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BF83Y UT WOS:A1996BF83Y00021 ER PT J AU Leshner, AI AF Leshner, AI TI Toward the Year 2000 SO SUBSTANCE USE & MISUSE LA English DT Editorial Material ID DOPAMINE TRANSPORTER; FOLLOW-UP; CLONING; EXPRESSION; RECEPTOR; CDNA RP Leshner, AI (reprint author), NIDA,NIH,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 1996 VL 31 IS 2 BP 207 EP 213 DI 10.3109/10826089609045808 PG 7 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA UD343 UT WOS:A1996UD34300005 PM 8834008 ER PT S AU Wise, SP AF Wise, SP BE Luders, HO TI Corticospinal efferents of the supplementary sensorimotor area in relation to the primary motor area SO SUPPLEMENTARY SENSORIMOTOR AREA SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 1994 Satellite Symposium on the Supplementary Motor Area CY MAY, 1994 CL CLEVELAND, OH ID ADJACENT CINGULATE CORTEX; SPINAL-CORD; MACAQUE MONKEY; CORTICAL PROJECTIONS; FRONTAL-LOBE; INTRACORTICAL MICROSTIMULATION; RETICULAR-FORMATION; PREMOTOR CORTEX; MESIAL AREA-6; NEURONS RP Wise, SP (reprint author), NIMH, NEUROPHYSIOL LAB, POOLESVILLE, MD 20837 USA. NR 62 TC 16 Z9 16 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 USA SN 0091-3952 BN 0-7817-0268-2 J9 ADV NEUROL JI Adv.Neurol. PY 1996 VL 70 BP 57 EP 69 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE52N UT WOS:A1996BE52N00005 PM 8615231 ER PT S AU Wise, SP AF Wise, SP BE Luders, HO TI Evolutionary and comparative neurobiology of the supplementary sensorimotor area SO SUPPLEMENTARY SENSORIMOTOR AREA SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 1994 Satellite Symposium on the Supplementary Motor Area CY MAY, 1994 CL CLEVELAND, OH ID CAT MOTOR CORTEX; ADJACENT CINGULATE CORTEX; CEREBRAL BLOOD-FLOW; MACAQUE MONKEY; RHESUS-MONKEY; INTRACORTICAL MICROSTIMULATION; CORTICOSPINAL PROJECTIONS; SOMATOTOPIC ORGANIZATION; HORSERADISH-PEROXIDASE; ELECTRICAL-STIMULATION RP Wise, SP (reprint author), NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837, USA. NR 132 TC 16 Z9 16 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 0091-3952 BN 0-7817-0268-2 J9 ADV NEUROL JI Adv.Neurol. PY 1996 VL 70 BP 71 EP 83 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE52N UT WOS:A1996BE52N00006 PM 8615232 ER PT S AU Hallett, M Toro, C AF Hallett, M Toro, C BE Luders, HO TI Generation of movement-related potentials in the supplementary sensorimotor area SO SUPPLEMENTARY SENSORIMOTOR AREA SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 1994 Satellite Symposium on the Supplementary Motor Area CY MAY, 1994 CL CLEVELAND, OH ID PRIMARY MOTOR CORTEX; CEREBRAL BLOOD-FLOW; VOLUNTARY MOVEMENTS; FINGER MOVEMENTS; SCALP; FIELDS; TOPOGRAPHY; STIMULATION; NERVE RP Hallett, M (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892, USA. NR 20 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 0091-3952 BN 0-7817-0268-2 J9 ADV NEUROL JI Adv.Neurol. PY 1996 VL 70 BP 147 EP 152 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE52N UT WOS:A1996BE52N00012 PM 8615195 ER PT S AU Hallett, M Toro, C AF Hallett, M Toro, C BE Luders, HO TI Dystonia and the supplementary sensorimotor area SO SUPPLEMENTARY SENSORIMOTOR AREA SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 1994 Satellite Symposium on the Supplementary Motor Area CY MAY, 1994 CL CLEVELAND, OH ID SOMATOSENSORY-EVOKED-POTENTIALS; POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; PARKINSONS-DISEASE; IDIOPATHIC DYSTONIA; MEDIAN NERVE; MOTOR AREA; ACTIVATION; SCALP; APOMORPHINE RP Hallett, M (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892, USA. NR 31 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 0091-3952 BN 0-7817-0268-2 J9 ADV NEUROL JI Adv.Neurol. PY 1996 VL 70 BP 471 EP 476 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE52N UT WOS:A1996BE52N00042 PM 8615228 ER PT S AU Marsden, CD Deecke, L Freund, HJ Hallett, M Passingham, RE Shibasaki, H Tanji, J Wiesendanger, M AF Marsden, CD Deecke, L Freund, HJ Hallett, M Passingham, RE Shibasaki, H Tanji, J Wiesendanger, M BE Luders, HO TI The functions of the supplementary motor area - Summary of a workshop SO SUPPLEMENTARY SENSORIMOTOR AREA SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 1994 Satellite Symposium on the Supplementary Motor Area CY MAY, 1994 CL CLEVELAND, OH ID ADJACENT CINGULATE CORTEX; MONKEY GLOBUS-PALLIDUS; PREMOTOR CORTEX; NEURONAL-ACTIVITY; MACAQUE MONKEY; SEQUENTIAL MOVEMENTS; PARKINSONS-DISEASE; CORTICAL AREAS; MESIAL AREA-6; SMA C1 UNIV VIENNA, UNIV HOSP NEUROL, A-1090 VIENNA, AUSTRIA. UNIV DUSSELDORF, DEPT NEUROL, D-40225 DUSSELDORF, GERMANY. NIH, NINDS, BETHESDA, MD 20892 USA. UNIV OXFORD, DEPT EXPTL PSYCHOL, OXFORD OX1 3UD, ENGLAND. KYOTO UNIV, SCH MED, DEPT BRAIN PATHOPHYSIOL, KYOTO 60601, JAPAN. TOHOKU UNIV, SCH MED, DEPT PHYSIOL, SENDAI, MIYAGI 980, JAPAN. UNIV HOSP BERN, DEPT NEUROL, CH-3010 BERN, SWITZERLAND. RP UCL NATL HOSP NEUROL & NEUROSURG, INST NEUROL, LONDON WC1N 3BG, ENGLAND. NR 45 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 USA SN 0091-3952 BN 0-7817-0268-2 J9 ADV NEUROL JI Adv.Neurol. PY 1996 VL 70 BP 477 EP 487 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE52N UT WOS:A1996BE52N00043 PM 8615229 ER PT S AU Wise, SP Fried, I Olivier, A Paus, T Rizzolatti, G Zilles, KJ AF Wise, SP Fried, I Olivier, A Paus, T Rizzolatti, G Zilles, KJ BE Luders, HO TI Workshop on the anatomic definition and boundaries of the supplementary sensorimotor area SO SUPPLEMENTARY SENSORIMOTOR AREA SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 1994 Satellite Symposium on the Supplementary Motor Area CY MAY, 1994 CL CLEVELAND, OH ID ADJACENT CINGULATE CORTEX; ELECTRICAL-STIMULATION; MACAQUE MONKEY; RHESUS-MONKEY; MOTOR AREA; INTRACORTICAL MICROSTIMULATION; SOMATOTOPIC ORGANIZATION; CORTICAL CONNECTIONS; FRONTAL-CORTEX; MESIAL AREA-6 C1 UNIV CALIF LOS ANGELES,SCH MED,SECT PSYCHIAT & BEHAV SCI,DEPT SURG,LOS ANGELES,CA 90095. MCGILL UNIV,MONTREAL NEUROL HOSP & INST,DIV NEUROSURG,MONTREAL,PQ H3A 2B4,CANADA. MCGILL UNIV,MONTREAL NEUROL HOSP & INST,DIV NEUROPHYSIOL,MONTREAL,PQ H3A 2B4,CANADA. UNIV PARMA,INST HUMAN PHYSIOL,I-43100 PARMA,ITALY. UNIV DUSSELDORF,INST BRAIN RES,D-40225 DUSSELDORF,GERMANY. RP Wise, SP (reprint author), NIMH,NEUROPSYCHOL LAB,POOLESVILLE,MD 20837, USA. RI Zilles, Karl/J-9704-2013 OI Zilles, Karl/0000-0001-9296-9959 NR 20 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 0091-3952 BN 0-7817-0268-2 J9 ADV NEUROL JI Adv.Neurol. PY 1996 VL 70 BP 489 EP 495 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE52N UT WOS:A1996BE52N00044 PM 8615230 ER PT J AU Cadet, JL Bolla, KI AF Cadet, JL Bolla, KI TI Chronic cocaine use as a neuropsychiatric syndrome: A model for debate SO SYNAPSE LA English DT Article DE behavioral neurology; affective states; attention; memory ID POSITRON EMISSION TOMOGRAPHY; BIOCHEMICAL MANIFESTATIONS; AFFECTIVE-ILLNESS; METABOLIC RATES; POLYDRUG USERS; DEPRESSION; DOPAMINE; STROKE; DISEASE; ABUSE AB In humans, chronic cocaine abuse is associated with changes in the central nervous system (CNS). Neuropathological changes include cerebrovascular events, EEG abnormalities, vasculitis, seizures, and decrements in neurobehavioral performance. The acute administration of cocaine is associated with acute psychotic episodes and paranoid states while withdrawal from the drug is often associated with depressed mood. The mechanistic basis of these behavioral states is not known. Given the structural and functional changes associated with cocaine use, we propose that the chronic heavy use of cocaine may result in a neuropsychiatric syndrome which might be associated with neuropsychological changes that are not obvious during routine clinical evaluation of drug-using individuals. This disconnection syndrome, because of its sublety, might have deleterious effects on both acute and long-term therapeutic interventions with these subjects. An approach which deals with cocaine abuse as a neuropsychiatric disorder might be more beneficial to the long-term goal of treating these patients. This approach entails a neurobehavioral evaluation which will be comprised of a thorough neurological and psychiatric examination, neuropsychological testing, and imaging studies. The results of this evaluation would provide a more rational basis for cognitive and/or pharmacological therapies. (C) 1996 Wiley-Liss, Inc. C1 JOHNS HOPKINS MED INST,DEPT NEUROL,BALTIMORE,MD 21224. RP Cadet, JL (reprint author), NIH,NIDA,INTRAMURAL RES PROGRAM,MOLEC NEUROPSYCHIAT SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 76 TC 14 Z9 14 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD JAN PY 1996 VL 22 IS 1 BP 28 EP 34 DI 10.1002/(SICI)1098-2396(199601)22:1<28::AID-SYN3>3.3.CO;2-K PG 7 WC Neurosciences SC Neurosciences & Neurology GA TM499 UT WOS:A1996TM49900003 PM 8822475 ER PT J AU Pilotte, NS Sharpe, LG Rountree, SD Kuhar, MJ AF Pilotte, NS Sharpe, LG Rountree, SD Kuhar, MJ TI Cocaine withdrawal reduces dopamine transporter binding in the shell of the nucleus accumbens SO SYNAPSE LA English DT Article DE [I-125]RTI-121; mesolimbic pathways; cocaine; withdrawal ID BRAIN REWARD REGIONS; EXTRACELLULAR DOPAMINE; VENTRAL STRIATUM; RAT-BRAIN; NEURONS; ABUSERS; METABOLISM; CLEARANCE; DORSAL; SYSTEM AB We have previously shown that withdrawal from repeated, intermittent infusions of cocaine in Lewis rats results in a long-lasting reduction in dopamine transporter levels in the nucleus accumbens. The reduction is dose-dependent, requires multiple injections as well as about a 10-day withdrawal period. In this investigation, we show that the decrease (34%) occurs in the shell rather than in the core of the nucleus accumbens, and that a second cycle of cocaine administration and withdrawal has no additional effect. Also, there were no changes in transporter binding in the caudate putamen, the olfactory tubercle or the ventral tegmental area. These results indicate that the limbic portions of the nucleus accumbens are involved in neurochemical adaptations during withdrawal from cocaine. (C) 1996 Wiley-Liss, Inc. C1 NIDA,DIV INTRAMURAL RES,NEUROSCI BRANCH,NEUROSCI LABS,BALTIMORE,MD 21224. NIDA,DIV INTRAMURAL RES,MOLEC BIOL LABS,BALTIMORE,MD 21224. NR 43 TC 42 Z9 42 U1 3 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD JAN PY 1996 VL 22 IS 1 BP 87 EP 92 DI 10.1002/(SICI)1098-2396(199601)22:1<87::AID-SYN10>3.0.CO;2-X PG 6 WC Neurosciences SC Neurosciences & Neurology GA TM499 UT WOS:A1996TM49900010 PM 8822482 ER PT J AU Phillips, LR Supko, JG Wolfe, TL Malspeis, L AF Phillips, LR Supko, JG Wolfe, TL Malspeis, L TI Syntheses of 3-chloro-7-[(chlorocarbonyl)methoxy]-4-methylcoumarin SO SYNTHETIC COMMUNICATIONS LA English DT Article ID NATURAL-PRODUCTS AB Two efficient syntheses of 3-chloro-7-[(chlorocarbonyl)methoxy]-4-methylcoumarin are described, one utilizing traditional chemistry starting from 3-chloro-7-hydroxy-4-methylcoumarin, while the other uses a novel reagent, sulfuryl chloride/thionyl chloride, in a one-pot reaction starting from 7-(carboxymethoxy)-4-methylcoumarin. RP Phillips, LR (reprint author), NCI,LAB PHARMACEUT CHEM,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,FREDERICK,MD 21702, USA. NR 13 TC 0 Z9 0 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0039-7911 J9 SYNTHETIC COMMUN JI Synth. Commun. PY 1996 VL 26 IS 9 BP 1805 EP 1814 DI 10.1080/00397919608002622 PG 10 WC Chemistry, Organic SC Chemistry GA UE952 UT WOS:A1996UE95200023 ER PT J AU Jankovic, D Sher, A AF Jankovic, D Sher, A TI Initiation and regulation of CD4+ T-cell function in host-parasite models SO TH1 AND TH2 CELLS IN HEALTH AND DISEASE SE CHEMICAL IMMUNOLOGY LA English DT Review ID IFN-GAMMA; SCHISTOSOMA-MANSONI; TOXOPLASMA-GONDII; TH2 CELLS; MEDIATED-IMMUNITY; INTERFERON-GAMMA; LEISHMANIA-MAJOR; LYMPHOCYTES-T; MICE; INTERLEUKIN-4 RP Jankovic, D (reprint author), NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,NIH,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 67 TC 23 Z9 23 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1015-0145 J9 CHEM IMMUNOL JI Chem.Immunol. PY 1996 VL 63 BP 51 EP 65 PG 15 WC Immunology SC Immunology GA BF13U UT WOS:A1996BF13U00004 PM 8934831 ER PT B AU Mark, SD Wang, W Fraumeni, JF Li, JY Taylor, PR Wang, GQ Guo, W Dawsey, SM Li, B Blot, WJ AF Mark, SD Wang, W Fraumeni, JF Li, JY Taylor, PR Wang, GQ Guo, W Dawsey, SM Li, B Blot, WJ BE Neve, J Chappuis, P Lamand, M TI The effect of nutritional supplementation on stroke mortality and blood pressure - Results from the Linxian Nutritional Intervention Trials SO THERAPEUTICS USES OF TRACE ELEMENTS LA English DT Proceedings Paper CT 5th International Congress on Trace Elements in Medicine and Biology - Therapeutic Uses of Trace Elements CY FEB 04-07, 1996 CL MERIBEL, FRANCE SP French Speaking Soc Study & Res Essential Trace Elements, French Minist Foreign Affairs, Joseph Fourier Univ, Grenoble, Volv Ctr Res Trace Elements, Labcatal Lab, Montrouge, Aguettant, Analab, Becton Dickinson, Behring, BIO2, Boehringer, Boiron, Ctr Natl Biologists, Credit Lyonnais, Fisons, Fumouze, Jobin Yvon, Johnson & Johnson, Kontron, Lavoisier Tec & Doc, Lero, Les Granions, Nestle, Olympus, Perkin Elomer, Randox, Richelet, Roche Posay, Roucous, Sanofi, Servier, Spin, Varian RP Mark, SD (reprint author), NCI,BIOSTAT BRANCH,DIV CANC ETIOL,6130 EXECUT BLVD,MSC 7368,ROOM 403,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45485-8 PY 1996 BP 395 EP 402 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Nutrition & Dietetics GA BH01E UT WOS:A1996BH01E00069 ER PT B AU Kidder, LH Goldstein, SR Levin, IW Lewis, EN AF Kidder, LH Goldstein, SR Levin, IW Lewis, EN BE Cogswell, CJ Kino, GS Wilson, T TI Raman imaging microscopy: A novel chemical imaging technique SO THREE-DIMENSIONAL MICROSCOPY: IMAGE ACQUISITION AND PROCESSING III SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Three-Dimensional Microscopy - Image Acquisition and Processing III CY JAN 30-FEB 01, 1996 CL SAN JOSE, CA SP Soc Imaging Sci & Technol, Soc Photo Opt Instrumentat Engineers DE spectroscopic imaging; Raman spectroscopy; acousto-optic tunable filter; chemical imaging C1 NIDDK,NIH,PHYS CHEM LAB,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2029-8 J9 P SOC PHOTO-OPT INS PY 1996 VL 2655 BP 140 EP 147 DI 10.1117/12.237471 PG 8 WC Instruments & Instrumentation; Microscopy; Optics SC Instruments & Instrumentation; Microscopy; Optics GA BF46V UT WOS:A1996BF46V00019 ER PT J AU Gralnick, HR Kramer, WS McKeown, LP Garfinkel, L Pinot, A Williams, SB Krutzsch, H AF Gralnick, HR Kramer, WS McKeown, LP Garfinkel, L Pinot, A Williams, SB Krutzsch, H TI Platelet adhesion at high shear rates: The roles of von Willebrand factor/GPIb and the beta(1) integrin alpha(2)beta(1) SO THROMBOSIS RESEARCH LA English DT Article DE thrombosis; VLA-2; GPIb-alpha ID HUMAN VONWILLEBRAND-FACTOR; GLYCOPROTEIN-IB-IX; ARTERIAL SUBENDOTHELIUM; PROTEIN-BINDING; COLLAGEN; FRAGMENT; DOMAINS; HEPARIN AB We have previously described a monomeric rvWf fragment, Leu504-Lys728 that contains one disulfide bond linking Cys509-Cys695. This fragment, VCL, has previously been shown to inhibit vWf-ristocetin, asialo-vWf, and botrocetin-induced vWf binding and aggregation of platelets. VCL inhibited 50% of vWf binding to heparin, but it did not inhibit vWf binding to type I collagen. At a high shear force (2600(-1) sec), VCL inhibited platelet adhesion to the subendothelial surface of human umbilical arteries. The maximum inhibition of platelet adhesion was 83 +/- 4% at a VCL concentration of 7.6 mu mol/L. Various monoclonal anti-Very Late Activation antigens (VLA) antibodies were added to the VCL and tested for their ability to enhance the inhibition of platelet adhesion at high shear forces. Of all of the VLA antibodies tested, only the anti-VLA-2 antibody (176D7) inhibited platelet aggregation in the absence of VCL and enhanced the inhibition of platelet adhesion in the presence of VCL. The VLA-2 antibody and VCL together inhibited 96 +/- 4% of platelet adhesion at high shear forces. C1 BIOTECHNOL GEN LTD,REHOVOT,ISRAEL. NCI,PATHOL LAB,BETHESDA,MD 20892. RP Gralnick, HR (reprint author), NIH,CTR CLIN,HEMATOL SERV,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2C390,BETHESDA,MD 20892, USA. NR 13 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD JAN 1 PY 1996 VL 81 IS 1 BP 113 EP 119 DI 10.1016/0049-3848(95)00219-7 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA TM682 UT WOS:A1996TM68200010 PM 8747526 ER PT J AU Shiraishi, N Waalkes, MP AF Shiraishi, N Waalkes, MP TI Acquired tolerance to cadmium-induced toxicity in rodent testes SO TOXIC SUBSTANCE MECHANISMS LA English DT Article ID LOW-MOLECULAR-MASS; WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; FISCHER F344/NCR RAT; BINDING PROTEINS; CALMODULIN INHIBITORS; LIPID-PEROXIDATION; TUMOR-INDUCTION; INJECTION SITE; ASCORBIC-ACID AB The testes are clearly one of the most sensitive organs in rodents to the acute toxic effects of cadmium. Relatively high doses (e.g., greater than or equal to 5.0 mu mol/kg, sc) of parenteral cadmium will rapidly induce a massive hemorrhagic necrosis of the testes in various species. It is well known that testicular effects of cadmium can be prevented by pretreatments or concurrent treatments with various metallic as well as nonmetallic substances. In the case of metal compounds, at least 12 agents have been reported to inhibit the acute toxic effects of high-dose cadmium on the testes, including zinc, selenium, and lour-dose cadmium. Among nonmetallic substances, several compounds have been shown to reduce the degree of cadmium-induced testicular lesions to a greater or lesser extent. Such agents potentially include steroid hormones, antioxidants, and calmodulin inhibitors. A om these studies, several possible mechanisms have been proposed to explain this chemically induced tolerance. This article reviews available literature on the topic and attempts to explore the possible mechanisms of acquired resistance to cadmium in the testes. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,INORGAN CARCINOGENESIS SECT,FREDERICK,MD 21702. NR 71 TC 14 Z9 15 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 1076-9188 J9 TOX SUBST MECH JI Tox. Subst. Mech. PD JAN-MAR PY 1996 VL 15 IS 1 BP 27 EP 42 PG 16 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA VU980 UT WOS:A1996VU98000004 ER PT J AU Malarkey, DE Maronpot, RR AF Malarkey, DE Maronpot, RR TI Polymerase chain reaction and in situ hybridization: Applications in toxicological pathology SO TOXICOLOGIC PATHOLOGY LA English DT Review DE review; molecular biology; mutations; oncogenes; tumor suppressor genes; reverse transcription; gene expression; toxicology ID COMPARATIVE GENOMIC HYBRIDIZATION; H-RAS ONCOGENE; INSITU HYBRIDIZATION; MESSENGER-RNA; DIFFERENTIAL DISPLAY; POINT MUTATIONS; GENE REARRANGEMENTS; DNA-POLYMERASE; NUCLEIC-ACIDS; REACTION PCR AB Polymerase chain reaction (PCR) and in situ hybridization (ISH) have revolutionized the study of genes and gene expression, and many of these molecular biology advances will greatly impact research in toxicological pathology. PCR is one of the most powerful tools in molecular biology and involves primer-mediated enzymatic in vitro amplification of specific target DNA sequences. Recent innovative methods utilizing PCR technology have been developed to detect mutations in neoplastic and small subpopulations of cells, to study biomarkers of genetic susceptibility and genes involved with carcinogen metabolism, to estimate mutation frequencies, to find novel genes induced by chemical exposure, and to characterize gene expression. LSH provides data on individual cells rather than an average of total cellular populations and allows analysis for heterogeneity. When combined with PCR, the sensitivity of ISH is elevated, and single-copy DNA sequences, single-base mutations, or low copies of messenger RNA (mRNA) can potentially be detected within individual cells. Herein are reviewed ISH- and PCR-based techniques such as single-strand conformation polymorphism analysis to detect point mutations, allelotypic analysis for loss of heterozygosity, differential display of mRNA to characterize gene expression, quantitative reverse transcriptase polymerase chain reaction, and in situ polymerase chain reaction with emphasis on current or potential applications in toxicological pathology. These new and evolving techniques offer tremendous potential in providing new insights into the molecular basis of toxicity and carcinogenesis. RP Malarkey, DE (reprint author), NIEHS,LAB EXPTL PATHOL,ENVIRONM CARCINOGENESIS PROGRAM,MAIL DROP B3-06,RES TRIANGLE PK,NC 27709, USA. NR 109 TC 6 Z9 6 U1 1 U2 3 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 1996 VL 24 IS 1 BP 13 EP 23 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA TX633 UT WOS:A1996TX63300004 PM 8839277 ER PT J AU Thompson, MB AF Thompson, MB TI Bile acids in the assessment of hepatocellular function SO TOXICOLOGIC PATHOLOGY LA English DT Review DE cell culture; isolated hepatocytes; ursodeoxycholic acid; cholestasis; cytoprotection; hepatic processing; collagen gel ID ISOLATED RAT HEPATOCYTES; LITHOCHOLATE-INDUCED CHOLESTASIS; FRESHLY ISOLATED SUSPENSIONS; PRIMARY BILIARY-CIRRHOSIS; PLASMA-MEMBRANE FLUIDITY; URSODEOXYCHOLIC ACID; ALPHA-NAPHTHYLISOTHIOCYANATE; CANALICULAR MEMBRANE; PRIMARY CULTURES; TAUROURSODEOXYCHOLIC ACID AB Bile acids, which are synthesized in the liver from cholesterol, are important in the production of bile flow, excretion of cholesterol, and intestinal digestion and absorption of fats and fat-soluble vitamins. Increases and/or alterations in concentrations of bile acids in serum are specific and sensitive indicators of hepatobiliary disorders. Synthesis of bile acids in hepatocytes involves steps in endoplasmic reticulum, cytosol, mitochondria, and peroxisomes. Other important hepatocellular processes involving bile acids include active uptake by the basolateral membrane, intracellular transport, P-450-mediated conjugations and hydroxylations, and canalicular secretion. Hydrophobic bile acids produce hepatotoxicity in vivo and in vitro. In experimental and epidemiologic studies, some of these forms have been identified as causative agents in the development of colon and liver (experimental only) cancer. Conversely, several hydrophilic forms, primarily ursodeoxycholic acid, have demonstrated cytoprotective properties in a variety of clinical and experimental hepatobiliary diseases and disorders. Because bile acids can have dramatically different properties and effects, determination of mechanisms of action of these compounds has become an active area of research. Primary isolated hepatocytes provide an opportunity to investigate bile acid-related functions and effects in well-designed, carefully controlled studies. Short-term cultures have been used to study a variety of issues related to bile acids, including cytotoxicity, synthesis, and hepatocellular processing. With these systems, however, many functions of mature hepatocytes, including those pertaining to bile acids, can be lost when cultures are maintained for more than several days. Recent developments in culture techniques permit long-term maintenance of functionally stable, differentiated cells. Pertaining to bile acid research, these systems remain to be fully characterized but, in appropriate situations, they should provide important alternatives to in vivo studies and short-term in vitro assays. RP Thompson, MB (reprint author), NIEHS,LAB EXPTL PATHOL,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 138 TC 13 Z9 13 U1 0 U2 2 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 1996 VL 24 IS 1 BP 62 EP 71 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA TX633 UT WOS:A1996TX63300009 PM 8839282 ER PT J AU Ward, JM Shibata, M Devor, DE AF Ward, JM Shibata, M Devor, DE TI Emerging issues in mouse liver carcinogenesis SO TOXICOLOGIC PATHOLOGY LA English DT Article DE hepatocarcinogenesis; bioassay; H-ras; nongenotoxic carcinogens; cell proliferation ID B6C3F1 MICE; HEPATOCELLULAR NEOPLASMS; METHYLENE-CHLORIDE; HEPATIC-LESIONS; C3H/HENCR MICE; TARGET ORGANS; TUMOR; DIETHYLNITROSAMINE; BIOASSAYS; INDUCTION AB The mouse liver is the primary target site for carcinogenesis of more than 200 chemicals (including pesticides, food additives, pharmaceuticals, and industrial intermediates) tested in long-term toxicity safety assessment assays. Mouse liver tumors develop through defined morphological stages (similar to those found in other species) whether their origin is of undetermined etiology (spontaneous) or induced by chemicals. The morphologic type of hepatocytes in the various stages of hepatocarcinogenesis is sometimes associated with the specific inducing agent. Liver tumors developing in toxic livers often have more benign appearances and may progress to carcinomas at a slower rate than tumors developing in histologically normal livers. Specific tumors, dependent on the inducing chemical, may regress under defined protocols. Genotoxic and nongenotoxic mouse hepatocarcinogens each may induce tumors of either high malignant or low malignant potential. Liver tumors with specific H-ras oncogene mutations may appear morphologically and biologically similar to those without proven ras mutations. Thus, distinguishing mechanism of carcinogenesis by liver tumor morphology and mutation spectra may be difficult. Additionally, the presence of liver tumors with a morphology and a ms oncogene mutation spectrum characteristic of spontaneous tumors in histologically normal livers of mice exposed to a nongenotoxic test chemical may indicate promotion of spontaneous hepatocarcinogenesis by one of several potential mechanisms. Further research into the mechanisms responsible for the increased incidences of liver tumors in mice exposed to test chemicals could enhance human cancer risk assessments. RP NCI, FREDERICK CANC RES & DEV CTR, VET & TUMOR PATHOL SECT, OFF LAB ANIM SCI, FAIRVIEW 201, FREDERICK, MD 21702 USA. NR 87 TC 19 Z9 19 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 1996 VL 24 IS 1 BP 129 EP 137 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA TX633 UT WOS:A1996TX63300017 PM 8839290 ER PT J AU Kohn, MC Sewall, CH Lucier, GW Portier, CJ AF Kohn, MC Sewall, CH Lucier, GW Portier, CJ TI A mechanistic model of effects of dioxin on thyroid hormones in the rat SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID TISSUE DISTRIBUTION; CANCER MORTALITY; RISK ASSESSMENT; DOSE-RESPONSE; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; THYROXINE; TCDD; INDUCTION; LIVER; RECEPTOR AB A physiological dosimetric model of the disposition of TCDD in the rat (Kohn et al., Toxicol. Appl. Pharmacol. 120, 138-154, 1993) was extended to include effects of dioxin on serum concentrations of thyroid hormones in the rat. The extended model included distribution of blood among major vessels and tissue capillary beds and resorption of TCDD released into the gut lumen from the liver by cell lysis consequent to cytotoxicity. TCDD metabolism was represented by Hill kinetics. Parameter values were estimated by fitting time-course data for a single subcutaneous injection of TCDD and dose-response data for biweekly oral dosing. The extended model included new compartments for the thyroid and thyroxine-sensitive tissues (e.g., pituitary, kidney, and brown fat), secretion and tissue uptake of thyroid hormones, binding of 3,5,3'-triiodothyronine (T-3) and 3,5,3',5'-tetraiodothyronine (thyroxine, T-4) to proteins in blood and tissues, deiodination of iodothyronines, and glucuronidation of T-4 by the hepatic UDP-glucuronosyltransferase (UGT) activity induced by TCDD. Secretion of thyroid hormones was modeled as regulated by thyrotropin (TSH), whose secretion was modeled as regulated by the hypothalamic factors thyrotropin releasing hormone and somatostatin. Release of the hypothalamic factors was modeled as under feedback control by the blood T-4 level. Induction of UGT was modeled as stimulated by the Ah receptor-TCDD complex. The extended model fit the observed dose-response of P450 isozymes and Ah and estrogen receptors following repeated oral doses with comparable accuracy as the earlier model. The fit to liver and fat TCDD levels following single and repeated oral and subcutaneous doses was improved over the earlier model. The revised model's predicted liver TCDD concentrations at very low doses were verified experimentally. The model reproduced the responses observed for blood T-3, T-4, and TSH after 31 weeks of biweekly oral dosing of rats with TCDD. The model also predicted responses of UGT mRNA and UGT enzymatic activity comparable to those observed in TCDD-treated rats in experiments whose data were not used in constructing the model. Calculated increases in blood TSH levels are consistent with prolonged stimulation of the thyroid and may represent an early stage in the induction of thyroid tumors identified in previous two-year bioassays. Thus, increases in UGT activity may be useful as a biomarker for tumorigenic changes in hormone levels subsequent to TCDD exposure. (C) 1996 Academic Press, Inc. C1 NIEHS, BIOCHEM RISK ANAL LAB, RES TRIANGLE PK, NC 27709 USA. RP NIEHS, LAB QUANTITAT & COMPUTAT BIOL, POB 12233, RES TRIANGLE PK, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 90 TC 68 Z9 72 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 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN PY 1996 VL 136 IS 1 BP 29 EP 48 DI 10.1006/taap.1996.0004 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA TR059 UT WOS:A1996TR05900004 PM 8560478 ER PT B AU Adamson, RH Thorgeirsson, UP Sugimura, T AF Adamson, RH Thorgeirsson, UP Sugimura, T BE Seiler, JP Kroftova, O Eybl, V TI Extrapolation of heterocyclic amine carcinogenesis data from rodents and nonhuman primates to humans SO TOXICOLOGY - FROM CELLS TO MAN SE ARCHIVES OF TOXICOLOGY : SUPPLEMENT LA English DT Proceedings Paper CT 1995 EUROTOX Congress CY AUG 27-30, 1995 CL PRAGUE, CZECH REPUBLIC C1 NCI,BETHESDA,MD 20892. NR 0 TC 43 Z9 44 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY BN 3-540-60673-4 J9 ARCH TOX S PY 1996 VL 18 BP 303 EP 318 PG 16 WC Toxicology SC Toxicology GA BF73E UT WOS:A1996BF73E00029 PM 8678807 ER PT S AU Gazzinelli, RT Amichay, D ShartonKersten, T Grunwald, E Farber, JM Sher, A AF Gazzinelli, RT Amichay, D ShartonKersten, T Grunwald, E Farber, JM Sher, A BE Gross, U TI Role of macrophage-derived cytokines in the induction and regulation of cell-mediated immunity to Toxoplasma gondii SO TOXOPLASMA GONDII SE Current Topics in Microbiology and Immunology LA English DT Review ID NECROSIS-FACTOR-ALPHA; NATURAL-KILLER-CELLS; IMMUNODEFICIENCY-VIRUS INFECTION; INTERFERON-GAMMA-PRODUCTION; CD4+ T-CELLS; IFN-GAMMA; MESSENGER-RNA; MURINE TOXOPLASMOSIS; ACCESSORY CELLS; HUMAN MONOCYTES C1 NIAID, PARASIT DIS LAB, NIH, BETHESDA, MD 20892 USA. FDN OSWALDO CRUZ, CTR PESQUISAS RENE RACHOU, BR-30190002 BELO HORIZONTE, MG, BRAZIL. NIAID, CLIN INVEST LAB, NIH, BETHESDA, MD 20892 USA. RP Gazzinelli, RT (reprint author), UNIV FED MINAS GERAIS, DEPT BIOCHEM & IMMUNOL, AV ANTONIO CARLOS 6627, BR-30161970 BELO HORIZONTE, MG, BRAZIL. NR 46 TC 44 Z9 46 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-61300-5 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 219 BP 127 EP 139 PG 13 WC Immunology; Microbiology SC Immunology; Microbiology GA BJ59J UT WOS:A1996BJ59J00012 PM 8791695 ER PT J AU Read, EJ AF Read, EJ TI Quality assurance for cell processing: No more blind faith SO TRANSFUSION LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; BACTERIAL-CONTAMINATION; CLINICAL-SIGNIFICANCE RP Read, EJ (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892, USA. NR 25 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 1996 VL 36 IS 1 BP 1 EP 4 DI 10.1046/j.1537-2995.1996.36196190508.x PG 4 WC Hematology SC Hematology GA TV890 UT WOS:A1996TV89000001 PM 8607147 ER PT J AU Lenfant, C AF Lenfant, C TI NHLBI information services: A whole new world SO TRANSFUSION LA English DT Editorial Material RP Lenfant, C (reprint author), NHLBI,NIH,BLDG 31,ROOM 5A52,31 CTR DR,MSC 2486,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 1996 VL 36 IS 1 BP 82 EP 83 DI 10.1046/j.1537-2995.1996.36196203524.x PG 2 WC Hematology SC Hematology GA TV890 UT WOS:A1996TV89000014 PM 8607160 ER PT J AU Hillyer, CD Klein, HG AF Hillyer, CD Klein, HG TI Immunotherapy and gene transfer in the treatment of the oncology patient: Role of transfusion medicine SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID BONE-MARROW TRANSPLANTATION; TUMOR-INFILTRATING LYMPHOCYTES; ACTIVATED KILLER CELLS; CHRONIC MYELOGENOUS LEUKEMIA; DONOR LEUKOCYTE INFUSIONS; VERSUS-HOST DISEASE; ADOPTIVE IMMUNOTHERAPY; RECOMBINANT INTERLEUKIN-2; MONOCLONAL-ANTIBODIES; T-CELLS C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. EMORY UNIV,SCH MED,DEPT PATHOL & LAB MED,ATLANTA,GA 30322. NR 111 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 1996 VL 10 IS 1 BP 1 EP 14 DI 10.1016/S0887-7963(96)80118-0 PG 14 WC Hematology SC Hematology GA TQ020 UT WOS:A1996TQ02000001 PM 8787926 ER PT J AU Arnheiter, H Frese, M Kambadur, R Meier, E Haller, O AF Arnheiter, H Frese, M Kambadur, R Meier, E Haller, O TI Mx transgenic mice - Animal models of health SO TRANSGENIC MODELS OF HUMAN VIRAL AND IMMUNOLOGICAL DISEASE SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID INFLUENZA-VIRUS RESISTANCE; VESICULAR STOMATITIS-VIRUS; MESSENGER-RNA SYNTHESIS; MOUSE HEPATITIS-VIRUS; THOGOTO VIRUS; RHIPICEPHALUS-APPENDICULATUS; CONFERS RESISTANCE; ANTIVIRAL ACTIVITY; MURINE MX1; WILD MICE C1 UNIV FREIBURG,INST MED MIKROBIOL & HYG,DEPT VIROL,D-79104 FREIBURG,GERMANY. RP Arnheiter, H (reprint author), NINCDS,LAB DEV NEUROGENET,NIH,BLDG 36,ROOM 5D04,36 CONVENT DR,MSC 4160,BETHESDA,MD 20892, USA. RI Frese, Michael/C-2286-2009; Frese, Michael/B-3283-2014 NR 88 TC 83 Z9 88 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 206 BP 119 EP 147 PG 29 WC Immunology; Microbiology SC Immunology; Microbiology GA BF03S UT WOS:A1996BF03S00008 PM 8608714 ER PT S AU Klotman, PE Notkins, AL AF Klotman, PE Notkins, AL BE Chisari, FV Oldstone, MBA TI Transgenic models of human immunodeficiency virus type-1 SO TRANSGENIC MODELS OF HUMAN VIRAL AND IMMUNOLOGICAL DISEASE SE Current Topics in Microbiology and Immunology LA English DT Review ID LONG TERMINAL REPEAT; HIV-ASSOCIATED NEPHROPATHY; TAT GENE; KAPOSIS SARCOMA; INVIVO ACTIVATION; DERMAL LESIONS; DNA DAMAGE; MICE; EXPRESSION; CELLS C1 NIDR, NIH, BETHESDA, MD 20892 USA. RP Klotman, PE (reprint author), MT SINAI MED CTR, DIV NEPHROL, BOX 1243, NEW YORK, NY 10029 USA. NR 49 TC 29 Z9 30 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-59341-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 206 BP 197 EP 222 PG 26 WC Immunology; Microbiology SC Immunology; Microbiology GA BF03S UT WOS:A1996BF03S00011 PM 8608718 ER PT J AU Wall, RJ Rexroad, CE Powell, A Shamay, A McKnight, R Hennighausen, L AF Wall, RJ Rexroad, CE Powell, A Shamay, A McKnight, R Hennighausen, L TI Synthesis and secretion of the mouse whey acidic protein in transgenic sheep SO TRANSGENIC RESEARCH LA English DT Article DE whey acidic protein gene; transgenic sheep; bioreactor; mammary gland ID MILK PROTEIN; ALVEOLAR DEVELOPMENT; MAMMARY DEVELOPMENT; GENE PROMOTER; HYBRID GENE; EXPRESSION; MICE; LACTATION; GLANDS; PIGS AB The synthesis of foreign proteins can be targeted to the mammary gland of transgenic animals, thus permitting commercial purification of otherwise unavailable proteins from milk. Genetic regulatory elements from the mouse whey acidic protein (WAP) gene have been used successfully to direct expression of transgenes to the mammary gland of mice, goats and pigs. To extend the practical usefulness of WAP promoter-driven fusion genes and further characterize WAP expression in heterologous species, we introduced a 6.8 kb DNA fragment containing the genomic form of the mouse WAP gene into sheep zygotes. Two lines of transgenic sheep were produced. The transgene was expressed in mammary tissue of both lines and intact WAP was secreted into milk at concentrations estimated to range from 100 to 500 mg/litre. Ectopic WAP gene expression was found in salivary gland, spleen, liver lung, heart muscle, kidney and bone marrow of one founder ewe. WAP RNA was not detected in skeletal muscle and intestine. These data suggest that unlike pigs, sheep may possess nuclear factors in a variety of tissues that interact with WAP regulatory sequences. Though the data presented are based on only two lines, these findings suggest WAP regulatory sequences may not be suitable as control elements for transgenes in sheep bioreactors. C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. RP Wall, RJ (reprint author), USDA ARS,GENE EVALUAT & MAPPING LAB,BELTSVILLE,MD 20705, USA. NR 22 TC 20 Z9 21 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD JAN PY 1996 VL 5 IS 1 BP 67 EP 72 DI 10.1007/BF01979923 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA TT630 UT WOS:A1996TT63000008 PM 8589741 ER PT B AU Gajdusek, DC AF Gajdusek, DC BE Court, L Dodet, B TI Kuru in childhood: Implications for the problem of whether bovine spongiform encephalopathy affects humans SO TRANSMISSIBLE SUBACUTE SPONGIFORM ENCEPHALOPATHIES: PRION DISEASES LA English DT Proceedings Paper CT IIIrd International Symposium on Transmissible Subacute Spongiform Encephalopathies - Prion Diseases CY MAR 18-20, 1996 CL PARIS, FRANCE SP Ctr Rech Serv Sante Armees, Direct Rech Technol, CEA DE kuru; Creutzfeldt-Jakob disease; infectious amyloidoses; nucleation; bovine spongiform encephalopathy; scrapie; fatal familial insomnia; Gerstmann-Straussler-Scheinker disease RP Gajdusek, DC (reprint author), NIH,CENT NERVOUS SYST STUDIES LAB,BLDG 36,ROOM 5 B21,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU EDITIONS SCIENTIFIQUE & MEDICALES ELSEVIER PI PARIS PA 141, RUE DE JAVEL, PARIS, FRANCE BN 2-906077-91-7 PY 1996 BP 15 EP 26 PG 12 WC Agriculture, Dairy & Animal Science; Infectious Diseases; Medicine, Research & Experimental; Veterinary Sciences SC Agriculture; Infectious Diseases; Research & Experimental Medicine; Veterinary Sciences GA BH12X UT WOS:A1996BH12X00001 ER PT B AU Priola, SA Chesebro, B Caughey, B AF Priola, SA Chesebro, B Caughey, B BE Court, L Dodet, B TI Formation of PrP-res in vitro SO TRANSMISSIBLE SUBACUTE SPONGIFORM ENCEPHALOPATHIES: PRION DISEASES LA English DT Proceedings Paper CT IIIrd International Symposium on Transmissible Subacute Spongiform Encephalopathies - Prion Diseases CY MAR 18-20, 1996 CL PARIS, FRANCE SP Ctr Rech Serv Sante Armees, Direct Rech Technol, CEA DE scrapie; prion protein RP Priola, SA (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUE & MEDICALES ELSEVIER PI PARIS PA 141, RUE DE JAVEL, PARIS, FRANCE BN 2-906077-91-7 PY 1996 BP 293 EP 298 PG 6 WC Agriculture, Dairy & Animal Science; Infectious Diseases; Medicine, Research & Experimental; Veterinary Sciences SC Agriculture; Infectious Diseases; Research & Experimental Medicine; Veterinary Sciences GA BH12X UT WOS:A1996BH12X00034 ER PT B AU Chesebro, B Priola, SA Race, RE AF Chesebro, B Priola, SA Race, RE BE Court, L Dodet, B TI Susceptibility to hamster scrapie agent in transgenic mice with neuron-specific expression of a hamster prion protein minigene SO TRANSMISSIBLE SUBACUTE SPONGIFORM ENCEPHALOPATHIES: PRION DISEASES LA English DT Proceedings Paper CT IIIrd International Symposium on Transmissible Subacute Spongiform Encephalopathies - Prion Diseases CY MAR 18-20, 1996 CL PARIS, FRANCE SP Ctr Rech Serv Sante Armees, Direct Rech Technol, CEA DE scrapie; transgenic mice; neuron-specific enolase; degenerative brain disease RP Chesebro, B (reprint author), NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,NIH,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUE & MEDICALES ELSEVIER PI PARIS PA 141, RUE DE JAVEL, PARIS, FRANCE BN 2-906077-91-7 PY 1996 BP 353 EP 359 PG 7 WC Agriculture, Dairy & Animal Science; Infectious Diseases; Medicine, Research & Experimental; Veterinary Sciences SC Agriculture; Infectious Diseases; Research & Experimental Medicine; Veterinary Sciences GA BH12X UT WOS:A1996BH12X00041 ER PT B AU Goldfarb, LG Cervenakova, L Brown, P Gajdusek, DC AF Goldfarb, LG Cervenakova, L Brown, P Gajdusek, DC BE Court, L Dodet, B TI Genotype-phenotype correlations in familial spongiform encephalopathies associated with insert mutations SO TRANSMISSIBLE SUBACUTE SPONGIFORM ENCEPHALOPATHIES: PRION DISEASES LA English DT Proceedings Paper CT IIIrd International Symposium on Transmissible Subacute Spongiform Encephalopathies - Prion Diseases CY MAR 18-20, 1996 CL PARIS, FRANCE SP Ctr Rech Serv Sante Armees, Direct Rech Technol, CEA DE spongiform encephalopathy; prion diseases; PRNP gene; mutation; 24-nucleotide repeat expansion; genotype-phenotype correlation RP Goldfarb, LG (reprint author), NIH,NINDS,CLIN NEUROGENET UNIT,BLDG 36,ROOM 4D03,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU EDITIONS SCIENTIFIQUE & MEDICALES ELSEVIER PI PARIS PA 141, RUE DE JAVEL, PARIS, FRANCE BN 2-906077-91-7 PY 1996 BP 425 EP 431 PG 7 WC Agriculture, Dairy & Animal Science; Infectious Diseases; Medicine, Research & Experimental; Veterinary Sciences SC Agriculture; Infectious Diseases; Research & Experimental Medicine; Veterinary Sciences GA BH12X UT WOS:A1996BH12X00051 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Cycle sequencing through CC-rich regions SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses a number of methods used to sequence through GC-rich sections of DNA, and why it is preferable to expose X-ray film to P-32 at -70 degrees C, For details on how to partake in the newsgroup, see the accompanying box. RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 8 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JAN PY 1996 VL 21 IS 1 BP 33 EP 34 DI 10.1016/S0968-0004(06)80026-5 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TR321 UT WOS:A1996TR32100010 PM 8848838 ER PT J AU Qazilbash, M Young, N Liu, J AF Qazilbash, M Young, N Liu, J TI Vectors and target cells for gene therapy of blood diseases SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Article ID INVIVO; EXPRESSION; VIRUS; DNA; TRANSPLANTATION; IMMUNOTHERAPY; LYMPHOCYTES; PROTEIN; TUMORS; LIVER AB Gene therapy is the introduction of genetic material into somatic cells in order to correct a genetic defect or provide a new therapeutic function. Since the advent of gene transfer technologies, hematopoietic stem cells and hematologic diseases have been the focus of intensive efforts: blood cells can be removed from the body easily and reintroduced following ex vivo manipulation. The major applications of gene therapy for hematologic diseases fall into four major categories: genetic marking of hematopoietic progenitor cells, replacement of a missing or defective gene in an inherited deficiency, gene therapy of neoplastic disorders, intracellular immunization against human immunodeficiency virus (HIV) infection or other viral disorders. This review summarizes the different methods used for gene delivery and focuses on target cells for hematologic diseases amenable to gene therapy. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. RP Qazilbash, M (reprint author), NHLBI,NCI,MED BRANCH,BETHESDA,MD 20892, USA. NR 37 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JAN PY 1996 VL 6 IS 1 BP 25 EP 30 DI 10.1016/1050-1738(95)00127-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TW450 UT WOS:A1996TW45000005 PM 21232271 ER PT J AU Weinberger, C AF Weinberger, C TI A model for farnesoid feedback control in the mevalonate pathway SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID COENZYME-A REDUCTASE; HORMONE RECEPTOR SUPERFAMILY; STEROL REGULATORY ELEMENT; CHOLESTEROL METABOLISM; 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE; ACTIVATED RECEPTOR; NUCLEAR RECEPTORS; OXYSTEROL BINDING; RETINOIC ACID; FATTY-ACIDS AB Mevalonate is the rate-limiting substrate leading to farnesyl pyrophosphate (FPP), the central intermediate for isoprenoids such as cholesterol, dolichols, ubiquinone, and carotenoids. One major challenge has been to identify the isoprenod effector molecules and transcription factors mediating negative regulation in this metabolic pathway. A nuclear receptor called FXR has recently been characterized that is activated by farnesyl pyrophosphate metabolites such as farnesol, farnesal, farnesoic acid, and methyl farnesoate. FXR expression in isoprenoidogenic tissues suggests a hypothesis that these intracellular ''farnesoids'' may be signals for transcriptional feedback control of cholesterol biosynthesis. RP Weinberger, C (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 58 TC 20 Z9 21 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD JAN-FEB PY 1996 VL 7 IS 1 BP 1 EP 6 DI 10.1016/1043-2760(95)00180-8 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TV942 UT WOS:A1996TV94200001 PM 18406718 ER PT J AU Hewitt, RE Corcoran, ML StetlerStevenson, WG AF Hewitt, RE Corcoran, ML StetlerStevenson, WG TI The activation, expression and function of gelatinase A (MMP-2) SO TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY LA English DT Review DE angiogenesis; gelatinase A; invasion; metastasis; type-IV collagenase ID BASEMENT-MEMBRANE COLLAGEN; STROMELYSIN GENE-EXPRESSION; C-TERMINAL DOMAIN; IV COLLAGENASE; TISSUE INHIBITOR; MATRIX METALLOPROTEINASE; 72-KDA GELATINASE; INTERSTITIAL COLLAGENASE; PLASMINOGEN-ACTIVATOR; HUMAN FIBROBLASTS AB Gelatinase A is a member of the Matrix Metalloproteinase (MMP) family. These enzymes are usually secreted as latent pro-enzymes, are activated by proteolytic cleavage of an amino terminal domain, and are inhibited by tissue inhibitor of metalloproteinases (TIMPs). They are involved in extracellular matrix remodeling, both in normal processes of growth and development, and in pathological processes such as tumor invasion and metastasis. Gelatinase A has a number of distinctive characteristics, that suggest it may play a unique role in these processes. Unlike most MMPs it is constitutively expressed by many cells and has a ubiquitous tissue distribution. Another unique feature is that this protease is activated on the cell surface by the recently discovered membrane-type MMP (MT-MMP). Expression of gelatinase A correlates with the aggressiveness of many tumors, which suggests that it may be a useful prognostic indicator, as well as a suitable target for anti-cancer therapies. C1 NCI, DIV CLIN SCI, PATHOL LAB, EXTRACELLULAR MATRIX PATHOL SECT, BETHESDA, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 79 TC 8 Z9 8 U1 0 U2 2 PU GAKUSHIN PUBL CO PI TOKYO PA YUSHOKAIN7F, 1-38-12 NIHONBASHIKAKIGARACHO, CHUO-KU, TOKYO, 103-0014, JAPAN SN 0915-7352 J9 TRENDS GLYCOSCI GLYC JI Trends Glycosci. Glycotechnol. PD JAN PY 1996 VL 8 IS 39 BP 23 EP 36 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TV129 UT WOS:A1996TV12900003 ER PT J AU Silver, R Silverman, AJ Vitkovic, L Lederhendler, II AF Silver, R Silverman, AJ Vitkovic, L Lederhendler, II TI Mast cells in the brain: Evidence and functional significance SO TRENDS IN NEUROSCIENCES LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; MICROGLIAL CELLS; RAT-BRAIN; SECRETION; INFLAMMATION; EXPRESSION; ESTRADIOL; INDUCTION; BEHAVIOR; TRIGGERS AB For the past two decades the brain has been considered to be an immune-privileged site that excludes circulating cells from the parenchyma, New evidence indicates that some hematocytes reside in the brain, while others traffic through it. Mast cells belong to both of these functional types. Moreover the appearance of mast cells in the CNS can be triggered behaviorally. After a brief period of courtship, for example, there is a marked increase in mast cells in the medial habenula of sexually active doves compared with controls, Exposure to gonadal steroids that occur endogenously or that are administered exogenously increases both the number of mast cells and their state of activation in the brain, These results show that hematopoietic cells can provide targeted delivery of neuromodulators to specific regions of the brain, thereby influencing neural-endocrine interactions. C1 COLUMBIA UNIV,DEPT PSYCHOL,NEW YORK,NY. COLUMBIA UNIV,COLL PHYS & SURG,DEPT ANAT & CELL BIOL,NEW YORK,NY. NIMH,DIV NEUROSCI & BEHAV SCI,ROCKVILLE,MD 20857. RP Silver, R (reprint author), BARNARD COLL,DEPT PSYCHOL,NEW YORK,NY 10027, USA. FU NICHD NIH HHS [HD 10665]; NIMH NIH HHS [MH 023290] NR 65 TC 153 Z9 158 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JAN PY 1996 VL 19 IS 1 BP 25 EP 31 DI 10.1016/0166-2236(96)81863-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA TP683 UT WOS:A1996TP68300009 PM 8787137 ER PT J AU Lazarus, LH Bryant, SD Salvadori, S Attila, M Jones, LS AF Lazarus, LH Bryant, SD Salvadori, S Attila, M Jones, LS TI Opioid infidelity: Novel opioid peptides with dual high affinity for delta- and mu-receptors SO TRENDS IN NEUROSCIENCES LA English DT Review ID DELTORPHIN-I; GUINEA-PIG; BRAIN; DERMORPHIN; BINDING; ENKEPHALIN; ANALOGS; SKIN; SELECTIVITY; SUBTYPES AB Deltorphins represent the paragon of delta-opioid-receptor ligands of natural origin, since they exceed the affinity and selectivity of the endogenous enkephalins by orders of magnitude. A series of opioid peptides have been developed in which the change in a single amino acid causes an extraordinary increase in mu-receptor binding while maintaining high affinity for the delta-receptor. The peptides appear to have a similar extended conformation in solution with a type-1 p-turn in the N-terminus region, suggesting that tertiary architecture plays a pivotal role in enabling the peptide to bind indiscriminately to mu- and delta-receptors. These dual-affinity peptide ligands can serve to mask delta- and mu-receptors while mapping kappa-receptors in the nervous system, to provide an understanding of the differences and similarities in the structure of the binding domains of delta- and mu-receptors, and might lead to a comprehensive new regime for the clinical management of acute and chronic pain. C1 UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. HELSINKI UNIV,DEPT PHARM,SF-00014 HELSINKI,FINLAND. UNIV S CAROLINA,DEPT ANAT & DEV BIOL,COLUMBIA,SC 29208. RP Lazarus, LH (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NINDS NIH HHS [NS27903] NR 63 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JAN PY 1996 VL 19 IS 1 BP 31 EP 35 DI 10.1016/0166-2236(96)81864-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA TP683 UT WOS:A1996TP68300010 PM 8787139 ER PT J AU Cecchini, S Ciatto, S Bonardi, R Grazzini, G Mazzotta, A AF Cecchini, S Ciatto, S Bonardi, R Grazzini, G Mazzotta, A TI Endometrial ultrasonography - An alternative to invasive assessment in women with postmenopausal vaginal bleeding SO TUMORI LA English DT Article DE endometrial carcinoma; diagnosis; ultrasonography ID HYSTEROSCOPY AB Aims and background: To test the reliability of endometrial sonography in selecting women with abnormal postmenopausal vaginal bleeding for further diagnostic assessment. Methods: Endometrial thickness was measured in 368 consecutive women by abdominal or vaginal sonography prior to invasive assessment (hysteroscopy, curettage). The association of abnormal endometrial thickness (4 mm or greater) with endometrial cancer was determined. Results: Abnormal endometrial thickness was observed in 116 of 368 women. Subsequent assessment diagnosed endometrial carcinoma in 16 subjects, 15 of whom had abnormal endometrial thickness. One case with normal endometrial thickness was suspected at sonography because of the irregular appearance of the endometrium. Conclusions: Had it been used to select subjects for further assessment, sonography would have missed no cancer, and unnecessary invasive assessment (under general anesthesia in 20% of cases) would have been spared in 68% (251/368) of the subjects. Endometrial sonography should be routinely used to select women with postmenopausal vaginal bleeding for further investigations. C1 CTR STUDIO & PREVENZ ONCOL,I-50131 FLORENCE,ITALY. NATL CANC INST,GENOA,ITALY. RI Grazzini, Grazia/K-8503-2016 OI Grazzini, Grazia/0000-0002-9713-3007 NR 6 TC 11 Z9 11 U1 0 U2 0 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD JAN-FEB PY 1996 VL 82 IS 1 BP 38 EP 39 PG 2 WC Oncology SC Oncology GA UD286 UT WOS:A1996UD28600007 PM 8623501 ER PT B AU Dahl, CA Strausberg, RL AF Dahl, CA Strausberg, RL BE Cohn, GE Soper, SA Chen, CHW Katzir, A TI Human genome project: Revolutionizing biology through leveraging technology SO ULTRASENSITIVE BIOCHEMICAL DIAGNOSTICS, PROCEEDINGS OF SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Ultrasensitive Biochemical Diagnostics CY JAN 31-FEB 02, 1996 CL SAN JOSE, CA SP Soc Photo Opt Instrumentat Engineers DE genome; DNA; technology; sequencing; mapping C1 NIH,SEQUENCING TECHNOL BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2054-9 J9 P SOC PHOTO-OPT INS PY 1996 VL 2680 BP 190 EP 201 DI 10.1117/12.237605 PG 12 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BF31M UT WOS:A1996BF31M00018 ER PT J AU Li, RL Cai, JW Tegeler, C Sorlie, P Metcalf, PA Heiss, G AF Li, RL Cai, JW Tegeler, C Sorlie, P Metcalf, PA Heiss, G TI Reproducibility of extracranial carotid atherosclerotic lesions assessed by B-mode ultrasound: The atherosclerosis risk in communities study SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE atherosclerosis; carotid arteries; plaque; acoustic shadowing; B-mode ultrasound; reproducibility; kappa statistic ID MEASUREMENT VARIABILITY; GENERAL-POPULATION; HIGH AGREEMENT; ARTERY PLAQUE; LOW KAPPA; PREVALENCE; THICKNESS; ULTRASONOGRAPHY; SONOGRAPHY; PARADOXES AB The reproducibility in the identification of carotid artery lesions using B-mode ultrasound was studied in a large random sample selected from the Atherosclerosis Risk in Communities (ARIC) Study, Carotid lesions were defined as plaque with or without acoustic shadowing (indicative of mineralization). A weighted kappa (kappa(w)) statistic was used as a chance-adjusted measure of repeatability, In the ARIC baseline survey, the kappa(w) values for the assessment of lesions on repeat reading were 0.47, 0.60 and 0.69 in the left common carotid artery, the carotid bifurcation and the internal carotid artery, respectively, In a repeat scanning, the kappa(w) values ranged from 0.59 to 0.79 in the left carotid segments, The results were similar in the left and right carotid arteries, Covariates (age, race, gender, body mass index, study center) did not influence the reproducibility, Similar results were also found in both the baseline survey and the first follow-up examination, In conclusion, reproducibility in the assessment of carotid lesions by B-mode ultrasound can be achieved in multicenter studies at fair to good levels of agreement. C1 UNIV N CAROLINA,DEPT EPIDEMIOL,SCH PUBL HLTH,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT BIOSTAT,SCH PUBL HLTH,CHAPEL HILL,NC 27599. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT NEUROL,WINSTON SALEM,NC 27103. NHLBI,NIH,BETHESDA,MD 20892. UNIV AUCKLAND,DEPT STAT,AUCKLAND,NEW ZEALAND. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55019, N01-HC-55018] NR 39 TC 39 Z9 39 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PY 1996 VL 22 IS 7 BP 791 EP 799 DI 10.1016/0301-5629(96)00084-1 PG 9 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA VJ568 UT WOS:A1996VJ56800002 PM 8923698 ER PT J AU Sonies, BC Wang, C Sapper, DJ AF Sonies, BC Wang, C Sapper, DJ TI Evaluation of normal and abnormal hyoid bone movement during swallowing by use of ultrasound duplex-Doppler imaging SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE ultrasound imaging; ultrasound duplex-Doppler imaging; hyoid bone motion; swallowing ID BOLUS VOLUME; TONGUE; MOTION AB We developed a new method to analyze normal and abnormal movements of the hyoid muscular region as an indicator of hyoid bone motion during swallowing using ultrasound duplex-Doppler imaging. Hyoid bone motion can be monitored by studying the Doppler shift spectra and B-mode images produced by ultrasound duplex imaging of the hyoid region muscular attachments. We can accurately determine swallowing duration and trajectory of hyoid bone movement. This procedure can assist in discriminating between normal and abnormal movements of the hyoid bone and the surrounding muscles during swallowing. This method appears to be a highly consistent measure. We suggest that Doppler spectrum analysis can be used for defining hyoid position and displaying accurate movement, which may be useful in the diagnosis of swallowing disorders. Copyright (C) 1996 World Federation for Ultrasound in Medicine & Biology C1 ALLIED IMAGING INT INC,GERMANTOWN,MD. RP Sonies, BC (reprint author), NIH,DEPT REHABIL MED,SPEECH LANGUAGE PATHOL SECT,BETHESDA,MD 20892, USA. NR 15 TC 18 Z9 20 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PY 1996 VL 22 IS 9 BP 1169 EP 1175 DI 10.1016/S0301-5629(96)00158-5 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA WB811 UT WOS:A1996WB81100004 PM 9123641 ER PT S AU Richters, JE AF Richters, JE BE Ferris, CF Grisso, T TI Disordered views of aggressive children - A late twentieth century perspective SO UNDERSTANDING AGGRESSIVE BEHAVIOR IN CHILDREN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Understanding Aggressive Behavior in Children CY SEP 29-OCT 02, 1995 CL NEW YORK, NY SP New York Acad Sci ID CEREBROSPINAL-FLUID MONOAMINE; CONDUCT DISORDER; DEVELOPMENTAL PSYCHOPATHOLOGY; COMMUNITY VIOLENCE; RESPONSE PERSEVERATION; ANTISOCIAL-BEHAVIOR; HARMFUL DYSFUNCTION; MENTAL DISORDER; BOYS; DELINQUENCY RP Richters, JE (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,5600 FISHERS LANE,ROOM 18C-17,ROCKVILLE,MD 20857, USA. OI Richters, John/0000-0002-6780-1828 NR 65 TC 4 Z9 4 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 1-57331-012-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 794 BP 208 EP 223 DI 10.1111/j.1749-6632.1996.tb32522.x PG 16 WC Psychology, Biological; Psychology, Developmental; Multidisciplinary Sciences; Psychiatry; Psychology, Social SC Psychology; Science & Technology - Other Topics; Psychiatry GA BG59Z UT WOS:A1996BG59Z00019 PM 8853604 ER PT S AU Ogawa, S Lubahn, DB Korach, KS Pfaff, DW AF Ogawa, S Lubahn, DB Korach, KS Pfaff, DW BE Ferris, CF Grisso, T TI Aggressive behaviors of transgenic estrogen-receptor knockout male mice SO UNDERSTANDING AGGRESSIVE BEHAVIOR IN CHILDREN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Understanding Aggressive Behavior in Children CY SEP 29-OCT 02, 1995 CL NEW YORK, NY SP New York Acad Sci C1 UNIV MISSOURI,DEPT BIOCHEM & CHILD HLTH,COLUMBIA,MO 65211. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP Ogawa, S (reprint author), ROCKEFELLER UNIV,NEUROBIOL & BEHAV LAB,BOX 275,1230 YORK AVE,NEW YORK,NY 10021, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 4 TC 18 Z9 18 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 1-57331-012-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 794 BP 384 EP 385 DI 10.1111/j.1749-6632.1996.tb32549.x PG 2 WC Psychology, Biological; Psychology, Developmental; Multidisciplinary Sciences; Psychiatry; Psychology, Social SC Psychology; Science & Technology - Other Topics; Psychiatry GA BG59Z UT WOS:A1996BG59Z00046 PM 8853623 ER PT S AU Nara, PL Merges, M Wu, SC Spouge, J AF Nara, PL Merges, M Wu, SC Spouge, J BE Brown, F Norrby, E Burton, D Mekalanos, J TI Plasma factors in human blood alter the entry properties of HIV-1: Implications for gp120-based vaccine approaches SO VACCINES 96 - MOLECULAR APPROACHES TO THE CONTROL OF INFECTIOUS DISEASES SE VACCINES (COLD SPRING HARBOR LABORATORY PRESS) LA English DT Proceedings Paper CT 13th Cold Spring Harbor Meeting on Molecular Approaches to the Control of Infectious Diseases CY SEP 13-17, 1995 CL COLD SPRING HARBOR, NY SP Cold Spring Harbor Lab, Amer Cyanamid Co, Amgen Inc, BASF Biores Corp, Beckman Instruments Inc, Becton Dickinson & Co, Bristol Myers Squibb Co, Chugai Pharm Co Ltd, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, Du Pont Merck Pharm Co, Forest Labs Inc, Genentech Inc, Glaxo, Hoffmann La Roche Inc, Human Genome Sci Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Marion Merrell Dow Inc, Mitsubishi Kasei Inst Life Sci, Monsanto Co, New England BioLabs Inc, Oncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Pfizer Inc, Res Genet Inc, Sandoz Res Inst, Schering Plough Corp, SmithKline Beecham Pharm, Sumitomo Pharm Co Ltd, Upjohn Co, Wellcome Res Labs, Borroughs Wellcome Co, Wyeth Ayerst Res, Zeneca Grp PLC C1 NCI,VIRUS BIOL SECT,LTCB,BCP,DCE,FCRDC,NIH,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 SN 0899-4056 BN 0-87969-479-3 J9 VACCINES PY 1996 BP 323 EP 332 PG 10 WC Immunology; Infectious Diseases; Medicine, Research & Experimental SC Immunology; Infectious Diseases; Research & Experimental Medicine GA BF80A UT WOS:A1996BF80A00053 ER PT S AU Chanock, RM AF Chanock, RM BE Brown, F Norrby, E Burton, D Mekalanos, J TI Reminiscences of Albert Sabin and his successful strategy for the development of the live oral poliovirus vaccine SO VACCINES 96 - MOLECULAR APPROACHES TO THE CONTROL OF INFECTIOUS DISEASES SE VACCINES (COLD SPRING HARBOR LABORATORY PRESS) LA English DT Proceedings Paper CT 13th Cold Spring Harbor Meeting on Molecular Approaches to the Control of Infectious Diseases CY SEP 13-17, 1995 CL COLD SPRING HARBOR, NY SP Cold Spring Harbor Lab, Amer Cyanamid Co, Amgen Inc, BASF Biores Corp, Beckman Instruments Inc, Becton Dickinson & Co, Bristol Myers Squibb Co, Chugai Pharm Co Ltd, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, Du Pont Merck Pharm Co, Forest Labs Inc, Genentech Inc, Glaxo, Hoffmann La Roche Inc, Human Genome Sci Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Marion Merrell Dow Inc, Mitsubishi Kasei Inst Life Sci, Monsanto Co, New England BioLabs Inc, Oncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Pfizer Inc, Res Genet Inc, Sandoz Res Inst, Schering Plough Corp, SmithKline Beecham Pharm, Sumitomo Pharm Co Ltd, Upjohn Co, Wellcome Res Labs, Borroughs Wellcome Co, Wyeth Ayerst Res, Zeneca Grp PLC C1 NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 SN 0899-4056 BN 0-87969-479-3 J9 VACCINES PY 1996 BP 335 EP 348 PG 14 WC Immunology; Infectious Diseases; Medicine, Research & Experimental SC Immunology; Infectious Diseases; Research & Experimental Medicine GA BF80A UT WOS:A1996BF80A00054 ER PT B AU Robbins, JB Schneerson, R Szu, SC Pozsgay, V AF Robbins, JB Schneerson, R Szu, SC Pozsgay, V BE Plotkin, SA Fantini, B TI Polysaccharide - Protein conjugate vaccines SO VACCINIA, VACCINATION, VACCINOLOGY: JENNER, PASTEUR AND THEIR SUCCESSORS LA English DT Proceedings Paper CT International Meeting on the History of Vaccinology - Vaccinia, Vaccination, Vaccinology: Jenner, Pasteur and Their Successors CY DEC 06-08, 1995 CL MARNES-LA-COQUETTE, FRANCE DE conjugates; Hib meningitis; herd immunity RP Robbins, JB (reprint author), NICHHD,NIH,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER EDITIONS SCIENTIFIQUES PI PARIS PA 29 RUE BUFFON, 75005 PARIS, FRANCE BN 2-906077-83-6 PY 1996 BP 135 EP 143 PG 3 WC History & Philosophy Of Science; Immunology; Medicine, Research & Experimental SC History & Philosophy of Science; Immunology; Research & Experimental Medicine GA BG02J UT WOS:A1996BG02J00017 ER PT B AU Fee, E AF Fee, E BE Plotkin, SA Fantini, B TI AIDS as a metaphor SO VACCINIA, VACCINATION, VACCINOLOGY: JENNER, PASTEUR AND THEIR SUCCESSORS LA English DT Proceedings Paper CT International Meeting on the History of Vaccinology - Vaccinia, Vaccination, Vaccinology: Jenner, Pasteur and Their Successors CY DEC 06-08, 1995 CL MARNES-LA-COQUETTE, FRANCE DE human immunodeficiency virus (HIV); acquired immune deficiency syndrome (AIDS); race; class; gender; homosexual heterosexual; gay community; injection drug users RP Fee, E (reprint author), NATL INST HLTH,NATL LIB MED,HIST MED DIV,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER EDITIONS SCIENTIFIQUES PI PARIS PA 29 RUE BUFFON, 75005 PARIS, FRANCE BN 2-906077-83-6 PY 1996 BP 349 EP 358 PG 4 WC History & Philosophy Of Science; Immunology; Medicine, Research & Experimental SC History & Philosophy of Science; Immunology; Research & Experimental Medicine GA BG02J UT WOS:A1996BG02J00042 ER PT B AU Mays, TD Mazan, K Asebey, EJ Boyd, MR Cragg, GM AF Mays, TD Mazan, K Asebey, EJ Boyd, MR Cragg, GM BE Brush, SB Stabinsky, D TI Quid pro quo: Alternatives for equity and conservation SO VALUING LOCAL KNOWLEDGE: INDIGENOUS PEOPLE AND INTELLECTUAL PROPERTY RIGHTS LA English DT Proceedings Paper CT Conference on Intellectual Property Rights and Indigenous Knowledge CY OCT 05-10, 1993 CL LAKE TAHOE, CA SP Natl Sci Fdn, Ethics & Values Studies Program, Soc Appl Anthr C1 NCI,OFF TECHNOL DEV,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ISLAND PRESS PI WASHINGTON PA 1718 CONNECTICUT AVE NW, SUITE 300, WASHINGTON, DC 20009 BN 1-55963-378-6 PY 1996 BP 259 EP 280 PG 22 WC International Relations; Social Issues SC International Relations; Social Issues GA BF14R UT WOS:A1996BF14R00013 ER PT B AU Grifo, FT Downes, DR AF Grifo, FT Downes, DR BE Brush, SB Stabinsky, D TI Agreements to collect biodiversity for pharmaceutical research: Major issues and proposed principles SO VALUING LOCAL KNOWLEDGE: INDIGENOUS PEOPLE AND INTELLECTUAL PROPERTY RIGHTS LA English DT Proceedings Paper CT Conference on Intellectual Property Rights and Indigenous Knowledge CY OCT 05-10, 1993 CL LAKE TAHOE, CA SP Natl Sci Fdn, Ethics & Values Studies Program, Soc Appl Anthr C1 NIH,FOGARTY INT CTR,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ISLAND PRESS PI WASHINGTON PA 1718 CONNECTICUT AVE NW, SUITE 300, WASHINGTON, DC 20009 BN 1-55963-378-6 PY 1996 BP 281 EP 304 PG 24 WC International Relations; Social Issues SC International Relations; Social Issues GA BF14R UT WOS:A1996BF14R00014 ER PT S AU Camus, E Maillard, JC Ruff, G Pepin, L Naves, M Matheron, G AF Camus, E Maillard, JC Ruff, G Pepin, L Naves, M Matheron, G BE Camus, E House, JA Uilenberg, G TI Genetic resistance of Creole goats to cowdriosis in Guadeloupe - Status in 1995 SO VECTOR-BORNE PATHOGENS: INTERNATIONAL TRADE AND TROPICAL ANIMAL DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Vector-Borne Pathogens - Challenges for the 21st-Century and International Trade and Animal Diseases / 3rd Meeting of Society-for-Tropical-Veterinary-Medicine CY MAY 08-12, 1995 CL SAN JOSE, COSTA RICA SP Soc Trop Vet Med, Bayer AG, UN FA0, Inter Amer Inst Cooperat Agr, Mallinckrodt Vet Inc, Pfizer Inc Anim Hlth, Rhone Merieux, USDA, Animal & Plant Hlth Inspect Serv, USDA, Int Serv, USDA, Natl Vet Serv Labs ID CATTLE C1 EMVT, CIRAD, PAP 97165, Guadeloupe. Univ Bern, Bern, Switzerland. NIH, Bethesda, MD 20892 USA. INRA, Pointe A Pitre, Guadeloupe. CIRAD, Montpellier, France. RP Camus, E (reprint author), EMVT, CIRAD, BP 515, PAP 97165, Guadeloupe. NR 11 TC 7 Z9 7 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 0-89766-955-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 791 BP 46 EP 53 DI 10.1111/j.1749-6632.1996.tb53510.x PG 8 WC Multidisciplinary Sciences; Parasitology; Veterinary Sciences SC Science & Technology - Other Topics; Parasitology; Veterinary Sciences GA BK04D UT WOS:000070968700005 PM 8784485 ER PT S AU House, C Alexander, KA Kat, PW O'Brien, SJ Mangiafico, J AF House, C Alexander, KA Kat, PW O'Brien, SJ Mangiafico, J BE Camus, E House, JA Uilenberg, G TI Serum antibody to Rift Valley fever virus in African carnivores SO VECTOR-BORNE PATHOGENS: INTERNATIONAL TRADE AND TROPICAL ANIMAL DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Vector-Borne Pathogens - Challenges for the 21st-Century and International Trade and Animal Diseases / 3rd Meeting of Society-for-Tropical-Veterinary-Medicine CY MAY 08-12, 1995 CL SAN JOSE, COSTA RICA SP Soc Trop Vet Med, Bayer AG, UN FA0, Inter Amer Inst Cooperat Agr, Mallinckrodt Vet Inc, Pfizer Inc Anim Hlth, Rhone Merieux, USDA, Animal & Plant Hlth Inspect Serv, USDA, Int Serv, USDA, Natl Vet Serv Labs ID DOMESTIC-ANIMALS; OUTBREAK; KENYA C1 USDA, APHIS, NVSL, FADDL, Greenport, NY 11944 USA. Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA. NCI, Frederick, MD 21702 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RP House, C (reprint author), USDA, APHIS, NVSL, FADDL, POB 848, Greenport, NY 11944 USA. RI Alexander, Kathleen/A-9765-2010 OI Alexander, Kathleen/0000-0001-7338-5341 NR 13 TC 5 Z9 5 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 0-89766-955-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 791 BP 345 EP 349 DI 10.1111/j.1749-6632.1996.tb53541.x PG 5 WC Multidisciplinary Sciences; Parasitology; Veterinary Sciences SC Science & Technology - Other Topics; Parasitology; Veterinary Sciences GA BK04D UT WOS:000070968700036 PM 8784515 ER PT J AU Polack, B Schwartz, I Berthelemy, M Belloc, C Manet, G Vuillaume, A Baron, T Gonda, MA Levy, D AF Polack, B Schwartz, I Berthelemy, M Belloc, C Manet, G Vuillaume, A Baron, T Gonda, MA Levy, D TI Serologic evidence for bovine immunodeficiency virus infection in France SO VETERINARY MICROBIOLOGY LA English DT Article DE bovine immunodeficiency virus; cattle; seroprevalence ID LEUKEMIA-VIRUS; ANEMIA VIRUS; CATTLE; LENTIVIRUS; CALVES; RETROVIRUS; RABBITS AB We report herein on the first serologic detection of antibodies to bovine immunodeficiency virus (BIV) in France. Serum samples from dairy and beef cattle from southwestern and western France (Landes and Vendee) were tested using a western blot assay with a recombinant 53 kDa gag precursor derived from the Louisiana BIV R29 isolate, We performed our study on the oldest animals from 37 different herds that were under serologic follow up for previous bovine leukemia virus infection. Overall, 398 selected bovine sera were assayed and 15 serum samples from 8 herds reacted with the recombinant 53 kDa BIV R29 gag, Interestingly, reactions obtained with French sera were weaker than with positive Louisiana sera, a finding that may indicate the occurrence of distinct French and Louisiana BIV variants. C1 ECOLE NATL VET,INRA,UNITE RECH IMMUNOPATHOL CELLULAIRE & MOLEC,F-94704 MAISONS ALFORT,FRANCE. LAB DEPT ANAL VET J LE PENNEC,F-85021 LA ROCHE SUR YON,FRANCE. LAB DEPT LANDES,F-40004 MT DE MARSAN,FRANCE. CTR NATL ETUD VET & ALIMENTAIRES,F-69342 LYON,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702. NR 32 TC 32 Z9 33 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD JAN PY 1996 VL 48 IS 1-2 BP 165 EP 173 DI 10.1016/0378-1135(95)00138-7 PG 9 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA TN936 UT WOS:A1996TN93600016 PM 8701572 ER PT S AU Pisegna, JR Moody, TW Wank, SA AF Pisegna, JR Moody, TW Wank, SA BE Arimura, A Said, SI TI Differential signaling and immediate-early gene activation by four splice variants of the human pituitary adenylate cyclase-activating polypeptide receptor (hPACAP-R) SO VIP, PACAP, AND RELATED PEPTIDES, 2ND INTERNATIONAL SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Symposium on VIP, PACAP, and Related Peptides CY OCT 04-07, 1995 CL NEW ORLEANS, LA SP New York Acad Sci, Japanese Pharm Collect, Takeda Chem Ind Inc, Biomeasure Inc, Entergy Corp, Metro Vis Partnership Fdn, NIH, Tulane Univ Med Ctr, Amer Peptides Inc, Fujisawa Pharm Co Ltd, Hoffmann La Roche Inc, Itoham Food Co, NOVO Nordisk A S, Biosci Corp, Peninsula Labs Inc, SmithKlein Beecham Pharm, Wyeth Ayerst Labs ID RAT-BRAIN; FUNCTIONAL EXPRESSION; TISSUE DISTRIBUTION; CELL-MEMBRANES; BINDING-SITES; G-PROTEINS; PACAP; PEPTIDE; TRANSDUCTION C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NCI,BIOMARKERS & PREVENT RES BRANCH,NIH,BETHESDA,MD 20892. NR 23 TC 21 Z9 21 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-983-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 805 BP 54 EP 66 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BH28Q UT WOS:A1996BH28Q00006 PM 8993393 ER PT S AU Gozes, I Lilling, G Davidson, A Bardea, A Reshef, A Glazer, R Zamostiano, R AshurFabian, O Ticher, A Ashkenazi, IE Moody, TW Rubinraut, S Fridkin, M Brenneman, DE AF Gozes, I Lilling, G Davidson, A Bardea, A Reshef, A Glazer, R Zamostiano, R AshurFabian, O Ticher, A Ashkenazi, IE Moody, TW Rubinraut, S Fridkin, M Brenneman, DE BE Arimura, A Said, SI TI Development of VIP agonists and antagonists with tissue and receptor specificity: Effects on behavioral maturation, sexual function, and the biologic clock SO VIP, PACAP, AND RELATED PEPTIDES, 2ND INTERNATIONAL SYMPOSIUM SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 2nd International Symposium on VIP, PACAP, and Related Peptides CY OCT 04-07, 1995 CL NEW ORLEANS, LA SP New York Acad Sci, Japanese Pharm Collect, Takeda Chem Ind Inc, Biomeasure Inc, Entergy Corp, Metro Vis Partnership Fdn, NIH, Tulane Univ Med Ctr, Amer Peptides Inc, Fujisawa Pharm Co Ltd, Hoffmann La Roche Inc, Itoham Food Co, NOVO Nordisk A S, Biosci Corp, Peninsula Labs Inc, SmithKlein Beecham Pharm, Wyeth Ayerst Labs ID VASOACTIVE-INTESTINAL-PEPTIDE; CYCLASE-ACTIVATING POLYPEPTIDE; NONINVASIVE IMPOTENCE TREATMENT; RAT SUPRACHIASMATIC NUCLEUS; ISOLEUCINE-MESSENGER-RNA; LUNG-CANCER GROWTH; NEUROBLASTOMA-CELLS; SUP-T1 LYMPHOBLASTS; NEURONAL SURVIVAL; PACAP RECEPTOR C1 TEL AVIV UNIV, SACKLER SCH MED, DEPT HUMAN GENET, IL-69978 TEL AVIV, ISRAEL. NCI, BIOMARKERS & PREVENT RES BRANCH, NIH, ROCKVILLE, MD 20850 USA. WEIZMANN INST SCI, DEPT ORGAN CHEM, IL-76100 REHOVOT, ISRAEL. NICHHD, SECT DEV & MOL PHARMACOL, DEV NEUROBIOL LAB, NIH, BETHESDA, MD 20842 USA. RP TEL AVIV UNIV, SACKLER SCH MED, DEPT CLIN BIOCHEM, IL-69978 TEL AVIV, ISRAEL. NR 59 TC 3 Z9 3 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 0-89766-984-3; 0-89766-983-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 805 BP 159 EP 171 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics; Pharmacology & Pharmacy GA BH28Q UT WOS:A1996BH28Q00014 PM 8993401 ER PT S AU Hill, JM McCune, SK Alvero, RJ Glazner, GW Brenneman, DE AF Hill, JM McCune, SK Alvero, RJ Glazner, GW Brenneman, DE BE Arimura, A Said, SI TI VIP regulation of embryonic growth SO VIP, PACAP, AND RELATED PEPTIDES, 2ND INTERNATIONAL SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Symposium on VIP, PACAP, and Related Peptides CY OCT 04-07, 1995 CL NEW ORLEANS, LA SP New York Acad Sci, Japanese Pharm Collect, Takeda Chem Ind Inc, Biomeasure Inc, Entergy Corp, Metro Vis Partnership Fdn, NIH, Tulane Univ Med Ctr, Amer Peptides Inc, Fujisawa Pharm Co Ltd, Hoffmann La Roche Inc, Itoham Food Co, NOVO Nordisk A S, Biosci Corp, Peninsula Labs Inc, SmithKlein Beecham Pharm, Wyeth Ayerst Labs ID VASOACTIVE-INTESTINAL-PEPTIDE; NEUROTROPHIC ACTION; SPINAL-CORD; RAT-BRAIN; RECEPTORS; SURVIVAL; MITOSIS; MOUSE C1 JOHNS HOPKINS UNIV HOSP,DEPT PEDIAT,DIV NEONATOL,BALTIMORE,MD 21287. RP Hill, JM (reprint author), NICHHD,SECT DEV & MOL PHARMACOL,LDN,NIH,BLDG 49,ROOM 5A38,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 23 TC 4 Z9 4 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-983-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 805 BP 259 EP 269 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BH28Q UT WOS:A1996BH28Q00021 PM 8993408 ER PT S AU Brenneman, DE Hill, JM Gozes, I Phillips, TM AF Brenneman, DE Hill, JM Gozes, I Phillips, TM BE Arimura, A Said, SI TI Vasoactive intestinal peptide releases interleukin-1 from astrocytes SO VIP, PACAP, AND RELATED PEPTIDES, 2ND INTERNATIONAL SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Symposium on VIP, PACAP, and Related Peptides CY OCT 04-07, 1995 CL NEW ORLEANS, LA SP New York Acad Sci, Japanese Pharm Collect, Takeda Chem Ind Inc, Biomeasure Inc, Entergy Corp, Metro Vis Partnership Fdn, NIH, Tulane Univ Med Ctr, Amer Peptides Inc, Fujisawa Pharm Co Ltd, Hoffmann La Roche Inc, Itoham Food Co, NOVO Nordisk A S, Biosci Corp, Peninsula Labs Inc, SmithKlein Beecham Pharm, Wyeth Ayerst Labs ID NEURONAL SURVIVAL; NEUROTROPHIC ACTION; HUMAN BRAIN; CULTURES; SYNERGISM; MICROGLIA; CYTOKINES; PROTEIN; TISSUE; PACAP C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT CLIN BIOCHEM,IL-69978 TEL AVIV,ISRAEL. GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,IMMUNOCHEM LAB,WASHINGTON,DC 20037. RP Brenneman, DE (reprint author), NICHHD,SECT DEV & MOL PHARMACOL,NIH,BETHESDA,MD 20892, USA. NR 31 TC 4 Z9 5 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-983-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 805 BP 280 EP 289 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BH28Q UT WOS:A1996BH28Q00023 PM 8993410 ER PT J AU Wideroff, L Schiffman, M Hubbert, N Kirnbauer, R Schiller, J Greer, C Manos, MM Dawsey, SM JunYao, L Brinton, L AF Wideroff, L Schiffman, M Hubbert, N Kirnbauer, R Schiller, J Greer, C Manos, MM Dawsey, SM JunYao, L Brinton, L TI Serum antibodies to HPV 16 virus-like particles are not associated with penile cancer in Chinese males SO VIRAL IMMUNOLOGY LA English DT Article ID HUMAN PAPILLOMAVIRUS DNA; INTRAEPITHELIAL NEOPLASIA; BOWENOID PAPULOSIS; SEXUAL PARTNERS; CARCINOMAS; RISK; BRAZIL; WIVES C1 NCI,CELLULAR ONCOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. CHIRON CORP,EMERYVILLE,CA 94608. