FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Notario, V DiPaolo, JA AF Notario, V DiPaolo, JA TI Molecular aspects of neoplasia of Syrian hamster cells transformed in vitro by chemical carcinogens SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 6th European Meeting of Environmental Hygiene CY JUN 03-05, 1997 CL GRAZ, AUSTRIA SP Med Inst Environm Hygiene, Univ Dusseldorf, Inst Hygiene, Univ Graz, Bayer AG, Mercedes-Benz, INBIFO DE neoplastic transformation; chemical carcinogens; Cph-carcinogenesis promotion hamster gene ID P53 GENE; RAS; FIBROBLASTS; ACTIVATION; PROMOTER; UPSTREAM; ONCOGENE; CPH AB The addition of environmental agents (carcinogens) induces transformation that can be quantitated. Its frequency follows a linear relationship with dose and is consistent with a one hit' phenomenon. Transformed colonies produce transformed lines with attributes of neoplastic cells including production of tumors. The results parallel in vivo activity. Although, molecular analysis of most animal assay indicate the presence of activated oncogenes belonging to the ras family, vas activation is a low frequency event in the neoplastic conversion of Syrian hamster cells just as is found with human malignancies. In our analysis of 22 independently derived lines N-ras activation was found only with sodium bisulfite transformed lines. A novel oncogene named carcinogenesis promotion hamster (cph) because its association with the carcinogenic process has been identified. This resulted from focusing on Syrian hamster cells transformed with a single dose of 3-methylcholanthrene (MCA) and cosmid-rescue-techniques from a third-cycle NIH3T3 transformant obtained by sequential transfections of genomic DNA from MCA-initiated hamster fetal cells. cph transforms NIH3T3 cells and acts synergistically with Ha-uas to transform murine fibroblasts. Gene expression analysis using cph genomic fragments from normal and neoplastic cells identifies a number of transcripts including a major mRNA of 2.5kb as well as several larger transcripts. cph is actively transcribed in different tissues and different species. In the hamster it is a single copy gene localized by I:ISH to the euchromatic short arm of the X chromosome, at region Xpa7. cph does not have any significant global homology to sequences deposited in date banks, confirming that it is a novel gene. The transforming gene codes for a truncated 246 amino acids whereas the normal cph has a residue of 469 amino acids. In conclusion cph oncogene is activated by a single point-mutation: its activation appears an important mechanism for the conversion of carcinogen treated hamster cells to malignancy and because homologous sequences occur in human DNA it may also be important to the neoplastic conversion of human cells. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Biol Lab, NIH, Div Basic Sci, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Radiat Med, Washington, DC 20007 USA. RP DiPaolo, JA (reprint author), NCI, Biol Lab, NIH, Div Basic Sci, Bldg 37-2A19, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA64472] NR 29 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD AUG PY 1998 VL 96-7 BP 221 EP 230 DI 10.1016/S0378-4274(98)00076-9 PG 10 WC Toxicology SC Toxicology GA 131PR UT WOS:000076584900031 PM 9820671 ER PT J AU Hill, EM Eling, T Nettesheim, P AF Hill, EM Eling, T Nettesheim, P TI Differentiation dependency of eicosanoid enzyme expression in human tracheobronchial cells SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 6th European Meeting of Environmental Hygiene CY JUN 03-05, 1997 CL GRAZ, AUSTRIA SP Med Inst Environm Hygiene, Univ Dusseldorf, Inst Hygiene, Univ Graz, Bayer AG, Mercedes-Benz, INBIFO DE differentiation; enzymes; metabolites ID HAMSTER TRACHEAL EPITHELIUM; ARACHIDONIC-ACID; MONOHYDROXYEICOSATETRAENOIC ACID; RELEASE; 15-LIPOXYGENASE; GENERATION AB The expression of 15-lipoxygenase (15-LO) and prostaglandin H synthase-2 (PGHS-2) was studied in retinoic acid (RA) sufficient and RA-deficient normal human tracheobronchial epithelial (NHTBE) cell cultures. In the absence of RA, in which the cultures became squamous metaplastic, neither 15-LO nor PGHS-2 were expressed. In RA-sufficient cultures, which differentiated into a mucociliary epithelium, both enzymes were expressed: PGHS-2 during early phases and 15-LO during late stages of differentiation. Depending on the stage of differentiation, the RA-sufficient cultures produced PGE, and in the presence of exogenous linoleic acid (LA) 13-HODE. Experiments are underway to examine the effects of inflammatory cytokines on eicosanoid metabolism and the role these metabolites play in airway diseases. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NIEHS, Pulm Pathobiol Lab, MD D201, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Nettesheim, P (reprint author), NIEHS, Pulm Pathobiol Lab, MD D201, POB 12233, Res Triangle Pk, NC 27709 USA. NR 21 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD AUG PY 1998 VL 96-7 BP 239 EP 244 DI 10.1016/S0378-4274(98)00078-2 PG 6 WC Toxicology SC Toxicology GA 131PR UT WOS:000076584900033 PM 9820673 ER PT J AU Cowan, EP Tabor, E Nemo, G Williams, A Lal, RB Busch, MP AF Cowan, EP Tabor, E Nemo, G Williams, A Lal, RB Busch, MP TI Studies to address reports of human T-lymphotropic virus type I tax sequences in US blood donors SO TRANSFUSION LA English DT Letter C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NHLBI, Transfus Med Branch, Bethesda, MD 20892 USA. Amer Red Cross, Holland Lab, REDS Study Chesapeake Reg, Rockville, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Irwin Mem Blood Ctr, REDS, San Francisco, CA USA. RP Cowan, EP (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 1998 VL 38 IS 8 BP 800 EP 801 DI 10.1046/j.1537-2995.1998.38898375523.x PG 2 WC Hematology SC Hematology GA 109GE UT WOS:000075312600018 PM 9709792 ER PT J AU Knechtle, SJ Fechner, JH Stavrou, S Neville, DM Dong, Y Hong, X Tsuchida, M Hamawy, MM AF Knechtle, SJ Fechner, JH Stavrou, S Neville, DM Dong, Y Hong, X Tsuchida, M Hamawy, MM TI Reversal of acute allograft rejection using immunotoxin SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Congress on New Dimensions in Transplantation - Weaving the Future CY FEB 16-19, 1998 CL FLORENCE, ITALY SP Novartis Pharma AG ID RHESUS-MONKEYS; TOLERANCE; DEPLETION C1 Univ Wisconsin, Dept Surg, Madison, WI USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Knechtle, SJ (reprint author), Univ Wisconsin Hosp, Dept Surg, 600 Highland Ave, Madison, WI 53792 USA. RI Fechner, John/C-5962-2016 OI Fechner, John/0000-0002-8220-7237 NR 5 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 1998 VL 30 IS 5 BP 2150 EP 2151 DI 10.1016/S0041-1345(98)00569-7 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 110ZM UT WOS:000075412900206 PM 9723422 ER PT J AU Jonker, M Slingerland, W Ossevoort, M Kuhn, E Neville, D Friend, P Calne, R AF Jonker, M Slingerland, W Ossevoort, M Kuhn, E Neville, D Friend, P Calne, R TI Induction of kidney graft acceptance by creating a window of opportunity for immunologic engagement (WOFIE) in rhesus monkeys SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Congress on New Dimensions in Transplantation - Weaving the Future CY FEB 16-19, 1998 CL FLORENCE, ITALY SP Novartis Pharma AG ID ALLOGRAFT TOLERANCE; RENAL-ALLOGRAFTS C1 Biomed Primate Res Ctr, NL-2280 GH Rijswijk, Netherlands. NIH, Bethesda, MD 20892 USA. Dept Surg, Cambridge, England. RP Jonker, M (reprint author), Biomed Primate Res Ctr, POB 3306, NL-2280 GH Rijswijk, Netherlands. NR 5 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 1998 VL 30 IS 5 BP 2441 EP 2443 DI 10.1016/S0041-1345(98)00679-4 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 110ZM UT WOS:000075412900313 PM 9723530 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI The HORMA domain: a common structural denominator in mitotic checkpoints, chromosome synapsis and DNA repair SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID CELL-CYCLE; PROTEIN; IDENTIFICATION; KINETOCHORES; MEIOSIS C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 22 TC 111 Z9 112 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD AUG PY 1998 VL 23 IS 8 BP 284 EP 286 DI 10.1016/S0968-0004(98)01257-2 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 113QU UT WOS:000075563400007 PM 9757827 ER PT J AU Rein, A Henderson, LE Levin, JG AF Rein, A Henderson, LE Levin, JG TI Nucleic-acid-chaperone activity of retroviral nucleocapsid proteins: significance for viral replication SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; HIV-1 REVERSE-TRANSCRIPTASE; HAMMERHEAD RIBOZYME CATALYSIS; HIGH-AFFINITY BINDING; DNA STRAND TRANSFER; RNA IN-VITRO; ANNEALING ACTIVITIES; ZINC FINGERS; H ACTIVITY AB Retrovirus particles contain a small, basic protein, the nucleocapsid (NC) protein, that possesses 'nucleic acid chaperone' activity - that is, the NC protein can catalyze the rearrangement of a nucleic acid molecule into the conformation that has the maximal number of base pairs. The molecular mechanism that underlies this effect is not understood. Because the chaperone activity is apparently crucial during the infectious process, NC is a potential target for antiviral therapy. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Retroviral Genet Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Rein, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Retroviral Genet Sect, Frederick, MD 21702 USA. NR 54 TC 317 Z9 322 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD AUG PY 1998 VL 23 IS 8 BP 297 EP 301 DI 10.1016/S0968-0004(98)01256-0 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 113QU UT WOS:000075563400010 PM 9757830 ER PT J AU Matsumoto, K Wolffe, AP AF Matsumoto, K Wolffe, AP TI Gene regulation by Y-box proteins: coupling control of transcription and translation SO TRENDS IN CELL BIOLOGY LA English DT Article ID MESSENGER-RIBONUCLEOPROTEIN PARTICLES; COLD-SHOCK DOMAIN; ACID BINDING-PROTEINS; XENOPUS-OOCYTES; SOMATIC-CELLS; RNA-BINDING; MASKING; YB-1; EXPRESSION; FAMILY AB Y-box proteins are multifunctional regulators of gene expression. In somatic cells, they have the capacity to exert positive and negative effects on both transcription and translation. In Xenopus oocytes, they help to mask maternal mRNA and couple the transcription of mRNA in the nucleus to its translational fate in the cytoplasm. This review describes how the capacity of the Y-box proteins to destabilize both RNA and DNA duplexes, together with their distribution between nuclear and cytoplasmic compartments, might explain these multiple roles. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Matsumoto, K (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. EM awlme@helix.nih.gov RI Matsumoto, Ken/F-9083-2013 OI Matsumoto, Ken/0000-0002-7864-3394 NR 53 TC 230 Z9 235 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD AUG PY 1998 VL 8 IS 8 BP 318 EP 323 DI 10.1016/S0962-8924(98)01300-2 PG 6 WC Cell Biology SC Cell Biology GA 104QX UT WOS:000075026200005 PM 9704408 ER PT J AU Klar, AJS AF Klar, AJS TI Propagating epigenetic states through meiosis: where Mendel's gene is more than a DNA moiety SO TRENDS IN GENETICS LA English DT Editorial Material ID FISSION YEAST; PROTEIN; RIK1; LOCI C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab,Dev Genet Sect, Frederick, MD 21702 USA. RP Klar, AJS (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab,Dev Genet Sect, POB B, Frederick, MD 21702 USA. EM klar@mail.ncifcrf.gov NR 21 TC 40 Z9 42 U1 1 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD AUG PY 1998 VL 14 IS 8 BP 299 EP 301 DI 10.1016/S0168-9525(98)01535-2 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 109HL UT WOS:000075316000002 PM 9724959 ER PT J AU Galperin, MY Brenner, SE AF Galperin, MY Brenner, SE TI Using metabolic pathway databases for functional annotation SO TRENDS IN GENETICS LA English DT Article C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Stanford Univ, Dept Biol Struct, Stanford, CA 94305 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, 8600 Rockville Pike, Bethesda, MD 20894 USA. RI Galperin, Michael/B-5859-2013; Brenner, Steven/A-8729-2008 OI Galperin, Michael/0000-0002-2265-5572; Brenner, Steven/0000-0001-7559-6185 NR 7 TC 14 Z9 14 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD AUG PY 1998 VL 14 IS 8 BP 332 EP 333 DI 10.1016/S0168-9525(98)01523-6 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 109HL UT WOS:000075316000010 PM 9724967 ER PT J AU Sartor, O Weinberger, M Moore, A Li, AL Figg, WD AF Sartor, O Weinberger, M Moore, A Li, AL Figg, WD TI Effect of prednisone on prostate-specific antigen in patients with hormone-refractory prostate cancer SO UROLOGY LA English DT Article ID FLUTAMIDE WITHDRAWAL; SURAMIN; ANDROGEN; HYDROCORTISONE; CARCINOMA; TRIAL; LIFE; DRUG AB Objectives. To evaluate the effects of prednisone on prostate-specific antigen (PSA) in a cohort of patients with "hormone-refractory" prostate cancer. Methods. Data were collected from 29 consecutive patients with hormone-refractory progressive prostate cancer who were treated with 10 mg of prednisone orally two times a day. Patients were included in this analysis only if other factors known to influence PSA levels (antiandrogen withdrawal, radiation, and/or other concomitant anticancer therapies) were definitively excluded as potentially confounding variables. Results. The mean and median PSA decline after initiating prednisone was 33% (95% confidence interval [CI] 20% to 46%) and 24% (range 0% to 99%), respectively. Ten patients (34%) had a PSA decline of more than 50% and 4 patients (14%) had PSA declines of more than 75%. The average and median time for progression-free survivals were 2.8 (95% CI 1.7 to 3.8) and 2.0 (range 0 to 11) months. Four (14%) patients had PSA declines lasting 6 months or more. Median survival was 12.8 months. Additional analyses indicated that a PSA decline of more than 50%, compared with less than 50%, was associated with a longer survival. Toxicities included steroid myopathy (n = 4), new-onset diabetes (n = 1), and dyspnea (n = 1). Conclusions. Prednisone (10 mg orally two times a day) can decrease PSA by more than 50% in approximately one third of patients with hormone-refractory progressive prostate cancer. On the basis of comparisons with other data sets, we hypothesize a dose-response relationship between glucocorticoid dose and PSA decline. UROLOGY 52: 252-256, 1998. (C) 1998, Elsevier Science Inc. All rights reserved. C1 Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, Dept Urol, New Orleans, LA 70112 USA. Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, Dept Med, New Orleans, LA 70112 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RP Sartor, O (reprint author), Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, Dept Urol, 2025 Gravier St,Suite 620, New Orleans, LA 70112 USA. RI Figg Sr, William/M-2411-2016 NR 21 TC 64 Z9 69 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD AUG PY 1998 VL 52 IS 2 BP 252 EP 256 DI 10.1016/S0090-4295(98)00149-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 104QT UT WOS:000075025800017 PM 9697790 ER PT J AU Salmaso, S Mastrantonio, P Wassilak, SGF Giuliano, M Anemona, A Giammanco, A Tozzi, AE degli Atti, MLC Greco, D AF Salmaso, S Mastrantonio, P Wassilak, SGF Giuliano, M Anemona, A Giammanco, A Tozzi, AE degli Atti, MLC Greco, D CA Stage II Working Grp TI Persistence of protection through 33 months of age provided by immunization in infancy with two three-component acellular pertussis vaccines SO VACCINE LA English DT Article DE pertussis; acellular vaccine; efficacy ID CONTROLLED TRIAL; VACCINATION; EFFICACY AB A large, randomized, placebo-controlled clinical trial in Italy on two three-component pertussis vaccines, given as DTaP in infancy, one manufactured by SmithKline and Beecham (SB) and one by Chiron Biocine (CB), found each vaccine to be 84% efficacious through the average age of 24 months. The cohort of children enrolled in the trial was followed with unmodified case ascertainment procedures for nine additional calendar months, during which partial unblinding occurred, for die unvaccinated randomized group, For the DTaP groups, the specific vaccine assignment remained double-blinded throughout the entire additional observation period. Pertussis was defined as paroxysmal cough lasting at least 21 days and confirmed by culture or serology. In the additional 9 months the observed absolute efficacy was 78% (95% CI, 62-87%) for SE DTaP vaccine and 89% (95% CT, 79-94%) for CB DTaP. The relative risk of developing pertussis in SE DTaP recipients compared to CB DTaP vaccinees was 1.99 (95% CI, 1.13-3.51), By combining observations fi om the initial and additional follow-up periods, the overall observed vaccine efficacy through art average age of 33 months of SE DTaP was 80% and of CB DTaP, 85% (C) 1998 Elsevier Science Ltd, All rights reserved. C1 Ist Super Sanita, Epidemiol & Biostat Lab, I-00161 Rome, Italy. Ist Super Sanita, Lab Bacteriol & Med Micol, I-00161 Rome, Italy. NIAID, NIH, Bethesda, MD 20892 USA. Univ Palermo, Dept Hyg & Microbiol, Palermo, Italy. RP Salmaso, S (reprint author), Ist Super Sanita, Epidemiol & Biostat Lab, Viale Regina Elena 299, I-00161 Rome, Italy. EM Salmaso@net.iss.it RI Tozzi, Alberto Eugenio/F-9494-2012; OI Tozzi, Alberto Eugenio/0000-0002-6884-984X; Quarto, Michele/0000-0002-1672-7170; Germinario, Cinzia Annatea/0000-0001-7467-9325; Lopalco, Pier Luigi/0000-0002-3181-8054 FU NIAID NIH HHS [N01-AI-25138] NR 21 TC 46 Z9 46 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG PY 1998 VL 16 IS 13 BP 1270 EP 1275 DI 10.1016/S0264-410X(98)00040-1 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZY766 UT WOS:000074657400005 PM 9682390 ER PT J AU Durbin, AP Wyatt, LS Siew, J Moss, B Murphy, BR AF Durbin, AP Wyatt, LS Siew, J Moss, B Murphy, BR TI The immunogenicity and efficacy of intranasally or parenterally administered replication-deficient vaccinia-parainfluenza virus type 3 recombinants in rhesus monkeys SO VACCINE LA English DT Article DE parainfluenza virus type 3; MVA-HN recombinant; MVA-F recombinant ID PARA-INFLUENZA; RSV RECOMBINANTS; GLYCOPROTEINS; IMMUNIZATION; ANTIBODIES; INDUCTION; CHILDREN; IMMUNITY; VECTOR; SUPPRESSES AB Immunization of rhesus monkeys with modified vaccinia Ankara (MVA) recombinants expressing the haemagglutinin-neuraminidase (HN) or fusion (F) glycoproteins of human parainfluenza virus type 3 (HPIV3) was compared with art intranasally-administered live, attenuated HPIV3 vaccine candidate, the cp45 derivative of the JS strain of wildtype HPIV3. The MVA recombinants, when given parenterally (i.m.) ol as a parenteral-local (i.m. and i.t.) combination, induced an antibody response comparable to that of cp45 and protected the upper and lower respiratory tracts of the rhesus monkeys against challenge with wildtype HPIV3. When given by the i.n. route alone, the MVA/PIV3 recombinants induced a serum antibody response that was comparable to that of cp45 and induced resistance in the lower respiratory tract. Despite the ability of the intranasally-administered MVA/PIV3 recombinants to stimulate a good serological response and to protect the lower respiratory tract, they unexpectedly failed to induce a significant level of resistance in the tipper respiratory tract. The live, attenuated virus vaccine candidate induced almost complete resistance in both the upper and lower tracts. The data thus identify two vaccine candidates that can protect both the upper and lower respiratory tracts of rhesus monkey, parenterally-administered MVA/PIV3 and intranasally-administered cp45. Further studies with these vaccines in non-human primates and humans should identify the relative merits of these immunogens for use in the very young infant. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Durbin, AP (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 35 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG PY 1998 VL 16 IS 13 BP 1324 EP 1330 DI 10.1016/S0264-410X(98)00010-3 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZY766 UT WOS:000074657400012 PM 9682397 ER PT J AU Portis, JL Lynch, WP AF Portis, JL Lynch, WP TI Dissecting the determinants of neuropathogenesis of the murine oncornaviruses SO VIROLOGY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; WILD MOUSE RETROVIRUS; INDUCED SPONGIFORM NEURODEGENERATION; TEMPERATURE-SENSITIVE MUTANT; LEUKEMIA-VIRUS INFECTION; ENDOTHELIAL-CELL TROPISM; MOTOR NEURON DISEASE; C RNA VIRUS; NEUROTROPIC RETROVIRUS; NEUROLOGICAL DISEASE C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. NE Ohio Univ, Coll Med, Dept Microbiol Immunol, Rootstown, OH 44272 USA. RP Portis, JL (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM jportis@nih.gov NR 118 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 1998 VL 247 IS 2 BP 127 EP 136 DI 10.1006/viro.1998.9240 PG 10 WC Virology SC Virology GA 110VX UT WOS:000075403000001 PM 9705905 ER PT J AU Whitehead, SS Firestone, CY Collins, PL Murphy, BR AF Whitehead, SS Firestone, CY Collins, PL Murphy, BR TI A single nucleotide substitution in the transcription start signal of the M2 gene of respiratory syncytial virus vaccine candidate cpts248/404 is the major determinant of the temperature-sensitive and attenuation phenotypes SO VIROLOGY LA English DT Article ID INFLUENZA-A VIRUS; SERONEGATIVE CHIMPANZEES; MAMMALIAN-CELLS; MESSENGER-RNA; TS PHENOTYPE; VIRAL-RNA; MUTATIONS; LIVE; MUTANTS; POLYMERASE AB Respiratory syncytial virus (RSV) cpts248/404 is a live-attenuated, temperature-sensitive (ts) vaccine candidate derived from cold-passaged cpRSV by two rounds of chemical mutagenesis and biological selection. Previous sequence analysis showed that these two steps introduced three single nucleotide substitutions into the cpRSV parent. Two of these occurred within the coding sequence for the L protein, and each resulted in a single amino acid substitution: Gln-831-Leu (248 mutation) and Asp-1183-Glu (404-L mutation). The third mutation resulted in a nucleotide substitution at position 9 of the cis-acting gene start signal of the M2 gene (404-M2 mutation). In the present study, the genetic basis of attenuation of cpts248/404 was defined by the introduction of each of these mutations (singly or in combination) into a full-length cDNA clone of cpRSV. Recombinant RSV derived from each mutant cDNA was analyzed to determine the contribution of each mutation to the ts and attenuation phenotypes of the virus. This analysis showed that the 248 mutation specifies a significant reduction of plaque formation at 38 degrees C and is responsible for an intermediate level of attenuation in mice. In contrast, the 404-L mutation did not contribute to the ts or attenuation phenotype alone or in combination with other mutations and is thus an incidental change. Unexpectedly, the 404-M2 mutation alone specified complete restriction of plaque formation at 37 degrees C and a high level of attenuation in mice. This indicates that the level of temperature sensitivity and attenuation of cpts248/404 can be attributed primarily to the 404-M2 mutation. Thus the cpts248/404 virus contains a set of ts and non-ts attenuating mutations, which likely accounts for its genetic stability. The recombinant version of this virus, rA2cp248/404, was phenotypically indistinguishable from cpts248/404 and represents a background into which additional mutations can be introduced as needed to obtain the desired level of attenuation for successful immunization of the very young human infant. C1 NIAID, Resp Viruses Sect, Infect Dis Lab, Bethesda, MD 20892 USA. RP Whitehead, SS (reprint author), NIAID, Resp Viruses Sect, Infect Dis Lab, 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI-000087, AI-000030] NR 47 TC 53 Z9 55 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 1998 VL 247 IS 2 BP 232 EP 239 DI 10.1006/viro.1998.9248 PG 8 WC Virology SC Virology GA 110VX UT WOS:000075403000012 PM 9705916 ER PT J AU Yu, GQ Zhou, Q Ding, I Gao, SS Zheng, ZY Zou, JX Li, YX Wang, LD AF Yu, GQ Zhou, Q Ding, I Gao, SS Zheng, ZY Zou, JX Li, YX Wang, LD TI Changes of p53 protein blood level in esophageal cancer patients and normal subjects from a high incidence area in Henan, China SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE esophageal neoplasms; p53 protein; p53 gene; enzyme-linked immunosorbent assay ID TUMOR-SUPPRESSOR GENE; PRECANCEROUS LESIONS; ACCUMULATION; CARCINOMA C1 Henan Med Univ, Canc Res Lab, Expt Ctr, Zhengzhou 450052, Henan Province, Peoples R China. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Wang, LD (reprint author), Henan Med Univ, Canc Res Lab, Expt Ctr, Zhengzhou 450052, Henan Province, Peoples R China. NR 4 TC 12 Z9 13 U1 0 U2 2 PU W J G PRESS PI BEIJING PA PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD AUG PY 1998 VL 4 IS 4 BP 365 EP 366 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 127AG UT WOS:000076327100025 ER PT J AU Mathews, JM Black, SR Burka, LT AF Mathews, JM Black, SR Burka, LT TI Disposition of butanal oxime in rat following oral, intravenous and dermal administration SO XENOBIOTICA LA English DT Article ID ALDEHYDE OXIDASE; N-BUTYRALDOXIME; METABOLISM; 1-AMINOBENZOTRIAZOLE; CYTOCHROME-P-450; INVIVO; DEHYDRATION; INHIBITION; MICROSOMES; ZONISAMIDE AB 1. The disposition of [1-C-14]butanal oxime (BOX) was determined in the rat after oral, i.v. and dermal administration. 2. Oral doses of [C-14]BOX (2 and 20 mg/kg) were predominantly excreted in the urine (> 42 %) and converted to (CO2)-C-14 (> 30 %) and about 10 % of the dose remained in the tissues 72 h post-dosing. 3. Eight and 16% of a 2 and 20 mg/kg dermal dose of BOX, respectively, were absorbed, due in part to rapid volatilization from the surface of the skin. 4. Oral doses of BOX were transformed into several polar and/or anionic metabolites that include sulphate conjugates and a significant amount of thiocyanate. 5. The effect of inhibitors on the metabolism of BOX was investigated using 1-aminobenzotriazole (ABT; an inhibitor of diverse cytochrome P450s) and trans-1,2-dichloroethylene (DCE; an inhibitor of CYP2E1). No thiocyanate anion was detected in the urine of rat treated with DCE or ABT. ABT markedly increased the production of (CO2)-C-14 and excretion as volatile metabolites. DCE had no effect on (CO2)-C-14 excretion, but increased exhalation of radiolabel. ABT also effectively blocked the expression of toxic effects attributable to cyanide in rat given near-lethal doses of BOX. 6. The data are consistent with two distinct pathways of metabolism for BOX, (1) reduction to an imine, hydrolysis and subsequent conversion of butyraldehyde to (CO2)-C-14 and (2) CYP3A-catalysed dehydration of BOX to butyronitrile followed by CYP2E1-catalysed release of cyanide. C1 Res Triangle Inst, Ctr Bioorgan Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Mathews, JM (reprint author), Res Triangle Inst, Ctr Bioorgan Chem, POB 12194, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [1-ES-15329] NR 29 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD AUG PY 1998 VL 28 IS 8 BP 767 EP 777 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 115BL UT WOS:000075643600005 PM 9741955 ER PT J AU Shapira, H Amit, I Revach, M Oron, Y Battey, JF AF Shapira, H Amit, I Revach, M Oron, Y Battey, JF TI G alpha(14) and G alpha(q) mediate the response to trypsin in Xenopus oocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-ALPHA-SUBUNITS; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE HYDROLYSIS; THYROTROPIN-RELEASING-HORMONE; PHOSPHOLIPASE-C; LAEVIS OOCYTES; HUMAN PLATELETS; CELL-LINES; GQ FAMILY; RECEPTOR; EXPRESSION AB Xenopus oocytes respond to trypsin with a characteristic chloride current, virtually indistinguishable from responses mediated by a large number of native and expressed G protein-coupled receptors. We studied the involvement of G proteins of the G alpha(q) family as possible mediators of this and other G protein-coupled receptor-mediated responses in Xenopus oocytes. We have cloned the third member of the G alpha(q) family, Xenopus G alpha(14), in addition to the previously cloned Xenopus G alpha(q) and Ga,, (Shapira, H., Way, J., Lipinsky, D., Oron, Y., and Battey, J. F. (1994) FEES Lett. 348, 89-92). Amphibian G alpha(14) is 354 amino acids long and is 93% identical to its mammalian counterpart. Based on the G alpha(14) cDNA sequence, we designed a specific antisense DNA oligonucleotide (antiG alpha(14)) that, together with antiG alpha(q) and antiG alpha(11), was used in antisense depletion experiments. 24 h after injection into oocytes, either antiG alpha(q) or antiG alpha(14) reduced the response to 1 mu g/ml trypsin by 70%, whereas antiG alpha(11) had no effect. A mixture of antiG alpha(q) and antiG alpha(14) virtually abolished the response. These data strongly suggest that G alpha(q) and G alpha(14) are the exclusive mediators of the trypsin-evoked response in Xenopus oocytes. Similar experiments with the expressed gastrin-releasing peptide receptor and muscarinic mi receptor revealed the coupling of G alpha(q) and G alpha(11) but not G alpha(14) to these receptors in oocytes. These results confirm the hypothesis that endogenous members of the Gag family discriminate among different native receptors in vivo. C1 Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. RP Shapira, H (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. EM hshapira@post.tau.ac.il NR 38 TC 17 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 31 PY 1998 VL 273 IS 31 BP 19431 EP 19436 DI 10.1074/jbc.273.31.19431 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106JB UT WOS:000075125200014 PM 9677362 ER PT J AU Huang, Y Putney, JW AF Huang, Y Putney, JW TI Relationship between intracellular calcium store depletion and calcium release-activated calcium current in a mast cell line (RBL-1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENTRY AB The kinetic relationship between depletion of endoplasmic reticulum calcium stores and the activation of a calcium release-activated calcium current (I-crac) was investigated in the RBL-1 mast cell line. The inositol trisphosphate receptor activator, inositol 2,4,5-trisphosphate ((2,4,5)IP3), the sarcoplasmic-endoplasmic reticulum calcium ATPase inhibitor, thapsigargin, and the calcium ionophore, ionomycin, were used to deplete stored calcium. For (2,4,5)IP3 and thapsigargin, a significant delay was observed between the initiation of calcium store depletion and the activation of I-crac. However, for ionomycin, little or no delay was observed. This may indicate that a specialized subcompartment of the endoplasmic reticulum functions as a regulator of calcium entry and that this compartment is relatively resistant to depletion by (2,4,5)IP3 and thapsigargin but not to depletion by ionomycin. For all three calcium-depleting agents, the rate of development of I-crac. once initiated, was relatively constant, suggesting an all-or-none mechanism. However, there were also clear experimental situations in which submaximal, graded depletion of stored calcium resulted in submaximal activation of I-crac. This complex behavior could also result from the existence of a specific subcompartment of endoplasmic reticulum regulating I-crac. The kinetic behavior of this compartment may not be accurately reflected by the kinetics of calcium changes in the bulk of endoplasmic reticulum. These findings add to the growing body of evidence suggesting specialization of the endoplasmic reticulum calcium stores with regard to the control of capacitative calcium entry. C1 NIEHS, Calcium Regulat Sect, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Calcium Regulat Sect, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 14 TC 65 Z9 66 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 31 PY 1998 VL 273 IS 31 BP 19554 EP 19559 DI 10.1074/jbc.273.31.19554 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106JB UT WOS:000075125200031 PM 9677379 ER PT J AU Kawai, H Sango, K Mullin, KA Proia, RL AF Kawai, H Sango, K Mullin, KA Proia, RL TI Embryonic stem cells with a disrupted GD3 synthase gene undergo neuronal differentiation in the absence of b-series gangliosides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IN-VITRO DIFFERENTIATION; NERVOUS-SYSTEM; EXPRESSION; METABOLISM; BRAIN AB The dramatic changes in the expression of GD3 and other b-series gangliosides during neuronal development and morphogenesis have led to a widely held belief that these gangliosides may be necessary for neuronal differentiation. To determine directly if GD3 and b-series gangliosides are required for neuronal differentiation, we have produced embryonic stem (ES) cells with both alleles of the GD3 synthase gene (GD3S) disrupted by successive rounds of gene targeting. The double-targeted ES cells were deficient in GD3 synthase activity and did not synthesize b-series gangliosides. Despite this deficit, the GD3S(-/-) ES cells could be induced to undergo neuronal differentiation. Neuronally differentiated wild-type and GD3S(-/-) ES cells formed a complex neurite network around the embryoid bodies, Both types of neuronal cells expressed the axon-specific cytoskeletal proteins, neurofilament-M, and growth-associated protein-43 as well as the dendrite-specific marker, microtubule-associated protein-a. Our results indicate that GD3 synthase and b-series gangliosides are not necessary for the neuronal differentiation of uncommitted precursor cells. C1 NIDDK, Sect Biochem Genet, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Proia, RL (reprint author), NIDDK, Sect Biochem Genet, Genet & Biochem Branch, NIH, Bldg 10,Rm 9D-20,10 Ctr Dr,MSC 1810, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 37 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 31 PY 1998 VL 273 IS 31 BP 19634 EP 19638 DI 10.1074/jbc.273.31.19634 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106JB UT WOS:000075125200042 PM 9677390 ER PT J AU Lin, HM Hutchcroft, JE Andoniou, CE Kamoun, M Band, H Bierer, BE AF Lin, HM Hutchcroft, JE Andoniou, CE Kamoun, M Band, H Bierer, BE TI Association of p59(fyn) with the T lymphocyte costimulatory receptor CD2 - Binding of the Fyn Src homology (SH) 3 domain is regulated by the Fyn SH2 domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; PROTEIN-TYROSINE KINASE; NATURAL-KILLER-CELLS; CYTOPLASMIC DOMAIN; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; ALTERNATIVE PATHWAY; PHOSPHATASE CD45; LIGAND AVIDITY; SURFACE LIGAND AB Human CD2 is a 50-55-kDa cell surface receptor specifically expressed on the surface of T lymphocytes and NK cells. Stimulation of human peripheral blood T cells with mitogenic pairs of anti-CD2 monoclonal antibodies (mAbs) is sufficient to induce interleukin-a production and T cell proliferation in the absence of an antigen-specific signal through the T cell receptor. CD2 has been shown previously to associate physically with the Src family protein-tyrosine kinases p56(lck) and p59(fyn). We now report that stimulation of T cells with mitogenic pairs of anti-CD2 mAbs enhanced the association of the Fyn polypeptide with the CD2 complex, whereas stimulation with single anti-CD2 mAb had minimal effect. Using glutathione S-transferase (GST) fusion proteins, we found that CD2 bound to the Src homology (SH) 3 domain of Fyn. Interestingly, the CD2-Fyn association was negatively regulated by the Fyn SH2 domain; CD2 bound poorly to GST fusion proteins expressing both the SH2 and SH3 domains of Fyn. However, the inhibitory effect of the Fyn SH2 domain on binding of the Fyn SH3 domain to CD2 was relieved by peptides containing a phosphorylated YEEI sequence that bound directly to the Fyn SH2 domain. In addition, we found that the ability of the Fyn SH2 domain to precipitate tyrosine-phosphorylated proteins, including the CD3 zeta chain, was enhanced after T cell stimulation with mitogenic pairs of CD2 mAbs. Finally, overexpression of a mutated Fyn molecule, in which the ability of the Fyn SH2 domain to bind phosphotyrosine-containing proteins was abrogated, inhibited CD2-induced transcriptional activation of the nuclear factor of activated T cells (NFAT), suggesting a functional involvement of the Fyn SH2 domain in CD2-induced T cell signaling. We thus propose that stimulation through the CD2 receptor leads to the tyrosine phosphorylation of intracellular proteins, including CD3 zeta itself, which in turn bind to the Fyn-SH2 domain, allowing the direct association of the Fyn SH3 domain with CD2 and the initiation of downstream signaling events. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Sci, Comm Immunol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Rheumatol & Immunol, Lymphocyte Biol Sect, Boston, MA 02115 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, NIH, Bldg 10,Rm 5D49,10 Ctr Dr, Bethesda, MD 20892 USA. EM biererb@nih.gov RI Andoniou, Christopher/B-6296-2013 NR 65 TC 28 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 31 PY 1998 VL 273 IS 31 BP 19914 EP 19921 DI 10.1074/jbc.273.31.19914 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106JB UT WOS:000075125200082 PM 9677430 ER PT J AU Markley, JL Bax, A Arata, Y Hilbers, CW Kaptein, R Sykes, BD Wright, PE Wuthrich, K AF Markley, JL Bax, A Arata, Y Hilbers, CW Kaptein, R Sykes, BD Wright, PE Wuthrich, K TI Recommendations for the presentation of NMR structures of proteins and Nucleic Acids (Reprinted from Pure and Applied Chemistry, vol 70, pgs 117-142, 1998) SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Reprint DE atom naming; biomolecular NMR; chemical shift referencing; database; deposition; nomenclature ID COUPLING-CONSTANTS; MAGNETIC-RESONANCE; 3-DIMENSIONAL STRUCTURES; FILE; CRYSTALLOGRAPHY; CONFORMATION; CONSTRAINTS; C-13; RING; H-1 AB The recommendations presented here are designed to support easier communication of NMR data and NMR structures of proteins and nucleic acids through unified nomenclature and reporting standards. Much of this document pertains to the reporting of data in journal articles; however, in the interest of the future development of structural biology, it is desirable that the bulk of the reported information be stored in computer-accessible form and be freely accessible to the scientific community in standardized formats for data exchange. These recommendations stem from an IUPAC-IUBMB-IUPAB inter-union venture with the direct involvement of ICSU and CODATA. The Task Group has reviewed previous formal recommendations and has extended them in the light of more recent developments in the field of biomolecular NMR spectroscopy. Drafts of the recommendations presented here have been examined critically by more than 50 specialists in the field and have gone through two rounds of extensive modification to incorporate suggestions and criticisms. (C) 1998 Academic Press. C1 ETH Honggerberg, Inst Mol Biol, CH-8093 Zurich, Switzerland. Univ Wisconsin, Dept Biochem, Madison, WI USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Water Res Inst, Tsukuba, Ibaraki, Japan. Univ Nijmegen, Biophys Chem Lab, Nijmegen, Netherlands. Univ Utrecht, Dept Chem, NL-3508 TC Utrecht, Netherlands. Univ Alberta, Dept Biochem, Edmonton, AB, Canada. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. RP Wuthrich, K (reprint author), ETH Honggerberg, Inst Mol Biol, CH-8093 Zurich, Switzerland. NR 63 TC 154 Z9 154 U1 0 U2 10 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 31 PY 1998 VL 280 IS 5 BP 933 EP 952 DI 10.1006/jmbi.1998.1852 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106XY UT WOS:000075177600015 PM 9671561 ER PT J AU Bartlett, JA Wasserman, SS Hicks, CB Dodge, RT Weinhold, KJ Tacket, CO Ketter, N Wittek, AE Palker, TJ Haynes, BF AF Bartlett, JA Wasserman, SS Hicks, CB Dodge, RT Weinhold, KJ Tacket, CO Ketter, N Wittek, AE Palker, TJ Haynes, BF CA DATRI 010 Study Grp TI Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen SO AIDS LA English DT Article DE vaccine; envelope proteins; antibodies; cellular immunity ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODIES; RHESUS-MONKEYS; GP120; EPITOPES; TYPE-1; IMMUNIZATION; RESPONSES; REGION; GP160 AB Objective: To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1(MN), and T-helper, cytotoxic T-lymphocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp120 third variable region (V3) of four clade B HIV-1 isolates, HIV-1(MN), HIV-1(RF), HIV-1(EV91), and HIV-1(CanOA). Design: A pilot, Phase I controlled trial [Division of AIDS Treatment Research Initiative (DATRI) 010] conducted at a single center. Methods: Ten HIV-infected, HLA-B7-positive patients with CD4 cells > 500 x 10(6)/l were enrolled. Eight patients received the C4-V3 PV immunogen emulsified in incomplete Freund's adjuvant in five intramuscular injections over 24 weeks, and two controls received incomplete Freund's adjuvant alone. All subjects were followed for 52 weeks. Results: Four out of eight C4-V3 PV recipients generated at least fourfold rise in serum antibody titers to at least three immunogen peptides in contrast to none of the control subjects. Four out of eight C4-V3 PV recipients and none of the controls had an at least fourfold rise in neutralizing antibodies to either HIV-1(MN), HIV-1(RF), or HIV-1(4489-5) laboratory-adapted HIV isolates. H-3-Thymidine incorporation assays of peripheral blood mononuclear cells increased at least fivefold over the baseline stimulation index to at least one of the immunogen peptides in two consecutive post-immunization timepoints in five out of eight C4-V3 PV recipients versus none of the controls. CD4 cell counts and plasma HIV RNA levels did not change in patients who received either C4-V3 PV or adjuvant alone. Adverse events consisted primarily of grade 1 injection site reactions in six subjects (four C4-V3 recipients, two controls). Conclusions: C4-V3 PV synthetic peptides demonstrated both immunogenicity and safety in HIV-iniected patients. (C) 1998 Lippincott-Raven Publishers. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Wyeth Lederle Vaccines & Pediat, Pearl River, NY USA. RP Bartlett, JA (reprint author), Duke Univ, Med Ctr, Dept Med, Box 3238, Durham, NC 27710 USA. FU NIAID NIH HHS [N01-AI-15123] NR 27 TC 35 Z9 35 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 30 PY 1998 VL 12 IS 11 BP 1291 EP 1300 DI 10.1097/00002030-199811000-00010 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 103QD UT WOS:000074968600010 PM 9708408 ER PT J AU Alessandro, R Masiero, L Lapidos, K Spoonster, J Kohn, EC AF Alessandro, R Masiero, L Lapidos, K Spoonster, J Kohn, EC TI Endothelial cell spreading on type IV collagen and spreading-induced FAK phosphorylation is regulated by Ca2+ influx SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID FOCAL ADHESION KINASE; PAXILLIN TYROSINE PHOSPHORYLATION; MEDIATED SIGNAL-TRANSDUCTION; SWISS 3T3 CELLS; EXTRACELLULAR-MATRIX; GROWTH-FACTOR; INTEGRIN; CYTOSKELETAL; STIMULATION; CALCIUM AB The interaction of endothelial cells with their basement membrane and local stroma is highly regulated. The observation that CAI, an inhibitor of Ca++ influx, inhibited human umbilical vein endothelial cell (HUVEC) adhesion suggested that Ca++ influx was a regulator of HUVEC-matrix interaction. Exposure of HUVEC cells to CAI or SK&F 96365, another Ca++ influx inhibitor, selectively blocked spreading but not attachment on type TV collagen but not type I collagen. Ca++ influx blockade also prevented spreading-induced FAR phosphorylation and kinase activity and secondary paxillin phosphorylation. No inhibitory effect was observed when the cells spread on type I collagen. The inhibitory effect of CAI on spreading and spreading-associated FAK phosphorylation and kinase activity was reversible. These data indicate that HUVEC cells have a selective requirement for Ca++ influx for spreading and downstream signaling on basement membrane type IV collagen. (C) 1998 Academic Press. C1 NCI, Mol Signaling Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 32 TC 37 Z9 37 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 30 PY 1998 VL 248 IS 3 BP 635 EP 640 DI 10.1006/bbrc.1998.8705 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 110TP UT WOS:000075396700036 PM 9703978 ER PT J AU Tomarev, SI Zinovieva, RD Chang, B Hawes, NL AF Tomarev, SI Zinovieva, RD Chang, B Hawes, NL TI Characterization of the mouse Prox1 gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DROSOPHILA-PROSPERO; HOMEOBOX; EXPRESSION; PROTEIN; CELLS AB Prox1, a vertebrate homologue of Drosophila prospero, encodes a divergent homeodomain protein. We have isolated and characterized full length mouse Prox1 cDNA and genomic clones. Mouse Prox1 gene mapped to position 106.3 cM from the centromere of Chromosome 1, which is very close to the retinal degeneration mutation, rd3. Although the coding sequence and exon-intron junctions of the Prox1 genes of wild type and rd3 mutant mice are identical, Northern blot analysis indicated that the ratio of the short (2.3 kb) and long (8 kb) forms of Prox1 mRNA is different in RNA isolated from wild type and rd3 retinas. Immunostaining of the eyes from wild type and rd3 animals also revealed differences in the distribution of Prox1 protein in the retina and lens. These data suggest that the rd3 mutation affects expression of the mouse Prox1 gene. (C) 1998 Academic Press. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Tomarev, SI (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bldg 6,Room 203,6 Ctr Dr,MSC 2730, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY05578, EY07757] NR 15 TC 47 Z9 49 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 30 PY 1998 VL 248 IS 3 BP 684 EP 689 DI 10.1006/bbrc.1998.8989 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 110TP UT WOS:000075396700044 PM 9703987 ER PT J AU Sharma, V Xu, M Ritter, LM AF Sharma, V Xu, M Ritter, LM TI Biochemical characterization of MIP-1 alpha nuclear protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; STEM-CELL PROLIFERATION; LEUCINE ZIPPER PROTEINS; HUMAN T-CELLS; TRANSCRIPTION FACTOR; CYTOKINE LD78; MITOGENIC ACTIVATION; FAMILY; GENE; IDENTIFICATION AB A family of hematopoietic specific transcription factors, MIP-1 alpha nuclear protein (MNP) family, has recently been identified. They are intimately involved in regulating the transcription of the huMIP-1 alpha gene in monocytes, T-cells, and transformed B-cells. One member of the family (MNP-1) is essential for promoter activity in monocytes and B-cells, while another (MNP-2) is required for full promoter activity in T-cells. A third member of the family (MNP-3) is expressed in PMA induced HL60 cells and probably has a role in monocyte differentiation. In this communication we demonstrate by two techniques that MNP-1 and MNP-2 are distinct but related factors, and we present further evidence to show that MNP-1 acts as a heterodimer. (C) 1998 Academic Press. C1 Univ W Florida, Dept Biol, Lab Cytokine Res, Pensacola, FL 32514 USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. NCI, Tumor Biol & Carcinogenesis Sect, LCCTP, NIH, Bethesda, MD 20892 USA. RP Sharma, V (reprint author), Univ W Florida, Dept Biol, Lab Cytokine Res, Pensacola, FL 32514 USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 30 PY 1998 VL 248 IS 3 BP 716 EP 721 DI 10.1006/bbrc.1998.9045 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 110TP UT WOS:000075396700050 PM 9703993 ER PT J AU Potterf, SB Hearing, VJ AF Potterf, SB Hearing, VJ TI Tyrosine transport into melanosomes is increased following stimulation of melanocyte differentiation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID AGOUTI SIGNAL PROTEIN; MAMMALIAN TYROSINASE; MURINE MELANOCYTES; MELANIN FORMATION; THYROID-CELLS; PIGMENTATION; MODULATION; MEMBRANE; SYSTEM; GENES AB A variety of physiological factors can stimulate differentiation of melanocytes to increase pigmentation, and critical to this process is the transport of the melanogenic substrate (tyrosine) into melanosomes. In this study, we examined whether stimulation of melanogenesis affects melanosomal tyrosine transport. Tyrosine uptake increased almost a-fold in melanosomes derived from melanocytes treated with melanocyte-stimulating hormone (MSH), which acts to increase intracellular cAMP levels, resulting in the up-regulation of many genes involved in melanogenesis. Stimulation of melanoma cells with dibutyryl cAMP increased melanosomal tyrosine transport 2- to 3-fold after 24 to 48 hrs, with peak levels occurring after 3 to 5 days of treatment, suggesting that de novo gene expression may be required. The cAMP-induced increase in melanosomal tyrosine transport could be effectively competed with phenylalanine or tryptophan, but not with dopamine or proline, suggesting either that a pool of transporters with greater tyrosine transporting ability pre-exists, or that a greater number of tyrosine transporters reside within the melanosomal membrane. These results illustrate a rare example of hormonal plasma membrane stimulation which transduces a signal for increased vesicular transport of an amino acid. (C) 1998 Aeademic Press. C1 NCI, Cell Biol Lab, Pigment Cell Biol Sect, NIH, Bethesda, MD 20892 USA. RP Potterf, SB (reprint author), NCI, Cell Biol Lab, Pigment Cell Biol Sect, NIH, Bethesda, MD 20892 USA. NR 22 TC 21 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 30 PY 1998 VL 248 IS 3 BP 795 EP 800 DI 10.1006/bbrc.1998.9019 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 110TP UT WOS:000075396700064 PM 9704007 ER PT J AU Bera, TK Tsukamoto, T Panda, DK Huang, T Guzman, RC Hwang, SI Nandi, S AF Bera, TK Tsukamoto, T Panda, DK Huang, T Guzman, RC Hwang, SI Nandi, S TI Defective retrovirus insertion activates c-Ha-ras protooncogene in an MNU-induced rat mammary carcinoma SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE defective retrovirus; activation of Ha-ras protooncogene; insertional mutation; mammary carcinogenesis ID NUCLEOTIDE-SEQUENCE; POINT MUTATIONS; ONCOGENE; CARCINOGENESIS; GENE; RETROTRANSPOSONS; METHYLUREA; INDUCTION; ELEMENT; VIRUS AB Endogenous retrovirus sequences are present in the genome of a wide variety of animal species. The activation of the proto-oncogenes of the ras family, particularly c-Ha-ras, by either point mutation or overexpression, has been shown to be associated with a vast number of different cancers. Here we report that the insertion of a defective retrovirus in the -1 intron of rat c-Ha-ras is responsible for the activation of the gene by over 10-fold overexpression in an MNU-induced rat mammary cancer. A portion of the 3' end of the retroviral sequence is expressed as a part of the c-Ha-ras transcript in the carcinoma tissue, indicating the direct involvement of this element in the transcription of the c-Ha-ras gene. The c-Ha-ras structural gene transcribed by the promoter of the defective retroviral element can neoplastically transform the NIH 3T3 cell line upon transfection. (C) 1998 Academic Press. C1 Univ Calif Berkeley, Canc Res Lab, Berkeley, CA 94720 USA. RP Bera, TK (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 4B20, Bethesda, MD 20892 USA. EM tkbera@helix.nih.gov FU NCI NIH HHS [CA-05388, CA-09041, CA-63369] NR 30 TC 8 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 30 PY 1998 VL 248 IS 3 BP 835 EP 840 DI 10.1006/bbrc.1998.9059 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 110TP UT WOS:000075396700071 PM 9704014 ER PT J AU Mariner, JM McMahon, JB O'Keefe, BR Nagashima, K Boyd, MR AF Mariner, JM McMahon, JB O'Keefe, BR Nagashima, K Boyd, MR TI The HIV-inactivating protein, cyanovirin-N, does not block gp120-mediated virus-to-cell binding SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; ENVELOPE GLYCOPROTEIN GP120; SOLUBLE CD4 BINDING; CHEMOKINE RECEPTOR; CD4-GP120 COMPLEX; TYPE-1; NEUTRALIZATION; ANTIBODY; DISSOCIATION; INFECTIVITY AB Concentrations of the potent, HN(human immunodeficiency virus) inactivating protein, cyanovirin-N (CV-N), which completely inhibit HIV-1 infectivity, do not block the binding of soluble CD4-receptor (sCD4) to HIV-1 lysates nor the attachment of intact HIV-1 virions to several target T-cell lines. Furthermore, in contrast to the known disassociative effects of sCD4 on viral envelope glycoproteins, treatment of HIVRF with high concentrations of CV-N results in complete viral inactivation but without apparent shedding of gp120 or other ultrastructural changes. These results are consistent with the view that the virucidal effects of CV-N result from interference with step(s) in the fusion process subsequent to the initial binding of the virus to target cells. (C) 1998 Academic Press. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Frederick Canc Res & Dev Ctr, Lab Cell & Mol Struct, SAIC, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 30 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 30 PY 1998 VL 248 IS 3 BP 841 EP 845 DI 10.1006/bbrc.1998.9060 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 110TP UT WOS:000075396700072 PM 9704015 ER PT J AU Chu, SC Marks-Konczalik, J Wu, HP Banks, TC Moss, J AF Chu, SC Marks-Konczalik, J Wu, HP Banks, TC Moss, J TI Analysis of the cytokine-stimulated human inducible nitric oxide synthase (iNOS) gene: Characterization of differences between human and mouse iNOS promoters SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE nitric oxide; transcription; cytokines; molecular biology; human ID NF-KAPPA-B; INTERFERON-GAMMA; TRANSCRIPTION FACTOR; BACTERIAL LIPOPOLYSACCHARIDE; MOLECULAR-CLONING; NUCLEAR FACTOR; MESSENGER-RNA; L-ARGININE; EXPRESSION; INDUCTION AB Expression of human inducible nitric oxide synthase (hiNOS) is under cytokine control and is transcriptionally regulated. The hiNOS and mouse iNOS (miNOS) genes are regulated differently by cytokines. To understand better the transcriptional regulation of the hiNOS gene, the 8.3-kb hiNOS promoter was characterized. Promoter activity was evaluated by transient transfection of hiNOS luciferase constructs in A549 human alveolar type II epithelium-like cells in the presence and absence of cytokines (IFN-gamma, IL-1 beta, and TNF-alpha). Important cytokine-responsive elements are located at -3685 to -5574 bp (containing two perfectly matched AP-1 sites which are not present in miNOS promoter) and -8093 to -8296 bp tone perfectly matched NF-kappa B site of the hiNOS promoter region. Likely, these two AP-1 sites and the upstream NF-kappa B Site are important in the transcriptional induction of hiNOS by cytokines. Our data demonstrate the molecular basis for the different cytokine-stimulated characteristics of hiNOS and miNOS genes. (C) 1998 Academic Press. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Marks-Konczalik, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 6D03,10 Ctr Dr,MSC 1590, Bethesda, MD 20892 USA. NR 41 TC 132 Z9 132 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 30 PY 1998 VL 248 IS 3 BP 871 EP 878 DI 10.1006/bbrc.1998.9062 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 110TP UT WOS:000075396700077 PM 9704020 ER PT J AU Nagaraja, R Jermak, C Trusgnich, M Yoon, J MacMillan, S McCauley, B Brownstein, B Schlessinger, D AF Nagaraja, R Jermak, C Trusgnich, M Yoon, J MacMillan, S McCauley, B Brownstein, B Schlessinger, D TI YAC/STS map of 15 Mb of Xp21.3-p11.3, at 100 kb resolution, with refined comparisons of genetic distances and DMD structure SO GENE LA English DT Article DE cytochrome b beta polypeptide; monoamine oxidase A; monoamine oxidase B; expressed sequence tags; intron ID HUMAN X-CHROMOSOME; MUSCULAR-DYSTROPHY; YAC-CONTIG; DUCHENNE; LIBRARIES; CLONING; MARKERS; REGION AB The 15 Mb region between DXS997 and DXS8054 in Xp21.3-p11.3 has been mapped at seven-fold average coverage in yeast artificial chromosomes (YACs) and 100 kb inter-sequence tagged site (STS) distance. YACs from six different collections show self-consistent maps. The STSs include 18 (CA) repeat and one tetranucleotide repeat marker that detect polymorphism, as well as eight well-studied genes, a second site for MXS1 sequences, and three expressed sequence tags (ESTs). One of the ESTs maps to intron 7 of Duchenne muscular dystrophy, and seems to be a processed intronic sequence with a poly(A) tail. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Washington Univ, Sch Med, Ctr Genet Med, St Louis, MO 63110 USA. RP Schlessinger, D (reprint author), NIA, Gerontol Res Ctr, Genet Lab, NIH, Box 31,4940 Eastern Ave, Baltimore, MD 21224 USA. EM davids@grc.nia.nih.gov FU NHGRI NIH HHS [HG00247] NR 26 TC 2 Z9 2 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 JUL 30 PY 1998 VL 215 IS 2 BP 259 EP 267 DI 10.1016/S0378-1119(98)00293-5 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 113WU UT WOS:000075577500005 PM 9714824 ER PT J AU Hill, SA Belland, RJ Wilson, J AF Hill, SA Belland, RJ Wilson, J TI The ihf mRNA levels decline as Neisseria gonorrhoeae enters the stationary growth phase SO GENE LA English DT Article DE integration host factor; Neisseria; transcription ID INTEGRATION HOST FACTOR; ESCHERICHIA-COLI; BETA-SUBUNIT; HIMA GENE; HIP GENE; DNA; EXPRESSION; PROTEIN; BACTERIA; OPERON AB Integration host factor (IHF) is a small heterodimeric DNA binding protein found in all Gram-negative bacteria and is implicated as a transcription cofactor of pilE in Neisseria gonorrhoeae (Hill, S.A., Samuels, D.S., Carlson, J.K., Wilson, J., Hogan, D., Lubke, L., Belland, R.J., 1997. Integration host factor is a transcriptional cofactor of pilE in Neisseria gonorrhoeae. Mel. Microbiol. 23, 649-656). The ihf genes (ihfA and ihfB) were cloned from N. gonorrhoeae through functional complementation of defined Escherichia coli ihf mutants for plating of phage lambda. The predicted aa sequences of each gonococcal IHF polypeptide showed extensive homology to other reported IHF polypeptide sequences. Northern blotting and primer extension analysis defined the tsp for each gene and indicated a disparity in ihfA and ihfB message levels over time, with ihfB mRNA being more abundant throughout the entire growth cycle. Furthermore, both the ihfA and ihfB message levels declined as cells entered the stationary growth phase. Overall, this study reveals several unique features of ihf transcription in the gonococcus which questions whether certain aspects if ihf transcriptional regulation are universally shared by all Gram-negative bacteria. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, Hamilton, MT 59840 USA. RP Hill, SA (reprint author), No Illinois Univ, Dept Biol Sci, De Kalb, IL 60115 USA. EM sahill@niu.edu NR 21 TC 7 Z9 9 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 JUL 30 PY 1998 VL 215 IS 2 BP 303 EP 310 DI 10.1016/S0378-1119(98)00285-6 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 113WU UT WOS:000075577500009 PM 9714829 ER PT J AU Cohen, OJ Fauci, AS AF Cohen, OJ Fauci, AS TI Transmission of multidrug-resistant human immunodeficiency virus - The wake-up call SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIAID, Bethesda, MD 20892 USA. RP Cohen, OJ (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 43 Z9 44 U1 1 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 30 PY 1998 VL 339 IS 5 BP 341 EP 343 DI 10.1056/NEJM199807303390511 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 104TL UT WOS:000075031400011 PM 9682050 ER PT J AU Castagnino, P Soriano, JV Montesano, R Bottaro, DP AF Castagnino, P Soriano, JV Montesano, R Bottaro, DP TI Induction of tissue inhibitor of metalloproteinases-3 is a delayed early cellular response to hepatocyte growth factor SO ONCOGENE LA English DT Article DE hepatocyte growth factor; TIMP-3; metalloproteinase; cell proliferation; gene induction ID ERYTHROID-POTENTIATING ACTIVITY; FACTOR SCATTER FACTOR; RECEPTOR TYROSINE KINASE; CHICKEN-EMBRYO FIBROBLASTS; MET PROTOONCOGENE PRODUCT; HUMAN SKIN FIBROBLASTS; KIDNEY-CELLS REQUIRES; TIMP GENE FAMILY; NIH 3T3 CELLS; EPITHELIAL-CELLS AB Hepatocyte growth factor (HGF) stimulates mitogenic, motogenic, and morphogenic responses in various cell types. We analysed HGF-responsive cells by differential display PCR to identify HGF-induced genes that mediate these biological events. One of the genes identified encoded a member of the tissue inhibitor of metalloproteinases (TIMP) family, TIMP3. HGF transiently induced TIMP-3 mRNA in keratinocytes as well as kidney and mammary epithelial cells maximally between 4 and 6 h post-stimulation. Increased TIMP3 protein secretion returned to basal levels within 18 h, while the expression of gelatinases A and B remained unchanged, suggesting that temporary suppression of matrix degradation is a delayed early response to HGF. Ectopic overexpression of TIMP-3 in cultured leiomyosarcoma cells conferred an epithelial morphology, reduced cell growth rate, anchorage-independent growth, and matrix invasion in vitro. Antisense suppression of TIMP3 was associated with a scattered, fibroblastic cell morphology, as well as enhanced proliferation, anchorage-independent growth, and matrix invasion. A survey of tumor cell lines revealed an inverse relationship between metastatic potential and TIMP3 expression level. These data suggest that early, transient TIMP3 expression mediates specific HGF-induced phenotypic changes, and that loss of TIMP3 expression may enhance the invasion potential of certain tumors. C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Ctr Med Univ Geneva, Dept Morphol, Geneva, Switzerland. RP Bottaro, DP (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 81 TC 23 Z9 26 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 30 PY 1998 VL 17 IS 4 BP 481 EP 492 DI 10.1038/sj.onc.1201957 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 104XY UT WOS:000075043000011 PM 9696042 ER PT J AU Sithanandam, G Ramakrishna, G Diwan, BA Anderson, LM AF Sithanandam, G Ramakrishna, G Diwan, BA Anderson, LM TI Selective mutation of K-ras by N-ethylnitrosourea shifts from codon 12 to codon 61 during fetal mouse lung maturation SO ONCOGENE LA English DT Article DE fetal lung; lung tumor; gestation stage; N-ethylnitrosourea; K-ras; mutation; K-ras p21 ID ONCOGENE ACTIVATION; GENE-MUTATIONS; DNA-DAMAGE; A/J MICE; TUMORS; 1-ETHYL-1-NITROSOUREA; CARCINOGENESIS; ADENOCARCINOMA; NITROSAMINES; MUTAGENESIS AB Fetal mouse lung before gestation day 17 shows unique sensitivity to causation of rapidly growing tumors by N-ethylnitrosourea (ENU). Since mouse lung tumors present a mutated K-ras oncogene, we hypothesized that this special susceptibility might reflect an unusual vulnerability of the K-ras gene. Of the lung tumors caused by ENU exposure of BALB/c mice on gestation day 14, 8/25 had a codon 12 mutation in K-ras, vs 4/25 in codon 61, Of 15 tumors after day 16 exposure, three had codon 12 and four codon 61 changes. Tumors from day 18 exposure had only codon 61 mutations (11/16), all A:T to G:C changes (CGA), By contrast, codon 12 (GGT) changes included G:C to T:A, to A:T,and to C:G, These results show significant (P<0.01) shift in the sensitivity of particular K-ras codons to ENU mutation, during fetal mouse lung maturation. In a test of a possible relationship to expression of K-ras, K-ras p21 was measured in lungs of fetal mice, and found to increase markedly on day 18 in comparison to days 14 and 16, Both alkylation of DIVA and base damage due to reactive oxygen species are postulated as mechanisms for mutation by ENU, whose efficacies vary with state of fetal lung maturation and K-rns expression. C1 SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Sithanandam, G (reprint author), SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NR 56 TC 19 Z9 19 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 30 PY 1998 VL 17 IS 4 BP 493 EP 502 DI 10.1038/sj.onc.1201958 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 104XY UT WOS:000075043000012 PM 9696043 ER PT J AU Zhou, HB Weinberg, CR AF Zhou, HB Weinberg, CR TI Evaluating effects of exposures on embryo viability and uterine receptivity in in vitro fertilization SO STATISTICS IN MEDICINE LA English DT Article ID EM ALGORITHM AB We consider models for the occurrence of pregnancy following in vitro fertilization. In this clinical protocol, implantation depends on two factors: the receptivity of the uterus and the viability of at least one of the embryos transferred to the uterus. This work is motivated by the need to identify reliable bio-markers for these two factors, in order to enhance the success rate for couples undergoing this procedure. We present a general latent variable structure model for outcomes that take either one of two possible forms: as summed Bernoullis, based on an ultrasound count of gestational sacs, or as aggregated Bernoullis, based only on the outcome of a biochemical pregnancy test. We allow both uterine receptivity and embryo viability to be influenced by covariates. The proposed latent variable structure allows us to utilize the existing statistical packages to maximize an otherwise intractable likelihood function. The method is sufficiently flexible to permit any valid choice of link function. We illustrate by applying the method to a recent study of in vitro fertilization carried out in North Carolina. The number of cells at transfer is evidently a marker for embryo viability. (C) 1998 John Wiley & Sons, Ltd. C1 Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Zhou, HB (reprint author), Univ N Carolina, Dept Biostat, CB 7400,McGavran Greenberg Hall, Chapel Hill, NC 27599 USA. NR 6 TC 24 Z9 24 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 30 PY 1998 VL 17 IS 14 BP 1601 EP 1612 DI 10.1002/(SICI)1097-0258(19980730)17:14<1601::AID-SIM870>3.0.CO;2-2 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 102ZF UT WOS:000074955600005 PM 9699232 ER PT J AU Wang, YX Marquardt, JL Wingfield, P Stahl, SJ Lee-Huang, S Torchia, D Bax, A AF Wang, YX Marquardt, JL Wingfield, P Stahl, SJ Lee-Huang, S Torchia, D Bax, A TI Simultaneous measurement of H-1-N-15, H-1-C-13 ', and N-15-C-13 ' dipolar couplings in a perdeuterated 30 kDa protein dissolved in a dilute liquid crystailine phase SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HUMAN UBIQUITIN; RELAXATION; INTERFERENCE; NMR C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. NIDR, Mol Struct Biol Unit, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 24 TC 62 Z9 63 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 29 PY 1998 VL 120 IS 29 BP 7385 EP 7386 DI 10.1021/ja980862o PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 106XF UT WOS:000075176000042 ER PT J AU Alberdi, E Hyde, CC Becerra, SP AF Alberdi, E Hyde, CC Becerra, SP TI Pigment epithelium-derived factor (PEDF) binds to glycosaminoglycans: Analysis of the binding site SO BIOCHEMISTRY LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCAN; FIBROBLAST GROWTH-FACTOR; NEUROTROPHIC ACTIVITY; BOVINE EYES; DATA-BANK; IDENTIFICATION; RETINA; CELLS; ACTIVATION; RECEPTORS AB Pigment epithelium-derived factor (PEDF), a neurotrophic protein, is a secreted serpin identified in extracellular matrixes. We show that PEDF extractions from the interphotoreceptor matrix are more efficient with increasing NaCl concentrations, indicating that ionic interactions mediate its association with this polyanionic matrix. We have used affinity chromatography and ultrafiltration to probe for direct binding of PEDF to glycosaminoglycans/polyanions. Correctly folded PEDF bound to immobilized heparin, chondroitin sulfate-A, -B, -C, and dextran sulfate columns and eluted from each with an increase in NaCl concentration. However, in the presence of urea, the protein lost its affinity for heparin. Binding of PEDF to heparan sulfate proteoglycan in solution was in a concentration-dependent fashion (half-maximal specific binding EC50 = 40 mu g/mL) and was sensitive to increasing NaCl concentrations. The glycosaminoglycan-binding region was analyzed using chemical modification and limited proteolysis. PEDF chemically modified on lysine residues by biotinylation lost its capacity for interacting with heparin, implicating the involvement of PEDF lysine residues in heparin binding. Cleavage of the serpin-exposed loop with chymotrypsin did not affect the heparin-binding property. A limited proteolysis product containing residues 21-similar to 260 bound to heparin with similar affinity as the intact PEDF. Homology modeling of PEDF based on the X-ray crystal structures of antithrombin III and ovalbumin shows a region at the center of beta-sheet A-strands 2 and 3-and helix F that has a basic electrostatic surface potential and is densely populated with lysines exposed to the surface (K134, K137, K189, K191, H212, and K214) that are available to interact with various glycosaminoglycans/polyanions. This region represents a novel site for glycosaminoglycan binding in a serpin, which in PEDF, is distinct and nonoverlapping from the PEDF neurotrophic active region. C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Becerra, SP (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bldg 6,Room 308,6 Ctr Dr MSC 2740, Bethesda, MD 20892 USA. EM pbecerra@helix.nih.gov OI Alberdi, Elena/0000-0002-8000-142X NR 37 TC 77 Z9 78 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 28 PY 1998 VL 37 IS 30 BP 10643 EP 10652 DI 10.1021/bi9802317 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108RZ UT WOS:000075280400012 PM 9692954 ER PT J AU Rhee, S Miles, EW Mozzarelli, A Davies, DR AF Rhee, S Miles, EW Mozzarelli, A Davies, DR TI Cryocrystallography and microspectrophotometry of a mutant (alpha D60N) tryptophan synthase alpha(2)beta(2) complex reveals allosteric roles of alpha Asp6O SO BIOCHEMISTRY LA English DT Article ID BIENZYME COMPLEX; SALMONELLA-TYPHIMURIUM; 3-DIMENSIONAL STRUCTURE; BETA-SUBUNIT; ACTIVE-SITE; COMMUNICATION; MECHANISM; ALPHA-2-BETA-2-COMPLEX; ENZYMES; LOOP AB We have investigated the role of Asp60 of the alpha-subunit in allosteric communication between the tryptophan synthase alpha- and beta-subunits. Crystallographic and microspectrophotometric studies have been carried out on a mutant (alpha D60N) tryptophan synthase alpha(2)beta(2) complex which has no observable alpha-activity, but has substantial beta-activity. Single-crystal polarized absorption spectra indicate that the external aldimine is the predominant L-serine intermediate and that the amount of the intermediate formed is independent of pH, monovalent cations, and allosteric effecters. The three-dimensional structure is reported for this mutant enzyme complexed with indole 3-propanol phosphate bound to the alpha-site and L-serine bound to the beta-site (alpha D60N-IPP-Ser), and this structure is compared with that of the unliganded mutant enzyme (alpha D60N). In the complex, L-serine forms a stable external aldimine with the pyridoxal phosphate coenzyme at the active site of the beta-subunit. The conformation of the unliganded mutant is almost identical to that of the wild type enzyme. However, the structure of the mutant complexed with IPP and serine exhibits ligand-induced conformational changes much smaller than those observed previously for another mutant enzyme in the presence of the same ligands (beta K87T-IPP-Ser) [Rhee, S., Parris, K. D., Hyde, C. C., Ahmed, S. A., Miles, E. W., and Davies, D. R. (1997) Biochemistry 36, 7664-7680]. The alpha D60N-IPP-Ser alpha(2)beta(2) complex does not undergo the following ligand-induced conformational changes: (1) the closure of the alpha-subunit loop 6 (residues 178-191), (2) the movement of the mobile subdomain (residues 93-189) of the beta-subunit, and (3) the rotation of the alpha-subunit relative to the beta-subunit. These observations show that alpha Asp60 plays important roles in the closure of loop 6 and in allosteric communication between the alpha- and beta-subunits. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. Univ Parma, Inst Biochem Sci, I-43100 Parma, Italy. RP Davies, DR (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Rm 338, Bethesda, MD 20892 USA. RI Mozzarelli, Andrea/C-3615-2014 OI Mozzarelli, Andrea/0000-0003-3762-0062 NR 34 TC 38 Z9 38 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 28 PY 1998 VL 37 IS 30 BP 10653 EP 10659 DI 10.1021/bi980779d PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108RZ UT WOS:000075280400013 PM 9692955 ER PT J AU Zhang, Y Ribeiro, JMC Guimaraes, JA Walsh, PN AF Zhang, Y Ribeiro, JMC Guimaraes, JA Walsh, PN TI Nitrophorin-2: A novel mixed-type reversible specific inhibitor of the intrinsic factor-X activating complex SO BIOCHEMISTRY LA English DT Article ID RAPID EXTRUSION PROCEDURE; COAGULATION FACTOR-X; FACTOR-IXA; HUMAN-PLATELETS; FACTOR-VIII; BLOOD-COAGULATION; RHODNIUS-PROLIXUS; STUART FACTOR; TISSUE FACTOR; BINDING-SITE AB Nitrophorin-2 (NP-2), isolated from salivary glands of the blood-sucking insect Rhodnius prolixus, has been shown to be a specific inhibitor of the intrinsic factor X-(FX)-activating complex. The inhibitory effect of NP-2 is most potent in the presence of both FVIIIa and phospholipids (artificial phospholipid vesicles or activated human platelets). Detailed kinetic analyses of the inhibitory mechanism of NP-2 demonstrated a decrease in both V-max and K-m of activated FIX-(FIXa)-catalyzed FX activation in the presence of FVIIIa and phospholipid vesicles, characteristic of a hyperbolic mixed-type reversible inhibitor. NP-2 exhibits a higher binding affinity for the enzyme-substrate complex, i.e., FIXa/FVIIIa/Ca2+/phospholipids/FX complex (K-i' = 6.2 nM) than for the enzyme complex, i.e., FIXa/FVIIIa/Ca2+/phospholipids (K-i = 16.5 nM). The same inhibitory kinetic mechanism is valid in platelet-mediated FIXa-catalyzed FX activation (K-i' = 5.9 nM and K-i = 12.6 nM, respectively). The fact that NP-2 increases the concentrations (EC50) of FIXa, FVIIIa, and phospholipid vesicles required for half-maximal rates of FX activation suggests that NP-2 interferes with the functioning of all three major components of the intrinsic FX-activating complex. NP-2 was found to inhibit FX activation when either phospholipids or FVIIIa are present, but not in the absence of both factors. Taken together, we conclude that NP-2 is a unique, potent, and highly specific inhibitor of the intrinsic FX-activating complex that inhibits FIXa bound either to the phospholipid or activated platelet surface or to the cofactor FVIIIa by interfering with the assembly of FX-activating complex on these surfaces. C1 Temple Univ, Sch Med, Sol Sherry Thrombosis Res Ctr, Dept Biochem, Philadelphia, PA 19140 USA. Temple Univ, Sch Med, Dept Med, Philadelphia, PA 19140 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Fed Univ Rio De Janeiro, Dept Biochem Med, ICB, Rio De Janeiro, Brazil. RP Walsh, PN (reprint author), Temple Univ, Sch Med, Sol Sherry Thrombosis Res Ctr, Dept Biochem, 3400 N Broad St, Philadelphia, PA 19140 USA. OI Guimaraes, Jorge A./0000-0001-6354-6789; Ribeiro, Jose/0000-0002-9107-0818 FU NHLBI NIH HHS [HL46213, HL55407, HL56914] NR 36 TC 41 Z9 41 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 28 PY 1998 VL 37 IS 30 BP 10681 EP 10690 DI 10.1021/bi973050y PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108RZ UT WOS:000075280400016 PM 9692958 ER PT J AU Wolff, J AF Wolff, J TI Promotion of microtubule assembly by oligocations: Cooperativity between charged groups SO BIOCHEMISTRY LA English DT Article ID CALF BRAIN MICROTUBULES; ORNITHINE DECARBOXYLASE; INVITRO RECONSTITUTION; TUBULIN POLYMERIZATION; PURIFIED TUBULIN; PROTEINS; THERMODYNAMICS; POLYCATIONS; PEPTIDE; CELLS AB The rate and, to a lesser degree, the extent of microtubule assembly from rat brain tubulin is enhanced by oligocations such as polyamines, melittin, polybasic drugs, oligolysines, and oligoarginines. The effect is cooperative for degrees of polymerization up to seven for oligolysines and up to five for oligoarginines and is interpreted as an interaction with up to seven closely spaced anionic charges. Microtubules so formed appear to be normal by electron microscopy, and by salt, colchicine, and cold sensitivities. Lysyl residues in excess of seven (or five for arginine) in larger oligomers interact nearly noncooperatively. Separation of lysyl charges by intercalation of alanyl residues reduced assembly promoting potency for hexalysines. The cooperative portion of the response is most likely associated with the highly acidic extreme C termini of tubulin because their removal with limited subtilisin treatment markedly reduces oligolysine potency. However, some cooperative interactions with oligocations can also occur with more widely spaced anionic charges elsewhere in tubulin. The potential role of oligocations in the intracellular regulation of microtubule assembly is discussed. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wolff, J (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 2A23, Bethesda, MD 20892 USA. NR 46 TC 36 Z9 37 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 28 PY 1998 VL 37 IS 30 BP 10722 EP 10729 DI 10.1021/bi980400n PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108RZ UT WOS:000075280400020 PM 9692962 ER PT J AU Kishore, N Tewari, YB Akers, DL Goldberg, RN Miles, EW AF Kishore, N Tewari, YB Akers, DL Goldberg, RN Miles, EW TI A thermodynamic investigation of reactions catalyzed by tryptophan synthase SO BIOPHYSICAL CHEMISTRY LA English DT Article DE enthalpy; apparent equilibrium constant; entropy; thermodynamics; tryptophan synthase ID SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; BIOCHEMICAL REACTIONS; AQUEOUS-SOLUTION; HEAT-CAPACITIES; BETA-SUBUNIT; EQUILIBRIUM; COMPLEX; VOLUMES; ALPHA AB Microcalorimetry and high-performance liquid chromatography have been used to conduct a thermodynamic investigation of the following reactions catalyzed by the tryptophan synthase alpha(2) beta(2) complex (EC 4.2.1.20) and its subunits: indole(aq) + L-serine(aq) = L-tryptophan(aq) + H2O(1); L-serine(aq) = pyruvate(aq) + ammonia(aq); indole(aq) + D-glyceraldehyde 3-phosphate(aq) = 1-(indol-3-yl)glycerol 3-phosphate(aq); L-serine(aq) + 1-(indol-3-yl)glycerol 3-phosphate(aq) = L-tryptophan(aq) + D-glyceraldehyde 3-phosphate(aq) + H2O(1). The calorimetric measurements led to standard molar enthalpy changes for all four of these reactions. Direct measurements yielded an apparent equilibrium constant for the third reaction; equilibrium constants for the remaining three reactions were obtained by using thermochemical cycle calculations. The results of the calorimetric and equilibrium measurements were analyzed in terms of a chemical equilibrium model that accounted for the multiplicity of the ionic states of the reactants and products. Thermodynamic quantities for chemical reference reactions involving specific ionic forms have been obtained. These quantities permit the calculation of the position of equilibrium of the above four reactions as a function of temperature, pH, and ionic strength. Values of the apparent equilibrium constants and standard transformed Gibbs free energy changes Delta(r)G'(o)(m) under approximately physiological conditions are given. Le Chatelier's principle provides an explanation as to why, in the metabolic pathway leading to the synthesis of L-tryptophan, the third reaction proceeds in the direction of formation of indole and D-glyceraldehyde 3-phosphate even though the apparent equilibrium constant greatly favors the formation of 1-(indol-3-yl) glycerol 3-phosphate. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Natl Inst Stand & Technol, Div Biotechnol, Gaithersburg, MD 20899 USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Goldberg, RN (reprint author), Natl Inst Stand & Technol, Div Biotechnol, Gaithersburg, MD 20899 USA. EM robert.goldberg@nist.gov NR 44 TC 8 Z9 8 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 EI 1873-4200 J9 BIOPHYS CHEM JI Biophys. Chem. PD JUL 27 PY 1998 VL 73 IS 3 BP 265 EP 280 DI 10.1016/S0301-4622(98)00151-3 PG 16 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 104VB UT WOS:000075035600007 PM 9700925 ER PT J AU Zukowska-Grojec, Z Karwatowska-Prokopczuk, E Rose, W Rone, J Movafagh, S Ji, H Yeh, YY Chen, WT Kleinman, HK Grouzmann, E Grant, DS AF Zukowska-Grojec, Z Karwatowska-Prokopczuk, E Rose, W Rone, J Movafagh, S Ji, H Yeh, YY Chen, WT Kleinman, HK Grouzmann, E Grant, DS TI Neuropeptide Y - A novel angiogenic factor from the sympathetic nerves and endothelium SO CIRCULATION RESEARCH LA English DT Article DE angiogenesis; chemotaxis; dipeptidyl peptidase IV; NPY; receptor; endothelial cell ID SMOOTH-MUSCLE CELLS; CAPILLARY-LIKE STRUCTURES; DIPEPTIDYL PEPTIDASE-IV; PROTEIN-KINASE-C; FUNCTIONAL EXPRESSION; GENE-EXPRESSION; RAT AORTA; RECEPTOR; CLONING; LAMININ AB Sympathetic nerves have long been suspected of trophic activity, but the nature of their angiogenic factor has not been determined. Neuropeptide Y (NPY), a sympathetic cotransmitter, is the most abundant peptide in the heart and the brain. It is released during nerve activation and ischemia and causes vasoconstriction and smooth muscle cell proliferation. Here we report the first evidence that NPY is angiogenic. At low physiological concentrations, in vitro, it promotes vessel sprouting and adhesion, migration, proliferation, and capillary tube formation by human endothelial cells. In vivo, in a murine angiogenic assay, NPY is angiogenic and is as potent as a basic fibroblast growth factor. The NPY action is specific and is mediated by Y1 and Y2 receptors. The expression of both receptors is upregulated during cell growth; however, Y2 appears to be the main NPY angiogenic receptor. Its upregulation parallels the NPY-induced capillary tube formation on reconstituted basement membrane (Matrigel); the Y2 agonist mimics the tube-forming activity of NPY, whereas the Y2 antagonist blocks it. Endothelium contains not only NPY receptors but also peptide itself, its mRNA, and the "NPY-converting enzyme" dipeptidyl peptidase IV (both protein and mRNA), which terminates the Y1 activity of NPY and cleaves the Tyr(1)-Pro(2) from NPY to form an angiogenic Y2 agonist, NPY3-36 Endothelium is thus not only the site of action of NPY but also the origin of the autocrine NPY system, which, together with the sympathetic nerves, may be important in angiogenesis during tissue development and repair. C1 Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. NIDR, Cell Biol Sect, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA. CHU Vaudois, Dept Hypertens, CH-1011 Lausanne, Switzerland. RP Zukowska-Grojec, Z (reprint author), Georgetown Univ, Med Ctr, Dept Physiol & Biophys, 3900 Reservoir Rd NW, Washington, DC 20007 USA. EM zzukow01@medlib.georgetown.edu FU NHLBI NIH HHS [HL-55310] NR 42 TC 266 Z9 270 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 27 PY 1998 VL 83 IS 2 BP 187 EP 195 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 103HP UT WOS:000075152100008 PM 9686758 ER PT J AU Speir, E Yu, ZX Ferrans, VJ Huang, ES Epstein, SE AF Speir, E Yu, ZX Ferrans, VJ Huang, ES Epstein, SE TI Aspirin attenuates cytomegalovirus infectivity and gene expression mediated by cyclooxygenase-2 in coronary artery smooth muscle cells SO CIRCULATION RESEARCH LA English DT Article DE antioxidant; atherosclerosis; cyclooxygenase; herpesvirus salicylate ID NF-KAPPA-B; PROSTAGLANDIN-G/H SYNTHASE; DEXAMETHASONE; FIBROBLASTS; INHIBITORS; ACTIVATION; RESTENOSIS; GROWTH; VIRUS AB Human cytomegalovirus (CMV) infection of smooth muscle cells generates reactive oxygen species (ROS) and thereby activates nuclear factor kappa B (NF kappa B), which causes expression of viral and cellular genes involved in immune and inflammatory responses. These changes could account for the mounting evidence suggesting that CMV may contribute causally to restenosis and atherosclerosis. We found that CMV induces ROS, at least partly, through a cyclooxygenase-2 (COX-2)-dependent pathway. Moreover, the viral immediate-early (IE) gene products, IE72 and IE84, have the capacity to transactivate the COX-2 promoter. Aspirin and indomethacin, both cyclooxygenase inhibitors as well as direct ROS scavengers, reduce CMV-induced ROS, probably through both of these activities. Sodium salicylate also has antiviral effects as the result of its potent antioxidant propel ties. Furthermore, by reducing ROS, aspirin and sodium salicylate inhibit CMV-induced NF kappa B activation, the ability of IE72 to transactivate its promoter, CMV IE gene expression after infection of SMCs, and CMV replication in SMCs. This is the first time aspirin has been shown to have antiviral effects. Thus, it is possible that aspirin has previously unrecognized therapeutic effects in various clinical situations, such as in viral infections (when used as an antipyretic agent) and in atherosclerosis (when used as an antiplatelet agent). C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Speir, E (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 27 TC 109 Z9 126 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 27 PY 1998 VL 83 IS 2 BP 210 EP 216 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 103HP UT WOS:000075152100011 PM 9686761 ER PT J AU Ooi, CE Dell'Angelica, EC Bonifacino, JS AF Ooi, CE Dell'Angelica, EC Bonifacino, JS TI ADP-ribosylation factor 1 (ARF1) regulates recruitment of the AP-3 adaptor complex to membranes SO JOURNAL OF CELL BIOLOGY LA English DT Article DE ARF; adaptin; coat; endosomes; BFA ID TRANS-GOLGI NETWORK; GTP-BINDING PROTEIN; CLATHRIN-ASSOCIATED PROTEINS; COATED VESICLES; BREFELDIN-A; BETA-COP; GUANINE-NUCLEOTIDE; PLASMA-MEMBRANE; SORTING SIGNALS; IN-VITRO AB Small GTP-binding proteins such as ADP-ribosylation factor 1 (ARF1) and Sar1p regulate the membrane association of coat proteins involved in intracellular membrane trafficking. ARF1 controls the clathrin coat adaptor AP-1 and the nonclathrin coat COPI, whereas Sar1p controls the nonclathrin coat COPII. In this study, we demonstrate that membrane association of the recently described AP-3 adaptor is regulated by ARF1. Association of AP-3 with membranes in vitro was enhanced by GTP gamma S and inhibited by brefeldin A (BFA), an inhibitor of ARF1 guanine nucleotide exchange. In addition, recombinant myristoylated ARF1 promoted association of AP-3 with membranes. The role of ARF1 in vivo was examined by assessing AP-3 subcellular localization when the intracellular level of ARF1-GTP was altered through overexpression of dominant ARF1 mutants or ARF1-GTPase-activating protein (GAP). Lowering ARF1-GTP levels resulted in redistribution of AP-3 from punctate membrane-bound structures to the cytosol as seen by immunofluorescence microscopy, In contrast, increasing ARF1-GTP levels prevented redistribution of AP-3 to the cytosol induced by BFA or energy depletion. Similar experiments with mutants of ARF5 and ARF6 showed that these other ARF family members had little or no effect on AP-3. Taken together, our results indicate that membrane recruitment of AP-3 is promoted by ARF1-GTP. This finding suggests that ARF1 is not a regulator of specific coat proteins, but rather is a ubiquitous molecular switch that acts as a transducer of diverse signals influencing coat assembly. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T Room 101, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 92 TC 140 Z9 143 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL 27 PY 1998 VL 142 IS 2 BP 391 EP 402 DI 10.1083/jcb.142.2.391 PG 12 WC Cell Biology SC Cell Biology GA 106CC UT WOS:000075111300008 PM 9679139 ER PT J AU Vallada, H Curtis, D Sham, P Kunugi, H Zhao, JH Murray, R McGuffin, P Nanko, S Owen, M Gill, M Collier, DA Antonarakis, S Housman, D Kazazian, H Nestadt, G Pulver, AE Straub, RE MacLean, CJ Walsh, D Kendler, KS DeLisi, L Polymeropoulos, M Coon, H Byerley, W Lofthouse, R Gershon, E Goldin, L Freedman, R Laurent, C Bodeau-Pean, S d'Amato, T Jay, M Campion, D Mallet, J Wildenauer, DB Lerer, B Albus, M Ackenheil, M Ebstein, RP Hallmayer, J Maier, W Gurling, H Curtis, D Kalsi, G Brynjolfsson, J Sigmundson, T Petursson, H Blackwood, D Muri, W StClair, D He, L Maguire, S Moises, HW Hwu, HG Yang, L Wiese, C Kristbjarnarson, H Levinson, DF Mowry, BJ Donis-Keller, H Hayward, NK Crowe, RR Silverman, JM Nancarrow, DJ Read, CM AF Vallada, H Curtis, D Sham, P Kunugi, H Zhao, JH Murray, R McGuffin, P Nanko, S Owen, M Gill, M Collier, DA Antonarakis, S Housman, D Kazazian, H Nestadt, G Pulver, AE Straub, RE MacLean, CJ Walsh, D Kendler, KS DeLisi, L Polymeropoulos, M Coon, H Byerley, W Lofthouse, R Gershon, E Goldin, L Freedman, R Laurent, C Bodeau-Pean, S d'Amato, T Jay, M Campion, D Mallet, J Wildenauer, DB Lerer, B Albus, M Ackenheil, M Ebstein, RP Hallmayer, J Maier, W Gurling, H Curtis, D Kalsi, G Brynjolfsson, J Sigmundson, T Petursson, H Blackwood, D Muri, W StClair, D He, L Maguire, S Moises, HW Hwu, HG Yang, L Wiese, C Kristbjarnarson, H Levinson, DF Mowry, BJ Donis-Keller, H Hayward, NK Crowe, RR Silverman, JM Nancarrow, DJ Read, CM CA Schizophrenia Collaborative Linkage Grp Chromo TI A transmission disequilibrium and linkage analysis of D22S278 marker alleles in 574 families: further support for a susceptibility locus for schizophrenia at 22q12 SO SCHIZOPHRENIA RESEARCH LA English DT Article DE psychosis; chromosome 22; complex disease genetics; combined analysis; TDT ID POTENTIAL LINKAGE; CHROMOSOME 22Q12-Q13.1; FOLLOW-UP AB Previously, a combined analysis by the Chromosome 22 Collaborative Linkage Group (1996; Am. J. Med Genet. 67, 40-45) used an affected sib-pair analysis of a single marker (D22S278) in 574 families multiply affected by schizophrenia and found some evidence for linkage (chi(2)=9.35, 1 df, p=0.001), suggesting the presence of a disease locus nearby on chromosome 22q12. In order to further investigate the importance of this result, we have performed the transmission disequilibrium test (TDT) and additional parametric and non-parametric linkage analysis of the same data. The most positive result obtained was an admixture lod score of 0.9 under the assumption of locus heterogeneity and dominant transmission. The result of the TDT analysis was significant at p=0.015 (allele-wise; chi(2)=22, 10 df) and p=0.00016 (genotype-wise; chi(2)=66.2, 30 df, empirical p value=0.0009). Overall, these results further strengthen the notion that there is a susceptibility locus for schizophrenia close to D22S278. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 Inst Psychiat, Dept Med Psychol, London SE5 8AF, England. Cardiff Univ, Dept Psychol Med, Cardiff CF4 4XN, S Glam, Wales. Teikyo Univ, Dept Psychiat, Tokyo, Japan. St Bartholomews & Royal London Sch Med & Dent, London, England. Univ Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. Univ Geneva, Geneva, Switzerland. MIT, Cambridge, MA 02139 USA. Univ Penn, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Virginia Commonwealth Univ Med Coll Virginia, Dept Psychiat & Human Genet, Richmond, VA USA. St Lomans Hosp, Dublin, Ireland. SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT USA. NIMH, Clin Neurogenet Branch, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. CNRS, Lab Genet Mol Neurotransmiss & Proc Neurodegenera, Paris, France. Univ Munich, Munich, Germany. Johannes Gutenberg Univ Mainz, D-6500 Mainz, Germany. Hadassah Herzog Psychogenet Program, Jerusalem, Israel. UCL, Sch Med, London W1N 8AA, England. Borgarspitalinn, Dept Psychiat, Reykjavik, Iceland. Western Gen Hosp, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland. Univ Edinburgh, Royal Edinburgh Hosp, Dept Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland. Kiel Univ Hosp, Dept Psychiat, Genet Mol Lab, Kiel, Germany. Natl Taiwan Univ Hosp, Dept Psychiat, Taipei, Taiwan. Natl Univ Hosp Reykjavik, Dept Psychiat, Reykjavik, Iceland. Med Coll Penn & Hahnemann Univ, Dept Psychiat, Philadelphia, PA 19129 USA. Univ Queensland, Brisbane, Qld, Australia. Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. RP Vallada, H (reprint author), Inst Psychiat, Dept Med Psychol, De Crespigny Pk,Denmark Hill, London SE5 8AF, England. RI turton, miranda/F-4682-2011; Gurling, Hugh/A-5029-2010; McGuffin, Peter/A-1565-2012; Antonarakis, Stylianos/N-8866-2014; hayward, nicholas/C-1367-2015; Vallada, Homero/D-1333-2014 OI McGuffin, Peter/0000-0002-9888-2907; Antonarakis, Stylianos/0000-0001-8907-5823; hayward, nicholas/0000-0003-4760-1033; Vallada, Homero/0000-0001-5123-8295 NR 19 TC 34 Z9 34 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL 27 PY 1998 VL 32 IS 2 BP 115 EP 121 PG 7 WC Psychiatry SC Psychiatry GA 107JN UT WOS:000075204800007 ER PT J AU Brown, P AF Brown, P TI On the origins of BSE SO LANCET LA English DT Editorial Material C1 NINDS, NIH, CNS Studies Lab, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NINDS, NIH, CNS Studies Lab, Bethesda, MD 20892 USA. NR 3 TC 11 Z9 11 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 25 PY 1998 VL 352 IS 9124 BP 252 EP 253 DI 10.1016/S0140-6736(05)60255-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 103TT UT WOS:000074974500004 PM 9690401 ER PT J AU Parks, LL Turney, MK Detera-Wadleigh, S Kovacs, WJ AF Parks, LL Turney, MK Detera-Wadleigh, S Kovacs, WJ TI An ACTH-producing small cell lung cancer expresses aberrant glucocorticoid receptor transcripts from a normal gene SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE corticotropin [secretion]; carcinoma; ectopic ACTH syndrome; glucocorticoid; lung neoplasms [secretion]; receptors; small cell [secretion] ID PROOPIOMELANOCORTIN GENE; ESTROGEN-RECEPTOR; MESSENGER-RNA; VARIANT; INHIBITION; RESISTANT; LINES AB ACTH production by non-pituitary tumors is generally not suppressible by exogenous glucocorticoid administration. We had postulated that defects in the glucocorticoid receptor (GR) signaling system might be responsible for this apparent glucocorticoid resistance and had previously demonstrated that DMS-79 cells, derived from an ectopic ACTR-producing tumor, express an abnormal GR mRNA. In this DMS-79 cell GR the sequence normally derived from exons 8 and 9 is replaced by sequence unmatched in the DNA databases. The protein encoded by this mRNA lacks the steroid-binding domain and does not function as a ligand-activated transcription factor. In the present work, we sought to identify the origin of the novel GR mRNA sequence. Southern blot analysis of DMS-79 genomic DNA showed no major structural alteration of the GR gene. Southern blotting of cosmid clones of the normal GR gene revealed that the novel DMS-79 GR mRNA sequence is derived from intron G, between exons 7 and 8. No splice site mutations were found in PCR-amplified DMS-79 DNA fragments surrounding the downstream splice junctions. Further sequencing indicated that the aberrant GR transcript appears to be generated by use of a consensus cleavage/polyadenylation signal found 3650 base pairs into the normal intron G. We conclude that abnormal GR pre-mRNA processing rather than a GR gene mutation confers glucocorticoid resistance on DMS-79 cells. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Vanderbilt Univ, Div Endocrinol, Sch Med, Nashville, TN 37232 USA. NIMH, Clin Neurogenet Branch, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. RP Kovacs, WJ (reprint author), Vanderbilt Univ, Div Endocrinol, Sch Med, Room 715 MRB II, Nashville, TN 37232 USA. EM William.Kovacs@mcmail.vanderbilt.edu OI Kovacs, William/0000-0002-3940-2109 FU NIDDK NIH HHS [T32 DK07061-22] NR 19 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUL 25 PY 1998 VL 142 IS 1-2 BP 175 EP 181 DI 10.1016/S0303-7207(98)00107-5 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 120BJ UT WOS:000075934400017 PM 9783913 ER PT J AU El-Ghundi, M George, SR Drago, J Fletcher, PJ Fan, T Nguyen, T Liu, C Sibley, DR Westphal, H O'Dowd, BF AF El-Ghundi, M George, SR Drago, J Fletcher, PJ Fan, T Nguyen, T Liu, C Sibley, DR Westphal, H O'Dowd, BF TI Disruption of dopamine D-1 receptor gene expression attenuates alcohol-seeking behavior SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE dopamine D-1 receptor-deficient mouse; motivation; reward; alcohol drinking; SCH-23390; sulpiride ID FREELY MOVING RATS; VENTRAL TEGMENTAL AREA; C57BL/6J INBRED MOUSE; NUCLEUS-ACCUMBENS; ETHANOL-CONSUMPTION; SYNAPTIC DOPAMINE; MUTANT MICE; RELEASE; ANTAGONISTS; D1 AB The role of the dopamine D-1 receptor subtype in alcohol-seeking behaviors was studied in mice genetically deficient in dopamine D-1 receptors (D-1 -/-). In two-tube free choice limited (1-5 h) and continuous (24 h) access paradigms, mice were exposed to water and increasing concentrations of ethanol (3%, 6% and 12% w/v). Voluntary ethanol consumption and preference over water were markedly reduced in D-1 -/- mice as compared to heterozygous (D-1 +/-) and wild-type (D-1 +/+) controls, whereas overall fluid consumption was comparable. When offered a single drinking tube containing alcohol as their only source of fluid for 24 h, D-1 -/- mice continued to drink significantly less alcohol than D-1 +/+ and D-1 +/- mice. Dopamine D-2 receptor blockade with sulpiride caused a small but significant reduction in alcohol intake and preference in D-1 +/+ mice and attenuated residual alcohol drinking in D-1 -/- mice. Dopamine D-1 receptor blockade with SCH-23390 very effectively reduced alcohol intake in D-1 +/+ and D-1 +/- mice to the level seen in untreated D-1 -/- mice. These findings suggest involvement of both dopamine D-1 and D-2 receptor mechanisms in alcohol-seeking behavior in mice; however, these implicate D-1 receptors as having a more important role in the motivation for alcohol consumption. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Toronto, Dept Med & Pharmacol, Toronto, ON M5S 1A8, Canada. Addict Res Fdn, Toronto, ON M5S 2S1, Canada. Monash Univ, Dept Anat, Clayton, Vic 3168, Australia. Clarke Inst Psychiat, Toronto, ON M5T 1R8, Canada. NINDS, Expt Therapeut Branch, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. RP George, SR (reprint author), Univ Toronto, Dept Med & Pharmacol, Med Sci Bldg,Room 4358,1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada. NR 36 TC 114 Z9 117 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 JUL 24 PY 1998 VL 353 IS 2-3 BP 149 EP 158 DI 10.1016/S0014-2999(98)00414-2 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 109QZ UT WOS:000075335800002 PM 9726645 ER PT J AU Novakova, M Ela, C Bowen, WD Hasin, Y Eilam, Y AF Novakova, M Ela, C Bowen, WD Hasin, Y Eilam, Y TI Highly selective sigma receptor ligands elevate inositol 1,4,5-trisphosphate production in rat cardiac myocytes SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE sigma receptor; cardiac myocyte; contractility; Ca2+, cytosolic; inositol 1,4,5-trisphosphate; phospholipase C ID METHYL-D-ASPARTATE; CA2+ RELEASE; SARCOPLASMIC-RETICULUM; BIOLOGICAL EVALUATION; BEHAVIORAL EVIDENCE; DORSAL HIPPOCAMPUS; CALCIUM DYNAMICS; MEMORY PROCESSES; MODULATING ROLE; HIGH-AFFINITY AB Exposure of cardiac myocytes from adult rat ventricles to the highly selective, high affinity sigma receptor ligands 1S,2R-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-( 1-pyrrolidinyl)-cyclohexylamine (BD-737) (0.1-100 nM) and N-[2-(3,4-dichlorophenyl)ethyl]N,N',N'-trimethylethylenediamine (BD-1047) (0.01-10 nM), caused potentiation of electrically-evoked amplitudes of contraction and Ca2+ transients, while exposure to 100 nM ED-1047 caused attenuation of these amplitudes. In addition, BD-737 (0.1-100 nM) and BD-1047 (10-100 nM) caused an increase in the incidence of spontaneous twitches. These effects were inhibited when the incubation with BD-737 was done in the presence of the phospholipase C inhibitor, neomycin, or after pre-incubation with thapsigargin or caffeine which deplete the sarcoplasmic reticulum Ca2+ stores. Inositol 1,4,5-trisphosphate (IP3) production in cardiac myocytes was determined by the IF, binding protein assay. Both substances caused an increase in the intracellular concentration of IP3. BD-737 caused a rapid transient increase to 3.2-fold in 1 min and stabilization at 2.1-fold of control thereafter. ED-1047 caused a gradual increase reaching 4.4-fold after 5 min. The results suggest that the effects of these sigma receptor ligands on contractility and spontaneous contractions are mediated by activation of phospholipase C and elevation of intracellular IP3 level. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Bacteriol, IL-91010 Jerusalem, Israel. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Dept Cardiol, IL-91120 Jerusalem, Israel. RP Eilam, Y (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Bacteriol, IL-91010 Jerusalem, Israel. EM eilam@md.huji.ac.il NR 71 TC 49 Z9 51 U1 0 U2 5 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 JUL 24 PY 1998 VL 353 IS 2-3 BP 315 EP 327 DI 10.1016/S0014-2999(98)00398-7 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 109QZ UT WOS:000075335800019 PM 9726662 ER PT J AU Zlotnick, A Stahl, SJ Wingfield, PT Conway, JF Cheng, NQ Steven, AC AF Zlotnick, A Stahl, SJ Wingfield, PT Conway, JF Cheng, NQ Steven, AC TI Shared motifs of the capsid proteins of hepadnaviruses and retroviruses suggest a common evolutionary origin SO FEBS LETTERS LA English DT Article DE HIV; retrovirus; hepatitis B virus; hepadnavirus; gag; capsid; capsid assembly ID HEPATITIS-B VIRUS; MULTIPLE ALIGNMENT; CORE PROTEIN AB The structure of the dimeric C-terminal domain of the HIV-1 capsid protein (CA), recently determined by X-ray crystallography (Gamble et al, (1997)), has a notable resemblance to the structure of the hepatitis B virus (HBV) capsid protein (Cp) dimer, previously determined by cryo-electron microscopy (Conway et al, (1997), Bottcher et al, (1997)). In both proteins, dimerization is effected by formation of a four-helix bundle, whereby each subunit contributes a helix-loop-helix and most of the interaction between subunits is mediated by one pair of helices. These are the first two observations of a motif that is common to the capsid proteins of two enveloped viruses and quite distinct from the eight-stranded anti-parallel beta-barrel found in most other virus capsid proteins solved to date (Harrison et al, (1996)). Motivated by the structural resemblance, we have examined retroviral and HBV capsid protein sequences and found weak but significant similarities between them. These similarities further support an evolutionary relationship between these two virus families of great medical importance - the hepadnaviruses (e,g, HBV) and retroviruses (e.g. HIV). (C) 1998 Federation of European Biochemical Societies. C1 NIAMS, Prot Express Lab, NIH, Bethesda, MD 20892 USA. NIAMS, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. RP Zlotnick, A (reprint author), Univ Oklahoma, Hlth Sci Ctr, POB 26901, Oklahoma City, OK 73190 USA. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 23 TC 21 Z9 22 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 JUL 24 PY 1998 VL 431 IS 3 BP 301 EP 304 DI 10.1016/S0014-5793(98)00755-8 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 106RY UT WOS:000075165300001 PM 9714530 ER PT J AU Stancato, LF Yu, CR Petricoin, EF Larner, AC AF Stancato, LF Yu, CR Petricoin, EF Larner, AC TI Activation of Raf-1 by interferon gamma and oncostatin M requires expression of the Stat1 transcription factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE PHOSPHORYLATION; ALPHA-INTERFERON; GENE-EXPRESSION; ACTIVE STAT1; RECEPTOR; PROTEIN; PATHWAY AB A primary signaling cascade responsible for the ex pression of cytokine-stimulated immediate early genes involves the activation of the Jak/Stat pathway. In addition to being tyrosine-phosphorylated, several signal transducers and activators of transcription (Stats), including Stat1 alpha, Stat3, and Stat4, are phosphorylated on a conserved serine residue, which is a consensus phosphorylation site for mitogen-activated protein kinases (MAPKs), Serine phosphorylation of Stat1 alpha is required for maximal transcriptional activation of early response genes by interferon gamma (IFN gamma) as well as the antiviral and antigrowth actions of this cytokine. Incubation of cells with either IFN gamma or oncostatin M (OSM) activates Raf-1, a serine/threonine kinase responsible for the ultimate activation of p42 MAPK. To examine whether any of the signaling components that are required for activation of the Jak/Stat pathway are also necessary for activation of Raf-1 by IFNs and OSM, we examined activation of Raf-1 in cell lines that are deficient in either Stat1 alpha or Stat2. Unexpectedly, incubation of Stat1-deficient, but not Stat2-deficient cells with IFN gamma or OSM for 5 min displayed no increase in Raf-1 activity. In peripheral blood lymphocytes Raf-1 was associated with Stat1, and this interaction was disrupted after incubation of cells with IFN gamma, Stat1-negative cells reconstituted with either Stat1 alpha or Stat1 alpha with a point mutation in the site where it is serine-phosphorylated displayed normal activation of Raf-1 by IFN gamma and OSM, However, activation of Raf-1 was not observed in lines that expressed Stat1 alpha containing a mutation in its tyrosine phosphorylation site or in its SH2 domain. These results provide the first example of a novel role of Stat1 alpha not as a transcription factor, but as a protein which may function to scaffold signaling components required for activation of the distinct Raf/MEK/MAPK signaling cascade. C1 NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, NIH, Frederick, MD 21701 USA. Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Larner, AC (reprint author), Cleveland Clin Fdn, Dept Immunol, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NCI NIH HHS [CA77366] NR 20 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 24 PY 1998 VL 273 IS 30 BP 18701 EP 18704 DI 10.1074/jbc.273.30.18701 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103TV UT WOS:000074974700007 PM 9668040 ER PT J AU Murga, C Laguinge, L Wetzker, R Cuadrado, A Gutkind, JS AF Murga, C Laguinge, L Wetzker, R Cuadrado, A Gutkind, JS TI Activation of Akt/protein kinase B by G protein-coupled receptors - A role for alpha and beta gamma subunits of heterotrimeric G proteins acting through phosphatidylinositol-3-OH kinase gamma SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT ACTIVATION; PATHWAY; CELLS; INHIBITION; APOPTOSIS; SIGNALS; AKT; RAS AB The serine/threonine protein kinase Akt has recently been shown to be implicated in the pathway leading to cell survival in response to serum and growth factors in a variety of cellular systems. However, the existence of a biochemical route connecting this kinase to the large family of receptors that signal through heterotrimeric G proteins is yet to be explored. in this study, we set out to investigate whether GTP-binding protein (G protein)coupled receptors (GPCRs) can stimulate Akt activity and survival pathways and, if so, to define the mechanism(s) whereby this class of cell surface receptors could regulate Akt function. Using ectopic expression of GPCRs in COS-7 cells as a model, we have observed that both mi and m2 muscarinic acetylcholine receptors, representative of those GPCRs coupled to G, and Gi proteins, respectively, can readily activate an epitope-tagged form of Akt kinase and prevent W-induced apoptosis. We have also found that the pathway connecting G proteins to Akt implicates signals emanating from G alpha(q), G alpha(i) and beta gamma dimers, but not from G alpha(s) Or G alpha(12), in each case acting through a pathway that involves a phosphatidylinositol-3-OH kinase activity. Moreover, our findings suggest a role for a novel py-sensitive complex, p101.phosphatidylinositol-3-OH kinase-gamma, in the transduction of signals leading to Akt stimulation and cell survival by GPCRs and open new avenues for research on the function of the large family of G protein-linked receptors in the regulation of anti-apoptotic pathways. C1 NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Univ Jena, Fac Med, Max Planck Res Unit Mol Cell Biol, D-07747 Jena, Germany. RP Gutkind, JS (reprint author), NIDR, Oral & Pharyngeal Canc Branch, NIH, 9000 Rockville Pike,Bldg 30,Rm 211, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; Murga, Cristina/E-1965-2014; OI Murga, Cristina/0000-0002-8964-4077; Cuadrado, Antonio/0000-0002-3444-9012 NR 32 TC 253 Z9 253 U1 3 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 24 PY 1998 VL 273 IS 30 BP 19080 EP 19085 DI 10.1074/jbc.273.30.19080 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103TV UT WOS:000074974700058 PM 9668091 ER PT J AU Raben, N Nagaraju, K Lee, E Kessler, P Byrne, B Lee, L LaMarca, M King, C Ward, J Sauer, B Plotz, P AF Raben, N Nagaraju, K Lee, E Kessler, P Byrne, B Lee, L LaMarca, M King, C Ward, J Sauer, B Plotz, P TI Targeted disruption of the acid alpha-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SKELETAL-MUSCLE; CELLS; EXPRESSION; THERAPY; MODELS; ENZYME; MOUSE; HEART; CDNA; SITE AB We have used gene targeting to create a mouse model of glycogen storage disease type II, a disease in which distinct clinical phenotypes present at different ages. As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid alpha-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter. By 3.5 weeks of age, these mice have markedly reduced mobility and strength. They grow normally, however, reach adulthood, remain fertile, and, as in the human adult disease, older mice accumulate glycogen in the diaphragm. By 8-9 months of age animals develop obvious muscle wasting and a weak, waddling gait. This model, therefore, recapitulates critical features of both the infantile and the adult forms of the disease at a pace suitable for the evaluation of enzyme or gene replacement. In contrast, in a second model, mutant mice with deletion of exon 6 (Delta 6/Delta 6), like the recently published acid cu-glucosidase knockout with disruption of exon 13 (Bijvoet, A. G., van de Kamp, E. H., Kroos, M., Ding, J. H., Yang, B. Z., Visser, P., Bakker, C. E., Verbeet, M. P., Oostra, B. A., Reuser, A. J. J., and van der Ploeg, A. T. (1998) Hum. Mel. Genet. 7, 53-62), have unimpaired strength and mobility (up to 6.5 months of age) despite indistinguishable biochemical and pathological changes. The genetic background of the mouse strains appears to contribute to the differences among the three models. C1 NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21218 USA. Univ Miami, Sch Med, Dept Mol Genet & Microbiol, Miami, FL 33101 USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL 33101 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. NCI, Anim Sci Branch, Off Lab Anim Resources, NIH, Bethesda, MD 20892 USA. NIDDK, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Raben, N (reprint author), NIAMS, Arthrit & Rheumatism Branch, NIH, Bldg 10,Rm 9N244,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 23 TC 149 Z9 150 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 24 PY 1998 VL 273 IS 30 BP 19086 EP 19092 DI 10.1074/jbc.273.30.19086 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103TV UT WOS:000074974700059 PM 9668092 ER PT J AU Gervais, JLM Seth, P Zhang, H AF Gervais, JLM Seth, P Zhang, H TI Cleavage of CDK inhibitor p21(Cip1/Waf1) by caspases is an early event during DNA damage-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIN-DEPENDENT KINASES; CELL-CYCLE; S-PHASE; ICE/CED-3 PROTEASE; GROWTH ARREST; P21; PCNA; DEATH; SUPPRESSION; REPLICATION AB Activation of the p53-mediated DNA dams.ge response induces either G(1) cell cycle arrest or apoptosis. The Gr, cell cycle arrest is in part caused by the p53-dependent transcriptional activation of the CDK inhibitor, p21(Cip1/)Waf1. We report here that human p21 protein is rapidly induced but selectively cleaved during the apoptotic response to gamma-irradiation. Such an event occurred early, well before the morphological appearance of apoptosis. Ectopical expression of p53 in tumor cells alone could induce p21 expression, followed by p21 cleavage and apoptosis, The cleavage of pal could be reproduced in extracts prepared from irradiated cells or by recombinant caspase-3, suggesting that a caspase-like activity is responsible for this cleavage, p21 binds independently to both CDK2 and proliferation cell nuclear antigen (PCNA). Our studies indicated that p21 cleavage by the caspase-like activity specifically abolished its interaction with PCNA, suggesting that p21 cleavage may interfere with normal PCNA-dependent repair. Our data suggest that pal may serve as a critical checkpoint regulator for both cell cycle arrest and apoptosis during the p53-mediated DNA damage response. Manipulation of the checkpoint regulators involved in cell cycle arrest and apoptosis may thus provide a novel strategy to cancer therapy. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. NCI, Med Breast Canc Sect, Med Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, H (reprint author), Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. NR 34 TC 181 Z9 186 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 24 PY 1998 VL 273 IS 30 BP 19207 EP 19212 DI 10.1074/jbc.273.30.19207 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103TV UT WOS:000074974700075 PM 9668108 ER PT J AU Venkatachalam, KV Akita, H Strott, CA AF Venkatachalam, KV Akita, H Strott, CA TI Molecular cloning, expression, and characterization of human bifunctional 3 '-phosphoadenosine 5 '-phosphosulfate synthase and its functional domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHORYLATED ENZYME INTERMEDIATE; SULFATE ACTIVATION LOCUS; ATP SULFURYLASE; SACCHAROMYCES-CEREVISIAE; PENICILLIUM-CHRYSOGENUM; ARABIDOPSIS-THALIANA; NUCLEOTIDE-SEQUENCE; RAT CHONDROSARCOMA; ESCHERICHIA-COLI; APS KINASE AB The universal sulfonate donor, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), is synthesized by the concerted action of ATP sulfurylase and adenosine 5'-phosphosulfate (APS) kinase, which in animals ale fused into a bifunctional protein. The cDNA for human PAPS synthase (hPAPSS) along with polymerase chain reaction products corresponding to several NH2- and COOH-terminal fragments were cloned and expressed in COS-l cells. A 1-268-amino acid fragment expressed APS kinase activity, whereas a 220-623 fragment evinced ATP sulfurylase activity. The 1-268 fragment and full-length hPAPSS (1-623) exhibited hyperbolic responses against APS substrate with equivalent K-m values (0.6 and 0.4 mu M, respectively). The 1-268 fragment demonstrated Michaelis-Menten kinetics against ATP as substrate (K-m 0.26 mM); however, full-length hPAPSS exhibited a sigmoidal response (apparent K-m 1.5 mM) suggesting cooperative binding. Catalytic efficiency (V-mac/K-m) of the 1-268 fragment was 64-fold higher than. full-length hPAPSS for ATP, The kinetic data suggest that the COOH-terminal domain of hPAPSS exerts a regulatory role over APS kinase activity located in that NH2-terminal domain of this bifunctional protein. In addition, the 1-268 fragment and full-length hPAPSS were overexpressed in Escherichia coli and column purified, Purified full-length hPAPSS, in contrast to the! COS-l cell-expressed cDNA construct, exhibited a hyperbolic response curve against ATP suggesting that hPAPSS is perhaps modified in vivo. C1 NICHD, Sect Steroid Regulat Endocrinol & Reprod, Res Branch, NIH, Bethesda, MD 20892 USA. RP Strott, CA (reprint author), NICHD, Sect Steroid Regulat Endocrinol & Reprod, Res Branch, NIH, Bldg 49,Rm 6A36, Bethesda, MD 20892 USA. EM cheastro@box-c.nih.gov NR 37 TC 42 Z9 45 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 JUL 24 PY 1998 VL 273 IS 30 BP 19311 EP 19320 DI 10.1074/jbc.273.30.19311 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103TV UT WOS:000074974700088 PM 9668121 ER PT J AU Ueda, A Takeshita, F Yamashiro, S Yoshimura, T AF Ueda, A Takeshita, F Yamashiro, S Yoshimura, T TI Positive regulation of the human macrophage stimulating protein gene transcription - Identification of a new hepatocyte nuclear factor-4 (HNF-4) binding element and evidence that indicates direct association between NF-Y and HNF-4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEROID-RECEPTOR SUPERFAMILY; TYROSINE KINASE; MOLECULAR-CLONING; SEQUENCE IDENTITY; GROWTH-FACTOR; EXPRESSION; MEMBER; YEAST; PURIFICATION; DOMAIN AB We previously reported that the transcription of the human macrophage stimulating protein (MSP) gene was positively regulated by the binding of NF-Y to the CAATT sequence in the promoter region of this gene. Here we confirmed our previous results and further characterized the MSP promoter. Luciferase assay with deletion constructs showed the importance of the region, +32 to +39, for the promoter activity in Hep3B cells. Two nuclear protein-DNA probe (+15 to +40) complexes, C1 and C2, were detected by electrophoretic mobility shift assay. C2 was specific to hepatoma cells and contained hepatocyte nuclear factor-4 (HNF-4). DNase I footprinting with recombinant HNF-4 located another HNF-4-binding site in the distal region, -89 to -54. Mutations in the CAATT or the proximal HNF-4-binding site significantly reduced the promoter activity in Hep3B cells and HNF-4-transfected HeLa cells, whereas mutations in the distal HNF-4-binding site had no effect. The close proximity between the CAATT and the proximal HNF-4-binding site suggested that a direct contact between NF-Y and HNF-4 might be important, Protein-protein interaction between the A-subunit of NF-Y and HNF-4 was detected by a yeast two-hybrid system. The binding of in vitro translated HNF-4 to immobilized NF-YA and in vitro translated NF-YA to immobilized HNF-4 was also detected. These results suggest the binding of HNF-4 to the proximal HNF-4-binding site directs the basal transcription of the MSP gene, and the maximal promoter activity may depend on the direct association between HNF-4 and NF-Y. C1 NCI, Immunopathol Sect, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Yokohama City Univ, Sch Med, Dept Internal Med 1, Yokohama, Kanagawa 236, Japan. RP Yoshimura, T (reprint author), NCI, Immunopathol Sect, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Bldg 560,Rm 12-71, Frederick, MD 21702 USA. NR 39 TC 26 Z9 27 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 24 PY 1998 VL 273 IS 30 BP 19339 EP 19347 DI 10.1074/jbc.273.30.19339 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103TV UT WOS:000074974700091 PM 9668124 ER PT J AU Torigoe, C Inman, JK Metzger, H AF Torigoe, C Inman, JK Metzger, H TI An unusual mechanism for ligand antagonism SO SCIENCE LA English DT Article ID T-CELL ACTIVATION; SIGNAL-TRANSDUCTION; RECEPTOR LIGANDS; LEUKEMIA-CELLS; IGE; ANTIGEN; PHOSPHORYLATION; AGGREGATION; COMPLEXES; KINASE AB The ratio of late to early events stimulated by the mast cell receptor for immunoglobulin E (IgE) correlated with the affinity of a ligand for the receptor-bound IgE. Because excess receptors clustered by a weakly binding ligand could hoard a critical initiating kinase, they prevented the outnumbered clusters engendered by the high-affinity ligands from launching the more complete cascade. A similar mechanism could explain the antagonistic action of some peptides on the activation of T cells. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Torigoe, C (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 39 TC 123 Z9 125 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 24 PY 1998 VL 281 IS 5376 BP 568 EP 572 DI 10.1126/science.281.5376.568 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 104KA UT WOS:000075012300043 PM 9677201 ER PT J AU Guo, SW Zheng, CJ Li, CC AF Guo, SW Zheng, CJ Li, CC TI Dilemma over genetics and population in China SO NATURE LA English DT Letter C1 Univ Minnesota, Inst Human Genet, Minneapolis, MN 55454 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. Natl Inst Deafness & Other Commun Disorders, Epidemiol Stat Data Syst Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. RP Guo, SW (reprint author), Univ Minnesota, Inst Human Genet, 1300 S 2nd St, Suite 300, Minneapolis, MN 55454 USA. NR 4 TC 1 Z9 1 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 23 PY 1998 VL 394 IS 6691 BP 313 EP 314 DI 10.1038/28481 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103QF UT WOS:000074968800016 PM 9690462 ER PT J AU Chen, LJ Burka, LT AF Chen, LJ Burka, LT TI Formation of o-nitrosobenzaldehyde from hydrolysis of o-nitrobenzyl tosylate. Evidence of intramolecular nucleophilic interaction SO TETRAHEDRON LETTERS LA English DT Article ID RATS AB Hydrolysis of o-nitrobenzyl tosylate in CH3CN:H2O (1:1, v/v) gave o-nitrobenzyl alcohol and o-nitrosobenzaldehyde in 1.8 : 1 ratio. Formation of o-nitrosobenzaldehyde indicates that the nitro group participates in the leaving of the tosylate group. o-Nitrosobenzaldehyde was reduced by biological thiols to give o-aminobenzaldehyde. Reaction of o-nitrosobenzaldehyde with 1 mol of benzylamine afforded 3-(N-benzylamino)anthranil (or its tautomer) as a major product. Published by Elsevier Science Ltd. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Chen, LJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 14 TC 15 Z9 15 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUL 23 PY 1998 VL 39 IS 30 BP 5351 EP 5354 DI 10.1016/S0040-4039(98)01068-5 PG 4 WC Chemistry, Organic SC Chemistry GA ZX853 UT WOS:000074562000017 ER PT J AU Willinger, M Hoffman, HJ Wu, KT Hou, JR Kessler, RC Ward, SL Keens, TG Corwin, MJ AF Willinger, M Hoffman, HJ Wu, KT Hou, JR Kessler, RC Ward, SL Keens, TG Corwin, MJ TI Factors associated with the transition to nonprone sleep positions of infants in the United States - The National Infant Sleep Position Study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DEATH-SYNDROME; RISK-FACTORS; NEW-ZEALAND; SIDS; EPIDEMIOLOGY; MORTALITY; TASMANIA; COHORT AB Context.-Studies have demonstrated strong associations between the prone sleep position (on the stomach) and sudden infant death syndrome (SIDS), In 1992, the American Academy of Pediatrics recommended that infants be placed to sleep laterally (on their side) or supine (on their back) to reduce SIDS risk, and in 1994, the national public education campaign "Back to Sleep" was launched. Objective.-To determine the typical sleep position of infants younger than 8 months in the United States, the changes that occurred after these recommendations, and the factors associated with the placement of infants prone or supine. Design.-Annual nationally representative telephone surveys. Setting.-The 48 contiguous states of the United States. Participants.-Nighttime caregivers of infants born within the last 7 months between 1992 and 1996, Approximately 1000 interviews were conducted per year. Main Outcome Measures.-The position the infant was usually placed in for sleep, and the position the infant was most commonly found in when checked during the night's sleep. Results.-Ninety-seven percent of respondents in each wave of the survey usually placed their infant to sleep in a specific position. Infants were placed in the prone position by 70% of caregivers in 1992, prior to the campaign, but only 24% in 1996, Supine and lateral placements increased during this time period, from 13% in 1992 to 35% in 1996 and from 15% in 1992 to 39% in 1996, respectively. Significant predictors of prone placement included maternal race reported as black (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.68-3.26), mother's age 20 to 29 years (OR, 1.28; 95% CI, 1.09-1.50), region reported as the mid-Atlantic (OR, 1.41; 95% CI, 1.12-1.78) or southern states (OR, 1.47; 95% CI, 1.22-1.70), mothers with a previous child (OR, 1.68; 95% CI, 1.43-1.97), and infants younger than 8 weeks (OR, 0.63; 95% CI, 0.46-0.85), Infants aged 8 to 15 weeks were significantly more likely to be placed nonprone over time compared with the other age groups. Most of the risk factors for prone were significantly related in the opposite direction to supine placement. Conclusions.-The prevalence of infants placed in the prone sleep position declined by 66% between 1992 and 1996, Although causality cannot be proved, SIDS rates declined approximately 38% during this period. To achieve further reduction in prone sleeping, efforts to promote the supine sleep position should be aimed at groups at high risk for prone placement. C1 NICHHD, Ctr Res Mothers & Children, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Epidemiol Stat & Data Syst Branch, NIH, Bethesda, MD USA. Univ So Calif, Childrens Hosp Los Angeles, Sch Med, Div Neonatol & Pediat Pulmonol, Los Angeles, CA USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Boston Univ, Med Ctr, Sch Med, Dept Pediat, Boston, MA 02118 USA. RP Willinger, M (reprint author), NICHHD, Ctr Res Mothers & Children, Pregnancy & Perinatol Branch, NIH, Execut Bldg,Room 4B03,6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. EM mw75q@nih.gov FU NICHD NIH HHS [HD-2-2996, HD-2-9067] NR 43 TC 162 Z9 165 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 22 PY 1998 VL 280 IS 4 BP 329 EP 335 DI 10.1001/jama.280.4.329 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 100FC UT WOS:000074804200032 PM 9686549 ER PT J AU Brenner, RA Simons-Morton, BG Bhaskar, B Mehta, N Melnick, VL Revenis, M Berendes, HW Clemens, JD AF Brenner, RA Simons-Morton, BG Bhaskar, B Mehta, N Melnick, VL Revenis, M Berendes, HW Clemens, JD TI Prevalence and predictors of the prone sleep position among inner-city infants SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DEATH-SYNDROME; PROGRAM; COHORT; HEALTH; RISK; SIDS; BACK; CARE AB Context.-The prone sleep position is associated with an increased risk of sudden infant death syndrome (SIDS), but few studies have assessed factors associated with the choice of infant sleep position. Objectives.-To describe infant sleep position in a cohort of infants born to predominantly low-income, inner-city mothers and to identify predictors of the prone sleep position in this population. Design.-Prospective birth cohort study. Patients and Setting.-Three hundred ninety-four mother-infant dyads, systematically selected from 3 District of Columbia hospitals between August 1995 and September 1996, Mothers were interviewed shortly after delivery and again at 3 to 7 months postpartum. Main Outcome Measures.-Position in which infants were placed for sleep on the night prior to the 3- to 7-month interview. Results.-At 3 to 7 months of age, 157 infants (40%) were placed for sleep in the prone position. Independent predictors of prone sleep position included poverty (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.10-2.99), black race (OR, 2.06; 95% CI, 1.05-4.04), presence of infant's grandmother in the home (OR, 1.83; 95% CI, 1.11-3.00), and intent, as measured shortly after delivery, to place the infant in the prone position (OR, 2.28; 95% CI, 1.44-3.60), Importantly, of the 43 mothers who observed their infants in the prone sleep position while in the hospital, 40 (93%) intended to place their infants prone at home. Conclusions.-A substantial proportion of infants in this predominantly low-income population were placed in the prone sleep position. Educational efforts should address both initial intentions and reinforcement of the correct sleep position, once initiated. Hospitals should ensure that healthy newborn infants are placed in the supine sleep position during the postpartum hospital stay. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Res Triangle Inst, Rockville, MD USA. Georgetown Univ Hosp, Div Neonatol, Washington, DC 20007 USA. Univ Dist Columbia, Dept Biol & Environm Sci, Washington, DC USA. Childrens Natl Med Ctr, Dept Neonatol, Washington, DC 20010 USA. RP Brenner, RA (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. EM BrennerR@nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU NICHD NIH HHS [U18-HD30447, U18-HD30450, U18-HD30458] NR 34 TC 70 Z9 71 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 22 PY 1998 VL 280 IS 4 BP 341 EP 346 DI 10.1001/jama.280.4.341 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 100FC UT WOS:000074804200034 PM 9686551 ER PT J AU Ron, E Doddy, MM Becker, DV Brill, AB Curtis, RE Goldman, MB Harris, BSH Hoffman, DA McConahey, WM Maxon, HR Preston-Martin, S Warshauer, ME Wong, FL Boice, JD AF Ron, E Doddy, MM Becker, DV Brill, AB Curtis, RE Goldman, MB Harris, BSH Hoffman, DA McConahey, WM Maxon, HR Preston-Martin, S Warshauer, ME Wong, FL Boice, JD CA Cooperative Thyrotoxicosis Therapy Follow Stud TI Cancer mortality following treatment for adult hyperthyroidism SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID THYROID-CANCER; I-131 THERAPY; GRAVES-DISEASE; THYROTOXICOSIS; CARCINOMA; WOMEN; RISK AB Context.-High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic I-131 to the development of cancer, its extensive medical use indicates the need for additional evaluation. Objective.-To evaluate cancer mortality among hyperthyroid patients, particularly after I-131 treatment. Design.-A retrospective cohort study. Setting.-Twenty-five clinics in the United States and 1 clinic in England. Patients.-A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91% had Graves disease, 79% were female, and 65% were treated with I-131. Main Outcome Measure.-Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism. Results.-Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86). Conclusions.-Neither hyperthyroidism nor I-131 treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following I-131 treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, I-131 appears to be a safe therapy for hyperthyroidism. C1 NCI, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Cornell Univ, Med Ctr, New York Hosp, New York, NY 10021 USA. Vanderbilt Univ, Nashville, TN USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. George Washington Univ, Washington, DC 20052 USA. Mayo Clin, Rochester, MN USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Univ So Calif, Los Angeles, CA 90089 USA. RP Ron, E (reprint author), NCI, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RI Brill, Aaron/H-3732-2014 OI Brill, Aaron/0000-0001-7538-086X FU NCI NIH HHS [N01-CP-41060] NR 39 TC 177 Z9 190 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 22 PY 1998 VL 280 IS 4 BP 347 EP 355 DI 10.1001/jama.280.4.347 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 100FC UT WOS:000074804200035 PM 9686552 ER PT J AU Ishii, Y Terao, T AF Ishii, Y Terao, T TI Manipulation of nuclear spin Hamiltonians by rf-field modulations and its applications to observation of powder patterns under magic-angle spinning SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID SOLID-STATE NMR; MAGNETIC-RESONANCE; COMPOSITE PULSES; ROTATING SOLIDS; C-13; SEQUENCES; DISTANCES; DYNAMICS; OXALATE AB A theoretical approach to design frequency-, phase-, and/or amplitude-modulated radio frequency (rf) fields for realizing Hamiltonian manipulations in nuclear magnetic resonance (NMR) is presented. In this approach, the evolution operator for a spin system under a general modulated rf field is represented without any a priori assumptions about the modulation wave form, using a time-dependent Euler transformation in the spin space. Then, the average internal Hamiltonian for a general periodic modulation can be expressed using the Euler angles. By equating it to the target Hamiltonian into which an internal Hamiltonian is desired to be modified, the time-dependent Euler angles are determined. General solutions of necessary modulations are obtained from the Euler angles with an infinite number of freely adjustable parameters. The great degree of freedom allows us to further improve the performance of the Hamiltonian manipulation. As useful examples of this approach, two amplitude-modulated fields and one phase-modulated rf field for restoring C-13 chemical-shift anisotropies or C-13-N-15 dipolar interactions under magic-angle spinning (MAS) were developed and experimentally demonstrated. In an experiment, the C-13 chemical-shift powder pattern of the methylen carbon in glycine was successfully observed under MAS with a spinning speed of 10 kHz by applying an amplitude-modulated rf field. It was found that the rotor-synchronous pi-pulse cycle developed by Tycko et al. [J. Magn. Reson. 85, 265 (1989)] for observing chemical-shift powder patterns under MAS does not satisfactorily work under the fast spinning speed because of the inevitably high duty ratio of pi-pulses. The presented method has the advantage of applicability to high-speed spinning. Moreover, Hamiltonian manipulations by the rf modulations require no critical adjustments of the experimental parameters, and are insensitive to rf inhomogeneity. (C) 1998 American Institute of Physics. C1 Kyoto Univ, Grad Sch Sci, Dept Chem, Kyoto 6068502, Japan. RP Ishii, Y (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Ishii, Yoshitaka/F-4558-2014 OI Ishii, Yoshitaka/0000-0002-7724-6469 NR 30 TC 23 Z9 24 U1 2 U2 9 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JUL 22 PY 1998 VL 109 IS 4 BP 1366 EP 1374 DI 10.1063/1.476689 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 108FP UT WOS:000075255600022 ER PT J AU Long, HW Tycko, R AF Long, HW Tycko, R TI Biopolymer conformational distributions from solid-state NMR: alpha-helix and 3(10)-helix contents of a helical peptide SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ALANINE-BASED PEPTIDES; ELECTRON-SPIN-RESONANCE; MAGIC-ANGLE; MOLECULAR-DYNAMICS; CHEMICAL-SHIFTS; EXCHANGE SPECTROSCOPY; CIRCULAR-DICHROISM; FORMING TENDENCIES; CARBONYL CARBONS; AQUEOUS-SOLUTION AB A new approach to the quantitative experimental analysis of conformational distributions in partially ordered biopolymers is described and used to determine the fractional contents of alpha-helical, 3(10)-helical, and random coil components in the conformational distributions of a 17-residue helix-forming peptide [Marqusee, S.; Baldwin, R. L. Proc. Natl. Acad. Sci., U.S.A. 1987, 84, 8898-8902]. The approach is based on solid-state NMR measurements that probe phi and psi dihedral angles at specific isotopically labeled sites, in particular two-dimensional magic-angle spinning NMR exchange spectra, carried out on glass-forming frozen solutions in glycerol/water. The data analysis employs a combination of constrained molecular dynamics simulations, to generate model dihedral angle distributions, and Bayesian statistics, to permit a quantitative determination of the relative probabilities of the possible fractional contents of alpha-helical, 3(10)-helical, and random coil components. The peptide is found to be highly alpha-helical in pure glycerol/water at low temperatures. Addition of urea has the primary effect of converting alpha-helical conformations to 3(10)-helical conformations, rather than to random coil conformations. These results provide experimental evidence for the role of 3(10)-helices as thermodynamic intermediates in the folding and unfolding of alpha-helical segments in peptides and proteins. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM tycko@helix.nih.gov NR 44 TC 89 Z9 89 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 22 PY 1998 VL 120 IS 28 BP 7039 EP 7048 DI 10.1021/ja974277j PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 104MY UT WOS:000075019400019 ER PT J AU Longley, MJ Ropp, PA Lim, SE Copeland, WC AF Longley, MJ Ropp, PA Lim, SE Copeland, WC TI Characterization of the native and recombinant catalytic subunit of human DNA polymerase gamma: Identification of residues critical for exonuclease activity and dideoxynucleotide sensitivity SO BIOCHEMISTRY LA English DT Article ID INFECTED INSECT CELLS; MITOCHONDRIAL-DNA; 3'->5' EXONUCLEASE; DROSOPHILA EMBRYOS; XENOPUS-LAEVIS; SUBSTRATE-SPECIFICITY; ZIDOVUDINE THERAPY; ESCHERICHIA-COLI; PURIFICATION; CLONING AB The human DNA polymerase gamma catalytic subunit was overexpressed in recombinant baculovirus-infected insect cells, and the 136 000 Da protein was purified to homogeneity. Application of the same purification protocol to HeLa mitochondrial lysates permitted isolation of native DNA polymerase gamma as a single subunit, allowing direct comparison of the native and recombinant enzymes without interference of other polypeptides. Both forms exhibited identical properties, and the DNA polymerase and 3' --> 5' exonuclease activities were shown unambiguously to reside in the catalytic polypeptide. The salt sensitivity and moderate processivity of the isolated catalytic subunit suggest other factors could be required to restore the salt tolerance and highly processive DNA synthesis typical of gamma polymerases. To facilitate our understanding of mitochondrial DNA replication and mutagenesis as well as cytotoxicity mediated by antiviral nucleotide analogues, we also constructed two site-directed mutant proteins of the human DNA polymerase gamma. Substituting alanine for two essential acidic residues in the exonuclease motif selectively eliminated the 3' --> 5' exonucleolytic function of the purified mutant polymerase gamma. Replacement of a tyrosine residue critical for sugar recognition with phenylalanine in polymerase motif B reduced dideoxynucleotide inhibition by a factor of 5000 with only minor effects on overall polymerase function. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 48 TC 121 Z9 123 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 21 PY 1998 VL 37 IS 29 BP 10529 EP 10539 DI 10.1021/bi980772w PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108RX UT WOS:000075280200024 PM 9671525 ER PT J AU Zhang, JZ Neamati, N Pommier, Y Nair, V AF Zhang, JZ Neamati, N Pommier, Y Nair, V TI Inhibition of HIV integrase by novel nucleotides bearing tricyclic bases SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID VIRUS TYPE-1 INTEGRASE; ANTIVIRAL AGENTS AB 5'-Monophosphates of several novel dideoxynucleosides bearing tricyclic nucleobases were synthesized. Both linear and angular ring-extended analogs of isomeric dideoxyadenosine 5'-monophosphate were discovered to have moderate to good inhibition of the viral-encoded enzyme, HIV integrase. The results suggest that the nucleotide binding site of HIV integrase can accommodate major modifications in the nucleobase, which is in stark contrast to the nucleotide binding site on HIV reverse transcriptase, (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Nair, V (reprint author), Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. NR 14 TC 12 Z9 13 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUL 21 PY 1998 VL 8 IS 14 BP 1887 EP 1890 DI 10.1016/S0960-894X(98)00327-8 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 103GW UT WOS:000075150500021 PM 9873453 ER PT J AU Gorlatov, SN Stadtman, TC AF Gorlatov, SN Stadtman, TC TI Human thioredoxin reductase from HeLa cells: Selective alkylation of selenocysteine in the protein inhibits enzyme activity and reduction with NADPH influences affinity to heparin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE selenoprotein; redox active centers; transformed cell lines; bromoacetate ID PURIFICATION; TRANSCRIPTION; BINDING AB Human thioredoxin reductase (TR) contains selenocysteine (Secys) in a redox center [cysteine (Cys)-497,Secys-498] near the C-terminus. The essential role of Secys in TR isolated from HeLa cells was demonstrated by the alkylation studies. Reaction of native NADPH reduced enzyme with bromoacetate at pH 6.5 inhibited enzyme activity 99%. Of the incorporated carboxymethyl (CM) group, 1.1 per subunit, >90%, was in CM-Secys-498. Alkylation at pH 8 increased the stoichiometry to 1.6 per subunit with additional modification of the Cys-59, Cys-64 disulfide center. A minor tryptic peptide containing both CM-Cys-497 and CM-Secys-498 was isolated from enzyme alkylated at pH 6.5 or at pH 8, Preparations of TR isolated from HeLa cells grown in a fermenter under high aeration contained selenium-deficient enzyme species that had 50% lower activity, Decreasing oxygen to an optimal level increased cell yield, and fully active TR containing one Se per subunit was present. Reduction of fully active enzyme with tris-(2-carboxyethyl) phosphine converted it from a low to a high heparin affinity form. The tris-(2-carboxyethyl) phosphine-reduced enzyme was oxygen-sensitive and lost selenium and catalytic activity unless maintained under strictly anaerobic conditions. This enzyme could be converted to an oxygen-insensitive species by addition of NADPH, indicating that bound pyridine nucleotide is important for enzyme stability. An induced enzyme conformation in which the essential Secys is shielded from oxidative damage could explain these effects. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, TC (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Room 108, Bethesda, MD 20892 USA. EM tcstadtman@nih.gov NR 23 TC 80 Z9 84 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8520 EP 8525 DI 10.1073/pnas.95.15.8520 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900021 PM 9671710 ER PT J AU Li-Smerin, Y Swartz, KJ AF Li-Smerin, Y Swartz, KJ TI Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SENSITIVE CALCIUM-CHANNEL; SEA-ANEMONE TOXIN; POTASSIUM CHANNEL; SCORPION TOXIN; PEPTIDE INHIBITOR; DEPENDENT BINDING; MYELINATED NERVE; SODIUM-CHANNELS; ALPHA-SUBUNIT; BETA-SUBUNIT AB Protein toxins from venomous animals exhibit remarkably specific and selective interactions with a wide variety of ion channels. Hanatoxin and grammotoxin are tno related protein toxins found in the venom of the Chilean Rose Tarantula, Phrixotrichus spatulata. Hanatoxin inhibits voltage-gated K+ channels and grammotoxin inhibits voltage-gated Ca2+ channels. Both toxins inhibit their respective channels by interfering with normal operation of the voltage-dependent gating mechanism. The sequence homology of hanatoxin and grammotoxin, as well as their similar mechanism of action, raises the possibility that they interact with the same region of voltage-gated Ca2+ and K+ channels. Here, we show that each toxin can interact with both voltage-gated Ca2+ and K+ channels and modify channel gating. Moreover, mutagenesis of voltage-gated K+ channels suggests that hanatoxin and grammotoxin recognize the same structural motif, We propose that these toxins recognize a voltage-sensing domain or module present in voltage-gated ion channels and that this domain has a highly conserved three-dimensional structure. C1 NINDS, Mol Physiol & Biophys Unit, NIH, Bethesda, MD 20892 USA. RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Unit, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA NS002945-13]; NIGMS NIH HHS [GM43949, R01 GM043949] NR 40 TC 131 Z9 135 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8585 EP 8589 DI 10.1073/pnas.95.15.8585 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900032 PM 9671721 ER PT J AU Vitale, N Horiba, K Ferrans, VJ Moss, J Vaughan, M AF Vitale, N Horiba, K Ferrans, VJ Moss, J Vaughan, M TI Localization of ADP-ribosylation factor domain protein 1 (ARD1) in lysosomes and Golgi apparatus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHROMAFFIN CELLS; MEMBRANE-PROTEIN; BINDING; EXOCYTOSIS; TRANSLOCATION; INVOLVEMENT; ARF AB ADP-ribosylation factor domain protein 1 (ARD1) is a member of the ADP ribosylation factor (ARF) family of guanine nucleotide-binding proteins that differs from other ARFs by the presence of a 46-kDa amino-terminal extension which acts as a GTPase-activating protein (GAP) for its ARF domain. Similar to ARF GAPs, the GAP domain of ARD1 contains a zinc finger motif and arginine residues that are critical for activity. It differs from other ARF GAPs in its covalent association with the GTP-binding domain and its specificity for the ARF domain of ARD1. ARFs are presumed to play a key role in the formation of intracellular transport vesicles and in their movement from one compartment to another. We report here that ARD1 overexpressed in cells, as a fusion or nonfusion protein, is localized in vesicular structures that are concentrated mainly in the perinuclear region, but are found also throughout the cytosol, Microscopic colocalization and subcellular fractionation studies showed that ARD1 was associated with the Golgi complex and lysosomal structures. ARD1 expressed as a green fluorescent fusion protein was initially associated with the Golgi network and subsequently localized to lysosomes, Lysosomal and Golgi membranes isolated from human liver by immunoaffinity contained native ARD1, Localization to these organelles, therefore, did not appear to be a result of overexpression. These observations suggest that the ARF-related protein ARD1 may play a role in the formation or function of lysosomes and in protein trafficking between Golgi and lysosomes. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Vitale, N (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Room 5N-307,Bldg 10, Bethesda, MD 20892 USA. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 NR 26 TC 16 Z9 17 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8613 EP 8618 DI 10.1073/pnas.95.15.8613 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900037 PM 9671726 ER PT J AU Espreafico, EM Coling, DE Tsakraklides, V Krogh, K Wolenski, JS Kalinec, G Kachar, B AF Espreafico, EM Coling, DE Tsakraklides, V Krogh, K Wolenski, JS Kalinec, G Kachar, B TI Localization of myosin-V in the centrosome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mitotic spindle ID MICROTUBULE-ORGANIZING CENTERS; UNCONVENTIONAL MYOSIN; CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; MITOTIC SPINDLE; DENDRITIC SPINE; PURKINJE-CELLS; PTK2 CELLS; GENE; BRAIN AB The perinuclear localization of myosin-V was investigated in a variety of cultured mammalian cells and in primary cultures of rat hippocampus. In all cells investigated, myosin-V immunoreactivity was associated with the centrosome. In interphase cells, myosin-V was found in pericentriolar material, and in both mother and daughter centrioles. These results were obtained by using two different fixation protocols with three different affinity-purified antibodies that recognized a single band in Western blots. During cell division, myosin-V staining was intense throughout the cytoplasm and was concentrated in a trail between migrating centrioles and in the mitotic spindle poles and spindle fibers. The centrosome targeting site was determined to reside within the globular tail domain, because centrosome association also was observed in living cells transfected with DNA encoding the tail domain fused with a green fluorescent protein tag, but not in cells transfected with the vector encoding green fluorescent protein by itself. C1 Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. USP, FMRP, Dept Morphol, BR-14049900 Ribeirao Preto, SP, Brazil. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06511 USA. RP Kachar, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, Lab Cellular Biol, NIH, Bldg 36,Room 5D15,MSC 4163, Bethesda, MD 20892 USA. EM kachar@pop.nidcd.nih.gov RI Espreafico, Enilza/O-3053-2016; OI Coling, Donald/0000-0001-6285-5336 NR 49 TC 63 Z9 64 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8636 EP 8641 DI 10.1073/pnas.95.15.8636 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900041 PM 9671730 ER PT J AU Zhu, LX Hathcock, KS Hande, P Lansdorp, PM Seldin, MF Hodes, RJ AF Zhu, LX Hathcock, KS Hande, P Lansdorp, PM Seldin, MF Hodes, RJ TI Telomere length regulation in mice is linked to a novel chromosome locus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN FIBROBLASTS; LYMPHOCYTES; YEAST; DNA AB Little is known about the mechanisms that regulate species-specific telomere length, particularly in mammalian species. The genetic regulation of telomere length was therefore investigated by using two inter-fertile species of mice, which differ in their telomere length. Mus musculus (telomere length >25 kb) and Mus spretus (telomere length 5-15 kb) were used to generate F1 crosses and reciprocal backcrosses, which were then analyzed for regulation of telomere length. This analysis indicated that a dominant and trans-acting mechanism exists capable of extensive elongation of telomeres in somatic cells after fusion of parental germline cells with discrepant telomere lengths. A genome wide screen of interspecific crosses, using M. spretus as the recurrent parent, identified a 5-centimorgan region on distal chromosome 2 that predominantly controls the observed species-specific telomere length regulation. This locus is distinct from candidate genes encoding known telomere-binding proteins or telomerase components. These results demonstrate that an unidentified gene(s) mapped to distal chromosome 2 regulates telomere length in the mouse. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Rowe Program Genet, Dept Biol Chem, Davis, CA 95616 USA. Univ Calif Davis, Rowe Program Genet, Dept Med, Davis, CA 95616 USA. British Columbia Canc Res Ctr, Terry Fox Lab Hematol Oncol, Vancouver, BC V5Z 1L3, Canada. NIA, NIH, Bethesda, MD 20892 USA. RP Hathcock, KS (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM Karen_Hathcock@nih.gov RI Hande, M. Prakash/B-1645-2008 OI Hande, M. Prakash/0000-0002-4511-6256 NR 33 TC 100 Z9 102 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8648 EP 8653 DI 10.1073/pnas.95.15.8648 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900043 PM 9671732 ER PT J AU Collins, C Rommens, JM Kowbel, D Godfrey, T Tanner, M Hwang, S Polikoff, D Nonet, G Cochran, J Myambo, K Jay, KE Froula, J Cloutier, T Kuo, WL Yaswen, P Dairkee, S Giovanola, J Hutchinson, GB Isola, J Kallioniemi, OP Palazzolo, M Martin, C Ericsson, C Pinkel, D Albertson, D Li, WB Gray, JW AF Collins, C Rommens, JM Kowbel, D Godfrey, T Tanner, M Hwang, S Polikoff, D Nonet, G Cochran, J Myambo, K Jay, KE Froula, J Cloutier, T Kuo, WL Yaswen, P Dairkee, S Giovanola, J Hutchinson, GB Isola, J Kallioniemi, OP Palazzolo, M Martin, C Ericsson, C Pinkel, D Albertson, D Li, WB Gray, JW TI Positional cloning of ZNF217 and NABC1: Genes amplified at 20q13.2 and overexpressed in breast carcinoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; EXON AMPLIFICATION; DNA AMPLIFICATION; CELL-LINES; CANCER; SEQUENCE; PROTEIN; COMPLEX; REGIONS AB We report here the molecular cloning of an approximate to 1-Mb region of recurrent amplification at 20q13.2 in breast cancer and other tumors and the delineation of a 260-kb common region of amplification. Analysis of the I-Mb region produced evidence for five genes, ZNF217, ZNF218, and NABC1, PIC1L (PIC1-like), CYP24, and a pseudogene CRP (Cyclophillin Related Pseudogene). ZNF217 and NABC1 emerged as strong candidate oncogenes and were characterized in detail. NABC1 is predicted to encode a 585-aa protein of unknown function and is overexpressed in most but not all breast cancer cell lints in which it was amplified. ZNF217 is centrally located in the 260-kb common region of amplification, transcribed in multiple normal tissues, and overexpressed in all cell lines and tumors in which it is amplified and in two in which it is not. ZNF217 is predicted to encode alternately spliced, Kruppel-like transcription factors of 1,062 and 1,108 aa, each having a DNA-binding domain (eight C2H2 zinc fingers) and a proline-rich transcription activation domain. C1 Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. Univ Toronto, Dept Genet, Toronto, ON M5G 1X8, Canada. Tampere Univ Hosp, Canc Genet Lab, FIN-33521 Tampere, Finland. Inst Med Technol, FIN-33521 Tampere, Finland. Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 2B5, Canada. NHGRI, Canc Genet Lab, NIH, Bethesda, MD 20892 USA. Life Technol Inc, Rockville, MD 20850 USA. Calif Pacific Med Ctr, Brush Canc Res Inst, San Francisco, CA 94619 USA. RP Collins, C (reprint author), Univ Calif San Francisco, Ctr Canc, 2340 Sutter St,Room N415, San Francisco, CA 94143 USA. RI Kallioniemi, Olli/H-5111-2011; Dairkee, Shanaz/D-6743-2012; Godfrey, Tony/A-5572-2013; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Godfrey, Tony/0000-0002-3283-6983; Kallioniemi, Olli/0000-0002-3231-0332 FU NCI NIH HHS [CA 58207, P50 CA058207] NR 45 TC 244 Z9 254 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8703 EP 8708 DI 10.1073/pnas.95.15.8703 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900053 PM 9671742 ER PT J AU Yu, SH Yu, DW Lee, E Eckhaus, M Lee, R Corria, Z Accili, D Westphal, H Weinstein, LS AF Yu, SH Yu, DW Lee, E Eckhaus, M Lee, R Corria, Z Accili, D Westphal, H Weinstein, LS TI Variable and tissue-specific hormone resistance in heterotrimeric G(s) protein alpha-subunit (G(s)alpha) knockout mice is due to tissue-specific imprinting of the Gs alpha gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ALBRIGHT HEREDITARY OSTEODYSTROPHY; GRADIENT GEL-ELECTROPHORESIS; GTP-BINDING PROTEIN; RAT ADIPOSE-CELLS; MOUSE CHROMOSOME-2; PARENTAL ORIGIN; PSEUDOHYPOPARATHYROIDISM; RECEPTOR; REGION; RESPONSES AB Albright hereditary osteodystrophy (AHO), an autosomal dominant disorder characterized by short stature, obesity, and skeletal defects, is associated with heterozygous inactivating mutations of GNASI, the gene encoding the heterotrimeric G protein alpha-subunit (G(s)alpha) that couples multiple receptors to the stimulation of adenylyl cyclase, It has remained unclear why only some AHO patients present with multihormone resistance and why AHO patients demonstrate resistance to some hormones [e.g., parathyroid hormone (PTH)] but not to others (e.g., vasopressin), even though all activate adenylyl cyclase, We generated mice with a null allele of the mouse homolog Gnas. Homozygous G, deficiency is embryonically lethal. Heterozygotes with maternal (m-/+) and paternal (+/p-) inheritance of the Gnas null allele have distinct phenotypes, suggesting that Gnas is an imprinted gene, PTH resistance is present in m-/+, but not +/p-, mice. G(s)alpha expression in the renal cortex (the site of PTH action) is markedly reduced in m-/+ but not in +/p- mice, demonstrating that the Gnas paternal allele is imprinted in this tissue. Gnas is also imprinted in brown and white adipose tissue. The maximal physiological response to vasopressin (urinary concentrating ability) is normal in both m-/+ and +/p- mice and Gnas is not imprinted in the renal inner medulla (the site of vasopressin action). Tissue-specific imprinting of Gnas is likely the mechanism for variable and tissue-specific hormone resistance in these mice and a similar mechanism might explain the variable phenotype in AHO. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Res Resources, Vet Resources Program, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 8C101, Bethesda, MD 20892 USA. RI Weinstein, Lee/I-5575-2015 NR 44 TC 271 Z9 275 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8715 EP 8720 DI 10.1073/pnas.95.15.8715 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900055 PM 9671744 ER PT J AU Webb, CP Van Aelst, L Wigler, MH Vande Woude, GF AF Webb, CP Van Aelst, L Wigler, MH Vande Woude, GF TI Signaling pathways in Ras-mediated tumorigenicity and metastasis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; MAP KINASE KINASE; MET PROTOONCOGENE; 3T3 CELLS; TRANSFORMATION; EXPRESSION; ACTIVATION; INVASION; SPECIFICITY; STIMULATION AB The effector domain mutants of oncogenic Ras, V12S35 Ras, V12G37 Ras, and V12C40 Ras were tested for their abilities to mediate tumorigenic and metastatic phenotypes in athymic nude mice when expressed in NIH 3T3 fibroblasts. All mutants displayed comparable tumorigenic properties, but only the mutant that activates the Raf mitogen-activated protein kinase kinase (MEK)-extracellular regulated kinase (ERK) 1/2 pathway, V12S35 Ras, induced tumors in the experimental metastasis assay. Furthermore, direct activation of the MEK-ERK1/2 pathway in NIH 3T3 cells by mos or a constitutively active form of MEK was sufficient to induce metastasis whereas R-Ras, which fails to activate the ERK1/2 pathway, is tumorigenic but nonmetastatic, The subcutaneous tumors and lung metastases derived from V12S35 Ras-transformed NIH 3T3 cells expressed higher levels of activated ERK1/2 in culture when compared with the parental cellular pool before injection, indicating that selection for cells with higher levels of activated ERK1/2 occurred during tumor growth and metastasis. By contrast, cells explanted from V12G37-Ras or V12C40-Ras-induced tumors did not show changes in the level of ERK1/2 activation when compared with the parental cells. When tumor-explanted cell lines derived from each of the effector domain mutants were passaged one additional time in vivo, all mediated rapid tumor growth, but, again, only cells derived from V12S35 Ras-tumors formed numerous metastatic lesions within the lung. These results show that the metastatic properties of the Ras effector domain mutants segregate, and that, whereas Ras-mediated tumorigenicity can arise independently of ERK1/2 activation, experimental metastasis appears to require constitutive activation of the ERK1/2 pathway. C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Program, Adv Biosci Labs, Frederick, MD 21072 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Vande Woude, GF (reprint author), NCI, Frederick Canc Res & Dev Ctr, Basic Res Program, Adv Biosci Labs, Frederick, MD 21072 USA. EM woude@ncifcrf.gov RI Webb, Craig/I-8123-2012; Tang, Amy/L-3226-2016; OI Tang, Amy/0000-0002-5772-2878; Wigler, Michael/0000-0003-4396-1971 NR 32 TC 165 Z9 180 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8773 EP 8778 DI 10.1073/pnas.95.15.8773 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900065 PM 9671754 ER PT J AU Zanusso, G Liu, DC Ferrari, S Hegyi, I Yin, XH Aguzzi, A Hornemann, S Liemann, S Glockshuber, R Manson, JC Brown, P Petersen, RB Gambetti, P Sy, MS AF Zanusso, G Liu, DC Ferrari, S Hegyi, I Yin, XH Aguzzi, A Hornemann, S Liemann, S Glockshuber, R Manson, JC Brown, P Petersen, RB Gambetti, P Sy, MS TI Prion protein expression in different species: Analysis with a panel of new mAbs SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; SCRAPIE PRIONS; RESISTANT; FORM; PRP AB By immunizing prion knockout mice (Prnp-/-) with recombinant murine prion protein (PrPc), we obtained a panel of mAbs specific for murine PrPc. These mAbs can be applied to immunoblotting, cell surface immunofluorescent staining, and immunohistochemistry at light and electron microscopy. These mAbs recognize both the normal (PrPc) and protease-resistant (PrPres) isoforms of PrP. Some mAbs are species restricted, while others react with PrP from a broad range of mammals including mice, humans, monkeys, cows, sheep, squirrels, and hamsters. Moreover, some of the mAbs selectively recognize different PrP glyco-forms as well as the metabolic fragments of PrPc. These newly generated PrPc antibodies will help to explore the biology of PrPc and to establish the diagnosis of prion diseases in both humans and animals. C1 Case Western Reserve Univ, Sch Med, Inst Pathol, Div Neuropathol, Cleveland, OH 44120 USA. Case Western Reserve Univ, Sch Med, Ctr Canc Res, Cleveland, OH 44120 USA. Case Western Reserve Univ, Sch Med, Skin Dis Res Ctr, Cleveland, OH 44120 USA. Univ Spital Zurich, Inst Neuropathol, Zurich, Switzerland. Inst Anim Hlth, Agr & Food Res Council, Edinburgh EH9 3JF, Midlothian, Scotland. Medical Research Council, Neuropathogenesis Unit, Edinburgh EH9 3JF, Midlothian, Scotland. Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44195 USA. ETH Zurich, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland. NIH, Cent Nervous Syst Studies Lab, Bethesda, MD 20892 USA. RP Sy, MS (reprint author), Case Western Reserve Univ, Sch Med, Inst Pathol, Div Neuropathol, BRB Room 933,10900 Euclid Ave, Cleveland, OH 44120 USA. EM MXS92@pocwru.edu RI Petersen, Robert/B-5075-2011; Aguzzi, Adriano/A-3351-2008; OI Petersen, Robert/0000-0002-3154-0072; ZANUSSO, Gianluigi/0000-0001-5199-6264; Aguzzi, Adriano/0000-0002-0344-6708 NR 30 TC 165 Z9 166 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8812 EP 8816 DI 10.1073/pnas.95.15.8812 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900072 PM 9671761 ER PT J AU Ambs, S Ogunfusika, MO Merriam, WG Bennett, WP Billiar, TR Harris, CC AF Ambs, S Ogunfusika, MO Merriam, WG Bennett, WP Billiar, TR Harris, CC TI Up-regulation of inducible nitric oxide synthase expression in cancer-prone p53 knockout mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INDUCED APOPTOSIS; INTERFERON-GAMMA; MOUSE THYMOCYTES; SMOOTH-MUSCLE; DNA DAMAGE; L-ARGININE; INDUCTION; CELLS; GROWTH; GENE AB High concentrations of nitric oxide (NO) cause DNA damage and apoptosis in many cell types, Thus, regulation of NO synthase (NOS) activity is essential for minimizing effects of cytotoxic and genotoxic nitrogen oxide species. We have shown previously that NO-induced p53 protein accumulation down-regulates basal and cytokine-modulated inducible NOS (NOS2) expression in human cells in vitro. To further characterize the feedback loop between NOS2 and p53, we have investigated NO production, i.e., urinary nitrate plus nitrite excretion, and NOS2 expression in homozygous p53 knockout (KO) mice. We report here that untreated p53 KO mice excreted 70% more nitrite plus nitrate than mice with wild-type (wt) p53. NOS2 protein expression was constitutively detected in the spleen of untreated p53 KO mice, whereas it was undetectable in the spleen of mt p53 controls. Upon treatment with heat-inactivated Corynebacterium parvum, urinary nitrite plus nitrate excretion of p53 KO mice exceeded that of wt controls by approximately 200%. C. parvum treatment also induced p53 accumulation in the liver. Splenectomy reduced the NO output of C. parvum-treated p53 KO mice but not of wt p53 controls. although NO production and NOS2 protein expression were increased similarly in KO and wt p53 mice 10 days after injection of C. parvum, NOS2 expression returned to baseline levels only in wt p53 controls while remaining up-regulated in p53 KO mice. These genetic and functional data indicate that p53 is an important trans-repressor of NOS2 expression in vivo and attenuates excessive NO production in a regulatory negative feedback loop. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15261 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2C01,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 56 TC 116 Z9 120 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8823 EP 8828 DI 10.1073/pnas.95.15.8823 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900074 PM 9671763 ER PT J AU Chun, TW Engel, D Berrey, MM Shea, T Corey, L Fauci, AS AF Chun, TW Engel, D Berrey, MM Shea, T Corey, L Fauci, AS TI Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE latency; primary infection; HAART therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VIVO; PLASMA; AIDS; RESPONSES AB The presence of latently infected, resting CD4(+) T cells carrying replication-competent HIV-I has been demonstrated in chronically infected individuals who are antiretroviral therapy naive as well as in those who are receiving highly active antiretroviral therapy (HAART), It is not clear, however, whether the establishment of a pool of latently infected CD4(+) T cells can be blocked by early initiation of HAART after primary infection. The present st;dy demonstrates that initiation of HAART in infected individuals as early as 10 days after the onset of symptoms of primary HIV-1 infection did not prevent generation of latently infected, resting CD4(+) T cells carrying integrated HIV-1 DNA as well as infectious HIV-I despite the successful control of plasma viremia shortly after institution of HAART. Furthermore, there was no correlation between either the duration of HAART at the time of study (range: 0.2-17 months) or the time of initiation of HAART after the onset of symptoms of primary HIV-1 infection (range: 0.3-4 months) and the frequencies of resting CD4(+) T cells carrying either integrated HIV-1 DNA or infectious virus. These results underscore the rapidity with which latent reservoirs are established in primary HIV-1 infection and indicate that it is unlikely that early treatment during primary infection can prevent establishment of a pool of latently infected, resting CD4(+) T cells as long as treatment is initiated after plasma viremia becomes evident. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Med, Seattle, WA 98104 USA. Univ Washington, Dept Lab Med, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Program Infect Dis, Seattle, WA 98104 USA. RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A32, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI-41535, T32 AI007140, T32AI-07140] NR 26 TC 463 Z9 467 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8869 EP 8873 DI 10.1073/pnas.95.15.8869 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900082 PM 9671771 ER PT J AU Player, MR Barnard, DL Torrence, PF AF Player, MR Barnard, DL Torrence, PF TI Potent inhibition of respiratory syncytial virus replication using a 2-5A-antisense chimera targeted to signals within the virus genomic RNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTISENSE OLIGODEOXYNUCLEOTIDES; THERAPEUTIC AGENTS; SEQUENCE-ANALYSIS; 2-5A ANTISENSE; GENE; OLIGONUCLEOTIDES; RIBONUCLEASE; SUBGROUP AB The 2-5A system is a recognized mechanistic component of the antiviral action of interferon. Interferon-induced 2-5A synthetase generates 2-5A, which, in turn, activates the latent constitutive RNase L that degrades viral RNA. Chemical conjugation of 2-5A to an antisense oligonucleotide can target the 2-5A-dependent RNase L to the antisense-specified RNA and effect its selective destruction. Such a 2-5A-antisense chimera (NIH351) has been developed that targets a consensus sequence within the respiratory syncytial virus (RSV) genomic RNA. NIH351 was 50- to 90-fold more potent against RSV strain A2 than was ribavirin, the presently approved drug for clinical management of RSV infection. It was similarly active against a variety of RSV strains of both A and B subgroups and possessed a cell culture selectivity index comparable to ribavirin. In addition, the anti-RSV activity of NIH351 was shown to be virus-specific and a result of a true antisense effect, because a scrambled nucleotide sequence in the antisense domain of NIH351 caused a significant decrease in antiviral activity. The 2-5A system's RNase L was implicated in the mechanism of action of NIH351 because a congener with a disabled 2-5A moiety was of greatly reduced anti-RSV effectiveness. These findings represent an innovative approach to the control of RSV replication. C1 NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Utah State Univ, Inst Antiviral Res, Logan, UT 84362 USA. RP Torrence, PF (reprint author), NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bldg 8,Room B2A02, Bethesda, MD 20892 USA. FU NIAID NIH HHS [N01-AI35178] NR 35 TC 46 Z9 51 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8874 EP 8879 DI 10.1073/pnas.95.15.8874 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900083 PM 9671772 ER PT J AU Valentin, A Lu, WH Rosati, M Schneider, R Albert, J Karlsson, A Pavlakis, GN AF Valentin, A Lu, WH Rosati, M Schneider, R Albert, J Karlsson, A Pavlakis, GN TI Dual effect of interleukin 4 on HIV-1 expression: Implications for viral phenotypic switch and disease progression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNCYTIUM-INDUCING PHENOTYPE; TYPE-1 INFECTION; T-CELLS; LYMPHOCYTES-B; IFN-GAMMA; INDIVIDUALS; RECEPTOR; AIDS; MIP-1-ALPHA AB We report that interleukin 4 (IL-4) inhibits the propagation of non-syncytia-inducing and increases the propagation of syncytia-inducing HIV-1 isolates by two mechanisms. It differentially regulates the two major HIV-I coreceptors, CCR5 and CXCR4, in human peripheral blood mononuclear cells, increasing CXCR4 and decreasing CCR5 expression in primary CD4(+) T-lymphocytes, In addition, IL-4 stimulates the expression of all HIV-1 isolates via a transcriptional activation mechanism. The combination of these effects results in increased propagation of CXCR4-using and inhibition of CCR5-using HIV-1 strains, IL-4 also activates HIV-1 expression in primary monocytes/macrophages but does not affect CCRS expression. These results identify IL-4 as an important regulator of HIV-1 and suggest a critical role for this cytokine in the control of viral evolution and in the phenotypic switch from non-syncytia-inducing to syncytia-inducing, which leads to accelerated disease progression. C1 NCI, Frederick Canc Res & Dev Ctr, Adv Biosci Labs, Basic Res Program,Human Retrovirus Sect, Frederick, MD 21702 USA. Swedish Inst Infect Dis Control, Dept Clin Virol, S-10521 Stockholm, Sweden. Soder Sjukhuset, Dept Dermatovenereol, S-10521 Stockholm, Sweden. RP Pavlakis, GN (reprint author), NCI, Frederick Canc Res & Dev Ctr, Adv Biosci Labs, Basic Res Program,Human Retrovirus Sect, Bldg 535,Room 212,POB B, Frederick, MD 21702 USA. NR 46 TC 92 Z9 92 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8886 EP 8891 DI 10.1073/pnas.95.15.8886 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900085 PM 9671774 ER PT J AU Young, DA Evans, CH Smith, TJ AF Young, DA Evans, CH Smith, TJ TI Leukoregulin induction of protein expression in human orbital fibroblasts: Evidence for anatomical site-restricted cytokine-target cell interactions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN DERMAL FIBROBLASTS; HUMAN-SKIN FIBROBLASTS; NF-KAPPA-B; GRAVES OPHTHALMOPATHY; INTERFERON-GAMMA; CONNECTIVE-TISSUE; GIANT GELS; T-CELLS; CYCLOOXYGENASE; SYNTHASE-2 AB The molecular basis for the profound inflammatory response and the accumulation of hyaluronan in orbital connective tissues seen in thyroid-associated ophthalmopathy is unknown. Moreover, the link between the orbital manifestations of Graves' disease and those in the pretibial skin, localized dermopathy, has yet to be established. We have reported recently that leukoregulin, an activated T lymphocyte-derived cytokine, dramatically induces hyaluronan synthesis and prostaglandin-endoperoxide H synthase 2 in human orbital fibroblasts in culture, In the current studies, utilizing giant two-dimensional gel electrophoresis, we find that orbital fibroblasts express constitutively a protein profile that distinguishes them from skin fibroblasts derived from the abdominal wall and from the pretibium, We further demonstrate that leukoregulin, when present in culture medium for 16 hr, up-regulates a set of orbital fibroblast proteins not present in untreated cultures or in fibroblasts from the abdominal wall, However, some of the same protein inductions are present in the pretibial fibroblasts, These leukoregulin-induced changes in protein expression are completely blocked by dexamethasone (10 nM), Our findings are the first to identify proteins that appear to be expressed and differentially regulated in an anatomical site-restricted manner in orbital and pretibial fibroblasts and seem to establish a molecular link between fibroblasts from the orbit and those in pretibial skin. C1 Albany Med Coll, Div Mol & Cellular Med A175, Dept Med, Albany, NY 12208 USA. Albany Med Coll, Dept Biochem & Mol Biol, Div Mol & Cellular Med, Albany, NY 12208 USA. Samuel S Stratton Vet Affairs Med Ctr, Albany, NY 12208 USA. Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Dept Biochem, Div Endocrinol & Metab,E Henry Keutmann Labs, Rochester, NY 14642 USA. NCI, Div Canc Etiol, Biol Lab, Bethesda, MD 20892 USA. RP Smith, TJ (reprint author), Albany Med Coll, Div Mol & Cellular Med A175, Dept Med, 47 New Scotland Ave, Albany, NY 12208 USA. OI Smith, Terry/0000-0002-6279-9685 FU NCI NIH HHS [CA 56833]; NEI NIH HHS [EY 08976, R01 EY011708, R01 EY008976]; NIDDK NIH HHS [DK 16177] NR 49 TC 43 Z9 45 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8904 EP 8909 DI 10.1073/pnas.95.15.8904 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900088 PM 9671777 ER PT J AU Horwitz, B Rumsey, JM Donohue, BC AF Horwitz, B Rumsey, JM Donohue, BC TI Functional connectivity of the angular gyrus in normal reading and dyslexia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE positron-emission tomography; human; brain; regional; cerebral ID POSITRON EMISSION TOMOGRAPHY; DEVELOPMENTAL DYSLEXIA; PET; BRAIN; CORTEX; ANATOMY; OBJECT; FACES; TASK AB The classic neurologic model for reading, based on studies of patients with acquired alexia, hypothesizes functional linkages between the angular gyrus in the left hemisphere and visual association areas in the occipital and temporal lobes, The angular gyrus also is thought to have functional links with posterior language areas (e,g,, Wernicke's area), because it is presumed to be involved in mapping visually presented inputs onto linguistic representations. Using positron emission tomography,we demonstrate in normal men that regional cerebral blood flow in the left angular gyrus shows strong within-task, across-subjects correlations (i,e., functional connectivity) with regional cerebral blood flow in extrastriate occipital and temporal lobe regions during single word reading. In contrast, the left angular gyrus is functionally disconnected from these regions in men with persistent developmental dyslexia, suggesting that the anatomical disconnection of the left angular gyrus from other brain regions that are part of the "normal" brain reading network in many cases of acquired alexia is mirrored by its functional disconnection in developmental dyslexia. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Horwitz, B (reprint author), NIA, Neurosci Lab, NIH, Bldg 10,Room 6C414,MSC 1588,9000 Rockville Pike, Bethesda, MD 20892 USA. EM horwitz@helix.nih.gov NR 39 TC 368 Z9 377 U1 1 U2 20 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 JUL 21 PY 1998 VL 95 IS 15 BP 8939 EP 8944 DI 10.1073/pnas.95.15.8939 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900094 PM 9671783 ER PT J AU Pettit, SC Sanchez, R Smith, T Wehbie, R Derse, D Swanstrom, R AF Pettit, SC Sanchez, R Smith, T Wehbie, R Derse, D Swanstrom, R TI HIV type 1 protease inhibitors fail to inhibit HTLV-I gag processing in infected cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TROPICAL SPASTIC PARAPARESIS; BLOOD MONONUCLEAR-CELLS; LEUKEMIA-VIRUS; PROVIRAL DNA; CROSS-RESISTANCE; MOLECULAR CLONE; STRUCTURAL CHARACTERIZATION; PROTEINASE-INHIBITOR; CLINICAL-TRIALS AB Protease inhibitors are currently the most effective antiviral agents against human immunodeficiency virus type 1 (HIV-1). In this study we determined the effect of four HIV-1 protease inhibitors on human T cell leukemia virus type 1 (HTLV-I). Rhesus monkey cells infected with HTLV-I were treated with different concentrations of indinavir, saquinavir, ritonavir, or nelfinavir, The effect of these inhibitors was monitored through their effect on the processing efficiency of the viral Gag protein in cells, the natural substrate for the viral protease, These inhibitors failed to block processing of HTLV-I Gag, To confirm these findings, human cells were cotransfected with plasmids encoding infectious copies of HIV-1 and HTLV-I, and the cells were subsequently treated with these same HIV-1 protease inhibitors, At concentrations between 5 and 50 times the IC50 for inhibition of HIV-1 replication, inhibition of HIV-1 Gag cleavage was apparent, In contrast, no effect on HTLV-I Gag processing was seen, At higher concentrations, HIV-1 Gag processing was essentially completely inhibited whereas HTLV-I Gag cleavage was still unaffected, Thus, these inhibitors are not effective inhibitors of HTLV-I Gag processing. Sequence alignments of the HIV-1 and HTLV-I viral proteases and processing sites suggest that the active site of the HTLV-I protease may have subtle differences in substrate recognition compared with the HIV-1 protease. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. NCI, Natl Canc Inst, Lab Leukocyte Biol, Frederick, MD 21702 USA. RP Swanstrom, R (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB7295,Rm 22-006, Chapel Hill, NC 27599 USA. EM risunc@med.unc.edu RI sebastianovitsch, stepan/G-8507-2013; Pettit, Steve/J-4536-2013 OI Pettit, Steve/0000-0002-1967-1491 FU NIAID NIH HHS [F32-AI08767, R01-AI32892] NR 68 TC 21 Z9 22 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL 20 PY 1998 VL 14 IS 11 BP 1007 EP 1014 DI 10.1089/aid.1998.14.1007 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 101ND UT WOS:000074874300011 PM 9686647 ER PT J AU Dikalov, S Grigor'ev, IA Voinov, M Bassenge, E AF Dikalov, S Grigor'ev, IA Voinov, M Bassenge, E TI Detection of superoxide radicals and peroxynitrite by 1-hydroxy-4-phosphonooxy-2,2,6,6-tetramethylpiperidine: Quantification of extracellular superoxide radicals formation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SPIN; REDUCTION AB The reactions of the new sterically hindered hydroxylamine 1-hydroxy-4-phosphonooxy-2,2,6,6-tetramethylpiperidine (PP-H) with superoxide radical and peroxynitrite have been studied. These reactions produce the nitroxide 4-phosphonooxy-2,2,6,6-tetramethyl-piperidinyloxy. The rate constant for reaction of superoxide with PP-H is determined as (8.4+/-0.6) . 10(2) M-1 s(-1). It was found that PP-H provides almost the same spin trapping efficacy as 1-hydroxy-3-carboxy-pyrrolidine (CP-H). The background oxidation of PP-H in blood is much less than for CP-H. The extremely slow PP-H penetration into the cells makes possible the study of extracellular formation of superoxide radical. The acute treatment of blood with nitroglycerin is shown to induce an extracellular superoxide radical formation. PP-H is more sensitive for detection of reactive oxygen species as compared with CP-H. PP-H is an effective scavenger of superoxide radical and of peroxynitrite, and can be used to quantify the extracellular formation of these reactive oxygen species. (C) 1998 Academic Press. C1 Russian Acad Sci, Inst Chem Kinet & Combust, Novosibirsk 630090, Russia. Russian Acad Sci, Inst Organ Chem, Novosibirsk 630090, Russia. Univ Freiburg, Inst Appl Physiol, D-7800 Freiburg, Germany. RP Dikalov, S (reprint author), NIEHS, POB 12233,MD F002, Res Triangle Pk, NC 27709 USA. NR 15 TC 40 Z9 43 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 20 PY 1998 VL 248 IS 2 BP 211 EP 215 DI 10.1006/bbrc.1998.8936 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 103HG UT WOS:000075151500001 PM 9675114 ER PT J AU Lei, XD Kaufman, S AF Lei, XD Kaufman, S TI Human white blood cells and hair follicles are good sources of mRNA for the pterin carbinolamine dehydratase/dimerization cofactor of HNF1 for mutation detection SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PTERIN-4A-CARBINOLAMINE DEHYDRATASE DEFICIENCY; PHENYLALANINE-HYDROXYLASE; 4A-CARBINOLAMINE DEHYDRATASE; ILLEGITIMATE TRANSCRIPTION; HOMEODOMAIN PROTEINS; GENE; DCOH; RAT; HYPERPHENYLALANINEMIA; PHENYLKETONURIA AB Pterin carbinolamine dehydratase/dimerization co-factor of HNF1 (PGD/DCoH) is a protein that has a dual function. It is a pterin 4 alpha-carbinolamine dehydratase that is involved in the regeneration of the cofactor tetrahydrobiopterin during the phenylalanine hydroxylase- catalyzed hydroxylation of phenylalanine. In addition, it is the dimerization cofactor of HNF1 that is able to activate the transcriptional activity of HNF1. Deficiencies in the gene for this dual functional protein result in hyperphenylalaninemia. Here we report for the first time that the PCD/DCoH mRNA is present in human white blood cells and hair follicles. Taking advantage of this finding, a sensitive, rapid and convenient method for screening mutations occurring in the coding region of this gene has been described. (C) 1998 Academic Press. C1 NIMH, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Lei, XD (reprint author), NIMH, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 20 PY 1998 VL 248 IS 2 BP 432 EP 435 DI 10.1006/bbrc.1998.8898 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 103HG UT WOS:000075151500042 PM 9675155 ER PT J AU Leary, SC Battersby, BJ Hansford, RG Moyes, CD AF Leary, SC Battersby, BJ Hansford, RG Moyes, CD TI Interactions between bioenergetics and mitochondrial biogenesis SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article DE myogenesis; muscle; C2C12; cytochrome oxydase; energy metabolism ID CYTOCHROME-C-OXIDASE; NUCLEAR RESPIRATORY FACTORS; TISSUE-SPECIFIC ISOFORMS; SYNTHASE BETA-SUBUNIT; GENE-EXPRESSION; MESSENGER-RNA; DIFFERENTIAL EXPRESSION; PROTEIN-SYNTHESIS; STRIATED-MUSCLE; HUMAN MYOBLASTS AB We studied the interaction between energy metabolism and mitochondrial biogenesis during myogenesis in C2C12 myoblasts. Metabolic rate was nearly constant throughout differentiation, although there was a shift in the relative importance of glycolytic and oxidative metabolism, accompanied by increases in pyruvate dehydrogenase activation state and total activity. These changes in mitochondrial bioenergetic parameters observed during differentiation occurred in the absence of a hypermetabolic stress. A chronic (3 day) energetic stress was imposed on differentiated myotubes using sodium azide to inhibit oxidative metabolism. When used at low concentrations, azide inhibited more than 70% of cytochrome oxidase (COX) activity without changes in bioenergetics (either lactate production or creatine phosphorylation) or mRNA for mitochondrial enzymes. Higher azide concentrations resulted in changes in bioenergetic parameters and increases in steady state COX II mRNA levels. Azide did not affect mtDNA copy number or mRNA levels for other mitochondrial transcripts, suggesting azide affects stability, rather than synthesis, of COX II mRNA. These results indicate that changes in bioenergetics can alter mitochondrial genetic regulation, but that mitochondrial biogenesis accompanying differentiation occurs in the absence of hypermetabolic challenge. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Moyes, CD (reprint author), Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada. RI Leary, Scot/B-3036-2012 NR 35 TC 54 Z9 56 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD JUL 20 PY 1998 VL 1365 IS 3 BP 522 EP 530 DI 10.1016/S0005-2728(98)00105-4 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 105PM UT WOS:000075082500017 PM 9711303 ER PT J AU Yadid, G Sotnik-Barkai, I Tornatore, C Baker-Cairns, B Harvey-White, J Pentchev, PG Goldin, E AF Yadid, G Sotnik-Barkai, I Tornatore, C Baker-Cairns, B Harvey-White, J Pentchev, PG Goldin, E TI Neurochemical alterations in the cerebellum of a murine model of Niemann-Pick type C disease SO BRAIN RESEARCH LA English DT Article DE Niemann-Pick type C disease; L-DOPA; serotonin; glycine; tyrosine hydroxylase; cerebellum ID TYROSINE-HYDROXYLASE; PURKINJE-CELLS; L-DOPA; SYNAPTIC CURRENTS; STORAGE DISORDER; RAT CEREBELLUM; MESSENGER-RNA; EXPRESSION; NEURONS; CHOLESTEROL AB Niemann-Pick disease Type C (NPC) is a progressive neurovisceral metabolic disorder that is caused in most patients by a defect in a recently found gene, NPC-I. Neurological damage includes visual disorders such as vertical supranuclear gaze palsy, movement disorders such as dystonia and ataxia, dementia, and seizures. So far the biochemical deficit, most likely manifested by delayed intracellular cholesterol transport, has not been correlated with the progressive neurological damage. A mutant Balb/C mouse with a defect in the same gene is used as a model to study NPC. Pathological examination of brain tissue obtained by autopsy from NPC patients or brains of affected NPC mice of different ages, revealed signs of extensive damage throughout the brain, including neurofibrillary tangles and intracellular storage of various compounds. Loss of cerebellar Purkinje cells was the most significant specific damage. The present study examined whether the neurochemical changes present in the NPC mouse brain were related to the pathological changes. The results show major alterations in the levels of serotonin and its main metabolite, 5-hydroxyindoleacetic acid, in the cerebellum and cortex of NPC mice. The levels of the inhibitory amino acid glycine were threefold higher in the cerebellum of NPC mice and those of glutamate and GABA decreased in the cortex. Tyrosine hydroxylase immunoreactivity was present in Purbinje cells, and the levels of L-DOPA increased specifically in the vermis of the cerebellum. These results are the first to indicate changes in neurotransmitters in NPC and that these could be correlated with some of the neuropathology of this disease. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Bar Ilan Univ, Dept Life Sci, IL-52900 Ramat Gan, Israel. NINDS, Mol Med Lab, NIH, Bethesda, MD 20892 USA. NINDS, Lab Monoaminerg Mechanism, NIH, Bethesda, MD 20892 USA. NINDS, Lab Dev Neurol, NIH, Bethesda, MD 20892 USA. NINDS, Lab Metab Neurol, NIH, Bethesda, MD 20892 USA. RP Yadid, G (reprint author), Bar Ilan Univ, Dept Life Sci, IL-52900 Ramat Gan, Israel. EM yadidg@brosh.cc.biu.ac.il NR 32 TC 18 Z9 18 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 20 PY 1998 VL 799 IS 2 BP 250 EP 256 DI 10.1016/S0006-8993(98)00449-1 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 106ML UT WOS:000075133300008 PM 9675302 ER PT J AU Porada, CD Tran, N Eglitis, M Moen, RC Troutman, L Flake, AW Zhao, Y Anderson, WF Zanjani, ED AF Porada, CD Tran, N Eglitis, M Moen, RC Troutman, L Flake, AW Zhao, Y Anderson, WF Zanjani, ED TI In utero gene therapy: Transfer and long-term expression of the bacterial neo(Gamma) gene in sheep after direct injection of retroviral vectors into preimmune fetuses SO HUMAN GENE THERAPY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; HUMAN GLUCOCEREBROSIDASE GENE; ADENOVIRUS-MEDIATED TRANSFER; IN-VITRO; PROGENITOR CELLS; RESISTANCE GENE; FETAL SHEEP; CORD-BLOOD; MICE; TRANSPLANTATION AB We investigated whether directly injecting retroviral vectors into preimmune fetuses could result in the transfer and long-term expression of exogenous genes. Twenty-nine preimmune sheep fetuses were injected with helper-free retroviral vector preparations. Twenty-two fetuses survived to term, 4 of which were sacrificed at birth. Of the remaining 18 animals, 3 were controls and 15 had received vector preparations. Twelve of these 15 animals demonstrated transduction of hematopoietic cells when blood and marrow were analyzed by neo(r)-specific PCR, Eight experimental sheep have been followed for 5 years, during which time we have consistently observed proviral DNA and G418-resistant hematopoetic progenitors. The G418-resistant colonies were positive when analyzed by neo(r)-specific PCR. neo(r) gene expression was also demonstrated using several immunological and biochemical methods, The transduction of hematopoietic stem cells was confirmed when lambs transplanted with bone marrow from in utero-transduced sheep exhibited neo(r) activity in marrow and blood. Vector distribution was widespread in primary animals without pathology. PCR analysis indicates that the germ line was not altered. These studies demonstrate that direct injection of an engineered retrovirus is a feasible means of safely delivering a foreign gene to a developing fetus and achieving long-term expression without modifying the germ line of the recipient. C1 Dept Vet Affairs Med Ctr, Reno, NV 89520 USA. NIH, Bethesda, MD 20892 USA. Baxter Healthcare Corp, Round Lake, IL 60073 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ So Calif, Sch Med, Norris Canc Ctr, Gene Therapy Labs, Los Angeles, CA 90033 USA. RP Zanjani, ED (reprint author), Vet Affairs Med Ctr, 151B,1000 Locust St, Reno, NV 89520 USA. FU NHLBI NIH HHS [HL49042, HL46556, HL52955] NR 48 TC 94 Z9 94 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL 20 PY 1998 VL 9 IS 11 BP 1571 EP 1585 DI 10.1089/hum.1998.9.11-1571 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 103LP UT WOS:000075157700007 PM 9694156 ER PT J AU Kondo, S Ishizaka, Y Okada, T Kondo, Y Hitomi, M Tanaka, Y Haqqi, T Barnett, GH Barna, BP AF Kondo, S Ishizaka, Y Okada, T Kondo, Y Hitomi, M Tanaka, Y Haqqi, T Barnett, GH Barna, BP TI FADD gene therapy for malignant gliomas in vitro and in vivo SO HUMAN GENE THERAPY LA English DT Article ID CISPLATIN-INDUCED APOPTOSIS; CELL-SURFACE ANTIGEN; BRAIN-TUMORS; DEATH DOMAIN; RECEPTOR SUPERFAMILY; MONOCLONAL-ANTIBODY; MEDIATED APOPTOSIS; CD95 FAS/APO-1; FAS; INDUCTION AB Fas/APO-1 (CD95), a cell surface cytokine receptor, triggers apoptotic cell death by specific agonist antibody, suggesting that Fas/APO-1 may be a promising target for treatment of tumors. In this study, we show that treatment with anti-Fas antibody effectively induced apoptosis in malignant glioma cell lines with high expression of Fas/APO-1 (n = 3), Malignant glioma cells with low or undetectable expression of Fas/APO-1 (n = 6), however, were resistant to Fas/APO-1-dependent cytotoxicity. The purpose of this study, therefore, was to determine whether resistant tumors could be made susceptible to apoptosis, FADD/MORT1 constitutes a novel protein that associates specifically with the cytoplasmic death domain of Fas/APO-1 and induces apoptosis, We investigated whether overexpression of FADD would induce apoptosis in malignant glioma cells without activating Fas/APO-1, Results indicated that about 85% of malignant glioma cells, regardless of Fas/APO-1 expression levels, underwent apoptosis after transient transfection with FADD expression vector. To further improve gene transfer of FADD into malignant glioma cells, we constructed a retroviral vector containing the FADD gene, The retroviral transfer of FADD gene significantly enhanced the transduction efficiency and effectively inhibited both in vitro and in vivo survival of malignant glioma cells through induction of apoptosis, These findings suggest that the FADD gene is a novel and useful tool for the treatment of malignant gliomas. C1 Cleveland Clin Fdn, Dept Neurosurg S80, Brain Tumor Neurooncol Ctr, Cleveland, OH 44195 USA. Int Med Ctr Japan, Res Inst, Dept Hematol, Tokyo 162, Japan. NIH, Clin Gene Therapy Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Biol Mol, Cleveland, OH 44195 USA. Tokyo Metropolitan Inst Med Sci, Dept Microbiol, Tokyo 113, Japan. Metrohlth Med Ctr, Rammel Kamp Ctr Educ & Res, Cleveland, OH 44109 USA. RP Kondo, S (reprint author), Cleveland Clin Fdn, Dept Neurosurg S80, Brain Tumor Neurooncol Ctr, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 43 TC 42 Z9 46 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL 20 PY 1998 VL 9 IS 11 BP 1599 EP 1608 DI 10.1089/hum.1998.9.11-1599 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 103LP UT WOS:000075157700009 PM 9694158 ER PT J AU Overwijk, WW Tsung, A Irvine, KR Parkhurst, MR Goletz, TJ Tsung, K Carroll, MW Liu, CL Moss, B Rosenberg, SA Restifo, NP AF Overwijk, WW Tsung, A Irvine, KR Parkhurst, MR Goletz, TJ Tsung, K Carroll, MW Liu, CL Moss, B Rosenberg, SA Restifo, NP TI gp100/pmel 17 is a murine tumor rejection antigen: Induction of "self"-reactive, tumoricidal T cells using high-affinity, altered peptide ligand SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE melanoma; tumor-associated antigen; gp100; xenoimmunization; CD8(+) T lymphocyte ID IN-VIVO; B-CELLS; MOUSE TYROSINASE; TOLERANCE; EXPRESSION; CTL; IMMUNOGENICITY; RECOGNITION; STABILITY; RESPONSES AB Many tumor-associated antigens are nonmutated, poorly immunogenic tissue differentiation antigens. Their weak immunogenicity may be due to "self'-tolerance. To induce autoreactive T cells, we studied immune responses to gp100/pmel 17, an antigen naturally expressed by both normal melanocytes and melanoma cells. Although a recombinant vaccinia virus (rVV) encoding the mouse homologue of gp100 was nonimmunogenic, immunization of normal C57BL/6 mice with the rVV encoding the human gp100 elicited a specific CD8+ T cell response. These lymphocytes were cross-reactive with mgp 100 in vitro and treated established Bib melanoma upon adoptive transfer. To understand the mechanism of the greater immunogenicity of the human version of gp100, we characterized a 9-amino acid (AA) epitope, restricted by H-2D(b), that was recognized by the T cells. The ability to induce specific T cells with human but not mouse gp100 resulted from differences within the major histocompatibility complex (MHC) class I-restricted epitope and not from differences elsewhere in the molecule, as was evidenced by experiments in which mice were immunized with rVV containing minigenes encoding these epitopes. Although the human (hgp100(25-33)) and mouse (mgp 100(25-33)) epitopes were homologous, differences in the three NH2-terminal AAs resulted in a 2-log increase in the ability of the human peptide to stabilize "empty" Db On RMA-S cells and a 3-log increase in its ability to trigger interferon gamma release by T cells. Thus, the fortuitous existence of a peptide homologue with significantly greater avidity for MHC class I resulted in the generation of self-reactive T cells. High-affinity, altered peptide ligands might be useful in the rational design of recombinant and synthetic vaccines that target tissue differentiation antigens expressed by tumors. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Vet Adm Med Ctr, Dept Surg, San Francisco, CA 94121 USA. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bldg 10,Rm 2B42, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 48 TC 320 Z9 326 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 20 PY 1998 VL 188 IS 2 BP 277 EP 286 DI 10.1084/jem.188.2.277 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 107XU UT WOS:000075236900006 PM 9670040 ER PT J AU Thornton, AM Shevach, EM AF Thornton, AM Shevach, EM TI CD4(+)CD25(+) immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE suppressor T cells; interleukin 2; autoimmune disease; self-tolerance; interleukin 2 receptor alpha chain (CD25) ID NATURAL SELF-TOLERANCE; AUTOIMMUNE-DISEASE; BASIC-PROTEIN; MICE; THYMECTOMY; SUBSET; PATHOGENESIS; MECHANISMS; BREAKDOWN; THYMUS AB Peripheral tolerance may be maintained by a population of regulatory/suppressor T cells that prevent the activation of autoreactive T cells recognizing tissue-specific antigens. We have previously shown that CD4(+)CD25(+) T cells represent a unique population of suppressor T cells that can prevent both the initiation of organ-specific autoimmune disease after day 3 thymectomy and the effector function of cloned autoantigen-specific CD4(+) T cells. To analyze the mechanism of action of these cells, we established an in vitro model system that mimics the function of these cells in vivo. Purified CD4(+)CD25(+) cells failed to proliferate after stimulation with interleukin (IL)-2 alone or stimulation through the T cell receptor (TCR). When cocultured With CD4(+)CD25(-) cells, the CD4(+)CD25(+) cells markedly suppressed proliferation by specifically inhibiting the production of TL-2. The inhibition was not cytokine mediated, was dependent on cell contact between the regulatory cells and the responders, and required activation of the suppressors via the TCR. Inhibition could be overcome by the addition to the cultures of IL-2 or anti-CD28, suggesting that the CD4(+)CD25(+) cells may function by blocking the delivery of a costimulatory signal. Induction of CD25 expression on CD25(-) T cells in vitro or in vivo did not result in the generation of suppressor activity. Collectively, these data support the concept that the CD4(+)CD25(+) T cells in normal mice may represent a distinct lineage of "professional" suppressor cells. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM ems1@box-e.nih.gov NR 40 TC 1803 Z9 1877 U1 2 U2 39 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 20 PY 1998 VL 188 IS 2 BP 287 EP 296 DI 10.1084/jem.188.2.287 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 107XU UT WOS:000075236900007 PM 9670041 ER PT J AU Grimm, MC Ben-Baruch, A Taub, DD Howard, OMZ Resau, JH Wang, JM Ali, H Richardson, R Snyderman, R Oppenheim, JJ AF Grimm, MC Ben-Baruch, A Taub, DD Howard, OMZ Resau, JH Wang, JM Ali, H Richardson, R Snyderman, R Oppenheim, JJ TI Opiates transdeactivate chemokine receptors: delta and mu opiate receptor-mediated heterologous desensitization SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE chemokine; chemokine receptor; opioid receptor; desensitization; neuropeptide ID CHEMOATTRACTANT RECEPTORS; OPIOID RECEPTORS; GENE-EXPRESSION; HUMAN MONOCYTES; BETA-ENDORPHIN; IMMUNE-SYSTEM; NITRIC-OXIDE; CELL-LINE; MORPHINE; CHEMOTAXIS AB An intact chemotactic response is vital for leukocyte trafficking and host defense. Opiates are known to exert a number of immunomodulating effects in vitro and in vivo, and we sought to determine whether they were capable of inhibiting chemokine-induced directional migration of human leukocytes, and if so, to ascertain the mechanism involved. The endogenous opioid met-enkephalin induced monocyte chemotaxis in a pertussis toxin-sensitive manner. Metenkephalin, as well as morphine, inhibited IL-8-induced chemotaxis of human neutrophils and macrophage inflammatory protein (MIP)-1 alpha, regulated upon activation, normal T expressed and secreted RANTES), and monocyte chemoattractant protein 1, but not MIP-1 beta-induced chemotaxis of human monocytes. This inhibition of chemotaxis was mediated by delta and mu but not kappa G protein-coupled opiate receptors. Calcium nux induced by chemokines was unaffected by met-enkephalin pretreatment. Unlike other opiate-induced changes in leukocyte function, the inhibition of chemotaxis was not mediated by nitric oxide. Opiates induced phosphorylation of the chemokine receptors CXCR1 and CXCR2, but neither induced internalization of chemokine receptors nor perturbed chemokine binding. Thus, inhibition of chemokine-induced chemotaxis by opiates is due to heterologous desensitization through phosphorylation of chemokine receptors. This may contribute to the defects in host defense seen with opiate abuse and has important implications for immunomodulation induced by several endogenous neuropeptides which act through G protein-coupled receptors. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, ABL Basic Res Program, Frederick, MD 21702 USA. Sci Applicat Int Corp, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NIA, Immunol Lab, Baltimore, MD 21224 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Grimm, MC (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, ABL Basic Res Program, Bldg 560,Rm 31-19, Frederick, MD 21702 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 39 TC 145 Z9 147 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 20 PY 1998 VL 188 IS 2 BP 317 EP 325 DI 10.1084/jem.188.2.317 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 107XU UT WOS:000075236900010 PM 9670044 ER PT J AU Kirk, KL AF Kirk, KL TI Louis Arthur Cohen 1926-1996 SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Biographical-Item C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD JUL 20 PY 1998 VL 90 IS 2 BP 165 EP 167 DI 10.1016/S0022-1139(98)00171-7 PG 3 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 102DT UT WOS:000074909100011 ER PT J AU Glanville, J Haines, M Auston, I AF Glanville, J Haines, M Auston, I TI Getting research findings into practice - Finding information on clinical effectiveness SO BRITISH MEDICAL JOURNAL LA English DT Article ID PRACTICE GUIDELINES; SYSTEMATIC REVIEWS; MEDICAL LITERATURE; USERS GUIDES; RECOMMENDATIONS; LIBRARY C1 Univ York, NHS Ctr Reviews & Disseminat, York YO1 5DD, N Yorkshire, England. Lib & Informat Commiss, London W1V 4BH, England. Natl Lib Med, Natl Informat Ctr Hlth Serv Res & Hlth Care Techn, Bethesda, MD 20894 USA. RP Glanville, J (reprint author), Univ York, NHS Ctr Reviews & Disseminat, York YO1 5DD, N Yorkshire, England. RI Glanville, Julie/C-2358-2008 NR 25 TC 41 Z9 41 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD JUL 18 PY 1998 VL 317 IS 7152 BP 200 EP 203 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 103FZ UT WOS:000075047800038 PM 9665910 ER PT J AU Mei, JJM Hursting, SD Perkins, SN Phang, JM AF Mei, JJM Hursting, SD Perkins, SN Phang, JM TI p53-independent inhibition of nitric oxide generation by cancer preventive interventions in ex vivo mouse peritoneal macrophages SO CANCER LETTERS LA English DT Article DE p53; nitric oxide; calorie restriction; DHEA; cancer prevention ID DIETARY RESTRICTION; SPONTANEOUS TUMORIGENESIS; SYNTHASE; MICE; DEHYDROEPIANDROSTERONE; INDUCTION; OXIDATION; CELLS; P53 AB We have previously reported that dietary interventions with purported anti-inflammatory activity delay spontaneous tumorigenesis in p53-deficient (p53(-/-)) mice. In the present study, 4 weeks of calorie restriction or the dietary administration of chemopreventive steroids dehydroepiandrosterone and 16 alpha-fluoro-5-androsten-17-one significantly reduced the inducible generation of nitric oxide (NO) in ex vivo peritoneal macrophages from male p53 wild-type and p53(-/-) mice relative to the respective ad libitum-fed controls; expression of inducible nitric oxide synthase II (NOS2) protein was also markedly decreased compared with respective controls. These findings suggest that the p53-independent suppression of inducible NO production observed in this study may contribute to the anti-cancer effects of these preventive interventions in p531(-/-) mice. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Lab Nutrit & Mol Regulat, Div Basic Sci, Frederick, MD 21702 USA. RP Phang, JM (reprint author), NCI, Lab Nutrit & Mol Regulat, Div Basic Sci, Frederick, MD 21702 USA. FU NCI NIH HHS [CA 16672] NR 21 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 17 PY 1998 VL 129 IS 2 BP 191 EP 197 DI 10.1016/S0304-3835(98)00102-5 PG 7 WC Oncology SC Oncology GA 107GY UT WOS:000075200300010 PM 9719461 ER PT J AU Rubinstein, YR Proctor, KN Bergel, M Murphy, B Johnson, AC AF Rubinstein, YR Proctor, KN Bergel, M Murphy, B Johnson, AC TI Interferon regulatory factor-1 is a major regulator of epidermal growth factor receptor gene expression SO FEBS LETTERS LA English DT Article DE epidermal growth factor receptor; promoter; gene regulation; interferon; DNA binding ID IFN-INDUCIBLE GENES; BREAST-CANCER; CELL-LINE; FACTOR-I; TRANSCRIPTION FACTOR; ALPHA-INTERFERON; EGF RECEPTOR; IRF-1; BETA; ACTIVATION AB Overexpression of the epidermal growth factor receptor (EGFR) occurs in many; tumors and in breast cancer correlates with poor prognosis for treatment. Here, we report that interferon regulatory factor-1 (IRF-1) induces EGFR promoter activity up to 200-fold compared to 3-10-fold induction by other regulators. The region of the promoter that is required for this induction was defined using deletion mutants. In addition, we found that IRF-1 and tricostatin A, a deacetylase inhibitor, have a synergistic effect on EGFR promoter activity. This indicates that the increase in EGFR promoter activity by IRF-1 may also involve changes in chromatin structure. These results identify IRF-1 as a major regulator of EGFR gene expression. (C) 1998 Federation of European Biochemical Societies. C1 NCI, Mol Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Mol Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Johnson, AC (reprint author), NCI, Mol Biol Lab, Div Basic Sci, Bldg 37,Room 2D18,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. NR 29 TC 18 Z9 19 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 JUL 17 PY 1998 VL 431 IS 2 BP 268 EP 272 DI 10.1016/S0014-5793(98)00774-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 104HT UT WOS:000075009200030 PM 9708917 ER PT J AU Kobayashi, S Yoshida, K Ohshima, T Esumi, N Paralkar, VM Wistow, GJ Kulkarni, AB AF Kobayashi, S Yoshida, K Ohshima, T Esumi, N Paralkar, VM Wistow, GJ Kulkarni, AB TI DNA sequence motifs are associated with aberrant homologous recombination in the mouse macrophage migration inhibitory factor (Mif) locus SO GENE LA English DT Article DE gene targeting; topoisomerase I; AT-rich sequence; intracisternal-A particle ID EMBRYONIC STEM-CELLS; VIRUS 40 RECOMBINANTS; SINGLE-STRANDED-DNA; CVP8-1-P2 ECORI RES; RAT-LIVER; ILLEGITIMATE RECOMBINATION; NUCLEOTIDE-SEQUENCE; GENE; INTEGRATION; BREAKAGE AB Homologous recombination is a precise genetic event that can introduce specific alteration in the genome. A planned targeted disruption by homologous recombination of the macrophage migration inhibitory factor (Mif) locus in mouse embryonic stem (ES) cells yielded the targeted clones, some of which had genomic rearrangements inconsistent with the expected homologous recombination event. A detailed characterization of the recombination breakpoints in two of these clones revealed several sequence motifs with possible roles in recombination. These motifs included short regions of sequence identity that may promote DNA. alignment, multiple 5'-AAGG/TTCC-3' tetrameres, topoisomerase I consensus sites, and AT-rich sequences that can promote DNA cleavage and recombination. A retrovirus-like intracisternal-A particle (IAP) family sequence was also identified upstream of the Mif gene, and the LTR of this IAP was involved in one of the recombinations. Identification and characterization of such sequence motifs will be valuable for the gene targeting experiments. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 NIDR, Gene Targeting Res & Core Facil, NIH, Bethesda, MD 20892 USA. NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA. RP Kulkarni, AB (reprint author), NIDR, Gene Targeting Res & Core Facil, NIH, Bldg 30,Room 132,30 Convent Dr, Bethesda, MD 20892 USA. NR 38 TC 4 Z9 4 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 JUL 17 PY 1998 VL 215 IS 1 BP 85 EP 92 DI 10.1016/S0378-1119(98)00271-6 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 109JG UT WOS:000075317900010 PM 9666087 ER PT J AU Allikmets, R Wasserman, WW Hutchinson, A Smallwood, P Nathans, J Rogan, PK Schneider, TD Dean, M AF Allikmets, R Wasserman, WW Hutchinson, A Smallwood, P Nathans, J Rogan, PK Schneider, TD Dean, M TI Organization of the ABCR gene: analysis of promoter and splice junction sequences SO GENE LA English DT Article DE ABC genes; splice sites; information theory ID TRANSCRIPTION FACTOR NRL; CIS-ACTING ELEMENT; UPSTREAM REGION; RHODOPSIN GENE; BINDING; PROTEIN; TRANSPORTER; EXPRESSION; SITES; DATABASE AB Mutations in the human ABCR gene have been associated with the autosomal recessive Stargardt disease (STGD), retinitis pigmentosa (RP19), and cone-rod dystrophy (CRD) and have also been found in a fraction of age-related macular degeneration (AMD) patients. The ABCR gene is st member of the ATP-binding cassette (ABC) transporter superfamily and encodes a rod photoreceptor-specific membrane protein. The cytogenetic location of the ABCR gene was refined to 1p22.3-1p22.2. The intron/exon structure was determined for the ABCR gene from overlapping genomic clones. ABCR spans over 100 kb and comprises 50 exons. Intron/exon splice site sequences are presented for all exons and analyzed for information content (Ri). Nine splice site sequence variants found in STGD and AMD patients are evaluated as potential mutations. The localization of splice sites reveals a high degree of conservation between other members of the ABC1 subfamily, e.g. the mouse Abc1 gene. Analysis of the 870-bp 5' upstream of the transcription start sequence reveals multiple putative photoreceptor-specific regulatory elements including a novel retina-specific transcription factor binding site. These results will be useful in further mutational screening of the ABCR gene in various retinopathies and for determining the substrate and/or function of this photoreceptor-specific ABC transporter. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Lab Genom Divers, FCRDC, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. SmithKline Beecham Pharmaceut, Bioinformat, King Of Prussia, PA 19406 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. Allegheny Univ Hlth Sci, Dept Human Genet, Pittsburgh, PA 15212 USA. NCI, Lab Expt & Computat Biol, FCRDC, Frederick, MD 21702 USA. RP Dean, M (reprint author), NCI, Lab Genom Divers, FCRDC, Frederick, MD 21702 USA. EM dean@fcrfvl.ncifcrf.gov RI Dean, Michael/G-8172-2012; Wasserman, Wyeth/I-4866-2015; Rogan, Peter/B-9845-2017; OI Dean, Michael/0000-0003-2234-0631; Rogan, Peter/0000-0003-2070-5254; Schneider, Thomas/0000-0002-9841-1531 FU NCI NIH HHS [CA74683-02] NR 39 TC 46 Z9 46 U1 0 U2 3 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 JUL 17 PY 1998 VL 215 IS 1 BP 111 EP 122 DI 10.1016/S0378-1119(98)00269-8 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 109JG UT WOS:000075317900013 PM 9666097 ER PT J AU Treister, A Sagi-Assif, O Meer, M Smorodinsky, NI Anavi, R Golan, I Meshel, T Kahana, O Eshel, R Katz, BZ Shevach, E Witz, IP AF Treister, A Sagi-Assif, O Meer, M Smorodinsky, NI Anavi, R Golan, I Meshel, T Kahana, O Eshel, R Katz, BZ Shevach, E Witz, IP TI Expression of Ly-6, a marker for highly malignant murine tumor cells, is regulated by growth conditions and stress SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CANCER METASTASIS; MULTIGENE FAMILY; 3T3 CELLS; ANGIOGENESIS AB Ly-6E.I is highly expressed in murine tumor cells with a high malignancy phenotype and may serve as a marker for such a phenotype. In this study, we examined the effects of various growth conditions and stress on the expression levels of Ly-6E.I by tumor cells. Previous preliminary results have shown that murine DA3 mammary tumor cells expressing high levels of Ly-6E.I (Ly-6(hi)) are more highly tumorigenic than the same tumor cells expressing low levels of this membrane protein (Ly-6(lo)). In this study, we demonstrate that mice bearing Ly-6(hi) DA3 tumors have a significantly higher burden of spontaneous pulmonary metastasis than mice bearing Ly-6(lo) DA3 tumors. Furthermore, the survival time of the former mice was significantly shorter than that of the latter ones. We further show that certain other members of the Ly-6 gene family such as Ly-6C.I and Ly-6G.I are coregulated with Ly-6E.I. This was shown to occur with respect to both DA3 cells as well as A3 tumor cells which are of fibroblast origin. However, these 2 cells differ with respect to regulation of Sca-2 (TSAI, another member of the Ly-6 family) expression on these cells. Levels of Sca-2 on A3 cells appear to be coregulated with Ly-6E.I (i.e., Ly-6(hi) A3 cells express high levels of Sca-2 and Ly-6(lo) A3 cells express low levels of Sca-2). These 2 Ly-6 proteins were, however, not coregulated on DA3 cells. Both Ly-6(hi) as well as Ly-6(lo) DA3 cells express equal levels of Sca-2. Levels of Thy-I, another glycosylphosphatidylinositol (GPI)-anchored protein expressed by A3 tumor cells, were equally expressed by both Ly-6(hi) and Ly-6(lo) A3 tumor cells. Levels of Ly-6 (but not those of CD44) on A3 tumor cells were upregulated on cells from dense cultures but were not influenced by the position of the cells in the cell cycle. Stress conditions such as serum starvation or heat shock upregulated the expression of Ly-6 by the 2 types of tumor cells but did not induce apoptosis in these cells. The kinetics of the stress-dependent upregulation of Ly-6 expression differed, however, between the epithelial and fibroblastic tumor cells. (C) 1998 Wiley-Liss, Inc. C1 Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, George S Wise Fac Life Sci, Ela Kodesz Inst Res Canc Dev, IL-69978 Tel Aviv, Israel. NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Witz, IP (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. EM ipwitz@post.tau.ac.il NR 25 TC 29 Z9 30 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 17 PY 1998 VL 77 IS 2 BP 306 EP 313 DI 10.1002/(SICI)1097-0215(19980717)77:2<306::AID-IJC22>3.0.CO;2-7 PG 8 WC Oncology SC Oncology GA ZW300 UT WOS:000074396200022 PM 9650569 ER PT J AU Druey, KM Sullivan, BM Brown, D Fischer, ER Watson, N Blumer, KJ Gerfen, CR Scheschonka, A Kehrl, JH AF Druey, KM Sullivan, BM Brown, D Fischer, ER Watson, N Blumer, KJ Gerfen, CR Scheschonka, A Kehrl, JH TI Expression of GTPase-deficient G(i alpha 2) results in translocation of cytoplasmic RGS4 to the plasma membrane SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID G-PROTEIN; RECEPTORS; FAMILY; DOMAIN; CELLS; GAIP AB The members of a recently identified protein family termed regulators of G-protein signaling (RGS) act as GTPase activating proteins for certain G(alpha) subunits in vitro, but their physiological effects in cells are uncertain in the face of similar biochemical activity and overlapping patterns of tissue expression. Consistent with its activity in in vitro GTPase-activating protein assays, RGS4 interacts efficiently with endogenous proteins of the G(i) and G(q) subclasses of G(alpha) subunits but not with G(12 alpha) or G(s alpha). Unlike other RGS proteins such as RGS9, RGS-GAIP, and Sst2p, which have been reported to be largely membrane-associated, a majority of cellular RGS4 is found as a soluble protein in the cytoplasm, However, the expression of a GTPase-deficient G(i alpha) subunit (G(i alpha 2)-Q204L) resulted in the translocation of both wild type RGS4 and a non-G(1 alpha)-binding mutant (L159F) to the plasma membrane. These data suggest that RGS4 may be recruited to the plasma membrane indirectly by G-protein activation and that multiple RGS proteins within a given cell might be differentially localized to determine a physiologic response to a G-protein-linked stimulus. C1 NIAID, Immunoregulat Lab, Rocky Mt Labs, NIH, Bethesda, MD 20892 USA. NIAID, Mol Biol Lab, Rocky Mt Labs, NIH, Bethesda, MD 20892 USA. NIMH, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, Rocky Mt Labs, NIH, Bldg 10,Rm 11B-13,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. RI Blumer, Kendall/C-5268-2012 FU NIDDK NIH HHS [DK38452] NR 26 TC 68 Z9 70 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 17 PY 1998 VL 273 IS 29 BP 18405 EP 18410 DI 10.1074/jbc.273.29.18405 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100RE UT WOS:000074828500063 PM 9660808 ER PT J AU Blakesley, VA Koval, AP Stannard, BS Scrimgeour, A LeRoith, D AF Blakesley, VA Koval, AP Stannard, BS Scrimgeour, A LeRoith, D TI Replacement of tyrosine 1251 in the carboxyl terminus of the insulin-like growth factor-I receptor disrupts the actin cytoskeleton and inhibits proliferation and anchorage-independent growth SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAPID COLORIMETRIC ASSAY; FOCAL ADHESION FORMATION; YEAST 2-HYBRID SYSTEM; MAP KINASE KINASE; IGF-I; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; RAT GLIOBLASTOMA; P85 SUBUNIT; PROTEIN AB Insulin-like growth factor (IGF)-I signaling through the IGF-I receptor modulates cellular adhesion and proliferation and the transforming ability of cells overexpressing the IGF-I receptor. Tyrosine phosphorylation of intracellular proteins is essential for this transduction of the IGF-I-induced mitogenic and tumorigenic signals. IGF-I induces specific cytoskeletal structure and the phosphorylation of proteins in the associated focal adhesion complexes. The determination of the exact pathways emanating from the IGF-I receptor that are involved in mediating these signals will contribute greatly to the understanding of IGF-I action. We have previously shown that replacement of tyrosine residues 1250 and 1251 in the carboxyl terminus of the IGF-I receptor abrogates IGF-I-induced cellular proliferation and tumor formation in nude mice. In this study, replacement of either tyrosine 1250 or 1251 similarly re duces the cells ability to grow in an anchorage-independent manner. The actin cytoskeleton and cellular localization of vinculin are disrupted by replacement of tyrosine 1251, Tyrosine residues 1250 and 1251 are not essential for tyrosine phosphorylation of two known substrates; insulin receptor substrate-1 and SHC, nor association of known downstream adaptor proteins to these substrates. In addition, these mutant IGF-I receptors do not affect IGF-I-stimulated p42/p44 mitogen-activated protein kinase activation or phosphatidylinositol (PI) 3'-kinase activity. Thus, it appears that in fibroblasts expressing tyrosine 1250 and 1251 mutant IGF-I receptors, the signal transduction pathways impacting on mitogenesis and tumorigenesis do not occur exclusively through the PI 3'-kinase or mitogen-activated protein kinase pathways. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Diabet Branch, NIH, Bldg 10 Rm 8S235A,10 Ctr Dr MSC 1770, Bethesda, MD 20892 USA. EM derek@helix.nih.gov RI Scrimgeour, Angus/D-6794-2013 NR 80 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 17 PY 1998 VL 273 IS 29 BP 18411 EP 18422 DI 10.1074/jbc.273.29.18411 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100RE UT WOS:000074828500064 PM 9660809 ER PT J AU Asano, K Phan, L Anderson, J Hinnebusch, AG AF Asano, K Phan, L Anderson, J Hinnebusch, AG TI Complex formation by all five homologues of mammalian translation initiation factor 3 subunits from yeast Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLI SHUTTLE VECTORS; PROTEIN-SYNTHESIS; ESCHERICHIA-COLI; RABBIT RETICULOCYTES; RESTRICTION SITES; PRT1 PROTEIN; FACTOR EIF-3; GENE; DNA; SYSTEM AB The PRT1, TIF34, GCD10, and SUI1 proteins of Saccharomyces cerevisiae were found previously to copurify with eukaryotic translation initiation factor 3 (eIF3) activity. Although TIF32, NIP1, and TIF35 are homologous to subunits of human eIF3, they were not known to be components of the yeast factor. We detected interactions between PRT1, TIF34, and TIF35 by the yeast two-hybrid assay and in vitro binding assays. Discrete segments (70-150 amino acids) of PRT1 and TIF35 were found to be responsible for their binding to TIF34, Temperature-sensitive mutations mapping in WD-repeat domains of TIF34 were isolated that decreased binding between TIF34 and TIF35 in vitro. The lethal effect of these mutations was suppressed by increasing TIF35 gene dosage, suggesting that the TIF34-TIF35 interaction is important for TIF34 function in translation. Pairwise in vitro interactions were also detected between PRT1 and TIF32, TIF32 and NIP1, and NIP1 and SUI1, Furthermore, PRT1, NIP1, TIF34, TIF35, and a polypeptide with the size of TIF32 were specifically coimmunoprecipitated from the ribosomal salt wash fraction. We propose that all five yeast proteins homologous to human eIF3 subunits are components of a stable heteromeric complex in vivo and may comprise the conserved core of yeast eIF3. C1 NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov NR 56 TC 115 Z9 117 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 17 PY 1998 VL 273 IS 29 BP 18573 EP 18585 DI 10.1074/jbc.273.29.18573 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100RE UT WOS:000074828500084 PM 9660829 ER PT J AU Cao, XL Tian, Y Zhang, TY Ito, Y AF Cao, XL Tian, Y Zhang, TY Ito, Y TI Separation and purification of 10-deacetylbaccatin III by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; Taxus chinensis; deacetylbaccatin III ID CHEMISTRY; TAXOL AB High-speed counter-current chromatography (HSCCC) was used for the separation and purification of 10-deacetylbaccatin III from the needle extract of Chinese yew (Taxus chinensis). The crude needle extract (500 mg/5 ml) was first separated with a two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (2:5:2:5, v/v) and the partially purified fraction was again purified with a different solvent system composed of n-hexane-chloroform-methanol-water (5:25:34:20, v/v). HPLC analysis of the final fraction showed that the purity of 10-deacetylbaccatin (20 mg) was over 98%. The chemical structure was confirmed by fast atom bombardment MS and H-1 NMR. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Beijing Inst New Technol Applicat, Beijing 100035, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Rm 7N322,10 Ctr Dr MSC 1676, Bethesda, MD 20892 USA. NR 9 TC 12 Z9 14 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 17 PY 1998 VL 813 IS 2 BP 397 EP 401 DI 10.1016/S0021-9673(98)00360-4 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 103FB UT WOS:000075146500019 PM 9700932 ER PT J AU Shih, P Pedersen, LG Gibbs, PR Wolfenden, R AF Shih, P Pedersen, LG Gibbs, PR Wolfenden, R TI Hydrophobicities of the nucleic acid bases: Distribution coefficients from water to cyclohexane SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE nucleic acid bases; hydrophobicity; cyclohexane; partition coefficients; free energy of transfer ID HYDRATION FREE-ENERGIES; SOLVATION FREE-ENERGIES; INITIO CONTINUUM MODEL; HYDROPHILIC CHARACTER; AQUEOUS-SOLUTION; POLARIZATION; PHASE AB To establish an experimental scale of hydrophobicities for the nucleic acid bases, comparable with a scale developed earlier for amino acid side-chains, these bases and their parent compounds (purine and pyrimidin-2-one) were converted to M-butylated and tetrahydrofurylated derivatives that are appreciably soluble in cyclohexane, a truly non-polar solvent that dissolves negligible water at saturation. Distribution measurements between neutral aqueous solution and cyclohexane, at varying solute concentrations, showed no evidence of self-association of the solute in either solvent, and the possibility of specific entrainment of water by solutes entering cyclohexane was ruled out by the results of experiments with tritiated water, in both the n-butyl and tetrahydrofuryl series, the bases span a range of similar to 5.3 kcal mol(-1) in their free energies of transfer from water to cyclohexane, and are arranged in the following rank, in order of decreasing hydrophobicity: purine> thymine>adenine > uracil > pyrimidin-2-one > hypoxanthine greater than or equal to cytosine greater than or equal to guanine. In both series of pyrimidin-2-ones, hydrophobicity decreases with introduction of an amino substituent, but addition of an exocyclic keto group results in a modest enhancement of hydrophobicity; and free energies of transfer are relatively insensitive to the position of N-alkyl substitution. In both series of purines, hydrophobicity decreases with the introduction of exocyclic amino and keto groups, the keto group having the greater effect; and free energies of transfer vary substantially depending on the position of N-alkyl substitution. Several additional compounds were examined to test recent predictions based on SM5.4/A, a quantum mechanical self-consistent-field solvation model; and that model was found to yield values in reasonable agreement with the experimental results. (C) 1998 Academic Press. C1 Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. NIEHS, Lab Quantitat & Computat Biol, Res Triangle Pk, NC 27709 USA. RP Wolfenden, R (reprint author), Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL-06350]; NIGMS NIH HHS [GM18325] NR 32 TC 51 Z9 51 U1 1 U2 9 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 17 PY 1998 VL 280 IS 3 BP 421 EP 430 DI 10.1006/jmbi.1998.1880 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 101QC UT WOS:000074878800009 PM 9665846 ER PT J AU Zhai, SP Dai, RK Wei, XX Friedman, FK Vestal, RE AF Zhai, SP Dai, RK Wei, XX Friedman, FK Vestal, RE TI Inhibition of methoxyresorufin demethylase activity by flavonoids in human liver microsomes SO LIFE SCIENCES LA English DT Article DE flavonoids; galangin; CYP1A2; human liver microsomes; inhibition; methoxyresorufin; phytochemicals ID NATURAL FLAVONOIDS; ACTIVATION; METABOLISM; CANCER; CYTOCHROMES-P-450; SUSCEPTIBILITY AB Flavonoids are a class of dietary phytochemicals with anticarcinogenic properties. A series of ten structurally related flavonoids were evaluated for their effect on methoxyresorufin O-demethylase (MROD) activity in human liver microsomes. Ail compounds inhibited this cytochrome P450 1A2 (CYP1A2) mediated activity. 3,5,7-Trihydoxyflavone (galangin) was the most potent inhibitor, followed by 3-hydroxyflavone and flavone. The relative inhibitory potency of flavonoids is related to their structures. The results suggest that flavonoids may modulate pharmacological and toxicological effects mediated by CYP1A2. Published by Elsevier Science Inc. C1 Vet Affairs Med Ctr, Res Serv 151, Clin Pharmacol & Gerontol Res Unit, Boise, ID 83702 USA. Mt State Med Res Inst, Canc Res Sect, Boise, ID 83702 USA. Idaho State Univ, Coll Pharm, Dept Pharmaceut Sci, Pocatello, ID 83209 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. RP Vestal, RE (reprint author), Vet Affairs Med Ctr, Res Serv 151, Clin Pharmacol & Gerontol Res Unit, 500 W Ft St, Boise, ID 83702 USA. EM rvestal@micron.net RI Friedman, Fred/D-4208-2016 NR 21 TC 9 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUL 17 PY 1998 VL 63 IS 8 BP PL119 EP PL123 DI 10.1016/S0024-3205(98)00323-3 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 105GG UT WOS:000075063900011 PM 9718089 ER PT J AU Kim, YC de Zwart, M Chang, L Moro, S Kunzel, JKVD Melman, N IJzerman, AP Jacobson, KA AF Kim, YC de Zwart, M Chang, L Moro, S Kunzel, JKVD Melman, N IJzerman, AP Jacobson, KA TI Derivatives of the triazoloquinazoline adenosine antagonist (CGS 15943) having high potency at the human A(2B) and A(3) receptor subtypes SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; RAT-BRAIN; CLONING; INHIBITOR; AGONISTS; SYSTEM AB The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS 15943) binds nonselectively to human A(1), A(2A), and A(3) receptors with high affinity. Acylated derivatives and one alkyl derivative of the 5-amino group and other modifications were prepared in an effort to enhance A(2B) or A(3) subtype potency. In general, distal modifications of the N-5-substituent were highly modulatory to potency and selectivity at adenosine receptors, as determined in radioligand binding assays at rat brain A(1) and A(2A) receptors and at recombinant human A(3) receptors. In Chinese hamster ovary cells stably transfected with human A(2B) receptor cDNA, inhibition of agonist-induced cyclic AMP production was measured. An N-5-(2-iodophenyl)acetyl derivative was highly selective for A(2A) receptors. An (R)-N-5-alpha-methyl-(phenylacetyl) derivative was the most potent derivative at A(3) receptors, with a K-i value of 0.36 nM. A bulky N-5-diphenylacetyl derivative, 13, displayed a K-i value of 0.59 nM at human A(3) receptors and was moderately selective for that subtype. Thus, a large, nondiscriminating hydrophobic region occurs in the Ag receptor in proximity to the N-5-substituent. A series of straight-chain N-5-aminoalkylacyl derivatives demonstrated that for A(2B) receptors the optimal chain length occurs with three methylene groups, i.e., the N-5-gamma-aminobutyryl derivative 27 which had a pA(2) value of 8.0 but was not selective for A(2B) receptors. At A(1), A(2A), and A(3) receptors however the optimum occurs with four methylene groups. An N-5-pivaloyl derivative, which was less potent than 27 at A(1), A(2A), and A(3) receptors, retained moderate potency at A(2B) receptors. A molecular model of the 27-A(2B) receptor complex based on the structure of rhodopsin utilizing a "cross-docking" procedure was developed in order to visualize the environment of the ligand binding site. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Leiden Amsterdam Ctr Drug Res, Div Med Chem, NL-2300 RA Leiden, Netherlands. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 NR 42 TC 99 Z9 99 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 16 PY 1998 VL 41 IS 15 BP 2835 EP 2845 DI 10.1021/jm980094b PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 101PU UT WOS:000074878000019 PM 9667972 ER PT J AU Ananthan, S Johnson, CA Carter, RL Clayton, SD Rice, KC Xu, H Davis, P Porreca, F Rothman, RB AF Ananthan, S Johnson, CA Carter, RL Clayton, SD Rice, KC Xu, H Davis, P Porreca, F Rothman, RB TI Synthesis, opioid receptor binding, and bioassay of naltrindole analogues substituted in the indolic benzene moiety SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BETA-CASOMORPHIN ANALOGS; MESSAGE ADDRESS CONCEPT; MOUSE VAS-DEFERENS; GUINEA-PIG BRAIN; PHARMACOLOGICAL CHARACTERIZATION; ANTISENSE OLIGODEOXYNUCLEOTIDE; FUNCTIONAL EXPRESSION; PEPTIDE RECEPTOR; DIFFERENTIAL ANTAGONISM; N-BENZYLNALTRINDOLES AB A series of analogues of the delta opioid receptor antagonist naltrindole (1) possessing a phenyl, phenoxy, or benzyloxy group at the 4'-, 5'-, 6'-, or - 7'-positions (4-15) and a 2-(2-pyridinyl)-ethenyl group at the 5'-position (16) on the indolic benzene ring were synthesized through Fischer indolization of naltrexone. Compounds 4-16 were evaluated for their affinities in opioid receptor binding assays in rat or guinea pig brain membranes and for their opioid antagonist and agonist activities in vitro on the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. All of the compounds displayed delta selectivity in binding to the delta, mu, and kappa opioid receptors. The binding potencies of most of the compounds at the delta, mu, and kappa sites, however, were lower than that of 1. Among positional isomers, the 7'-substituted compounds in general had higher affinities than 6'-, 5'-, or 4'-substituted analogues, indicating that bulky groups are tolerated better at the 7'-position than at other positions. The affinity of the compounds were also determined at putative subtypes of the delta and kappa receptors: delta(cx-1) (mu-like), delta(cx-2) (delta-like), and the kappa(2b) Site in an attempt to identify subtype selective agents. Although none were identified, the data revealed a different rank-order of potency beteween mu vs delta(cx-1), delta(cx-2) vs delta, and the kappa(2b) vs mu, delta, and kappa(1). The antagonist potencies of the compounds in the MVD were in agreement with their binding affinities at the delta site in. rat brain membrane, The most potent member of the series, the 7'-phenoxy compound 14, binds to the delta site with a K-i of 0.71 nM, shows >40-fold delta over mu and delta over kappa binding selectivity, add exhibits delta receptor antagonist potency in the MVD with a K-e of 0.25 nM, properties which are comparable to the delta receptor affinity and antagonist potency of naltrindole (K-i = 0.29 nM, K-e = 4.49 nM). Interestingly, many members of the series were found to possess significant partial to full agonist activities in the MVD (6, 9, 10, 13, 16) or GPI (6, 11, 14, 15). Among the compounds studied, the highest agonist activity in the MVD was displayed by 16 (IC50 = 220 nM), and the highest agonist activity in the GPI was displayed by 14 (IC50 = 450 nM). The overall affinity and activity profile of compound 14 is, therefore, that of a nonpeptide ligand possessing mixed mu agonist/delta antagonist properties. Recently there has been considerable interest in such compounds possessing mu agonist/delta antagonist activities because of their potential therapeutic usefulness as analgesics with low propensity to produce tolerance and dependence side effects. The results of the present study suggest that morphinan derivatives related to 16 and 14 may provide useful leads for the development of potent nonpeptide ligands possessing delta agonist or mixed delta antagonist/mu agonist activities. C1 So Res Inst, Dept Organ Chem, Birmingham, AL 35255 USA. Univ Arizona, Coll Med, Hlth Sci Ctr, Dept Pharmacol, Tucson, AZ 85724 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. RP Ananthan, S (reprint author), So Res Inst, Dept Organ Chem, Birmingham, AL 35255 USA. FU NIDA NIH HHS [DA08883] NR 62 TC 28 Z9 29 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 16 PY 1998 VL 41 IS 15 BP 2872 EP 2881 DI 10.1021/jm980083i PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 101PU UT WOS:000074878000022 PM 9667975 ER PT J AU Akiri, G Nahari, D Finkelstein, Y Le, SY Elroy-Stein, O Levi, BZ AF Akiri, G Nahari, D Finkelstein, Y Le, SY Elroy-Stein, O Levi, BZ TI Regulation of vascular endothelial growth factor (VEGF) expression is mediated by internal initiation of translation and alternative initiation of transcription SO ONCOGENE LA English DT Article DE vascular endothelial growth factor (VEGF); internal ribosome entry site (IRES); 5 ' untranslated region; translational regulation; angiogenesis ID FACTOR MESSENGER-RNA; SMOOTH-MUSCLE CELLS; FACTOR GENE; PERMEABILITY FACTOR; EPITHELIAL-CELLS; IN-VIVO; HYPOXIA; PROTEIN; ANGIOGENESIS; SEQUENCES AB Vascular Endothelial Growth Factor (VEGF) is very potent angiogenic agent that has a central role in normal physiological angiogenesis as well as in tumor angiogenesis, VEGF expression is induced by hypoxia and hypoglycemia, and thus was suggested to promote neovascularization during tumor outgrowth, Yet, the molecular mechanism that governs VEGF expression is not fully characterized, VEGF induction is attributed in part to increased levels of transcription and RNA stability, Previously, we demonstrated that the 5' Untranslated Region (5' UTR) of VEGF has an important regulatory role in its expression. VEGF has an exceptionally long 5' UTR (1038 bp) which is highly rich in G+C nucleotides, This suggests that secondary structures in the 5' UTR might be essential for VEGF expression through transcriptional and post-transcriptional control mechanisms, as demonstrated for other growth factors, In this communication, we provide evidence that a computer predicted Internal Ribosome Entry Site (IRES) structure is biologically active and is located at the 3' end of the UTR, In addition, the results demonstrate that an alternative transcriptional initiation site for VEGF exists in the 5' UTR of VEGF, This alternative initiation site is 633 bp downstream of the main transcription start site and the resulting 5' UTR includes mainly the IRES structure. Therefore, our results suggest that VEGF is subjected to regulation at either translational level through a mechanism of ribosome internal initiation and/or transcriptional level through alternative initiation. C1 Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel. NCI, Lab Expt & Computat Biol, DBS, NIH, Frederick, MD 21702 USA. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. RP Levi, BZ (reprint author), Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel. NR 52 TC 184 Z9 190 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 16 PY 1998 VL 17 IS 2 BP 227 EP 236 DI 10.1038/sj.onc.1202019 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZZ211 UT WOS:000074706700011 PM 9674707 ER PT J AU Abbott, RD Yano, K Hakim, AA Burchfiel, CM Sharp, DS Rodriguez, BL Curb, JD AF Abbott, RD Yano, K Hakim, AA Burchfiel, CM Sharp, DS Rodriguez, BL Curb, JD TI Changes in total and high-density lipoprotein cholesterol over 10- and 20-year periods (the Honolulu Heart Program) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PHYSICAL-ACTIVITY; DISEASE; RISK; MEN; STROKE; HEALTH; AGE AB Limited data are available on patterns of change in lipids and lipoproteins as persons age. The purpose of this report is to describe the 10-year change in total and high-density lipoprotein (HDL) cholesterol according to suspected determinants in 898 Japanese-American men enrolled in the Honolulu Heart Program. Data are based on examinations that occurred from 1970 to 1972 and at repeat examinations received 10 and 20 years later, At the last examination, men were aged 71 to 93 years. Mean reductions in total cholesterol in the second 10 years of follow-up (24 mg/dl) were more than double the reductions observed in the first 10 years (9 mg/dl). Levels of total cholesterol declined and levels of HDL cholesterol increased regardless of beginning levels of systolic blood pressure, body mass index, physical activity, cigarette smoking status, or the use of treatment for hypertension or elevated total cholesterol, Men with prevalent coronary heart disease experienced greater reductions (p <0.05) in total cholesterol during the second 10 years of follow-up (32 mg/dl) versus men without coronary heart disease (22 mg/dl), Adjustment for baseline covariates failed to alter these findings appreciably. We conclude that alterations in total and HDL cholesterol with advancing age may be expected to occur regardless of risk factor status, disease prevalence, or pharmacologic intervention. In the presence of such effects, evaluation of treatment programs to alter levels of total and HDL cholesterol in older persons should consider the possibility that even in the absence of intervention, changes could also occur due to aging alone. (C) 1998 by Excerpta Medico, Inc. C1 Univ Virginia, Sch Med, Div Biostat, Charlottesville, VA 22908 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Kuakini Med Ctr, Honolulu Heart Program, Honolulu, HI USA. NHLBI, Epidemiol & Biometry Program, Honolulu Epidemiol Res Sect, Honolulu, HI USA. Univ Hawaii, John A Burns Sch Med, Div Clin Epidemiol, Honolulu, HI 96822 USA. RP Abbott, RD (reprint author), Univ Virginia, Sch Med, Div Biostat, Box 600, Charlottesville, VA 22908 USA. FU NCRR NIH HHS [P20 RR/AI11091]; NHLBI NIH HHS [N01-HC-05102] NR 24 TC 26 Z9 26 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 15 PY 1998 VL 82 IS 2 BP 172 EP 178 DI 10.1016/S0002-9149(98)00310-5 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101MT UT WOS:000074873300009 PM 9678287 ER PT J AU Spencer, RGS Cox, TS Kaplan, PW AF Spencer, RGS Cox, TS Kaplan, PW TI Global T-wave inversion associated with nonconvulsive status epilepticus SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NIA, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. RP Spencer, RGS (reprint author), NIA, NIH, Baltimore, MD 21224 USA. NR 5 TC 7 Z9 7 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 15 PY 1998 VL 129 IS 2 BP 163 EP 164 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 101CL UT WOS:000074852000023 PM 9669983 ER PT J AU Wang, XT Martindale, JL Liu, YS Holbrook, NJ AF Wang, XT Martindale, JL Liu, YS Holbrook, NJ TI The cellular response to oxidative stress: influences of mitogen-activated protein kinase signalling pathways on cell survival SO BIOCHEMICAL JOURNAL LA English DT Article ID NF-KAPPA-B; INDUCED APOPTOSIS; JNK ACTIVATION; C-JUN; GAMMA-RADIATION; DEATH; CASCADE; PHOSPHORYLATION; INHIBITOR; INJURY AB The mammalian response to stress is complex, often involving multiple signalling pathways that act in concert to influence cell fate. To examine potential interactions between the signalling cascades, we have focused on the effects of a model oxidant stress in a single cell type through an examination of the relative influences of mitogen-activated protein kinases (MAPKs) as well as two proposed apoptosis regulators, nuclear factor kappa B (NF-kappa B) and Bcl-2, in determining cell survival. Treatment of HeLa cells with H2O2 resulted in a time- and dose-dependent induction of apoptosis accompanied by sustained activation of all three MAPK subfamilies: extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38. This H2O2-induced apoptosis was markedly enhanced when ERK2 activation was selectively inhibited by PD098059, Apoptosis decreased when JNK/SAPK activation was inhibited by expression of a dominant negative mutant form of SAPK/ERK kinase 1. Inhibition of the p38 kinase activity with p38-specific inhibitors SB202190 and SB203580 had no effect on cell survival. Because NF-kappa B activation by H2O2 is potentially related to both the ERK and JNK/SAPK signalling pathways, we examined the effects of inhibiting the activation of NF-kappa B; this interference had no effect on the cellular response to H2O2, Overexpression of the anti-apoptotic protein Bcl-2 significantly decreased the apoptosis seen after treatment with H2O2 without altering ERK or JNK/SAPK activities. Our results suggest that ERK and JNK/SAPK act in opposition to influence cell survival in response to oxidative stress, whereas neither p38 nor NF-kappa B affects the outcome. Bcl-2 acts independently and downstream of ERK and JNK/SAPK to enhance the survival of H2O2-treated cells. C1 NIA, Gene Express & Aging Sect, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. RP Holbrook, NJ (reprint author), NIA, Gene Express & Aging Sect, Biol Chem Lab, NIH, 5600 Nathan Shock Dr,Box 12, Baltimore, MD 21224 USA. RI Liu, Yusen/E-3527-2011 NR 47 TC 592 Z9 606 U1 2 U2 12 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 15 PY 1998 VL 333 BP 291 EP 300 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106AV UT WOS:000075108300009 PM 9657968 ER PT J AU Soh, Y Song, BJ Jeng, JJ Kallarakal, AT AF Soh, Y Song, BJ Jeng, JJ Kallarakal, AT TI Critical role of Arg(433) in rat transketolase activity as probed by site-directed mutagenesis SO BIOCHEMICAL JOURNAL LA English DT Article ID WERNICKE-KORSAKOFF-SYNDROME; PENTOSE BIOSYNTHESIS; SACCHAROMYCES-CEREVISIAE; 3-DIMENSIONAL STRUCTURE; NUCLEOTIDE-SEQUENCE; ALZHEIMERS-DISEASE; DEPENDENT ENZYME; ABNORMALITY; YEAST; GENE AB It has been shown that one arginine per monomer at an unknown position is essential for enzyme activity of the homodimeric transketolase (TK) [Kremer, Egan and Sable (1980) J. Biol. Chem. 255, 2405-2410]. To identify the critical arginine, four highly conserved arginine residues of rat TK (Arg(102), Arg(350), Arg(433) and Arg(506)) were replaced with alanine by site-directed mutagenesis. Wild-type and mutant TK proteins were produced in Escherichia coli and characterized. The Arg(102) --> Ala mutant exhibited similar catalytic activity to the wild-type enzyme, whereas Arg(350) --> Ala, Arg(506) --> Ala and Arg(433) --> Ala mutants exhibited 36.7, 37.0 and 6.1%, of the wild-type activity respectively. Three recombinant proteins (wild-type, Arg(350) --> Ala and Arg(433) --> Ala) were purified to apparent homogeneity using Ni2+-affinity chromatography and further characterized. All these proteins were able to form homodimers (148 kDa), as shown by immunoblot analysis subsequent to non-denaturing gel electrophoresis. The Arg(433) --> Ala mutant protein was less stable than the wild-type and Arg(350) --> Ala proteins at 55 degrees C. Kinetic analyses revealed that both V-max and K-m values were markedly affected in the Arg(433) -->Ala mutant. The K-m values for two substrates xylulose 5-phosphate and ribose 5-phosphate were 11.5- and 24.3-fold higher respectively. The k(cat)/K-m values of the Arg(433) --> Ala mutant for the two substrates were less than 1% of those of the wild-type protein. Molecular modelling of the rat TK revealed that Arg(433) of one monomer has three potential hydrogen-bond interactions with the catalytically important highly conserved loop of the other monomer. Thus, our biochemical analyses and modelling data suggest the critical role of the previously uncharacterized Arg(433) in TK activity. C1 NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 12501 Washington Ave, Rockville, MD 20852 USA. NR 32 TC 16 Z9 16 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 15 PY 1998 VL 333 BP 367 EP 372 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106AV UT WOS:000075108300018 PM 9657977 ER PT J AU Wolkersdorfer, GW Bornstein, SR AF Wolkersdorfer, GW Bornstein, SR TI Tissue remodelling in the adrenal gland SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE adrenal gland; apoptosis; interaction; zonation ID CLASS-II MOLECULES; BOVINE ADRENOCORTICAL-CELLS; MESSENGER-RIBONUCLEIC-ACID; NECROSIS-FACTOR-ALPHA; HLA CLASS-II; ANGIOTENSIN-II; IN-VIVO; MONOCLONAL-ANTIBODY; NUCLEAR ANTIGEN; C-FOS AB Adaptation of the adrenal gland to the demands of the organism is regulated functionally and structurally. Three common hypotheses on zonation in the adrenal-gland, the migrational, zonal, and transformation field theories, try independently to reconcile the findings on structure, proliferation, and cell death. The classical theories on zonation are revisited in the light of recent data on cell death and renewal; In accordance with data on cell death as immunoreactivity against FAS (CD 95), an apoptosis;inducing receptor, in situ end labelling of fragmented DNA, and ultrastructural analyses, programmed cell death (PCD) occurs throughout the whole organ. The angiotensin II receptor subtypes described in the adrenal allow an additional regulation of tissue homeostasis by proliferative and even by the antiproliferative effects of the angiotensin II type 2 receptor. Proto-oncogenes are involved in the regulation of cell cycle and PCD, and adrenocorticotropin asserts its tissue integrating and differentiating effects by regulating proto-oncogenes such as c-jun, c-Jos, jun-B and c-myc. Polypeptides involved in proliferation and DNA repair, such as proliferating cell nuclear antigen and Ki-67, have been found within zones of expected cell senescence. The expression of the class II major histocompatibility complex on normal adrenocortical cells allows cell-to-cell communication with the immune system and may trigger the Fas/Fas-ligand system to permit tissue regression and decreasing activity in both systems. In summary, new data allow us to reappraise and to reconcile the classical theories. Apoptosis is a physiological process in the adrenal gland. There is a differential regulation of apoptosis in the different zones. An investigation of this process may elucidate the basic mechanisms of adrenal zonation. (C) 1998 Elsevier Science Inc. C1 Univ Leipzig, Dept Internal Med 3, D-04103 Leipzig, Germany. NICHHD, NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Wolkersdorfer, GW (reprint author), Univ Leipzig, Dept Internal Med 3, Ph Rosenthal Str 27, D-04103 Leipzig, Germany. EM wolkg@server3.medizin.uni-leipzig.de NR 96 TC 41 Z9 43 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 15 PY 1998 VL 56 IS 2 BP 163 EP 171 DI 10.1016/S0006-2952(98)00067-7 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZZ819 UT WOS:000074770300003 PM 9698069 ER PT J AU Ciolino, HP Daschner, PJ Wang, TTY Yeh, GC AF Ciolino, HP Daschner, PJ Wang, TTY Yeh, GC TI Effect of curcumin on the aryl hydrocarbon receptor and cytochrome P450 1A1 in MCF-7 human breast carcinoma cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE curcumin; aryl hydrocarbon receptor; cytochrome P450 1A1; dimethylbenzanthracene; DNA adducts; MCF-7 cells ID RAT-LIVER; DNA; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; BINDING; CANCER; ANTIOXIDANT; COMPLEX; CYP1A1; LINES AB We examined the interaction of curcumin,a dietary constituent and chemopreventive compound, with the carcinogen activation pathway mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 mammary epithelial carcinoma cells. Curcumin caused a rapid accumulation.of cytochrome P450 1A1 (CYP1A1) mRNA in a time- and concentration-dependent manner, and CYP1A1 monooxygenase activity increased as measured by ethoxyresorufin-O-deethylation. Curcumin activated the DNA-binding capacity of the AhR for the xenobiotic responsive element of CYP1A1 as measured by the electrophoretic-mobility shift assay (EMSA). Curcumin was able to compete with the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin for binding to the AhR in isolated MCF-7 cytosol, indicating that it interacts directly with the receptor. Although curcumin could activate the AhR on its own, it partially inhibited the activation of AhR, as measured by EMSA, and partially decreased the accumulation of CYP1A1 mRNA caused by the mammary carcinogen dimethylbenzanthracene (DMBA). Curcumin competitively inhibited CYP1A1 activity in DMBA-treated cells and in microsomes isolated from DMBA-treated cells. Curcumin also inhibited the metabolic activation of DMBA, as measured by the formation of DMBA-DNA adducts, and decreased DMBA-induced cytotoxicity. These results suggest that the chemopreventive effect of curcumin may be due, in part, to its ability to compete with aryl hydrocarbons for both the AhR and CYP1A1. Curcumin may thus be a natural ligand and substrate of the AhR pathway. (C) 1998 Elsevier Science Inc. C1 NCI, Frederick Canc Res & Dev Ctr, LNMR,NIH, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Cellular Def & Carcinogenesis Sect, Div Basic Sci,NIH, Frederick, MD 21702 USA. RP Ciolino, HP (reprint author), NCI, Frederick Canc Res & Dev Ctr, LNMR,NIH, Div Basic Sci, Bldg 560,Rm 12-05,POB B, Frederick, MD 21702 USA. NR 32 TC 152 Z9 158 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 15 PY 1998 VL 56 IS 2 BP 197 EP 206 DI 10.1016/S0006-2952(98)00143-9 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZZ819 UT WOS:000074770300007 PM 9698073 ER PT J AU Parr, AL Drake, JC Gress, RE Schwartz, G Steinberg, SM Allegra, CJ AF Parr, AL Drake, JC Gress, RE Schwartz, G Steinberg, SM Allegra, CJ TI 5-fluorouracil-mediated thymidylate synthase induction in malignant and nonmalignant human cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE TS; 5-FU; chemotherapeutic drugs; enzyme induction; translational autoregulation ID CANCER; FLUOROURACIL; PROTEIN; QUANTITATION; INTERFERON; LEUCOVORIN; BINDING; GAMMA; LINE AB Thymidylate synthase (TS, EC 2.1.1.45) is an important: target enzyme for the fluoropyrimidines used in cancer chemotherapy. Studies have documented a 2- to 4-fold induction of TS protein following 5-fluorouracil (5-FU) treatment of malignant cells. We measured the effect that 5-FU exposure had on TS protein expression in nonmalignant human breast (MCF-10 and HBL-100), colorectal (ATCC Co18, Co112, and Co33), and bone marrow cells along with malignant breast (MCF-7) and colon (NCI-H630) cells. Twenty-four hours after plating, cells were treated with 0.01 to 10 mu M of 5-FU for a period of 24 hr. TS was quantitated by Western immunoblot using monoclonal antibody TS106. Absolute levels of TS in nonmalignant cells were substantially lower than in the malignant lines, ranging from approximately 40% in HBL-100 cells to less than 10% in the colon lines. An approximately two-fold induction in the level of TS was found for all cell lines examined, and there was a strong dependence on 5-FU exposure concentration in free TS levels of MCF-WT, and total TS levels of H630-WT, normal bone marrow, and MCF 10 cells. The induction of TS following 5-FU exposure is a generally observed phenomenon in both malignant and nonmalignant cells, suggesting that a selective means for inhibiting this induction may be critical for the development of alternative therapeutic strategies using 5-FU and the antifolate TS inhibitors. (C) 1998 Elsevier Science Inc. C1 Natl Naval Med Ctr, Natl Canc Inst, Med Branch, Bethesda, MD 20889 USA. NCI, Biostat & Data Management Sect, Div Clin Sci, Bethesda, MD 20892 USA. RP Parr, AL (reprint author), Natl Naval Med Ctr, Natl Canc Inst, Med Branch, Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM parra@navmed.nci.nih.gov NR 16 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 15 PY 1998 VL 56 IS 2 BP 231 EP 235 DI 10.1016/S0006-2952(98)00152-X PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZZ819 UT WOS:000074770300011 PM 9698077 ER PT J AU Yamazaki, H Inoue, K Chiba, K Ozawa, N Kawai, T Suzuki, Y Goldstein, JA Guengerich, FP Shimada, T AF Yamazaki, H Inoue, K Chiba, K Ozawa, N Kawai, T Suzuki, Y Goldstein, JA Guengerich, FP Shimada, T TI Comparative studies on the catalytic roles of cytochrome P450 2C9 and its Cys- and Leu-variants in the oxidation of Warfarin, flurbiprofen, and diclofenac by human liver microsomes SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE CYP2C9; polymorphism; warfarin; flurbiprofen; diclofenac; RT-PCR ID GENETIC-POLYMORPHISM; ALLELIC VARIANT; MEPHENYTOIN HYDROXYLATION; CYP2C SUBFAMILY; 4'-HYDROXYLATION; PURIFICATION; EXPRESSION; SUBSTRATE; METABOLISM; REDUCTASE AB S-Warfarin 7-hydroxylation, S-flurbiprofen 4'-hydroxylation, and diclofenac 4'-hydroxylation activities were determined in Liver microsomes of 30 humans of which 19 were wild-type (Arg144.Ile359), 8 were heterozygous Cys (Cys144.Ile359), and 3 were heterozygous Leu (Arg144.Leu359) allelic variants of the cytochrome P450 2C9 (CYP2C9) gene. All of the human samples examined contained P450 protein(s) immunoreactive with anti-CYP2C9 antibodies in liver microsomes. Individuals with the Cys144 allele of CYP2C9 had similar, but slightly lower, activities for the oxidations of these substrates than those of wild-type CYP2C9. One of the three human samples heterozygous for the Leu359 allele had very low V-max and high K-m values for the oxidation of three substrates examined, while the other two individuals gave kinetic parameters comparable to those seen in the wild-type and Cys144 CYP2C9. Reverse transcriptase-polymerase chain reaction analysis, however, showed that all of the three human samples with the heterozygous Leu359 variant were found to express both Ile359 and Leu359 variants at relatively similar extents in liver RNA of three humans. These results suggest that the Cys144 variant of CYP2C9 catalyzes the CYP2C9 substrates at rates comparative to, but slightly lower than, those of wild-type CYP2C9, while the Leu359-allelic variant has slower rates for the oxidation of these drug substrates. Activities for the oxidation-of these CYP2C9 substrates in humans with heterozygous Leu359 allele is likely to be dependent on the levels of expression of each of the wild- and Leu-variants in the livers. However, one of the humans with a heterozygous Leu allele was found to have very low activities towards the oxidation of CYP2C9 substrates. The basis of this defect in catalytic functions towards CYP2C9 substrates is unknown. (C) 1998 Elsevier Science Inc. C1 Osaka Prefectural Inst Publ Hlth, Higashinari Ku, Osaka 537, Japan. Pharmacia & Upjohn KK, Tsukuba Res Labs, Tsukuba, Ibaraki 30042, Japan. NIEHS, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. RP Shimada, T (reprint author), Osaka Prefectural Inst Publ Hlth, Higashinari Ku, 3-69 Nakamichi 1 Chome, Osaka 537, Japan. RI Suzuki, Yasuhiko/F-6890-2012; OI Yamazaki, Hiroshi/0000-0002-1068-4261 FU NCI NIH HHS [R35 CA44353]; NIEHS NIH HHS [P30 ES00267] NR 40 TC 125 Z9 128 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 15 PY 1998 VL 56 IS 2 BP 243 EP 251 DI 10.1016/S0006-2952(98)00133-6 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZZ819 UT WOS:000074770300013 PM 9698079 ER PT J AU Hogge, DE Willman, CL Kreitman, RJ Berger, M Hall, PD Kopecky, KJ McLain, C Tagge, EP Eaves, CJ Frankel, AE AF Hogge, DE Willman, CL Kreitman, RJ Berger, M Hall, PD Kopecky, KJ McLain, C Tagge, EP Eaves, CJ Frankel, AE TI Malignant progenitors from patients with acute myelogenous leukemia are sensitive to a diphtheria toxin-granulocyte-macrophage colony-stimulating factor fusion protein SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; HUMAN GM-CSF; MULTIDRUG-RESISTANCE; BLAST CELLS; IMMUNOTOXIN; EXPRESSION; RECEPTOR; MURINE; INTERLEUKIN-3 AB We have previously demonstrated that human granulocyte-macrophage colony-stimulating factor (GM-CSF) fused to a truncated diphtheria toxin (DT388-GMCSF) kills acute myelogenous leukemia (AML) cell lines bearing the GM-CSF receptor. We now report that exposure of malignant cells from 50 different patients with AML for 48 hours in culture to DT388-GMCSF reduces by a median of 1.6 logs (range, 0 to 3.7 logs) the number of leukemic cells capable of forming colonies in semisolid media (leukemic colony-forming cells [CFU-L]) with a median IC50 of 3 x 10(-12) mol/L (range, 5 to > 4,000 x 10(-12) mol/L), Furthermore, the cell kill is dependent on the presence of high-affinity GM-CSF receptors on leukemic blasts, because CFU-L from 27 of 28 AML samples expressing greater than or equal to 35 GM-CSF receptors per cell were inhibited by the toxin, whereas the colony growth from all 4 leukemic samples (2 AML, 1 acute lymphoblastic leukemia [ALL], and 1 prolymphocytic leukemia [PLL]) that had less than 35 receptors per cell was unaffected by the drug. Sensitivity of CFU-L to DT388-GMCSF was seen regardless of the clinical responsiveness of the patient's leukemia to standard chemotherapy agents. In contrast, clonogenic cells from normal bone marrow formed colonies at near control numbers after exposure to much higher toxin concentrations (4 x 10(-9) mol/L) than those required to kill CFU-L from most patients, Thus, leukemic progenitors isolated directly from the peripheral blood of most AML patients show the same sensitivity to DT388-GMCSF as previously demonstrated for AML cell lines. Under the same conditions of exposure, normal hematopoietic progenitors are relatively unaffected by DT388-GMCSF, suggesting its potential as a therapeutic agent in AML. (C) 1998 by The American Society of Hematology. C1 British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. Univ New Mexico, Ctr Canc, Dept Pathol, Albuquerque, NM 87131 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA. Fred Hutchinson Canc Res Ctr, SWOG, Ctr Stat, Seattle, WA 98104 USA. Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. RP Frankel, AE (reprint author), Hanes 4046,Med Ctr Dr, Winston Salem, NC 27157 USA. FU NCI NIH HHS [CA 12213, CA76178] NR 36 TC 43 Z9 44 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1998 VL 92 IS 2 BP 589 EP 595 PG 7 WC Hematology SC Hematology GA ZZ245 UT WOS:000074710100034 PM 9657759 ER PT J AU Gutierrez, MI Spangler, G Kingma, D Raffeld, M Guerrero, I Misad, O Jaffe, ES Magrath, IT Bhatia, K AF Gutierrez, MI Spangler, G Kingma, D Raffeld, M Guerrero, I Misad, O Jaffe, ES Magrath, IT Bhatia, K TI Epstein-Barr virus in nasal lymphomas contains multiple ongoing mutations in the EBNA-1 gene SO BLOOD LA English DT Article ID NUCLEAR ANTIGEN; CELL LYMPHOMAS; EPIDEMIOLOGY; DIAGNOSIS; INFECTION; CARCINOMA; SEQUENCE; DNA AB We have described 5 major subtypes of Epstein-Barr virus (EBV) based on variations in EBNA-1 sequences. These include P-ala (identical to the prototype B95.8 virus), P-thr, V-pro, V-leu, and V-val. Normal individuals often carry multiple EBV subtypes, the most common being P-ala, whereas EBV-associated tumors examined to date always contain a single subtype, which only on rare occasion is P-ala, The primary hypotheses that these observations generate are as follows: (1) Each of these EBV subtypes are naturally occurring, and in normal individuals the multiplicity of subtypes results from multiple infections. (2) EBV subtypes in normal individuals are generated in vivo from a single infecting virus subtype by mutations in EBNA-1. The second hypothesis essentially excludes the possibilities that the nonrandom association of certain subtypes with lymphomas is secondary to the geographic distribution of EBV subtypes and, if proven correct, could provide strong support for a direct role of EBV in tumorigenesis. In this report, we provide evidence for the latter hypothesis. We show that the P-ala EBV subtype present in most nasal lymphomas undergoes and accumulates multiple mutations consistent with the generation of variant species of EBNA-1 in vivo. This phenomenon is similar to the generation of quasispecies in RNA viruses and is the first description of in vivo generation of subtypes in DNA viruses. In RNA-based viruses, including human immunodeficiency virus and hepatitis C virus, the emergence of quasispecies is linked to replication infidelity and significantly influences disease processes through its effect on viral tropism, the emergence of viruses resistant to the host defenses or to therapy and pathogenicity. The present data thus raise important questions relating to the mechanisms whereby these mutations are generated in EBV and their relevance to the pathogenicity of EBV associated lymphomas. C1 NCI, Lymphoma Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol Pathol Sect, Pathol Branch, NIH, Bethesda, MD 20892 USA. Inst Nacl Enfermedades Neoplas, Lima, Peru. Ctr Invest Canc Maes Heller, Lima, OH USA. RP Bhatia, K (reprint author), NCI, Lymphoma Biol Sect, Pediat Oncol Branch, NIH, Bldg 10,Room 13N240,10 Ctr Dr MSC 1928, Bethesda, MD 20892 USA. EM BhatiaK@Pbmac.nci.nih.gov NR 23 TC 39 Z9 39 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1998 VL 92 IS 2 BP 600 EP 606 PG 7 WC Hematology SC Hematology GA ZZ245 UT WOS:000074710100036 PM 9657761 ER PT J AU Dawsey, SM Fleischer, DE Wang, GQ Zhou, B Kidwell, JA Lu, N Lewin, KJ Roth, MJ Tio, TL Taylor, PR AF Dawsey, SM Fleischer, DE Wang, GQ Zhou, B Kidwell, JA Lu, N Lewin, KJ Roth, MJ Tio, TL Taylor, PR TI Mucosal iodine staining improves endoscopic visualization of squamous dysplasia and squamous cell carcinoma of the esophagus in Linxian, China SO CANCER LA English DT Article DE endoscopy; iodine staining; early detection; esophageal neoplasms; squamous cell carcinoma; precursor lesions; China ID LUGOL DYE ENDOSCOPY; CANCER; DIAGNOSIS; RESECTION; LESIONS; HISTOLOGY; POPULATION; STOMACH; TRIAL; HEAD AB BACKGROUND. In previous studies in the high risk population of Linxian, China, the majority of foci of high grade (moderate and severe) squamous dysplasia (HGD) and invasive squamous carcinoma (CA) of the esophagus were associated with endoscopically visible lesions that could be targeted for biopsy, but some foci of HGD were missed by routine endoscopic examination. This study examined whether spraying the mucosa with Lugol's iodine solution, which stains normal epithelium brown but leaves dysplasia and carcinoma unstained, could improve endoscopic detection and delineation of these lesions. METHODS. Two hundred twenty-five Linxian adults with balloon cytologic evidence of dysplasia or carcinoma underwent endoscopy. All visible lesions were described and photographed before and after staining with 1.2% Lugol's iodine solution. Biopsies were taken from all lesions visible before staining, from all unstained lesions (USLs) after applying the stain, and from representative control areas of stained mucosa. RESULTS. Two hundred fifty-three USLs and 255 control sites were biopsied. No complications occurred. Ninety-four biopsy sites contained HGD and 20 contained CA. Before staining, the sensitivity of visible lesions for identifying HGD or CA was 62%, and the specificity was 79%. After staining, the sensitivity of USLs for identifying HGD or CA was 96%, and the specificity was 63%. Eighty-eight percent of the HGD and CA lesions were larger or more clearly defined after staining. The diagnostic lesions in 17 of 31 patients with moderate dysplasia (55%), 8 of 35 patients with severe dysplasia (23%), and none of the 19 patients with invasive carcinoma (0%) were identified only after staining. CONCLUSIONS. Mucosal iodine staining improved endoscopic detection and delineation of HGD and CA in these patients. This simple technique is highly sensitive for identifying these precursor and invasive squamous lesions, and it should be used whenever optimal visualization of squamous mucosal abnormalities is required. Cancer 1998;83:220-31. (C) 1998 American Cancer Society. C1 NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Georgetown Univ Hosp, Div Gastroenterol, Washington, DC 20007 USA. Chinese Acad Med Sci, Inst Canc, Dept Endoscopy, Beijing 100021, Peoples R China. Chinese Acad Med Sci, Inst Canc, Dept Cytol, Beijing 100021, Peoples R China. Chinese Acad Med Sci, Inst Canc, Dept Pathol, Beijing 100021, Peoples R China. RP Dawsey, SM (reprint author), NCI, Canc Prevent Studies Branch, 6006 Execut Blvd,Room 321,MSC 7058, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CN-45586] NR 62 TC 148 Z9 165 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 15 PY 1998 VL 83 IS 2 BP 220 EP 231 PG 12 WC Oncology SC Oncology GA ZY706 UT WOS:000074651200004 PM 9669803 ER PT J AU Risinger, JI Umar, A Glaab, WE Tindall, KR Kunkel, TA Barrett, JC AF Risinger, JI Umar, A Glaab, WE Tindall, KR Kunkel, TA Barrett, JC TI Single gene complementation of the hPMS2 defect in HEC-1-A endometrial carcinoma cells SO CANCER RESEARCH LA English DT Article ID MISMATCH REPAIR DEFICIENCY; MICROSATELLITE INSTABILITY; HETERODUPLEX REPAIR; TUMOR-CELLS; CANCER; TOLERANCE; MUTATION; EXTRACTS; LINES; MICE AB Results from the analysis of human tumor cell lines with mutations in DNA mismatch repair genes have contributed to the understanding of the functions of these gene products in DNA mismatch repair, microsatellite instability, cell cycle checkpoint control, transcription-coupled nucleotide excision repair, and resistance to cytotoxic agents. However, complementation of human DNA mismatch repair defects by introduction of a single cloned gene or cDNA,,which would serve to directly prove or disprove their involvement in these processes, has not been accomplished. sere, we introduce a wild-type copy of the hPMS2 cDNA by stable transfection into the PMS2 mutant HEC-1-A cell Line. HEC-1-A cells expressing wild type hPMS2 exhibit increased microsatellite stability, have a reduced mutation rate at the endogenous hypoxanthine phosphoribosyltransferase locus and extracts from these cells are able to perform strand-specific mismatch repair, These results demonstrate that the hPMS2 gene is integral to the maintenance of genome stability. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233,Mail Drop C215, Res Triangle Pk, NC 27709 USA. NR 22 TC 36 Z9 36 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1998 VL 58 IS 14 BP 2978 EP 2981 PG 4 WC Oncology SC Oncology GA 101DQ UT WOS:000074854700015 PM 9679958 ER PT J AU Butler, AA Blakesley, VA Tsokos, M Pouliki, V Wood, TL LeRoith, D AF Butler, AA Blakesley, VA Tsokos, M Pouliki, V Wood, TL LeRoith, D TI Stimulation of tumor growth by recombinant human insulin-like growth factor-I (IGF-I) is dependent on the dose and the level of IGF-I receptor expression SO CANCER RESEARCH LA English DT Article ID CELLULAR PROLIFERATION; TRANSGENIC MICE; GENE-EXPRESSION; SUPPRESSOR WT1; HUMAN CANCER; TUMORIGENESIS; INHIBITION; CELLS; APOPTOSIS; OVEREXPRESSION AB The insulin-like growth factors (IGF) I and II regulate metabolism, mitogenesis, differentiation, and apoptosis, The therapeutic uses of IGF-I have been discussed extensively; however, excessive activity of the IGF Ligands and IGF-I receptor has been suggested as a factor in tumorigenesis, The inhibition of apoptosis by IGF-I is believed to be particularly important for the stimulation of tumor growth, This study examined whether systemic recombinant human IGF-I (rhIGF-I) therapy affects the growth of fibrosarcomas derived from fibroblasts expressing the IGF-I receptor at high or naturally occurring densities (1.9 x 10(5) compared with 1.6 x 10(4) IGF-I receptors/cell) in athymic nude mice. Treatment with 4 or 10 mg/kg rhIGF-I resulted in a marked reduction in the tumor latency and stimulated the growth of fibrosarcomas that overexpressed the IGF-I receptor. The latency and growth of fibrosarcomas expressing parental levels of the IGF-I receptor were not affected by rhIGF-I therapy. Analysis of mitosis by histone H3 mRNA in situ hybridization and of apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling assay indicated that rNGF-I-stimulated tumor growth was associated with a marked increase in mitogenesis; however, there was no evidence for any significant effect on apoptosis, These data imply that: (a) systemic rhIGF-I can stimulate the growth of tumors directly by stimulating mitosis; and (b) a reasonable level of IGF-I receptor expression is required for stimulation of tumor growth by systemic rhIGF-I. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Pathol Lab, NIH, Bethesda, MD 20892 USA. Penn State Univ, Coll Med, Dept Anat & Neurosci, Hershey, PA 17033 USA. RP LeRoith, D (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10,Room 8S235A,10 Ctr Dr,MSC 1770, Bethesda, MD 20892 USA. NR 48 TC 62 Z9 64 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1998 VL 58 IS 14 BP 3021 EP 3027 PG 7 WC Oncology SC Oncology GA 101DQ UT WOS:000074854700023 PM 9679966 ER PT J AU Harada, M Tamada, K Abe, K Yasumoto, K Kimura, G Nomoto, K AF Harada, M Tamada, K Abe, K Yasumoto, K Kimura, G Nomoto, K TI Role of the endogenous production of interleukin 12 in immunotherapy SO CANCER RESEARCH LA English DT Article ID LYMPHOCYTE MATURATION FACTOR; CELL STIMULATORY FACTOR; IFN-GAMMA PRODUCTION; MHC CLASS-I; T-CELLS; MEDIATED-IMMUNITY; LEISHMANIA-MAJOR; TUMOR-REGRESSION; DENDRITIC CELLS; CD40 LIGAND AB Previous studies demonstrated that injecting mice with the cytokine interleukin 12 (IL-12) could significantly suppress the growth of a number of tumors, including murine B16 melanoma. In this report, the persistence of the antitumor effects of IL-12 is investigated. The i.p. injection of IL-12 (0.1 mu g) on days 14, 16, 18, 20, and 22 was found to significantly suppress the growth of s.c. inoculated B16 melanoma for up to 2 weeks after the last injection of IL-12, Interestingly, the IL-12 serum level 4 days after the last injection of IL-12 was significantly elevated in tumor-bearing mice compared with that of IL-12-treated normal mice. The in vivo depletion of either CD4(+) or CD8(+) T cells abrogated the antitumor activity of IL-12 and diminished the apparent autocrine stimulation of IL-12 release seen after IL-12 treatment. Resection of the tumor-draining lymph nodes (LNs) but not of the spleen abrogated the antitumor effect of IL-12 treatment as well as the elevation of serum IL-12, Expression of mRNA encoding IL-12 as well as CD40 Ligand (CD40L) was detected in the tumor-draining LNs but not in the spleen of tumor-bearing mice after IL-12 treatment. Furthermore, the antitumor activity observed after IL-12 treatment was diminished by the in vivo administration of either anti-IL-12 or anti-CD40L monoclonal antibodies. Collectively, these results suggest that the endogenous production of IL-12 resulting from the CD40-CD40L interaction between antigen-presenting cells and CD4(+) T cells in the tumor-draining LNs may play a role in the persistence of the antitumor effects seen after IL-12 treatment. C1 Kyushu Univ, Dept Virol, Med Inst Bioregulat, Fukuoka 81282, Japan. Kyushu Univ, Dept Immunol, Med Inst Bioregulat, Fukuoka 81282, Japan. Univ Occupat & Environm Hlth, Dept Surg 2, Kitakyushu, Fukuoka 807, Japan. RP Harada, M (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. NR 27 TC 14 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1998 VL 58 IS 14 BP 3073 EP 3077 PG 5 WC Oncology SC Oncology GA 101DQ UT WOS:000074854700030 PM 9679973 ER PT J AU Takayama, S Krajewski, S Krajewska, M Kitada, S Zapata, JM Kochel, K Knee, D Scudiero, D Tudor, G Miller, GJ Miyashita, T Yamada, M Reed, JC AF Takayama, S Krajewski, S Krajewska, M Kitada, S Zapata, JM Kochel, K Knee, D Scudiero, D Tudor, G Miller, GJ Miyashita, T Yamada, M Reed, JC TI Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 and its variants in normal tissues and tumor cell lines SO CANCER RESEARCH LA English DT Article ID IN-VIVO; IMMUNOHISTOCHEMICAL ANALYSIS; BCL-2 PROTEIN; CLONING; DEATH; IDENTIFICATION; LOCALIZATION; GENE; DNA AB BAG-1 is a multifunctional protein that blocks apoptosis and interacts with several types of proteins, including Bcl-2 family proteins, the kinase Raf-1, certain tyrosine kinase growth factor receptors, and steroid hormone receptors, possibly by virtue of its ability to regulate the Hsp70/Hsc70 family of molecular chaperones. Two major forms of the human and mouse BAG-1 proteins were detected by immunoblotting. The longer human and mouse BAG-1 proteins (BAG-1L) appear to arise through translation initiation at noncanonical CTG codons located upstream of and in-frame with the usual ATG codon used for production of the originally described BAG-1 protein. Immunoblotting experiments using normal tissues revealed that BAG-1L is far more restricted in its expression and is present at lower levels than the more prevalent BAG-1 protein. Human but not mouse tissues also produce small amounts of an additional isoform of BAG-1 of intermediate size (BAG-1M) that probably arises through translation initiation at yet another site involving an ATG codon. All three isoforms of human BAG-1 (BAG-1, BAG-1M, and BAG-1L) retained the ability to bind Hsc70. Subcellular fractionation and immunofluorescence confocal microscopy studies indicated that BAG-1L often resides in the nucleus, consistent with the presence of a nuclear localization sequence in the NH2-terminal unique domain of this protein. In immunohistochemical assays, BAG-1 immunoreactivity was detected in a wide variety of types of cells in normal adult tissues and was localized to either cytosol, nucleus, or both, depending on the particular type of cell. In some cases, cytosolic BAG-1 immunostaining was clearly associated with organelles resembling mitochondria, consistent with the reported interaction of BAG-1 with Bcl-2 and related proteins. Furthermore, experiments using a green fluorescence protein (GFP)-BAG-1 fusion protein demonstrated that overexpression of Bcl-2 in cultured cells can cause intracellular redistribution of GFP-BAG-1, producing a membranous pattern typical of Bcl-2 family proteins. The BAG-1 protein was found at high levels in several types of human tumor cell lines among the 67 tested, particularly leukemias, breast, prostate, and colon cancers. In contrast to normal tissues, which only rarely expressed BAG-1L, tumor cell lines commonly contained BAG-1L protein, including most prostate, breast, and leukemia cell lines, suggesting that a change in BAG-1 mRNA translation frequently accompanies malignant transformation. C1 Burnham Inst, La Jolla, CA 92037 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Natl Childrens Med Res Ctr, Dept Genet, Tokyo 154, Japan. RP Reed, JC (reprint author), Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Zapata, Juan/J-6304-2014 OI Zapata, Juan/0000-0002-0110-0009 FU NCI NIH HHS [CA67329] NR 32 TC 171 Z9 185 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1998 VL 58 IS 14 BP 3116 EP 3131 PG 16 WC Oncology SC Oncology GA 101DQ UT WOS:000074854700037 PM 9679980 ER PT J AU Guo, NH Zabrenetzky, VS Chandrasekaran, L Sipes, JM Lawler, J Krutzsch, HC Roberts, DD AF Guo, NH Zabrenetzky, VS Chandrasekaran, L Sipes, JM Lawler, J Krutzsch, HC Roberts, DD TI Differential roles of protein kinase C and pertussis toxin-sensitive G-binding proteins in modulation of melanoma cell proliferation and motility by thrombospondin 1 SO CANCER RESEARCH LA English DT Article ID INTEGRIN-ASSOCIATED PROTEIN; HEPARIN-BINDING; I REPEATS; PLATELET THROMBOSPONDIN; EXTRACELLULAR-MATRIX; SIGNAL TRANSDUCTION; TYROSINE KINASES; TUMOR-GROWTH; ADHESION; CHEMOTAXIS AB Thrombospondin 1 (TSP1) is an angiogenesis inhibitor that decreases tumor growth. We non report that TSP1 directly inhibits the proliferation of human melanoma cells. TSP1, peptides, and a recombinant fragment from the type I repeats, but not peptides that bind CD36 or CD47, inhibit the proliferation of A2058 melanoma cells. In contrast, chemotaxis is mediated by peptides or recombinant fragments from the procollagen, type I, type III, and cell-binding domains. The antiproliferative activity of TSP1 is mediated by a different signal transduction pathway than those mediating motility responses to the same protein, Activators of protein kinase A and protein kinase C inhibit chemotaxis but not the antiproliferative activity of TSP1, whereas the antiproliferative activity is reversed by inhibiting the tyrosine kinase or phosphatase activities. TSP1-mediated chemotaxis is partially dependent on a pertussis toxin (PT)-sensitive G-binding protein, whereas haptotaxis is not. Chemotaxis stimulated by the procollagen domain and the CD47-binding sequences from the COOH-terminal domain are also sensitive to PT, but responses to the type I and type III domains are not sensitive to PT. Residual chemotaxis to TSP1 in the presence of PT may therefore be mediated by the activities of the type I or type III repeats. Thus, TSP1 elicits several intracellular signals in melanoma tells that result from interactions with several domains of this protein and differentially affect growth and motility. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 66 TC 38 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1998 VL 58 IS 14 BP 3154 EP 3162 PG 9 WC Oncology SC Oncology GA 101DQ UT WOS:000074854700041 PM 9679984 ER PT J AU Lai, CJ Bray, M Men, R Cahour, A Chen, W Kawano, H Tadano, M Hiramatsu, K Tokimatsu, I Pletnev, A Arakai, S Shameem, G Rinaudo, M AF Lai, CJ Bray, M Men, R Cahour, A Chen, W Kawano, H Tadano, M Hiramatsu, K Tokimatsu, I Pletnev, A Arakai, S Shameem, G Rinaudo, M TI Evaluation of molecular strategies to develop a live dengue vaccine SO CLINICAL AND DIAGNOSTIC VIROLOGY LA English DT Article DE dengue virus; dengue haemorrhagic fever dengue shock syndrome (DHF/DSS); deletion mutants; chimeric viruses; live vaccine ID NUCLEOTIDE-SEQUENCE; SECONDARY STRUCTURE; TYPE-4 VIRUS; GENOME RNA; REGION; GENES; NEUROVIRULENCE; CONSTRUCTION; EXPRESSION; PROTEINS AB Background: Millions of individuals are estimated to become infected with dengue virus each year, particularly in tropical and subtropical regions. Mortality is low but infection can lead to a severe form of dengue, characterised by haemorrhage and shock. A safe and effective vaccine against dengue is still not available. Objective: To use the successful construction of dengue type 4 virus (DEN4) cDNA, which yields infectious RNA transcripts, to provide a new approach to the development of safe and effective dengue vaccines. Study design: The 3' and 5' noncoding (NC) regions of the genome were targeted to construct DEN4 deletion mutants, because the sequences in these regions are thought to play an important role in the regulation of viral replication DEN4 cDNA was also employed to construct a viable chimeric virus with dengue type 1, 2 or 3 antigenicity, by substitution of heterotypic structural protein genes. Results: Most viable mutants, recovered from the cDNA constructs, were partially restricted for growth in simian cells as analysed by plaque morphology assay and viral yield analysis. Several 3' NC deletion mutants which exhibited a range of growth restriction in cell culture were further evaluated for infectivity and immunogenicity in rhesus monkeys. Occurrence and duration of viraemia were reduced for these deletion mutants, compared to the wild type DEN4. Analysis of antibody response to infection in rhesus monkeys also indicated that some of these mutants were attenuated. These DEN4 deletion mutants represent promising live dengue vaccine candidates that merit further clinical evaluation. Chimera DEN1/DEN4 or DEN2/DEN4 which expresses DEN1 or DEN2 antigenicity were also used to infect monkeys. Most monkeys immunised with these chimeric viruses, singly or in combination, developed high titres of neutralising antibodies and were protected against homotypic wild type DEN1 or DEN2 challenge. Conclusions: DEN4 and its derived chimeric viruses of other three dengue serotype specificity, that contain appropriate attenuating mutations, have a potential use in a tetravalent live vaccine against dengue. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIAID, Infect Dis Lab, Mol Viral Biol Sect, NIH, Bethesda, MD 20892 USA. RP Lai, CJ (reprint author), NIAID, Infect Dis Lab, Mol Viral Biol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM clai@atlas.niaid.nih.gov NR 25 TC 25 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0197 J9 CLIN DIAGN VIROL JI Clin. Diagn. Virol. PD JUL 15 PY 1998 VL 10 IS 2-3 BP 173 EP 179 DI 10.1016/S0928-0197(98)00035-X PG 7 WC Virology SC Virology GA 116QR UT WOS:000075736500011 PM 9741643 ER PT J AU Guidry, G Landis, SC AF Guidry, G Landis, SC TI Target-dependent development of the vesicular acetylcholine transporter in rodent sweat gland innervation SO DEVELOPMENTAL BIOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; CHOLINERGIC SYMPATHETIC INNERVATION; NEUROTRANSMITTER PLASTICITY INVIVO; VASOACTIVE INTESTINAL POLYPEPTIDE; CILIARY GANGLION NEURONS; DIFFERENTIATION FACTORS; SYNAPTIC VESICLES; ACETYLTRANSFERASE; EXPRESSION; IMMUNOREACTIVITY AB Descriptive studies have delineated a developmental change in neurotransmitter phenotype from noradrenergic to cholinergic in the sympathetic innervation of sweat glands in rodent footpads. Transplantation and culture experiments provide evidence that interactions with the target tissue induce this change. Recent studies with an antiserum that recognizes the vesicular acetylcholine transporter (VAChT) suggest, however, that the development of cholinergic function in sympathetic neurons, including those that innervate sweat glands, occurs prior to and does not require target contact. To clarify these apparently contradictory findings, we directly compared the appearance of VAChT immunoreactivity in the sympathetic neurons that innervate sweat glands with the time that axons contact this target. We find that VAChT immunoreactivity is not detectable in either the axons or cell bodies of sweat gland neurons until several days after target innervation. Before and during VAChT acquisition, the developing sweat gland innervation contains vesicular stores of catecholamines. An analysis of mutant mice that lack sweat glands was undertaken to determine whether VAChT expression requires target interactions and revealed that VAChT does not appear in the absence of glands. These findings, together with previous studies, confirm the target dependence of cholinergic function in the sympathetic neurons that innervate sweat glands. (C) 1998 Academic Press. C1 NINDS, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. RP Guidry, G (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. NR 49 TC 50 Z9 50 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 1998 VL 199 IS 2 BP 175 EP 184 DI 10.1006/dbio.1998.8929 PG 10 WC Developmental Biology SC Developmental Biology GA 110DQ UT WOS:000075365200001 PM 9698438 ER PT J AU Rebagliati, MR Toyama, R Fricke, C Haffter, P Dawid, IB AF Rebagliati, MR Toyama, R Fricke, C Haffter, P Dawid, IB TI Zebrafish nodal-related genes are implicated in axial patterning and establishing left-right asymmetry SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Danio rerio; zebrafish; nodal-related; forebrain; mesoderm; left-right asymmetry; organizer ID PROTEIN-KINASE-A; BETA-LIKE GENE; SPEMANN ORGANIZER; MESODERM INDUCTION; XENOPUS-EMBRYOS; MUTANT EMBRYOS; WILD-TYPE; NO TAIL; EXPRESSION; SPECIFICATION AB Nodal-related 1 (ndr1) and nodal-related 2 (ndr2) genes in zebrafish encode members of the nodal subgroup of the transforming growth factor-beta superfamily. We report the expression patterns and functional characteristics of these factors, implicating them in the establishment of dorsal-ventral polarity and left-right asymmetry. Ndr1 is expressed maternally, and ndr2 and ndr2 are expressed during blastula stage in the blastoderm margin. During gastrulation, ndr expression subdivides the shield into two domains: a small group of noninvoluting cells, the dorsal forerunner cells, express ndr1, while ndr2 RNA is found in the hypoblast layer of the shield and later in notochord, prechordal plate, and overlying anterior neurectoderm. During somitogenesis, ndr2 is expressed asymmetrically in the lateral plate as are nodal-related genes of other organisms, and in a small domain in the left diencephalon, providing the first observation of asymmetric gene expression in the embryonic forebrain. RNA injections into Xenopus animal caps showed that Ndr1 acts as a mesoderm inducer, whereas Ndr2 is an efficient neural but very inefficient mesoderm inducer. We suggest that Ndr1 has a role in mesoderm induction, while Ndr2 is involved in subsequent specification and patterning of the nervous system and establishment of laterality. (C) 1998 Academic Press. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Max Planck Inst Entwicklungsbiol, D-72076 Tubingen, Germany. RP Rebagliati, MR (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 79 TC 211 Z9 215 U1 1 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 1998 VL 199 IS 2 BP 261 EP 272 DI 10.1006/dbio.1998.8935 PG 12 WC Developmental Biology SC Developmental Biology GA 110DQ UT WOS:000075365200009 PM 9698446 ER PT J AU Reszka, KJ Matuszak, Z Chignell, CF AF Reszka, KJ Matuszak, Z Chignell, CF TI Lactoperoxidase-catalyzed oxidation of melanin by reactive nitrogen species derived from nitrite (NO2-): An EPR study SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE EPR; melanin; nitrite; nitrogen dioxide radical; lactoperoxidase; free radical ID HYDROGEN-PEROXIDE; FREE-RADICALS; DIOXIDE; OXIDE; MECHANISM; DEGRADATION; POTENTIALS; RESONANCE; REDUCTION; NITRATION AB The reaction of synthetic DOPA melanin (DM) with lactoperoxidase (LPO), hydrogen peroxide, and nitrite (NO2-) has been investigated using EPR. We observed that in the presence of nitrite LPO/H2O2 generated large amount of melanin radicals, as evidenced by a strong, up to Ii-fold, increase in the intensity of the melanin EPR signal. In contrast, when nitrite was omitted the increase was much less, ca. 30%, which, nevertheless, indicates that DM can be metabolized directly by LPO/H2O2. When the nitrite was present, the concentration of melanin radicals was linearly dependent on [NO2-] (for [NO2-] <5 mM), and increased when [LPO] and [H2O2] increased (at constant [NO2-]). We propose that the mechanism for the generation of melanin radicals by the LPO/H2O2/nitrite system involves oxidation of NO2- by LPO/H2O2 to a reactive metabolite, most likely the nitrogen dioxide radical ((NO2)-N-.), which subsequently reacts with melanin 5,6-dihydroxyindole subunits producing the respective semiquinone radicals. Because melanin and (NO2)-N-. generating systems (nitrite, peroxidase enzymes, hydrogen peroxide) may coexist in cells in vivo, our results suggest that melanin could function as a natural scavenger of this highly reactive nitrogen species. This property may be relevant to the physiological functions of the melanin pigments in vivo. (C) 1998 Elsevier Science Inc. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Reszka, KJ (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM RESZKA@NIEHS.NIH.GOV NR 44 TC 22 Z9 22 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUL 15 PY 1998 VL 25 IS 2 BP 208 EP 216 DI 10.1016/S0891-5849(98)00058-6 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA ZW039 UT WOS:000074367500011 PM 9667498 ER PT J AU Gao, JL Chen, H Filie, JD Kozak, CA Murphy, PM AF Gao, JL Chen, H Filie, JD Kozak, CA Murphy, PM TI Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse SO GENOMICS LA English DT Article ID FORMYL PEPTIDE RECEPTOR; CHEMOTACTIC RECEPTOR; CDNA; IDENTIFICATION; EXPRESSION; CHEMOATTRACTANTS; PURIFICATION; LEUKOCYTES; HOMOLOG; CLONING AB The humam formylpeptide receptor (FPR) gene cluster has three members: FPR1 and FPRL1, which are expressed in neutrophils and monocytes and encode seven-transmembrane-domain chemotactic receptors specific for N-formylpeptides, and FPRL2, whose function is unknown. The FPRL1 receptor is also a lipoxin A4 receptor. Using probes for the three human genes we have cloned six distinct mouse genes, designated Fpr1 and Fpr-rs1 through Fpr-rs5 which form a cluster on chromosome 17 in a region of conserved synteny with human chromosome 19. Fpr1 encodes a functional receptor and is clearly the orthologue of FPR1.. Both Fpr-rs1 and Fpr-rs2 have higher sequence homology to FPRL1 than to FPRL2; Fpr-rs1 is 97% identical in amino acid sequence to a previously reported cDNA that encodes a lipoxin A4 receptor, whereas the putative ligand for Fpr-rs2 is unknown. Fpr-rs3, Fpr-rs4, and Fpr-rs5 appear to lack human counterparts and are most similar in sequence to FPRL1. RNA for Fpr1, Fpr-rs1, and Fpr-rs2 is present in leukocytes, spleen, and lung whereas RNA for Fpr-rs3 was detected only in skeletal muscle. We did not detect Fpr-rs4 or Fpr-rs5 RNA in any tissue tested. Moreover, Fpr-rs5 has a stop codon in the protein-coding region corresponding to transmembrane domain VI and may not encode a functional receptor. These results suggest that the FPR gene cluster has undergone differential expansion in mammals with FPRL2, Fpr-rs2, Fpr-rs3, Fpr-rs4, and Fpr-rs5 arising after divergence of human and mouse. (C) 1998 Academic Press. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Gao, JL (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N113, Bethesda, MD 20892 USA. NR 31 TC 86 Z9 92 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 15 PY 1998 VL 51 IS 2 BP 270 EP 276 DI 10.1006/geno.1998.5376 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 111WK UT WOS:000075461300013 PM 9722950 ER PT J AU Cole, KA Chuaqui, RF Katz, K Pack, S Zhuang, ZP Cole, CE Lyne, JC Linehan, WM Liotta, LA Emmert-Buck, MR AF Cole, KA Chuaqui, RF Katz, K Pack, S Zhuang, ZP Cole, CE Lyne, JC Linehan, WM Liotta, LA Emmert-Buck, MR TI cDNA sequencing and analysis of POV1 (PB39): A novel gene up-regulated in prostate cancer SO GENOMICS LA English DT Article ID IDENTIFICATION; HYBRIDIZATION; KAI1 AB We recently identified a novel gene (PB39) (HGMW-approved symbol POV1) whose expression is up-regulated in human prostate cancer using tissue microdissection-based differential display analysis. In the present study we report the fall-length sequencing of PB39 cDNA, genomic localization of the PB39 gene, and genomic sequence of the mouse homologue. The foil-length human cDNA is 2317 nucleotides in length and contains an open reading frame of 559 amino acids which does not show homology with any reported human genes. The N-terminus contains charged amino acids and a helical loop pattern suggestive of an srp leader sequence for a secreted protein. Fluorescence in situ hybridization using PB39 cDNA as probe mapped the gene to chromosome 11p11.1-p11.2. Comparison of PB39 cDNA sequence with murine sequence available in the public database identified a region of previously sequenced mouse genomic DNA showing 67% amino acid sequence homology with human PB39. Based on alignment and comparison to the human cDNA the mouse genomic sequence suggests there are at least 14 exons in the mouse gene spread over approximately 100 kb of genomic sequence. Further analysis of PB39 expression in human tissues shows the presence of a unique splice variant mRNA that appears to be primarily associated with fetal tissues and tumors. Interestingly, the unique splice variant appears in prostatic intraepithelial neoplasia, a microscopic precursor lesion of prostate cancer. The current data support the hypothesis that PB39 plays a role in the development of human prostate cancer and will be useful in the analysis of the gene product ire further human and murine studies. (C) 1998 Academic Press. C1 NCI, Pathol Lab, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NCI, NIH, Bethesda, MD 20894 USA. NCI, Urol Oncol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathol Lab, Div Clin Sci, NIH, 10-2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mbuck@helix.nih.gov RI Pack, Svetlana/C-2020-2014; Cole, Kristina/M-3922-2015 NR 14 TC 27 Z9 29 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 15 PY 1998 VL 51 IS 2 BP 282 EP 287 DI 10.1006/geno.1998.5359 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 111WK UT WOS:000075461300015 PM 9722952 ER PT J AU O'Brien, SJ AF O'Brien, SJ TI AIDS: A role for host genes SO HOSPITAL PRACTICE LA English DT Article ID HIV-1 INFECTION; RESISTANCE AB Suspicion that human genes affect the natural history of AIDS has been confirmed by discoveries of three such genes, one of which confers near-total immunity in about 1% of Caucasians. The findings suggest a novel therapeutic target: not HIV but the hosts cooperation with it. They also herald an era in which genomes are seen as having been shaped by the evolutionary pressures of infection, and may thus hold evolution-tested therapies. C1 NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21701 USA. NR 12 TC 16 Z9 17 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD JUL 15 PY 1998 VL 33 IS 7 BP 53 EP + PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 100GR UT WOS:000074808400004 PM 9679506 ER PT J AU Hatch, CL Goodman, SN AF Hatch, CL Goodman, SN TI Perceived value of providing peer reviewers with abstracts and preprints of related published and unpublished papers SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 3rd International Congress on Peer Review in Biomedical Publication CY SEP, 1997 CL PRAGUE, CZECH REPUBLIC SP Journal of the Amer Med Assoc, British Med J, Project HOPE ID QUALITY AB Context.-Many journals provide peer reviewers with written instructions regarding review criteria,such as the originality of results, but little research has been done to investigate ways to improve or facilitate the peer review task. Objective.-To assess the value that peer reviewers place on receipt of supplemental materials (eg, abstracts of related papers and preprints of related unpublished manuscripts). Design.-Questionnaire survey sent to all 733 peer reviewers recruited by the Journal of the National Cancer Institute to review 356 manuscripts consecutively sent out for review from February 24, 1997, through January 16, 1998. The inclusion of supplemental materials with manuscript review packages was optional. Main Outcome Measure.-The peer reviewers' assessment of the actual or potential usefulness of supplemental materials on the performance of peer review. Results.-A total of 481 (66%) of 733 questionnaires were returned, Of the 471 respondents' questionnaires that could be used, 217 (46%) indicated that they received abstracts, and 44 (10%) of 458 respondents indicated that they received preprints. Higher proportions of peer reviewers who received supplemental materials than those who had not received them felt that they were (or would be) useful to them when reviewing the manuscript (63% [95% confidence interval (CI), 57%-69%] vs 45% [95% CI, 38%-52%]; P < .001) and to the peer review process in general (80% [95% CI, 75%-85%] vs 64% [95% CI, 58%-70%]; P <,001). Conclusion.-The majority of respondents indicated that supplemental materials helped (or would have helped) them evaluate manuscripts and valued them more highly when they actually received them. C1 Journal Natl Canc Inst, Bethesda, MD USA. Johns Hopkins Univ, Div Biostat, Baltimore, MD 21205 USA. RP Hatch, CL (reprint author), Execut Plaza N,Room 635H,6130 Execut Blvd, Rockville, MD 20892 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 15 PY 1998 VL 280 IS 3 BP 273 EP 274 DI 10.1001/jama.280.3.273 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZZ204 UT WOS:000074706000024 PM 9676679 ER PT J AU Winter, CC Gumperz, JE Parham, P Long, EO Wagtmann, N AF Winter, CC Gumperz, JE Parham, P Long, EO Wagtmann, N TI Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; CLASS-I MOLECULES; CLONES; LYSIS; PROTECTION; P58; SPECIFICITY; DOMAINS; ALLELES; LINE AB Cytotoxicity of human NK cells is under negative control of killer cell Ig-like receptors (KIR) specific for HLA class I. To determine the specificity of five KIR containing two Ig domains (KIR2D), direct binding of soluble recombinant KIR2D to a panel of HLA class I transfectants was assayed. One soluble KIR2D, derived from an inhibitory receptor with a long cytoplasmic tail (KIR2DL1), bound to HLA-C allotypes containing asparagine 77 and lysine 80 in the heavy chain, as expected, since these allotypes inhibit lysis by NK cells expressing KTR2DL1. Surprisingly, another KIR2D (KIR2DL2), which inhibits NK lysis of cells expressing HLA-C molecules with serine 77 and asparagine 80, bound to HLA-C allotypes carrying either amino acid motif, Expression of the KIR2DL receptors in NK cells using recombinant vaccinia viruses confirmed these patterns of recognition, and identified KIR2DL3 as another KIR reacting with both groups of HLA-C allotypes, Mutagenesis of amino acid 44 in KIR2DL1 and KIR2DL2 suggested this residue controls the affinity of KIR for the 77/80 motif of HLA-C molecules. Two other soluble KIR2D, derived from noninhibitory receptors with short cytoplasmic tails (KIR2DS), did not bind to any of the HLA class I allotypes tested. One of these receptors (KIR2DS2) is closely related in sequence to KIR2DL2, Substitution of tyrosine 45 with the phenylalanine conserved in other KIR was sufficient to permit specific binding of KIR2DS2 to HLA-C. These results show that KIR2DL receptors are specific for HLA-C, but that recognition of HLA-C allotypes appears more permissive than indicated by previous functional experiments. C1 NIAID, NIH Twinbrook 2, Immunogenet Lab, Rockville, MD 20852 USA. Stanford Univ, Dept Struct Biol, Stanford, CA 94305 USA. Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA. RP Long, EO (reprint author), NIAID, NIH Twinbrook 2, Immunogenet Lab, 12441 Parklawn Dr, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 FU NIAID NIH HHS [AI-17892, AI-22039] NR 32 TC 280 Z9 288 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1998 VL 161 IS 2 BP 571 EP 577 PG 7 WC Immunology SC Immunology GA ZZ428 UT WOS:000074728400006 PM 9670929 ER PT J AU Ahuja, SS Mummidi, S Malech, HL Ahuja, SK AF Ahuja, SS Mummidi, S Malech, HL Ahuja, SK TI Human dendritic cell (DC)-based anti-infective therapy: Engineering DCs to secrete functional IFN-gamma and IL-12 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; IN-VITRO; INTERFERON-GAMMA; BONE-MARROW; PERIPHERAL-BLOOD; LANGERHANS CELLS; GENE-TRANSFER; INTERLEUKIN-12; VIVO; LEISHMANIA AB An imbalance in the Th1- and Th2-type cytokine responses may allow certain microbes to modify the host response to favor their own persistence. We now show that infection/pulsing of human CD34(+) peripheral blood hemopoietic progenitor cell-derived dendritic cells (DCs) with Leishmania donovani promastigotes, Histoplasma capsulatam, and Mycobacterium kansasii impairs the constitutive production of IL-12 from these cells. Thus, strategies aimed at modulating a dysregulated Th1/Th2 response to infection would be of great interest. To both augment the host immune response and deliver potent immunomodulatory cytokines such as IL-12 and IFN-gamma, our goal is to develop a therapeutic strategy using genetically modified, microbial Ag-pulsed DCs, Toward developing such immunotherapies, we used retrovirus-mediated somatic gene transfer techniques to engineer human DCs to secrete biologically active IL-12 and IFN-gamma. DCs pulsed with microbial antigens (e,g,, leishmania and histoplasma Ags) were capable of inducing proliferative responses in autologous CD4(+) lymphocytes. CD4(+) lymphocytes cocultured with IE-la-transduced autologous DCs had enhanced Ag-specific proliferative responses compared with CD4+ lymphocytes cocultured with nontransduced or IFN-gamma-transduced DCs, In this cell culture model system we demonstrate that IL-12 has a negative effect on IL-4 secretion that is independent of its ability to induce IFN-gamma secretion. Taken together, these results indicate that IL-12-transduced DCs may be specifically suited in inducing or down-modulating Ag-specific Th1 or Th2 responses, respectively, and thus may be useful as adjunctive therapy in those intracellular infections in which a dominant Th1 response is critical for the resolution of infection. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Ahuja, SS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM ahuja@uthscsa.edu RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 FU NCI NIH HHS [P50 CA58183] NR 66 TC 46 Z9 48 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1998 VL 161 IS 2 BP 868 EP 876 PG 9 WC Immunology SC Immunology GA ZZ428 UT WOS:000074728400042 PM 9670965 ER PT J AU Bettinotti, MP Kim, CJ Lee, KH Roden, M Cormier, JN Panelli, M Parker, KK Marincola, FM AF Bettinotti, MP Kim, CJ Lee, KH Roden, M Cormier, JN Panelli, M Parker, KK Marincola, FM TI Stringent allele/epitope requirements for MART-1/Melan A immunodominance: Implications for peptide-based immunotherapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; MELANOMA ANTIGEN GP100; MAJOR HISTOCOMPATIBILITY COMPLEX; IN-VITRO STIMULATION; HUMAN GENE MAGE-3; PERIPHERAL-BLOOD; HLA-A2 MELANOMAS; CELL CLONES; SYNTHETIC PEPTIDES AB The exclusiveness of the relationship between peptide and HLA alleles, combined with their extensive polymorphism, emphasizes the need for immunization strategies based on endogenous processing of full length proteins (containing multiple epitopic determinants) for presentation to T cells. This could allow vaccination regardless of the patient's HLA phenotype, assuming that individual molecules can be efficient T cell Ags in association with various HLA alleles, An endogenous system of Ag presentation was developed using dendritic cells infected with recombinant viral vectors expressing the melanoma-associated Ag MART-I! Melan A. CD8(+) T cells from melanoma patients were activated in vitro by coincubation with infected dendritic cells and tested for recognition of HLA-A-matched melanoma targets. This allowed the analysis of T cell induction in association with any HLA-A allele of a given patient's phenotype, In this system, MART-1/Melan A could not efficiently immunize in association with HLA-A alleles other than A*0201, including the one residue variant from A*0201: HLA-A*0226. Clonal analysis of MART-1/Melan A-specific CTL confirmed that MART-1/Melan A immunodominance is strongly restricted to the AAGIGILTV/HLA-A*0201 combination. The stringent epitope/allele requirements for MART-1/Melan A/TCR interactions were not associated with limitations in the TCR repertoire. In conclusion, autologous induction of MART-1/Melan A CTL by whole Ag processing and presentation is restricted to a unique allele/ligand combination and is excluded by minimal changes in HLA structure. Thus, whole protein vaccination for small m,w, Ags may provide no further advantage over a peptide-based approach. C1 NCI, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. NCI, HLA Lab, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NIAID, Biol Resources Branch, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Div Clin Sci, Bldg 10,Room 2B56, Bethesda, MD 20892 USA. EM marincola@nih.gov NR 64 TC 42 Z9 42 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1998 VL 161 IS 2 BP 877 EP 889 PG 13 WC Immunology SC Immunology GA ZZ428 UT WOS:000074728400043 PM 9670966 ER PT J AU Zuo, J Ferguson, TA Hernandez, YJ Stetler-Stevenson, WG Muir, D AF Zuo, J Ferguson, TA Hernandez, YJ Stetler-Stevenson, WG Muir, D TI Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting chondroitin sulfate proteoglycan SO JOURNAL OF NEUROSCIENCE LA English DT Article DE chondroitin sulfate proteoglycan; matrix metalloproteinase; neuronal regeneration; neurite inhibitor; basal lamina; peripheral nerve; laminin; cryoculture ID NERVE GROWTH-FACTOR; RAT SCIATIC-NERVE; ROOT ENTRY ZONE; EXTRACELLULAR-MATRIX; CELL-SURFACE; GELATINASE-A; PROMOTING ACTIVITY; PERIPHERAL-NERVE; SCHWANN-CELLS; SPINAL-CORD AB Chondroitin sulfate proteoglycans (CSPGs) are implicated in the regulation of axonal growth. We previously reported that the neurite-promoting activity of laminin is inhibited by association with a Schwann cell-derived CSPG and that endoneurial laminin may be inhibited by this CSPG as well [Zuo J, Hernandez YJ, Muir D (1998) Chondroitin sulfate proteoglycan with neurite-inhibiting activity is upregulated after peripheral nerve injury. J Neurobiol 34:41-54]. Mechanisms regulating axonal growth were studied by using an in vitro bioassay in which regenerating embryonic dorsal root ganglionic neurons (DRGn) were grown on sections of normal adult nerve. DRGn achieved slow neuritic growth on sections of normal nerve, which was reduced significantly by treatment with metalloproteinase inhibitors. Similar results were obtained on a synthetic substratum composed of laminin and inhibitory CSPG. DRGn expressed the matrix metalloproteinase, MMP-2, which was transported to the growth cone. Recombinant MMP-2 inactivated the neurite-inhibiting CSPG without hindering the neurite-promoting potential of laminin. Similarly, neuritic growth by DRGn cultured on normal nerve sections was increased markedly by first treating the nerve sections with MMP-2. The proteolytic deinhibition by MMP-2 was equivalent to and nonadditive with that achieved by chondroitinase, suggesting that both enzymes inactivated inhibitory CSPG. Additionally, the increases in neuritic growth resulting from treating nerve sections with MMP-2 or chondroitinase were blocked by anti-laminin antibodies. From these results we conclude that MMP-2 provides a mechanism for the deinhibition of laminin in the endoneurial basal lamina and may play an important role in the regeneration of peripheral nerve. C1 Univ Florida, Coll Med, Gainesville, FL 32610 USA. Univ Florida, Inst Brain, Dept Pediat, Div Neurol, Gainesville, FL 32610 USA. Univ Florida, Inst Brain, Dept Neurosci, Gainesville, FL 32610 USA. NCI, Extracellular Matrix Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Muir, D (reprint author), Univ Florida, Coll Med, Box 100296, Gainesville, FL 32610 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NINDS NIH HHS [NS31255] NR 55 TC 204 Z9 207 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1998 VL 18 IS 14 BP 5203 EP 5211 PG 9 WC Neurosciences SC Neurosciences & Neurology GA ZY294 UT WOS:000074605700011 PM 9651203 ER PT J AU Berke, JD Paletzki, RF Aronson, GJ Hyman, SE Gerfen, CR AF Berke, JD Paletzki, RF Aronson, GJ Hyman, SE Gerfen, CR TI A complex program of striatal gene expression induced by dopaminergic stimulation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; striatum; CREB; differential display PCR; immediate-early genes; neuronal plasticity; addiction ID ELEMENT-BINDING PROTEIN; ACTIVITY-REGULATED GENE; C-FOS EXPRESSION; RAT STRIATUM; STRIATOPALLIDAL NEURONS; DIFFERENTIAL DISPLAY; RECEPTOR ACTIVATION; SYNAPTIC ACTIVITY; NMDA RECEPTORS; GROWTH-FACTOR AB Dopamine acting in the striatum is necessary for normal movement and motivation. Drugs that change striatal dopamine neurotransmission can have long-term effects on striatal physiology and behavior; these effects are thought to involve alterations in gene expression. Using the 6-hydroxydopamine lesion model of Parkinson's disease and differential display PCR, we have identified a set of more than 30 genes whose expression rapidly increases in response to stimulation of striatal dopamine D-1 receptors. The induced mRNAs include both novel and previously described genes, with diverse time courses of expression. Some genes are expressed at near-maximal levels within 30 min, whereas others show no substantial induction until 2 hr or more after stimulation. Some of the induced genes, such as CREM, CHOP, and MAP kinase phosphatase-1, may be components of a homeostatic response to excessive stimulation. Others may be part of a genetic program involved in cellular and synaptic plasticity. A very similar set of genes is induced in unlesioned animals by administration of the psychostimulant cocaine or the antipsychotic eticlopride, although in distinct striatal cell populations. In contrast to some previously described early genes, most of the novel genes are not induced in cortex by apomorphine, indicating specificity of induction. Thus we have identified novel components of a complex, coordinated genetic program that is induced in striatal cells in response to various dopaminergic manipulations. C1 NINDS, Mol Plast Sect, Bethesda, MD 20892 USA. Harvard Univ, Program Neurosci, Boston, MA 02115 USA. NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Berke, JD (reprint author), NINDS, Mol Plast Sect, 36-4C-24,36 Convent Dr, Bethesda, MD 20892 USA. NR 50 TC 241 Z9 246 U1 1 U2 14 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1998 VL 18 IS 14 BP 5301 EP 5310 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZY294 UT WOS:000074605700021 PM 9651213 ER PT J AU Schreurs, BG Gusev, PA Tomsic, D Alkon, DL Shi, T AF Schreurs, BG Gusev, PA Tomsic, D Alkon, DL Shi, T TI Intracellular correlates of acquisition and long-term memory of classical conditioning in Purkinje cell dendrites in slices of rabbit cerebellar lobule HVI SO JOURNAL OF NEUROSCIENCE LA English DT Article DE rabbit; cerebellum; classical conditioning; nictitating membrane; eyelid; Purkinje cell; slice; dendritic recording; long-term depression ID NICTITATING-MEMBRANE RESPONSE; POSITRON-EMISSION TOMOGRAPHY; SPATIAL SYNAPTIC INTEGRATION; HIPPOCAMPAL PYRAMIDAL CELLS; ESSENTIAL INVOLVEMENT; INTERPOSITUS NUCLEUS; CORTEX; DEPRESSION; CURRENTS; LESIONS AB Intradendritic recordings in Purkinje cells from a defined area in parasaggital slices of cerebellar lobule HVI, obtained after rabbits were given either paired (classical conditioning) or explicitly unpaired (control) presentations of lone and periorbital electrical stimulation, were used to assess the nature and duration of conditioning-specific changes in Purkinje cell dendritic membrane excitability. We found a strong relationship between the level of conditioning and Purkinje cell dendritic membrane excitability after initial acquisition of the conditioned response. Moreover, conditioning-specific increases in Purkinje cell excitability were still present 1 month after classical conditioning. Although dendritically recorded membrane potential, input resistance, and amplitude of somatic and dendritic spikes were not different in cells from paired or control animals, the size of a potassium channel-mediated transient hyperpolarization was significantly smaller in cells from animals that received classical conditioning. In slices of lobule HVI obtained from naive rabbits, the conditioning-related increases in membrane excitability could be mimicked by application of potassium channel antagonist tetraethylammonium chloride, iberiotoxin, or 4-aminopyridine. However, only 4-aminopyridine was able to reduce the transient hyperpolarization. The pharmacological data suggest a role for potassium channels and, possibly, channels mediating an I-A-like current, in learning-specific changes in membrane excitability. The conditioning-specific increase in Purkinje cell dendritic excitability produces an afterhyperpolarization, which is hypothesized to release the cerebellar deep nuclei from inhibition, allowing conditioned responses to be elicited via the red nucleus and accessory abducens motorneurons. C1 NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. NINDS, Behav Neurosci Unit, NIH, Bethesda, MD 20892 USA. RP Schreurs, BG (reprint author), NINDS, Lab Adapt Syst, NIH, Bldg 36,Room B205, Bethesda, MD 20892 USA. OI Schreurs, Bernard/0000-0002-5776-0807 NR 73 TC 99 Z9 100 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1998 VL 18 IS 14 BP 5498 EP 5507 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZY294 UT WOS:000074605700038 PM 9651230 ER PT J AU Zhao, HM Wenthold, RJ Petralia, RS AF Zhao, HM Wenthold, RJ Petralia, RS TI Glutamate receptor targeting to synaptic populations on Purkinje cells is developmentally regulated SO JOURNAL OF NEUROSCIENCE LA English DT Article DE AMPA; cerebellum; climbing fiber; delta; parallel fiber; synaptogenesis ID CHANNEL DELTA-2 SUBUNIT; DEVELOPING RAT-BRAIN; AMINO-ACID RECEPTOR; NMDA RECEPTOR; IMMUNOCYTOCHEMICAL LOCALIZATION; MULTIPLE INNERVATION; CLIMBING FIBERS; NERVOUS-SYSTEM; EXPRESSION; CEREBELLUM AB Selective targeting of neurotransmitter receptors to specific synapse populations occurs in adult neurons, but little is known about the development of these receptor distribution patterns. In this study, we demonstrate that a specific developmental switch occurs in the targeting of a receptor to an identified synapse population. Localization of delta and AMPA glutamate receptors at parallel and climbing fiber synapses on the developing Purkinje cells was studied using postembedding immunogold. Delta receptors were found to be abundant on postsynaptic membranes at parallel fiber synapses from postnatal day 10 (P10) to adult. In contrast, delta receptors were found to be high at climbing fiber synapses only at P10 and P14. Thus, a major finding of this paper is that high levels of delta receptors are transiently expressed in climbing fiber synapses in the second postnatal week. Labeling of synapses with anti-delta receptor antibody at P10 was limited to the postsynaptic membrane of excitatory synapses and was absent from GABAergic synapses. Unlike delta receptor immunolabeling, AMPA receptor immunolabeling (GluR2/3 and GluR2 antibodies) was high in the postsynaptic membranes of synapses at early postnatal ages (P2 and P5) and was higher in climbing fiber synapses than in parallel fiber synapses from P10 to adult. The present study shows that synapse-specific targeting of glutamate receptors in Purkinje cells is developmentally regulated, with the postsynaptic receptor composition established during synapse maturation. This composition is not dependent on the nature of the initial establishment of synaptic connections. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. RP Petralia, RS (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 36-5D08,36 Convent Dr,MSC 4162, Bethesda, MD 20892 USA. NR 53 TC 98 Z9 98 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1998 VL 18 IS 14 BP 5517 EP 5528 PG 12 WC Neurosciences SC Neurosciences & Neurology GA ZY294 UT WOS:000074605700040 PM 9651232 ER PT J AU Jones, S Yakel, JL AF Jones, S Yakel, JL TI Ca2+ influx through voltage-gated Ca2+ channels regulates 5-HT3, receptor channel desensitization in rat glioma x mouse neuroblastoma hybrid NG108-15 cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SENSITIVE CALCIUM CHANNELS; DORSAL HORN NEURONS; NMDA RECEPTORS; HIPPOCAMPAL-NEURONS; ACTIVATION; INACTIVATION; RESPONSES; POTENTIATION; MODULATION; CALMODULIN AB 1. The kinetics of desensitization of the 5-HT3 receptor (5-HT3R)-gated ion channel were investigated using whole-cell and perforated-patch recording techniques in NG108-15 cells. 2. Rapid application of 5-HT (50 mu M) elicited a 5-HT3R-mediated inward current response that desensitized completely in the continued presence of agonist. In the whole-cell recording configuration (holding potential of -70 mV) while buffering internal calcium (Ca-i(2+)) with 5 mM EGTA (0.5 mM added Ca2+; with an estimated free [Ca2+] of 30 nM), the rate of desensitization was initially rapid (with a half-time of similar to 230 ms), but dramatically slowed with time by 1120 +/- 160%. 3. This slowing in the rate of desensitization was reduced by stronger Ca2+ buffering (20 mM BAPTA, without added Ca2+), or by the bath application of cadmium (100 mu M) to block voltage-gated Ca2+ channels. The rate of desensitization was also dependent on membrane potential. 4. In perforated-patch recordings, the rate of desensitization remained constant. However, a slowing in the desensitization rate could be induced by depolarizing cells immediately prior to the application of 5-HT. 5. The depolarization-induced slowing was blocked by incubating cells with BAPTA-AM (a membrane-permeant analogue of BAPTA) or by the bath application of cadmium. 6. These data suggest that Ca2+ influx through a cadmium-sensitive voltage-gated Ca2+ channel increases the cytoplasmic Ca2+ concentration ([Ca2+](i)) and induces a dramatic slowing in the kinetics of desensitization of the 5-HT3R channel. These data provide evidence for cross-talk between voltage-gated Ca2+ channels and 5-HT(3)Rs in NG108-15 cells. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Lab Signal Transduct, NIH, F2-08,POB 12233,104 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 43 TC 17 Z9 19 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 15 PY 1998 VL 510 IS 2 BP 361 EP 370 DI 10.1111/j.1469-7793.1998.361bk.x PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 106JE UT WOS:000075125500004 PM 9705989 ER PT J AU Ma, XM Lightman, SL AF Ma, XM Lightman, SL TI The arginine vasopressin and corticotrophin-releasing hormone gene transcription responses to varied frequencies of repeated stress in rats SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID MESSENGER-RNA RESPONSES; PITUITARY-ADRENAL AXIS; PARAVENTRICULAR NUCLEUS; IMMOBILIZATION STRESS; ENHANCES VASOPRESSIN; NEURONS; EXPRESSION; CRF; SECRETION; ADRENOCORTICOTROPIN AB 1. Rats habituate to repeated exposure to homotypic stressors. The present studies were designed to define how altered frequency of exposure to a stressor affects the development of habituation and how this habituation is reflected in alterations in basal expression and responsiveness of hypothalamic corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) messenger and heteronuclear RNA (hnRNA). 2. Rats were exposed to a 60 min period of restraint stress every 7th day, every 3rd day, alternate days or daily for 2 weeks and their response to a final episode of stress on day 15 was compared with that of a control group of unstressed rats. 3. The response of plasma corticosterone to the final stressor on day 15 was diminished in animals which had been stressed on only two previous occasions, 7 days apart, and diminished further with increasing frequency of previous stressors until it failed to respond at all in animals stressed daily. 4. The pattern of CRH hnRNA and mRNA responses were similar, decreasing with increasing frequency of exposure to the stressor, while AVP mRNA responses increased in response to repeated stress. 5. The gradual emergence of increased AVP transcription at a time of diminishing CRH response suggests that repeated stress results in a specific facilitation of AVP gene expression, perhaps by impairment of corticosterone feedback. C1 Univ Bristol, Dorothy Crowfoot Hodgkin Labs, Dept Med, Bristol BS2 8HW, Avon, England. RP Ma, XM (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. EM Max@cc1.nichd.nih.gov NR 42 TC 132 Z9 136 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 15 PY 1998 VL 510 IS 2 BP 605 EP 614 DI 10.1111/j.1469-7793.1998.605bk.x PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 106JE UT WOS:000075125500022 PM 9706007 ER PT J AU Cornilescu, G Marquardt, JL Ottiger, M Bax, A AF Cornilescu, G Marquardt, JL Ottiger, M Bax, A TI Validation of protein structure from anisotropic carbonyl chemical shifts in a dilute liquid crystalline phase SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NMR R-FACTOR; SPECTRA; MODEL C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Cornilescu, Gabriel/H-3113-2011 OI Cornilescu, Gabriel/0000-0002-1204-8904 NR 23 TC 610 Z9 613 U1 1 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 15 PY 1998 VL 120 IS 27 BP 6836 EP 6837 DI 10.1021/ja9812610 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 101EK UT WOS:000074856500038 ER PT J AU Manns, A Strickler, HD Hanchard, B Manassaram, DM Waters, D Ablashi, DV AF Manns, A Strickler, HD Hanchard, B Manassaram, DM Waters, D Ablashi, DV TI Age- and sex-specific seroprevalence of human herpesvirus 8 in Jamaica SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. George Washington Univ, Sch Publ Hlth, Washington, DC USA. George Washington Univ, Hlth Serv, Washington, DC USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Informat Corp, Frederick, MD USA. Adv Biotechnol Inc, Columbia, MD USA. Georgetown Univ, Sch Med, Washington, DC USA. RP Manns, A (reprint author), NIH, Execut Plaza N,Suite 434, Bethesda, MD 20892 USA. RI Luppi, Mario/J-3668-2016 OI Luppi, Mario/0000-0002-0373-1154 NR 6 TC 14 Z9 14 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 15 PY 1998 VL 90 IS 14 BP 1102 EP 1103 DI 10.1093/jnci/90.14.1102 PG 2 WC Oncology SC Oncology GA 100XR UT WOS:000074841100015 PM 9672261 ER PT J AU Swanson, CA Brown, CC Alavanja, MCR Brownson, RC AF Swanson, CA Brown, CC Alavanja, MCR Brownson, RC TI More about: Saturated fat intake and lung cancer risk among nonsmoking women in Missouri - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA. RP Swanson, CA (reprint author), NIH, Execut Plaza N,Rm 443, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 15 PY 1998 VL 90 IS 14 BP 1105 EP 1105 PG 1 WC Oncology SC Oncology GA 100XR UT WOS:000074841100018 ER PT J AU Zhang, L Rubinow, DR Ma, W Marks, JM Feldman, AN Barker, JL Tathan, TA AF Zhang, L Rubinow, DR Ma, W Marks, JM Feldman, AN Barker, JL Tathan, TA TI GABA receptor subunit mRNA expression in brain of conflict, yoked control and control rats SO MOLECULAR BRAIN RESEARCH LA English DT Article DE conflict; behavior; GABA; hybridization ID MESSENGER-RNAS; ALPHA-SUBUNIT; A RECEPTORS; ACID AB Animal conflict models have been used for years as a preclinical screen for predicting anxiolytic therapeutic efficacy. Anxiolytics, including benzodiazepines, increase punished responding. This suggests that the punished behavior may be mediated by the GABA receptor. To evaluate this hypothesis, we performed in situ hybridization histochemistry studies of GABA receptor subunits (alpha 1-alpha 4) and synthetic enzymes glutamic acid decarboxylase (GAD(65) and GAD(67)) in four groups of rats: conflict (punishment), yoked controls (rats shocked without conflict training history), fixed interval only controls (rats that worked for food but were not shocked) and untreated controls. With conflict behavioral training, bilateral reduction of mRNA for the GABA(A) alpha 1 subunit was seen relative to controls in the cortex, thalamus and hippocampus. In contrast, alteration of alpha 2 mRNA levels appeared only in the yoked control group, with increased levels seen in the thalamus and cortex and decreased levels in the hippocampus. There were no differences in the alpha 2 mRNA level between the control and the conflict behavioral trained animals. Further, no significant differences were found between groups in the mRNA levels for the alpha 3 subunit, alpha 4 subunit, GAD(65), and GAD(67). These results suggest that the behaviors related to conflict and uncontrollable aversive stimuli (yoked control group) are accompanied and perhaps mediated by selective changes in the GABA(A) alpha(1) or alpha 2 subunits, respectively. These findings highlight the potential usefulness of the conflict model as a means of elucidating the biological underpinnings of anxiety disorder. Published by Elsevier Science B.V. All rights reserved. C1 NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Rubinow, DR (reprint author), NIMH, Behav Endocrinol Branch, NIH, Bldg 10,Room 3N238,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. EM rubinowd@irp.nimh.nih.gov NR 53 TC 12 Z9 13 U1 0 U2 0 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 JUL 15 PY 1998 VL 58 IS 1-2 BP 16 EP 26 DI 10.1016/S0169-328X(98)00061-8 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 107XJ UT WOS:000075236000003 ER PT J AU Hirata, H Asanuma, M Cadet, JL AF Hirata, H Asanuma, M Cadet, JL TI Superoxide radicals are mediators of the effects of methamphetamine on Zif268 (Egr-1, NGFI-A) in the brain: evidence from using CuZn superoxide dismutase transgenic mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE c-fos mRNA; methamphetamine; oxidative stress; Zif268 mRNA; Egr-1 ID MESSENGER-RNA EXPRESSION; INDUCED UP-REGULATION; IMMEDIATE-EARLY GENE; C-FOS; TRANSCRIPTION FACTORS; RAT STRIATUM; INDUCED NEUROTOXICITY; IONIZING-RADIATION; OXIDATIVE STRESS; GROWTH-FACTORS AB Administration of methamphetamine (METH) to mammals is known to cause deleterious effects to brain monoaminergic systems. These toxic effects are thought to be due to oxidative stress. Acute administration of METH causes activation of immediate-early genes (IEGs) such as c-fos and Zif268 mRNA in rodent brains. However, the exact mechanisms involved in these changes have not been completely clarified. As a first step towards assessing a possible role for free radicals in METH-induced changes in IEGs, we have used CuZn superoxide dismutase (SOD) transgenic (Tg) mice and have quantified the effects of METH on c-fos and Zif268 mRNAs by in situ hybridization techniques. Mice were injected with 25 mg/kg of METH and sacrificed at various time points afterwards. There were significant METH-induced increases in both c-fos and Zif268 mRNAs in the frontal cortex and striatum of both strains of animals. interestingly, the increases in Zif268 were markedly attenuated in the CuZn SOD-Tg mice; the increases in c-fos were also attenuated, but to a significantly lesser degree. These results indicate that superoxide radicals might play an important role in the activation of Zif268 after METH administration. Because IEGs are modulators of gene expression, these results also raise the possibility that oxidative mechanisms might be important factors in neuroadaptive changes caused by stimulant drugs. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, 5500 Nathan Shock Dr,POB 5180, Baltimore, MD 21224 USA. NR 39 TC 21 Z9 21 U1 0 U2 0 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 JUL 15 PY 1998 VL 58 IS 1-2 BP 209 EP 216 DI 10.1016/S0169-328X(98)00055-2 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 107XJ UT WOS:000075236000021 ER PT J AU Iwata, N Virkkunen, M Linnoila, M Goldman, D AF Iwata, N Virkkunen, M Linnoila, M Goldman, D TI Identification of a naturally occurring Pro(15)-Ser(15) substitution in the serotonin(5A) receptor gene in alcoholics and healthy volunteers SO MOLECULAR BRAIN RESEARCH LA English DT Article DE serotonin receptor; alcoholism; single-stranded conformational polymorphism (SSCP); polymorphism; genetic variation; point mutation; amino acid substitution ID DNA; POLYMORPHISMS; DEPENDENCE; ABUSE AB We screened the serotonin(5A) receptor gene coding region in 186 unrelated alcoholic patients and 187 controls. A relatively abundant amino acid substitution and two synonymous DNA substitutions were detected. Two synonymous variants, A12T and C789T, had rarer-allele frequencies of 23% and 1%, respectively. The Pro15Ser substitution is located in the amino terminal, extracellular domain of the receptor adjacent to a putative phosphorylation site. Pro15Ser had rarer-allele frequencies of 8.1% and 5.9% in Finnish alcoholic patients and controls, respectively (p = n.s.). (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIAAA, Neurogenet Lab, DICBR, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, DICBR, Bethesda, MD 20892 USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. RP Iwata, N (reprint author), NIAAA, Neurogenet Lab, DICBR, NIH, 12420 Parklawn Dr,Pk 5,Rm 451,MSC 8110, Bethesda, MD 20892 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 21 TC 7 Z9 7 U1 0 U2 0 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 JUL 15 PY 1998 VL 58 IS 1-2 BP 217 EP 220 DI 10.1016/S0169-328X(98)00111-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 107XJ UT WOS:000075236000022 ER PT J AU Domachowske, JB Dyer, KD Adams, AG Leto, TL Rosenberg, HF AF Domachowske, JB Dyer, KD Adams, AG Leto, TL Rosenberg, HF TI Eosinophil cationic protein RNase 3 is another RNaseA-family ribonuclease with direct antiviral activity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; MOLECULAR-CLONING; GENE FAMILY; PLACENTAL RIBONUCLEASE; NEUROTOXIN; CELLS; INHIBITION; INFECTION; EVOLUTION; SEQUENCE AB Eosinophil cationic protein (ECP) is one of two RNase A-superfamily ribonucleases found in secretory granules of human eosinophilic leukocytes, Although the physiologic function of eosinophils [and thus of the two eosinophil ribonucleases, ECP and eosinophil-derived neurotoxin (EDN)] remains controversial, we have recently shown that isolated human eosinophils promote ribonuclease-dependent toxicity toward extracellular virions of the single-stranded RNA virus, respiratory syncytial virus, group B (RSV-B), We have also shown that recombinant human EDN (rhEDN) can act alone as a ribonuclease-dependent antiviral agent. In this work, we provide a biochemical characterization of recombinant human ECP (rhECP) prepared in baculovirus, and demonstrate that rhECP also promotes ribonuclease-dependent antiviral activity. The rhECP described here is N-glycosylated, as is native ECP, and has similar to 100-fold more ribonuclease activity than nonglycosylated rhECP prepared in bacteria. The enzymatic activity of rhECP was sensitive to inhibition by placental ribonuclease inhibitor (RI). Although rhECP was not as effective as rhEDN at reducing viral infectivity (500 nM rhECP reduced infectivity of RSV-B similar to 6 fold; 500 nM rhEDN, >50 fold), the antiviral activity appears to be unique to the eosinophil ribonucleases; no reduction in infectivity was promoted by bovine RNase A, by the amphibian ribonuclease, onconase, nor by the closely-related human ribonuclease, RNase k6. Interestingly, combinations of rhEDN and rhECP did not result in either a synergistic or even an additive antiviral effect. Taken together, these results suggest that that the interaction between the eosinophil ribonucleases and the extracellular virions of RSV-B may be specific and saturable. C1 SUNY Hlth Sci Ctr, Dept Pediat, Syracuse, NY 13210 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), SUNY Hlth Sci Ctr, Dept Pediat, Syracuse, NY 13210 USA. EM hr2k@nih.gov NR 45 TC 134 Z9 139 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 15 PY 1998 VL 26 IS 14 BP 3358 EP 3363 DI 10.1093/nar/26.14.3358 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 102WF UT WOS:000074948500007 PM 9649619 ER PT J AU Mattay, VS Callicott, JH Bertolino, A Santha, AKS Van Horn, JD Tallent, KA Frank, JA Weinberger, DR AF Mattay, VS Callicott, JH Bertolino, A Santha, AKS Van Horn, JD Tallent, KA Frank, JA Weinberger, DR TI Hemispheric control of motor function: a whole brain echo planar fMRI study SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE fMRI; motor function; cortex; hemispheric dominance; functional imaging ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; VOLUNTARY MOVEMENTS; CORTICAL AREAS; RHESUS-MONKEY; HAND MOVEMENT; SENSORY STIMULATION; SENSORIMOTOR CORTEX; PREFRONTAL CORTEX; BASAL GANGLIA AB The aim of this study was to explore whether recruitment of the ipsilateral motor cortex during non-dominant motor movement reflects left hemispheric control of motor function or simply the greater complexity or unfamiliarity of the motor task. BOLD fMRI was performed in normal right-handers during two motor tasks: (1) sequential finger movements (SM task) with the right or left hand; and (2) random finger movements (RM task) with the right hand. In all subjects, activation was predominantly in the contralateral motor areas (primary sensorimotor, lateral premotor, parietal and supplementary motor regions) and ipsilateral cerebellum. While the ipsilateral motor areas were also activated, single subject analysis revealed these areas to be more extensive and to be seen in more subjects during the non-dominant hand SM task and dominant hand RM task than during the more familiar dominant hand SM task. Similarly, group analysis also revealed ipsilateral activation in the primary sensorimotor and lateral premotor areas, but only during the non-dominant SM task and the dominant hand RM task. Non-dominant hand movements, perhaps because they are less 'automatic', appear to require more cortical activity similar to complex tasks with the dominant hand, and result in greater recruitment of ipsilateral cortical motor areas and striatum. The study also illustrates how potentially meaningful subtleties seen on individual maps may be obscured with group averaging approaches. Published by Elsevier Science Ireland Ltd. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIH, Lab Diagnost Radiol Branch, OIR, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bldg 10,Rm 4C-101,9000 Rockville Pl, Bethesda, MD 20892 USA. EM weinberd@dirpc.nimh.nih.gov RI Callicott, Joseph/C-9102-2009 OI Callicott, Joseph/0000-0003-1298-3334 NR 57 TC 67 Z9 72 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JUL 15 PY 1998 VL 83 IS 1 BP 7 EP 22 DI 10.1016/S0925-4927(98)00023-7 PG 16 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 114HP UT WOS:000075603300002 PM 9754701 ER PT J AU Albert, PS Waclawiw, MA AF Albert, PS Waclawiw, MA TI A two-state Markov chain for heterogeneous transitional data: A quasi-likelihood approach SO STATISTICS IN MEDICINE LA English DT Article ID LONGITUDINAL DATA-ANALYSIS; BINARY SEQUENCES; REGRESSION; MODELS; PANEL AB Many chronic diseases are measured by repeated binary data where the scientific interest is on the transition process between two states of disease activity. Examples include: depression; schizophrenia; multiple sclerosis, and respiratory illness, The course for many of these diseases is inherently heterogeneous, making it difficult to make inference on the transition process. This paper presents a model that incorporates heterogeneity by allowing the transition probabilities to vary randomly across subjects. In the proposed quasi-likelihood formulation for a two-state Markov chain, only the first two moments of the bivariate distribution on the transition probabilities are specified, and we develop a generalized estimating equations (GEE) approach for estimating the mean and variance of this distribution. In addition to estimating the model parameters, we discuss the estimation of derived quantities of the transition matrix such as estimating the expected first passage times and we discuss how we can introduce covariate dependence into the model. We use this methodology to summarize the transitioning pattern of respiratory illness in a group of children with intra-uteral growth retardation, and we conduct a simulation to investigate the finite sample properties of our procedure and to demonstrate marked bias if heterogeneity is ignored. (C) 1998 John Wiley & Sons, Ltd. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), NHLBI, Off Biostat Res, Rockledge 2,Room 8223 MSC 7938, Bethesda, MD 20892 USA. NR 23 TC 23 Z9 23 U1 2 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1998 VL 17 IS 13 BP 1481 EP 1493 DI 10.1002/(SICI)1097-0258(19980715)17:13<1481::AID-SIM858>3.0.CO;2-H PG 13 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 ZY940 UT WOS:000074678800005 PM 9695193 ER PT J AU Armstrong, N Buckley, P Oberley, T Fechner, J Dong, YC Hong, XN Kirk, A Neville, D Knechtle, S AF Armstrong, N Buckley, P Oberley, T Fechner, J Dong, YC Hong, XN Kirk, A Neville, D Knechtle, S TI Analysis of primate renal allografts after T-cell depletion with anti-CD3-CRM9 SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the American-Society-of-Transplant-Surgeons CY MAY 10-16, 1997 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Surgeons ID BLOOD-TRANSFUSION ENHANCEMENT; CYTOKINE GENE-EXPRESSION; INTERFERON-GAMMA; PERIPHERAL TOLERANCE; MESSENGER-RNA; CLASS-I; PATHOLOGICAL FEATURES; MONOCLONAL-ANTIBODIES; CARDIAC ALLOGRAFT; REJECTION AB Background. FN18-CRM9 is a CD3-specific immunotoxin that is capable of depleting CD3(+) T cells. Pretreatment of rhesus monkeys with this agent before transplantation can induce donor-specific tolerance and "split tolerance" to renal allografts. Methods. Heterotopic renal transplants were performed on monkeys that received posttransplant FN18-CRM9. Histological and immunohistological staining, as well as analysis of the intragraft cytokine profile by reverse transcriptase polymerase chain reaction, was performed on percutaneous allograft biopsies. Results. Experimental monkeys had significant prolongation of allograft survival. Although an interstitial, mononuclear cell infiltrate was seen in all of the renal transplants, there was minimal evidence of acute cellular rejection. Histological evidence of alloantibody-mediated damage was detected 3 to 5 months after transplantation in the monkeys treated with FN18-CRM9. Immunohistology demonstrated the reappearance of CD3(+) and CD4(+) T cells, as well as CD20(+) B cells, in the grafts. Cytokine analysis demonstrated expression of interferon-gamma. An intact anti-donor IgG response was seen. Conclusion. Treatment of monkeys with FN18-CRM9 immediately after transplantation significantly prolongs renal allograft survival. Allograft biopsies demonstrate a lack of acute cellular rejection; however, alloantibody-mediated graft damage and rejection occur, with an intact anti donor IgG response, The intra graft expression of the interferon-gamma may reflect this ongoing humoral rejection. These data suggest that even a brief period of T-cell allosensitization may lead to humorally mediated allograft damage. Efforts to achieve tolerance with posttransplant FN18-CRM9 will require modification of the protocol to deplete T cells before allosensitization exposure or to supplement the posttransplant immunomodification strategy. C1 Univ Wisconsin, Dept Surg, Sch Med, Madison, WI 53792 USA. Univ Wisconsin, Dept Pathol & Lab Med, Sch Med, Madison, WI 53792 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Knechtle, S (reprint author), Univ Wisconsin Hosp, H4-769 CSC,600 Highland Ave, Madison, WI 53792 USA. RI Fechner, John/C-5962-2016 OI Fechner, John/0000-0002-8220-7237 NR 49 TC 39 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 1998 VL 66 IS 1 BP 5 EP 13 DI 10.1097/00007890-199807150-00002 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 101VR UT WOS:000074889300002 PM 9679815 ER PT J AU Freeman, JH Shi, T Schreurs, BG AF Freeman, JH Shi, T Schreurs, BG TI Pairing-specific long-term depression prevented by blockade of PKC or intracellular Ca2+ SO NEUROREPORT LA English DT Article DE calphostin C; cerebellum; conditioning; EGTA; learning; LTD; parallel fibers; PKC; plasticity; Purkinje cell ID PROTEIN-KINASE-C; RABBIT CEREBELLAR SLICE; CONDITIONED-RESPONSES; MAMMALIAN BRAIN; CLIMBING FIBER; MEMORY; STIMULATION; HIPPOCAMPUS; RECEPTORS; LESIONS AB LONG-TERM depression was established in cerebellar Purkinje cells using 20 pairings of a brief, high frequency train of parallel fiber stimulation with a subsequent 100 ms depolarizing current injection. Effects were assessed on the peak amplitude of Purkinje cell excitatory post synaptic potentials (EPSPs) elicited by single parallel fiber test pulses. Intradendritically recorded Purkinje cell EPSPs exhibited long-term (>20 min) reduction in peak amplitude following paired stimulation but not if pretreated with the protein kinase C inhibitor calphostin C or iontophoretically injected with the calcium chelator EGTA. The similarity of the stimulation protocol and behavioral conditioning paradigms suggests pairing-specific long-term synaptic depression is a valuable model for understanding the cellular mechanisms underlying cerebellar cortical contributions to learning. Neuro Report 9: 2237-2241 (C) 1998 Rapid Science Ltd. C1 NINDS, Behav Neurosci Unit, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. RP Schreurs, BG (reprint author), NINDS, Behav Neurosci Unit, Lab Adapt Syst, NIH, Bldg 36,Room B205, Bethesda, MD 20892 USA. OI Schreurs, Bernard/0000-0002-5776-0807 NR 25 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 13 PY 1998 VL 9 IS 10 BP 2237 EP 2241 DI 10.1097/00001756-199807130-00016 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 101KY UT WOS:000074869200016 PM 9694206 ER PT J AU Vaupel, DB Mukhin, AG Kimes, AS Horti, AG Koren, AO London, ED AF Vaupel, DB Mukhin, AG Kimes, AS Horti, AG Koren, AO London, ED TI In vivo studies with [I-125]5-I-A-85380, a nicotinic acetylcholine receptor radioligand SO NEUROREPORT LA English DT Article DE autoradiography; binding; nicotine; nicotinic acetylcholine receptor; radiotracer ID CENTRAL NERVOUS-SYSTEM; RAT-BRAIN; ALPHA-BUNGAROTOXIN; BINDING-SITES; H-3 NICOTINE; MOUSE-BRAIN; IN-VITRO; LOCALIZATION; EPIBATIDINE AB 5-[I-125]iodo-3-(2(S)-azetidinylmethoxy)pyridine ([I-125]5-I-A-85380) was evaluated in the mouse as a potential in vivo imaging ligand for central nicotinic acetylcholine receptors (nAChRs). After i.v. administration of [I-125]5-I-A-85380, peak brain levels of radioactivity were measured within 1 h and declined slowly over 4 h. [I-125]5-I-A-85380 binding was saturable, and both its pharmacology, based upon inhibition studies, and its pattern of accumulation in brain regions having high nAChR densities were consistent with an interaction at alpha 4 beta 2 nAChR agonist binding sites. The thalamus:cerebellum radioactivity ratio, a measure of specific labeling, reached 37. Therefore, radiolabeled 5-I-A-85380 has excellent potential as an imaging radiotracer for nAChRs, particularly with single photon emission computed tomography, when I-123 is incorporated into the molecule. NeuroReport 9: 2311-2317 (C) 1998 Rapid Science Ltd. C1 NIDA, Brain Imaging Ctr, Intramural Res Program, Baltimore, MD 21224 USA. RP Vaupel, DB (reprint author), NIDA, Brain Imaging Ctr, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 20 TC 37 Z9 38 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 13 PY 1998 VL 9 IS 10 BP 2311 EP 2317 DI 10.1097/00001756-199807130-00030 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 101KY UT WOS:000074869200030 PM 9694220 ER PT J AU Bookheimer, SY Zeffiro, TA Blaxton, TA Gaillard, WD Malow, B Theodore, WH AF Bookheimer, SY Zeffiro, TA Blaxton, TA Gaillard, WD Malow, B Theodore, WH TI Regional cerebral blood flow during auditory responsive naming: evidence for cross-modality neural activation SO NEUROREPORT LA English DT Article DE language; naming; positron emission tomography (PET); regional cerebral blood flow (rCBF); semantic processing ID POSITRON EMISSION TOMOGRAPHY; OBJECT; KNOWLEDGE; LANGUAGE; ANATOMY; CORTEX; COLOR; BRAIN; FACE AB ONE issue of continuing debate in language research concerns whether the brain holds separate representations for semantic information through the auditory us visual modalities. Regardless of whether we hear, see or read meaningful information, our brains automatically activate both auditory and visual semantic associations to the sensory input. The prominent models for how the brain makes these cross-modality associations holds that semantic information conveyed through either sensory input modality is represented in a shared semantic system comprising the traditionally identified language areas in the brain. A few recent case reports as well as activation imaging studies, have challenged this notion by demonstrating category-specific organization within the semantic system in spatially discrete brain regions. Neither view posits a role for primary sensory cortices in semantic processing. We obtained positron emission tomographic (PET) images while subjects performed an auditory responsive naming task, an auditory analog to visual object naming. Subjects heard and responded to descriptions of concrete objects while blindfolded to prevent visual stimulation. Our results showed that, in addition to traditional language centers, auditory language input produced reciprocal activation in primary and secondary visual brain regions, just as if the language stimuli had entered in the visual modality. These findings provide evidence for a distributed semantic system in which sensory-specific semantic modules are mutually interactive, operating directly onto early sensory processing centers. NeuroReport 9: 2409-2413 (C) 1998 Rapid Science Ltd. C1 Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Brain Mapping Div, Los Angeles, CA 90024 USA. NIH, Lab Diagnost Radiol Res, Off Clin Director, Bethesda, MD 20892 USA. NINDS, Epolepsy Res Branch, Bethesda, MD 20892 USA. RP Bookheimer, SY (reprint author), Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Brain Mapping Div, 710 Westwood Plaza, Los Angeles, CA 90024 USA. NR 21 TC 61 Z9 61 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 13 PY 1998 VL 9 IS 10 BP 2409 EP 2413 DI 10.1097/00001756-199807130-00047 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 101KY UT WOS:000074869200047 PM 9694237 ER PT J AU Cloninger, CR Kaufmann, CA Faraone, SV Malaspina, D Svrakic, DM Harkavy-Friedman, J Suarez, BK Matise, TC Shore, D Lee, H Hampe, CL Wynne, D Drain, C Markel, PD Zambuto, CT Schmitt, K Tsuang, MT AF Cloninger, CR Kaufmann, CA Faraone, SV Malaspina, D Svrakic, DM Harkavy-Friedman, J Suarez, BK Matise, TC Shore, D Lee, H Hampe, CL Wynne, D Drain, C Markel, PD Zambuto, CT Schmitt, K Tsuang, MT TI Genome-wide search for schizophrenia susceptibility loci: The NIMH Genetics Initiative and Millennium Consortium SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE schizophrenia; genetics; linkage; family study ID DIAGNOSTIC INTERVIEW; LINKAGE STRATEGIES; COMPLEX TRAITS; TRANSMISSION; MODELS AB Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors, The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P <.0001) and number of alleles per marker (9.2 vs. 8,4, P <.0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P <.01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment. Am. J, Med, Genet, (Neuropsychiatr, Genet,) 81:275-281, 1998, (C) 1998 Wiley-Liss, Inc. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Columbia Univ, Sch Med, Dept Psychiat, New York, NY USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. NIMH, Rockville, MD 20857 USA. Millennium Pharmaceut, Cambridge, MA USA. RP Cloninger, CR (reprint author), Washington Univ, Sch Med, Dept Psychiat, 4940 Childrens Pl, St Louis, MO 63110 USA. RI Cloninger, Claude/F-5357-2012; OI Cloninger, Claude/0000-0003-3096-4807; Harkavy-Friedman, Jill/0000-0002-1449-0667; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH31302, U01 MH46276, U01 MH46289] NR 18 TC 55 Z9 55 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 10 PY 1998 VL 81 IS 4 BP 275 EP 281 DI 10.1002/(SICI)1096-8628(19980710)81:4<275::AID-AJMG1>3.0.CO;2-T PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZX390 UT WOS:000074511000001 PM 9674971 ER PT J AU Kaufmann, CA Suarez, B Malaspina, D Pepple, J Svrakic, D Markel, PD Meyer, J Zambuto, CT Schmitt, K Matise, TC Friedman, JMH Hampe, C Lee, H Shore, D Wynne, D Faraone, SV Tsuang, MT Cloninger, CR AF Kaufmann, CA Suarez, B Malaspina, D Pepple, J Svrakic, D Markel, PD Meyer, J Zambuto, CT Schmitt, K Matise, TC Friedman, JMH Hampe, C Lee, H Shore, D Wynne, D Faraone, SV Tsuang, MT Cloninger, CR TI NIMH Genetics Initiative Millennium Schizophrenia Consortium: Linkage analysis of African-American pedigrees SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE schizophrenia; linkage analysis; African-American; NIMH Genetics Initiative ID GENOME-WIDE SEARCH; SUSCEPTIBILITY GENES; VULNERABILITY LOCUS; PERICENTRIC REGION; CARIBBEAN PATIENTS; MARFAN-SYNDROME; CHROMOSOME 6P; MEMBER METHOD; NO EVIDENCE; DIAGNOSIS AB The NIMH Genetics Initiative is a multi-site collaborative study designed to create a national resource for genetic studies of complex neuropsychiatric disorders. Schizophrenia pedigrees have been collected at three sites: Washington University, Columbia University, and Harvard University. This article-one in a series that describes the results of a genome-wide scan with 459 short-tandem repeat (STR) markers for susceptibility loci in the NIMH Genetics Initiative schizophrenia sample-presents results for African-American pedigrees, The African-American sample comprises 30 nuclear families and 98 subjects. Seventy-nine of the family members were considered affected by virtue of having received a DSMIII-R diagnosis of schizophrenia (n = 71) or schizoaffective disorder, depressed (n = 8). The families contained a total of 42 independent sib pairs. While no region demonstrated evidence of significant linkage using the criteria suggested by Lander and Kruglyak, several regions, including chromosomes 6q16-6q24, 8pter-8q12, 9q32-9q34, and 15p13-15q12, showed evidence consistent with linkage (P = 0.01-0.05), providing independent support of findings reported in other studies. Moreover, the fact that different genetic loci were identified in this and in the European-American samples, lends credence to the notion that these genetic differences together with differences in environmental exposures may contribute to the reported differences in disease prevalence, severity, comorbidity, and course that has been observed in different racial groups in the United States and elsewhere. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81: 282-289, 1998. (C) 1998 Wiley-Liss, Inc. C1 Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10025 USA. Washington Univ, Sch Med, St Louis, MO USA. Harvard Univ, Sch Med, Boston, MA USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Rockefeller Univ, New York, NY 10021 USA. NIMH, Rockville, MD 20857 USA. RP Kaufmann, CA (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, 722 W 168th St,Unit 58, New York, NY 10025 USA. EM cak2@columbia.edu RI Cloninger, Claude/F-5357-2012; OI Cloninger, Claude/0000-0003-3096-4807; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K02 MH00682, P20 MH50727, U01 MH46289] NR 60 TC 218 Z9 225 U1 4 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 10 PY 1998 VL 81 IS 4 BP 282 EP 289 DI 10.1002/(SICI)1096-8628(19980710)81:4<282::AID-AJMG2>3.0.CO;2-W PG 8 WC Genetics & Heredity SC Genetics & Heredity GA ZX390 UT WOS:000074511000002 PM 9674972 ER PT J AU Leonard, S Gault, J Moore, T Hopkins, J Robinson, M Olincy, A Adler, LE Cloninger, CR Kaufmann, CA Tsuang, MT Faraone, SV Malaspina, D Svrakic, DM Freedman, R AF Leonard, S Gault, J Moore, T Hopkins, J Robinson, M Olincy, A Adler, LE Cloninger, CR Kaufmann, CA Tsuang, MT Faraone, SV Malaspina, D Svrakic, DM Freedman, R TI Further investigation of a chromosome 15 locus in schizophrenia: Analysis of affected sibpairs from the NIMH Genetics Initiative SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE human chromosome pair 15; genetic linkage; nicotinic receptor; polymorphism; auditory evoked potential ID AUDITORY EVOKED-RESPONSES; NICOTINIC RECEPTORS; LINKAGE ANALYSIS; NORMALIZATION; HETEROGENEITY; PHYSIOLOGY; STRATEGIES; RELATIVES; DEFICITS AB Linkage of a neurophysiological deficit associated with schizophrenia, i.e., the failure to inhibit the auditory P50 response, was previously reported at chromosome 15q14, The marker with the highest pairwise lod score, D15S1360, was isolated from a yeast artificial chromosome containing a candidate gene, the alpha 7-nicotinic acetylcholine receptor gene, In the present study, this linkage was further investigated in a subset of the NIMH Genetics Initiative schizophrenia families, These families have not been studied neurophysiologically, as were the families in the original report, Therefore, the DSMIII-R diagnosis of schizophrenia was used as the affected phenotype, Twenty families fulfilled the criteria of at least one sibpair concordant for schizophrenia, along with their two parents or another affected relative outside the nuclear family, available for genotyping. Sibpair analysis showed a significant proportion of D15S1360 alleles shared identical-by-descent (0.58; P < 0.0024). The results further support the involvement of this chromosomal locus in the genetic transmission of schizophrenia, Am, J, Med, Genet, (Neuropsychiatr, Genet,) 81:308-312, 1998, (C) 1998 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat C268 71, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Vet Adm Med Ctr, Denver, CO 80220 USA. Washington Univ, NIMH Genet Initiat, St Louis, MO USA. Columbia Univ, NIMH Genet Initiat, New York, NY USA. Harvard Univ, NIMH Genet Initiat, Cambridge, MA 02138 USA. RP Freedman, R (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat C268 71, 4200 E 9th Ave, Denver, CO 80262 USA. RI Cloninger, Claude/F-5357-2012; OI Cloninger, Claude/0000-0003-3096-4807; Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [DA09457]; NIMH NIH HHS [MH38321, MH44212] NR 39 TC 100 Z9 102 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 10 PY 1998 VL 81 IS 4 BP 308 EP 312 DI 10.1002/(SICI)1096-8628(19980710)81:4<308::AID-AJMG6>3.0.CO;2-P PG 5 WC Genetics & Heredity SC Genetics & Heredity GA ZX390 UT WOS:000074511000006 PM 9674976 ER PT J AU Ogryzko, VV Kotani, T Zhang, XL Schiltz, RL Howard, T Yang, XJ Howard, BH Qin, J Nakatani, Y AF Ogryzko, VV Kotani, T Zhang, XL Schiltz, RL Howard, T Yang, XJ Howard, BH Qin, J Nakatani, Y TI Histone-like TAFs within the PCAF histone acetylase complex SO CELL LA English DT Article ID TATA-BINDING PROTEIN; TRANSCRIPTIONAL ACTIVATION; TFIID COMPLEX; MOLECULAR-CLONING; CELL-CYCLE; ADA2; ACETYLTRANSFERASE; COACTIVATOR; INTERACTS; TAF(II)40 AB PCAF histone acetylase plays a role in regulation of transcription, cell cycle progression, and differentiation. Here, we show that PCAF is found in a complex consisting of more than 20 distinct polypeptides. Strikingly, some polypeptides are identical to TBP-associated factors (TAFs), which are subunits of TFIID. Like TFIID, histone fold-containing factors are present within the PCAF complex. The histone H3- and H2B-like subunits within the PCAF complex are identical to those within TFIID, namely, hTAF(II)31 and hTAF(II)20/15, respectively. The PCAF complex has a novel histone H4-like subunit with similarity to hTAF(II)80 that interacts with the histone H3-like domain of hTAF(II)31. Moreover, the PCAF complex has a novel subunit with WD40 repeats having a similarity to hTAF(II)100. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Nakatani, Y (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 51 TC 435 Z9 446 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 10 PY 1998 VL 94 IS 1 BP 35 EP 44 DI 10.1016/S0092-8674(00)81219-2 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 100AB UT WOS:000074790800007 PM 9674425 ER PT J AU Gasior, M Swiader, M Przybylko, M Borowicz, K Turski, WA Kleinrok, Z Czuczwar, SJ AF Gasior, M Swiader, M Przybylko, M Borowicz, K Turski, WA Kleinrok, Z Czuczwar, SJ TI Felbamate demonstrates low propensity for interaction with methylxanthines and Ca2+ channel modulators against experimental seizures in mice SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE felbamate; nicardipine; nifedipine; flunarizine; Bay K 8644; aminophylline; caffeine; convulsion; drug interaction ID COMMON ANTIEPILEPTIC DRUGS; NMDA RECEPTOR ANTAGONISTS; ANTICONVULSANT ACTIVITY; INDUCED CONVULSIONS; PROTECTIVE ACTIVITY; BAY K-8644; AMINOPHYLLINE; EFFICACY; ELECTROCONVULSIONS; NIMODIPINE AB The aim of this study was to determine the interaction potential of the new antiepileptic drug felbamate (2-phenyl-1,3-propanediol dicarbamate) with three Ca2+ channel blockers (nicardipine, nifedipine, and flunarizine), one Ca2+ channel activator (Bay K 8644; 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridine carboxylic acid), and two methylxanthines (caffeine and aminophylline (theophylline(2).ethylenediamine)) which are all known to markedly change protective effects of conventional antiepileptic drugs. To do so, the maximal electroshock seizure test in mice (an experimental model predicting drug efficacy in the treatment of human generalized tonic-clonic seizures) was employed to (1) quantify changes in the protective efficacy and potency of felbamate produced by adjunct drugs and (2) assess the ability of aminophylline and caffeine to affect protective efficacy afforded by a submaximal protective dose of felbamate against maximal electroshock-induced seizures. Doses of adjunct drugs were selected based on their effects on the threshold for electroconvulsions and on appropriate Literature. Nicardipine (10-30 mg/kg), nifedipine (5-20 mg/kg), flunarizine (2.5-10 mg/kg), Bay K 8644 (2.5-5 mg/kg), and aminophylline (50-75 mg/kg) did not change the protective efficacy and potency of felbamate against maximal electroshock-induced tonic convulsions. Aminophylline in the dose of 100 mg/kg, however, diminished the protective potency of felbamate as evidenced by a statistically significant increase in the protective ED50 value of felbamate (a dose, in mg/kg, predicted to protect 50% of mice against convulsive stimulus) from 79.6 to 118 mg/kg; P < 0.05). Aminophylline and caffeine only at high doses (100 and 161.7 mg/kg, respectively) significantly diminished the protective efficacy of felbamate (110 mg/kg) from 96% to 27% and 40% (P < 0.05), respectively. In conclusion, felbamate shows low interaction potential with Ca2+ channel modulators and methylxanthines. Such low interaction potential clearly differentiates felbamate from conventional antiepileptic drugs where protective effects are readily altered by the compounds tested in the present study. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Med Univ Sch, Dept Pharmacol, PL-20090 Lublin, Poland. Inst Rural Med, Dept Clin Toxicol, PL-20090 Lublin, Poland. RP Gasior, M (reprint author), NIDA, Addict Res Ctr, Preclin Pharmacol Lab, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 40 TC 11 Z9 11 U1 0 U2 1 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 JUL 10 PY 1998 VL 352 IS 2-3 BP 207 EP 214 DI 10.1016/S0014-2999(98)00375-6 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 105UJ UT WOS:000075091700010 PM 9716356 ER PT J AU Dvorak, JA Nagao, E AF Dvorak, JA Nagao, E TI Kinetic analysis of the mitotic cycle of living vertebrate cells by atomic force microscopy SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE atomic force microscopy; light microscopy; mitosis; mechanical properties of cell; tubulin; actin AB The atomic force microscope (AFM) is becoming an important tool for qualitative and quantitative analyses of biological material. However, the difficulties involved in maintaining long-term, steady-state physiologic conditions and the problems associated with analyzing force curves generated from highly viscoelastic biological structures impede the use of the AFM for studies of kinetic processes in living vertebrate cells. In this report, we describe a simple method to track reproducibly kinetic changes in the localized stiffness of vertebrate cells. We tested our method on a study of vertebrate cells in mitosis and found a marked but transient decrease in stiffness occurs in the mitotic spindle region during anaphase. We propose that physical-chemical changes in the mitotic apparatus, most probably, changes in the state of polymerization of interzonal spindle fibers which also have been reported to undergo a marked reduction in birefringence during anaphase, are responsible for the observed decrease in stiffness. Our methodology affords a new approach to studying mitotic events and should be applicable to studies of a variety of viscoelastic properties of living cells, (C) 1998 Academic Press. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP NIAID, Parasit Dis Lab, NIH, Bldg 4,Room B2-11,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 27 Z9 28 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 10 PY 1998 VL 242 IS 1 BP 69 EP 74 DI 10.1006/excr.1998.4077 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 102MD UT WOS:000074927400008 PM 9665803 ER PT J AU Smith, ML Bortnick, RA Sheikh, MS Fornace, AJ AF Smith, ML Bortnick, RA Sheikh, MS Fornace, AJ TI Chromatin relaxation by overexpression of mutant p53, HPV16-E6, or cyclin G transgenes SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE p53; histone H1; cell cycle checkpoints; topoisomerases ID DNA-DAMAGE; HISTONE H1; P53-REGULATED PROTEIN; HUMAN-CELLS; HELA-CELLS; SENSITIVITY; APOPTOSIS; ARREST; GENE; PHOSPHORYLATION AB In this study, using a cell line that carries endogenous wild-type p53 genes, we show that transfection of cells with mutant p53, HPV16-E6, or cyclin G transgenes results in the disruption of higher-order chromatin structure, as evidenced by enhanced sensitivity to micrococcal nuclease. Multiple mechanisms may contribute to this phenotype, including histone H1 phosphorylation, direct binding of oncoproteins to nuclear matrix attachment sites, and altered expression of component genes of the p53 pathway, whose products may function in maintenance of chromatin structure. (C) 1998 Academic Press. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Smith, ML (reprint author), NCI, Div Basic Sci, NIH, Bldg 37,Room 5C09, Bethesda, MD 20892 USA. EM smithml@box-s.nih.gov RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 50 TC 13 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 10 PY 1998 VL 242 IS 1 BP 235 EP 243 DI 10.1006/excr.1998.4078 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 102MD UT WOS:000074927400026 PM 9665821 ER PT J AU O'Keefe, BR Erim, T Beutler, JA Cardellina, JH Gulakowski, RJ Krepps, BL McMahon, JB Sowder, RC Johnson, DG Buckheit, RW Halliday, S Boyd, MR AF O'Keefe, BR Erim, T Beutler, JA Cardellina, JH Gulakowski, RJ Krepps, BL McMahon, JB Sowder, RC Johnson, DG Buckheit, RW Halliday, S Boyd, MR TI Isolation and characterization of adociavirin, a novel HIV-inhibitory protein from the sponge Adocia sp. SO FEBS LETTERS LA English DT Article DE human immunodeficiency virus; macrophage; anti-HIV protein; sponge protein; gp120 ID NATURAL-PRODUCTS; MACROPHAGE; INFECTION; BINDING; ASSAY AB Aqueous extracts of the New Zealand sponge Adocia sp, (Haplosclerida) displayed potent anticytopathic activity in CEM-SS cells infected with HIV-1, Protein fractions of the extract bound both to the viral coat protein gp120 and to the cellular receptor CD4, but not to other tested proteins. The purified active protein, named adociavirin, was characterized by isoelectric focusing, amino acid analysis, MALDI-TOF mass spectrometry and N-terminal sequencing. Adociavirin, a disulfide-linked homodimer with a native molecular weight of 37 kDa, was active against diverse strains and isolates of HIV-1, as well as HIV-2, with EC50 values ranging from 0.4 nM to > 400 nM, The anti-HIV potency of adociavirin appears dependent on host cell type, with macrophage cultures being the most sensitive and peripheral blood lymphocytes the most resistant, (C) 1998 Federation of European Biochemical Societies. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21702 USA. Frederick Res Ctr, So Res Inst, Frederick, MD 21701 USA. NCI, AIDS Vaccine Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Bldg 1052,Rm 121, Frederick, MD 21702 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 24 TC 8 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 JUL 10 PY 1998 VL 431 IS 1 BP 85 EP 90 DI 10.1016/S0014-5793(98)00736-4 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 102AW UT WOS:000074901900018 PM 9684871 ER PT J AU Vaughan, M AF Vaughan, M TI G protein-coupled receptors minireview series SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Editorial Material C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Vaughan, M (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 10 PY 1998 VL 273 IS 28 BP 17297 EP 17297 DI 10.1074/jbc.273.28.17297 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KW UT WOS:000074816100001 PM 9651308 ER PT J AU Rother, KI Imai, Y Caruso, M Beguinot, F Formisano, P Accili, D AF Rother, KI Imai, Y Caruso, M Beguinot, F Formisano, P Accili, D TI Evidence that IRS-2 phosphorylation is required for insulin action in hepatocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-I; SELECTIVE INHIBITOR WORTMANNIN; RECEPTOR SUBSTRATE-1 IRS1; PROTEIN-KINASE-B; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; GLUCOSE-TRANSPORT; TARGETED DISRUPTION; HEMATOPOIETIC-CELLS; GLYCOGEN-SYNTHASE AB Insulin receptor substrates (IRSs) are tyrosine-phosphorylated following stimulation with insulin, insulinlike growth factors (IGFs), and interleukins. A key questionis whether different IRSs play different roles to mediate insulin's metabolic and growth-promoting effects. In a novel system of insulin receptor-deficient hepatocytes, insulin fails to (i) stimulate glucose phosphorylation, (ii) enhance glycogen synthesis, (iii) suppress glucose production, and (iv) promote mitogenesis, However, insulin's ability to induce IRS-1 and gab-1 phosphorylation and binding to phosphatidylinositol (PI) 3-kinase is unaffected, by virtue of the compensatory actions of IGF-1 receptors, In contrast, phosphorylation of IRS-2 and generation of IRS-2/PI 3-kinase complexes are markedly reduced. Thus, absence of insulin receptors selectively reduces IRS-2, but not IRS-1 phosphorylation, and the impairment of IRS-S activation is associated with lack of insulin effects. To address whether phosphorylation of additional IRSs is also affected, we analyzed phosphotyrosine-containing proteins in PI 3-kinase immunoprecipitates from insulin-treated cells, However, these experiments indicate that IRS-1 and IRS-2 are the main PI 3-kinase bound proteins in hepatocytes, These data identify IRS-2 as the main effector of both the metabolic and growth-promoting actions of insulin through PI 3-kinase in hepatocytes, and IRS-1 as the main substrate mediating the mitogenic actions of IGF-1 receptors. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Div Endocrinol, Chapel Hill, NC 27514 USA. Univ Naples, Sch Med, Dipartimento Biol & Patol Cellulare, Naples, Italy. Univ Naples, Sch Med, CNR, Ctr Endocrinol & Oncol Sperimentale, Naples, Italy. RP Accili, D (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg 10,Rm 10D 18, Bethesda, MD 20892 USA. OI Formisano, Pietro/0000-0001-7020-6870 NR 63 TC 125 Z9 128 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 10 PY 1998 VL 273 IS 28 BP 17491 EP 17497 DI 10.1074/jbc.273.28.17491 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KW UT WOS:000074816100032 PM 9651339 ER PT J AU Al-Hasani, H Kinck, CS Cushman, SW AF Al-Hasani, H Kinck, CS Cushman, SW TI Endocytosis of the glucose transporter GLUT4 is mediated by the GTPase dynamin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT ADIPOSE-CELLS; TEMPERATURE-SENSITIVE MUTANT; COATED VESICLE FORMATION; PHOSPHATIDYLINOSITOL 3-KINASE; PLASMA-MEMBRANE; BREFELDIN-A; 1-PHOSPHATIDYLINOSITOL 3-KINASE; SUBCELLULAR TRAFFICKING; 3T3-L1 ADIPOCYTES; INSULIN-RECEPTOR AB To study the role of the GTPase dynamin in GLUT4 intracellular recycling, we have overexpressed dynamin-1 wild type and a GTPase-negative mutant (K44A) in primary rat adipose cells. Transfection was accomplished by electroporation using an hemagglutinin (HA)-tagged GLUT4 as a reporter protein. In cells expressing HA GLUT4 alone, insulin results in an approximate to 7-fold increase in cell surface anti-HA antibody binding. Studies with wortmannin indicate that the kinetics of HA-GLUT4-trafficking parallel those of the native GLUT4 and in addition, that newly synthesized HA-GLUT4 goes to the plasma membrane before being sorted into the insulin responsive compartments. Short term (4 h) coexpression of dynamin-K44A and HA-GLUT4 increases the amount of cell surface HA-GLUT4 in both the basal and insulin-stimulated states. Under conditions of maximal expression of dynamin-K44A (24 h), most or all of the intracellular HA-GLUT4 appears to be present on the cell surface in the basal state, and insulin has no further effect. Measurements of the kinetics of HA-GLUT4 endocytosis show that dynamin-K44A blocks internalization of the glucose transporters. In contrast, expression of dynamin wild type decreases the amount of cell surface HA-GLUT4 in both the basal and insulin stimulated states. These data demonstrate that the endocytosis of GLUT4 is largely mediated by processes which require dynamin. C1 NIDDK, EDMNS, DB, NIH, Bethesda, MD 20892 USA. RP Al-Hasani, H (reprint author), NIDDK, EDMNS, DB, NIH, Bldg 10,Rm 5N102,10 Ctr Dr,MSC 1420, Bethesda, MD 20892 USA. EM hadi@helix.nih.gov NR 60 TC 78 Z9 78 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 10 PY 1998 VL 273 IS 28 BP 17504 EP 17510 DI 10.1074/jbc.273.28.17504 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KW UT WOS:000074816100034 PM 9651341 ER PT J AU Solomon, C Sebag, M White, JH Rhim, J Kremer, R AF Solomon, C Sebag, M White, JH Rhim, J Kremer, R TI Disruption of vitamin D receptor-retinoid X receptor heterodimer formation following ras transformation of human keratinocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR HORMONE RECEPTORS; D RESPONSE ELEMENT; THYROID-HORMONE; ACID RECEPTORS; CO-REPRESSOR; DIFFERENTIATION; BINDING; 1,25-DIHYDROXYVITAMIN-D3; CELLS; GENE AB A partial resistance to the growth inhibitory influence of 1,25-dihydroxyvitamin D-3 is apparent when immortalized keratinocytes are transformed by the ras oncogene. The vitamin D receptor (VDR) was isolated, analyzed, and found to be identical in normal, immortalized, and ras-transformed keratinocytes. Subsequently, nuclear extracts from immortalized and ras-transformed keratinocytes were analyzed in gel mobility shift assays utilizing labeled vitamin D response elements or thyroid hormone response elements. A specific protein DNA complex that was shown to contain VDR using an anti-VDR antibody was identified in both types of extracts; however, the addition of an anti-retinoid X receptor (RXR) antibody identified RXR in the complex of both normal and immortalized keratinocyte cell extracts, but not in ras-transformed keratinocytes. Furthermore, transfection of ras-transformed keratinocytes with wild-type human RXR alpha rescued VDR.RXR and thyroid hormone receptor.RXR complexes as demonstrated by a supershift in the presence of the anti-RXR antibody. Both cell lines were found to express RXR alpha message in equal amounts. Western blot analysis revealed that RXR alpha protein from ras-transformed keratinocytes was indistinguishable from that from immortalized keratinocytes and from control cells. These results suggest a causal relationship between resistance to the growth inhibitory influences of 1,25-dihydroxyvitamin D-3 and disruption of the VDR.RXR complex in malignant keratinocytes. C1 McGill Univ, Dept Med, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Physiol, Montreal, PQ H3A 1A1, Canada. NCI, Mol Oncol Lab, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. RP Kremer, R (reprint author), Royal Victoria Hosp, Calcium Res Lab, Rm H4-67,687 Pine Ave W, Montreal, PQ H3A 1A1, Canada. OI White, John/0000-0002-4785-2687 NR 29 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 10 PY 1998 VL 273 IS 28 BP 17573 EP 17578 DI 10.1074/jbc.273.28.17573 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KW UT WOS:000074816100044 PM 9651351 ER PT J AU Zeng, HW Jackson, DA Oshima, H Simons, SS AF Zeng, HW Jackson, DA Oshima, H Simons, SS TI Cloning and characterization of a novel binding factor (GMEB-2) of the glucocorticoid modulatory element SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE AMINOTRANSFERASE GENE; TRANSCRIPTION FACTORS; RESPONSE ELEMENT; RECEPTOR; CELL; EXPRESSION; INDUCTION; ACTIVATION; SUPPRESSIN; UPSTREAM AB The 21-base pair glucocorticoid modulatory element (GME) of the rat tyrosine aminotransferase gene is the only cis-acting element known to modulate the transcriptional activity of receptors bound to glucocorticoid response elements. Specifically, the GME increases the activity of complexes bound both by physiological concentrations of glucocorticoids, due to a left shift in the dose-response curve, and by saturating concentrations of anti-glucocorticoids. For this reason, the nuclear protein(s) that has been demonstrated to bind to the GME is of major interest as a possible transcription factor with hitherto undescribed properties. Subsequent studies indicated that not one but two proteins of 88 and 67 kDa (= GMEB-1 and -2, respectively) formed a heteromeric complex with double-stranded GME oligonucleotides in gel shift assays and participated in the expression of GME activity (Oshima, H., Szapary, D., and Simons, S. S., Jr. (1995) J. Biol. Chem. 270, 21895-21910). Here, we report the use of polymerase chain reaction of degenerate oligonucleotides and 5'- and 3'-rapid amplification of cDNA ends to clone two cDNAs of 2.0 and 1.9 kilobase pairs that probably result hom alternative splicing. Both cDNAs encoded open reading frames containing all four previously sequenced peptides. The longer 2.0-kilobase pair cDNA encoded an open reading frame for an acidic, 529-amino acid protein and afforded a major 67-kDa and a minor 58-kDa protein after in vitro transcription/translation. Both proteins were recognized by a mono-epitopic antibody raised against a peptide of GMEB-2. The in vitro translated protein bound to GME DNA in gel shift assays. However, the binding to GME DNA increased markedly after mixing with authentic GMEB-1 to give a gel-shifted complex that was similar to that derived hom HTC cell cytosol. GMEB-2 shares a unique domain (KDWKR) with proteins derived from diverse organisms as follows: Drosophila (DEAF-I), rat (Suppressin), and Caenorhabditis elegans (three unknown open reading frames). Collectively, these data suggest that the 67-kDa GMEB-2 not only is an important factor for the modulation of glucocorticoid receptor bound to glucocorticoid response elements but also may belong to a novel family of transcription factors. C1 NIDDK, LMCB, Steroid Hormone Sect, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, LMCB, Steroid Hormone Sect, NIH, Bldg 8,Rm B2A-07, Bethesda, MD 20892 USA. RI Jackson, David/E-9984-2014 NR 47 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 10 PY 1998 VL 273 IS 28 BP 17756 EP 17762 DI 10.1074/jbc.273.28.17756 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KW UT WOS:000074816100069 PM 9651376 ER PT J AU Marekov, LN Steinert, PM AF Marekov, LN Steinert, PM TI Ceramides are bound to structural proteins of the human foreskin epidermal cornified cell envelope SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROLINE-RICH PROTEIN-1; STRATUM-CORNEUM; CROSS-LINKING; LIPIDS; TRANSGLUTAMINASES; CORNEOCYTE; INVOLUCRIN; LORICRIN AB An important component of barrier function in human epidermis is contributed by ceramides that are bound by ester linkages to undefined proteins of the cornified cell envelope (CE), In this paper, we have examined the protein targets for the ceramide attachment. By partial saponification of isolated foreskin epidermal CEs followed by limited proteolysis, we have recovered several lipopeptides. Biochemical and mass spectroscopic characterization revealed that all contained near stoichiometric amounts of ceramides of masses ranging from about 690 to 890 atomic mass units, of which six quantitatively major species were common. The array of ceramides was similar to that obtained from pig skin, the composition of which is known, thereby providing strong indirect data for their fatty acid and sphingosine compositions, The recovered peptides accounted for about 20% of the total foreskin CE ceramides, By amino acid sequencing, about 35% of the peptides were derived from ancestral glutamine glutamate-rich regions of involucrin, an important CE structural protein. Another 18% derived from rod domain sequences of periplakin and envoplakin, which are also known or suspected CE proteins. Other peptides were too short for unequivocal identification. Together, these data indicate that involucrin, envoplakin, periplakin, and possibly other structural proteins serve as substrates for the attachment of ceramides by ester linkages to the CE for barrier function in human epidermis. C1 NIAMSD, Lab Shin Biol, NIH, Bethesda, MD 20892 USA. RP Steinert, PM (reprint author), NIAMSD, Lab Shin Biol, NIH, Bldg 6,Rm 425, Bethesda, MD 20892 USA. EM pemast@helix.nih.gov NR 37 TC 131 Z9 135 U1 0 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 10 PY 1998 VL 273 IS 28 BP 17763 EP 17770 DI 10.1074/jbc.273.28.17763 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KW UT WOS:000074816100070 PM 9651377 ER PT J AU Suy, S Mitchell, JB Ehleiter, D Haimovitz-Friedman, A Kasid, U AF Suy, S Mitchell, JB Ehleiter, D Haimovitz-Friedman, A Kasid, U TI Nitroxides tempol and tempo induce divergent signal transduction pathways in MDA-MB 231 breast cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; FLOW CYTOMETRIC DETECTION; TUMOR-NECROSIS-FACTOR; C-JUN; MAP KINASE; PHOSPHATIDYLSERINE EXPRESSION; SPHINGOMYELIN PATHWAY; INDUCED APOPTOSIS; TERMINAL KINASES; OXIDATIVE DAMAGE AB Tempol and tempo are stable free radical nitroxides that possess antioxidant properties. In this study, we examined the effects of these compounds on components of the mitogen-activated protein kinase signal transduction cascade. Tempo treatment (15 min), of MDA-MB 231 human breast cancer cells resulted in significant levels of tyrosine phosphorylation of several as yet unidentified proteins compared with equimolar concentration of tempol (10 mM). Both compounds caused tyrosine phosphorylation and activation of Raf-l protein kinase (30 min, 2-3-fold). Interestingly, however, only tempol caused increased extracellular signal-regulated kinase 1 activity (2 h, similar to 3-fold). On the other hand, tempo, but not tempol, potently activated stress-activated protein kinase (2 h, >3-fold). Consistent with these data, tempol was found to be noncytotoxic, whereas tempo induced apoptotic cell death (2 h, >50%). Tempo treatment also resulted in significant elevation of ceramide levels at 30 min (54% over control) and 1 h (71% over control) posttreatment, preceding stress-activated protein kinase activation and apoptosis. These data suggest that in the absence of an environmental oxidative stress, tempol and tempo elicit distinct cellular signaling pathways. The recognition of the molecular mechanisms of nitroxide action may have important implications for biological effectiveness of these compounds. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Dept Radiat Med, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NCI, Div Radiat Biol, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Kasid, U (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Dept Radiat Med, E208,Res Bldg,3970 Reservoir Rd NW, Washington, DC 20007 USA. FU NCI NIH HHS [CA58984, CA68322/OD68322, CA74175] NR 80 TC 39 Z9 40 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 10 PY 1998 VL 273 IS 28 BP 17871 EP 17878 DI 10.1074/jbc.273.28.17871 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KW UT WOS:000074816100085 PM 9651392 ER PT J AU Kostenis, E Zeng, FY Wess, J AF Kostenis, E Zeng, FY Wess, J TI Functional characterization of a series of mutant G protein alpha(q) subunits displaying promiscuous receptor coupling properties SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE-NUCLEOTIDE-BINDING; HETEROTRIMERIC G-PROTEINS; G-BETA-GAMMA; PHOSPHOLIPASE-C; AMINO-TERMINUS; MUSCARINIC RECEPTOR; SYNTHETIC PEPTIDES; PALMITOYLATION; IDENTIFICATION; MYRISTOYLATION AB The N termini of two G protein alpha subunits, alpha(q) and alpha(11), differ from those of other alpha subunits in that they display a unique, highly conserved six-amino acid extension (MTLESI(M)). We recently showed that an alpha(q) deletion mutant lacking these six amino acids (in contrast to wild type alpha(q)) was able to couple to several different G(s)- and G(L/o)-coupled receptors, apparently due to promiscuous receptor/G protein coupling (Kostenis, E., Degtyarev, M. Y., Conklin, B. R., and Wess, J. (1997) J. Biol. Chem. 272, 19107-19110). To study which specific amino acids within the N-terminal segment of alpha(q/11) are critical for constraining the receptor coupling selectivity of these subunits, this region of alpha(q) was subjected to systematic deletion and alanine scanning mutagenesis. All mutant alpha(q) constructs (or wild type alpha(q) as a control) were coexpressed (in COS-7 cells) with the m2 muscarinic or the D2 dopamine receptors, two prototypical G(L/o)-coupled receptors, and Ligand-induced increases in inositol phosphate production were determined as a measure of G protein activation. Surprisingly, all 14 mutant G proteins studied (but not wild type alpha(q)) gained the ability to productively interact with the two G(L/o)-linked receptors, Similar results were obtained when we examined the ability of selected mutant alpha(q) subunits to couple to the G(s)-coupled beta 2-adrenergic receptor, Additional experiments indicated that the functional promiscuity displayed by all investigated mutant alpha(q) constructs was not due to overexpression (as compared with wild type alpha(q)), lack of palmitoylation, or initiation of translation at a downstream ATG codon (codon seven). These data are consistent with the notion that the six-amino acid extension characteristic for alpha(q/11) subunits forms a tightly folded protein subdomain that is critical for regulating the receptor coupling selectivity of these subunits. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-05, Bethesda, MD 20892 USA. NR 60 TC 48 Z9 51 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 10 PY 1998 VL 273 IS 28 BP 17886 EP 17892 DI 10.1074/jbc.273.28.17886 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KW UT WOS:000074816100087 PM 9651394 ER PT J AU Gopal-Srivastava, R Cvekl, A Piatigorsky, J AF Gopal-Srivastava, R Cvekl, A Piatigorsky, J TI Involvement of retinoic acid retinoid receptors in the regulation of murine alpha B-crystallin small heat shock protein gene expression in the lens SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HOMEOBOX-CONTAINING GENE; RESPONSE ELEMENT; TRANSCRIPTIONAL REGULATION; ARGININOSUCCINATE LYASE; MOUSE EMBRYOGENESIS; DELTA-CRYSTALLIN; TRANSGENIC MICE; PAIRED DOMAIN; EYELESS GENE; MUTANT MICE AB Crystallins are a diverse group of abundant soluble proteins that are responsible for the refractive properties of the transparent eye lens. me showed previously that Pax-6 can activate the alpha B-crystallin/small heat shock protein promoter via the lens specific regulatory regions LSR1 (-147/-118) and LSR2 (-78/-46). Here we demonstrate that retinoic acid can induce the accumulation of alpha B-crystallin in N/N1003A lens cells and that retinoic acid receptor heterodimers (retinoic acid receptor/retinoid X receptor; RAR/RXR) can transactivate LSR1 and LSR2 in cotransfection experiments. DNase I footprinting experiments demonstrated that purified RAR/RXR heterodimers will OCCUPY sequences resembling retinoic acid response elements within LSR1 and LSR2. Electrophoretic mobility shift assays using antibodies indicated that LSR1 and LSR2 can interact with endogenous RAR/RXR complexes in extracts of cultured lens cells. Pax-6 and RAR/RXR together had an additive effect on the activation of alpha B-promoter in the transfected lens cells. Thus, the alpha B-crystallin gene is activated by Pax-6 and retinoic acid receptors, making these transcription factors examples of proteins that have critical roles in early development as well as in the expression of proteins characterizing terminal differentiation. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP NEI, Mol & Dev Biol Lab, NIH, Bldg 6,Rm 201, Bethesda, MD 20892 USA. EM joram@helix.nih.gov RI Cvekl, Ales/B-2427-2013 NR 71 TC 44 Z9 45 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 JUL 10 PY 1998 VL 273 IS 28 BP 17954 EP 17961 DI 10.1074/jbc.273.28.17954 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KW UT WOS:000074816100095 PM 9651402 ER PT J AU Oka, H Ito, Y Yamada, S Kagami, T Hayakawa, J Harada, K Atsumi, E Suzuki, M Suzuki, M Odani, H Akahori, S Maeda, K Nakazawa, H Ito, Y AF Oka, H Ito, Y Yamada, S Kagami, T Hayakawa, J Harada, K Atsumi, E Suzuki, M Suzuki, M Odani, H Akahori, S Maeda, K Nakazawa, H Ito, Y TI Separation of lac dye components by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; food analysis; laccaic acids; lac dye; dyes ID 2-PHASE SOLVENT SYSTEMS AB High-speed counter-current chromatography has been successfully applied to the separation of the lac dye components. A 25-mg quantity of the sample was separated using a two-phase solvent system composed of tert.-butyl methyl ether-n-butanol-acetonitrile-water (2.2:1:5). The fractions were analyzed by high-performance liquid chromatography and electrospray tandem mass spectrometry. The separation yielded 2.6 mg of 97.2% purl laccaic acid C, 9.5 mg of 98.1% pure laccaic acid A, 3.6 mg of 98.2% pure laccaic acid B, and 0.5 mg of a 95.0% pure anthraquinonedicarboxylic acid with a molecular mass of 360. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 462, Japan. Dept Hlth, Food Safety & Vet Affairs Div, Naka Ku, Nagoya, Aichi 46001, Japan. Meijo Univ, Fac Pharm, Tempaku Ku, Nagoya, Aichi 468, Japan. Nagoya Univ, Branch Hosp, Dept Internal Med, Nagoya, Aichi 461, Japan. Hoshi Univ, Fac Pharmaceut Sci, Shinagawa Ku, Tokyo 142, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Oka, H (reprint author), Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagare 7-6,Tsuji Machi, Nagoya, Aichi 462, Japan. NR 21 TC 26 Z9 27 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 10 PY 1998 VL 813 IS 1 BP 71 EP 77 DI 10.1016/S0021-9673(98)00311-2 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 101GW UT WOS:000074862100008 PM 9697316 ER PT J AU Litvinovich, SV Brew, SA Aota, S Akiyama, SK Haudenschild, C Ingham, KC AF Litvinovich, SV Brew, SA Aota, S Akiyama, SK Haudenschild, C Ingham, KC TI Formation of amyloid-like fibrils by self-association of a partially unfolded fibronectin type III module SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE fibronectin; amyloid fibril; protein folding; self-association; extracellular matrix ID DOMAIN-STRUCTURE; EXTRACELLULAR-MATRIX; CIRCULAR-DICHROISM; BINDING FRAGMENT; IN-VITRO; PROTEIN; REGION; SEQUENCE; SITE; RECONSTRUCTION AB The ninth type III module of murine fibronectin was expressed in E. coli and folded into a compact homogeneous monomer whose unfolding and refolding were then investigated by fluorescence, circular dichroism, calorimetry and electron microscopy. The isolated module is unusually labile under physiological conditions. When heated at 1 deg. C/minute it exhibits an irreversible endothermic transition between 35 and 42 degrees C depending on the protein concentration. The transition is accompanied by changes in secondary and tertiary structure with partial exposure of the single tryptophan and increased binding of the hydrophobic probe, 1,8-anilinonaphthalene-sulfonate. The partially unfolded intermediate undergoes rapid self-association leading to the formation of large stable multimers that, like the original monomer, contain substantial amounts of beta sheet structure. The multimers melt and dissociate reversibly in a second endothermic transition between 60 and 90 degrees C also depending on the protein concentration. This second transition destroys the remaining secondary structure and further exposes the tryptophan. Visualization of negatively stained specimens in the electron microscope reveals that partially unfolded rmIII-9 slowly forms amyloid-like fibrils of similar to 10 nm width and indeterminate length. A subdomain swapping mechanism is proposed in which beta strands from one partially unfolded molecule interact with complementary regions of another to form oligomers and polymers. The possibility that similar interactions could play a role in the formation of fibrils by fibronectin in vivo is discussed. (C) 1998 Academic Press. C1 Amer Red Cross, Holland Lab, Rockville, MD 20855 USA. George Washington Univ, Sch Med, Inst Biomed Sci, Washington, DC USA. NIDR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ingham, KC (reprint author), Amer Red Cross, Holland Lab, Rockville, MD 20855 USA. FU NHLBI NIH HHS [HL21791] NR 53 TC 150 Z9 153 U1 0 U2 9 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 10 PY 1998 VL 280 IS 2 BP 245 EP 258 DI 10.1006/jmbi.1998.1863 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 101FA UT WOS:000074857900007 PM 9654449 ER PT J AU Wassermann, EM Wedegaertner, FR Ziemann, U George, MS Chen, R AF Wassermann, EM Wedegaertner, FR Ziemann, U George, MS Chen, R TI Crossed reduction of human motor cortex excitability by 1-Hz transcranial magnetic stimulation SO NEUROSCIENCE LETTERS LA English DT Article DE transcranial magnetic stimulation; motor cortex; basal ganglia; inhibition; long-term depression ID LONG-TERM DEPRESSION; BASAL GANGLIA; FACILITATION; HIPPOCAMPUS; CONNECTIONS; INHIBITION; MYOCLONUS; DISEASE; HAND AB Electrophysiological studies have shown that 1-Hz repetitive transcranial magnetic stimulation (rTMS) of the primary motor area (M1) can produce a local decrease in excitability. Functional imaging data suggest that this change may be bilateral. In normal subjects, we measured motor evoked potential (MEP) amplitude at a series of stimulation intensities in the contralateral M1 before and after 15 min of active or sham rTMS at just above the MEP threshold. The slope of the curve relating MEP amplitude and stimulation intensity was decreased in the unstimulated hemisphere by active but not sham rTMS. This demonstrates that rTMS can condition cortical excitability at a distance of one or more synapses and suggest that decreased excitability to TMS is a correlate of decreased blood flow and metabolism. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. RP Wassermann, EM (reprint author), NINDS, Med Neurol Branch, NIH, 10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 22 TC 167 Z9 168 U1 0 U2 5 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 JUL 10 PY 1998 VL 250 IS 3 BP 141 EP 144 DI 10.1016/S0304-3940(98)00437-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 105UT UT WOS:000075092500001 PM 9708852 ER PT J AU Wawer, MJ Gray, RH Sewankambo, NK Serwadda, D Paxton, L Berkley, S McNairn, D Wabwire-Mangen, F Li, CJ Nalugoda, F Kiwanuka, N Lutalo, T Rookmeyer, R Kelly, R Quinn, TC AF Wawer, MJ Gray, RH Sewankambo, NK Serwadda, D Paxton, L Berkley, S McNairn, D Wabwire-Mangen, F Li, CJ Nalugoda, F Kiwanuka, N Lutalo, T Rookmeyer, R Kelly, R Quinn, TC TI A randomized, community trial of intensive sexually transmitted disease control for AIDS prevention, Rakai, Uganda SO AIDS LA English DT Article DE sexually transmitted disease (STD) control; AIDS prevention; randomized controlled trial; STD mass treatment; STD/HIV prevalence; Uganda ID LIGASE CHAIN-REACTION; IMMUNODEFICIENCY-VIRUS TYPE-1; UNCOMPLICATED GONORRHEA; CHLAMYDIA-TRACHOMATIS; NEISSERIA-GONORRHOEAE; TRICHOMONAS-VAGINALIS; HIV-INFECTION; RISK-FACTORS; HAEMOPHILUS-DUCREYI; RURAL TANZANIA AB Objective: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence. Study design: Randomized, controlled, community-based trial in Rakai District, Uganda. Methods: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services. Results: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis. Conclusions: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting. (C) 1998 Lippincott-Raven Publishers. C1 Columbia Univ, Sch Publ Hlth, Ctr Populat & Family Hlth, New York, NY 10032 USA. Johns Hopkins Univ, Baltimore, MD USA. Makerere Univ, Kampala, Uganda. Rockefeller Fdn, New York, NY USA. Uganda Virus Res Inst, Rakai Project, Entebbe, Uganda. NIH, Bethesda, MD 20892 USA. RP Wawer, MJ (reprint author), Columbia Univ, Sch Publ Hlth, Ctr Populat & Family Hlth, 60 Haven Ave,B-3, New York, NY 10032 USA. RI Quinn, Thomas/A-2494-2010; OI Sewankambo, Nelson/0000-0001-9362-053X FU NIAID NIH HHS [R01-AI 34826]; NICHD NIH HHS [5P30-HD 06268] NR 66 TC 150 Z9 151 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 9 PY 1998 VL 12 IS 10 BP 1211 EP 1225 DI 10.1097/00002030-199810000-00014 PG 15 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZY083 UT WOS:000074584900014 PM 9677171 ER PT J AU Perichon, R Moser, AB Wallace, WC Cunningham, SC Roth, GS Moser, HW AF Perichon, R Moser, AB Wallace, WC Cunningham, SC Roth, GS Moser, HW TI Peroxisomal disease cell lines with cellular plasmalogen deficiency have impaired muscarinic cholinergic signal transduction activity and amyloid precursor protein secretion SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE peroxisome; plasmalogen; amyloid precursor protein; signal transduction; muscarinic cholinergic receptor ID PLATELET-ACTIVATING-FACTOR; ALZHEIMERS-DISEASE; BRAIN; FIBROBLASTS; PROPENSITY; OXIDATION; RELEASE; LIVER; RATS; ACID AB We tested whether alterations in membrane lipid composition associated with peroxisomal diseases affect muscarinic cholinergic signal transduction activity and amyloid precursor protein (APP) secretion in cultured human skin fibroblasts and Chinese hamster ovary (CHO) mutants. We found that in cell lines from patients with peroxisomal disorders where plasmalogen levels were low, the low-Km GTPase activity was not induced by carbachol, and APP secretion was reduced. This effect on signal transduction activity was not associated with decreased levels of the M1-muscarinic cholinergic receptor or its associated heterotrimeric G-protein. Specifically, this decrease was associated with a plasmalogen deficiency since a CHO cell line with only a deficit in plasmalogens was as severely affected as were generalized peroxisomal disorder cell lines, Thus, plasmalogens appear to be implicated in muscarinic cholinergic signal transduction and secretion of APP. These results provide new insights about the pathophysiology of peroxisomal diseases and may be relevant to Alzheimer's disease where reduced plasmalogen levels have been reported. (C) 1998 Academic Press. C1 NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Kennedy Krieger Inst, Neurogenet Sect, Lab Peroxisomal Dis, Baltimore, MD 21205 USA. RP Perichon, R (reprint author), NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 31 TC 22 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 9 PY 1998 VL 248 IS 1 BP 57 EP 61 DI 10.1006/bbrc.1998.8909 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZZ706 UT WOS:000074758800011 PM 9675085 ER PT J AU Al-Jafari, AA Kamal, MA Greig, NH Alhomida, AS Perry, ER AF Al-Jafari, AA Kamal, MA Greig, NH Alhomida, AS Perry, ER TI Kinetics of human erythrocyte acetylcholinesterase inhibition by a novel derivative of physostigmine: Phenserine SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CHOLINESTERASE AB The effect of phenserine, a novel cholinesterase inhibitor, was assessed for the first time on kinetic parameters of human erythrocyte acetylcholinesterase (AChE). Phenserine (0.025-0.40 mu M) inhibited the activity of human erythrocyte AChE in a concentration-dependent fashion, the IC50 was 0.0453 mu M. The Michaelis-Menten constant (K-m) for the hydrolysis of acetylthiocholine iodide was found to be 0.124 mM and the V-max was 0.980 mu mol/min/mg protein. Dixon as well as Lineweaver-Burk plots and their secondary replots indicated that the nature of the inhibition was of the noncompetitive type. The value of K-i was estimated as 0.048 mu M by the primary and secondary replots of the Dixon as well as secondary replots of the Line Neaver-Burk plot. A novel relationship between K-i and substrate concentration was also identified which permits more precise prediction of the specific type of noncompetitive inhibition of various enzymes by a wide variety of drugs, chemicals and, in some circumstances, by their own substrates. (C) 1998 Academic Press. C1 King Saud Univ, Coll Sci, Dept Biochem, Riyadh 11451, Saudi Arabia. NIA, NIH, Baltimore, MD 21224 USA. Newcastle Gen Hosp, MRC, Neurochem Pathol Unit, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. RP Al-Jafari, AA (reprint author), King Saud Univ, Coll Sci, Dept Biochem, POB 2455, Riyadh 11451, Saudi Arabia. EM JAFARI@KSU.EDU.SA RI Kamal, Mohammad/H-9643-2012; Kamal, Mohammad/J-4622-2013; OI Kamal, Mohammad/0000-0003-1862-173X; Kamal, Mohammad Amjad/0000-0003-0088-0565 NR 29 TC 34 Z9 35 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 9 PY 1998 VL 248 IS 1 BP 180 EP 185 DI 10.1006/bbrc.1998.8931 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZZ706 UT WOS:000074758800033 PM 9675107 ER PT J AU Burke, W Thomson, E Khoury, MJ McDonnell, SM Press, N Adams, PC Barton, JC Beutler, E Brittenham, G Buchanan, A Clayton, EW Cogswell, ME Meslin, EM Motulsky, AG Powell, LW Sigal, E Wilfond, BS Collins, FS AF Burke, W Thomson, E Khoury, MJ McDonnell, SM Press, N Adams, PC Barton, JC Beutler, E Brittenham, G Buchanan, A Clayton, EW Cogswell, ME Meslin, EM Motulsky, AG Powell, LW Sigal, E Wilfond, BS Collins, FS TI Hereditary hemochromatosis - Gene discovery and its implications for population-based screening SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IRON OVERLOAD; AFRICAN-AMERICANS; IDIOPATHIC HEMOCHROMATOSIS; COST-EFFECTIVENESS; HEALTH-INSURANCE; CYSTIC-FIBROSIS; MOLECULAR-BASIS; BLOOD-DONORS; PHENYLKETONURIA; PREVALENCE AB Objective.