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NCI,CANC PREVENT STUDIES BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. CHINESE ACAD MED SCI,BEIJING 100037,PEOPLES R CHINA. RP Wideroff, L (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892, USA. RI Hernandez, Jessica/G-6527-2011; Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 23 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PY 1996 VL 9 IS 1 BP 23 EP 25 DI 10.1089/vim.1996.9.23 PG 3 WC Immunology; Virology SC Immunology; Virology GA UL052 UT WOS:A1996UL05200003 PM 8733916 ER PT J AU Boyer, JC Bebenek, K Kunkel, TA AF Boyer, JC Bebenek, K Kunkel, TA TI Analyzing the fidelity of reverse transcription and transcription SO VIRAL POLYMERASES AND RELATED PROTEINS SE METHODS IN ENZYMOLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; DNA-SYNTHESIS; IN-VITRO; HIV-1; RNA; MECHANISM; EXTENSION; TEMPLATES; REGION C1 NIEHS,GENET MOL LAB,RES TRIANGLE PK,NC 27709. RP Boyer, JC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. NR 29 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 275 BP 523 EP 537 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG51N UT WOS:A1996BG51N00027 PM 9026657 ER PT J AU Boyer, PL Hughes, SH AF Boyer, PL Hughes, SH TI Site-directed mutagenic analysis of viral polymerases and related proteins SO VIRAL POLYMERASES AND RELATED PROTEINS SE METHODS IN ENZYMOLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 REVERSE-TRANSCRIPTASE; PHI-29 DNA-POLYMERASE; AMINO-ACID MOTIF; HIGH-LEVEL RESISTANCE; NUCLEOSIDE ANALOG RESISTANCE; EXONUCLEASE ACTIVE-SITE; POL GENE-MUTATIONS; T7 RNA-POLYMERASE; NONNUCLEOSIDE INHIBITORS RP Boyer, PL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. NR 110 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 275 BP 538 EP 555 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG51N UT WOS:A1996BG51N00028 PM 9026658 ER PT J AU Sanna, PP deLogu, A Williamson, RA Hom, YL Straus, SE Bloom, FE Burton, DR AF Sanna, PP deLogu, A Williamson, RA Hom, YL Straus, SE Bloom, FE Burton, DR TI Protection of nude mice by passive immunization with a type-common human recombinant monoclonal antibody against HSV SO VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; COMBINATORIAL LIBRARIES; INFECTION; RESISTANCE; ACYCLOVIR; MECHANISM; CLEARANCE; THERAPY; SPREAD AB Herpes simplex viral disease is an important cause of morbidity and mortality in man, Although the development of very effective nucleoside analogs with a high therapeutic index has greatly improved the clinical management of herpetic infections, the emergence of drug-resistant viral strains has become a cause of serious concern both because of its clinical implications and in terms of viral ecology. The present report is the first demonstration of the in vivo protective activity of a type-common human recombinant monoclonal antibody derived from a combinatorial antibody library. Athymic nude mice were infected with HSV type 1 either intracutaneously in the flank or by corneal scarification. Beside reducing mortality rates when administered before infection, the antibody dramatically and significantly prolonged survival times (P < 0.0001) when administered up to 24 hr postinfection, a time when the virus had already reached the peripheral nervous system. This suggests that the antibody may act, at least in parr, by interfering with axonal transport of the virus and/or with viral expression. These results indicate that human recombinant antibodies isolated by antigen selection from combinatorial libraries can be effective in vivo. Such antibodies could complement antiviral chemotherapy and represent valuable tools for the prophylaxis of infections by the herpes simplex viruses. (C) 1996 Academic Press, Inc. C1 SCRIPPS RES INST, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. RW JOHNSON PHARMACEUT RES INST, SAN DIEGO, CA 92121 USA. NIAID, CLIN INVEST LAB, MED VIROL SECT, BETHESDA, MD 20892 USA. RP Sanna, PP (reprint author), SCRIPPS RES INST, DEPT NEUROPHARMACOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. FU NIAID NIH HHS [AI33292, AI36192]; NIMH NIH HHS [MH47680] NR 38 TC 29 Z9 29 U1 2 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 1 PY 1996 VL 215 IS 1 BP 101 EP 106 DI 10.1006/viro.1996.0011 PG 6 WC Virology SC Virology GA TP815 UT WOS:A1996TP81500011 PM 8553581 ER PT J AU Crowe, JE Firestone, CY Whitehead, SS Collins, PL Murphy, BR AF Crowe, JE Firestone, CY Whitehead, SS Collins, PL Murphy, BR TI Acquisition of the ts phenotype by a chemically mutagenized cold-passaged human respiratory syncytial virus vaccine candidate results from the acquisition of a single mutation in the polymerase (L) gene SO VIRUS GENES LA English DT Article DE respiratory syncytial virus; temperature sensitive mutant; viral polymerase ID TEMPERATURE-SENSITIVE MUTANT; SERONEGATIVE CHIMPANZEES; GENOMIC RNA; RSV; IMMUNOGENICITY; MUTAGENESIS; ATTENUATION; EXPRESSION; CHILDREN; EFFICACY AB A cold-passaged (cp) temperature-sensitive (fs) mutant of human respiratory syncytial virus designated RSV cpts-248 was previously derived by random chemical mutagenesis of the non-ts mutant cp-RSV that possesses one or more host range mutations. We previously demonstrated in rodents and seronegative chimpanzees that the cpts-248 virus is more attenuated than cp-RSV and is more stable genetically than previously isolated RSV ts mutants. In the present study, we determined that the acquisition of the ts phenotype and the increased attenuation of the cpts-248 virus are associated with a single nucleotide substitution at nucleotide 10,989 that results in a change in the coding region (amino acid position 831) of the polymerase gene. The identification of this attenuating ts mutation is important because cpts-248 was used as the parent virus for the generation of a number of further attenuated mutants that are currently being evaluated as candidate vaccine strains in clinical trials in infants. Furthermore, technology now exists to rationally design new vaccine candidates by incorporating multiple attenuating mutations, such as the one identified here, into infectious viruses that are genetically stable and appropriately attenuated. RP Crowe, JE (reprint author), NIAID,RESP VIRUSES SECT,INFECT DIS LAB,NIH,7 CTR DR MSC-0720,BETHESDA,MD 20892, USA. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 22 TC 30 Z9 42 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PY 1996 VL 13 IS 3 BP 269 EP 273 DI 10.1007/BF00366988 PG 5 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA WG147 UT WOS:A1996WG14700011 PM 9035372 ER PT J AU Le, SY Siddiqui, A Maizel, JV AF Le, SY Siddiqui, A Maizel, JV TI A common structural core in the internal ribosome entry sites of picornavirus, hepatitis C virus, and pestivirus SO VIRUS GENES LA English DT Article DE translation control; internal ribosome entry site; phylogenetic comparative analysis; RNA folding and common structure ID 5' NONTRANSLATED REGION; CELLULAR 57-KILODALTON PROTEIN; COMPARATIVE SEQUENCE-ANALYSIS; CAP-INDEPENDENT TRANSLATION; HUMAN RHINOVIRUS RNA; SECONDARY STRUCTURE; POLIOVIRUS RNA; UNTRANSLATED REGION; 5'-UNTRANSLATED REGION; 5'-NONCODING REGION AB Cap-independent translations of viral RNAs of enteroviruses and rhinoviruses, cardioviruses and aphthoviruses, hepatitis A and C viruses (HAV and HCV), and pestivirus are initiated by the direct binding of 40S ribosomal subunits to a cis-acting genetic element termed the internal ribosome entry site (IRES) or ribosome landing pad (RLP) in the 5' noncoding region (5'NCR). RNA higher ordered structure models for these IRES elements were derived by a combined approach using thermodynamic RNA folding, Monte Carlo simulation, and phylogenetic comparative analysis. The structural differences among the three groups of picornaviruses arise not only from point mutations, but also from the addition or deletion of structural domains. However, a common core can be identified in the proposed structural models of these IRES elements from enteroviruses and rhinoviruses, cardioviruses and aphthoviruses, and HAV. The common structural core identified within the picornavirus IRES is also conserved in the 5'NCR of the divergent viruses, HCV, and pestiviruses. Furthermore, the proposed structural motif shares a structural feature similar to that observed in the catalytic core of the group I intron, The conserved structural motif from these divergent sequences that looks like the common core region of group I introns is probably a crucial element involved in the IRES-dependent translation. C1 UNIV COLORADO,SCH MED,DEPT BIOCHEM BIOPHYS & GENET,DEPT MICROBIOL,DENVER,CO 80262. UNIV COLORADO,SCH MED,PROGRAM MOL BIOL,DENVER,CO 80262. RP Le, SY (reprint author), NCI,DIV CANC BIOL DIAG & CTR,NIH,MATH BIOL LAB,BLDG 469,ROOM 151,FREDERICK,MD 21702, USA. NR 44 TC 53 Z9 53 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PY 1996 VL 12 IS 2 BP 135 EP 147 DI 10.1007/BF00572952 PG 13 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA VF285 UT WOS:A1996VF28500004 PM 8879130 ER PT J AU Song, JW Baek, LJ Gavrilovskaya, IN Mackow, ER Hjelle, B Yanagihara, R AF Song, JW Baek, LJ Gavrilovskaya, IN Mackow, ER Hjelle, B Yanagihara, R TI Sequence analysis of the complete S genomic segment of a newly identified hantavirus isolated from the white-footed mouse (Peromyscus leucopus): Phylogenetic relationship with other sigmodontine rodent-borne hantaviruses SO VIRUS GENES LA English DT Article DE New York virus; hantavirus; evolution; genetic diversity; hantavirus pulmonary syndrome ID PROSPECT-HILL VIRUS; SOUTHWESTERN UNITED-STATES; PULMONARY SYNDROME; HEMORRHAGIC-FEVER; RENAL SYNDROME; GENETIC IDENTIFICATION; HANTAAN VIRUS; DISEASE; REITHRODONTOMYS; MANICULATUS AB Four Corners (FC) or Sin Nombre virus, a hantavirus harbored by the deer mouse (Peromyscus maniculatus), is the principal etiologic agent of hantavirus pulmonary syndrome (HPS). Recently, a hantavirus, designated New York (NY) virus, isolated from a white-footed mouse (Peromyscus leucopus) captured on Shelter Island, New York, was molecularly linked to a fatal case of HPS occurring in the northeastern United States. To clarify the genetic and phylogenetic relationship between NY and FC viruses and other sigmodontine rodent-borne hantaviruses, we amplified and sequenced the entire S genomic segment of NY virus. The S segment of NY virus was 2078 nucleotides long, with an open reading frame of 1284 nucleotides in the virus complementary strand, capable of encoding a protein of 428 amino acids, and with a 752-nucleotide long 3'-noncoding region, comprised of numerous imperfect repeats. Pairwise analysis indicated that NY virus was more similar to FC virus than to other sigmodontine rodent-borne hantaviruses, differing from strains of FC virus by 16.6-17.8% and 7.0-8.2% at the nucleotide and amino acid levels, respectively. As determined by the maximum parsimony and neighbor-joining methods, NY virus formed a separate lineage from FC virus and was phylogenetically distinct from hantaviruses harbored by other sigmodontine rodents. Whether or not NY and FC viruses represent distinct viral species is unclear. Further analyses of hantaviruses harbored by white-footed mice are needed to clarify the genetic diversity and evolution of Peromyscus-borne hantaviruses. C1 NINCDS, CENT NERVOUS SYST STUDIES LAB, NIH, BETHESDA, MD 20892 USA. SUNY STONY BROOK, DEPT MED, STONY BROOK, NY 11794 USA. VET ADM MED CTR, NORTHPORT, NY 11768 USA. UNIV NEW MEXICO, SCH MED, DEPT PATHOL, ALBUQUERQUE, NM 87131 USA. FU NIAID NIH HHS [R01 AI36336] NR 43 TC 11 Z9 11 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PY 1996 VL 12 IS 3 BP 249 EP 256 PG 8 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA VG570 UT WOS:A1996VG57000006 PM 8883362 ER PT B AU Lee, C Unser, M Ketter, TA AF Lee, C Unser, M Ketter, TA BE Ansari, R Smith, MJT TI Automated connectivity-based thresholding segmentation of midsagittal brain MR images SO VISUAL COMMUNICATIONS AND IMAGE PROCESSING '96 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Visual Communications and Image Processing 96 CY MAR 17-20, 1996 CL ORLANDO, FL SP Soc Photo Opt Instrumentat Engineers, IEEE Circuits & Syst Soc DE magnetic resonance images (MRI); segmentation; thresholding; brain; connectivity C1 NIH,BEIP,NCRR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2103-0 J9 P SOC PHOTO-OPT INS PY 1996 VL 2727 BP 713 EP 724 DI 10.1117/12.233286 PN 1-3 PG 12 WC Optics SC Optics GA BF32D UT WOS:A1996BF32D00067 ER PT S AU Davatzikos, C Vaillant, M Resnick, S Prince, JL Letovsky, S Bryan, RN AF Davatzikos, C Vaillant, M Resnick, S Prince, JL Letovsky, S Bryan, RN BE Hohne, KH Kikinis, R TI Morphological analysis of brain structures using spatial normalization SO VISUALIZATION IN BIOMEDICAL COMPUTING SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT 4th International Conference on Visualization in Biomedical Computing (VBC 96) CY SEP 22-25, 1996 CL HAMBURG, GERMANY SP German Res Council, IEEE, German Soc Comp Sci, German Soc Med Informat Biometr & Epidemiol AB We present an approach for analyzing the morphology of anatomical structures of the brain, which uses an elastic transformation to normalize brain images into a reference space. The properties of this transformation are used as a quantitative description of the size and shape of brain structures; inter-subject comparisons are made by comparing the transformations themselves. The utility of this technique is demonstrated on a small group of eigth men and eight women, by comparing the shape and size of their corpus callosum, the main structure connecting the two hemispheres of the brain. Our analysis found the posterior region of the female corpus callosum to be larger than its corresponding region in the males. The average callosal shape of each group was also found, demonstrating visually the callosal shape differences between the two groups. C1 NIA, LAB PERSONAL & COGNIT, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, DEPT ELECT & COMP ENGN, BALTIMORE, MD 21218 USA. RP Davatzikos, C (reprint author), JOHNS HOPKINS UNIV, DEPT RADIOL, BALTIMORE, MD 21218 USA. RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 NR 11 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-61649-7 J9 LECT NOTES COMPUT SC PY 1996 VL 1131 BP 355 EP 360 PG 6 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Mathematics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Mathematics; Radiology, Nuclear Medicine & Medical Imaging GA BH80E UT WOS:A1996BH80E00045 ER PT B AU Ludlow, CL Lou, G AF Ludlow, CL Lou, G BE Davis, PJ Fletcher, NH TI Observations on human laryngeal muscle control SO VOCAL FOLD PHYSIOLOGY: CONTROLLING COMPLEXITY AND CHAOS SE VOCAL FOLD PHYSIOLOGY SERIES LA English DT Proceedings Paper CT 9th Vocal Fold Physiology Symposium CY MAY 21-25, 1995 CL UNIV SYDNEY, SYDNEY, AUSTRALIA SP Voice Fdn, Univ Sydney, Fac Hlth Sci HO UNIV SYDNEY C1 NIDCD,VOICE & SPEECH SECT,NIH,BETHESDA,MD. NR 0 TC 6 Z9 6 U1 0 U2 0 PU SINGULAR PUBLISHING GROUP INC PI SAN DIEGO PA 4284 41ST ST, SAN DIEGO, CA 92105-1197 BN 1-56593-714-7 J9 VOCAL FOLD PY 1996 BP 201 EP 218 PG 18 WC Acoustics; Multidisciplinary Sciences; Physiology SC Acoustics; Science & Technology - Other Topics; Physiology GA BF97R UT WOS:A1996BF97R00014 ER PT S AU Ludlow, CL Barkmeier, J Edgar, J Ambalavanar, R AF Ludlow, CL Barkmeier, J Edgar, J Ambalavanar, R BE Clements, MP TI The relevance of molecular biology to voice and voice disorders SO VOICE UPDATE SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 1st World Voice Congress on Voice Update CY APR 09-13, 1995 CL OPORTO, PORTUGAL DE neurobiology; neuroplasticity; neurotoxicity; neurotransmission AB Our focus is to explore how the expansion of knowledge and techniques in molecular biology have potential for advancing our understanding of voice and voice disorders. Questions can be posed pertinent to the control of laryngeal development: the progenitor cell systems, patterns of laryngeal development and development of the neural control systems. Of greater importance to most voice disorders, however, are the mechanisms controlling laryngeal function throughout the life span and following injury. Topics for investigation include: the control of cell growth, differentiation, and cell death during development and thereafter; neurotropic factors affecting innervation and reinnervation: neuromuscular plasticity resulting from injury or activity; central plasticity and cell excitability following inflammation, stimulation or injury to peripheral afferents; detection of proto-oncogene expression following neuronal activity to determine the functional neuronal pathways; neurotransmitter systems controlling laryngeal function; and immunologic responses to inflammation. C1 Natl Inst Deafness & Other Commun Disorders, Voice & Speech Sect, Bethesda, MD USA. RP Ludlow, CL (reprint author), 10 Ctr Dr MSC 1416, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82230-5 J9 INT CONGR SER PY 1996 VL 97 BP 301 EP 310 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA BK09Q UT WOS:000071182700038 ER PT J AU Miller, YM Klein, HG AF Miller, YM Klein, HG TI Growth factors and their impact on transfusion medicine SO VOX SANGUINIS LA English DT Review ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; AUTOLOGOUS BLOOD DONATION; PHASE-III TRIAL; MYELODYSPLASTIC SYNDROMES; ADOPTIVE IMMUNOTHERAPY; ORTHOPEDIC PATIENTS; MYELOID-LEUKEMIA; DOUBLE-BLIND AB Hematopoietic growth factors, glycoproteins that stimulate self-renewal, differentiation, and proliferation of responsive hematopoietic cells, promise to revolutionize transfusion medicine. Recombinant DNA technology has made several of these cytokines available at pharmacologic doses, and new candidate agents for clinical application appear regularly. Growth factors prescribed for patients have already reduced the requirement for red blood cell and granulocyte transfusions in selected clinical circumstances. A lineage-specific thrombopoietin will likely limit the need for platelet transfusions, Hematopoietic cytokine injections have also been used to increase the number of red blood cells, granulocytes and circulating primitive progenitor cells in blood donors. Cytokine-stimulated peripheral blood progenitor cell infusions have complemented and, in some instances, replaced bone marrow for adjunctive cancer chemotherapy and for bone marrow transplantation. Finally, synergistic combinations of cytokines can effect ex vivo expansion of lymphocytes and of progenitor cells to provide novel blood components. Hematopoietic growth factors are still expensive and their long-term effects remain to be determined. However, as the biologic activities of cytokines and the physiology of hematopoietic progenitor cells become better understood, the clinical application of novel cellular components may redefine the concept of blood transfusion. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 48 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 1996 VL 71 IS 4 BP 196 EP 204 DI 10.1046/j.1423-0410.1996.7140196.x PG 9 WC Hematology SC Hematology GA VV932 UT WOS:A1996VV93200002 PM 8958642 ER PT J AU Blaese, RM Culver, K Kohn, D Morgan, R Miller, AD Anderson, WF Touraine, R Ramsey, WJ Ram, Z Oldfield, E AF Blaese, RM Culver, K Kohn, D Morgan, R Miller, AD Anderson, WF Touraine, R Ramsey, WJ Ram, Z Oldfield, E TI Gene therapy SO VOX SANGUINIS LA English DT Article; Proceedings Paper CT 24th Congress of the International-Society-of-Blood-Transfusion CY MAR 31-APR 05, 1996 CL MAKUHARI MESSE, JAPAN SP Int Soc Blood Transfus DE retroviral vector; adenosine deaminase; HSV-thymidine kinase, glioblastoma multiforme; T cells; cord blood stem cells C1 NINCDS,NIH,BETHESDA,MD 20892. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RP Blaese, RM (reprint author), NCHGR,NIH,BETHESDA,MD 20892, USA. OI Miller, Dusty/0000-0002-3736-3660 NR 3 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 1996 VL 70 SU 3 BP 21 EP 23 PG 3 WC Hematology SC Hematology GA UQ611 UT WOS:A1996UQ61100005 ER PT B AU Aldroubi, A AF Aldroubi, A BE Unser, MA Aldroubi, A Laine, AF TI Oblique multiwavelet bases: Examples SO WAVELET APPLICATIONS IN SIGNAL AND IMAGE PROCESSING IV, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 4th Conference on Wavelet Applications in Signal and Image Processing CY AUG 06-09, 1996 CL DENVER, CO SP Soc Photo Opt Instrumentat Engineers DE multiwavelet; multiscaling function; oblique wavelet bases; biorthogonal wavelet; semiorthogonal wavelet; perfect reconstruction filter bank; vector filter bank C1 NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2213-4 J9 P SOC PHOTO-OPT INS PY 1996 VL 2825 BP 54 EP 64 DI 10.1117/12.255271 PN 1-2 PG 11 WC Optics SC Optics GA BG61S UT WOS:A1996BG61S00006 ER PT B AU Vrhel, MJ Lee, C Unser, M AF Vrhel, MJ Lee, C Unser, M BE Unser, MA Aldroubi, A Laine, AF TI Comparison of algorithms for the fast computation of the continuous wavelet transform SO WAVELET APPLICATIONS IN SIGNAL AND IMAGE PROCESSING IV, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 4th Conference on Wavelet Applications in Signal and Image Processing CY AUG 06-09, 1996 CL DENVER, CO SP Soc Photo Opt Instrumentat Engineers DE wavelet; continuous wavelet transform; fast algorithms; oblique projection C1 NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,NATL CTR RES RESOURCES,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2213-4 J9 P SOC PHOTO-OPT INS PY 1996 VL 2825 BP 422 EP 431 DI 10.1117/12.255253 PN 1-2 PG 10 WC Optics SC Optics GA BG61S UT WOS:A1996BG61S00040 ER PT B AU Unser, M Thevenaz, P Aldroubi, A AF Unser, M Thevenaz, P Aldroubi, A BE Unser, MA Aldroubi, A Laine, AF TI Construction of shift-orthogonal wavelets using splines SO WAVELET APPLICATIONS IN SIGNAL AND IMAGE PROCESSING IV, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 4th Conference on Wavelet Applications in Signal and Image Processing CY AUG 06-09, 1996 CL DENVER, CO SP Soc Photo Opt Instrumentat Engineers DE splines; wavelet basis; biorthogonal wavelets; perfect reconstruction filterbanks; approximation properties; image coding C1 NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,NATL CTR RES RESOURCES,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2213-4 J9 P SOC PHOTO-OPT INS PY 1996 VL 2825 BP 465 EP 473 DI 10.1117/12.255257 PN 1-2 PG 9 WC Optics SC Optics GA BG61S UT WOS:A1996BG61S00044 ER PT S AU Castle, PE Dean, J AF Castle, PE Dean, J BE Gupta, SK Doberska, C TI Molecular genetics of the zona pellucida: Implications for immunocontraceptive strategies SO ZONA PELLUCIDA GLYCOPROTEINS AND IMMUNOCONTRACEPTION SE JOURNAL OF REPRODUCTION AND FERTILITY, SUPPLEMENTS LA English DT Proceedings Paper CT International Symp on Prospects of Zona Pellucida Glycoproteins for Immunocontraception, at 7th Annual Conf of Indian-Society-for-the-Study-of-Reproduction-and-Fertility CY DEC 02-05, 1995 CL NEW DELHI, INDIA SP Indian Soc Study Reprod & Fertil, Natl Inst Immunol, New Delhi C1 NIDDK, CELLULAR & DEV BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOURNALS REPRODUCTION & FERTILITY LTD PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE CB5 8DT, ENGLAND SN 0449-3087 BN 0-906545-30-7 J9 J REP FER S PY 1996 IS 50 BP 1 EP 8 PG 8 WC Developmental Biology; Immunology; Reproductive Biology SC Developmental Biology; Immunology; Reproductive Biology GA BG27U UT WOS:A1996BG27U00001 ER PT S AU Alexander, NJ Schlaff, WD AF Alexander, NJ Schlaff, WD BE Gupta, SK Doberska, C TI Highlights of the symposium SO ZONA PELLUCIDA GLYCOPROTEINS AND IMMUNOCONTRACEPTION SE JOURNAL OF REPRODUCTION AND FERTILITY, SUPPLEMENTS LA English DT Proceedings Paper CT International Symp on Prospects of Zona Pellucida Glycoproteins for Immunocontraception, at 7th Annual Conf of Indian-Society-for-the-Study-of-Reproduction-and-Fertility CY DEC 02-05, 1995 CL NEW DELHI, INDIA SP Indian Soc Study Reprod & Fertil, Natl Inst Immunol, New Delhi C1 NIH, POPULAT RES CTR, CONTRACEPT DEV BRANCH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOURNALS REPRODUCTION & FERTILITY LTD PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE CB5 8DT, ENGLAND SN 0449-3087 BN 0-906545-30-7 J9 J REP FER S PY 1996 IS 50 BP 191 EP 194 PG 4 WC Developmental Biology; Immunology; Reproductive Biology SC Developmental Biology; Immunology; Reproductive Biology GA BG27U UT WOS:A1996BG27U00023 ER PT J AU Drew, PD Franzoso, G Carlson, LM Biddison, WE Siebenlist, U Ozato, K AF Drew, PD Franzoso, G Carlson, LM Biddison, WE Siebenlist, U Ozato, K TI Interferon regulatory factor-2 physically interacts with NF-kappa B in vitro and inhibits NF-kappa B induction of major histocompatibility class I and beta 2-microglobulin gene expression in transfected human neuroblastoma cells SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE major histocompatibility complex; neuroblastoma; NF-kappa B; interferon regulatory factor-2; protein-protein interaction ID MHC CLASS-I; ONCOPROTEIN BCL-3; BINDING-PROTEIN; ENHANCER; SEQUENCE; DNA; ELEMENTS; TRANSACTIVATION; TRANSCRIPTION; HOMODIMERS AB Most neural cells constitutively lack major histocompatibility complex (MHC) class I and beta 2-microglobulin gene expression. Cytokines and viruses may, however, induce expression of these genes in some neural cells, and this correlates with factor binding to the NF-kappa B and interferon stimulated response elements of these genes. Here, we demonstrate that NF-kappa B is capable of inducing MHC class I and beta 2-microglobulin gene expression when transiently co-transfected into CHP-126 neuroblastomas, and that IRF-2 represses this induction, Interferon regulatory factor-2 (IRF-2) repression of MHC class I and beta 2-microglobulin gene expression in CHP-126 neuroblastomas may demonstrate a mechanism by which virus persists in neural cells. We show here that IRF-2 physically interacts in vitro with NF-kappa B. This interaction may contribute to the repression of the expression of these genes. Our demonstration that IRF family members, in addition to IRF-2, physically interact in vitro with NF-kappa B (p50 and p65), provides a general mechanism by which these transcription factors may, in concert, regulate the expression of a variety of genes involved in immune responses in the brain. C1 NICHHD,NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NICHHD,LAB MOLEC GROWTH REGULAT,BETHESDA,MD 20892. RP Drew, PD (reprint author), NICHHD,NINDS,NEUROIMMUNOL BRANCH,BLDG 10,RM 5B16,BETHESDA,MD 20892, USA. NR 37 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC 31 PY 1995 VL 63 IS 2 BP 157 EP 162 DI 10.1016/0165-5728(95)00140-9 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA TP159 UT WOS:A1995TP15900007 PM 8550813 ER PT J AU Xu, JL Prorok, PC AF Xu, JL Prorok, PC TI Non-parametric estimation of the post-lead-time survival distribution of screen-detected cancer cases SO STATISTICS IN MEDICINE LA English DT Article ID NATURAL-HISTORY; MORTALITY; DISEASE; DECONVOLUTION AB The goal of screening programmes for cancer is early detection and treatment with a consequent reduction in mortality from the disease. Screening programmes need to assess the true benefit of screening, that is, the length of time of extension of survival beyond the time of advancement of diagnosis (lead-time). This paper presents a non-parametric method to estimate the survival function of the post-lead-time survival (or extra survival time) of screen-detected cancer cases based on the observed total life time, namely, the sum of the lead-time and the extra survival time. We apply the method to the well-known data set of the HIP (Health Insurance Plan of Greater New York) breast cancer screening study. We make comparisons with the survival of other groups of cancer cases not detected by screening such as interval cases, cases among individuals who refused screening, and randomized control cases. As compared with Waiter and Stitt's model, in which they made parametric assumptions for the extra survival time, our non-parametric method provides a better fit to HIP data in the sense that our estimator for the total survival time has a smaller sum of squares of residuals. RP Xu, JL (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892, USA. NR 21 TC 12 Z9 12 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 30 PY 1995 VL 14 IS 24 BP 2715 EP 2725 DI 10.1002/sim.4780142410 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 TN247 UT WOS:A1995TN24700008 PM 8619110 ER PT J AU Fauci, A AF Fauci, A TI Immunopathogenic mechanisms of human immunodeficiency virus disease: Implications for therapy SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 19th International Congress of Chemotherapy (19th ICC) CY JUL 16-21, 1995 CL MONTREAL, CANADA ID INFECTION RP Fauci, A (reprint author), NIH,DEPT HLTH & HUMAN SERV,BLDG 31,ROOM 7A03,31 CTR DR MSC 2520,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 29 PY 1995 VL 99 SU 6A BP S59 EP S60 DI 10.1016/S0002-9343(99)80290-3 PN 1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA TV449 UT WOS:A1995TV44900015 PM 8585539 ER PT J AU Gallo, RC AF Gallo, RC TI The treatment of AIDS and cancer in the third millennium SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 19th International Congress of Chemotherapy (19th ICC) CY JUL 16-21, 1995 CL MONTREAL, CANADA RP Gallo, RC (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,37 CONVENT DR,MSC-4255,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 29 PY 1995 VL 99 SU 6A BP S6 EP S10 DI 10.1016/S0002-9343(99)80278-2 PN 1 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA TV449 UT WOS:A1995TV44900003 PM 8585540 ER PT J AU Parkinson, DR AF Parkinson, DR TI Present status of biological response modifiers in cancer SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 19th International Congress of Chemotherapy (19th ICC) CY JUL 16-21, 1995 CL MONTREAL, CANADA ID INTERLEUKIN-2; ANTITUMOR RP Parkinson, DR (reprint author), NCI,NIH,6130 EXECUT BLVD,EPN-715,BETHESDA,MD 20852, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 29 PY 1995 VL 99 SU 6A BP S54 EP S56 DI 10.1016/S0002-9343(99)80288-5 PN 1 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA TV449 UT WOS:A1995TV44900013 PM 8585537 ER PT J AU Wittes, RE AF Wittes, RE TI Promoting synergism in an era of change SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 19th International Congress of Chemotherapy (19th ICC) CY JUL 16-21, 1995 CL MONTREAL, CANADA ID CARE RP Wittes, RE (reprint author), NCI,DIV CANC TREATMENT DIAGNOSIS & CTR,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 29 PY 1995 VL 99 SU 6A BP S87 EP S90 DI 10.1016/S0002-9343(99)80300-3 PN 1 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA TV449 UT WOS:A1995TV44900025 PM 8585549 ER PT J AU Chang, YC Wickes, BL KwonChung, KJ AF Chang, YC Wickes, BL KwonChung, KJ TI Further analysis of the CAP59 locus of Cryptococcus neoformans: Structure defined by forced expression and description of a new ribosomal protein-encoding gene SO GENE LA English DT Article DE capsule; GAL7; fungus; L27 ribosomal protein; polysaccharide; virulence; transmembrane protein ID VIRULENCE; SEQUENCE; MUTANTS; SUBUNIT AB Cryptococcus neoformans (Cn) produces an extracellular polysaccharide capsule that is an essential factor for virulence. We previously isolated a gene, CAP59, which is necessary for capsule formation. To dissect the functional region of CAP59, we placed it under control of the Cn GAL7 promoter (pGAL7), Among the several pGAL7::CAP59 fusion constructs, only the one containing the entire open reading frame of CAP59 was able to complement the acapsular phenotype under galactose induction. A missense mutation in the coding region abolished complementation by the fusion construct. We also found that the CAP59 locus is contiguous to a convergently transcribed L27 ribosomal protein-encoding gene (CL27), The distance between the cDNA ends of these two genes is only 25 bp. CL27 has two introns near its N terminus. The translated CL27 protein is 183 amino acids (aa) in length with an estimated molecular mass of 20 kDa, and the first 34 aa at the N terminus may be a targeting peptide for mitochondria. A high degree of restriction-fragment-length polymorphism was detected in the DNA sequence containing CAP59 and CL27. C1 NIAID, CLIN INVEST LAB, BETHESDA, MD 20892 USA. UNIV CALIF SAN FRANCISCO, DEPT LAB MED, SAN FRANCISCO, CA 94143 USA. NR 18 TC 24 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD DEC 29 PY 1995 VL 167 IS 1-2 BP 179 EP 183 DI 10.1016/0378-1119(95)00640-0 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA TQ460 UT WOS:A1995TQ46000031 PM 8566774 ER PT J AU Wang, XY OhtakaMaruyama, C Pisano, MM Jaworski, CJ Chepelinsky, AB AF Wang, XY OhtakaMaruyama, C Pisano, MM Jaworski, CJ Chepelinsky, AB TI Isolation and characterization of the 5'-flanking sequence of the human ocular lens MIP gene SO GENE LA English DT Article DE eye lens fiber membrane; major intrinsic protein; promoter; transcriptional regulation; regulatory element; Alu repeat ID CRYSTALLIN GENE; CHLORAMPHENICOL ACETYLTRANSFERASE; REGULATORY ELEMENTS; MAMMALIAN-CELLS; EXPRESSION; PROMOTER; PROTEIN; METHYLATION; REPRESSION AB The MIP (major intrinsic protein) gene, a member of an ancient family of membrane channel genes, encodes the predominant fiber cell membrane protein of the ocular lens. Its specific expression in the lens fibers is temporally and spatially regulated during development. To study the regulation of expression of MIP and delineate the regulatory elements underlying its tissue specificity and ontogenic profile, we have cloned 2840 bp of the human MIP 5'-flanking sequence. The human MIP 5'-flanking sequence contains three complete Alu repetitive elements in tandem at position between nt -1699 and -2684 (nt -1699/-2684). These Alu elements appear to have had a complex evolutionary history with insertions at different times. We have fused DNA fragments containing MIP 5'-flanking sequences to the bacterial cat reporter gene encoding chloramphenicol acetyltransferase and assayed them in primary cultures of chicken lens cells. We have mapped two negative regulatory regions in the human MIP 5'-flanking sequences -1564/-1696 and -948/-1000. We demonstrated that the human MIP 5'-flanking sequence -253/+42 contains a functional promoter in lens cells but is inactive in kidney epithelial cells or mouse fibroblasts, suggesting that this sequence contains regulatory elements responsible for the lens-specific expression of MIP. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 27 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 29 PY 1995 VL 167 IS 1-2 BP 321 EP 325 DI 10.1016/0378-1119(95)00637-0 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA TQ460 UT WOS:A1995TQ46000056 PM 8566800 ER PT J AU Burbelo, PD Miyamoto, S Utani, A Brill, S Yamada, KM Hall, A Yamada, Y AF Burbelo, PD Miyamoto, S Utani, A Brill, S Yamada, KM Hall, A Yamada, Y TI p190-B, a new member of the Rho GAP family, and Rho are induced to cluster after integrin cross-linking SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING-PROTEIN; RECEPTOR TYROSINE KINASES; CELL-ADHESION; FIBRONECTIN RECEPTOR; FOCAL ADHESIONS; EXTRACELLULAR-MATRIX; SIGNAL TRANSDUCTION; CYTOPLASMIC DOMAIN; ACTIVATING PROTEIN; MOLECULAR-CLONING AB p120(GAP) forms distinct complexes with two phosphoproteins, p62 and p190, Here we have cloned a cDNA encoding a protein with 51% amino acid identity to p190 (hereafter designated p190-A) and have designated it p190-B. The N-terminal portion of p190-B contained several motifs characteristic of a GTPase domain, while its C terminus contained a Rho GAP domain, A recombinant Rho GAP domain polypeptide showed GAP activity for RhoA, Rac1, and G25K/CDC42Hs. Immunoprecipitation and immunofluorescence studies demonstrated that p190-B protein was expressed in a variety of cells and was localized diffusely in the cytoplasm and in fibrillar patterns that co-localized with the alpha(5) beta(1) integrin receptor for fibronectin, Adhesion of fibronectin-coated latex beads to cells resulted in recruitment of significant amounts of p190-B and Rho to the plasma membrane beneath the site of bead binding, In contrast, beads coated with polylysine or concanavalin A were unable to recruit p190-B or Rho, Additionally, anti-beta(1) or anti-alpha(5) integrin antibody-coated beads were also able to recruit large amounts of p190-B and Rho, These results identify a novel second member of the p190 family and establish the existence of a novel transmembrane link between integrins and a new protein p190-B and Rho. C1 NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. RP Burbelo, PD (reprint author), UCL, MRC, MOLEC CELL BIOL LAB, CRC ONCOGENE & SIGNAL TRANSDUCT GRP, GOWER ST, LONDON WC1E 6BT, ENGLAND. RI Burbelo, Peter/B-1027-2009; OI Yamada, Kenneth/0000-0003-1512-6805 NR 57 TC 90 Z9 91 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 29 PY 1995 VL 270 IS 52 BP 30919 EP 30926 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TN444 UT WOS:A1995TN44400015 PM 8537347 ER PT J AU Maraboeuf, F Voloshin, O CameriniOtero, RD Takahashi, M AF Maraboeuf, F Voloshin, O CameriniOtero, RD Takahashi, M TI The central aromatic residue in loop L2 of RecA interacts with DNA - Quenching of the fluorescence of a tryptophan reporter inserted in L2 upon binding to DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRANDED DNA; ESCHERICHIA-COLI; ENERGY-TRANSFER; PROTEIN; RECOMBINATION; BACTERIOPHAGE-T4; STOICHIOMETRY; MUTAGENESIS; ORIENTATION; COMPLEXES AB To determine the role of the central aromatic residue in one of the DNA binding domains in Escherichia coli RecA protein, we have constructed a protein in which a tryptophan fluorescence reporter is inserted in the place of phenylalanine residue 203 in loop L2, a putative DNA binding site, and measured its fluorescence, The modified protein is active both in vivo and in vitro, The binding of nucleotide cofactor (ATP or its analog adenosine 5'-O-3-thiotriphosphate) does not modify the fluorescence, By contrast, the binding of DNA, both in the absence and presence of cofactor, strongly decreases the fluorescence in intensity (40-65%) and shifts the emission peak from 344 to 337 nm. The change occurs both with single- and double-stranded DNA and also upon the binding of a second single-stranded DNA. The results indicate that the residue 203 is in fact close to the first and second DNA binding sites. However, the quenching is not total and depends only slightly can the nature of DNA bases, thus suggesting an indirect interaction with DNA bases. C1 INST CURIE, F-91405 ORSAY, FRANCE. NIDDK, GENET & BIOCHEM BRANCH, BETHESDA, MD 20892 USA. RP Maraboeuf, F (reprint author), CNRS, URA 1342, ETUD MUTAGENESE & CANCEROGENESE GRP, F-91405 ORSAY, FRANCE. NR 34 TC 28 Z9 28 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 29 PY 1995 VL 270 IS 52 BP 30927 EP 30932 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TN444 UT WOS:A1995TN44400016 PM 8537348 ER PT J AU FernandezRuiz, J Doudet, DJ Aigner, TG AF FernandezRuiz, J Doudet, DJ Aigner, TG TI Long-term cognitive impairment in MPTP-treated Rhesus monkeys SO NEUROREPORT LA English DT Article DE MPTP; spatial memory; dopamine; Parkinson; caudate nucleus; frontal cortex ID DOPAMINERGIC-NEURONS; PARKINSONISM; DEFICITS; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; DEPLETION; MODEL AB FOLLOWING MPTP administration, monkeys manifest cognitive deficits on tasks known to assess the fronto-striatal system; there are, however, no data regarding long-term cognitive effects. In this study, we examined the cognitive abilities of monkeys 10 years after MPTP administration. MPTP-treated monkeys and age-matched controls performed a spatial delayed response task with fixed and random delays. The MPTP-treated monkeys were impaired in both versions of the task. Both groups performed at the same level at very short delays suggesting that the nature of the impairment is related to a spatial memory deficit that is still apparent 10 years after treatment. These results suggest that, like Parkinson's patients, the MPTP-treated primates display spatial deficits. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. UNIV BRITISH COLUMBIA,DIV NEUROL,DEPT MED,VANCOUVER,BC V67 2B5,CANADA. RI Fernandez-Ruiz, Juan/B-6154-2012 OI Fernandez-Ruiz, Juan/0000-0002-4038-0904 NR 18 TC 22 Z9 22 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 29 PY 1995 VL 7 IS 1 BP 102 EP 104 DI 10.1097/00001756-199512000-00024 PG 3 WC Neurosciences SC Neurosciences & Neurology GA TX369 UT WOS:A1995TX36900024 PM 8742427 ER PT J AU Safieddine, S Eybalin, M AF Safieddine, S Eybalin, M TI Expression of mGluR1 alpha mRNA receptor in rat and guinea pig cochlear neurons SO NEUROREPORT LA English DT Article DE excitatory amino acids; mGluR1 alpha; spiral ganglion neurons; cochlea; rat; guinea pig; in situ hybridization ID METABOTROPIC GLUTAMATE RECEPTOR; NMDA RECEPTORS; MESSENGER-RNAS; ACID AB GLUTAMATE or a parent substance is thought to be the afferent neurotransmitter in the auditory system. In situ hybridization showed that mGluR1 alpha mRNA was expressed by type I and type II spiral ganglion neurons in the cochlea. The glial cells surrounding the type I spiral ganglion neurons lacked such expression. The hybridization signal was low compared to that reported for non-NMDA receptors, suggesting that mGluR1 alpha receptors, as is the case for NMDA receptors, play a minor role in auditory transmission. The uniform expression of mGluR1 alpha mRNAs along the cochlear spiral suggests their co-expression in spiral ganglion neurons with NMDA and non-NMDA receptors and thus functional cooperation. C1 CHU MONTPELLIER,LAB NEUROBIOL AUDIT,INSERM,UNITE 254,F-34592 MONTPELLIER,FRANCE. RP Safieddine, S (reprint author), NIDCD,NIH,9000 ROCKVILLE PIKE,BLDG 36,ROOM 5D08,BETHESDA,MD 20892, USA. RI EYBALIN, Michel/A-9895-2011 OI EYBALIN, Michel/0000-0001-9086-1856 NR 25 TC 15 Z9 15 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 29 PY 1995 VL 7 IS 1 BP 193 EP 196 PG 4 WC Neurosciences SC Neurosciences & Neurology GA TX369 UT WOS:A1995TX36900046 PM 8742449 ER PT J AU Ikari, H Zhang, L Chernak, JM Mastrangeli, A Kato, S Kuo, H Crystal, RG Ingram, DK Roth, GS AF Ikari, H Zhang, L Chernak, JM Mastrangeli, A Kato, S Kuo, H Crystal, RG Ingram, DK Roth, GS TI Adenovirus-mediated gene transfer of dopamine D-2 receptor cDNA into rat striatum SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Huntington's disease; Parkinson's disease; aging; motor performance; neurotransmitter receptor; gene therapy ID HERPES-SIMPLEX VIRUS; DISEASE; INVIVO; BRAIN; NEURONS; EXPRESSION; EPITHELIUM; VECTORS; THERAPY; SYSTEM AB A robust feature of mammalian aging associated with diminished motor control is the loss of dopamine D-2 receptors from the neostriatum. Decline in this neurotransmitter receptor is also observed in neurodegenerative disorders, such as Huntington's disease and late-stage Parkinson's disease. We have constructed a replication-deficient adenoviral vector to transfer rat dopamine D-2 receptor cDNA to brain as a possible therapeutic strategy. Using tissue culture cells infected with this vector, we detected dopamine D-2 receptor mRNA by Northern analysis and functional receptor protein in membrane preparations as specific binding of the dopamine D-2 receptor ligand, [H-3]spiperone. In vivo demonstration involved autoradiographic analysis of [H-3]spiperone binding in rat striatum following injection of the adenoviral vector. Dopamine D-2 receptor expression was amplified markedly above normal concentrations in the injection site, whereas no increased expression was observed in sites receiving control treatments. These results demonstrate the potential of gene therapy using adenoviral vectors to transfer neurotransmitter receptor proteins to the brain to reverse deficiencies in specific neurodegenerative disorders. C1 NATHAN W SHOCK LABS,CTR GERONTOL RES,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. NIA,BALTIMORE,MD 21224. CORNELL UNIV,SCH MED,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. YAMAGATA UNIV,SCH MED,DEPT INTERNAL MED 1,YAMAGATA 99023,JAPAN. NR 28 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC 28 PY 1995 VL 34 IS 2 BP 315 EP 320 DI 10.1016/0169-328X(95)00185-U PG 6 WC Neurosciences SC Neurosciences & Neurology GA TN597 UT WOS:A1995TN59700015 ER PT J AU Hillier, SL Nugent, RP Eschenbach, DA Krohn, MA Gibbs, RS Martin, DH Cotch, MF Edelman, R Pastorek, JG Rao, AV McNellis, D Regan, JA Carey, JC Klebanoff, MA AF Hillier, SL Nugent, RP Eschenbach, DA Krohn, MA Gibbs, RS Martin, DH Cotch, MF Edelman, R Pastorek, JG Rao, AV McNellis, D Regan, JA Carey, JC Klebanoff, MA TI Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AMNIOTIC-FLUID INFECTION; CHLAMYDIA-TRACHOMATIS; GESTATIONAL-AGE; PREGNANT-WOMEN; VAGINAL FLORA; GRAM STAIN; LABOR; PREMATURITY AB Background. Bacterial vaginosis is believed to be a risk factor for preterm delivery. We undertook a study of the association between bacterial vaginosis and the preterm delivery of infants with low birth weight after accounting for other known risk factors. Methods. In this cohort study, we enrolled 10,397 pregnant women from seven medical centers who had no known medical risk factors for preterm delivery. At 23 to 26 weeks' gestation, bacterial vaginosis was determined to be present or absent on the basis of the vaginal pH and the results of Gram's staining. The principal outcome variable was the delivery at less than 37 weeks' gestation of an infant with a birth weight below 2500 g. Results. Bacterial vaginosis was detected in 16 percent of the 10,397 women. The women with bacterial vaginosis were more likely to be unmarried, to be black, to have low incomes, and to have previously delivered low-birth-weight infants. In a multivariate analysis, the presence of bacterial vaginosis was related to preterm delivery of a low-birth-weight infant (odds ratio, 1.4; 95 percent confidence interval to 1.8). Other risk factors that were significantly associated with such a delivery in this population were the previous delivery of a low-birthweight infant (odds ratio, 6.2; 95 percent confidence interval, 4.6 to 8.4), the loss of an earlier pregnancy (odds ratio, 1.7, 1.3 to 2.2), primigravidity (odds ratio, 1.6; 1.1 to 1.9), smoking (odds ratio, 1.4, 1.1 to 1.7); and black race (odds ratio, 1.4; 1.1 to 1.7). Among women with bacterial vaginosis, the highest risk of preterm delivery of a low-birth-weight infant was found among those with both vaginal bacteroides and Mycoplasma hominis (odds ratio, 2.1; 95 percent confidence interval, 1.5 to 3.0). Conclusions. Bacterial vaginosis was associated with the preterm delivery of low-birth-weight infants independently of other recognized risk factors. C1 UNIV WASHINGTON, SEATTLE, WA 98195 USA. NICHHD, BETHESDA, MD 20892 USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. LOUISIANA STATE UNIV, NEW ORLEANS, LA USA. NIAID, BETHESDA, MD 20892 USA. RES TRIANGLE INST, RES TRIANGLE PK, NC 27709 USA. COLUMBIA UNIV, NEW YORK, NY USA. UNIV OKLAHOMA, OKLAHOMA CITY, OK USA. OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z99 EY999999]; NIAID NIH HHS [AI-4-2532]; NICHD NIH HHS [HD-3-2832, HD-3-2836] NR 29 TC 752 Z9 778 U1 2 U2 13 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 28 PY 1995 VL 333 IS 26 BP 1737 EP 1742 DI 10.1056/NEJM199512283332604 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TM169 UT WOS:A1995TM16900004 PM 7491137 ER PT J AU Evans, MV Mathews, HB AF Evans, MV Mathews, HB TI Session summary: Toxicokinetic interactive mechanisms SO TOXICOLOGY LA English DT Article DE chemical exposure; chemical mixtures; toxicokinetics; mathematical models C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Evans, MV (reprint author), US EPA,NATL HLTH & ENVIRONM EFFECTS RES LAB,EXPTL TOXICOL BRANCH,PHARMACOKINET BRANCH,RES TRIANGLE PK,NC 27711, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD DEC 28 PY 1995 VL 105 IS 2-3 BP 209 EP 210 DI 10.1016/0300-483X(95)03214-Z PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA TQ614 UT WOS:A1995TQ61400012 ER PT J AU Lei, PS Ogawa, Y Kovac, P AF Lei, PS Ogawa, Y Kovac, P TI Synthesis of the methyl alpha-glycoside of a trisaccharide mimicking the terminus of the O antigen of Vibrio cholerae O:1, serotype Inaba SO CARBOHYDRATE RESEARCH LA English DT Article DE oligosaccharide; trisaccharide; O-antigen; Vibrio cholerae O:1 ID BRUCELLA-A ANTIGEN; CARBOHYDRATE-CHEMISTRY; BETA-GLYCOSIDES; LIPOPOLYSACCHARIDE; (1->6)-BETA-D-GALACTOOLIGOSACCHARIDES; DETERMINANTS; ANTIBODY; ABORTUS; BINDING; ACCESS AB Coupling of methyl 4-amino-4,6-dideoxy-2-O-4-methoxybenzyl-alpha-D-mannopyranoside, obtained from the corresponding 4-azido derivative by treatment with H2S, with 3-deoxy-L-glycero-tetronolactone gave the crystalline methyl 4-(3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-2-O-4-methoxybenzyl-alpha-D-mannopyranoside (7). Subsequent acetylation of 7, followed by O-demethoxybenzylation of the 8 formed gave the crystalline methyl 3-O-acetyl-4,6-dideoxy-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-alpha-D-mannopyranoside (9), which was used as the key intermediate in the construction of the title trisaccharide. To make a glycosyl donor allowing the extension of the oligosaccharide chain at O-2, compound 9 was converted, via conventional transformations, into 3-O-acetyl-2-O-bromoacetyl-4,6-dideoxy-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-alpha-D-mannopyranosyl chloride (12). Condensation of 12 with 9 afforded the disaccharide 20 having a selectively removable protecting group at O-2(2). The latter was O-debromoacetylated, and the disaccharide nucleophile thus obtained was treated with 2,3-di-O-acetyl-4,6-dideoxy-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-alpha-D-mannopyranosyl chloride to give, after O-deacetylation, the target, title trisaccharide. The constituent monosaccharide of the O-specific polysaccharide antigen of Vibrio cholerae serotype Inaba, 4-(3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-D-mannopyranose (18), was obtained from the peracetate of its methyl alpha-glycoside by acetolysis, followed by O-deacetylation. The amorphous compound 18 was characterized by H-1 and C-13 NMR spectroscopy and through its crystalline alpha-per-O-acetyl derivative. C1 NIDDK,BETHESDA,MD 20892. NR 27 TC 23 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD DEC 27 PY 1995 VL 279 BP 117 EP 131 DI 10.1016/0008-6215(95)00281-2 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA TM287 UT WOS:A1995TM28700009 PM 8593618 ER PT J AU Petrakova, E Glaudemans, CPJ AF Petrakova, E Glaudemans, CPJ TI Synthesis of the methyl alpha-glycosides of some isomalto-oligosaccharides specifically deoxygenated at position C-4 SO CARBOHYDRATE RESEARCH LA English DT Article DE synthesis; methyl glycosides; alpha-isomalto-oligosaccharides; deoxyoligosaccharides ID STEREOSELECTIVE GLYCOSYLATION; SILVER PERCHLORATE; CHLORIDE; SUGARS; THIOGLYCOSIDES; GLUCOSIDES; CATALYST; ALCOHOLS AB Methyl alpha-isomaltoside and methyl alpha-isomaltotrioside specifically deoxygenated at position C-4 of various glucopyranosyl units were synthesized by condensation of either 1,6-di-O-acetyl-2,3-di-O-benzyl-4-deoxy-alpha,beta-D-xylo-hexopyranose (7) or 1,6-di-O-acetyl-2,3,4-tri-O-benzyl-alpha,beta-D-glucopyranose (10) [mediated by silver perchlorate and tin(IV) chloride] with suitably blocked derivatives of methyl alpha-D-glucopyranoside, its 4-deoxy analog 6, or methyl 4'-deoxy alpha-isomaltoside (13), respectively. RP Petrakova, E (reprint author), NIDDK,BETHESDA,MD 20892, USA. NR 20 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD DEC 27 PY 1995 VL 279 BP 133 EP 150 DI 10.1016/0008-6215(95)00280-4 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA TM287 UT WOS:A1995TM28700010 PM 8593619 ER PT J AU Lin, JT Coy, DH Mantey, SA Jensen, RT AF Lin, JT Coy, DH Mantey, SA Jensen, RT TI Comparison of the peptide structural requirements for high affinity interaction with bombesin receptors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE gastrin-releasing peptide; neuromedin B; bombesin; structure-function study ID GASTRIN-RELEASING PEPTIDE; SWISS 3T3 CELLS; CENTRAL-NERVOUS-SYSTEM; PANCREATIC ACINAR-CELLS; GUINEA-PIG PANCREAS; NEUROMEDIN-B; ANTAGONIST ACTIVITY; DISPERSED ACINI; LUNG-CANCER; RAT STOMACH AB Recently it has been established that both a gastrin-releasing peptide (GRP)-preferring bombesin receptor and a neuromedin B-preferring bombesin receptor mediate the mammalian actions of bombesin-related peptides. Because many tissues used for studies of the structure-activity relationship of these peptides possess both receptor subtypes and none possess only the neuromedin B-preferring subtype, there is minimal information on the peptide structural features determining receptor selectivity and it is unknown whether the determinants of agonism at both bombesin receptor subtypes are similar. In the present study we have used native cells either possessing only one bombesin receptor subtype or stably transfected with one subtype to study in detail the peptide structural requirements for interacting and activating each receptor subtype. For the naturally occurring agonists, at the GRP-preferring bombesin receptor the relative affinities were litorin = ranatensin = bombesin > GRP much greater than neuromedin B, phyllolitorin and at the neuromedin B-preferring bombesin receptor were litorin=neuromedin B=ranatensin > bombesin, phyllolitorin much greater than GRP. For the GRP-preferring bombesin receptor the heptapeptide and for the neuromedin B-preferring bombesin receptor the octapeptide was the minimal carboxyl fragment interacting with the receptor/or causing biologic activity, and the nonapeptide and full decapeptide, respectively, were the minimal required for full affinity. Making neuromedin B more bombesin- or GRP-like by replacing amino acids in position 3, 6, and 9 demonstrated that position 3 was the most important, followed by position 9 for receptor subtype selectivity. A conformationally restricted GRP analogue, [D-Cys(6),D-Ala(11),Cys(14)]bombesin-(6-14) had a significantly higher affinity for GRP-preferring bombesin receptor than NMB receptor. These results demonstrate that: (1) the structure-function relations for the two mammalian bombesin receptors have important differences; (2) suggest that the active conformation of neuromedin B must differ markedly from the beta-sheet model proposed for GRP; and (3) suggest that one important function of the NH2 terminus of GRP and neuromedin B is determining receptor subtype selectivity. C1 NIH,NIDDK,DDB,BETHESDA,MD 20892. TULANE UNIV,MED CTR,PEPTIDE RES LABS,NEW ORLEANS,LA 70112. FU NCI NIH HHS [CA45153] NR 62 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD DEC 27 PY 1995 VL 294 IS 1 BP 55 EP 69 DI 10.1016/0014-2999(95)00510-2 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TN777 UT WOS:A1995TN77700007 PM 8788416 ER PT J AU Bell, JA Beglan, CL AF Bell, JA Beglan, CL TI MK-801 blocks the expression but not the development of tolerance to morphine in the isolated spinal cord of the neonatal rat SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE MK-801; spinal cord; morphine tolerance; NMDA receptor antagonist; ventral root potential ID ASPARTATE RECEPTOR ANTAGONIST; SUBSTANCE-P; INVITRO; DEPENDENCE; MECHANISMS; POTENTIALS; ACTIVATION; RESPONSES; CAPSAICIN; THRESHOLD AB This study investigated the role of (MK-801; [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclo-hepten-5, 10-imine hydrogen maleate) in the development and expression of tolerance to morphine in the isolated spinal cord of the neonatal rat. Neonatal rats were treated chronically (3 or 4 days) with either morphine, morphine + MK-801, MK-801 alone or saline. Morphine, in a concentration-dependent manner, depressed a delayed ventral root potential produced by supramaximal electrical stimulation of an ipsilateral dorsal root. Chronic treatment of neonates with morphine alone, morphine with MK-801 and MK-801 alone produced tolerance to morphine depression of the ventral root potential. Acute MK-801 (300 nM) did not depress the ventral root potential but enhanced the depressant effects of acute morphine on the ventral root potential in saline-treated controls. Acute MK-801 (300 nM) appeared to reverse tolerance in all of the drug-treated groups. We conclude that MK-801 can mask the expression of morphine tolerance by enhancing the acute depressant effects of morphine. RP Bell, JA (reprint author), NIDA,DIV INTRAMURAL RES,NEUROIMAGING & DRUG ACT SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 36 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD DEC 27 PY 1995 VL 294 IS 1 BP 289 EP 296 DI 10.1016/0014-2999(95)00547-1 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TN777 UT WOS:A1995TN77700034 PM 8788443 ER PT J AU Bell, JA Beglan, CL AF Bell, JA Beglan, CL TI Co-treatment with MK-801 potentiates naloxone-precipitated morphine withdrawal in the isolated spinal cord of the neonatal rat SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE MK-801; morphine withdrawal; spinal cord; naloxone; morphine dependence ID RECEPTOR ANTAGONIST MK-801; NMDA RECEPTOR; TOLERANCE; DEPENDENCE; ATTENUATION; BINDING; NEURONS AB The effects of acute and chronic administration of (MK-801; [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate) were assessed on morphine dependence in the isolated spinal cord of the neonatal rat and on behavioral measures in intact adult rats. Neonatal rats were treated chronically (3 or 4 days) with injections of either morphine, morphine + MK-801, or saline. Naloxone (10 mu M) which increased baseline ventral root spontaneous firing, induced more activity in spinal cords from morphine-treated neonates than in saline controls. In spinal cords from neonates receiving MK-801 with morphine, naloxone-induced spontaneous firing was significantly greater than in saline-treated and morphine alone-treated neonates. Acute MK-801 attenuated naloxone-induced firing in the morphine-treated group. Chronic co-treatment with MK-801 increased locomotor signs of withdrawal and decreased mastication in intact adult rats which had been treated chronically with morphine. MK-801-induced enhancement of morphine withdrawal is consistent with upregulation of NMDA receptors. RP Bell, JA (reprint author), NIDA,DIV INTRAMURAL RES,NEUROIMAGING & DRUG ACT SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 19 TC 15 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD DEC 27 PY 1995 VL 294 IS 1 BP 297 EP 301 DI 10.1016/0014-2999(95)00548-X PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TN777 UT WOS:A1995TN77700035 PM 8788444 ER PT J AU Sau, AK Chary, KVR Govil, G Chen, CQ Howard, FB Miles, HT AF Sau, AK Chary, KVR Govil, G Chen, CQ Howard, FB Miles, HT TI Evidence for A(+)(anti)-G(syn) mismatched base-pairing in d-GGTAAGCGTACC SO FEBS LETTERS LA English DT Article DE A:G base pairing; mismatch base pair; DNA, nuclear Overhauser enhancement spectroscopy; clean total correlation spectroscopy ID NUCLEAR MAGNETIC-RESONANCE; DIMENSIONAL NMR-SPECTROSCOPY; DNA DUPLEX; OLIGONUCLEOTIDES; MACROMOLECULES; ASSIGNMENTS; ACIDS AB Two-dimensional MMR spectroscopy has been used to study the structure and hydrogen bonding scheme of A:G mismatched base pairing in d-GGTAAGCGTACC at pH 5.8, Under the conditions of our study, the molecule forms a B-DNA helix, with the mismatched bases in the A(+)(anti)-G(syn) conformation, The adenosine exists in the protonated form, The NOESY spectrum in 90% H2O + 10% (H2O)-H-2 has been used to assign all observable imino and amino protons including those involved in the A(+)(anti)-G(syn) base pair, Both the proton donors in the A:G mismatched inter-base hydrogen bonding are situated on adenosine. C1 TATA INST FUNDAMENTAL RES,CHEM PHYS GRP,BOMBAY 400005,MAHARASHTRA,INDIA. NATL INST HLTH,NIDDK,BETHESDA,MD 20892. NR 22 TC 9 Z9 9 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 27 PY 1995 VL 377 IS 3 BP 301 EP 305 DI 10.1016/0014-5793(95)01362-8 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TM338 UT WOS:A1995TM33800004 PM 8549742 ER PT J AU Cohen, BE Lee, G Arispe, N Pollard, HB AF Cohen, BE Lee, G Arispe, N Pollard, HB TI Cyclic 3'-5'-adenosine monophosphate binds to annexin I and regulates calcium-dependent membrane aggregation and ion channel activity SO FEBS LETTERS LA English DT Article DE cAMP; ATP; annexin I; calcium; membrane aggregation; channel activity ID ISOLATED CHROMAFFIN GRANULES; GENE ACTIVATOR PROTEIN; BILAYER-MEMBRANES; SYNEXIN; RESOLUTION; FORMS; IDENTIFICATION; CALPACTIN; FAMILY; FUSION AB The annexin (Anx) gene family comprises a set of calcium-dependent membrane binding proteins, which have been implicated in a wide variety of cellular processes including membrane fusion and calcium channel activity. We report here that cAMP activates Ca2+-dependent aggregation of both phosphatidylserine (PS) liposomes and bovine chromaffin granules driven by [des 1-12]annexin I (lipocortin I, AnxI). The mechanism of cAMP action involves an increase in Ansi-dependent cooperativity on the rate of such a reaction without affecting the corresponding k(1/2) values, Cyclic AMP causes the values of the Hill coefficient (n(H)) for AnxI to change from 3 to 6 in both PS liposomes and chromaffin granules, By contrast, ATP inhibits the rate of aggregation activity without affecting the cooperativity or the extent of aggregation process, We were also able to photolabel Ansi specifically with an 8-azido analogue of cAMP by a calcium-independent process, Such a process is saturable, yielding a K-d = 0.8 mu M by Scatchard analysis, Specific displacement occurs in the presence of cAMP and ATP. Finally, me found that cAMP alters the conductance of calcium channels formed by AnxI in planar lipid bilayers, We interpret these data to indicate that AnxI binds both calcium and cAMP independently, and that both actions have functional consequences, This is the first report of a nucleotide binding function for a member of the annexin gene family. C1 NIDDKD, CELL BIOL & GENET LAB, BETHESDA, MD 20892 USA. NR 29 TC 28 Z9 28 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD DEC 27 PY 1995 VL 377 IS 3 BP 444 EP 450 DI 10.1016/0014-5793(95)01395-4 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TM338 UT WOS:A1995TM33800035 PM 8549773 ER PT J AU KATZEL, LI BLEECKER, ER COLMAN, EG ROGUS, EM SORKIN, JD GOLDBERG, AP AF KATZEL, LI BLEECKER, ER COLMAN, EG ROGUS, EM SORKIN, JD GOLDBERG, AP TI EFFECTS OF WEIGHT-LOSS VS AEROBIC EXERCISE TRAINING ON RISK-FACTORS FOR CORONARY-DISEASE IN HEALTHY, OBESE, MIDDLE-AGED AND OLDER MEN - A RANDOMIZED CONTROLLED TRIAL SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; BODY-FAT DISTRIBUTION; PRECIPITATION PROCEDURE; CARDIOVASCULAR-DISEASE; ABDOMINAL OBESITY; OVERWEIGHT MEN; BLOOD-LIPIDS; PLASMA; WOMEN; GLUCOSE AB Objective.-To compare the effects of weight loss vs aerobic exercise training on coronary artery disease risk factors in healthy sedentary, obese, middle-aged and older men. Design.-Randomized controlled trial. Subjects.-A total of 170 obese (body mass index, 30+/-1 kg/m(2) [mean+/-SEM]), middle-aged and older (61+/-1 years) men. Interventions.-A g-month diet-induced weight loss intervention, 9-month aerobic exercise training program, and a weight-maintenance control group. Main Outcome Measures.-Change in body composition, maximal aerobic capacity (VO(2)max), blood pressure, lipoprotein concentrations, and glucose tolerance. Results.-Forty-four of 73 men randomized to weight loss completed the intervention and had a 10% mean reduction in weight (-9.5+/-0,.7 kg; P<.001), with no change in VO(2)max, Forty-nine of 71 men randomized to aerobic exercise completed the intervention, increased their VO(2)max by a mean of 17% (P<.001), and did not change their weight, whereas the 18 men who completed in the control group had no significant changes in body composition or VO(2)max. Weight loss decreased fasting glucose concentrations by 2%, insulin by 18%, and glucose and insulin areas during the oral glucose tolerance test (OGTT) by 8% and 26%, respectively (P<.01). By contrast, aerobic exercise did not improve fasting glucose or insulin concentrations or glucose responses during the OGTT but decreased insulin areas by 17% (P<.001). In analysis of variance, the decrement in fasting glucose and insulin levels and glucose areas with intervention differed between weight loss and aerobic exercise when compared with the control group (P<.05). Similarly, weight loss but not aerobic exercise increased high-density lipoprotein cholesterol levels (+13%) and decreased blood pressure compared with the control group. In multiple regression analyses, the improvement in lipoproteins and glucose metabolism was related primarily to the reduction in obesity. Conclusions.-These results suggest that weight loss is the preferred treatment to improve coronary artery disease risk factors in overweight, middle-aged and older men. C1 UNIV MARYLAND,SCH MED,DEPT MED,DIV GERONTOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DIV PULM MED,BALTIMORE,MD 21201. VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,BALTIMORE,MD. NIA,GERONTOL RES CTR,METAB SECT,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. FU NIA NIH HHS [T32 AG002109, P01 AG04402, 5-K08-AG00497] NR 36 TC 208 Z9 209 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 27 PY 1995 VL 274 IS 24 BP 1915 EP 1921 DI 10.1001/jama.274.24.1915 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA TL169 UT WOS:A1995TL16900032 PM 8568984 ER PT J AU Xing, GQ Zhang, LX Zhang, L Heynen, T Yoshikawa, T Smith, M Weiss, S DeteraWadleigh, S AF Xing, GQ Zhang, LX Zhang, L Heynen, T Yoshikawa, T Smith, M Weiss, S DeteraWadleigh, S TI Rat PPAR delta contains a CGG triplet repeat and is prominently expressed in the thalamic nuclei SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; CHAIN FATTY-ACIDS; PEROXISOME-PROLIFERATOR; FRAGILE-X; GLUCOCORTICOID RECEPTOR; ZELLWEGER SYNDROME; RESPONSE ELEMENT; ARACHIDONIC-ACID; CLOFIBRIC ACID; GENE AB We have isolated a new rat sequence containing motifs of a nuclear hormone receptor from a brain cDNA library. The deduced amino acid sequence encoded by the cDNA clone showed a strong homology to the human NUCI and the mouse peroxisome proliferator activated receptor delta (PPAR delta). We therefore refer to this new clone as rat PPAR delta (rPPAR delta). The new feature of rPPAR delta is a 14 CGG triplet repeat on the 5' untranslated region, not previously reported in either NUCI or mPPAR delta. We found that rPPAR delta was expressed as a 3.5-kb transcript which showed a wide distribution in adult rat tissues. Abundant expression was detected in brain, heart, skeletal muscle, kidney and lung. Weaker expression was noted in the liver, spleen and testis. To determine the specific brain localization of rPPAR delta we performed in situ hybridization analysis. Prominent expression was observed in the thalamus, particularly in the posterior part of the ventral medial nucleus, a site responsive to pain and cold stress. These results raise the possibility that PPAR delta might play a role in modulating response to thermal and pain sensations. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Xing, GQ (reprint author), NIMH,CLIN NEUROGENET BRANCH,UNIT GENE MAPPING & EXPRESS,BLDG 10,BETHESDA,MD 20892, USA. NR 42 TC 67 Z9 67 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 26 PY 1995 VL 217 IS 3 BP 1015 EP 1025 DI 10.1006/bbrc.1995.2871 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TM602 UT WOS:A1995TM60200042 PM 8554552 ER PT J AU Luu, NX Driscoll, WJ Martin, BM Strott, CA AF Luu, NX Driscoll, WJ Martin, BM Strott, CA TI Molecular cloning and expression of a guinea pig 3-hydroxysteroid sulfotransferase distinct from chiral-specific 3 alpha-hydroxysteroid sulfotransferase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article AB A guinea pig adrenal hydroxysteroid sulfotransferase (gpHST2) has been cloned that is distinct from guinea pig hydroxysteroid sulfotransferase that stereoselectively acts on 3 alpha-hydroxylated neutral steroids (gp3 alpha HST, redesignated gpHST1). The deduced amino acid sequences for gpHST1 and gpHST2 are 86% identical; however, whereas gpHST1 selectively acts on 3 alpha-hydroxylated steroids, gpHST2 demonstrates a clear preference (but not exclusive specificity) for 3 beta-hydroxylated steroids suggesting that gpHST2 is similar to a previously reported guinea pig hydroxysteroid sulfotransferase that selectively acts on 3 beta-hydroxylated neutral steroids (gp3 beta HST). Additionally, gpHST2 (33 K) is the same size as gp3 beta HST and larger than gpHST1 (32 K), contains amino acid sequences identical to peptides obtained from gp3 beta HST and cross-reacts with antibodies raised against purified gp3 beta HST. Nonetheless, gpHST2 can sulfonate both 3 alpha- and 3 beta-hydroxylated neutral steroids, suggesting that either gp3 beta HST does not have the exquisite stereoselectivity previously indicated or this subfamily of hydroxysteroid sulfotransferases is larger than originally thought. (C) 1995 Academic Press, Inc. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,STEROID REGULAT SECT,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD 20892. NR 15 TC 12 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 26 PY 1995 VL 217 IS 3 BP 1078 EP 1086 DI 10.1006/bbrc.1995.2879 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TM602 UT WOS:A1995TM60200050 PM 8554560 ER PT J AU Schultheiss, T Emerson, SU Purcell, RH GaussMuller, V AF Schultheiss, T Emerson, SU Purcell, RH GaussMuller, V TI Polyprotein processing in echovirus 22: A first assessment SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HEPATITIS-A VIRUS; EXPRESSION; 3C-PROTEINASE; PURIFICATION; TRANSLATION; SEQUENCE; PROTEASE; RNA AB The major steps of the polyprotein processing of Echovirus 22 (EV22), a highly unusual member of the picornavirus family, have been characterized for the first time by employing in vitro assay systems. Cell-free expression of a P1-2ABC precursor as well as VP1-2A yielded autoproteolytically inactive proteins, suggesting that the 2A region of the EV22 polyprotein does not contain a proteolytic activity. The intra- and intermolecular cleavage specificity of proteinase 3C, the major proteolytic enzyme in picornaviruses, was studied by expressing the enzyme of EV22 in a bacterial system as well as in the framework of precursor molecules generated by in vitro transcription/translation in a cell-free system. A VP1-2A precursor could very efficiently be cleaved in tt ans by the recombinant 3C, whereas the junction between P2 and P3 remained uncleaved. Expression of the complete P3-region in the cell-free system led to the autocatalytic release of large amounts of p22, a protein of the predicted molecular weight of the EV22 proteinase 3C that nas recognized by an antibody raised against the recombinant enzyme. (C) 1995 Academic Press, Inc. C1 UNIV LUBECK,INST MED MIKROBIOL,D-23538 LUBECK,GERMANY. RP Schultheiss, T (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,7 CTR DR 0740,BETHESDA,MD 20892, USA. NR 23 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 26 PY 1995 VL 217 IS 3 BP 1120 EP 1127 DI 10.1006/bbrc.1995.2885 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TM602 UT WOS:A1995TM60200056 PM 8554566 ER PT J AU Seltzer, AM Zorad, S Saavedra, JM AF Seltzer, AM Zorad, S Saavedra, JM TI Stimulation of angiotensin II AT(1) receptors in rat median eminence increases phosphoinositide hydrolysis SO BRAIN RESEARCH LA English DT Article DE angiotensin receptor; median eminence; second messenger system; quantitative autoradiography ID ANTERIOR-PITUITARY; PROLACTIN SECRETION; LUTEINIZING-HORMONE; AT1 RECEPTORS; FEMALE RAT; BRAIN; SUBTYPES; EXPRESSION; CELLS; MODULATION AB The aim of our study was to determine the second messenger systems for angiotensin II in the rat median eminence. Angiotensin II AT(1) receptors are highly expressed in the median eminence and binding is selectively inhibited by the guanine nucleotide GTP gamma S, indicating possible coupling to G-proteins. In male rats, angiotensin II increased phosphatidylinositol hydrolysis about 45% over basal values, with an EC(50) Of about 2.7 nM. This effect was antagonized by 10 mu M losartan, the selective AT(1) antagonist, but not by the AT(2) competitor PD 123319. Conversely, angiotensin II, 1 mu M, did not alter basal or forskolin-stimulated cAMP production, and failed to influence cGMP production. These results support a role for angiotensin II, through stimulation of AT(1) receptors and increased phosphatidylinositol hydrolysis, in the median eminence. Angiotensin II increased the phosphatidylinositol hydrolysis not only in male rats but also in ovariectomized rats, with or without estrogen-progesterone replacement. However, angiotensin II (up to 1 mu M) failed to increase the phosphatidylinositol hydrolysis in randomly selected intact female rats. Estrogen treatment did not alter the number or affinity of median eminence AT(1) receptors in ovariectomized rats. The increase in phosphatidylinositol hydrolysis resulting from stimulation of median eminence AT(1) receptors appears to be sexually dimorphic, but hormonal manipulations failed to point to a role for reproductive hormones in this phenomenon. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,BETHESDA,MD 20892. NR 28 TC 7 Z9 7 U1 0 U2 0 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 24 PY 1995 VL 705 IS 1-2 BP 24 EP 30 DI 10.1016/0006-8993(95)01100-5 PG 7 WC Neurosciences SC Neurosciences & Neurology GA TQ998 UT WOS:A1995TQ99800003 PM 8821729 ER PT J AU Kuo, H Ingram, DK Crystal, RG Mastrangeli, A AF Kuo, H Ingram, DK Crystal, RG Mastrangeli, A TI Retrograde transfer of replication deficient recombinant adenovirus vector in the central nervous system for tracing studies SO BRAIN RESEARCH LA English DT Article DE replication deficient recombinant adenovirus; beta-galactosidase; retrograde transport; neural tracing; rat striatum ID INVIVO GENE-TRANSFER; AXONAL-TRANSPORT; NEURONS; BRAIN; VIRUS; RAT; THERAPY; DISEASE; LIGHT AB We assessed the application of a replication deficient recombinant adenovirus vector as a retrograde tracer in neural pathway studies. The adenovirus vector, Ad.RSV beta gal, containing the intracellular marker gene, B-galactosidase, was injected directly into the laterodorsal striatum of rats. The retrograde transport of the vector from the injection site was clearly visible in the cerebral cortex, thalamic nucleus, and substantia nigra. No evidence for anterograde transport of the vector was found. When the vector was injected into the genu of the corpus callosum, little uptake of the vector by fibers was noted which suggested that uptake by fibers-of-passage should not be a problem in tracing studies. The present study demonstrates that adenoviral vectors can be useful retrograde tracers in the study of afferent connections within the central nervous system. C1 NIA,MOLEC PHYSIOL & GENET SECT,GRC,BALTIMORE,MD 21224. CORNELL MED CTR,NEW YORK HOSP,DIV PULM & CRIT CARE MED,PULM RES LABS,NEW YORK,NY 10021. NR 25 TC 47 Z9 48 U1 0 U2 2 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 24 PY 1995 VL 705 IS 1-2 BP 31 EP 38 DI 10.1016/0006-8993(95)01065-3 PG 8 WC Neurosciences SC Neurosciences & Neurology GA TQ998 UT WOS:A1995TQ99800004 PM 8821730 ER PT J AU Sanovich, E Bartus, RT Friden, PM Dean, RL Le, HQ Brightman, MW AF Sanovich, E Bartus, RT Friden, PM Dean, RL Le, HQ Brightman, MW TI Pathway across blood-brain barrier opened by the bradykinin agonist, RMP-7 SO BRAIN RESEARCH LA English DT Article DE RMP-7; bradykinin analog; blood-brain barrier; tight junction; permeability; lanthanum; hypotension ID DRUG-INDUCED HYPOTENSION; TUMOR BARRIERS; BINDING-SITES; PERMEABILITY; RAT; ENDOTHELIUM; CAPILLARY; BREAKDOWN; DELIVERY; VESSELS AB The route taken by lanthanum (MW 139) across cerebral endothelium was delineated when the blood-brain barrier was opened by RMP-7, a novel bradykinin agonist. Balb C mice were infused through a jugular vein with LaCl3 with or without RMP-7 (5 mu g/kg). Ten minutes later, the brains were fixed with aldehydes and processed for electron microscopy. The patency of the junctions between endothelial cells was estimated by counting the number of junctions penetrated by LaCl3. Tracer penetrated the junctions in about 25% of microvessels in vehicle infused, control mice and about 58% in the RMP-7 group, where more junctions per vessel were also penetrated. The LaCl3 then penetrated the basal lamina in about 20% of all microvessels in the RMP-7 group, versus 0.50% in the control group. From the basal lamina, the tracer entered perivascular spaces in about 13% of all microvessels in the RMP-7 group and about 0.07% in the controls. Very few endocytic pits or vesicles in the RMP-7 group were labeled, so LaCl3 did not cross endothelium by transcytosis. The increased number of tight junctions penetrated by tracer and its spread into periendothelial basal lamina and interstitial clefts indicated, therefore, a paracellular route of exudation in the RMP-7 treated animals. C1 ALKERMES INC,CAMBRIDGE,MA 02139. RP Sanovich, E (reprint author), NIH,NEUROBIOL LAB,9000 ROCKVILLE PIKE,ROOM 2A-21,BLDG 36,BETHESDA,MD 20892, USA. NR 52 TC 83 Z9 87 U1 0 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 24 PY 1995 VL 705 IS 1-2 BP 125 EP 135 DI 10.1016/0006-8993(95)01143-9 PG 11 WC Neurosciences SC Neurosciences & Neurology GA TQ998 UT WOS:A1995TQ99800017 PM 8821743 ER PT J AU deOliveira, AM Viswanathan, M Heemskerk, FMJ Saavedra, JM AF deOliveira, AM Viswanathan, M Heemskerk, FMJ Saavedra, JM TI Expression of a novel angiotensin II receptor subtype in gerbil brain SO BRAIN RESEARCH LA English DT Article DE hippocampus; circumventricular organ; guanine nucleotide; brain angiotensin system; receptor pharmacology; quantitative autoradiography ID BINDING-SITE; RAT-BRAIN; IDENTIFICATION; ANTAGONISTS; ISCHEMIA; DISTINCT AB Angiotensin II receptors are highly localized in adult gerbil brain. Apparent receptor number is high in subfornical organ, vascular organ of the lamina terminalis, nucleus of the solitary tract, hippocampus, and in the anterior pituitary gland. In the hippocampus, binding is localized to the stratum oriens, radiatum, the lacunar molecular layers of the CA1 subfield, and the molecular layer of the gyrus dentatus, with a medial to lateral and anterior to posterior gradient in receptor expression. Binding is absent from the pyramidal layer of the CA1 subfield and from the granular cell layer of the gyrus dentatus, areas rich in angiotensin IV binding. Characterization in the hippocampus revealed the presence of a high affinity receptor, sensitive to incubation with the guanine nucleotide GTP gamma S, and displaced by angiotensin II = angiotensin III < Sar(1)-Ile(8)-angiotensin II, but not by angiotensin IV or other angiotensin fragments, the AT(1) receptor antagonist losartan, or the AT(2) ligands CGP 42112 or PD 123177. In other brain areas, binding was equally insensitive to displacement by AT(1) or AT(2) ligands, with the exception of binding in the olfactory bulb, which was totally displaced by CGP 42112 and PD 123177, but not by losartan. In the gerbil, most of the brain and pituitary angiotensin II receptors are different from the AT(1), AT(2) and AT(4) subtypes, and should be considered 'atypical' until further characterization. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,BETHESDA,MD 20892. NR 25 TC 21 Z9 21 U1 0 U2 1 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 24 PY 1995 VL 705 IS 1-2 BP 177 EP 187 DI 10.1016/0006-8993(95)01158-7 PG 11 WC Neurosciences SC Neurosciences & Neurology GA TQ998 UT WOS:A1995TQ99800022 PM 8821748 ER PT J AU Krzywkowski, P Jacobowitz, DM Lamour, Y AF Krzywkowski, P Jacobowitz, DM Lamour, Y TI Calretinin-containing pathways in the rat forebrain SO BRAIN RESEARCH LA English DT Article DE calretinin; tract tracing; retrograde labelling; immunohistochemistry; calcium binding protein; nigro-striatal pathway ID CALCIUM-BINDING PROTEINS; MONKEY HIPPOCAMPAL-FORMATION; IMMUNOHISTOCHEMICAL LOCALIZATION; NONPYRAMIDAL CELLS; BRAIN; IMMUNOREACTIVITY; CALBINDIN-D28K; COLOCALIZATION; PARVALBUMIN; NEURONS AB The anatomy of pathways containing the calcium binding protein calretinin was investigated in the forebrain of the rat, using a combination of immunohistochemical and retrograde tract tracing techniques. Numerous well identified pathways do contain calretinin, whereas others do not. Pathways arising from the substantia nigra/ventral tegmental area, the dorsal raphe, the lateral mammillary nucleus, the supramammillary nucleus, the triangular septal and septo-fimbrial nuclei, several thalamic nuclei, the parabrachial nucleus, the peripeduncular nucleus, the medial amygdala contain at least some calretinin. The proportion of projection neurons containing calretinin ranged from 2% (dorsal raphe to caudate) to about 75% (triangular septal nucleus to habenula, medial amygdala to the ventromedial hypothalamus). More than 50% of the nigro-striatal neurons contain calretinin immunoreactivity. In contrast, other pathways do not contain any calretinin immunoreactivity (for instance the pathways arising from cerebral cortex, locus coeruleus, cholinergic forebrain nuclei), although calretinin may be present in local neurons in these structures. The present study demonstrates that calretinin is not associated specifically with projection neurons or local neurons, identified transmitter systems or functionnally related pathways in the forebrain of the rat. C1 INSERM,U161,F-75014 PARIS,FRANCE. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 28 TC 16 Z9 16 U1 0 U2 1 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 24 PY 1995 VL 705 IS 1-2 BP 273 EP 294 DI 10.1016/0006-8993(95)01167-6 PG 22 WC Neurosciences SC Neurosciences & Neurology GA TQ998 UT WOS:A1995TQ99800033 PM 8821759 ER PT J AU Dragnev, KH Nims, RW Lubet, RA AF Dragnev, KH Nims, RW Lubet, RA TI The chemopreventive agent diallyl, sulfide - A structurally atypical phenobarbital-type inducer SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE diallyl sulfide; phenobarbital; CYP; chemoprevention; liver enzymes; nuclear transcription factors ID RAT-LIVER; ORGANOSULFUR COMPOUNDS; CYTOCHROME-P450-2B1/2 GENES; METABOLIZING ENZYMES; EPOXIDE HYDROLASE; MESSENGER-RNA; INDUCTION; CARCINOGENESIS; CANCER; BINDING AB Diallyl sulfide (DAS), a known chemopreventive agent, was administered i.g. (200 or 500 mg/kg body wt/day) to male F344/NCr rats for 4 days. Livers were removed, and hepatic levels of a variety of drug-metabolizing enzymes were determined with either catalytic assays or by quantifying levels of total cellular RNA coding for the individual genes of interest The high dose of DAS induced the cytochrome P450 (CYP) 2B subfamily to near maximal levels [i.e. similar to those induced by phenobarbital (PB)] and induced the CYP3A subfamily, while having minimal effects on the levels of the CYP1A subfamily. In addition, DAS induced the glutathione 5-transferase alpha subfamily, the glutathione S-transferase mu subfamily, and epoxide hydrolase. Unlike PB, however, DAS was also able to induce quinone oxidoreductase. In fact, the pleiotropic hepatic response to DAS appeared to be similar to that elicited by PB, with the exception that only DAS induced quinone oxidoreductase. Finally, we determined that DAS induced the levels of a specific nuclear binding protein that appears to be associated with the induction of various genes that are part of the pleiotropic response caused by PB-type inducers. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. MICROBIOL ASSOCIATES INC,IN VITRO TOXICOL,ROCKVILLE,MD 20850. NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. NR 43 TC 23 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 22 PY 1995 VL 50 IS 12 BP 2099 EP 2104 DI 10.1016/0006-2952(95)02117-5 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL488 UT WOS:A1995TL48800019 PM 8849338 ER PT J AU Jensen, JP Bates, PW Yang, M Vierstra, RD Weissman, AM AF Jensen, JP Bates, PW Yang, M Vierstra, RD Weissman, AM TI Identification of a family of closely related human ubiquitin conjugating enzymes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REPAIR GENE RAD6; N-END RULE; CELL ANTIGEN RECEPTOR; PROTEIN-DEGRADATION; ACTIVATING ENZYME; CARRIER PROTEIN; CYCLE GENE; YEAST; CLONING; EXPRESSION AB Two very closely related human E2 ubiquitin conjugating enzymes, UbcH5B and UbcH5C, have been iden tified. These enzymes are products of distinct genes and are 88-89% identical in amino acid sequence to the recently described human E2, UbcH5 (now designated UbcH5A), UbcH5A-C are homologous to a family of five ubiquitin conjugating enzymes from Arabidopsis thaliana, AtUBC8-12. They are also closely related to Saccharomyces cerevisiae ScUBC4 and ScUBC5, which are involved in the stress response, and play a central role in the targeting of short-lived regulatory proteins for degradation, mRNAs encoding UbcH5A-C were co-expressed in all cell lines and tissues evaluated, with UbcH5C transcripts generally expressed at the highest levels, Analysis of Southern blots suggests that there are likely to be other related members of this family, Both UbcH5B and UbcH5C form thiol ester adducts with ubiquitin, and have activities similar to UbcH5A and AtUBC8 in the conjugation of ubiquitin to target proteins in the presence of the human ubiquitin protein ligase E6-AP. These results establish the existence of a highly conserved, and widely expressed, family of human ubiquitin conjugating enzymes. C1 NCI,IMMUNE CELL BIOL LAB,BETHESDA,MD 20892. UNIV WISCONSIN,DEPT HORT,MADISON,WI 53706. NR 52 TC 99 Z9 103 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 22 PY 1995 VL 270 IS 51 BP 30408 EP 30414 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TL675 UT WOS:A1995TL67500032 PM 8530467 ER PT J AU Cieplak, W Mead, DJ Messer, RJ Grant, CCR AF Cieplak, W Mead, DJ Messer, RJ Grant, CCR TI Site-directed mutagenic alteration of potential active-site residues of the A subunit of Escherichia coli heat-labile enterotoxin - Evidence for a catalytic role for glutamic acid 112 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLTRANSFERASE ACTIVITY; AERUGINOSA EXOTOXIN-A; PERTUSSIS TOXIN; CHOLERA-TOXIN; PSEUDOMONAS-AERUGINOSA; DIPHTHERIA-TOXIN; RIBOSYLATION FACTOR; NUCLEOTIDE BINDING; VIBRIO-CHOLERAE; S-1 SUBUNIT AB Escherichia coli heat-labile enterotoxin (LT) and the related cholera toxin exert their effects on eukaryotic cells through the ADP-ribosylation of guanine nucleotide-binding proteins of the adenylate cyclase complex. The availability of the crystal structure for LT has permitted the tentative identification of residues that lie within or are vicinal to a presumptive NAD(+)-binding site and thus may play a role in substrate binding or catalysis. Using a plasmid clone encoding the A subunit of LT, we have introduced substitutions at such potential active-site residues and analyzed the enzymatic properties of the resultant mutant analogs. Enzymatic analyses, employing both transducin and agmatine as acceptor substrates, revealed that substitutions at serine 61, glutamic acid 110, and glutamic acid 112 resulted in reduction of enzyme activity to <10% of wild type levels, Kinetic analyses indicated that alteration of these sites affected the catalytic rate of the enzyme and had little or no effect on the binding of either NAD(+) or agmatine. Of the mutant analogs analyzed, only glutamic acid 112 appeared to represent an essential catalytic residue as judged by the relative effects on k(cat) and k(cat)/K-m. The results provide formal evidence that glutamic acid 112 of the A subunit of LT represents a functional homolog or analog of catalytic glutamic acid residues that have been identified in several other bacterial ADP-ribosylating toxins and that it may play an essential role in rendering NAD(+) susceptible to nucleophilic attack by an incoming acceptor substrate. RP Cieplak, W (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 46 TC 28 Z9 28 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 22 PY 1995 VL 270 IS 51 BP 30545 EP 30550 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TL675 UT WOS:A1995TL67500051 PM 8530486 ER PT J AU Prasad, K Barouch, W Martin, BM Greene, LE Eisenberg, E AF Prasad, K Barouch, W Martin, BM Greene, LE Eisenberg, E TI Purification of a new clathrin assembly protein from bovine brain coated vesicles and its identification as myelin basic protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OLIGODENDROGLIAL MEMBRANE SHEETS; UNCOATING ATPASE; ORGANIZATION; POLYPEPTIDES; CYTOSKELETON AB The multimeric clathrin assembly proteins AP-1 and AP-2 with molecular masses of similar to 270 kDa and the monomeric clathrin assembly proteins AP(180) and auxilin with molecular masses of similar to 90 kDa catalyze the assembly of clathrin into artificial clathrin baskets under physiological conditions. We have now identified a much smaller similar to 20-kDa clathrin assembly protein in 0.5 M Tris, pH 7.0, extracts of bovine brain coated vesicles and purified it to near homogeneity. A polyclonal antibody against this protein did not cross-react with any of the other assembly proteins, and sequencing data suggest that this new protein is similar or identical to myelin basic protein (MBP). At a molar ratio of 3 molecules per clathrin triskelion, MBP catalyzes polymerization of clathrin into artificial baskets that appear structurally similar to the baskets assembled by the other assembly proteins. In addition, like the other baskets, the clathrin-MBP baskets are uncoated by hsp70. MBP represents a significant fraction of the total assembly protein activity present ent in 0.5 M Tris, pH 7.0, extracts of coated vesicles. It is not clear if it acts as an assembly protein in vivo, but because it is well characterized and easily available, MBP will be a useful protein to investigate the mechanism of clathrin assembly and disassembly in vitro. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 36 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 22 PY 1995 VL 270 IS 51 BP 30551 EP 30556 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TL675 UT WOS:A1995TL67500052 PM 8530487 ER PT J AU Torok, DS Ziffer, H Meshnick, SR Pan, XQ Ager, A AF Torok, DS Ziffer, H Meshnick, SR Pan, XQ Ager, A TI Syntheses and antimalarial activities of N-substituted 11-azaartemisinins SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PLASMODIUM-FALCIPARUM; ARTEMISININ; DERIVATIVES; CHEMISTRY; MALARIA; INVITRO AB A two-step reaction sequence between artemisinin and methanolic ammonia followed by treatment with Amberlyst 15 yielded 11-azaartemisinin in 65% yield. Substituting a variety of primary alkyl- and heteroaromatic amines for ammonia in the reaction sequence yields N-substituted 11-azaartemisinins in similar or greater yield. When Amberlyst 15 is replaced by a mixture of sulfuric acid/silica gel, both 11-azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin, are formed in 45% and 15% yields, respectively. In vitro and in vivo test data for a number of novel N-substituted 11-azaartemisinins, against drug-resistant strains of Plasmodium falciparum, show they possess antimalarial activities equal to or greater than that of artemisinin. The most active derivative, N-(2'-acetaldehydo)-11-azaartemisinin, 17, was 26 times more active in vitro and 4 times more active in vivo than artemisinin. C1 NIH,BETHESDA,MD 20892. UNIV MICHIGAN,SCH PUBL HLTH,DEPT EPIDEMIOL,ANN ARBOR,MI 48109. UNIV MIAMI,SCH MED,CTR TROP PARASIT DIS,DEPT MICROBIOL & IMMUNOL,MIAMI,FL 33177. NR 20 TC 45 Z9 47 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 22 PY 1995 VL 38 IS 26 BP 5045 EP 5050 DI 10.1021/jm00026a012 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TM545 UT WOS:A1995TM54500012 PM 8544181 ER PT J AU Robinson, MB Hopkins, K Batshaw, ML McLaughlin, BA Heyes, MP OsterGranite, ML AF Robinson, MB Hopkins, K Batshaw, ML McLaughlin, BA Heyes, MP OsterGranite, ML TI Evidence of excitotoxicity in the brain of the ornithine carbamoyltransferase deficient sparse fur mouse SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE urea cycle; quinolinic acid; excitotoxicity; NMDA; ornithine carbamoyltransferase deficiency; animal model; sparse fur mouse ID UREA-CYCLE ENZYMOPATHIES; QUINOLINIC ACID; CONGENITAL HYPERAMMONEMIA; CEREBROSPINAL-FLUID; SODIUM BENZOATE; RAT STRIATUM; TRYPTOPHAN; LESIONS; MICE; NEUROTOXICITY AB Ornithine carbamoyltransferase deficiency (OCTD) is the most common inborn error of urea synthesis. An X-linked disorder, OCTD males commonly present with hyperammonemic coma in the newborn period. There is a high rate of mortality and morbidity, with most survivors sustaining severe brain damage and resultant developmental disabilities. Although ammonia is presumed to be the principal neurotoxin, there is evidence that other neurochemical alterations may also be involved. The OCTD sparse fur (spf/Y) mouse has proven to be a useful model of this disease with similar metabolic and neurochemical alterations to those found in the human disease. In this study, the levels of the tryptophan derived excitotoxin quinolinic acid were examined in the brains of spf/Y mice. In addition, the neuropathology was examined using both Light and electron microscopic approaches. Consistent with reports in children with urea cycle disorders, the levels of tryptophan and quinolinic acid were increased two-fold in various brain regions of the spf/Y mouse. Quinolinic acid, an agonist at the N-methyl-D-aspartate (NMDA) receptors, is known to produce selective cell loss in the striatum. We found a significant loss of medium spiny neurons and increased numbers of reactive oligodendroglia and microglia in the striatum of spf/Y mice. These neurochemical and neuropathological observations are consistent with an excitotoxic influence on brain injury in OCTD. It leads us to suggest that administration of NMDA receptor antagonists may ameliorate brain damage in children with inborn errors of urea synthesis. C1 UNIV PENN,SCH MED,CHILDRENS SEASHORE HOUSE,PHILADELPHIA,PA 19104. UNIV PENN,CHILDRENS HOSP PHILADELPHIA,SCH MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. UNIV CALIF RIVERSIDE,DIV BIOMED SCI,RIVERSIDE,CA 92521. NIMH,BETHESDA,MD 20892. RP Robinson, MB (reprint author), ABRAMSON PEDIAT RES CTR,NEUROSCI RES ROOM 502,34TH & CIVIC CTR BLVD,PHILADELPHIA,PA 19104, USA. RI McLaughlin, BethAnn/D-9580-2012 OI McLaughlin, BethAnn/0000-0003-0228-6500 NR 38 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD DEC 21 PY 1995 VL 90 IS 1-2 BP 35 EP 44 DI 10.1016/0165-3806(96)83484-5 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA TL489 UT WOS:A1995TL48900004 ER PT J AU WOOSTER, R BIGNELL, G LANCASTER, J SWIFT, S SEAL, S MANGION, J COLLINS, N GREGORY, S GUMBS, C MICKLEM, G BARFOOT, R HAMOUDI, R PATEL, S RICE, C BIGGS, P HASHIM, Y SMITH, A CONNOR, F ARASON, A GUDMUNDSSON, J FICENEC, D KELSELL, D FORD, D TONIN, P BISHOP, DT SPURR, NK PONDER, BAJ EELES, R PETO, J DEVILEE, P CORNELISSE, C LYNCH, H NAROD, S LENOIR, G EGILSSON, V BARKADOTTIR, RB EASTON, DF BENTLEY, DR FUTREAL, PA ASHWORTH, A STRATTON, MR AF WOOSTER, R BIGNELL, G LANCASTER, J SWIFT, S SEAL, S MANGION, J COLLINS, N GREGORY, S GUMBS, C MICKLEM, G BARFOOT, R HAMOUDI, R PATEL, S RICE, C BIGGS, P HASHIM, Y SMITH, A CONNOR, F ARASON, A GUDMUNDSSON, J FICENEC, D KELSELL, D FORD, D TONIN, P BISHOP, DT SPURR, NK PONDER, BAJ EELES, R PETO, J DEVILEE, P CORNELISSE, C LYNCH, H NAROD, S LENOIR, G EGILSSON, V BARKADOTTIR, RB EASTON, DF BENTLEY, DR FUTREAL, PA ASHWORTH, A STRATTON, MR TI IDENTIFICATION OF THE BREAST-CANCER SUSCEPTIBILITY GENE BRCA2 SO NATURE LA English DT Article AB IN Western Europe and the United States approximately 1 in 12 women develop breast cancer. A small proportion of breast cancer cases, in particular those arising at a young age, are attributable to a highly penetrant, autosomal dominant predisposition to the disease. The breast cancer susceptibility gene, BRCA2, was recently localized to chromosome 13q12-q13. Here we report the identification of a gene in which we have detected six different germline mutations in breast cancer families that are likely to be due to BRCA2. Each mutation causes serious disruption to the open reading frame of the transcriptional unit. The results indicate that this is the BRCA2 gene. C1 INST CANC RES,HADDOW LABS,EPIDEMIOL SECT,SUTTON SM2 5NG,SURREY,ENGLAND. INST CANC RES,HADDOW LABS,CRC CTR CELL & MOLEC BIOL,SUTTON SM2 5NG,SURREY,ENGLAND. INST CANC RES,CHESTER BEATTY LABS,LONDON SW3 6JB,ENGLAND. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. SANGER CTR,HINXTON CB10 1RQ,CAMBS,ENGLAND. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. DUKE UNIV,MED CTR,DIV GYNECOL ONCOL,DURHAM,NC 27710. UNIV HOSP ICELAND,CELL BIOL LAB,IS-121 REYKJAVIK,ICELAND. IMPERIAL CANC RES FUND,CLARE HALL LABS,POTTERS BAR EN6 3LD,HERTS,ENGLAND. MCGILL UNIV,DEPT MED,DIV MED GENET,MONTREAL,PQ H3G 1A4,CANADA. MCGILL UNIV,DEPT MED,DIV HUMAN GENET,MONTREAL,PQ H3G 1A4,CANADA. IMPERIAL CANC RES FUND,GENET EPIDEMIOL LAB,LEEDS LS2 9LU,W YORKSHIRE,ENGLAND. ADDENBROOKES HOSP,CRC HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 2QQ,ENGLAND. LEIDEN UNIV,DEPT HUMAN GENET & PATHOL,2300 RA LEIDEN,NETHERLANDS. CREIGHTON UNIV,SCH MED,DEPT PREVENT MED & PUBL HLTH,OMAHA,NE 68178. INT AGCY RES CANC,F-69372 LYON 08,FRANCE. UNIV CAMBRIDGE,INST PUBL HLTH,DEPT COMMUNITY MED,CRC GENET EPIDEMIOL GRP,CAMBRIDGE CB2 2SR,ENGLAND. WOMENS COLL HOSP,TORONTO,ON M5S 1B2,CANADA. WASHINGTON UNIV,SCH MED,CTR GENOME SEQUENCING,ST LOUIS,MO. RP WOOSTER, R (reprint author), INST CANC RES,HADDOW LABS,MOLEC CARCINOGENESIS SECT,15 COTSWOLD RD,SUTTON SM2 5NG,SURREY,ENGLAND. RI Biggs, Patrick/H-3355-2014; OI Biggs, Patrick/0000-0002-0285-4101; Bishop, Tim/0000-0002-8752-8785 FU Wellcome Trust NR 13 TC 2101 Z9 2150 U1 11 U2 96 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD DEC 21 PY 1995 VL 378 IS 6559 BP 789 EP 792 DI 10.1038/378789a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TL419 UT WOS:A1995TL41900029 PM 8524414 ER PT J AU CUNNION, RE PARRILLO, JE AF CUNNION, RE PARRILLO, JE TI IMMUNOSUPPRESSIVE THERAPY FOR MYOCARDITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. RP CUNNION, RE (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 21 PY 1995 VL 333 IS 25 BP 1713 EP 1713 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TL401 UT WOS:A1995TL40100021 PM 7477235 ER PT J AU Zhan, SL Shapiro, DN Helman, LJ AF Zhan, SL Shapiro, DN Helman, LJ TI Loss of imprinting of IGF2 in Ewing's sarcoma SO ONCOGENE LA English DT Article DE IGF2; Ewing's sarcoma; genomic imprinting; pediatric sarcoma ID FACTOR-II GENE; GROWTH-FACTOR; WILMS-TUMOR; METHYLATION; EXPRESSION; RELAXATION; TRANSLOCATION; FUSION AB yInsulin-like Growth Factor 2 (IGF2) has recently been demonstrated to be maternally imprinted in both mice and humans, We previously reported loss of imprinting (LOI) of IGF2 in rhabdomyosarcoma (RMS) where IGF2 has been shown to act as an autocrine growth factor and play an important role in pathogenesis, Since IGF2 does not appear to play a role in the pathogenesis of Ewing's sarcoma, we sought to determine whether normal IGF2 imprinting was maintained in these tumors, Of 32 Ewing's tumors examined for imprinting of IGF2, 10 were informative heterozygotes and three of these expressed IGF2 biallelically. Furthermore, all three tumors with LOI and five of seven tumors with normal imprinting transcribed IGF2 mRNA at lower levels while relatively higher levels of IGFS expression was observed in the remaining two tumors with normal imprinting, These data demonstrate altered imprinting of IGF2 occurs some Ewing's sarcomas, However, LOI of IGF2 Ewing's sarcoma was not associated with increased expression of IGF2 mRNA, suggesting that LOI may not be involved in the regulation of IGF2 expression and may be related to genetic or epigenetic abnormalities in tumors independent of IGF2 expression. C1 NCI, PEDIAT BRANCH, MOLEC ONCOL SECT, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DEPT EXPTL ONCOL, MEMPHIS, TN 38101 USA. FU NCI NIH HHS [CA-21765, CA-23099] NR 31 TC 56 Z9 57 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD DEC 21 PY 1995 VL 11 IS 12 BP 2503 EP 2507 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TP188 UT WOS:A1995TP18800005 PM 8545106 ER PT J AU Givol, I Givol, D Rulong, S Resau, J Tsarfaty, I Hughes, SH AF Givol, I Givol, D Rulong, S Resau, J Tsarfaty, I Hughes, SH TI Overexpression of human p21(waf1/cip1) arrests the growth of chicken embryo fibroblasts transformed by individual oncogenes SO ONCOGENE LA English DT Article DE retrovirus; growth suppressor; cell cycle; waf1/cip1; p53 ID CYCLIN-DEPENDENT KINASES; SARCOMA VIRUS; P53; DNA; VECTORS; CELLS; EXPRESSION; INHIBITOR; PROTEIN; P21 AB In normal cells, cell growth and division is controlled by the interplay between proto-oncogenes and tumor genes, Cancer cells usually have both suppressor activated an suppressor gene, High level expression of a tumor suppressor, p53, can block the growth of cancer cells, waf1/cip1 is transactivated by the tumor suppressor p53 and the p21(waf1/cip1)protein is itself a suppressor of cell growth, To test the effect of growth suppression genes on the growth of cells transformed by individual oncogenes, we have used replication-competent retroviral vectors to induce high level expression of p53 and p21(waf1/cip1). Overexpression of p21(waf1/cip1) arrests chicken embryo fibroblasts (CEF) transformed by v-Src, tf-Ras, c-Mos and c-Myc. These data suggest that p21(waf1/cip1) might be a useful tool in gene therapy for human cancer. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. WEIZMANN INST SCI,DEPT MOLEC CELL BIOL,IL-76100 REHOVOT,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN MICROBIOL,IL-69978 TEL AVIV,ISRAEL. NR 41 TC 29 Z9 30 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 21 PY 1995 VL 11 IS 12 BP 2609 EP 2618 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TP188 UT WOS:A1995TP18800017 PM 8545118 ER PT J AU Taylor, ICA Roy, S Varmus, HE AF Taylor, ICA Roy, S Varmus, HE TI Overexpression of the Sky receptor tyrosine kinase at the cell surface or in the cytoplasm results in ligand-independent activation SO ONCOGENE LA English DT Article DE Sky receptor tyrosine kinase; dimerization; isoforms ID PROTEIN; ONCOGENE AB Most receptor tyrosine kinases are activated by dimerization induced by their cognate ligands, Protein S, an abundant serum protein previously shown to be a potent anticoagulation factor, has been proposed to be a ligand for the Sky tyrosine kinase (Stitt et al., 1995), Here we show that Sky, when expressed to high levels, is tyrosine phosphorylated even in the absence of a ligand, Furthermore, a version of Sky (termed Sky Delta SS) engineered to be overexpressed in the cytoplasm and thus in a ligand-free environment, can function as a dimeric tyrosine kinase, Sky Delta SS can transform RatB1a fibroblasts and thus retains all the properties of the full-length Sky kinase, These data suggest that Sky, when overexpressed either at the cell surface or in the cytoplasm, is competent to form dimers even in the absence of its ligand. We also demonstrate that an isoform of Sky, originally reported as Brt and here termed Sky Isoform I, resides in the cytoplasm, Therefore, the activities of Sky Delta SS we describe may reflect those of the naturally occurring Isoform I. C1 NCI,BETHESDA,MD 20892. NR 21 TC 30 Z9 30 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 21 PY 1995 VL 11 IS 12 BP 2619 EP 2626 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TP188 UT WOS:A1995TP18800018 PM 8545119 ER PT J AU Lengye, E Singh, B Gum, R Nerlov, C Sabichi, A Birrer, M Boyd, D AF Lengye, E Singh, B Gum, R Nerlov, C Sabichi, A Birrer, M Boyd, D TI Regulation of urokinase-type plasminogen activator expression by the v-mos oncogene SO ONCOGENE LA English DT Article DE urokinase; mos; MAPK; AP-1 ID PROTEIN-KINASE ACTIVITY; GENE-EXPRESSION; MAP KINASE; PHORBOL-ESTER; SARCOMA-VIRUS; C-JUN; TRANSFORMATION; PRODUCT; RAS; FOS AB We undertook a study to determine if the serine-threonine kinase-encoding v-mos oncogene regulated the expression of the urokinase-type plasminogen activator. An expression vector encoding v-mos, but not a kinase-inactive mutant, stimulated urokinase promoter activity in CAT assays employing a squamous cell carcinoma cell line, The induction of urokinase promoter activity by v-mos was mediated, in part, via an increased AP-1 activity since (a) mutation of 2 AP-1 binding sites (at -1967 and -1885), or the co-expression of a transactivation domain-lacking c-jun mutant reduced the induction of the urokinase promoter by v-mos and (b) expression of v-mos increased the activity of a CAT reporter driven by three AP-1 tandem repeats, The stimulation of the urokinase promoter by v-mos was partially countered by co-expression of an ERK1/ERK2-inactivating phosphatase. Western blotting and zymographic analysis indicated that v-mos-transformed NM3T3 cells (MSV NIH-3T3) secreted more urokinase compared with NIH3T3 cells and this was associated with a higher level of activated ERK1 and ERK2, Expression of a catalytically-inactive MAPKK mutant reduced the activity of a urokinase promoter-driven CAT reporter in the MSV NIH-3T3 cells, In conclusion, the data herein indicate that urokinase expression is regulated by v-mos through a MAPKK-dependent signaling pathway. C1 MD ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030. MD ANDERSON CANC CTR,DEPT HEAD & NECK SURG,HOUSTON,TX 77030. MD ANDERSON CANC CTR,DEPT MOLEC BIOL,HOUSTON,TX 77030. UNIV COPENHAGEN,INST MICROBIOL,COPENHAGEN,DENMARK. NIH,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD. RI Lengyel, Ernst/D-9220-2014 OI Lengyel, Ernst/0000-0001-8624-1507 FU NCI NIH HHS [R01CA58311]; NIDCR NIH HHS [R01DE10845] NR 53 TC 18 Z9 18 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 21 PY 1995 VL 11 IS 12 BP 2639 EP 2648 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TP188 UT WOS:A1995TP18800020 PM 8545121 ER PT J AU RiveroLezcano, OM Marcilla, A Robbins, KC AF RiveroLezcano, OM Marcilla, A Robbins, KC TI Mutations in the non-catalytic domains of Fyn and Fgr tyrosine kinases reveal differences in mechanisms of their regulation SO ONCOGENE LA English DT Article DE Fyn; Fgr; tyrosine kinase; mutation; SH2 and SH3 domains ID PROTEIN-KINASES; SH2 DOMAIN; C-SRC; GENE; PROTOONCOGENE; ACTIVATION; P60C-SRC; BINDING AB Non-catalytic domains of tyrosine kinases from the Src family are believed to be regulated intra- and intermolecularly through protein-protein interactions. We have deleted the SH2 and SH3 domains from Fyn and Fgr and have generated two point mutations in residues completely conserved in all members of the Src family. The dramatically different biological effects of these mutations suggest that non-catalytic domains regulate Src family kinase activities through distinctly different mechanisms. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RI marcilla, antonio/F-9996-2010; Rivero-Lezcano, Octavio/J-9089-2015 OI marcilla, antonio/0000-0003-0004-0531; Rivero-Lezcano, Octavio/0000-0002-8793-0731 NR 20 TC 4 Z9 4 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 21 PY 1995 VL 11 IS 12 BP 2675 EP 2679 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TP188 UT WOS:A1995TP18800024 PM 8545125 ER PT J AU Bettelheim, FA Zeng, FF Bia, Y Tumminia, SJ Russell, P AF Bettelheim, FA Zeng, FF Bia, Y Tumminia, SJ Russell, P TI Lens hydration in transgenic mice containing HIV-1 protease linked to the lens alpha A-crystallin promoter SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE HIV-1 protease; mouse lens; cataractogenesis; total water; nonfreezable water ID OPTICAL ANISOTROPY; CATARACT; FLUCTUATION; CALPAIN; EYE AB Two constructs of transgenic mice, TG(61) and TG(72), containing HIV-1 protease linked to lens alpha A-crystallin promoter develop cataract. The TG(61) construct exhibits cataractogenesis in utero while in the TG(72) construct frank opacities appear 24 days (homozygotes) and 26 days (hemizygotes) after birth, Differential scanning calorimetry and thermogravimetric analysis studies indicate that the hydration of lenses is strongly correlated with cataractogenesis, In all clear lenses (normal and precataractous) the total water content was the same, 68%, and increased upon opacification. The bound water, measured as percentage nonfreezable water of the total water, decreased upon cataract formation, indicating a syneretic process. On the other hand, the bound water expressed as grams of nonfreezable water per gram dry weight increases upon opacification. This implies that proteolysis and subsequent enhanced hydration is the primary supramolecular event in cataractogenesis and that syneresis in the lens of transgenic mice is of secondary importance. (C) 1995 Academic Press, Inc. C1 NEI,LAB MECHANISM OCULAR DIS,BETHESDA,MD 20892. RP Bettelheim, FA (reprint author), ADELPHI UNIV,DEPT CHEM,GARDEN CITY,NY 11530, USA. FU NEI NIH HHS [EY-02571] NR 20 TC 12 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC 20 PY 1995 VL 324 IS 2 BP 223 EP 227 DI 10.1006/abbi.1995.0034 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TN196 UT WOS:A1995TN19600004 PM 8554313 ER PT J AU Uchida, K Itakura, K Kawakishi, S Hiai, H Toyokuni, S Stadtman, ER AF Uchida, K Itakura, K Kawakishi, S Hiai, H Toyokuni, S Stadtman, ER TI Characterization of epitopes recognized by 4-hydroxy-2-nonenal specific antibodies SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID LOW-DENSITY LIPOPROTEIN; SMOOTH-MUSCLE CELLS; LIPID-PEROXIDATION; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; ENDOTHELIAL-CELLS; PROTEIN ADDUCTS; OXIDATION; LIVER; DEGRADATION; PRODUCTS AB In the present study, we have raised anti-peptide antibodies directed to the major membrane lipid peroxidation product 4-hydroxy-2-nonenal (HNE) attached covalently to histidine, and their specificities were compared with those of the polyclonal antibodies (anti-HNE-protein antibodies) raised against HNE-treated keyhole limpet hemocyanin (K. Uchida eb al. (1993) Proc. Natl. Acad. Sci. USA 90, 8742-8746), The anti-HNE-histidyl peptide antibodies (anti-HNE-histidine antibodies) were prepared by immunizing rabbits with a HNE-conjugated heptapeptide (Gly(3)-His-Gly(3), amide) coupled to the carrier protein. The antisera were purified on an affinity gel prepared by covalent attachment of a HNE-conjugated heptapeptide (Ala(3)-His-Ala(3) amide). Among the structurally defined 4-hydroxy-2-alkenal-amino acid adducts tested, binding of anti-HNE-histidine antibodies to the HNE-treated protein was not only inhibited by HNE-histidine, HNE-cysteine, and HNE-lysine, but also by 4-hydroxy-2-octenal-histidine and 4-hydroxy-2-decenal-histidine adducts. Cross-reactivity studies revealed that both anti-HNE-protein antibodies had the highest affinity for the HNE-treated protein and that neither of the antibodies cross-reacted with the protein treated with aldehydes including malondialdehyde, 1-hexanal, 2-hexenal, or 2-nonenal. These results suggest that the dominant epitope recognized by antibodies is the 2-CH3(CH2)n-5-hydroxytetrahydrofuran (n greater than or equal to 3) moiety of the Michael adducts. The immunohistochemical analysis of atherosclerotic lesions of human aorta demonstrated that these antibodies reacted strongly with granular cytoplasmic elements of foam cells and weakly with elements in the surrounding sclerotic stroma. (C) 1995 Academic Press, Inc. C1 KYOTO UNIV,FAC MED,DEPT PATHOL,SAKYO KU,KYOTO 606,JAPAN. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RP Uchida, K (reprint author), NAGOYA UNIV,SCH AGR,LAB FOOD & BIODYNAM,NAGOYA,AICHI 46401,JAPAN. RI Toyokuni, Shinya/C-1358-2010 OI Toyokuni, Shinya/0000-0002-5757-1109 NR 29 TC 114 Z9 118 U1 1 U2 8 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC 20 PY 1995 VL 324 IS 2 BP 241 EP 248 DI 10.1006/abbi.1995.0036 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TN196 UT WOS:A1995TN19600006 PM 8554315 ER PT J AU TSAI, AM BETENBAUGH, MJ SHILOACH, J AF TSAI, AM BETENBAUGH, MJ SHILOACH, J TI THE KINETICS OF RCC1 INCLUSION-BODY FORMATION IN ESCHERICHIA-COLI SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE CHROMOSOME CONDENSATION PROTEIN; INCLUSION BODY; ESCHERICHIA COLI ID SOLUBLE RECOMBINANT PROTEINS; SUPEROXIDE-DISMUTASE; GROWTH-RATE; EXPRESSION; BODIES; GENE; TEMPERATURE; AGGREGATION; REGULATOR; UREA AB The Regulator of Chromosome Condensation protein (RCC1) is located in both the soluble and inclusion body (IB) fractions of the whole cell lysate when expressed in Escherichia coli BL21 (pLysS) at temperatures below 30 degrees C. When bacterial growth was carried out at 20 degrees C, the majority of the RCC1 remained soluble up to 5.5 h postinduction. When the temperature was raised to 25 degrees C, RCC1 IB was dominant by 1.5 h postinduction. The shift in RCC1 IB formation with temperature suggests that in addition to increased translation rates, folding and aggregation processes may contribute to RCC1 IB formation at higher temperatures. (C) 1995 John Wiley & Sons, Inc. C1 NIDDK,BIOTECHNOL UNIT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT CHEM ENGN,BALTIMORE,MD 21218. RI Betenbaugh, Michael J./A-3252-2010 OI Betenbaugh, Michael J./0000-0002-6336-4659 NR 28 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD DEC 20 PY 1995 VL 48 IS 6 BP 715 EP 718 DI 10.1002/bit.260480620 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA TF749 UT WOS:A1995TF74900019 PM 18623541 ER PT J AU VonLubitz, DKJE Lin, RCS Jacobson, KA AF VonLubitz, DKJE Lin, RCS Jacobson, KA TI Cerebral ischemia in gerbils: Effects of acute and chronic treatment with adenosine A(2A) receptor agonist and antagonist SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE adenosine; ischemia; adenosine receptor; therapy; (gerbil) ID BLOOD-FLOW; RAT-BRAIN; INVITRO; MK-801 AB Despite significant progress in understanding of the potential of adenosine A(1) receptor-based therapies in treatment of cerebral ischemia and stroke, very little is known about the effect of selective stimulation of adenosine A(2 alpha) receptors on the outcome of a cerebrovascular arrest. In view of a major role played by adenosine A(2) receptors in the regulation of cerebral blood flow, we have investigated the effect of both acute and chronic administration of the selective adenosine receptor agonist 2-[(2-aminoethylamino)-carbonylethylphenyethylamino]-5'-N-ethylcarboxoamidoadenosine (APEC) and antagonist 8-(3-chlorostyryl)caffeine (CSC) on the outcome of 10 min ischemia in gerbils. Acute treatment with APEC improved recovery of postischemic blood flow and survival without affecting neuronal preservation in the hippocampus. Acute treatment with CSC had no effect on the cerebral blood flow but resulted in a very significant protection of hippocampal neurons. Significant improvement of survival was present during the initial 10 days postischemia. Due to subsequent deaths of animals treated acutely with CSC, the end-point mortality (14 days postischemia) in this group did not differ statistically from that seen in the controls. It is, however, possible that the late mortality in the acute CSC group was caused by the systemic effects of brain ischemia that are not subject to the treatment with this drug. Chronic treatment with APEC resulted in a statistically significant improvement in all studied measures. Although chronic treatment with CSC improved postischemic blood flow, its effect on neuronal preservation was minimal and statistically insignificant. Mortality remained unaffected. The results indicate that the acute treatment with adenosine A(2 alpha) receptor antagonists may have a limited value in treatment of global ischemia. However, since administered CSC has no effect on the reestablishment of postischemic blood flow, treatment of stroke with adenosine A(2 alpha) receptor antagonists may not be advisable. Additional studies are necessary to elucidate whether chronically administered drugs acting at adenosine A(2 alpha) receptors may be useful in treatment of stroke and other neurodegenerative disorders. C1 HAHNEMANN UNIV,MED COLL PENN,PHILADELPHIA,PA 19102. RP VonLubitz, DKJE (reprint author), NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 35 TC 109 Z9 109 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD DEC 20 PY 1995 VL 287 IS 3 BP 295 EP 302 DI 10.1016/0014-2999(95)00498-X PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL717 UT WOS:A1995TL71700011 PM 8991804 ER PT J AU Fujita, M Enomoto, T Yoshino, K Nomura, T Buzard, GS Inoue, M Okudaira, Y AF Fujita, M Enomoto, T Yoshino, K Nomura, T Buzard, GS Inoue, M Okudaira, Y TI Microsatellite instability and alterations in the hMSH2 gene in human ovarian cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; GENOMIC INSTABILITY; ASSOCIATION; MUTATIONS; CARCINOMA; HOMOLOG; CELLS; COLON AB The role of the replication error-positive (RER(+)) phenotype in the development of specific subtypes of sporadic ovarian carcinomas was examined by screening for the presence of microsatellite instability (MI) in 47 tumors. The overall frequency of ovarian MI was 17% only. However, MI occurred in 50% of the ovarian endometrioid-type tumors, which was significantly more often than in all the other histological subtypes combined (8%). Five of the 8 RER(+) tumors exhibited most marked type I instability, possibly representing a different mechanism than for the remaining type 2 tumors. The cDNA of the mutation suppression gene hMSH2, the gene most often associated with MI, was screened for alterations in 8 MI-positive and 5 MI-negative ovarian tumors. Only 3 changes were found. Complete loss of hMSH2 mRNA expression was detected in I tumor, while another expressed only an abnormal transcript containing a deletion of exon 3, One additional RER(+) serous adenocarcinoma contained a rare polymorphism with a nonconservative amino acid change. One of 8 RER(+) tumors showed loss of heterozygosity at the hMSH2 loci. Genetic instability, caused in part by alterations in the hMSH2 gene, may play an important role in the sporadic endometrioid subtype of ovarian tumors. Other mutator-phenotype genes may be responsible for the remaining cases of RER(+) ovarian tumors. (C) 1995 Wiley-Liss, Inc. C1 OSAKA UNIV,SCH MED,DEPT OBSTET & GYNECOL,FAC MED,SUITA,OSAKA 565,JAPAN. OSAKA UNIV,FAC MED,DEPT RADIAT BIOL,OSAKA 565,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BCDP,FREDERICK,MD 21702. KANAZAWA UNIV,FAC MED,DEPT OBSTET & GYNECOL,KANAZAWA,ISHIKAWA 920,JAPAN. NR 34 TC 114 Z9 116 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 20 PY 1995 VL 64 IS 6 BP 361 EP 366 DI 10.1002/ijc.2910640602 PG 6 WC Oncology SC Oncology GA TQ488 UT WOS:A1995TQ48800001 PM 8550235 ER PT J AU HENRARD, DR GOEDERT, J AF HENRARD, DR GOEDERT, J TI PERCENTAGE OF CD4 LYMPHOCYTES AND RISK OF AIDS - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI,ROCKVILLE,MD. RP HENRARD, DR (reprint author), INST PASTEUR,PARIS,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 20 PY 1995 VL 274 IS 23 BP 1836 EP 1836 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TK147 UT WOS:A1995TK14700016 ER PT J AU LAUNER, LJ MASAKI, K PETROVITCH, H FOLEY, D HAVLIK, RJ AF LAUNER, LJ MASAKI, K PETROVITCH, H FOLEY, D HAVLIK, RJ TI THE ASSOCIATION BETWEEN MIDLIFE BLOOD-PRESSURE LEVELS AND LATE-LIFE COGNITIVE FUNCTION - THE HONOLULU-ASIA AGING STUDY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY HEART-DISEASE; WHITE MATTER LESIONS; MINI-MENTAL STATE; JAPANESE MEN; HYPERTENSION; STROKE; HAWAII; CALIFORNIA; MORTALITY; DEMENTIA AB Objective.-To assess the long-term relationship of midlife blood pressure levels to late-life cognitive function. Design.-The 4678 surviving cohort members of the prospective Honolulu Heart Program (baseline, 1965-1968) were examined a fourth time in 1991 through 1993 and given a cognitive test. Participants.-The subjects were 3735 Japanese-American men living in Hawaii in the community or in institutions, with an average age of 78 years at the fourth examination. Main Outcome Measures.-Cognitive function, measured by the 100-point Cognitive Abilities Screening Instrument (CASI), was categorized into good (reference: a CASI score of 92 to 100), intermediate (<92 to 82), and poor (<82). Midlife systolic blood pressure (SEP) and diastolic blood pressure (DBP) values were measured in 1965, 1968, and 1971. A respondent was classified into the following categories if two of three measurements fell into the following groups: for SEP, <110, 110 to 139, 140 to 159, and greater than or equal to 160 mm Hg; and for DBP, <80, 80 to 89, 90 to 94, and greater than or equal to 95 mm Hg. Results.-When we controlled for age and education, the risk for intermediate and poor cognitive function increased progressively with increasing level of midlife SEP category (P for trend <.03 and <.001, respectively). for every 10-mm Hg increase in SEP there was an increase in risk for intermediate cognitive function of 7% (95% confidence interval [C], 3% to 11%) and for poor cognitive function of 9% (95% CI, 3% to 16%). Adjustment for prevalent stroke, coronary heart disease, and subclinical atherosclerosis reduced the strength of the relationship between midlife SEP and poor cognitive function to 5% (95% CI, 0% to 12%). The level of cognitive function was not associated with midlife DBP. Conclusions.-Midlife SEP is a significant predictor of reduced cognitive function in later life. Early control of SEP levels may reduce the risk for cognitive impairment in old age. C1 ERASMUS UNIV ROTTERDAM,SCH MED,DEPT EPIDEMIOL & BIOSTAT,BILTHOVEN,NETHERLANDS. UNIV HAWAII,DEPT MED,HONOLULU,HI. KUAKINI MED CTR,HONOLULU,HI 96817. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. RP LAUNER, LJ (reprint author), NATL INST PUBL HLTH & ENVIRONM PROTECT,POB 1,3720 BA BILTHOVEN,NETHERLANDS. FU NHLBI NIH HHS [N01-HR-02901]; NIA NIH HHS [N01-AG-4-2149] NR 43 TC 520 Z9 535 U1 2 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 20 PY 1995 VL 274 IS 23 BP 1846 EP 1851 DI 10.1001/jama.274.23.1846 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TK147 UT WOS:A1995TK14700025 PM 7500533 ER PT J AU MAX, MB DONOVAN, M MIASKOWSKI, CA WARD, SE GORDON, D BOOKBINDER, M CLEELAND, CS COYLE, N KISS, M THALER, HT JANJAN, N WEINSTEIN, S EDWARDS, T AF MAX, MB DONOVAN, M MIASKOWSKI, CA WARD, SE GORDON, D BOOKBINDER, M CLEELAND, CS COYLE, N KISS, M THALER, HT JANJAN, N WEINSTEIN, S EDWARDS, T TI QUALITY IMPROVEMENT GUIDELINES FOR THE TREATMENT OF ACUTE PAIN AND CANCER PAIN SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MEDICAL-STUDENTS; ATTITUDES; PATIENT; MANAGEMENT; CARE; UNDERTREATMENT; INPATIENTS; KNOWLEDGE; EDUCATION; CHILDREN AB Objective.-To develop quality improvement (QI) guidelines and programs to improve treatment outcomes for patients with acute pain and cancer pain. Participants.-Twenty-four members of the American Pain Society (APS) participated in preparing the statement, including 15 nurses (oncology, general medical-surgical nursing, pediatrics, and QI research), seven physicians (clinical pharmacology, neurology, anesthesiology, radiation oncology, and physiatry), one psychologist, and one statistician. Participants were self-selected from the 3000 members of the APS, which supported the process and held annual open committee meetings and scientific symposia beginning in 1988. Evidence.-MEDLINE was searched (1980 to 1995) to identify all articles on pain assessment, treatment of acute pain or cancer pain, and QI or education related to pain. Consensus Process.-Following panel discussions, one member (M.B.M.) prepared successive drafts and circulated them to the panel and APS membership for comments. After publication of a prototype version in 1991, 14 panelists carried out formal studies of implementation of the guidelines at three medical centers. This article was prepared based on this research, a new literature review, and suggestions from 50 pain clinicians and researchers. Conclusions.-Quality improvement programs to improve treatment of acute pain and cancer pain should include five key elements: (1) Assuring that a report of unrelieved pain raises a ''red flag'' that attracts clinicians' attention; (2) making information about analgesics convenient where orders are written; (3) promising patients responsive analgesic care and urging them to communicate pain; (4) implementing policies and safeguards for the use of modem analgesic technologies, and (5) coordinating and assessing implementation of these measures. Several short-term studies suggest that this QI approach may improve patient satisfaction and facilitate recognition of institutional obstacles to optimal pain treatment, but it is not a panacea for undertreated pain. By making the magnitude of the problem apparent and committing the institution to change, pain treatment QI programs can provide a foundation for a multifaceted approach that includes education of clinicians and patients, design of informational tools to minimize errors in prescribing, and improved coordination of the process of assessing and treating pain. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. KAISER SUNNYSIDE MED CTR,DEPT NURSING,CLACKAMAS,OR. UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL NURSING,SAN FRANCISCO,CA 94143. UNIV WISCONSIN,SCH NURSING,PAIN RES GRP,MADISON,NJ. UNIV WISCONSIN,CTR COMPREHENS CARE,MADISON,NJ. UNIV WISCONSIN,DEPT NURSING,MADISON,NJ. MEM SLOAN KETTERING CANC CTR,DEPT NURSING,NEW YORK,NY 10021. UNIV WISCONSIN,DEPT NEUROL,PAIN RES GRP,MADISON,WI 53706. MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT EPIDEMIOL & BIOSTAT,NEW YORK,NY 10021. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT RADIOTHERAPY,HOUSTON,TX. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT NEUROONCOL,HOUSTON,TX. UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT ANESTHESIOL,SEATTLE,WA 98104. AMER PAIN SOC,GLENVIEW,IL 60025. NR 67 TC 402 Z9 409 U1 4 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 20 PY 1995 VL 274 IS 23 BP 1874 EP 1880 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA TK147 UT WOS:A1995TK14700031 ER PT J AU Tjandra, N Feller, SE Pastor, RW Bax, A AF Tjandra, N Feller, SE Pastor, RW Bax, A TI Rotational diffusion anisotropy of human ubiquitin from N-15 NMR relaxation SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MODEL-FREE APPROACH; MAGNETIC-RESONANCE RELAXATION; CORRELATION SPECTROSCOPY; BACKBONE DYNAMICS; CROSS-CORRELATION; PROTEINS; MACROMOLECULES; SIMULATIONS; DIPOLAR; TIMES AB . Longitudinal and transverse N-15 NMR relaxation times in human ubiquitin have been measured at 600-MHz H-1 frequency with a reproducibility of better than 1%. Two independent measurements of the N-15-{H-1} NOE indicate a random error of ca. 0.01, and no values were larger than the theoretical maximum. The relaxation data are incompatible with isotropic rotational diffusion but agree well with an axially symmetric rotational diffusion tensor with a diffusion anisotropy, D-parallel to/D-perpendicular to Of 1.17 There is no statistically significant further improvement in the fit between the experimental data and those predicted by a fully asymmetric diffusion tensor, confirming that the rotational diffusion tensor of ubiquitin is axially symmetric within experimental uncertainty. The relative ratio of the principal components of the inertia tensor calculated from the X-ray structure is 1.00:0.90:0.64, and the axis with the smallest inertia component makes an angle of 11 degrees with the unique axis of the experimentally determined diffusion tenser. Hydrodynamic calculations agree well with experimental results, provided half a shell of bound water is included and flexibility of the C-terminal residues is accounted for either by omitting them from the calculations or by using conformations for these residues obtained from a Langevin dynamics simulation. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,BETHESDA,MD 20892. NR 34 TC 604 Z9 605 U1 1 U2 41 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 20 PY 1995 VL 117 IS 50 BP 12562 EP 12566 DI 10.1021/ja00155a020 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA TL733 UT WOS:A1995TL73300020 ER PT J AU TOMAR, SL HENNINGFIELD, JE AF TOMAR, SL HENNINGFIELD, JE TI ADDITIONAL EVIDENCE IMPLICATING MOIST SNUFF AS A POTENT CARCINOGEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID SMOKELESS TOBACCO CESSATION; NICOTINE C1 NATL INST DRUG ABUSE,ADDICT RES CTR,CLIN PHARMACOL BRANCH,BALTIMORE,MD 21224. RP TOMAR, SL (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,OFF SMOKING & HLTH,ATLANTA,GA 30341, USA. NR 30 TC 3 Z9 3 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 20 PY 1995 VL 87 IS 24 BP 1822 EP 1824 DI 10.1093/jnci/87.24.1822 PG 3 WC Oncology SC Oncology GA TK066 UT WOS:A1995TK06600003 PM 7494220 ER PT J AU ABRAMS, JS PHILLIPS, PH FRIEDMAN, MA AF ABRAMS, JS PHILLIPS, PH FRIEDMAN, MA TI MEETING HIGHLIGHTS - A REAPPRAISAL OF RESEARCH RESULTS FOR THE LOCAL TREATMENT OF EARLY-STAGE BREAST-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID EXTENSIVE INTRADUCTAL COMPONENT; COLLAGEN VASCULAR DISEASES; RANDOMIZED CLINICAL-TRIAL; RADIATION-THERAPY; CONTRALATERAL BREAST; CONSERVATIVE SURGERY; CONSERVING TREATMENT; TUMOR RECURRENCE; ADJUVANT CHEMOTHERAPY; GEOGRAPHIC-VARIATION C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. EMMES CORP,POTOMAC,MD. NR 102 TC 33 Z9 33 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 20 PY 1995 VL 87 IS 24 BP 1837 EP 1845 DI 10.1093/jnci/87.24.1837 PG 9 WC Oncology SC Oncology GA TK066 UT WOS:A1995TK06600009 PM 7494227 ER PT J AU STURGEON, SR SCHAIRER, C GAIL, M MCADAMS, M BRINTON, LA HOOVER, RN AF STURGEON, SR SCHAIRER, C GAIL, M MCADAMS, M BRINTON, LA HOOVER, RN TI GEOGRAPHIC-VARIATION IN MORTALITY FROM BREAST-CANCER AMONG WHITE WOMEN IN THE UNITED-STATES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID REPRODUCTIVE FACTORS; FAMILY HISTORY; SURVIVAL; RISK; AGE; DIAGNOSIS AB Background: For several decades, mortality from breast cancer has been higher in the northeastern part of the United States than in other regions, particularly the South. Rates have also been somewhat higher in the Midwest and West than in the South, especially among older women. The reasons for these geographic variations are not well understood. Purpose: The objective of this study was to evaluate geographic differences in U.S. breast cancer mortality rates in 1987, after taking into account regional differences in the distribution of recognized breast cancer risk factors (e.g., late age at first live birth) and certain prognostic factors (e.g., mammography use). Methods: The 1987 breast cancer mortality rates for four regions of the country were obtained from the National Center for Health Statistics. Regional data on the distribution of breast cancer risk factors were obtained from 1987 National Health Interview Cancer Epidemiology Supplement interviews with 9778 white women aged 20-79 years. Regional data on the distribution of mammography use were obtained from 1987 National Health Interview Cancer Control Supplement interviews with 3795 white women aged 50-79 years. Results: Age-adjusted mortality ratios (MRs) among women 50 years and older were 1.15, 1.18, and 1.30 in the West, Midwest, and Northeast, respectively, compared with the South. Corresponding MRs among women 20-49 years old were 1.01, 1.08, and 1.07 in the West, Midwest, and Northeast, respectively, compared with the South. After adjustment for recognized risk factors and certain prognostic factors, MRs among older women were 1.13 (95% confidence interval [CI] = 1.04-1.23), 1.08 (95% CI = 1.01-1.16), and 1.13 (95% CI = 1.04-1.23) in the West, Midwest, and Northeast, respectively, compared with the South. Corresponding MRs among younger women were 0.94 (95% CP = 0.76-1.16), 1.05 (95% CI = 0.92-1.18), and 0.99 (95% CI = 0.86-1.14), respectively. Conclusion: Before adjustment for regional differences in recognized risk factors and prognostic factors, mortality excesses among younger women in the Northeast, Midwest, and West were less than 10% compared with the South. After adjustment, MRs were near unity for all regions. Among older women, the excess mortality was more substantial before adjustment for relevant factors, ranging from 15% in the West to 30% in the Northeast. Approximately 50% of the excesses in the Northeast and Midwest and 10% of the excess in the West could be explained on the basis of regional differences in the prevalence of recognized breast cancer risk factors and prognostic factors. After adjustment for these factors, the magnitude of excess in breast cancer mortality in the Northeast (13%) was comparable to that in the West (13%) but still slightly higher than that in the Midwest (8%). C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 26 TC 77 Z9 77 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 20 PY 1995 VL 87 IS 24 BP 1846 EP 1853 DI 10.1093/jnci/87.24.1846 PG 8 WC Oncology SC Oncology GA TK066 UT WOS:A1995TK06600010 PM 7494228 ER PT J AU FENTON, RG KELLER, CJ HANNA, N TAUB, DD AF FENTON, RG KELLER, CJ HANNA, N TAUB, DD TI INDUCTION OF T-CELL IMMUNITY AGAINST RAS ONCOPROTEINS BY SOLUBLE-PROTEIN OR RAS-EXPRESSING ESCHERICHIA-COLI SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LYMPHOCYTES-T; TUMOR-CELLS; CLONES; PROTOONCOGENES; RECOGNITION; MUTATIONS; MOLECULES; RESPONSES; MELANOMA; PEPTIDES AB Background: Point mutations in the ras proto-oncogene that activate its oncogenic potential occur in approximately 30% of human cancers. Previous studies have demonstrated that T-cell immunity against some forms of mutant Ras proteins could be elicited, and some effectiveness against tumors expressing activated Pas has been reported, Purpose: The goal of this study was to determine if immunization of mice with two forms of mutant Pas protein can induce high levels of Pas mutation-specific T-cell immunity in vitro and tumor regression in vivo, Methods: Mice (BALB/c or C3H/HeJ) were immunized subcutaneously at 2-week intervals with purified Pas oncoproteins mixed with the immunologic adjuvants Antigen Formulation or QS-21, both of which have been shown to enhance the induction of T-cell-mediated immunity when included as components of soluble protein vaccines, In some experiments, mice were immunized directly with heat-killed Escherichia coli that had been induced to express one of the mutant Pas proteins, Spleen cells plus lymph node cells from Ras-immunized mice were tested in vitro for lysis of syngeneic Ras-expressing tumor cells and proliferation in response to mutant Pas peptides. For some of the cytolytic activity experiments, the spleen cells mere grown under T(H)1 conditions (growth in presence of interleukin 2, interferon gamma, and an antibody directed against interleukin 4 to stimulate a cell-mediated immune response) or T(H)2 conditions (growth in presence of interleukins 2 and 4 to stimulate a humoral immune response). The specificity of immunity was examined in vivo by challenge of Pas-immunized mice with syngeneic tumor cells expressing mutant Pas oncoproteins (HaBalb, i,e,, BALB/c mouse cells expressing Ras with arginine substituted at amino acid position 12 [Arg 12 Pas]; C3HL61, i,e., C3H/HeJ mouse cells expressing Pas with leucine substituted at position 61 [Leu 61 Ras]), Ten mice per group were used in each experiment. Results: Proliferative and cytolytic T-cell responses directed against the Arg 12 Pas protein were generated in BALB/c mice, resulting in protection against challenge with cells expressing Arg 12 Pas and therapeutic benefit in mice bearing established tumors expressing this protein, In C3H/HeJ mice, high levels of cytolytic and proliferative responses were induced against Leu 61 Pas. Immunization with heat-killed E, coli genetically engineered to express Leu 61 Pas also led to the induction of anti-Pas T-cell immunity, T cells grown under T(H)1 conditions were cytolytic against Pas-transformed tumor cells, whereas those grown under T(H)2 conditions were not, Conclusions: Immunization as described here leads to Ras mutation-specific antitumor immunity in vitro and in vivo, with therapeutic efficacy in an established tumor model. C1 SCI APPLICAT INT CORP,CLIN SERV PROGRAM,MCLEAN,VA 22102. IDEC PHARMACEUT CORP,SAN DIEGO,CA. RP FENTON, RG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CLIN SCI,CLIN RES BRANCH,POB B,BLDG 567,RM 207,FREDERICK,MD 21702, USA. NR 35 TC 40 Z9 40 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 20 PY 1995 VL 87 IS 24 BP 1853 EP 1861 DI 10.1093/jnci/87.24.1853 PG 9 WC Oncology SC Oncology GA TK066 UT WOS:A1995TK06600011 PM 7494229 ER PT J AU HOFFMANN, D DJORDJEVIC, MV FAN, JG ZANG, E GLYNN, T CONNOLLY, GN AF HOFFMANN, D DJORDJEVIC, MV FAN, JG ZANG, E GLYNN, T CONNOLLY, GN TI 5 LEADING US COMMERCIAL BRANDS OF MOIST SNUFF IN 1994 - ASSESSMENT OF CARCINOGENIC N-NITROSAMINES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TOBACCO-SPECIFIC NITROSAMINES; CANCER; NONSMOKERS; STORAGE; NITRITE; ACIDS; RATS AB Background: Moist snuff is the only tobacco product in the United States with increasing sales (an increase of 38.4% between 1981 and 1993) and with increased consumption, primarily by male adolescents aged 12-18 years old and young adults aged 19 years old or older, It is known from previous studies that levels of nicotine and the proportion of unprotonated (free) nicotine, as well as the pH, which affects nicotine delivery, vary considerably among the leading snuff brands, Whether concentrations of major carcinogens, such as the nicotine-derived tobacco-specific N-nitrosamines (TSNAs), like N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), also vary among these brands has not been determined previously, Purpose: Our purpose was threefold: 1) to determine the concentrations of major carcinogenic nicotine-derived N-nitrosamines in each of the five most popular moist snuff brands; 2) to analyze the quantitative differences in the various snuff components (e,g,, NNN) between two major brand categories: a category comprising the brands known to have high levels of unprotonated nicotine (Copenhagen, Skoal fine cut, and Kodiak) versus a category comprising the brands known to have low levels (Hawken and Skoal Bandits); and 3) to compare the differences in the concentrations of nicotine (previously determined), NNN, NNK, and total TSNAs between these two major brand categories, Methods: Three boxes of each of the five leading U,S, moist snuff brands were bought in July 1994 from retailers in six areas and transferred immediately to the analytical laboratory, After extraction, N-nitrosamino acids and TSNAs were determined on a gas chromatograph interfaced with a thermal energy analyzer (CC-TEA) and integrator, Each 5-g sample of ground, freeze-dried tobacco was extracted twice, and each extract was analyzed twice by CC-TEA, All P values reported are two sided, Results: Copenhagen, Skoal fine cut, and Kodiak as a group had statistically significant higher levels of nicotine (P = .0017), NNN (P<.0001), NNK (P = .0119), and total TSNAs (P<.0001) than the Hawken and Skoal Bandits group, Concentrations (means +/- SD) of nicotine, NNN, NNK, and total TSNAs comparing the two major brand categories are as follows: nicotine-11.6 +/- 1.01 mg/g versus 6.96 +/- 3.62 mg/g (P = .0017), NNN-7.74 +/- 1.70 mu g/g versus 4.17 +/- 1.35 mu g/g (P<.0001), NNK-1.23 +/- 0.68 mu g/g versus 0.61 +/- 0.41 mu g/g (P = .0119), and total TSNAs-14.3 +/- 3.82 mu g/g versus 6.3 +/- 2.56 mu g/g (P<.0001). Conclusions: The three leading U,S, snuff brands (Copenhagen, Skoal fine cut, and Kodiak; making up 92% of the U,S, market) showed not only high levels of pH, nicotine, and unprotonated (free) nicotine, but also high concentrations of the strongly carcinogenic TSNAs in comparison with the fourth and fifth best selling moist snuff brands, Hawken and Skoal Bandits (3% of the U,S, market). C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. MASSACHUSETTS DEPT PUBL HLTH,BOSTON,MA 02116. RP HOFFMANN, D (reprint author), AMER HLTH FDN,1 DANA RD,VALHALLA,NY 10595, USA. FU NCI NIH HHS [CA29580] NR 49 TC 70 Z9 72 U1 0 U2 7 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 20 PY 1995 VL 87 IS 24 BP 1862 EP 1869 DI 10.1093/jnci/87.24.1862 PG 8 WC Oncology SC Oncology GA TK066 UT WOS:A1995TK06600012 PM 7494230 ER PT J AU KRATZKE, RA OTTERSON, GA LINCOLN, CE EWING, S OIE, H GERADTS, J KAYE, FJ AF KRATZKE, RA OTTERSON, GA LINCOLN, CE EWING, S OIE, H GERADTS, J KAYE, FJ TI IMMUNOHISTOCHEMICAL ANALYSIS OF THE P16(INK4) CYCLIN-DEPENDENT KINASE INHIBITOR IN MALIGNANT MESOTHELIOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; CELL LUNG-CANCER; PROTEIN; PHOSPHORYLATION; IDENTIFICATION; SUPPRESSION; DELETIONS; 9P AB Background: The identification in 1994 of the CDKN2 gene as a target for mutations in a wide range of human cancers, including malignant mesothelioma, has been controversial because subsequent studies have detected a lower frequency of CDKN2 gene mutations in primary tumors than in cultured cell lines, These reports raised the hypothesis that another gene, distinct from CDKN2, might be the target of the chromosome 9p21 deletions frequently observed in these tumors, Purpose: To address whether inactivation of CDKN2 function is an essential event in the etiology of malignant mesothelioma, we examined p16(INK4) protein expression in primary thoracic mesotheliomas, in nonmalignant pleural tissues, and in independent mesothelioma cell lines, We also studied the growth rate of tumor cell lines following stable transfection of CDKN2 gene, Methods: Retinoblastoma (Rb) and p16(INK4) protein expression was determined by immunohistochemical analysis from archival paraffin specimens of 12 primary thoracic mesotheliomas and a nonmalignant pleural biopsy specimen, In addition, protein immunoblot analysis for Rb and p16(INK4) expression was conducted on 15 independent mesothelioma cell lines, and the ability of a transfected CDKN2 gene to suppress the growth of the mesothelioma cell lines H2373 and H2461 in vitro was examined, Results: We demonstrated abnormal p16(INK4) expression in 12 of 12 primary mesothelioma specimens and in 15 of 15 mesothelioma cell lines, All tumor specimens and the tumor cell lines showed expression of wild-type Rb protein, In addition, we have confirmed the ability of a transfected CDKN2 gene to suppress growth of two independent mesothelioma cell lines, Conclusions: Immunohistochemical analysis of the p16(INK4) gene product is feasible in archival biopsy samples, With this analysis, CDKN2 gene inactivation can be determined in tumors that are contaminated with nonmalignant cells, Furthermore, since loss of p16(INK4) protein expression can result from both genetic (gene mutations) and epigenetic (abnormal DNA hypermethylation) mechanisms, as we and others have shown recently, examination of protein expression is a highly sensitive method for analyzing the CDKN2 status in large numbers of tumor samples, Implications: This study suggests that inactivation of the CDKN2 gene is an essential step in the etiology of malignant mesotheliomas, Defining the role of the p16(INK4):Rb tumor suppressor pathway and its immediate downstream substrates will be an important goal in designing future therapeutic strategies. C1 USN,NCI,DIV CANC TREATMENT,ONCOL BRANCH,BETHESDA,MD. DEPT VET AFFAIRS MED CTR,DIV HEMATOL ONCOL,MINNEAPOLIS,MN. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. RED CROSS BLOOD CTR,HOLLAND LABS,ROCKVILLE,MD. VET ADM MED CTR,DEPT PATHOL,MINNEAPOLIS,MN. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC. RI kaye, frederic/E-2437-2011 NR 42 TC 106 Z9 108 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 20 PY 1995 VL 87 IS 24 BP 1870 EP 1875 DI 10.1093/jnci/87.24.1870 PG 6 WC Oncology SC Oncology GA TK066 UT WOS:A1995TK06600013 PM 7494231 ER PT J AU Steller, MA Delgado, CH Zou, ZQ AF Steller, MA Delgado, CH Zou, ZQ TI Insulin-like growth factor II mediates epidermal growth factor-induced mitogenesis in cervical cancer cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CULTURED HUMAN-FIBROBLASTS; IGF-1 RECEPTOR; ENDOMETRIAL CANCER; BINDING-PROTEINS; RIBONUCLEIC-ACID; DNA-SYNTHESIS; 3T3 CELLS; SOMATOMEDIN; EXPRESSION; OVEREXPRESSION AB There is increasing evidence that activation of the insulin-like growth factor I (IGF-I) receptor plays a major role in the control of cellular proliferation of many cell types. We studied the mitogenic effects of IGF-I, IGF-II, and epidermal growth factor (EGF) on growth-arrested HT-3 cells, a human cervical cancer cell line. All three growth factors promoted dose-dependent increases in cell proliferation. In untransformed cells, EGF usually requires stimulation by a ''progression'' factor such as IGF-I, IGF-II, or insulin (in supraphysiologic concentrations) in order to exert a mitogenic effect. Accordingly, we investigated whether an autocrine pathway involving IGF-I or IGF-II participated in the EGF-induced mitogenesis of HT-3 cells. With the RNase protection assay, IGF-I mRNA was not detected. However, IGF-II mRNA increased in a time dependent manner following EGF stimulation, The EGF-induced mitogenesis was abrogated in a dose-dependent manner by IGF-binding protein 5 (IGFBP-5), which binds to IGF-II and neutralizes it. An antisense oligonucleotide to IGF-II also inhibited the proliferative response to EGF. In addition, prolonged, but not short-term, stimulation with EGF resulted in autophosphorylation of the IGF-I receptor, and coincubations with both EGF and IGFBP-5 attenuated this effect. These data demonstrate that autocrine secretion of IGF-II in HT-3 cervical cancer cells can participate in EGF-induced mitogenesis and suggest that autocrine signals involving the IGF-I receptor occur ''downstream'' of competence growth factor receptors such as the EGF receptor. RP Steller, MA (reprint author), NCI,SURG BRANCH,GYNECOL ONCOL SECT,BLDG 10,ROOM 2B-42,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 40 TC 40 Z9 41 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 1995 VL 92 IS 26 BP 11970 EP 11974 DI 10.1073/pnas.92.26.11970 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TL421 UT WOS:A1995TL42100006 PM 8618825 ER PT J AU Migita, M Medin, JA Pawliuk, R Jacobson, S Nagle, JW Anderson, S Amiri, M Humphries, RK Karlsson, S AF Migita, M Medin, JA Pawliuk, R Jacobson, S Nagle, JW Anderson, S Amiri, M Humphries, RK Karlsson, S TI Selection of transduced CD34(+) progenitors and enzymatic correction of cells from Gaucher patients, with bicistronic vectors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MEDIATED GENE-TRANSFER; BONE-MARROW CELLS; HUMAN GLUCOCEREBROSIDASE GENE; HUMAN ADENOSINE-DEAMINASE; LONG-TERM EXPRESSION; RECOMBINANT RETROVIRUSES; MULTIDRUG RESISTANCE; HUMAN MDR1; DISEASE; TRANSPLANTATION AB The gene transfer efficiency of human hematopoietic stem cells is still inadequate for efficient gene therapy of most disorders. To overcome this problem, a selectable retroviral vector system for gene therapy has been developed for gene therapy of Gaucher disease, We constructed a bicistronic retroviral vector containing the human glucocerebrosidase (GC) cDNA and the human small cell surface antigen CD24 (243 bp). Expression of both cDNAs was controlled by the long terminal repeat enhancer/promoter of the Molony murine leukemia virus, The CD24 selectable marker was placed downstream of the GC cDNA and its translation was enhanced by inclusion of the long 5' untranslated region of encephalomyocarditis virus internal ribosomal entry site. Virus-producing GP+envAM12 cells were created by multiple supernatant transductions to create vector producer cells, The vector LGEC has a high titer and can drive expression of GC and the cell surface antigen CD24 simultaneously in transduced MH 3T3 cells and Gaucher skin fibroblasts, These transduced cells have been successfully separated from untransduced cells by fluorescence-activated cell sorting, based on cell surface expression of CD24, Transduced and sorted NIH 3T3 cells showed higher GC enzyme activity than the unsorted population,demonstrating coordinated expression of both genes. Fibroblasts from Gaucher patients were transduced and sorted for CD24 expression, and GC enzyme activity was measured, The transduced sorted Gaucher fibroblasts had a marked increase in enzyme activity (149%) compared with virgin Gaucher fibroblasts (17% of normal GC enzyme activity), Efficient transduction of CD34(+) hematopoietic progenitors (20-40%) was accomplished and fluorescence-activated cell sorted CD24(+)-expressing progenitors generated colonies, all of which (100%) were vector positive, The sorted, CD24-expressing progenitors generated erythroid burst-forming units, colony-forming units (CFU)-granulocyte, CFU-macrophage, CFU-granulocyte/macrophage, and CFU-mix hematopoietic colonies, demonstrating their ability to differentiate into these myeloid lineages in vitro. The transduced, sorted progenitors raised the GC enzyme levels in their progeny cells manyfold compared with untransduced CD34(+) progenitors. Collectively, this demonstrates the development of high titer, selectable bicistronic vectors that allow isolation of transduced hematopoietic progenitors and cells that have been metabolically corrected. C1 NINCDS,DEV & METAB NEUROL BRANCH,MOLEC & MED GENET SECT,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NINCDS,NEUROGENET SECT,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. BRITISH COLUMBIA CANC AGCY,TERRY FOX LAB,VANCOUVER,BC V5Z 1L3,CANADA. GENET THERAPY INC,GAITHERSBURG,MD 20878. OI Humphries, Richard/0000-0003-0540-7005 NR 46 TC 51 Z9 51 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 1995 VL 92 IS 26 BP 12075 EP 12079 DI 10.1073/pnas.92.26.12075 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TL421 UT WOS:A1995TL42100028 PM 8618847 ER PT J AU Driscoll, WJ Komatsu, K Strott, CA AF Driscoll, WJ Komatsu, K Strott, CA TI Proposed active site domain in estrogen sulfotransferase as determined by mutational analysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEINS; BINDING; P21 AB Point mutations were selectively introduced into a cDNA for guinea pig estrogen sulfotransferase (gpEST); each construct was then expressed in Chinese hamster ovary fil cells. The molecular site chosen for study is a conserved GXXGXXK sequence that resembles the P-loop-type nucleotide-binding motif for ATP- and GTP-binding proteins and is located near the C terminus of all steroid and phenol(aryl) sulfotransferases for which the primary structures are known. Preliminary experiments demonstrated that the GXXGXXK motif is essential for binding the activated sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS). The present study was undertaken to ascertain the relative importance of each individual residue of the motif, While the mutation of a single motif residue had little effect on the interaction between gpEST and PAPS as determined by kinetic analysis and photoaffinity labeling, the mutation of any two residues in concert resulted in an approximate 10-fold increase in the K-m for PAPS and reduced photoaffinity labeling, The mutation of all three motif residues resulted in an inactive enzyme and complete loss of photoaffinity labeling, Interestingly, several mutants also displayed a striking effect on the Ii, for the steroid substrate; double mutants, again, demonstrated greater perturbations (8- to 28-fold increase) than did single mutants. Unexpectedly, whereas the mutation of nonmotif residues had a negligible effect on the K-m for PAPS, a marked increase in the K-m for the estrogen substrate (>30-fold) was noted, On the basis of these findings, it is concluded that the sequence GISGDWKN within the C-terminal domain of gpEST represents a critical component of the active site. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,STEROID REGULAT SECT,BETHESDA,MD 20892. NR 17 TC 36 Z9 38 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 1995 VL 92 IS 26 BP 12328 EP 12332 DI 10.1073/pnas.92.26.12328 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TL421 UT WOS:A1995TL42100079 PM 8618895 ER PT J AU Johnen, G Kowlessur, D Citron, BA Kaufman, S AF Johnen, G Kowlessur, D Citron, BA Kaufman, S TI Characterization of the wild-type form of 4a-carbinolamine dehydratase and two naturally occurring mutants associated with hyperphenylalaninemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE phenylalanine hydroxylase-stimulating protein; dimerization cofactor for hepatocyte nuclear factor 1 ID HYDROXYLASE-STIMULATING PROTEIN; PHENYLALANINE-HYDROXYLASE; RAT-LIVER; 7-SUBSTITUTED PTERINS; HOMEODOMAIN PROTEINS; COFACTOR; 7-TETRAHYDROBIOPTERIN; TETRAHYDROBIOPTERIN; PHENYLKETONURIA; PURIFICATION AB The characterization of 4a-carbinolamine dehydratase with the enzymatically synthesized natural substrate revealed non-Michaelis-Menten kinetics. A Hill coefficient of 1.8 indicates that the dehydratase exists as a multisubunit enzyme that shows cooperativity. A mild form of hyperphenylalaninemia with high 7-biopterin levels has been linked to mutations in the human 4a-carbinolamine dehydratase gene. We have now cloned and expressed two mutant forms of the protein based on a patient's DNA sequences, The kinetic parameters of the mutant C82R reveal a 60% decrease in V-max but no change in K-m (approximate to 5 mu M), suggesting that the cysteine residue is not involved in substrate binding, Its replacement by arginine possibly causes a conformational change in the active center. Like the wild-type enzyme, this mutant is heat stable and forms a tetramer. The susceptibility to proteolysis of C82R, however, is markedly increased in vitro compared with the wild-type protein, We have also observed a decrease in the expression levels of C82R protein in transfected mammalian cells, which could be due to proteolytic instability, The 18-amino acid-truncated mutant Glu-87 --> termination could not be completely purified and characterized due to minute levels of expression and its extremely low solubility as a fusion protein. No dehydratase activity was detected in crude extracts from transformed bacteria or transfected mammalian cells, Considering the decrease in specific activity and stability of the mutants, we conclude that the patient probably has less than 10% residual dehydratase activity, which could be responsible for the mild hyperphenylalaninemia and the high 7-biopterin levels. RP Johnen, G (reprint author), NIMH,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 31 TC 17 Z9 17 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 1995 VL 92 IS 26 BP 12384 EP 12388 DI 10.1073/pnas.92.26.12384 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TL421 UT WOS:A1995TL42100091 PM 8618906 ER PT J AU Schapiro, MB Murphy, DGM Hagerman, RJ Azari, NP Alexander, GE Miezejeski, CM Hinton, VJ Horwitz, B Haxby, JV Kumar, A White, B Grady, CL AF Schapiro, MB Murphy, DGM Hagerman, RJ Azari, NP Alexander, GE Miezejeski, CM Hinton, VJ Horwitz, B Haxby, JV Kumar, A White, B Grady, CL TI Adult fragile X syndrome: Neuropsychology, brain anatomy, and metabolism SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE fragile X syndrome; cerebral glucose metabolism; positron emission tomography (PET); brain; mental retardation; computed tomography (CT); autism; development ID LINKED MENTAL-RETARDATION; OBSESSIVE-COMPULSIVE DISORDER; CEREBRAL GLUCOSE-UTILIZATION; EMISSION TOMOGRAPHIC DATA; DOWNS-SYNDROME; COGNITIVE FUNCTION; AUTISTIC-CHILDREN; INFANTILE-AUTISM; MALES; CHILDHOOD AB To understand the implications of suboptimal gene expression in fragile X syndrome [fra(X)], we sought to define the central nervous abnormalities in fra(X) syndrome to determine if abnormalities in specific brain regions or networks might explain the cognitive and behavioral abnormalities in this syndrome. Cranial and ventricular volumes were measured with quantitative computed tomography (CT), regional cerebral metabolic rates for glucose (rCMRglc) were measured with [18-F]-2-fluoro-2-deoxy-D-glucose (18FDG), and patterns of cognition were determined with neuropsychological testing in ten healthy, male patients with karyotypically proven fra(X) syndrome (age range 20-30 yr). Controls for the CT studies were 20 healthy males (age range 21-37 yr), controls for the PET studies were 9 healthy males (age range 22-31 yr), and controls for the neuropsychological tests were 10 young adult, male Down syndrome (DS) subjects (age range 22-31 yr). The mean mental age of the fra(X) syndrome group was 5.3 yr (range 3.5-7.5 yr; Stanford-Binet Intelligence Scale). Despite comparable levels of mental retardation, the fra(X) subjects showed poorer attention/short term memory in comparison to the DS group. Further, the fra(X) subjects showed a relative strength in verbal compared to visuospatial attention/short term memory. As measured with quantitative CT, 8 fra(X) subjects had a significant (P < 0.05) 12% greater intracranial volume (1,410 +/- 86 cm(3)) as compared to controls (1,254 +/- 122 cm(3)). Volumes of the right and left lateral ventricles and the third ventricle did not differ between groups. Seven of eight patients had greater right lateral ventricle volumes than left, as opposed to 9 out of 20 controls (P < 0.05). Global gray matter CMR-glc in nine fra(X) patients was 9.79 +/- 1.28 mg/100 g/minute and did not differ from 8.84 +/- 1.31 mg/100 g/minute in the controls. R/L asymmetry in metabolism of the superior parietal lobe was significantly higher in the patients than controls. A preliminary principal component analysis of metabolic data showed that the fra(X) subjects tended to form a separate subgroup that is characterized by relative elevation of normalized metabolism in the lenticular nucleus, thalamus, and premotor regions. Further, a discriminant function, that reflected rCMRglc interactions of the right lenticular and left premotor regions, distinguished the fra(X) subjects from controls. These regions are part of a major group of functionally and anatomically related brain regions and appear disturbed as well in autism with which fra(X) has distinct behavioral similarities. These results show a cognitive profile in fra(X) syndrome that is distinct from that of Down syndrome, that the larger brains in fragile X syndrome are not accompanied by generalized cerebral cortical atrophy or hypoplasia, and that distinctive alterations in resting regional glucose metabolism, measured with 18 FDG and PET, occur in fra(X) syndrome. (C) 1995 Wiley-Liss, Inc.* C1 CHILDRENS HOSP,CHILD DEV UNIT,DENVER,CO 80218. NEW YORK STATE INST BASIC RES DEV DISABIL,NEW YORK STATE OFF MENTAL RETARDAT & DEV,STATEN ISL,NY 10314. NIDDKD,CTR CLIN,BIOL CHEM LAB,CYTOGENET UNIT,BETHESDA,MD 20892. RP Schapiro, MB (reprint author), NIA,CTR CLIN,NEUROSCI LAB,BRAIN AGING & DEMENTIA SECT,BLDG 10,ROOM 6C414,BETHESDA,MD 20892, USA. NR 92 TC 61 Z9 61 U1 3 U2 11 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 18 PY 1995 VL 60 IS 6 BP 480 EP 493 DI 10.1002/ajmg.1320600603 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA TK751 UT WOS:A1995TK75100002 PM 8825884 ER PT J AU Persico, AM Wang, ZW Black, DW Andreasen, NC Uhl, GR Crowe, RR AF Persico, AM Wang, ZW Black, DW Andreasen, NC Uhl, GR Crowe, RR TI Exclusion of close linkage between the synaptic vesicular monoamine transporter locus and schizophrenia spectrum disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE norepinephrine; epinephrine; serotonin dopamine; histamine ID CDNA AB The principal brain synaptic vesicular monoamine transporter (VMAT2) is responsible for the reuptake of serotonin, dopamine, norepinephrine, epinephrine, and histamine from the cytoplasm into synaptic vesicles, thus contributing to determination of the size of releasable neurotransmitter vesicular pools. Potential involvement of VMAT2 gene variants in the etiology of schizophrenia and related disorders was tested using polymorphic VMAT2 gene markers in 156 subjects from 16 multiplex pedigrees with schizophrenia, schizophreniform, schizoaffective, and schizotypal disorders and mood incongruent psychotic depression, Assuming genetic homogeneity, complete (theta = 0.0) linkage to the schizophrenia spectrum was excluded under both dominant and recessive models, Allelic variants at the VMAT2 locus do not appear to provide major genetic contributions to the etiology of schizophrenia spectrum disorders in these pedigrees. (C) 1995 Wiley-Liss, Inc.* C1 NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. LIBERO IST UNIV CAMPUS BIOMED,NEUROSCI LAB,ROME,ITALY. UNIV IOWA,COLL MED,DEPT PSYCHIAT,IOWA CITY,IA. FU NIMH NIH HHS [MH-00735, MH-43212] NR 16 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 18 PY 1995 VL 60 IS 6 BP 563 EP 565 DI 10.1002/ajmg.1320600616 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA TK751 UT WOS:A1995TK75100015 PM 8825897 ER PT J AU NOH, DY SHIN, SH RHEE, SG AF NOH, DY SHIN, SH RHEE, SG TI PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE-C AND MITOGENIC SIGNALING SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID EPIDERMAL GROWTH-FACTOR; CELL ANTIGEN RECEPTOR; BETA-GAMMA-SUBUNITS; PROTEIN-TYROSINE KINASE; INOSITOL TRISPHOSPHATE FORMATION; RAT-LIVER NUCLEI; SWISS 3T3 CELLS; ALPHA-SUBUNITS; SH3 DOMAINS; GQ CLASS C1 NHLBI,CELL SIGNALING LAB,BETHESDA,MD 20892. FU FIC NIH HHS [F05 TW04926] NR 143 TC 244 Z9 246 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD DEC 18 PY 1995 VL 1242 IS 2 BP 99 EP 113 DI 10.1016/0304-419X(95)00006-0 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA TH862 UT WOS:A1995TH86200001 PM 7492569 ER PT J AU Laufs, J Schumacher, S Geisler, N Jupin, I Gronenborn, B AF Laufs, J Schumacher, S Geisler, N Jupin, I Gronenborn, B TI Identification of the nicking tyrosine of geminivirus Rep protein SO FEBS LETTERS LA English DT Article DE plant DNA virus; replication initiation; nucleotidyl transferases; covalent protein DNA link; rolling circle replication ID GOLDEN MOSAIC-VIRUS; SINGLE-STRANDED-DNA; WHEAT DWARF VIRUS; SITE-DIRECTED MUTAGENESIS; REPLICATION PROTEIN; 3'-5' EXONUCLEASE; ESCHERICHIA-COLI; ACTIVE-SITE; GENE-EXPRESSION; POLYMERASE-I AB The replication initiator (Rep) proteins of geminiviruses perform a DNA cleavage and strand transfer reaction at the viral origin of replication, As a reaction intermediate, Rep proteins become covalently linked to the 5' end of the cleaved DNA, We have used tomato yellow leaf curl virus Rep protein for in vivo and in vitro analyses, Isolating a covalent peptide-nucleotide complex, we have identified the amino acid of Rep which mediates cleavage and links the protein to DNA, We show that tyrosine-103, located in a conserved sequence motif, initiates DNA cleavage and is the physical link between geminivirus Rep protein and its origin DNA. C1 CNRS,INST SCI VEGETALES,F-91198 GIF SUR YVETTE,FRANCE. NIDDK,PHYS CHEM LAB,BETHESDA,MD 20892. MAX PLANCK INST BIOPHYS CHEM,D-37077 GOTTINGEN,GERMANY. NR 50 TC 52 Z9 55 U1 0 U2 3 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 18 PY 1995 VL 377 IS 2 BP 258 EP 262 DI 10.1016/0014-5793(95)01355-5 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TM328 UT WOS:A1995TM32800037 PM 8543063 ER PT J AU Meyer, CC Calis, KA AF Meyer, CC Calis, KA TI New hemodialysis membranes and vancomycin clearance SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID HIGH-FLUX HEMODIALYSIS; POLYACRYLONITRILE; PHARMACOKINETICS C1 NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. RP Meyer, CC (reprint author), UNIV MISSOURI,SCH PHARM,KANSAS CITY,MO 64108, USA. NR 13 TC 4 Z9 4 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD DEC 15 PY 1995 VL 52 IS 24 BP 2794 EP 2796 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TK757 UT WOS:A1995TK75700004 PM 8748565 ER PT J AU KOUMENIS, IL VESTAL, ML YERGEY, AL ABRAMS, S DEMING, SN HUTCHENS, TW AF KOUMENIS, IL VESTAL, ML YERGEY, AL ABRAMS, S DEMING, SN HUTCHENS, TW TI QUANTITATION OF METAL ISOTOPE RATIOS BY LASER-DESORPTION TIME-OF-FLIGHT MASS-SPECTROMETRY SO ANALYTICAL CHEMISTRY LA English DT Article ID STABLE ISOTOPES; ZINC-ABSORPTION; IONIZATION; IDENTIFICATION; MAGNESIUM; NUTRITION; CALCIUM; INFANTS; PROBE AB Laser desorption time-of-flight mass spectrometry (LD/TOF-MS) is evaluated for the determination of stable metal isotope ratios, The isotope ratios of five metal ions (Cu, Ca, Mg, Fe, Zn) in atomic absorption standard solutions and two metal ions (Ca, Mg) in human serum samples are determined. With an existing LD/TOF-MS instrument we show that the technique can overcome the difficulties of the most commonly used methods for measuring metal isotope ratios: (1) all metals are ionizable without surface treatment, thus overcoming the major drawback of thermal ionization mass spectrometry (TIMS); (2) there is no matrix involved to interfere with the metal ion detection, thus overcoming the major disadvantage of inductively coupled plasma mass spectrometry (ICPMS); (3) there is no interference from hydride ions, a major disadvantage of fast atom bombardment secondary ionization mass spectrometry; (4) a mixture of metals can be detected simultaneously using a single laser wavelength, overcoming the major disadvantage of resonance ionization mass spectrometry; (5) accuracy and precision comparable to ICPMS can be achieved with the current instrumentation; (6) precision comparable to TIMS is feasible; and most importantly (7) high precision can be achieved on very small quantities of material because the LD/TOF-MS instrument permits all masses to be monitored simultaneously and very small differences in isotope ratio can be detected. C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. VESTEC CORP,HOUSTON,TX 77054. BAYLOR COLL MED,USDA ARS,CHILDRENS NUTR RES CTR,DEPT PEDIAT,PROT STRUCT LAB,HOUSTON,TX 77030. UNIV HOUSTON,DEPT CHEM,HOUSTON,TX 77004. OI Abrams, Steven/0000-0003-4972-9233 FU NICHD NIH HHS [R43-HD29334-01]; NIDDK NIH HHS [R01-DK 438 50-01] NR 32 TC 18 Z9 19 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD DEC 15 PY 1995 VL 67 IS 24 BP 4557 EP 4564 DI 10.1021/ac00120a020 PG 8 WC Chemistry, Analytical SC Chemistry GA TK585 UT WOS:A1995TK58500020 PM 8633789 ER PT J AU DIBISCEGLIE, AM CONJEEVARAM, HS FRIED, MW SALLIE, R PARK, Y YURDAYDIN, C SWAIN, M KLEINER, DE MAHANEY, K HOOFNAGLE, JH WRIGHT, D AF DIBISCEGLIE, AM CONJEEVARAM, HS FRIED, MW SALLIE, R PARK, Y YURDAYDIN, C SWAIN, M KLEINER, DE MAHANEY, K HOOFNAGLE, JH WRIGHT, D TI RIBAVIRIN AS THERAPY FOR CHRONIC HEPATITIS-C - A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE RIBAVIRIN; HEPATITIS C; HEPATITIS C VIRUSES; AMINOTRANSFERASES; RNA, VIRAL ID RECOMBINANT INTERFERON-ALFA; ALPHA-INTERFERON; FOLLOW-UP; LIVER; RNA AB Objective: To evaluate ribavirin, an oral antiviral agent, as therapy for chronic hepatitis C. Design: Randomized, double-blind, placebo-controlled study. Setting: Clinical Center of the National Institutes of Health, a tertiary referral research hospital. Patients: 29 patients with chronic hepatitis C who received oral ribavirin (600 mg twice daily) for 12 months and 29 controls with chronic hepatitis C who received placebo for 12 months. Measurements: Effects of therapy were evaluated by measuring serum aminotransferase and hepatitis C virus (HCV) RNA levels before, during, and for 6 months after therapy and by histologic examination of liver specimens before and at the end of treatment. Results: Patients treated with ribavirin had a prompt decrease in serum aminotransferase levels (54% overall) compared with levels before treatment and levels in controls (5% decrease). Serum aminotransferase levels became normal or nearly normal in 10 patients treated with ribavirin (35% [95% CI, 18% to 54%]) but in no controls (0% [CI, 0% to 12%]). Aminotransferase levels remained normal in only 2 patients after ribavirin therapy was discontinued (7% [CI, 1% to 23%]). Serum HCV RNA levels did not change during or after therapy. Liver biopsy specimens showed a decrease in hepatic inflammation and necrosis among ribavirin-treated patients whose aminotransferase levels became normal. Conclusions: Ribavirin has beneficial effects on serum aminotransferase levels and histologic findings in the liver in patients with chronic hepatitis C, but these effects are not accompanied by changes in HCV RNA levels and are not sustained when ribavirin therapy is discontinued. Thus, ribavirin alone for periods as long as 12 months is unlikely to be of value as therapy for chronic hepatitis C. C1 NIDDKD,LIVER DIS SECT,DIGEST DIS BRANCH,BETHESDA,MD 20892. OI Kleiner, David/0000-0003-3442-4453 NR 24 TC 284 Z9 287 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 15 PY 1995 VL 123 IS 12 BP 897 EP & PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA TK120 UT WOS:A1995TK12000001 PM 7486483 ER PT J AU FARNER, NL VOSS, SD LEARY, TP GAN, J HAKIMI, J EVANS, G JU, G SONDEL, PM AF FARNER, NL VOSS, SD LEARY, TP GAN, J HAKIMI, J EVANS, G JU, G SONDEL, PM TI DISTINCTION BETWEEN GAMMA(C) DETECTION AND FUNCTION IN YT LYMPHOID-CELLS AND IN THE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RESPONSIVE HUMAN MYELOID CELL-LINE, TF-1 SO BLOOD LA English DT Article ID RECEPTOR-BETA-CHAIN; SEVERE COMBINED IMMUNODEFICIENCY; HUMAN IL-2 RECEPTOR; NATURAL-KILLER-CELLS; INTERLEUKIN-2 RECEPTOR; LIGAND-BINDING; ALPHA-CHAIN; SIGNAL TRANSDUCTION; EXPRESSION; AFFINITY AB Peripheral blood monocytes respond to interleukin-2 (IL-2) and express the gamma common (gamma(c)) subunit of the IL-2 receptor (IL-2R) complex. However, the role of IL-2 in myeloid development has recently become of interest for several reasons, including the effect gamma(c) mutations may or may not have on myeloid development in patients with XSCID. Many studies of IL-2 function in the myeloid cell lineage have been performed on a murine background. To study gamma(c) expression and function in human myeloid precursors, we introduced the human myelomonocytic cell line, Tf-1, with a retroviral vector containing the human IL-2R beta subunit to create functional human intermediate IL-2R consisting of beta gamma(c) dimers. We have characterized this transfected variant of Tf-1 (Tf-1 beta) with regard to its response to IL-2. Unlike the parental Tf-1 cell line that is deficient in both IL-2R alpha and IL-2R beta expression, the Tf-1 beta transfectant binds and responds to IL-2 through intermediate-affinity IL-2Rs. Scatchard analyses indicate the number of intermediate-affinity receptors on Tf-1 beta is similar to the number found on the well-characterized YT cell line. However, detection of gamma(c) on Tf-1 beta cells is dramatically less than on YT cells by Western blot analysis and is undetectable by flow cytometric studies and surface iodinations. The gamma(c) component on YT cells is readily detected by all three methods. We conclude from these studies that the intermediate-affinity IL-2Rs on the Tf-1 cell line behave differently than those on YT cells with respect to gamma(c) detection. Either the gamma(c) molecule itself is different, or the cellular environment in which it functions is altered. Elucidation of gamma(c) function on this cell line will allow for its use as a model in which other cytokines using gamma(c) (including IL-2, IL-4, and IL-15) can be studied on the same cellular background. (C) 1995 by The American Society of Hematology. C1 UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI 53792. UNIV WISCONSIN,DEPT HUMAN ONCOL,MADISON,WI. UNIV WISCONSIN,DEPT PEDIAT,MADISON,WI. UNIV WISCONSIN,DEPT GERIATR,MADISON,WI. HOFFMANN LA ROCHE INC,ROCHE RES CTR,DEPT INFLAMMAT AUTOIMMUNE DIS,NUTLEY,NJ 07110. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [CM-87290, CA-32685, P30-CA14520-2] NR 49 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1995 VL 86 IS 12 BP 4568 EP 4578 PG 11 WC Hematology SC Hematology GA TK479 UT WOS:A1995TK47900022 PM 8541547 ER PT J AU NAGARAJAN, S BRODSKY, RA YOUNG, NS MEDOF, ME AF NAGARAJAN, S BRODSKY, RA YOUNG, NS MEDOF, ME TI GENETIC-DEFECTS UNDERLYING PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA THAT ARISES OUT OF APLASTIC-ANEMIA SO BLOOD LA English DT Article ID DECAY-ACCELERATING FACTOR; CELL-LINES; ERYTHROCYTES; LYMPHOCYTES; DEFICIENCY; COMPLEMENT AB Treatment of severe aplastic anemia with antithymocyte globulin (ATG) and cyclosporin leads to clinical remission in a large proportion of patients. As many as 10% to 57% of these patients, however, develop paroxysmal nocturnal hemoglobinuria (PNH). We and others have observed that this secondary PNH appears to be more indolent than classical PNH, which results from an acquired mutation in the PIG-A gene. in the present study, we compared PIG-A mRNA transcripts in affected cells from patients with secondary PNH and patients with classical PNH. All four of our aplastic patients who developed PNH had a negative Ham test at diagnosis. Two of the four showed a positive Ham test within 3 months after ATG/cyclosporin administration, one developed a positive test at 6 months, and another at 18 months after immunosuppressive therapy. Ali four patients remain transfusion-independent with no thrombotic episodes after a mean follow-up of 30 months (range, 6 to 63 months). Reverse transcription-polymerase chain reaction (RT-PCR) of PIG-A transcripts in DAF(-)/CD59(-) neutrophils or lymphocyte lines of the four patients showed PIG-A abnormalities in all cases. Transition of C-163 to T was found in one, a 14-bp deletion (positions 1141 to 1154) was found in the second, deletion of C-39 was found in the third, and two mutations, transition of C-55 to T and transversion of T-762 to A, were found in the fourth. These abnormalities compared with findings of abnormal RNA splicing causing a 133-bp deletion, a 4-bp insertion (between positions 578 and 579), loss of A(767), and loss of C-575 in four patients with primary PNH. We conclude that secondary PNH that evolves out of aplastic anemia, like classical PNH, is associated with mutations in the PIG-A gene. The apparent indolent nature of this disease probably reflects early detection. (C) 1995 by The American Society of Hematology. C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. FU NIAID NIH HHS [AI23598]; NIDDK NIH HHS [P01DK38181] NR 24 TC 67 Z9 68 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1995 VL 86 IS 12 BP 4656 EP 4661 PG 6 WC Hematology SC Hematology GA TK479 UT WOS:A1995TK47900033 PM 8541558 ER PT J AU LEE, JH LEITMAN, SF KLEIN, HG AF LEE, JH LEITMAN, SF KLEIN, HG TI A CONTROLLED COMPARISON OF THE EFFICACY OF HETASTARCH AND PENTASTARCH IN GRANULOCYTE COLLECTIONS BY CENTRIFUGAL LEUKAPHERESIS SO BLOOD LA English DT Article ID HYDROXYETHYL STARCH; COAGULATION; BLOOD; TRANSFUSIONS; DONORS AB Compared with hetastarch (HS), the low molecular weight analog pentastarch (PS) has been reported to be equally effective for granulocyte collection by centrifugal leukapheresis, to result in fewer adverse donor reactions (ADR), and to have a more rapid elimination profile, We prospectively compared the granulocyte collection efficiency (GCE), granulocyte yield, and ADR in 72 randomly paired granulocytapheresis procedures from 36 volunteer donors using the model CS-3000 Plus Blood Cell Separator (CS) and either PS or HS as the sedimenting agent. Paired collections from each donor allowed us to compare the two agents directly while controlling for intrinsic donor differences. in 33 of 36 (92%) donors, HS procedures were significantly more efficient than PS procedures (P < .001). As an average, HS collections yielded 2.3 +/- 0.67 x 10(10) granulocytes at 58% +/- 8.8% GCE, whereas PS procedures resulted in 1.4 +/- 0.76 x 10(10) granulocytes at 33% +/- 15% GCE. No starch-induced ADR were seen with either agent. For granulocyte harvests using the CS, (1) in most donors, using HS as the red blood cell sedimenting agent during centrifugal leukapheresis results in significantly higher (nearly twofold) GCE and larger granulocyte yields in comparison with using PS, (2) ADR were not observed with either agent, and (3) the potential benefit of more rapid PS elimination should be balanced against significantly lower granulocyte yields. This is a US government work. There are no restrictions on its use. RP LEE, JH (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,ROOM 1C711,BETHESDA,MD 20892, USA. NR 26 TC 27 Z9 28 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1995 VL 86 IS 12 BP 4662 EP 4666 PG 5 WC Hematology SC Hematology GA TK479 UT WOS:A1995TK47900034 PM 8541559 ER PT J AU Bronstein, DM PerezOtano, I Sun, V Sawin, SBM Chan, J Wu, GC Hudson, PM Kong, LY Hong, JS McMillian, MK AF Bronstein, DM PerezOtano, I Sun, V Sawin, SBM Chan, J Wu, GC Hudson, PM Kong, LY Hong, JS McMillian, MK TI Glia-dependent neurotoxicity and neuroprotection in mesencephalic cultures SO BRAIN RESEARCH LA English DT Article DE lipopolysaccharide; astrocyte; microglia; 6-hydroxydopamine; tyrosine hydroxylase; dopamine; Parkinson's disease; Substantia nigra ID DOPAMINERGIC-NEURONS; SUBSTANTIA-NIGRA; NEUROTROPHIC FACTOR; CELL-CULTURE; GROWTH; ASTROCYTES; MICROGLIA; TOXICITY; SURVIVAL; BRAIN AB Dopaminergic neurotoxicities of 6-hydroxydopamine (6-OHDA) and the lipopolysaccharide (LPS) were compared in rat mesencephalic cultures plated on poly-L-lysine or on glial monolayers. In the neuron-enriched cultures plated on polylysine, 6-OHDA killed 89% Of the tyrosine hydroxylase (TH)-immunopositive neurons, but LPS was not neurotoxic. Conversely, in mixed neuron/glial cultures, 6-OHDA killed only 27% of the TH-immunopositive neurons while LPS killed 70%. The mixed neuronal/glial mesencephalic culture offers a better in vitro model for studying possible mechanisms involved in Parkinson's disease. C1 NIEHS,ENVIRONM NEUROSCI LAB,RES TRIANGLE PK,NC 27709. NR 40 TC 142 Z9 149 U1 2 U2 7 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 15 PY 1995 VL 704 IS 1 BP 112 EP 116 DI 10.1016/0006-8993(95)01189-7 PG 5 WC Neurosciences SC Neurosciences & Neurology GA TM242 UT WOS:A1995TM24200016 PM 8750970 ER PT J AU HO, PTC ZIMMERMAN, K WEXLER, LH BLANEY, S JAROSINSKI, P WEAVERMCCLURE, L IZRAELI, S BALIS, FM AF HO, PTC ZIMMERMAN, K WEXLER, LH BLANEY, S JAROSINSKI, P WEAVERMCCLURE, L IZRAELI, S BALIS, FM TI A PROSPECTIVE EVALUATION OF IFOSFAMIDE-RELATED NEPHROTOXICITY IN CHILDREN AND YOUNG-ADULTS SO CANCER LA English DT Article DE IFOSFAMIDE; NEPHROTOXICITY; PHOSPHATURIA; GLYCOSURIA; AMINOACIDURIA; BETA(2)-MICROGLOBULIN; SARCOMA ID ISOPHOSPHAMIDE NSC-109724; PEDIATRIC ONCOLOGY; FANCONI SYNDROME; TOXICITY; IPHOSPHAMIDE; DYSFUNCTION; CHILDHOOD; RICKETS; MESNA AB Background. Ifosfamide has been associated with proximal renal tubular dysfunction resembling Fanconi-like syndrome and leading to rickets in young children. The characteristic manifestations of this nephrotoxicity include phosphaturia and hypophosphatemia, glycosuria, aminoaciduria, renal tubular acidosis, and urinary loss of low molecular weight serum proteins. However, the relationship between acute ifosfamide nephrotoxicity, which is frequently subclinical, and long term renal damage is unclear. In this prospective study, the laboratory features of ifosfamide-induced acute nephrotoxicity were characterized further and correlated with the development of chronic nephropathy. Methods. The renal function of newly diagnosed children and young adults with high risk sarcomas was followed during therapy with a high dose ifosfamide-containing regimen. Serum and urine were collected regularly immediately before and after Ii-day cycles of ifosfamide throughout treatment for determination of the fractional excretion of electrolytes (sodium, potassium, phosphate, magnesium, calcium) and glucose and urinary excretion of amino acids and beta(2)-microglobulin. Results. Significant changes in the renal threshold of phosphate excretion, the fractional excretion of calcium and glucose, and the urinary excretion of beta(2)-microglobulin were observed when comparing pretreatment values with those at the end of a 5-day treatment cycle. The median renal threshold of phosphate excretion decreased from 1.22 to 0.82 mmol/L (P < 0.0001). The median fractional excretions of calcium and glucose increased from 1.05% to 1.68% (P < 0.0001) and 0.05% to 0.08% (P = 0.0006), respectively. Beta(2)-microglobulin excretion increased by 70-fold from 0.02 to 1.42 mg/mmol (P < 0.0001). Except for glucose and beta(2)-microglobulin excretion, renal parameters returned to baseline before the next ifosfamide treatment cycle. Acute aminoaciduria was observed in 21 of 23 patients. Chronic nephrotoxicity, as defined by the development of a Fanconi-like syndrome or chronic tubular electrolyte loss requiring oral supplementation, developed in the three patients with the highest urinary excretion of beta(2)-microglobulin after ifosfamide therapy. Conclusions, Prospectively, high dose ifosfamide was associated with a 4% incidence of Fanconi-like syndrome; however, evidence of acute reversible subclinical nephrotoxicity was observed for all patients. Severe beta(2)-microglobulinuria appeared to be a prognostic laboratory indicator for the development of chronic nephrotoxicity. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,INVEST DRUG BRANCH,BETHESDA,MD 20892. NR 36 TC 40 Z9 42 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 1995 VL 76 IS 12 BP 2557 EP 2564 DI 10.1002/1097-0142(19951215)76:12<2557::AID-CNCR2820761223>3.0.CO;2-9 PG 8 WC Oncology SC Oncology GA TJ106 UT WOS:A1995TJ10600022 PM 8625085 ER PT J AU WANG, XW GIBSON, MK VERMEULEN, W YEH, H FORRESTER, K STURZBECHER, HW HOEIJMAKERS, JHJ HARRIS, CC AF WANG, XW GIBSON, MK VERMEULEN, W YEH, H FORRESTER, K STURZBECHER, HW HOEIJMAKERS, JHJ HARRIS, CC TI ABROGATION OF P53-INDUCED APOPTOSIS BY THE HEPATITIS-B VIRUS-X GENE SO CANCER RESEARCH LA English DT Note ID HEPATOCELLULAR-CARCINOMA; SV40-TRANSFORMED CELLS; TUMOR-ANTIGEN; P53 GENE; PROTEIN; RETINOBLASTOMA; TRANSFORMATION; PATHWAY; DNA AB The p53 tumor suppressor gene product is a transcriptional transactivator and a potent apoptotic inducer. The fact that many of the DNA tumor virus oncoproteins bind to p53 and affect these p53 functions indicates that this interaction is an important step in oncogenic transformation, We and others have recently demonstrated that the hepatitis B virus oncoprotein, HBx, can form a complex with p53 and inhibit its DNA consensus sequence binding and transcriptional transactivator activity, Using a microinjection technique, we report here that HBx efficiently blocks p53-mediated apoptosis and describe the results of studies exploring two possible mechanisms of HBx action. First, inhibition of apoptosis mag be a consequence of the failure of p53, in the presence of HBx, to upregulate genes, such as p21(WAF1), Bax, or Fas, that are involved in the apoptotic pathway, Data consistent with this hypothesis include HBx reduction of p53-mediated p21(WAF1) expression, Alternatively, HBx could affect p53 binding to the TFIIH transcription-nucleotide excision repair complex as HBx binds to the COOH terminus of p53 and inhibits its binding to XPB or XPD. Binding of p53 to these constituents of the core TFIIH is a process that may be involved in apoptosis, Because the HBx gene is frequently integrated into the genome of hepatocellular carcinoma cells, inhibition of p53-mediated apoptosis by HBx may provide a clonal selective advantage for hepatocytes expressing this integrated viral gene during the early stages of human liver carcinogenesis. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. ERASMUS UNIV ROTTERDAM,CTR MED GENET,DEPT CELL BIOL & GENET,3000 DR ROTTERDAM,NETHERLANDS. UNIV HAMBURG,HEINRICH PETTE INST,D-20251 HAMBURG,GERMANY. RI Wang, Xin/B-6162-2009 NR 46 TC 276 Z9 285 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1995 VL 55 IS 24 BP 6012 EP 6016 PG 5 WC Oncology SC Oncology GA TK211 UT WOS:A1995TK21100005 PM 8521383 ER PT J AU CHHABRA, SK SOULIOTIS, VL HARBAUGH, JW KRASNOW, SW JONES, AB ANDERSON, LM KYRTOPOULOS, SA AF CHHABRA, SK SOULIOTIS, VL HARBAUGH, JW KRASNOW, SW JONES, AB ANDERSON, LM KYRTOPOULOS, SA TI O-6-METHYLGUANINE DNA ADDUCT FORMATION AND MODULATION BY ETHANOL IN PLACENTA AND FETAL TISSUES AFTER EXPOSURE OF PREGNANT PATAS MONKEYS TO N-NITROSODIMETHYLAMINE SO CANCER RESEARCH LA English DT Note ID LIVER; TUMORS AB Perinatal nitrosamine exposures may contribute to childhood cancer risk. To test primate fetal susceptibility to formation of cancer initiation-related DNA adducts from nitrosamines, pregnant patas monkeys were given 1.0 or 0.1 mg/kg N-nitrosodimethylamine. Appreciable levels of the promutagenic O-6-methylguanine adduct occurred in placental and fetal liver DNA after both doses and were lower but detectable in other fetal tissues after the higher dose. Coadministered ethanol (1.6 g/kg) reduced adducts in placenta and fetal liver by one-half and increased levels in other fetal tissues to the same degree. Thus, primate placenta and fetal tissues have a significant, ethanol-modulated capacity to activate N-nitrosodimethylamine, supporting implication of nitrosamines in human perinatal carcinogenesis and of alcohol as a modulating factor. C1 NATL HELLEN RES FDN, INST BIOL RES & BIOTECHNOL, CHEM CARCINOGENESIS LAB, GR-11635 ATHENS, GREECE. BIOQUAL INC, ROCKVILLE, MD 20850 USA. RP CHHABRA, SK (reprint author), NCI, FREDERICK CANC RES & DEV CTR, COMPARAT CARCINOGENESIS LAB, PERINATAL CARCINOGENESIS SECT, FREDERICK, MD 21702 USA. NR 23 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1995 VL 55 IS 24 BP 6017 EP 6020 PG 4 WC Oncology SC Oncology GA TK211 UT WOS:A1995TK21100006 PM 8521384 ER PT J AU BOYER, JC UMAR, A RISINGER, JI LIPFORD, JR KANE, M YIN, S BARRETT, JC KOLODNER, RD KUNKEL, TA AF BOYER, JC UMAR, A RISINGER, JI LIPFORD, JR KANE, M YIN, S BARRETT, JC KOLODNER, RD KUNKEL, TA TI MICROSATELLITE INSTABILITY, MISMATCH REPAIR DEFICIENCY, AND GENETIC-DEFECTS IN HUMAN CANCER CELL-LINES SO CANCER RESEARCH LA English DT Article ID NONPOLYPOSIS COLON-CANCER; ENDOMETRIAL CARCINOMA; COLORECTAL-CANCER; ESTABLISHMENT; MUTATIONS; HOMOLOG; LOCUS AB The instability of short repetitive sequences in tumor DNA can result from defective repair of replication errors due to mutations in any of several genes required for mismatch repair. Understanding this repair pathway and how defects lead to cancer is being facilitated by genetic and biochemical studies of tumor cell lines. In the present study, we describe the mismatch repair status of extracts of 22 tumor cell Lines derived from several tissue types. Ten were found to be defective in strand-specific mismatch repair, including cell lines from tumors of the colon, ovary, endometrium, and prostate. The repair defects were independent of whether the signal for strand specificity, a nick, was 5' or 3' to the mismatch. All 10 defective cell lines exhibited microsatellite instability. Repair activity was restored to 9 of these 10 extracts by adding a second defective extract made from cell lines having known mutations in either the hMSH2 or hMLH1 genes. Subsequent analyses revealed mutations in hMSH2 (4 lines) and hMLH1 (5 Lines) that could explain the observed microsatellite instability and repair defects. Overall, this study strengthens the correlation between microsatellite instability and defective mismatch repair and the suggestion that diminuition in mismatch repair activity is a step in carcinogenesis common to several types of cancer. It also provides an extensive panel of repair-proficient and repair-deficient cell lines for future studies of mismatch repair. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. DANA FARBER CANC INST,DIV MOLEC & CELLULAR BIOL,BOSTON,MA 02115. DANA FARBER CANC INST,MOLEC BIOL CORE FACIL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. NR 67 TC 298 Z9 299 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1995 VL 55 IS 24 BP 6063 EP 6070 PG 8 WC Oncology SC Oncology GA TK211 UT WOS:A1995TK21100016 PM 8521394 ER PT J AU TSUKIYAMA, T WU, C AF TSUKIYAMA, T WU, C TI PURIFICATION AND PROPERTIES OF AN ATP-DEPENDENT NUCLEOSOME REMODELING FACTOR SO CELL LA English DT Article ID HEAT-SHOCK GENES; HYPERSENSITIVE SITES; DROSOPHILA EMBRYOS; HISTONE OCTAMER; DNASE-I; CHROMATIN; TRANSCRIPTION; PROTEIN; INVITRO; RESOLUTION AB We report the purification of an ATP-dependent nucleosome remodeling factor (NURF) from Drosophila embryo extracts. NURF is composed of at least four polypeptides that act in concert with the GAGA transcription factor to alter chromatin structure at the hsp70 promoter. The energy requirement is attributed to an ATPase activity that is stimulated by nucleosomes but not by free DNA or histones, suggesting that NURF acts directly on a nucleosome to perturb its structure. This finding and the physical properties of NURF contrast sharply with the multisubunit SW12/SNF2 complex, which has also been shown to alter nucleosomes in an ATP-dependent manner. The results suggest that two distinct systems may be involved in remodeling chromatin for transcription. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 45 TC 456 Z9 464 U1 2 U2 10 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 15 PY 1995 VL 83 IS 6 BP 1011 EP 1020 DI 10.1016/0092-8674(95)90216-3 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TK745 UT WOS:A1995TK74500019 PM 8521501 ER PT J AU TSUKIYAMA, T DANIEL, C TAMKUN, J WU, C AF TSUKIYAMA, T DANIEL, C TAMKUN, J WU, C TI ISWI, A MEMBER OF THE SW12/SNF2 ATPASE FAMILY, ENCODES THE 140-KDA SUBUNIT OF THE NUCLEOSOME REMODELING FACTOR SO CELL LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL ACTIVATION; DROSOPHILA; CHROMATIN; PROTEIN; ANTENNAPEDIA; EXPRESSION AB The generation of an accessible heat shock promoter in chromatin in vitro requires the concerted action of the GAGA transcription factor and NURF, an ATP-dependent nucleosome remodeling factor. NURF is composed of four subunits and is biochemically distinct from the SW12/SNF2 multiprotein complex, a transcriptional activator that also appears to alter nucleosome structure. We have obtained protein microsequence and immunological evidence identifying the 140 kDa subunit of NURF as ISWI, previously of unknown function but highly related to SW12/SNF2 only in the ATPase domain. The ISWI protein is localized to the cell nucleus and is expressed throughout Drosophila development at levels as high as 100,000 molecules/cell. The convergence of biochemical and genetic studies on ISWI and SW12/SNF2 underscores these ATPases and their close relatives as key components of independent systems for chromatin remodeling. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV CALIF SANTA CRUZ,DEPT BIOL,SANTA CRUZ,CA 95064. FU NIGMS NIH HHS [R01 GM49883] NR 44 TC 285 Z9 288 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 15 PY 1995 VL 83 IS 6 BP 1021 EP 1026 DI 10.1016/0092-8674(95)90217-1 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TK745 UT WOS:A1995TK74500020 PM 8521502 ER PT J AU TOPOL, IA BURT, SK RASHIN, AA AF TOPOL, IA BURT, SK RASHIN, AA TI CAN CONTEMPORARY DENSITY-FUNCTIONAL THEORY YIELD ACCURATE THERMODYNAMICS FOR HYDROGEN-BONDING SO CHEMICAL PHYSICS LETTERS LA English DT Article ID INTERMOLECULAR FORCES; INTERACTION ENERGY; BONDED COMPLEXES; SYSTEMS; POTENTIALS; PROTEINS; DIMERS; FIELD; MODEL AB Thermodynamic characteristics of dimerization were calculated for six molecules (including water, alcohols, and carboxylic acids) using density functional theory (DFT) methods and compared to corresponding experimental data. Basis set superposition error for different basis sets including polarization and diffuse Gaussian functions was calculated using the full counterpoise procedure. Ten out of twelve thermodynamic dimerization characteristics calculated with DZVPD/TZVPD basis sets agree with one of the available experimental values with near chemical accuracy (approximate to 1 kcal/mol). It is concluded that DFT/DZVPD/TZVPD calculations can yield not only accurate molecular dipole moments, but also rather accurate thermodynamics of hydrogen bonding. C1 BIOCHEMCOMP INC,TEANECK,NJ 07666. RP TOPOL, IA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. NR 35 TC 52 Z9 52 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD DEC 15 PY 1995 VL 247 IS 1-2 BP 112 EP 119 DI 10.1016/0009-2614(95)01178-X PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA TK159 UT WOS:A1995TK15900018 ER PT J AU Yang, SW Nash, HA AF Yang, SW Nash, HA TI Comparison of protein binding to DNA in vivo and in vitro: Defining an effective intracellular target SO EMBO JOURNAL LA English DT Article DE DNA-protein interaction; Escherichia coli; integration host factor; in vivo footprinting ID INTEGRATION HOST FACTOR; SITE-SPECIFIC RECOMBINATION; COLI IHF PROTEIN; ESCHERICHIA-COLI; LAC REPRESSOR; IDENTIFICATION; CONSTANT AB We have quantitatively evaluated the affinity of a set of target sites for the integration host factor (IHF) protein of Escherichia coli by their performance as competitors in an electrophoretic mobility shift assay. We also determined how well each of these sites is filled by IHF in vivo, The data show that several natural sites have an affinity not much greater than that required for intracellular occupancy, The data also indicate that very little of the IHF in a cell is present as free protein available for binding, suggesting that binding to non-specific targets dominates the operation of this system. The correlation between in vitro affinity and in vivo occupancy provides a ready means to assess the likely physiological significance of putative IHF sites, It also provides a general method to assess the importance of non-specific interactions by DNA binding proteins inside a cell. RP Yang, SW (reprint author), NIMH, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 43 TC 71 Z9 72 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD DEC 15 PY 1995 VL 14 IS 24 BP 6292 EP 6300 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TP210 UT WOS:A1995TP21000023 PM 8557048 ER PT J AU Blaese, RM AF Blaese, RM TI Steps toward gene therapy .2. Cancer and AIDS SO HOSPITAL PRACTICE LA English DT Article ID BRAIN-TUMORS AB Strategies under investigation-in some cases in clinical trials-include the delivery of ''suicide genes'' to induce the self-destruction of infected or tumorous cells and the delivery of genes to facilitate T-cell recognition of such cells. The HIV life cycle offers many additional attack points for therapeutic genes designed to prevent the expression of viral genes or to impede the function of essential HIV proteins. RP Blaese, RM (reprint author), NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892, USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD DEC 15 PY 1995 VL 30 IS 12 BP 37 EP & PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA TL634 UT WOS:A1995TL63400009 PM 8522626 ER PT J AU MEYERS, K METZGER, DS MCLELLAN, AT NAVALINE, H SHEON, AR WOODY, GE AF MEYERS, K METZGER, DS MCLELLAN, AT NAVALINE, H SHEON, AR WOODY, GE TI WILL PREVENTIVE HIV VACCINE EFFICACY TRIALS BE POSSIBLE WITH FEMALE INJECTION-DRUG USERS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE WOMEN; IDU; HIV INFECTION; AIDS; VACCINE TRIALS ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS EPIDEMIC; WOMEN; DISEASE AB This article examines whether preventive HIV vaccine trials will be viable among female injection drug users (IDUs). Of the 137 women who completed baseline serologic and behavioral assessments, 121 (88%) were seronegative; all enrolled in Project Jumpstart in Philadelphia (PA, U.S.A.), a vaccine preparedness initiative cosponsored by NIAID and NIDA. Subjects were seen every 3 months for risk and vaccine opinion assessment, risk reduction counseling, and HIV antibody testing. The baseline prevalence rate of HIV infection was 12% (16 of 137) with an annual incidence rate of 3.5% (4 of 114) during the first year. Of the 121 baseline seronegative women, 28% shared needles and 52% engaged in unprotected intercourse. Sixty percent of the baseline seronegative women reported being willing to be one of the first people to try an HIV vaccine. According to logistic regression, needle sharers were 12.8 times more likely, women who engaged in sex for drugs or money 6.6 times more likely, out-of-treatment women 3.5 times more likely, and those who believed that vaccines can prevent disease acquisition 3 times more likely to report willingness to try an HIV vaccine than their respective counterparts. At 1-year postbaseline assessment, 98% of the women had behavioral data collected and 95% had serologic specimens collected, Given that seroconversions occur and that these women engage in risk behaviors, report willingness to try an HIV vaccine, and can be retained for longitudinal assessment, they appear to be suitable participants for preventive HIV vaccine efficacy trials. Nonetheless, work is required to insure that these women make informed and knowledgeable decisions regarding trial enrollment. C1 UNIV PENN,PHILADELPHIA VET MED CTR,CTR STUDIES ADDICT,PHILADELPHIA,PA. NIAID,DIV AIDS,VACCINE EFFICACY TRIALS & EPIDEMIOL BRANCH,BETHESDA,MD 20892. RI Metzger, David/D-9499-2012 FU NIAID NIH HHS [Y01-AI-20025-01]; NIDA NIH HHS [R01-DA05593] NR 35 TC 19 Z9 19 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD DEC 15 PY 1995 VL 10 IS 5 BP 577 EP 585 DI 10.1097/00042560-199510050-00012 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TJ244 UT WOS:A1995TJ24400013 PM 8548338 ER PT J AU ROBERTS, BJ SONG, BJ SOH, Y PARK, SS SHOAF, SE AF ROBERTS, BJ SONG, BJ SOH, Y PARK, SS SHOAF, SE TI ETHANOL INDUCES CYP2E1 BY PROTEIN STABILIZATION - ROLE OF UBIQUITIN CONJUGATION IN THE RAPID DEGRADATION OF CYP2E1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID RAT-LIVER; MICROSOMAL CYTOCHROME-P-450; INDUCTION; INACTIVATION; SUBSTRATE; REDUCTASE; ACETONE; ENZYME; SYSTEM; P-450 AB In the present study, we demonstrate that ethanol induces CYP2E1 by protein stabilization in vivo. The control half-life of CYP2E1 was determined to be 6-7 h followed by a slower secondary phase. The half-life of ethanol-stabilized CYP2E1 was calculated to be 38 h. The mechanism underlying the rapid degradation of GYP2E1 was also investigated and appears to involve the ubiquitin-proteasome proteolytic pathway. An in vitro assay using the cytosolic fraction was developed to further characterize CYP2E1 degradation Using this assay, 40-50% loss of CYP2E1 was observed in 1 h, coincident with the formation of high M(r) ubiquitin-CYP2E1 conjugates. At concentrations approximating those found in vivo, ethanol protects CYP2E1 from cytosolic degradation. No loss of CYP2B1/2 was observed under identical conditions, suggesting that this reaction is specific for certain P-450s which are rapidly turned over. C1 NIAAA,NEUROGENET LAB,BETHESDA,MD 20892. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP ROBERTS, BJ (reprint author), NIAAA,CLIN STUDIES LAB,10 CTR DR MSC-1256,BETHESDA,MD 20892, USA. NR 24 TC 195 Z9 204 U1 4 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1995 VL 270 IS 50 BP 29632 EP 29635 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK380 UT WOS:A1995TK38000004 PM 8530344 ER PT J AU COMBADIERE, C AHUJA, SK VANDAMME, J TIFFANY, HL GAO, JL MURPHY, PM AF COMBADIERE, C AHUJA, SK VANDAMME, J TIFFANY, HL GAO, JL MURPHY, PM TI MONOCYTE CHEMOATTRACTANT PROTEIN-3 IS A FUNCTIONAL LIGAND FOR CC CHEMOKINE RECEPTOR-1 AND RECEPTOR-2B SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; MOLECULAR-CLONING; COUPLED RECEPTORS; RANTES; DESENSITIZATION; IDENTIFICATION; EXPRESSION; BINDING; MCP-3 AB The CC chemokine monocyte chemoattractant protein-3 (MCP-3) activates human monocytes, lymphocytes, basophils, and eosinophils. MCP-3 has been reported to induce [Ca2+](i) changes in cells transfected with the monocyte-selective MCP-1 receptor 2B (CC CBR2B) and competes for I-125-MCP-1 binding on CC CKR2B, suggesting that it may mediate monocyte responses to MCP-3. However, we now show that MCP-3 is a ligand and potent agonist for the macrophage inflammatory protein-1 alpha (MIP-1 alpha)/regulated on activation, normal T expressed, and secreted protein (RANTES) receptor CC CKR1 (rank order for [Ca2+](i) changes MIP-1 alpha > MCP-3 > RANTES), which is expressed in monocytes > neutrophils > eosinophils. I-125-MCp-3 bound directly to CC CKR1 and CC CKR2B (K-i = 8 and 7 nM, respectively). Binding to CC CKR1 was competed by all CC chemokines tested except MCP-1. In contrast, binding to CC CKR2B was competed only by MCP-3 and MCP-1. Both MCP-1 and MCP-3 were equipotent agonists (EC(50) = 10 nM for [Ca2+](i) changes). Thus, MCP-3 is a functional ligand for both CC CKR1 and CC CKR2B, which otherwise have distinct selectivities for CC chemokines. These data suggest that monocyte responses to MCP-3 could be mediated by both CC CHR2B and CC CKR1, whereas eosinophil responses to MCP-3 could be mediated by CC CKR1. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. CATHOLIC UNIV LEUVEN,REGA INST,B-3000 LOUVAIN,BELGIUM. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 36 TC 139 Z9 141 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1995 VL 270 IS 50 BP 29671 EP 29675 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK380 UT WOS:A1995TK38000014 PM 8530354 ER PT J AU VANDIJKEN, P DEHAAS, JR CRAXTON, A ERNEUX, C SHEARS, SB VANHAASTERT, PJM AF VANDIJKEN, P DEHAAS, JR CRAXTON, A ERNEUX, C SHEARS, SB VANHAASTERT, PJM TI A NOVEL, PHOSPHOLIPASE C-INDEPENDENT PATHWAY OF INOSITOL 1,4,5-TRISPHOSPHATE FORMATION IN DICTYOSTELIUM AND RAT-LIVER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYOINOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE; DISCOIDEUM; CELLS; 1,3,4,5-TETRAKISPHOSPHATE; HEXAKISPHOSPHATE; 3,4,5,6-TETRAKISPHOSPHATE; PHOSPHORYLATION; 3-PHOSPHATASE; DEGRADATION; PHOSPHATES AB In an earlier study a mutant Dictyostelium cell-line (plc(-)) was constructed in which all phospholipase C activity was disrupted and nonfunctional, yet these cells had nearly normal Ins(1,4,5)P-3 levels (Drayer, A. L., Van Der Kaay, J., Mayr, G. W, Van Haastert, P. J. M. (1990) EMBO J. 13, 1601-1609). We have now investigated if these cells have a phospholipase C-independent de novo pathway of Ins(1,4,5)P-3 synthesis. We found that homogenates of plc(-) cells produce Ins(1,4,5)P-3 from endogenous precursors. The enzyme activities that performed these reactions were located in the particulate cell fraction, whereas the endogenous substrate was soluble and could be degraded by phytase. We tested various potential inositol polyphosphate precursors and found that the most efficient were Ins(1,3,4,5,6)P-3, Ins(1,3,4,5)P-4, and Ins(1,4,5,6)P-4. The utilization of Ins(1,3,4,5,6)P-5, which can be formed independently of phospholipase C by direct phosphorylation of inositol (Stephens, L. R. and Irvine, R. F. (1990) Nature 346, 580-582), provides Dictyostelium with an alternative and novel pathway of de novo Ins(1,4,5)P-3 synthesis. We further discovered that Ins(1,3,4,5,6)P-5 was converted to Ins(1,4,5)P-3 via both Ins(1,3,4,5)P-4 and Ins(1,4,5,6)P-4. In the absence of calcium no Ins(1,4,5)P-3 formation could be observed; half-maximal activity was observed at low micromolar calcium concentrations. These reaction steps could also be performed by a single enzyme purified from rat liver, namely, the multiple inositol polyphosphate phosphatase. These data indicate that organisms as diverse as rat and Dictyostelium possess enzyme activities capable of synthesizing the second messengers Ins(1,4,5)P-3 and Ins(1,3,4,5)P-4 via a novel phospholipase C-independent pathway. C1 UNIV GRONINGEN,DEPT BIOCHEM,9747 AG GRONINGEN,NETHERLANDS. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INOSITOL LIPID SECT,RES TRIANGLE PK,NC 27709. FREE UNIV BRUSSELS,INST RECH INTERDISCIPLINAIRE,B-1070 BRUSSELS,BELGIUM. NR 34 TC 38 Z9 38 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1995 VL 270 IS 50 BP 29724 EP 29731 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK380 UT WOS:A1995TK38000022 PM 8530362 ER PT J AU ANDERSON, DM KUMAKI, S AHDIEH, M BERTLES, J TOMETSKO, M LOOMIS, A GIRI, J COPELAND, NG GILBERT, DJ JENKINS, NA VALENTINE, V SHAPIRO, DN MORRIS, SW PARK, LS COSMAN, D AF ANDERSON, DM KUMAKI, S AHDIEH, M BERTLES, J TOMETSKO, M LOOMIS, A GIRI, J COPELAND, NG GILBERT, DJ JENKINS, NA VALENTINE, V SHAPIRO, DN MORRIS, SW PARK, LS COSMAN, D TI FUNCTIONAL-CHARACTERIZATION OF THE HUMAN INTERLEUKIN-15 RECEPTOR-ALPHA CHAIN AND CLOSE LINKAGE OF IL15RA AND IL2RA GENES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-CHAIN; IL-2 RECEPTOR; MOLECULAR-CLONING; BETA-CHAIN; SUPERFAMILY; EXPRESSION; COMPONENT; MOUSE; CELLS; SEQUENCE AB Interleukins-2 and -15 (IL-2 and IL-15) are cytokines with overlapping but distinct biological effects. Their receptors share two subunits (the IL-2R beta and -gamma chains) that are essential for signal transduction. The IL-2 receptor requires an additional IL-2-specific alpha subunit for high affinity IL-2 binding, Recently, a murine IL-15-specific alpha subunit was identified, cloned, and shown to be structurally related to IL-2R alpha. However, the murine IL-15R alpha alone bound IL-15 with a 1000-fold higher affinity than that seen with IL-2R alpha and IL-2. We now extend these studies into the human system with the isolation of three differentially spliced human IL-15R alpha variants that are all capable of high affinity binding of IL-15. The cytoplasmic domain of IL-15R alpha, like that of IL-2R alpha, is dispensable for mitogenic signaling, suggesting that the primary role of the alpha chains is to confer high affinity binding. At high concentrations, IL-15, like P2, is able to signal through a complex of IL-2R beta and -gamma in the absence of the cu subunit. Furthermore, the IL15RA and IL2RA genes have a similar intron-exon organization and are closely linked in both human and murine genomes. However, the distribution of expression of the lL-15R alpha is much wider than that of the IL-2R alpha, suggesting a broader range of cellular targets for IL-15. C1 IMMUNEX RES & DEV CORP, DEPT BIOCHEM, SEATTLE, WA 98101 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. ST JUDE CHILDRENS RES HOSP, DEPT EXPTL ONCOL, MEMPHIS, TN 38101 USA. ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38101 USA. UNIV TENNESSEE, COLL MED, DEPT PEDIAT, MEMPHIS, TN 38163 USA. RP ANDERSON, DM (reprint author), IMMUNEX RES & DEV CORP, DEPT MOLEC BIOL, 51 UNIV ST, SEATTLE, WA 98101 USA. FU NCI NIH HHS [CA 23099, CA 01702, CA 21765] NR 48 TC 281 Z9 288 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 15 PY 1995 VL 270 IS 50 BP 29862 EP 29869 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK380 UT WOS:A1995TK38000043 PM 8530383 ER PT J AU ANDERSON, KS KIM, AY QUILLEN, JM SAYERS, E YANG, XJ MILES, EW AF ANDERSON, KS KIM, AY QUILLEN, JM SAYERS, E YANG, XJ MILES, EW TI KINETIC CHARACTERIZATION OF CHANNEL IMPAIRED MUTANTS OF TRYPTOPHAN SYNTHASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; ALPHA-SUBUNIT; BETA-SUBUNIT; L-SERINE; MECHANISM; COMPLEX; INTERMEDIATE; PHOSPHATE; BINDING AB Tryptophan synthase, an alpha(2) beta(2) tetrameric complex, is a classic example of an enzyme that is thought to ''channel'' a metabolic intermediate (indole) from the active site of the alpha subunit to the active site of the beta subunit. The solution of the three-dimensional structure of the enzyme from Salmonella typhimurium provided physical evidence for a 25-Angstrom hydrophobic tunnel which connects the alpha and beta active sites (Hyde, C. C., Ahmed, S. A, Padlan, E. A., Miles, E. W., and Davies, D. R. (1988) J. Biol. Chem. 263, 17857-17871). Using rapid reaction kinetics, we have previously established that indole is indeed channeled and have identified three essential kinetic features which govern efficient channeling. In the current study we have probed the necessity of these features by using site-directed mutagenesis to alter these requirements. We now report the kinetic characterization of two mutants which contain substitutions to block or restrict the tunnel (beta C170F and beta C170W). Preliminary kinetic and structural evidence of a restricted tunnel in the beta C170W has been provided (Schlichting, I., Yang, X W., Miles, E.W., Kim, A. Y., and Anderson, K. S. (1994) J. Biol. Chem. 269, 26591-26593). The rapid kinetic analysis of these mutant proteins shows that these mutations interfere with efficient channeling of the indole metabolite such that indole can be observed in single enzyme turnover of the physiologically relevant alpha beta reaction. In addition, the beta C170W mutant appears to be impaired in alpha beta intersubunit communication. C1 NIDDKD, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. RP ANDERSON, KS (reprint author), YALE UNIV, SCH MED, DEPT PHARMACOL, 333 CEDAR ST, NEW HAVEN, CT 06520 USA. FU NIGMS NIH HHS [GM45343] NR 29 TC 25 Z9 26 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1995 VL 270 IS 50 BP 29936 EP 29944 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK380 UT WOS:A1995TK38000053 PM 8530393 ER PT J AU LEVYTOLEDANO, R BLAETTLER, DH LAROCHELLE, WJ TAYLOR, SI AF LEVYTOLEDANO, R BLAETTLER, DH LAROCHELLE, WJ TAYLOR, SI TI INSULIN-INDUCED ACTIVATION OF PHOSPHATIDYLINOSITOL (PI)3-KINASE - INSULIN-INDUCED PHOSPHORYLATION OF INSULIN-RECEPTORS AND INSULIN-RECEPTOR SUBSTRATE-1 DISPLACES PHOSPHORYLATED PLATELET-DERIVED GROWTH-FACTOR RECEPTORS FROM BINDING-SITES ON PI-3-KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE; ASSOCIATION; PROTEIN; INVITRO; IRS-1; PHOSPHOTYROSINE; STIMULATION; ENDOCYTOSIS; MUTATION; PATHWAY AB Phosphatidylinositol (PI) 3-kinase is an enzyme that functions in the signaling pathways downstream from multiple cell surface receptors, The p85 regulatory subunit of PI 3-kinase binds to phosphotyrosine residues of various phosphoproteins including the platelet-derived growth factor (PDGF) receptor, the insulin receptor, and insulin receptor substrate-1 (IRS-1). Using NIH-3T3 cells overexpressing the human insulin receptor, we demonstrate that the p85 regulatory subunit of PI 3-kinase binds to phosphorylated PDGF receptor in cells incubated in the absence of insulin. When insulin is added, p85 is released from phosphorylated PDGF receptors and binds to phosphorylated insulin receptors and insulin receptor substrate-1. Moreover, insulin-induced dissociation of PDGF receptors from binding sites on PI 3-kinase requires a functional insulin receptor and is not prevented by vanadate treatment. In contrast, insulin activation does not displace PDGF receptors from binding sites on Ras GTPase-activating protein. This competition for binding to PI 3-kinase provides a mechanism for cross-talk among signaling pathways initiated by distinct peptide hormones and growth factors such as insulin and PDGF. C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 26 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1995 VL 270 IS 50 BP 30018 EP 30022 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK380 UT WOS:A1995TK38000064 PM 8530404 ER PT J AU MALKOV, VV CAMERINIOTERO, RD AF MALKOV, VV CAMERINIOTERO, RD TI PHOTOCROSS-LINKS BETWEEN SINGLE-STRANDED-DNA AND ESCHERICHIA-COLI RECA PROTEIN MAP TO LOOPS L1 (AMINO-ACID-RESIDUES 157-164) AND L2 (AMINO-ACID-RESIDUES 195-209) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CROSS-LINKING; RECOMBINATION; COMPLEXES; ATP AB To function as a repair and recombination protein, RecA has to be assembled as an active filament on single-stranded DNA in the presence of ATP or its analogs. We have identified amino acids in the primary DNA binding site of RecA that interact with single-stranded DNA by photocross-linking. A nucleoprotein complex consisting of RecA protein bound to a monosubstituted oligonucleotide bearing a 5-iododeoxyuracil cross-linking moiety was irradiated with long wavelength ultraviolet radiation to effect cross-linking with RecA protein. Subsequent trypsin digestion, followed by purification and peptide sequencing, revealed the cross-linking of two independent peptides, amino acid residues 153-169 and 199-216. Met(164) from loop L1 and Phe(203) from loop L2 were determined to be the exact points of cross-linking, Thus, our data confirm and extend predictions about the DNA binding domain of RecA protein based on the molecular structure of RecA (Story, R. M., Weber, I. T., and Steitz, T.A. (1992) Nature 355, 318-325). C1 NIDDK,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 24 TC 59 Z9 59 U1 3 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1995 VL 270 IS 50 BP 30230 EP 30233 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK380 UT WOS:A1995TK38000094 PM 8530434 ER PT J AU ZHANG, YH FELLER, SE BROOKS, BR PASTOR, RW AF ZHANG, YH FELLER, SE BROOKS, BR PASTOR, RW TI COMPUTER-SIMULATION OF LIQUID/LIQUID INTERFACES .1. THEORY AND APPLICATION TO OCTANE/WATER SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID LIQUID-VAPOR INTERFACE; MOLECULAR-DYNAMICS SIMULATIONS; WATER-INTERFACE; ION; EQUILIBRIUM; SURFACES AB Statistical ensembles for simulating liquid interfaces at constant pressure and/or surface tension are examined, and equations of motion for molecular dynamics are obtained by various extensions of the Andersen extended system approach. Valid ensembles include: constant normal pressure and surface area; constant tangential pressure and length normal to the interface; constant volume and surface tension; and constant normal pressure and surface tension. Simulations at 293 K and 1 atm normal pressure show consistent results with each other and with a simulation carried out at constant volume and energy. Calculated surface tensions for octane/water (61.5 dyn/cm), octane/vacuum (20.4 dyn/cm) and water/vacuum (70.2 dyn/cm) are in very good agreement with experiment (51.6, 21.7, and 72.8 dyn/cm, respectively). The practical consequences of simulating with two other approaches commonly used for isotropic systems are demonstrated on octane/water: applying equal normal and tangential pressures leads to an instability; and applying a constant isotropic pressure of 1 atm leads to a large positive normal pressure. Both results are expected for a system of nonzero surface tension. Mass density and water polarization profiles in the liquid/liquid and liquid/vapor interfaces are also compared. C1 NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. RP ZHANG, YH (reprint author), US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 59 TC 230 Z9 234 U1 2 U2 44 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 15 PY 1995 VL 103 IS 23 BP 10252 EP 10266 DI 10.1063/1.469927 PG 15 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA TK564 UT WOS:A1995TK56400039 ER PT J AU Davenpeck, KL Chrest, FJ Sterbinsky, SA Bickel, CA Bochner, BS AF Davenpeck, KL Chrest, FJ Sterbinsky, SA Bickel, CA Bochner, BS TI Carboxyfluorescein diacetate labeling does not affect adhesion molecule expression or function in human neutrophils or eosinophils SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE carboxyfluorescein diacetate; flow cytometry; neutrophil; eosinophil; adhesion ID VASCULAR ENDOTHELIAL-CELLS; INTEGRIN VLA-4; ADHERENCE; BASOPHILS; DISTINCT; SELECTIN; VCAM-1 AB Fluorescently labeled leukocytes are commonly used in in vitro and in vivo experimental systems. However, the effects of fluorescent labeling on the expression and function of leukocyte adhesion molecules has not been examined in part because the extreme intensity of fluorescence tends to obscure signals from other fluorochromes used for dual color analysis. We have utilized a novel technique involving a 7-amino-4-methylcoumarin-3-acetic acid (AMCA) fluorophore-conjugated F(ab')(2) fragment excitable in the ultraviolet wavelength range (350-450 nm) and dual-laser flow cytometry to determine if labeling of human neutrophils and eosinophils with the fluorescent dye 5-(6)-carboxyfluorescein diacetate (CFDA) alters surface expression of the primary leukocyte adhesion molecules involved in leukocyte-endothelial interactions. Simultaneously, adhesion molecule function was assessed by comparing the ability of CFDA-labeled vs. control cells to adhere to cultured human umbilical vein endothelial cells (HUVEC) and purified immobilized adhesion molecules. Isolated human eosinophils and neutrophils were fluorescently labeled by incubation with CFDA. Flow cytometric comparisons of labeled and unlabeled cells demonstrated that fluorescence labeling of neutrophils and eosinophils with CFDA did not alter basal surface expression of the beta(2) integrins (i.e., CD11a CD11b or, CD18). Stimulation of neutrophils with fMLP and eosinophils with PMA resulted in increased surface expression of CD11b and CD18 which was not altered by CFDA labeling. Likewise, CFDA labeling of neutrophils and eosinophils did not significantly alter their integrin-dependent adhesion to activated HUVEC under static or rotational conditions. Similarly, adhesion to immobilized recombinant E- and P-selectin was unaltered. These data demonstrate that fluorescent labeling of human neutrophils and eosinophils with CFDA does not alter surface expression or function of several adhesion molecules necessary for leukocyte-endothelial interactions. The use of CFDA-labeIed cells in experiments employing intravital microscopy should therefore provide valid information on adhesion molecule function in vivo. C1 JOHNS HOPKINS UNIV,SCH MED,DIV CLIN IMMUNOL,DEPT MED,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,BALTIMORE,MD 21224. NR 31 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 15 PY 1995 VL 188 IS 1 BP 79 EP 89 DI 10.1016/0022-1759(95)00206-5 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA TN543 UT WOS:A1995TN54300009 PM 8551041 ER PT J AU Prussin, C Metcalfe, DD AF Prussin, C Metcalfe, DD TI Detection of intracytoplasmic cytokine using flow cytometry and directly conjugated anti-cytokine antibodies SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE flow cytometry; cytokine; monensin; intracellular immunofluorescence; T cell; Th-1 cell; Th-2 cell; IL-5 ID GAMMA-PRODUCING CELLS; INTERFERON-GAMMA; IL-5 AB Recently, there have been several reports demonstrating improvements in the flow cytometric detection of intracellular cytokines. These advances, although significant, have not yielded techniques that have easily been translated into broad use. To address this issue, we have coupled a fixation and permeabilization method with the use of directly labelled monoclonal anti-cytokine antibodies, providing both improved signal and simpler staining. The kinetics of in situ cytokine production in both CD4 and CD8 cells are shown for IL-2, IL-4, IL-5 and IFN-gamma. Based on these data, 6 h was chosen for optimal detection of this combination of cytokines. We show the specificity of this technique by blocking cytokine staining using a molar excess of recombinant cytokine. Additionally, unlabelled anti-cytokine antibodies are demonstrated to block specific staining of labelled antibody, providing an objective means to place statistical markers. Using such controls, we routinely detected as few as 0.1% false positive cells, allowing the flow cytometric detection of IL-5, which is below the threshold of detection of published methods. To further prove the specificity of staining, we stained using two anti-IL-5 mAbs known to recognize different epitopes and demonstrate that the same cells stain with both antibodies. Without permeabilization we could detect a fraction of cells with low intensity staining for cytokine. This staining was further examined using differential two color staining for intracellular and extracellular cytokine, clearly demonstrating no cells staining exclusively for extracellular cytokine, confirming a lack of passive transfer of cytokine to nearby cells. We show that cytokine flow cytometry is useful in examining the increased IL-5 production characteristic of eosinophilic states and that IL-5 production is limited to the CD27 negative subpopulation. These data illustrate the unique capability of cytokine flow cytometry to correlate cytokine expression with cell surface phenotype without cell separation. In summary, using directly conjugated anti-cytokine antibodies, cytokine flow cytometry becomes a specific and versatile technique for the assessment of complex cytokine production phenotypes in fresh ex vivo T cell subpopulations. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. OI Prussin, Calman/0000-0002-3917-3326 NR 19 TC 371 Z9 382 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 15 PY 1995 VL 188 IS 1 BP 117 EP 128 DI 10.1016/0022-1759(95)00209-X PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA TN543 UT WOS:A1995TN54300012 PM 8551029 ER PT J AU MASTELLER, EL LEE, KP CARLSON, LM THOMPSON, CB AF MASTELLER, EL LEE, KP CARLSON, LM THOMPSON, CB TI EXPRESSION OF SIALYL LEWIS(X) AND LEWIS(X) DEFINES DISTINCT STAGES OF CHICKEN B-CELL MATURATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LIGHT-CHAIN GENE; BURSA; FABRICIUS; ONTOGENY; REARRANGEMENT; DIVERSITY; OLIGOSACCHARIDES; DIVERSIFICATION; PRECURSORS; REPERTOIRE AB Commitment of cells to the B lineage in chickens occurs only during a brief period of embryogenesis, B cell progenitors then progress through discrete developmental stages resulting in the production of mature B cells that are competent to form a functioning humoral immune system in the adult bird. During embryogenesis, chicken B cell precursors undergo tissue and developmental stage-specific changes in cell-surface glycosylation, Immature B cell progenitors that migrate to the bursa of Fabricius express the carbohydrate epitope sialyl Lewis(x). Such cells undergo initial clonal expansion within the bursa without undergoing gene conversion, Beginning between days 15 and 17 of embryogenesis, B cells in the bursa undergo a tissue specific change in surface glycosylation that results in the loss of sialyl Lewis(x) expression and the acquisition of the related carbohydrate structure Lewis(x), Expression of Lewis(x) identifies B lymphocytes that have begun to undergo gene conversion, Before emigration from the bursa, bursal lymphocytes undergo another phenotypic switch in glycosylation and down-regulate Lewis(x) expression, Therefore, developmental switches in glycosylation allow us to distinguish three populations of B cells in the bursa of Fabricius at defined stages of development and suggest that regulation of cell-surface glycosylation plays a role in B cell development in the chicken. C1 UNIV CHICAGO,HOWARD HUGHES MED INST,GWEN KNAPP CTR LUPUS & IMMUNOL RES,CHICAGO,IL 60637. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20889. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. NIAID,BETHESDA,MD 20892. FU NCI NIH HHS [R37 CA48023] NR 31 TC 29 Z9 30 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1995 VL 155 IS 12 BP 5550 EP 5556 PG 7 WC Immunology SC Immunology GA TJ631 UT WOS:A1995TJ63100013 PM 7499837 ER PT J AU ROGERS, MJ MCCONKEY, GA LI, J MCCUTCHAN, TF AF ROGERS, MJ MCCONKEY, GA LI, J MCCUTCHAN, TF TI THE RIBOSOMAL DNA LOCI IN PLASMODIUM-FALCIPARUM ACCUMULATE MUTATIONS INDEPENDENTLY SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE EVOLUTION; GENE EXPRESSION; INTERNAL TRANSCRIBED SPACER; MALARIA; MUTATION ID RNA GENES; EVOLUTION; EXPRESSION; EUKARYOTES; SEQUENCES; PATTERNS; MALARIA AB Homogeneity of rDNA sequence within a cell is maintained by mechanisms working at the DNA level. The imperative to maintain homogeneity is thought to result from pressure to maintain the sequence of the rRNA transcript. We have investigated the extent of sequence variation within and between members of a species that is unable to utilize some standard mechanisms of rDNA sequence correction. We have compared the sequence of the internal transcribed spacer (ITS1) located between the 18 S rRNA and 5.8 S rRNA genes of five different loci of a single Plasmodium falciparum genotype. The ITS1 sequences are identical at 80 to 91% of the positions among the three asexually expressed genes (A-types) and 75% between the two genes expressed during sporogony (S-types), with only 42 to 57% identity between the types. This is rather startling in that the differences described here for a single genome are greater than those normally seen when comparing rDNA units from distantly related organisms. We observe an apparent conservation of secondary structure within ITS1 sequences from the different transcription units, which would reflect a level of selection at the rRNA but the organism seems to be quite tolerant of primary sequence variation. Investigation of the mature coding region within the 18 S rRNA genes did not reveal sequence variation within A- and S-types from a single genotype. However, comparison of the 18 S rRNA coding region from 17 geographically distinct strains reveals up to 10% sequence variation within a 400 nucleotide region. Hence homogeneity of rRNA units within a species does not seem to be an imperative driven totally by selection at the RNA level. The extraordinary maintenance of homogeneity within rDNA units normally seen within a species appears to have significance beyond those that can be ascribed to the events involved in processing, assembly and function of the ribosome. (C) 1995 Academic Press Limited C1 NIAID,PARASIT DIS LAB,GROWTH & DEV SECT,BETHESDA,MD 20892. NR 31 TC 32 Z9 33 U1 0 U2 3 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 15 PY 1995 VL 254 IS 5 BP 881 EP 891 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK477 UT WOS:A1995TK47700009 PM 7500358 ER PT J AU Tzeng, SF Deibler, GE Neuberger, TJ DeVries, GH AF Tzeng, SF Deibler, GE Neuberger, TJ DeVries, GH TI Two mitogenic regions of myelin basic protein interact with different receptors to induce Schwann cell proliferation in a cAMP dependent process SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Schwann cell proliferation; myelin basic protein; intracellular cAMP; FGF receptor; ganglioside GM1 ID FIBROBLAST GROWTH-FACTORS; PERIPHERAL-NERVE; P53; DEGENERATION; GANGLIOSIDES; MACROPHAGES; LYMPHOCYTES; ASTROCYTES; RESPONSES; DOMAINS AB Previous studies have shown that myelin basic protein (MBP) is mitogenic for Schwann cells (SCs) in the presence of elevated intracellular cAMP, Two mitogenic regions of MBP have been identified: one mitogenic region within the first 44 residues of the amino-terminus (1-44) and the other mitogenic region within the terminal 15 residues of the carboxyl end of the molecule (152-167), Unlike the mitogenic effect of a myelin enriched fraction (MEF), the mitogenic effect of MBP was not reduced by the addition of the lysosomal inhibitor, ammonium chloride, These data indicate that MBP causes SC proliferation by direct interaction of MBP with a surface receptor. Using Scatchard analysis of the binding of MBP to SCs, we report that treatment with forskolin does not cause the upregulation of receptors for MBP, Moreover, MBP blocks the cross-linking of I-125-bFGF with two fibroblast growth factor (FGF) receptors having apparent molecular weights of 140 kDa and 120 kDa, respectively, Since neither TGF-beta nor PDGF-BB displaced cell surface bound I-125-MBP, we conclude that MBP binds to the FGF receptor rather than other growth factor receptors. Furthermore, only MBP(1-44) interacted with ganglioside GM1, whereas MBP(152-167) did not interact with this ganglioside, These results are consistent with the view that ganglioside GM1 mediates the mitogenic effects of MBP(1-44), while the FGF receptor mediates the mitogenic effect of MBP(152-167). Intracellular cAMP of SCs was transiently increased after the addition of macrophage conditioned medium, suggesting that macrophages may produce factors in vivo which can transiently elevate intracellular cAMP levels, allowing a wave of SC proliferation in response to MBP-related mitogens. (C) 1995 Wiley-Liss, Inc. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT BIOCHEM & MOLEC BIOPHYS,RICHMOND,VA 23298. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. AMGEN INC,BOULDER,CO. FU NINDS NIH HHS [NS 15408] NR 38 TC 17 Z9 18 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD DEC 15 PY 1995 VL 42 IS 6 BP 758 EP 767 DI 10.1002/jnr.490420604 PG 10 WC Neurosciences SC Neurosciences & Neurology GA TM786 UT WOS:A1995TM78600003 PM 8847737 ER PT J AU Tzeng, SF Deibler, GE DeVries, GH AF Tzeng, SF Deibler, GE DeVries, GH TI Exogenous myelin basic protein promotes oligodendrocyte death via increased calcium influx SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE myelin basic protein; oligodendrocytes; ganglioside GM1; calcium influx; cell death ID NERVOUS-SYSTEM; CELL-SURVIVAL; GANGLIOSIDES; PROLIFERATION; ASTROCYTES; TISSUE AB Treatment of cultured oligodendrocytes (OLGs) with micromolar quantities of myelin basic protein (MBP) caused a rapid, MBP-dose-dependent cell death, In contrast, a 72-hr incubation of OLGs with MBP peptides (1-44, 47-87, 88-151, or 152-167) at comparable concentrations had no effect on cell viability, MBP and MBP peptides (1-44 and 88-151) have been shown to interact with ganglioside GM1 (Tzeng et al.: J Neurochem Res: 42:758-767, 1995), This interaction has been reported to increase calcium influx, Therefore, using the fluorescent dye Indo-1 and an ACAS laser cytometer, we examined the level of intracellular calcium in OLGs after MBP treatment, MBP was shown to provoke a rapid, dramatic, and sustained rise of intracellular calcium in most OLGs, The levels of elevated intracellular calcium were sustained and did not return to baseline even after 10 min, This increase of intracellular calcium was suppressed in the presence of EGTA, indicating that the [Ca2+](i) rise was due to the entry of extracellular calcium, Incubation of cultured OLGs with MBP peptides (1-44 or 88-151) caused a modest and transitory elevation of intracellular calcium ions in a lower percentage of OLGs, The potent OLG cytotoxicity of intact MBP and the loss of potency after proteolysis raise the possibility that MBP proteolysis during demyelination protects OLGs from death. (C) 1995 Wiley-Liss, Inc. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT BIOCHEM & MOLEC BIOPHYS,RICHMOND,VA 23298. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. FU NINDS NIH HHS [NS 15408] NR 28 TC 9 Z9 9 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD DEC 15 PY 1995 VL 42 IS 6 BP 768 EP 774 DI 10.1002/jnr.490420605 PG 7 WC Neurosciences SC Neurosciences & Neurology GA TM786 UT WOS:A1995TM78600004 PM 8847738 ER PT J AU Bell, JA Beglan, CL London, ED AF Bell, JA Beglan, CL London, ED TI Interaction of ascorbic acid with the neurotoxic effects of NMDA and sodium nitroprusside SO LIFE SCIENCES LA English DT Article DE neurons; NMDA; neurotoxicity; nitric oxide; neuroprotection ID NITRIC-OXIDE; RECEPTOR; NEURONS AB We have previously shown that ascorbic acid (AA) protects cortical neurons in culture from the toxic effects of NMDA. In the present study, we examined the interactions of AA with toxicity produced by nitric oxide (NO) that is generated from the breakdown of sodium nitroprusside (SNP), and with NMDA toxicity measured 24 h later. AA enhanced SNP toxicity, but it reduced toxicity of NMDA. We propose that these data support a model wherein AA produces neuroprotection by an action at the NMDA receptor, and indirectly with respect to NO. This effect occurs probably by antagonizing Ca2+ influx starting the cascade of biochemical events that lead to the production of NO. C1 NIDA,INTRAMURAL RES PROGRAM,NEUROIMAGING & DRUG ACT SECT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21205. NR 9 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD DEC 15 PY 1995 VL 58 IS 4 BP 367 EP 371 DI 10.1016/0024-3205(95)02296-1 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA TK714 UT WOS:A1995TK71400011 ER PT J AU Scheffel, U Taylor, GF Kepler, JA Carroll, FI Kuhar, MJ AF Scheffel, U Taylor, GF Kepler, JA Carroll, FI Kuhar, MJ TI In vivo labeling of neuronal nicotinic acetylcholine receptors with radiolabeled isomers of norchloroepibatidine SO NEUROREPORT LA English DT Article DE nicotine; nicotinic receptor; epibatidine; norchloroepibatidine; cholinergic receptor; acetylcholine ID POSITRON EMISSION TOMOGRAPHY; RAT-BRAIN MEMBRANES; CHOLINERGIC RECEPTORS; ALPHA-BUNGAROTOXIN; BINDING-SITES; H-3 NICOTINE; MOUSE-BRAIN; ACETYLCHOLINE AB IN VITRO binding studies have shown that epibatidine and its norchloro analogues have high affinities for the cholinergic nicotinic receptor. In this study, the in vivo binding characteristics of [H-3](+)norchloroepibatidine (NCEPB) and [H-3](-)NCEPB in mice were examined. After injection of [H-3](+)NCEPB, radioactivity levels in all brain regions examined increased and then decreased, with different regions accumulating different levels of radioactivity. The regional distribution of radioactivity at later times paralleled the distribution of nicotinic receptor binding in vitro. The ratio of radioactivity in the superior colliculus to that in the cerebellum a reflection or estimate of total: non-specific binding, was strikingly high at 8 h (about 35). Drugs known to bind to nicotinic receptors reduced [H-3](+)NCEPB binding, while atropine and spiperone, muscarinic and dopaminergic drugs respectively, did not. [H-3](-)NCEPB had a similar regional distribution to [H-3](+)NCEPB. Pretreatment with increasing doses of non-radioactive (-)NCEPB resulted in saturation of in vivo binding of [H-3](-)NCEPB. These data indicate that [H-3](+) and (-)NCEPB are useful in vivo binding ligands for the cholinergic nicotinic receptor. C1 NIDA,DIV INTRAMURAL RES,NEUROSCI BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,DIV NUCL MED,BALTIMORE,MD 21205. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. FU NINDS NIH HHS [NS15080] NR 20 TC 29 Z9 29 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 15 PY 1995 VL 6 IS 18 BP 2483 EP 2488 DI 10.1097/00001756-199512150-00011 PG 6 WC Neurosciences SC Neurosciences & Neurology GA TQ662 UT WOS:A1995TQ66200011 PM 8741747 ER PT J AU Beauregard, M Malkova, L Bachevalier, J AF Beauregard, M Malkova, L Bachevalier, J TI Stereotypies and loss of social affiliation after early hippocampectomy in primates SO NEUROREPORT LA English DT Article DE social behavior; stereotypy; hippocampal formation; schizophrenia; nonhuman primates ID MONKEYS MACACA; RATS; SCHIZOPHRENIA; AMYGDALA; LESIONS; MULATTA; INFANT; DAMAGE AB THE present study was aimed at determining whether early hippocampal damage alters the development of normal social interactions. Results showed that, at 2 months of age, animals with neonatal hippocampal lesions presented minor disturbances in initiation of social interactions. These subtle changes in behavior were less evident at 6 months, although at this age, the operated animals displayed more withdrawals in response to an increase in aggressive responses from their unoperated peers. Finally, in adulthood, the amount of time spent by the operated monkeys in social contacts with their normal peers was markedly less than that in normal dyads. Only in adulthood did the operated animals exhibit more locomotor stereotypies than normal controls. This finding suggest that the hippocampal formation may directly or indirectly affect the maintenance of social bounds in primates. C1 UNIV TEXAS,HLTH SCI CTR,DEPT NEUROBIOL & ANAT,HOUSTON,TX 77030. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. FU NIMH NIH HHS [MH49278] NR 26 TC 36 Z9 36 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 15 PY 1995 VL 6 IS 18 BP 2521 EP 2526 DI 10.1097/00001756-199512150-00018 PG 6 WC Neurosciences SC Neurosciences & Neurology GA TQ662 UT WOS:A1995TQ66200018 PM 8741754 ER PT J AU Johren, O Inagami, T Saavedra, JM AF Johren, O Inagami, T Saavedra, JM TI AT(1A), AT(1B), and AT(2) angiotensin II receptor subtype gene expression in rat brain SO NEUROREPORT LA English DT Article DE angiotensin II receptors; brain angiotensin system; receptor subtypes; in situ hybridization ID MESSENGER-RNAS; AUTORADIOGRAPHY; LOCALIZATION; REVEALS; CLONING; NUCLEI; AT1 AB WE localized the gene expression of angiotensin II receptor subtypes (AT(1A), AT(1B), and AT(2)) in 2-week-old rat brain by in situ hybridization using subtype specific riboprobes. AT(1A) receptor mRNA but not AT(1B) or AT(2) receptor mRNA was expressed in the subfornical organ and paraventricular nucleus of the hypothalamus. AT(1B) as well as AT(1A) receptor mRNA were found in the cerebral cortex and hippocampus. Conversely, AT(2) receptor mRNA, but not AT(1A) or AT(1B), was expressed in the medial geniculate nucleus and inferior olive. Our results indicate that AT(1A) receptors are involved in the well known central functions of angiotensin II. These results also support the hypothesis of the involvement of AT(2) receptors in sensory and motor function. C1 VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. RP Johren, O (reprint author), NATL INST MENTAL HLTH,CLIN SCI LAB,PHARMACOL SECT,10 CTR DR MSC 1514,BLDG 10,ROOM 2D-45,BETHESDA,MD 20982, USA. RI Johren, Olaf/G-6967-2011 NR 24 TC 84 Z9 84 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 15 PY 1995 VL 6 IS 18 BP 2549 EP 2552 PG 4 WC Neurosciences SC Neurosciences & Neurology GA TQ662 UT WOS:A1995TQ66200024 PM 8741760 ER PT J AU COCCHI, F DEVICO, AL GARZINODEMO, A ARYA, SK GALLO, RC LUSSO, P AF COCCHI, F DEVICO, AL GARZINODEMO, A ARYA, SK GALLO, RC LUSSO, P TI IDENTIFICATION OF RANTES, MIP-1-ALPHA, AND MIP-1-BETA AS THE MAJOR HIV-SUPPRESSIVE FACTORS PRODUCED BY CD8(+) T-CELLS SO SCIENCE LA English DT Article ID VIRUS-REPLICATION; FUNCTIONAL EXPRESSION; PROGENITOR CELLS; BINDING-PROTEIN; LINE PF-382; INFECTION; MIGRATION; RECEPTORS; MONOCYTE; INVITRO AB Evidence suggests that CD8(+) T lymphocytes are involved in the control of human immunodeficiency virus (HIV) infection in vivo, either by cytolytic mechanisms or by the release of HIV-suppressive factors (HIV-SF). The chemokines RANTES, MIP-1 alpha, and MIP-1 beta were identified as the major HIV-SF produced-by CD8(+) T cells. Two active proteins purified from the culture supernatant of an immortalized CD8(+) T cell clone revealed sequence identity with human RANTES and MIP-1 alpha. RANTES, MIP-1 alpha, and MIP-1 beta were released by both immortalized and primary CD8(+) T cells. HIV-SF activity produced by these cells was completely blocked by a combination of neutralizing antibodies against RANTES, MIP-1 alpha, and MIP-1 beta. Recombinant human RANTES, MIP-1 alpha, and MIP-1 beta induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). These data may have relevance for the prevention and therapy of AIDS. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. ADV BIOSCI LABS,KENSINGTON,MD 20852. NR 48 TC 2369 Z9 2415 U1 6 U2 64 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 15 PY 1995 VL 270 IS 5243 BP 1811 EP 1815 DI 10.1126/science.270.5243.1811 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TK476 UT WOS:A1995TK47600043 PM 8525373 ER PT J AU YOSHIMOTO, T BENDELAC, A WATSON, C HULI, J PAUL, WE AF YOSHIMOTO, T BENDELAC, A WATSON, C HULI, J PAUL, WE TI ROLE OF NK1.1(+) T-CELLS IN A T(H)2 RESPONSE AND IN IMMUNOGLOBULIN-E PRODUCTION SO SCIENCE LA English DT Article ID MURINE IMMUNE-SYSTEM; POLYCLONAL ACTIVATION; LYMPHOKINE SECRETION; INTERLEUKIN-4; ANTIBODY; CD4+; CD1; GENERATION; INVIVO; FAMILY AB Immune responses dominated by interleukin-4 (IL-4)-producing T helper type 2 (T(H)2) cells or by interferon gamma (IFN-gamma)-producing T helper type 1 (T(H)1) cells express distinctive protection against infection with different pathogens. Interleukin-4 promotes the differentiation of naive CD4(+) T cells into IL-4 producers and suppresses their development into IFN-gamma producers. CD1-specific splenic CD4(+)NK1.1(+) T cells, a numerically minor population, produced IL-4 promptly on in vivo stimulation. This T cell population was essential for the induction of IL-4-producing cells and for switching to immunoglobulin E, an IL-4-dependent event, in response to injection of antibodies to immunoglobulin D. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544. NR 27 TC 438 Z9 443 U1 1 U2 1 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 15 PY 1995 VL 270 IS 5243 BP 1845 EP 1847 DI 10.1126/science.270.5243.1845 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TK476 UT WOS:A1995TK47600053 PM 8525383 ER PT J AU ERNST, JA CLUBB, RT ZHOU, HX GRONENBORN, AM CLORE, GM AF ERNST, JA CLUBB, RT ZHOU, HX GRONENBORN, AM CLORE, GM TI USE OF NMR TO DETECT WATER WITHIN NONPOLAR PROTEIN CAVITIES - RESPONSE SO SCIENCE LA English DT Article ID ROTATING-FRAME; INTERLEUKIN-1-BETA; SPECTROSCOPY; IDENTIFICATION; RESOLUTION RP ERNST, JA (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008; Zhou, Huan-Xiang/M-5170-2016 OI Clore, G. Marius/0000-0003-3809-1027; Zhou, Huan-Xiang/0000-0001-9020-0302 NR 19 TC 15 Z9 15 U1 0 U2 2 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 15 PY 1995 VL 270 IS 5243 BP 1848 EP 1849 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TK476 UT WOS:A1995TK47600055 ER PT J AU DAHM, PF GAIL, MH ROSENBERG, PS PEE, D AF DAHM, PF GAIL, MH ROSENBERG, PS PEE, D TI DETERMINING THE VALUE OF ADDITIONAL SURROGATE EXPOSURE DATA FOR IMPROVING THE ESTIMATE OF AN ODDS RATIO SO STATISTICS IN MEDICINE LA English DT Article ID LOG-LINEAR MODELS; CATEGORICAL-DATA; MISCLASSIFICATION; ERRORS AB We consider the design of both cohort and case-control studies in which an initial ('stage 1') sample of complete data on an error-free disease indicator (D), a correct ('gold-standard') dichotomous exposure measurement (X) and an error-prone exposure measurement (Z) are available, We calculate the amount of additional information on the odds ratio relating D to X that one can obtain from a second ('stage 2') sample of measurements only on D and Z, If one allows for differential measurement error in Z, there is often little advantage in having more than four times as much data in stage 2 data as in stage 1. With the assumption that a non-differential measurement error model is reasonable, larger amounts of stage 2 data can be useful, Simulations indicate that stage 1 samples of modest size (50 cases in case-control studies and 50 failures in cohort studies) yield sufficiently reliable estimates of needed parameters to assist in determining an appropriate size for the stage 2 sample, These ideas apply in settings either where the amount of stage 1 data is limited and fixed by external constraints or where one has gathered stage 1 data in advance to avoid collecting superfluous stage 2 data. C1 TEXAS A&M UNIV,DEPT STAT,COLLEGE STN,TX 77843. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD 20850. RP DAHM, PF (reprint author), NCI,BIOSTAT BRANCH,6130 EXECUT BLVD,EPN 431,ROCKVILLE,MD 20892, USA. FU NCI NIH HHS [CA57030] NR 16 TC 5 Z9 5 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 15 PY 1995 VL 14 IS 23 BP 2581 EP 2598 DI 10.1002/sim.4780142307 PG 18 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 TK133 UT WOS:A1995TK13300006 PM 8746890 ER PT J AU Boussaoud, D diPellegrino, G Wise, SP AF Boussaoud, D diPellegrino, G Wise, SP TI Frontal lobe mechanisms subserving vision-for-action versus vision-for-perception SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the European-Brain-and-Behaviour-Society CY SEP 16-18, 1993 CL MADRID, SPAIN SP European Brain & Behav Soc DE attention; action; intention; frontal cortex; motor cortex; premotor cortex; neglect; primate; visually guided movement ID POSTERIOR PARIETAL CORTEX; SUPERIOR TEMPORAL SULCUS; MONKEY CEREBRAL-CORTEX; PRIMATE MOTOR CORTEX; RHESUS-MONKEY; CORTICAL CONNECTIONS; VISUAL RESPONSES; MACAQUE MONKEY; CORTICOCORTICAL CONNECTIONS; PREFRONTAL CORTEX AB In the typical course of daily events, we often gaze at an object, attend to its features and its place, reach toward it and grasp it, all with an awareness of what we are doing at the time. But behavior is not always thus. Gaze, attention, limb movement direction and awareness can be behaviorally dissociated from each other, and this review focuses on one such dissociation: that between the perception of an object and the use of that object's inherent spatial and nonspatial information for mediating visuomotor control. We review evidence that partially different neuronal systems underlie these two aspects of visual information processing. In neurophysiological studies of the primate frontal lobe, it has been possible to demonstrate that neural signals appearing to be visual responses reflect, at least in part, the motor significance of a stimulus. This finding has been confirmed, in separate studies, for both spatial and nonspatial visual information and supports the hypothesis that some frontal cortex activity reflects the selection and guidance of action rather than the properties of visual stimuli, per se. These findings are discussed in the context of neuropsychological studies indicating that accurate and appropriate movements are possible without perceptual awareness of the information guiding those movements. C1 UNIV VERONA,DIPARTIMENTO SCI NEUROL & VIS FISIOL UMANA,I-37134 VERONA,ITALY. NIMH,LAB SYST NEUROSCI,NIH ANIM CTR,POOLESVILLE,MD 20837. RP Boussaoud, D (reprint author), INSERM,U94,16 AVE DOYEN LEPINE,F-69500 BRON,FRANCE. RI Boussaoud, Driss/B-6932-2008 NR 145 TC 29 Z9 29 U1 0 U2 4 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 14 PY 1995 VL 72 IS 1-2 BP 1 EP 15 DI 10.1016/0166-4328(96)00055-1 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA TP481 UT WOS:A1995TP48100001 PM 8788851 ER PT J AU Guzman, K Randell, SH Nettesheim, P AF Guzman, K Randell, SH Nettesheim, P TI Epidermal growth factor regulates expression of the mucous phenotype of rat tracheal epithelial cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MUCIN GENE-EXPRESSION; FACTOR-ALPHA; FETAL; DISEASE; AIRWAYS; TARGET; LUNG AB The purpose of this study was to determine whether epidermal growth factor (EGF) regulates mucous differentiation of airway epithelial cells in culture. Reduction of the EGF concentration below 25 ng/ml, which is the concentration routinely used in rat tracheal epithelial cell cultures, resulted in a 2 to 3-fold decrease in the percentage of mucous cells as determined by a mucin monoclonal antibody. The amount of secreted mucin decreased more than 10-fold within 5 days after reducing the EGF concentration. MUC5 gene expression, which was previously shown to correlate with mucous differentiation, was also reduced more than 8-fold. Addition of 25 ng/ml EGF to EGF-deprived cultures resulted in rapid induction of MUGS expression. Following tissue injury and during inflammation the release of EGF and its functional analogue TGF alpha have been observed and may he involved in the mucus hypersecretion characteristic of many airway diseases. (C) 1995 Academic Press, Inc. C1 UNIV N CAROLINA,CHAPEL HILL,NC 27599. RP Guzman, K (reprint author), NIEHS,PULM PATHOBIOL LAB,POB 12233,LPP,MD D2-03,RES TRIANGLE PK,NC 27709, USA. NR 31 TC 30 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 14 PY 1995 VL 217 IS 2 BP 412 EP 418 DI 10.1006/bbrc.1995.2792 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TK408 UT WOS:A1995TK40800005 PM 7503716 ER PT J AU Rao, PV Huang, QL Horwitz, J Zigler, JS AF Rao, PV Huang, QL Horwitz, J Zigler, JS TI Evidence that alpha-crystallin prevents non-specific protein aggregation in the intact eye lens SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE alpha-crystallin; chaperone; protein aggregation; cataract; lens; thermal denaturation ID HEAT-SHOCK PROTEIN; MOLECULAR-WEIGHT PROTEIN; NIH 3T3 FIBROBLASTS; B-CRYSTALLIN; EXPRESSION; CATARACT; TISSUES; CHAPERONE; STRESS; ACCUMULATION AB The ocular lens is a transparent organ comprised of a highly concentrated and highly ordered matrix of structural proteins, called crystallins, which are probably the longest lived proteins of the body. Lens transparency is dependent upon maintenance of the short range order of the crystallin matrix. This transparency must be maintained for decades in the absence of normal protein synthesis or repair capacity. We present evidence here that alpha-crystallin, one of the major lens proteins, plays a central role in vivo in stabilizing the other crystallins and preventing uncontrolled aggregation of these progressively modified and aging molecules. alpha-Crystallin has previously been shown to suppress non-specific aggregation of denaturing proteins in simple binary systems through a chaperone-like activity. Our studies using soluble homogenates of monkey lenses demonstrate a strong resistance to heat induced non-specific aggregation when the complete complement of crystallins is present; in contrast, if alpha-crystallin is selectively removed prior to heating, the remaining crystallins undergo extensive non-specific aggregation as indicated by light scattering. When alpha-crystallin is present it complexes with denaturing proteins forming a soluble heavy molecular weight (HMW) fraction but no insolubilization is observed, while when alpha-crystallin is absent there is heavy insolubilization and no HMW formed. When intact monkey lenses were heated it could be demonstrated that soluble HMW was generated. Similar HMW protein appears in vivo in the human lens as a function of age. These findings suggest that the soluble HMW protein present in the human lens is the product of the chaperone-like function of alpha-crystallin and that under physiological conditions alpha-crystallin inhibits the uncontrolled aggregation of damaged proteins, thereby preventing the formation of light scattering centers and opacification of the lens. C1 UNIV CALIF LOS ANGELES,SCH MED,JULES STEIN EYE INST,LOS ANGELES,CA 90024. RP Rao, PV (reprint author), NEI,BLDG 6,RM 237,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NEI NIH HHS [R-37-EY03897] NR 59 TC 100 Z9 102 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD DEC 14 PY 1995 VL 1245 IS 3 BP 439 EP 447 DI 10.1016/0304-4165(95)00125-5 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TL154 UT WOS:A1995TL15400025 PM 8541324 ER PT J AU Deerfield, DW Pedersen, LG AF Deerfield, DW Pedersen, LG TI An ab initio quantum mechanical study of thioesters SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Article DE ab initio quantum mechanical calculation; isomer; thioester ID FATTY ACYLATION; COVALENT BINDING; COENZYME-A; PROTEINS; HYDROLYSIS; SUBSTRATE; MOLECULES; ALGORITHM; PATHWAY; SPECTRA AB Model thioesters have been studied using ab initio quantum mechanical computations to determine the geometry and difference in energy for inherent rotamers. The Z isomer of the thioester is found to be 4.9 kcal mol(-1) (Delta G(298)(0) more Stable than the E isomer, with the barrier for rotation (Z --> E) 10.1 kcal mol(-1) (Delta G(298)double dagger). Parameters for molecular mechanics computations are provided. C1 UNIV N CAROLINA, DEPT CHEM, CHAPEL HILL, NC 27599 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. RP Deerfield, DW (reprint author), PITTSBURGH SUPERCOMP CTR, 4400 5TH AVE, PITTSBURGH, PA 15213 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 35 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 J MOL STRUC-THEOCHEM JI Theochem-J. Mol. Struct. PD DEC 14 PY 1995 VL 358 BP 99 EP 106 DI 10.1016/0166-1280(96)87754-2 PG 8 WC Chemistry, Physical SC Chemistry GA TQ455 UT WOS:A1995TQ45500012 ER PT J AU OLSEN, JH BOICE, JD SEERSHOLM, N BAUTZ, A FRAUMENI, JF AF OLSEN, JH BOICE, JD SEERSHOLM, N BAUTZ, A FRAUMENI, JF TI CANCER IN THE PARENTS OF CHILDREN WITH CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SOFT-TISSUE SARCOMA; CHILDHOOD-CANCER; BREAST-CANCER; RETINOBLASTOMA PATIENTS; RELATIVES; RISK; MORTALITY; SURVIVORS; FAMILIES; MOTHERS AB Background. Certain types of cancer in children and young adults have been linked with an increased risk of cancer in close relatives. However, the relation between childhood cancer and familial risk remains to be fully assessed in population-based studies. Methods. We conducted a nationwide study in Denmark of 11,380 parents of children with cancer. The children were identified from records in the Danish Cancer Registry; their parents were identified from population registers. The occurrence and rate of cancer in the parents were determined with use of the Cancer Registry's files and compared with national incidence rates for various categories of tumor. Results. Overall, 1445 cancers were diagnosed in the parents, as compared with 1496 expected from national incidence rates, to yield standardized incidence ratios of 1.0 (95 percent confidence interval, 0.9 to 1.0) for all parents, 1.0 for mothers, and 0.9 for fathers. The lower rate of cancer among fathers reflected their lower standardized incidence ratio for lung cancer (0.8; 95 percent confidence interval, 0.6 to 0.9), as calculated from 114 observations. Conclusions. Genetic determinants are important in several types of childhood cancer, but the genetic susceptibility to tumors does not generally extend to the parents of children with cancer, nor do the patterns of incidence point to the influence of shared environmental factors. Thus, cancer in children should not be viewed as a general marker for an increased risk of cancer in the patients' parents. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD. RP OLSEN, JH (reprint author), DANISH CANC SOC,DIV CANC EPIDEMIOL,STRANDBOULEVARDEN 49,DK-2100 COPENHAGEN,DENMARK. NR 32 TC 72 Z9 74 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 14 PY 1995 VL 333 IS 24 BP 1594 EP 1599 DI 10.1056/NEJM199512143332403 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TK065 UT WOS:A1995TK06500003 PM 7477194 ER PT J AU CLAYTON, EW STEINBERG, KK KHOURY, MJ THOMSON, E ANDREWS, L KAHN, MJE KOPELMAN, LM WEISS, JO AF CLAYTON, EW STEINBERG, KK KHOURY, MJ THOMSON, E ANDREWS, L KAHN, MJE KOPELMAN, LM WEISS, JO TI INFORMED CONSENT FOR GENETIC RESEARCH ON STORED TISSUE SAMPLES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Objective.-To develop recommendations for obtaining adequate informed consent in the future when gathering tissue samples that may be used for genetic studies and defining the circumstances under which it is necessary to obtain further consent if tissue samples already in hand are to be used for such research. Participants.-Scientists, ethicists, lawyers, and consumers selected by the National Center for Human Genome Research and the Centers for Disease Control and Prevention to represent a wide array of opinions. Evidence.-Statutes, regulations, and cases and articles on law and ethics. Consensus Process.-Initial workshop, followed by circulation of several drafts of this document with opportunities for comment by workshop participants and others as well as smaller meetings involving participants with widely differing views. Conclusions.-Genetic research using stored tissue samples poses an array of benefits and risks to individuals, researchers, and society, As a result, the workshop participants conclude that (1) informed consent is required for all genetic research using linkable samples unless conditions for limitation or waiver are met; (2) informed consent is not required for genetic research using anonymous samples but may be considered if identifiers are to be removed from currently linkable samples; (3) institutional review boards could usefully review all protocols that propose to use samples for genetic research; and (4) further work regarding these issues is warranted. C1 VANDERBILT UNIV,DEPT PEDIAT,NASHVILLE,TN. VANDERBILT UNIV,SCH LAW,NASHVILLE,TN 37240. CTR DIS CONTROL & PREVENT,BIRTH DEFECTS & GENET DIS BRANCH,MOLEC BIOL BRANCH,ATLANTA,GA 30341. NATL CTR HUMAN GENOME RES,BETHESDA,MD. CHICAGO KENT COLL LAW,CHICAGO,IL. NATL BREAST CANC COALIT,WASHINGTON,DC. VIRGINIA BREAST CANC FDN,RICHMOND,VA. E CAROLINA UNIV,SCH MED,DEPT MED HUMANITIES,GREENVILLE,NC. ALLIANCE GENET SUPPORT GRP,CHEVY CHASE,MD. NR 20 TC 203 Z9 205 U1 0 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 13 PY 1995 VL 274 IS 22 BP 1786 EP 1792 DI 10.1001/jama.274.22.1786 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA TJ225 UT WOS:A1995TJ22500030 PM 7500511 ER PT J AU FALCK, JR REDDY, KK YE, JH SAADY, M MIOSKOWSKI, C SHEARS, SB TAN, Z SAFRANY, S AF FALCK, JR REDDY, KK YE, JH SAADY, M MIOSKOWSKI, C SHEARS, SB TAN, Z SAFRANY, S TI SYNTHESIS AND STRUCTURE OF CELLULAR MEDIATORS - INOSITOL POLYPHOSPHATE DIPHOSPHATES SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PHOSPHATES AB The first total syntheses of 1-O-[(phosphonooxy)hydroxyphosphinyl]-2,3,4,5,6-pentakis-O-phosphono-D- myo-inositol (10) and its antipode (11) were achieved from enantiopure 2,3:5,6-di-O-cyclohexylidene-D-myo-inositol (6). The critical pyrophosphate function was introduced, in the presence of flanking phosphate triesters, by mild LiCN-mediated cleavage of a mixed phosphate methyl ester, isolation of the resultant lithium salt, and addition to dibenzyl chlorophosphonate. The benzyl esters were removed by catalytic hydrogenolysis over Pd in t-BuOH/H2O in the presence of NaHCO3. Comparisons of synthetic and enzyme-devived pyrophosphates with two phosphatases suggests natural material has the stereochemical configuration in 10. C1 UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,DALLAS,TX 75235. UNIV LOUIS PASTEUR STRASBOURG 1,CNRS,CHIM BIOORGAN LAB,F-67401 ILLKIRCH GRAFFENS,FRANCE. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INOSITOL LIPID SECT,RES TRIANGLE PK,NC 27709. RP FALCK, JR (reprint author), UNIV TEXAS,SW MED CTR,DEPT MOLEC GENET,DALLAS,TX 75235, USA. OI Falck, John/0000-0002-9219-7845 NR 33 TC 19 Z9 19 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 13 PY 1995 VL 117 IS 49 BP 12172 EP 12175 DI 10.1021/ja00154a017 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA TK382 UT WOS:A1995TK38200017 ER PT J AU Chastain, PD Eichler, EE Kang, S Nelson, DL Levene, SD Sinden, RR AF Chastain, PD Eichler, EE Kang, S Nelson, DL Levene, SD Sinden, RR TI Anomalous rapid electrophoretic mobility of DNA containing triplet repeats associated with human disease genes SO BIOCHEMISTRY LA English DT Article ID GEL-ELECTROPHORESIS; ESCHERICHIA-COLI; TRANSCRIPTION; PATTERNS; JUNCTION; CELLS AB Eight human genetic diseases have been associated with the expansion of CTG or CGG triplet repeats. The molecular etiology behind expansion is unknown but may involve participation of an unusual DNA structure in replication, repair, or recombination. We show that DNA fragments containing CTG triplet repeats derived from the human myotonic dystrophy gene migrate up to 20% faster than expected in nondenaturing polyacrylamide gels, suggesting the presence of an unusual DNA helix structure within the CTG triplet repeats. The anomalous migration is dependent upon the number of tripler repeats, the length of the flanking DNA, and the percentage and temperature of the polyacrylamide. The effect could be reduced by the addition of actinomycin D. Applying a reptation model for electrophoresis, the results are consistent with a 20% increase in persistence length of the DNA. PCR products containing CTG or CGG repeats from the spinocerebellar ataxia type I gene (SCA1) or the fragile X FMR1 gene, respectively, also showed higher electrophoretic mobility. These are the first sequences of defined length for which a dramatic increase in mobility can be attributed to sequence-dependent structural elements in DNA. C1 BAYLOR COLL MED,DEPT MOLEC & HUMAN GENET,HOUSTON,TX 77030. UNIV TEXAS,CELL & MOLEC BIOL PROGRAM,RICHARDSON,TX 75083. NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892. RP Chastain, PD (reprint author), TEXAS A&M UNIV,DEPT BIOCHEM & BIOPHYS,CTR GENOME RES,INST BIOSCI & TECHNOL,2121 W HOLCOMBE BLVD,HOUSTON,TX 77030, USA. RI Levene, Stephen/G-3100-2010; OI Levene, Stephen/0000-0003-2778-5162 FU NICHD NIH HHS [HD29256]; NIEHS NIH HHS [ES05508]; NIGMS NIH HHS [GM47898] NR 37 TC 67 Z9 67 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 12 PY 1995 VL 34 IS 49 BP 16125 EP 16131 DI 10.1021/bi00049a027 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK392 UT WOS:A1995TK39200027 PM 8519769 ER PT J AU Gao, XM Margolis, RL Leeds, P Hough, C Post, RM Chuang, DM AF Gao, XM Margolis, RL Leeds, P Hough, C Post, RM Chuang, DM TI Carbamazepine induction of apoptosis in cultured cerebellar neurons: Effects of N-methyl-D-aspartate, aurintricarbocylic acid and cycloheximide SO BRAIN RESEARCH LA English DT Article DE carbamazepine; apoptosis; DNA fragmentation; cerebellar granule cell; N-methyl-D-aspartate; aurintricarboxylic acid; cycloheximide ID PROGRAMMED CELL-DEATH; GRANULE CELLS; FACTOR DEPRIVATION; NERVOUS-SYSTEM; GROWTH; RECEPTOR; NMDA; ANTICONVULSANTS; EXCITOTOXICITY; ENDONUCLEASE AB We have previously demonstrated that carbamazepine (CBZ) at concentrations above the therapeutic range is toxic to cultured cerebellar granule cells. Here, we ask whether the effect of CBZ involves neuronal apoptosis or necrosis. Treatment of cultured cerebellar granule cells with CBZ for 3 days resulted in a concentration-dependent fragmentation of DNA revealed as a laddered pattern in agarose gel electrophoresis, a phenomenon characteristic of apoptosis. Pretreatment of cells with N-methyl-D-aspartate (NMDA) blocked CBZ-induced DNA fragmentation and neurotoxicity as assayed by loss of mitochondrial activity with MTT or by [H-3]ouabain binding to Na+/K+-ATPase. Aurintricarboxylic acid (ATA), a polyanionic dye, also markedly suppressed DNA fragmentation and cell death detected by morphological examination. A considerable level of DNA ladder formation was detected in untreated cells and this basal DNA fragmentation was also blocked by NMDA and ATA. Moreover, NMDA and ATA prevented CBZ-induced chromatin condensation as revealed by DNA binding with the fluorescent dye Hoechst 33258. Pretreatment of cells with cycloheximide, a protein synthesis inhibitor, prevented CBZ-induced cell death detected morphologically and attenuated CBZ-induced neurotoxicity assessed by mitochondrial activity and [H-3]ouabain binding assays. Taken together, our results suggest that CBZ-induces death of cerebellar granule cells by an apoptotic process that is sensitive to NMDA, ATA and cycloheximide. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. NR 38 TC 28 Z9 28 U1 0 U2 1 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 12 PY 1995 VL 703 IS 1-2 BP 63 EP 71 DI 10.1016/0006-8993(95)01066-1 PG 9 WC Neurosciences SC Neurosciences & Neurology GA TL152 UT WOS:A1995TL15200007 PM 8719616 ER PT J AU Rosenberg, GA Estrada, EY Dencoff, JE StetlerStevenson, WG AF Rosenberg, GA Estrada, EY Dencoff, JE StetlerStevenson, WG TI Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood-brain barrier: An expanded therapeutic window SO BRAIN RESEARCH LA English DT Article DE blood-brain barrier; brain edema; matrix metalloproteinase; plasminogen activator; tumor necrosis factor-alpha; rat ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CAPILLARY ENDOTHELIAL-CELLS; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; MATRIX METALLOPROTEINASES; FACTOR CACHECTIN; COLLAGENASE; INHIBITORS; EXPRESSION; INTERLEUKIN-1 AB Proteolytic damage is a late event in the molecular cascade initiated by brain injury. Earlier, we proposed that matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) are important in secondary brain injury. We have shown that intracerebral injection of activated 72-kDa type IV collagenase (gelatinase A) opens the blood-brain barrier, and that during hemorrhagic brain injury there is endogenous production of 92-kDa type IV collagenase (gelatinase B) and uPA. Therefore, to study the functional link between proteolytic enzymes and blood-brain barrier damage, we induced MMP expression by infusing tumor necrosis factor-alpha (TNF) intracerebrally in rats. Initially, the effect on capillary permeability of increasing doses of TNF, using [C-14]sucrose uptake, was measured. Then, the time-course of the capillary permeability change was studied at 4, 16, 24 and 72 h. Expression of MMP and uPA was measured by zymography at 24 h after TNF injection and compared to saline-injected controls. A dose-dependent increase in capillary permeability was seen 24 h after TNF injection. Maximal uptake of [C-14]sucrose occurred at 24 h compared to saline-injected controls (P < 0.05). Zymography showed production of gelatinase B, which was significantly greater than in saline-injected controls at 24 h (P < 0.05). Batimastat, a synthetic inhibitor to metalloprotinases, reduced sucrose uptake at 24 h (P < 0.0001), and was effective even when given 6 h after TNF (P < 0.01). Thus, gelatinase B is the intermediate substance linking TNF to modulation of capillary permeability. Agents that interfere with transcription of proteolytic enzymes or block their action may reduce delayed capillary injury, extending the therapeutic window. C1 VET AFFAIRS MED CTR,NEUROL SERV,ALBUQUERQUE,NM. NCI,PATHOL LAB,BETHESDA,MD 20892. RP Rosenberg, GA (reprint author), UNIV NEW MEXICO,SCH MED,DEPT NEUROBIOL & PHYSIOL,ALBUQUERQUE,NM 87131, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NINDS NIH HHS [R01 NS21169-08] NR 39 TC 204 Z9 211 U1 0 U2 2 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 12 PY 1995 VL 703 IS 1-2 BP 151 EP 155 DI 10.1016/0006-8993(95)01089-0 PG 5 WC Neurosciences SC Neurosciences & Neurology GA TL152 UT WOS:A1995TL15200018 PM 8719627 ER PT J AU Szallasi, A Nilsson, S FarkasSzallasi, T Blumberg, PM Hokfelt, T Lundberg, JM AF Szallasi, A Nilsson, S FarkasSzallasi, T Blumberg, PM Hokfelt, T Lundberg, JM TI Vanilloid (capsaicin) receptors in the rat: Distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment SO BRAIN RESEARCH LA English DT Article DE [H-3]resiniferatoxin autoradiography; vanilloid receptor; capsaicin-sensitive neuron; axonal transport; nodose ganglia; capsazepine ID INDUCED NEURONAL DEGENERATION; PRIMARY SENSORY NEURONS; URINARY-BLADDER; RESINIFERATOXIN; BINDING; ANALOG AB Vanilloid (capsaicin) receptors were visualized by [H-3]resiniferatoxin (RTX) autoradiography in the brain of newborn as well as adult (both control and colchicine-treated) rats. Specific labelling was seen in the brain stem only, in the nucleus of the solitary tract extending into the area postrema and the spinal sensory nucleus of the trigeminal nerve. Also, a strong signal was seen in the dorsal horn, dorsal root, trigeminal and nodose ganglia. Membranes obtained from the cervical, thoracic, and lumbar segments of the spinal cord showed similar affinities for RTX and likewise for capsaicin and capsazepine; maximal receptor density was similar in the cervical and thoracic segments (approximately 70 fmol/mg protein) but was twice as high in the lumbar segment. 24 h after ligation of the vagal or the sciatic nerves, a strong accumulation of specific RTX binding sites was observed mainly proximal to the ligature, implying intraaxonal receptor transport from the nodose and dorsal root ganglia, respectively, to the periphery. Systemic (s.c.) vanilloid treatment depleted specific [H-3]RTX binding sites from the brain stem, the sensory (dorsal root as well as trigeminal) ganglia, and the spinal cord. RTX was approximately 200-fold more potent than capsaicin for eliminating vanilloid receptors from the spinal cord. The present results suggest a discrete expression of vanilloid receptors in the brain stem (sensory nuclei); although intrinsic vanilloid receptor-expressing neurons are thought to exist in the rat brain, they remain undetected by the present [H-3]RTX autoradiography methodology. C1 KAROLINSKA INST,DEPT NEUROSCI,S-17177 STOCKHOLM,SWEDEN. NCI,BETHESDA,MD 20892. RP Szallasi, A (reprint author), KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,DIV PHARMACOL,S-17177 STOCKHOLM,SWEDEN. NR 41 TC 149 Z9 151 U1 0 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 12 PY 1995 VL 703 IS 1-2 BP 175 EP 183 DI 10.1016/0006-8993(95)01094-7 PG 9 WC Neurosciences SC Neurosciences & Neurology GA TL152 UT WOS:A1995TL15200021 PM 8719630 ER PT J AU Ohshima, T Murray, GJ Nagle, JW Quirk, JM Kraus, MH Barton, NW Brady, RO Kulkarni, AB AF Ohshima, T Murray, GJ Nagle, JW Quirk, JM Kraus, MH Barton, NW Brady, RO Kulkarni, AB TI Structural organization and expression of the mouse gene encoding alpha-galactosidase A SO GENE LA English DT Article DE recombinant genomic DNA; exon; intron; promoter; lysosomal enzyme; Fabry disease ID A-GENE; SEQUENCE; DNA; TRANSCRIPTION; EVOLUTION AB alpha-Galactosidase A (alpha-D-galactoside galactohydrolase, EC 3.2.1.22; alpha GalA) is a lysosomal enzyme that hydrolyses the alpha-D-galactosyl residues from glycosphingolipids. Fabry disease, an inherited X-linked recessive human metabolic disorder, results from a mutation in the alpha GalA gene at Xq22. As a prerequisite for generating a mouse model of Fabry disease by gene targeting, we have isolated and characterized the mouse alpha GalA gene and cDNA. A cloned mouse alpha GalA cDNA encoded a putative precursor protein of 419 amino acids (aa), including a 31-aa signal peptide (SP), The deduced aa sequence showed high homology (79%) with the human alpha GalA protein. Nucleotide sequence analysis of genomic clones revealed that the overall structure and organization of the gene was very similar to that of human alpha GalA. All exon-intron splice junctions conformed to the GT/AG consensus sequence. Comparison of genomic and cDNA sequences revealed the ocurrence of two putative polyadenylation signals whose alternative use results in the two mouse alpha GalA transcripts of 1.4 and 3.6 kb. The 5'-flanking region of mouse alpha GalA had no typical TATA box. Several putative promoter-associated elements including Sp1, AP1 and a potential cAMP-responsive element (CRE) were identified. Northern blot analysis revealed the widespread tissue distribution of mouse alpha GalA transcripts. Lower expression levels, however, were observed in some tissues, implying tissue-specific differences in alpha GalA promoter function. C1 NINCDS,MOUSE GENET & HUMAN DIS MODELS UNIT,BETHESDA,MD 20892. NINCDS,ENZYMOL & GENET SECT,BETHESDA,MD 20892. NINCDS,CLIN INVEST & THERAPEUT SECT,BETHESDA,MD 20892. NIH,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,NEUROGENET SECT,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. NR 19 TC 20 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 12 PY 1995 VL 166 IS 2 BP 277 EP 280 DI 10.1016/0378-1119(95)00592-7 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA TL600 UT WOS:A1995TL60000015 PM 8543175 ER PT J AU Chambers, C Cvekl, A Sax, CM Russell, P AF Chambers, C Cvekl, A Sax, CM Russell, P TI Sequence, initial functional analysis and protein-DNA binding sites of the mouse beta B2-crystallin-encoding gene SO GENE LA English DT Article DE gene expression; promoter; transcription factor; PAX-6 ID LENS EPITHELIAL-CELLS; CRYSTALLIN GENE; EYE LENS; EXPRESSION; ENHANCER AB An 800-bp fragment of genomic DNA upstream from the origin of transcription of the mouse beta B2-crystallin-encoding gene (beta B2-Cry) has been isolated and its nucleotide sequence determined. Promoter fragments 275 to + 30 or -110 to + 30, fused to cat reporter gene, activated transcription in transiently transfected rabbit lens epithelial cells, but not in various non-lens cells, The beta B2-Cry mouse promoter contains a typical TATA-box located approx. 25 bp upstream from the transcription start point. Binding sites (upstream from the TATA-box) for transcription factors possibly involved in the regulation of gene expression have been identified by DNaseI footprinting analysis and lens cell nuclear extracts. Most notably is the binding of the Pax-6 paired domain (PrD) which correlates with the binding of lens cell nuclear proteins at the -80 to -40 region. C1 NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. RI Cvekl, Ales/B-2427-2013 NR 20 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 12 PY 1995 VL 166 IS 2 BP 287 EP 292 DI 10.1016/0378-1119(95)00615-X PG 6 WC Genetics & Heredity SC Genetics & Heredity GA TL600 UT WOS:A1995TL60000017 PM 8543177 ER PT J AU Weghorst, CM Buzard, GS Calvert, RJ Hulla, JE Rice, JM AF Weghorst, CM Buzard, GS Calvert, RJ Hulla, JE Rice, JM TI Cloning and sequence of a processed p53 pseudogene from rat: A potential source of false 'mutations' in PCR fragments of tumor DNA SO GENE LA English DT Article DE F344; exon-based primer; cDNA-like; mutational hot spot; PCR co-amplification ID SUPPRESSOR GENE; EVOLUTION AB We describe here the nucleotide (nt) sequence of a p53 processed pseudogene (psi-gene) from the normal F344 rat genome. Exon-derived primers were utilized to amplify and clone a 1447-bp polymerase chain reaction (PCR) product corresponding to the coding regions of exons 2-11 of the functional gene, This psi-gene is a cDNA-like sequence possessing 87% homology with the functional rat p53. We have also partially characterized two additional and distinctly different putative rat p53 psi-genes, focussing on the sequences surrounding the reported rat p53 mutational hot spots of codons 202(R) and 211(R) within exon 6/7, Each of these three psi-gene sequences contained various single- and/or double-nt substitutions, small deletions and insertions that distinguish them from p53, One substitution, 211(R) CGG-->CAG, found both in the cloned psi-gene and in one of the partially characterized, putative psi-genes, corresponded precisely with the sequence that has been reported as a mutation at one of the hot spots. Co-amplification of one or more of the p53 psi-genes with portions of the functional p53 is likely, if exon-based primers are utilized for PCR amplification of rat p53. Consequently, psi-gene sequences are potential sources of sequence variations that can be misidentified as somatic cell mutations by direct sequencing of inappropriately generated PCR products. C1 NCI, COMPARAT CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. US FDA, OFF SPECIAL NUTR, LAUREL, MD 20708 USA. PACIFIC NW LAB, MOLEC BIOL SECT, RICHLAND, WA 99352 USA. NR 24 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 12 PY 1995 VL 166 IS 2 BP 317 EP 322 DI 10.1016/0378-1119(95)00629-X PG 6 WC Genetics & Heredity SC Genetics & Heredity GA TL600 UT WOS:A1995TL60000023 PM 8543183 ER PT J AU Gelernter, J Vandenbergh, D Kruger, SD Pauls, DL Kurlan, R Pakstis, AJ Kidd, KK Uhl, G AF Gelernter, J Vandenbergh, D Kruger, SD Pauls, DL Kurlan, R Pakstis, AJ Kidd, KK Uhl, G TI The dopamine transporter protein gene (SLC6A3): Primary linkage mapping and linkage studies in Tourette syndrome SO GENOMICS LA English DT Article ID RECEPTOR; EXCLUSION; PEDIGREE; DISPLAYS AB The dopamine transporter, the molecule responsible for presynaptic reuptake of dopamine and a major site of action of psychostimulant drugs, including cocaine, is encoded by locus SLC6A3 (alias DAT1), The protein's actions and DAT's specific localization to dopaminergic neurons make it a candidate gene for several psychiatric illnesses. Alleles at this locus have been reported to be associated with cocaine-induced paranoia and attention deficit disorder, SLC6A3 has been mapped to distal chromosome 5p, using physical methods. Our goal was to place SLC6A3 in the genetic linkage map and to test for linkage to Tourette syndrome. Genetic linkage methods were used to place SLC6A3 in the genetic linkage map. Four extended pedigrees (one of which overlaps with CEPH) were typed. Linkage with Tourette syndrome (TS) was also examined. SLC6A3 showed close linkage with several markers previously mapped to distal chromosome 5p, including D5S11 (Z(max) = 16.0, theta(M) = theta(F) = 0.03, results from four families) and D5S678 (Z(max) = 7.84, theta(M) = theta(F) = 0, results from two families). Observed crossovers established that SLC6A3 is a distal marker close to D5S10 and D5S678, but these three distal markers could not be ordered, Linkage between TS and SLC6A3 could be excluded independently in two branches of a large kindred segregating TS; the lod score in a third family was also negative, but not significant: Cumulative results show a lod score of -6.2 at theta = 0 and of -3.9 at theta = 0.05 (dominant model, narrow disease definition). SLC6A3 thus maps to distal chromosome 5p by linkage analysis, in agreement with previous physical mapping data. A mutation at SLC6A3 is not causative for TS in the two large families that generated significant negative lod scores (if the parameters of our analyses were correct) and is unlikely to be causative in the family that generated a negative lod score that did not reach significance. These results do not exclude a role for the dopamine transporter in influencing risk for TS in combination with other loci. (C) 1995 Academic Press, Inc. C1 YALE UNIV,SCH MED,DEPT PSYCHIAT,DIV MOLEC PSYCHIAT,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,CTR CHILD STUDY,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. UNIV ROCHESTER,SCH MED & DENT,DEPT NEUROL,ROCHESTER,NY 14627. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NIDA,DIV INTRAMURAL RES,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. RP Gelernter, J (reprint author), VET ADM MED CTR,950 CAMPBELL AVE,W HAVEN,CT 06516, USA. FU NIMH NIH HHS [MH00931, MH25642, MH30929] NR 23 TC 26 Z9 26 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC 10 PY 1995 VL 30 IS 3 BP 459 EP 463 DI 10.1006/geno.1995.1265 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TN858 UT WOS:A1995TN85800008 PM 8825631 ER PT J AU Dong, QH Shenker, A Way, J Haddad, BR Lin, KI Hughes, MR McBride, OW Spiegel, AM Battey, J AF Dong, QH Shenker, A Way, J Haddad, BR Lin, KI Hughes, MR McBride, OW Spiegel, AM Battey, J TI Molecular cloning of human g alpha(q) cDNA and chromosomal localization of the g alpha(q) gene (GNAQ) and a processed pseudogene SO GENOMICS LA English DT Article ID STIMULATORY G-PROTEIN; PHOSPHOLIPASE-C; ALPHA-SUBUNITS; SIGNAL TRANSDUCTION; HEREDITARY OSTEODYSTROPHY; MUTATIONS; MOUSE; CELLS; ACTIVATION; TUMORS AB G alpha(q) is the alpha subunit of one of the heterotrimeric GTP-binding proteins that mediates stimulation of phospholipase C beta. We report the isolation and characterization of cDNA clones from a frontal cortex cDNA library encoding human G alpha(q) The encoded protein is 359 amino acids long and is identical in all but one amino acid residue to mouse G alpha(q). Analysis of human genomic DNA reveals an intronless sequence with strong homology to human G alpha(q) cDNA. In comparison to G alpha(q) cDNA, this genomic DNA sequence includes several small deletions and insertions that alter the reading frame, multiple single base changes, and a premature termination codon in the open reading frame, hallmarks of a processed pseudogene, Probes derived from human G alpha(q) cDNA sequence map to both chromosomes 2 and 9 in high stringency genomic blot analyses of DNA from a panel of human-rodent hybrid cell Lines. PCR primers that selectively amplify the pseudogene sequence generate a product only when DNA containing human chromosome 2 is used as the template, indicating that the authentic G alpha(q) gene (GNAQ) is located on chromosome 9. Regional localization by FISH analysis places GNAQ at 9q21 and the pseudogene at 2q14.3-q21. C1 NCI,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NATL INST DEAFNESS & OTHER COMMUN DIS,BETHESDA,MD 20892. RP Dong, QH (reprint author), NIDDKD,METAB DIS BRANCH,BLDG 10,ROOM 8C101,10 CTR DR MSC 1752,BETHESDA,MD 20892, USA. NR 32 TC 22 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC 10 PY 1995 VL 30 IS 3 BP 470 EP 475 DI 10.1006/geno.1995.1267 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TN858 UT WOS:A1995TN85800010 PM 8825633 ER PT J AU Santoro, T Maguire, J McBride, OW Avraham, KB Copeland, NG Jenkins, NA Kelly, K AF Santoro, T Maguire, J McBride, OW Avraham, KB Copeland, NG Jenkins, NA Kelly, K TI Chromosomal organization and transcriptional regulation of human GEM and localization of the human and mouse GEM loci encoding an inducible ras-like protein SO GENOMICS LA English DT Article ID GENETIC-LINKAGE MAP; MUSCLE AB The mitogen-induced gene, GEM, encodes a GTP-binding protein that belongs to a new family within the Ras superfamily. The regulated expression pattern of Gem suggests a role for this protein in cellular responses to growth stimulation. To facilitate the assessment of the possible role of GEM in heritable and spontaneous disease processes, the genomic organization of human GEM and the chromosomal localization of human and murine GEM have been determined. GEM has been localized to the long arm of human chromosome 8 (8q13-q21) between the D8S85 and CA2 loci by genetic linkage analysis using an MspI restriction fragment length polymorphism within GEM. No consistent somatic chromosomal alterations or heritable diseases are associated with this region. Mouse Gem maps to the proximal region of chromosome 4 between Mos and Cga. To gain insight into the transcriptional regulation of GEM, we have established the transcription initiation site of GEM in human T cells and defined a 5' upstream region sufficient for mitogen-responsive, inducible transcription. (C) 1995 Academic Press, Inc. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NIGMS NIH HHS [GM15909-02] NR 20 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC 10 PY 1995 VL 30 IS 3 BP 558 EP 564 DI 10.1006/geno.1995.1277 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TN858 UT WOS:A1995TN85800020 PM 8825643 ER PT J AU Brodsky, G Otterson, GA Parry, BB Hart, I Patterson, D Kaye, FJ AF Brodsky, G Otterson, GA Parry, BB Hart, I Patterson, D Kaye, FJ TI Localization of STCH to human chromosome 21q11.1 SO GENOMICS LA English DT Article C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. RP Brodsky, G (reprint author), ELEANOR ROOSEVELT INST CANC RES,1899 GAYLORD ST,DENVER,CO 80206, USA. RI kaye, frederic/E-2437-2011 FU NCI NIH HHS [CA49981]; NICHD NIH HHS [HD17449] NR 7 TC 12 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC 10 PY 1995 VL 30 IS 3 BP 627 EP 628 DI 10.1006/geno.1995.1291 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TN858 UT WOS:A1995TN85800034 PM 8825657 ER PT J AU RAVUSSIN, E AF RAVUSSIN, E TI OBESITY IN BRITAIN - RISING TREND MAY BE DUE TO PATHOENVIRONMENT SO BRITISH MEDICAL JOURNAL LA English DT Letter RP RAVUSSIN, E (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 5 TC 13 Z9 13 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD DEC 9 PY 1995 VL 311 IS 7019 BP 1569 EP 1569 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TK214 UT WOS:A1995TK21400051 PM 8520412 ER PT J AU JOHREN, O VISWANATHAN, M SAAVEDRA, JM AF JOHREN, O VISWANATHAN, M SAAVEDRA, JM TI EXPRESSION OF NON-ANGIOTENSIN-II [I-125]CGP-42112 BINDING-SITES ON ACTIVATED MICROGLIA AFTER KAINIC-ACID-INDUCED NEURODEGENERATION SO BRAIN RESEARCH LA English DT Article DE AT(2) RECEPTOR; AUTORADIOGRAPHY; OX-42; ED1; IMMUNOHISTOCHEMISTRY; KAINIC ACID; GLIOSIS; HIPPOCAMPUS; ANGIOTENSIN ID RAT-BRAIN; RECEPTOR SUBTYPES; MONONUCLEAR PHAGOCYTES; HETEROGENEITY; HIPPOCAMPUS; MACROPHAGES; RESPONSES; CELLS; RNA; DEGENERATION AB [I-125]CGp 42112, first developed to identify angiotensin II receptor subtype 2 (AT(2)), was recently shown to bind to a novel non-angiotensin binding site in injured rat brain tissue. We addressed the question whether non-angiotensin [I-125]CGp 42112 binding appears after kainic acid induced hippocampal neurodegeneration, a process of neuronal cell death at a distance from the toxin injection site, After intraventricular kainic acid injection, we found non-angiotensin [I-125]]CGP 42112 binding in the hippocampal areas CA3 (4 and 14 days after injection), CA1 and CA4 and the subiculum (14 days after injection). In addition, 14 days after kainic acid injection, [I-125]CGp 42112 binding was found in 50% of the animals, in the thalamus, amygdala and piriform cortex, areas receiving projections from the hippocampus and suffering kainic acid induced delayed neurodegenaration. The loss of neurons in these regions was accompanied by an accumulation of activated microglia as demonstrated by immunostaining with the specific antibodies OX-42 and ED1. The time course and regional pattern of OX-42/ED1 positive immunostaining was identical with the appearance and distribution of the non-angiotensin [[I-125]CGP 42112 binding site. The non-angiotensin [I-125]CGP 42112 binding was not detected in brain regions unaffected by kainic acid injection. Our findings indicate the expression of a novel [I-125]CGP 42112 binding site on activated microglia. This site appears at a distance from the lesion and may be of importance in the process of neuronal death and brain tissue repair. RP JOHREN, O (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,ROOM 2D-45,10 CTR DR,MSC 1514,BETHESDA,MD 20892, USA. RI Johren, Olaf/G-6967-2011 NR 43 TC 11 Z9 11 U1 0 U2 0 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 8 PY 1995 VL 702 IS 1-2 BP 153 EP 161 DI 10.1016/0006-8993(95)01035-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA TJ908 UT WOS:A1995TJ90800019 PM 8846070 ER PT J AU MENENDEZARIAS, L WEBER, IT OROSZLAN, S AF MENENDEZARIAS, L WEBER, IT OROSZLAN, S TI MUTATIONAL ANALYSIS OF THE SUBSTRATE-BINDING POCKET OF MURINE LEUKEMIA-VIRUS PROTEASE AND COMPARISON WITH HUMAN-IMMUNODEFICIENCY-VIRUS PROTEASES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTALLOGRAPHIC STRUCTURE; ASPARTIC PROTEASE; ESCHERICHIA-COLI; HIV PROTEINASES; INHIBITORS; SITE AB The differences in substrate specificity between Moloney murine leukemia virus protease (MuLV PR) and human immunodeficiency virus (HIV) PR were investigated by site-directed mutagenesis. Various amino acids, which are predicted to form the substrate binding site of MuLV PR, were replaced by the equivalent ones in HIV-1 and HIV-2 PRs. The expressed mutants were assayed with the substrate Val-Ser-Gln-Asn-Tyr down arrow Pro-Ile-Val-Gln-NH2 (down arrow indicates the cleavage site) and a series of analogs containing single amino acid substitutions in positions P-4(Ser) to P-3'(Val). Mutations at the predicted S-2/S-2,' subsites of MuLV PR have a strong influence on the substrate specificity of this enzyme, as observed with mutants H37D, V39I, V54I, A57I, and L92I. On the other hand, substitutions at the flap region of MuLV PR often rendered enzymes with low activity (e,g, W53I/Q55G). Three amino acids (His-37, Val-39, and Ala-57) were identified as the major determinants of the differences in substrate specificity between MuLV and HIV PRs. C1 THOMAS JEFFERSON UNIV, JEFFERSON CANC INST, DEPT PHARMACOL, PHILADELPHIA, PA 19107 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOLEC VIROL & CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. RP MENENDEZARIAS, L (reprint author), UNIV AUTONOMA MADRID, CSIC, CTR BIOL MOLEC SEVERO OCHOA, E-28049 CANTO BLANCO, SPAIN. RI Menendez Arias, Luis /G-2436-2016; Menendez Arias, Luis/N-7447-2016 OI Menendez Arias, Luis/0000-0002-1251-6640 FU NCI NIH HHS [CA58166, N01-CO-74101] NR 37 TC 16 Z9 16 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 1995 VL 270 IS 49 BP 29162 EP 29168 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ227 UT WOS:A1995TJ22700023 PM 7493942 ER PT J AU HERNANDEZSANCHEZ, C BLAKESLEY, V KALEBIC, T HELMAN, L LEROITH, D AF HERNANDEZSANCHEZ, C BLAKESLEY, V KALEBIC, T HELMAN, L LEROITH, D TI THE ROLE OF THE TYROSINE KINASE DOMAIN OF THE INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR IN INTRACELLULAR SIGNALING, CELLULAR PROLIFERATION AND TUMORIGENESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3'-KINASE; PHOSPHORYLATION SITES; BINDING-SITE; IRS-1; AUTOPHOSPHORYLATION; TRANSDUCTION; CELLS; SUBSTRATE-1; PROTEIN; SPECIFICITY AB Insulin and insulin-like growth factor (IGF-I) receptors are heterotetrameric proteins consisting of two alpha- and two beta-subunits and members of the transmembrane tyrosine kinase receptors. Specific ligand binding to the receptor triggers a cascade of intracellular events, which begins with autophosphorylation of several tyrosine residues of the beta-subunit of the receptor. The triple cluster in the tyrosine kinase domain of the beta-subunit is the earliest and major autophosphorylation site. Previous studies have shown that substitutions of these three tyrosines by phenylalanines of both insulin and IGF-I receptors practically abolish any activation of cellular signaling pathways. We have studied the effect of double tyrosine mutations on IGF-I-induced receptor autophosphorylation, activation of Shc and IRS-1 pathways, and cell proliferation and tumorigenicity. Substitution of tyrosines 1131/1135 blocks any detectable autophosphorylation, whereas substitution of tyrosines 1131/1136 or 1135/1136 only reduces autophosphorylation levels in some clones by similar to 50%. Nevertheless, all the cells expressing IGF-I receptors with double tyrosine substitutions demonstrated markedly reduced signaling through Shc and IRS-1 pathways. In addition, they were unable to respond to IGF-I-stimulated cell growth in culture, and tumor formation in nude mice was abrogated. These data suggest that the presence of tyrosine 1131 or 1135 essential for receptor autophosphorylation, whereas the presence of each of these tyrosines is necessary for a fully functional receptor. C1 NIDDK,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,MOLEC ONCOL SECT,BETHESDA,MD 20892. RI Hernandez Sanchez, Catalina/N-1737-2014 OI Hernandez Sanchez, Catalina/0000-0002-0846-5019 NR 48 TC 65 Z9 65 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 1995 VL 270 IS 49 BP 29176 EP 29181 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ227 UT WOS:A1995TJ22700025 PM 7493944 ER PT J AU LUJAN, HD MOWATT, MR CONRAD, JT BOWERS, B NASH, TE AF LUJAN, HD MOWATT, MR CONRAD, JT BOWERS, B NASH, TE TI IDENTIFICATION OF A NOVEL GIARDIA-LAMBLIA CYST WALL PROTEIN WITH LEUCINE-RICH REPEATS - IMPLICATIONS FOR SECRETORY GRANULE FORMATION AND PREOTEIN ASSEMBLY INTO THE CYST WALL SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY; ANTIGENS; MURIS; GALACTOSAMINE; LOCALIZATION; CARBOHYDRATE; INHIBITOR; PATHWAY; INVITRO; KINASE AB Giardia lamblia trophozoites, like most intestinal parasitic protozoa, undergo fundamental biological changes to survive outside the intestine of their mammalian host by differentiating into infective cysts. This complex process entails the coordinated production, processing, and transport of cyst wall constituents for assembly into a protective cyst wall. Yet, little is known about this process and the identity of cyst wall constituents. We previously identified a 26-kDa cyst wall protein, CWP1. In the present work, using monoclonal antibodies to cyst wall antigens, we cloned the gene that encodes a novel 39-kDa cyst wall protein, CWP2. Expression of CWP1 and CWP2 was induced during encystation with identical kinetics. Soon after synthesis, these two proteins combine to form a stable complex, which is concentrated within the encystation-specific secretory granules before incorporation into the cyst wall. Both proteins contain five tandem copies of a 24-residue leucine-rich repeat, a motif implicated in protein-protein interactions. Unlike CWP1, CWP2 has an extremely basic 121-residue COOH-terminal extension that might be involved in the sorting of these proteins to the secretory granules. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. RP LUJAN, HD (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,RM 126,,BETHESDA,MD 20892, USA. NR 61 TC 147 Z9 148 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 1995 VL 270 IS 49 BP 29307 EP 29313 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ227 UT WOS:A1995TJ22700044 PM 7493963 ER PT J AU COSS, MC WINTERSTEIN, D SOWDER, RC SIMEK, SL AF COSS, MC WINTERSTEIN, D SOWDER, RC SIMEK, SL TI MOLECULAR-CLONING, DNA-SEQUENCE ANALYSIS, AND BIOCHEMICAL-CHARACTERIZATION OF A NOVEL 65-KDA FK506-BINDING PROTEIN (FKBP65) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEROID-RECEPTOR COMPLEXES; RAPAMYCIN-BINDING-PROTEIN; CIS-TRANS ISOMERASE; HEAT-SHOCK PROTEIN; CYCLOSPORINE-A; LYMPHOCYTES-T; IMMUNOSUPPRESSANT FK506; SIGNAL TRANSDUCTION; FK-506; IMMUNOPHILIN AB We have identified a mouse gene encoding a 65-kDa protein (FKBP65) that shares homology with members of the FK506-binding protein (FKBP) class of immunophilins. Predicted amino acid sequence shows that this protein shares significant homology with FKBP12 (46%), FKBP13 (43%), FKBP25 (35%), and FKBP52 (26%). FKBP65 contains four predicted peptidylprolyl cis-trans-isomerase (PPIase) signature domains, and, although similar in size, is distinct from FKBP52 (also identified as FKBP59, hsp56, or HBI), which contains three FKBP12-like PPIase domains. With N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as the substrate, recombinant FKBP65 is shown to accelerate the isomerization of the prolyl peptide bond with a catalytic efficiency similar to other family members. This isomerization activity is inhibited by FK506 and rapamycin, but is not sensitive to Cyclosporin A. Based on Northern blot analysis, FKBP65 mRNA transcripts are present in lung, spleen, heart, brain, and testis. A polyclonal antibody, raised against a COOH-terminal peptide (amino acid residues 566-581), was used to immunoprecipitate FKBP65 from NIH3T3 cells and demonstrate that FKBP65 is a glycoprotein. in addition, [P-32]orthophosphate labeling experiments show that FKBP65 is also a phosphoprotein. These results suggest that FKBP65 is a new FKBP family member. C1 NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 41 TC 53 Z9 55 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 1995 VL 270 IS 49 BP 29336 EP 29341 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ227 UT WOS:A1995TJ22700048 PM 7493967 ER PT J AU GROSSMANN, M SZKUDLINSKI, MW TROPEA, JE BISHOP, LA THOTAKURA, NR SCHOFIELD, PR WEINTRAUB, BD AF GROSSMANN, M SZKUDLINSKI, MW TROPEA, JE BISHOP, LA THOTAKURA, NR SCHOFIELD, PR WEINTRAUB, BD TI EXPRESSION OF HUMAN THYROTROPIN IN CELL-LINES WITH DIFFERENT GLYCOSYLATION PATTERNS COMBINED WITH MUTAGENESIS OF SPECIFIC GLYCOSYLATION SITES - CHARACTERIZATION OF A NOVEL ROLE FOR THE OLIGOSACCHARIDES IN THE IN-VITRO AND IN-VIVO BIOACTIVITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; ASPARAGINE-LINKED OLIGOSACCHARIDES; FRTL-5 THYROID-CELLS; HAMSTER OVARY CELLS; HUMAN TSH RECEPTORS; GLYCOPROTEIN HORMONES; ALPHA-SUBUNIT; SIALYLATED OLIGOSACCHARIDES; CARBOHYDRATE MOIETY; STIMULATING-HORMONE AB We used a novel approach to study the role of the Asn-linked oligosaccharides for human thyrotropin (hTSH) activity. Mutagenesis of Asn (N) within individual glycosylation recognition sequences to Gln (Q) was combined with expression of wild type and mutant hTSH in cell Lines with different glycosylation patterns. The in vitro activity of hTSH lacking the Asn(alpha 52) oligosaccharide (alpha Q52/TSH beta) expressed in CHO-K1 cells (sialylated oligosaccharides) was increased 6-fold compared with wild type, whereas the activities of alpha Q78/TSH beta and alpha/TSH beta Q23 were increased 2-3-fold. Deletion of the Asn(alpha 52) oligosaccharide also increased the thyrotropic activity of human chorionic gonadotropin, in contrast to previous findings at its native receptor. The in vitro activity of wild type hTSH expressed in CHO-LEC2 cells (sialic acid-deficient oligosaccharides), CHO-LEC1 cells (Man(5)GlcNAc(2) intermediates), and 293 cells (sulfated oligosaccharides) was 5-8-fold higher than of wild type from CHO-K1 cells. In contrast to CHO-K1 cells, there was no difference in the activity between wild type and selectively deglycosylated mutants expressed in these cell lines. Thus, in hTSH, the oligosaccharide at Asn(alpha 52) and, specifically, its terminal sialic acid residues attenuate in vitro activity, in contrast to the previously reported stimulatory role of this chain for human chorionic gonadotropin and human follitropin activity. The increased thyrotropic activity of alpha Q52/CG beta suggests that receptor-related mechanisms may be responsible for these differences among the glycoprotein hormones. Despite their increased in vitro activity, alpha Q52/TSH beta, and alpha Q78/TSH beta from CHO-K1 cells had a faster serum disappearance rate and decreased effect on T-4 production in mice. These findings highlight the importance of individual oligosaccharides in maintaining circulatory half-life and hence in vivo activity of hTSH. C1 GARVAN INST MED RES,SYDNEY,NSW 2010,AUSTRALIA. RP GROSSMANN, M (reprint author), NIDDK,MOLEC & CELLULAR ENDOCRINOL LAB,BLDG 10,ROOM 8D14,BETHESDA,MD 20892, USA. RI Schofield, Peter/C-9669-2011 OI Schofield, Peter/0000-0003-2967-9662 NR 47 TC 44 Z9 44 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 1995 VL 270 IS 49 BP 29378 EP 29385 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ227 UT WOS:A1995TJ22700054 PM 7493973 ER PT J AU RUSSO, T ZAMBRANO, N ESPOSITO, F AMMENDOLA, R CIMINO, F FISCELLA, M JACKMAN, J OCONNOR, PM ANDERSON, CW APPELLA, E AF RUSSO, T ZAMBRANO, N ESPOSITO, F AMMENDOLA, R CIMINO, F FISCELLA, M JACKMAN, J OCONNOR, PM ANDERSON, CW APPELLA, E TI A P53-INDEPENDENT PATHWAY FOR ACTIVATION OF WAF1/CIP1 EXPRESSION FOLLOWING OXIDATIVE STRESS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WILD-TYPE P53; PROTEIN KINASE-C; IONIZING-RADIATION; TRANSCRIPTION FACTOR; GENE; DNA; BINDING; GROWTH; CELLS; WILD-TYPE-P53 AB Incubating human cells in diethylmaleate (DEM) depletes the intracellular pool of reduced glutathione (GSH) and increases the concentration of oxidative free radicals. We found that DEM-induced oxidative stress reduced the ability of p53 to bind its consensus recognition sequence and to activate transcription of a p53-specific reporter gene. Nevertheless, DEM treatment induced expression of WAF1/CIP1 but not GADD45 mRNA. The fact that N-acetylcysteine, a precursor of GSH that blocks oxidative stress, prevented WAF1/CIP1 induction by DEM suggests that WAF1/CIP1 induction probably was a consequence of the ability of DEM to reduce intracellular GSH levels. DEM induced WAF1/CIP1 expression in Saos-2 and T98G cells, both of which lack functional p53 protein. DEM treatment did not produce an increase in membrane-associated protein kinase C, but ERK2, a mitogen-activated protein kinase, was phosphorylated in a manner consistent with ERK2 activation. DEM treatment also produced a dose-dependent delay in cell cycle progression, which at low concentrations (0.25 mM) consisted of a G(2)/M arrest and at higher concentrations (1 mM) also involved G(1) and S phase delays. Our results indicate that oxidative stress induces WAF1/CIP1 expression and arrests cell cycle progression through a mechanism that is independent of p53. This mechanism may provide for cell cycle checkpoint control under conditions that inactivate p53. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. UNIV NAPLES FEDERICO II,DIPARTIMENTO BIOCHIM & BIOTECNOL MED,I-80131 NAPLES,ITALY. GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20007. NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. RI Zambrano, Nicola/B-9352-2014; Russo, Tommaso/K-1331-2016; Esposito, Franca/K-2024-2016 OI Zambrano, Nicola/0000-0001-9395-3481; Russo, Tommaso/0000-0003-4426-0106; Esposito, Franca/0000-0001-9340-6875 NR 59 TC 212 Z9 217 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 1995 VL 270 IS 49 BP 29386 EP 29391 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ227 UT WOS:A1995TJ22700055 PM 7493974 ER PT J AU BAE, HW GEISER, AG KIM, DH CHUNG, MT BURMESTER, JK SPORN, MB ROBERTS, AB KIM, SJ AF BAE, HW GEISER, AG KIM, DH CHUNG, MT BURMESTER, JK SPORN, MB ROBERTS, AB KIM, SJ TI CHARACTERIZATION OF THE PROMOTER REGION OF THE HUMAN TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE THREONINE KINASE; SMOOTH-MUSCLE CELLS; EXPRESSION CLONING; FACTOR-BETA-1; PROTEOGLYCAN; INHIBITION; ACTIVIN; COMPLEX; FAMILY AB Diminished cellular responsiveness to transforming growth factor-beta (TGF-beta) is frequently correlated with decreased transcription of the type II receptor for TGF-beta (TGF-beta RII). We have cloned and characterized the human TGF-beta RII promoter and, using S1 nuclease mapping and 5' rapid amplification of cDNA ends polymerase chain reaction, have identified five alternative transcription start sites within the region -33 to +57. DNA transfection experiments and electrophoretic mobility shift assays have revealed the existence of five distinct regulatory regions including two positive regulatory elements and two negative regulatory elements in addition to the core promoter region. The first positive regulatory element (-219 to -172) interacts with two distinct nuclear protein complexes, at least one of which appears to be a previously unidentified transcription factor. The second positive regulatory element (+1 to +35) also interacts with two separate protein complexes, both of which appear to be novel transcription factors. Deletion of either positive regulatory element markedly decreased expression of the target gene, suggesting that both positive regulatory elements are necessary for basal expression levels of TGF-beta RII. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 34 TC 114 Z9 114 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 1995 VL 270 IS 49 BP 29460 EP 29468 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ227 UT WOS:A1995TJ22700066 PM 7493985 ER PT J AU ZHOU, LM HE, XS LI, GY DECOSTA, BR SKOLNICK, P AF ZHOU, LM HE, XS LI, GY DECOSTA, BR SKOLNICK, P TI SYNTHESIS OF N,N'-SUBSTITUTED PIPERAZINE AND HOMOPIPERAZINE DERIVATIVES WITH POLYAMINE-LIKE ACTIONS AT N-METHYL-D-ASPARTATE RECEPTORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID INHIBITOR ALPHA-DIFLUOROMETHYLORNITHINE; RECOGNITION SITE; HIPPOCAMPAL-NEURONS; MK-801 BINDING; NMDA RECEPTOR; ANTAGONIST; COMPLEX; GLYCINE; CHANNEL; ACID AB A series of N,N'-substituted piperazine and homopiperazine derivatives have been synthesized with the objective of producing compounds that interact with polyamine modulatory sites on N-methyl-D-aspartate (NMDA) receptors. These novel compounds exhibited polyamine-like actions, enhancing [H-3]MK-801 binding to NMDA receptors in rat forebrain membranes. The potencies of N,N'-bis(2-aminoacetyl)homopiperazine (15), N,N'-bis(N-methyl-4-aminobutyl)piperazine (7), and N,N'-bis(3-aminopropyl)homopiperazine (11) (EC(50) 18.0, 21.3, and 24.4 mu M, respectively) to enhance [H-3]MK-801 binding were comparable to that of spermine (EC(50) 5.2 mu M). However, the efficacies of 15, 7, and 11 in this measure were lower (by similar to 40%, 32%, and 24%, respectively) than spermine, which may be indicative of partial agonist actions. Like spermine, the ability of these piperazine and homopiperazine derivatives to enhance [H-3]MK-801 binding could be inhibited by both a competitive polyamine antagonist (arcaine) and a specific, noncompetitive polyamine antagonist (conantokin-G). However, unlike endogenous polyamines; high concentrations (up to 1 mM) of these novel polyamine-like compounds did not inhibit [H-3]MK-801 binding. N,N'-Aminoalkylated and aminoacylated piperazine and homopiperazine derivatives may prove useful for studying polyamine recognition sites associated with NMDA receptors. C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 36 TC 12 Z9 12 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 8 PY 1995 VL 38 IS 25 BP 4891 EP 4896 DI 10.1021/jm00025a006 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TJ646 UT WOS:A1995TJ64600006 PM 8523402 ER PT J AU Mizuta, K Iwasa, KH Simonds, WF Tachibana, M AF Mizuta, K Iwasa, KH Simonds, WF Tachibana, M TI Ultrastructural localization of G-protein G(s) in the organ of Corti SO NEUROSCIENCE LETTERS LA English DT Article DE the organ of Corti; G-protein, G(s); immunogold method ID GUINEA-PIG COCHLEA; OUTER HAIR-CELLS; INNER-EAR; ADENYLATE-CYCLASE; IDENTIFICATION; INHIBITION AB Immunocytochemical localization of a stimulatory GTP-binding protein G(s) in the organ of Corti in the inner ear was examined with a post-embedding immunogold technique, using antibodies raised against a synthetic decapeptide (RIMHLRQYELL) of the C-terminus of the a subunit of G(s). Immunoreactivity was strong on the membranes of supporting cells in the reticular lamina, including inner and outer pillar cells and the phalangeal process of Deiters' cells. Immunolabeling also was seen on the membranes of cell bodies of those cells which surround nerve fibers, basilar fibers, outer spiral fibers and afferent nerve endings at outer hair cells. Gold particles also labeled the membrane of inner phalangeal cells and border cells. In contrast, outer and inner hair cells were not labeled. Possible roles of G(s) in the organ of Corti are discussed. C1 NIDOCD,MOLEC GENET LAB,ROCKVILLE,MD 20850. NIDOCD,CELLULAR BIOL LAB,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. OI Iwasa, Kuni/0000-0002-9397-7704 NR 18 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 8 PY 1995 VL 201 IS 2 BP 147 EP 150 DI 10.1016/0304-3940(95)12149-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA TK809 UT WOS:A1995TK80900013 PM 8848239 ER PT J AU COON, SL ROSEBOOM, PH BALER, R WELLER, JL NAMBOODIRI, MAA KOONIN, EV KLEIN, DC AF COON, SL ROSEBOOM, PH BALER, R WELLER, JL NAMBOODIRI, MAA KOONIN, EV KLEIN, DC TI PINEAL SEROTONIN N-ACETYLTRANSFERASE - EXPRESSION CLONING AND MOLECULAR ANALYSIS SO SCIENCE LA English DT Article ID RAT PINEAL; GLAND; MELATONIN; DECREASE AB Pineal serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, or AA-NAT) generates the large circadian rhythm in melatonin, the hormone that coordinates daily and seasonal physiology in some mammals. Complementary DNA encoding ovine AA-NAT was cloned. The abundance of AA-NAT messenger RNA (mRNA) during the day was high in the ovine pineal gland and somewhat lower in retina. AA-NAT mRNA was found unexpectedly in the pituitary gland and in some brain regions. The night-to-day ratio of ovine pineal AA-NAT mRNA is less than 2. In contrast, the ratio exceeds 150 in rats. AA-NAT represents a family within a large superfamily of acetyltransferases. C1 NICHHD, DEV NEUROBIOL LAB, NEUROBIOL SECT, BETHESDA, MD 20892 USA. GEORGETOWN UNIV, DEPT BIOL, WASHINGTON, DC 20057 USA. NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. NR 37 TC 271 Z9 278 U1 0 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 8 PY 1995 VL 270 IS 5242 BP 1681 EP 1683 DI 10.1126/science.270.5242.1681 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ293 UT WOS:A1995TJ29300053 PM 7502081 ER PT J AU POTTER, M MOCK, B AF POTTER, M MOCK, B TI MOUSE GENETICS - CONCEPTS AND APPLICATIONS - SILVER,LM SO SCIENCE LA English DT Book Review RP POTTER, M (reprint author), NCI,GENET LAB,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 4 U2 8 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 8 PY 1995 VL 270 IS 5242 BP 1692 EP 1693 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ293 UT WOS:A1995TJ29300057 ER PT J AU Viviano, CJ Bakewell, WE Dixon, D Dethloff, LA Hook, GER AF Viviano, CJ Bakewell, WE Dixon, D Dethloff, LA Hook, GER TI Altered regulation of surfactant phospholipid and protein A during acute pulmonary inflammation SO BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM LA English DT Article DE surfactant; inflammation; lavage; silica; activation ID TUMOR-NECROSIS-FACTOR; SILICA-TREATED RATS; INDUCED LUNG INJURY; II CELLS; LAVAGE FLUID; SP-A; BRONCHOALVEOLAR LAVAGE; ALVEOLAR MACROPHAGES; COLLAGEN-METABOLISM; QUARTZ AB Biochemical changes in the pulmonary surfactant system caused by exposure to toxicants are often accompanied by an influx of inflammatory cells into the lungs. We have investigated the possibility that the inflammatory and surfactant biochemical effects might be connected. Go-treatment with dexamethasone, a synthetic anti-inflammatory glucocorticoid, mitigated the increases in free cells and total intracellular surfactant phospholipid normally seen in animals given silica alone, suggesting a relationship between the free cell population of the alveoli and the surfactant system during alveolitis. Furthermore, we have investigated whether induction of the surfactant system is a universal response to alveolar inflammation. Inflammation was induced in the lungs by intratracheal injections of titanium dioxide, silica, bleomycin or lipopolysaccharide (LPS) suspended in isotonic saline. Inflammatory cell and surfactant responses were measured at 3 days and 14 days following injection. There was a distinct alveolar inflammatory cell profile following administration of each agent, at each time point, indicating a dynamic inflammatory cell population during the course of the study. Furthermore, surfactant phospholipid and protein A (SP-A) pools exhibited unique responses to the inflammatory agents. Only silica-treated lungs maintained elevated levels of surfactant phospholipids and SP-A throughout the course of the experiment. We conclude that both the surfactant components and the inflammatory cell population of the alveoli undergo dynamic changes following treatment with these inflammatory agents and that activation of the surfactant system is not a universal response to alveolar inflammation, since surfactant components were not always elevated during times of increased alveolar cellularity. The unique inflammatory cell infiltrate elicited by silica is of particular interest in that surfactant components were elevated throughout the course of the experiment in this group. Indeed, we have shown that the size of the intracellular pool of surfactant Is directly proportional to the number of polymorphonuclear leukocytes but not alveolar macrophages or lymphocytes in the alveoli following silica treatment. Finally, our data suggest that the phospholipid and SP-A components of surfactant respond differentially to the pulmonary toxicants in this study. C1 NIEHS,LAB EXPTL LAB,RES TRIANGLE PK,NC 27709. NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. RP Viviano, CJ (reprint author), UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599, USA. FU NIEHS NIH HHS [ES-07126-07, ES-07126-08] NR 47 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2760 J9 BBA-LIPID LIPID MET JI Biochim. Biophys. Acta-Lipids Lipid Metab. PD DEC 7 PY 1995 VL 1259 IS 3 BP 235 EP 244 DI 10.1016/0005-2760(95)00167-0 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TM246 UT WOS:A1995TM24600006 PM 8541330 ER PT J AU FAUCI, AS AF FAUCI, AS TI HIV - AN ELUSIVE SOLUBLE SUPPRESSOR SO NATURE LA English DT Editorial Material ID VIRUS-REPLICATION; INFECTION RP FAUCI, AS (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 8 TC 7 Z9 7 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD DEC 7 PY 1995 VL 378 IS 6557 BP 561 EP 561 DI 10.1038/378561a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ221 UT WOS:A1995TJ22100052 PM 8524384 ER PT J AU UNGEWICKELL, E UNGEWICKELL, H HOLSTEIN, SEH LINDNER, R PRASAD, K BAROUCH, W MARTIN, B GREENE, LE EISENBERG, E AF UNGEWICKELL, E UNGEWICKELL, H HOLSTEIN, SEH LINDNER, R PRASAD, K BAROUCH, W MARTIN, B GREENE, LE EISENBERG, E TI ROLE OF AUXILIN IN UNCOATING CLATHRIN-COATED VESICLES SO NATURE LA English DT Article ID ESCHERICHIA-COLI DNAJ; HEAT-SHOCK PROTEINS; BOVINE BRAIN; ATPASE; BINDING; DISSOCIATION; HYDROLYSIS; HOMOLOGS; BASKETS; DOMAIN AB CLATHRIN-coated vesicles transport selected integral membrane proteins from the cell surface and the a trans-Golgi network to the endosomal system(1,2). Before fusing with their target the vesicles must be stripped of their coats, This process is effected by the chaperone protein hsp70c together with a 100K cofactor(3) which we here identify as the coat protein auxilin. Auxilin binds with high affinity to assembled clathrin lattices and, in the presence of ATP, recruits hsp70c. Dissociation of the lattice does not depend as previously supposed on clathrin light chains or on the aminoterminal domain of the heavy chain4,5. The presence of a J-domain at its carboxy terminus now defines auxilin as a member of the DnaJ protein family. In conjunction with hsp70, DnaJ proteins catalyse protein folding, protein transport across membranes and the selective disruption of protein-protein interactions(6-8). We show that deletion of the J-domain of auxilin results in the loss of cofactor activity. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP UNGEWICKELL, E (reprint author), WASHINGTON UNIV,SCH MED,CTR IMMUNOL,660 S EUCLID AVE,ST LOUIS,MO 63110, USA. NR 30 TC 333 Z9 336 U1 5 U2 15 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD DEC 7 PY 1995 VL 378 IS 6557 BP 632 EP 635 DI 10.1038/378632a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ221 UT WOS:A1995TJ22100082 PM 8524399 ER PT J AU WILCOX, AJ WEINBERG, CR BAIRD, DD AF WILCOX, AJ WEINBERG, CR BAIRD, DD TI TIMING OF SEXUAL INTERCOURSE IN RELATION TO OVULATION - EFFECTS ON THE PROBABILITY OF CONCEPTION, SURVIVAL OF THE PREGNANCY, AND SEX OF THE BABY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID URINARY ESTROGEN; NORMAL MEN; TEMPERATURE; SPERMATOZOA; SPERM AB Background. The timing of sexual intercourse in relation to ovulation strongly influences the chance of conception, although the actual number of fertile days in a woman's menstrual cycle is uncertain. The timing of intercourse may also be associated with the sex of the baby. Methods. We recruited 221 healthy women who were planning to become pregnant. At the same time the women stopped using birth-control methods, they began collecting daily urine specimens and keeping daily records of whether they had sexual intercourse. We measured estrogen and progesterone metabolites in urine to estimate the day of ovulation. Results. In a total of 625 menstrual cycles for which the dates of ovulation could be estimated, 192 pregnancies were initiated, as indicated by increases in the urinary concentration of human chorionic gonadotropin around the expected time of implantation. Two thirds (n=129) ended in live births. Conception occurred only when intercourse took place during a six-day period that ended on the estimated day of ovulation. The probability of conception ranged from 0.10 when intercourse occurred five days before ovulation to 0.33 when it occurred on the day of ovulation itself. There was no evident relation between the age of sperm and the viability of the conceptus, although only 6 percent of the pregnancies could be firmly attributed to sperm that were three or more days old. Cycles producing male and female babies had similar patterns of intercourse in relation to ovulation. Conclusions. Among healthy women trying to conceive, nearly all pregnancies can be attributed to intercourse during a six-day period ending on the day of ovulation. For practical purposes, the timing of sexual intercourse in relation to ovulation has no influence on the sex of the baby. C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. RP WILCOX, AJ (reprint author), NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 34 TC 538 Z9 548 U1 5 U2 36 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 7 PY 1995 VL 333 IS 23 BP 1517 EP 1521 DI 10.1056/NEJM199512073332301 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA TH157 UT WOS:A1995TH15700001 PM 7477165 ER PT J AU GLOTH, FM GUNDBERG, CM HOLLIS, BW HADDAD, JG TOBIN, JD AF GLOTH, FM GUNDBERG, CM HOLLIS, BW HADDAD, JG TOBIN, JD TI VITAMIN-D DEFICIENCY IN HOMEBOUND ELDERLY PERSONS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID POSTMENOPAUSAL WOMEN; POPULATION; SERUM; OSTEOCALCIN; CALCIUM AB Objective.-To assess the vitamin D status in homebound, community-dwelling elderly persons; sunlight-deprived elderly nursing home residents; and healthy, ambulatory elderly persons. Design.-A cohort analytic study. Participants.-Of 244 subjects at least 65 years old, 116 subjects (85 women and 31 men) had been confined indoors for at least 6 months, either in private dwellings in the community (the Hopkins Elder Housecall Program) or in a teaching nursing home (The Johns Hopkins Geriatrics Center). The 128 control subjects, a healthy ambulatory group, came from the Baltimore Longitudinal Study on Aging. All subjects were free of diseases or medications that might interfere with their vitamin D status. Main Outcome measures.-Serum levels of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-[OH]D-2) were measured in all subjects. In a subgroup of 80 subjects, serum levels of intact parathyroid hormone (PTH), ionized calcium, and osteocalcin and intake of vitamin D (through 3-day food records) were assessed. A randomly selected cohort of sunlight-deprived subjects also had serum levels of vitamin D binding protein measured. Results.-In sunlight-deprived subjects overall, the mean 25-OHD level was 30 nmol/L (12 ng/mL) (range, <10 to 77 nmol/L [<4 to 31 ng/mL]) and the mean 1,25(OH)(2)D level was 52 pmol/L (20 pg/mL) (range, 18 to 122 pmol/L [7 to 47 pg/mL]). In the sunlight-deprived subjects, 54% of community dwellers and 38% of nursing home residents had serum levels of 25-OHD below 25 nmol/L (10 ng/mL) (normal range, 25 to 137 nmol/L [10 to 55 ng/mL]). A significant inverse relationship existed between 25-OHD (ie, Log [25-OHD]) and PTH when they were analyzed together (r=-0.42; R(2)=0.18; P<.001) and for each cohort separately. All other parameters measured, except ionized calcium, differed significantly from the Baltimore Longitudinal Study Group means. The mean (SD) daily intakes of vitamin D (121 [132] IU) and calcium (583 [322] mg) were below the recommended dietary allowance only in the community-dwelling homebound population. The mean vitamin D binding protein level in the sunlight-deprived subgroup was in the normal range. Conclusions.-Despite a relatively high degree of vitamin supplementation in the United States, homebound elderly persons are likely to suffer from vitamin D deficiency. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21205. JOHNS HOPKINS BAYVIEW MED CTR,BALTIMORE,MD. YALE UNIV,SCH MED,DEPT ORTHOPED,NEW HAVEN,CT. MED UNIV S CAROLINA,CHILDRENS HOSP,DEPT PEDIAT,CHARLESTON,SC 29425. UNIV PENN,DIV ENDOCRINOL,PHILADELPHIA,PA 19104. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP GLOTH, FM (reprint author), UNION MEM HOSP,DEPT MED,DIV GERIATR,201 E UNIV PKWY,BALTIMORE,MD 21218, USA. FU NCRR NIH HHS [MO1 RR02719]; NIA NIH HHS [5 T32 AG00120-03]; NIAMS NIH HHS [AR 38460] NR 26 TC 315 Z9 324 U1 4 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 6 PY 1995 VL 274 IS 21 BP 1683 EP 1686 DI 10.1001/jama.274.21.1683 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA TH151 UT WOS:A1995TH15100024 PM 7474272 ER PT J AU SLEE, DH LASLO, KL ELDER, JH OLLMANN, IR GUSTCHINA, A KERVINEN, J ZDANOV, A WLODAWER, A WONG, CH AF SLEE, DH LASLO, KL ELDER, JH OLLMANN, IR GUSTCHINA, A KERVINEN, J ZDANOV, A WLODAWER, A WONG, CH TI SELECTIVITY IN THE INHIBITION OF HIV AND FIV PROTEASE - INHIBITORY AND MECHANISTIC STUDIES OF PYRROLIDINE-CONTAINING ALPHA-KETO AMIDE AND HYDROXYETHYLAMINE CORE STRUCTURES SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID FELINE IMMUNODEFICIENCY VIRUS; PROTECTED AMINO-ACIDS; ESTER DERIVATIVES; RNA-POLYMERASE; PEPTIDES; CATS; PROTEINASES; EXPRESSION; INFECTION; DIKETONE AB This paper describes the development of new pyrrolidine-containing alpha-keto amide and hydroxyethylamine core structures as mechanism based inhibitors of the HIV and FIV proteases. It was found that the alpha-keto amide core structure 2 is approximately 300-fold better than the corresponding hydroxyethylamine isosteric structure and 1300-fold better than the corresponding phosphinic acid derivative as an inhibitor of the HIV protease. The alpha-keto amide is however not hydrated until it is bound to the HIV protease as indicated by the NMR study and the X-ray structural analysis. Further analysis of the inhibition activities of hydroxyethylamine isosteres containing modified pyrrolidine derivatives revealed that a cis-methoxy group at C-4 of the pyrrolidine would improve the binding 5-and 25-fold for the trans-isomer. When this strategy was applied to the alpha-keto amide isostere, a cis-benzyl ether at C-4 was found to enhance binding 3-fold. Of the core structures prepared as inhibitors of the HIV protease, none show significant inhibitory activity against the mechanistically identical FIV protease, and additional complementary groups are needed to improve inhibition. C1 SCRIPPS CLIN & RES FDN,LA JOLLA,CA 92037. NCI,FREDERICK CANC RES & DEV CTR,MACROMOLEC STRUCT LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 50 TC 73 Z9 74 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 6 PY 1995 VL 117 IS 48 BP 11867 EP 11878 DI 10.1021/ja00153a008 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA TJ047 UT WOS:A1995TJ04700008 ER PT J AU SCHATZKIN, A FREEDMAN, LS LANZA, E TANGREA, J AF SCHATZKIN, A FREEDMAN, LS LANZA, E TANGREA, J TI DIET AND COLORECTAL-CANCER - STILL AN OPEN QUESTION SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LARGE-BOWEL CANCER; POLYPS; FIBER; COLON; RISK; EPIDEMIOLOGY; RECTUM; MEAT; FAT C1 NATL CANC INST,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD. NATL CANC INST,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD. NR 29 TC 18 Z9 18 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 6 PY 1995 VL 87 IS 23 BP 1733 EP 1735 DI 10.1093/jnci/87.23.1733 PG 3 WC Oncology SC Oncology GA TG662 UT WOS:A1995TG66200002 PM 7473825 ER PT J AU MCKEARNEY, JW AF MCKEARNEY, JW TI NATIONAL-CANCER-INSTITUTE RESPONSE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP MCKEARNEY, JW (reprint author), NCI,OFF INT AFFAIRS,6130 EXECUT BLVD,MSC 7301,EPN,RM 100,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 6 PY 1995 VL 87 IS 23 BP 1806 EP 1807 DI 10.1093/jnci/87.23.1806-a PG 2 WC Oncology SC Oncology GA TG662 UT WOS:A1995TG66200025 ER PT J AU Shechter, Y Li, JP Meyerovitch, J Gefel, D Bruck, R Elberg, G Miller, DS Shisheva, A AF Shechter, Y Li, JP Meyerovitch, J Gefel, D Bruck, R Elberg, G Miller, DS Shisheva, A TI Insulin-like actions of vanadate are mediated in an insulin-receptor-independent manner via nonreceptor protein tyrosine kinases and protein phosphotyrosine phosphatases SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Vanadium Symposium CY JUL 29-31, 1994 CL MONTREAL, CANADA SP Canadian Diabet Assoc, Fonds Rech Sante Quebec, Juvenile Diabet Fdn Canada, Marion Merrell Dow Canada, McGill Univ, Med Res Council Canada, Medisense Canada Inc, Merck Frosst, Canada Inc, Miles Canada Inc DE vanadium salts; insulin action; cytosolic protein tyrosine kinase; protein phosphotyrosine phosphatase; molybdate-permolybdate; tungstate-pertungstate ID ISOLATED RAT ADIPOCYTES; BLOOD-GLUCOSE; DIABETIC RATS; FA/FA RATS; VANADIUM; ACTIVATION; OXIDATION; CELLS; IONS AB Most or all mammalian cells contain vanadium at a concentration of 0.1-1.0 mu M. The bulk of the vanadium in cells is probably in the reduced vanadyl (IV) form. Although this element is essential and should be present in the diet in minute quantities, no known physiological role for vanadium has been found thus far. In the years 1975-1980 the vanadate ion was shown to act as an efficient inhibitor of Na+,K+-ATPase and of other related phosphohydrolyzes as well. In 1980 it was observed that vanadate vanadyl, when added to intact rat adipocytes, mimics the biological actions of insulin in stimulating hexose uptake and glucose oxidation. This initiated a long, currently active, field of research among basic scientists and diabetologists. Several of the aspects studied are reviewed here. C1 CHAIM SHEBA MED CTR,DEPT PEDIAT,TEL AVIV,ISRAEL. KAPLAN HOSP,DEPT INTERNAL MED B,IL-76100 REHOVOT,ISRAEL. WOLFSON GOVT HOSP,DEPT GASTROENTEROL,IL-58100 HOLON,ISRAEL. NIEHS,RES TRIANGLE PK,NC 27709. RP Shechter, Y (reprint author), WEIZMANN INST SCI,DEPT HORMONE RES,IL-76100 REHOVOT,ISRAEL. NR 41 TC 52 Z9 52 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD DEC 6 PY 1995 VL 153 IS 1-2 BP 39 EP 47 DI 10.1007/BF01075917 PG 9 WC Cell Biology SC Cell Biology GA TM620 UT WOS:A1995TM62000006 PM 8927046 ER PT J AU Wivel, N AF Wivel, N TI Human gene transfer trials SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Article; Proceedings Paper CT International Meeting on Targeting of Novel Therapeutic, to the Liver and GI Tract CY SEP 21-22, 1995 CL NIH, BETHESDA, MD SP NIDDKD HO NIH RP Wivel, N (reprint author), NIH,OFF RECOMBINANT DNA ACT,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 1 U2 1 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 5 PY 1995 VL 17 IS 3 BP 211 EP 212 DI 10.1016/0169-409X(95)00053-A PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TN045 UT WOS:A1995TN04500002 ER PT J AU LEAK, LV CADET, JL GRIFFIN, CP RICHARDSON, K AF LEAK, LV CADET, JL GRIFFIN, CP RICHARDSON, K TI NITRIC-OXIDE PRODUCTION BY LYMPHATIC ENDOTHELIAL-CELLS IN-VITRO SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RELAXING FACTOR; SYNTHASE; MACROPHAGES; EXPRESSION; ARGININE; CLONING; BRAIN AB The present study demonstrates that confluent monolayer cultures of lymphatic endothelial cells produce and secrete NO. Immunofluorescent studies showed that eNOS activity can be stimulated with Ca ionophore to enhance the production of NO. Cells and various cytokines stimulated the production of iNOS which showed the greatest increase in activity at 4 hrs and declined at 18 and 24 hrs. These studies provide evidence that, within the lymphatic vascular lumen, nitric oxide may be produced by the lymphatic endothelium which interact with various vasoactive substances to regulate lymphatic vascular tone. In addition, the production of NO by LEC may be important in the regulation of lymphatic vascular tone in order to more readily accommodate sudden fluctuations in lymph flow and pressure that normally occur during the process of lymph formation and propulsion. (C) 1995 Academic Press, Inc. C1 NIDA,NEUROSCI BRANCH,MOLEC NEUROPSYCHIAT SECT,BALTIMORE,MD 21224. RP LEAK, LV (reprint author), HOWARD UNIV,COLL MED,DEPT ANAT,ERNEST E JUST LAB CELLULAR BIOL,WASHINGTON,DC 20059, USA. FU NIGMS NIH HHS [S06GM08016] NR 22 TC 24 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 5 PY 1995 VL 217 IS 1 BP 96 EP 105 DI 10.1006/bbrc.1995.2750 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TJ020 UT WOS:A1995TJ02000014 PM 8526945 ER PT J AU LI, H CHEN, HC HUANG, FL AF LI, H CHEN, HC HUANG, FL TI IDENTIFICATION OF A RAPIDLY DEPHOSPHORYLATING 95-KDA PROTEIN AS ELONGATION-FACTOR-2 DURING 8-BR-CAMP TREATMENT OF N1E115 NEUROBLASTOMA-CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MOUSE NEURO-BLASTOMA; FACTOR-II; KINASE-C; DIFFERENTIATION; EXPRESSION; OUTGROWTH; EPSILON; ALPHA AB Treatment of 8-Br-cAMP promotes neurite outgrowth and neuronal differentiation in N1E115 mouse neuroblastoma cells. Prior or simultaneous treatment of PMA blocks 8-Br-cAMP-mediated neurite outgrowth. Phosphorylation of cellular proteins during these treatments was examined in a permeabilized cell system. While PMA promotes phosphorylation of the heat-stable protein kinase C substrates MARCKS and neuromodulin, 8-Br-cAMP hastens the dephosphorylation of a protein of M(r) 95k (p95). Extensively purified, N-terminal sequenced, and judged from its phosphorylation properties, p95 was identified as the eukaryotic elongation factor-2 (eEF-2), whose dephosphorylation has been reported to be related to an increase in protein synthesis. It is likely 8-Br-cAMP stimulates dephosphorylation of eEf-2, promotes protein synthesis that eventually leads to neuronal differentiation in N1E115 cells. (C) 1995 Academic Press, Inc. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 18 TC 5 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 5 PY 1995 VL 217 IS 1 BP 131 EP 137 DI 10.1006/bbrc.1995.2754 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TJ020 UT WOS:A1995TJ02000018 PM 8526900 ER PT J AU Softky, W AF Softky, W TI McCulloch-Pitts strikes back: A biophysical interpretation of cortical neurons as sub-millisecond binary devices SO MATHEMATICS AND COMPUTERS IN SIMULATION LA English DT Article; Proceedings Paper CT Joint CHPC/IMACS Workshop on Computational Issues in Neurosciences CY MAY 14-15, 1993 CL UNIV TEXAS, CTR HIGH PERFORMANCE COMP, AUSTIN, TX SP Univ Texas, CHPC, IMACS, Univ Texas, Dept Appl Res & Dev HO UNIV TEXAS, CTR HIGH PERFORMANCE COMP DE noise; irregularity; dendritic spikes; coincidence detection; coding; timescale; information; correlation; nonlinearity; voltage-gated conductances ID PYRAMIDAL NEURONS; STRIATE CORTEX; VISUAL-CORTEX; SPIKE TRAINS; POTENTIALS; INTEGRATION; CAT AB McCulloch and Pitts originally thought that cortical neurons computed using single spikes, with temporal resolution well under a millisecond. But the most popular current simplification of those neurons is as devices which perform computations based on real-valued firing rates, averaged over many spikes and over much longer times. However, single-spike computation has many advantages over pure analog computation: (1) it is more consistent with the observed firing irregularity of cortical cells, (2) it better explains and makes use of the observed correlations in cortical firing, (3) it is more consistent with the biophysics of active cortical dendrites, and (4) it has a far higher information capacity. The only problem is that we have not yet observed it. Or have we? RP Softky, W (reprint author), NIH,MRB 9190,WISCONSIN AVE 350,BETHESDA,MD 20814, USA. NR 27 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4754 J9 MATH COMPUT SIMULAT JI Math. Comput. Simul. PD DEC 5 PY 1995 VL 40 IS 1-2 BP 71 EP 79 DI 10.1016/0378-4754(95)00018-8 PG 9 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA TL296 UT WOS:A1995TL29600005 ER PT J AU GonzalezLima, F McIntosh, AR AF GonzalezLima, F McIntosh, AR TI Analysis of neural network interactions related to associative learning using structural equation modeling SO MATHEMATICS AND COMPUTERS IN SIMULATION LA English DT Article; Proceedings Paper CT Joint CHPC/IMACS Workshop on Computational Issues in Neurosciences CY MAY 14-15, 1993 CL UNIV TEXAS, CTR HIGH PERFORMANCE COMP, AUSTIN, TX SP Univ Texas, CHPC, IMACS, Univ Texas, Dept Appl Res & Dev HO UNIV TEXAS, CTR HIGH PERFORMANCE COMP DE neural networks; structural equation modeling; Pavlovian conditioning; auditory learning; path analysis; 2-deoxyglucose; fluorodeoxyglucose; neuroimaging; brain mapping; neural pathway; covariance analysis ID LONG-TERM HABITUATION; AUDITORY-SYSTEM; BRAIN-REGIONS; RAT-BRAIN; 2-DEOXYGLUCOSE; CORTEX; FLUORODEOXYGLUCOSE; ACTIVATION; PLASTICITY; PATTERNS AB Brain imaging techniques have the potential of providing information about functional interactions within entire neural networks. Large quantities of data can be obtained from mapping studies, but computational techniques are needed to make sense of the complex network interactions that take place in the brain. Structural equation modeling may provide such a technique by combining the anatomical connectivity with the covariation in the activity between brain regions. Functional strengths of anatomical connections between the structures that form a neural network can be quantified by assigning numerical values to the links. Changes in these values are used as indices of how information is processed and modified within the brain in a given situation. We used brain metabolic data from auditory learning experiments to explain how structural models of the auditory system reveal the patterns of network interactions related to opposite learned associative properties of the same sound. This analysis supports the hypothesis that associative learning is an emergent network property, distributed among interacting brain regions. Understanding such a property requires a network analysis of the patterns of interactions between brain regions, rather than the traditional analysis of regions one at a time. C1 UNIV TEXAS,DEPT PSYCHOL,AUSTIN,TX 78712. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RP GonzalezLima, F (reprint author), UNIV TEXAS,INST NEUROSCI,AUSTIN,TX 78712, USA. RI McIntosh, Anthony/G-4955-2011; OI Gonzalez-Lima, Francisco/0000-0001-9856-0775; McIntosh, Anthony/0000-0002-1784-5662 NR 60 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4754 J9 MATH COMPUT SIMULAT JI Math. Comput. Simul. PD DEC 5 PY 1995 VL 40 IS 1-2 BP 115 EP 140 DI 10.1016/0378-4754(95)00022-X PG 26 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA TL296 UT WOS:A1995TL29600009 ER PT J AU BOYD, J RISINGER, JI WISEMAN, RW MERRICK, BA SELKIRK, JK BARRETT, JC AF BOYD, J RISINGER, JI WISEMAN, RW MERRICK, BA SELKIRK, JK BARRETT, JC TI REGULATION OF MICROFILAMENT ORGANIZATION AND ANCHORAGE-INDEPENDENT GROWTH BY TROPOMYOSIN-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; TUMOR-SUPPRESSOR GENE; HAMSTER EMBRYO CELLS; V-HA-RAS; MESSENGER-RNA; CYTOSKELETAL FRAMEWORK; SKIN FIBROBLASTS; CULTURED-CELLS; ACTIN; PROTEINS AB Variants of chemically immortalized Syrian hamster embryo cells that had either retained (supB(+)) or lost (supB(-)) the ability to suppress tumorigenicity when hybridized with a fibrosarcoma cell line were subcloned. Both supB cell types are nontumorigenic; however, the supB(-) but not supB(+) cells exhibit conditional anchorage-independent growth. Alterations of actin microfilament organization were observed in supB(-) but not supB(+) cells that corresponded to a significant reduction of the actin-binding protein tropomyosin 1 (TM-1) in supB(-) cells. To examine the possibility of a direct relationship between TM-1 expression and the supB(-) phenotype, supB(+) cells were transfected with an expression vector containing the TM-1 cDNA in an antisense orientation. The antisense-induced reduction of TM-1 levels in supB(+) clones caused a microfilament reorganization and conferred anchorage-independent growth potential that were indistinguishable from those characteristic of supB(-) cells. These data provide direct evidence that TM-1 regulates both microfilament organization and anchorage-independent growth and suggest that microfilament alterations are sufficient for anchorage-independent growth. C1 NIEHS,MOLEC CARCINOGENESIS LAB,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. NR 55 TC 76 Z9 76 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11534 EP 11538 DI 10.1073/pnas.92.25.11534 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200045 PM 8524798 ER PT J AU GELPERIN, D WEIGLE, J NELSON, K ROSEBOOM, P IRIE, K MATSUMOTO, K LEMMON, S AF GELPERIN, D WEIGLE, J NELSON, K ROSEBOOM, P IRIE, K MATSUMOTO, K LEMMON, S TI 14-3-3-PROTEINS - POTENTIAL ROLES IN VESICULAR TRANSPORT AND RAS SIGNALING IN SACCHAROMYCES-CEREVISIAE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SHUTTLE VECTORS; PSEUDOMONAS-AERUGINOSA; EXOENZYME-S; KINASE-II; YEAST; PATHWAY; FAMILY; DNA; OVEREXPRESSION; TRANSDUCTION AB Deletion of the clathrin heavy-chain gene, CHC1, in the budding yeast Saccharomyces cerevisiae results in growth, morphological, and membrane trafficking defects, and in some strains chc1-Delta is lethal. A previous study identified five genes which, in multicopy, rescue inviable strains of Chc(-) yeast. Now we report that one of the suppressor loci, BMH2/SCD3, encodes a protein of the 14-3-3 family. The 14-3-3 proteins are abundant acidic proteins of approximate to 30 kDa with numerous isoforms and a diverse array of reported functions. The Bmh2 protein is >70% identical to the mammalian epsilon-isoform and >90% identical to a previously reported yeast 14-3-3 protein encoded by BMH1. Single deletions of BMH1 or BMH2 have no discernible phenotypes, but deletion of both BMH1 and BMH2 is lethal. High-copy BMH1 also rescues inviable strains of Chc(-) yeast, although not as well as BMH2. In addition, the slow growth of viable strains of Chc(-) yeast is further impaired when combined with single bmh mutations, often resulting in lethality. Overexpression of BMH genes also partially suppresses the temperature sensitivity of the cdc25-1 mutant, and high-copy TPK1, encoding a cAMP-dependent protein kinase, restores Bmh(-) yeast to viability. High-copy TPK1 did not rescue Chc(-) yeast. These genetic interactions suggest that budding-yeast 14-3-3 proteins are multifunctional and may play a role in both vesicular transport and Ras signaling pathways. C1 CASE WESTERN RESERVE UNIV,DEPT MOLEC BIOL & MICROBIOL,CLEVELAND,OH 44106. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NAGOYA UNIV,DEPT MOLEC BIOL,CHIKUSA KU,NAGOYA,AICHI 46401,JAPAN. FU NHLBI NIH HHS [HL07415]; NICHD NIH HHS [HD07104] NR 37 TC 123 Z9 126 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11539 EP 11543 DI 10.1073/pnas.92.25.11539 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200046 PM 8524799 ER PT J AU COLLINS, PL HILL, MG CAMARGO, E GROSFELD, H CHANOCK, RM MURPHY, BR AF COLLINS, PL HILL, MG CAMARGO, E GROSFELD, H CHANOCK, RM MURPHY, BR TI PRODUCTION OF INFECTIOUS HUMAN RESPIRATORY SYNCYTIAL VIRUS FROM CLONED CDNA CONFIRMS AN ESSENTIAL ROLE FOR THE TRANSCRIPTION ELONGATION-FACTOR FROM THE 5'-PROXIMAL OPEN READING FRAME OF THE M2 MESSENGER-RNA IN GENE-EXPRESSION AND PROVIDES A CAPABILITY FOR VACCINE DEVELOPMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEGATIVE-STRAND RNA VIRUS; PARAMYXOVIRUS; REVERSE GENETICS; POLYMERASE ID RNA AB Infectious human respiratory syncytial virus (RSV) was produced by the intracellular coexpression of five plasmid-borne cDNAs, One cDNA encoded a complete positive-sense version of the RSV genome (corresponding to the replicative intermediate RNA or antigenome), and each of the other four encoded a separate RSV protein, namely, the major nucleocapsid N protein, the nucleocapsid P phosphoprotein, the major polymerase L protein, or the protein from the 5' proximal open reading frame of the M2 mRNA [M2(ORF1)]. RSV was not produced if any of the five plasmids was omitted, The requirement for the M2(ORF1) protein is consistent with its recent identification as a transcription elongation factor and confirms its importance for RSV gene expression, It should thus be possible to introduce defined changes into infectious RSV. This should be useful for basic studies of RSV molecular biology and pathogenesis; in addition, there are immediate applications to the development of live attenuated vaccine strains bearing predetermined defined attenuating mutations. RP COLLINS, PL (reprint author), NIAID,INFECT DIS LAB,7 CTR DR,MSC 0720,BETHESDA,MD 20892, USA. NR 21 TC 306 Z9 314 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11563 EP 11567 DI 10.1073/pnas.92.25.11563 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200051 PM 8524804 ER PT J AU LIU, J CONKLIN, BR BLIN, N YUN, J WESS, J AF LIU, J CONKLIN, BR BLIN, N YUN, J WESS, J TI IDENTIFICATION OF A RECEPTOR G-PROTEIN CONTACT SITE CRITICAL FOR SIGNALING SPECIFICITY AND G-PROTEIN ACTIVATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE G PROTEIN-COUPLED RECEPTORS; HYBRID RECEPTORS; PHOSPHATIDYLINOSITOL HYDROLYSIS; PROTEIN-PROTEIN INTERACTIONS; SITE-DIRECTED MUTAGENESIS ID MUSCARINIC RECEPTOR; COUPLED RECEPTORS; PHOSPHOLIPASE-C; BETA-GAMMA; SUBUNITS; BINDING; SUBTYPES; SELECTIVITY; HYDROLYSIS; G(Q)ALPHA AB Each G protein-coupled receptor recognizes only a distinct subset of the many structurally closely related G proteins expressed within a cell. How this selectivity is achieved at a molecular level is not well understood, particularly since no specific point-to point contact sites between a receptor and its cognate G protein(s) have been identified. In this study, we demonstrate that a 4-aa epitope on the m2 muscarinic acetylcholine receptor, a prototypical G(i/o)-coupled receptor, can specifically recognize the C-terminal 5 aa of alpha subunits of the G(i/o) protein family. The m2 receptor residues involved in this interaction are predicted to be located on one side of an alpha-helical receptor region present at the junction between the third intracellular loop and the sixth transmembrane domain. Coexpression studies with hybrid m2/m3 muscarinic receptors and mutant G-protein alpha(q), subunits showed that the receptor/G-protein contact site identified in this study is essential for coupling specificity and G-protein activation. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,DEPT MED,SAN FRANCISCO,CA 94141. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,DEPT PHARMACOL,SAN FRANCISCO,CA 94141. NR 30 TC 173 Z9 177 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11642 EP 11646 DI 10.1073/pnas.92.25.11642 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200067 PM 8524820 ER PT J AU HAMER, L JOHNSTON, M GREEN, ED AF HAMER, L JOHNSTON, M GREEN, ED TI ISOLATION OF YEAST ARTIFICIAL CHROMOSOMES FREE OF ENDOGENOUS YEAST CHROMOSOMES - CONSTRUCTION OF ALTERNATE HOSTS WITH DEFINED KARYOTYPIC ALTERATIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHROMOSOME FRAGMENTATION; KAR1-MEDIATED TRANSFER; GENOME MAPPING ID SACCHAROMYCES-CEREVISIAE; RECOMBINATION SYSTEM; GEL-ELECTROPHORESIS; GENE DISRUPTION; DNA-MOLECULES; SELECTION; SEPARATION; TRANSFORMATION; DELETION; VECTORS AB An intrinsic feature of yeast artificial chromosomes (YACs) is that the cloned DNA is generally in the same size range (i.e., approximate to 200-2000 kb) as the endogenous yeast chromosomes. As a result, the isolation of YAC DNA, which typically involves separation by pulsed-field gel electrophoresis, is frequently confounded by the presence of a comigrating or closely migrating endogenous yeast chromosome(s). We have developed a strategy that reliably allows the isolation of any YAC free of endogenous yeast chromosomes. Using recombination-mediated chromosome fragmentation, a set of Saccharomyces cerevisiae host strains was systematically constructed, Each strain contains defined alterations in its electrophoretic karyotype, which provide a large-size interval devoid of endogenous chromosomes (i.e., a karyotypic ''window''). All of the constructed strains contain the kar1-Delta 15 mutation, thereby allowing the efficient transfer of a YAC from its original host into an appropriately selected window strain using the karl-transfer procedure. This approach pro,ides a robust and efficient means to obtain relatively pure YAC DNA regardless of YAC size. C1 WASHINGTON UNIV, SCH MED, DEPT GENET, ST LOUIS, MO 63110 USA. NIH, NATL CTR HUMAN GENOME RES, DIAGNOST DEV BRANCH, BETHESDA, MD 20892 USA. OI Johnston, Mark/0000-0002-4932-7229 NR 32 TC 16 Z9 16 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11706 EP 11710 DI 10.1073/pnas.92.25.11706 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200080 PM 8524833 ER PT J AU KOLESNITCHENKO, V WAHL, LM TIAN, H SUNILA, I TANI, Y HARTMANN, DP COSSMAN, J RAFFELD, M ORENSTEIN, J SAMELSON, LE COHEN, DI AF KOLESNITCHENKO, V WAHL, LM TIAN, H SUNILA, I TANI, Y HARTMANN, DP COSSMAN, J RAFFELD, M ORENSTEIN, J SAMELSON, LE COHEN, DI TI HUMAN-IMMUNODEFICIENCY-VIRUS-1 ENVELOPE-INITIATED G(2)-PHASE PROGRAMMED CELL-DEATH SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CDC2 PROTEIN-KINASE; T-CELL; TYROSINE PHOSPHORYLATION; THYMOCYTE APOPTOSIS; CYCLIN-A; INFECTION; ACTIVATION; RECEPTOR; ANTIGEN; CD4 AB Despite intensive investigation, no clearly defined mechanism explaining human immunodeficiency virus (HIV)-induced cell killing has emerged. HIV-1 infection is initiated through a high-affinity interaction between the HIV-1 external envelope glycoprotein (gp120) and the CD4 receptor on T cells. Cell killing is a later event intimately linked by in vitro genetic analyses with the fusogenic properties of the HIV envelope glycoprotein gp120 and transmembrane glycoprotein gp41. In this report, we describe aberrancies in cell cycle regulatory proteins initiated by cell-cell contact between T cells expressing HIV-1 envelope glycoproteins and other T cells expressing CD4 receptors. Cells rapidly accumulate cyclin B protein and tyrosine-hyperphosphorylated p34cdc2 (cdk1) kinase, indicative of cell cycle arrest at G(2) phase. Moreover, these cells continue to synthesize cyclin B protein, enlarge and display an abnormal ballooned morphology, and disappear from the cultures in a pattern previously described for cytoxicity induced by DNA synthesis (S phase) inhibitors. Similar changes are observed in peripheral blood mononuclear cells infected in vitro with pathogenic primary isolates of HIV-1. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT PATHOL,WASHINGTON,DC 20037. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20052. NR 43 TC 35 Z9 35 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11889 EP 11893 DI 10.1073/pnas.92.25.11889 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200117 PM 8524869 ER PT J AU KOONIN, EV TATUSOV, RL RUDD, KE AF KOONIN, EV TATUSOV, RL RUDD, KE TI SEQUENCE SIMILARITY ANALYSIS OF ESCHERICHIA-COLI PROTEINS - FUNCTIONAL AND EVOLUTIONARY IMPLICATIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROTEIN SEQUENCE SIMILARITY; ESCHERICHIA COLI GENOME; PARALOGOUS PROTEIN CLUSTERS; ANCIENT CONSERVED REGIONS ID RNA; METHYLTRANSFERASE; FIBRILLARIN; DATABASES; DNA AB A computer analysis of 2328 protein sequences comprising about 60% of the Escherichia coli gene products was performed using methods for database screening with individual sequences and alignment blocks. A high fraction of E. coli proteins-86%-shows significant sequence similarity to other proteins in current databases; about 70% show conservation at least at the level of distantly related bacteria, and about 40% contain ancient conserved regions (ACRs) shared with eukaryotic or Archaeal proteins. For >90% of the E. coli proteins, either functional information or sequence similarity, or both, are available. Forty-six percent of the E. coli proteins belong to 299 clusters of paralogs (intraspecies homologs) defined on the basis of pairwise similarity. Another 10% could be included in 70 superclusters using motif detection methods. The majority of the clusters contain only two to four members. In contrast, nearly 25% of all E. coli proteins belong to the four largest superclusters-namely, permeases, ATPases and GTPases with the conserved ''Walker-type'' motif, helix-turn-helix regulatory proteins, and NAD(FAD)-binding proteins. We conclude that bacterial protein sequences generally are highly conserved in evolution, with about 50% of all ACR-containiug protein families represented among the E. coli gene products. With the current sequence databases and methods of their screening, computer analysis yields useful information on the functions and evolutionary relationships of the vast majority of genes in a bacterial genome. Sequence similarity with E. coli proteins allows the prediction of functions for a number of important eukaryotic genes, including Several whose products are implicated in human diseases. RP KOONIN, EV (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 35 TC 87 Z9 88 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11921 EP 11925 DI 10.1073/pnas.92.25.11921 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200124 PM 8524875 ER PT J AU YOSHIMOTO, T BENDELAC, A HULI, J PAUL, WE AF YOSHIMOTO, T BENDELAC, A HULI, J PAUL, WE TI DEFECTIVE IGE PRODUCTION BY SJL MICE IS LINKED TO THE ABSENCE OF CD4(+), NK1.1(+) T-CELLS THAT PROMPTLY PRODUCE INTERLEUKIN-4 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CD1; CYTOKINE; INTERFERON ID STIMULATORY FACTOR-I; LYMPHOKINE SECRETION; INTERFERON-GAMMA; EXPRESSION; RECEPTOR; ANTIBODY; IL-4; CD4+; SUPPRESSION; ACTIVATION AB SJL mice produce little or no IgE in response to polyclonal stimulation with anti-IgD antibody and fail to express interleukin 4 (IL-4) mRNA in the spleen 5 days after injection of anti-IgD, in contrast to other mouse strains that produce substantial amounts of IgE and IL-4. Because IL-4 is critical in IgE production, the possibility that SJL mice are poor IgE producers because their naive T cells fail to differentiate into IL-4 producers must be seriously considered. IL-4 itself is the principal factor determining that naive T cells develop into IL-4 producers. A major source of IL-4 for such differentiation is a population of CD1-specific CD4(+) T cells that express NK1.1. These cells produce IL-4 within 90 min of anti-CD3 injection. T cells from SJL mice fail to produce IL-4 in response to injection of anti-CD3. Similarly, SJL T cells and CD4(+) thymocytes do not produce IL-4 in response to acute in vitro stimulation. SJL T cells show a marked deficiency in CD4(+) cells that express the surface receptors associated with the NK1.1(+) T-cell phenotype. This result indicates that the SJL defect in IgE and IL-4 production is associated with, and may be due to, the absence of the CD4(+), NK1.1(+) T-cell population. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544. NR 28 TC 228 Z9 231 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11931 EP 11934 DI 10.1073/pnas.92.25.11931 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200126 PM 8524877 ER PT J AU NASIOULAS, G HUGHES, SH FELBER, BK WHITCOMB, JM AF NASIOULAS, G HUGHES, SH FELBER, BK WHITCOMB, JM TI PRODUCTION OF AVIAN-LEUKOSIS VIRUS-PARTICLES IN MAMMALIAN-CELLS CAN BE MEDIATED BY THE INTERACTION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS PROTEIN REV AND THE REV-RESPONSIVE ELEMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ROUS-SARCOMA VIRUS; VIRAL MESSENGER-RNA; RETROVIRUS RNA; LEUKEMIA-VIRUS; SPLICE SITES; GENE-PRODUCT; GAG GENE; EXPRESSION; TYPE-1; TRANSLATION AB In human immunodeficiency virus type 1-infected cells, the efficient expression of viral proteins from unspliced and singly spliced RNAs is dependent on two factors: the presence in the cell of the viral protein Rev and the presence in the viral RNA of the Rev-responsive element (RRE). We show here that the HIV-1 Rev/RRE system can increase the expression of avian leukosis virus (ALV) structural proteins in mammalian cells (D-17 canine osteosarcoma) and promote the release of mature ALV virions from these cells. In this system, the Rev/RRE interaction appears to facilitate the export of full-length unspliced ALV RNA from the nucleus to the cytoplasm, allowing increased production of the ALV structural proteins. Gag protein is produced in the cytoplasm of the ALV-transfected cells even in the absence of a ReV/RRE interaction. However, a functional Rev/RRE interaction increases the amount of Gag present intracellularly and, more strikingly, results in the release of mature ALV particles into the supernatant. RCAS virus containing an RRE is replication-competent in chicken embryo fibroblasts; however, we have been unable to determine whether the particles produced in D-17 cells are as infectious as the particles produced in chicken embryo fibroblasts. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,GENE EXPRESS EUKARYOTES SECT,FREDERICK,MD 21702. NR 74 TC 28 Z9 28 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11940 EP 11944 DI 10.1073/pnas.92.25.11940 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200128 PM 8524879 ER PT J AU THOMPSON, DB OSSOWSKI, V JANSSEN, RC KNOWLER, WC BOGARDUS, C AF THOMPSON, DB OSSOWSKI, V JANSSEN, RC KNOWLER, WC BOGARDUS, C TI LINKAGE BETWEEN STATURE AND A REGION ON CHROMOSOME-20 AND ANALYSIS OF A CANDIDATE GENE, BONE MORPHOGENETIC PROTEIN-2 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE STATURE; LINKAGE ANALYSIS; BONE MORPHOGENETIC PROTEIN 2; BMP2 ID QUANTITATIVE TRAIT; DIABETES-MELLITUS; PIMA-INDIANS; MARKERS AB Sib-pair linkage analysis of the quantitative trait, stature, in over 500 Pima Indians indicates that a genetic determinant of governing stature is located on chromosome 20, Analysis of 10 short tandem repeat polymorphisms localized this linkage to a 3.2cM region that includes D20S98 and D20S66, Using all possible sib-pair combinations, linkage was detected to both stature (P = 0.0001) and to leg length (P = 0.001), but not to sitting height, Single-strand conformational polymorphism analysis of exon 3 of the bone morphogenetic protein 2 (BMP2) gene, a candidate gene in this region, in genomic DNA of 20 of the tallest and 20 of the shortest individuals did not show any consistent differences associated with leg length or height, Sequence analysis of the region encoding the mature protein revealed a single nucleotide substitution, a T to G transversion, not detected by single-strand conformational polymorphism (SSCP) analysis, This transversion results in a conservative amino acid substitution of glycine for valine at codon 80 of BMP2. The frequency of this allele was 0.23 in the sample, No significant differences in height were noted in persons carrying either allele, This indicates that this structural alteration in the mature BMP2 protein does not contribute to the differences in stature observed in the Pima Indians, nor is this structural change in the mature protein likely to be responsible for the linkage observed with stature on chromosome 20. (C) 1995 Wiley-Liss, Inc.* RP THOMPSON, DB (reprint author), NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,4212 N 16TH ST,PHOENIX,AZ 85016, USA. FU NCRR NIH HHS [1 P41 RR03655] NR 32 TC 19 Z9 19 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 4 PY 1995 VL 59 IS 4 BP 495 EP 500 DI 10.1002/ajmg.1320590417 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA TG908 UT WOS:A1995TG90800016 PM 8585571 ER PT J AU SCREMIN, CL BOAL, JH WILK, A PHILLIPS, LR ZHOU, L BEAUCAGE, SL AF SCREMIN, CL BOAL, JH WILK, A PHILLIPS, LR ZHOU, L BEAUCAGE, SL TI 1-(2-DEOXY-ALPHA-D-ERYTHRO-PENTOFURANOSYL)-2-(THYMIN-1-YL)ETHANE AND 1-(2-DEOXY-BETA-D-ERYTHRO-PENTOFURANOSYL)-2-(THYMIN-1-YL)ETHANE DERIVATIVES AS CONFORMATIONAL PROBES FOR ALTDNA OLIGONUCLEOTIDES SO TETRAHEDRON LETTERS LA English DT Article AB The novel deoxyribonucleoside analogues 1a,b have been synthesized in a straightforward manner from 2-deoxy-D-ribose. These modified nucleosides have also been converted to the phosphoramidite derivatives 13a,b and 14a,b for potential incorporation into oligodeoxyribonucleotides according to defined internucleotidic motifs. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV ALLERGEN PROD & PARASITOL,BETHESDA,MD 20892. NCI,DEV THERAPEUT PROGRAM,PHARMACEUT CHEM LAB,FREDERICK,MD 21701. NR 14 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD DEC 4 PY 1995 VL 36 IS 49 BP 8953 EP 8956 DI 10.1016/0040-4039(95)01932-8 PG 4 WC Chemistry, Organic SC Chemistry GA TH701 UT WOS:A1995TH70100014 ER PT J AU Anderson, NB AF Anderson, NB TI Integrating Behavioral and Social Sciences Research at the NIH SO ACADEMIC MEDICINE LA English DT Article C1 DUKE UNIV,DEPT PSYCHOL,DURHAM,NC 27706. NIH,OFF BEHAV & SOCIAL SCI RES,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD DEC PY 1995 VL 70 IS 12 BP 1106 EP 1107 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA TL701 UT WOS:A1995TL70100016 PM 7495455 ER PT J AU Rossio, JL Bess, J Henderson, LE Cresswell, P Arthur, LO AF Rossio, JL Bess, J Henderson, LE Cresswell, P Arthur, LO TI HLA class II on HIV particles is functional in superantigen presentation to human T cells: Implications for HIV pathogenesis SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SELECTIVE LOSS; ANTIGEN PRESENTATION; IMMUNE-RESPONSES; AIDS; INFECTION; DEATH; ACTIVATION; LYMPHOCYTES; APOPTOSIS AB The mechanisms of immune suppression by the human immunodeficiency virus, HIV-1, are more complex than simple helper T cell deletion via infection and viral-induced lysis, Since the recent description of cellular proteins associated with HIV suggests that these proteins may be active in viral pathogenesis, the nature of HLA class II gene product carried on HIV, one of the most abundant of the human components carried with the virus, was examined, HN bearing HLA-DR was shown to act with bacterial superantigen, staphylococcal enterotoxin A (SEA), to stimulate highly purified human T lymphocytes, T cell stimulation by wildtype HIV was shown by both induction of proliferation and by production of the cytokine interleukin 2 (IL-2), In contrast, HIV produced from mutant cells lacking class Il genes were unable to cooperate with SEA to activate T cells, Neither whole HIV nor several proteins purified from HIV (gp120, gp41, p24, p7, and p6) exhibited superantigen-like activity in this system, HLA-DR-bearing HIV could, in the continued presence of SEA, induce T cell apoptosis, as detected by nuclear fragmentation and morphological criteria, These data indicate that human cellular proteins associated with HIV may be biologically active, and these proteins should be considered in mechanisms of viral pathogenicity and immunogenicity. C1 YALE UNIV,SCH MED,HOWARD HUGHES MED INST,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. RP Rossio, JL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,INC DYNCORP,PROGRAM RESOURCES,AIDS VACCINE PROGRAM,FREDERICK,MD 21702, USA. RI Bess, Jr., Julian/B-5343-2012 NR 43 TC 60 Z9 61 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 1995 VL 11 IS 12 BP 1433 EP 1439 DI 10.1089/aid.1995.11.1433 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA TM191 UT WOS:A1995TM19100002 PM 8679286 ER PT J AU Cho, SG Kindt, TJ Zhao, TM Sawasdikosol, S Hague, BF AF Cho, SG Kindt, TJ Zhao, TM Sawasdikosol, S Hague, BF TI Replication of HIV type I in rabbit cell lines is not limited by deficiencies in tat, rev, or long terminal repeat function SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL; INFECTION; RETROVIRUS; IDENTIFICATION; ELEMENT AB HIV-1 infection has been documented in rabbits, but infection proceeds slowly in this species, Human and rabbit cell lines were compared in order to identify barriers to efficient HIV-1 infection of rabbit cells, A direct comparison of human and rabbit CD4 as receptor for HIV-1 indicated that the rabbit CD4 homolog did not function well even when expressed by human cells, Examination of viral RNA production indicated that the major HN transcripts were produced in HIV-infected rabbit cells, but were present at levels significantly lower than those found for human cells. Ability of HIV-1 LTRs to direct protein expression in human and rabbit cells was compared using gene constructs with the chloramphenicol acetyltransferase (cat) gene flanked by HIV-1 LTRs, Chloramphenicol acetyltransferase protein expression was equivalent In rabbit and human cell lines transfected with the HIV-1/CAT constructs and cotransfections with the HIV-1 tat gene led to similar increases in CAT expression, Subsequent transfections with an infectious molecular HIV clone yielded approximately equal levels of HIV protein expression in rabbit and human cell lines, suggesting that major barriers to virus production in rabbit lines exist at steps prior to transcription of the viral genome. Because HTLV-I replicates with high efficiency in rabbit cells, a chimeric virus clone was constructed consisting of the 5' portion of HIV-1 through the nef coding sequence followed by the 3' HTLV-I LTR. Transfection of most rabbit cell lines with the chimera produced levels of p24(gag) protein higher than those transfected with the parent HIV-1 clone, By contrast, the unmodified HIV clone replicated more efficiently in all human cell lines tested. C1 NIAID,TWINBROOK 2 FACIL,LIG,ROCKVILLE,MD 20852. NR 34 TC 12 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 1995 VL 11 IS 12 BP 1487 EP 1493 DI 10.1089/aid.1995.11.1487 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA TM191 UT WOS:A1995TM19100009 PM 8679293 ER PT J AU Maisto, SA Connors, GJ Allen, JP AF Maisto, SA Connors, GJ Allen, JP TI Contrasting self-report screens for alcohol problems: A review SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE alcohol problems; screening; contrast studies ID MAST; CAGE; QUESTIONNAIRES; DRINKING; VALIDITY AB Current trends in conceptions of alcohol problems and provision of health care put increased emphasis on identifying individuals whose alcohol use and problems cover a range of severity, The purpose of this study is to begin to provide information on the relative utility of self-report measures designed to identify (screen for) individuals with alcohol problems, To achieve this goal, the empirical literature on contrasts of self-report screening measures was reviewed, and 13 relevant studies across diverse settings and subject populations were identified, The review showed that the CAGE, the Michigan Alcoholism Screening Test (MAST), and the short MAST (sMAST) have been the most widely studied self-report instruments to screen for alcohol problems, Direct comparisons show the MAST to be more sensitive than the CAGE, but with elderly patients the CAGE may perform better than the MAST, Furthermore, available data suggest that the CAGE and the sMAST perform comparably. Finally, the CAGE, MAST, and sMAST all perform best when predicting criteria most similar to those the instruments were designed to reflect. The study concludes with a discussion of priorities for research on screening instruments. C1 NIAAA,ROCKVILLE,MD 20852. RES INST ADDICT,BUFFALO,NY. RP Maisto, SA (reprint author), SYRACUSE UNIV,DEPT PSYCHOL,430 HUNTINGTON HALL,SYRACUSE,NY 13244, USA. NR 24 TC 94 Z9 95 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1995 VL 19 IS 6 BP 1510 EP 1516 DI 10.1111/j.1530-0277.1995.tb01015.x PG 7 WC Substance Abuse SC Substance Abuse GA TL691 UT WOS:A1995TL69100022 PM 8749818 ER PT J AU Litten, RZ Allen, JP Fertig, JB AF Litten, RZ Allen, JP Fertig, JB TI gamma-Glutamyltranspeptidase and carbohydrate deficient transferrin: Alternative measures of excessive alcohol consumption SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE CDT; GGT; biochemical markers; screening ID MITOCHONDRIAL ASPARTATE-AMINOTRANSFERASE; ANION-EXCHANGE CHROMATOGRAPHY; HEAVY DRINKING; LABORATORY MARKERS; DESIALYLATED TRANSFERRIN; GLUTAMYL-TRANSPEPTIDASE; LIVER-DISEASES; SERUM; MEN; CDT AB Both gamma-glutamyltranspeptidase and carbohydrate-deficient transferrin have been extensively researched as biological markers of heavy alcohol consumption. The current study briefly describes each test, identifies subject variables that influence their relative sensitivities and specificities, and examines issues surrounding use of the two markers in combination. In addition, this study suggests five design features that should characterize projects evaluating the validity of biochemical markers. RP Litten, RZ (reprint author), NIAAA,TREATMENT RES BRANCH,WILLCO BLDG,SUITE 505,6000 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 37 TC 64 Z9 64 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1995 VL 19 IS 6 BP 1541 EP 1546 DI 10.1111/j.1530-0277.1995.tb01021.x PG 6 WC Substance Abuse SC Substance Abuse GA TL691 UT WOS:A1995TL69100028 PM 8749824 ER PT J AU Asthana, S Raffaele, KC Berardi, A Greig, NH Haxby, JV Schapiro, MB Soncrant, TT AF Asthana, S Raffaele, KC Berardi, A Greig, NH Haxby, JV Schapiro, MB Soncrant, TT TI Treatment of Alzheimer disease by continuous intravenous infusion of physostigmine SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; memory; physostigmine; steady-state infusion ID CHRONIC ORAL PHYSOSTIGMINE; SENILE DEMENTIA; PRESENILE-DEMENTIA; CHOLINERGIC SYSTEM; MEMORY; LECITHIN; ANALOGS; NEURONS; CORTEX; BRAIN AB Physostigmine, a reversible and nonselective cholinesterase inhibitor, administered by steady-state, continuous intravenous infusion to carefully selected subjects with mild-moderate Alzheimer disease, produced significant but modest improvement in memory in five of nine subjects. Drug dosing was limited by the occurrence of adverse effects. Apparent tolerance to adverse effects was observed in two subjects when the dose of physostigmine was escalated slowly over at least 2 weeks. Steady-state cholinesterase inhibition by physostigmine appears to produce sustained cognitive improvement in some subjects with Alzheimer disease without substantially altering its therapeutic index. C1 NIA,UNIT PHARMACOL & PHARMACOKINET,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 69 TC 15 Z9 16 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD WIN PY 1995 VL 9 IS 4 BP 223 EP 232 PG 10 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA UG602 UT WOS:A1995UG60200009 PM 8749612 ER PT J AU Cassedy, JH AF Cassedy, JH TI The gifts of civilization: Germs and genocide in Hawai'i - Bushnell,OA SO AMERICAN HISTORICAL REVIEW LA English DT Book Review RP Cassedy, JH (reprint author), NATL LIB MED,BETHESDA,MD 20894, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER HISTORICAL REVIEW PI WASHINGTON PA 400 A ST SE, WASHINGTON, DC 20003 SN 0002-8762 J9 AM HIST REV JI Am. Hist. Rev. PD DEC PY 1995 VL 100 IS 5 BP 1676 EP 1676 DI 10.2307/2170084 PG 1 WC History SC History GA TM223 UT WOS:A1995TM22300224 ER PT J AU MCKENDALL, GR FORMAN, S SOPKO, G BRAUNWALD, E WILLIAMS, DO AF MCKENDALL, GR FORMAN, S SOPKO, G BRAUNWALD, E WILLIAMS, DO TI VALUE OF RESCUE PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY FOLLOWING UNSUCCESSFUL THROMBOLYTIC THERAPY IN PATIENTS WITH ACUTE MYOCARDIAL-INFARCTION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PLASMINOGEN-ACTIVATOR; TIMI TRIAL; PHASE-II; REPERFUSION AB Rescue percutaneous transluminal coronary angioplasty (PTCA) has been advocated as a mechanical method tb achieve reperfusion in instances where the myocardial infarct artery remains occluded after thrombolytic therapy, Most prior reports of rescue. PTCA have been observational and analyses of value have, been inconclusive. To evaluate the benefit of rescue PTCA, we studied 133 patients enrolled in the Thrombolysis in Myocardial Infarction Phase I Open Label and Phase II trials who had an occluded infarct-related artery after thrombolytic therapy. According to protocol, 100 consecutive patients had no rescue PTCA performed (no rescue group), and 33 consecutive patients underwent protocol-directed rescue PTCA (rescue group), The 2 cohorts were compared for clinical and angiographic outcome. Baseline characteristics of the 2 groups were similar. Rescue PTCA was attempted in each rescue group patient and was successful in 82%, At 21 days the mortality rate was 12% in the rescue group and 7% in the no rescue group (p = NS). Failed rescue PTCA was associated with a mortality of 33%, Reinfarction occurred in 6% of patients in the rescue group, and in 5% of those in the no rescue group (p = NS), At 21 days, mean left ventricular ejection fraction was 51 +/- 13% in the rescue group and 48 +/- 12% in the no rescue group (p = NS), We conclude that the routine use of rescue PTCA does not appear to offer significant benefit beyond that of contemporary medical therapy after thrombolytic failure. C1 MARYLAND MED RES INST,BALTIMORE,MD. NHLBI,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RP MCKENDALL, GR (reprint author), BROWN UNIV,RHODE ISL HOSP,DIV CARDIOL,APC 434A,593 EDDY ST,PROVIDENCE,RI 02903, USA. NR 16 TC 42 Z9 45 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 1995 VL 76 IS 16 BP 1108 EP 1111 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TG532 UT WOS:A1995TG53200002 PM 7484892 ER PT J AU GARCIA, CE KILCOYNE, CM CARDILLO, C CANNON, RO QUYYUMI, AA PANZA, JA AF GARCIA, CE KILCOYNE, CM CARDILLO, C CANNON, RO QUYYUMI, AA PANZA, JA TI EVIDENCE THAT ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH HYPERCHOLESTEROLEMIA IS NOT DUE TO INCREASED EXTRACELLULAR NITRIC-OXIDE BREAKDOWN BY SUPEROXIDE ANIONS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FOREARM RESISTANCE VESSELS; SMOOTH-MUSCLE; DEPENDENT RELAXATION; RELAXING FACTOR; RABBIT AORTA; ATHEROSCLEROSIS; ACETYLCHOLINE; VASODILATION; RELEASE AB Patients with hypercholesterolemia have impaired endothelium-dependent vasodilation due to decreased nitric oxide activity. The present study aimed to determine whether this form of endothelial dysfunction is related to enhanced extracellular breakdown of nitric oxide by superoxide onions. To this end, the vascular responses to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct smooth muscle dilator) were studied before and after combined administration of copper-zinc superoxide dismutase (a scavenger of superoxide anions with poor intracellular penetrance; 6,000 U/min) in 20 normal controls (11 men and 9 women, age 50 +/- 6 years) and in 20 hypercholesterolemic patients (10 men and 10 women, age 49 +/- 9 years). Drugs were infused into the brachial artery and the response of the forearm vasculature was measured by plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypercholesterolemic patients compared with normal controls (maximal flow 8.8 +/- 2 vs 12.7 +/- 3 ml/min/100 mi, respectively; p<0.03); however, no difference was observed in the response to sodium nitroprusside (9.7 +/- 2 and 9.5 +/- 3 ml/min/100 mi). In normal controls, the infusion;of superoxide dismutase did not significantly modify the response to acetylcholine (maximal flow 12.7 +/- 3 vs 12.1 +/- 3 ml/min/100 mi before and after superoxide dismutase, respectively). Similarly, in hypercholesterolemic patients, the infusion of superoxide dismutase did not alter the response to acetylcholine (maximal flow 8.8 +/- 2 and 8.9 +/- 2 ml/min/100 mi). A subset of 19 subjects (8 normal and 11 patients) received a 60-minute infusion of superoxide dismutase at 24,000 U/min without alteration in their response to acetylcholine. Superoxide dismutase did not modify the response to sodium nitroprusside in either group. These findings confirm previous observations of impaired endothelium-dependent vasodilation in hypercholesterolemic patients, but do not support the concept of increased extracellular destruction of nitric oxide by superoxide onions as the mechanism responsible for this abnormality. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 26 TC 27 Z9 28 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 1995 VL 76 IS 16 BP 1157 EP 1161 DI 10.1016/S0002-9149(99)80327-0 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TG532 UT WOS:A1995TG53200014 PM 7484902 ER PT J AU BLOT, WJ LI, JY TAYLOR, PR GUO, WD DAWSEY, SM LI, B AF BLOT, WJ LI, JY TAYLOR, PR GUO, WD DAWSEY, SM LI, B TI THE LINXIAN TRIALS - MORTALITY-RATES BY VITAMIN-MINERAL INTERVENTION GROUP SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ESOPHAGEAL CANCER; STOMACH CANCER; VITAMINS; MINERALS; BETA-CAROTENE; VITAMIN E; SELENIUM; MORTALITY; RANDOMIZED TRIALS ID DISEASE-SPECIFIC MORTALITY; CANCER INCIDENCE; SUPPLEMENTATION; CHINA AB Two randomized nutrition intervention trials were conducted in Linxian, an area of northcentral China with some of the world's highest rates of esophageal and stomach cancer and a population with a chronically low intake of several nutrients. One trial used a factorial design that allowed us to assess the effects in nearly 30 000 participants of daily supplementation with four nutrient combinations: retinol and zinc; riboflavin and niacin; vitamin C and molybdenum; and beta-carotene, alpha-tocopherol, and selenium. The second trial provided daily multiple vitamin-mineral supplementation;or placebo in 3318 persons with esophageal dysplasia, a precursor to esophageal cancer. After supplements were given for 5.25 y in the general population trial, small but significant reductions in total [relative risk (RR) = 0.91] and cancer (RR = 0.87) mortality were observed in subjects receiving beta-carotene, alpha-tocopherol, and selenium but not the other nutrients. The reductions were greater in women than men, and in those under compared with over the age of 55; however, differences by sex or age were not significant. After multiple vitamin and mineral supplements were given for 6 y in the smaller dysplasia trial, reductions in total (RR = 0.93) and cancer (RR = 0.96) mortality were observed but these were not significant. The largest reductions were for cerebrovascular disease mortality, but the effects differed by sex: a significant reduction was observed in men (RR = 0.45) but not women (RR = 0.90). Restoring adequate intake of certain nutrients may help to lower the risk of cancer and other diseases in this high-risk population. C1 CHINESE ACAD MED SCI, INST CANC, BEIJING 100021, PEOPLES R CHINA. NCI, BETHESDA, MD 20892 USA. RP BLOT, WJ (reprint author), INT EPIDEMIOL INST, ROCKVILLE, MD 20850 USA. NR 7 TC 95 Z9 97 U1 0 U2 4 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1995 VL 62 IS 6 SU S BP 1424 EP 1426 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TK019 UT WOS:A1995TK01900020 PM 7495242 ER PT J AU ALBANES, D HEINONEN, OP HUTTUNEN, JK TAYLOR, PR VIRTAMO, J EDWARDS, BK HAAPAKOSKI, J RAUTALAHTI, M HARTMAN, AM PALMGREN, J GREENWALD, P AF ALBANES, D HEINONEN, OP HUTTUNEN, JK TAYLOR, PR VIRTAMO, J EDWARDS, BK HAAPAKOSKI, J RAUTALAHTI, M HARTMAN, AM PALMGREN, J GREENWALD, P TI EFFECTS OF ALPHA-TOCOPHEROL AND BETA-CAROTENE SUPPLEMENTS ON CANCER INCIDENCE IN THE ALPHA-TOCOPHEROL BETA-CAROTENE CANCER PREVENTION STUDY SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE CANCER; INTERVENTION TRIALS; BETA-CAROTENE; VITAMIN-E; ALPHA-TOCOPHEROL; VITAMINS; ANTIOXIDANTS ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; EPIDEMIOLOGIC EVIDENCE; RETINOL; VEGETABLES; LINXIAN; FRUIT; CHINA AB The Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study was a placebo-controlled, randomized intervention trial testing the hypothesis that beta-carotene and alpha-tocopherol (vitamin E) supplements prevent lung and other cancers. The study is predicated on a substantial body of evidence supporting a role in cancer prevention for these micronutrients. Based on the 2 x 2 factorial study design, 29 133 eligible male cigarette smokers aged 50-69 y were randomly assigned to receive beta-carotene (20 mg), alpha-tocopherol (50 mg), beta-carotene and alpha-tocopherol, or placebo daily for 5-8 y. Capsule compliance was high (median = 99%). beta-Carotene treatment did not result in a decrease in cancer at any of the major sites but rather in an increase at several sites, most notably lung, prostate, and stomach (number of cases 474 compared with 402, 138 compared with 112, and 70 compared with 56, respectively). The vitamin E group had fewer incident cancers of the prostate and colorectum compared with the group not receiving vitamin E (number of cases 99 compared with 151 and 68 compared with 81, respectively), but more cancers of the stomach (70 compared with 56). In contrast to these intervention-based findings for beta-carotene and vitamin E supplements, we observed lower lung cancer rates in men with higher amounts of both serum and dietary beta-carotene and vitamin E at baseline. C1 NATL PUBL HLTH INST, HELSINKI, FINLAND. RP ALBANES, D (reprint author), NCI, 6130 EXECUT PLAZA N, MSC 7326 ROOM 211, BETHESDA, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 28 TC 229 Z9 233 U1 1 U2 13 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1995 VL 62 IS 6 SU S BP 1427 EP 1430 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TK019 UT WOS:A1995TK01900021 PM 7495243 ER PT J AU ZHANG, YH KRAMER, TR TAYLOR, PR LI, JY BLOT, WJ BROWN, CC GUO, WD DAWSEY, SM LI, B AF ZHANG, YH KRAMER, TR TAYLOR, PR LI, JY BLOT, WJ BROWN, CC GUO, WD DAWSEY, SM LI, B TI POSSIBLE IMMUNOLOGICAL INVOLVEMENT OF ANTIOXIDANTS IN CANCER PREVENTION SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ANTIOXIDANTS; MICRONUTRIENTS; BETA-CAROTENE; VITAMIN E; SELENIUM; IMMUNE RESPONSES; T-LYMPHOCYTES; WHOLE-BLOOD CULTURES; CANCER MORTALITY ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; ELDERLY SUBJECTS; BETA-CAROTENE; SUPPLEMENTATION; LINXIAN; CHINA AB The people of Linxian County, China have one of the world's highest rates of esophageal cancer. Two intervention trials were conducted to determine whether supplementation with specific vitamins and minerals could lower mortality from or incidence of cancer in this population and whether supplementation with multiple vitamins and minerals would reduce esophageal and gastric cardia cancer in persons with esophageal dysplasia. About 30 000 general population (GP) subjects in the GP trial were randomly assigned to one of eight intervention groups according to a one-half replicate of a 2(4) factorial experimental design and were supplemented for 5.25 y with four combinations of micronutrients at doses from one to two times the US recommended dietary allowance (RDA). About 3000 subjects in whom dysplasia was diagnosed in the dysplasia trial were randomly assigned to groups receiving daily supplementation with 14 vitamins and 12 minerals at two to three times the US RDA or placebo for 6 y. Results of the dysplasia trial indicate that in individuals with esophageal dysplasia, micronutrient supplementation had little effect on T lymphocyte responses. In contrast, male participants in the GP trial who were supplemented with beta-carotene, vitamin E, and selenium showed significantly (P < 0.05) higher mitogenic responsiveness of T lymphocytes in vitro than those not receiving these micronutrients. C1 BEIJING UNION MED COLL, BEIJING, PEOPLES R CHINA. USDA, BELTSVILLE HUMAN NUTR RES CTR, BELTSVILLE, MD 20705 USA. NCI, BETHESDA, MD 20892 USA. RP ZHANG, YH (reprint author), CHINESE ACAD MED SCI, INST CANC, POB 2258, BEIJING 100021, PEOPLES R CHINA. NR 15 TC 18 Z9 18 U1 1 U2 1 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1995 VL 62 IS 6 SU S BP 1477 EP 1482 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TK019 UT WOS:A1995TK01900026 PM 7495248 ER PT J AU LEVINE, M DHARIWAL, KR WELCH, RW WANG, YH PARK, JB AF LEVINE, M DHARIWAL, KR WELCH, RW WANG, YH PARK, JB TI DETERMINATION OF OPTIMAL VITAMIN-C REQUIREMENTS IN HUMANS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Antioxidant Vitamins and Beta-Carotene in Disease Prevention CY OCT 10-12, 1994 CL BERLIN, GERMANY SP NCI, Natl Fdn Canc Res, NHLBI, Krebsforsch Int eV, Soc Free Rad Res Int, F Hoffmann La Roche Ltd DE VITAMIN-C; ASCORBIC ACID; RECOMMENDED DIETARY ALLOWANCE; RDA ID CHROMAFFIN GRANULE MEMBRANE; GAMMA-BUTYROBETAINE HYDROXYLASE; TRANSMEMBRANE ELECTRON-TRANSFER; ASCORBIC-ACID TRANSPORT; LOW-DENSITY-LIPOPROTEIN; STEADY-STATE TURNOVER; NOREPINEPHRINE BIOSYNTHESIS; HUMAN-NEUTROPHILS; CARNITINE BIOSYNTHESIS; CHRONIC-HEMODIALYSIS AB Although the recommended dietary allowance provides an estimate for vitamin C ingestion in humans, optimal vitamin C requirements are unknown. We define optimal vitamin C requirements operationally based on the following: dose-function relations, availability in the food supply, steady state concentrations in plasma and tissues achieved at each dose of vitamin C, urinary excretion, bioavailability, toxicity, and epidemiologic observations. Optimal vitamin C requirements can be estimated when information is available for at least some of these criteria. C1 NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NR 137 TC 65 Z9 67 U1 0 U2 5 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1995 VL 62 IS 6 SU S BP S1347 EP S1356 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TK019 UT WOS:A1995TK01900008 ER PT J AU TAYLOR, PR WANG, GQ DAWSEY, SM GUO, WD MARK, SD LI, JY BLOT, WJ LI, B AF TAYLOR, PR WANG, GQ DAWSEY, SM GUO, WD MARK, SD LI, JY BLOT, WJ LI, B TI EFFECT OF NUTRITION INTERVENTION ON INTERMEDIATE END-POINTS IN ESOPHAGEAL AND GASTRIC CARCINOGENESIS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Antioxidant Vitamins and Beta-Carotene in Disease Prevention CY OCT 10-12, 1994 CL BERLIN, GERMANY SP NCI, Natl Fdn Canc Res, NHLBI, Krebsforsch Int eV, Soc Free Rad Res Int, F Hoffmann La Roche Ltd DE NUTRITION INTERVENTION; VITAMINS; MINERALS; INTERMEDIATE END-POINTS; ESOPHAGEAL NEOPLASM; GASTRIC NEOPLASM ID DISEASE-SPECIFIC MORTALITY; CANCER INCIDENCE; SUPPLEMENTATION; LINXIAN; TRIALS; CHINA AB A nutrition intervention trial involving > 3000 participants was conducted in Linxian, China, where the esophageal and stomach cancer mortality rates are among the highest in the world and suspicion exists that chronic deficiencies of multiple nutrients are etiologically involved. The trial was randomized, double-blind, and placebo-controlled and tested the effect of multivitamin and multimineral supplements in reducing cancer incidence and mortality in adults with cytologically detected esophageal dysplasia. Endoscopic and cytologic examinations of samples of trial participants during the intervention allowed evaluation of intermediate endpoints in esophageal and gastric carcinogenesis, including asymptomatic histologic precancerous lesions acid early invasive cancer, epithelial proliferation, and cytologic abnormalities. Results from these ancillary studies suggest that multivitamin and multimineral supplementation may decrease proliferation and enhance cytologic reversion to nondysplasia. C1 CHINESE ACAD MED SCI,INST CANC,BEIJING 100021,PEOPLES R CHINA. INT EPIDEMIOL INST,ROCKVILLE,MD. RP TAYLOR, PR (reprint author), NCI,EXECUT PLAZA N,ROOM 211,BETHESDA,MD 20896, USA. NR 9 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1995 VL 62 IS 6 SU S BP S1420 EP S1423 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TK019 UT WOS:A1995TK01900019 ER PT J AU KRAMER, A MALONEY, EM MORGAN, OSC RODGERSJOHNSON, P MANNS, A MURPHY, EL LARSEN, S CRANSTON, B MURPHY, J BENICHOU, J BLATTNER, WA AF KRAMER, A MALONEY, EM MORGAN, OSC RODGERSJOHNSON, P MANNS, A MURPHY, EL LARSEN, S CRANSTON, B MURPHY, J BENICHOU, J BLATTNER, WA TI RISK-FACTORS AND COFACTORS FOR HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I (HTLV-I)-ASSOCIATED MYELOPATHY/TROPICAL SPASTIC PARAPARESIS (HAM/TSP) IN JAMAICA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE HTLV-I; LYMPHOMA; T-CELL; PARAPARESIS; TROPICAL SPASTIC; SEXUALLY TRANSMITTED DISEASES ID HTLV-I; BLOOD-TRANSFUSION; ATTRIBUTABLE RISK; TRANSMISSION; ANTIBODIES; INFECTION; LYMPHOMA AB Human T-cell lymphotropic virus type I (HTLV-I) has been etiologically associated with a neurologic syndrome called HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as with adult T-cell leukemia/lymphoma. The authors sought to quantify the risk in Jamaica of HAM/TSP associated with HTLV-I infection and cofactors associated with this disease among infected individuals. Between 1988 and 1989, prevalent and incident HAM/TSP patients and controls with other neurologic diseases were enrolled in a retrospective study. A second control group was composed of HTLV-I-seropositive, asymptomatic carriers in Jamaica, ascertained in a separate study conducted in 1988. Although HTLV-I seropositivity was not a component of the case definition for HAM/TSP, all 43 HAM/TSP patients were HTLV-I seropositive compared with two (4.0%) of the controls with other neurologic diseases. Given HTLV-I seropositivity, one cofactor associated with the risk of HAM/TSP was young age at initial heterosexual intercourse (odds ratio = 4.00, 95% confidence interval 1.29-12.46 for individuals aged less than or equal to 15; odds ratio = 4.26, 95% confidence interval 1.41-12.90 for individuals aged 16-17 years at initial intercourse). Among individuals who reported this early age at initial sexual intercourse, an increased risk of HAM/TSP was associated with having reported more than five lifetime sexual partners (odds ratio = 2.88, 95% confidence interval 0.90-8.70). Neither an early age at initial sexual intercourse or the number of lifetime sexual partners was a risk factor for adult T-cell leukemia/lymphoma. These data support the hypothesis that HAM/TSP is associated with sexually acquired HTLV-I infection, whereas adult T-cell leukemia/lymphoma is not. C1 NATL INST HLTH,NATL CANC INST,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20852. UNIV W INDIES,DEPT MED,KINGSTON 7,JAMAICA. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. UNIV BIELEFELD,SCH PUBL HLTH,W-4800 BIELEFELD,GERMANY. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV SEXUALLY TRANSMITTED DIS LAB RES,ATLANTA,GA 30341. UNIV W INDIES,DEPT PATHOL,KINGSTON 7,JAMAICA. RES TRIANGLE INST,WASHINGTON,DC. NATL CANC INST,DIV CANC ETIOL,EPIDEMIOL METHODS SECT,ROCKVILLE,MD. FU NCI NIH HHS [N01-CP-31006] NR 37 TC 33 Z9 36 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1995 VL 142 IS 11 BP 1212 EP 1220 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TG259 UT WOS:A1995TG25900011 PM 7485068 ER PT J AU LEBOWITZ, BD GOTTLIEB, GL AF LEBOWITZ, BD GOTTLIEB, GL TI CLINICAL RESEARCH IN THE MANAGED CARE ENVIRONMENT SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article AB The authors present the conclusions of a workshop devoted to the challenges to clinical research in the changing environment of managed care and health care reform. They identify problems and concerns with current conditions and discuss promising opportunities for new approaches to research. RP LEBOWITZ, BD (reprint author), NIMH,MENTAL DISORDERS AGING RES BRANCH,ROOM 18-105,5600 FISHERS LANE,ROCKVILLE,MD 20815, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD WIN PY 1995 VL 3 IS 1 BP 21 EP 25 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA PZ077 UT WOS:A1995PZ07700003 ER PT J AU SUNDERLAND, T AF SUNDERLAND, T TI GROWING OLDER AND WISER - COPING WITH EXPECTATIONS, CHALLENGES, AND CHANGES IN THE LATER YEARS - BILLIG,N SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Book Review RP SUNDERLAND, T (reprint author), NIMH,GERIATR PSYCHIAT SECT,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD WIN PY 1995 VL 3 IS 1 BP 87 EP 89 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA PZ077 UT WOS:A1995PZ07700014 ER PT J AU VOLPE, DA COLE, K SANDEEN, MA KOHN, EC AF VOLPE, DA COLE, K SANDEEN, MA KOHN, EC TI IN-VITRO AND IN-VIVO MYELOTOXICITY OF CAI TO HUMAN AND MURINE HEMATOPOIETIC PROGENITOR CELLS SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE CFU-GM; BFU-E; COMPARATIVE ID CALCIUM; L651582; AGENT AB Carboxyamido-triazole (CAI), an agent that targets calcium-sensitive signal transduction pathways, has both antiproliferative and antimetastatic properties, The objective of this study was to evaluate the myelotoxicity of CAI to normal human and murine hematopoietic cells, In vitro toxicity of CAI was determined by inhibition of myeloid [colony-forming unit-granulocyte/macrophage (CFU-Sm)] and erythroid [burst-forming unit-erythroid (BFU-e)] colony formation in clonal assays, The effects of oral CAI on CD2F1 mouse marrow and splenic cellularity, marrow progenitor content, and peripheral blood cell counts were assessed in relation to plasma CAI levels, In vitro, CAI caused a concentration-dependent inhibition of CFU-gm and BFU-e colonies following continuous drug exposure, Murine CFU-gm and BFU-e were inhibited > 90% by in and 15 mu g/mL CAI, respectively, However, suppression of human CFU-Sm and BFU-e did not exceed 65% at the same concentrations, In vivo, CAI reduced the number of CFU-Sm and BFU-e per femur after the initial dose and through day 4, Variations in colony inhibition paralleled changes in CAI plasma concentrations, While colony inhibition increased in vitro with escalating drug concentrations, this was not observed in vivo with additional CAI doses, The low toxicity of CAI in vivo combined with the significant difference between toxicity for human and mouse progenitors in vitro suggests a relatively low adverse potential to the bone marrow for this new signal transduction inhibitory agent. (C) 1995 Wiley-Liss, Inc. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP VOLPE, DA (reprint author), US FDA,DIV CLIN PHARMACOL,8301 MUIRKIRK RD,ROOM 2009,LAUREL,MD 20708, USA. RI Cole, Kristina/M-3922-2015 NR 13 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 1995 VL 50 IS 4 BP 277 EP 282 DI 10.1002/ajh.2830500409 PG 6 WC Hematology SC Hematology GA TF794 UT WOS:A1995TF79400008 PM 7485102 ER PT J AU KLITZ, W STEPHENS, JC GROTE, M CARRINGTON, M AF KLITZ, W STEPHENS, JC GROTE, M CARRINGTON, M TI DISCORDANT PATTERNS OF LINKAGE DISEQUILIBRIUM OF THE PEPTIDE-TRANSPORTER LOCI WITHIN THE HLA CLASS-II REGION SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; GENE CONVERSION; MHC; POLYMORPHISM; EVOLUTION; RECOMBINATION; POPULATION; VARIANTS; ALLELES AB Disequilibrium between genetic markers is expected to decline monotonically with recombinational map distance. We present evidence from the HLA class II region that seems to violate this principle. Pairwise disequilibrium values were calculated for six loci ranging in physical separation from 15 kb to 550 kb. The histocompatibility Loci DRB1, DQA1, and DQB1, located on the distal end of the class II region, behave as a single evolutionary unit within which extremely high linkage disequilibrium exists. Lower but still significant levels of disequilibrium are present between these loci and DPB1, located at the proximal edge of the HLA complex. The peptide-transporter loci TAP1 and TAP2, located in the intervening region, reveal no disequilibrium with each other and low or negligible disequilibrium with the flanking loci. The action of two genetic processes is required to account for this phenomenon: a recombinational hotspot operating between TAP1 and TAP2, to eliminate disequilibrium between these loci, and at the same time selection operating on particular combinations of alleles across the DR-DP region, to create disequilibrium in the favored haplotypes. The forces producing the patterns of disequilibrium observed here have implications for the mapping of trait loci and disease genes: markers of TAP1, for example, would give a false impression as to the influence of DPB1 on a trait known to be associated with DQB1. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP KLITZ, W (reprint author), UNIV CALIF BERKELEY,DEPT INTEGRAT BIOL,3060 VALLEY LIFE SCI,BERKELEY,CA 94720, USA. FU NIGMS NIH HHS [GM07127, GM35326] NR 44 TC 103 Z9 103 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 1995 VL 57 IS 6 BP 1436 EP 1444 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA TE655 UT WOS:A1995TE65500022 PM 8533774 ER PT J AU KAPLAN, NL WIER, BS AF KAPLAN, NL WIER, BS TI ARE MOMENT BOUNDS ON THE RECOMBINATION FRACTION BETWEEN A MARKER AND A DISEASE LOCUS TOO GOOD TO BE TRUE - ALLELIC ASSOCIATION MAPPING REVISITED FOR SIMPLE GENETIC-DISEASES IN THE FINNISH POPULATION SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LINKAGE DISEQUILIBRIUM; HAPLOTYPES; FINLAND AB In the past several years, allelic association has helped map a number of rare genetic diseases in the human genome. A commonly used upper bound on the recombination fraction between the disease gene and an associated marker is known to be biased downward, so there is the possibility that an investigator could be misled. This upper bound is based on a moment equation that can be derived within the context of a Poisson branching process, so its performance can be compared with a recently proposed likelihood bound. We show that the confidence level of the moment upper bound is much lower than expected, while the confidence level of the likelihood bound is in line with expectation. The effects of mutation at either the marker or disease locus on the upper bounds are also investigated. Results indicate that mutation is not an important force for typical mutation rates, unless the recombination fraction between the marker and disease locus is very small or the disease allele is very rare in the general population. Finally, the impact of sample size on the likelihood bound is investigated. The results are illustrated with data on 10 simple genetic diseases in the Finnish population. C1 N CAROLINA STATE UNIV, DEPT STAT, PROGRAM STAT GENET, RALEIGH, NC 27695 USA. RP KAPLAN, NL (reprint author), NIEHS, STAT & BIOMATH BRANCH, POB 12233, RES TRIANGLE PK, NC 27709 USA. FU NIGMS NIH HHS [GM45344] NR 23 TC 28 Z9 28 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 1995 VL 57 IS 6 BP 1486 EP 1498 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA TE655 UT WOS:A1995TE65500027 PM 8533779 ER PT J AU KRUG, J CHIAVELLI, M BORAWSKI, G DEVANEY, M MELANSON, A EPSTEIN, D BERSON, F LATINA, M MELAMED, S BERRY, I EVANS, C JOHNSON, E JOYNER, M KITTAY, R LINDENMEYER, A MCGEE, R PIVABOWE, D SMITH, TJ STOUT, K WAY, R WILENSKY, J TESSLER, H FROHLICHSTEIN, D ANDERSON, J JEDNOCK, N UVA, R NAIL, C SOPRYCH, K MILLMAN, K SIEGEL, H SPIGELMAN, V SPRINCZ, M BECKMAN, H CYRLIN, M FAZIO, R CZEDIK, C RITCH, R PODOLSKY, M STEINBERGER, D AGGARWALA, K AZIM, J JOHNSON, M MASINI, FR NOWACK, M NUNEZ, J STOCK, L SWEENEY, V CUNNINGHAM, J KRANTZ, J MARANAN, L TERRERO, A THEERTHAM, M SPAETH, G KATZ, LJ BECKERSHOFF, C NICHOLS, J SLAGLE, J CAPRIOLI, J SIMMONS, S STRANG, S CAPONE, M MOLINEAUX, J PETRAKIS, P SAMMARTINO, M SANDY, R WILSON, R WITTKOWSKI, D VELATHOMAS, MA HARBIN, T LEEF, D GEMMILL, M GILMAN, J MOORE, K SWORDS, R WRIGHT, J CAMPBELL, D GOMEZ, S CARLTON, S FRANK, MK LASALLE, J MAIO, M NICHOLAS, P SNIPES, C WEBER, P KAPETANSKY, F MCKINNEY, K COVER, N MOORE, D RICHMOND, WR SAVAGE, S WEISENBURGER, D CLARK, M JONES, S SIMMONS, L KLEWIN, K POWERS, J PHILLIPS, J SUCHLA, L WIPPLINGER, W BAUER, D LANGE, C SOPA, J BENCE, D GUNDERSEN, B HELT, P KAVANAGH, J RICHIE, M WOLF, C LEE, PF HSU, CT PLACHTE, S CHERRIER, K MEHU, M MINCKLER, D BAERVELDT, G BENAVENTE, A CLARK, T DELGADO, S GOODMAN, M GRIFFAY, E TRUJILLO, M ZIMMERMAN, T AREND, L LARSON, K THIELE, R VICKERS, N HERSHCLER, J DURANT, W DAVIS, M HAYMORE, D MEINERT, C STERNBERG, A AMENDLIBERCCI, D BROWN, V DODGE, J GERCZAK, C ISAACSON, M LEVINE, C MAGUIRE, M MEINERT, J NOWAKOWSKI, D TONASCIA, J TONASCIA, S HAWKINS, B BONDS, B CANNER, J CONNOR, K DICKERSIN, K GUNTHER, G THOMAS, B TU, N XU, C DEPIANO, D SLAGLE, S BARONE, L GROSS, P JACKSON, M MORGANSTERN, S STRONG, C WILENSKY, J TADELMAN, M FRIGO, D RICHTER, B THOMSON, A KURINIJ, N DUDLEY, P SURAN, A RADIUS, R LACHIN, J DUEKER, D GAASTERLAND, D KAUFMAN, P SEIGEL, D AF KRUG, J CHIAVELLI, M BORAWSKI, G DEVANEY, M MELANSON, A EPSTEIN, D BERSON, F LATINA, M MELAMED, S BERRY, I EVANS, C JOHNSON, E JOYNER, M KITTAY, R LINDENMEYER, A MCGEE, R PIVABOWE, D SMITH, TJ STOUT, K WAY, R WILENSKY, J TESSLER, H FROHLICHSTEIN, D ANDERSON, J JEDNOCK, N UVA, R NAIL, C SOPRYCH, K MILLMAN, K SIEGEL, H SPIGELMAN, V SPRINCZ, M BECKMAN, H CYRLIN, M FAZIO, R CZEDIK, C RITCH, R PODOLSKY, M STEINBERGER, D AGGARWALA, K AZIM, J JOHNSON, M MASINI, FR NOWACK, M NUNEZ, J STOCK, L SWEENEY, V CUNNINGHAM, J KRANTZ, J MARANAN, L TERRERO, A THEERTHAM, M SPAETH, G KATZ, LJ BECKERSHOFF, C NICHOLS, J SLAGLE, J CAPRIOLI, J SIMMONS, S STRANG, S CAPONE, M MOLINEAUX, J PETRAKIS, P SAMMARTINO, M SANDY, R WILSON, R WITTKOWSKI, D VELATHOMAS, MA HARBIN, T LEEF, D GEMMILL, M GILMAN, J MOORE, K SWORDS, R WRIGHT, J CAMPBELL, D GOMEZ, S CARLTON, S FRANK, MK LASALLE, J MAIO, M NICHOLAS, P SNIPES, C WEBER, P KAPETANSKY, F MCKINNEY, K COVER, N MOORE, D RICHMOND, WR SAVAGE, S WEISENBURGER, D CLARK, M JONES, S SIMMONS, L KLEWIN, K POWERS, J PHILLIPS, J SUCHLA, L WIPPLINGER, W BAUER, D LANGE, C SOPA, J BENCE, D GUNDERSEN, B HELT, P KAVANAGH, J RICHIE, M WOLF, C LEE, PF HSU, CT PLACHTE, S CHERRIER, K MEHU, M MINCKLER, D BAERVELDT, G BENAVENTE, A CLARK, T DELGADO, S GOODMAN, M GRIFFAY, E TRUJILLO, M ZIMMERMAN, T AREND, L LARSON, K THIELE, R VICKERS, N HERSHCLER, J DURANT, W DAVIS, M HAYMORE, D MEINERT, C STERNBERG, A AMENDLIBERCCI, D BROWN, V DODGE, J GERCZAK, C ISAACSON, M LEVINE, C MAGUIRE, M MEINERT, J NOWAKOWSKI, D TONASCIA, J TONASCIA, S HAWKINS, B BONDS, B CANNER, J CONNOR, K DICKERSIN, K GUNTHER, G THOMAS, B TU, N XU, C DEPIANO, D SLAGLE, S BARONE, L GROSS, P JACKSON, M MORGANSTERN, S STRONG, C WILENSKY, J TADELMAN, M FRIGO, D RICHTER, B THOMSON, A KURINIJ, N DUDLEY, P SURAN, A RADIUS, R LACHIN, J DUEKER, D GAASTERLAND, D KAUFMAN, P SEIGEL, D TI THE GLAUCOMA LASER TRIAL (GLT) AND GLAUCOMA LASER TRIAL FOLLOW-UP-STUDY .7. RESULTS SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; CLINICAL RESEARCH; PRIMARY THERAPY; TRABECULOPLASTY; CHARTS AB PURPOSE: To determine differences between the two treatment groups of the Glaucoma Laser Trial with respect to intraocular pressure, visual fields, optic disk cupping, and therapy for primary open-angle glaucoma. METHODS: The Glaucoma Laser Trial was a multicenter, randomized clinical trial designed to assess the efficacy and safety of starting treatment for primary open-angle glaucoma with argon laser trabeculoplasty vs starting with topical medication. The Glaucoma Laser Trial Follow-up Study was a follow up study of 203 of the 271 patients who enrolled in the Glaucoma Laser Trial. By the dose of the Glaucoma Laser Trial Follow-up Study, median duration of follow-up since diagnosis of primary open-angle glaucoma was seven years (maximum, nine years). RESULTS: Over the course of the Glaucoma Laser Trial and Glaucoma Laser Trial Follow-up Study, the eyes treated initially with argon laser trabeculoplasty had lower intraocular pressure and better visual field and optic disk status than their fellow eyes treated initially with topical medication, As compared to eyes initially treated with medication, eyes initially treated with laser trabeculoplasty had 1.2 mm Hg greater reduction in intraocular pressure (P < .001) and 0.6 dB greater improvement in the visual field (P < .001) from entry into the Glaucoma Laser Trial. The overall difference between eyes with regard to change in ratio of optic cup area to optic disk area from entry into the Glaucoma Laser Trial was -0.01 (P = .005), which indicated slightly more deterioration for eyes initially treated with medication. CONCLUSIONS: Initial treatment with argon laser trabeculoplasty was at least as efficacious as initial treatment with topical medication. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NEW YORK EYE & EAR INFIRM,NEW YORK,NY 10003. EMORY EYE CTR,ATLANTA,GA. OHIO STATE UNIV,COLUMBUS,OH 43210. MED COLL WISCONSIN,MILWAUKEE,WI 53226. ALBANY MED COLL,ALBANY,NY. ESTELLE DOHENY EYE FDN,LOS ANGELES,CA 90033. OCHSNER CLIN & ALTON OCHSNER MED FDN,NEW ORLEANS,LA. UNIV ARIZONA,TUCSON,AZ. JOHNS HOPKINS UNIV,CTR COORDINATING,BALTIMORE,MD. WILLS EYE HOSP & RES INST,CTR DISC STEREOPHOTOG READING,PHILADELPHIA,PA. UNIV ILLINOIS,EYE & EAR INFIRM,CTR VISUAL FIELD READING,CHICAGO,IL 60612. SINAI HOSP DETROIT,CHAIRMANS OFF,DETROIT,MI. NEI,PROJECT OFF,BETHESDA,MD 20892. NEI,COMM STEERING,BETHESDA,MD 20892. NEI,COMM EXECUT,BETHESDA,MD 20892. NEI,COMM TREATMENT EFFECTS MONITORING & ADVISORY,BETHESDA,MD 20892. NEI,COMM DESIGN & QUAL ASSURANCE,BETHESDA,MD 20892. NEI,COMM WRITING,BETHESDA,MD 20892. RP KRUG, J (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,GLT COORDINATING CTR,615 N WOLFE ST,RM 5010,BALTIMORE,MD 21205, USA. RI Dickersin, Kay/A-4576-2008 NR 24 TC 132 Z9 134 U1 0 U2 5 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 1995 VL 120 IS 6 BP 718 EP 731 PG 14 WC Ophthalmology SC Ophthalmology GA TJ657 UT WOS:A1995TJ65700003 ER PT J AU KOIVISTO, P HYYTINEN, E PALMBERG, C TAMMELA, T VISAKORPI, T ISOLA, J KALLIONIEMI, OP AF KOIVISTO, P HYYTINEN, E PALMBERG, C TAMMELA, T VISAKORPI, T ISOLA, J KALLIONIEMI, OP TI ANALYSIS OF GENETIC CHANGES UNDERLYING LOCAL RECURRENCE OF PROSTATE CARCINOMA DURING ANDROGEN DEPRIVATION THERAPY SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ALLELIC LOSS; CANCER; DELETION AB The molecular mechanisms and genetic changes that lead to the progression of prostate cancer during endocrine therapy are poorly characterized. Here, paired specimens from both untreated primary tumors and from local recurrences were collected from 10 prostate cancer patients treated by conventional androgen deprivation therapy. The genetic progression of the tumors was studied by using interphase fluorescence in situ hybridization and chromosome-specific probes. Six primary tumors (60%) and all ten recurrent tumors were aneuploid by fluorescence in situ hybridization. The recurrent tumors also showed a high degree of chromosome copy number variability from one cell to another. Increased copy number of chromosome X was particularly common in the recurrent tumors. In addition, specific high level amplification of the androgen receptor (AR) gene (Xq12) was detected in three highly aneuploid recurrent tumors. Our findings suggest that hormone-refractory prostate cancers are genetically very complex and show intratumor genetic heterogeneity. Increased copy number of chromosome X and the amplification of the androgen receptor (AR) gene may confer proliferative advantage during androgen deprivation and thus contribute to the development of recurrence. C1 UNIV TAMPA,INST MED TECHNOL,CANC GENET LAB,TAMPERE,FINLAND. NATL INST HLTH,NATL CTR HUMAN GENOME RES,BETHESDA,MD. RP KOIVISTO, P (reprint author), TAMPERE UNIV HOSP,DEPT CLIN CHEM,DIV UROL,CANC GENET LAB,POB 2000,SF-33521 TAMPERE,FINLAND. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 31 TC 43 Z9 44 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 1995 VL 147 IS 6 BP 1608 EP 1614 PG 7 WC Pathology SC Pathology GA TJ665 UT WOS:A1995TJ66500012 PM 7495286 ER PT J AU NII, A STEINGRIMSSON, E COPELAND, NG JENKINS, NA WARD, JM AF NII, A STEINGRIMSSON, E COPELAND, NG JENKINS, NA WARD, JM TI MILD OSTEOPETROSIS IN THE MICROPHTHALMIA OAK-RIDGE MOUSE - A MODEL FOR INTERMEDIATE AUTOSOMAL RECESSIVE OSTEOPETROSIS IN HUMANS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SKELETAL MUTATION; C-FOS; BONE; MICE; PROTOONCOGENE; HETEROGENEITY; OSTEOCLASTS; DEFECTS; MARKER AB Mutations at the mouse microphthalmia (mi) locus affect coat color, eye development, and mast cells. The original allele, mi, also shows severe osteopetrosis. Mice homozygous for the microphthalmia-Oak Ridge (Mi(or)) mutation are white, microphthalmic animals with retarded incisor development. To investigate whether this mutation causes osteopetrosis, we examined skeletal tissues of the Mi(or) mouse. A typical osteopetrotic lesion, accumulation of unresorbed primary spongiosa, was found at the metaphyses of long bones and at the costochondral junctions in Mi(or)/Mi(or) mice from 10 days to 37 days of age, whereas no accumulation was seen at the mid-diaphyses in these bones. The osteopetrotic conditions of Mi(or)/Mi(or) mice increased progressively during the first 5 weeks after birth. However, adult Mi(or)/Mi(or) mice 3 months or older showed improvement of the osteopetrotic condition, although the disease was not completely resolved. Ultrastructurally, osteoclasts of Mi(or)/Mi(or) mice had well developed ruffled borders. These results show that the Mi(or) mutation has milder osteopetrotic changes than the original mi mutation, a surprising observation given that both mutations affect the same functional domain of the mi protein, a basic-Helix-Loop-Helix-Zipper transcription factor. The Mi(or) phenotype resembles the intermediate autosomal recessive osteopetrosis in humans. C1 NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD. FU NCI NIH HHS [N01-CO-46000] NR 33 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 1995 VL 147 IS 6 BP 1871 EP 1882 PG 12 WC Pathology SC Pathology GA TJ665 UT WOS:A1995TJ66500036 PM 7495310 ER PT J AU Perfetti, R Rafizadeh, CM Liotta, AS Egan, JM AF Perfetti, R Rafizadeh, CM Liotta, AS Egan, JM TI Age-dependent reduction in insulin secretion and insulin mRNA in isolated islets from rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE islets of Langerhans; glucagon; somatostatin; aging ID PANCREATIC BETA-CELLS; ENVIRONMENTAL-FACTORS; GLUCOSE; RELEASE; GENE; GLUCOKINASE; POPULATION; SEQUENCE AB Aging is an etiologic factor in non-insulin-dependent diabetes mellitus. To characterize the beta-cell abnormalities that occur with age, we investigated glucose-stimulated insulin release, pancreatic insulin content, and mRNA levels for islet-specific genes in aging Wistar rats. Ten minutes after glucose stimulation, 6-mo-old islets had similar to 40% more cells secreting insulin than 24-mo-old islets (P < 0.0001); after 1 h, 67 +/- 1.0% islets from B-mo-old rats secreted insulin, compared with 51 +/- 3.5% from 24-mo-old rats (P < 0.0001). The amount of insulin secreted by each beta-cell was also less in the older animals (P < 0.0001). Despite increases in islet size (P < 0.0001) and beta-cell number (P < 0.0001) with age, whole pancreas insulin content showed that 24-mo-old pancreas had less insulin than 8-mo-old pancreas (0.61 +/- 0.06 vs. 0.84 +/- 0.08 mu g/mg pancreatic protein; P < 0.05). Finally, insulin mRNA levels declined to 50% of the newborn value in 24-mo-old islets (P < 0.0001), whereas glucagon mRNA levels showed a very modest decline with age. Somatostatin mRNA levels did not vary significantly. In summary, it appears that in Wistar rats there is a progressive decline in beta-cell activity with age. This decline may represent the biological features of the age-dependent risk of developing diabetes. RP Perfetti, R (reprint author), NIA, GERONTOL RES CTR,CLIN PHYSIOL LAB,DIABET UNIT, RM 2B02, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 30 TC 38 Z9 38 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 1995 VL 269 IS 6 BP E983 EP E990 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA TL957 UT WOS:A1995TL95700001 PM 8572206 ER PT J AU Kishore, BK Chou, CL Knepper, MA AF Kishore, BK Chou, CL Knepper, MA TI Extracellular nucleotide receptor inhibits AVP-stimulated water permeability in inner medullary collecting duct SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE intracellular calcium; phosphoinositide pathway; adenosine 3',5'-cyclic monophosphate; vasopressin; forskolin; protein kinase C; rat ID PROTEIN-KINASE-C; ION-TRANSPORT; CELLS; VASOPRESSIN; ATP; ACTIVATION; FORSKOLIN; TUBULES; PGE2 AB The P-2u class of nucleotide receptors is linked to mobilization of intracellular Ca2+ in many cell types, including the renal collecting duct cells. In the present studies, we examined the effects of nucleotides (ATP, UTP, and ADP; 10 mu M each) on the arginine vasopressin (AVP, 0.1 nM)-stimulated osmotic water permeability (P-f) in in vitro perfused terminal inner medullary collecting ducts (IMCD) of rat. ATP or UTP, when added to the bath, decreased the AVP-stimulated P-f by similar to 40%. These effects were reversible upon withdrawal of the nucleotides. However, addition of ADP to the bath or sham exchange of the bath had no significant effect on the P-f. Furthermore, ATP did not have any significant effect on the P-f stimulated either by a membrane-permeant, nonhydrolyzable adenosine 3',5'-cyclic monophosphate (cAMP) analogue [8-(4-chlorophenylthio)-cAMP, 0.1 mM] or by forskolin (1 mu M). In line with these findings, ATP decreased the AVP-stimulated cAMP levels in IMCD suspensions to similar to 68%. In addition, ATP did not exert an inhibitory effect on the AVP-stimulated P-f in the presence of calphostin C (150 nM), an inhibitor of protein kinase C. These results lead us to conclude the following: 1) agonist occupancy of the putative nucleotide receptor in the terminal IMCD causes an inhibition of AVP-stimulated P-f; and 2) this effect is due to a decrease in cellular cAMP levels, most likely resulting from activation of the phosphoinositide signaling pathway. C1 NHLBI, LKEM, BETHESDA, MD 20892 USA. NR 30 TC 82 Z9 82 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD DEC PY 1995 VL 269 IS 6 BP F863 EP F869 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA TM209 UT WOS:A1995TM20900013 PM 8594881 ER PT J AU Terris, J Ecelbarger, CA Marples, D Knepper, MA Nielsen, S AF Terris, J Ecelbarger, CA Marples, D Knepper, MA Nielsen, S TI Distribution of aquaporin-4 water channel expression within rat kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE collecting duct; water permeability; MIWC channel; aquaporins; aquaporin-3; aquaporin-2 ID MEDULLARY COLLECTING DUCT AB The aquaporins are a family of transmembrane proteins that function as molecular water channels. Recently, a mercurial-insensitive water channel [MIWC or aquaporin-4 (AQP4)] has been cloned, and its mRNA was found to be expressed strongly in kidney inner medulla and several nonrenal tissues. We prepared affinity-purified polyclonal antipeptide antibodies to AQP4 to define the regional distribution and cellular location of this water channel within the kidney. Immunoblotting of membrane fractions from different regions of the kidney revealed strongest expression in the base of the renal inner medulla, with detectable levels also in the inner medullary tip, but little or no expression in the outer medulla or cortex. Immunocytochemistry (light microscopy) revealed renal AQP4 labeling exclusively in the collecting duct principal cells, chiefly in the proximal two-thirds of the inner medullary collecting duct (IMCD). Little or no expression was seen in the outer medullary and cortical collecting ducts. Immunoelectron microscopy demonstrated AQP4 labeling of the basolateral membrane of IMCD cells, with relatively little labeling of intracellular vesicles. Differential centrifugation of inner medullary homogenates also revealed a lack of distribution to the vesicle-enriched fraction, which contains the vasopressin-regulated water channel, aquaporin-2. In contrast to aquaporin-2 and aquaporin-3, water restriction of rats did not increase the level of AQP4 expression. These results suggest a possible role for AQP4 in the basolateral exit of water from the IMCD. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. AARHUS UNIV, INST ANAT, DEPT CELL BIOL, DK-8000 AARHUS, DENMARK. FU NIDDK NIH HHS [DK-08832-02] NR 18 TC 222 Z9 226 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD DEC PY 1995 VL 269 IS 6 BP F775 EP F785 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA TM209 UT WOS:A1995TM20900003 PM 8594871 ER PT J AU DOUDET, D HOMMER, D HIGLEY, JD ANDREASON, PJ MONEMAN, R SUOMI, SJ LINNOILA, M AF DOUDET, D HOMMER, D HIGLEY, JD ANDREASON, PJ MONEMAN, R SUOMI, SJ LINNOILA, M TI CEREBRAL GLUCOSE-METABOLISM, CSF 5-HIAA LEVELS, AND AGGRESSIVE-BEHAVIOR IN RHESUS-MONKEYS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CEREBROSPINAL-FLUID MONOAMINE; 5-HYDROXYINDOLEACETIC ACID; RAT; SEROTONIN; INVOLVEMENT; ANESTHESIA; ETHANOL; BRAIN AB Objective: Considerable evidence suggests that low concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in CSF are associated with a history of aggressive behavior in both human and nonhuman primates. The purpose of this investigation was to examine the relationships among CSF 5-HIAA concentration, history of aggressive behavior, and cerebral glucose metabolism in a group of nonhuman primates whose CSF 5-HIAA had been sampled several times over the preceding 2 years and whose social behavior had been observed since birth. Method: The subjects were nine adult male rhesus monkeys studied under isoflurane anesthesia. Cerebral glucose utilization was measured by [F-18]fluorodeoxyglucose positron emission tomography. Aggressiveness ratings were made by a primatologist who had had frequent contact with the animals over several years. Results: There was a significant negative correlation between ratings of aggressive behavior and CSF 5-HIAA concentrations. There was also a negative correlation between the dose of pentobarbital required to induce anesthesia and level of CSF 5-HIAA. Moreover, there were significant negative correlations between CSF 5-HIAA levels and both whole brain glucose utilization and regional glucose utilization in the orbital-frontal cortex. Conclusions: These results suggest that both increased aggressiveness and low concentrations of CSF 5-HIAA are associated with higher brain glucose metabolism in rhesus monkeys tinder standardized anesthesia. Aggressive nonhuman primates with low CSF 5-HIAA concentrations may have ''innate'' tolerance toward functional gamma-aminobutyric acid A receptor agonists such as pentobarbital, isoflurane, and possibly alcohol. C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. NR 32 TC 79 Z9 81 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 1995 VL 152 IS 12 BP 1782 EP 1787 PG 6 WC Psychiatry SC Psychiatry GA TG924 UT WOS:A1995TG92400015 PM 8526246 ER PT J AU Torrey, EF AF Torrey, EF TI Jails and prisons - America's new mental hospitals SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material RP Torrey, EF (reprint author), NIMH,NEUROPSYCHIAT RES HOSP,WASHINGTON,DC 20032, USA. NR 5 TC 90 Z9 97 U1 1 U2 4 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 1995 VL 85 IS 12 BP 1611 EP 1613 DI 10.2105/AJPH.85.12.1611 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TK931 UT WOS:A1995TK93100002 PM 7503330 ER PT J AU KrebsSmith, SM Cook, DA Subar, AF Cleveland, L Friday, J AF KrebsSmith, SM Cook, DA Subar, AF Cleveland, L Friday, J TI US adults' fruit and vegetable intakes, 1989 to 1991: A revised baseline for the Healthy People 2000 objective SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NUTRITION AB Objectives. This study provides revised baseline data for the Healthy People 2000 objective related to fruit and vegetable intakes, accounting for fruits and vegetables from all sources and measuring servings in a manner consistent with current dietary guidance. Methods. Dietary data from 8181 adults in the US Department of Agriculture's 1989-1991 Continuing Surveys of Food Intakes by Individuals were examined. All foods were disaggregated into their component ingredients; all fruit and vegetable ingredients were assigned specific weights to correspond to a serving as defined by current dietary guidance materials; and the number of servings was tallied. Results. While mean intakes of fruits and vegetables-4.3 servings per day-were not far from the Year 2000 objective, only 32% of American adults' intakes met the objective; When more stringent standards were set either to compensate for higher 'calorie levels or to achieve the balance between fruits and vegetables suggested in current guidance, only 24% and 12%, respectively, met the recommendations. Conclusions. These results suggest: a need to develop strategies for overcoming barriers to eating fruits and vegetables. C1 USDA,HYATTSVILLE,MD. RP KrebsSmith, SM (reprint author), NCI,DCPC,EXECUT PLAZA N,RM 313,6130 EXECUT BLVD,MSC 7344,BETHESDA,MD 20892, USA. NR 25 TC 156 Z9 163 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 1995 VL 85 IS 12 BP 1623 EP 1629 DI 10.2105/AJPH.85.12.1623 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TK931 UT WOS:A1995TK93100007 PM 7503335 ER PT J AU Simpson, KN Biddle, AK Rabinovich, NR AF Simpson, KN Biddle, AK Rabinovich, NR TI A model for estimating the impact of changes in children's vaccines SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES; MEASLES; IMMUNIZATION; PERTUSSIS; COSTS; BENEFITS; RISKS AB Objectives. To assist in strategic planning for the improvement of vaccines and vaccine programs, an economic model was developed and tested that estimates the potential impact of vaccine innovations on health outcomes and costs associated with vaccination and illness. Methods. A multistep, iterative process of data extraction/integration was used to develop the model and the scenarios. Parameter replication, sensitivity analysis, and expert review were used to validate the model. Results. The greatest impact on the improvement of health is expected to result from the production of less reactogenic vaccines that require fewer inoculations for immunity. The greatest economic impact is predicted from improvements that decrease the number of inoculations required. Conclusions. Scenario analysis may be useful for integrating health outcomes and economic data into decision making. For childhood infections, this analysis indicates that large cost savings can be achieved in the future if we can improve vaccine efficacy so that the number of required inoculations is reduced. Such an improvement represents a large potential ''payback'' for the United States and might benefit other countries. C1 NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. RP Simpson, KN (reprint author), UNIV N CAROLINA,SCH PUBL HLTH,DEPT HLTH POLICY & ADM,CAMPUS BOX 7400,CHAPEL HILL,NC 27599, USA. OI Biddle, Andrea/0000-0003-0273-7439 FU NIMHD NIH HHS [263-MD-14293] NR 36 TC 2 Z9 2 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 1995 VL 85 IS 12 BP 1666 EP 1672 DI 10.2105/AJPH.85.12.1666 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TK931 UT WOS:A1995TK93100014 PM 7503342 ER PT J AU OGNIBENE, FP AF OGNIBENE, FP TI PNEUMOCYSTIS-CARINII PNEUMONIA - A MAJOR COMPLICATION OF IMMUNOSUPPRESSIVE THERAPY IN PATIENTS WITH WEGENERS GRANULOMATOSIS - REPLY SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter RP OGNIBENE, FP (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC PY 1995 VL 152 IS 6 BP 2202 EP 2202 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA TH533 UT WOS:A1995TH53300067 ER PT J AU BROWN, ML HOUN, F SICKLES, EA KESSLER, LG AF BROWN, ML HOUN, F SICKLES, EA KESSLER, LG TI SCREENING MAMMOGRAPHY IN COMMUNITY PRACTICE - POSITIVE PREDICTIVE VALUE OF ABNORMAL FINDINGS AND YIELD OF FOLLOW-UP DIAGNOSTIC PROCEDURES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID MEDICAL AUDIT; BREAST-CANCER; LESIONS; PROGRAM AB OBJECTIVE. The purpose of this study was to gather from 50 community mammography practices that were included in the National Survey of Mammography Facilities data concerning abnormal findings on screening mammograms to determine the frequency of various recommendations made for patients who had abnormal findings and to compare these recommendations with the frequency with which the procedures were actually performed. We also determined the positive predictive value of screening mammograms (the number of cancers detected per 100 abnormal findings) and the yield (the number of cancers detected per 100 procedures done) of various diagnostic procedures done because of abnormal findings. MATERIALS AND METHODS, We identified 1717 screening mammograms done in the last half of 1991 that had abnormal findings, Radiologic recommendations and follow-up procedures, including repeat standard (screening) mammography, additional mammographic views, sonography, clinical breast examination, needle aspiration, needle biopsy, and open biopsy, were identified for all of the cases from the radiologic records, and follow-up data were obtained from referring physicians. The positive predictive value and yield in the National Survey of Mammography Facilities were compared with data from the mammography screening practice of the University of California at San Francisco (UCSF), a facility noted for its clinical efficiency. RESULTS. We estimate that 11% of all screening mammograms resulted in a recommendation for further diagnostic procedures. These 1717 mammograms with abnormal findings led to the following recommendations and procedures: repeat standard (screening) mammography, 610 (recommended)/635 (performed); additional mammographic views, 785/707; sonography, 400/345; biopsy, 189/229; and needle aspiration, 21/51. More procedures were done than were recommended in some cases because the results of certain procedures often led to the performance of other, additional procedures. The positive predictive value for screening examinations with abnormal findings was 3.5%, and the yield for open biopsy was 21%. In the UCSF data base, the positive predictive value for examinations with abnormal findings was 10%, and the yield for open biopsy was 34%. CONCLUSION. The positive predictive value for examinations with abnormal findings and the yield for diagnostic procedures performed as a result of abnormal findings in 50 community radiologic facilities were higher than those reported in some earlier studies, a fact that raised concern about the induced cost of screening mammography. However, these values were low compared with those in the UCSF data base. This fact was particularly true of repeat standard (screening) mammography. C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20850. UNIV CALIF SAN FRANCISCO,MED CTR,DEPT RADIOL,SAN FRANCISCO,CA 94143. RP BROWN, ML (reprint author), NCI,APPL RES BRANCH,EPN-313,BETHESDA,MD 20892, USA. NR 22 TC 132 Z9 132 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1995 VL 165 IS 6 BP 1373 EP 1377 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TF768 UT WOS:A1995TF76800013 PM 7484568 ER PT J AU Klein, HG AF Klein, HG TI Allogeneic transfusion risks in the surgical patient SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT Consensus Conference on Blood Management - Surgical Practice Guidelines CY JAN 12-14, 1995 CL DALLAS, TX SP Ortho Biotech Inc ID PERIOPERATIVE BLOOD-TRANSFUSION; HUMAN-IMMUNODEFICIENCY-VIRUS; POSTOPERATIVE INFECTION; CANCER RECURRENCE; COLORECTAL-CANCER; HOMOLOGOUS BLOOD; SURGERY; DISEASE; COLON; ACTIVATION AB The risk of blood transfusion-associated complications has been reduced in the past 10 years through technical advances in testing of blood, viral inactivation of noncellular blood components, enforcement of stringent donor selection criteria, and the use of alternatives to allogeneic transfusion. Even so, a zero-risk blood supply is unfeasible. The general public perceives infectious complications to be the most significant risk: although the greatest fear is associated with transmission of human immunodeficiency virus (HIV), at least three hepatitis viruses are transmissible by all blood components. Human immunodeficiency virus accounts for <20 cases per year of transfusion-related acquired immunodeficiency syndrome in the United States. The three important noninfectious complications are alloimmunization, which is common but clinically insignificant; immunosuppression, the clinical significance of which is controversial; and graft-versus-host disease, a lethal complication most likely to affect patients who are immunosuppressed, have cancer, or are recipients of bone marrow transplants. RP Klein, HG (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,ROOM 1C-711,BETHESDA,MD 20892, USA. NR 46 TC 47 Z9 48 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD DEC PY 1995 VL 170 IS 6A SU S BP S21 EP S26 DI 10.1016/S0002-9610(99)80054-3 PG 6 WC Surgery SC Surgery GA TQ511 UT WOS:A1995TQ51100004 PM 8546242 ER PT J AU KAPADIA, SB ROMAN, LN KINGMA, DW JAFFE, ES FRIZZERA, G AF KAPADIA, SB ROMAN, LN KINGMA, DW JAFFE, ES FRIZZERA, G TI HODGKINS-DISEASE OF WALDEYERS-RING - CLINICAL AND HISTOIMMUNOPHENOTYPIC FINDINGS AND ASSOCIATION WITH EPSTEIN-BARR-VIRUS IN 16 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE HODGKINS DISEASE; WALDEYERS RING; EPSTEIN-BARR VIRUS ID REED-STERNBERG CELLS; LYMPHOMA LENNERTS LYMPHOMA; SMALL NUCLEAR-RNA; MONOCLONAL-ANTIBODIES; LYMPHOPROLIFERATIVE DISORDERS; INSITU HYBRIDIZATION; MALIGNANT-LYMPHOMAS; EMBEDDED TISSUES; VIRAL GENOMES; EXPRESSION AB Waldeyer's ring is an uncommon, rarely reported primary site for Hodgkin's disease. We report a series of 16 such cases culled from the files of the Armed Forces Institute of Pathology and the National Cancer Institute. The patients' median age was 41 years (range, 14-74), and they presented with airway obstruction or unilateral tonsillar enlargement. The disease was localized to the Waldeyer's ring (stage I) in 46% of patients and extended to the cervical lymph nodes (stage II) in 39% and to the spleen (stage LII) in 15%. Local radiation therapy, with or without chemotherapy, obtained a complete response in all but two patients. There was local recurrence in one patient and distant spread in three others. All patients for whom follow-up is available are alive without evidence of disease at 9 to 216 months (median, 20 months) except two who died of widespread Hodgkin's disease and two others who died of other causes. Histologically, eight cases were classified as mixed cellularity type (50%), four as nodular sclerosis (25%), and one as lymphocyte predominance, nodular (LPn; 6.3%); three others that showed interfollicular involvement were unclassified (18.7%). The Reed-Sternberg (RS) and atypical mononuclear cells in most cases of mixed cellularity and interfollicular types and all cases of nodular sclerosis had the classic immunophenotype (CD45-, CD20- and/or CD45RO -, CD15 + and/or CD30+). In the single case of LPn, they were of B-cell lineage (CD45+, CD20+, CD45RO-, CD15-, CD30-). In situ hybridization performed on routinely processed sections revealed Epstein-Barr virus (EBV) EBER1 mRNA in RS cells of eight of 12 cases studied (67%) only in mixed cellularity and nodular sclerosis, but not in LPn. We conclude that, however rarely, Hodgkin's disease of typical morphology and immunophenotype can originate in Waldeyer's ring. The incidence of EBV detection in the RS cells in our study is greater than that usually seen in nodal Hodgkin's disease in the United States. The greater prevalence of EBV-related Hodgkin's disease at this site is probably a reflection of the fact that the Waldeyer's ring is a reservoir for EBV. C1 ARMED FORCES INST PATHOL,DEPT OTOLARYNG PATHOL,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,DEPT HEMATOPATHOL,WASHINGTON,DC 20306. NCI,PATHOL LAB,DIV HEMATOPATHOL,BETHESDA,MD 20892. NR 59 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 1995 VL 19 IS 12 BP 1431 EP 1439 DI 10.1097/00000478-199512000-00010 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA TG926 UT WOS:A1995TG92600010 PM 7503365 ER PT J AU Lenfant, C Savage, PJ AF Lenfant, C Savage, PJ TI The early natural history of atherosclerosis and hypertension in the young: National Institutes of Health Perspectives SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT Bogalusa Heart Study 20th Anniversary Symposium CY APR 27-28, 1994 CL NEW ORLEANS, LA DE child; adolescence; cardiovascular disease; hypertension ID RISK-FACTORS; OVERWEIGHT; CHILDREN; DISEASE; ADULTS; CARDIA AB Atherosclerotic cardiovascular disease begins decades before its clinical manifestations first appear, Early detection may offer the best chance for prevention, The National Heart, Lung, and Blood Institute has sponsored several population studies that have described the development of cardiovascular disease risk factors and their relationship to the emergence of early atherosclerotic lesions. Clinical trials are underway testing interventions to lower risk factors in the young. Guidelines for clinicians have been promulgated, Advances in molecular biology and noninvasive imaging techniques will provide new opportunities to explore the interaction of genetic and environmental factors in the initiation of cardiovascular disease. In the future, individuals at high risk for progression of atherosclerosis may be identified earlier, when prevention will be more successful. C1 NHLBI,BETHESDA,MD 20892. NR 16 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD DEC PY 1995 VL 310 SU 1 BP S3 EP S7 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA TM072 UT WOS:A1995TM07200004 PM 7503121 ER PT J AU GORELICK, DA AF GORELICK, DA TI ALCOHOL AND ALCOHOL-PROBLEMS - EDWARDS,G, PETERS,TJ SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Book Review C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. RP GORELICK, DA (reprint author), NIDA,TREATMENT BRANCH,INTRAMURAL RES PROGRAM,LEXINGTON,KY 40583, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD WIN PY 1995 VL 4 IS 1 BP 95 EP 96 PG 2 WC Substance Abuse SC Substance Abuse GA QE516 UT WOS:A1995QE51600013 ER PT J AU Milman, G AF Milman, G TI Biological mechanisms of HIV sexual transmission SO ANNALS OF MEDICINE LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; SEMEN; INFECTION; TYPE-1 RP Milman, G (reprint author), NIAID,DIV AIDS,SOLAR BLDG,ROOM 2C06,BETHESDA,MD 20892, USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0785-3890 J9 ANN MED JI Ann. Med. PD DEC PY 1995 VL 27 IS 6 BP 621 EP 623 DI 10.3109/07853899509019246 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA TL687 UT WOS:A1995TL68700001 PM 8652139 ER PT J AU Deuschl, G Toro, C Matsumoto, J Hallett, M AF Deuschl, G Toro, C Matsumoto, J Hallett, M TI Movement-related cortical potentials in writer's cramp SO ANNALS OF NEUROLOGY LA English DT Article ID SUPPLEMENTARY MOTOR AREA; RECIPROCAL INHIBITION; FOCAL DYSTONIA; HAND CRAMPS; FINGER MOVEMENTS; SCALP; MUSCLES; TOPOGRAPHY; PHYSIOLOGY; RESPONSES AB Movement-related cortical potentials in response to simple, self-paced, brisk index finger abduction movements were recorded in patients with simple and complex writer's cramp and compared with those of age-matched control subjects. Analysis of the movement-related cortical potential waveforms showed that the Bereitschaftspotential, the peak of the negative slope, and the frontal peak of the motor potential did not differ in the two groups, except for the average amplitude of the early part of the negative-slope peak, which was decreased in the patient group during the interval of 300 to 200 msec prior to electromyographic onset. This finding was restricted to the electrodes overlying the contralateral and midline central electrodes. Movement-related cortical potentials from patients and control subjects could be equally accounted for by a four-dipole source model with sources located in the contralateral and ipsilateral sensorimotor regions and the supplementary motor area. There was a trend for a reduction in the strength of the sensorimotor sources active during the premotor period in the patient group, but the difference did not reach a significant level for any individual source. No differences were found between the movement-related cortical potentials elicited by movements of the affected and unaffected hand, or between those of patients with simple or complex hand cramps. This result suggests a deficiency of contralateral motor cortex activation just prior to the initiation of voluntary movements in patients with focal dystonia. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,BETHESDA,MD 20892. RI Deuschl, Gunther/A-7986-2010; Abbott, J./B-2976-2008 OI Abbott, J./0000-0001-6468-7284 NR 30 TC 93 Z9 93 U1 0 U2 4 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1995 VL 38 IS 6 BP 862 EP 868 DI 10.1002/ana.410380606 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TK287 UT WOS:A1995TK28700005 PM 8526458 ER PT J AU PascualLeone, A Wassermann, EM Sadato, N Hallett, M AF PascualLeone, A Wassermann, EM Sadato, N Hallett, M TI The role of reading activity on the modulation of motor cortical outputs to the reading hand in Braille readers SO ANNALS OF NEUROLOGY LA English DT Article ID FREQUENCY-DISCRIMINATION TASK; ADULT OWL MONKEYS; CORTEX; REPRESENTATION; REORGANIZATION; PLASTICITY; MECHANISMS; MAMMALS AB We studied the cortical motor output maps of the first dorsal interosseous (FDI) of both hands and the abductor digiti minimi of the reading hand in 6 blind proficient Braille readers. The maps were generated using transcranial magnetic stimulation. We compared the maps obtained on a day in which they worked as Braille proofreaders (reading Braille for approximately 6 hours) with the maps obtained on a day they took off from work. On the work day, the maps for the FDI of the reading hand were significantly larger after the working shift than in the morning after having been off work for 2 days. These changes were not seen for the same muscle on the day off work or on any of the 2 days in the other two muscles studied. These results illustrate the rapid modulation in motor cortical outputs in relation to preceding activity and emphasize the importance of precise timing in studies of the neurophysiological correlates of skill acquisition. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. CSIC,INST RAMON Y CAJAL,E-28006 MADRID,SPAIN. RP PascualLeone, A (reprint author), UNIV VALENCIA,DEPT FISIOL,UNIDAD NEUROBIOL,AVDA BLASCO IBANEZ 17,E-46010 VALENCIA,SPAIN. NR 27 TC 96 Z9 99 U1 1 U2 6 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1995 VL 38 IS 6 BP 910 EP 915 DI 10.1002/ana.410380611 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TK287 UT WOS:A1995TK28700010 PM 8526463 ER PT J AU Kaler, SG Buist, NRM Holmes, CS Goldstein, DS Miller, RC Gahl, WA AF Kaler, SG Buist, NRM Holmes, CS Goldstein, DS Miller, RC Gahl, WA TI Early copper therapy in classic Menkes disease patients with a novel splicing mutation SO ANNALS OF NEUROLOGY LA English DT Article ID KINKY-HAIR SYNDROME; CANDIDATE GENE; DEFICIENCY; TRANSPORT; JUNCTIONS; ENCODES; MUTANTS; DEFECT; MOUSE AB To correlate genotype with response to early copper histidine therapy in Menkes disease, an X-linked disorder of copper transport, we performed mutational analysis in 2 related males who began treatment at the age of 10 days and prenatally at 32 weeks' gestation, respectively. A G to T transversion at the -1 exonic position of a splice donor site was identified, predicting a glutamine to histidine substitution at codon 724 of the Menkes copper-transporting ATPase gene. The Q724H mutation disrupts proper splicing and generates five mutant transcripts that skip from one to four exons. None of these transcripts is predicted to encode a functional copper transport protein. Copper histidine treatment normalized circulating copper and ceruloplasmin levels but did not improve the baseline deficiency of dopamine-beta-hydroxylase, a copper-dependent enzyme. At the age of 36 months, the first patient was living and had neurodevelopmental abilities ranging from 10 to 15 months. The second patient also showed delayed neurodevelopment and died of pulmonary complications at the age of 51/2 months. We conclude that early copper histidine therapy does not normalize neurological outcome in patients with the Q724H splicing mutation, and suggest that preservation of some residual Menkes ATPase activity may be a general prerequisite for significant clinical efficacy from such treatment. C1 NICHHD, HUMAN GENET BRANCH, UMAN BIOCHEM GENET SECT, BETHESDA, MD 20892 USA. GEORGE WASHINGTON UNIV, WASHINGTON, DC USA. CHILDRENS NATL MED CTR, DEPT MED GENET, WASHINGTON, DC 20010 USA. CHILDRENS NATL MED CTR, DEPT PEDIAT, WASHINGTON, DC 20010 USA. OREGON HLTH SCI UNIV, DEPT PEDIAT, PORTLAND, OR 97201 USA. NATL NAVAL MED CTR, DIV MATERNAL FETAL MED, BETHESDA, MD USA. RP Kaler, SG (reprint author), NINCDS, CLIN NEUROSCI BRANCH, BLDG 10, ROOM 5N-214, 10 CTR DR MSC 1424, BETHESDA, MD 20892 USA. NR 41 TC 56 Z9 56 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1995 VL 38 IS 6 BP 921 EP 928 DI 10.1002/ana.410380613 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TK287 UT WOS:A1995TK28700012 PM 8526465 ER PT J AU LUDLOW, CL YAMASHITA, T SCHULZ, GM DELEYIANNIS, FWB AF LUDLOW, CL YAMASHITA, T SCHULZ, GM DELEYIANNIS, FWB TI ABNORMALITIES IN LONG-LATENCY RESPONSES TO SUPERIOR LARYNGEAL NERVE-STIMULATION IN ADDUCTOR SPASMODIC DYSPHONIA SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE ADDUCTOR SPASMODIC DYSPHONIA; SENSORY STIMULATION; SUPERIOR LARYNGEAL NERVE ID BLINK REFLEX; PARKINSONS-DISEASE; MOVEMENT-DISORDERS; SPASTIC DYSPHONIA; GLOTTIC CLOSURE; EXCITABILITY; DYSTONIA; PATIENT; NUCLEUS; TREMOR AB Sensorimotor responses to repeated electrical stimulation of the superior laryngeal nerve were compared in 8 patients with adductor spasmodic dysphonia (ADSD) and 11 normal controls to determine if adductor response disinhibition occurred in ADSD. Pairs of electrical pulses were presented at interstimulus intervals varying from 100 to 5,000 milliseconds (ms). Three responses were measured in thyroarytenoid muscles: ipsilateral R1 responses at 17 ms and ipsilateral and contralateral R2 responses between 60 and 75 ms. Conditioned response characteristics, the percent occurrence and percentage amplitude of initial responses, were measures of response inhibition. As a group, the patients had reduced response inhibition: their conditioned ipsilateral R1 response amplitudes were increased, as was the frequency of their conditioned contralateral muscle responses (p less than or equal to .002) compared to normal. However, the patients' initial responses were normal in latency and frequency characteristics, demonstrating that the brain stem mechanisms for these responses were intact. These results suggest a central disinhibition of laryngeal responses to sensory input in ADSD. RP LUDLOW, CL (reprint author), NIDCD,DIV INTRAMURAL RES,VOICE & SPEECH SECT,BLDG 10,ROOM 5D38,10 CTR DR MSC 1416,BETHESDA,MD 20892, USA. OI Schulz, Geralyn/0000-0003-3831-8105; Ludlow, Christy/0000-0002-2015-6171 NR 29 TC 38 Z9 38 U1 1 U2 4 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD DEC PY 1995 VL 104 IS 12 BP 928 EP 935 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA TJ663 UT WOS:A1995TJ66300003 PM 7492063 ER PT J AU GEBER, A HITCHCOCK, CA SWARTZ, JE PULLEN, FS MARSDEN, KE KWONCHUNG, KJ BENNETT, JE AF GEBER, A HITCHCOCK, CA SWARTZ, JE PULLEN, FS MARSDEN, KE KWONCHUNG, KJ BENNETT, JE TI DELETION OF THE CANADIDA-GLABRATA ERG3 AND ERG11 GENES - EFFECT ON CELL VIABILITY, CELL-GROWTH, STEROL COMPOSITION, AND ANTIFUNGAL SUSCEPTIBILITY SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CANDIDA-ALBICANS; SACCHAROMYCES-CEREVISIAE; AZOLE-RESISTANT; LANOSTEROL 14-ALPHA-DEMETHYLASE; SEQUENCE; CYTOCHROME-P450; MUTANTS; DEMETHYLASE; CLONING; YEAST AB We have cloned and sequenced the structural genes encoding the Delta(5,6) sterol desaturase (ERG3 gene) and the 14 alpha-methyl sterol demethylase (ERG11 gene) from Candida glabrata L5 (leu2). Single and double mutants of these genes were created by gene deletion, The phenotypes of these mutants, including sterol profiles, aerobic viabilities, antifungal susceptibilities, and generation times, were studied, Strain L5D (erg3 Delta::LEU2) accumulated mainly ergosta-7,22-dien-3 beta-ol, was aerobically viable, and remained susceptible to antifungal agents but had a slower generation time than its parent strain, L5LUD (LEU2 erg11 Delta::URA3) strains required medium supplemented with ergosterol and an anaerobic environment for growth, A spontaneous aerobically viable mutant, L5LUD40R (LEU2 erg11 Delta::URA3), obtained from L5LUD (LEU2 erg11 Delta::URA3), was found to accumulate lanosterol and obtusifoliol, was resistant to azole antifungal agents, demonstrated some increase in resistance to amphotericin B, and exhibited a 1.86-fold increase in generation time in comparison with L5 (leu2). The double-deletion mutant L5DUD61 (erg3 Delta::LEU2 erg11 Delta::URA3) was aerobically viable, produced mainly 14 alpha-methyl fecosterol, and had the same antifungal susceptibility pattern as L5LUD40R (LEU2 erg11 Delta::URA3), and its generation time was threefold greater than that of L5 (leu2). Northern (RNA) analysis revealed that the single-deletion mutants had a marked increase in message for the undeleted ERG3 and ERG11 genes. These results indicate that differences in antifungal susceptibilities and the restoration of aerobic viability exist between the C.glabrata ergosterol mutants created in this study and those sterol mutants with similar genetic lesions previously reported for Saccharomyces cerevisiae. C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20037. PFIZER LTD,CENT RES,SANDWICH CT13 9NJ,KENT,ENGLAND. RP GEBER, A (reprint author), NIAID,CLIN INVEST LAB,BLDG 10,11C304,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Pullen, Frank/B-7552-2012 NR 36 TC 112 Z9 120 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 1995 VL 39 IS 12 BP 2708 EP 2717 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TH293 UT WOS:A1995TH29300023 PM 8593007 ER PT J AU BUCKHEIT, RW KINJERSKI, TL FLIAKASBOLTZ, V RUSSELL, JD STUP, TL PALLANSCH, LA BROUWER, WG DAO, DC HARRISON, WA SCHULTZ, RJ BADER, JP YANG, SS AF BUCKHEIT, RW KINJERSKI, TL FLIAKASBOLTZ, V RUSSELL, JD STUP, TL PALLANSCH, LA BROUWER, WG DAO, DC HARRISON, WA SCHULTZ, RJ BADER, JP YANG, SS TI STRUCTURE-ACTIVITY AND CROSS-RESISTANCE EVALUATIONS OF A SERIES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-SPECIFIC COMPOUNDS RELATED TO OXATHIIN CARBOXANILIDE SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; NONNUCLEOSIDE INHIBITORS; ANTIVIRAL ACTIVITY; TIBO DERIVATIVES; HIV-1-SPECIFIC INHIBITORS; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; NATURAL-PRODUCTS; VIRAL RESISTANCE; BINDING-SITE AB A series of compounds related to the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) oxathiin carboxanilide (UC84) were evaluated for activity against the human immunodeficiency virus (HIV) to determine structural requirements for anti-HN activity, Twenty-seven compounds representative of the more than 400 Uniroyal Chemical Company (UC) compounds were evaluated for structure-activity relationships. Several of the compounds evaluated were highly active, with 50% effective concentrations in the nanomolar range and therapeutic indices of > 1,000. Highly synergistic anti-HIV activity was observed for each compound when used in combination with 3'-azido-3'-deoxythymidine; additive to slightly synergistic interactions were observed with the compounds used in combination with dideoxycytidine. In combination with the NNRTI costatolide, only UC38 synergistically inhibited HIV type 1. Residues in the RT which, when mutated, impart resistance to the carboxanilide compounds were defined by evaluation of the UC compounds against a panel of NNRTI-resistant virus isolates selected in cell culture, against virus variants with site-directed mutations, and against RTs containing defined single amino acid changes. The mutations included changes in RT amino acids 100, 101, 103, 106, 108, and 181. The results with isolates selected in cell culture indicate that the carboxanilide compounds interact with the RT at two vulnerable sites, selecting UC resistant virus isolates,vith the Y-to-C mutation at position 181 (Y181C) or the L100I substitution. A resistant virus isolate containing both Y181C and K101E amino acid changes and another with both Y181C and V106A mutations were isolated. In combination with calanolide A, an NNRTI which retains activity against virus isolates with the single Y181C mutation, UC10 rapidly selected a virus isolate,vith the K103N mutation. The merits of selecting potential candidate anti-HIV agents to be used in rational combination drug design as part of an armamentarium of highly active anti-HIV compounds are discussed. C1 UNIROYAL CHEM CO LTD,GUELPH,ON,CANADA. NCI,ANTIVIRAL EVALUAT BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,ANTIVIRAL EVALUAT BRANCH,BETHESDA,MD 20892. RP BUCKHEIT, RW (reprint author), FREDERICK RES CTR,SO RES INST,VIROL RES GRP,431 AVIAT WAY,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CM-37818] NR 54 TC 69 Z9 69 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 1995 VL 39 IS 12 BP 2718 EP 2727 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TH293 UT WOS:A1995TH29300024 PM 8593008 ER PT J AU BLANEY, SM DANIEL, MJ HARKER, AJ GODWIN, K BALIS, FM AF BLANEY, SM DANIEL, MJ HARKER, AJ GODWIN, K BALIS, FM TI PHARMACOKINETICS OF LAMIVUDINE AND BCH-189 IN PLASMA AND CEREBROSPINAL-FLUID OF NONHUMAN-PRIMATES SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MODEL AB 2'-Deoxy-3'-thiacytidine is a dideoxycytidine analog with a sulfur in place of the 3' carbon of the ribose. There are two enantiomeric forms of the compound, both of which inhibit human immunodeficiency virus type 1 and 2 replication in vitro. However, the (-) enantiomer (lamivudine) appears to be significantly less cytotoxic to uninfected lymphocytes than is the (+) enantiomer. Lamivudine has entered initial clinical trials, and the present study was designed to describe the pharmacokinetic behavior of this compound in both plasma and cerebrospinal fluid (CSF) of primates. Lamivudine was administered as an intravenous bolus dose of 20 mg/kg to five nonhuman primates, and plasma and CSF (ventricular and lumbar) were sampled at frequent intervals for 24 h after administration. Urine samples were also obtained from two animals. The same dose of the racemate (BCH-189) was administered to one animal. The drug was quantitated in CSF and plasma with a reverse-phase high-pressure liquid chromatography technique. Elimination of lamivudine from plasma was biexponential, with a mean alpha phase half-life of 5.4 min, a mean beta phase half-life of 84 min, and a total clearance of 6.1 liters/h. The total clearance of the same dose of BCH-189 in a single animal was 11.0 liters/h. In two animals from which urine was obtained for 12 h postadministration, 32 and 59% of the drug was recovered unchanged. The deamination product of lamivudine was not detected. The CSF/plasma ratio of lamivudine was significantly higher when the drug was measured in the lumbar CSF (mean, 0.41) than when it was measured in the ventricular CSF (mean, 0.079). The measured CSF/plasma ratio for ventricular CSF is equivalent to that of other dideoxycytidine analogs, confirming the importance of the nucleobase in determining the degree of CSF penetration. The difference in lamivudine exposure in ventricular and lumbar CSF suggests that there is a transport mechanism for efflux of cytidine analogs from ventricular CSF. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. GLAXO GRP RES LTD,GREENFORD UB6 0HE,MIDDX,ENGLAND. NR 17 TC 40 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 1995 VL 39 IS 12 BP 2779 EP 2782 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TH293 UT WOS:A1995TH29300035 PM 8593019 ER PT J AU Nichiporov, D Kostjuchenko, V Puhl, JM Bensen, DL Desrosiers, MF Dick, CE McLaughlin, WL Kojima, T Coursey, BM Zink, S AF Nichiporov, D Kostjuchenko, V Puhl, JM Bensen, DL Desrosiers, MF Dick, CE McLaughlin, WL Kojima, T Coursey, BM Zink, S TI Investigation of applicability of alanine and radiochromic detectors to dosimetry of proton clinical beams SO APPLIED RADIATION AND ISOTOPES LA English DT Article ID RADIATION AB Cancer therapy studies using proton accelerators are underway in several major medical centers in the U.S., Russia, Japan and elsewhere. To facilitate dosimetry intercomparisons between these laboratories, alanine-based detectors produced at the National Institute of Standards and Technology and commercially available radiochromic films were studied for their possible use as passive transfer dosimeters for clinical proton beams. Evaluation of characteristics of these instruments, including the LET dependence of their response of proton energy, was carried out at the Institute of Theoretical and Experimental Physics. Results of absolute dose measurements were regarded as a preliminary step of dose intercomparison between ITEP and NIST. Measurements made in a number of experiments showed average agreement between the ITEP and NIST dosimetry standards to 2.5%. C1 INST THEORET & EXPTL PHYS, MOSCOW 117259, RUSSIA. JAPAN ATOM ENERGY RES INST, TAKASAKI, GUMMA, JAPAN. NATL INST HLTH, NCI, BETHESDA, MD USA. RP US TECHNOL ADM, NATL INST STAND & TECHNOL, PHYS LAB, DIV IONIZING RADIAT, GAITHERSBURG, MD 20899 USA. NR 26 TC 29 Z9 32 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD DEC PY 1995 VL 46 IS 12 BP 1355 EP 1362 DI 10.1016/0969-8043(95)00213-W PG 8 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA TK625 UT WOS:A1995TK62500010 PM 8563704 ER PT J AU DARLING, TN CARDENAS, AA BEARD, JS SAU, P YEE, CL ZONE, JJ YANCEY, KB AF DARLING, TN CARDENAS, AA BEARD, JS SAU, P YEE, CL ZONE, JJ YANCEY, KB TI A CHILD WITH ANTIBODIES TARGETING BOTH LINEAR IGA BULLOUS DERMATOSIS AND BULLOUS PEMPHIGOID ANTIGENS SO ARCHIVES OF DERMATOLOGY LA English DT Article ID BASEMENT-MEMBRANE ZONE; AUTOANTIBODIES; ADULTS; IDENTIFICATION; COEXISTENCE; DEPOSITION; DISEASE AB Background: Some patients with subepidermal blistering diseases show clinical, histologic, and immunopathologic features of both linear IgA bullous dermatosis and bullous pemphigoid. Such patients can be further characterized by defining the target of their circulating autoantibodies. We present the first case report of a child with linear deposits of IgA and IgG with circulating autoantibodies characteristic of both linear IgA bullous dermatosis and bullous pemphigoid. Observations: Widely distributed subepidermal vesicles showing neutrophils in the dermal papillae developed in a 3-year-old boy. Direct immunofluorescence microscopy of perilesional skin revealed linear deposits of IgA, IgG, and C3 in the epidermal basement membrane. The patient responded to therapy with dapsone, and after 6 months, it was possible to discontinue treatment. Circulating IgA antibodies from this child bound the epidermal side of 1-mol/L saline-split skin and immunoblotted the 97-kd linear IgA bullous dermatosis antigen. Circulating IgG antibodies bound the epidermal and, at low titer, dermal sides of split skin. These IgG antibodies immunoblotted and immunoprecipitated bullous pemphigoid antigens 1 and 2. Conclusions: Linear deposits of IgA and IgG in the epidermal basement membrane of patients with subepidermal bullous lesions may signify the coexistence of circulating autoantibodies directed against linear IgA bullous dermatosis and bullous pemphigoid antigens. C1 WALTER REED ARMY MED CTR,DERMATOL SERV,WASHINGTON,DC 20307. UNIV UTAH,HLTH SCI CTR,DIV DERMATOL,SALT LAKE CITY,UT. RP DARLING, TN (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,BETHESDA,MD 20892, USA. OI Darling, Thomas/0000-0002-5161-1974 NR 30 TC 22 Z9 22 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 1995 VL 131 IS 12 BP 1438 EP 1442 DI 10.1001/archderm.131.12.1438 PG 5 WC Dermatology SC Dermatology GA TJ638 UT WOS:A1995TJ63800013 PM 7492135 ER PT J AU VINE, AK BLODI, BA ELNER, SG JOHNSON, MW JESSUP, LM PIERSON, CL WILLIS, J MCIVER, F STANLEY, S SNEED, SR CAPONE, A AABERG, TM LIM, JI STERNBERG, P COFFMAN, DS MOORE, CN GARDNER, SK NOLTE, FS FREMSTAD, A GIBBS, D GILMAN, J SWORDS, R AGUILAR, HE MEREDITH, TA LAKHANPAL, V CHRISTIAN, FD HOOD, MA SCHWALBE, RS BILLINGS, EE BUIE, W MALLONEE, JJ MILLAR, MA VERBEEK, S CAMPOCHIARO, PA PALARDY, CB REYNOLDS, L DICK, JD CAIN, D DAMICO, DJ FREDERICK, AR MORLEY, MG PESAVENTO, RD PULIAFITO, CA TOPPING, TM FINN, SM RAYMOND, LA BAKER, AS PATON, B EVANS, C NAPOLI, J KIEMAN, C MAKRIS, K REIDY, WT WHITE, R GARFINKEL, RA PILKERTON, AR FRANTZ, RA ABERNATHY, GB BARBACCIA, JG ENSEY, HR ORMES, CA PARK, CH CAPLAN, J RUSSELL, K TOMA, R PACKO, KH DEBUSTROS, S FLOOD, TP GLAZER, L DEALBA, M EVANICH, E MONTWILL, MA ROTHMAN, JJ RUDERMAN, G BEARD, M LANDAU, W SHEN, MH GORDON, M GRAFF, S KWIATKOWSKI, K PAPPAS, L BRYANT, D DOHERTY, D MORINI, F ARREDONDO, L GARRETSON, BR GERENA, C HUNT, M KINNAIRD, SM RICE, TA NOVAK, MA ROWE, PS JAMIESON, S NEWBERY, D RECH, GR DUL, MJ KINSER, L STROZEWSKI, K CLARKRATH, S DELISIO, M DEMPSEY, DL KUKULA, D PINTERSMITH, A SMITHBREWER, S LUDWIG, T CHAMBERS, RB DAVIDORF, FH TAYLOR, CS HALE, KN BUESCHING, WJ CHAUDHURI, C SHORTLIDGE, GR COVER, NJ KEATING, MJ SAVAGE, SJ ANDRZEJEWSKA, P CORNETET, S MILLIRON, JD RICHMOND, R SCHNEIDER, L WEISENBERGER, D CANTRILL, HL RAMSAY, RC BRALLIER, AB JOHNSON, TP ROSSING, EE KNAUTH, KA MONAHAN, MM OESTREICH, NW CLARK, KF GLENNEN, AM YARIAN, DL GREEN, SN LEFF, SR MASCIULLI, L LUCIDO, MM LUDWIG, EJ MARANO, CL PETERS, L JOHO, K VOLKERT, DC ANDERSEN, F COFFEY, D SCHLOSSER, A HONEYWELL, A MAMES, RN DRIEBE, WT STERN, GA FRANCIS, A ZAM, ZS COOPER, R GASKINS, D SHAMIS, DJ WILLINGHAM, M BARKER, K ROSA, H FRIEDMAN, SM GARDNER, TW BLANKENSHIP, GW COYLE, CJ BERO, CJ HALAS, C SCHICK, S WALKER, J CUNNINGHAM, D LAMBERT, HM CLOGSTON, PS GARDNER, SN OSATO, MS FRADY, PM CARR, L SHIGLEY, J LOPEZ, PF CHONG, LP CISNEROS, L PADILLA, M YEE, EM NAKAMURA, T WALONKER, AF NICHOLS, T HUETE, ME LIGGETT, PE OBER, RR QUILLENTHOMAS, B WILLIAMS, M BARR, CC BLOOM, SM GREENE, PJ WHITTINGTON, GK MARTIN, ME WATSON, G JENKINSCURRY, B GILKEY, LA HUELSMAN, S HAN, DP BURTON, TC MIELER, WF PULIDO, JS REESER, FH NEWMAN, JL WERNER, KA PISARZEWICZ, PJ REINERIO, NA WALLOCH, MLK WILMER, Z LAABS, J PHILLIPS, J PICCHIOTTINO, R WIPPLINGER, W ABRAMS, GW JURKIEWICZ, DT LEET, ML MANDEL, P METZGER, K SUCHLA, L ZARLING, D BALLES, MW RYAN, EH KNOBLOCH, WH COOK, SM LUKE, DG FERRIERI, P SCHIMINSKY, NM GENIA, A PHILIPH, DA STINSON, EK WRIGHT, LM MCMICHAEL, MC MIELKE, SJ PONWITH, LJ PAVAN, PR PAUTLER, SE COATS, ML KIRK, NM MILLARD, SM CASTELLANO, FC EDWARDS, CR MARQUARDT, A MCCORMACK, AJ MCCORMICK, MT RENSHAW, B RESTUCCIA, A CAMPBELL, M CHRISTOPHER, N GARRETT, LS HALKIAS, DG HOTHERSALL, K MICKLER, K MINNICK, TS BURR, C SAXON, W ARCACHA, MA CARLTON, S EDISON, SK MALLIS, MJ SAYERS, TL SUDDS, TW TIBERIA, RJ WOLABAUGH, S BRADFORD, RH PARKE, DW WOLF, TC SHOFNER, LM TOBEY, LE JENSEN, HG SANCHEZ, D SHOFNER, J BURRIS, R DRAKE, KK GRISSOM, KR ROWSEY, JJ WILKINSON, CP BROWN, GC BENSON, WE FEDERMAN, JL LUCIER, AC MAGUIRE, JI SARIN, LK SHAKIN, EP SIVALINGAM, A TASMAN, W VANDER, JF WARD, N WEISBECKER, CA AGNEW, CL LAMBERT, R TOMER, T CARLSON, K RANCHINE, G SERFASS, MS DOFT, BH BERGREN, RL LOBES, LA OLSEN, KR RINKOFF, JS METZ, DJ LEONARD, MN KARENCHAK, LM KOWALSKI, RP WELLMAN, LA WILCOX, LA CAMPBELL, AF STEINBERG, DR VAGSTAD, GL FLOOK, KA GOOD, MM KEENEN, BJ MELLINGER, KA MARGHERIO, RR COX, MS MURPHY, PL LUCAROTTI, R MARTIN, S BAND, J BOSTIC, G CUMMING, K MANATREY, PE MITCHELL, B REGAN, VS BRIDGES, C COX, S HOUSTON, G JOHNSON, J STREASIK, P WOOD, B BLUMENKRANZ, MS CAYO, L KAYE, V VALENZUELA, CL ORGEL, IK POLINER, LS TORNAMBE, PE CANNON, SV NIELSEN, JL CARLSON, A CHAN, P DRAKE, L GRIM, M PETERSON, C BORG, LA GILLYATT, J BEYER, C HAMMER, ME GRIZZARD, WS SHANNON, TL TRAYNOM, JR COLLADO, MJ MCMANUS, DW SWEENEY, DE ADAMS, DH WATSON, TT ANTWORTH, MV ARAOS, JG GREENWALD, MA HABIB, M MYERS, SK OCKERS, KM THIBODEAU, JA WATKINS, B FRAMBACH, DA MORALES, R NELSEN, PT ROSENTHAL, JG MINTZ, FV BIEDENBACH, M LEONARDY, NJ ORGER, IK LAWNICZAK, SM BORK, C HAGEAGE, G HUNTER, EB MARSHALL, MJ ROMAN, P HILL, R HOFBAUER, T LEMANOWICZ, J CUPPLES, HP GUZMAN, GI BRODEUR, RJ YEE, D DELAHA, EC GEYER, SL SLOVIS, S SHIELDS, W LAUBER, S MICHELITSCH, K AF VINE, AK BLODI, BA ELNER, SG JOHNSON, MW JESSUP, LM PIERSON, CL WILLIS, J MCIVER, F STANLEY, S SNEED, SR CAPONE, A AABERG, TM LIM, JI STERNBERG, P COFFMAN, DS MOORE, CN GARDNER, SK NOLTE, FS FREMSTAD, A GIBBS, D GILMAN, J SWORDS, R AGUILAR, HE MEREDITH, TA LAKHANPAL, V CHRISTIAN, FD HOOD, MA SCHWALBE, RS BILLINGS, EE BUIE, W MALLONEE, JJ MILLAR, MA VERBEEK, S CAMPOCHIARO, PA PALARDY, CB REYNOLDS, L DICK, JD CAIN, D DAMICO, DJ FREDERICK, AR MORLEY, MG PESAVENTO, RD PULIAFITO, CA TOPPING, TM FINN, SM RAYMOND, LA BAKER, AS PATON, B EVANS, C NAPOLI, J KIEMAN, C MAKRIS, K REIDY, WT WHITE, R GARFINKEL, RA PILKERTON, AR FRANTZ, RA ABERNATHY, GB BARBACCIA, JG ENSEY, HR ORMES, CA PARK, CH CAPLAN, J RUSSELL, K TOMA, R PACKO, KH DEBUSTROS, S FLOOD, TP GLAZER, L DEALBA, M EVANICH, E MONTWILL, MA ROTHMAN, JJ RUDERMAN, G BEARD, M LANDAU, W SHEN, MH GORDON, M GRAFF, S KWIATKOWSKI, K PAPPAS, L BRYANT, D DOHERTY, D MORINI, F ARREDONDO, L GARRETSON, BR GERENA, C HUNT, M KINNAIRD, SM RICE, TA NOVAK, MA ROWE, PS JAMIESON, S NEWBERY, D RECH, GR DUL, MJ KINSER, L STROZEWSKI, K CLARKRATH, S DELISIO, M DEMPSEY, DL KUKULA, D PINTERSMITH, A SMITHBREWER, S LUDWIG, T CHAMBERS, RB DAVIDORF, FH TAYLOR, CS HALE, KN BUESCHING, WJ CHAUDHURI, C SHORTLIDGE, GR COVER, NJ KEATING, MJ SAVAGE, SJ ANDRZEJEWSKA, P CORNETET, S MILLIRON, JD RICHMOND, R SCHNEIDER, L WEISENBERGER, D CANTRILL, HL RAMSAY, RC BRALLIER, AB JOHNSON, TP ROSSING, EE KNAUTH, KA MONAHAN, MM OESTREICH, NW CLARK, KF GLENNEN, AM YARIAN, DL GREEN, SN LEFF, SR MASCIULLI, L LUCIDO, MM LUDWIG, EJ MARANO, CL PETERS, L JOHO, K VOLKERT, DC ANDERSEN, F COFFEY, D SCHLOSSER, A HONEYWELL, A MAMES, RN DRIEBE, WT STERN, GA FRANCIS, A ZAM, ZS COOPER, R GASKINS, D SHAMIS, DJ WILLINGHAM, M BARKER, K ROSA, H FRIEDMAN, SM GARDNER, TW BLANKENSHIP, GW COYLE, CJ BERO, CJ HALAS, C SCHICK, S WALKER, J CUNNINGHAM, D LAMBERT, HM CLOGSTON, PS GARDNER, SN OSATO, MS FRADY, PM CARR, L SHIGLEY, J LOPEZ, PF CHONG, LP CISNEROS, L PADILLA, M YEE, EM NAKAMURA, T WALONKER, AF NICHOLS, T HUETE, ME LIGGETT, PE OBER, RR QUILLENTHOMAS, B WILLIAMS, M BARR, CC BLOOM, SM GREENE, PJ WHITTINGTON, GK MARTIN, ME WATSON, G JENKINSCURRY, B GILKEY, LA HUELSMAN, S HAN, DP BURTON, TC MIELER, WF PULIDO, JS REESER, FH NEWMAN, JL WERNER, KA PISARZEWICZ, PJ REINERIO, NA WALLOCH, MLK WILMER, Z LAABS, J PHILLIPS, J PICCHIOTTINO, R WIPPLINGER, W ABRAMS, GW JURKIEWICZ, DT LEET, ML MANDEL, P METZGER, K SUCHLA, L ZARLING, D BALLES, MW RYAN, EH KNOBLOCH, WH COOK, SM LUKE, DG FERRIERI, P SCHIMINSKY, NM GENIA, A PHILIPH, DA STINSON, EK WRIGHT, LM MCMICHAEL, MC MIELKE, SJ PONWITH, LJ PAVAN, PR PAUTLER, SE COATS, ML KIRK, NM MILLARD, SM CASTELLANO, FC EDWARDS, CR MARQUARDT, A MCCORMACK, AJ MCCORMICK, MT RENSHAW, B RESTUCCIA, A CAMPBELL, M CHRISTOPHER, N GARRETT, LS HALKIAS, DG HOTHERSALL, K MICKLER, K MINNICK, TS BURR, C SAXON, W ARCACHA, MA CARLTON, S EDISON, SK MALLIS, MJ SAYERS, TL SUDDS, TW TIBERIA, RJ WOLABAUGH, S BRADFORD, RH PARKE, DW WOLF, TC SHOFNER, LM TOBEY, LE JENSEN, HG SANCHEZ, D SHOFNER, J BURRIS, R DRAKE, KK GRISSOM, KR ROWSEY, JJ WILKINSON, CP BROWN, GC BENSON, WE FEDERMAN, JL LUCIER, AC MAGUIRE, JI SARIN, LK SHAKIN, EP SIVALINGAM, A TASMAN, W VANDER, JF WARD, N WEISBECKER, CA AGNEW, CL LAMBERT, R TOMER, T CARLSON, K RANCHINE, G SERFASS, MS DOFT, BH BERGREN, RL LOBES, LA OLSEN, KR RINKOFF, JS METZ, DJ LEONARD, MN KARENCHAK, LM KOWALSKI, RP WELLMAN, LA WILCOX, LA CAMPBELL, AF STEINBERG, DR VAGSTAD, GL FLOOK, KA GOOD, MM KEENEN, BJ MELLINGER, KA MARGHERIO, RR COX, MS MURPHY, PL LUCAROTTI, R MARTIN, S BAND, J BOSTIC, G CUMMING, K MANATREY, PE MITCHELL, B REGAN, VS BRIDGES, C COX, S HOUSTON, G JOHNSON, J STREASIK, P WOOD, B BLUMENKRANZ, MS CAYO, L KAYE, V VALENZUELA, CL ORGEL, IK POLINER, LS TORNAMBE, PE CANNON, SV NIELSEN, JL CARLSON, A CHAN, P DRAKE, L GRIM, M PETERSON, C BORG, LA GILLYATT, J BEYER, C HAMMER, ME GRIZZARD, WS SHANNON, TL TRAYNOM, JR COLLADO, MJ MCMANUS, DW SWEENEY, DE ADAMS, DH WATSON, TT ANTWORTH, MV ARAOS, JG GREENWALD, MA HABIB, M MYERS, SK OCKERS, KM THIBODEAU, JA WATKINS, B FRAMBACH, DA MORALES, R NELSEN, PT ROSENTHAL, JG MINTZ, FV BIEDENBACH, M LEONARDY, NJ ORGER, IK LAWNICZAK, SM BORK, C HAGEAGE, G HUNTER, EB MARSHALL, MJ ROMAN, P HILL, R HOFBAUER, T LEMANOWICZ, J CUPPLES, HP GUZMAN, GI BRODEUR, RJ YEE, D DELAHA, EC GEYER, SL SLOVIS, S SHIELDS, W LAUBER, S MICHELITSCH, K TI RESULTS OF THE ENDOPHTHALMITIS VITRECTOMY STUDY - A RANDOMIZED TRIAL OF IMMEDIATE VITRECTOMY AND OF INTRAVENOUS ANTIBIOTICS FOR THE TREATMENT OF POSTOPERATIVE BACTERIAL ENDOPHTHALMITIS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID INFECTIOUS ENDOPHTHALMITIS; INTRAVITREAL GENTAMICIN; MANAGEMENT; CEPHALOSPORIN AB Objective: To determine the roles of immediate pars plana vitrectomy (VIT) and systemic antibiotic treatment in the management of postoperative endophthalmitis. Design: Investigator-initiated, multicenter, randomized clinical trial. Setting: Private and university-based retina-vitreous practices. Patients: A total of 420 patients who had clinical evidence of endophthalmitis within 6 weeks after cataract surgery or secondary intraocular lens implantation. Interventions: Random assignment according to a 2 X 2 factorial design to treatment with VIT or vitreous tap or biopsy (TAP) and to treatment with or without systemic antibiotics (ceftazidime and amikacin). Main Outcome Measures: A 9-month evaluation of visual acuity assessed by an Early Treatment Diabetic Retinopathy Study acuity chart and media clarity assessed both clinically and photographically. Results: There was no difference in final visual acuity or media clarity with or without the use of systemic antibiotics. In patients whose initial visual acuity was hand motions or better, there was no difference in visual outcome whether or not an immediate VIT was performed. However, in the subgroup of patients with initial light perception-only vision, VIT produced a threefold increase in the frequency of achieving 20/40 or better acuity (33% vs 11%), approximately a twofold chance of achieving 20/100 or better acuity (56% vs 30%), and a 50% decrease in the frequency of severe visual loss (20% vs 47%) over TAP. In this group of patients, the difference between VIT and TAP was statistically significant (P < .001, log rank test for cumulative visual acuity scores) over the entire range of vision. Conclusions: Omission of systemic antibiotic treatment can reduce toxic effects, costs, and length of hospital stay. Routine immediate VIT is nor necessary in patients with better than light perception vision at presentation but is of substantial benefit for those who have light perception-only vision. C1 EMORY EYE CTR,ATLANTA,GA. UNIV MARYLAND,EYE ASSOCIATES,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RETINA GRP WASHINGTON,CHEVY CHASE,MD. RUSH UNIV,INGALLS HOSP,CHICAGO,IL 60612. RETINA ASSOCIATES INC,CLEVELAND,OH. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV MINNESOTA,EDINA,MN. RETINA VITREOUS CTR PA,EDISON,PA. UNIV FLORIDA,GAINESVILLE,FL 32611. PENN STATE UNIV,HERSHEY,PA 17033. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV SO CALIF,LOS ANGELES,CA 90089. UNIV LOUISVILLE,KENTUCKY LIONS EYE RES INST,LOUISVILLE,KY 40292. MED COLL WISCONSIN,MILWAUKEE,WI 53226. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV S FLORIDA,N TAMPA,FL. DEAN A MCGEE EYE INST,OKLAHOMA CITY,OK. THOMAS JEFFERSON UNIV,WILLS EYE HOSP,PHILADELPHIA,PA 19107. ASSOCIATED RETINAL CONSULTANTS PC,ROYAL OAK,MI. RETINA CONSULTANTS,SAN DIEGO,CA. UNIV S FLORIDA,S TAMPA,FL. RETINA CONSULTANTS NW OHIO,TOLEDO,OH. RETINA VITREOUS ASSOCIATES INC,TOLEDO,OH. GEORGETOWN UNIV,WASHINGTON,DC 20057. RETINA VITREOUS CONSULTANTS,PITTSBURGH,PA. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. EYE ASSOCIATES,ALBANY,NY. EYE & EAR INST PITTSBURGH,PITTSBURGH,PA 15213. UNIV MISSOURI,COLUMBIA,MO 65211. UNIV PITTSBURGH,MED CTR,PITTSBURGH,PA 15260. UNIV PITTSBURGH,CTR COORDINATING,PITTSBURGH,PA 15260. UNIV WISCONSIN,CTR PHOTOGRAPH READING,MADISON,WI 53706. CARNEGIE MELLON UNIV,PITTSBURGH,PA 15213. DUKE UNIV,CTR EYE,DURHAM,NC 27706. NIH,BETHESDA,MD 20892. UNIV ILLINOIS,CHICAGO,IL 60680. NEI,PROGRAM OFF,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV MICHIGAN,ANN ARBOR,MI 48109. RI Pavan, Peter/B-6473-2013 NR 29 TC 566 Z9 580 U1 4 U2 25 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 1995 VL 113 IS 12 BP 1479 EP 1496 PG 18 WC Ophthalmology SC Ophthalmology GA TJ063 UT WOS:A1995TJ06300001 ER PT J AU Henson, DE Fielding, LP Grignon, DJ Page, DL Hammond, ME Nash, G Pettigrew, NM Gorstein, F Hutter, RVP AF Henson, DE Fielding, LP Grignon, DJ Page, DL Hammond, ME Nash, G Pettigrew, NM Gorstein, F Hutter, RVP TI College of American pathologists conference XXVI on clinical relevance of prognostic markers in solid tumors - Summary SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material ID CANCER C1 HARPER GRACE HOSP,DEPT PATHOL,DETROIT,MI. LATTER DAY ST HOSP,SALT LAKE CITY,UT. HLTH SCI CTR,WINNIPEG,MB,CANADA. ST BARNABAS HOSP,DEPT PATHOL,LIVINGSTON,NJ. GENESEE HOSP,DEPT SURG,ROCHESTER,NY. RP Henson, DE (reprint author), NCI,EARLY DETECT BRANCH,EPN ROOM 305,BETHESDA,MD 20892, USA. NR 10 TC 66 Z9 66 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 1995 VL 119 IS 12 BP 1109 EP 1112 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA TK591 UT WOS:A1995TK59100008 PM 7503658 ER PT J AU AlboresSaavedra, J Henson, DE AF AlboresSaavedra, J Henson, DE TI Adenomyomatous hyperplasia of the gallbladder with perineural invasion SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Note ID NONINVASIVE CARCINOMA; ASCHOFF SINUS AB We report three examples of either localized or segmental adenomyomatous hyperplasia of the gallbladder in association with cholelithiasis, Two patients were women, 58 and 81 years of age, and the third was a 62-year-old man, The finding of perineural invasion by epithelial ductal structures in two cases and of perineural and intraneural invasion in the third case led to initial diagnoses of well-differentiated adenocarcinoma, The presence of mucinous metaplasia in some of the cystically dilated ductal structures and the diffuse proliferation of pyloric-type glands probably contributed to the erroneous diagnosis of adenocarcinoma, Although the mechanism by which the epithelial structures invade perineural spaces is unknown, we offer two possible explanations: (1) extension and growth of epithelial ductal structures along tissue planes of least resistance, such as the perineural space, and (2) growth of hyperplastic nerve trunks in close proximity to or within epithelial structures. The pattern of perineural invasion in cases of adenomyomatous hyperplasia should not be confused with adenocarcinoma. Attention to the general architecture of the lesion and the bland cytologic features of the glands and ductal structures should prevent this misinterpretation. The gallbladder should be added to the list of organs in which perineural invasion by benign epithelial structures has been described. C1 NCI,EARLY DETECT BRANCH,BETHESDA,MD. RP AlboresSaavedra, J (reprint author), UNIV TEXAS,SW MED CTR,DEPT PATHOL,DIV ANAT PATHOL,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. NR 15 TC 19 Z9 20 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 1995 VL 119 IS 12 BP 1173 EP 1176 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA TK591 UT WOS:A1995TK59100020 PM 7503670 ER PT J AU SHARRETT, AR CHAMBLESS, LE HEISS, G PATON, CC PATSCH, W AF SHARRETT, AR CHAMBLESS, LE HEISS, G PATON, CC PATSCH, W TI ASSOCIATION OF POSTPRANDIAL TRIGLYCERIDE AND RETINYL PALMITATE RESPONSES WITH ASYMPTOMATIC CAROTID-ARTERY ATHEROSCLEROSIS IN MIDDLE-AGED MEN AND WOMEN - THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE ATHEROSCLEROSIS; CAROTID ARTERY DISEASES; LIPOPROTEINS ID DENSITY LIPOPROTEIN TRIGLYCERIDE; APOLIPOPROTEIN-E; DISEASE; PLASMA; METABOLISM; HYPERTRIGLYCERIDEMIA; AMPLIFICATION; CHOLESTEROL; INSULIN; OBESITY AB Blood lipid alterations after a fatty meal may be atherogenic, but there is little information regarding their associations with disease independent of fasting lipids. Asymptomatic atherosclerosis cases (n=229) and 373 control subjects free of atherosclerosis, as defined by carotid intima-media thickness on ultrasound images, were given a fatty meal with vitamin A, followed by 3.5- and 8-hour measurements of triglycerides (TGs), TG-rich lipoprotein TGs, apoproteinB48, and retinyl palmitate. Among white men and women but not among blacks, case status was associated with greater postprandial responses of TGs and TG-rich lipoprotein TGs, but only in nonobese persons (body mass index <30 kg/m(2)). The associations were strong and significant after controlling for coronary risk factors (odds ratio, approximate to 2.0) and fasting TGs (odds ratio, 1.5). Associations with other postprandial lipid measurements did not persist after controlling for fasting lipids. Elevated postprandial TGs appear to be an independent risk factor for carotid intimal thickening in nonobese whites. The lack of such a relation in obese subjects and the lipid profile they manifest suggest that postprandial TGs must be accompanied by accumulation of TG-rich lipoprotein remnants atherogenic. C1 UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,METHODIST HOSP,HOUSTON,TX 77030. RP SHARRETT, AR (reprint author), NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,ROCKLEDGE BLDG,ROOM 8164,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [N01-HC55015, N01-HC55016, UO1 HL45467] NR 41 TC 112 Z9 120 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscl. Thromb. Vasc. Biol. PD DEC PY 1995 VL 15 IS 12 BP 2122 EP 2129 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA TJ368 UT WOS:A1995TJ36800005 PM 7489232 ER PT J AU BURCHFIEL, CM CURB, JD SHARP, DS RODRIGUEZ, BL ARAKAKI, R CHYOU, PH YANO, K AF BURCHFIEL, CM CURB, JD SHARP, DS RODRIGUEZ, BL ARAKAKI, R CHYOU, PH YANO, K TI DISTRIBUTION AND CORRELATES OF INSULIN IN ELDERLY MEN - THE HONOLULU HEART PROGRAM SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE ASIAN AMERICANS; HYPERTENSION; INSULIN; LIPOPROTEINS; OBESITY ID CARDIOVASCULAR RISK-FACTORS; IMPAIRED GLUCOSE-TOLERANCE; SYNDROME SYNDROME-X; BLOOD-PRESSURE; PLASMA-INSULIN; PHYSICAL-ACTIVITY; ESSENTIAL-HYPERTENSION; PIMA-INDIANS; YOUNG-ADULTS; RESISTANCE AB The role of insulin in cardiovascular disease is uncertain, and studies in elderly or minority populations are infrequent. Fasting and 2-hour insulin concentrations and their cross-sectional associations with cardiovascular risk factors were examined in 3562 elderly (aged 71 to 93 years) Japanese American men from the Honolulu Heart Program who were reexamined between 1991 and 1993. Insulin distributions were skewed (mean and median: 16.8 and 12 mu U/mL for fasting; 117.2 and 93 mu U/mL for 2-hour); fasting but not 2-hour insulin levels declined significantly with age (P<.0001 and P=.54, respectively). Factors most strongly correlated with insulin included measures of obesity, fat distribution, and levels of triglyceride, glucose (r=.38 to r=.50 fasting, r=.21 to r=.27 2-hour), and HDL cholesterol (1 =-.41 and r=-.22, respectively). Other correlates included fibrinogen, hematocrit, heart rate, blood pressure, cigarettes per day (all positive), alcohol, physical activity, and forced vital capacity (negative). Associations were also evident across risk factor quintiles. Insulin levels were significantly elevated in men with hypertension and diabetes. In multiple linear regression analyses, log(10) fasting insulin was positively and independently associated with body mass index, triglycerides, glucose, fibrinogen, hematocrit, heart rate, diabetes, and hypertension and negatively associated with HDL cholesterol, physical activity, and forced vital capacity. In general, results were similar for log(10) 2-hour insulin and when subjects who fasted <12 hours or had diabetes were excluded. Substitution of medication use and blood pressure for hyper tension indicated independent associations of medication use but not blood pressure with insulin. These findings suggest that fasting and 2-hour insulin levels are associated with several key features of insulin resistance syndrome in elderly Japanese American men. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,EPIDEMIOL & BIOMETRY PROGRAM,HONOLULU,HI 96817. KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. UNIV HAWAII,JOHN A BURNS SCH MED,HONOLULU,HI. FU NHLBI NIH HHS [N01-HC-05102] NR 69 TC 36 Z9 36 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscl. Thromb. Vasc. Biol. PD DEC PY 1995 VL 15 IS 12 BP 2213 EP 2221 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA TJ368 UT WOS:A1995TJ36800018 PM 7489245 ER PT J AU Aguie, GA Rader, DJ Clavey, V Traber, MG Torpier, G Kayden, HJ Fruchart, JC Brewer, HB Castro, G AF Aguie, GA Rader, DJ Clavey, V Traber, MG Torpier, G Kayden, HJ Fruchart, JC Brewer, HB Castro, G TI Lipoproteins containing apolipoprotein B isolated from patients with abetalipoproteinemia and homozygous hypobetalipoproteinemia: Identification and characterization SO ATHEROSCLEROSIS LA English DT Article DE abetalipoproteinemia; hypobetalipoproteinemia; apo B-containing lipoprotein particles; vitamin E ID TRIGLYCERIDE TRANSFER PROTEIN; LINKED IMMUNOSORBENT-ASSAY; VITAMIN-E; HUMAN-PLASMA; C-III; GENE; QUANTIFICATION; DISEASE; SERUM AB Abetalipoproteinemia (ABL) and homozygous hypobetalipoproteinemia (HBL) are inherited disorders which are classically characterized by progressive retinal and spinocerebellar disease, fat-soluble vitamin deficiency, and absence of apolipoprotein (apo) B from the plasma, Using immunoaffinity chromatography with an anti-apo B antiserum, we isolated apo B-containing lipoprotein (LpB) particles from the plasma of 4 ABL and 2 HBL patients, The LpB particles were characterized and compared with low density lipoprotein (LDL) and LpB isolated from normal plasma. The ABL/HBL LpB particles were similar in size and charge to normal LpB particles but were relatively enriched in several other apolipoproteins. They contained alpha-tocopherol in a ratio to cholesterol that was proportionately much higher than the very low ratio of alpha-tocopherol to cholesterol in plasma. They bound saturably to fibroblasts and were internalized and degraded similarly to LDL. Hence, the molecular defects in ABL and HBL permit the secretion of a very small number of ape B-containing lipoproteins which may be important for transport of alpha-tocopherol to peripheral tissues. C1 UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. INST PASTEUR,INSERM,U325,F-59019 LILLE,FRANCE. NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NYU,SCH MED,DEPT MED,NEW YORK,NY. OI Traber, Maret/0000-0002-2892-4024 NR 25 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 1995 VL 118 IS 2 BP 183 EP 191 DI 10.1016/0021-9150(95)05605-X PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TN563 UT WOS:A1995TN56300002 PM 8770313 ER PT J AU RAUSCHECKER, JP AF RAUSCHECKER, JP TI REVERBERATIONS OF HEBBIAN THINKING SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID EARLY VISUAL EXPERIENCE; CORTEX; PLASTICITY; SYNAPSES AB Cortical reverberations may induce synaptic changes that underlies developmental plasticity as well as long-term memory. They may be especially important for the consolidation of synaptic changes. Reverberations in cortical networks should have particular significance during development, when large numbers of new representations are formed. This includes the formation of representation across different sensory modalities. RP RAUSCHECKER, JP (reprint author), NIMH,NEUROPSYCHOL LAB,COGNIT NEUROSCI SECT,BETHESDA,MD 20892, USA. RI Rauschecker, Josef/A-4120-2013 NR 30 TC 2 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 1995 VL 18 IS 4 BP 642 EP 643 PG 2 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA TP353 UT WOS:A1995TP35300020 ER PT J AU Watts, AG Kelly, AB SanchezWatts, G AF Watts, AG Kelly, AB SanchezWatts, G TI Neuropeptides and thirst: The temporal response of corticotropin-releasing hormone and neurotensin neuromedin N gene expression in rat limbic forebrain neurons to drinking hypertonic saline SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID CENTRAL AMYGDALOID NUCLEUS; MESSENGER-RNA REGULATION; PARABRACHIAL NUCLEUS; INSITU HYBRIDIZATION; STRIA TERMINALIS; EFFERENT PROJECTIONS; OSMOTIC STIMULATION; BED NUCLEUS; CIRCUMVENTRICULAR ORGAN; PARAVENTRICULAR NUCLEUS AB The authors have demonstrated in rats that the ingestion of hypertonic saline for 5 days provides an increasingly complex dehydrating stimulus to the rats. Initially, the stimulus leads to cellular dehydration, but extracellular dehydration develops as ingestion continues beyond 3 days. The initial cellular dehydration provokes modifications to corticotropin-releasing hormone and neurotensin/neuromedin N messenger RNAs (mRNAs) in some neurons of the limbic forebrain, changes that are either maintained or are modified as extracellular dehydration develops. Those changes in mRNA content occur in neurosecretory neurons as well as in neurons in hypothalamic and telencephalic regions associated with behavior and autonomic regulation. The authors propose that alterations in peptide mRNAs are allied to altered neuronal signaling processes that direct the different components of the homeostatic response to dehydration. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP Watts, AG (reprint author), UNIV SO CALIF,DEPT BIOL SCI,NEURAL INFORMAT & BEHAV RES PROGRAM,HEDCO NEUROSCI BLDG, MC 2520,LOS ANGELES,CA 90089, USA. FU NINDS NIH HHS [NS 29728] NR 67 TC 34 Z9 34 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD DEC PY 1995 VL 109 IS 6 BP 1146 EP 1157 DI 10.1037//0735-7044.109.6.1146 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA TK946 UT WOS:A1995TK94600011 PM 8748964 ER PT J AU Elmer, GI George, FR AF Elmer, GI George, FR TI Genetic differences in the operant rate-depressant effects of ethanol between four inbred mouse strains SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE alcohol; behavior; fixed ratio schedule; genetics; mice ID SHORT-SLEEP MICE; INDUCED LOCOMOTOR ACTIVATION; LONG-SLEEP; GENOTYPIC CORRELATIONS; BEHAVIORAL-RESPONSES; WITHDRAWAL SEIZURES; ALKO RATS; TOLERANCE; SELECTION; RESISTANT AB The use of genetically defined populations in studies of ethanol on schedule-controlled behavior can help determine genetically covarying responses to ethanol as well as the role of environmental constraints in the expression of gene effects. The purpose of the present study was to investigate the rate-depressant effects of ethanol in four inbred mouse strains, A/J, CBA/J, C3H/HeJ and DBA/2J. Ethanol dose-dependently decreased high rates of behavior maintained by fixed-ratio responding far water in all four strains. In general, DBA/2J mice were the least sensitive to the rate-depressant effects of ethanol, with an ED(50) averaging 19-29% greater than the other three inbred strains. The results of this experiment demonstrate that genetic factors play a role in determining responsivity to even a complex learned behavioral sequence such as lever press responding under a fixed-ratio schedule, and that sensitivity to the effects of ethanol on fixed-ratio responding for water is not genetically related to acute narcotic effects or reinforcing effects of ethanol. C1 SW INST DRUG & ALCOHOL STUDIES,ALBUQUERQUE,NM 87190. NIDA,DIV INTRAMURAL RES,PRECLIN PHARMACOL BRANCH,BEHAV PHARMACOL & GENET SECT,BALTIMORE,MD 21224. NR 34 TC 6 Z9 6 U1 2 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD DEC PY 1995 VL 6 IS 8 BP 794 EP 800 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA TK393 UT WOS:A1995TK39300004 ER PT J AU Fishbein, WN Foellmer, JW Davis, JI Kirsch, IR AF Fishbein, WN Foellmer, JW Davis, JI Kirsch, IR TI Detection of very-rare-copy DNA in 0.2-ml dried human blood blots SO BIOCHEMICAL AND MOLECULAR MEDICINE LA English DT Article ID POLYMERASE CHAIN-REACTION; ATAXIA-TELANGIECTASIA; RECOMBINATION; LYMPHOCYTES; SEQUENCES; GENES; SPOTS AB A nested PCR assay for chromosome 7 inversions (as identified by the presence of T-cell receptor trans-rearrangements) can detect as rare a frequency as 1 copy in 300,000 leukocytes, To identify such rare occurrences from dried blood blots, the most conveniently obtained and stored samples for field population studies, demands a DNA extraction method that will provide both high quality and high yield, We have satisfied this requirement by extracting proteins and other components directly from the minced filter with phenol, before extracting the DNA with Chelex-water. This provides a near maximal yield of denatured DNA of sufficient quality to detect these translocations with a sensitivity equivalent to that of DNA purified from whole blood samples, Blots stored 6 months worked as well as fresh blots. In addition, we present a method for obtaining native DNA from the dried blots, although at a much lower yield. The successful use of blood blots to detect such rare events signals the feasibility of large-scale field studies involving diagnostic molecular epidemiology. (C) 1995 Academic Press,Inc. C1 NCI,NAVY MED ONCOL BRANCH,ACQUIRED GENE REARRANGEMENT SECT,BETHESDA,MD 20205. RP Fishbein, WN (reprint author), ARMED FORCES INST PATHOL,DEPT ENVIRONM PATHOL,DIV BIOCHEM PATHOL,WASHINGTON,DC 20306, USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1077-3150 J9 BIOCHEM MOL MED JI Biochem. Mol. Med. PD DEC PY 1995 VL 56 IS 2 BP 152 EP 157 DI 10.1006/bmme.1995.1070 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA TR748 UT WOS:A1995TR74800010 PM 8825078 ER PT J AU Mannen, H Li, SSL AF Mannen, H Li, SSL TI The lactate dehydrogenase gene from nematode Caenorhabditis elegans contains only two of six introns conserved in the protein-encoding sequence of LDH genes from bird and mammals SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID GENOMIC ORGANIZATION; NUCLEOTIDE AB The protein-encoding region of L-lactate dehydrogenase (LDH) gene from nematode, Caenorhabditis elegans, was amplified by polymerase-chain-reaction from total genomic DNA and its nucleotide sequence determined. A comparison of this genomic sequence with the published sequence of nematode LDH cDNA reveals the presence of two introns of 57 and 47 nucleotides at codon no. 82 and 279-280, respectively. The positions of the two introns present in this invertebrate LDH gene correspond to the second and sixth introns of vertebrate LDH genes. The protein-coding sequence of human LDH-A (muscle),LDH-B (heart) and LDH-C (testis), mouse LDH-A, and duck LDH-B genes has previously been shown to be interrupted by six introns at the homologous positions. C1 NIEHS, GENET LAB, NIH, RES TRIANGLE PK, NC 27709 USA. NR 13 TC 2 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD DEC PY 1995 VL 37 IS 6 BP 1057 EP 1061 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VG877 UT WOS:A1995VG87700004 PM 8747535 ER PT J AU KEARSE, KP ROBERTS, JP WIEST, DL SINGER, A AF KEARSE, KP ROBERTS, JP WIEST, DL SINGER, A TI DEVELOPMENTAL REGULATION OF ALPHA-BETA-T-CELL ANTIGEN RECEPTOR ASSEMBLY IN IMMATURE CD4(+)CD8(+) THYMOCYTES SO BIOESSAYS LA English DT Review ID ENDOPLASMIC-RETICULUM; CD4+CD8+ THYMOCYTES; CHAINS; EXPRESSION; DEGRADATION; COMPLEX; PROTEIN; EVENTS; BIOSYNTHESIS; ASSOCIATION AB Most lymphocytes of the T cell lineage develop along the CD4/CD8 pathway and express antigen receptors on their surfaces consisting of clonotypic alpha beta chains associated with invariant CD3-gamma delta epsilon components and zeta chains, collectively referred to as the T cell antigen receptor complex (TCR). Expression of the TCR complex is dynamically regulated during T cell development, with immature CD4(+)CD8(+) thymocytes expressing only 10% of the number of (alpha beta TCR complexes on their surfaces expressed by mature CD4(+) and CD8(+) T cells. Recent evidence demonstrates that low surface TCR density on CD4(+)CD8(+) thymocytes results from the limited survival of a single TCR component within the ER, the TCR alpha chain, which has a half life of only 15 minutes in immature thymocytes, compared to >75 minutes in mature T cells. Instability of TCR alpha proteins in immature CD4(+)CD8(+) thymocytes represents a novel mechanism by which expression of the multisubunit TCR complex is quantitatively regulated during T cell development. In the current review we discuss our recent findings concerning the assembly, intracellular transport, and expression of alpha beta TCR complexes in CD4(+)CD8(+) thymocytes and comment on the functional significance of TCR alpha instability during T cell development. RP KEARSE, KP (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. OI Wiest, David/0000-0002-0792-3188 NR 41 TC 14 Z9 15 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD DEC PY 1995 VL 17 IS 12 BP 1049 EP 1054 DI 10.1002/bies.950171209 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA TK391 UT WOS:A1995TK39100008 PM 8634066 ER PT J AU BAUMANN, MH GENDRON, TM BECKETTS, KM HENNINGFIELD, JE GORELICK, DA ROTHMAN, RB AF BAUMANN, MH GENDRON, TM BECKETTS, KM HENNINGFIELD, JE GORELICK, DA ROTHMAN, RB TI EFFECTS OF INTRAVENOUS COCAINE ON PLASMA-CORTISOL AND PROLACTIN IN HUMAN COCAINE ABUSERS SO BIOLOGICAL PSYCHIATRY LA English DT Article DE COCAINE; PROLACTIN; CORTISOL; HUMAN ID NEUROENDOCRINE RESPONSES; DOPAMINE; NOMIFENSINE; INHIBITORS; HORMONE AB The aim of the present work was to examine the cortisol and prolactin responses to acute cocaine administration in human cocaine users. Each subject served as his own control during intravenous saline placebo and cocaine (40 mg) infusion sessions, Cocaine significantly elevated plasma cortisol but did not affect prolactin, The rise in cortisol coincided with an increase in heart rate and blood pressure after cocaine, In agreement with studies in animals, our data suggest that cocaine activates the hypothalamic-pituitary-adrenal axis in humans. However, based on the wed-known importance of dopamine as a prolactin-inhibiting factor, the failure of cocaine to suppress prolactin in the present study raises questions concerning the role of dopamine in the mechanism of acute cocaine action in humans. RP BAUMANN, MH (reprint author), NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. NR 21 TC 70 Z9 71 U1 0 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD DEC 1 PY 1995 VL 38 IS 11 BP 751 EP 755 DI 10.1016/0006-3223(95)00083-6 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TG972 UT WOS:A1995TG97200007 PM 8580229 ER PT J AU TSURUTA, JK OBRIEN, DA AF TSURUTA, JK OBRIEN, DA TI SERTOLI-CELL SPERMATOGENIC CELL-INTERACTION - THE INSULIN-LIKE GROWTH FACTOR-II CATION-INDEPENDENT MANNOSE 6-PHOSPHATE RECEPTOR MEDIATES CHANGES IN SPERMATOGENIC CELL GENE-EXPRESSION IN MICE SO BIOLOGY OF REPRODUCTION LA English DT Article ID TUBULAR BASOLATERAL MEMBRANES; GTP-BINDING PROTEINS; INOSITOL TRISPHOSPHATE; RIBONUCLEIC-ACID; CYCLIC PROTEIN-2; CANINE KIDNEY; IGF-II; RAT; RNA; STIMULATION AB The insulin-like growth factor (IGF)-II/cation-independent mannose 6-phosphate receptor (Cl-MPR) is a multifunctional receptor with distinct binding sites for IGF-II and mannose 6-phosphate (M6P)-bearing glycoproteins. We used the immediate-early response gene c-fos to assay early changes in gene expression in spermatogenic cells in response to ligands for this receptor that are present in the seminiferous epithelium. We confirmed that c-fos behaves as an immediate-early response gene in spermatogenic cells after stimulation of protein kinase C with phorbol ester or after intercellular calcium levels are raised with calcium ionophore. After determining that IGF-II mRNA is present in Sertoli cells, we treated spermatogenic cells with this growth factor and found that it increased c-fos mRNA levels in a dose-dependent manner. Similarly, Sertoli cell-conditioned medium (SCM) caused a dose-dependent increase in c-fos levels in spermatogenic cells isolated from adult mice. This effect was inhibited in the presence of 5 mM M6P, demonstrating that this change in c-fos gene expression was mediated by the IGF-II/Cl-MPR. In addition, SCM treatment of purified pachytene spermatocytes and round spermatids caused a dose-dependent increase in 18S rRNA levels that was completely abolished in the presence of M6P. Our results provide direct evidence that IGF-II/Cl-MPR ligands secreted by Sertoli cells can modulate gene expression in spermatogenic cells and strongly suggest that they are important in the regulation of spermatogenesis. C1 UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27599. NIEHS,GAMETE BIOL SECT,RES TRIANGLE PK,NC 27709. RP TSURUTA, JK (reprint author), UNIV N CAROLINA,DEPT PEDIAT,REPROD BIOL LABS,CHAPEL HILL,NC 27599, USA. FU NICHD NIH HHS [P32T-HD07315, HD26485, P30-HD18968, R01 HD026485] NR 49 TC 20 Z9 21 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1526 JEFFERSON ST, MADISON, WI 53711-2106 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD DEC PY 1995 VL 53 IS 6 BP 1454 EP 1464 DI 10.1095/biolreprod53.6.1454 PG 11 WC Reproductive Biology SC Reproductive Biology GA TF460 UT WOS:A1995TF46000027 PM 8562703 ER PT J AU Proschan, MA Hunsberger, SA AF Proschan, MA Hunsberger, SA TI Designed extension of studies based on conditional power SO BIOMETRICS LA English DT Article DE conditional power; study extension; type I error rate ID MONITORING CLINICAL-TRIALS; I ERROR RATE AB We propose a flexible method of extending a study based on conditional power. The possibility for extension when the p value at the planned end is small but not statistically significant is built in to the design of the study. The significance of the treatment difference at the planned end is used to determine the number of additional observations needed and the critical value necessary for use after accruing those additional observations. It may therefore be thought of as a two-stage procedure. Even though the observed treatment difference at stage 1 is used to make decisions, the Type I error rate is protected. RP Proschan, MA (reprint author), NHLBI,OFF BIOSTAT RES,BETHESDA,MD 20892, USA. NR 11 TC 275 Z9 278 U1 2 U2 11 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1995 VL 51 IS 4 BP 1315 EP 1324 DI 10.2307/2533262 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA TQ156 UT WOS:A1995TQ15600010 PM 8589224 ER PT J AU Shih, JH Louis, TA AF Shih, JH Louis, TA TI Inferences on the association parameter in copula models for bivariate survival data SO BIOMETRICS LA English DT Article ID DISTRIBUTIONS; MARGINALS; FAMILIES AB We investigate two-stage parametric and two-stage semi-parametric estimation procedures for the association parameter in copula models for bivariate survival data where censoring in either or both components is allowed. We derive asymptotic properties of the estimators and compare their performance by simulations. Both parametric and semi-parametric estimators of the association parameter are efficient at independence, and the parameter estimates in the margins have high efficiency and are robust to misspecification of dependency structures. In addition, we propose a consistent variance estimator for the semi-parametric estimator of the association parameter. We apply the proposed methods to an AIDS data set for illustration. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,MINNEAPOLIS,MN 55455. RP Shih, JH (reprint author), NHLBI,2 ROCKLEDGE CTR,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [N01-AI-05073] NR 29 TC 253 Z9 257 U1 0 U2 11 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1995 VL 51 IS 4 BP 1384 EP 1399 DI 10.2307/2533269 PG 16 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA TQ156 UT WOS:A1995TQ15600017 PM 8589230 ER PT J AU Nam, JM AF Nam, JM TI Interval estimation and significance testing for cyclic trends in seasonality studies SO BIOMETRICS LA English DT Article DE confidence interval; cyclic trends; power and sample size; seasonality; test of significance AB The statistical analysis for detecting a seasonal trend in epidemiologic studies has traditionally employed Edwards' method (1961, Annals of Human Genetics 25, 83-85) or a modification (Roger, 1977, Biometrika 64, 152-155) which are formulated under a simple harmonic model with two parameters, amplitude and phase angle. In seasonality studies, researchers usually have known seasons at which peak and trough incidences occur. Utilizing this information, we present the most efficient interval estimation of the ratio of maximum and minimum seasonal frequencies and the uniformly most powerful unbiased test for detecting the seasonal variation using the general theory of Bartlett (1953, Biometrika 40, 12-19). The asymptotic power function and the approximate formula for sample size are derived. A simulation study shows that actual values of power of this score test are satisfactorily close to nominal values even for small samples. The proposed simple score test is more powerful and requires substantially smaller samples for a specific power than the standard Edwards or Roger tests. An alternative method based on the logarithm of the maximum likelihood estimator of the ratio is comparable to the simple score method. RP Nam, JM (reprint author), NCI,BIOSTAT BRANCH,ROCKVILLE,MD 20892, USA. NR 12 TC 20 Z9 21 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1995 VL 51 IS 4 BP 1411 EP 1417 DI 10.2307/2533271 PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA TQ156 UT WOS:A1995TQ15600019 PM 8589231 ER PT J AU MINTON, AP AF MINTON, AP TI MACROMOLECULAR CROWDING - A FOREWORD SO BIOPHYSICAL CHEMISTRY LA English DT Article RP MINTON, AP (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,PHYS BIOCHEM SECT,BLDG 8,BETHESDA,MD 20892, USA. NR 1 TC 20 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD DEC PY 1995 VL 57 IS 1 BP 1 EP 2 DI 10.1016/0301-4622(95)00064-5 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA TB471 UT WOS:A1995TB47100001 ER PT J AU MINTON, AP AF MINTON, AP TI A MOLECULAR-MODEL FOR THE DEPENDENCE OF THE OSMOTIC-PRESSURE OF BOVINE SERUM-ALBUMIN UPON CONCENTRATION AND PH SO BIOPHYSICAL CHEMISTRY LA English DT Article DE BOVINE SERUM ALBUMIN; OSMOTIC PRESSURE; PROTEINS ID HEMOGLOBIN AB Expressions derived from the effective hard particle model of Minton and Edelhoch (Biopolymers, 21 (1982) 451) account quantitatively for the combined data of Kanal et al, (Biophys. J., 66 (1994) 153) describing the osmotic pressure of bovine serum albumin as a function of protein concentration (less than or equal to ca, 100 g/l) and pH (3-8) in buffered 0.1 M NaCl. The best fit of the model yields a molar mass of 68360 and a pH-dependent value of the effective specific volume ranging from a minimum of -0.17 cm(3)/g at pH 4.6 (the isoelectric point) to maxima of 3.1 cm(3)/g at pH 3.0 and 2.2 cm(3)/g at pH 8.0. These values are shown to be consistent with the magnitude of known attractive and repulsive electrostatic interactions between proteins in solution. RP MINTON, AP (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,PHYS BIOCHEM SECT,BETHESDA,MD 20892, USA. NR 13 TC 44 Z9 45 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD DEC PY 1995 VL 57 IS 1 BP 65 EP 70 DI 10.1016/0301-4622(95)00046-Z PG 6 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA TB471 UT WOS:A1995TB47100009 PM 8534837 ER PT J AU MURPHY, LD ZIMMERMAN, SB AF MURPHY, LD ZIMMERMAN, SB TI CONDENSATION AND COHESION OF LAMBDA-DNA IN CELL-EXTRACTS AND OTHER MEDIA - IMPLICATIONS FOR THE STRUCTURE AND FUNCTION OF DNA IN PROKARYOTES SO BIOPHYSICAL CHEMISTRY LA English DT Article DE NUCLEOID; ESCHERICHIA COLI; MACROMOLECULAR CROWDING; PROTEIN HU; DNA-BINDING PROTEINS; SPERMIDINE ID INVERSION GEL-ELECTROPHORESIS; HISTONE-LIKE PROTEINS; ESCHERICHIA-COLI; EXCLUDED VOLUME; POLYMER-SOLUTIONS; LIGHT-SCATTERING; SUPERCOILED DNA; COMPACT FORM; END LIGATION; HU PROTEIN AB DNA added to concentrated extracts of Escherichia coli undergoes a reversible transition to a readily-sedimentable ('condensed') form. The transition occurs over a relatively small increment in extract concentration. The extract appears to play two roles in this transition, supplying both DNA-binding protein(s) and a crowded environment that increases protein binding and favors compact DNA conformations. The two roles of the extract are suggested by properties of fractions prepared by absorption of extracts with DNA-cellulose. The DNA-binding fraction and the DNA-nonbinding fractions from these columns are separately poorer condensing agents than the original extract, but when rejoined are similar to the original extract in the amount required for condensation. The dual role for the extract is supported by model studies of condensation with combinations of purified DNA-binding materials (protein HU or spermidine) and concentrated solutions of crowding agents (albumin or polyethylene glycol 8000); in each case, crowding agents and DNA-binding materials jointly reduce the amounts of each other required for condensation. The condensation reaction as studied in extracts or in the purified systems may be a useful approach to the forces which stabilize the compact form of DNA within the bacterial nucleoid. The effect of condensation on the reactivity of the DNA was measured by changes in the rate of cohesion between duplex DNA molecules bearing the complementary single-strand termini of lambda DNA. Condensation caused large increases in the rates of cohesion of both lambda DNA and of restriction fragments of lambda DNA bearing the cohesive termini. Cohesion products of lambda DNA made in vitro are a mixture of linear and circular aggregates, whereas those made in vivo are cyclic monomers. We suggest a simple mechanism based upon condensation at the site of viral injection which may explain this discrepancy. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 85 TC 63 Z9 66 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD DEC PY 1995 VL 57 IS 1 BP 71 EP 92 DI 10.1016/0301-4622(95)00047-2 PG 22 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA TB471 UT WOS:A1995TB47100010 PM 8534838 ER PT J AU PODGORNIK, R STREY, HH RAU, DC PARSEGIAN, VA AF PODGORNIK, R STREY, HH RAU, DC PARSEGIAN, VA TI WATCHING MOLECULES CROWD - DNA DOUBLE HELICES UNDER OSMOTIC-STRESS SO BIOPHYSICAL CHEMISTRY LA English DT Article DE DNA; OSMOTIC STRESS; MOLECULAR CROWDING; X-RAY SCATTERING ID LIQUID-CRYSTALS; HYDRATION; POLYMERS; FORCES; PHASES AB Simultaneous measurements on the packing and energetics of high-density liquid crystalline DNA phases show that the crowding of long DNA polyelectrolytes at ever increasing concentrations is accomplished through straightening of the random coils that the double helix assumes in dilute solution. X-ray scattering by ordered phases reveals that the local straightening of the molecules is also accompanied by their progressive immobilization and confinement within the molecular 'cages' created by neighboring molecules. These effects can be dearly observed through the measured energies of DNA packing under osmotic stress and through the changes in structural and dynamic characteristics of X-ray scattering from DNA in ordered arrays at different concentrations. The character of the confinement of large DNA motions for a wide range of DNA concentrations is dominated by the soft potentials of direct interaction. We do not see the power-law variation of energy vs. volume expected from space-filling fluctuations of molecules that enjoy no interaction except the hard clash of steric repulsion. Rather, in highly concentrated DNA mesophases we see a crowding of molecules through electrostatic or hydration repulsion that confines their movements and positions. This view is based on directly measured packing energies as well as on concurrently measured structural parameters while the DNA double helices are condensed under an externally applied osmotic pressure. C1 NIDDK,DCRT,STRUCT BIOL LAB,BETHESDA,MD 20892. NIDDK,DIV INTRAMURAL RES,BETHESDA,MD 20892. RI Strey, Helmut/B-5456-2009; Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 24 TC 42 Z9 43 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD DEC PY 1995 VL 57 IS 1 BP 111 EP 121 DI 10.1016/0301-4622(95)00058-6 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA TB471 UT WOS:A1995TB47100013 PM 8534834 ER PT J AU Seshadri, K Rao, VSR Vishveshwara, S AF Seshadri, K Rao, VSR Vishveshwara, S TI Interaction of substrate uridyl 3',5'-adenosine with ribonuclease A: A molecular dynamics study SO BIOPHYSICAL JOURNAL LA English DT Article ID ORBITAL CALCULATIONS; NUCLEIC-ACIDS; FORCE-FIELD; PHOSPHATE; HYDROLYSIS; SIMULATION; MECHANISM; CATALYSIS; STEP; IMIDAZOLE AB A wealth of information available from x-ray crystallographic structures of enzyme-ligand complexes makes it possible to study interactions at the molecular level. However, further investigation is needed when i) the binding of the natural substrate must be characterized, because ligands in the stable enzyme-ligand complexes are generally inhibitors or the analogs of substrate and transition state, and when ii) ligand binding is in part poorly characterized. We have investigated these aspects i? the binding of substrate uridyl 3',5'-adenosine (UpA) to ribonuclease A (RNase A). Based on the systematically docked RNase A-UpA complex resulting from our previous study, we have undertaken a molecular dynamics simulation of the complex with solvent molecules. The molecular dynamics trajectories of this complex are analyzed to provide structural explanations for varied experimental observations on the ligand binding at the B2 subsite of ribonuclease A. The present study suggests that B2 subsite stabilization can be effected by different active site groups, depending on the substrate conformation. Thus when adenosine ribose pucker is O4'-endo, Gln69 and Glu111 form hydrogen-bonding contacts with adenine base, and when it is C2'-endo, Asn71 is the only amino acid residue in direct contact with this base. The latter observation is in support of previous mutagenesis and kinetics studies. Possible roles for the solvent molecules in the binding subsites are described. Furthermore, the substrate conformation is also examined along the simulation pathway to see if any conformer has the properties of a transition state. This study has also helped us to recognize that small but concerted changes in the conformation of the substrate can result in substrate geometry favorable for 2',3' cyclization. The identified geometry is suitable for intraligand proton transfer between 2'-hydroxyl and phosphate oxygen atom. The possibility of intraligand proton transfer as suggested previously and the mode of transfer before the formation of cyclic intermediate during transphosphorylation are discussed. C1 INDIAN INST SCI,MOLEC BIOPHYS UNIT,BANGALORE 560012,KARNATAKA,INDIA. LMMB,NATL CANC INST,ROCKVILLE,MD 20892. NR 34 TC 11 Z9 11 U1 1 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 1995 VL 69 IS 6 BP 2185 EP 2194 PG 10 WC Biophysics SC Biophysics GA TV018 UT WOS:A1995TV01800002 PM 8599627 ER PT J AU Chizmadzhev, YA Cohen, FS Shcherbakov, A Zimmerberg, J AF Chizmadzhev, YA Cohen, FS Shcherbakov, A Zimmerberg, J TI Membrane mechanics can account for fusion pore dilation in stages SO BIOPHYSICAL JOURNAL LA English DT Article ID VIRAL ENVELOPE PROTEIN; SECRETORY VESICLE; CELL-FUSION; EXOCYTOSIS; FORMS; STALK AB Once formed, fusion pores rapidly enlarge to semi-stable conductance values. The membranes lining the fusion pore are continuous bilayer structures, so variations of conductance in time reflect bending and stretching of membranes, We therefore modeled the evolution of fusion pores using the theory of the mechanics of deforming homogeneous membranes, We calculated the changes in length and width of theoretical fusion pores according to standard dynamical equations of motion. Theoretical fusion pores quickly achieve semi-stable dimensions, which correspond to energy minima located in a canyon between energy barriers. The height of the barrier preventing pore expansion diminishes along the dimensions of length and width. The bottom of the canyon slopes gently downward along increasing length. As a consequence, theoretical fusion pores slowly lengthen and widen as the dimensions migrate along the bottom of the canyon, until the barrier vanishes and the pore rapidly enlarges, The dynamics of growth is sensitive to tension, spontaneous curvature, bending elasticity, and mobilities. This sensitivity can account for the quantitative differences in pore evolution observed in two experimental systems: HA-expressing cells fusing to planar bilayer membranes and beige mouse mast cell degranulation. We conclude that the mechanics of membranes could cause the phenomenon of stagewise growth of fusion pores. C1 NICHHD,THEORET & PHYS BIOL LAB,NIH,BETHESDA,MD 20892. RUSH MED COLL,DEPT PHYSIOL,CHICAGO,IL 60612. AN FRUMKIN ELECTROCHEM INST,MOSCOW,RUSSIA. RI Chizmadzhev, Yuri/L-1984-2013 FU NIGMS NIH HHS [GM27367] NR 31 TC 47 Z9 47 U1 4 U2 6 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 1995 VL 69 IS 6 BP 2489 EP 2500 PG 12 WC Biophysics SC Biophysics GA TV018 UT WOS:A1995TV01800030 PM 8599655 ER PT J AU Yu, X Angov, E CarmeriniOtero, RD Egelman, EH AF Yu, X Angov, E CarmeriniOtero, RD Egelman, EH TI Structural polymorphism of the RecA protein from the thermophilic bacterium Thermus aquaticus SO BIOPHYSICAL JOURNAL LA English DT Article ID ATP-GAMMA-S; ESCHERICHIA-COLI; DNA COMPLEXES; ELECTRON-MICROSCOPY; UVSX PROTEIN; RECOMBINATION; FILAMENTS; RAD51; ASSOCIATION; INHIBITION AB The Escherichia coli RecA protein has served as a model for understanding protein-catalyzed homologous recombination, both in vitro and in vivo. Although RecA proteins have now been sequenced from over 60 different bacteria, almost all of our structural knowledge about RecA has come from studies of the E. coli protein. We have used electron microscopy and image analysis to examine three different structures formed by the RecA protein from the thermophilic bacterium Thermus aquaticus. This protein has previously been shown to catalyze an in vitro strand exchange reaction at an optimal temperature of about 60 degrees C. We show that the active filament formed by the T. aquaticus RecA on DNA in the presence of a nucleotide cofactor is extremely similar to the filament formed by the E. coli protein, including the extension of DNA to a 5.1-Angstrom rise per base pair within this filament. This parameter appears highly conserved through evolution, as it has been observed for the eukaryotic RecA analogs as well. We have also characterized bundles of filaments formed by the T. aquaticus RecA in the absence of both DNA and nucleotide cofactor, as well as hexameric rings of the protein formed under all conditions examined. The bundles display a very large plasticity of mass within the RecA filament, as well as showing a polymorphism in filament-filament contacts that may be important to understanding mutations that affect surface residues on the RecA filament. C1 UNIV MINNESOTA,SCH MED,DEPT CELL BIOL & NEUROANAT,MINNEAPOLIS,MN 55455. NIDDK,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. RI Egelman, Edward/A-2488-2009 FU NIGMS NIH HHS [GM35269] NR 40 TC 22 Z9 25 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 1995 VL 69 IS 6 BP 2728 EP 2738 PG 11 WC Biophysics SC Biophysics GA TV018 UT WOS:A1995TV01800054 PM 8599679 ER PT J AU Parsegian, VA Bezrukov, SM Vodyanoy, I AF Parsegian, VA Bezrukov, SM Vodyanoy, I TI Watching small molecules move: Interrogating ionic channels using neutral solutes SO BIOSCIENCE REPORTS LA English DT Article; Proceedings Paper CT Meeting on Membrane Dynamics and Permeability CY SEP 08, 1995 CL ROYAL SOC, LONDON, ENGLAND SP London Membrane Grp & Cell Surface Res Fund HO ROYAL SOC DE electric noise; ion channel; osmotic stress; sizing ID PROBING ALAMETHICIN CHANNELS; WATER-SOLUBLE POLYMERS; OSMOTIC ACTION; MEMBRANES AB Whether they are small enough to wriggle through the current-carrying part of an ionic channel or big enough to be kept outside and thus able to exert an osmotic stress on the channel space, polymers interact with channels in several instructive ways. The osmotic stress of excluded polymers allows one to measure the number of water molecules that come out of the channel in transitions between various ''open'' to ''closed'' states. The loss of osmotic activity, due to the partial or completely unrestricted admission of small polymers becomes a measure of the transfer probabilities of polymers from solution to small cavities: it provides an opportunity to study polymer conformation in a perfectly sieved preparation. Current fluctuations due to the partial blockage by a transient polymer are convened into estimates of times of passage and diffusion constants of polymers in channels. These estimates show how a channel whose functional stares last for milliseconds is able to average over the interactions with polymers, interactions that last only microseconds. One sees clearly that in this averaging, the macromolecular channel is large enough to react like a macroscopic object to the chemical potentials of the species that modulate its activity. C1 NIH,STRUCT BIOL LAB,DCRT,BETHESDA,MD 20892. RUSSIAN ACAD SCI,ST PETERSBURG NUCL PHYS INST,ST PETERSBURG 188350,RUSSIA. OFF NAVAL RES EUROPE,LONDON NW1 5TH,ENGLAND. RP Parsegian, VA (reprint author), NIDDK,DIV INTRAMURAL RES,NIH,BETHESDA,MD 20892, USA. NR 13 TC 23 Z9 23 U1 1 U2 4 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0144-8463 J9 BIOSCIENCE REP JI Biosci. Rep. PD DEC PY 1995 VL 15 IS 6 BP 503 EP 514 DI 10.1007/BF01204353 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UH431 UT WOS:A1995UH43100010 PM 9156580 ER PT J AU ZIMMERMAN, PA SHAPIRO, M TANG, J NUTMAN, TB UNNASCH, TR AF ZIMMERMAN, PA SHAPIRO, M TANG, J NUTMAN, TB UNNASCH, TR TI OPTIMIZING PROBE SELECTION IN DIRECTED HETERODUPLEX ANALYSIS USING HDPROBE-1.1 SO BIOTECHNIQUES LA English DT Article ID DNA; MISMATCHES; POLYMERASE; DISEASE AB Directed heteroduplex analysis (DHDA) has proven to be a powerful technique for rapid genotyping in human populations. This strategy should also have widespread utility in differentiating closely related organisms of medical and public health importance through identification of DNA sequence polymorphisms. Identifying an optimal probe sequence for use in DHDA has required empirical testing of both the positive and negative strands of a number of potential probes. To identify optimal probes more efficiently, a computer program has been developed that predicts the number of potential stable and unstable mismatches between a probe and its target sequences in DHDA. This information can then be used to predict-from among a group of potential probes-which one will be the most successful in differentiating closely related homologues of a targeted gene sequence. This approach was tested on a number of probe and target sequences derived from the mitochondrial NADH dehydrogenase subunit 4 gene of the West African black fly, Simulium damnosum sensu lato. The number of unstable mismatches predicted to occur in a given heteroduplex by the computer program was found to be important in differentiating closely related species. Therefore, this strategy is useful in identifying informative probes in the development of new DHDA-based assays. C1 UNIV MASSACHUSETTS,AMHERST,MA. UNIV ALABAMA,BIRMINGHAM,AL. RP ZIMMERMAN, PA (reprint author), NIAID,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. OI Tang, Jianming/0000-0003-0137-7486 FU NIAID NIH HHS [AI33008] NR 15 TC 8 Z9 8 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 1995 VL 19 IS 6 BP 972 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ086 UT WOS:A1995TJ08600020 PM 8747664 ER PT J AU WALDMANN, TA WHITE, JD CARRASQUILLO, JA REYNOLDS, JC PAIK, CH GANSOW, OA BRECHBIEL, MW JAFFE, ES FLEISHER, TA GOLDMAN, CK TOP, LE BAMFORD, R ZAKNOEN, S ROESSLER, E KASTENSPORTES, C ENGLAND, R LITOU, H JOHNSON, JA JACKSONWHITE, T MANNS, A HANCHARD, B JUNGHANS, RP NELSON, DL AF WALDMANN, TA WHITE, JD CARRASQUILLO, JA REYNOLDS, JC PAIK, CH GANSOW, OA BRECHBIEL, MW JAFFE, ES FLEISHER, TA GOLDMAN, CK TOP, LE BAMFORD, R ZAKNOEN, S ROESSLER, E KASTENSPORTES, C ENGLAND, R LITOU, H JOHNSON, JA JACKSONWHITE, T MANNS, A HANCHARD, B JUNGHANS, RP NELSON, DL TI RADIOIMMUNOTHERAPY OF INTERLEUKIN-2R-ALPHA-EXPRESSING ADULT T-CELL LEUKEMIA WITH YTTRIUM-90-LABELED ANTI-TAC SO BLOOD LA English DT Article ID MULTICHAIN INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODY; HUMANIZED ANTIBODY; CIS-DIAMMINEDICHLOROPLATINUM; HODGKINS-DISEASE; LYMPHOMA; IMMUNOGLOBULIN; EXPRESSION; INDUCTION; APOPTOSIS AB Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by the retrovirus human T-cell lymphotropic virus-I. It is an aggressive leukemia with a median survival time of 9 months; no chemotherapy regimen appears successful in inducing long-term disease-free survival. The scientific basis of the present study is that ATL cells express high-affinity interleukin-2 receptors identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this difference, we administered anti-Tac armed with Yttrium-90 (Y-90) to 18 patients with ATL initially (first 9 patients) in a phase I dose-escalation trial and subsequently (second group of 9 patients) in a phase II trial involving a uniform 10-mCi dose of Y-90-labeled anti-Tac. Patients undergoing a remission were permitted to receive up to eight additional doses. At the 5- to 15-mCi doses used. 9 of 16 evaluable patients responded to Y-90 anti-Tac with a partial (7 patients) or complete (2 patients) remission. The responses observed represent improved efficacy in terms of length of remission when compared with previous results with unmodified anti-Tac. Clinically meaningful (greater than or equal to grade 3) toxicity was largely limited to the hematopoietic system. In conclusion, radioimmunotherapy with Y-90 anti-Tac directed toward the IL-2R expressed on ATL cells may provide a useful approach for treatment of this aggressive malignancy. This is a US government work. There are no restrictions on its use. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. UNIV W INDIES,DEPT PATHOL,KINGSTON 7,JAMAICA. RP WALDMANN, TA (reprint author), NCI,METAB BRANCH,BLDG 10,ROOM 4N115,BETHESDA,MD 20892, USA. RI Carrasquillo, Jorge/E-7120-2010 NR 59 TC 178 Z9 180 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1995 VL 86 IS 11 BP 4063 EP 4075 PG 13 WC Hematology SC Hematology GA TG663 UT WOS:A1995TG66300007 PM 7492762 ER PT J AU FARINA, SF GIRARD, LJ VANIN, EF NIENHUIS, AW BODINE, DM AF FARINA, SF GIRARD, LJ VANIN, EF NIENHUIS, AW BODINE, DM TI DYSREGULATED EXPRESSION OF GATA-1 FOLLOWING RETROVIRUS-MEDIATED GENE-TRANSFER INTO MURINE HEMATOPOIETIC STEM-CELLS INCREASES ERYTHROPOIESIS SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; DNA-BINDING PROTEIN; ERYTHROID-DIFFERENTIATION; MOUSE; PROMOTER; ENHANCER; MICE; SEQUENCE; FAMILY; DEATH AB Retrovirus-mediated gene transfer was used to study the effects of dysregulated expression of the zinc-finger transcription factor, GATA-1, which has been shown to be required for erythropoiesis. A retroviral vector (PGK-GATA-1) was constructed with the murine GATA-1 gene linked to the human phosphoglycerate kinase (PGK) promoter. Expression of GATA-1 was demonstrated by super-shift analysis with a monoclonal antibody against murine GATA-1 using extracts of nonerythroid cytotoxic T-lymphocyte line (CTLL) cells transduced with the PGK-GATA-1 virus. Mouse bone marrow cells were transduced in vitro and transplanted into recipient animals. Polymerase chain reaction (PCR) analysis performed on DNA extracted from peripheral blood 12 to 40 weeks posttransplantation demonstrated the presence of the PGK-GATA-1 provirus. Proviral integrity and copy number were demonstrated by Southern blot analysis of DNA from spleen, thymus, and bone marrow tissues from the long-term animals. At 16 weeks posttransplant, animals that received cells transduced by the GATA-1 virus maintained a lower white blood cell (WBC) count and absolute neutrophil count (ANC) and a higher red blood cell (RBC) count than control animals that received cells transduced with a Virus containing a neo' gene. Erythropoiesis was stimulated in GATA-1 and control animals by phlebotomy. GATA-1 animals required more extensive phlebotomy to reach a hematocrit less than 25 and their hematocrit returned to normal levels sooner than control animals. The affect of twice-daily injections of 10 U recombinant erythropoietin (epo) was also examined. The hematocrit of GATA-1 animals showed a more rapid and elevated response to epo than the hematocrit of control animals. These data suggest that dysregulated expression of GATA-1 in primitive hematopoietic cells enlarges the pool of epo-responsive erythroid progenitor cells. (C) 1995 by The American Society of Hematology. C1 NIH, NATL CTR HUMAN GENOME RES, HEMATOPOISIS SECT, BETHESDA, MD 20892 USA. GENET THERAPY INC, GAITHERSBURG, MD USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. NR 62 TC 27 Z9 28 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 1995 VL 86 IS 11 BP 4124 EP 4133 PG 10 WC Hematology SC Hematology GA TG663 UT WOS:A1995TG66300014 PM 7492769 ER PT J AU MOJCIK, CF SALOMON, DR CHANG, AC SHEVACH, EM AF MOJCIK, CF SALOMON, DR CHANG, AC SHEVACH, EM TI DIFFERENTIAL EXPRESSION OF INTEGRINS ON HUMAN THYMOCYTE SUBPOPULATIONS SO BLOOD LA English DT Article ID CELLULAR ADHESION MOLECULES; HUMAN THYMIC DEVELOPMENT; HUMAN FETAL THYMUS; IMMATURE THYMOCYTES; T-CELLS; REGULATED EXPRESSION; POSITIVE SELECTION; ACTIVATION ANTIGEN; SURFACE-ANTIGEN; STROMAL CELLS AB Integrins represent a candidate group of cell surface receptors that may control the homing and population of the thymus by T-cell precursors and the subsequent migration of developing thymocytes through the thymic architecture. We have used multiparameter flow cytometric methods to characterize the expression of several members of the integrin family (alpha 3 beta 1, alpha 4 beta 1, alpha 5 beta 1, alpha 6 beta 1, and alpha L beta 2) on thymocyte subpopulations and have correlated integrin expression with other well-defined thymocyte differentiation markers. alpha 4 beta 1 was expressed by all thymocytes, but expression was highest on CD4(-)CD8(-) double-negative (DN) cells, high on CD(+)CD8(+) double-positive (DP) cells. and lowest on mature single-positive (SP) cells. alpha 3 beta 1, alpha 5 beta 1, and alpha 6 beta 1 were present on 13%, 63%, and 26% of thymocytes, respectively, with maximal levels of expression on DN and SP cells, and low levels of expression on de cells. Simultaneous analysis of alpha 4 beta 1, alpha 5 beta 1, and CD3 expression suggested a pathway of T-cell differentiation in the thymus in which the majority of the DN cells were alpha 4 beta 1(hi)alpha 5 beta 1(hi), the Dp cells alpha 4 beta 1(hi)alpha 5 beta 1(lo/-), the most mature SP cells were alpha 4 beta 1(lo)alpha 5 beta 1(int). The stage-specific expression of integrins strongly implies their functional involvement during T-cell maturation in the thymus. This is a US government work. There are no restrictions on its use. C1 NIAID, CELLULAR IMMUNOL SECT, IMMUNOL LAB, MOLEC STRUCT LAB, BETHESDA, MD 20892 USA. SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. RI Salomon, Daniel/E-9380-2012 NR 59 TC 24 Z9 24 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1995 VL 86 IS 11 BP 4206 EP 4217 PG 12 WC Hematology SC Hematology GA TG663 UT WOS:A1995TG66300024 PM 7492779 ER PT J AU WANG, LM MICHIELI, P LIE, WR LIU, F LEE, CC MINTY, A SUN, XJ LEVINE, A WHITE, MF PIERCE, JH AF WANG, LM MICHIELI, P LIE, WR LIU, F LEE, CC MINTY, A SUN, XJ LEVINE, A WHITE, MF PIERCE, JH TI THE INSULIN-RECEPTOR SUBSTRATE-1-RELATED 4PS SUBSTRATE BUT NOT THE INTERLEUKIN-2R-GAMMA CHAIN IS INVOLVED IN INTERLEUKIN-13-MEDIATED SIGNAL-TRANSDUCTION SO BLOOD LA English DT Article ID TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; MOLECULAR-CLONING; SH3 DOMAIN; PROTEIN; EXPRESSION; ACTIVATION; KINASE; RAS; SUPERFAMILY AB Interleukin-13 (IL-13) induced a potent mitogenic response in IL-3-dependent TF-1 cells and DNA synthesis to a lesser extent in MO7E and FDC-P1 cells. IL-13 stimulation of these lines, like IL-4 and insulin-like growth factor-1 (IGF-1), resulted in tyrosine phosphorylation of a 170-kD substrate. The tyrosine-phosphorylated 170-kD substrate strongly associated with the 85-kD subunit of phosphoinositol-3 (PI-3) kinase and with Grb-2. Anti-4PS serum readily detected the 170-kD substrate in lysates from both TF-1 and FDC-P1 cells stimulated with IL-13 or IL-4. These data provide evidence that IL-13 induces tyrosine phosphorylation of the 4PS substrate, providing an essential interface between the IL-13 receptor and signaling molecules containing SH2 domains. IL-13 and IL-4 stimulation of murine L cell fibroblasts, which endogenously express the IL-4 receptor (IL-4R alpha) and lack expression of the IL-2 receptor gamma subunit (IL-2R gamma). resulted in tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1)/4PS. Enhanced tyrosine phosphorylation of IRS-1/4PS was observed in response to IL-4, but not IL-13 treatment of L cells transfected with the IL-2R gamma chain. These results indicate that IL-13 does not use the IL-2R gamma subunit in its receptor complex and that expression of IL-2R gamma enhances, but is not absolutely required for mediating IL-4-induced tyrosine phosphorylation of IRS-1/4PS. This is a US government work. There are no restrictions on its use. C1 NIH,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. MONSANTO CO,SEARLE RES & DEV,ST LOUIS,MO. CORNELL MED SCH,NEW YORK,NY. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC. SANOFI RES LAB,LABERGE,FRANCE. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA. RI Michieli, Paolo/A-2588-2011 NR 44 TC 32 Z9 32 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1995 VL 86 IS 11 BP 4218 EP 4227 PG 10 WC Hematology SC Hematology GA TG663 UT WOS:A1995TG66300025 PM 7492780 ER PT J AU Vitkovic, L Chatham, JJ daCunha, A AF Vitkovic, L Chatham, JJ daCunha, A TI Distinct expressions of three cytokines by IL-1-stimulated astrocytes in vitro and in AIDS brain SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article ID COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INFECTED PROMONOCYTE CLONE; ASTROGLIAL CELL PRODUCTION; HIV-1 EXPRESSION; GENE-EXPRESSION; INDUCTION; LIPOPOLYSACCHARIDE; INTERLEUKIN-1 AB Interleukin-1 (n-1) is elevated in brain tissue of individuals who died with acquired immunodeficiency syndrome (AIDS) and other diseases where this cytokine likely stimulates reactive astrocytosis. IL-1 stimulates, among others, production of interleukin-6 (IL-6), granulocyte macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) in cultured astrocytes and astrocytoma cell lines. These and other cytokines may contribute to the neuropathogenesis after infection by human immunodeficiency virus type-1 (HIV-1). For example, concentration of TNF-alpha is increased in brain tissue of individuals who died with AIDS and correlates with the severity of AIDS Dementia Complex (ADC). TNF-alpha and IL-6 have been immunocytochemically detected in brain tissue but they have not been localized to astrocytes. We, therefore, examined the expression of IL-6, GM-CSF, and TNF-alpha in human primary astrocytes and astrocytoma cell lines U251 and 253 exposed to IL-1 in serum-free medium. In addition, we immunocytochemically assayed GM-CSF expression by astrocytes in brain tissue (n = 8). The three cytokines were differentially induced in cultured astrocytes by IL-1. The astrocytoma cell lines recapitulated cytokine-specific patterns of expression in astrocytes. The patterns were characterized by amounts produced, compartmentalization (intra- and/or extracellular), time courses, and optimal doses of IL-1 for induction. GM-SCF-like immunoreactivity was detected in some but not all, GFAP(+) cells. GM-CSF+/GFAP(+) cells were detected in only three of seven cases containing GM-CSF immunoreactivity. Thus, a discrepancy may exist between human astrocytic cytokine expression in vitro and in tissue. Novel methods therefore may need to be developed to recapitulate in vitro the heterogeneity of astrocytic cytokine expression in AIDS and other brain tissue. (C) 1995 Academic Press, Inc. C1 TUFTS UNIV, SCH MED, BOSTON, MA 02111 USA. NIMH, CELL BIOL LAB, MOLEC NEUROSCI SECT, BETHESDA, MD 20892 USA. RP Vitkovic, L (reprint author), NIMH, DIV NEUROSCI & BEHAV SCI, 5600 FISHERS LANE, RM 11C-06, ROCKVILLE, MD 20857 USA. NR 32 TC 25 Z9 25 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 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD DEC PY 1995 VL 9 IS 4 BP 378 EP 388 DI 10.1006/brbi.1995.1035 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA TP941 UT WOS:A1995TP94100011 PM 8903854 ER PT J AU ACEVEDO, LD GALDZICKI, Z MCINTOSH, AR RAPOPORT, SI AF ACEVEDO, LD GALDZICKI, Z MCINTOSH, AR RAPOPORT, SI TI INCREASED INWARD CURRENT IN SEPTAL NEURONS FROM THE TRISOMY-16, MOUSE, A MODEL FOR DOWNS-SYNDROME SO BRAIN RESEARCH LA English DT Article DE TRISOMY 16 MOUSE; DOWNS SYNDROME; SEPTUM; NEURON CULTURE; MEMBRANE CURRENT; ACTION POTENTIAL ID DORSAL-ROOT GANGLION; HIPPOCAMPAL THETA-RHYTHM; ELECTROPHYSIOLOGICAL PROPERTIES; BASAL FOREBRAIN; ALZHEIMERS-DISEASE; NUCLEUS BASALIS; SPATIAL-MEMORY; SODIUM CURRENT; MEDIAL SEPTUM; ANIMAL-MODEL AB We examined the electrophysiological properties of neurons cultured from the septum of the trisomy 16 mouse fetus, an animal model for Down's syndrome. The passive membrane properties were not different between trisomic and diploid septal neurons. We distinguished low-firing and high-firing populations of neurons based on differences in the firing rate evoked during current injection. Low-firing neurons fired three or fewer action potentials, high-firing neurons fired four or more. The membrane currents of low-firing trisomic neurons were not different from those of low-firing diploid neurons. However, high-firing trisomic neurons had an increased inward current and conductance, and a greater inward-to-outward conductance ratio. The increased current and conductance were independent of the passive electrical properties. The increased inward current in high-firing trisomic neurons was correlated with action potentials having faster depolarization rates. This greater excitability among this population of trisomic septal neurons, coupled with. a reduced excitation in hippocampal neurons, may compromise septohippocampal and memory function. RP ACEVEDO, LD (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C103,BETHESDA,MD 20892, USA. RI McIntosh, Anthony/G-4955-2011; OI McIntosh, Anthony/0000-0002-1784-5662 NR 35 TC 12 Z9 12 U1 0 U2 0 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 1 PY 1995 VL 701 IS 1-2 BP 89 EP 98 DI 10.1016/0006-8993(95)00979-6 PG 10 WC Neurosciences SC Neurosciences & Neurology GA TJ267 UT WOS:A1995TJ26700011 PM 8925303 ER PT J AU CHOW, WH MCLAUGHLIN, JK HRUBEC, Z FRAUMENI, JF AF CHOW, WH MCLAUGHLIN, JK HRUBEC, Z FRAUMENI, JF TI SMOKING AND BILIARY-TRACT CANCERS IN A COHORT OF US VETERANS SO BRITISH JOURNAL OF CANCER LA English DT Note DE BILIARY TRACT NEOPLASM; CIGARETTE SMOKING; COHORT STUDY ID UNITED-STATES VETERANS; GALLBLADDER CANCER; RISK; GALLSTONES; DEATH AB Except for gallstones, the risk factors for cancers of the biliary tract (CBTs) are poorly understood. Recent case-control studies have suggested cigarette smoking as a potential risk factor, In a cohort study of nearly 250 000 US veterans whose mortality was followed for up to 26 years, we evaluated the risk of CBT associated with tobacco use. Relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated. A total of 303 CBT deaths were observed during the follow-up period. Compared with those who had never used any tobacco, current cigarette smokers at entry to the cohort had a 50% excess risk of CBT (RR=1.5, CI=1.1-2.0). A nearly 2-fold risk was observed among those who smoked more than 20 cigarettes per day and among those who started smoking under age 20. Non-significant increases in risk occurred among smokers of other forms of tobacco. This cohort study is consistent with reports that smoking is a risk factor for CBT, but further studies are needed to clarify whether the effect is specific for certain subsites and whether it reflects an association with pre-existent gallstones. RP CHOW, WH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,EPN 415,BETHESDA,MD 20852, USA. NR 21 TC 12 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD DEC PY 1995 VL 72 IS 6 BP 1556 EP 1558 DI 10.1038/bjc.1995.547 PG 3 WC Oncology SC Oncology GA TH550 UT WOS:A1995TH55000035 PM 8519677 ER PT J AU BOSCH, F CAMPO, E JARES, P PITTALUGA, S MUNOZ, J NAYACH, I PIRIS, MA DEWOLFPEETERS, C JAFFE, ES ROZMAN, C MONTSERRAT, E CARDESA, A AF BOSCH, F CAMPO, E JARES, P PITTALUGA, S MUNOZ, J NAYACH, I PIRIS, MA DEWOLFPEETERS, C JAFFE, ES ROZMAN, C MONTSERRAT, E CARDESA, A TI INCREASED EXPRESSION OF THE PRAD-1/CCND1 GENE IN HAIRY-CELL LEUKEMIA SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE HAIRY CELL LEUKEMIA; T(11-14); PRAD1/CCND1; CYCLIN D1; ONCOGENES ID CANDIDATE ONCOGENE; CYCLE PROGRESSION; CHROMOSOME 11Q13; BCL-1 GENE; LEUKEMIA; OVEREXPRESSION; REARRANGEMENT; TRANSLOCATION; LYMPHOMAS; CLONING AB The PRAD-1/CCND1 gene encodes Cyclin D1, a cyclin involved in cell cycle regulation at the G(1)-S transition. Over-expression of this gene is a highly specific molecular marker of mantle cell lymphomas (MCLs), but it may also be up-regulated in some chronic lymphoproliferative disorders, mainly chronic lymphocytic leukaemia. We have examined PRAD-1/CCND1 gene expression by Northern blot and Western blot analysis in a series of 18 hairy cell leukaemias (HCLs), nine other splenic malignant lymphoproliferative disorders, and three normal/reactive spleens, Over-expression of the mRNA PRAD-1/CCND1 gene was observed in 16/18 HCLs, including one case of hairy cell leukaemia variant, whereas this molecular alteration was not found in other cases examined, mRNA levels varied from case to case, but they were lower than those observed in MCLs. At the protein level, Western blotting analysis showed Cyclin D1 protein expression in the 11 HCLs analysed. No bcl-1 rearrangements were seen with the MTC, p94PS and PRAD-1 (lambda-P1-4) probes used, and no PRAD-1/CCND1 gene amplification was detected in any case. These findings indicate that PRAD-1/CCND1 is over-expressed at mRNA and protein levels in a high number of HCLs. However, the levels of expression are much lower than in MCLs, and this expression is not associated with bcl-1 rearrangements or PRAD-1/CCND1 gene amplification. C1 UNIV BARCELONA,HOSP CLIN,DEPT ANAT PATHOL,E-08036 BARCELONA,SPAIN. UNIV BARCELONA,HOSP CLIN,POSTGRAD SCH HAEMATOL FARRERAS VALENTI,BARCELONA,SPAIN. UNIV LLEIDA,DEPT BASIC MED SCI,LLEIDA,SPAIN. CATHOLIC UNIV LEUVEN,DEPT PATHOL,B-3000 LOUVAIN,BELGIUM. NATL CANC INST,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD. HOSP VIRGEN DE LA SALUD,DEPT ANAT PATHOL,TOLEDO,SPAIN. NR 39 TC 73 Z9 74 U1 0 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 1995 VL 91 IS 4 BP 1025 EP 1030 DI 10.1111/j.1365-2141.1995.tb05429.x PG 6 WC Hematology SC Hematology GA TJ609 UT WOS:A1995TJ60900041 PM 8547115 ER PT J AU ZIPPIN, C LUM, D HANKEY, BF AF ZIPPIN, C LUM, D HANKEY, BF TI COMPLETENESS OF HOSPITAL CANCER CASE REPORTING FROM THE SEER PROGRAM OF THE NATIONAL-CANCER-INSTITUTE SO CANCER LA English DT Article DE CANCER REGISTRY; COMPLETENESS; QUALITY CONTROL; CASE-FINDING ID REGISTRATION; ENGLAND; WALES AB Background. To ascertain the quality of data entering a population-based reporting system, an essential requirement is to study levels of completeness of case-ascertainment and reporting. This study represents an effort to quantify completeness of case reporting in the SEER (Surveillance, Epidemiology, and End Results) Program of the National Cancer Institute. Methods. Hospitals in each of the participating SEER areas were stratified according to their annual hospital cancer caseload for the year 1987. Within each caseload stratum, a random sample of hospitals was selected for inclusion in this study. Files in the medical record, pathology, and radiation oncology departments in each hospital were reviewed for SEER reportable cases, These cases were then matched against SEER case listings to identify unreported cases. Results. The crude estimated completeness of reporting for 1987 in the six participating SEER areas was 97.7% and the registry-caseload standardized rate was 96.8%, Variation was noted by SEER registry, hospital cancer caseload, and casefinding source (hospital department). Three-quarters of unreported cases were of invasive disease and one-fourth were in situ, primarily of the cervix uteri. Conclusions. There is variation in completeness of casefinding among SEER registries, hospital size, and hospital department source. Additional factors that appear to be related to case ascertainment are cancer site or type and who performs the casefinding function (hospital registry or central registry staff). C1 UNIV CALIF SAN FRANCISCO,CANC RES INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA 94143. NCI,DIV CANC PREVENT & CONTROL,CANC STAT BRANCH,BETHESDA,MD 20892. RP ZIPPIN, C (reprint author), UNIV CALIF SAN FRANCISCO,SCH MED,DEPT BIOSTAT & EPIDEMIOL,CANC PATIENT DATA PROGRAM,SAN FRANCISCO,CA 94143, USA. FU NCI NIH HHS [N01 CN 05247] NR 5 TC 215 Z9 215 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 1995 VL 76 IS 11 BP 2343 EP 2350 DI 10.1002/1097-0142(19951201)76:11<2343::AID-CNCR2820761124>3.0.CO;2-# PG 8 WC Oncology SC Oncology GA TF104 UT WOS:A1995TF10400023 PM 8635041 ER PT J AU WALSH, TJ WHITCOMB, PO REVANKAR, SG PIZZO, PA AF WALSH, TJ WHITCOMB, PO REVANKAR, SG PIZZO, PA TI SUCCESSFUL TREATMENT OF HEPATOSPLENIC CANDIDIASIS THROUGH REPEATED CYCLES OF CHEMOTHERAPY AND NEUTROPENIA SO CANCER LA English DT Article DE CANDIDIASIS; HEPATOSPLENIC CANDIDIASIS; CHRONIC DISSEMINATED CANDIDIASIS; ANTIFUNGAL THERAPY; NEUTROPENIA ID HEPATIC CANDIDIASIS; IMMUNOCOMPROMISED PATIENTS; SYSTEMIC CANDIDIASIS; FUNGAL-INFECTIONS; AMPHOTERICIN-B; FLUCONAZOLE; TOMOGRAPHY; LEUKEMIA AB Background. Hepatosplenic candidiasis (HSC) or chronic disseminated candidiasis is an increasingly recognized problem in patients with cancer. Whether patients with HSC should continue to receive antineoplastic therapy, which may cause neutropenia with the risk for progressive HSC or breakthrough fungemia, can be a major dilemma. Patients with HSC at the National Cancer Institute continue antineoplastic therapy, when possible, during antifungal therapy for HSC, despite repeated bouts of neutropenia. Therefore, whether this strategy resulted in breakthrough fungemia or progression of HSC was investigated. Methods. All patients consecutively treated at the National Cancer Institute at the Warren-Grant Magnuson Clinical Center from 1982-1992 for HSC were prospectively studied for therapeutic and outcome variables of antifungal and antineoplastic management. Each case was summarized on a time-event line to quantify the duration of simultaneous periods of antineoplastic therapy and antifungal therapy (AFT). Results. Sixteen patients (median age, 22 years) with HSC were studied. Eleven patients had relapsed tumor and 5 had newly diagnosed tumor. During antifungal therapy for HSC, 12 of 16 patients were neutropenic for a median of 10 days (range, 6-91 days) and 11 were profoundly neutropenic for a median of 13 days (range, 1-55 days). Hepatosplenic candidiasis was successfully treated with complete antifungal response in 12 patients and a partial response in 2; 2 patients continued to receive AFT. No patient had breakthrough fungemia and two patients had progression of HSC, only one episode of which occurred during neutropenia. Conclusions. Hepatosplenic candidiasis in patients with cancer may be treated successfully under careful observation through repeated courses of chemotherapy-induced neutropenia without progression of hepatosplenic candidiasis or breakthrough fungemia. RP WALSH, TJ (reprint author), NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,RM 13N-240,BETHESDA,MD 20892, USA. NR 19 TC 64 Z9 65 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 1995 VL 76 IS 11 BP 2357 EP 2362 DI 10.1002/1097-0142(19951201)76:11<2357::AID-CNCR2820761126>3.0.CO;2-H PG 6 WC Oncology SC Oncology GA TF104 UT WOS:A1995TF10400025 PM 8635043 ER PT J AU BRESLOW, RA ALBERG, AJ HELZLSOUER, KJ BUSH, TL NORKUS, EP MORRIS, JS SPATE, VE COMSTOCK, GW AF BRESLOW, RA ALBERG, AJ HELZLSOUER, KJ BUSH, TL NORKUS, EP MORRIS, JS SPATE, VE COMSTOCK, GW TI SEROLOGICAL PRECURSORS OF CANCER - MALIGNANT-MELANOMA, BASAL AND SQUAMOUS-CELL SKIN-CANCER, AND PREDIAGNOSTIC LEVELS OF RETINOL, BETA-CAROTENE, LYCOPENE, ALPHA-TOCOPHEROL, AND SELENIUM SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SUBSEQUENT RISK; VITAMIN-E; CLINICAL-TRIAL; SERUM LEVELS; FINNISH MEN; FOLLOW-UP AB To determine the association between prediagnostic serum levels of retinol, beta-carotene, lycopene, alpha-tocopherol, and selenium and the subsequent risk of malignant melanoma, and basal and squamous cell skin cancer, a nested case-control study among residents of Washington County, MD, was performed. Cases with melanoma (n = 30), basal cell (n = 32), and squamous cell (n = 37) skin cancer who were admitted to hospital for treatment or biopsy of metastatic lesions were each matched by age, sex, and race with two controls. There were no significant associations between serum micronutrient levels and the risk of subsequent skin cancer. C1 NCI,CANC PREVENT FELLOWSHIP PROGRAM,BETHESDA,MD 20852. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. OUR LADY MERCY MED CTR,BRONX,NY 10466. UNIV MISSOURI,REACTOR RES FACIL,COLUMBIA,MO 65211. FU NCI NIH HHS [CA47503, CA01522, CA36390] NR 32 TC 57 Z9 57 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 1995 VL 4 IS 8 BP 837 EP 842 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA TJ523 UT WOS:A1995TJ52300006 PM 8634654 ER PT J AU JI, BT CHOW, WH GRIDLEY, G MCLAUGHLIN, JK DAI, Q WACHOLDER, S HATCH, MC GAO, YT FRAUMENI, JF AF JI, BT CHOW, WH GRIDLEY, G MCLAUGHLIN, JK DAI, Q WACHOLDER, S HATCH, MC GAO, YT FRAUMENI, JF TI DIETARY FACTORS AND THE RISK OF PANCREATIC-CANCER - A CASE-CONTROL STUDY IN SHANGHAI, CHINA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PAST MEDICAL HISTORY; NUTRITIONAL FACTORS; EXOCRINE PANCREAS; TRYPSIN-INHIBITOR; NUTRIENT INTAKE; MORTALITY; HAMSTERS; ALCOHOL; FOODS AB In Shanghai, China, age-adjusted incidence rates for pancreatic cancer have increased steadily, beginning in the early 1970s. To examine the effects of diet on this cancer, a population-based case-control study was conducted. Cases (n = 451) were permanent residents of Shanghai, 30-74 years of age, newly diagnosed with pancreatic cancer between October 1, 1990 and June 30, 1993. Deceased cases (19%) were excluded from the study. Controls (n = 1552) were selected among Shanghai residents, frequency matched to cases by gender and age. Information on usual adult dietary intake was obtained by trained interviewers in person, using a food frequency questionnaire. Dietary associations were measured by odds ratios and 95% confidence intervals. Risks of pancreatic cancer were inversely associated with consumption of vegetables (P for trend among men = 0.03; among women = 0.15) and fruits (P among men 0.02; among women = 0.08). Reductions in risk were related also to intake of dietary fiber and micronutrients abundant in plant sources, such as vitamins C and E and carotene. There was also an inverse association with egg consumption (P for trend among men = 0.08; among women = 0.001). No consistent positive associations were observed with intake of other food groups, including preserved animal foods, fresh red meat, organ meat, poultry, and staple foods. On the other hand, risks increased with frequency of consumption of preserved vegetables and foods that were deep fried, grilled, cured, or smoked, providing clues to the possible role of nitrosamines, polycyclic aromatic hydrocarbons, and heterocyclic aromatic amines. The inverse associations observed with intake of dietary fat and protein in our study were unexpected, although these findings were based on consumptions well below the average intake in Western countries, where most previous studies on pancreatic cancer were conducted. Our results suggest that dietary variations have contributed little to the rising trends of pancreatic cancer in Shanghai. However, given the improving food availability and changing dietary patterns in China, further study of dietary and nutritional risk factors for pancreatic cancer appears warranted. C1 COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY 10032. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CP-05626] NR 51 TC 96 Z9 97 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 1995 VL 4 IS 8 BP 885 EP 893 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA TJ523 UT WOS:A1995TJ52300014 PM 8634662 ER PT J AU BLAESE, M BLANKENSTEIN, T BRENNER, M COHENHAGUENAUER, O GANSBACHER, B RUSSELL, S SORRENTINO, B VELU, T AF BLAESE, M BLANKENSTEIN, T BRENNER, M COHENHAGUENAUER, O GANSBACHER, B RUSSELL, S SORRENTINO, B VELU, T TI VECTORS IN CANCER-THERAPY - HOW WILL THEY DELIVER SO CANCER GENE THERAPY LA English DT Review ID RETROVIRAL VECTORS; LEUKEMIA-VIRUS; GENE-TRANSFER; CELLS C1 ST JUDE CHILDRENS RES HOSP, DIV BONE MARROW TRANSPLANTAT, MEMPHIS, TN 38101 USA. NIH, NATL CTR HUMAN GENOME RES, CLIN GENE THERAPY BRANCH, BETHESDA, MD 20892 USA. MAX DELBRUCK CENTRUM MOLEK MED, BERLIN, GERMANY. HOP ST LOUIS, DEPT MED ONCOL, F-75475 PARIS 10, FRANCE. HOP ST LOUIS, INST HEMATOL, F-75475 PARIS 10, FRANCE. MEM SLOAN KETTERING CANC CTR, LEUKEMIA SERV, NEW YORK, NY 10021 USA. ERASME UNIV HOSP, DEPT MED GENET, B-1070 BRUSSELS, BELGIUM. UNIV CAMBRIDGE, CTR MRC, CAMBRIDGE CTR PROT ENGN, CAMBRIDGE CB2 2QH, ENGLAND. ST JUDE CHILDRENS RES HOSP, DEPT EXPTL HEMATOL, MEMPHIS, TN 38105 USA. NR 33 TC 50 Z9 51 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 EI 1476-5500 J9 CANCER GENE THER JI Cancer Gene Ther. PD DEC PY 1995 VL 2 IS 4 BP 291 EP 297 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA TD705 UT WOS:A1995TD70500005 PM 8548583 ER EF