-To evaluate the role of genetic testing in screening for hereditary hemochromatosis to help guide clinicians, policymakers, and researchers. Participants.-An expert panel was convened on March 3, 1997, by the Centers for Disease Control and Prevention (CDC) and the National Human Genome Research Institute (NHGRI), with expertise in epidemiology, genetics, hepatology, iron overload disorders, molecular biology, public health, and the ethical, legal, and social implications surrounding the discovery and use of genetic information. Evidence.-The group reviewed evidence regarding the clinical presentation, natural history, and genetics of hemochromatosis, including current data on the candidate gene for hemochromatosis (HFE) and on the ethical and health policy implications of genetic testing for this disorder. Consensus Process.-Consensus was achieved by group discussion confirmed by a voice vote. A draft of the consensus statement was prepared by a writing committee and subsequently reviewed and revised by all members of the expert group over a 1-year period. Conclusions.-Genetic testing is not recommended at this time in population-based screening for hereditary hemochromatosis, due to uncertainties about prevalence and penetrance of HFE mutations and the optimal care of asymptomatic people carrying HFE mutations. In addition, use of a genetic screening test raises concerns regarding possible stigmatization and discrimination. Tests for HFE mutations may play a role in confirming the diagnosis of hereditary hemochromatosis in persons with elevated serum iron measures, but even this use is limited by uncertainty about genotype-phenotype correlations. To address these questions, the expert group accorded high priority to population-based research to define the prevalence of HFE mutations, age and sex-related penetrance of different HFE genotypes, interactions between HFE genotypes and environmental modifiers, and psychosocial outcomes of genetic screening for hemochromatosis. C1 Univ Washington, Dept Med, Seattle, WA 98105 USA. Univ Washington, Dept Genet, Seattle, WA 98195 USA. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Off Genet & Dis Prevent, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Nutr & Phys Act, Atlanta, GA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Med, Los Angeles, CA USA. Univ Western Ontario, Dept Med, London, ON, Canada. So Iron Disorders Ctr, Birmingham, AL USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA. Case Western Reserve Univ, Metrohlth Med Ctr, Dept Med, Cleveland, OH USA. Univ Wisconsin, Sch Business, Madison, WI 53706 USA. Vanderbilt Univ, Dept Pediat, Nashville, TN USA. Vanderbilt Univ, Sch Law, Nashville, TN 37240 USA. Univ Queensland, Dept Med, Brisbane, Qld 4000, Australia. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Mercator Genet, Menlo Park, CA USA. Univ Arizona, Dept Pediat, Tucson, AZ 85721 USA. RP Burke, W (reprint author), Univ Washington, Dept Med, Box 354765,4245 Roosevelt Way NE, Seattle, WA 98105 USA. EM wburke@u.washington.edu NR 61 TC 228 Z9 233 U1 3 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 8 PY 1998 VL 280 IS 2 BP 172 EP 178 DI 10.1001/jama.280.2.172 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZY321 UT WOS:000074608400034 PM 9669792 ER PT J AU Qiao, LX Wang, SM George, C Lewin, NE Blumberg, PM Kozikowski, AP AF Qiao, LX Wang, SM George, C Lewin, NE Blumberg, PM Kozikowski, AP TI Structure-based design of a new class of protein kinase C modulators SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID TUMOR PROMOTERS; PHORBOL ESTERS; STEREOCHEMISTRY; TELEOCIDINS; MODEL C1 Georgetown Univ, Med Ctr, Drug Discovery Program, Washington, DC 20007 USA. USN, Res Lab, Washington, DC 20375 USA. NCI, Mol Mechanisms Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Kozikowski, AP (reprint author), Georgetown Univ, Med Ctr, Drug Discovery Program, Washington, DC 20007 USA. RI Wang, Shaomeng/E-9686-2010 NR 16 TC 28 Z9 29 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 8 PY 1998 VL 120 IS 26 BP 6629 EP 6630 DI 10.1021/ja980513u PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA ZZ420 UT WOS:000074727600036 ER PT J AU Hallock, YF Cardellina, JH Schaffer, M Bringmann, G Francois, G Boyd, MR AF Hallock, YF Cardellina, JH Schaffer, M Bringmann, G Francois, G Boyd, MR TI Korundamine A, a novel HIV-inhibitory and antimalarial "hybrid" naphthylisoquinoline alkaloid heterodimer from Ancistrocladus korupensis SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID MICHELLAMINE-B; HEYNEANUS AB A unique heterodimeric naphthylisoquinoline alkaloid, korundamine A (2), comprised of two different monomeric biaryl halves, has been isolated from the Cameroonian tropical liana Ancistrocladus korupensis. Korundamine A is the first "hybrid" dimer found in the Ancistrocladaceae; rr! vitro, it demonstrated anticytopathic activity against HIV-1 and antimalarial activity against Plasmodium falciparum. Published by Elsevier Science Ltd. C1 Natl Canc Inst, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), Natl Canc Inst, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag, Bldg 1052,Room 121, Frederick, MD 21702 USA. NR 20 TC 36 Z9 38 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUL 7 PY 1998 VL 8 IS 13 BP 1729 EP 1734 DI 10.1016/S0960-894X(98)00304-7 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 101MA UT WOS:000074871700031 PM 9873424 ER PT J AU Marquez, VE Sharma, R Wang, SM Lewin, NE Blumberg, PM Kim, IS Lee, J AF Marquez, VE Sharma, R Wang, SM Lewin, NE Blumberg, PM Kim, IS Lee, J TI Conformationally constrained analogues of diacylglycerol (DAG). 14. Dissection of the roles of the sn-1 and sn-2 carbonyls in DAG mimetics by isopharmacophore replacement SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PROTEIN-KINASE-C; PHORBOL ESTER BINDING; 5-DISUBSTITUTED TETRAHYDRO-2-FURANONE TEMPLATE AB The replacement of the sn-l and sn-2 carbonyl esters in DAG-surrogate lactones by sulfonate esters showed that their isosteric properties in protein kinase C binding are controlled by the location of the hydrophobic alkyl chain on the molecule. The CO and SO2 groups appear to be true isosteres only when they are adjacent to the alkyl chain, which is presumed to insert normal to the lipid bilayer. Published by Elsevier Science Ltd. C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Cellular Carcinogenesis & Tumor Promot, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Med Chem Lab, Coll Pharm, Kwanak Ku, Seoul 151742, South Korea. RP Marquez, VE (reprint author), NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 17 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUL 7 PY 1998 VL 8 IS 13 BP 1757 EP 1762 DI 10.1016/S0960-894X(98)00307-2 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 101MA UT WOS:000074871700036 PM 9873429 ER PT J AU Diodati, JG Dakak, N Gilligan, DM Quyyumi, AA AF Diodati, JG Dakak, N Gilligan, DM Quyyumi, AA TI Effect of atherosclerosis on endothelium-dependent inhibition of platelet activation in humans SO CIRCULATION LA English DT Article DE endothelium; atherosclerosis; blood flow; nitric oxide; platelets ID NITRIC-OXIDE SYNTHASE; EPICARDIAL CORONARY-ARTERIES; RELAXING FACTOR; L-ARGININE; SMOOTH-MUSCLE; SODIUM-NITROPRUSSIDE; VASOMOTOR RESPONSE; RISK-FACTORS; WHOLE-BLOOD; VASCULAR ENDOTHELIUM AB Background-We investigated whether luminal release of nitric oxide (NO) contributes to inhibition of platelet activation and whether these effects are reduced in patients with atherosclerosis. Methods and Results-Femoral blood flow velocity and ex vivo whole blood platelet aggregation by impedance aggregometry were measured in femoral venous blood during femoral arterial infusion of acetylcholine (ACh; 30 mu g/min) in 30 patients, 19 of whom had angiographic atherosclerosis. Measurements were repeated with sodium nitroprusside (40 mu g/min), L-arginine (160 mu mol/min), and N-G-monomethyl-L-arginine (L-NMMA; 16 mu mol/min). There was significant inhibition of collagen-induced platelet aggregation with ACh (45+/-9.5% lower, P<0.001), and this inhibition was greater in patients without atherosclerosis (68.7+/-10.4% reduction) than in those with atherosclerosis (32.5+/-8.1%, P=0.04). The magnitude of inhibition correlated with vasodilation with ACh, indicating an association between the smooth muscle and antiplatelet effects of endothelium-dependent stimulation. Neither L-NMMA nor sodium nitroprusside altered platelet aggregation. L-Arginine inhibited platelet aggregation equally in vitro (34+/-8% reduction, P<0.01) and in vivo (37+/-3% reduction, P<0.01). Conclusions Stimulation of NO release into the vascular lumen with ACh inhibits platelet aggregation, an effect that is attenuated in patients with atherosclerosis and endothelial dysfunction. Basal NO release does not appear to contribute to platelet passivation in vivo. L-Arginine inhibited platelet aggregation by its direct action on platelets. These findings provide a pathophysiological basis for the observed increase in thrombotic events in atherosclerosis. Use of L-arginine and other strategies to improve endothelial NO activity may impact favorably on thrombotic events in atherosclerosis. C1 McGill Univ, Jewish Gen Hosp, Div Cardiol, Dept Med, Montreal, PQ H3T 1E2, Canada. NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. RP Diodati, JG (reprint author), McGill Univ, Jewish Gen Hosp, Div Cardiol, Dept Med, 3755 Cote Ste Catherine Rd,Suite E-206, Montreal, PQ H3T 1E2, Canada. EM mc72@musica.mcgill.ca NR 79 TC 72 Z9 72 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 7 PY 1998 VL 98 IS 1 BP 17 EP 24 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZY127 UT WOS:000074589000005 PM 9665055 ER PT J AU Kwon, YT Reiss, Y Fried, VA Hershko, A Yoon, JK Gonda, DK Sangan, P Copeland, NG Jenkins, NA Varshavsky, A AF Kwon, YT Reiss, Y Fried, VA Hershko, A Yoon, JK Gonda, DK Sangan, P Copeland, NG Jenkins, NA Varshavsky, A TI The mouse and human genes encoding the recognition component of the N-end rule pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ubiquitin; proteolysis; E3; N-recognin; Ubr1 ID UBIQUITIN-PROTEIN LIGASE; SHORT-LIVED PROTEIN; BINDING-SITES; ENZYME; DEGRADATION; ASPARAGINE; SEQUENCE; RESIDUE; AMIDASE; INVIVO AB The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. The N-end rule pathway is one proteolytic pathway of the ubiquitin system. The recognition component of this pathway, called N-recognin or E3, binds to a destabilizing N-terminal residue of a substrate protein and participates in the formation of a substrate-linked multiubiquitin chain. We report the cloning of the mouse and human Ubr1 cDNAs and genes that encode a mammalian N-recognin called E3 alpha. Mouse UBR1p (E3 alpha) is a 1,757-residue (200-kDa) protein that contains regions of sequence similarity to the 225-kDa Ubr1p of the yeast Saccharomyces cerevisiae. Mouse and human UBR1p have apparent homologs in other eukaryotes as well, thus defining a distinct family of proteins, the UBR family. The residues essential for substrate recognition by the yeast Ubr1p are conserved in the mouse UBR1p. The regions of similarity among the UBR family members include a putative zinc finger and RING-H2 finger, another zinc-binding domain. Ubr1 is located in the middle of mouse chromosome 2 and in the syntenic 15q15-q21.1 region of human chromosome 15. Mouse Ubr1 spans approximate to 120 kilobases of genomic DNA and contains approximate to 50 exons. Ubr1 is ubiquitously expressed in adults, with skeletal muscle and heart being the sites of highest expression. In mouse embryos, the Ubr1 expression is highest in the branchial arches and in the tail and limb buds. The cloning of Ubr1 makes possible the construction of Ubr1-lacking mouse strains, a prerequisite for the functional understanding of the mammalian N-end rule pathway. C1 CALTECH, Div Biol, Pasadena, CA 91125 USA. Tel Aviv Univ, Dept Biochem, IL-69978 Tel Aviv, Israel. New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA. Technion Israel Inst Technol, Fac Med, Biochem Unit, IL-31096 Haifa, Israel. Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, Adv Biosci Labs,Basic Res Program, Frederick, MD 21702 USA. RP Varshavsky, A (reprint author), CALTECH, Div Biol, 147-75,1200 E Calif Blvd, Pasadena, CA 91125 USA. EM avarsh@cco.caltech.edu FU NIDDK NIH HHS [R56 DK039520, DK39520, R37 DK039520, R01 DK039520]; NIGMS NIH HHS [GM31530, R01 GM031530]; NINDS NIH HHS [NS29542] NR 33 TC 120 Z9 124 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 7 PY 1998 VL 95 IS 14 BP 7898 EP 7903 DI 10.1073/pnas.95.14.7898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZZ317 UT WOS:000074717300013 PM 9653112 ER PT J AU Tsai, L Szweda, PA Vinogradova, O Szweda, LI AF Tsai, L Szweda, PA Vinogradova, O Szweda, LI TI Structural characterization and immunochemical detection of a fluorophore derived from 4-hydroxy-2-nonenal and lysine SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LIPID-PEROXIDATION; OXIDATIVE STRESS; FLUORESCENT; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; MITOCHONDRIA; INVOLVEMENT; LIPOFUSCIN; PRODUCTS; PROTEIN AB Aging and the progression of certain degenerative diseases are accompanied by increases in intracellular fluorescent material, termed "lipofuscin" and ceroid, respectively. These pigments are observed within granules composed, in part, of damaged protein and lipid. Modification of various biomolecules by aldehyde products of lipid peroxidation is believed to contribute to lipofuscin and ceroid formation, However, little direct evidence currently exists because the structures responsible for the fluorescent, cross-linked nature of this material are not well characterized. In this study, we have identified a fluorescent product formed in the reaction of N-alpha-acetyllysine and 4-hydroxy-2-nonenal (HNE), a major product of lipid peroxidation and the most reactive of these compounds under physiological conditions [Esterbauer, H,, Shaur, R, J, & Zollner, H. (1991) Free Radical Biol, Med. 11, 81-128], This fluorescent compound, characterized as a 2-hydroxy-3-imino-1,2-dihydropyrrol derivative, appears to form upon oxidative cyclization of the nonfluorescent 2:1 lysine-HNE Michael adduct-Schiff base cross-link. Polyclonal antibody was raised to the N-alpha-acetyllysine-HNE fluorophore and found to be highly specific to the chromophore structure of the compound. This antibody has been used to conclusively demonstrate that the lysine-HNE derivative of this fluorophore forms on protein upon exposure to HNE. The results of this study therefore provide the basis for future investigations on the contribution(s) of HNE-derived fluorophore formation to lipofuscin and ceroid accumulation. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. RP Szweda, PA (reprint author), NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. EM pas4@po.cwru.edu OI Vinogradova, Olga/0000-0001-5101-7361 NR 23 TC 105 Z9 109 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 7 PY 1998 VL 95 IS 14 BP 7975 EP 7980 DI 10.1073/pnas.95.14.7975 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZZ317 UT WOS:000074717300026 PM 9653125 ER PT J AU Fridolfsson, AK Cheng, H Copeland, NG Jenkins, NA Liu, HC Raudsepp, T Woodage, T Chowdhary, B Halverson, J Ellegren, H AF Fridolfsson, AK Cheng, H Copeland, NG Jenkins, NA Liu, HC Raudsepp, T Woodage, T Chowdhary, B Halverson, J Ellegren, H TI Evolution of the avian sex chromosomes from an ancestral pair of autosomes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HIGHLY CONSERVED REGION; HUMAN X-CHROMOSOME; DNA-SEQUENCES; PSEUDOAUTOSOMAL REGION; DOSAGE COMPENSATION; W-CHROMOSOME; MARSUPIAL-X; CHICKEN; BIRDS; LINKAGE AB Among the mechanisms whereby sex is determined in animals, chromosomal sex determination is found in a wide variety of distant taxa. The widespread but not ubiquitous occurrence, not even within lineages, of chromosomal sex determination suggests that sex chromosomes have evolved independently several times during animal radiation, but firm evidence for this is lacking. The most favored model for this process is gradual differentiation of ancestral pairs of autosomes, As known for mammals, sex chromosomes may have a very ancient origin, and it has even been speculated that the sex chromosomes of mammals and birds would share a common chromosomal ancestry. In this study we shelved that the two genes, ATP5A1 and CHD1, so far assigned to the female-specific W chromosome of birds both exist in a very closely related copy on the Z chromosome but are not pseudoautosomal, This indicates a common ancestry of the two sex chromosomes, consistent with the evolution from a pair of autosomes. Comparative mapping demonstrates, however, that ATP5A1 and CHD1 are not sex-linked among eutherian mammals; this is also not the case for the majority of other genes so far assigned to the avian Z chromosome. Our results suggest that the evolution of sex chromosomes has occurred independently in mammals and birds. C1 Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Ctr Biomed, S-75124 Uppsala, Sweden. ARS, Avian Dis & Oncol Lab, USDA, E Lansing, MI 48823 USA. Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL Basic Res Program, Ft Detrick, MD 21702 USA. NIH, Genet & Mol Biol Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Perkin Elmer AgGen, Livermore, CA 95616 USA. RP Ellegren, H (reprint author), Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Ctr Biomed, Box 597, S-75124 Uppsala, Sweden. EM Hans.Ellegren@bmc.uu.se NR 49 TC 161 Z9 171 U1 0 U2 16 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 JUL 7 PY 1998 VL 95 IS 14 BP 8147 EP 8152 DI 10.1073/pnas.95.14.8147 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZZ317 UT WOS:000074717300056 PM 9653155 ER PT J AU Soto, H Wang, W Strieter, RM Copeland, NG Gilbert, DJ Jenkins, NA Hedrick, J Zlotnik, A AF Soto, H Wang, W Strieter, RM Copeland, NG Gilbert, DJ Jenkins, NA Hedrick, J Zlotnik, A TI The CC chemokine 6Ckine binds the CXC chemokine receptor CXCR3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTERFERON-INDUCIBLE PROTEIN-10; IN-VIVO; IP-10; ANGIOGENESIS; EXPRESSION; CLONING AB We cloned the mouse homologue of the chemokine receptor CXCR3, which is located in mouse chromosome X. We screened a large panel of chemokines for their ability to induce a calcium flux in mouse CXCR3-transfected cells and identified a new ligand for this receptor, the recently reported CC chemokine 6Ckine. This represents an example of a CC chemokine, which binds to a CXC chemokine receptor. Like other ligands of this receptor, 6Ckine has angiostatic properties. 6Ckine is known to chemoattract T cells, In line with this, CXCR3 is expressed preferentially in Th1 cells and in lymphoid organs of the IL-10(-/-) mouse that develops chronic colitis. Its ability to attract T cells as well as its angiostatic properties suggest that 6Ckine may be an effective anti-tumor agent. C1 DNAX Res Inst Mol & Cellular & Mol Biol, Palo Alto, CA 94304 USA. Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. NCI, Mammalian Genet Lab, Adv BioSci Labs,Basic Res Program, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Zlotnik, A (reprint author), DNAX Res Inst Mol & Cellular & Mol Biol, Palo Alto, CA 94304 USA. RI Zlotnik, Albert/C-3791-2011 FU NCI NIH HHS [CA66180] NR 39 TC 188 Z9 199 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 JUL 7 PY 1998 VL 95 IS 14 BP 8205 EP 8210 DI 10.1073/pnas.95.14.8205 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZZ317 UT WOS:000074717300066 PM 9653165 ER PT J AU Suzuki, K Lavaroni, S Mori, A Ohta, M Saito, J Pietrarelli, M Singer, DS Kimura, S Katoh, R Kawaoi, A Kohn, LD AF Suzuki, K Lavaroni, S Mori, A Ohta, M Saito, J Pietrarelli, M Singer, DS Kimura, S Katoh, R Kawaoi, A Kohn, LD TI Autoregulation of thyroid-specific gene transcription by thyroglobulin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID THYROTROPIN RECEPTOR GENE; FACTOR-I; NUCLEAR-PROTEIN; FRTL-5 CELLS; EXPRESSION; PROMOTER; CLONING; TTF-1; IMMUNOGLOBULINS; RECOGNITION AB Thyroglobulin (TG), the primary synthetic product of the thyroid, is the macromolecular precursor of thyroid hormones. TG synthesis, iodination, storage in follicles, and degradation control thyroid hormone formation and secretion into the circulation. Thyrotropin (TSH), via its receptor (TSHR), increases thyroid hormone levels by upregulating expression of the sodium iodide symporter (NIS), thyroid peroxidase (TPO), and TG genes. TSH does this by modulating the expression and activity of several thyroid-specific transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, which coordinately regulate NIS, TPO, TG, and the TSHR. Major histocompatibility complex class I gene expression, which also is regulated by TTF-1 and Pax-8 in the thyroid, is decreased simultaneously. This helps maintain self-tolerance in the face of TSH-increased gene products necessary for thyroid hormone formation. In this report we show that follicular TG counter-regulates TSH-increased, thyroid-specific gene transcription by suppressing expression of the TTF-1, TTF-2, and Pax-8 genes. This decreases expression of the TG, TPO, NIS, and TSHR genes, but increases class I expression. TG acts transcriptionally, targeting, for example, a sequence within 1.15 kb of the 5' flanking region of TTF-1. TG does not affect ubiquitous transcription factors regulating TG, TPO, NIS, and/or TSHR gene expression. The inhibitory effect of TG on gene expression is not duplicated by thyroid hormones or iodide and may be mediated by a TG-binding protein on the apical membrane. We hypothesize that TG-initiated, transcriptional regulation of thyroid-restricted genes is a normal, feedback, compensatory mechanism that limits follicular function and contributes to follicular heterogeneity. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Yamanashi Med Univ, Dept Pathol, Yamanashi 40938, Japan. RP Kohn, LD (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 9C101B, Bethesda, MD 20892 USA. NR 41 TC 89 Z9 92 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 7 PY 1998 VL 95 IS 14 BP 8251 EP 8256 DI 10.1073/pnas.95.14.8251 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZZ317 UT WOS:000074717300074 PM 9653173 ER PT J AU Hampson, AJ Grimaldi, M Axelrod, J Wink, D AF Hampson, AJ Grimaldi, M Axelrod, J Wink, D TI Cannabidiol and (-)Delta(9)-tetrahydrocannabinol are neuroprotective antioxidants SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CORTICAL ASTROCYTES; BUTYLATED HYDROXYTOLUENE; RECEPTOR ANTAGONIST; CYCLIC-AMP; RAT-BRAIN; NEUROTOXICITY; CULTURE; NEURONS; MICE AB The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate, Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (-)Delta(9)-tetrahydrocannabinol (THC), Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-D-aspartate receptors, 2-amino-3- (4-butyl-3-hydroxyisoxazol-5-yl) propionic acid receptors, or kainate receptors, N-methyl-D-aspartate receptor-induced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants, Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry, Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or alpha-tocopherol, indicating it to be a potent antioxidant, These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia. C1 NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. NINDS, Lab Adapt Syst, Bethesda, MD 20892 USA. NCI, Radiol & Biol Branch, Bethesda, MD 20892 USA. RP Hampson, AJ (reprint author), NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. NR 28 TC 388 Z9 404 U1 8 U2 41 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 JUL 7 PY 1998 VL 95 IS 14 BP 8268 EP 8273 DI 10.1073/pnas.95.14.8268 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZZ317 UT WOS:000074717300077 PM 9653176 ER PT J AU Saunders, HMH Koizumi, K Odenwald, W Nirenberg, M AF Saunders, HMH Koizumi, K Odenwald, W Nirenberg, M TI Neuroblast pattern formation: Regulatory DNA that confers the vnd/NK-2 homeobox gene pattern on a reporter gene in transgenic lines of Drosophila SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE embryonic neurogenesis; epidermogenesis; gene regulation ID CENTRAL-NERVOUS-SYSTEM; EARLY NEUROGENESIS; VISCERAL MESODERM; AUTO-REGULATION; MELANOGASTER; EXPRESSION; NK-2; TRANSFORMATION; TRANSCRIPTION; CHROMOSOME AB DNA fragments -0.57, -2.2, -2.9, -5.3, and -8.4 kb in length from the upstream regulatory region of the vnd/NK-2 gene were cloned in the 5'-flanking region of a beta-galactosidase (beta-gal) reporter gene in the P-element pCaSpeR-AUG-beta-gal, and the effects of the DNA on the pattern and time of expression of beta-gal were determined in transgenic embryos, Embryos from 11 lines transformed with -8.4 kb of vnd/NK-2 regulatory DNA expressed beta-gal patterns that closely resemble those of vnd/NK-2, In embryos from four lines transformed with -5.3 kb of vnd/NK-2 DNA, beta-gal was found in the normal vnd/NK-2 pattern in the nerve cord but not in part of the cephalic region. beta-Gal patterns in embryos from transgenic lines containing -0.57, -2.2, or -2.9 kb of vnd/NK-2 DNA did not resemble vnd/NK-2, Null vnd/NK-2 mutant embryos containing the homozygous P-element p [-8.4 to + 0,34 beta-gal] expressed little beta-gal in contrast to siblings with a wild-type vnd/NK-2 gene, We conclude that (i) the 8.4-kb DNA fragment from the vnd/NK-2 gene contains the nucleotide sequences required to generate the normal pattern of vnd/NK-2 gene expression, sequences that may be involved in the switch between neuroblast vs. epidermoblast pathways of development, (ii) the 5'-flanking region of the vnd/NK-2 gene between -5.3 and -8.4 kb is required for vnd/NK-2 gene expression in the most dorsoanterior part of the cephalic region, and (iii) vnd/NK-2 protein is required, directly or indirectly, for maintenance of vnd/NK-2 gene expression. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NINDS, Neurogenet Unit, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Nirenberg, M (reprint author), NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NR 20 TC 18 Z9 18 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 7 PY 1998 VL 95 IS 14 BP 8316 EP 8321 DI 10.1073/pnas.95.14.8316 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZZ317 UT WOS:000074717300085 PM 9653184 ER PT J AU Parchi, P Chen, SG Brown, P Zou, WQ Capellari, S Budka, H Hainfellner, J Reyes, PF Golden, GT Hauw, JJ Gajdusek, DC Gambetti, P AF Parchi, P Chen, SG Brown, P Zou, WQ Capellari, S Budka, H Hainfellner, J Reyes, PF Golden, GT Hauw, JJ Gajdusek, DC Gambetti, P TI Different patterns of truncated prion protein fragments correlate with distinct phenotypes in P102L Gerstmann-Straussler-Scheinker disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; FATAL FAMILIAL INSOMNIA; SPONGIFORM ENCEPHALOPATHY; CEREBRAL AMYLOIDOSIS; TRANSMISSION; SCRAPIE; POLYMORPHISM; MUTATION; VARIANT; BRAIN AB The clinicopathological phenotype of the Gerstmann-Straussler-Scheinker disease (GSS) variant linked to the codon 102 mutation in the prion protein (PrP) gene (GSS P102L) shows a high heterogeneity. This variability also is observed in subjects with the same prion protein gene PRNP haplotype and is independent from the duration of the disease, Immunoblot analysis of brain homogenates from GSS P102L patients showed two major protease-resistant PrP fragments (PrP-res) with molecular masses of approximate to 21 and 8 kDa, respectively, The 21-kDa fragment, similar to the PrP-res type 1 described in Creutzfeldt-Jakob disease, was found in five of the seven subjects and correlated with the presence of spongiform degeneration and "synaptic" pattern of PrP deposition whereas the 8-kDa fragment, similar to those described in other variants of GSS, was found in all subjects in brain regions showing PrP-positive multicentric amyloid deposits. These data further indicate that the neuropathology of prion diseases largely depends on the type of PrP-res fragment that forms in vivo. Because the formation of PrP-res fragments of 7-8 kDa with ragged N and C termini is not a feature of Creutzfeldt-Jakob disease or fatal familial insomnia but appears to be shared by most GSS subtypes, it may represent a molecular marker for this disorder. C1 Case Western Reserve Univ, Inst Pathol, Div Neuropathol, Cleveland, OH 44106 USA. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. Univ Vienna, Inst Neurol, A-1097 Vienna, Austria. AKH, Austrian Reference Ctr Human Prion Dis, Vienna, Austria. Hop Salpetriere, Lab Neuropathol R Esocourolle, F-75651 Paris, France. Thomas Jefferson Univ, Coll Med, Dept Neurol, Philadelphia, PA 19107 USA. Vet Affairs Med Ctr, Res Serv, Coatesville, PA 19320 USA. RP Parchi, P (reprint author), Case Western Reserve Univ, Inst Pathol, Div Neuropathol, 2085 Adelbert Rd, Cleveland, OH 44106 USA. EM pxp21@po.cwru.edu RI capellari, sabina/F-5545-2012; Chen, Shu/O-4750-2014; Parchi, Piero/L-9833-2015; OI Chen, Shu/0000-0001-7180-3001; Parchi, Piero/0000-0002-9444-9524; Budka, Herbert/0000-0002-1933-1577 FU NIA NIH HHS [AG-08155, AG08992] NR 30 TC 136 Z9 138 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 7 PY 1998 VL 95 IS 14 BP 8322 EP 8327 DI 10.1073/pnas.95.14.8322 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZZ317 UT WOS:000074717300086 PM 9653185 ER PT J AU Hoelzel, AR Potter, CW Best, PB AF Hoelzel, AR Potter, CW Best, PB TI Genetic differentiation between parapatric 'nearshore' and 'offshore' populations of the bottlenose dolphin SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE population genetics; marine mammals; resource specialization ID DNA AB The existence of nearshore and offshore populations of the bottlenose dolphin has been documented throughout its range. In several cases the two regional forms have been shown to be morphologically distinct, although there is considerable overlap for most characters. The populations off the eastern coast of North America have been the subject of a long-term programme of research on their distribution and movements. In this study, we compare mitochondrial and nuclear genetic markers between dolphins classified as either nearshore or offshore type. These putative populations were found to be distinct at both nuclear and mitochondrial genetic markers. Further, the level of variation among the nearshore dolphins was reduced compared with the offshore population. A broader geographical comparison suggests a shared lineage between offshore dolphins from the western North Atlantic and both offshore and nearshore dolphins from the eastern Atlantic. These results are consistent with local differentiation based on habitat or resource specialization in the western North Atlantic, and suggest differences in the character of the nearshore/offshore distinction in different parts of the world. C1 Univ Durham, Dept Biol Sci, Durham DH1 3LE, England. Smithsonian Inst, Museum Nat Hist, Washington, DC 20560 USA. Univ Pretoria, Mammal Res Inst, ZA-0002 Pretoria, South Africa. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Hoelzel, AR (reprint author), Univ Durham, Dept Biol Sci, South Rd, Durham DH1 3LE, England. NR 29 TC 105 Z9 112 U1 5 U2 17 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD JUL 7 PY 1998 VL 265 IS 1402 BP 1177 EP 1183 PG 7 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA 102RR UT WOS:000074938500006 PM 9699311 ER PT J AU Zohar, O AF Zohar, O TI Elimination of sensory inputs induces growth and synaptic changes in crayfish motor axons SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE adult; axonal growth; crayfish; neuromuscular junction; stretch receptor; synapse formation ID PERIPHERAL-NERVE INJURY; NEUROMUSCULAR-JUNCTIONS; EXCITATORY AXON; RELEASE; SPECIFICITY; OUTGROWTH; CALCIUM; DISUSE AB Damage to motor neurons induces regeneration processes including axonal growth and change of synaptic properties. Sensory axons that run along the motor axons are also damaged, but their possible role in the motor neuron's regeneration is generally ignored. Here, the effect of eliminating some sensory inputs from intact motor axons on the motor axon's properties was studied. Micro-dissecting one of the segmental, bilateral, sensory stretch receptor pairs of the crayfish abdomen induced the deep extensor abdominal motor axons to grow and changed their synaptic properties. The results demonstrate directly probably for the first time, that change in sensory neuron activity can induce motor axons to grow, form new synapses, and change their synaptic properties. C1 Interuniv Red Sea Res Ctr Eilat, IL-88103 Eilat, Israel. RP Zohar, O (reprint author), NINDS, NIH, LAS, 36 Convent Dr,MSC 4124, Bethesda, MD 20892 USA. EM zohar@codon.nih.gov NR 32 TC 1 Z9 1 U1 0 U2 0 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD JUL 7 PY 1998 VL 265 IS 1402 BP 1211 EP 1217 DI 10.1098/rspb.1998.0422 PG 7 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA 102RR UT WOS:000074938500012 ER PT J AU Rutter, JJ Baumann, MH Waterhouse, BD AF Rutter, JJ Baumann, MH Waterhouse, BD TI Systemically administered cocaine alters stimulus-evoked responses of thalamic somatosensory neurons to perithreshold vibrissae stimulation SO BRAIN RESEARCH LA English DT Article DE somatosensory thalamus; cocaine; microdialysis; sensory system; norepinephrine; serotonin ID SOMATIC SENSORY RESPONSES; AFFERENT SYNAPTIC INPUTS; MOVING VISUAL-STIMULI; POSTERIOR GROUP POM; MEDIAL NUCLEUS VPM; RAT THALAMUS; ROSTRAL SECTOR; SINGLE UNITS; INNERVATION; SEROTONIN AB Previous studies have shown that systemically administered cocaine can transiently alter responses of primary somatosensory cortical neurons to threshold level stimulation of peripheral receptive fields. The goal of the present investigation was 2-fold: (1) characterize the effects of systemic cocaine on stimulus-evoked responses of the ventral posterior medial (VPM) thalamic neurons which relay somatosensory information to the cortex and (2) determine the time course and magnitude of changes in monoamine levels within the somatosensory thalamus following systemic administration of cocaine. Extracellularly recorded responses of single VPM thalamic neurons to whisker stimulation were monitored before and after cocaine administration in halothane anaesthetized rats. Each cell was first characterized by assessing its response profile to a range of perithreshold level deflections of the optimal whisker on the contralateral face. Drug effects on stimulus-response curves, response magnitude and latency were determined from quantitative analysis of spike train data. The results indicate that cocaine elicits a predictable augmentation or attenuation of the sensory response magnitude, with the direction of the change inversely related to the initial magnitude of the stimulus-evoked discharge. In addition, cocaine consistently reduced the response time of somatosensory thalamic neurons to peripheral receptive field stimulation. At the same dose and over the same time period, cocaine also produced marked elevation of norepinephrine and serotonin levels within the ventrobasal thalamus, as determined by in vivo microdialysis. These results suggest that cocaine-induced increases in norepinephrine and serotonin are responsible for drug-related modulation of the transfer of sensory signals through primary thalamocortical relay circuits. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Allegheny Univ Hlth Sci, Dept Neurobiol & Anat, Philadelphia, PA 19102 USA. NIDA, Clin Psychopharmacol Sect, Addict Res Ctr, NIH, Baltimore, MD 21224 USA. RP Rutter, JJ (reprint author), Allegheny Univ Hlth Sci, Dept Neurobiol & Anat, MS 408,3200 Henry Ave, Philadelphia, PA 19129 USA. EM rutter@auhs.edu FU NIDA NIH HHS [R01 DA05117] NR 48 TC 19 Z9 19 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 JUL 6 PY 1998 VL 798 IS 1-2 BP 7 EP 17 DI 10.1016/S0006-8993(98)00320-5 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 106MJ UT WOS:000075133100002 PM 9666059 ER PT J AU Morales, M Criado, JR Sanna, PP Henriksen, SJ Bloom, FE AF Morales, M Criado, JR Sanna, PP Henriksen, SJ Bloom, FE TI Acute ethanol induces c-fos immunoreactivity in GABAergic neurons of the central nucleus of the amygdala SO BRAIN RESEARCH LA English DT Article DE GAD; interneuron; drug addiction; extended amygdala ID BRAIN-STEM; HORSERADISH-PEROXIDASE; RAT; PROJECTIONS; WITHDRAWAL; FOREBRAIN; STRESS; SYSTEM; CAT AB The central nucleus of the amygdala (CNA) is a component of the brain reward pathway which is believed to represent an anatomical substrate for drugs of abuse. Previous studies have shown that acute ethanol administration induces the expression of c-fos in the CNA of rat brains. We report here, that over 70% of these c-fos immunoreactive neurons are GABAergic. This observation provides the first anatomical evidence that GABAergic neurons of the CNA are responsive to acute ethanol exposure and suggest that the GABAergic system of the CNA is a key neuronal substrate for ethanol actions on the central nervous system. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Scripps Res Inst, Dept Neuropharmacol, Alcohol Res Ctr, La Jolla, CA 92037 USA. RP Morales, M (reprint author), NIDA, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIAAA NIH HHS [AA 06420] NR 24 TC 36 Z9 36 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 JUL 6 PY 1998 VL 798 IS 1-2 BP 333 EP 336 DI 10.1016/S0006-8993(98)00457-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 106MJ UT WOS:000075133100042 PM 9666163 ER PT J AU Chun, TW Engel, D Mizell, SB Ehler, LA Fauci, AS AF Chun, TW Engel, D Mizell, SB Ehler, LA Fauci, AS TI Induction of HIV-1 replication in latently infected CD4(+) T cells using a combination of cytokines SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE HIV-1; latency; resting CD4(+) T cells; cytokines; antiretroviral therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR-ALPHA; INTERLEUKIN-1 RECEPTOR ANTAGONIST; BLOOD MONONUCLEAR-CELLS; TNF-ALPHA; U1 CELLS; PERIPHERAL-BLOOD; MONOCYTIC CELLS; KAPPA-B; EXPRESSION AB Although it has been demonstrated that certain cytokines, particularly proinflammatory cytokines, can enhance ongoing viral replication in peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals, it is unclear what role these cytokines play in the induction of HIV-1 replication in latently infected, resting CD4(+) T cells. This study demonstrates that the in vitro combination of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha together with the immunoregulatory cytokine IL-2 are potent inducers of viral replication in highly purified, latently infected, resting CD4(+) T cells derived from HIV-infected individuals who are antiretroviral therapy-naive as well as those who are receiving highly active antiretroviral therapy (HAART). Viral replication induced by this combination of cytokines was completely suppressed in the presence of HAART in vitro. Given that an array of cytokines, including IL-6, TNF-alpha, and IL-2, are copiously expressed in the microenvironment of the lymphoid tissues, which harbor the latent viral reservoirs, induction of HIV by this combination of cytokines may in part explain the commonly observed reappearance of detectable plasma viremia in HIV-infected individuals in whom HAART was discontinued. Moreover, since it is likely that these infected cells die upon activation of virus and that HAART prevents spl-ead of virus to adjacent cells, the observation that this combination of cytokines can markedly induce viral replication in this reservoir may have important implications for the activation-mediated diminution of the latent reservoir of HIV in patients receiving HAART. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 6A32, Bethesda, MD 20892 USA. NR 47 TC 256 Z9 258 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 6 PY 1998 VL 188 IS 1 BP 83 EP 91 DI 10.1084/jem.188.1.83 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 101GP UT WOS:000074861500009 PM 9653086 ER PT J AU Cohen, JI Nguyen, H AF Cohen, JI Nguyen, H TI Varicella-zoster virus ORF61 deletion mutants replicate in cell culture, but a mutant with stop codons in ORF61 reverts to wild-type virus SO VIROLOGY LA English DT Article ID READING FRAME-61 PROTEIN; HERPES-SIMPLEX VIRUSES; GENE-EXPRESSION; REGULATORY PROTEIN; ZINC-FINGER; IN-VITRO; ICP0; LATENCY; DNA; REACTIVATION AB Varicella-zoster virus (VZV) ORF61 encodes a phosphoprotein that transactivates VZV promoters. Transfection of cells with cosmid DNAs, including a cosmid with a large deletion in ORF61, resulted in a VZV ORF61 deletion mutant that was impaired for growth in vitro and could be partially complemented by growth in neuroblastoma or osteosarcoma cell lines. Cells infected with the VZV ORF61 deletion mutant expressed norma I levels of an immediate-early VZV protein, but had reduced levels of a late protein and showed abnormal syncytia. Carboxy terminal truncation mutants of VZV ORF61 protein have a transrepressing phenotype and inhibit the infectivity of cotransfected wild-type viral DNA. Transfection of cells with cosmid DNAs, including a cosmid with stop codons that should result in an ORF61 truncation mutant expressing a transrepressing protein that retains the RING finger domain, resulted in a viral genome which reverted back to the wild-type sequence. BAL-31 exonuclease was used to produce deletions at the site of the stop codons in ORF61 of the cosmid, resulting in loss of the RING finger domain. Transfection of tissue culture cells with the ORF61 BAL-31 deletion mutants and other cosmid DNAs yielded viable viruses. Thus, while deletion mutants lacking the RING finger domain of ORF61 replicate in cell culture, a mutant with stop codons that retains this domain could not be propagated and reverted to wild-type virus. C1 NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bldg 10,Rm 11N214, Bethesda, MD 20892 USA. NR 37 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 5 PY 1998 VL 246 IS 2 BP 306 EP 316 DI 10.1006/viro.1998.9198 PG 11 WC Virology SC Virology GA ZY286 UT WOS:000074604900012 PM 9657949 ER PT J AU Huber, R Schlessinger, D Pilia, G AF Huber, R Schlessinger, D Pilia, G TI Multiple Sp1 sites efficiently drive transcription of the TATA-less promoter of the human glypican 3 (GPC3) gene SO GENE LA English DT Article DE proteoglycan; DNA sequence; transcription factor; transcriptional regulation ID SIMPSON-GOLABI-BEHMEL; FIBROBLAST GROWTH-FACTOR; RNA-POLYMERASE-II; OVERGROWTH SYNDROME; BINDING; ACTIVATION; RECEPTOR; PURIFICATION; EXPRESSION; INITIATOR AB Simpson-Golabi-Behmel Syndrome (SGBS) is an X-linked disease characterized by pre- and postnatal overgrowth. Recently, we have shown that mutations in the glypican family gene, GPC3, cause SGBS. This gene is predominantly expressed in the same mesoderm-derived tissues that overgrow in its absence. To investigate the basis for promoter function, 3.3 kb of GC-rich DNA 5' of the transcribed region were fused to a luciferase cDNA, transfected into Caco-2 and NT2 cells, and assayed for activity. Deletion analysis identified a 218-bp fragment upstream of the transcription start site that conferred more than 80% of maximal reporter gene activation. This fragment contains five putative Spl binding sites, three of which (centered at nt -14, -34, and -92) were active when assessed by DNaseI footprinting and gel shift/supershift assays. Additionally, Sp1 specifically transactivated transcription in Sp1-deficient Drosophila SL2 cells, demonstrating the functionality of Spl on the GPC3 promoter. A full-length promoter construct was also highly active in HeLa cells, which do not express endogenous GPC3. These results indicate that the GPC3 promoter is dependent on Spl for proper activation, but tissue-specific repression in non-expressing cells must involve either DNA that lies outside the region tested or auxiliary structural features of chromatin. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Inst Ric Talassemie & Anemie Mediterranee, Cagliari, Italy. RP Huber, R (reprint author), 5600 Nathan Shock Dr,GRC 4F01, Baltimore, MD 21224 USA. EM huberr@grc.nia.nih.gov FU NCI NIH HHS [CA72548]; NIGMS NIH HHS [GM07067] NR 30 TC 34 Z9 34 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 JUL 3 PY 1998 VL 214 IS 1-2 BP 35 EP 44 DI 10.1016/S0378-1119(98)00233-9 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 109JL UT WOS:000075318400005 PM 9651473 ER PT J AU Ashcroft, NR Kosinski, ME Wickramasinghe, D Donovan, PJ Golden, A AF Ashcroft, NR Kosinski, ME Wickramasinghe, D Donovan, PJ Golden, A TI The four cdc25 genes from the nematode Caenorhabditis elegans SO GENE LA English DT Article DE cell cycle; dual-specificity phosphatase; gene family; genomic database; homologs ID PROTEIN-TYROSINE-PHOSPHATASE; CRYSTAL-STRUCTURE; FISSION YEAST; CELL-CYCLE; C-ELEGANS; M-PHASE; SEQUENCE; IDENTIFICATION; ALIGNMENT; CATALYSIS AB During eukaryotic evolution, multicellular organisms have evolved multiple members of gene families that may display unique, partially overlapping, or redundant functions during development. More than 75% of the C. elegans genome has been sequenced, which represents approximately 95% of the coding sequences. This provides a unique opportunity to identify most, if not all, of the members of a given gene family. We have searched the C. elegans genome database for members of a key family of cell cycle regulators, the CDC25 phosphatases, and have identified four genes. The four C. elegans genes represent a larger family within a single organism than has been reported so far in Drosophila, mice and humans. An amino acid comparison revealed a high degree of similarity and identity within the phosphatase domain. This analysis also identified an expanded consensus sequence that can be used to discover new members of the CDC25 phosphatase family. However, the four C. elegans sequences display a few novel amino acid substitutions in the residues surrounding the invariant catalytic motif CX5R. These data demonstrate the value of genome database searching for identifying new members of known gene families, understanding genetic diversity, and for studying gene structure. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Golden, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, POB B,Bldg 539, Frederick, MD 21702 USA. EM golden@ncifcrf.gov NR 35 TC 31 Z9 38 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 JUL 3 PY 1998 VL 214 IS 1-2 BP 59 EP 66 DI 10.1016/S0378-1119(98)00228-5 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 109JL UT WOS:000075318400008 PM 9651482 ER PT J AU Saarikoski, ST Husgafvel-Pursiainen, K Hirvonen, A Vainio, H Gonzalez, FJ Anttila, S AF Saarikoski, ST Husgafvel-Pursiainen, K Hirvonen, A Vainio, H Gonzalez, FJ Anttila, S TI Localization of CYP1A1 mRNA in human lung by in situ hybridization: Comparison with immunohistochemical findings SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MONOCLONAL-ANTIBODIES; CANCER PATIENTS; INSITU HYBRIDIZATION; MESSENGER-RNA; AH-RECEPTOR; SUSCEPTIBILITY; EXPRESSION; GENE; POLYMORPHISMS; SMOKING AB Cytochrome P4501A1 (CYP1A1) is involved in the bioactivation of polycyclic aromatic hydrocarbons into their reactive epoxide metabolites. CYP1A1 is considered to be important with regard to individual susceptibility to lung cancer since phenotypic and genotypic polymorphisms of CYP1A1 have been associated with an increased risk of lung cancer in a number of studies. We examined here the expression and localization of CYP1A1 mRNA in human lung tissue using in site hybridization with a CYP1A1-specific RNA probe. A centrilobular expression of CYP1A1 mRNA was observed in the peripheral lung. The expression was intense in bronchiolar epithelium of peripheral lung, especially in terminal cuboidal epithelium. Type II alveolar epithelial cells were also intensely labelled, Type I alveolar epithelial cells and vascular epithelium exhibited binding but the hybridization signals were less intense. Our results are in good agreement with our previous work on immunohistochemical localization of CYP1A1 protein, in which we used the 1-7- 1 MAb that recognizes both CYP1A1 and CYP1A2. In serial sections analyzed with in situ hybridization and immunohistochemistry, a similar distribution of CYP1A1 mRNA and CYP1A protein was observed. CYP1A1 mRNA is thus expressed in human lungs and the expression is particularly intense in the cell types involved in the development of peripheral lung cancers. (C) 1998 Wiiey-Liss, Inc. C1 Finnish Inst Ouccpat Hlth, FIN-00250 Helsinki, Finland. Int Agcy Res Canc, F-69372 Lyon, France. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Anttila, S (reprint author), Finnish Inst Ouccpat Hlth, Toepliuksenkatu 41 AA, FIN-00250 Helsinki, Finland. NR 26 TC 33 Z9 35 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 3 PY 1998 VL 77 IS 1 BP 33 EP 39 DI 10.1002/(SICI)1097-0215(19980703)77:1<33::AID-IJC7>3.0.CO;2-0 PG 7 WC Oncology SC Oncology GA ZU571 UT WOS:000074211400007 PM 9639391 ER PT J AU Essand, M Pastan, I AF Essand, M Pastan, I TI Anti-prostate immunotoxins: Cytotoxicity of E4 antibody-pseudomonas exotoxin constructs SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID B-CELL LYMPHOMA; SINGLE-CHAIN IMMUNOTOXINS; HIGH-LEVEL EXPRESSION; ESCHERICHIA-COLI; BINDING; RADIOIMMUNOTHERAPY; REGRESSION; CARCINOMA; SPHEROIDS; GENES AB E4 is a monoclonal antibody (MAb) that reacts with a surface antigen present on normal prostate and prostate cancers. Using this antibody, 2 immunotoxins were generated, one being a chemical conjugate with a mutant truncated form of Pseudomonas exotoxin A (PE), E4-PE35KDEL. The other is a recombinant single chain immunotoxin, E4(FV)PE38KDEL. The affinity of the conjugated immunotoxin was similar to the hybridoma-produced MAb E4, revealing that conjugation did not impair the binding ability. The affinity of the recombinant immunotoxin (10 nM) was 10-fold lower than that of the MAb, probably reflecting differences of bivalent (MAb) vs, monovalent (Fv) binding. Antigen positive prostate, breast and colon carcinoma cell lines showed cytotoxic response to the E4 immunotoxins while antigen negative cells were not affected. The ICS, value, representing a 50% inhibition of cellular protein synthesis, ranged from 0.3 to 20 ng/ml for E4-PE35KDEL and from 2 to 100 ng/ml for E4(FV)-PE38KDEL. Therefore, the E4-derived immunotoxins may be useful for the treatment of prostate as well as breast and colon cancers. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, 9000 Rockville Pike,Bldg 37,Room 4E16, Bethesda, MD 20892 USA. NR 23 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 3 PY 1998 VL 77 IS 1 BP 123 EP 127 DI 10.1002/(SICI)1097-0215(19980703)77:1<123::AID-IJC19>3.0.CO;2-F PG 5 WC Oncology SC Oncology GA ZU571 UT WOS:000074211400019 PM 9639403 ER PT J AU Hrycyna, CA Ramachandra, M Ambudkar, SV Ko, YH Pedersen, PL Pastan, I Gottesman, MM AF Hrycyna, CA Ramachandra, M Ambudkar, SV Ko, YH Pedersen, PL Pastan, I Gottesman, MM TI Mechanism of action of human P-glycoprotein ATPase activity - Photochemical cleavage during a catalytic transition state using orthovanadate reveals cross-talk between the two ATP sites SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING SITES; MULTIDRUG TRANSPORTER; VANADATE; MYOSIN; RESISTANCE; PHOTOCLEAVAGE; ANTIBODIES; PROTEINS; CELLS; MUTANTS AB Human P-glycoprotein (P-gp), an ATP-dependent efflux pump responsible for cross-resistance of human cancers to a variety of lipophilic compounds, is composed of two homologous halves, each containing six transmembrane domains and an ATP-binding/utilization domain. To determine whether each site can hydrolyze ATP simultaneously, we used an orthovanadate (Vi)-induced ADP-trapping technique (P-gp.MgADP.Vi). In analogy with other ATPases, a photochemical peptide bond cleavage reaction occurs within the Walker A nucleotide binding domain consensus sequence (GX(4)GK(T/S)) when the molecule is trapped with Vi in an inhibited catalytic transition state (P-gp.MgADP.Vi) and incubated in the presence of ultraviolet light. Upon reconstitution into proteoliposomes, histidine-tagged purified P-gp from baculovirus-infected insect cells had drug-stimulated ATPase activity. Reconstituted P-gp was incubated with either ATP or 8-azido-ATP in the presence or absence of Vi under ultraviolet (365 nm) light on ice for 60 min. The resultant products were separated by SDS-polyacrylamide gel electrophoresis and subjected to immunoblotting with seven different human P-gp-specific antibodies covering the entire length of the molecule. Little to no degradation of P-gp was observed in the absence of Vi. In the presence of Vi, products of approximately 28, 47, 94, and 110 kDa were obtained, consistent with predicted molecular weights from cleavage at either of the ATP sites but not both sites, An additional Vi-dependent cleavage site was detected at or near the trypsin site in the linker region of P-gp. These results suggest that both the amino-and carboxyl-terminal ATP sites can hydrolyze ATP. However, there is no evidence that ATE can be hydrolyzed simultaneously by both sites. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. RP NCI, Cell Biol Lab, NIH, Bldg 37,Rm 1A-09,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Ambudkar, Suresh/B-5964-2008 NR 28 TC 83 Z9 83 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 3 PY 1998 VL 273 IS 27 BP 16631 EP 16634 DI 10.1074/jbc.273.27.16631 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZX700 UT WOS:000074545200001 PM 9642211 ER PT J AU Deb, TB Wong, L Salomon, DS Zhou, GC Dixon, JE Gutkind, JS Thompson, SA Johnson, GR AF Deb, TB Wong, L Salomon, DS Zhou, GC Dixon, JE Gutkind, JS Thompson, SA Johnson, GR TI A common requirement for the catalytic activity and both SH2 domains of SHP-2 in mitogen-activated protein (MAP) kinase activation by the ErbB family of receptors - A specific role for SHP-2 in MAP, but not c-jun amino-terminal kinase activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE-PHOSPHATASE; SIGNAL-TRANSDUCTION; INSULIN; SEVENLESS; SHPTP2; CELLS; PHOSPHORYLATION; STIMULATION; EXPRESSION; HEREGULIN AB The ErbB family of receptors, which include the epidermal growth factor receptor (EGFR), ErbB2, ErbB3, and ErbB4 mediate the actions of a family of bioactive polypeptides. EGF signals through EGFR, whereas heregulin (HRG) signaling is initiated through binding to either ErbB3 or ErbB4. In this report we studied the role of protein-tyrosine phosphatase SHP-2 in ErbB-mediated activation of mitogen-activated protein kinase (MAPK) by overexpressing SHP-2 mutants in COS-7 cells. We demonstrate that enzymatic activity and both NH2- and COOH-terminal SH2 domains of SHP-2 are required for EGF-induced MAPK activation, but not for c-Jun amino-terminal kinase stimulation or MAPK activation which occurred in response to myristoylated son of sevenless, activated Ras, or phorbol ester. Dominant-negative forms of SHP-2 had no effect on EGF-stimulated interaction of GRB2 with EGFR or SHC, nor did they influence phosphorylation of SHC and SHC/EGFR association. The same mutant SHP-2 structures that inhibited EGF-mediated stimulation of MAPK also blocked HRG alpha/beta-induced MAPK activation. EGF or HRG beta caused SHP-2 SH2 domains to engage multiple phosphotyrosine proteins, and mutation of either domain disrupted these associations. These results demonstrate that SHP-2 performs a common and essential function(s) in ligand-stimulated MAPK activation by the ErbB family of receptors. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. NCI, NIH, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA. NIDR, NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. Berlex Biosci, Dept Prot Chem & Biophys, Richmond, CA 94804 USA. RP Johnson, GR (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bldg 29A,Rm 3B-16,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 25 TC 72 Z9 72 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 3 PY 1998 VL 273 IS 27 BP 16643 EP 16646 DI 10.1074/jbc.273.27.16643 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZX700 UT WOS:000074545200004 PM 9642214 ER PT J AU Motojima, K Passilly, P Peters, JM Gonzalez, FJ Latruffe, N AF Motojima, K Passilly, P Peters, JM Gonzalez, FJ Latruffe, N TI Expression of putative fatty acid transporter genes are regulated by peroxisome proliferator-activated receptor alpha and gamma activators in a tissue- and inducer-specific manner SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-SEQUENCE; LIPOPROTEIN-LIPASE; BINDING-PROTEIN; PPAR-GAMMA; RAT-LIVER; DIFFERENTIATION; CLONING; HEPATOCARCINOGENICITY; LIGAND; MOUSE AB Regulation of gene expression of three putative long-chain fatty acid transport proteins, fatty acid translocase (FAT), mitochondrial aspartate aminotransferase (mAspAT), and fatty acid transport protein (FATP), by drugs that activate peroxisome proliferator-activated receptor (PPAR) alpha and gamma were studied using normal and obese mice and rat hepatoma cells. FAT mRNA was induced in liver and intestine of normal mice and in hepatoma cells to various extents only by PPAR alpha-activating drugs. FATP mRNA was similarly induced in liver, but to a lesser extent in intestine. The induction time course in the liver was slower for FAT and FATP mRNA than that of an mRNA encoding a peroxisomal enzyme. An obligatory role of PPAR alpha in hepatic FAT and FATP induction was demonstrated, since an increase in these mRNAs was not observed in PPAR alpha-null mice. Levels of mAspAT mRNA were higher in liver and intestine of mice treated with peroxisome proliferators, while levels in hepatoma cells were similar regardless of treatment. In white adipose tissue of KKAy obese mice, thiazolidinedione PPAR gamma activators (pioglitazone and troglitazone) induced FAT and FATP more efficiently than the PPAR alpha activator, clofibrate. This effect was absent in brown adipose tissue. Under the same conditions, levels of mAspAT mRNA did not change significantly in these tissues. In conclusion, tissue-specific expression of FAT and FATP genes involves both PPAR alpha and -gamma. Our data suggest that among the three putative long-chain fatty acid transporters, FAT and FATP appear to have physiological roles. Thus, peroxisome proliferators not only influence the metabolism of intracellular fatty acids but also cellular uptake, which is likely to be an important regulatory step in lipid homeostasis. C1 Toho Univ, Sch Pharmaceut Sci, Dept Biochem, Funabashi, Chiba 274, Japan. Univ Bourgogne, Lab Biol Mol & Cellulaire, F-21004 Dijon, France. NIH, Lab Metab, Bethesda, MD 20892 USA. RP Motojima, K (reprint author), Toho Univ, Sch Pharmaceut Sci, Dept Biochem, Funabashi, Chiba 274, Japan. EM motojima@phar.toho-u.ac.jp RI Peters, Jeffrey/D-8847-2011 NR 32 TC 372 Z9 386 U1 1 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 3 PY 1998 VL 273 IS 27 BP 16710 EP 16714 DI 10.1074/jbc.273.27.16710 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZX700 UT WOS:000074545200015 PM 9642225 ER PT J AU Hahm, SH Eiden, LE AF Hahm, SH Eiden, LE TI Five discrete cis-active domains direct cell type-specific transcription of the vasoactive intestinal peptide (VIP) gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HELIX-LOOP-HELIX; OCTAMER-BINDING-PROTEINS; NEURON-SPECIFIC ENHANCER; ACHAETE-SCUTE HOMOLOG-1; STAT PROTEINS; DNA-BINDING; EXPRESSION; SEQUENCE; COACTIVATOR; POLYPEPTIDE AB Vasoactive intestinal peptide (VIP) is a neuromodulator expressed with great anatomical specificity throughout the nervous system. Cell-specific expression of the VIP gene is mediated by a tissue specifier element (TSE) located within a 2.7-kilobase (kb) region between -5.2 and -2.5 kb upstream from the transcription start site, and requires an intact promoter proximal VIP-CRE (cyclic AMP-responsive element) (Hahm, S, H,, and Eiden, L, E, (1997) J, Neurochem, 67, 1872-1881), We now report that the TSE comprises a 425 base pair domain located between -4.7 and -4.2 kb containing two AT-rich octamer-like sequences. The 425-base pair TSE is sufficient to provide full cell-specific regulation of the VIP gene, when fused to the 5' proximal 1.55 kb of the VIP gene. Mutational analysis and gel shift assays of these octamer-like sequences indicate that the binding of proteins related to the ubiquitously expressed POU-homeodomain proteins Oct-1 and/or Oct-2 to these octamer-like sequences plays a central role for the function of the TSE, The TSE interacts with three additional discrete domains besides the cAMP response element, which are located within the proximal 1.55 kb of the VIP gene, to provide cell-specific expression. An upstream domain from -1.55 to -1.37 kb contains E-boxes and MEF2-like motifs, and deletion of this domain results in complete abrogation of cell-specific transcriptional activity, The region from -1.37 to -1.28 kb contains a STAT motif, and further removal of this domain allows the upstream TSE to act as an enhancer in both SH-EP and HeLa cells. The sequence from -1.28 to -0.9 kb containing a noncanonical AP-1 binding sequence (Symes, A, Gearan, T,, Eby, J,, and Fink, J, S, (1997) J. Biol, Chem. 272, 9648-9654), is absolutely required for TSE-dependent cell-specific expression of the VIP gene. Thus, five discrete domains of the VIP gene provide a combination of enhancer and repressor activities, each completely contingent on VIP gene context, that together result in cell-specific transcription of the VIP gene. C1 NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Hahm, SH (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, 36 Convent Dr,MSC 4090,Bldg 36,Rm 2D10, Bethesda, MD 20892 USA. OI Eiden, Lee/0000-0001-7524-944X NR 37 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 3 PY 1998 VL 273 IS 27 BP 17086 EP 17094 DI 10.1074/jbc.273.27.17086 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZX700 UT WOS:000074545200064 PM 9642274 ER PT J AU Baden, HA Sarma, SP Kapust, RB Byrd, RA Waugh, DS AF Baden, HA Sarma, SP Kapust, RB Byrd, RA Waugh, DS TI The amino-terminal domain of human STAT4 - Overproduction, purification, and biophysical characterization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-15 NMR RELAXATION; ESCHERICHIA-COLI; BACKBONE DYNAMICS; DNA-BINDING; PROTEINS; CODONS; SPECTROSCOPY; SENSITIVITY; EXPRESSION; DIFFUSION AB The multifunctional signal transducer and activator of transcription (STAT) proteins relay signals from the cell membrane to the nucleus in response to cytokines and growth factors. STAT4 becomes activated when cells are treated with interleukin-12, a key cytokine regulator of cell-mediated immunity. Upon activation, dimers of STAT4 bind cooperatively to tandem interferon-gamma activation sequences (GAS elements) near the interferon-gamma gene and stimulate its transcription. The amino-terminal domain of STAT4 (STAT4(1-124)) is required for cooperative binding interactions between STAT4 dimers and activation of interferon-gamma transcription in response to interleukin-12. me have overproduced this domain of human STAT4 (hSTAT4(1-124)) in Escherichia coli and purified it to homogeneity for structural studies. The circular dichroism spectrum of hSTAT4(1-124) indicates that it has a well ordered conformation in solution. The translational diffusion constant of hSTAT4(1-124) was determined by nuclear magnetic resonance methods and found to be consistent with that of a dimer. The rotational correlation time (tau(c)) of hSTAT4(1-124) was estimated from N-15 relaxation to be 16 ns; this value is consistent with a 29-kDa dimeric protein. These results, together with the number of signals observed in the two-dimensional H-1-N-15 heteronuclear single quantum coherence spectrum of uniformly N-15-labeled protein, indicate that hSTAT4(1-124) forms a stable, symmetric homodimer in solution. Cooperativity in native STAT4 probably results from a similar or identical interaction between the amino-terminal domains of adjacent dimers bound to DNA. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Prot Engn Grp, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol NMR Sect, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Prot Engn Grp, Frederick, MD 21702 USA. RI Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 NR 29 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 3 PY 1998 VL 273 IS 27 BP 17109 EP 17114 DI 10.1074/jbc.273.27.17109 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZX700 UT WOS:000074545200067 PM 9642277 ER PT J AU Oka, H Harada, K Ito, Y Ito, Y AF Oka, H Harada, K Ito, Y Ito, Y TI Separation of antibiotics by counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Review DE counter-current chromatography; reviews; solvent systems; antibiotics ID COIL PLANET CENTRIFUGE; MULTILAYER COILS; ROTARY SEALS; WATER FREE; ELUCIDATION; PURIFICATION; BACITRACIN; COMPONENTS; APPARATUS; PHASE AB This paper reviews recent applications of counter-current chromatography (CCC) to the separation of antibiotics. It also covers the recent development of CCC instruments and the optimization of the two-phase solvent system. The CCC technique offers a high resolving power when the proper solvent system is carefully selected and becomes a powerful tool to separate various components from antibiotics complexes. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 462, Japan. Meijo Univ, Fac Pharm, Tempa Ku, Nagoya, Aichi 468, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Oka, H (reprint author), Aichi Prefectural Inst Publ Hlth, Kita Ku, Tsuji Machi, Nagoya, Aichi 462, Japan. NR 55 TC 65 Z9 78 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 3 PY 1998 VL 812 IS 1-2 BP 35 EP 52 DI 10.1016/S0021-9673(97)01277-6 PG 18 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZX854 UT WOS:000074562100004 PM 9691308 ER PT J AU Wade, PA Jones, PL Vermaak, D Wolffe, AP AF Wade, PA Jones, PL Vermaak, D Wolffe, AP TI A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase SO CURRENT BIOLOGY LA English DT Article ID GENE-EXPRESSION; CHROMATIN; DERMATOMYOSITIS; ACETYLATION; AUTOANTIGEN; YEAST AB Chromatin structure plays a crucial regulatory role in the control of gene expression. In eukaryotic nuclei, enzymatic complexes can alter this structure by both targeted covalent modification and ATP-dependent chromatin remodeling. Modification of histone amino termini by acetyltransferases and deacetylases correlates with transcriptional activation and repression [1-3], cell growth [4], and tumorigenesis [5], Chromatin-remodeling enzymes of the Snf2 superfamily use ATP hydrolysis to restructure nucleosomes and chromatin, events which correlate with activation of transcription [6,7], We purified a multi-subunit complex from Xenopus laevis eggs which contains six putative subunits including the known deacetylase subunits Rpd3 and RbAp48/p46 [8] as well as substoichiometric quantities of the deacetylase associated protein Sin3 [9-13], In addition, we identified one of the other components of the complex to be Mi-2, a Snf2 superfamily member previously identified as an autoantigen in the human connective tissue disease dermatomyositis [14,15]. We found that nucleosome-stimulated ATPase activity precisely copurified with both histone deacetylase activity and the deacetylase enzyme complex. This association of a histone deacetylase with a Snf2 superfamily ATPase suggests a functional link between these two disparate classes of chromatin regulators. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T Room 106, Bethesda, MD 20892 USA. EM awlme@helix.nih.gov NR 24 TC 329 Z9 331 U1 0 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 2 PY 1998 VL 8 IS 14 BP 843 EP 846 DI 10.1016/S0960-9822(98)70328-8 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZY173 UT WOS:000074593600022 PM 9663395 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI Correspondence - A colipase fold in the carboxy-terminal domain of the Wnt antagonists - the Dickkopfs SO CURRENT BIOLOGY LA English DT Letter ID LIPASE PROCOLIPASE COMPLEX C1 Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. NR 14 TC 28 Z9 29 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 2 PY 1998 VL 8 IS 14 BP R477 EP R478 DI 10.1016/S0960-9822(98)70309-4 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZY173 UT WOS:000074593600005 PM 9663378 ER PT J AU John, CS Lim, BB Vilner, BJ Geyer, BC Bowen, WD AF John, CS Lim, BB Vilner, BJ Geyer, BC Bowen, WD TI Substituted halogenated arylsulfonamides: A new class of sigma receptor binding tumor imaging agents SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID H-3 (+)-PENTAZOCINE; ANTIPSYCHOTIC-DRUGS; MALIGNANT-MELANOMA; OPIOID RECEPTORS; CELL-LINES; LIGANDS; AFFINITY; CARCINOMA; POTENT; SITE AB The discovery of a series of novel halogenated arylsulfonamides (HAS) as new sigma receptor binding tumor imaging agents is described. Several substituted halogenated sulfonamides have been prepared and characterized. Target compounds were examined for their affinity for sigma(1) and sigma(2) receptor subtypes using guineapig brain membranes and rat liver membranes, respectively. A number of substituted halogenated sulfonamides displayed subnanomolar affinities for sigma(1) sites add low nanomolar affinities for sigma(2) subtype receptors. A limited structure-activity relationship study of this chemical series is discussed. The radioiodination (I-125) of one congener member (4-[I-125]iodo-N-[2-(1'-piperidinyl)ethyl]benzenesulfonamide 4-[I-125]IPBS) was accomplished in high yields. The in vitro competition binding studies of 4-[I-125]IPBS in guinea pig brain membranes with sigma receptor binding ligands confirmed its sigma pharmacology. The rank order of potency was BD1008 [N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)- ethylamine)> 4-IPBS > haloperidol > (+)-pentazocine > DTG (1,3-di-o-tolylguanidine) > (-)-pentazocine. The inhibition constants (IC50) were 0.70, 1.46, 6.28, 10.4, 87.2, and 152 nM, respectively, and are consistent with labeling of sigma(1) receptors. The tumor imaging potential of 4-[I-125]IPBS was studied in C57 black mice bearing B16 melanoma xenograft. A high tumor uptake of 4-[I-125]IPBS was observed (7.40% ID/g) at 1 h postinjection. The wash out of activity from the tumor was slow at 6 h postinjection (7.22% ID/g). The tumor also had the highest amount of radioactivity (1.54% ID/g) at 24 h postinjection. These results demonstrate that radiohalogenated benzenesulfonamides could be a potentially useful class of compounds in nuclear oncologic scintigraphy. C1 George Washington Univ, Med Ctr, Dept Radiol, Radiopharmaceut Chem Sect, Washington, DC 20037 USA. NIDDKD, Unit Receptor Biochem & Pharmacol, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP John, CS (reprint author), George Washington Univ, Med Ctr, Dept Radiol, Radiopharmaceut Chem Sect, 2300 I St NW,661 Ross Hall, Washington, DC 20037 USA. FU NCI NIH HHS [CA58496] NR 30 TC 29 Z9 30 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 2 PY 1998 VL 41 IS 14 BP 2445 EP 2450 DI 10.1021/jm9800447 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ZZ241 UT WOS:000074709700003 PM 9651150 ER PT J AU Cox, ED Diaz-Arauzo, H Huang, Q Reddy, MS Ma, CR Harris, B McKernan, R Skolnick, P Cook, JM AF Cox, ED Diaz-Arauzo, H Huang, Q Reddy, MS Ma, CR Harris, B McKernan, R Skolnick, P Cook, JM TI Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (Zk 93423) at wild type and recombinant GABA(A) receptors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BENZODIAZEPINE-RECEPTOR; A RECEPTORS; ETHANOL SENSITIVITY; INVERSE AGONISTS; BETA-CARBOLINES; XENOPUS OOCYTES; PHARMACOPHORE; PHARMACOLOGY; LIGANDS; BINDING AB A pharmacophore and an alignment rule have previously been reported for BzR agonist ligands. The design and synthesis of 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (B-PBC, 24, IC50 = 8.1 nM) was based on this pharmacophore. When evaluated in vivo this ligand exhibited anticonvulsant/anxiolytic activity but was devoid of the muscle relaxant/ ataxic effects of "classical" 1,4-benzodiazepines (i.e., diazepam). Significantly, 6-PBC 24 also reversed diazepam-induced muscle relaxation in mice. The 3-substituted analogues 40-46 and 48 of 6-PBC 24 and Zk 93423 27 (IC50 = 1 nM) were synthesized and evaluated in vitro to determine what affect these modifications would have on the binding affinity at recombinant BzR subtypes. With the exception of;the 3-amino ligands 40 and 41, all the beta-carbolines were found to exhibit high binding affinity at BzR sites. The 3-propyl ether derivative 45 was also evaluated in vivo and found to be devoid of any proconvulsant or anticonvulsant activity at doses up to 40 mg/kg. The 6-(1-naphthylmethyloxy) and 6-octyloxy analogues 25, 26, 28, and 29 of B-PBC 24 were synthesized to further evaluate the proposed alignment of agonists vs inverse agonists in the pharmacophore of the :BzR. In addition, ligands 26 and 29 were designed to probe the dimensions of lipophilic pocket L-beta at the agonist site. The activity of 29 was evaluated in vivo; however, this analogue elicited no pharmacological effects at doses up to 80 mg/kg. These and other related beta-carbolines were also examined in five recombinant GABA(A) receptor subtypes. Ligands 52-61 all exhibited moderate: to high affinity at GABA(A) receptors containing alpha(1) subunits. These ligands will be useful in further defining the pharmacophore at alpha(1)beta(3)gamma(2) receptors. C1 Univ Wisconsin, Dept Chem, Milwaukee, WI 53201 USA. Merck Sharp & Dohme Ltd, Res Labs, Harlow CM20 2QR, Essex, England. NIDDKD, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Cook, JM (reprint author), Univ Wisconsin, Dept Chem, POB 413, Milwaukee, WI 53201 USA. NR 42 TC 61 Z9 64 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 2 PY 1998 VL 41 IS 14 BP 2537 EP 2552 DI 10.1021/jm970460b PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ZZ241 UT WOS:000074709700011 PM 9651158 ER PT J AU Jeong, LS Buenger, G McCormack, JJ Cooney, DA Hao, Z Marquez, VE AF Jeong, LS Buenger, G McCormack, JJ Cooney, DA Hao, Z Marquez, VE TI Carbocyclic analogues of the potent cytidine deaminase inhibitor 1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NEPLANOCIN-A; BIOLOGICAL-ACTIVITY; URACIL NUCLEOSIDES; CRYSTAL-STRUCTURE; THYMIDINE; OLIGONUCLEOTIDES; PRODUCTS AB Three carbocylic analogues of the potent cytidine deaminase inhibitor (CDA) zebularine [1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2- one-, 1a] were synthesized. The selected pseudosugar templates correspond, respectively, to the cyclopentenyl moiety of neplanocin A (compound 4), the cyclopentyl moiety of aristeromycin (compound 5), and a newly designed, rigid bicyclo[3.1,0]hexane moiety (compound 6). These three carba-nucleoside versions of zebularine were fashioned to overcome the inherent instability of the parent drug. Each target compound was approached differently using either convergent or linear approaches. The immediate precursor to the cyclopentenyl analogue 4 was obtained by a Mitsunobu coupling of pseudosugar 7 with 2-hydroxypyrimidine. The cyclopentyl analogue 5 was linearly constructed from carbocyclic amine 17, and the final target 6 was similarly constructed from the carbobicyclic amine 27. Of the three target compounds, only 5 showed a significant level of inhibition against human CDA, but it was 16 times less potent than zebularine (K-i = 38 mu M vs K-i(apparent) = 2.3 mu M). Although these carbocyclic analogues appeared to be more stable than zebularine, replacement of the electronegative CO4' oxygen for the less electronegative carbon in 4-6 presumably reduces the capacity of the pyrimidin-2(1H)-one ring to form a covalent hydrate, a step considered crucial for the compound to function as a transition-state inhibitor of the enzyme. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Vermont, Coll Med, Dept Pharmacol, Burlington, VT 05401 USA. Univ Vermont, Vermont Reg Canc Ctr, Burlington, VT 05401 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 39 TC 29 Z9 29 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 2 PY 1998 VL 41 IS 14 BP 2572 EP 2578 DI 10.1021/jm980111x PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ZZ241 UT WOS:000074709700014 PM 9651161 ER PT J AU Adams, RJ McKie, VC Hsu, L Files, B Vichinsky, E Pegelow, C Abboud, M Gallagher, D Kutlar, A Nichols, FT Bonds, DR Brambilla, D Woods, G Olivieri, N Driscoll, C Miller, S Wang, W Hurlett, A Scher, C Berman, B Carl, E Jones, AM Roach, ES Wright, E Zimmerman, RA Waclawiw, M Pearson, H Powars, D Younkin, D El-Gammal, T Seibert, J Moye, L Espeland, M Murray, R McKinley, R McKinley, S Hagner, S Weiner, S Estow, S Yelle, M Brock, K Carter, E Chiarucci, K Debarr, M Feron, P Harris, S Hoey, L Jacques, K Kuisel, L Lewis, N Lindsey, R Martin, B McMeechan, C Muracca, M Rey, K Roath, G Hackney-Stephens, E Sumter, L Talbot, A Taplin, G Whittle, C Woods, P Harbin, J Holley, L Jackson, B Kutlar, F Miller, B Odo, N Sahm, M Schweitzer, J Winstead, A Swift, T Allen, F Allen, K Beasley, M Ejantkar, A Houston, E Hunter, D Luden, J Ottenlips, J Trocio, S Hernandez, C McKie, K McMorrow-Touhy, AM Perry, R Bello, J Luban, N Moser, F Caplan, L DeWitt, D Riela, A Babyn, P Cure, J Davis, P Fiqueroa, R Gaensler, E Hotson, W Kodroff, M Langston, J Lewin, J Rho, T Seidel, G Sutton, C Vezina, G Whitman, M Al-Mateen, M Barfield, J Caragan, A Curless, R Facchini, S Flemming, F Holden, K MacGregor, D Murphy, J Packer, R Park, Y Rose, A Sutton, C Wiznitzer, M AF Adams, RJ McKie, VC Hsu, L Files, B Vichinsky, E Pegelow, C Abboud, M Gallagher, D Kutlar, A Nichols, FT Bonds, DR Brambilla, D Woods, G Olivieri, N Driscoll, C Miller, S Wang, W Hurlett, A Scher, C Berman, B Carl, E Jones, AM Roach, ES Wright, E Zimmerman, RA Waclawiw, M Pearson, H Powars, D Younkin, D El-Gammal, T Seibert, J Moye, L Espeland, M Murray, R McKinley, R McKinley, S Hagner, S Weiner, S Estow, S Yelle, M Brock, K Carter, E Chiarucci, K Debarr, M Feron, P Harris, S Hoey, L Jacques, K Kuisel, L Lewis, N Lindsey, R Martin, B McMeechan, C Muracca, M Rey, K Roath, G Hackney-Stephens, E Sumter, L Talbot, A Taplin, G Whittle, C Woods, P Harbin, J Holley, L Jackson, B Kutlar, F Miller, B Odo, N Sahm, M Schweitzer, J Winstead, A Swift, T Allen, F Allen, K Beasley, M Ejantkar, A Houston, E Hunter, D Luden, J Ottenlips, J Trocio, S Hernandez, C McKie, K McMorrow-Touhy, AM Perry, R Bello, J Luban, N Moser, F Caplan, L DeWitt, D Riela, A Babyn, P Cure, J Davis, P Fiqueroa, R Gaensler, E Hotson, W Kodroff, M Langston, J Lewin, J Rho, T Seidel, G Sutton, C Vezina, G Whitman, M Al-Mateen, M Barfield, J Caragan, A Curless, R Facchini, S Flemming, F Holden, K MacGregor, D Murphy, J Packer, R Park, Y Rose, A Sutton, C Wiznitzer, M TI Prevention of a first stroke by transfusions in children with sickle, cell anemia and abnormal results on transcranial Doppler ultrasonography SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DISEASE; ANGIOGRAPHY; THERAPY AB Background Blood transfusions prevent recurrent stroke in children with sickle cell anemia, but the value of transfusions in preventing a first stroke is unknown. We used transcranial Doppler ultrasonography to identify children with sickle cell anemia who were at high risk for stroke and then randomly assigned them to receive standard care or transfusions to prevent a first stroke. Methods To enter the study, children with sickle cell anemia and no history of stroke had to have undergone two transcranial Doppler studies that showed that the time-averaged mean blood-flow velocity in the internal carotid or middle cerebral artery was 200 cm per second or higher. The patients were randomly assigned to receive standard care or transfusions to reduce the hemoglobin S concentration to less than 30 percent of the total hemoglobin concentration. The incidence of stroke (cerebral infarction or intracranial hemorrhage) was compared between the two groups. Results A total of 130 children (mean [+/- SD] age, 8.3 +/- 3.3 years) were enrolled; 63 were randomly assigned to receive transfusions, and 67 to receive standard care. At base line, the transfusion group had a slightly lower mean hemoglobin concentration (7.2 vs. 7.6 g per deciliter, P = 0.001) and hematocrit (20.4 vs. 21.7 percent, P = 0.002). Ten patients dropped out of the transfusion group, and two patients crossed over from the standard-care group to the transfusion group. There were 10 cerebral infarctions and ? intracerebral hematoma in the standard-care group, as compared with 1 infarction in the transfusion group - a 92 percent difference in the risk of stroke (P<0.001). This result led to the early termination of the trial. Conclusions Transfusion greatly reduces the risk of a first stroke in children with sickle cell anemia who have abnormal results on transcranial Doppler ultrasonography. (N Engl J Med 1998;339:5-11.) (C) 1998. Massachusetts Medical Society. C1 Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA. Med Coll Georgia, Dept Pediat Hematol & Oncol, Augusta, GA 30912 USA. Med Coll Georgia, Dept Med, Augusta, GA 30912 USA. Emory Univ, Sch Med, Sickle Cell Ctr, Atlanta, GA USA. E Carolina Univ, Sch Med, Dept Pediat Hematol & Oncol, Greenville, NC USA. Childrens Hosp Oakland, Dept Hematol & Oncol, Oakland, CA 94609 USA. Univ Miami, Sch Med, Sickle Cell Ctr, Miami, FL USA. Med Univ S Carolina, Pediat Sickle Cell Program, Charleston, SC 29425 USA. New England Res Inst, Watertown, MA 02172 USA. NHLBI, Bethesda, MD 20892 USA. Childrens Mercy Hosp, Dept Hematol & Oncol, Kansas City, MO 64108 USA. Hosp Sick Children, Dept Hematol & Oncol, Toronto, ON M5G 1X8, Canada. Childrens Natl Med Ctr, Dept Hematol & Oncol, Washington, DC 20010 USA. SUNY Hlth Sci Ctr, Pediat Sickle Cell Program, Brooklyn, NY 11203 USA. St Jude Childrens Res Hosp, Dept Hematol & Oncol, Memphis, TN 38105 USA. Columbia Presbyterian Med Ctr, Dept Pediat Hematol, New York, NY 10032 USA. Tulane Univ, Sch Med, Dept Pediat Hematol & Oncol, New Orleans, LA 70112 USA. Rainbow Babies & Childrens Hosp, Dept Pediat Hematol & Oncol, Cleveland, OH 44106 USA. Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA. Univ Texas, SW Med Ctr, Dept Pediat Neurol, Dallas, TX USA. New England Res Inst, Watertown, MA 02172 USA. Childrens Hosp Philadelphia, Dept Neuroradiol, Philadelphia, PA 19104 USA. NHLBI, Bethesda, MD 20892 USA. RP Adams, RJ (reprint author), Med Coll Georgia, Dept Neurol, 1467 Harper St,HB-2060, Augusta, GA 30912 USA. RI Hsu, Lewis/A-3360-2008; Roach, Ewell/E-3958-2011 FU NHLBI NIH HHS [U10 HL 52016, U10 HL 52193] NR 30 TC 827 Z9 843 U1 7 U2 22 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 2 PY 1998 VL 339 IS 1 BP 5 EP 11 DI 10.1056/NEJM199807023390102 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZX285 UT WOS:000074500000002 PM 9647873 ER PT J AU Willenberg, HS Stratakis, CA Marx, C Ehrhart-Bornstein, M Chrousos, GP Bornstein, SR AF Willenberg, HS Stratakis, CA Marx, C Ehrhart-Bornstein, M Chrousos, GP Bornstein, SR TI Aberrant interleukin-1 receptors in a cortisol-secreting adrenal adenoma causing Cushing's syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GASTRIC-INHIBITORY POLYPEPTIDE; CELLS; STEROIDOGENESIS; GLAND C1 NICHHD, NIH, Ctr Clin, Bethesda, MD 20892 USA. Univ Leipzig, Dept Internal Med 3, D-7010 Leipzig, Germany. NIMH, NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Bornstein, SR (reprint author), NICHHD, NIH, Ctr Clin, Bldg 10,Rm 10N262, Bethesda, MD 20892 USA. NR 20 TC 81 Z9 81 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 2 PY 1998 VL 339 IS 1 BP 27 EP 31 DI 10.1056/NEJM199807023390105 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA ZX285 UT WOS:000074500000005 PM 9647876 ER PT J AU Song, JS Swann, PG Szallasi, Z Blank, U Blumberg, PM Rivera, J AF Song, JS Swann, PG Szallasi, Z Blank, U Blumberg, PM Rivera, J TI Tyrosine phosphorylation-dependent and -independent associations of protein kinase C-delta with Src family kinases in the RBL-2H3 mast cell line: regulation of Src family kinase activity by protein kinase C-delta SO ONCOGENE LA English DT Article DE PKC-delta; Src; Lyn; mast cell; Fc epsilon RI ID HIGH-AFFINITY RECEPTOR; FOCAL ADHESION KINASE; BASOPHILIC LEUKEMIA-CELLS; N-TERMINAL REGION; IGE-RECEPTOR; IMMUNOGLOBULIN-E; SIGNAL-TRANSDUCTION; INSULIN-RECEPTOR; CROSS-LINKING; GAMMA-CHAIN AB Src kinases and protein kinase C (PKC) have been well studied for their role in oncogenic and normal cellular processes. Herein we report on a novel regulatory pathway mediated by the interaction of PKC-delta with p53/56(Lyn) (Lyn) and with p6o(Src) (Src) that results in the phosphorylation and increased activity of Lyn and Src, In the RBL-2H3 mast cell line, the interaction of PKC-delta with Lyn required the activation of the high affinity receptor for IgE (Fc epsilon RI) while the interaction with Src was constitutive. Increased complex formation of PKC-delta with Lyn or Src led to increased serine phosphorylation and activity of the Src family kinases, Conversely, Lyn was found to phosphorylate Lyn-associated and recombinant PKC-delta in vitro and the tyrosine 52 phosphorylated PKC-delta was recruited to associate with the Lyn SH2 domain. The constitutive association of PKC-delta with Src did not result in the tyrosine phosphorylation of PKC-delta prior to or after Fc epsilon RI engagement, However in cells over-expressing PKC-delta, Fc epsilon RI engagement resulted in the dramatic inhibition of Src activity and some inhibition of Lyn activity, Thus, the interaction and cross-talk of PKC-delta with Src family kinases suggests a novel and inter-dependent mechanism for regulation of enzymatic activity that may serve an important role in cellular responses. C1 NIAMS, Sect Chem Immunol, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. Inst Pasteur, F-75724 Paris 15, France. RP Rivera, J (reprint author), NIAMS, Sect Chem Immunol, Bethesda, MD 20892 USA. NR 65 TC 94 Z9 96 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 2 PY 1998 VL 16 IS 26 BP 3357 EP 3368 DI 10.1038/sj.onc.1201886 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZX689 UT WOS:000074544100002 PM 9692543 ER PT J AU Cmarik, JL Li, Y Ogram, SA Min, HZ Reeves, R Colburn, NH AF Cmarik, JL Li, Y Ogram, SA Min, HZ Reeves, R Colburn, NH TI Tumor promoter induces high mobility group HMG-Y protein expression in transformation-sensitive but not -resistant cells SO ONCOGENE LA English DT Article DE HMG-I(Y); tumor promotion; gene expression; neoplastic transformation; 12-O-tetradecanoylphorbol acetate ID MOUSE EPIDERMAL-CELLS; JB6 CELLS; GENE-EXPRESSION; NEOPLASTIC TRANSFORMATION; NUCLEAR PROTEINS; THYROID-CELLS; E-SELECTIN; C PROTEIN; BETA GENE; HMG-I(Y) AB Elevated levels of high mobility group (HMG) nonhistone chromosomal proteins I and Y, alternatively spliced members of the HMG-I(Y) family of architectural transcription factors? have been linked with human cancer and with neo-plastic and metastatic phenotypes in model systems, To investigate whether HMG-I(Y) proteins may influence susceptibility to neoplastic transformation, HMG-I(Y) mRNA and protein levels mere compared in the JB6 murine model of neoplastic progression, HMG-I(Y) mRNAs were expressed at very low levels in preneoplastic, transformation-resistant (P-) cell lines and were constitutively expressed at much higher levels in both transformation-sensitive (P+) and transformed (Tx) tumorigenic cell lines. HMG-I(Y) mRNAs mere induced to higher levels by the tumor promoter 12-O-tetradecanoylphorbol acetate (TPA) and were sustained longer in P+ than in P- cells. Nevertheless, in both P- and P+ cells, primer extension analysis revealed that the same four major HMG-I(Y) gene transcription start sites were utilized with or without TPA treatment. RT-PCR revealed that there nas always slightly more Y than I form mRNA present in all of the variant JB6 cell lines. Immunoblotting indicated that both HMG-I and -Y proteins increased in P+ cells in response to TPA treatment. Remarkably, in P- cells treated with TPA, only HMG-I (and not HMG-Y) protein levels increased. This unique differential TPA-induction of the HMG-Y protein in JB6 variants suggests a role for HMG-Y in mediating tumor promoter-induced neoplastic transformation, Furthermore, these results demonstrate that HMG-I and Y protein translation and/or stability is differently regulated in JB6 P- cells and provide the first indication that I and Y proteins may have different functions. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Washington State Univ, Dept Biochem & Biophys, Pullman, WA 99164 USA. Washington State Univ, Dept Genet & Cell Biol, Pullman, WA 99164 USA. RP Cmarik, JL (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Frederick, MD 21702 USA. FU NIGMS NIH HHS [R01-GM46352] NR 53 TC 28 Z9 28 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 2 PY 1998 VL 16 IS 26 BP 3387 EP 3396 DI 10.1038/sj.onc.1201888 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZX689 UT WOS:000074544100005 PM 9692546 ER PT J AU Simons-Morton, DG Goff, DC Osganian, S Goldberg, RJ Raczynski, JM Finnegan, JR Zapka, J Eisenberg, MS Proschan, MA Feldman, HA Hedges, JR Luepker, RV AF Simons-Morton, DG Goff, DC Osganian, S Goldberg, RJ Raczynski, JM Finnegan, JR Zapka, J Eisenberg, MS Proschan, MA Feldman, HA Hedges, JR Luepker, RV CA REACT Res Group TI Rapid early action for coronary treatment: Rationale, design, and baseline characteristics SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE acute myocardial infarction; community intervention ID ACUTE MYOCARDIAL-INFARCTION; THROMBOLYTIC THERAPY; MEDIA CAMPAIGN; CHEST PAIN; HEART-ATTACK; IMMEDIATE ANGIOPLASTY; PREHOSPITAL DELAY; PUBLIC-EDUCATION; PATIENT DELAY; RISK-FACTORS AB Objective: Early reperfusion for acute myocardial infarction (AMI) can reduce morbidity and mortality, yet there is often delay in accessing medical care after symptom onset. This report describes the design and baseline characteristics of the Rapid Early Action for Coronary Treatment (REACT) community trial, which is testing community intervention to reduce delay. Methods: Twenty U.S. communities were pair-matched and randomly assigned within pairs to intervention or comparison. Four months of baseline data collection was followed by an 18-month intervention of community organization and public, patient, and health professional education. Primary cases were community residents seen in the ED with chest pain, admitted with suspected acute cardiac ischemia, and discharged with a diagnosis related to coronary heart disease. The primary outcome was delay time from symptom onset to ED arrival. Secondary outcomes included delay time in patients with MI/unstable angina, hospital case-fatality rate and length of stay, receipt of reperfusion, and ED/emergency medical services utilization. Impact on public and patient knowledge, attitudes, and intentions was measured by telephone interviews. Characteristics of communities and cases and comparability of paired communities at baseline were assessed. Results: Baseline cases are 46% female, 14% minorities, and 73% aged greater than or equal to 55 years, and paired communities have similar demographics characteristics. Median delay time (available for 72% of cases) is 2.3 hours and does not vary between treatment conditions (p > 0.86). Conclusions: REACT communities approximate the demographic distribution of the United States and there is baseline comparability between the intervention and comparison groups. The REACT trial will provide valuable information for community educational programs to reduce patient delay for AMI symptoms. C1 NHLBI, DECA, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. New England Res Inst, Watertown, MA 02172 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Univ Alabama, Sch Med, Birmingham, AL USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. Seattle King Cty Dept Publ Hlth, King Cty Dept Emergency Med Serv, Seattle, WA USA. Oregon Hlth Sci Univ, Sch Med, Dept Emergency Med, Portland, OR 97201 USA. RP Simons-Morton, DG (reprint author), NHLBI, DECA, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM simonsd@gwgate.nhlbi.nih.gov FU NHLBI NIH HHS [U01-HL-53149, U01-HL-53141, U01-HL-53412] NR 59 TC 44 Z9 44 U1 1 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUL PY 1998 VL 5 IS 7 BP 726 EP 738 PG 13 WC Emergency Medicine SC Emergency Medicine GA 100KJ UT WOS:000074815100014 PM 9678398 ER PT J AU Dunten, P Jaffe, H Aksamit, RR AF Dunten, P Jaffe, H Aksamit, RR TI Crystallization of 5-keto-4-deoxyuronate isomerase from Escherichia coli SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID ERWINIA-CHRYSANTHEMI; S-ADENOSYLHOMOCYSTEINASE; PECTIN DEGRADATION; SEQUENCE ANALYSIS; HYDROLASE; GENE; KDGR AB 5-keto-4-deoxyuronate isomerase from Escherichia coli has been crystallized after partial purification. The isomerase was found to be enriched in preparations of an unrelated recombinant protein. Crystals of the isomerase were obtained from two different precipitants despite the fact that the recombinant protein represented roughly 90% of the total protein present. The crystals diffract to 2.7 Angstrom resolution and are suitable for a structure determination. The role of the isomerase in E. coli is uncertain, as E. coli is not known to degrade the polysaccharides which are potential sources of 5-keto-4-deoxyuronate. C1 Swedish Univ Agr Sci, Dept Biol Mol, BMC Box 590, S-75124 Uppsala, Sweden. NINDS, LNC, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NIMH, Lab Comparat & Gen Biochem, NIH, Bethesda, MD 20892 USA. US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Dunten, P (reprint author), Hoffmann La Roche Inc, 340 Kingsland St, Nutley, NJ 07110 USA. EM dunten@xray.bmc.uu.se NR 14 TC 4 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0907-4449 EI 1399-0047 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL 1 PY 1998 VL 54 BP 678 EP 680 DI 10.1107/S090744499701785X PN 4 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 103BZ UT WOS:000074962500031 PM 9761873 ER PT J AU Teo, B Kidd, RD Mack, J Tiwari, A Hernandez, D Phillips, AT Farber, GK AF Teo, B Kidd, RD Mack, J Tiwari, A Hernandez, D Phillips, AT Farber, GK TI Crystallization and preliminary X-ray studies of Pseudomonas putida histidine ammonium-lyase SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; ACTIVE-SITE; CARBANION INTERMEDIATE; ESCHERICHIA-COLI; DEHYDROALANINE; IDENTIFICATION; PURIFICATION; RESIDUE; ELIMINATION; SERINE-143 AB Histidine ammonium-lyase from P. putida was expressed in Escherichia coli, purified to homogeneity, and crystallized by the vapour-diffusion method using polyethylene glycol 3350 as the precipitant. The crystals, which diffract to at least 2.5 Angstrom resolution, exhibit the symmetry of space group P2(1)2(1)2(1), with unit-cell parameters a = 89.7, b = 138.2 and c = 164.8 Angstrom. The asymmetric unit contains a tetramer, and the crystals have a V-m value of 2.41 Angstrom(3) Da(-1). C1 Penn State Univ, Dept Biochem & Mol Biol, Althouse Lab 108, University Pk, PA 16802 USA. NIH, NIAMS, LSBR, Bethesda, MD 20892 USA. RP Teo, B (reprint author), Penn State Univ, Dept Biochem & Mol Biol, Althouse Lab 108, University Pk, PA 16802 USA. FU NIDDK NIH HHS [DK 47838] NR 25 TC 4 Z9 4 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL 1 PY 1998 VL 54 BP 681 EP 683 DI 10.1107/S0907444997017848 PN 4 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 103BZ UT WOS:000074962500032 PM 9761874 ER PT J AU Buonanno, A Cheng, J Venepally, P Weis, J Calvo, S AF Buonanno, A Cheng, J Venepally, P Weis, J Calvo, S TI Activity-dependent regulation of muscle genes: repressive and stimulatory effects of innervation SO ACTA PHYSIOLOGICA SCANDINAVICA LA English DT Article; Proceedings Paper CT Symposium on Skeletal Muscle - Development and Adaptation, at the Scandinavian-Physiological-Society Meeting CY NOV 14-16, 1997 CL OSLO, NORWAY SP Scandinavian Physiol Soc ID ADULT SKELETAL-MUSCLE; RECEPTOR-LACZ TRANSGENE; LIGHT-CHAIN GENE; ELECTRICAL-ACTIVITY; MYOGENIN GENE; MYOD FAMILY; SATELLITE CELLS; IN-VIVO; NEUROMUSCULAR-JUNCTION; UPSTREAM SEQUENCES C1 NICHHD, Dev Neurobiol Lab, Mol Neurobiol Unit, NIH, Bethesda, MD 20892 USA. Univ Bern, Inst Pathol, Bern, Switzerland. RP Buonanno, A (reprint author), NICHHD, Dev Neurobiol Lab, Mol Neurobiol Unit, NIH, Bldg 49,Room 5A-38, Bethesda, MD 20892 USA. RI Weis, Joachim/G-1984-2014 OI Weis, Joachim/0000-0003-3280-6773 NR 63 TC 17 Z9 17 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0001-6772 J9 ACTA PHYSIOL SCAND JI Acta Physiol. Scand. PD JUL PY 1998 VL 163 IS 3 BP S17 EP S26 PG 10 WC Physiology SC Physiology GA 105PU UT WOS:000075083200017 PM 9715746 ER PT J AU Dawson, DA AF Dawson, DA TI Measuring alcohol consumption: limitations and prospects for improvement SO ADDICTION LA English DT Editorial Material ID DRINKING; FREQUENCY; QUANTITY C1 NIAAA, DBE, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, DBE, NIH, Willco Bldg,Suite 514,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 15 TC 57 Z9 58 U1 0 U2 2 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD JUL PY 1998 VL 93 IS 7 BP 965 EP 968 PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA ZX580 UT WOS:000074532500001 PM 9744127 ER PT J AU Dawson, DA AF Dawson, DA TI Reply to the commentaries by Dr Dawson SO ADDICTION LA English DT Editorial Material ID ALCOHOL-CONSUMPTION; GENERAL-POPULATION C1 NIAAA, Div Biometry & Epidemiol, NIH, Bethesda, MD USA. RP Dawson, DA (reprint author), NIAAA, Div Biometry & Epidemiol, NIH, Bethesda, MD USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD JUL PY 1998 VL 93 IS 7 BP 975 EP 977 PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA ZX580 UT WOS:000074532500007 ER PT J AU Saif, MW Greenberg, BR AF Saif, MW Greenberg, BR TI Abdominal presentation of Burkitt's lymphoma in an HIV-positive patient SO AIDS PATIENT CARE AND STDS LA English DT Article ID NON-HODGKINS-LYMPHOMA; CHEMOTHERAPY; TRIAL AB The incidence of non-Hodgkin's lymphoma (NHL) has greatly increased in the AIDS population. It has been estimated that 8% to 27% of newly diagnosed cases of NHL are related to AIDS.' The vast majority are clinically aggressive B cell-derived lymphomas. AIDS-associated NHLs are classified according to their anatomic site of location into three classes: (1) systemic (both nodal as well as extranodal), (2) primary central nervous system, and (3) body cavity-based lymphomas.(2) We present a case report of a patient with HIV infection who presented with abdominal pain and distension and was found to have an intraabdominal type of Burkitt's lymphoma. This case underlines the following points: 1. Tn the evaluation of acute abdominal disease in a patient with AIDS, both AIDS-related infections as well as malignancies should be sought in the differential diagnosis. 2. Computed tomographic scanning of the abdomen is the modality of choice for characterization of disease as well as direction of appropriate therapy. 3. AIDS-related NHL remains an important biologic model for investigating the development and progression of lymphomas in the immune-deficient host. 4. With the improved survival of patients with AIDS secondary to better prevention and treatment of infections, there may be an increase in AIDS-associated malignancies; therefore, further research pertaining to the development and characterization of therapy modalities of such malignant tumors is mandatory. C1 Univ Connecticut, Sch Med, Dept Internal Med, Farmington, CT USA. RP Saif, MW (reprint author), NCI, 4700 Bradley Blvd, Chevy Chase, MD 20815 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JUL PY 1998 VL 12 IS 7 BP 567 EP 571 DI 10.1089/apc.1998.12.567 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 109WE UT WOS:000075346700009 PM 15462008 ER PT J AU Berkower, I Bridgewater, J AF Berkower, I Bridgewater, J TI Genetic control of the immune response to HIV type 1 envelope glycoprotein 120 in mice: Effects of MHC and transgenic human CD4 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; RECOMBINANT GP160; T-CELLS; NEUTRALIZING ANTIBODIES; CANDIDATE VACCINE; MURINE LEUKEMIA; GP120; INFECTION; IDENTIFICATION AB HIV infection elicits a strong immune response to viral proteins, including broadly cross-reactive antibodies to envelope glycoprotein 120 (gp120), However, vaccination with recombinant gp120 generally produces lower titered antibodies with narrow specificity. We have examined host genes that may control the strength and breadth of the response to gp120 vaccines. Because of the complexity of the human MHC, we have focused on the response of MHC congenic mice, which share an identical genetic background, differing only in H-2 type. The antibody response to gp120 varied markedly with H-2 type. H-2(a) and H-2(k) mice gave consistently high antibody titers, while H-2(s) mice gave 100-fold lower titers, and H-2(b) mice gave low to intermediate responses, Nearly the same genetic control applied for antibodies to both unique and shared determinants and on a variety of different genetic backgrounds, Transgenic mice expressing human CD4 gave the same titers as normal H-2-matched controls, MHC-linked genetic control of the quantity and quality of antibodies indicate a requirement for T cell help in producing antibodies to unique and shared determinants of gp120. C1 US FDA, Immunoregulat Lab, DAPP, Off Vaccine Res,Ctr Biol, Bethesda, MD 20892 USA. RP Berkower, I (reprint author), US FDA, Immunoregulat Lab, DAPP, Off Vaccine Res,Ctr Biol, Bldg 29,Room 523,NIH Campus, Bethesda, MD 20892 USA. NR 54 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL 1 PY 1998 VL 14 IS 10 BP 893 EP 900 DI 10.1089/aid.1998.14.893 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZW769 UT WOS:000074446500009 PM 9671218 ER PT J AU Goldman, D Urbanek, M Guenther, D Robin, R Long, JC AF Goldman, D Urbanek, M Guenther, D Robin, R Long, JC TI A functionally deficient DRD2 variant [Ser311Cys] is not linked to alcoholism and substance abuse SO ALCOHOL LA English DT Article; Proceedings Paper CT Conference on Molecular Genetics of Alcoholism and Other Addictive/Compulsive Disorders CY FEB 10, 1997 CL UCLA, LOS ANGELES, CALIFORNIA HO UCLA DE DRD2; alcoholism; Taq1A; Ser311Cys; American Indians ID DOPAMINE-D2 RECEPTOR GENE; TAQI A1 ALLELE; ASSOCIATION; LINKAGE; LOCUS; SCHIZOPHRENIA; POPULATIONS; HAPLOTYPES; GENOTYPE; RFLP AB Association studies with the DRD2 Taq1A marker have been variable in implicating DRD2 as a "Reward Deficiency Syndrome Gene" for alcoholism and substance abuse. Given that the Taq1A marker is not functionally significant, second-generation studies on the DRD2 receptor to identify functional variants and evaluate their effect on the phenotype are the logical step towards confirming and extending the DRD2 hypothesis. This article discusses the implications and process of progress made in these directions. The new findings are the description of structural variants in the D-2 receptor, the demonstration that one of these, Ser311Cys, largely prevents signal transduction following receptor activation and the use of Ser311Cys in a large association and sib-pair linkage anlysis in an American Indian isolate. In this particular population, the Cys311 variant is far more abundant (0.16) than in Caucasians (0.03). Genotyping of Ser311Cys, the DRD2 intron 2 STR, and the Taq1A marker in 459 subjects, including 373 sib-pairs and 15 Cys311/Cys311 homozygous individuals, revealed no association to alcoholism, substance use disorders, or schizophrenia. The implication is that a DRD2 variant that dramatically impairs receptor function was not sufficient to significantly alter alcoholism vulnerability in a relatively large and also genetically and environmentally homogeneous sample. Published by Elsevier Science Inc. C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. RP Goldman, D (reprint author), 12501 Washington Ave, Rockville, MD 20852 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NCRR NIH HHS [1 P41 RR03655] NR 26 TC 34 Z9 34 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUL PY 1998 VL 16 IS 1 BP 47 EP 52 DI 10.1016/S0741-8329(97)00176-6 PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA ZT888 UT WOS:000074138100008 PM 9650635 ER PT J AU Herrington, DM Fong, J Sempos, CT Black, DM Schrott, HG Rautaharju, P Bachorik, PS Blumenthal, R Khan, S Wenger, NK AF Herrington, DM Fong, J Sempos, CT Black, DM Schrott, HG Rautaharju, P Bachorik, PS Blumenthal, R Khan, S Wenger, NK CA HERS Study Grp TI Comparison of the Heart and Estrogen/Progestin Replacement Study (HERS) cohort with women with coronary disease from the National Health and Nutrition Examination Survey III (NHANES III) SO AMERICAN HEART JOURNAL LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; MYOCARDIAL-INFARCTION; ESTROGEN REPLACEMENT; CLINICAL-TRIALS; ARTERY DISEASE; FRAMINGHAM; MORTALITY; PROGNOSIS; THERAPY; ANGINA AB Background The Heart and Estrogen/Progestin Replacement Study (HERS) is the first large clinical trial designed to test the efficacy of postmenopausal estrogen/progestin therapy for secondary prevention of coronary heart disease (CHD). To examine the representativeness of the HERS cohort to the general population of postmenopausal women with CHD, we compared the baseline cardiovascular risk factor data from HERS with similar data from women presumed to have CHD from the National Health and Nutrition Examination Survey (NHANES) III. Methods Age, race, and cardiovascular disease risk factors were compared in the 2763 postmenopausal women younger than 80 years old, with a uterus, and with documented CHD in HERS versus 145 similarly aged women with clinical or electrocardiographic evidence of CHD from phase I of NHANES III. Results There were fewer current smokers in HERS (13%) than in the NHANES cohort (21.7%, p = 0.05). Similarly, a history of hypertension was less prevalent in HERS (58.6%) than in the NHANES cohort (69.3%, p = 0.03). Women with fasting triglyceride levels >3.39 mmol/l or fasting glucose revels >16.6 mmol/l were excluded from HERS, resulting in fewer diabetics (22.9% vs 29.5%, p = 0.26) and lower serum triglyceride levels (1.88 mmol/L vs 2.25 mmol/L, p = 0.19) in HERS versus the NHANES cohort. Systolic and diastolic blood pressure, body mass index, physical activity, and total IDL and HDL cholesterol were not significantly different between the two groups. Conclusions The HERS cohort had fewer CHD risk factors than women with myocardial infarction or angina in NHANES Ill, although comparison is hindered by differences in selection criteria. The many women with diabetes and hypertriglyceridemia in the NHANES cohort emphasizes the importance of testing strategies for secondary prevention of CHD in this high-risk subgroup. C1 Wake Forest Univ, Sch Med, Div Cardiol, Winston Salem, NC 27157 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. Univ Iowa, Dept Prevent Med, Iowa City, IA 52242 USA. Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA USA. RP Herrington, DM (reprint author), Wake Forest Univ, Sch Med, Div Cardiol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM dmh@osler.card.bgsm.edu NR 49 TC 32 Z9 32 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 1998 VL 136 IS 1 BP 115 EP 124 DI 10.1016/S0002-8703(98)70191-7 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZY323 UT WOS:000074608700022 PM 9665228 ER PT J AU Sheps, DS McMahon, RP Pepine, CJ Stone, PH Goldberg, AD Taylor, H Cohen, JD Becker, LC Chaitman, B Knatterud, GL Kaufmann, PG AF Sheps, DS McMahon, RP Pepine, CJ Stone, PH Goldberg, AD Taylor, H Cohen, JD Becker, LC Chaitman, B Knatterud, GL Kaufmann, PG TI Heterogeneity among cardiac ischemic and anginal responses to exercise, mental stress, and daily life SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; MYOCARDIAL-ISCHEMIA; PSYCHOPHYSIOLOGICAL INVESTIGATIONS; PECTORIS; TREADMILL; PIMI AB The objectives of this study were to compare and contrast indicators of ischemia in a well-characterized group of 196 patients with coronary artery disease, documented angiographically or by verified history of myocardial infarction, and a positive exercise test result. Myocardial ischemia occurs frequently in response to everyday stressors in patients with coronary artery disease. The Psychophysiological Interventions in Myocardial Ischemia study provides a unique opportunity to study neuroendocrine and psychological manifestations of ischemia. Patients with exercise-induced ischemia underwent exercise radionuclide ventriculography and electrocardiographic monitoring and 2 laboratory mental stressors (Speech and Stroop) after being withdrawn from cardiac medications. In addition, 48-hour ambulatory electrocardiograms were recorded during routine daily activities. Patients with a history of angina within the past 3 months reported angina during the bicycle or treadmill test with a much higher frequency than patients without such an anginal history (77% vs 26%). Election fraction (EF) responses to the Stroop test were abnormal in 48% of patients with an abnormal EF response to the Speech task, versus 17% in patients with a normal EF response (p < 0.01). Seventy-six percent of patients had an abnormal EF response to bicycle exercise. Three indicators of ischemia (ST-segment depression, wall motion abnormality, and EF response) were compared during the same laboratory stressor and across different types of stress tests. Presence of the 3 indicators was only moderately associated during exercise, and only weak or nonsignificant associations occurred among the presence of the 3 ischemic markers during mental stress. Occurrence of the same ischemic markers was moderately associated between the 2 mental stress tasks, but few associations were found between the occurrence of the same ischemic marker during exercise and mental stress. There is a marked heterogeneity of responses to psychological and exercise stress testing using electrocardiography, ambulatory electrocardiography, or radionuclide criteria for ischemia during stress. The heterogeneity may be related to differences in the magnitude or types of physiologic responses provoked and to differences in the sensitivity and specificity of the different tests used to identify ischemia, (C) 1998 by Excerpta Medico,Inc. C1 Maryland Med Res Inst, PIMI Clin Coordinating Ctr, Baltimore, MD 21210 USA. E Tennessee State Univ, Coll Med, Div Cardiol, Johnson City, TN 37614 USA. Univ Florida, Gainesville, FL USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. St Louis Univ, Med Ctr, St Louis, MO USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA. NHLBI, Behav Med Res Grp, Bethesda, MD 20892 USA. RP Sheps, DS (reprint author), Maryland Med Res Inst, PIMI Clin Coordinating Ctr, 600 Wyland Ave, Baltimore, MD 21210 USA. RI McMahon, Robert/C-5462-2009 FU NHLBI NIH HHS [HV 18114, HV 18119, HV 18120] NR 25 TC 4 Z9 4 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 1998 VL 82 IS 1 BP 1 EP 6 DI 10.1016/S0002-9149(98)00228-8 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZZ194 UT WOS:000074705000001 PM 9670999 ER PT J AU Aster, RH George, JN McMillan, R Ganguly, P AF Aster, RH George, JN McMillan, R Ganguly, P TI Workshop on autoimmune (idiopathic) thrombocytopenic purpura: Pathogenesis and new approaches to therapy SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article C1 Blood Ctr SE Wisconsin Inc, Blood Res Inst, Milwaukee, WI 53201 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Oklahoma, Sch Med, Oklahoma City, OK USA. Scripps Res Inst, La Jolla, CA USA. NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA. RP Aster, RH (reprint author), Blood Ctr SE Wisconsin Inc, Blood Res Inst, POB 2178, Milwaukee, WI 53201 USA. FU NHLBI NIH HHS [R01 HL013629] NR 0 TC 7 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUL PY 1998 VL 58 IS 3 BP 231 EP 234 DI 10.1002/(SICI)1096-8652(199807)58:3<231::AID-AJH12>3.0.CO;2-C PG 4 WC Hematology SC Hematology GA ZX381 UT WOS:000074510000012 PM 9687283 ER PT J AU Hartsough, MT Steeg, PS AF Hartsough, MT Steeg, PS TI Nm23-H1: Genetic alterations and expression patterns in tumor metastasis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID NUCLEOSIDE DIPHOSPHATE KINASE; BREAST-CARCINOMA CELLS; MULTISTEP PHOSPHORELAY; MUTATION; CANCER; OVEREXPRESSION; NEUROBLASTOMA; CHROMOSOME-17; SUBSTITUTION; TRANSFECTION C1 NCI, Womens Canc Sect, NIH, Bethesda, MD 20892 USA. RP Hartsough, MT (reprint author), NCI, Womens Canc Sect, NIH, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 33 TC 17 Z9 22 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1998 VL 63 IS 1 BP 6 EP 10 DI 10.1086/301942 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA ZZ726 UT WOS:000074761000002 PM 9634538 ER PT J AU Wassif, CA Maslen, C Kachilele-Linjewile, S Lin, D Linck, LM Connor, WE Steiner, RD Porter, FD AF Wassif, CA Maslen, C Kachilele-Linjewile, S Lin, D Linck, LM Connor, WE Steiner, RD Porter, FD TI Mutations in the human sterol Delta(7)-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DEFECTIVE CHOLESTEROL-BIOSYNTHESIS; PLASMA; YEAST AB The Smith-Lemli-Opitz syndrome (SLOS; also known as "RSH syndrome" [MIM 270400]) is an autosomal recessive multiple malformation syndrome due to a defect in cholesterol biosynthesis. Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and typically have low serum cholesterol levels. On the basis of this biochemical abnormality, it has been proposed that mutations in the human sterol Delta(7)-reductase (7-DHC reductase; E.C.1.3.1.21) gene cause SLOS. However, one could also propose a defect in a gene that encodes a protein necessary for either the expression or normal function of sterol Delta(7)-reductase. We cloned cDNA encoding a human sterol Delta(7)-reductase (DHCR7) on the basis of its homology with the sterol Delta(7)-reductase from Arabidopsis thaliana, and we confirmed the enzymatic function of the human gene product by expression in SLOS fibroblasts. SLOS fibroblasts transfected with human sterol Delta(7)-reductase cDNA showed a significant reduction in 7-DHC levels, compared with those in SLOS fibroblasts transfected with the vector alone. Using radiation-hybrid mapping, we show that the DHCR7 gene is encoded at chromosome 11q12-13. To establish that defects in this gene cause SLOS, we sequenced cDNA clones from SLOS patients. In three unrelated patients we have identified four different mutant alleles. Our results demonstrate both that the cDNA that we have identified encodes the human sterol Delta(7)-reductase and that mutations in DHCR7 are responsible for at least some cases of SLOS. C1 NICHHD, Heritable Disorders Branch, NIH, Unit Mol Dysmorphol, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Congenital Heart Res Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Endocrinol Diabet Clin Nutr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Doembecher Childrens Hosp, Child Dev & Rehabil Ctr, Dept Pediat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Doembecher Childrens Hosp, Child Dev & Rehabil Ctr, Dept Mol & Med Genet, Portland, OR 97201 USA. RP Porter, FD (reprint author), NICHHD, Heritable Disorders Branch, NIH, Unit Mol Dysmorphol, Bldg 10,Room 9S241,10 Ctr Dr, Bethesda, MD 20892 USA. OI Wassif, Christopher/0000-0002-2524-1420 FU NCRR NIH HHS [5 M01 RR 00334] NR 27 TC 270 Z9 276 U1 3 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1998 VL 63 IS 1 BP 55 EP 62 DI 10.1086/301936 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA ZZ726 UT WOS:000074761000010 PM 9634533 ER PT J AU Young, TL Ronan, SM Drahozal, LA Wildenberg, SC Alvear, AB Oetting, WS Atwood, LD Wilkin, DJ King, RA AF Young, TL Ronan, SM Drahozal, LA Wildenberg, SC Alvear, AB Oetting, WS Atwood, LD Wilkin, DJ King, RA TI Evidence that a locus for familial high myopia maps to chromosome 18p SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TANDEM REPEAT POLYMORPHISMS; MULTILOCUS LINKAGE ANALYSIS; DOMINANT JUVENILE GLAUCOMA; GENETIC-LINKAGE; MARFAN-SYNDROME; HUMAN GENOME; CONSTRUCTION; REFRACTION; INFANTS; SYSTEM AB Myopia, or nearsightedness, is the most common human eye disorder. A genomewide screen was conducted to map the gene(s) associated with high, early-onset, autosomal dominant myopia. Eight families that each included two or more individuals with greater than or equal to-6.00 diopters (D) myopia, in two or more successive generations, were identified. Myopic individuals had no clinical evidence of connective-tissue abnormalities, and the average age at diagnosis of myopia was 6.8 years. The average spherical component refractive error for the affected individuals was -9.48 D. The families contained 82 individuals; of these, DNA was available for 71 (37 affected). Markers nanking or intragenic to the genes for Stickler syndrome types 1 and 2 (chromosomes 12q13.1-q13.3 and 6p21.3, respectively), Marfan syndrome (chromosome 15q21.1), and juvenile glaucoma (chromosome 1q21-q31) were also analyzed. No evidence of linkage was found for markers for the Stickler syndrome types 1 and 2, the Marfan syndrome, or the juvenile glaucoma loci. After a genomewide search, evidence of significant linkage was found on chromosome 18p. The maximum LOD score was 9.59, with marker D18S481, at a recombination fraction of .0010. Haplotype analysis further refined this myopia locus to a 7.6-cM interval between markers D18S59 and D18S1138 on 18p11.31. C1 Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. NIH, Med Genet Branch, Natl Human Genome Res Inst, Bethesda, MD USA. RP Young, TL (reprint author), Univ Minnesota, Dept Ophthalmol, Box 493,420 Delaware St, Minneapolis, MN 55455 USA. NR 50 TC 147 Z9 168 U1 2 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1998 VL 63 IS 1 BP 109 EP 119 DI 10.1086/301907 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA ZZ726 UT WOS:000074761000017 PM 9634508 ER PT J AU Fedorova, OV Anderson, DE Bagrov, AY AF Fedorova, OV Anderson, DE Bagrov, AY TI Plasma marinobufagenin-like and ouabain-like immunoreactivity in adrenocorticotropin-treated rats SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article; Proceedings Paper CT 12th Meeting of the American-Society-of-Hypertension CY JUN, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Hypertens DE adrenocorticotropin; rats; hypertension; Na,K-ATPase; antagonists and inhibitors; bufodienolide ID ACTH-DEPENDENT HYPERTENSION; DIGITALIS-LIKE COMPOUNDS; INHIBITOR; ATPASE; NA,K-ATPASE; HYPOVENTILATION; SHEEP; PUMP AB Recently, an endogenous digitalis-like factor (EDLF) was shown to be stimulated in corticotropin (ACTH) hypertension in the rat. We have shown that mammalian plasma contains a vasoconstrictor Na,K-ATPase inhibitor, which cross-reacts with an antibody to amphibian EDLF, marinobufagenin. In the present experiment, the effect of 8 days of intramuscular ACTH treatment (0.5 mg/kg/day) of male Fisher 344xNB rats on blood pressure, plasma ouabain-like and marinobufagenin-like immunoreactivity, and on the activity of Na,K-ATPase in aortic sarcolemma were studied. The ACTH treatment for 8 days resulted in increased systolic blood pressure (151 +/- 12.4 v 121 +/- 4.0 mm Hg, P <.01), inhibition of Na,K-ATPase in aortic sarcolemma (2.99 +/- 0.35 v 5.43 +/- 0.17 mu mol ADP/mg(prot)/h), and increases in plasma concentration of marinobufagenin-like (0.44 +/- 0.06 v 0.21 +/- 0.05 nmol/L), but not ouabain-like (0.09 +/- 0.01 v 0.10 +/- 0.04 nmol/L) immunoreactivity. In dissociation enhanced lanthanide fluoroimmunoassay (DELFIA), serial dilutions of plasma from ACTH-treated rats extracted with 25% and 80% acetonitrile, respectively, demonstrated parallelism to the calibration curves of ouabain and marinobufagenin. These findings suggest that an endogenous bufodienolide Na,K-ATPase inhibitor, rather than an endogenous ouabain-like compound, is increased after 8 days of treatment of rats with ACTH. Am T Hypertens 1998;11:796-802 (C) 1998 American Journal of Hypertension, Ltd. C1 NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. IM Sechenov Evolutionary Physiol & Biochem Inst, Pharmacol Lab, St Petersburg 194223, Russia. RP Fedorova, OV (reprint author), NIA, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM fedorovo@grc.nia.nih.gov NR 37 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUL PY 1998 VL 11 IS 7 BP 796 EP 802 DI 10.1016/S0895-7061(98)00042-9 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZZ734 UT WOS:000074761800005 PM 9683040 ER PT J AU Figgs, LW Stewart, PA Blair, A AF Figgs, LW Stewart, PA Blair, A TI The impact of initial job assignment on formaldehyde exposure among African-American and white formaldehyde industry workers SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE African-American; occupation; formaldehyde; exposure ID MORTALITY AB We compared initial job assignments of African-American and white employees at eight worksites that used formaldehyde between 1940 and 1979. Unexposed workers were excluded. Median, ambient air formaldehyde, 8-hour, time-weighted average (TWA(g)) exposure estimates were determined for each worksite. Job assignments with TWAs above the worksite's median TWA(g) were called high formaldehyde exposed(HFE). Job assignments with TWAs less than or equal to the worksite's median TWA(g) for the same period were called lower formaldehyde exposed (LFE). Two worksites assigned black workers to HFE jobs in significantly higher proportions than white workers in some decades. One worksite assigned white workers in significantly higher proportions than black workers to HFE jobs in some decades. One worksite assigned racial groups in nearly equal proportions from 1940 to 1969. The remaining sites showed insignificant assignment disproportions (alpha = 0.05; Chi-square less than or equal to 3.841, 1 degree of freedom) for any period. Na major trend was apparent across all plants and decades. (C) 1998 Wiley-Liss, Inc.dagger C1 St Louis Univ, Sch Publ Hlth, St Louis, MO 63108 USA. NCI, Epidemiol & Biostat Program, Occupat Studies Branch, Bethesda, MD 20892 USA. RP Figgs, LW (reprint author), St Louis Univ, Sch Publ Hlth, 3663 Lindell Blvd, St Louis, MO 63108 USA. EM figgslw@wpogate.slu.edu NR 21 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 1998 VL 34 IS 1 BP 57 EP 64 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZP971 UT WOS:000073807300008 PM 9617388 ER PT J AU Coresh, J Toto, RD Kirk, KA Whelton, PK Massry, S Jones, C Agodoa, L Van Lente, F AF Coresh, J Toto, RD Kirk, KA Whelton, PK Massry, S Jones, C Agodoa, L Van Lente, F CA AASK Pilot Study Investigators TI Creatinine clearance as a measure of GFR in screenees for the African-American study of kidney disease and hypertension pilot study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE creatinine clearance; GFR; black patients ID GLOMERULAR-FILTRATION RATE; SERUM CREATININE; RENAL-FUNCTION; INULIN; IOTHALAMATE; TC-99M-DTPA; PREDICTION; HEALTH; ADULTS; BLACK AB Serum creatinine and endogenous creatinine clearance (CrCl) are widely used measures of renal function. This study compares the precision, bias, and sources of error in using different CrCl measures to estimate the glomerular filtration rate (GFR) in 118 men and women screened for the African-American Study of Kidney Disease and Hypertension (AASK) pilot study. We measured serum creatinine, 24-hour CrCl, and CrCl during timed clearance periods conducted simultaneously with an I-125-iothalamate GFR study. Serum creatinine was measured using two different kinetic rate Jaffe methods (CX3 and Hitachi). After standardization for body surface area, the different measures of renal function available for each individual were compared with the I-125-iothalamate GFR simultaneous to the CrCl. In a subset of 50 participants, the CrCl measures were compared with a follow-up GFR (fGFR). The mean I-125-iothalamate GFR was 65.2 (SD, 26.4), with a range of 11 to 122 mL/min/1.73 m(2). The mean +/- SD percentage differences from the GFR were -9% +/- 22% for the Cockcroft-Gault estimated CrCl, 1% +/- 29% for the 24-hour CrCl, and 8% +/- 16% for the CX3 simultaneous CrCl. The Hitachi method overestimated serum creatinine and underestimated GFR. Compared with an fGFR, the mean +/- SD differences were 2% +/- 19% for the first GFR, -6% +/- 20% for the Cockcroft-Gault estimated CrCl, 10% +/- 28% for the 24-hour CrCl, and 14% +/- 29% for the CX3 simultaneous CrCl. Thus, the increased precision with which the timed CrCl predicted its simultaneous GFR did not extend to improved ability to predict a future GFR. The fractional excretion of creatinine, measured as the ratio of the CX3 simultaneous CrCl to I-125-iothalamate clearance, increased with decreasing GFR but was lower than expected (mean +/- SD of 1.21 +/- 0.16 for GFRs between 20 and 40 mL/min/1.73 m(2)). The lower fractional excretion explains why the 24-hour and Cockcroft-Gault CrCls did not overestimate GFR, but the reasons for this lower excretion are uncertain. Creatinine assay specificity and calibration are important sources of variability that must be examined in any CrCl measure of GFR. We conclude that despite requiring substantially more time and effort, neither the outpatient 24-hour urine nor the timed CrCl offered increased precision over a calculation based on serum creatinine, sex, age, and weight in predicting GFR. (C) 1998 by the National Kidney Foundation, Inc. C1 Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Vanderbilt Sch Med, Dept Med, Nashville, TN USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70118 USA. Univ So Calif, Dept Med, Div Nephrol, Los Angeles, CA USA. NIDDKD, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Clin Pathol, Cleveland, OH USA. RP Coresh, J (reprint author), Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument,Suite 2-600, Baltimore, MD 21205 USA. FU NIDDK NIH HHS [DK I U01 DK45430-02, DK48362-01A1] NR 34 TC 93 Z9 95 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 1998 VL 32 IS 1 BP 32 EP 42 DI 10.1053/ajkd.1998.v32.pm9669421 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA ZX599 UT WOS:000074534400005 PM 9669421 ER PT J AU Romero, R Gomez, R Ghezzi, F Yoon, BY Mazor, M Edwin, SS Berry, SM AF Romero, R Gomez, R Ghezzi, F Yoon, BY Mazor, M Edwin, SS Berry, SM TI A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Society-of-Perinatal-Obstetricians CY JAN 20-26, 1997 CL ANAHEIM, CA SP Soc Perinatal Obstetricians DE preterm premature rupture of membranes; intrauterine infection; human parturition; fetal physiology; interleukin-6 ID AMNIOTIC-FLUID GLUCOSE; TUMOR-NECROSIS-FACTOR; PREMATURE RUPTURE; INTRAAMNIOTIC INFECTION; GRAM STAIN; MEMBRANES; INTERLEUKIN-1; LABOR; AMNIOCENTESIS; CYTOKINES AB OBJECTIVE: There is no evidence for the participation of the human fetus in the mechanisms responsible for the onset of preterm labor. We propose that preterm labor in the setting of infection results from the actions of proinflammatory cytokines secreted as part of the fetal and/or maternal host response to microbial invasion. The objective of this study was to determine whether a systemic fetal inflammatory response, defined as an elevation of fetal plasma interleukin-6 concentrations, has a temporal relationship with the commencement of labor. STUDY DESIGN: After informed consent was obtained, amniocentesis and cordocentesis were performed in 41 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultured for both aerobic and anaerobic bacteria, as well as for mycoplasmas. Fetal plasma interleukin-8 was assayed by a sensitive and specific immunoassay. Statistical analyses included contingency tables and survival analysis with time-dependent Cox regression hazard modeling. RESULTS: Microbial invasion of the amniotic cavity was present in 58.5% (24/41) of patients. Fetuses with fetal plasma interleukin-8 concentrations >11 pg/mL had a higher rate of spontaneous preterm delivery within 48 and 72 hours of the procedure than those with fetal plasma interleukin-8 levels less than or equal to 11 pg/mL (88% vs 29% and 88% vs 35%, respectively; P < .05 for all comparisons). Moreover, patients with initiation of labor and delivery within 48 hours of the procedure had a higher proportion of fetuses with plasma interleukin-8 values >11 pg/mL than patients delivered >48 hours (58% [7/12] vs 8% [1/13], respectively; P < .05). Survival analysis indicated that fetuses with elevated fetal plasma interleukin-8 levels had a shorter cordocentesis-to-delivery interval than those without elevated fetal plasma interleukin-6 concentrations (median 0.8 days [range 0.1 to 5] vs median 6 days [range 0.2 to 33.6], respectively; P < .05). Time-dependent Cox regression hazard modeling indicated that fetal plasma interleukin-6 level was the only covariate significantly associated with the duration of pregnancy after we adjusted for gestational age, amniotic fluid interleukin-6 level, and the microbiologic state of the amniotic cavity (P < .01). CONCLUSION: A systemic fetal proinflammatory cytokine response is followed by the onset of spontaneous preterm parturition in patients with preterm premature rupture of membranes. C1 Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, Bethesda, MD USA. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. Ben Gurion Univ Negev, Dept Obstet Gynecol, IL-84105 Beer Sheva, Israel. Hosp Dr Sotero del Rio, Dept Obstet Gynecol, Puente Alto, Chile. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011; OI Ghezzi, Fabio/0000-0003-3949-5410 NR 25 TC 348 Z9 354 U1 0 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 1998 VL 179 IS 1 BP 186 EP 193 DI 10.1016/S0002-9378(98)70271-6 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 107GQ UT WOS:000075199300030 PM 9704786 ER PT J AU Gomez, R Romero, R Ghezzi, F Yoon, BH Mazor, M Berry, SM AF Gomez, R Romero, R Ghezzi, F Yoon, BH Mazor, M Berry, SM TI The fetal inflammatory response syndrome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Society-of-Perinatal-Obstetricians CY JAN 20-26, 1997 CL ANAHEIM, CA SP Soc Perinatal Obstetricians DE preterm labor; intrauterine infection; fetal homeostasis; inflammatory response; neonatal morbidity ID PRETERM PREMATURE RUPTURE; BLOOD-CELL COUNT; INTRAAMNIOTIC INFECTION; BIOPHYSICAL PROFILE; INTACT MEMBRANES; UMBILICAL-CORD; GRAM STAIN; LABOR; INTERLEUKIN-6; GLUCOSE AB OBJECTIVE: The objective of this study was to determine the frequency and clinical significance of a systemic inflammatory response as defined by an elevated plasma interleukin-g concentration in fetuses with preterm labor or preterm premature rupture of membranes. STUDY DESIGN: Amniocenteses and cordocenteses were performed in 157 patients with preterm labor and preterm premature rupture of membranes. Written informed consent and multi-institutional review board approvals were obtained. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Amniotic fluid and fetal plasma interleukin-6 concentrations were measured with a sensitive and specific immunoassay. Statistical analyses included contingency tables, receiver operating characteristic curve analysis, and multiple logistic regression. RESULTS: One hundred five patients with preterm labor and 52 patients with preterm premature rupture of membranes were included in this study. The overall prevalence of severe neonatal morbidity (defined as the presence of respiratory distress syndrome, suspected or proved neonatal sepsis, pneumonia, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis) among survivors was 34.8% (54/155). Neonates in whom severe neonatal morbidity developed had higher concentrations of fetal plasma interleukin-6 than fetuses without development of severe neonatal morbidity (median 14.0 pg/mL, range 0.5 to 900 vs median 5.2 pg/mL, range 0.3 to 900, respectively; P < .005). Multivariate analysis was performed to explore the relationship between the presence of a systemic fetal inflammatory response and subsequent neonatal outcome. To preserve a meaningful temporal relationship between the results of fetal plasma interleukin-6 concentrations and the occurrence of severe neonatal morbidity, the analysis was restricted to 73 fetuses delivered within 7 days of cordocentesis who survived. The prevalence of severe neonatal morbidity in this subset of patients was 53.4% (39n3). A fetal plasma interleukin-6 cutoff value of 11 pg/mL was used to define the presence of a systemic inflammatory response. The prevalence of a fetal plasma interleukin-6 level >11 pg/mL was 49.3% (36/73). Fetuses with fetal plasma interleukin-8 concentrations >11 pg/mL had a higher rate of severe neonatal morbidity than did those with fetal plasma interleukin-8 levels less than or equal to 11 pg/mL (77.8% [28/36] vs 29.7% [11/37], respectively; P < .001). Stepwise logistic regression analysis demonstrated that the fetal plasma interleukin-g concentration was an independent predictor of the occurrence of severe neonatal morbidity (odds ratio 4.3, 95% confidence interval 1 to 18.5) when adjusted for gestational age at delivery, the cause of preterm delivery (preterm labor or preterm premature rupture of membranes), clinical chorioamnionitis, the cordocentesis-to-delivery interval, amniotic fluid culture, and anmiotic fluid interleukin-6 results. CONCLUSION: A systemic fetal inflammatory response, as determined by an elevated fetal plasma interleukin-B value, is an independent risk factor for the occurrence of severe neonatal morbidity. C1 Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, Puente Alto, Chile. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. Ben Gurion Univ Negev, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011; OI Ghezzi, Fabio/0000-0003-3949-5410 NR 26 TC 602 Z9 629 U1 3 U2 22 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 1998 VL 179 IS 1 BP 194 EP 202 DI 10.1016/S0002-9378(98)70272-8 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 107GQ UT WOS:000075199300031 PM 9704787 ER PT J AU Quintanilla-Martinez, L Thieblemont, C Fend, F Kumar, S Pinyol, M Campo, E Jaffe, ES Raffeld, M AF Quintanilla-Martinez, L Thieblemont, C Fend, F Kumar, S Pinyol, M Campo, E Jaffe, ES Raffeld, M TI Mantle cell lymphomas lack expression of p27(kip1), a cyclin-dependent kinase inhibitor SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MICE LACKING; D1; GENE; OVEREXPRESSION; CANCER; GROWTH; HYPERPLASIA; FIBROBLASTS; MUTATIONS; TUMORS AB p27(Kip1) is a cyclin-dependent kinase inhibitor that regulates the decision to enter S phase or withdraw from the cell cycle. In resting cells, the level of p27(Kip1) provides an inhibitory threshold above which G1 cyclin D/E/cyclin-dependent kinases accumulate before activation; however, in cycling cells, p27(Kip1) protein is sequestered by high levels of active cyclin D/cyclin-dependent kinase 4 complexes. As a group, the cyclin-dependent kinase inhibitors have been proposed to act as tumor suppressor genes, and several members have been implicated in the pathogenesis of a variety of human cancers. We examined p27(Kip1) expression in 116 non-Hodgkin's lymphomas including 50 cases of MCL (40 typical and 10 blastic variants), 21 follicular lymphomas, 20 diffuse large B-cell lymphomas, 16 chronic lymphocytic leukemias, 8 marginal zone B-cell lymphomas, and 1 splenic marginal zone lymphoma, and correlated its expression with that of the proliferation marker Ki67 (MiB1) and with p53. p27(Kip1) gene structure was analyzed by Southern blot in the group of MCLs, In all cases of non-Hodgkin's lymphoma other than MCL, p27(Kip1) expression was inversely related to the proliferation index as measured by Ki67, In contrast, in typical MCL, p27(Kip1) expression was negative in 35 of 40 (88%) cases, irrespective of the proliferative rate (median 15%; range 2 to 90%). Paradoxically, in the blastic variant of MCL, 8 of 10 (80%) cases showed expression of p27(Kip1), despite a high proliferation rate (median 60%; range 52 to 100%). However, the staining in most of the cases was less intense than in the reactive T lymphocytes, Deletions of p27(Kip1) gene were not found in any of the 25 cases examined. p53 expression was found in 15 of 50 cases of MCL: 7 of 10 (70%) in the blastic variant and 8 of 40 (20%) in the typical MCL (70% vs. 20%, P < 0.0045), These results demonstrate that MCLs, in contrast to other non-Hodgkin's lymphomas and normal lymphoid tissue, fail to correlate p27(Kip1) expression with the proliferation rate. This peculiar uncoupling of p27(Kip1) protein expression from the proliferation rate may be related to the high levels of cyclin D1 expressed in MCL and is likely to have profound effects on cell cycle regulation and contribute to the pathogenesis of MCL. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Barcelona, Hosp Clin Prov, Barcelona, Spain. RP Raffeld, M (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mraff@box-m.nih.gov OI Campo, elias/0000-0001-9850-9793 NR 40 TC 83 Z9 84 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1998 VL 153 IS 1 BP 175 EP 182 DI 10.1016/S0002-9440(10)65558-7 PG 8 WC Pathology SC Pathology GA ZX920 UT WOS:000074568700022 PM 9665478 ER PT J AU Lubensky, IA Pack, S Ault, D Vortmeyer, AO Libutti, SK Choyke, PL Walther, MM Linehan, WM Zhuang, ZP AF Lubensky, IA Pack, S Ault, D Vortmeyer, AO Libutti, SK Choyke, PL Walther, MM Linehan, WM Zhuang, ZP TI Multiple neuroendocrine tumors of the pancreas in vonHippel-Lindau disease patients - Histopathological and molecular genetic analysis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; CLINICAL-SIGNIFICANCE; ENDOCRINE NEOPLASIA; SUPPRESSOR GENE; SHORT ARM; LESIONS; PHEOCHROMOCYTOMA; CHROMOSOME-3; PREVALENCE AB Although pancreatic neuroendocrine turners (NETs) in von Hippel-Lindau (VHL) disease have been reported, their pathological features have not been characterized. In addition, it is unknown whether alterations of the VHL gene are responsible for pancreatic NET development, To evaluate NETs in VHL patients, we performed histopathological analysis of 30 pancreatic tumors in 14 patients. In addition, DNA from NETs and normal pancreatic tissue from 6 patients with documented germ-line VHL gene mutations was studied for allelic deletions of the second copy of the VHL gene by fluorescence in situ hybridization and polymerase chain reaction-based single-strand conformational polymorphism analysis. Morphologically, the tumors were characterized by solid, trabecular, and/or glandular architecture and prominent stromal collagen bands. Sixty percent of the tumors revealed at least focally clear-cell cytology, All tumors were positive for panendocrine immunohistochemistry markers (chromogranin A and/or synaptophysin); 35% of NETs demonstrated focal positivity for pancreatic polypeptide, somatostatin, insulin, and/or glucagon; and no immunostaining for pancreatic and gastrointestinal hormones was observed in 65% of tumors. Dense core neurosecretory granules were evident by electron microscopic examination, and the clear cells additionally revealed abundant Intracytoplasmic lipid. All NETs that were subjected to genetic analysis showed allelic loss of the second copy of the VHL gene. We conclude that multiple, nonfunctional pancreatic NETs occur in VHL patients. Stromal collagen bands and clear-cell morphology are important histological features of VHL-associated NETs, The presence of allelic deletions of the VHL gene in pancreatic NETs provides direct molecular evidence for a role of the gene in their tumorigenesis and establishes NET as an independent tamer type of VHL disease. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Zhuang, ZP (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 29 TC 145 Z9 148 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1998 VL 153 IS 1 BP 223 EP 231 DI 10.1016/S0002-9440(10)65563-0 PG 9 WC Pathology SC Pathology GA ZX920 UT WOS:000074568700027 PM 9665483 ER PT J AU Trempus, CS Ward, S Farris, G Malarkey, D Faircloth, RS Cannon, RE Mahler, JF AF Trempus, CS Ward, S Farris, G Malarkey, D Faircloth, RS Cannon, RE Mahler, JF TI Association of v-Ha-ras transgene expression with development of erythroleukemia in Tg.AC transgenic mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; EMBRYONIC STEM-CELLS; ERYTHROID DEVELOPMENT; HEMATOPOIETIC-CELLS; GLOBIN GENE; MOUSE; DIFFERENTIATION; PROLIFERATION; NEOPLASMS AB A transgenic mouse line (Tg,AC) carrying an activated v-Ha-ras oncogene fused to the embryonic zeta-globin promoter develops an array of spontaneous epithelial and mesenchymal neoplasms. In this report we describe the morphological, immunophenotypic, and molecular features of a unique hematopoietic neoplasm in these mice. The cardinal lesion of this disease is marked hepatomegaly due to leukemic proliferation and infiltration. In the peripheral blood, there is a marked increase in the number of metarubricytes and other less differentiated erythroid progenitor cells. Leukemic cells stain positively with an erythroid-associated nuclear transcription factor (GATA-1), Using a reverse transcription polymerase chain reaction assay, co-expression of GATA-1 and endogenous zeta-globin genes is detected in hematopoietic tissues of nonleukemic transgenic and nontransgenic mice, ras transgene expression is, however, detected only in normal bone marrow and leukemic tissues of transgenic mice, and 5' mapping experiments using S1 protection analysis of total RNA from leukemic tissue indicates that transcription of the transgene mRNA is initiated from the natural zeta-globin promoter start site, supporting the belief that the zeta-globin promoter directs v-Ha-ras expression in erythroid progenitor cells, ultimately leading to leukemic transformation. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. RP Mahler, JF (reprint author), NIEHS, Lab Expt Pathol, Mail Drop B3-06,POB 12233, Res Triangle Pk, NC 27709 USA. NR 30 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1998 VL 153 IS 1 BP 247 EP 254 DI 10.1016/S0002-9440(10)65565-4 PG 8 WC Pathology SC Pathology GA ZX920 UT WOS:000074568700029 PM 9665485 ER PT J AU Tseng, M Williams, RC Maurer, KR Schanfield, MS Knowler, WC Everhart, JE AF Tseng, M Williams, RC Maurer, KR Schanfield, MS Knowler, WC Everhart, JE TI Genetic admixture and gallbladder disease in Mexican Americans SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Article DE cholelithiasis; genetics; admixture; Mexican-American ID SAN-ANTONIO; GALLSTONE DISEASE; FAMILIAL OCCURRENCE; DIABETES-MELLITUS; STARR COUNTY; PREVALENCE; TEXAS; POPULATIONS; INDIANS; EPIDEMIOLOGY AB Gallbladder disease is a common source of morbidity in the Mexican American population. Genetic heritage has been proposed as a possible contributor, but evidence for this is limited. Because gallbladder disease has been associated with Native American heritage, genetic admixture may serve as a useful proxy for genetic susceptibility to the disease in epidemiologic studies. The objective of our study was to examine the possibility that gallbladder disease is associated with greater Native American admixture in Mexican Americans, This study used data from the Hispanic Health and Nutrition Examination Survey and was based on 1,145 Mexican Americans who underwent gallbladder ultrasonography and provided usable phenotypic information. We used the GM and KM immunoglobulin antigen system to generate estimates of admixture proportions and compared these for individuals with and without gallbladder disease. Overall, the proportionate genetic contributions from European, Native American, and African ancestries in our sample were 0.575, 0.390, and 0.035, respectively. Admixture proportions did not differ between cases and noncases: Estimates of Native American admixture for the two groups were 0.359 and 0.396, respectively, but confidence intervals for estimates overlapped. This study found no evidence for the hypothesis that greater Native American admixture proportion is associated with higher prevalence of gallbladder disease in Mexican Americans, Reasons for the finding that Native American admixture proportions did not differ between cases and noncases are discussed. Improving our understanding of the measurement, use, and limitations of genetic admixture may increase its usefulness as an epidemiologic tool as well as its potential for contributing to our understanding of disease distributions across populations. (C) 1998 Wiley-Liss, Inc.dagger C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27599 USA. Arizona State Univ, Dept Anthropol, Tempe, AZ 85287 USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Analyt Genet Testing Ctr Inc, Denver, CO 80231 USA. NIDDKD, Phoenix, AZ 85014 USA. NIDDKD, Bethesda, MD 20892 USA. RP Tseng, M (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM tseng@niehs.nih.gov RI Tseng, Marilyn/B-9334-2016 OI Tseng, Marilyn/0000-0002-9969-9055 FU NIDDK NIH HHS [P30 DK34987, T32 DK07634] NR 40 TC 17 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 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD JUL PY 1998 VL 106 IS 3 BP 361 EP 371 DI 10.1002/(SICI)1096-8644(199807)106:3<361::AID-AJPA8>3.0.CO;2-P PG 11 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 102JY UT WOS:000074922200008 PM 9696151 ER PT J AU Rantanen, T Guralnik, JM Izmirlian, G Williamson, JD Simonsick, EM Ferrucci, L Fried, LP AF Rantanen, T Guralnik, JM Izmirlian, G Williamson, JD Simonsick, EM Ferrucci, L Fried, LP TI Association of muscle strength with maximum walking speed in disabled older women SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE mobility; walking; muscle strength; aging ID MEN; POWER; 75-YEAR-OLD; ABILITY; PEOPLE AB Our aim was to study the association of lower limb strength with maximum walking speed in disabled older women and to try to detect the reserve capacity threshold for maximum walking speed and the minimum strength required for walking at a speed of 1.22 m . s(-1), which is required in crossing signaled intersections. The data are from the baseline of Women's Health and Aging Study, a population-based study on causes and course of disability. Altogether, 1,002 disabled women participated in the tests, which took place at their homes. Maximum isometric hip flexion and knee extension forces were measured on both sides using a handheld dynamometer. For analytic purposes, knee extension torque/body mass ratio (KET/ BM) was calculated. Maximum walking speed was measured with a stopwatch during a 4-m walk. KET/BM had a significant effect on walking speed after controlling for number of chronic conditions, balance, use of walking aid, joint pain, age, and body height and mass. A total of 42.3% of the variation in maximum walking speed was explained by these variables. The cumulative percentage distribution of KET/BM of those able to attain a maximum walking speed of 1.22 m . s(-1) (n = 148) was flat to the level of 1.1 N . m . kg(-1), after which it turned upward, indicating that the probability of attaining 1.22 m . s(-1) started to increase after that level. By using segmented linear regression analysis, 2.3 N . m . kg(-1) was found to be the cutoff point beyond which an increase in KET/BM did not correspond to an increase in maximum walking speed. Muscle strength was positively but not linearly associated with maximum walking speed. Strength testing may help to identify people close to functional thresholds and, thus, at risk of impaired walking, who would benefit most from strengthening exercises. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Natl Res Inst, Dept Geriatr, I Fratini, Florence, Italy. RP Rantanen, T (reprint author), NIA, Epidemiol Demog & Biometry Program, NIH, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C-309, Bethesda, MD 20892 USA. RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 NR 23 TC 124 Z9 127 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JUL-AUG PY 1998 VL 77 IS 4 BP 299 EP 305 DI 10.1097/00002060-199807000-00008 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 109VQ UT WOS:000075344900007 PM 9715919 ER PT J AU Chen, PX Mathews, PM Good, PJ Rossier, BC Geering, K AF Chen, PX Mathews, PM Good, PJ Rossier, BC Geering, K TI Unusual degradation of alpha-beta complexes in Xenopus oocytes by beta-subunits of Xenopus gastric H-K-ATPase SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE intracellular transport; oligomerization; pre-Golgi degradation; Xenopus oocyte expression ID INTRACELLULAR-TRANSPORT; FUNCTIONAL EXPRESSION; NA,K-ATPASE; H,K-ATPASE; RNA; NA,K-PUMPS; SEQUENCE; ISOFORMS AB The catalytic alpha-subunit of oligomeric P-type ATPases such as Na-K-ATPase and H-K-ATPase requires association with a beta-subunit after synthesis in the endoplasmic reticulum (ER) to become stably expressed and functionally active. In this study, we have expressed the beta-subunit of Xenopus gastric H-K-ATPase (beta HK) in Xenopus oocytes together with alpha-subunits of H-K-ATPase (alpha HK) or Na-K-ATPase (alpha NK) and have followed the biosynthesis, assembly, and cell surface expression of functional pumps. Immunoprecipitations of Xenopus beta HK from metabolically labeled oocytes show that it is well expressed and, when synthesized without alpha-subunits, can leave the ER and become fully glycosylated. Xenopus beta HK can associate with both coexpressed alpha HK and alpha NK, but the alpha-beta complexes formed are degraded rapidly in or close to the ER and do not produce functional pumps at the cell surface as assessed by Rb-86 uptake. A possible explanation of these results is that Xenopus beta HK may contain a tissue-specific signal that is important in the formation or correct targeting of functional alpha-beta complexes in the stomach but that cannot be recognized in Xenopus oocytes and in consequence leads to cellular degradation of the alpha-beta complexes in this experimental system. C1 Univ Lausanne, Inst Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland. NICHHD, Genet Mol Lab, Bethesda, MD 20892 USA. RP Geering, K (reprint author), Univ Lausanne, Inst Pharmacol & Toxicol, Bugnon 27, CH-1005 Lausanne, Switzerland. NR 24 TC 7 Z9 8 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 1998 VL 275 IS 1 BP C139 EP C145 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ZX377 UT WOS:000074509500015 PM 9688844 ER PT J AU Pothoulakis, C Castagliuolo, I Leeman, SE Wang, CC Li, HZ Hoffman, BJ Mezey, E AF Pothoulakis, C Castagliuolo, I Leeman, SE Wang, CC Li, HZ Hoffman, BJ Mezey, E TI Substance P receptor expression in intestinal epithelium in Clostridium difficile toxin A enteritis in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE intestinal inflammation; neuropeptides; neurokinin-1 receptor ID GUINEA-PIG; ULCERATIVE-COLITIS; MOLECULAR CHARACTERIZATION; GASTROINTESTINAL-TRACT; NEUROKININ-1 RECEPTOR; FUNCTIONAL CDNA; MESSENGER-RNAS; NEURONS; CELLS; ANTAGONIST AB We previously reported that the inflammatory effects of Clostridium difficile toxin A on rat intestine can be significantly inhibited with a specific neurokinin-l receptor (NK-1R) antagonist. In this study we investigated the localization and expression of NK-1R mRNA and protein in rat intestine by in situ hybridization, Northern blot analysis, and immunohistochemistry, respectively, after exposure to toxin A. Northern blot analysis showed increased mucosal levels of NK-1R mRNA starting 30 min after toxin A administration. In situ hybridization showed that toxin A increased NK-1R mRNA expression in intestinal epithelial cells after 30, 120, and 180 min. In rats pretreated with the NK-1R antagonist CP-96345 the increase in NK-1R mRNA levels after exposure to toxin A was inhibited, indicating that NK-1R upregulation is substance P (SP) dependent. One hour after exposure to toxin A many of the intestinal epithelial cells showed staining for NK-1R compared with controls. Specific I-125-SP binding to purified epithelial cell membranes obtained from ileum exposed to toxin A for 15 min was increased twofold over control and persisted for 4 h. This report provides evidence that NK-1R expression is increased in the intestinal epithelium shortly after exposure to toxin A and may be important in toxin A-induced inflammation. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA. NIMH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Pothoulakis, C (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, E Campus,Dana 601,330 Brookline Ave, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-47343] NR 42 TC 72 Z9 78 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUL PY 1998 VL 275 IS 1 BP G68 EP G75 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA ZZ396 UT WOS:000074725200010 PM 9655686 ER PT J AU Narasimhan, SR Yang, L Gerwin, BI Broaddus, VC AF Narasimhan, SR Yang, L Gerwin, BI Broaddus, VC TI Resistance of pleural mesothelioma cell lines to apoptosis: relation to expression of Bcl-2 and Bax SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE mesothelial cell; p53; reactive oxygen species; asbestos; cancer ID MALIGNANT MESOTHELIOMA; CROCIDOLITE ASBESTOS; P53 EXPRESSION; IN-VITRO; DEATH; PROTEIN; CANCER; MUTATIONS; GENE; DIFFERENTIATION AB A failure of normal apoptosis, often due to mutant p53, may contribute to the formation of a cancer and to its resistance to therapy. Mesothelioma, an asbestos-induced tumor, is highly resistant to therapy but generally expresses wild-type p53. We asked whether mesothelioma was resistant to apoptosis and whether resistance was associated with altered expression of the antiapoptotic protein Bcl-2 or proapoptotic protein Bax. We found that three mesothelioma cell lines (1 with wild-type p53) were highly resistant to apoptosis induced by oxidant stimuli (asbestos, H2O2) or nonoxidant stimuli (calcium ionophore) compared with primary cultured mesothelial cells. By immunostaining, one of these three lines expressed Bcl-2 but only during mitosis. By immunoblotting, 3 of 14 additional mesothelioma lines (9 of 14 with wild type p53) expressed Bcl-2 but all 14 of 14 expressed the proapoptotic Bax, giving a low ratio of Bcl-2 to Bax. We conclude that mesothelioma cell lines are resistant to apoptosis and that the failure in apoptosis is not explained by Bcl-2 but by other mechanisms that counteract the proapoptotic effect of Bax. C1 San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. San Francisco Gen Hosp, Lung Biol Ctr, San Francisco, CA 94110 USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. RP Broaddus, VC (reprint author), Univ Calif San Francisco, Lung Biol Ctr, Box 0854, San Francisco, CA 94143 USA. FU NIEHS NIH HHS [ES-06331, ES-08985] NR 46 TC 66 Z9 67 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUL PY 1998 VL 275 IS 1 BP L165 EP L171 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA ZX388 UT WOS:000074510700020 PM 9688948 ER PT J AU Kopin, IJ Rundqvist, B Friberg, P Lenders, J Goldstein, DS Eisenhofer, G AF Kopin, IJ Rundqvist, B Friberg, P Lenders, J Goldstein, DS Eisenhofer, G TI Different relationships of spillover to release of norepinephrine in human heart, kidneys, and forearm SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE catecholamines; normetanephrine; metanephrine; kinetics; sympathetic nervous system ID ELECTROCHEMICAL DETECTION; LIQUID-CHROMATOGRAPHY; SYMPATHETIC ACTIVITY; PLASMA; KINETICS; CIRCULATION; CATECHOLAMINES; METANEPHRINES; HYPERTENSION; METABOLISM AB Spillover of norepinephrine (NE) into plasma is used frequently as an index of NE release and therefore of sympathetic nerve activity. An important limitation of NE spillover is that it reflects not only release but also uptake processes that intervene before the transmitter reaches the circulation. To overcome this limitation, we developed a method for estimating NE release based on measurements of the specific activities of [H-3]NE in plasma and interstitial fluid during intravenous infusion of [H-3]NE. We applied this method to examine relationships among NE release, tissue uptake, and spillover in the human heart, kidneys, and forearm. The sum of uptake and spillover of released NE provided an estimate of NE release into the interstitial fluid. In the kidneys, NE release averaged three times NE spillover, in skeletal muscle, 12 times NE spillover, and in the heart, >20 times NE spillover. Thus NE release greatly and variably exceeds NE spillover from these organs, so that assessing regional sympathetic function requires an understanding of the relationship of NE spillover to NE release. C1 NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Gothenburg Univ, Dept Physiol, S-41345 Gothenburg, Sweden. Univ Nijmegen St Radboud Hosp, Dept Internal Med, NL-6523 GA Nijmegen, Netherlands. RP Kopin, IJ (reprint author), NINDS, Clin Neurosci Branch, NIH, Bldg 10,Rm 4D-20,10 Ctr Dr,MSC 1424, Bethesda, MD 20892 USA. NR 38 TC 33 Z9 33 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUL PY 1998 VL 275 IS 1 BP R165 EP R173 PG 9 WC Physiology SC Physiology GA ZX401 UT WOS:000074512100023 PM 9688975 ER PT J AU Leon, LR White, AA Kluger, MJ AF Leon, LR White, AA Kluger, MJ TI Role of IL-6 and TNF in thermoregulation and survival during sepsis in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE acute phase response; fever; hypothermia; anorexia; cecal ligation and puncture ID TUMOR-NECROSIS-FACTOR; HUMAN-MONOCYTES; FACTOR-ALPHA; IN-VIVO; FEVER; LIPOPOLYSACCHARIDE; INTERLEUKIN-6; LETHALITY; CYTOKINE; SHOCK AB Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) have been implicated as key mediators in inflammation, morbidity, and mortality associated with sepsis. We examined the role of IL-6 and TNF-cr signaling on hypothermia, fever, cachexia, anorexia, and survival during sepsis induced by cecal ligation and puncture (CLP) in male and female gene knockout mice. Male wild-type mice developed an initial hypothermia and subsequent fever during sepsis. Male IL-6 knockout mice did not develop fever; rather, they maintained a profound hypothermia during sepsis. Male TNF p55/p75 receptor (TNFR) knockout mice had attenuated hypothermia, but developed a virtually identical fever as wild-type mice. Cachexia did not differ between male wild-type and IL-6 or TNFR knockout mice, whereas anorexia was prolonged in IL-6 knockout mice. Due to the rapid lethality of sepsis in female mice, survival was the only variable we were able to statistically compare among female genotypes. Female wildtype mice had significantly decreased survival compared with male wild-type mice. Survival was significantly enhanced in male and female TNFR knockout mice compared with their wild-type controls. Lack of IL-6 did not affect male or female lethality. These data support the hypothesis that IL-6 is a key mediator of fever and food intake, whereas TNF is responsible for the initial hypothermia and lethality of sepsis in both sexes of mice. The enhanced lethality of CLP-treated female mice supports a role for sex steroids during sepsis. C1 Lovelace Resp Res Inst, Albuquerque, NM 87185 USA. RP Leon, LR (reprint author), NIDDK, Diabet Branch, NIH, Bldg 10,Room 8N-252,10 Ctr Dr MSC 1770, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI-27556] NR 32 TC 141 Z9 144 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUL PY 1998 VL 275 IS 1 BP R269 EP R277 PG 9 WC Physiology SC Physiology GA ZX401 UT WOS:000074512100036 PM 9688988 ER PT J AU Kishore, BK Wade, JB Schorr, K Inoue, T Mandon, B Knepper, MA AF Kishore, BK Wade, JB Schorr, K Inoue, T Mandon, B Knepper, MA TI Expression of synaptotagmin VIII in rat kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE exocytosis; endocytosis; aquaporin; sodium-potassium-chloride cotransporter; sodium/calcium exchanger ID REGULATED WATER CHANNEL; COLLECTING DUCT; ANTIDIURETIC-HORMONE; PLASMA-MEMBRANE; VASOPRESSIN; IDENTIFICATION; TUBULE; CELLS; RECEPTORS; PROTEINS AB The synaptotagmins are a family of integral membrane proteins proposed to function as regulators of both exocytosis and endocytosis. Here, we have used immunochemical techniques and RT-PCR to assess sites of renal expression of synaptotagmin VIII. A polyclonal antibody was raised to a synthetic peptide corresponding to the carboxy-terminal 21 amino acids of mouse synaptotagmin VIII. On immunoblots of membrane fractions from renal cortex and medulla (and in several other tissues), the antibody labeled a 52-kDa band (absent with preimmune IgG). Immunofluorescence localization was carried out in tissue sections from rat kidney. The synaptotagmin VIII antibody labeled early proximal tubules, thin ascending limbs, thick ascending limbs, connecting tubules, and collecting ducts. In collecting ducts, both type A and B intercalated cells exhibited basolateral labeling, whereas principal cells were labeled chiefly in the apical and subapical portion of the cells. Thick ascending limbs were labeled in both the basolateral and apical regions. RT-PCR experiments using total RNA extracted from cortex and medulla or microdissected inner medullary collecting ducts gave a single band of appropriate size. Sequencing of the PCR product confirmed that the amplified target is synaptotagmin VIII. We conclude that synaptotagmin VIII is broadly expressed among renal tubule epithelia, raising the possibility that it is involved in regulation of transport and/or cell remodeling at several sites in the nephron and collecting duct. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [Z01-HL-01282-KE]; NIDDK NIH HHS [DK-27847] NR 33 TC 22 Z9 23 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 1998 VL 275 IS 1 BP F131 EP F142 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA ZZ261 UT WOS:000074711700018 PM 9689015 ER PT J AU Elman, I Adler, CM Malhotra, AK Bir, C Pickar, D Breier, A AF Elman, I Adler, CM Malhotra, AK Bir, C Pickar, D Breier, A TI Effect of acute metabolic stress on pituitary-adrenal axis activation in patients with schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEXAMETHASONE SUPPRESSION TEST; PSYCHIATRIC-PATIENTS; VOLUNTEERS; STATE AB Objective: Although several lines of evidence suggest that stress plays a role in the course of schizophrenia, studies that have assessed stress-relevant neurobiological measures have not produced consistent results. The authors examined the effects of acute metabolic stress induced by 2-deoxy-D-glucose (2-DG) on pituitary-adrenal axis activation. Method: Thirteen patients with schizophrenia and 11 healthy comparison subjects were administered pharmacological doses of 2-DG (40 mg/kg). The subjects' arterial plasma was then assayed for levels of adrenocorticotropic hormone (ACTH) and cortisol. Results: 2-DG induced significant increases in the measured hormones in both groups, and ACTH elevations were significantly greater in patients with schizophrenia than in comparison subjects. Conclusions: Patients with schizophrenia have an exaggerated ACTH response to acute metabolic stress exposure. C1 NIMH, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Elman, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, W End House,16 Blossom St, Boston, MA 02114 USA. NR 19 TC 55 Z9 56 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 1998 VL 155 IS 7 BP 979 EP 981 PG 3 WC Psychiatry SC Psychiatry GA ZX603 UT WOS:000074534800026 PM 9659871 ER PT J AU Hyland, A Cummings, KM Shopland, DR Lynn, WR AF Hyland, A Cummings, KM Shopland, DR Lynn, WR TI Prevalence of cigar use in 22 North American communities: 1989 and 1993 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PIPE AB Objectives. This study examined the prevalance fate of and characteristics associated with cigar use. Methods. Data were derived from population-based telephone surveys of adults conducted in 22 North Americas communities in 1989 and 1993 as part of the National Cancer Institute's Community Intervention Trial for Smoking Cessation. Results. Averaged across the 22 communities, the prevalance rate of regular cigar use increased 133%; from 1989 to 1993. Regular cigar use increased in every gender, age, rate, income, education; and smoking status category;. Conclusion. These results confirm other data indicating that cigar use is increasing. C1 New York State Dept Hlth, Roswell Pk Canc Inst, Dept Canc Control & Epidemiol, Buffalo, NY 14263 USA. Natl Canc Inst, Smoking & Tobacco Control Program, Rockville, MD USA. Natl Canc Inst, Canc Control Sci Program, Rockville, MD USA. RP Cummings, KM (reprint author), New York State Dept Hlth, Roswell Pk Canc Inst, Dept Canc Control & Epidemiol, Elm & Carlton Sts, Buffalo, NY 14263 USA. EM mcummings@sc3102.med.buffalo.edu NR 15 TC 11 Z9 11 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1998 VL 88 IS 7 BP 1086 EP 1089 DI 10.2105/AJPH.88.7.1086 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZY340 UT WOS:000074610600019 PM 9663159 ER PT J AU Ozdemirli, M Fanburg-Smith, JC Hartmann, DP Shad, AT Lage, JM Magrath, IT Azumi, N Harris, NL Cossman, J Jaffe, ES AF Ozdemirli, M Fanburg-Smith, JC Hartmann, DP Shad, AT Lage, JM Magrath, IT Azumi, N Harris, NL Cossman, J Jaffe, ES TI Precursor B-lymphoblastic lymphoma presenting as a solitary bone tumor and mimicking Ewing's sarcoma - A report of four cases and review of the literature SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE lymphoblastic lymphoma; bone; Ewing's sarcoma; CD79a; CD99 ID POLYMERASE CHAIN-REACTION; NON-HODGKINS LYMPHOMA; ROUND-CELL TUMOR; MALIGNANT-LYMPHOMA; EXPRESSING CYTOKERATIN; NEUROECTODERMAL TUMOR; GENE REARRANGEMENTS; NON-T; DIAGNOSIS; LEUKEMIA AB Precursor B-lymphoblastic lymphoma (B-LBL) may present as a solitary bone tumor. Fewer than 10 cases with a proven precursor B-cell phenotype have been reported in the English literature. In this report, we describe four cases of B-lymphoblastic lymphoma presenting as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma. Three tumors occurred in the tibia and one in the humerus. In all four cases, the initial diagnosis was either "Ewing's sarcoma" or "consistent with Ewing's sarcoma." All four patients were female. Three were children and one was an adult; mean age was 12.5 years (range, 4 to 31 years). All had extremity pain without significant constitutional symptoms. In three cases, the tumors were osteolytic on radiographic evaluation, and in one case, osteosclerotic. Immunohistochemical stains on paraffin-embedded tissue showed that the neoplastic cells expressed terminal deoxynucleotidyl transferase, CD43, vimentin, and CD99 (MIC2 gene product) in all cases. Three cases were negative for CD45. CD79a was positive in all four cases studied; however, CD20 (L26) was positive in only two of four cases. CD3 was negative in all cases. Two cases showed focal granular cytoplasmic staining for keratin. Two cases analyzed by polymerase chain reaction (PCR) revealed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene. Follow-up revealed that the three pediatric patients, who received a high-dose multiagent chemotherapy regime for LBL, are disease free at follow-up intervals of more than 1, 11, and 12 years, respectively. The adult patient died two years after diagnosis with disseminated disease. Although rare, B-lymphoblastic lymphoma should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoblastic lymphoma. A Limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99 and even for keratin, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because LBL usually is curable in the pediatric age group with appropriate therapy. C1 Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA. RP Azumi, N (reprint author), Georgetown Univ, Med Ctr, Dept Pathol, 3900 Reservoir Rd NW, Washington, DC 20007 USA. NR 49 TC 62 Z9 64 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 1998 VL 22 IS 7 BP 795 EP 804 DI 10.1097/00000478-199807000-00002 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA ZY335 UT WOS:000074610100002 PM 9669342 ER PT J AU Varmus, HE Guerrant AF Varmus, HE Guerrant TI National Institutes of Health in the tropics SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 1997 CL ORLANDO, FLORIDA SP Amer Soc Trop Med & Hyg C1 NIH, Bethesda, MD 20892 USA. RP Varmus, HE (reprint author), NIH, Bldg 1,Room 126,1 Ctr Dr,MSC 0148, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUL PY 1998 VL 59 IS 1 BP 24 EP 28 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA ZZ953 UT WOS:000074786000005 PM 9684621 ER PT J AU Guszczynski, T Copeland, TD AF Guszczynski, T Copeland, TD TI A binding shift assay for the zinc-bound and zinc-free HIV-1 nucleocapsid protein by capillary electrophoresis SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID CARBONIC-ANHYDRASE; GENOMIC RNA; FINGERS; FLUORESCENCE; CONSTANTS; PARTICLES AB Affinity capillary electrophoresis was used to detect a shift in mobility when a zinc ion binds to the highly basic nucleocapsid protein (NCp7) of HIV-1. NCp7 contains two Cys-X-2-Cys-X-4-His-X-4-Cys zinc fingers. With constant concentrations of NCp7 as a receptor and various concentrations of zinc as a ligand in the sample buffer and the electrophoresis buffer, we observed changes in electrophoretic mobilities of NCp7 protein when complexes were formed with zinc. Scatchard analysis of the mobility indicates the presence of at least two types of binding sites for zinc. At pH 6.0, one site is shown to bind zinc strongly with a binding constant K-b = 3.25 x 10(5) M-1 and the second site has a K-b = 1.8 x 10(5) M-1. The binding of zinc to the first zinc finger decreased the affinity of zinc for the second zinc finger approximately twofold. The Hill coefficient for this negative cooperativity is 0.9. A series of NCp7 mutants were also examined in the assay to determine their ability to bind zinc. This assay affords a quick method to observe a zinc ion binding to NCp7 and to calculate binding constants. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Copeland, TD (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Bldg 560,POB B, Frederick, MD 21701 USA. NR 21 TC 27 Z9 27 U1 2 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUL 1 PY 1998 VL 260 IS 2 BP 212 EP 217 DI 10.1006/abio.1998.2694 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZZ723 UT WOS:000074760700014 PM 9657880 ER PT J AU Sempos, CT Durazo-Arvizu, R McGee, DL Cooper, RS Prewitt, TE AF Sempos, CT Durazo-Arvizu, R McGee, DL Cooper, RS Prewitt, TE TI The influence of cigarette smoking on the association between body weight and mortality. The Framingham Heart Study revisited SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE obesity; Metropolitan Relative Weight; body mass index; mortality; death; Framingham Heart Study ID MASS INDEX; MEN; WOMEN AB PURPOSE: To calculate for two measures of obesity, the Metropolitan Relative Weight (MRW) and body mass index (BMI), the value at which minimum mortality occurs. This was done to retest the hypothesis, in the Framingham Heart Study data, that the association between obesity and mortality can be obscured by an interaction between the measure of obesity and smoking. In the original analysis of the Framingham data it was suggested that there was a U- or J-shaped relationship between MRW and death in smokers but a linear relationship in nonsmokers. The design and setting were those of the NHLBI Framingham Heart Study. METHODS: The 5209 members of the Framingham Heart Study underwent a baseline examination in 1948-1952 (Exam 1) and they were reexamined at approximately two-year intervals over a 30-year period. The study included both men (n = 2336) and women (n = 2873) in the age range of 28 to 62 years. After excluding persons with missing baseline data, the analytic sample size was 5163. Additional analyses were conducted by deleting persons with cardiovascular disease (CVD) at baseline (n = 135), the sample used by the original paper by Garrison and colleagues, and persons who died within the first four years of follow-up (n = 62). The main outcome measures consisted of thirty-year survival through Exam 16, approximately in 1980, as influenced by MRW or BMI, age, and smoking status at baseline (Exam 1). RESULTS: We were able to show that the sample sizes of male nonsmokers were too small to test the hypothesis within age groups < 40 and 40-49 years. In men ages 50-62 there was a significant age adjusted quadratic relationship between BMI or MRW, and risk of death. The estimated BMI at the minimum risk of death for smokers (24.5) and nonsmokers (23.8) were not statistically different. Identical results were found for MRW (minimum: smokers = 112.5, nonsmokers = 111.4). In men and women ages 28-62 there appeared to be a u- or j-shaped relationship between the 30-year crude mortality rate and MRW. After excluding persons with missing data, CVD at baseline, and persons who died within the first four years of follow-up, the age adjusted estimated BMI value at the minimum risk of death was nearly identical for men and women and for smokers and nonsmokers (Men: smokers = 22.8, nonsmokers = 22.8; Women: smokers = 22.9, nonsmokers = 23.3). Additionally, the estimates of the minimum were always below the mean. Identical results were found without deleting persons with CVD at baseline and deaths in the first four years of follow-up. Identical results were found for MRW. CONCLUSIONS: Reanalysis of the Framingham Heart Study data does not support the hypothesis that there is an interaction between smoking and measures of obesity. Moreover, the estimated BMI or MRW at the minimum risk of death was similar for men and women smokers and nonsmokers alike even after deleting prevalent cases of CVD and deaths within the first four years of follow-up. Published by Elsevier Science Inc. C1 Loyola Univ, Stritch Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. RP Sempos, CT (reprint author), NHLBI, Epidemiol & Biometry Program, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr,Room 8150, Bethesda, MD 20892 USA. NR 17 TC 28 Z9 29 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 1998 VL 8 IS 5 BP 289 EP 300 DI 10.1016/S1047-2797(97)00233-0 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZX194 UT WOS:000074488800003 PM 9669611 ER PT J AU Wagenknecht, LE Craven, TE Preisser, JS Manolio, TA Winders, S Hulley, SB AF Wagenknecht, LE Craven, TE Preisser, JS Manolio, TA Winders, S Hulley, SB TI Ten-year trends in cigarette smoking among young adults, 1986-1996: The CARDIA study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE smoking; young adults; epidemiology; African Americans ID REGRESSION-MODELS; UNITED-STATES; MISSING DATA; WOMEN AB PURPOSE: To calculate ten-year smoking trends in a longitudinal cohort of young adults, and to characterize trends by race, sex, education, and birth cohere. METHODS: Data on cigarette smoking have been collected for ten years (1986-1996) from 5115 black and white men and women, aged 18-30 years, participating in the Coronary Artery Risk Development In Young Adults (CARDIA) study, Regression analysis adjusting for intra-person correlation over time and weighting for factors affecting follow up was used to estimate change in smoking rates. RESULTS: Overall, smoking rates declined in white women (-0.50%/year, p < 0.001) and white men (-0.24%/year, p = 0.03). Rates remained stable in black women and increased in black men (0.37%/year, p = 0.01). Declining rates were generally observed in white women of all educational levels and birth cohorts and in several subgroups of white men. Increasing rates among black men could be attributed primarily to increasing rates in the youngest birth cohort. Among black men and women, prevalence of smoking in 1986 was considerably lower in the youngest birth cohort compared to the oldest; however, the increasing rates of change in smoking rates observed among the youngest birth cohorts (and decreasing rates in the oldest) lessened the disparity in prevalence rates across birth cohorts by 1996. Smoking initiation rates were highest among black men; cessation rates were highest among white women. CONCLUSIONS: These findings confirm that declines in smoking prevalence are not occurring across all groups, and reveal populations in special need of targeted interventions, particularly young black men. Published by Elsevier Science Inc. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Alabama, Dept Med, Behav Med Unit, Birmingham, AL 35294 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Wagenknecht, LE (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM lwagenkn@rc.phs.bgsm.edu FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48049, N01-HC-48048] NR 31 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 1998 VL 8 IS 5 BP 301 EP 307 DI 10.1016/S1047-2797(97)00211-1 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZX194 UT WOS:000074488800004 PM 9669612 ER PT J AU Khong, HT McCarthy, J AF Khong, HT McCarthy, J TI Chlorambucil-induced pulmonary disease: a case report and review of the literature SO ANNALS OF HEMATOLOGY LA English DT Review DE chlorambucil; chronic lymphocytic leukemia; interstitial pneumonitis; pulmonary fibrosis ID CHRONIC LYMPHOCYTIC-LEUKEMIA; THERAPY; INFECTIONS; TOXICITY AB A 77-year-old man developed pneumonitis while on chlorambucil therapy for chronic lymphocytic leukemia, with a cumulative dose of 2700 mg. The condition improved promptly with the discontinuation of the drug and initiation of steroids. A case report and review of the literature are presented in this paper. C1 NCI, Med Branch, Bethesda, MD 20892 USA. Baylor Coll Med, Div Hematol Oncol, Houston, TX 77030 USA. RP Khong, HT (reprint author), NCI, Med Branch, Bldg 10,Room 12 N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD JUL-AUG PY 1998 VL 77 IS 1-2 BP 85 EP 87 DI 10.1007/s002770050418 PG 3 WC Hematology SC Hematology GA 119WJ UT WOS:000075920900015 PM 9760160 ER PT J AU Langford, CA Klippel, JH Balow, JE James, SP Sneller, MC AF Langford, CA Klippel, JH Balow, JE James, SP Sneller, MC TI Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease - Part 2: Inflammatory bowel disease, systemic vasculitis, and therapeutic toxicity SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID CHURG-STRAUSS-SYNDROME; PULSE CYCLOPHOSPHAMIDE THERAPY; ACTIVE CROHNS-DISEASE; TERM FOLLOW-UP; RHEUMATOID-ARTHRITIS; WEGENERS GRANULOMATOSIS; POLYARTERITIS-NODOSA; ULCERATIVE-COLITIS; RANDOMIZED TRIAL; NECROTIZING VASCULITIS AB When cytotoxic agents were introduced, their ability to disrupt nucleic acid and protein synthesis led to their effective use for the treatment of neoplastic disease. During the course of this use, however, it became apparent that these agents also suppress the immune system. This usually unwelcome effect was subsequently studied and beneficially directed toward the treatment of non-neoplastic diseases in which autoimmune mechanisms were considered important to pathogenesis. As a result of these investigations, cytotoxic agents and, more recently, cyclosporine have emerged to become an important part of the therapeutic regimen for many autoimmune diseases. Nonetheless, these medications may still cause treatment-induced illness or even death. It is therefore particularly important to weigh the benefits and risks of cytotoxic therapy when treating a non-neoplastic disease. This two-part Clinical Staff Conference reviews data on the efficacy and toxicity of cytotoxic drugs and cyclosporine in selected autoimmune diseases. In part 2, we focus on the role of these agents in treating inflammatory bowel disease and systemic vasculitis and review the toxic effects of these agents. C1 NIAID, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Div Gastroenterol, Baltimore, MD 21201 USA. RP Langford, CA (reprint author), NIAID, NIH, Bldg 10,Room 11B-13, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK47708] NR 75 TC 52 Z9 52 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 1 PY 1998 VL 129 IS 1 BP 49 EP 58 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA ZX413 UT WOS:000074513300008 PM 9653000 ER PT J AU Levin, MC Krichavsky, M Berk, J Foley, S Rosenfeld, M Dalmau, J Chang, G Posner, JB Jacobson, S AF Levin, MC Krichavsky, M Berk, J Foley, S Rosenfeld, M Dalmau, J Chang, G Posner, JB Jacobson, S TI Neuronal molecular mimicry in immune-mediated neurologic disease SO ANNALS OF NEUROLOGY LA English DT Article ID I-ASSOCIATED MYELOPATHY; VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; CYTOTOXIC LYMPHOCYTES-T; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD LESIONS; PROVIRAL DNA; PARANEOPLASTIC ENCEPHALOMYELITIS; AUTOIMMUNE-DISEASE; GENE-EXPRESSION AB Molecular mimicry is implicated in the pathogenesis of autoimmune diseases such as diabetes mellitus, rheumatoid arthritis, and multiple sclerosis (MS). Cellular and antibody-mediated immune responses to shared viral-host antigens have been associated with the development of disease in these patients. Patients infected with human T-lymphotropic virus type I (HTLV-I) develop HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an immune-mediated disorder of the central nervous system (CNS) that resembles some forms of MS. Damage to neuronal processes in the CNS of HAM/TSP patients is associated with an activated cellular and antibody-mediated immune response. In this study, IgG isolated from HAM/TSP patients was immunoreactive with uninfected neurons and this reactivity was HTLV-I specific. HAM/TSP IgG stained uninfected neurons in human CNS and cell lines but not nonneuronal cells. Neuronal western blots showed IgG reactivity with a single 33-kd band in all HAM/TSP patients tested. By contrast, no neuron-specific IgG reactivity could be demonstrated from HTLV-I seronegative controls and, more important, from HTLV-I seropositive, neurologically asymptomatic individuals. Both immunocytochemical staining and western blot reactivity were abolished by preincubating HAM/TSP IgG with HTLV-I protein lysate but not by control proteins. Staining of CNS tissue by a monoclonal antibody to HTLV-I tax (an immunodominant HTLV-I antigen) mimicked HAM/TSP IgG immunoreactivity. There was no staining by control antibodies. Absorption of HAM/TSP IgG with recombinant HTLV-I tax protein or preincubation of CNS tissue with the monoclonal antibody to HTLV-I tax abrogated the immunocytochemical and western blot reactivity of HAM/TSP IgG. Furthermore, in situ human IgG localized to neurons in HAM/TSP brain but not in normal brain. These data indicate that HAM/TSP patients develop an antibody response that targets uninfected neurons, yet reactivity is blocked by HTLV-I, suggesting viral-specific autoimmune reactivity to the CNS, the damaged target organ in HAM/TSP. C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. RP Levin, MC (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Link Bldg 415,855 Monroe Ave, Memphis, TN 38163 USA. OI Rosenfeld, Myrna/0000-0001-5095-2534; Dalmau, Josep/0000-0001-5856-2813 NR 42 TC 45 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 1998 VL 44 IS 1 BP 87 EP 98 DI 10.1002/ana.410440115 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZZ257 UT WOS:000074711300013 PM 9667596 ER PT J AU Kass, ES Salman, S Montgomery, WW AF Kass, ES Salman, S Montgomery, WW TI Chronic maxillary atelectasis in a child SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID SINUS C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kass, ES (reprint author), NCI, Tumor Immunol & Biol Lab, Bldg 10,Room 8B07,10 Ctr Dr MSC 1750, Bethesda, MD 20892 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUL PY 1998 VL 107 IS 7 BP 623 EP 625 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 101CW UT WOS:000074852900014 PM 9682860 ER PT J AU Li, QD Bostick-Bruton, F Reed, E AF Li, QD Bostick-Bruton, F Reed, E TI Effect of interleukin-1 alpha and tumour necrosis factor-alpha on cisplatin-induced ERCC-1 mRNA expression in a human ovarian carcinoma cell line SO ANTICANCER RESEARCH LA English DT Article DE cisplatin; ovarian cancer; ERCC-1; IL-1 alpha; TNF-alpha; hyperthermia ID INTERSTRAND CROSS-LINKS; DNA EXCISION-REPAIR; HYPERTHERMIC ENHANCEMENT; CIS-DIAMMINEDICHLOROPLATINUM(II); RESISTANCE; CYTOTOXICITY; SENSITIZATION; INHIBITION; MECHANISM; ADDUCTS AB Enhanced expression of the human excision repair enzyme ERCC-1 is associated with cellular and clinical resistance to cisplatin in human ovarian cancer. High levels of expression of ERCC-1 appear to be associated with increased activity of the nucleotide excision repair pathway. We therefore began to examine the effect of some cisplatin resistance modulators on cisplatin-induced ERCC-1 mRNA expression in the human ovarian carcinoma cell line, A2780/CP70. Cisplatin exposure to A2780/CP70 cells in culture resulted in a four-to five-fold induction for steady-state ERCC-1 mRNA, that was dose-and time-dependent. The biological agents interleukin (IL)-1a and tumour necrosis factor (TNF)-a have been shown to enhance cisplatin cytotoxicity in vitro. IL-la inhibited cisplatin induction of ERCC-1 mRNA levels in our system. The effect of IL-1a was sequence dependent in that the maximum inhibitory effect was observed with 24-hour pretreatment with IL-1a. By contrast, TNF-a had little effect on ERCC-1 mRNA induction by cisplatin. Low-temperature hyperthermia (42 degrees C) almost completely suppressed ERCC-1 mRNA induction in these cells. These findings suggest that the enhancement effect of some agents on cisplatin sensitivity in ovarian tumour Cells may be through downregulating ERCC-1 expression. C1 NCI, Med Ovarian Canc Sect, Dev Therapeut Dept, Med Branch,Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Ovarian Canc Sect, Dev Therapeut Dept, Med Branch,Div Clin Sci,NIH, Bldg 10,Room 13N248,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 39 TC 16 Z9 17 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 1998 VL 18 IS 4A BP 2283 EP 2287 PG 5 WC Oncology SC Oncology GA 105HY UT WOS:000075068700002 PM 9703867 ER PT J AU Sathyamoorthy, N Gilsdorf, JS Wang, TTY AF Sathyamoorthy, N Gilsdorf, JS Wang, TTY TI Differential effect of genistein on transforming growth factor beta 1 expression in normal and malignant mammary epithelial cells SO ANTICANCER RESEARCH LA English DT Article DE genistein; TGF-beta 1 mRNA; MCF-7 and human mammary epithelial cells ID BREAST-CANCER CELLS; JAPANESE MEN; BIOCHANIN-A; PROLIFERATION; STIMULATION; INHIBITION; ESTROGEN; WOMEN; DIET AB Our present study demonstrates that the isoflavone genistein exerts a differential response in normal and malignant breast epithelial cells. The addition of genistein results in a dose-dependent increase in TGF-beta 1 mRNA expression in normal human mammary epithelial cells (HMEC) but not in tumor-derived MCF-7 cells. Genistein inhibits the growth and also causes an increase in apoptosis of HMEC. I;he increased expression of TGF-beta 1 may contribute to the growth inhibitory as well as apoptotic effects of genistein on HMEC. C1 NCI, LNMR, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. RP Sathyamoorthy, N (reprint author), NCI, LNMR, Frederick Canc Res & Dev Ctr, NIH, Bldg 560-12-27,POB B, Frederick, MD 21702 USA. NR 23 TC 36 Z9 37 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 1998 VL 18 IS 4A BP 2449 EP 2453 PG 5 WC Oncology SC Oncology GA 105HY UT WOS:000075068700026 PM 9703891 ER PT J AU Miyazaki, H Miyazaki, Y Geber, A Parkinson, T Hitchcock, C Falconer, DJ Ward, DJ Marsden, K Bennett, JE AF Miyazaki, H Miyazaki, Y Geber, A Parkinson, T Hitchcock, C Falconer, DJ Ward, DJ Marsden, K Bennett, JE TI Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BINDING CASSETTE TRANSPORTER; AZOLE-RESISTANT; ANTIFUNGAL AGENTS; ORAL CANDIDOSIS; ENCODING GENE; ALBICANS; YEAST; IDENTIFICATION; SEQUENCE; SACCHAROMYCES AB Sequential Candida glabrata isolates were obtained from the mouth of a patient infected with human immunodeficiency virus type 1 who was receiving high doses of fluconazole for oropharyngeal thrush. Fluconazole-susceptible colonies were replaced by resistant colonies that exhibited both increased fluconazole efflux and increased transcripts of a gene which codes for a protein with 72.5% identity to Pdr5p, an ABC multidrug transporter in Saccharomyces cerevisiae. The deduced protein had a molecular mass of 175 kDa and was composed of two homologous halves, each,vith six putative transmembrane domains and highly conserved sequences of ATP-binding domains. When the earliest and most azole-susceptible isolate of C. glabrata from this patient was exposed to fluconazole, increased transcripts of the PDR5 homolog appeared, linking azole exposure to regulation of this gene. C1 NIAID, Ctr Clin, Clin Mycol Sect, Lab Clin Invest,NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Pfizer Ltd, Cent Res, Dept Discovery Biol, Sandwich CT13 9NJ, Kent, England. Dupont Circle Phys Grp, Washington, DC USA. RP Bennett, JE (reprint author), NIAID, Ctr Clin, Clin Mycol Sect, Lab Clin Invest,NIH, Rm 11C304, Bethesda, MD 20892 USA. NR 42 TC 92 Z9 96 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1998 VL 42 IS 7 BP 1695 EP 1701 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ZX610 UT WOS:000074535500029 PM 9661006 ER PT J AU Mueller, BU Anderson, BD Farley, MQ Murphy, R Zuckerman, J Jarosinski, P Godwin, K McCully, CL Mitsuya, H Pizzo, PA Balis, FM AF Mueller, BU Anderson, BD Farley, MQ Murphy, R Zuckerman, J Jarosinski, P Godwin, K McCully, CL Mitsuya, H Pizzo, PA Balis, FM TI Pharmacokinetics of the protease inhibitor KNI-272 in plasma and cerebrospinal fluid in nonhuman primates after intravenous dosing and in human immunodeficiency virus-infected children after intravenous and oral dosing SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HIV-1 PROTEASE; SAFETY; PHARMACOLOGY; SAQUINAVIR; RITONAVIR; RATS AB KNI-272 is a human immunodeficiency virus (HIV) protease inhibitor with potent activity in vitro. We studied the pharmacokinetics of KNI-272 in the plasma and cerebrospinal fluid (CSF) of a nonhuman primate model and after intravenous and oral administration to children with HIV infection. Plasma and CSF were sampled over 24 h after the administration of an intravenous dose of 50 mg of KNI-272 per kg of body weight (approximately 1,000 mg/m(2)) to three nonhuman primates, The pharmacokinetics of KNI-272 were also studied in 18 children (9 males and 9 females; median age, 9.4 years) enrolled in a phase I trial of four dose levels of KNI-272 (100, 200, 330, and 500 mg/m(2) per dose given four times daily). The plasma concentration-time profile of KNI-272 in the nonhuman primate model was characterized by considerable interanimal variability and rapid elimination (clearance, 2.5 liters/h/kg; terminal half-life, 0.54 h), The level of drug exposure achieved in CSF, as measured by the area under the KNI-272 concentration-time curve, was only 1% of that achieved in plasma. The pharmacokinetics of KNI-272 in children were characterized by rapid elimination (clearance, 276 ml/min/m(2); terminal half-life, 0.43 h), limited (12%) and apparently saturable bioavailability, and limited distribution (volume of distribution at steady state, 0,11 liter/kg), The concentrations in plasma were maintained above a concentration that is active in vitro for less than half of the S-h dosing interval. There was no significant increase in CD4 cell counts or decrease in p24 antigen or HIV RNA levels. The pharmacokinetic profile of KNI-272 may limit the drug's efficacy in vivo. it appears that KNI-272 will play a limited role in the treatment of HIV-infected children. C1 NCI, Pediat Branch, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NIH, Dept Pharm, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Mueller, BU (reprint author), Childrens Hosp, Dept Med, Hunnewell 302,300 Longwood Ave, Boston, MA 02115 USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1998 VL 42 IS 7 BP 1815 EP 1818 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ZX610 UT WOS:000074535500050 PM 9661027 ER PT J AU Szajek, LP Channing, MA Eckelman, WC AF Szajek, LP Channing, MA Eckelman, WC TI Automated synthesis of 6-[F-18]fluoro-L-DOPA using modified polystyrene supports with bound 6-mercuric DOPA precursors SO APPLIED RADIATION AND ISOTOPES LA English DT Article AB Polystyrene polymer substrates were prepared having protected L-DOPA precursors mercurated in the 6-position. When treated with gaseous [F-18]acetyl hypofluorite followed by HI hydrolysis, 6-[F-18]fluoro-3,4-dihydroxy-L-phenylalanine (6-[F-18]fluoro-L-DOPA) was obtained in 2-23% overall chemical yield. The highest yield was obtained using P-CH2CO2Hg(pro-DOPA), where P = polystyrene and pro-DOPA is protected L-DOPA. These modified polystyrene supports are easily prepared, require no special storage treatment, and are convenient to use in an automated 6-[F-18]fluoro-L-DOPA production system. Published by Elsevier Science Ltd. C1 NIH, Warren Grant Magnuson Clin Ctr, PET Dept, Bethesda, MD 20892 USA. RP Szajek, LP (reprint author), NIH, Warren Grant Magnuson Clin Ctr, PET Dept, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 9 TC 15 Z9 15 U1 0 U2 1 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 JUL PY 1998 VL 49 IS 7 BP 795 EP 804 DI 10.1016/S0969-8043(97)00304-7 PG 10 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA ZF479 UT WOS:000072901600009 ER PT J AU Boni, R Matt, D Burg, G Tronnier, M Vortmeyer, A Zhuang, Z AF Boni, R Matt, D Burg, G Tronnier, M Vortmeyer, A Zhuang, Z TI Ultraviolet-induced acute histological changes in irradiated nevi are not associated with allelic loss SO ARCHIVES OF DERMATOLOGY LA English DT Article ID MALIGNANT-MELANOMA; UV-RADIATION; MOUSE SKIN; MELANOCYTES AB Background: Transformed melanocytes in atypical nevi, which are thought to be precursors of melanoma, are frequently deleted on chromosomes Ip, 9q, and 9p21(p16 locus). Single UV irradiation induces histological changes that are similar to those of atypical nevi and, in part, of melanoma in situ. Objective: To determine the effects of UV irradiation on benign melanocytic nevi in vivo. Design: We investigated one half of a symmetric nevus 1 week after a single UV exposure with 4 times the patient's minimal erythema dose and compared it with the nonirradiated, shielded half of the same nevus. Two to 3 areas containing 5 to 30 melanocytes in 7 nevi were microdissected (a total of 18 areas in each nonirradiated and irradiated part), followed by a single-step DNA extraction. Extracted genomic DNA was amplified using a polymerase chain reaction with polymorphic markers D1S450 (Ip), D9S12 (9q), IFNA, and D9S171 (9p21) and subjected to autoradiography. Observations: Two, 3, 2, and 2 of 18 areas were homozygous for D1S450, D9S12, IFNA, and D9S171, respectively. No allelic loss could be demonstrated in either nonirradiated or irradiated nevi. Conclusions: Acute histological changes demonstrated in melanocytic nevi after UV irradiation are not followed by allelic loss on identical chromosomal areas found in dysplastic melanocytes of atypical nevi. This finding supports the hypothesis that initial nonspecific genetic events may occur after UV irradiation, followed by an increase in various repair mechanisms potentially leading to specific genetic damage and loss of heterozygosity; however, loss of heterozygosity is not detectable at an early stage. C1 Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. Univ Lubeck, Dept Dermatol, D-2400 Lubeck, Germany. NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. RP Boni, R (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. NR 15 TC 12 Z9 12 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 1998 VL 134 IS 7 BP 853 EP 856 DI 10.1001/archderm.134.7.853 PG 4 WC Dermatology SC Dermatology GA 101QZ UT WOS:000074880800012 PM 9681349 ER PT J AU Fox, SD Roman, JM Issaq, HJ Nims, RW AF Fox, SD Roman, JM Issaq, HJ Nims, RW TI Metabolic conversion of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) in the male F344/NCr rat SO ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID 1,1-DICHLORO-2,2-BIS(PARA-CHLOROPHENYL)ETHANE AB 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) levels were measured by capillary gas chromatography with electron capture detection in liver and blood serum of male F344/NCr rats exposed for 2 weeks to DDD at dietary concentrations ranging from 8.51 ppm to 2,000 ppm. DDD burdens in serum ranged from <0.006 mu M (limit of detection) in control rats to 1.1 mu M in the rats fed DDD at 2,000 ppm. The corresponding liver burdens in these animals ranged from <0.006 mu mol/kg liver (controls) to 11 mu mol/kg liver in rats fed DDD at 2,000 ppm. Levels of DDE in serum or liver were undetectable (<0.006 mu M in serum; <0.006 mu mol/kg liver) in rats fed control diet or diet containing 8.51 or 25.5 ppm DDD. The liver and serum burdens of DDE increased with dietary DDD concentration, reaching a maximum of 0.53 mu M in serum and 4.7 mu mol/kg liver in rats fed 2,000 ppm DDD. As a percentage of total DDD equivalents detected in liver or serum, the DDE burdens increased to a maximum of 36% and 31% in the serum and liver, respectively, of rats fed 689 ppm DDD. The possibility that the DDE might have been generated artifactually in the diet prior to administration to the rats was ruled out by analysis with capillary gas chromatography of the diet containing 2,000 ppm DDD, The identification of DDE as a metabolite in liver extracts of rats fed 2,000 ppm DDD was confirmed with GC-MS. The results confirmed the presence of DDE as a metabolite of DDD. C1 NCI, Frederick Canc Res & Dev Ctr, Chem & Synth Anal Lab, SAIC Frederick, Frederick, MD 21701 USA. NCI, Frederick Canc Res & Dev Ctr, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Nims, RW (reprint author), MA BioServ Inc, 9900 Blackwell Rd, Rockville, MD 20850 USA. NR 9 TC 9 Z9 10 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0090-4341 J9 ARCH ENVIRON CON TOX JI Arch. Environ. Contam. Toxicol. PD JUL PY 1998 VL 35 IS 1 BP 104 EP 108 PG 5 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA ZR850 UT WOS:000074020800017 PM 9601927 ER PT J AU Epps, RP AF Epps, RP TI Cancer screening - A challenge in today's changing practice of medicine SO ARCHIVES OF FAMILY MEDICINE LA English DT Editorial Material C1 NCI, NIH, Bethesda, MD 20892 USA. RP Epps, RP (reprint author), NCI, NIH, 6130 Execut Blvd,EPN 241, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 3 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1063-3987 J9 ARCH FAM MED JI Arch. Fam. Med. PD JUL-AUG PY 1998 VL 7 IS 4 BP 315 EP 316 DI 10.1001/archfami.7.4.315 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 100JY UT WOS:000074814100005 PM 9682683 ER PT J AU Yanovski, SZ AF Yanovski, SZ TI Large patients and lack of preventive health care - Physician or patient driven? SO ARCHIVES OF FAMILY MEDICINE LA English DT Editorial Material C1 NIDDKD, Obes & Eating Disorders Program, Bethesda, MD 20982 USA. RP Yanovski, SZ (reprint author), NIDDKD, Obes & Eating Disorders Program, Bldg 45,Room 6AN-18, Bethesda, MD 20982 USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1063-3987 J9 ARCH FAM MED JI Arch. Fam. Med. PD JUL-AUG PY 1998 VL 7 IS 4 BP 385 EP 385 DI 10.1001/archfami.7.4.385 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 100JY UT WOS:000074814100018 PM 9682695 ER PT J AU Nielsen, DA Virkkunen, M Lappalainen, J Eggert, M Brown, GL Long, JC Goldman, D Linnoila, M AF Nielsen, DA Virkkunen, M Lappalainen, J Eggert, M Brown, GL Long, JC Goldman, D Linnoila, M TI A tryptophan hydroxylase gene marker for suicidality and alcoholism SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CROSS-FOSTERING ANALYSIS; FLUID MONOAMINE METABOLITES; AMINO-ACID SUBSTITUTIONS; QUANTITATIVE-TRAIT LOCI; IMPULSIVE FIRE SETTERS; RECEPTOR GENE; CEREBROSPINAL-FLUID; 5-HYDROXYINDOLEACETIC ACID; VIOLENT OFFENDERS; AFFECTIVE-DISORDER AB Background: Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Low turnover rate of this monoamine neurotransmitter is associated with impaired impulse control. We previously reported that, in Finns, TPH genotype was associated with suicidality, a pathophysiological mechanism that may involve impaired impulse control. Methods: Association and sib-pair linkage analyses of a polymorphism in intron 7 of the TPH gene with suicidality, alcoholism, and the Karolinska Scales of Personality were conducted in 804 Finnish alcoholic offenders, controls, and their relatives, in a sample that included 369 sib pairs. Results: The association of the TPH 17 779C (L) allele to suicidality in impulsive offenders reported previously was replicated in a new group of Finnish offenders (P=.001, n=122). The intron 7 variant in the TPH gene showed significant evidence for linkage to suicidality (P=.006 in unaffected sib pairs), severe suicide attempts (P=.006 in unaffected sib pairs; regression: P=.01), alcoholism (P=.003 in unaffected sib-pairs; regression: P=.02), and Karolinska Scales of Personality socialization score (regression: P=.002). Conclusions: The status of the TPH A779C allele as a marker for suicidality was replicated and linkage with alcoholism and Karolinska Scales of Personality socialization score was also observed. A functional variant(s) in or close to the TPH gene may predispose individuals to suicidality and other behaviors thought to be influenced by serotonin. C1 NIAAA, Mol Genet Sect, NIH, Rockville, MD 20852 USA. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NIAAA, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. RP Nielsen, DA (reprint author), NIAAA, Mol Genet Sect, NIH, Pk 5,Room 451,12420 Parklawn Dr, Rockville, MD 20852 USA. EM nielsen@helix.nih.gov RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NCRR NIH HHS [1 P41 RR03655] NR 66 TC 224 Z9 230 U1 10 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 1998 VL 55 IS 7 BP 593 EP 602 DI 10.1001/archpsyc.55.7.593 PG 10 WC Psychiatry SC Psychiatry GA ZZ514 UT WOS:000074737000002 PM 9672049 ER PT J AU Litvan, I MacIntyre, A Goetz, CG Wenning, GK Jellinger, K Verny, M Bartko, JJ Jankovic, J McKee, A Brandel, JP Chaudhuri, KR Lai, EC D'Olhaberriague, L Pearce, RKB Agid, Y AF Litvan, I MacIntyre, A Goetz, CG Wenning, GK Jellinger, K Verny, M Bartko, JJ Jankovic, J McKee, A Brandel, JP Chaudhuri, KR Lai, EC D'Olhaberriague, L Pearce, RKB Agid, Y TI Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies SO ARCHIVES OF NEUROLOGY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; MULTIPLE SYSTEM ATROPHY; RICHARDSON-OLSZEWSKI-SYNDROME; ALZHEIMERS-DISEASE; SENILE DEMENTIA; INTERNATIONAL WORKSHOP; DIFFERENTIAL-DIAGNOSIS; NATURAL-HISTORY; GAZE PALSY; CRITERIA AB Background: Whether Parkinson disease (PD) and dementia with Lewy bodies (DLB) represent 2 distinct nosologic entities or are diverse phenotypes of Lewy body disease is subject to debate. Objectives: To determine the accuracy of the diagnoses of lewy body disease, PD, and DLB by validating the clinical diagnoses of 6 neurologists with the neuropathologic findings and to identify early predictors of the diagnoses. Methods: Six raters who were unaware of the neuropathologic diagnoses analyzed 105 clinical vignettes corresponding to 29 cases of Lewy body disease (post hoc analysis of 15 patients with PD and 14 with DLB) and 76 patients without PD or DLB whose cases were confirmed through autopsy findings. Main Outcome Measures: Sensitivity and positive predictive value (PPV) were chosen as validity measures and the kappa statistic as a reliability measure, Results: Interrater reliability for the diagnoses of Lewy body disease and PD was moderate for the first visit and substantial for the last, whereas agreement for diagnosis of DLB was fair for the first visit and slight for the last. Median sensitivity for diagnosis of Lewy body disease was 56.9% for the first visit and 67.2% for the last; median PPV was 60.0% and 77.4%, respectively. Median sensitivity for the diagnosis of PD was 73.3% for the first visit and 80.0% for the last; median PPV was 45.9% and 64.1%, respectively. Median sensitivity for the diagnosis of DLB was 17.8% for the first visit and 28.6% for the last; median PPV was 75.0% for the first visit and 55.8% for the last. The raters' results were similar to those of the primary neurologists. Several features differentiated PD from DLB, predicted each disorder, and could be used as clinical pointers. Conclusions: The low PPV with relatively high sensitivity for the diagnosis of PD suggests overdiagnosis. Conversely, the extremely low sensitivity for the diagnosis of DLB suggests underdiagnosis. Although the case mix included in the study may not reflect the frequency of these disorders in practice, limiting the clinical applicability of the validity measures, the raters' results were similar to those of the primary neurologists who were not exposed to such limitations. Overall, our study confirms features suggested to predict these disorders, except for the early presence of postural imbalance, which is not indicative of either disorder. C1 NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Div Epidemiol & Res Studies, Bethesda, MD 20892 USA. Rush Med Coll, Dept Neurol, Chicago, IL 60612 USA. Lainz Hosp, Ludwig Boltzmann Inst Clin Neurobiol, A-1130 Vienna, Austria. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Inst Neurol, London WC1N 3BG, England. Inst Psychiat, Dept Neurol, London SE5 8AF, England. Parkinsons Dis Soc, Brain Bank, Res Ctr, London, England. Hop La Pitie Salpetriere, Federat Neurol, Paris, France. Hop La Pitie Salpetriere, Raymond Escourolle Neuropathol Lab, Paris, France. RP Litvan, I (reprint author), NINDS, Neuroepidemiol Branch, NIH, Fed Bldg,Room 714, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 91 TC 205 Z9 206 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 1998 VL 55 IS 7 BP 969 EP 978 DI 10.1001/archneur.55.7.969 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 101CN UT WOS:000074852200010 PM 9678315 ER PT J AU Hirsch, R Lethbridge-Cejku, M Hanson, R Scott, WW Reichle, R Plato, CC Tobin, JD Hochberg, MC AF Hirsch, R Lethbridge-Cejku, M Hanson, R Scott, WW Reichle, R Plato, CC Tobin, JD Hochberg, MC TI Familial aggregation of osteoarthritis - Data from the Baltimore Longitudinal Study on Aging SO ARTHRITIS AND RHEUMATISM LA English DT Article ID KNEE OSTEOARTHRITIS; GRADING SCALES; RELIABILITY; WOMEN; HAND AB Objective. To evaluate the familial aggregation of osteoarthritis (OA) in a cohort of healthy volunteers drawn from a community setting. Methods. Hand radiographs obtained between 1978 and 1991 and bilateral standing knee radiographs obtained between 1984 and 1991 were read for changes of OA, using Kellgren-Lawrence (K-L) scales. The hand sites were distal interphalangeal (DIP) joints, proximal interphalangeal (PIP) joints, and first carpometacarpal (CMC1) joints, For each joint group, the presence of OA in at least 1 joint in a joint group, the number of affected digits in each joint group, and the sum of the K-L grade across all joints were analyzed. Polyarticular OA was recorded if there were OA findings in 2 of 3 hand joint groups plus 1 or both knees. Data from 167 families with hand radiographs, 157 families with knee radiographs, and 148 families with both hand and knee radiographs were analyzed for sib-sib correlations. Results. After adjustment for age, sex, and body mass index, clinically relevant sib-sib common correlations were found for OA of the DIP, PIP, and CMC1 joints, for OA at 2 or 3 hand sites, and for polyarticular OA (r = 0.33-0.81) when OA was defined according to the number of affected joints or as the sum of the K-L grade across all joints. Conclusion. These results from a cohort of volunteers drawn from a community setting and ascertained without regard to OA status demonstrate familial aggregation of OA and contribute to the evidence for heritability of OA. C1 NIAMSD, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NIDDKD, Phoenix, AZ 85016 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIA, Baltimore, MD 21224 USA. Dept Vet Affairs Med Ctr, Baltimore, MD USA. RP Hirsch, R (reprint author), Natl Arthrit & Musculoskeletal & Skin Dis Informa, 1 AMS Circle, Bethesda, MD 20892 USA. NR 15 TC 86 Z9 86 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 1998 VL 41 IS 7 BP 1227 EP 1232 DI 10.1002/1529-0131(199807)41:7<1227::AID-ART13>3.0.CO;2-N PG 6 WC Rheumatology SC Rheumatology GA ZY088 UT WOS:000074585400012 PM 9663480 ER PT J AU Iribarren, C Sempos, CT Eckfeldt, JH Folsom, AR AF Iribarren, C Sempos, CT Eckfeldt, JH Folsom, AR TI Lack of association between ferritin level and measures of LDL oxidation: The ARIC Study SO ATHEROSCLEROSIS LA English DT Article; Proceedings Paper CT 4th International Conference on Prevention Cardiology CY JUN 29-JUL 03, 1997 CL MONTREAL, CANADA DE cardiovascular diseases; iron; lipid peroxidation ID CARDIOVASCULAR RISK-FACTORS; LOW-DENSITY-LIPOPROTEIN; BODY IRON STORES; CORONARY-ARTERY DISEASE; EASTERN FINNISH MEN; SERUM FERRITIN; CAROTID ATHEROSCLEROSIS; HEART-DISEASE; MYOCARDIAL-INFARCTION; ACUTE-PHASE AB Body iron status has been implicated in atherosclerotic cardiovascular disease. The main hypothesis was that high iron status was associated with increased oxidation of LDL. The associations of serum ferritin (a marker of iron status) and dietary iron intake with the susceptibility of LDL to in vitro oxidation (lag phase) and autoantibodies against MDA-modified LDL (two markers of oxidation stress) were examined among 281 men and 192 women with a mean age of 59 years (S.D. = 5) who participated in the Atherosclerosis Risk in Communities (ARIC) Study visit 2 in 1990 through 1992. Lag phase duration and the autoantibodies against MDA-modified LDL were weakly correlated with each other (r = 0.19, P = 0.001 in men; r = 0.15, P = 0.03 in women). In linear regression analysis adjusting for age, field center, blood storage time, and carotid atherosclerosis case-control status, there was no association between ferritin level and the lag-phase, or between ferritin level and autoantibodies against MDA-modified LDL in either sex. Further adjustment for traditional cardiovascular risk factors (smoking, vitamin supplement use, body mass index, LDL cholesterol, hypertension and diabetes) did not alter these null results. Ferritin was significantly and positively correlated with body mass index in both sexes (r = 0.21 among men and r = 0.22 among women) and with the waist-to-hip ratio among women (r = 0.26). In addition, among women, ferritin was positively correlated with orosomucoid (r = 0.24) and with sialic acid (r = 0.19). Dietary iron was not associated with the parameters of LDL oxidation or with ferritin level. These findings do not support a role of body iron stores in promoting oxidation of LDL. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. RP Iribarren, C (reprint author), Kaiser Permanente, Div Res, 3505 Broadway, Oakland, CA 94611 USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 44 TC 30 Z9 31 U1 1 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 JUL PY 1998 VL 139 IS 1 BP 189 EP 195 DI 10.1016/S0021-9150(98)00070-7 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 103WT UT WOS:000074981400022 PM 9699907 ER PT J AU Gao, WY Zhou, BS Johns, DG Mitsuya, H Yen, Y AF Gao, WY Zhou, BS Johns, DG Mitsuya, H Yen, Y TI Role of the M2 subunit of ribonucleotide reductase in regulation by hydroxyurea of the activity of the anti-HIV-1 agent 2 ',3 '-dideoxyinosine SO BIOCHEMICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 3rd National Conference on Retroviruses and Opportunistic Infections CY JAN 28-FEB 02, 1996 CL WASHINGTON, D.C. DE dideoxynucleosides; combination therapy; antiviral drugs; drug resistance; HIV-1 mutants; HIV-1 replication ID HUMAN-IMMUNODEFICIENCY-VIRUS; HYDROXAMATE COMPOUNDS; NUCLEOSIDE ANALOGS; CELLS; DNA; PHOSPHORYLATION; REPLICATION; LYMPHOCYTES; EXPRESSION; DIDANOSINE AB The ribonucleotide reductase inhibitor hydroxyurea exhibits potent synergism, even at low, non-cytotoxic concentrations, with the anti HIV-1 dideoxynucleoside 2',3'-dideoxyinosine, bringing about failure of HIV DNA synthesis and, thus, of HIV replication. To elucidate the incompletely defined role of hydroxyurea in the hydroxyurea/dideoxyinosine interaction and, in particular, to identify the reasons for the unusual selective inhibitory action of the combination on retroviral rather than on cellular DNA synthesis, we prepared specific cDNA probes to determine the effects of low-level hydroxyurea on mammalian cell ribonucleotide reductase M1 and M2 subunit mRNA, while simultaneously quantitating the effects of the drug on cell cycle and on deoxynucleoside triphosphate pools. While dTTP, dCTP, and dGTP pools changed little or even increased in the presence of low-level hydroxyurea, there took place a rapid and specific inhibition of M2-subunit-catalyzed generation of dATP, with consequent slowing of cellular DNA synthesis and prolongation of S phase. However, the latter effect, in turn, resulted in increased M2 subunit mRNA transcription (a process blocked in G(0)/G(1)-phase cells, with full-length functional M2 transcripts being generated only during S phase) and, hence, in a return to normal levels of dATP and to a normal rate of cellular DNA synthesis. Because of this self-regulating mechanism, hydroxyurea-induced host-cell toxicity was; obviated under conditions where HIV DNA synthesis, a process sensitive to both dATP depletion and the chain-terminating properties of the other inhibitory component of the combination (ddATP derived from dideoxyinosine), was unable to recover. BIOCHEM PHARMACOL 56;1:105-112, 1998. (C) 1998 Elsevier Science Inc. C1 NCI, Expt Retrovirol Sect, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA. RP Gao, WY (reprint author), NCI, Expt Retrovirol Sect, Med Branch, Div Clin Sci,NIH, Bldg 37,Rm 5B22, Bethesda, MD 20892 USA. NR 25 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 1 PY 1998 VL 56 IS 1 BP 105 EP 112 DI 10.1016/S0006-2952(98)00127-0 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 100UF UT WOS:000074833200013 PM 9698094 ER PT J AU Wink, DA Vodovotz, Y Cook, JA Krishna, MC Kim, S Coffin, D DeGraff, W Deluca, AM Liebmann, J Mitchell, JB AF Wink, DA Vodovotz, Y Cook, JA Krishna, MC Kim, S Coffin, D DeGraff, W Deluca, AM Liebmann, J Mitchell, JB TI The role of nitric oxide chemistry in cancer treatment SO BIOCHEMISTRY-MOSCOW LA English DT Review DE nitric oxide; cancer; oncology ID TUMOR-BEARING MICE; CYTOTOXICITY IN-VITRO; L-ARGININE; PERITONEAL-MACROPHAGES; ANTITUMOR RESPONSES; SYNTHASE ACTIVITY; NECROSIS-FACTOR; TARGET-CELLS; FPG PROTEIN; IFN-GAMMA AB Over the last decade the role of nitric oxide (NO) in various disease states has become apparent. In cancer, NO plays a variety of roles which are at times contradictory. On one hand, NO is involved in different etiological mechanisms as well as promoting tumor growth. Yet, NO derived from leukocytes plays a seminal role in their tumoricidal activity. In cancer treatment, NO also has diverse effects. Whereas in vitro, NO can enhance the cytotoxic efficacy of some chemotherapeutic agents as well as radiation, NO donors can provide whole body protection against these same agents. This manuscript will discuss some mechanisms involved with NO and cancer treatment modalities and the potential application of these findings to cancer therapy. C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. Cardiol Res Fdn, Washington, DC 20010 USA. Medlant Res Inst, Washington, DC 20010 USA. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. EM wink@box-w.nih.gov NR 65 TC 52 Z9 57 U1 0 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA CONSULTANTS BUREAU, 233 SPRING ST, NEW YORK, NY 10013 USA SN 0006-2979 J9 BIOCHEMISTRY-MOSCOW+ JI Biochem.-Moscow PD JUL PY 1998 VL 63 IS 7 BP 802 EP 809 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126MF UT WOS:000076296700007 PM 9721332 ER PT J AU Ciotti, M Chen, F Rubaltelli, FF Owens, IS AF Ciotti, M Chen, F Rubaltelli, FF Owens, IS TI Coding defect and a TATA box mutation at the bilirubin UDP-glucuronosyltransferase gene cause Crigler-Najjar type I disease SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE Crigler-Najjar types I and II; bilirubin UDP-glucuronosyltransferase activity and gene; TATA box mutation; compound heterozygotes ID GILBERTS-SYNDROME; COMPLEX LOCUS; COS-1 CELLS; IDENTIFICATION; PATIENT; EXPRESSION; TRANSFERASE; DIAGNOSIS; CLONING AB Mutations at the bilirubin UDP-glucuronosyltransferase (transferase) gene in a severely hyperbilirubinemic Crigler-Najjar (CN) type I individual was compared with that in a moderately hyperbilirubinemic CN II individual. The CN-I (CF) patient in this study sustained a TATA box insertional mutation which was paired with a coding defect at the second allele, unlike all coding defects previously seen in CN-I patients. The sequence of the mutant TATA box, [A(TA)(8)A], also seen in the CN-II patient, was compared with that at the wild-type box, [A(TA) IA]. Transcriptional activity with [A(TA)(8)A] was 10-15% that with the wild-type box when present in the -1.7 kb upstream regulatory region (URR) of the bilirubin transferase UGT1A1 gene which was fused to the chloramphenicol acetyl transferase reporter gene, pCAT 1.7H, and transfected into HepG2 cells. Also, a construct with a TA deletion, [A(TA)(6)A], was prepared and used as a control; transcriptional activity was 65% normal. The coding region defect, R336W, seen in CF (CN-I) was placed in the bilirubin transferase UGT1A1 [HUG-Brl] cDNA, and its corresponding protein was designated UGT1A1*32. The UGT1A1*32 protein supported 0-10% normal bilirubin glucuronidation when expressed in COS-1 cells. The I294T coding defect seen at the second allele in SM (CN-II) generated the UGT1A1*33 mutant protein which supported 40-55% normal activity with a normal K-m (2.5 mu M) for bilirubin. The hyperbilirubinemia seen in SM decreased in response to phenobarbital treatment, unlike that seen in CF. Parents of the patients were carriers of the respective mutations uncovered in the offspring. The TATA box mutation paired with a deleterious missense mutation is, therefore, completely repressive in the CN-I patient, and is responsible for a lethal genotype/phenotype; but when homozygous, i.e. paired with itself, as previously reported in the literature, it is far less repressive and generates the mild Gilbert's phenotype. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Florence, Cattedra Neonatol, I-50134 Florence, Italy. RP Owens, IS (reprint author), NICHHD, Heritable Disorders Branch, NIH, Bldg 10,Room 9S-242, Bethesda, MD 20892 USA. EM owens@helix.nih.gov NR 32 TC 37 Z9 38 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD JUL 1 PY 1998 VL 1407 IS 1 BP 40 EP 50 DI 10.1016/S0925-4439(98)00030-1 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZZ716 UT WOS:000074759900005 PM 9639672 ER PT J AU Frankel, AE Hall, PD McLain, C Safa, AR Tagge, EP Kreitman, RJ AF Frankel, AE Hall, PD McLain, C Safa, AR Tagge, EP Kreitman, RJ TI Cell-specific modulation of drug resistance in acute myeloid leukemic blasts by diphtheria fusion toxin, DT388-GMCSF SO BIOCONJUGATE CHEMISTRY LA English DT Article ID BONE-MARROW TRANSPLANTATION; DISSEMINATED DAUDI-LYMPHOMA; MULTIDRUG-RESISTANCE; PROGENITOR CELLS; GENE-EXPRESSION; CANCER CELLS; NUDE-MICE; GM-CSF; IMMUNOTOXIN; CHEMOTHERAPY AB Radiochemotherapy-resistant blasts commonly cause treatment failure in acute myeloid leukemia !AML), and their resistance is due, in part, to overexpression of multidrug resistance (mdr! proteins. We reasoned that targeted delivery of protein synthesis inactivating toxins to leukemic blasts would reduce the cellular concentrations of relatively short half-life resistance proteins and sensitize the cells to cytotoxic drugs. To test this hypothesis, we employed human granulocyte-macrophage colony-stimulating factor fused to truncated diphtheria toxin (DT388-GMCSF). The human AML cell line HL60 and its vincristine-resistant sublines, HL60Vinc and HL60VCR, were incubated in vitro for 24 h with varying concentrations of toxin. Doxorubicin was added for an additional 24 h, and cell cytotoxicity was assayed by thymidine incorporation and colony formation in semisolid medium. DT388-GMCSF sensitized HL60Vinc and HL60VCR but not HL60 to doxorubicin. Combination indices for three log cell kill varied from 0.2 to 0.3. In contrast, pretreatment with doxorubicin followed by toxins failed to show synergy. At least in the case of the vincristine-resistant cell lines, modulation of drug resistance correlated with reduction in membrane P-glycoprotein concentrations based on immunoblots with C219 antibody, flow cytometry with MRK16 antibody, and cell uptake of doxorubicin. These observations suggest clinical trials of combination therapy may be warranted in patients with refractory AML. Further, targeted toxins may represent a novel class of cell-specific modulators of drug resistance for a number of malignancies. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Expt Oncol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Frankel, AE (reprint author), Hollings Canc Ctr, Room 311,86 Jonathan Lucas St, Charleston, SC 29401 USA. NR 39 TC 24 Z9 24 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL-AUG PY 1998 VL 9 IS 4 BP 490 EP 496 DI 10.1021/bc980015a PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 102KP UT WOS:000074923700008 PM 9667951 ER PT J AU Smith, GD Keizer, JE Stern, MD Lederer, WJ Cheng, HP AF Smith, GD Keizer, JE Stern, MD Lederer, WJ Cheng, HP TI A simple numerical model of calcium spark formation and detection in cardiac myocytes SO BIOPHYSICAL JOURNAL LA English DT Article ID RAT-HEART CELLS; RAPID BUFFERING APPROXIMATION; SARCOPLASMIC-RETICULUM; CA2+ SPARKS; SKELETAL-MUSCLE; INOSITOL TRISPHOSPHATE; VENTRICULAR MYOCYTES; ELEMENTARY EVENTS; RELEASE; CHANNEL AB The elementary events of excitation-contraction coupling in heart muscle are Ca2+ sparks, which arise from one or more ryanodine receptors in the sarcoplasmic reticulum (SR). Here a simple numerical model is constructed to explore Ca2+ spark formation, detection, and interpretation in cardiac myocytes. This model includes Ca2+ release, cytosolic diffusion, resequestration by SR Ca2+-ATPases, and the association and dissociation of Ca2+ with endogenous Ca2+-binding sites and a diffusible indicator dye (fluo-3). Simulations in a homogeneous, isotropic cytosol reproduce the brightness and the time course of a typical cardiac Ca2+ spark, but underestimate its spatial size (similar to 1.1 mu m VS similar to 2.0 mu m). Back-calculating [Ca2+](i) by assuming equilibrium with indicator fails to provide a good estimate of the free Ca2+ concentration even when using blur-free fluorescence data. A parameter sensitivity study reveals that the mobility, kinetics, and concentration of the indicator are essential determinants of the shape of Ca2+ sparks, whereas the stationary buffers and pumps are less influential, Using a geometrically more complex version of the model, we show that the asymmetric shape of Ca2+ sparks is better explained by anisotropic diffusion of Ca2+ ions and indicator dye rather than by subsarcomeric inhomogeneities of the Ca2+ buffer and transport system. In addition, we examine the contribution of off-center confocal sampling to the variance of spark statistics. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Univ Maryland, Dept Mol Biol & Biophys, Baltimore, MD 21201 USA. NIH, Math Res Branch, Bethesda, MD 20814 USA. Univ Calif Davis, Inst Theoret Dynam, Davis, CA 95616 USA. Univ Calif Davis, Sect Neurobiol Physiol & Behav, Davis, CA 95616 USA. RP Cheng, HP (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Lederer, William/B-1285-2010; OI Smith, Gregory/0000-0002-1054-6790 NR 52 TC 154 Z9 158 U1 4 U2 11 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1998 VL 75 IS 1 BP 15 EP 32 PG 18 WC Biophysics SC Biophysics GA 108BM UT WOS:000075246200002 PM 9649364 ER PT J AU Misra, S AF Misra, S TI Contribution of proton release to the B2 photocurrent of bacteriorhodopsin SO BIOPHYSICAL JOURNAL LA English DT Article ID ORIENTED PURPLE MEMBRANE; LIGHT-INDUCED CURRENTS; CHROMOPHORE ISOMERIZATION; HALOBACTERIUM-HALOBIUM; EXTRACELLULAR SURFACE; PHOTOCYCLE; FORMS; COMPONENT AB The contribution of proton release from the so-called proton release group to the microsecond B2 photocurrent from bacteriorhodopsin (bR) oriented in polyacrylamide gels was determined. The fraction of the B2 current due to proton release was resolved by titration of the proton release group in M. At pH values below the pK(a), of the proton release group in M, the proton release group cannot release its proton during the first half of the bacteriorhodopsin photocycle. At these pH values, the B2 photocurrent is due primarily to translocation of the Schiff base proton to Asp(85). The B2 photocurrent was measured in wild-type bR gels at pH 4.5-7.5, in 100 mM KCl/50 mM phosphate. The B2 photocurrent area (proportional to the amount of charge moved) exhibits a pH dependence with a pK(a), of 6.1. This is suggested to be the pK(a), of the proton release group in M; the value obtained is in good agreement with previous results obtained by examining photocycle kinetics and pH-sensitive dye signals. In the mutant Glu(204)Gln, the B2 photocurrent of the mutant membranes was pH independent between pH 4 and 7. Because the proton release group is incapacitated, and early proton release is eliminated in the Glu(204)Gln mutant, this supports the idea that the pH dependence of the B2 photocurrent in the wild type reflects the titration of the proton release group. In wild-type bacteriorhodopsin; proton release contributes approximately half of the B2 area at pH 7.5. The B2 area in the Glu(204)Gln mutant is similar to that in the wild type at pH 4.5; in both cases, the B2 current is likely due only to movement of the Schiff base proton to Asp(85). C1 Univ Illinois, Dept Cell & Struct Biol, Urbana, IL 61801 USA. Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA. RP Misra, S (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Rm 433,5 Ctr Dr, Bethesda, MD 20892 USA. OI Misra, Saurav/0000-0002-1385-8554 FU NIGMS NIH HHS [GM52023] NR 34 TC 12 Z9 12 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1998 VL 75 IS 1 BP 382 EP 388 PG 7 WC Biophysics SC Biophysics GA 108BM UT WOS:000075246200033 PM 9649395 ER PT J AU Berardelli, A Rothwell, JC Hallett, M Thompson, PD Manfredi, M Marsden, CD AF Berardelli, A Rothwell, JC Hallett, M Thompson, PD Manfredi, M Marsden, CD TI The pathophysiology of primary dystonia SO BRAIN LA English DT Review DE dystonia; cortical areas; spinal cord; brainstem ID IDIOPATHIC TORSION DYSTONIA; SOMATOSENSORY-EVOKED-POTENTIALS; MOVEMENT-RELATED POTENTIALS; MASSETER INHIBITORY REFLEX; HUMAN MOTOR CORTEX; F-18 DOPA UPTAKE; RECIPROCAL INHIBITION; SPASMODIC TORTICOLLIS; WRITERS CRAMP; BLINK REFLEX AB Go-contraction and overflow of EMG activity of inappropriate muscles are typical features of all dystonic movements whether voluntary or involuntary. Voluntary movements are slow and more variable than normal, and there is particular difficultly switching between component movements of a complex task, Reduced spinal cord and brainstem inhibition is common to many reflex studies (long-latency reflexes, cranial reflexes and reciprocal inhibition), These reflex abnormalities may contribute to the difficulties in voluntary movements but cannot be causal as they can occur outside the clinically involved territory, Clinical and neurophysiological studies have emphasized the possible role of sensory feedback in the generation of dystonic movements, Abnormalities of cortical and basal ganglia function have been described in functional imaging and neurophysiological studies of patients with dystonia and in animal models of primary dystonia, Studies of cortical function have shown reduced preparatory activity in the EEG before the onset of voluntary movements, whilst magnetic brain stimulation has revealed changes in motor cortical excitability, Functional imaging of the brain in primary dystonia has suggested reduced pallidal inhibition of the thalamus with consequent overactivity of medial and prefrontal cortical areas and underactivity of the primary motor cortex during movements. These findings are supported by preliminary neuronal recordings from the globus pallidus and the thalamus at the time of stereotaxic surgery in patients with dystonia, All this evidence suggests that primary dystonia results from a functional disturbance of the basal ganglia, particularly in the striatal control of the globus pallidus (and substantia nigra pars reticulata), This causes altered thalamic control of cortical motor planning and executive areas, and abnormal regulation of brainstem and spinal cord inhibitory interneuronal mechanisms. C1 Univ Roma La Sapienza, Dipartimento Sci Neurol, I-00185 Rome, Italy. Mediterranean Neurol Inst, Pozzilli, IS, Italy. UCL Natl Hosp Neurol & Neurosurg, Human Movement & Balance Unit, Neurol Inst, London WC1N 3BG, England. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Royal Adelaide Hosp, Univ Dept Med, Adelaide, SA 5000, Australia. RP Berardelli, A (reprint author), Univ Roma La Sapienza, Dipartimento Sci Neurol, Viale Univ 30, I-00185 Rome, Italy. OI Rothwell, John/0000-0003-1367-6467 NR 117 TC 513 Z9 520 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 1998 VL 121 BP 1195 EP 1212 DI 10.1093/brain/121.7.1195 PN 7 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 101XF UT WOS:000074892900002 PM 9679773 ER PT J AU Sadato, N Pascual-Leone, A Grafman, J Deiber, MP Ibanez, V Hallett, M AF Sadato, N Pascual-Leone, A Grafman, J Deiber, MP Ibanez, V Hallett, M TI Neural networks for Braille reading by the blind SO BRAIN LA English DT Article DE blind; Braille; visual cortex; multimodal plasticity; PET ID POSITRON-EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; FREQUENCY-DISCRIMINATION TASK; HUMAN EXTRASTRIATE CORTEX; MOTOR CORTICAL OUTPUTS; FUNCTIONAL-ANATOMY; VISUAL-CORTEX; TACTILE DISCRIMINATION; OCCIPITAL CORTEX; MACAQUE MONKEY AB To explore the neural networks used for Braille reading, we measured regional cerebral blood flow with PET during tactile tasks performed both by Braille readers blinded early in life and by sighted subjects. Eight proficient Braille readers were studied during Braille reading with both right and left index fingers. Eight-character, non-contracted Braille-letter strings mere used, and subjects were asked to discriminate between words and non-words. To compare the behaviour of the brain of the blind and the sighted directly, non-Braille tactile tasks were performed by six different blind subjects and 10 sighted control subjects using the right index finger. The tasks included a non-discrimination task and three discrimination tasks (angle, width and character). Irrespective of reading finger (right or left), Braille reading by the blind activated the inferior parietal lobule, primary visual cortex, superior occipital gyri, fusiform gyri, ventral premotor area, superior parietal lobule, cerebellum and primary sensorimotor area bilaterally, also the right dorsal premotor cortex, right middle occipital gyrus and right prefrontal area. During non-Braille discrimination tasks, in blind subjects, the ventral occipital regions, including the primary visual cortex and fusiform gyri bilaterally were activated while the secondary somatosensory area was deactivated. The reverse pattern was found in sighted subjects where the secondary somatosensory area was activated while the ventral occipital regions were suppressed. These findings suggest that the tactile processing pathways usually linked in the secondary somatosensory al:ea are rerouted in blind subjects to the ventral occipital cortical regions originally reserved for visual shape discrimination. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Cognit Neurosci Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Beth Israel Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Fukui Med Sch, Biomed Imaging Res Ctr, Fukui 91011, Japan. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. RI Pascual-Leone, Alvaro/G-6566-2011; Deiber, Marie-Pierre/M-5949-2014; OI Grafman, Jordan H./0000-0001-8645-4457 NR 77 TC 216 Z9 219 U1 0 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 1998 VL 121 BP 1213 EP 1229 DI 10.1093/brain/121.7.1213 PN 7 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 101XF UT WOS:000074892900003 PM 9679774 ER PT J AU McLean, CA Ironside, JW Alpers, MP Brown, PW Cervenakova, L Anderson, R Masters, CL AF McLean, CA Ironside, JW Alpers, MP Brown, PW Cervenakova, L Anderson, R Masters, CL TI Comparative neuropathology of kuru with the new variant of Creutzfeldt-Jakob disease: Evidence for strain of agent predominating over genotype of host SO BRAIN PATHOLOGY LA English DT Article ID PRION PROTEIN GENOTYPE; SPONGIFORM ENCEPHALOPATHY; NERVOUS-SYSTEM; PHENOTYPE; PATHOLOGY; CJD AB The three major influences on the phenotype of the transmissible spongiform encephalopathies are believed to be strain of agent, route of infection and host genotype, We have compared the pathologic profiles and genotypes of the new variant of Creutzfeldt-Jakob disease (vCJD) and kuru. The comparison reveals that there are distinct lesional differences particularly in the prion protein (PrP) load and distribution as seen by immunohistochemistry. The clinico-pathologic phenotypes and the genotypes of these two diseases are sufficiently different to suggest that the strain of agent may play a greater role than any presumptive common route of peripherally acquired infection. C1 Univ Melbourne, Dept Pathol, Melbourne, Vic 3052, Australia. Western Gen Hosp, CJD Surveillance Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Papua New Guinea Inst Med Res, EHP, Goroka, Papua N Guinea. NIH, Bethesda, MD 20892 USA. RP McLean, CA (reprint author), Univ Melbourne, Dept Pathol, Grattan St, Melbourne, Vic 3052, Australia. NR 37 TC 44 Z9 45 U1 0 U2 2 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 1998 VL 8 IS 3 BP 429 EP 437 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZX067 UT WOS:000074476100001 PM 9669694 ER PT J AU Chima, SC Ng, T Ryschkewitsch, C Agostini, H Stoner, G Fan, KJ AF Chima, SC Ng, T Ryschkewitsch, C Agostini, H Stoner, G Fan, KJ TI Molecular epidemiology of human polyomavirus JC in a US urban population: Survival of strains from Africa in modern African Americans. SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. Howard Univ, Dept Pathol, Washington, DC 20059 USA. RI Chima, Sylvester Chidi/N-5564-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 1998 VL 8 IS 3 BP 580 EP 580 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZX067 UT WOS:000074476100021 ER PT J AU Ambs, S Bennett, WP Merriam, WG Ogunfusika, MO Oser, SM Khan, MA Jones, RT Harris, CC AF Ambs, S Bennett, WP Merriam, WG Ogunfusika, MO Oser, SM Khan, MA Jones, RT Harris, CC TI Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53 SO BRITISH JOURNAL OF CANCER LA English DT Article DE angiogenesis; lung cancer; tumour-suppressor gene ID WILD-TYPE P53; IN-VIVO; PERMEABILITY FACTOR; TUMOR-GROWTH; ANGIOGENESIS; HYPOXIA; GENE; INDUCTION; PROTEIN; MUTANT AB Vascular endothelial growth factor (VEGF) expression and mutations of cancer-related genes increase with cancer progression. This correlation suggests the hypothesis that oncogenes and tumour suppressors regulate VEGF, and a significant correlation between p53 alteration and increased VEGF expression in human lung cancer was reported recently. To further examine this hypothesis, we analysed VEGF protein expression and mutations in p53 and K-ras in 27 non-small-cell lung cancers (NSCLC): 16 squamous cell, six adenocarcinomas, one large cell, two carcinoids and two undifferentiated tumours. VEGF was expressed in 50% of the squamous cell carcinomas (SCC) and carcinoids but none of the others. p53 mutations occurred in 14 tumours (52%), and K-ras mutations were found in two adenocarcinomas and one SCC; there was no correlation between the mutations and VEGF expression. As nitric oxide also regulates angiogenesis, we examined NOS expression in NSCLC. The Ca2+-dependent NOS activity, which indicates NOS1 and NOS3 expression, was significantly reduced in lung carcinomas compared with adjacent non-tumour tissue (P < 0.004). Although the Ca2+-independent NOS activity, which indicates NOS2 expression, was low or undetectable in non-tumour tissues and most carcinomas, significant activity occurred in three SCC. In summary, our data do not show a direct regulation of VEGF by p53 in NSCLC. Finally, we did not find the up-regulation of NOS isoforms during NSCLC progression that has been suggested for gynaecological and breast cancers. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2C01,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 38 TC 97 Z9 108 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1998 VL 78 IS 2 BP 233 EP 239 DI 10.1038/bjc.1998.470 PG 7 WC Oncology SC Oncology GA ZZ530 UT WOS:000074738700063 PM 9683299 ER PT J AU Lancaster, JM Berchuck, A Carney, ME Wiseman, R Taylor, JA AF Lancaster, JM Berchuck, A Carney, ME Wiseman, R Taylor, JA TI Progesterone receptor gene polymorphism and risk for breast and ovarian cancer SO BRITISH JOURNAL OF CANCER LA English DT Letter ID FRAGMENT-LENGTH-POLYMORPHISM; CARCINOMA C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Div Gynecol Oncol, Durham, NC 27710 USA. RP Lancaster, JM (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI taylor, jack/0000-0001-5303-6398 NR 2 TC 51 Z9 52 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1998 VL 78 IS 2 BP 277 EP 277 DI 10.1038/bjc.1998.480 PG 1 WC Oncology SC Oncology GA ZZ530 UT WOS:000074738700071 PM 9683307 ER PT J AU Kurzrock, R Gratwohl, A Paquette, R Wyres, M Okamoto, D Young, N AF Kurzrock, R Gratwohl, A Paquette, R Wyres, M Okamoto, D Young, N TI Trilineage responses seen with stem cell factor (Stemgen (R), SCF) and filgrastim (G-CSF) treatment in aplastic anemia (AA) patients (pts) SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. NHLBI, Bethesda, MD 20892 USA. Univ Basel Hosp, CH-4031 Basel, Switzerland. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 1 SU S BP 2 EP 2 PG 1 WC Hematology SC Hematology GA 104TK UT WOS:000075031300005 ER PT J AU Shu, XO Wen, W Buckey, J Brondum, J Linet, H Robison, L AF Shu, XO Wen, W Buckey, J Brondum, J Linet, H Robison, L TI Lifestyle factors and risk of childhood acute lymphocytic leukemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 Univ So Calif, Los Angeles, CA 90089 USA. Univ S Carolina, Columbia, SC 29208 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 1 SU S BP 19 EP 19 PG 1 WC Hematology SC Hematology GA 104TK UT WOS:000075031300070 ER PT J AU Kollia, P Stavroyianni, N Stamatopoulos, K Loukopoulos, D Noguchi, CT Yataganas, X AF Kollia, P Stavroyianni, N Stamatopoulos, K Loukopoulos, D Noguchi, CT Yataganas, X TI Detection of transferrin receptor (CD71) mRNA transcripts in acute myeloid leukemia at diagnosis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 NIH, Biol Chem Lab, Bethesda, MD 20892 USA. Univ Athens, Laikon Gen Hosp, Dept Med 1, Athens, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 1 SU S BP 103 EP 103 PG 1 WC Hematology SC Hematology GA 104TK UT WOS:000075031300406 ER PT J AU Cobo, F Sole, M Bosch, F Esteve, J Pinyol, M Hernandez, L Lopez-Guillermo, A Rafel, M Raffeld, M Jaffe, ES Montserrat, E Campo, E AF Cobo, F Sole, M Bosch, F Esteve, J Pinyol, M Hernandez, L Lopez-Guillermo, A Rafel, M Raffeld, M Jaffe, ES Montserrat, E Campo, E TI Expression or potentially oncogenic HIV-8 genes in HIV-, EBV-negative primary effusion lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 Hosp Clin Barcelona, Dept Hematol, Hematopathol Unit, Barcelona, Spain. Hosp Clin Barcelona, Dept Pathol, Hematopathol Unit, Barcelona, Spain. Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 1 SU S BP 122 EP 122 PG 1 WC Hematology SC Hematology GA 104TK UT WOS:000075031300479 ER PT J AU Adya, N Castilla, L Liu, PP AF Adya, N Castilla, L Liu, PP TI Functional role of CBF beta-SMMHC in leukemogenesis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 1 SU S BP 157 EP 157 PG 1 WC Hematology SC Hematology GA 104TK UT WOS:000075031300620 ER PT J AU Martens, ACM Rozemuller, H Terpstra, W Rombouts, EJC Kreitman, RJ FitzGerald, DJ Lowenberg, B Touw, IP Hagenbeek, A AF Martens, ACM Rozemuller, H Terpstra, W Rombouts, EJC Kreitman, RJ FitzGerald, DJ Lowenberg, B Touw, IP Hagenbeek, A TI Diphtheria toxin fused to GM-CSF can be used for in vivo targeting of primary AML cells in immunodeficient mice SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 EUR, Inst Hematol, Rotterdam, Netherlands. NIH, Mol Biol Lab, Bethesda, MD USA. Univ Utrecht Hosp, Dept Hematol, Utrecht, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 1 SU S BP 329 EP 329 PG 1 WC Hematology SC Hematology GA 104TK UT WOS:000075031301311 ER PT J AU Whitcup, SM Cunningham, ET Polis, MA Fortin, E AF Whitcup, SM Cunningham, ET Polis, MA Fortin, E TI Spontaneous and sustained resolution of CMV retinitis in patients receiving highly active antiretroviral therapy SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Letter C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Francis I Proctor Fdn Res Ophthalmol, San Francisco, CA 94143 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Whitcup, SM (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10 Rm 10N 202, Bethesda, MD 20892 USA. NR 4 TC 14 Z9 14 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUL PY 1998 VL 82 IS 7 BP 845 EP 846 PG 2 WC Ophthalmology SC Ophthalmology GA 103GT UT WOS:000075096800039 PM 9924390 ER PT J AU Peoples, RW Weight, FF AF Peoples, RW Weight, FF TI Inhibition of excitatory amino acid-activated currents by trichloroethanol and trifluoroethanol in mouse hippocampal neurones SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE alcohol; anaesthetic; chloral hydrate; receptor; ion channel; neuronal excitability; glutamate receptor; NMDA receptor ID D-ASPARTATE RECEPTORS; ETHANOL WITHDRAWAL SEIZURES; INDUCED NORADRENALINE; ALCOHOL-INTOXICATION; XENOPUS OOCYTES; NERVOUS-SYSTEM; ION CURRENT; RAT-BRAIN; RELEASE; ANESTHETICS AB 1 The effects of the active metabolite of chloral derivative sedative-hypnotic agents, 2,2,2-trichloroethanol (trichloroethanol), and its analog 2,2,2-trifluoroethanol (trifluoroethanol), were studied on ion current activated by the excitatory amino acids N-methyl-D-aspartate (NMDA) and kainate in mouse hippocampal neurones in culture using whole-cell patch-clamp recording. 2 Both trichloroethanol and trifluoroethanol inhibited excitatory amino acid-activated currents in a concentration-dependent manner. Trichloroethanol inhibited NMDA- and kainate-activated currents with IC50 values of 6.4 and 12 mM, respectively, while trifluoroethanol inhibited NMDA- and kainate-activated currents with IC50 values of 28 and 35 mM, respectively. 3 Both trichloroethanol and trifluoroethanol appeared to be able to inhibit excitatory amino acid-activated currents by 100 per cent. 4 Concentration-response analysis of NMDA- and kainate-activated current revealed that trichloroethanol decreased the maximal response to both agonists without significantly affecting their EC50 values. 5 Both trichloroethanol and trifluoroethanol inhibited excitatory amino acid-activated currents more potently than did ethanol. The inhibitory potency of trichloroethanol and trifluoroethanol appears to be associated with their increased hydrophobicity. 6 The observation that trichloroethanol inhibits excitatory amino acid-activated currents at anaesthetic concentrations suggests that inhibition of excitatory amino acid receptors may contribute to the CNS depressant effects of chloral derivative sedative-hypnotic agents. C1 NIAAA, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Peoples, RW (reprint author), NIAAA, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 41 TC 22 Z9 22 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUL PY 1998 VL 124 IS 6 BP 1159 EP 1164 DI 10.1038/sj.bjp.0701949 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 103HH UT WOS:000074965000020 PM 9720786 ER PT J AU Cidlowski, JA Webster, J McKay, L Bofetiado, D Oakley, R Jewell, C AF Cidlowski, JA Webster, J McKay, L Bofetiado, D Oakley, R Jewell, C TI Mechanisms of gene activation and repression by the glucocorticoid receptor SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUL PY 1998 VL 124 SU S MA 147P BP U78 EP U78 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 109ZF UT WOS:000075353700148 ER PT J AU Clifford, JJ Tighe, O Croke, DT Drago, J Sibley, DR Waddington, JL AF Clifford, JJ Tighe, O Croke, DT Drago, J Sibley, DR Waddington, JL TI Behavioural responsivity to the selective D-2-like agonist RU 24213 in transgenic mice with D-1A dopamine receptor 'knockout' SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 Royal Coll Surg Ireland, Dept Clin Pharmacol, Dublin 2, Ireland. Royal Coll Surg Ireland, Dept Biochem, Dublin 2, Ireland. Monash Univ, Dept Anat, Clayton, Vic 3168, Australia. NINDS, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUL PY 1998 VL 124 SU S MA 11P BP U10 EP U10 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 109ZF UT WOS:000075353700012 ER PT J AU Gonzalez, FJ AF Gonzalez, FJ TI Impact of gene knockout models in xenobiotic metabolism and chemical carcinogenesis SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 NCI, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUL PY 1998 VL 124 SU S MA 152P BP U80 EP U80 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 109ZF UT WOS:000075353700153 ER PT J AU Regier, DA Rae, DS Narrow, WE Kaelber, CT Schatzberg, AF AF Regier, DA Rae, DS Narrow, WE Kaelber, CT Schatzberg, AF TI Prevalence of anxiety disorders and their comorbidity with mood and addictive disorders SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; UNITED-STATES; DEPRESSION; FAMILY; LIFETIME AB Background The co-occurrence of anxiety disorders with other mental, addictive, and physical disorders has important implications for treatment and for prediction of clinical course and associated morbidity. Method Cross-sectional and prospective data on 20 291 individuals from the Epidemiologic Catchment Area (ECA) study were analysed to determine one-month, current disorders. one-year incidence, and one-year and lifetime prevalence of anxiety, mood, and addictive disorders, and to identify the onset and offset of disorders within the one-year prospective period. Results Nearly half (47.2%) of those meeting lifetime criteria for major depression also have met criteria for a comorbid anxiety disorder.The average age of onset. of any lifetime anxiety disorder (16.4 years) and social phobia (11.6 years) among those with major depression was much younger than the onset age for major depression (23.2 years) and panic disorder. Conclusions Anxiety disorders, especially social and simple phobias, appear to have an early onset in adolescence with potentially severe consequences. predisposing those affected to greater vulnerability to major depression and addictive disorders. C1 NIMH, Div Epidemiol & Serv Res, NIH, Rockville, MD 20857 USA. Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Regier, DA (reprint author), NIMH, Div Epidemiol & Serv Res, NIH, Room 10-105,5600 Fishers Lane,Parklawn Bldg, Rockville, MD 20857 USA. NR 15 TC 216 Z9 221 U1 10 U2 30 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JUL PY 1998 VL 173 SU 34 BP 24 EP 28 PG 5 WC Psychiatry SC Psychiatry GA 102ZW UT WOS:000074957000005 PM 9829013 ER PT J AU Schatzberg, AF Samson, JA Rothschild, AJ Bond, TC Regier, DA AF Schatzberg, AF Samson, JA Rothschild, AJ Bond, TC Regier, DA TI McLean Hospital Depression Research Facility: early-onset phobic disorders and adult-onset major depression SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID NATIONAL COMORBIDITY SURVEY; ANXIETY DISORDERS; PANIC DISORDER; SOCIAL PHOBIA; FAMILY; SECONDARY; CHILDREN; HISTORY; RISK AB Background This study explores the temporal relationship between anxiety and major depressive disorders in a cohort of patients with current major depression. Method Current prevalence and lifetime history of specific anxiety disorders were assessed using the Structured Clinical Interview for DSM - III - R Diagnosis (SCID - P) in 85 patients with DSM - III - R major depression. Consensus DSM - III - R diagnoses were assigned by art least two psychiatrists or psychologists. Results Twenty-nine per cent met criteria for at least one current anxiety disorder and 34% had at least one anxiety disorder at some point in their lives. The mean (s. d.) age of onset of anxiety disorder in the depressed patients with comorbid social or simple phobia(15 (9) years) was significantly younger than was that of their major depression (25 (9) years). In contrast, the mean (s.d.) age of onset of anxiety in patients with comorbid panic or OCD (20 (8) years) was similar to that seen for their major depression (21 (9) years). In patients with major depression with comorbid anxiety disorders, both the social phobia (10 of 13) and simple phobia (4 of 4) were more commonly reported to start at least two years prior to their major depression in contrast to depressives with comorbid panic (3 of 10 subjects) - Fisher's exact test, P = 0.01. Conclusions Early-onset social and simple phobias appear to be risk factors for later onset of major depression. C1 Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Univ Massachusetts, Sch Med, Dept Psychiat, Amherst, MA 01003 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. NIMH, Div Epidemiol & Serv Res, Rockville, MD USA. RP Schatzberg, AF (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, 401 Quarry Rd, Stanford, CA 94305 USA. NR 30 TC 29 Z9 31 U1 1 U2 2 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JUL PY 1998 VL 173 SU 34 BP 29 EP 34 PG 6 WC Psychiatry SC Psychiatry GA 102ZW UT WOS:000074957000006 PM 9829014 ER PT J AU McShane, LM Kulldorff, M Wargovich, MJ Woods, C Purewal, M Freedman, LS Corle, DK Burt, RW Mateski, DJ Lawson, M Lanza, E O'Brien, B Lake, W Moler, J Schatzkin, A AF McShane, LM Kulldorff, M Wargovich, MJ Woods, C Purewal, M Freedman, LS Corle, DK Burt, RW Mateski, DJ Lawson, M Lanza, E O'Brien, B Lake, W Moler, J Schatzkin, A TI An evaluation of rectal mucosal proliferation measure variability sources in the polyp prevention trial: Can we detect informative differences among individuals' proliferation measures amid the noise? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EPITHELIAL-CELL PROLIFERATION; CONTROLLED CLINICAL-TRIAL; NUCLEAR ANTIGEN; CALCIUM; CANCER; IMMUNOHISTOCHEMISTRY AB We assessed components of total variability of bromodeoxyuridine (BrdUrd) and proliferating cell nuclear antigen (PCNA) assays of rectal mucosal proliferation in a subset of 390 participants from the U, S, National Cancer Institute's multicenter Polyp Prevention Trial. Biopsies were blindly double-scored by two technicians. For those participants for whom at least one evaluable biopsy was obtained, a mean of 2.0 and 2.6 biopsies, and 6.2 and 8.7 crypts/biopsy were evaluated, respectively, with the BrdUrd and PCNA assays, Factors such as clinical center, scorer, and month of biopsy collection significantly affected the observed values of the labeling index (LI) and proliferative height (PH), Therefore, it is essential to control or adjust for these variables in proliferation studies. Sources of random variation for LI and PH measures remaining after the aforementioned factors include between-participant variation and several sources of within-participant variation, including variation over time, between biopsies, and between multiple measurements on the same biopsy. Both LI and PH measurements exhibited substantial variability over time, between biopsies, and from reading-to-reading of the same biopsy. When other sources of variability have been accounted for, the PCNA LI seems to have little between-participant variation. This brings into question its utility as a marker in colorectal cancer studies. The PCNA PH showed significant between-participant variability and may hold some promise as a useful marker in colorectal cancer studies. Results for BrdUrd were less conclusive, The BrdUrd LI showed marginally significant between-participant variation, whereas the corresponding variation for PH was nonsignificant. C1 NCI, Biotmetr Res Branch, CTEP, DCTD, Bethesda, MD 20892 USA. MD Anderson Cancer Ctr, Houston, TX 77030 USA. Univ Utah, Salt Lake City, UT 84132 USA. Kaiser Permanente Med Ctr, Sacramento, CA 95825 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. WESTAT Corp, Rockville, MD 20850 USA. Informat Management Serv, Rockville, MD 20852 USA. RP McShane, LM (reprint author), NCI, Biotmetr Res Branch, CTEP, DCTD, Execut Plaza N,Room 739,6130 Execut Blvd MSC 7434, Bethesda, MD 20892 USA. RI Kulldorff, Martin/H-4282-2011; OI Kulldorff, Martin/0000-0002-5284-2993; Moler, James/0000-0001-8738-6898 NR 25 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 1998 VL 7 IS 7 BP 605 EP 612 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZZ309 UT WOS:000074716500008 PM 9681529 ER PT J AU Aran, JM Gottesman, MM Pastan, I AF Aran, JM Gottesman, MM Pastan, I TI Construction and characterization of bicistronic retroviral vectors encoding the multidrug transporter and beta-galactosidase or green fluorescent protein SO CANCER GENE THERAPY LA English DT Article DE P-glycoprotein; beta-galactosidase; GFP; retroviral vector ID MURINE SARCOMA-VIRUS; RESISTANCE GENE; P-GLYCOPROTEIN; BONE-MARROW; CELL-LINES; MONOCLONAL-ANTIBODIES; TRANSGENIC MICE; DRUG-RESISTANCE; TUMOR-CELLS; EXPRESSION AB Multidrug resistance (MDR) can be conferred by overexpression of the adenosine triphosphate-driven multidrug transporter P-glycoprotein (Pgp) known as MDR1. Thus, two potential applications of the MDR1 gene that may be useful in gene therapy are the protection of bone marrow cells from the cytotoxic effects of chemotherapy regimens in cancer patients and its possible use as an in vivo selectable gene when linked to a therapeutic gene. In this study, we have designed two retroviral bicistronic expression vectors by linking the MDR1 gene to the reporters known as beta-galactosidase and the red-shifted green fluorescent protein (GFP). We report the creation of stable producer cell lines that synthesize virus particles carrying the MDR-internal ribosomal entry sire (IRES)-lacZ and the MDR-IRES-GFP transgenes. These transcriptional fusions allow coordinate expression of Pgp and the reporter gene product to easily mark the MDR phenotype. Using the MDR-IRES-lacZ retrovirus, we demonstrate that periodic pulses of cytotoxic drug selection with a Pgp substrate enable sustained, long-term expression of the reporter beta-galactosidase in otherwise unstable transductants. We have also incorporated the improved features of GFP as a reporter gene into our MDR-IRES-GFP retrovirus. This vector allows rapid and specific identification of MDR1 gene transfer and expression in living cells either by fluorescence microscopy or by fluorescence-activated cell sorter analysis. These two MDR/reporter gene systems should be useful for in vivo studies, the evaluation of the potential of the MDR1 gene in gene therapy applications, and as a monitor of the selective efficacy of its MDR phenotype. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 39 TC 19 Z9 20 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JUL-AUG PY 1998 VL 5 IS 4 BP 195 EP 206 PG 12 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 103HV UT WOS:000075152600001 PM 9694071 ER PT J AU Cheson, BD AF Cheson, BD TI New prospects in the treatment of indolent lymphomas with purine analogues SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Review DE purine analogues; fludarabine; cladribine; pentostatin; indolent lymphomas ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; HAIRY-CELL LEUKEMIA; PHASE-II TRIAL; LOW-GRADE LYMPHOMA; PREVIOUSLY UNTREATED PATIENTS; CONTINUOUS-INFUSION SCHEDULE; ADVANCED MYCOSIS-FUNGOIDES; TERM FOLLOW-UP; FLUDARABINE PHOSPHATE AB PURPOSE To review the activity of the purine analogues fludarabine, cladribine (2-chlorodeoxyadenosine [2-CdA]), and pentostatin (2'-deoxycoformycin) in the treatment of indolent lymphoid malignancies, including chronic lymphocytic leukemia, hairy cell leukemia, and indolent non-Hodgkin's lymphomas (NHLs). PATIENTS AND METHODS Patients with previously untreated, relapsed, or refractory indolent NHL and other indolent lymphoid malignancies who have been treated with purine analogues. RESULTS Purine analogues have revolutionized the treatment of indolent lymphomas. Fludarabine induces responses in almost 50% of patients with relapsed or refractory indolent NHL and produces complete remissions (CRs) in 10% to 15% of patients. In patients receiving fludarabine as initial treatment, CRs are achieved in almost 40%, with an overall response rate of 70% and a median time to progression > 1 year. Response rates with 2-CdA in previously treated patients appear similar to those with fludarabine, although less durable. Fludarabine and 2-CdA achieve a higher number of durable responses in Waldenstrom's macroglobulinemia than are generally achieved with alkylating agents in this disease. Pentostatin appears to be less active in NHL. Newer purine analogues currently in clinical trials in lymphomas include gemcitabine and compound 506U. Promising activity has been reported with the combination of fludarabine, mitoxantrone, dexamethasone, and fludarabine plus cyclophosphamide. Combinations of 2-CdA with other agents are also in development. Toxicities associated with these purine analogues primarily include moderate myelosuppression, profound immunosuppression, neurotoxicity at higher than recommended doses, and a possible increase in secondary malignancies. CONCLUSION The purine analogues should provide the basis for new treatment strategies with the goal of curing patients with indolent NHL. For progress to continue, patients must be referred to important and innovative clinical research trials. C1 NCI, Med Sect, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Cheson, BD (reprint author), NCI, Med Sect, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Execut Plaza N,Room 741, Bethesda, MD 20892 USA. NR 105 TC 13 Z9 13 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JUL PY 1998 VL 4 SU 2 BP S27 EP S36 PG 10 WC Oncology SC Oncology GA 104TG UT WOS:000075031000005 PM 9672772 ER PT J AU Longo, DL AF Longo, DL TI Solving the puzzle of follicular lymphoma SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Editorial Material C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Longo, DL (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr,Box 9, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JUL PY 1998 VL 4 SU 2 BP S1 EP S4 PG 4 WC Oncology SC Oncology GA 104TG UT WOS:000075031000001 PM 9672768 ER PT J AU Ciolino, HP Wang, TTY Yeh, GC AF Ciolino, HP Wang, TTY Yeh, GC TI Diosmin and diosmetin are agonists of the aryl hydrocarbon receptor that differentially affect cytochrome P450 1A1 activity SO CANCER RESEARCH LA English DT Article ID CANCER PREVENTION; CELL-LINES; FLAVONOIDS; DNA; INDUCTION; FRUIT; DIET; TUMORIGENESIS; VEGETABLES; QUERCETIN AB We investigated the effect of the chemopreventive compound diosmin and its aglycone form, diosmetin, on the carcinogen activation pathway mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 human breast epithelial cancer cells. Treatment of the cells with diosmin caused a dose-dependent increase in the metabolism of the mammary carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), as assessed by increased formation of DMBA-DNA adducts and by DMBA-induced cytotoxicity. In contrast, treatment of the cells with diosmetin decreased both parameters. Diosmetin, but not diosmin, directly inhibited cytochrome P450 1A1 (CYP1A1) activity in a noncompetitive manner in microsomes isolated from DMBA-treated cells, as assayed by ethyoxyresorufin-O-deethylase activity. Treatment of the cells with diosmin or diosmetin, on the other hand, caused a dose-and time-dependent increase in CYP1A1 activity in intact cells that was comparable to that induced by DMBA or by the aryl hydrocarbon benzo(a)pyrene. Both diosmin and diosmetin caused an increase in the transcription of the CYP1A1 gene, as measured by increased levels of CYP1A1 mRNA. Both compounds caused the activation of the DNA-binding capacity of the AhR for the xenobiotic-responsive element of CYP1A1. These results indicate that diosmin and diosmetin are natural dietary agonists of the AhR, causing a potent increase in CYP1A1 transcription and CYP1A1 activity; however, only diosmetin is capable of inhibiting CYP1A1 enzyme activity, thus inhibiting carcinogen activation. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Nutr & Mol Regulat, Div Basic Sci,NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Cellular Def & Carcinogenesis Sect, Div Basic Sci,NIH, Frederick, MD 21702 USA. RP Ciolino, HP (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Nutr & Mol Regulat, Div Basic Sci,NIH, Bldg 560,Room 12-05,POB B, Frederick, MD 21702 USA. EM hciolino@mail.ncifcrf.gov NR 46 TC 92 Z9 96 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1998 VL 58 IS 13 BP 2754 EP 2760 PG 7 WC Oncology SC Oncology GA ZX317 UT WOS:000074503400015 PM 9661887 ER PT J AU Miller, CE Mulard, LA Padlan, EA Glaudemans, CPJ AF Miller, CE Mulard, LA Padlan, EA Glaudemans, CPJ TI Binding of modified fragments of the Shigella dysenteriae type 1 O-specific polysaccharide to monoclonal IgM 3707 E9 and docking of the immunodeterminant to its modeled Fv SO CARBOHYDRATE RESEARCH LA English DT Article DE deoxyfluoro sugars; protein structure; ligand/antibody binding ID D-GALACTOPYRANOSIDES; V-GENES; ANTIBODY; ANTIGEN; PROTEIN; MURINE; OLIGOSACCHARIDES; DERIVATIVES; SALMONELLA; COMPLEX AB The O-specific polysaccharide (O-SP) of Shigella dysenteriae type 1 has been shown by others to have the structure --> 3)-alpha-L-Rhap-(1 --> 3)-alpha-L-Rhap-(1 --> 2)-alpha-D-Galp-(1 --> 3)-alpha-D-GlcpNAc-(1 -->. We have shown in the past that IgM 3707 E9, an anti S. dysenteriae type 1 O-SP monoclonal antibody, binds specifically to the -alpha-L-Rhap-(1 --> 2)-alpha-D-Galp- determinant of the polysaccharide. In this report we show that determinant to have hydrogen bonds, necessary for binding to the antibody, involving positions 3, 4 and 6 of the galactopyranosyl residue. The hydroxyl groups of the rhamno-pyranosyl moiety of the immunodeterminant appear not to partake in hydrogen-bond interactions with the antibody. A model is presented of the Fv of IgM 3707 E9 based on our previously established cDNA-sequence and two known, highly homologous immunoglobulin crystal structures. The methyl glycoside of the immunodeterminant alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-D-galactopyranose is docked to the combining area of the Fv. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Glaudemans, CPJ (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. NR 37 TC 5 Z9 6 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUL PY 1998 VL 309 IS 3 BP 219 EP 226 DI 10.1016/S0008-6215(98)00133-5 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 113WB UT WOS:000075575900001 PM 9742688 ER PT J AU Solomons, KRH Freeman, S Schwalbe, CH Shears, SB Nelson, DJ Xie, WW Bruzik, KS Kaetzel, MA AF Solomons, KRH Freeman, S Schwalbe, CH Shears, SB Nelson, DJ Xie, WW Bruzik, KS Kaetzel, MA TI Synthesis of D-1,2-dideoxy-l,2-diffuoro-myo-inositol 3,4,5,6-tetrakisphosphate and its enantiomer as analogues of myo-inositol 3,4,5,6-tetrakisphosphate SO CARBOHYDRATE RESEARCH LA English DT Article DE inositol polyphosphates; chloride current; myo-inositol 3,4,5,6-tetrakisphosphate; crystal structure ID ACINAR-CELLS; 1,3,4-TRISPHOSPHATE; 1,4,5,6-TETRAKISPHOSPHATE AB DL-3,4,5,6-Tetra-O-benzyl-1-deoxy-1-fluoro-scyllo-inositol was resolved using (-)-(1S, 4R)-camphanyl chloride. The diastereoisomers formed were separated and the structure of D-3,4,5,6-tetra-O-benzyl-2-(1S,4R)-camphanyl-1-deoxy-1-fluoro-scyllo-inositol was solved by X-ray crystallography to an R-factor of 4.2%. A series of manipulations led to the preparation of 0-1,2-dideoxy-1,2-difluoro-myo-inositol 3,4,5,6-tetrakisphosphate and its enantiomer. The D-1,2-difluoro enantiomer stereospecifically inhibited CaMK II-activated Cl- current, but with low potency; however, efficacy of this compound was greatly enhanced by myo-inositol 3,4,5,6-tetrakisphosphate itself. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PL, Lancs, England. Aston Univ, Dept Pharmaceut & Biol Sci, Birmingham B4 7ET, W Midlands, England. NIEHS, Inositide Signaling Sect, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. Univ Cincinnati, Coll Med, Dept Cellular & Mol Physiol, Cincinnati, OH 45267 USA. RP Freeman, S (reprint author), Univ Manchester, Sch Pharm & Pharmaceut Sci, Oxford Rd, Manchester M13 9PL, Lancs, England. RI Freeman, Sally/G-1141-2015 OI Freeman, Sally/0000-0002-3831-9151 NR 23 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUL PY 1998 VL 309 IS 4 BP 337 EP 343 DI 10.1016/S0008-6215(98)00146-3 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 116UD UT WOS:000075742500005 ER PT J AU Shiao, YH Lee, SH Kasprzak, KS AF Shiao, YH Lee, SH Kasprzak, KS TI Cell cycle arrest, apoptosis and p53 expression in nickel(II) acetate-treated Chinese hamster ovary cells SO CARCINOGENESIS LA English DT Article ID INDUCED CARCINOGENESIS; CYTOMETRY; INDUCTION AB Nickel(II) compounds are known human and animal carcinogens, In this study, the effects of nickel(II) acetate on cell cycle, apoptosis and p53 expression were investigated in order to unveil the elements of early cellular responses to the metal, Chinese hamster ovary (CHO) cells were grown for 72 h in Ham's F-12 medium containing 0, 40, 80, 160, 240, 320, 480 or 640 mu M nickel(LI) acetate, DNA fragmentation, representative of apoptosis, was examined by agarose gel electrophoresis, The distribution of cells among various phases of cell cycle was determined by DNA flow cytometry, Expression of p53 protein was measured by the Western blotting technique. DNA fragmentation was detectable in cells treated with greater than or equal to 160 mu M nickel(II) and its intensity increased with increasing nickel(II) concentration. The proportion of cells at S phase declined in a nickel(II) concentration-dependent manner. The decline was accompanied by an increase of cell proportion in G(2)/M phase and the increase became statistically significant in cells exposed to at least 480 mu M nickel(II). Expression of p53 protein was not different from that in the control among samples treated with less than or equal to 480 mu M nickel(II), However, an extra fraction that migrated close to the p53 protein fraction was detected in cells treated with 640 mu M nickel(II). Our findings suggest that nickel(II) modulates cellular response through effecters involved in both G(2)/M arrest and apoptosis regulatory pathways, The proportion of cells arrested at G(2)/M phase or undergoing apoptosis depends directly on nickel(II) concentration. High concentration of nickel(II) appears to up-regulate protein(s) other than the common form of p53 protein. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21702 USA. RP Shiao, YH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21702 USA. EM shiao@ncifcrf.gov NR 23 TC 61 Z9 66 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1998 VL 19 IS 7 BP 1203 EP 1207 DI 10.1093/carcin/19.7.1203 PG 5 WC Oncology SC Oncology GA 101TM UT WOS:000074884300005 PM 9683178 ER PT J AU Snyderwine, EG Davis, CD Schut, HAJ Roberts-Thomson, SJ AF Snyderwine, EG Davis, CD Schut, HAJ Roberts-Thomson, SJ TI Proliferation, development and DNA adduct levels in the mammary gland of rats given 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and a high fat diet SO CARCINOGENESIS LA English DT Article ID SPRAGUE-DAWLEY RATS; FOOD-DERIVED CARCINOGEN; WESTERN-STYLE DIET; HETEROCYCLIC AMINES; BREAST-CANCER; COOKED FOODS; PHIP; 7,12-DIMETHYLBENZANTHRACENE; SUSCEPTIBILITY; RISK AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic amine derived from cooked meat that is a mammary gland carcinogen in rats, A carcinogenic dose-regimen of PhIP (75 mg/kg, p.o., 10 doses, once per day) was administered to 43-day old female Sprague-Dawley rats, and the rats were then placed on a defined high fat (23.5% corn oil) or low fat (5% corn oil) diet for up to 6 weeks. At various times after carcinogen and diet, and prior to carcinogenesis, we examined the percentage of proliferating cells in terminal end bud (TEB) epithelial structures of the rat mammary gland by proliferating cell nuclear antigen staining, mammary gland architecture by whole mounting, and PhIP-DNA adduct levels in mammary epithelial cells by the P-32-post-labeling assay. Immediately after dosing, the percentage of proliferating epithelial cells in TEBs was significantly higher in PhIP-treated rats than in control rats receiving vehicle only [7.5 +/- 0.9% (n = 99) versus 4.2 +/- 0.6% (n = 127), respectively], The mammary glands of PhIP-treated rats showed a significantly lower density of alveolar buds (ABs) and a higher density of TEBs than control rats, which suggests that PhIP exposure partially inhibited the normal glandular differentiation of TEBs to ABs, After 6 weeks on the diet, proliferation in TEBs was statistically higher in rats given PhIP plus a high fat diet than in rats given vehicle plus a low fat diet. The mammary glands from rats on a high fat diet also showed a statistically higher density of TEBs when compared with rats on a low fat diet [2.08 +/- 0.34% versus 1.04 +/- 0.20%, respectively (n = 6)], PhIP-DNA adduct levels were relatively high in mammary epithelial cells of treated rats. At 3 h after the last dose of PhIP, DNA adduct levels [relative adduct labeling (RAL) x 10(7), mean +/- SE] were 10.5 +/- 1.7 (n = 8) and 0.9 +/- 0.2 (n = 7) in epithelial cells isolated from mammary gland and in the liver, respectively, DNA adduct removal rates from the mammary gland were not different between rats on the high fat and low fat diets. Adducts were still detected after 6 weeks on either diet. Thus, events that occurred prior to neoplasia in the mammary glands of PhIP-treated rats include formation of PhIP-DNA adducts at relatively high levels, and enhanced proliferation in TEBs (putative sites of origin of mammary gland carcinomas) and partial inhibition of TEE differentiation. The high fat diet, a promoter of PhIP-induced mammary gland carcinogenesis, appeared to sustain the proliferative effect of PhIP in mammary gland TEBs at a time when PhIP-DNA adducts are still detectable. These early events may contribute to the targeting and carcinogenicity of PhIP to the mammary gland of rats. C1 NCI, Div Basic Sci, Expt Carcinogenesis Lab, Chem Carcinogenesis Sect,NIH, Bethesda, MD 20892 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. RP Snyderwine, EG (reprint author), NCI, Div Basic Sci, Expt Carcinogenesis Lab, Chem Carcinogenesis Sect,NIH, Bldg 37,Room 3C28, Bethesda, MD 20892 USA. RI Roberts-Thomson, Sarah/B-4282-2011 OI Roberts-Thomson, Sarah/0000-0001-8202-5786 NR 51 TC 30 Z9 30 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1998 VL 19 IS 7 BP 1209 EP 1215 DI 10.1093/carcin/19.7.1209 PG 7 WC Oncology SC Oncology GA 101TM UT WOS:000074884300006 PM 9683179 ER PT J AU Weisz, J Fritz-Wolz, G Clawson, GA Benedict, CM Abendroth, C Creveling, CR AF Weisz, J Fritz-Wolz, G Clawson, GA Benedict, CM Abendroth, C Creveling, CR TI Induction of nuclear catechol-O-methyltransferase by estrogens in hamster kidney: Implications for estrogen-induced renal cancer SO CARCINOGENESIS LA English DT Article ID HUMAN BREAST CANCERS; INDUCED CARCINOGENESIS; METABOLIC-ACTIVATION; CELL CARCINOMA; MICROSOMES; MECHANISM; ENZYMES; LOCALIZATION; METHYLATION; EXPRESSION AB Catecholestrogens are postulated to contribute to carcinogenesis by causing DNA damage mediated by reactive oxygen species generated during redox cycling between catechol and quinone estrogens, and by quinone estrogens that can form depurinating adducts, The above hypothesis is based principally on studies of the cancers that develop in renal cortex of hamsters treated with primary estrogens: Hamster kidney can catalyze 2- and it-hydroxylation of estrogens and support their redox cycling, and the kidneys of estradiol-treated hamsters show evidence of oxidative cellular and DNA damage, Here we used immunocyto-chemisty to test the postulate that catechol-O-methyltransferase (COMT), the enzyme that can prevent oxidation of catecholestrogens to their quinone derivatives, would be induced in renal cortex of hamsters treated with estradiol or ethinyl estradiol, In kidneys of control hamsters, COMT was localized in cytoplasm of epithelial cells of proximal convoluted tubules, predominantly in the juxtamedullary region where the estrogen-induced cancers arise, After 2- or 4-weeks of treatment with either estrogen, COMT was seen in epithelial cells of proximal convoluted tubules throughout the cortex, and many cells also showed intense nuclear COMT immunoreactivity, Estradiol-induced renal cancers were negative for COMT, but were surrounded by tubules with intense cytoplasmic and nuclear immunostaining, The nucleus-associated COMT was shown by immunoblot analysis to be the soluble form of the enzyme, Using reverse transcription-polymerase chain reaction amplification, hamster kidney COMT was shown to lack the putative nuclear localization signal sequence present in human COMT. A second phase II enzyme, CuZn-superoxide dismutase (CuZnSOD), was shown by immunocytochemistry to remain extranuclear in proximal convoluted tubules of estrogen-treated hamsters, which indicates entry of COMT into the nucleus to be selective, The findings are consistent with the catechol/quinone estrogen hypothesis of estrogen-induced cancer, while the translocation of the enzyme to the nucleus following estrogen treatment suggests a response to a threat to the genome by electrophilic products of catechols. C1 Penn State Univ, Milton S Hershey Med Ctr, Dept Obstet & Gynecol, Hershey, PA 17033 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Pathol, Hershey, PA 17033 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. Penn State Univ, Milton S Hershey Med Ctr, Cell & Mol Biol Program, Hershey, PA 17033 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Weisz, J (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Dept Obstet & Gynecol, Hershey, PA 17033 USA. FU NCI NIH HHS [R55 CA58739-O1, CA21141-17] NR 41 TC 28 Z9 30 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1998 VL 19 IS 7 BP 1307 EP 1312 DI 10.1093/carcin/19.7.1307 PG 6 WC Oncology SC Oncology GA 101TM UT WOS:000074884300020 PM 9683193 ER PT J AU Shah, AM Sollott, SJ Lakatta, EG AF Shah, AM Sollott, SJ Lakatta, EG TI Physio-pharmacological evaluation of myocardial performance: an integrative approach SO CARDIOVASCULAR RESEARCH LA English DT Review DE contractive function; endothelial function; myocytes; ventricular function ID RAT CARDIAC MYOCYTES; NITRIC-OXIDE SYNTHASE; INTRACELLULAR CALCIUM TRANSIENTS; BETA-ADRENERGIC STIMULATION; PIG VENTRICULAR MYOCYTES; GUINEA-PIG; MYOFILAMENT RESPONSIVENESS; MAMMALIAN HEART; CYTOSOLIC PH; ADULT-RAT C1 Univ Wales Coll Med, Dept Cardiol, Cardiff CF4 4XN, S Glam, Wales. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Shah, AM (reprint author), Univ Wales Coll Med, Dept Cardiol, Heath Pk, Cardiff CF4 4XN, S Glam, Wales. EM shaham2@cf.ac.uk OI Shah, Ajay/0000-0002-6547-0631 NR 85 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JUL PY 1998 VL 39 IS 1 BP 148 EP 154 DI 10.1016/S0008-6363(98)00107-2 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 102JP UT WOS:000074921300012 PM 9764196 ER PT J AU Martinez, A Cuttitta, F Teitelman, G AF Martinez, A Cuttitta, F Teitelman, G TI Expression pattern for adrenomedullin during pancreatic development in the rat reveals a common precursor with other endocrine cell types SO CELL AND TISSUE RESEARCH LA English DT Article DE adrenomedullin; pancreas; development; immunocytochemistry; colocalizations; rat (Sprague Dawley) ID NEURAL CREST ORIGIN; GASTROINTESTINAL-TRACT; INSULIN-SECRETION; ADRENAL-GLAND; PEPTIDE; GLUCAGON; LOCALIZATION; POLYPEPTIDE; PROGENITOR; AUTOCRINE AB Adrenomedullin is an alpha-amidated 52-amino acid peptide involved in many physiological actions, among others the regulation of insulin secretion. Using immunohistochemical methods, we found that adrenomedullin immunoreactivity first appears at day 11.5 of embryonic development in the rat, coinciding with the appearance of pancreatic glucagon. The early appearance of adrenomedullin in the developing pancreas may indicate an active involvement in either the morphogenesis of the organ or its endocrine/paracrine/autocrine hormone regulation during intrauterine life. We also investigated the pattern of colocalizations of adrenomedullin with the other pancreatic hormones. At some point during development all the cell types express adrenomedullin, progressively evolving towards the adult pattern where only the pancreatic polypeptide cells contain a strong immunoreactivity for adrenomedullin. At this point the remaining cells of the islet are, in general, weakly stained. This sequential and time-dependent expression of adrenomedullin suggests a tight regulation similar to that observed for other modulatory substances responsible for embryonic morphogenesis. C1 NCI, Cell & Canc Biol Dept, Div Clin Sci, NIH, Rockville, MD 20850 USA. SUNY Hlth Sci Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA. RP Martinez, A (reprint author), NCI, Cell & Canc Biol Dept, Div Clin Sci, NIH, 9610 Med Ctr Dr,Room 300, Rockville, MD 20850 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 31 TC 26 Z9 27 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JUL PY 1998 VL 293 IS 1 BP 95 EP 100 DI 10.1007/s004410051101 PG 6 WC Cell Biology SC Cell Biology GA 115NP UT WOS:000075671800009 PM 9634601 ER PT J AU Isaacs, JS Hardman, R Carman, TA Barrett, JC Weissman, BE AF Isaacs, JS Hardman, R Carman, TA Barrett, JC Weissman, BE TI Differential subcellular p53 localization and function in N- and S-type neuroblastoma cell lines SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID WILD-TYPE P53; BREAST EPITHELIAL-CELLS; NEURO-BLASTOMA CELLS; TELOMERASE ACTIVITY; CYTOPLASMIC SEQUESTRATION; NUCLEAR-LOCALIZATION; IMMORTAL CELLS; STEM-CELLS; PROTEIN; EXPRESSION AB Neuroblastoma (NB) cells in vitro are capable of bidirectional transdifferentiation, resulting in two distinct, yet reversible, phenotypes of neuroblastic (N-type) and nonneuronal (S-type) Schwann-like cells. Our previous studies suggested that the wild-type p53 protein is subject to differential regulation in a subset of neuronal cell types. To further test this hypothesis, we compared p53 function in three matched pairs of N- and S-type cell lines, each pair originating from an individual NE tumor. Our data show that although p53 remains cytoplasmically sequestered in a punctate pattern in N-type cells after DNA damage, the protein is diffusely distributed in the S-type cells and is additionally capable of translocating to the nucleus and mediating a biological response to this damage. Our data,therefore, suggest that the p53 protein may be differentially regulated by a neuronal cellular environment and that the sequestration of p53 in NE may be reversible. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Toxicol Curriculum, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. RP Weissman, BE (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM Weissman@med.unc.edu FU NCI NIH HHS [CA 63176] NR 81 TC 27 Z9 29 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUL PY 1998 VL 9 IS 7 BP 545 EP 555 PG 11 WC Cell Biology SC Cell Biology GA 102KA UT WOS:000074922400005 PM 9690622 ER PT J AU Olson, DC Deng, CX Hanahan, D AF Olson, DC Deng, CX Hanahan, D TI Fibroblast growth factor receptor 4, implicated in progression of islet cell carcinogenesis by its expression profile, does not contribute functionally SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID ONCOGENE-INDUCED TUMORIGENESIS; EPITHELIAL-CELLS; TRANSGENIC MICE; FGF-RECEPTORS; MULTISTAGE TUMORIGENESIS; EMBRYONAL CARCINOMA; SIGNAL-TRANSDUCTION; HUMAN BREAST; 2ND SIGNAL; FACTOR-II AB Fibroblast growth factor receptor 4 (FGFR4) gene expression is activated in late-stage beta-cell tumors that develop in transgenic mice harboring SV40 large T antigen (Tag) gene that is under the transcriptional control of the insulin promoter (RIP-Tag), The FGFR4 gene was active in cell lines derived from tumors but not in cells derived from hyperplastic islets. We used both gain-of-function and loss-of-function FGFR4 transgenic mice to determine whether FGFR4 modulates islet cell tumorigenesis and, if so, to identify the nature of the effect. Both types of FGFR4 transgenic mice were viable and fertile and developed islet tumors when crossed with RIP-Tag mice. Remarkably, there was no significant perturbation in the tumorigenesis pathway resulting from either chronic up-regulation or absence of FGFR4 gene expression, Analyses included the incidence and size of tumors, rate of cell proliferation, cell density, and life span. We conclude that FGFR4 gene activation is a marker of but is not causal for beta-cell transformation. C1 Univ Calif San Francisco, Hormone Res Inst, San Francisco, CA 94143 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Hanahan, D (reprint author), Univ Calif San Francisco, Hormone Res Inst, Box 0534 HSW1090,513 Parnassus Ave, San Francisco, CA 94143 USA. RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [1F32CA69714] NR 47 TC 19 Z9 19 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUL PY 1998 VL 9 IS 7 BP 557 EP 564 PG 8 WC Cell Biology SC Cell Biology GA 102KA UT WOS:000074922400006 PM 9690623 ER PT J AU Perichon, R Bourre, JM Kelly, JF Roth, GS AF Perichon, R Bourre, JM Kelly, JF Roth, GS TI The role of peroxisomes in aging SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE peroxisome; aging; lipid metabolism; oxidative stress ID RAT-LIVER PEROXISOMES; CHAIN FATTY-ACIDS; ALPHA-LINOLENIC ACID; ACYL-COA OXIDASE; X-LINKED ADRENOLEUKODYSTROPHY; RENAL ZELLWEGER SYNDROME; CHRONIC FOOD RESTRICTION; CLOFIBRATE-TREATED MICE; HUMAN SKIN FIBROBLASTS; FREE-RADICAL THEORY AB Reactive oxygen species and alterations in membrane lipid homeostasis are thought to be important events in aging process and aging-related degenerative diseases. The peroxisome is a small cellular organelle involved in both oxygen and lipid metabolism, and defects in peroxisomal function are associated with major, and often fatal, changes at the neurological level during human development. Recent reports of aging-related changes in peroxisomal function raised the hypothesis that peroxisomes may also have a significant role in the aging process and aging-related degenerative diseases. This review presents the current data on changes in peroxisomal function during aging and discusses the implications of these changes for health. C1 NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Hop Fernand Widal, Lab Neuro Pharmaco Nutr, INSERM, U26, F-75475 Paris 10, France. RP Perichon, R (reprint author), NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 116 TC 39 Z9 41 U1 0 U2 2 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JUL PY 1998 VL 54 IS 7 BP 641 EP 652 DI 10.1007/s000180050192 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 105KK UT WOS:000075072100003 PM 9711231 ER PT J AU Mathews, JM Etheridge, AS Raymer, JH Black, SR Pulliam, DW Bucher, JR AF Mathews, JM Etheridge, AS Raymer, JH Black, SR Pulliam, DW Bucher, JR TI Selective inhibition of cytochrome P450 2E1 in vivo and in vitro with trans-1,2-dichloroethylene SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID RAT HEPATIC CYTOCHROME-P-450; PHENETHYL ISOTHIOCYANATE; IN-VIVO; MONOOXYGENASE ACTIVITIES; NITROSAMINE METABOLISM; GENETIC POLYMORPHISMS; LIVER MICROSOMES; DIALLYL SULFIDE; DISULFIRAM; PYRAZOLE AB The effect of trans-1,2-dichloroethylene (DCE), an inhibitor of cytochrome P450 (P450) 2E1, on the catalytic activities and total content of hepatic P450 was determined in vivo and in vitro. Hepatic microsomes were prepared from groups of rats prior to dosing and at 2, 5, 12, and 24 h postdosing, and total P450 content and the activities of P450 1A2, P450 2A1, P450 2B, P450 2C6, P450 2C11, P450 2D1, P450 2E1, and P450 3A were determined. The lowest dose of DCE that yielded maximal inactivation of P450 2E1 was found to be 100 mg/kg. Significant decreases in total content of P450 or the activities of P450 1A2, P450 2A1, P450 2B, P450 2C6, P450 2C11, P450 2D1, and P450 3A were not observed during the 24 h following administration of DCE (100 mg/kg ip), but P450 2E1 activity was diminished about 65% at 2 and 5 h after DCE treatment and returned to control levels at 24 h. Additionally, there was little or no significant effect on the activities of hepatic cytosolic alcohol dehydrogenase or mitochondrial or microsomal aldehyde dehydrogenases 5 h postdosing. DCE showed the same selectivity for P450 inactivation in vitro, and P450 2E1 activity was inhibited by >80% without affecting the other isozymes. However, DCE (5 mM) also proved to be a good competitive inhibitor of the probe activities of P450 1A2 and P450 2C6. The in vivo inhibition of P450 2E1 was accompanied by decreases in the levels of the immunoreactive protein, and an additional immunoreactive band appeared at ca. 30 kDa in the Western blot of microsomes from DCE-treated rats, possibly arising from proteolytic degradation of P450 2E1 protein after covalent modification by the inhibitor. DCE is an effective, relatively nontoxic inhibitor of P450 2E1 in vivo and in vitro that has greater selectivity than other agents currently used. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Mathews, JM (reprint author), Res Triangle Inst, POB 12194,3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA. EM mathews@rti.org FU NIEHS NIH HHS [N01-ES-4-5380] NR 55 TC 27 Z9 29 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL PY 1998 VL 11 IS 7 BP 778 EP 785 DI 10.1021/tx970227g PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 103XU UT WOS:000074983800014 PM 9671540 ER PT J AU Barlow, T Takeshita, J Dipple, A AF Barlow, T Takeshita, J Dipple, A TI Deamination and Dimroth rearrangement of deoxyadenosine-styrene oxide adducts in DNA SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ALKYLATION PRODUCTS; GUANOSINE; ARALKYLATION; 1-POSITION; EPOXIDES AB In reactions between styrene oxide and the ring nitrogen at the 1-position of deoxyadenosine, the epoxide is opened at both the alpha-(benzylic) and beta-carbons. The 1-substituted nucleosides formed are unstable and subsequently undergo either Dimroth rearrangement to give N-6-substituted deoxyadenosines or deamination to give 1-substituted deoxyinosines. alpha N-6-Substituted compounds are also formed from direct reaction at the exocyclic nitrogen. Kinetic experiments revealed that relative rates of deamination of 1-substituted deoxyadenosine-styrene oxides and 1-substituted adenosine-styrene oxides were similar. However, the rate of Dimroth rearrangement in beta 1-substituted adenosine-styrene oxides was similar to 2.3-fold greater than that of beta 1-substituted deoxyadenosine-styrene oxides and similar to 1.5-fold greater in alpha 1-substituted adenosine-styrene oxides relative to alpha 1-substituted deoxyadenosine-styrene oxides. Analysis of the products formed from reactions of styrene oxide with [H-3]deoxyadenosine and [H-3]deoxyadenosine incorporated into native and denatured DNA showed that; the double-helical DNA structure reduced the levels of adducts formed 5-fold relative to denatured DNA but did not present a complete barrier to formation of either N-6-substituted deoxyadenosine- or 1-substituted deoxyinosine-styrene oxide adducts in native DNA. Additionally, in denatured and native DNA the product distributions were altered in favor of formation of beta 1-substituted deoxyinosine-styrene oxide adducts with respect to reactions of the nucleoside. The ratio of retained to inverted configuration of alpha N-6-substituted products was higher in DNA than in nucleoside reactions. These experiments indicate that in addition to the N-6-position, the ring nitrogen at the 1-position of deoxyadenosine is available, to some extent, for reaction in native DNA. In styrene oxide-DNA reactions, formation of 1-substituted adenines can lead to deaminated products where both Watson-Crick hydrogen-bonding sites are disrupted. C1 NCI, Chem Carcinogenesis Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Barlow, T (reprint author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 2QH, England. NR 32 TC 37 Z9 37 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL PY 1998 VL 11 IS 7 BP 838 EP 845 DI 10.1021/tx980038d PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 103XU UT WOS:000074983800021 PM 9671547 ER PT J AU Barnas, GM Gilbert, TB Krasna, MJ McGinley, MJ Fiocco, M Orens, JB AF Barnas, GM Gilbert, TB Krasna, MJ McGinley, MJ Fiocco, M Orens, JB TI Acute effects of bilateral lung volume reduction surgery on lung and chest wall mechanical properties SO CHEST LA English DT Article DE airways; elastance; resistance; respiratory mechanics ID RESPIRATORY SYSTEM; NORMAL RANGE; EMPHYSEMA; PRESSURE AB Study objectives: To characterize acute changes in the dynamic, passive mechanical propel-ties of the lungs and chest wall, elastance (E) and resistance (R), caused by lung volume reduction surgery (LVRS). Design: Prospective data collection. Patients: Nine anesthetized/paralyzed patients with severe emphysema, Interventions: Bilateral LVRS. Measurements and results: From measurements of airway and esophageal. pressures and flow during mechanical ventilation throughout the physiologic range of breathing frequency (f) and tidal volume (VT), E and R of the total respiratory system (Ers and Rrs), lungs (EL and RL), and chest wall (Ecw and Rcw) immediately before and after LVRS were calculated. After surgery, Ers, EL, Rrs, and RL were all greatly increased at each combination off and VT (p<0.05). Ecw and Rcw showed no consistent changes (p>0.05),The increases in EL were greatest in those patients with the lowest residual volumes, highest FEV, values, and highest maximum voluntary ventilations measured 3 months preoperatively (p<0,05); the increases in RL were greatest in those patients with the lowest preoperative residual volumes (p<0,05). The largest increases in RL mere in those patients with the largest decreases in residual volume and total lung capacity, measured 3 months postoperatively, caused by LVRS (p<0.05). Conclusion: Acute effects of LVRS are large increases in lung elastic tension and resistance; these increases need to be considered in immediate postoperative care, and can be predicted roughly from results of preoperative pulmonary function tests. C1 Univ Maryland, Dept Anesthesiol, Baltimore, MD 21201 USA. Univ Maryland, Dept Physiol, Baltimore, MD 21201 USA. Univ Maryland, Dept Pulm Med, Baltimore, MD 21201 USA. Univ Maryland, Dept Surg, Baltimore, MD 21201 USA. RP Barnas, GM (reprint author), Natl Inst Deafness & Other Commun Disorders, Div Extramural Act, Bethesda, MD 20892 USA. NR 25 TC 8 Z9 8 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 1998 VL 114 IS 1 BP 61 EP 68 DI 10.1378/chest.114.1.61 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 100VY UT WOS:000074837100014 PM 9674448 ER PT J AU Gladwin, MT Plorde, JJ Martin, TR AF Gladwin, MT Plorde, JJ Martin, TR TI Clinical application of the Mycobacterium tuberculosis direct test - Case report, literature review, and proposed clinical algorithm SO CHEST LA English DT Article DE acid-fast; AMPLICOR; Gen-Probe; Mycobacterium avium complex; Mycobacterium tuberculosis; Mycobacterium tuberculosis direct test; nontuberculous mycobacterium ID POLYMERASE CHAIN-REACTION; RESPIRATORY SPECIMENS; RIBOSOMAL-RNA; PULMONARY TUBERCULOSIS; AMPLIFICATION; DIAGNOSIS; COMPLEX; PERFORMANCE; AMPLICOR AB The relatively new Mycobacterium tuberculosis direct test (MTDT) enzymatically amplifies M tuberculosis complex 16s ribosomal RNA, The sensitivity of the test ranges from 75 to 100%, with specificity of 95 to 100%, positive predictive value between 78% and 100%, and negative predictive value between 95% and 100%. Similar test characteristics have been documented in nonrespiratory specimens and in specimens that ultimately grow nontuberculous mycobacterium (NTM), This test allows for rapid identification of M tuberculosis In the smear-positive patient and may greatly improve sensitivity over acid-fast bacilli smear a.lone, A negative test result with a positive smear suggests infection with NTM or Mycobacterium avium complex. We present a case that illustrates the value of MTDT for analysis of tissue specimens in immunocompromised patients with suspected mycobacterial disease and review the rapidly developing literature about this test. We propose an algorithm using MTDT, acid-fast smear, and mycobacterial culture for the diagnosis and treatment of the immunocompromised patient with suspected mycobacterial infection. C1 Dept Vet Affairs Med Ctr, Med Res Serv, Seattle, WA USA. Dept Vet Affairs Med Ctr, Lab Serv, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. RP Gladwin, MT (reprint author), NIH, Bldg 10,Room 7D43,10 Ctr Dr, Bethesda, MD 20892 USA. NR 26 TC 5 Z9 5 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 1998 VL 114 IS 1 BP 317 EP 323 DI 10.1378/chest.114.1.317 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 100VY UT WOS:000074837100053 PM 9674487 ER PT J AU Hildesheim, A Bratti, MC Edwards, RP Schiffman, M Rodriguez, AC Herrero, R Alfaro, M Morera, LA Ermatinger, SV Miller, BT Crowley-Nowick, PA AF Hildesheim, A Bratti, MC Edwards, RP Schiffman, M Rodriguez, AC Herrero, R Alfaro, M Morera, LA Ermatinger, SV Miller, BT Crowley-Nowick, PA TI Collection of cervical secretions does not adversely affect pap smears taken immediately afterward SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID ANTIBODIES AB Collection of cervical secretions for local immunological assessment requires that the secretions be collected prior to the Pap smear to avoid contamination with blood. The objective of the present study was to determine whether gentle collection of cervical secretions prior to a Pap smear collection influences the quality of the Pap smear. A total of 266 women were recruited. Half of the participants were assigned to collection of cervical secretions prior to Pap smear collection with Weck-cel sponges. The remaining half had only the Pap smear collection performed. Pap smear slides were reviewed and evaluated for quality by the Bethesda System adequacy criteria without knowledge of randomization. The proportions of limited or inadequate slides in the two study groups were compared by using the Pearson chi-square test. No significant differences were observed between the two study groups when overall Pap smear quality was evaluated (P = 0.29). Comparison of the two study groups with respect to individual adequacy criteria, including presence of air drying artifact, presence of obscuring blood, absence of metaplastic or endocervical cells from the transformation zone, scant cellularity, and presence of obscuring inflammatory cells, also revealed no significant differences between the two study groups. Results from the present study suggest that the collection of cervical secretions with Weck-cel sponges does not adversely impact the quality of subsequently obtained Pap smears. C1 NCI, Environm Epidemiol Branch, Interdisciplinary Studies Sect, Bethesda, MD 20892 USA. Johns Hopkins Hosp, John K Frost Cytopathol Lab, Baltimore, MD 21287 USA. US Social Secur Adm, San Jose, Costa Rica. Minist Hlth, San Jose, Costa Rica. Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Serv, Pittsburgh, PA 15213 USA. RP Hildesheim, A (reprint author), NCI, Environm Epidemiol Branch, Interdisciplinary Studies Sect, 6130 Execut Blvd,EPN 443, Bethesda, MD 20892 USA. NR 17 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JUL PY 1998 VL 5 IS 4 BP 491 EP 493 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZY123 UT WOS:000074588900013 PM 9665954 ER PT J AU Fedorova, OV Doris, PA Bagrov, AY AF Fedorova, OV Doris, PA Bagrov, AY TI Endogenous marinobufagenin-like factor in acute plasma volume expansion SO CLINICAL AND EXPERIMENTAL HYPERTENSION LA English DT Article; Proceedings Paper CT International Conference on Natriuretic and Digitalis-Like Factors CY JUN 01-02, 1997 CL SAN FRANCISCO, CALIFORNIA SP NIH, CIBA Pharm, BION Inc, Wyeth Ayerst Lab, Inst Ricerche Sigma Tau, Novartis Pharm DE Na/K ATPase; ouabain; marinobufagenin; plasma; pituitary; volume expansion; dog; rat ID DIGITALIS-LIKE FACTORS; OUABAIN-LIKE IMMUNOREACTIVITY; NA,K-ATPASE; HYPOVENTILATION; INHIBITION; RATS AB The aim of the study was to further investigate the nature of endogenous digitalis-like factors stimulated by acute plasma volume expansion (VE). 10 male Fisher 344XNB rats were given intravenous (iv) saline infusion (4% of the body mass) for 30 min, which caused a fall in % hematocrit (35.9+/-0.69 vs. 41.8+/-1.05; vs. 10 controls, P<0.01). EDLF was measured in C-18 reverse-phase extracted (32%+/-80% acetonitrile) tissues. VE was associated with an increase in plasma marinobufagenin-like factor (MLF)(0.49+/-0.05 vs. 0.2+/-0.06 nmol/L, P<0.01) and pituitary ouabain-like compound (OLC) (30.9+/-3.12 vs. 3.2+/-2.3 pmol/g, P<0.01). Plasma OLC decreased (0.087+/-0.018 vs. 0.21+/-0.04 nmol/L, P<0.02), and pituitary MLF did not change (0.05+/-0.01 vs. 0.07+/-0.02 pmol/g) after VE. Chloroform extracted urine from 5 volume-expanded male mongrel dogs was fractionated on reverse-phase HPLC columns in a linear gradient of 0-80% acetonitrile. The material cross-reacting with marinobufagenin antibody eluted from HPLC column as a single peak, demonstrated absorbance at 300 nm, and was distinct from ouabain-like material. Digoxin antibodies interacted with both marinobufagenin-like and ouabain-like immunoreactive material. These results provide further evidence for the presence of a bufodienolide EDLF in the mammals, and demonstrate that EDLF response to VE includes stimulation of brain OLC and plasma bufodienolide. C1 NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. IM Sechenov Evolutionary Physiol & Biochem Inst, St Petersburg 194223, Russia. Univ Texas, Hlth Sci Ctr, Inst Mol Med, Houston, TX 77030 USA. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, 4940 Eastern Ave, Baltimore, MD 21224 USA. FU NIDDK NIH HHS [DDK45538] NR 26 TC 77 Z9 78 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1064-1963 J9 CLIN EXP HYPERTENS JI Clin. Exp. Hypertens. PD JUL-AUG PY 1998 VL 20 IS 5-6 BP 581 EP 591 DI 10.3109/10641969809053236 PG 11 WC Pharmacology & Pharmacy; Peripheral Vascular Disease SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA 100WK UT WOS:000074838200011 PM 9682914 ER PT J AU Gonick, HC Ding, Y Vaziri, ND Bagrov, AY Fedorova, OV AF Gonick, HC Ding, Y Vaziri, ND Bagrov, AY Fedorova, OV TI Simultaneous measurement of marinobufagenin ouabain, and hypertension-associated protein in various disease states. SO CLINICAL AND EXPERIMENTAL HYPERTENSION LA English DT Article; Proceedings Paper CT International Conference on Natriuretic and Digitalis-Like Factors CY JUN 01-02, 1997 CL SAN FRANCISCO, CALIFORNIA SP NIH, CIBA Pharm, BION Inc, Wyeth Ayerst Lab, Inst Ricerche Sigma Tau, Novartis Pharm DE hypertension-associated protein; Na-K-ATPase inhibition ouabain; bufodienolide ID VOLUME-EXPANDED DOGS; HUMAN-PLASMA; STRUCTURAL-ANALYSIS; INHIBITOR; IMMUNOREACTIVITY; EXPANSION AB We have previously demonstrated that a 12 M hypertension-associated protein (HAP) is elevated in essential hypertension and that this protein has the characteristics of natriuresis, inhibition of Na-K-ATPase, displaces H-3-ouabain from binding sites, and is vasoconstrictive je vitro. In the present study, plasma from 101 patients ware examined [25 normals (N)age 50, 7 with acute congestive heart failure (CHF), 24 with chronic renal failure (CRP),on dialysis, 5 with idiopathic hyperaldosteronism (PA) and essential hypertension, untreated (EHT)]. Plasma was extracted with 32% acetonitrile, then analyzed by DELFIA for marinobufagenin and ouabain. In addition, from 32 patients (6 N <50, 6 N >50, 5 CHF, 5 CRF, 6 EHT, and 4 PA) SDS gradient gels were obtained. The 12 kD bands were extracted, analyzed for Na-K-ATPase inhibition, marinobufagenin and ouabain, and compared to 14 kD and 21 kD bands. Marinobufagenin was found to be elevated in CRF, EHT, PA and CHF. Ouabain was increased only in PA. When the relative optical densities of the 12 kD and 21 kD bands were contrasted, CRF, PA, and EHT were found to be increased and CHF to be decreased in the 12 kD band, with no discernible changes in the 21 kD bands. Following extraction of the bands, Na-K-ATPase inhibitory activity measured 38% in 18 pooled 12 kD bands, with essentially no activity found in the 14 kD or 21 kD bands. only the 12 kD HAP band possessed all of the attributes of natriuretic hormone. C1 Cedars Sinai Med Ctr, Burns & Allen Res Inst, Los Angeles, CA 90048 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92868 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Gonick, HC (reprint author), Cedars Sinai Med Ctr, Burns & Allen Res Inst, 8700 Beverly Blvd, Los Angeles, CA 90048 USA. FU NHLBI NIH HHS [1R13 HL58538-01] NR 21 TC 77 Z9 78 U1 1 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1064-1963 J9 CLIN EXP HYPERTENS JI Clin. Exp. Hypertens. PD JUL-AUG PY 1998 VL 20 IS 5-6 BP 617 EP 627 DI 10.3109/10641969809053240 PG 11 WC Pharmacology & Pharmacy; Peripheral Vascular Disease SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA 100WK UT WOS:000074838200015 PM 9682918 ER PT J AU Takao, S Takebayashi, Y Che, XM Shinchi, H Natsugoe, S Miyadera, K Yamada, Y Akiyama, S Aikou, T AF Takao, S Takebayashi, Y Che, XM Shinchi, H Natsugoe, S Miyadera, K Yamada, Y Akiyama, S Aikou, T TI Expression of thymidine phosphorylase is associated with a poor prognosis in patients with ductal adenocarcinoma of the pancreas SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL GROWTH-FACTOR; HUMAN COLORECTAL-CARCINOMA; GASTRIC-CARCINOMA; ANGIOGENIC FACTOR; TUMOR ANGIOGENESIS; BREAST-CANCER; METASTASIS; PURIFICATION; NEOVASCULARIZATION; ANTIBODIES AB Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor and has angiogenic activity. In this study, we investigated the expression of dThdPase in ductal adenocarcinoma of the pancreas and examined the correlation between dThdPase expression and clinicopathological factors and clinical outcome. dThdPase expression was demonstrated by immunohistochemistry in the cytoplasm of tumor cells in 59% of the 54 patients studied. The expression of dThdPase correlated significantly with a poor prognosis (P = 0.013), Significant correlations were also observed between dThdPase expression and extrapancreatic neural plexus invasion and the presence of postoperative hepatic metastases (P = 0.05 and 0.03, respectively). The average microvessel count in dThdPase-positive tumors was significantly higher than that in dThdPase-negative tumors (P < 0,0001). These findings suggest that dThdPase expression in pancreatic adenocarcinoma enhances the abilities of tumor invasion and/or metastasis through its angiogenic properties. C1 Kagoshima Univ, Sch Med, Inst Canc Res, Dept Surg 1, Kagoshima 890, Japan. Kagoshima Univ, Sch Med, Inst Canc Res, Dept Canc Chemotherapy, Kagoshima 890, Japan. NIH, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Xian Med Univ, Dept Surg, Xian 710061, Peoples R China. Taisho Pharmaceut Co Ltd, Omiya, Saitama 357, Japan. RP Takao, S (reprint author), Kagoshima Univ, Sch Med, Inst Canc Res, Dept Surg 1, Sakuragaoka 8-35-1, Kagoshima 890, Japan. EM sonshin@med6.kufm.kagoshima-u.ac.jp NR 49 TC 67 Z9 68 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 1998 VL 4 IS 7 BP 1619 EP 1624 PG 6 WC Oncology SC Oncology GA ZY111 UT WOS:000074587700006 PM 9676835 ER PT J AU Zhou, J Mulshine, JL Ro, JY Avis, I Yu, R Lee, JJ Morice, R Lippman, SM Lee, JS AF Zhou, J Mulshine, JL Ro, JY Avis, I Yu, R Lee, JJ Morice, R Lippman, SM Lee, JS TI Expression of heterogeneous nuclear ribonucleoprotein A2/B1 in bronchial epithelium of chronic smokers SO CLINICAL CANCER RESEARCH LA English DT Article ID LUNG-CANCER DETECTION; RESPIRATORY EPITHELIUM; SMALL-CELL; SPUTUM; CHEMOPREVENTION; CARCINOMA; PROTEIN; ISOTRETINOIN; RETINOIDS; CYTOLOGY AB The monoclonal antibody 703D4, which binds heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1), has been reported to detect lung cancer more than a year earlier than routine chest X-ray or cytomorphology, To explore the biological basis of this detection, we studied the expression of this antigen in the central airways of smokers with evidence of bronchial metaplasia using specimens from a previously reported, randomized retinoid chemoprevention trial. By analyzing 1078 available biopsy specimens from 147 individuals at baseline and 68 individuals who completed the intervention, we frequently detected overexpression of hnRNP A2/B1 in normal and abnormal bronchial epithelium (i.e., in 41% of normal and 37% of squamous metaplasia samples), There was Ho correlation between hnRNP A2/B1 overexpression and the different histological changes. In cases with hnRNP A2/B1 overexpression, immunoreactivity was homogeneously expressed in all biopsied sites, For the 68 cases with serial biopsies, there was no significant modulation of hnRNP expression by retinoid intervention or smoking status. With lung cancer cell lines, 0.5-4 mu M concentrations of 13-cis-retinoic acid reduced hnRNP A2/B1 overexpression by immunocytochemistry. We conclude that hnRNP A2/B1 overexpression is frequently found in central airways of chronic smokers, consistent with the pattern of expression that we reported previously in airways surrounding resected primary lung cancers. Oral 13-cis-retinoic acid at a dose of 1 mg/kg has no demonstrable effects on modulating hnRNP A2/B1 expression in proximal bronchial epithelium. C1 NCI, Intervent Sect, Cell & Canc Biol Dept, Med Branch,Div Clin Sci, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Pathol, Houston, TX 77030 USA. RP Mulshine, JL (reprint author), NCI, Intervent Sect, Cell & Canc Biol Dept, Med Branch,Div Clin Sci, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mulshinej@bprb.nci.nih.gov NR 42 TC 29 Z9 38 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 1998 VL 4 IS 7 BP 1631 EP 1640 PG 10 WC Oncology SC Oncology GA ZY111 UT WOS:000074587700008 PM 9676837 ER PT J AU Weil, RJ Vortmeyer, AO Huang, S Boni, R Lubensky, IA Pack, S Marx, SJ Zhuang, ZP Oldfield, EH AF Weil, RJ Vortmeyer, AO Huang, S Boni, R Lubensky, IA Pack, S Marx, SJ Zhuang, ZP Oldfield, EH TI 11q13 allelic loss in pituitary tumors in patients with multiple endocrine neoplasia syndrome type 1 SO CLINICAL CANCER RESEARCH LA English DT Article ID RETINOBLASTOMA GENE; ADENOMAS; MUTATIONS; DISEASE; CHROMOSOME-11; ORIGIN; MEN-1 AB Pituitary adenomas may develop sporadically or as part of the multiple endocrine neoplasia type 1 (MEN 1) syndrome. The gene responsible for MEN 1 syndrome was recently identified and cloned. Low rates of MEN 1 gene mutations and deletions have been reported in sporadic pituitary adenomas, To elucidate the role of the MEN 1 gene in the pathogenesis of MEN 1-associated pituitary tumors, we examined pituitary adenomas from 11 MEN 1 patients for the presence of 11q13 allelic loss. Ten of the 11 pituitary tumors were informative by PCR-based loss of heterozygosity analysis. Using a combination of family pedigree analysis and restriction analysis directed at the mutated allele in 8 of the 10 informative cases, it was demonstrated in all 8 cases that it is the wild-type allele that undergoes deletion. All 11 tumors, 4 of which were growth hormone secreting, were additionally analyzed for mutation in the Gs alpha subunit (gsp) gene, None of the tumors (0 of 11 tumors) revealed a gsp gene mutation. Therefore, genetic alterations of the MEN 1 gene seem to play a dominant role in MEN 1-associated pituitary tumorigenesis, whereas gsp gene mutations do not seem to be a frequent event in either growth hormone-secreting or other types of MEN 1-associated pituitary tumors. These results suggest that MEN 1-associated pituitary tumors develop via genetic pathways that differ from those of most sporadic pituitary tumors. C1 NINCDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weil, RJ (reprint author), NINCDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D 37, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 35 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 1998 VL 4 IS 7 BP 1673 EP 1678 PG 6 WC Oncology SC Oncology GA ZY111 UT WOS:000074587700012 PM 9676841 ER PT J AU Khumalo, H Gomo, ZAR Gangaidzo, IT Moyo, VM Mandishona, E Saungweme, T Rouault, TA Gordeuk, VR MacPhail, AP AF Khumalo, H Gomo, ZAR Gangaidzo, IT Moyo, VM Mandishona, E Saungweme, T Rouault, TA Gordeuk, VR MacPhail, AP TI Effect of ascorbic acid administration on serum concentration of transferrin receptors SO CLINICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; IRON-METABOLISM; FERRITIN C1 Univ Zimbabwe, Sch Med, Dept Chem Pathol, Avondale Harare, Zimbabwe. Univ Zimbabwe, Sch Med, Dept Med, Avondale Harare, Zimbabwe. George Washington Univ, Med Ctr, Dept Med, Div Hematol & Oncol, Washington, DC 20037 USA. Univ Witwatersrand, Dept Med, ZA-2196 Parktown, Johannesburg, South Africa. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Gomo, ZAR (reprint author), Univ Zimbabwe, Sch Med, Dept Chem Pathol, Box A178, Avondale Harare, Zimbabwe. FU NICHD NIH HHS [1-HD 3-3196] NR 22 TC 4 Z9 5 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUL PY 1998 VL 44 IS 7 BP 1573 EP 1575 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA ZX975 UT WOS:000074574200038 PM 9665447 ER PT J AU Segal, BM Shevach, EM AF Segal, BM Shevach, EM TI The straight talk on immune deviation SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Editorial Material ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INTERFERON-GAMMA; TH2 CELLS; INDUCTION; CYTOKINES C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Segal, BM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Segal, Benjamin/0000-0002-0906-6319 NR 23 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD JUL PY 1998 VL 88 IS 1 BP 1 EP 3 DI 10.1006/clin.1998.4559 PG 3 WC Immunology; Pathology SC Immunology; Pathology GA 110EL UT WOS:000075367100001 PM 9683543 ER PT J AU Caspi, NR AF Caspi, NR TI IL-12 in autoimmunity SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Review ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TRANSFORMING GROWTH FACTOR-BETA-1; CELL STIMULATORY FACTOR; INTERFERON-GAMMA-PRODUCTION; COLLAGEN-INDUCED ARTHRITIS; BLOOD MONONUCLEAR-CELLS; TUMOR-NECROSIS-FACTOR; IFN-GAMMA; IN-VIVO; T-CELLS C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. RP Caspi, NR (reprint author), NEI, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA. NR 117 TC 43 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD JUL PY 1998 VL 88 IS 1 BP 4 EP 13 PG 10 WC Immunology; Pathology SC Immunology; Pathology GA 110EL UT WOS:000075367100002 ER PT J AU Levine, PH Whiteside, TL Friberg, D Bryant, J Colclough, G Herberman, RB AF Levine, PH Whiteside, TL Friberg, D Bryant, J Colclough, G Herberman, RB TI Dysfunction of natural killer activity in a family with chronic fatigue syndrome SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE chronic fatigue syndrome; natural killer cells; NK activity; familial CFS ID CELL-ACTIVITY; CYTO-TOXICITY; IMMUNOLOGICAL ABNORMALITIES; STRESS; CANCER; DEFINITION; INFECTION; MELANOMA AB A family was identified with 5 of 6 siblings and 3 other immediate family members who had developed chronic fatigue syndrome (CFS) as adults. All 8 met criteria for the CFS case definition as recommended by the Centers for Disease Control and Prevention. Sixty-eight blood samples were obtained over a period of 2 years from 20 family members (8 affected, 12 unaffected) and 8 normal controls. All blood samples were tested for NK activity in 4-h Cr-51-release assays and for the number of circulating CD3-CD56(+) and CD3-CD16(+) by flow cytometry. NK activity of the affected immediate family members (cases, n = 8) was significantly lower (P = 0.006, two-sided) than that of the concurrently tested normal controls. The results for unaffected family members were intermediate between these two groups, and the pairwise comparison of unaffected family members to either cases or controls showed no statistically significant difference (P = 0.29, two-sided). No differences were seen between the groups in the absolute number of CD3-CD56(+) or CD3-CD16(+) lymphocytes in the peripheral blood. Familial CFS was associated with persistently low NR activity, which was documented in 6/8 cases and in 4/12 unaffected family members. In the family with 5 of 6 siblings who had documented CFS, 2 of their offspring had pediatric malignancies. Low NR activity in this family may be a result of a genetically determined immunologic abnormality predisposing to CFS and cancer. C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA 15213 USA. Res Triangle Inst, Rockville, MD 20892 USA. RP Levine, PH (reprint author), NCI, Viral Epidemiol Branch, EPN 434, Bethesda, MD 20892 USA. NR 32 TC 29 Z9 32 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD JUL PY 1998 VL 88 IS 1 BP 96 EP 104 DI 10.1006/clin.1998.4554 PG 9 WC Immunology; Pathology SC Immunology; Pathology GA 110EL UT WOS:000075367100014 PM 9683556 ER PT J AU Tassiulas, IO Aksentijevich, I Salmon, JE Kim, Y Yarboro, CH Vaughan, EM Davis, JC Scott, DL Austin, HA Klippel, JH Balow, JE Gourley, MF Boumpas, DT AF Tassiulas, IO Aksentijevich, I Salmon, JE Kim, Y Yarboro, CH Vaughan, EM Davis, JC Scott, DL Austin, HA Klippel, JH Balow, JE Gourley, MF Boumpas, DT TI Angiotensin I converting enzyme gene polymorphisms in systemic lupus erythematosus: decreased prevalence of DD genotype in African American patients SO CLINICAL NEPHROLOGY LA English DT Article DE activity index; chronicity index; lupus nephritis; race ID INSERTION DELETION POLYMORPHISM; ESSENTIAL-HYPERTENSION; MYOCARDIAL-INFARCTION; CONTROLLED TRIAL; IGA NEPHROPATHY; RENAL-DISEASE; NEPHRITIS; RISK; ASSOCIATION; METHYLPREDNISOLONE AB The presence of the D (deletion) allele at the angiotensin converting enzyme (ACE) gene has been associated with a) adverse Vascular events contributing to early mortality and b) progressive deterioration of renal function in a variety of chronic glomerular diseases, We investigated the potential role of ACE polymorphisms in patients with systemic lupus erythematosus (SLE). Two hundred and sixteen (216) SLE patients (121 Caucasians; 78 African Americans; and 17 other) and 200 normal controls were studied, 134 patients had evidence of renal disease. ACE genotypes were determined by a polymerase chain reaction based assay. The frequency of genotype DD was increased in African American normal controls compared to Caucasians (55% vs. 37%, p = 0.017) and in African American normal controls vs. African American Iupus patients (55% vs, 30%, D = 0.008), Trend analysis of the genotype distribution across the three African American groups (renal, non-renal, controls) revealed a trend of increased frequency of I and decreased frequency of D as Likelihood of renal disease increases (p = 0.008). No association between any ACE genotype with parameters of renal disease and/or response to therapy was identified. African American patients with Iupus have a lower frequency of DD genotype as compared to African American normal controls. Further studies will be necessary to address whether this is due to decreased survival of these patients, a protective effect of DD genotype from developing the disease or a chance sample effect. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Dept Nursing, Ctr Clin, NIH, Bethesda, MD 20892 USA. NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. Hosp Special Surg, New York, NY 10021 USA. RP Tassiulas, IO (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bldg 10,Rm 9S209,10 Ctr Dr MSC 1828, Bethesda, MD 20892 USA. NR 29 TC 26 Z9 27 U1 0 U2 2 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD JUL PY 1998 VL 50 IS 1 BP 8 EP 13 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA ZZ267 UT WOS:000074712300002 PM 9710341 ER PT J AU Heldt, N Boellaard, JW Brown, P Cervenakova, L Doerr-Schott, J Thomas, C Scherer, C Rohmer, F AF Heldt, N Boellaard, JW Brown, P Cervenakova, L Doerr-Schott, J Thomas, C Scherer, C Rohmer, F TI Gerstmann-Straussler-Scheinker disease with A117V mutation in a second French-Alsatian family SO CLINICAL NEUROPATHOLOGY LA English DT Article DE GSS; amyloid plaques; kuru plaques; A117V mutation ID CREUTZFELDT-JAKOB DISEASE; AMYLOID PLAQUES; PRION PROTEIN; SPONGIFORM ENCEPHALOPATHIES; DEMENTIA; VARIANT AB We report a kindred of French/Alsatian origin with symptoms of Gerstmann-Straussler-Scheinker disease over 3 generations. In the propositus, cerebellar signs and memory disturbance were the presenting features, followed by other neurological manifestations. Biopsy of the cerebral cortex showed numerous multicentric and "kuru"-type amyloid plaques that on immune-light and electron microscopy stained with antibody to prion protein. Molecular genetic analysis revealed an A117V mutation in the open reading frame of the prion protein gene. Questions as to pathology and spread of this mutation are discussed. C1 Hop Hautepierre, Serv Anat Pathol Gen, F-67098 Strasbourg, France. Univ Tubingen, Inst Hirnforsch, Tubingen, Germany. NINDS, CNS Studies Lab, NIH, Bethesda, MD 20892 USA. Hop Bel Air, Serv Neurol, Thionville, France. Hop Civil, Serv Neurol, Strasbourg, France. RP Heldt, N (reprint author), Hop Hautepierre, Serv Anat Pathol Gen, F-67098 Strasbourg, France. NR 21 TC 6 Z9 6 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0722-5091 J9 CLIN NEUROPATHOL JI Clin. Neuropathol. PD JUL-AUG PY 1998 VL 17 IS 4 BP 229 EP 234 PG 6 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 100QF UT WOS:000074826300010 PM 9707339 ER PT J AU Dunn, RT Frye, MS Kimbrell, TA Denicoff, KD Leverich, GS Post, RM AF Dunn, RT Frye, MS Kimbrell, TA Denicoff, KD Leverich, GS Post, RM TI The efficacy and use of anticonvulsants in mood disorders SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE anticonvulsants; mood disorders ID NEWER ANTIEPILEPTIC DRUGS; BIPOLAR AFFECTIVE-DISORDER; MANIC-DEPRESSIVE ILLNESS; TRANSCRANIAL MAGNETIC STIMULATION; REFRACTORY AFFECTIVE-DISORDERS; LITHIUM CARBONATE PROPHYLAXIS; THYROTROPIN-RELEASING-HORMONE; SPONTANEOUSLY EPILEPTIC RATS; AMYGDALA-KINDLED SEIZURES; TREATMENT-RESISTANT MANIA AB Carbamazepine and valproate have utility in the acute and prophylactic treatment of mood disorders that appears comparable with that of lithium, but there are emerging differences as well, including responsiveness in some lithium-nonresponsive illness subtypes. Carbamazepine and valproate are generally well tolerated, but each has its own adverse effect profile and proclivity for pharmacokinetic interactions. The high potency (anticonvulsant) benzodiazepines have utility in mood disorders as adjuncts to mood stabilizers and often can obviate the need for neuroleptics. Several small studies suggest that the dihydropyridine L-type calcium channel blockers can be useful mood stabilizers, and several new antiepileptic agents, especially lamotrigine and gabapentin, may have mood-stabilizing properties. The actions of electroconvulsive therapy as they relate to activation of endogenous anticonvulsant processes, and the potential therapeutic effects of nonconvulsive repeated transcranial magnetic stimulation of brain, are promising areas of mood disorder research. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Dunn, RT (reprint author), NIMH, Biol Psychiat Branch, 10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 335 TC 39 Z9 39 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD JUL-AUG PY 1998 VL 21 IS 4 BP 215 EP 235 PG 21 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 107QX UT WOS:000075221700002 PM 9704164 ER PT J AU Deutsch, SI Mastropaolo, J Powell, DG Rosse, RB Bachus, SE AF Deutsch, SI Mastropaolo, J Powell, DG Rosse, RB Bachus, SE TI Inbred mouse strains differ in their sensitivity to an antiseizure effect of MK-801 SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE MK-801; seizures; genetics ID ANTAGONISTS; BINDING AB The ability of MK-801 to antagonize the electrical precipitation of tonic hindlimb extension was studied in four inbred mouse strains (BALB/c, C57BL/6, AKR, and DBA/2) and the outbred NM Swiss strain, using an incremental electroconvulsive shock (IECS) procedure. Strains differed in the threshold voltages required for the electrical precipitation of tonic hindlimb extension. They also differed in their sensitivity to antagonism of electrically precipitated tonic hindlimb extension by MK-801. The BALB/c, C57BL, and DBA strains required a significant elevation of the threshold voltage for the elicitation of tonic hindlimb extension in response to 0.18 mg/kg of MK-801, the lowest dose tested; whereas the AKR and NIH Swiss strains did not respond to this dose with an increase of threshold voltage for the elicitation of tonic hindlimb extension. Moreover, a higher percentage of BALB/c mice were maximally protected against seizure elicitation by MK-801 over a dosage range of 0.18 to 0.56 mg/kg, compared to the other strains. The demonstration of strain differences suggests that genetic factors influence the anticonvulsant properties of MK-801. C1 Dept Vet Affairs Med Ctr, Psychiat Serv 116A, Washington, DC 20422 USA. Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. NIMH, Clin Brain Disorders Branch, NIH, Neurosci Ctr & St Elizabeths, Washington, DC USA. RP Deutsch, SI (reprint author), Dept Vet Affairs Med Ctr, Psychiat Serv 116A, 50 Irving St NW, Washington, DC 20422 USA. NR 7 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD JUL-AUG PY 1998 VL 21 IS 4 BP 255 EP 257 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 107QX UT WOS:000075221700006 PM 9704168 ER PT J AU Bradham, DM Horton, WE AF Bradham, DM Horton, WE TI In vivo cartilage formation from growth factor modulated articular chondrocytes SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID FACTOR-BETA; LIMB BUD; COLLAGEN; MATRIX; CHONDROGENESIS; CULTURE; EMBRYO; AGE; EXPRESSION; SEQUENCES AB Recent procedures for autologous repair of cartilage defects may be difficult in elderly patients because of the loss of stem cells and chondrocytes that occurs with age and the slow in vitro proliferation of chondrocytes from aged cartilage. In this study secondary chondroprogenitor cells were obtained by modulating the phenotype of articular chondrocytes with growth factors and stimulating the proliferation of these cells in culture, Chondrocytes isolated from the articular cartilage of mature New Zealand White rabbits were exposed to a combination of transforming growth factor beta and basic fibroblast growth factor treatment, These cells ceased the production of Collagen II (a marker for the chondrocyte phenotype) and underwent a 136-fold increase in cell number. Next, the cells were placed in high density culture and reexpressed the chondrocyte phenotype in vitro and formed hyaline cartilage in an in vivo assay. Primary chondrocytes obtained from articular cartilage of elderly humans could be manipulated in a similar fashion in vitro. These human secondary chondroprogenitor cells formed only cartilage tissue when assayed in vivo and in tissue bioreactors. This approach may be essential for autologous repair of degenerated articular cartilage in elderly patients with osteoarthritis. C1 NIA, Biol Chem Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Horton, WE (reprint author), NIA, Biol Chem Lab, Gerontol Res Ctr, NIH, ML 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 32 TC 30 Z9 32 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUL PY 1998 IS 352 BP 239 EP 249 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA ZZ288 UT WOS:000074714400028 PM 9678053 ER PT J AU Castle, PE Hoen, TE Whaley, KJ Cone, RA AF Castle, PE Hoen, TE Whaley, KJ Cone, RA TI Contraceptive testing of vaginal agents in rabbits SO CONTRACEPTION LA English DT Article DE rabbit; vaginal agents; contraception; antifertility ID SPERM TRANSPORT; MONOCLONAL-ANTIBODIES; REPRODUCTIVE-TRACT; FEMALE RABBIT; PREGNANCY; WOMEN; INHIBITORS; FERTILITY; DISEASE; ACROSIN AB Development of new vaginal products, such as microbiocides and contraceptives, requires in vivo testing of their effect on fertility. Rabbits, unlike smaller laboratory animals such as rats and mice, which inseminate in the uterus, inseminate vaginally and thus are valuable as animal models for testing vaginal agents for contraceptive effects. Rabbits are inexpensive and easy to handle compared to nonhuman primates, and have frequently been used for testing the effects of vaginal agents on fertility. We review the pertinent literature and report findings that provide guidance for effectively using and improving the rabbit contraceptive model in testing new vaginal products. (C) 1998 Elsevier Science Inc. All rights reserved. C1 Johns Hopkins Univ, Thomas C Jenkins Dept Biophys, Baltimore, MD USA. RP Castle, PE (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 6,Room B1-26,6 Ctr Dr,MSC 2715, Bethesda, MD 20892 USA. EM pc95p@nih.gov FU NIGMS NIH HHS [GM-43873] NR 53 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD JUL PY 1998 VL 58 IS 1 BP 51 EP 60 DI 10.1016/S0010-7824(98)00059-6 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 115FT UT WOS:000075653400009 PM 9743897 ER PT J AU Varma, A Kwon-Chung, KJ AF Varma, A Kwon-Chung, KJ TI Construction of stable episomes in Cryptococcus neoformans SO CURRENT GENETICS LA English DT Article DE transformation; yeast; plasmids; Cryptococcus neoformans ID AUTONOMOUS REPLICATION; YEAST TELOMERES; FOREIGN DNA; TRANSFORMATION; SEQUENCES; GENE; VIRULENCE; PLASMIDS AB We report the generation of stable plasmids constructed by inserting specific DNA sequences into previously known unstable vectors. These sequences were obtained from a DNA library recovered from a previously reported stable minichromosome created by electroporative transformation in Cryptococcus neoformans (Varma and Kwon-Chung 1994). A 6-kb insert from this minichromosome significantly enhanced both the frequencies at which URA5 transformants were obtained as well as the stability of their uracil prototrophy on non-selective media. A 1.5-kb sequence of this insert contained telomeric sequence repeats which when introduced into plasmids resulted in significant increases in transformation frequency. A 1081-bp sequence (STAB), present in the remainder of the insert, had an ARS-like function enhancing the episomal maintenance of plasmids in the transformants regardless of the gene (ADE2/URA5) used as a selection marker. C1 NIAID, Mol Microbiol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. NR 24 TC 17 Z9 18 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0172-8083 J9 CURR GENET JI Curr. Genet. PD JUL PY 1998 VL 34 IS 1 BP 60 EP 66 DI 10.1007/s002940050366 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 109FH UT WOS:000075310300007 PM 9683676 ER PT J AU Hu, WS Hayes, MM Wang, RYH Shih, JWK Lo, SC AF Hu, WS Hayes, MM Wang, RYH Shih, JWK Lo, SC TI High-frequency DNA rearrangements in the chromosomes of clinically isolated Mycoplasma fermentans SO CURRENT MICROBIOLOGY LA English DT Article ID GENETIC ELEMENT; IDENTIFICATION; SEQUENCES; AIDS AB Mycoplasma fermentans is currently being examined as an agent potentially associated with human disease. Several strains of M. fermentans were isolated from patients with respiratory tract disease and AIDS. Two of these clinical strains, M64 and SK6, were triple-filter-cloned and designated as the parental clones in this study. Genomic DNA of randomly picked subclones in four and five subsequent generations passed from the parental M64 and SK6 clones were analyzed by using a radiolabeled M. fermentans-specific insertion sequence (IS)-like element as the probe. The hybridization patterns of DNA restriction fragments revealed high frequencies of chromosomal changes accompanied with excision or new insertion of the IS-like element in M. fermentans chromosome. The findings indicate M. fermentans has an effective mechanism(s) to produce a rapid gene rearrangement that may be mediated by one or more copies of the IS-like element. C1 Armed Forces Inst Pathol, Dept Infect & Parasit Dis Pathol, Amer Registry Pathol, Washington, DC 20306 USA. Natl Yang Ming Univ, Sch Med Technol & Engn, Inst Biotechnol Med, Taipei 11221, Taiwan. Natl Yang Ming Univ, Sch Med Technol & Engn, Fac Med Technol, Taipei 11221, Taiwan. NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Lo, SC (reprint author), Armed Forces Inst Pathol, Dept Infect & Parasit Dis Pathol, Amer Registry Pathol, Bldg 54,Room 4091, Washington, DC 20306 USA. FU NIAID NIH HHS [R01 AI-31830] NR 15 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD JUL PY 1998 VL 37 IS 1 BP 1 EP 5 DI 10.1007/s002849900327 PG 5 WC Microbiology SC Microbiology GA ZV040 UT WOS:000074262300001 PM 9625781 ER PT J AU Rankin, TL Tong, ZB Castle, PE Lee, E Gore-Langton, R Nelson, LM Dean, J AF Rankin, TL Tong, ZB Castle, PE Lee, E Gore-Langton, R Nelson, LM Dean, J TI Human ZP3 restores fertility in Zp3 null mice without affecting order-specific sperm binding SO DEVELOPMENT LA English DT Article DE order-specific sperm binding; Zona pellucida; human fertilization; mouse fertility; sperm-egg interaction; transgene; mouse ID ZONA-PELLUCIDA PROTEIN; O-LINKED OLIGOSACCHARIDES; RECEPTOR ACTIVITY; ACROSOME REACTION; MONOCLONAL-ANTIBODIES; MOUSE OOCYTES; EGG ENVELOPE; STRUCTURAL-ANALYSIS; GLYCOPROTEIN ZP3; CROSS-REACTIVITY AB The mammalian zona pellucida surrounding ovulated eggs mediates sperm binding at fertilization, provides a postfertilization block to polyspermy, and facilitates passage of pre-implantation embryos down the oviduct, Although the three zona proteins (ZP1, ZP2, ZP3) are well conserved, mammalian fertilization is relatively specific and human sperm do not bind to the mouse zona pellucida, There are considerable in vitro data that ZP3 acts as a primary sperm adhesion molecule in mice and, by analogy, a similar role has been postulated for human ZP3, Genetically altered mice lacking ZP3 (Zp3(tm/tm)) do not form a zona pellucida and are infertile, To rescue this phenotype, transgenic mice expressing human ZP3 (67% identical to mouse ZP3) were produced and bred with Zp3(tm/tm) null mice. The resultant human ZP3 rescue females had chimeric zonae pellucidae composed of mouse ZP1, mouse ZP2 and human ZP3, Human ZP3 expressed in mouse oocytes had an apparent mass (64 kDa) indistinguishable from native human ZP3 and distinct from mouse ZP3 (83 kDa). Despite the presence of human ZP3? human sperm did not bind to the chimeric zona pellucida, and notwithstanding the absence of mouse ZP3, mouse sperm bound to ovulated eggs in vitro and fertility was restored in vivo. These data have implications regarding the molecular basis of mouse and human sperm binding to their respective zonae pellucidae. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Suburban Hosp, Dept Reprod Med, Bethesda, MD 20892 USA. RP Rankin, TL (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 65 TC 127 Z9 138 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1998 VL 125 IS 13 BP 2415 EP 2424 PG 10 WC Developmental Biology SC Developmental Biology GA 102ZQ UT WOS:000074956500007 PM 9609824 ER PT J AU Harfe, BD Branda, CS Krause, M Stern, MJ Fire, A AF Harfe, BD Branda, CS Krause, M Stern, MJ Fire, A TI MyoD and the specification of muscle and non-muscle fates during postembryonic development of the C-elegans mesoderm SO DEVELOPMENT LA English DT Article DE MyoD; C-elegans; muscle; coelomocyte; vulval muscle; hlh-1; lin-12 ID CAENORHABDITIS-ELEGANS; GENE FAMILY; CELL FATES; MYOGENIC CONVERSION; HOMOLOG HLH-1; HOMEOTIC GENE; UP-REGULATION; EXPRESSION; MYF-5; NEMATODE AB Basic-helix-loop helix factors of the myoD/myf5/myogenin/MRF4 family have been implicated in acquisition and elaboration of muscle cell fates. Here we describe both myogenic and non-myogenic roles for the Caenorhabditis elegans member of this family (CeMyoD) in postembryonic mesodermal patterning. The postembryonic mesodermal lineage in C, elegans provides a paradigm for many of the issues in mesodermal fate specification: a single mesoblast ('M') divides to generate 14 striated muscles, 16 non-striated muscles, and two non-muscle cells. To study CeMyoD function in the M lineage, we needed to circumvent an embryonic requirement for the protein. Two approaches were used: (1) isolation of mutants that decrease CeMyoD levels while retaining viability, and (2) analysis of genetic mosaics that had lost CeMyoD in the M lineage. With either manipulation, we observed a series of cell-fate transformations affecting a subset of both striated muscles and non-muscle cells. In place of these normal fates, the affected lineages produced a number of myoblast-like cells that initially failed to differentiate, instead swelling to acquire a resemblance to sex myoblasts (M-lineage-derived precursors to non-striated uterine and vulval muscles). Like normal ses myoblasts, the ectopic myoblast-like cells were capable of migration and proliferation followed by differentiation of progeny cells into vulval and uterine muscle, Our results demonstrate a cell-intrinsic contribution of CeMyoD to specification of both non-muscle and muscle fates. C1 Carnegie Inst Washington, Dept Embryol, Baltimore, MD 21210 USA. Johns Hopkins Univ, Grad Program Biol, Baltimore, MD 21218 USA. Yale Univ, Dept Genet, New Haven, CT 06520 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Fire, A (reprint author), Carnegie Inst Washington, Dept Embryol, 115 W Univ Pkwy, Baltimore, MD 21210 USA. EM fire@mail1.ciwemb.edu OI Krause, Michael/0000-0001-6127-3940 FU NIGMS NIH HHS [GM37706, GM50504, R01 GM037706, T32GM07231] NR 54 TC 53 Z9 57 U1 2 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1998 VL 125 IS 13 BP 2479 EP 2488 PG 10 WC Developmental Biology SC Developmental Biology GA 102ZQ UT WOS:000074956500014 PM 9609831 ER PT J AU Hallonet, M Hollemann, T Wehr, R Jenkins, NA Copeland, NG Pieler, T Gruss, P AF Hallonet, M Hollemann, T Wehr, R Jenkins, NA Copeland, NG Pieler, T Gruss, P TI Vax1 is a novel homeobox-containing gene expressed in the developing anterior ventral forebrain SO DEVELOPMENT LA English DT Article DE Emx; Not1; Pax6; Dlx1; brain patterning; homeobox; neural differentiation; forebrain; olfactory placode; anterior neural ridge; ganglionic eminence; Xenopus ID NEURAL PLATE; EMPTY SPIRACLES; OLFACTORY PLACODE; MOUSE OTX2; BOX GENE; RESTRICTED EXPRESSION; POSTERIOR AXIS; NERVOUS-SYSTEM; ROSTRAL BRAIN; SMALL-EYE AB The vertebrate forebrain is formed at the rostral end of the neural plate under the regulation of local and specific signals emanating from both the endomesoderm and neuroectoderm, The development of the rostral and ventral forebrain in particular was difficult to study, mainly because no specific markers are available to date. Here, we report the identification of Vax1, a novel homeobox-containing gene identified in mouse, Xenopus and human. It is closely related to members of the Not and Emx gene families, all of which are required for the formation of structures where they are expressed. In mouse and Xenopus, Vax1 expression first occurs in the rostral neural plate, in the medial anterior neural ridge and adjacent ectoderm, Later, at midgestation in the mouse and tadpole stage in Xenopus, the expression remains confined in the derivatives of this territory which differentiate into rostromedial olfactory placode, optic nerve and disc, and anterior ventral forebrain, Together, these observations suggest that Vax1 could have an early evolutionary origin and could participate in the specification and formation of the rostral and ventral forebrain in vertebrates, Comparison of the limits of the expression territory of Vax1 with that of Dlx1, Pax6 and Emx1 indicates that the corticostriatal ridge is a complex structure with distinct identifiable genetic compartments. Besides, the study of Vax1 expression in Pax6-deficient homozygous brains indicates that its regulation is independent of Pax6, although the expression patterns of these two genes appear complementary in wild-type animals. Vax1 chromosomal location is mapped at the distal end of the mouse chromosome 19, linked with that of Emx2. These two genes may have arisen by tandem duplication. The Vax1 gene is thus an interesting new tool to study the rostral ventral forebrain patterning, morphogenesis and evolution as well as the terminal differentiation of the forebrain in mouse and Xenopus. C1 Max Planck Inst Biophys Chem, Dept Mol & Cell Biol, D-37077 Gottingen, Germany. Univ Gottingen, Dept Dev Biochem, D-37073 Gottingen, Germany. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Gruss, P (reprint author), Max Planck Inst Biophys Chem, Dept Mol & Cell Biol, Fassberg 11, D-37077 Gottingen, Germany. EM pgruss@gwdg.de NR 87 TC 72 Z9 77 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1998 VL 125 IS 14 BP 2599 EP 2610 PG 12 WC Developmental Biology SC Developmental Biology GA 110DN UT WOS:000075365000007 PM 9636075 ER PT J AU Hoang, BH Thomas, JT Abdul-Karim, FW Correia, KM Conlon, RA Luyten, FP Ballock, RT AF Hoang, BH Thomas, JT Abdul-Karim, FW Correia, KM Conlon, RA Luyten, FP Ballock, RT TI Expression pattern of two Frizzled-related genes, Frzb-1 and Sfrp-1, during mouse embryogenesis suggests a role for modulating action of Wnt family members SO DEVELOPMENTAL DYNAMICS LA English DT Article DE mouse; embryogenesis; frizzled-like proteins; Wnt; limb ID INT-1 PROTOONCOGENE; SONIC-HEDGEHOG; LIMB; DROSOPHILA; POLARITY; TOOTH; MORPHOGENESIS; ABNORMALITIES; WINGLESS; MULTIPLE AB Wnt proteins have been implicated in regulating growth and pattern formation in a variety of tissues during embryonic development. We previously identified Frzb-1, a gene which encodes a secreted protein with homology in the ligand binding domain to the Wnt receptor Frizzled, but lacking the domain encoding the putative seven transmembrane segments. Frzb-1 has recently been shown to bind to Wnt proteins in vitro, and to inhibit the activity of Xenopus Wnt-8 in vivo. We report now that mFrzb-1 and Wnt transcripts display both complementary and overlapping expression patterns at multiple sites throughout embryonic development. By Northern analysis, the expression of mFrzb-1 in the developing mouse embryo is greatest from 10.5 to 12.5 days postcoitum (dpc). In the early embryo, mFrzb-1 is expressed in the primitive streak, presomitic mesoderm, somites, and brain. Later, mFrzb-1 exhibits sharp boundaries of expression in the limb bud, branchial arches, facial mesenchyme, and in cartilaginous elements of the appendicular skeleton. We conclude from these experiments that Frzb-1 is expressed at a time and location to modulate the action of Wnt family members during development of the limbs and central nervous system. Dev. Dyn. 1998;212:364-372, (C) 1998 Wiley-Liss,Inc. C1 Univ Hosp Cleveland, Rainbow Babies & Childrens Hosp, Dept Orthopaed, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Hosp Cleveland, Dept Pathol, Cleveland, OH 44106 USA. RP Ballock, RT (reprint author), Univ Hosp Cleveland, Rainbow Babies & Childrens Hosp, Dept Orthopaed, Cleveland, OH 44106 USA. NR 39 TC 70 Z9 74 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUL PY 1998 VL 212 IS 3 BP 364 EP 372 DI 10.1002/(SICI)1097-0177(199807)212:3<364::AID-AJA4>3.0.CO;2-F PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA ZX385 UT WOS:000074510400004 PM 9671940 ER PT J AU Kadoya, Y Nomizu, M Sorokin, LM Yamashina, S Yamada, Y AF Kadoya, Y Nomizu, M Sorokin, LM Yamashina, S Yamada, Y TI Laminin alpha 1 chain G domain peptide, RKRLQVQLSIRT, inhibits epithelial branching morphogenesis of cultured embryonic mouse submandibular gland SO DEVELOPMENTAL DYNAMICS LA English DT Article DE basement membrane; laminin alpha 2; laminin-1; morphogenesis; organ culture; synthetic peptide; submandibular gland ID TERMINAL GLOBULAR DOMAIN; SYNTHETIC PEPTIDES; BASEMENT-MEMBRANE; A-CHAIN; IN-VITRO; MONOCLONAL-ANTIBODIES; NEURITE OUTGROWTH; INTEGRIN SUBUNIT; CELL-ADHESION; BINDING-SITE AB Active sequences from the laminin alpha 1 and alpha 2 chain carboxyl-terminal globular domains (G domain) have been identified by screening overlapping synthetic peptides in a number of biological assays (Nomizu et al. [1995] J. Biol. Chem. 270:0583-20590; Nomizu et al. [1996] FEES Lett, 396:37-42). We have tested the activity of these peptides in submandibular gland explants of embryonic day 13 mice to determine the functional sites involved in organ development. The laminin al chain peptide, RKRLQVQLSIRT (residues 2719-2730 and designated AG-73), significantly inhibited epithelial branching morphogenesis. In contrast, other cell adhesive laminin oil chain peptides including the AASIKVAVSADR and NRWHSIYTRFG; failed to inhibit the branching. MG-73, a homologue of AG-73 from the laminin alpha 2 chain, did not inhibit the branching. The alpha 2 chain peptide had no effect, which may be due to the low levels of this laminin chain in day 13 mice. Laminin alpha 2 chain-specific monoclonal antibodies strongly reacted with the basement membranes of developed acini but only weakly stained embryonic day 13 submandibular epithelium. The expression of E-cadherin and alpha 6 integrin, as detected by immunofluorescence, were unchanged in both AG-73 and control scramble peptide-treated epithelial cells of the explants. In contrast, immunostaining of nidogen/entactin showed that explants treated with AG-73 for 3 days had a discontinuous basement membrane. Explants treated for 3 days with control peptide showed a normal basement membrane. These results suggest that the region containing the AG-73 sequence of the laminin alpha 1 chain is crucial for development of submandibular gland at early embryonic stages. The discontinuous basement membrane in AG-73-treated explants may indicate an important role for this region in basement membrane assembly. Dev. Dyn. 1998;212:394-402. (C) 1998 Wiley-Liss, Inc. C1 Kitasato Univ, Sch Med, Dept Anat, Sagamihara, Kanagawa 228, Japan. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Univ Erlangen Nurnberg, Inst Expt Med, D-8520 Erlangen, Germany. RP Kadoya, Y (reprint author), Kitasato Univ, Sch Med, Dept Anat, 1-15-1 Kitasato, Sagamihara, Kanagawa 228, Japan. NR 47 TC 36 Z9 36 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUL PY 1998 VL 212 IS 3 BP 394 EP 402 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA ZX385 UT WOS:000074510400007 PM 9671943 ER PT J AU Vannucci, SJ Clark, RR Koehler-Stec, E Li, K Smith, CB Davies, P Maher, F Simpson, IA AF Vannucci, SJ Clark, RR Koehler-Stec, E Li, K Smith, CB Davies, P Maher, F Simpson, IA TI Glucose transporter expression in brain: Relationship to cerebral glucose utilization SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT 3rd International Conference on Brain Energy Metabolism CY JUL 26-29, 1997 CL WATERVILLE VALLEY, NEW HAMPSHIRE SP NIH, HINDS, NICHHD, Int Soc Neurochem, S Karger AG, Clin Ref Lab Inc, Paragon Biotech, Cambridge Isotope Labs Inc, Isotec Inc, Ross Abbot Labs, Becton Dickinson Labware DE glucose transport; cerebral glucose utilization; neurons; glia; Alzheimer's disease; cerebral development; dehydration ID POSITRON EMISSION TOMOGRAPHY; CEREBELLAR GRANULE NEURONS; PRIMARY CULTURED NEURONS; RAT-BRAIN; ALZHEIMERS-DISEASE; GROWTH-FACTOR; GENE-EXPRESSION; MESSENGER-RNA; GLUT1; PROTEINS AB Glucose is the principle energy source for mammalian brain. Delivery of glucose from the blood to the brain requires its transport across the endothelial cells of the blood-brain barrier and across the plasma membranes of neurons and glia, which is mediated by the facilitative glucose transporter proteins. The two primary glucose transporter isoforms which function in cerebral glucose metabolism are GLUT1 and GLUT3. GLUT1 is the primary transporter in the blood-brain barrier, choroid plexus, ependyma, and glia; GLUT3 is the neuronal glucose transporter. The levels of expression of both transporters are regulated in concert with metabolic demand and regional rates of cerebral glucose utilization. We present several experimental paradigms in which alterations in energetic demand and/or substrate supply affect glucose transporter expression. These include normal cerebral development in the rat, Alzheimer's disease, neuronal differentiation in vitro, and dehydration in the rat. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Pediat, Hershey, PA 17033 USA. NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. RP Simpson, IA (reprint author), NIDDK, Diabet Branch, NIH, Bldg 10,Rm 5N102,10 Ctr Dr, Bethesda, MD 20892 USA. EM ians@bdg10.niddk.nih.gov FU NICHD NIH HHS [R29 HD31521] NR 50 TC 101 Z9 103 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD JUL-OCT PY 1998 VL 20 IS 4-5 BP 369 EP 379 DI 10.1159/000017333 PG 11 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 135UA UT WOS:000076819900014 PM 9778574 ER PT J AU Hewlett, BS Lamb, ME Shannon, D Leyendecker, B Scholmerich, A AF Hewlett, BS Lamb, ME Shannon, D Leyendecker, B Scholmerich, A TI Culture and early infancy among central African foragers and farmers SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID MATERNAL RESPONSIVENESS; MOTHER-INFANT; SOCIETIES; PATTERNS; MULTIPLE AB Everyday infant experiences among the Aka hunter-gatherers and the neighboring Ngandu farmers were observed and compared. Twenty Aka and 21 Ngandu 3- to 4-month-olds and 20 Aka and 20 Ngandu 9- to 10-month-olds were observed for 3 hr On each of 4 days so that all 12 daylight hr were covered. The Aka infants were more likely to be held, fed, and asleep or drowsy, whereas Ngandu infants were more likely to be alone and to fuss or cry, smile, vocalize, or play. The amount of crying, soothing, feeding, and sleeping declined over time in both groups. Distal social interaction increased over time among the Ngandu but not among the Aka. Despite striking cultural differences on many variables, however, functional context systematically affected the relative prominence of the infants' behavior in both cultural groups. C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20814 USA. Washington State Univ, Dept Anthropol, Pullman, WA 99164 USA. Univ Halle Wittenberg, Fak Psychol, Halle, Germany. RP Lamb, ME (reprint author), NICHHD, Sect Social & Emot Dev, 9190 Rockville Pike, Bethesda, MD 20814 USA. EM lamb@ssed.nichd.nih.gov RI Schoelmerich, Axel/C-9039-2009 OI Schoelmerich, Axel/0000-0002-9844-3920 NR 37 TC 44 Z9 45 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JUL PY 1998 VL 34 IS 4 BP 653 EP 661 DI 10.1037//0012-1649.34.4.653 PG 9 WC Psychology, Developmental SC Psychology GA 101JE UT WOS:000074865200006 PM 9681257 ER PT J AU Bornstein, MH Haynes, OM Azuma, H Galperin, C Maital, S Ogino, M Painter, K Pascual, L Pecheux, MG Rahn, C Toda, S Venuti, P Vyt, A Wright, B AF Bornstein, MH Haynes, OM Azuma, H Galperin, C Maital, S Ogino, M Painter, K Pascual, L Pecheux, MG Rahn, C Toda, S Venuti, P Vyt, A Wright, B TI A cross-national study of self-evaluations and attributions in parenting: Argentina, Belgium, France, Israel, Italy, Japan, and the United States SO DEVELOPMENTAL PSYCHOLOGY LA English DT Review ID CHILD-ABUSE; MOTHERS; INFANT; SATISFACTION; MOTIVATION; CULTURES; OUTCOMES; EMOTION; BELIEFS; IDEAS AB This study investigated and compared ideas about parenting in Argentine, Belgian, French, Israeli, Italian, Japanese, and U.S. mothers of 20-month-olds. Mothers evaluated their competence, satisfaction, investment, and role balance in parenting and rated attributions of successes and failures in 7 parenting tasks to their own ability, effort, or mood, to difficulty of the task, or to child behavior. Few cross-cultural similarities emerged; rather, systematic culture effects for both self-evaluations and attributions were common, such as varying degrees of competence and satisfaction in parenting, and these effects are interpreted in terms of specific cultural proclivities and emphases. Child gender was not an influential factor. Parents' self-evaluations and attributions help to explain how and why parents parent and provide further insight into the broader cultural contexts of children's development. C1 NICHHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, Comparat Ethol Lab, NIH, Bldg 31,Room B2B15,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 121 TC 77 Z9 77 U1 4 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JUL PY 1998 VL 34 IS 4 BP 662 EP 676 DI 10.1037/0012-1649.34.4.662 PG 15 WC Psychology, Developmental SC Psychology GA 101JE UT WOS:000074865200007 PM 9681258 ER PT J AU Chen, XY Hastings, PD Rubin, KH Chen, HC Cen, GZ Stewart, SL AF Chen, XY Hastings, PD Rubin, KH Chen, HC Cen, GZ Stewart, SL TI Child-rearing attitudes and behavioral inhibition in Chinese and Canadian toddlers: A cross-cultural study SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID UNINHIBITED CHILDREN; SOCIAL WITHDRAWAL; DEPRESSED MOOD; UNITED-STATES; UNFAMILIAR; PEER; PRESCHOOLERS; PARENTS; PATTERNS; SHYNESS AB Behavioral inhibition data were collected from samples of 2-year-olds from the People's Republic of China and Canada. Information on child-rearing attitudes and beliefs was obtained from mothers of the children. Chinese toddlers were significantly more inhibited than their Canadian counterparts. Inhibition was associated positively with mothers' punishment orientation and negatively with mothers' acceptance and encouragement of achievement in the Canadian sample. However, the directions of the relations were opposite in the Chinese sample; child inhibition was associated positively with mothers' warm and accepting attitudes and negatively with rejection and punishment orientation. The results indicated different adaptational meanings of behavioral inhibition across cultures. C1 Univ Western Ontario, Dept Psychol, London, ON N6A 5C2, Canada. NIMH, Sect Dev Psychopathol, Rockville, MD 20857 USA. Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. Beijing Normal Univ, Inst Dev Psychol, Beijing 100875, Peoples R China. Shandong Teachers Univ, Dept Educ Adm, Shanghai, Peoples R China. Univ Waterloo, Dept Psychol, Waterloo, ON N2L 3G1, Canada. RP Chen, XY (reprint author), Univ Western Ontario, Dept Psychol, London, ON N6A 5C2, Canada. NR 71 TC 207 Z9 223 U1 2 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JUL PY 1998 VL 34 IS 4 BP 677 EP 686 DI 10.1037/0012-1649.34.4.677 PG 10 WC Psychology, Developmental SC Psychology GA 101JE UT WOS:000074865200008 PM 9681259 ER PT J AU Gu, K Cowie, CC Harris, MI AF Gu, K Cowie, CC Harris, MI TI Mortality in adults with and without diabetes in a national cohort of the US population, 1971-1993 SO DIABETES CARE LA English DT Article ID HEART-DISEASE MORTALITY; CARDIOVASCULAR-DISEASE; RISK-FACTORS; MEN; MELLITUS; WOMEN; PREVALENCE; SURVIVAL; IMPACT AB OBJECTIVE - To examine 22-year mortality (1971-1993), causes of death, life expectancy, and survival in a national sample of diabetic and nondiabetic adults according to age, sex, and race. RESEARCH DESIGN AND METHODS - A representative national cohort of 14,374 adults aged 25-74 years was identified in 1971-1975 in the First National Health and Nutrition Examination Survey (NHANES I). Diabetes was ascertained by medical history interview The cohort was followed for mortality through 1992-1993, with verification of vital status for 96.2% (n = 13,830). Causes of death were determined from death certificates. RESULTS - Diabetic subjects comprised 5.1%;, of the cohort and accounted for 10.6% of the deaths. Mortality for diabetic subjects increased from 12.4 per 1,000 person-years for those aged 25-44 years at baseline to 89.7 per 1,000 person-years for those aged 65-74 years. The age-adjusted mortality rate was 57% higher for diabetic men than for diabetic women; the rate was 27% higher for diabetic non-Hispanic blacks than for diabetic non-Hispanic whites. Mortality rates were highest for insulin-treated subjects and for those with greater than or equal to 15 years' duration of diabetes. Diabetes was listed on the death certificate as the underlying cause of death for only 7.7% of diabetic men and 13.4% of diabetic women. Considering multiple causes of death, heart disease was listed the most frequently and was present on 69.5% of death certificates of people with diabetes. Death rates were higher for diabetic than for nondiabetic subjects in all age, sex, and race groups. The relative risk of death (diabetic versus nondiabetic subjects) declined with age from a value of 3.6 for those aged 25-44 years at baseline to 1.5 for those aged 65-74 years. The relative risk was elevated in diabetic subjects for all major causes of death except malignant neoplasms. Survival of diabetic subjects was lower than that of nondiabetic subjects in all age, sex, and race groups. Median life expectancy was 8 years lower for diabetic adults aged 55-64 years and 4 years lower for those aged 65-74 years. CONCLUSIONS - In this representative national sample of adults, mortality rates were higher for diabetic men than for diabetic women and for diabetic blacks than for diabetic The study confirms the substantially higher risk of death, lower survival, and lower life of diabetic adults compared with nondiabetic adults. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Harris, MI (reprint author), NIDDKD, NIH, Natcher Bldg,Room 5AN24,45 Ctr Dr,MSC 6600, Bethesda, MD 20892 USA. NR 19 TC 483 Z9 496 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1998 VL 21 IS 7 BP 1138 EP 1145 DI 10.2337/diacare.21.7.1138 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZW496 UT WOS:000074416800020 PM 9653609 ER PT J AU Wilson, C Nelson, R Nicolson, M Pratley, R AF Wilson, C Nelson, R Nicolson, M Pratley, R TI Plasma leptin concentrations: no difference between diabetic Pima Indians with and without nephropathy SO DIABETOLOGIA LA English DT Letter ID INSULIN C1 NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Wilson, C (reprint author), NIDDK, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. NR 7 TC 13 Z9 16 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUL PY 1998 VL 41 IS 7 BP 861 EP 862 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZY440 UT WOS:000074621500019 PM 9686932 ER PT J AU Domanski, MJ Follman, D Kravitz, M Mirsky, I AF Domanski, MJ Follman, D Kravitz, M Mirsky, I TI Noninvasive assessment of regional and global myocardial contractility in normal control subjects and in patients with dilated cardiomyopathies SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE echocardiography; contractility; carotid pulse tracings; dilated cardiomyopathy ID PRESSURE-OVERLOAD HYPERTROPHY; LEFT-VENTRICULAR MECHANICS; FIBER SHORTENING RELATION; WALL STRESS-VELOCITY; ARTERIAL-HYPERTENSION; CONSCIOUS DOGS; RESPONSES; PRELOAD; SHEEP; INDEX AB The aim of the present study was to develop a new noninvasive approach for the assessment of regional and global myocardial contractility without the need for pharmacological intervention to alter load. Thirty-four healthy adults and five adults with dilated cardiomyopathy (DCM) were studied. Patients with diabetes mellitus and hyperthyroidism were eliminated from the study. The remainder underwent echocardiography, sphygmomanometric blood pressure determination, and carotid pulse tracings. Left ventricular cross section in the parasternal long-axis four- and two-chamber views was divided into 20 segments. Associated measurements of end-systolic pressure and left ventricular ejection time enabled shortening, shortening rate, and ejection fraction/afterload relationships to be determined. A discriminant analysis showed that the ejection fraction/afterload relationship in patients with DCM differed substantially from that of control subjects and was the most sensitive in this regard. Endocardial shortening, mid-wall shortening, and ejection fraction/afterload relationships demonstrated linearity or nonlinearity for control subjects. This study thus permits the assessment of contractility in individual subjects without the need for drug interventions because load alteration stems from the variation of wall stress from base to apex in, the left ventricle. More importantly, the approach may be applied to patients with segmental abnormalities of contractile function. C1 NHLBI, Clin Trials Grp, NIH, Bethesda, MD 20892 USA. RP Domanski, MJ (reprint author), NHLBI, Clin Trials Grp, NIH, Bethesda, MD 20892 USA. NR 29 TC 2 Z9 2 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD JUL PY 1998 VL 15 IS 5 BP 429 EP 441 DI 10.1111/j.1540-8175.1998.tb00629.x PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZZ796 UT WOS:000074768000003 ER PT J AU Radko, SP Chrambach, A AF Radko, SP Chrambach, A TI Parallelism between width and asymmetry of peaks of rigid, spherical particles in capillary zone electrophoresis using polymer solutions SO ELECTROPHORESIS LA English DT Article DE capillary electrophoresis; polymer solution; peak dispersion; peak asymmetry ID GEL-ELECTROPHORESIS; DNA; MODEL; POLYACRYLAMIDE; DISPERSION; ADSORPTION; SIMULATION AB Peak width and peak asymmetry of rigid spherical particles in the size range of 3-100 nm radius (R) were measured in capillary zone electrophoresis (CZE), using buffered uncross-linked polyacrylamide of M-r 5.0 X 10(6). Polymer concentration-dependent spreading of peak width and peak asymmetry were found to parallel one another. The parallelism holds whether the particle size is within the "small" (R < 20 nm) or "large" (R > 20 nm) size ranges previously found to differ in the mechanism of particle size dependent retardation of electrophoretic migration (S. P. Radko and A. Chrambach, Electrophoresis 1996, 17, 1094-1102). In application to the "small" particle size range, the parallelism between band width and band asymmetry can be qualitatively interpreted to be consistent with the Giddings-Weiss mechanism (G. H. Weiss et al., Electrophoresis 1996, 17, 1325-1332) of electrophoresis in polymer-containing media which postulates a dependence of band width and band asymmetry on the equilibrium between "stationary" and "mobile" states of the particle. C1 NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. NR 20 TC 4 Z9 4 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 1998 VL 19 IS 10 BP 1620 EP 1624 DI 10.1002/elps.1150191017 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 108XD UT WOS:000075290300016 PM 9719536 ER PT J AU Zakharov, SF Kwok, SH Sokoloff, H Chang, HT Radko, SP Chrambach, A AF Zakharov, SF Kwok, SH Sokoloff, H Chang, HT Radko, SP Chrambach, A TI The band areas of proteins determined by fluorescent scanning in the commercial automated gel electrophoresis apparatus SO ELECTROPHORESIS LA English DT Article DE band area; protein; automated electrophoresis; automated apparatus ID RESOLUTION; DNA; MOBILITY; BUFFER; SYSTEM AB An automated gel electrophoresis apparatus, recently available commercially, allows one to follow the band during electrophoresis in real time, and lends itself therefore to an evaluation of bandwidth as a function of migration time (the dispersion coefficient), resolution and band shape. These determinations assume the constancy of band area with migration time and at various gel concentrations. The purpose of the present study was to verify these assumptions. Representative proteins and sodium dodecyl sulfate (SDS)-proteins, either natively fluorescent or fluorescein carboxylate labeled, were found to exhibit band areas which approach constancy as a function of migration time in both agarose and polyacrylamide gel electrophoresis, provided that (i) the protein concentration under the band was low enough to obviate self-quenching of fluorescence; (ii) the separation of the protein of interest from contaminants had progressed sufficiently during the time at which band areas were measured; (iii) the baseline under the peak was sufficiently well defined. However, band areas decrease with increasing gel concentration. Protein peaks exhibited leading and trailing tails. The ratio of the combined tail area to total area appeared to be near-constant at varying migration times. However, that ratio increases with increasing gel concentration. The tail area does not appear to be an artifact of fluorometric detection since it is reproduced upon fluorimetric analysis of the protein eluted from gel slices after electrophoresis. However, it may be due to photochemical destruction under the conditions of repetitive fluorometric peak detection. C1 NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NIH, Phys Sci Lab, Div Comp Res & Technol, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. RI Chang, Huan-Tsung/C-1183-2011; OI Chang, Huan-Tsung/0000-0002-5393-1410 NR 11 TC 2 Z9 2 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 1998 VL 19 IS 10 BP 1625 EP 1630 DI 10.1002/elps.1150191018 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 108XD UT WOS:000075290300017 PM 9719537 ER PT J AU Fauci, AS AF Fauci, AS TI New and reemerging diseases: The importance of biomedical research SO EMERGING INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Conference on Emerging Infectious Diseases CY MAR 08-11, 1998 CL ATLANTA, GEORGIA SP Ctr Dis Control & Prevent, Council State & Terr Epidemiologists, Amer Soc Microbiol, Natl Fdn CDC, Alliance Prudent Use Antibiot, Amer Acad Pediat, Amer Assoc Blood Banks, Amer Assoc Hlth Plans, Amer Canc Soc, Amer Coll Prevent Med, Amer Hosp Assoc, Amer Med Assoc, Amer Mosquito Control Assoc, Amer Publ Hlth Assoc, Amer Sexually Transmitted Dis Assoc, Amer Soc Clin Pathologists, Amer Soc Trop Med & Hyg, Amer Vet Med Assoc, Assoc Amer Vet Med Coll, Assoc Sch Publ Hlth, Assoc State & Terr Directors Hlth Promot & Publ Hlth Educ, Assoc State & Terr Hlth Officials, Assoc State & Terr Publ Hlth Lab Directors, Assoc Teachers Prevent Med, Burroughs Wellcome Fund, Emory Univ, Sch Med, Fogarty Int Ctr, US FDA, Indian Hlth Serv, Infect Dis Soc Amer, Int Life Sci Inst, Int Soc Infect Dis, Int Soc Travel Med, Int Union Hlth Promot & Educ, Int Union Microbiol Soc, Minor Hlth Profess Fdn, Morehouse Sch Med, NASA, Natl Assoc City & County Hlth Officials, Natl Assoc State Publ Hlth Vetinarians, Natl Council Int Hlth, Natl Fdn Infect Dis, Natl Hispan Med Assoc, NIAID, Natl Med Assoc, NOAA, Off Sci & Technol Policy, Pan Amer Hlth Org, Emory Univ, Rollins Sch Publ Hlth, Soc Healthcare Epidemiol Amer, Soc Occupat & Environm Hlth, Soc Publ Hlth Educ, Carter Ctr, Henry J Kaiser Family Fdn, HMO Grp, Robert Wood Johnson Fdn, Rockefeller Fdn, World Bank, Us Agcy Int Dev, USDA, US Dept Def, US Dept State, US Dept Justice, US Dept Vet Affairs, US EPA, WHO C1 NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 9 Z9 10 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUL-SEP PY 1998 VL 4 IS 3 BP 374 EP 378 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 111JP UT WOS:000075433800008 PM 9716949 ER PT J AU Rabadan-Diehl, C Aguilera, G AF Rabadan-Diehl, C Aguilera, G TI Glucocorticoids increase vasopressin V1b receptor coupling to phospholipase C SO ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; MESSENGER-RIBONUCLEIC-ACID; SMOOTH-MUSCLE-CELLS; ANTERIOR-PITUITARY; ADRENOCORTICOTROPIN RELEASE; CELLULAR-LOCALIZATION; ALPHA-SUBUNITS; CHRONIC STRESS; ADRENAL AXIS; G-PROTEINS AB Vasopressin (VP) stimulates pituitary ACTH secretion after binding to V1b VP receptors (V1b-R) coupled to phospholipase C (PLC). This effect of VP on ACTH secretion, unlike that of CRH, is resistant to glucocorticoid feedback. To determine whether changes in V1b-R expression or signaling mediate the refractoriness to glucocorticoids, the effects of glucocorticoids on pituitary VP binding, V1b-R messenger RNA (mRNA) and VP-stimulated inositol phosphate (IP) formation were studied in vivo and in vitro in the rat. Dexamethasone injection for 7 days decreased VP binding but increased V1b-R mRNA, indicating that mRNA levels do not reflect receptor number. In spite of the binding loss, VP-stimulated TP formation was enhanced in dexamethasone-treated rats, suggesting that glucocorticoids increase the coupling efficiency of the V1b receptor to phospholipase C. Pretreatment of pituitary cells in vitro with dexamethasone or corticosterone, also potentiated IP formation by low and high doses of VP, indicating that glucocorticoids act directly in the pituitary and not through changes in hypothalamic factors. The effect is mediated by glucocorticoid receptors because it was blocked by glucocorticoid but not mineralocorticoid antagonists. Dexamethasone potentiated the stimulation of IP by other PLC-dependent ligands (GnRH, TRH) but not that by the calcium ionophore, ionomycin, suggesting a site of action between the receptor and PLC. After treatment with dexamethasone, in vivo or in vitro, Western blot analysis revealed marked increases in the GTP binding protein, Ga,, which may account for the potentiating effect of glucocorticoid on ligand-stimulated IF. The data demonstrate that glucocorticoids increase coupling of the V1b-R with PLC thereby providing a mechanism by which VP facilitates corticotroph responsiveness in spite of elevated levels of plasma glucocorticoids during stress. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Rabadan-Diehl, C (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. EM rabadanc@cc1.nichd.nih.gov NR 48 TC 49 Z9 51 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1998 VL 139 IS 7 BP 3220 EP 3226 DI 10.1210/en.139.7.3220 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZV802 UT WOS:000074342700025 PM 9645696 ER PT J AU Chan, EC Falconer, J Madsen, G Rice, KC Webster, EL Chrousos, GP Smith, R AF Chan, EC Falconer, J Madsen, G Rice, KC Webster, EL Chrousos, GP Smith, R TI A corticotropin-releasing hormone type I receptor antagonist delays parturition in sheep SO ENDOCRINOLOGY LA English DT Article ID ARGININE-VASOPRESSIN; FETAL SHEEP; INTRAFETAL INFUSION; ACTH-SECRETION; LATE-GESTATION; LATE PREGNANCY; FOETAL LAMBS; OVINE FETUS; PITUITARY; ADRENOCORTICOTROPIN AB In sheep, corticotropin-releasing hormone (CRH) can stimulate the fetal release of ACTH to produce a cortisol surge which leads to the onset of parturition. We tested the hypothesis that fetal CRH is a primary factor in the onset of parturition in sheep by using a Type I CRH receptor antagonist, antalarmin, to block the endogenous action of CRH. Pregnant ewes were cannulated at 130-135 days of gestation. Five catheters were placed into the amniotic sac, fetal femoral artery, fetal tarsal vein, maternal jugular vein and carotid artery. After 5 days' recovery, blood samples from maternal and fetal vessels were collected at the following times: a day before the start of infusion, at {-1, 0, 1, 2, 4, 8 and 24} h, on the first day of infusion, and thereafter daily throughout a 10-day infusion. Animals (n = 6 per group) received infusions into a fetal vein of either a vehicle comprising 1:1 mixture of ethanol and polyethoxylated castor oil (Cremophor EL) or antalarmin (50 g/L) in the vehicle at a rate of 0.3 mL/h. The plasma samples were assayed for ACTH and cortisol using commercial RIA kits. Fetuses infused with vehicle delivered at a mean gestational age of 141.8 +/- 0.9 days compared with antalarmin-infused sheep at 148.8 +/- 1.6 days (P = 0.0036, unpaired Student's t-test). Fetal ACTH and cortisol did not change in the antalarmin-infused sheep after 3 days' infusion compared to significant increases in vehicle-infused sheep (P = 0.004 and P = 0.016 respectively, ANOVA). These data show that CRH receptor antagonism in the fetus can delay the onset of parturition. It supports the hypothesis that hypothalamic CRH drives fetal production of ACTH and is essential for the onset of parturition triggered by a surge in fetal cortisol. C1 John Hunter Hosp, Maternal Hlth Res Ctr, HRMC, Newcastle, NSW 2310, Australia. NICHD, Dev Endocrinol Branch, Bethesda, MD 20817 USA. NIDDK, Med Chem Branch, NIH, Bethesda, MD 20817 USA. RP Chan, EC (reprint author), John Hunter Hosp, Maternal Hlth Res Ctr, HRMC, Locked Bag 1, Newcastle, NSW 2310, Australia. NR 26 TC 47 Z9 48 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1998 VL 139 IS 7 BP 3357 EP 3360 DI 10.1210/en.139.7.3357 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZV802 UT WOS:000074342700042 PM 9645712 ER PT J AU Alavanja, MCR Sandler, DP McDonnell, CJ Lynch, CF Pennybacker, M Zahm, SH Lubin, J Mage, D Steen, WC Wintersteen, W Blair, A AF Alavanja, MCR Sandler, DP McDonnell, CJ Lynch, CF Pennybacker, M Zahm, SH Lubin, J Mage, D Steen, WC Wintersteen, W Blair, A TI Factors associated with self-reported, pesticide-related visits to health care providers in the Agricultural Health Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cancers; farmers; health care visits; noncancer toxicity; occupational exposure; pesticides ID OCCUPATIONAL EXPOSURE; APPLICATORS; CALIFORNIA; HERBICIDES; PATTERNS; 2,4-D AB To investigate factors associated with pesticide-related visits to health care providers (i.e., doctor or hospital visits), responses to self-administered questionnaires received from 35,879 licensed restricted-use pesticide applicators participating in the Agricultural Health Study were analyzed. (In Iowa, applicators are actually certified, whereas in North Carolina they are licensed; for ease of reference, the term license will be used for both states in this paper.) The cohort reported a total of more than 10.9 million pesticide-application days. These applications were associated with one or more pesticide-related health care visits by 2,214 applicators (7.0% of the applicator cohort for whom health care visit data were available). The odds of a pesticide-related health care visit were increased for commercial applicators compared to private applicators [odds ratio (OR = 1.77; 95% confidence interval (CI), 1.52-2.06)] and for applicators who used insecticides 70 times or more in their lifetime compared to those who used insecticides less frequently (OR = 1.43; CI, 1.26-1.63). After adjusting for the number of applications in a logistic regression model, significantly higher odds of health care visits were observed among North Carolina applicators compared to Iowa applicators (OR = 1.35; CI, 1.17-1.52), among applicators who mixed their own pesticides (OR = 1.65; CI, 1.22-2.23), and among applicators who personally repaired their pesticide application equipment at least once per year (OR = 1.12; CI, 1.06-1.25). Significantly lower odds were found among female versus male applicators (OR = 0.68; CI, 0.46-0.99) and among applicators who graduated from high school versus those who did not (OR = 0.82; CI, 0.71-0.94 for high school graduates and OR = 0.79; CI, 0.68-0.91 for those with at least some college). Several methods of pesticide application to crops, seed, or stored grain were also associated with significantly elevated odds ratios of health care visits. These observations suggest that several steps can be taken to reduce the number of health care visits resulting from occupational exposure to pesticides. The implications of this pattern of pesticide-related health care visits may have etiologic implications for cancer and other chronic diseases. C1 NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. SRA Technol Inc, Falls Church, VA 22042 USA. Univ Iowa, Iowa City, IA 52242 USA. Battelle Survey Res Associates, Durham, NC 27713 USA. US EPA, Res Triangle Pk, NC 27711 USA. US EPA, Athens, GA 30605 USA. Iowa State Univ, Ames, IA 50011 USA. RP Alavanja, MCR (reprint author), NCI, Epidemiol & Biostat Program, EPN-418,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Zahm, Shelia/B-5025-2015; OI Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [N01-CP-21095, N01-CP-33047, N01-CP-33048] NR 24 TC 12 Z9 12 U1 0 U2 4 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1998 VL 106 IS 7 BP 415 EP 420 DI 10.1289/ehp.98106415 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110KW UT WOS:000075380700022 PM 9637799 ER PT J AU Boorman, GA AF Boorman, GA TI Ethical questions on the use of magnetic field reports - Response SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Boorman, GA (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1998 VL 106 IS 7 BP A314 EP A315 DI 10.2307/3434049 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110KW UT WOS:000075380700003 ER PT J AU Li, GH Baker, SP Langlois, JA Kelen, GD AF Li, GH Baker, SP Langlois, JA Kelen, GD TI Are female drivers safer? An application of the decomposition method SO EPIDEMIOLOGY LA English DT Article DE case fatality rates; decomposition; death rates; epidemiologic methods; exposure; incidence density; injury; traffic safety ID RISK; INJURY; AGE; ALCOHOL; ACCIDENTS; DISEASE; RATES; CRASH AB Using the decomposition method and national data for the year 1990, we examined gender and age differences in involvement rates in fatal motor vehicle crashes. The fatal crash involvement rate per driver is expressed as a multiplicative function of the crash fatality rate (defined as the proportion of fatal crashes involved among all crashes involved), crash incidence density (that is, number of crashes per million person-miles), and exposure prevalence (that is, annual average miles driven per driver). The fatal crash involvement rate per 10,000 drivers for men was three times that for women (5.3 vs 1.7) and was highest among teenagers. Of the male-female discrepancy in the fatal crash involvement rates, 51% was attributable to the difference between sexes in crash fatality rates, 41% to the difference in exposure prevalence, and 8% to the difference in crash incidence density. Age-related variations in the fatal crash involvement rates resulted primarily from the differences in crash incidence density. The results indicate that, despite having lower fatal crash involvement rates, female drivers do not seem to be safer than their male counterparts when exposure is considered. The decomposition method is valuable as both a conceptual framework and an exploratory tool for understanding the contributing factors related to cause-specific injury mortality and the differences in death rates among populations. C1 Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Ctr Injury Res & Policy, Baltimore, MD 21287 USA. NIA, Epidemiol Demog & Biometry Program, Washington, DC USA. RP Li, GH (reprint author), Johns Hopkins Univ, Sch Med, Dept Emergency Med, 600 N Wolfe St,Marburg B194A, Baltimore, MD 21287 USA. OI Kelen, Gabor/0000-0002-3236-8286 FU NIAAA NIH HHS [R29AA09963]; PHS HHS [R49/CCR302486] NR 24 TC 48 Z9 49 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 1998 VL 9 IS 4 BP 379 EP 384 DI 10.1097/00001648-199807000-00006 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZV261 UT WOS:000074286900006 PM 9647900 ER PT J AU Silverman, DT AF Silverman, DT TI Diesel exhaust and lung cancer - Reply SO EPIDEMIOLOGY LA English DT Letter C1 NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. RP Silverman, DT (reprint author), NCI, Occupat Epidemiol Branch, EPN 418, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 1998 VL 9 IS 4 BP 474 EP 474 DI 10.1097/00001648-199807000-00022 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZV261 UT WOS:000074286900022 ER PT J AU Wuyts, A Proost, P Lenaerts, JP Ben-Baruch, A Van Damme, J Wang, JM AF Wuyts, A Proost, P Lenaerts, JP Ben-Baruch, A Van Damme, J Wang, JM TI Differential usage of the CXC chemokine receptors 1 and 2 by interleukin-8, granulocyte chemotactic protein-2 and epithelial-cell-derived neutrophil attractant-78 SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE calcium; chemokine; chemotaxis; desensitization; receptor ID FUNCTIONAL-CHARACTERIZATION; ACTIVATING PEPTIDE-78; EXPRESSION; BETA; LESTR/FUSIN; SEQUENCE; CLONING; LIGAND; ENA-78; SDF-1 AB The inflammatory response is mediated by a family of chemotactic cytokines, designated chemokines. The receptor usage of the CXC chemokine granulocyte chemotactic protein-2 (GCP-2) was compared with that of interleukin-8 (IL-8) and epithelial-cell-derived neutrophil attractant-78 (ENA-78). Chemokine activities were evaluated by measurement of intracellular calcium increase and by chemotaxis and binding assays, using CXC chemokine receptor (CXCR)-transfected cell lines. GCP-2 was equally potent at inducing a rise in [Ca(2+)](i) in both CXCR1-transfected and CXCR2-transfected cells (minimal effective concentration 3 nM). IL-8 augmented the [Ca(2+)](i) more efficiently in CXCR1-transfectants than in CXCR2- transfectants, whereas for ENA-78, threefold higher concentrations were necessary to obtain a calcium response in CXCR1-transfected cells than in CXCR2-transfectants. GCP-2 desensitized the calcium increase induced by IL-8 in both CXCR1-transfected and CXCR2-transfected cells, but ENA-78 only affected the IL-8-induced calcium response in CXCR2-transfectants The half-maximal effective concentrations for migration of CXCR2-transfectants in response to GCP-2 and ENA-78 were similar (0.1 nM), whereas GCP-2 was tenfold more potent than ENA-78 an CXCR1-transfectants. Half-maximal migration of CXCR1-transfected and CXCR2-transfected cells was obtained with IL-8 at concentrations of no more than 0.01 nM. Radiolabeled IL-8 could efficiently be displaced from CXCR2 by IL-8, GCP-2 and ENA-78. In contrast, only IL-8 and GCP-2 but not ENA-78, competed for (125)I-IL-8 binding to CXCR1. From these data, it can be concluded that, in addition to IL-8, GCP-2, but not ENA-78, efficiently binds to both CXCR1 and CXCR2. The differential receptor usage of the structurally related ELR(+)CXC chemokines GCP-2 and ENA-78 is indicative of a different role in inflammatory reactions. C1 Katholieke Univ Leuven, Rega Inst, Lab Mol Immunol, B-3000 Louvain, Belgium. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Van Damme, J (reprint author), Katholieke Univ Leuven, Rega Inst, Lab Mol Immunol, Minderbroedersstr 10, B-3000 Louvain, Belgium. EM jozef.vandamme@rega.kuleuven.ac.be NR 32 TC 99 Z9 108 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUL 1 PY 1998 VL 255 IS 1 BP 67 EP 73 DI 10.1046/j.1432-1327.1998.2550067.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZY905 UT WOS:000074674300008 PM 9692902 ER PT J AU Noguchi, K Murata, T Cho-Chung, YS AF Noguchi, K Murata, T Cho-Chung, YS TI 8-chloroadenosine 3 ',5 '-monophosphate (8-Cl-cAMP) selectively eliminates protein kinase A type I to induce growth inhibition in c-ras-transformed fibroblasts SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE cAMP phosphodiesterase; cell cycle; growth inhibition; protein kinase A; site-selective cAMP analogue ID HL-60 LEUKEMIA-CELLS; CYCLIC-AMP ANALOGS; RI-ALPHA-SUBUNIT; ADENOSINE METABOLITE; 8-CHLORO-CYCLIC AMP; EPITHELIAL-CELLS; DOWN-REGULATION; DIFFERENTIATION; CAMP; PHOSPHODIESTERASE AB 8-Chloroadenosine 3',5'-monophosphate (8-Cl-cAMP), a site-selective cyclic adenosine 3',5'-monophosphate (cAMP) analogue, exhibits growth inhibition in a broad spectrum of cancer cell lines. We investigated the effect of 8-Cl-cAMP on c-ras-transformed mouse fibroblasts (MP3/3T3) which were established by transfection of Balb3T3 cells (Balb3T3) with the point-mutated c-ras gene [G12-->V12]. 8-Cl-cAMP (2-5 mu M) exerted over 80% growth inhibition by day 4 on MP3/3T3, while inhibiting parental Balb3T3 cell growth less than 40%. In order to distinguish the effect of 8-Cl-cAMP from that of 8-chloroadenosine (8-Cl-adenosine), we examined the effect of 8-Cl-cAMP in serum-fi ee medium. 8-Cl-cAMP demonstrated a potent growth inhibition of MP3/3T3 cells cultured in serum-free medium, suggesting that the growth inhibitory effect of 8-Cl-cAMP was not due to its hydrolysed product, 8-Cl-adenosine. In addition, both Balb3T3 and MP3/3T3 contained cAMP phosphodiesterases mainly composed of isozyme IV which has previously been reported to be insensitive towards the hydrolysis of 8-Cl-cAMP. Non-transformed Balb3T3 cells contained only type II cAMP-dependent protein kinase (PKA), whereas transformed MP3/3T3 exhibited a marked increase in type I PKA. The growth inhibition of MP3/3T3 by 8-Cl-cAMP accompanied almost complete elimination of type I PKA without affecting type II PKA. Moreover, 8-Cl-cAMP induced an arrest in the G(0)/G(1)-phase of the cell cycle in MP3/3T3. 8-Cl-adenosine had little or no effect on the cell cycle kinetics of MP3/3T3 cells. These results show that 8-Cl-cAMP is a novel cAMP analogue which selectively eliminates type I PKA to induce growth inhibition in transformed fibroblasts. Published by Elsevier Science Ltd. All rights reserved. C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 5B05, Bethesda, MD 20892 USA. NR 35 TC 28 Z9 29 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 1998 VL 34 IS 8 BP 1260 EP 1267 DI 10.1016/S0959-8049(98)00051-3 PG 8 WC Oncology SC Oncology GA 104VP UT WOS:000075037000029 PM 9849489 ER PT J AU Puthucode, RN Pugazhenthi, U Quail, JW Stables, JP Dimmock, JR AF Puthucode, RN Pugazhenthi, U Quail, JW Stables, JP Dimmock, JR TI Anticonvulsant activity of various aryl, arylidene and aryloxyaryl semicarbazones SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE semicarbazone; anticonvulsant activity; binding site hypothesis; structure-activity relationship; X-ray crystallography ID ANTIEPILEPTIC DRUG DEVELOPMENT; MAXIMAL ELECTROSHOCK SCREEN AB A number of aryl, arylidene and aryloxyaryl semicarbazones were evaluated as candidate anticonvulsants. In particular, insertion of an olefinic group between the carbimino carbon atom and an aryl ring (referred to as the proximal ring) led to series 6 in which there was retention in activity and 6b,c were shown to be useful lead molecules. At the doses utilized, neurotoxicity was absent in these compounds when given orally to rats. Attachment of a 2-naphthyloxy group at the 4 position of the proximal ring gave 7 whose high activity in the rat oral maximal electroshock (MES) screen suggested that the binding site of the second aryl ring was capable of accommodating groups with molecular refractivity values of over 40. The greatest activity was displayed by a series of aryloxyaryl semicarbazones 8 which had oral activity in the MES screen substantially greater than phenytoin and with protection indices of over 100. A binding site hypothesis formulated as a result of the biodata generated was in accord with the information obtained by X-ray crystallography. (C) Elsevier, Paris. C1 Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. Univ Saskatchewan, Dept Chem, Saskatoon, SK S7N 5C9, Canada. NINDS, Bethesda, MD 20892 USA. RP Dimmock, JR (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. NR 15 TC 28 Z9 31 U1 1 U2 3 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD JUL-AUG PY 1998 VL 33 IS 7-8 BP 595 EP 607 DI 10.1016/S0223-5234(98)80018-4 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 116XN UT WOS:000075750500003 ER PT J AU Inoue, Y Takemura, A Kawano, K Kitama, T Miles, FA AF Inoue, Y Takemura, A Kawano, K Kitama, T Miles, FA TI Dependence of short-latency ocular following and associated activity in the medial superior temporal area (MST) on ocular vergence SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE ocular following; convergence; viewing distance; MST; monkey ID VIEWING DISTANCE; EYE-MOVEMENTS; NEURAL ACTIVITY; LINEAR MOTION; ALERT MONKEY; RESPONSES; NEURONS; TRANSLATION; NUCLEUS; CORTEX AB Motion of a large-field pattern elicits short-latency ocular following responses (OFR) in the monkey, which are mediated at least in part by the medial superior temporal area of the cortex (MST). The magnitude of the OFR is known to be inversely related to viewing distance, and we investigated the dependence of OFR and the associated neuronal activity in the MST on a major cue to viewing distance, ocular vergence, in alert monkeys (Macaca fuscata). The vergence angle, expressed in terms of the apparent viewing distance, ranged from infinity to 16.6 cm (0-6 m(-1)). The magnitude of the initial OFR increased monotonically with increases in convergence at a mean (+/- SD) rate of 19.6 +/- 4.5%/m(-1) in four monkeys (over the range 0-4 m(-1)). in two monkeys, we recorded the single unit activity of 160 MST neurons that responded to motion of a large-field pattern with directional selectivity. The mean latency (+/- SD) of the MST discharges elicited by large-field motion was 50 +/- 7.5 ms (n = 115), which preceded the onset of OFR by an average of 10 +/- 9.9 ms. The discharge modulation elicited by large-field motion showed a significant dependence on vergence in 91/160 neurons (57%), 72 of which (79%) increased their firing rate with increasing convergence ("near" neurons), and the remainder increasing their firing rate with decreasing convergence ("far" neurons). However, on average, the sensivity of these MST neurons to vergence was only about 30% of that shown by the OFR. It could be that only those neurons that are very sensitive to vergence angle contribute to the OFR, but it is also possible that much of the modulation of OFR with vergence occurs downstream from the MST or in alternative pathways (yet to be discovered) that contribute to OFR. C1 Electrotech Lab, Neurosci Sect, Tsukubashi, Ibaraki 305, Japan. Univ Tsukuba, Inst Basic Med Sci, Tsukubashi, Ibaraki 305, Japan. Yamanashi Med Univ, Dept Physiol, Yamanashi 40938, Japan. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Inoue, Y (reprint author), Electrotech Lab, Neurosci Sect, 1-1-4 Umezono, Tsukubashi, Ibaraki 305, Japan. NR 33 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUL PY 1998 VL 121 IS 2 BP 135 EP 144 DI 10.1007/s002210050445 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZY709 UT WOS:000074651500003 PM 9696382 ER PT J AU Jernigan, HM Zigler, JS Liu, Y Blum, PS Merola, LO Stimbert, CD AF Jernigan, HM Zigler, JS Liu, Y Blum, PS Merola, LO Stimbert, CD TI Effects of xylose on monkey lenses in organ culture: A model for study of sugar cataracts in a primate SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE rhesus monkey lens; Macaca mulatta; human lens; sugar cataract; organ culture; diabetes; xylose; galactose; choline transport; phosphocholine synthesis; phosphorylcholine ID RAT LENSES; ALDOSE REDUCTASE; SORBITOL PATHWAY; OXIDATIVE STRESS; PHOSPHORYLCHOLINE; PHOSPHORYLETHANOLAMINE; CATARACTOGENESIS; DEHYDROGENASE; QUANTITATION; INVITRO AB Lenses exposed to high concentrations of xylose in organ culture produce xylitol, and they lose transparency and exhibit other changes characteristic of cataracts. Most previous studies of this model system for cataractogenesis have employed rat or rabbit lenses, where the activity of the enzyme aldose reductase has been definitely implicated as the initiating factor. Since lenses from this species have much higher aldose reductase activity and have other differences relative to human lenses, the relevance of these findings to the human lens is uncertain. To determine the effects of xylose on the lenses of a primate, lenses from the rhesus monkey (Macaca mulatta) were incubated 24-48 hr in control medium or in TC-199 medium containing 30 mM xylose. Xylose caused a general haziness, focal swelling of epithelial cells, and swollen peripheral fiber cells, but the changes were much less pronounced than in rat lenses under similar conditions. Monkey lenses exposed to 30 mM glucose, galactose or xylose accumulated measurable sorbitol, dulcitol or xylitol, respectively, but the amounts were much lower than in rat lenses, perhaps reflecting the lower aldose reductase and higher sorbitol dehydrogenase activities in monkey lenses. The damage to monkey lenses appeared to be limited to the outer layers. In monkey lenses, xylose caused little, if any, change in membrane transport of choline or alpha-aminoisobutyrate, but severely depressed synthesis of phosphorylcholine (P-choline), and increased leakage of P-choline into the culture medium, leading to a decrease in the P-choline concentration within 24-48 hr. In summary, xylose-induced damage to monkey lenses in organ culture Is qualitatively similar to that seen in rat lenses, but the changes are much less rapid and severe. Culture of monkey lenses with xylose provides a model system to extend previous studies of sugar cataractogenesis in rats to a species more closely related to humans. (C) 1998 Academic Press. C1 Univ Tennessee, Dept Biochem, Memphis, TN 38163 USA. Univ Tennessee, Dept Ophthalmol, Memphis, TN 38163 USA. NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Jernigan, HM (reprint author), Univ Tennessee, Dept Biochem, 956 Court Ave,Room D222, Memphis, TN 38163 USA. FU NEI NIH HHS [EY07938] NR 35 TC 11 Z9 11 U1 1 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUL PY 1998 VL 67 IS 1 BP 61 EP 71 PG 11 WC Ophthalmology SC Ophthalmology GA 105EZ UT WOS:000075060900007 PM 9702179 ER PT J AU Devereux, TR Kaplan, NL AF Devereux, TR Kaplan, NL TI Use of quantitative trait loci to map murine lung tumor susceptibility genes SO EXPERIMENTAL LUNG RESEARCH LA English DT Article; Proceedings Paper CT 2nd International Mouse Lung Tumorigenesis Symposium CY JUN 18-20, 1997 CL COLUMBUS, OHIO ID INDUCED PULMONARY ADENOMAS; INTESTINAL NEOPLASIA; RESISTANCE LOCUS; MOUSE; MICE; IDENTIFICATION; CHROMOSOME-4; ACTIVATION; CARCINOMAS; MUTATION AB During the last decade new methods for mapping quantitative trait loci (QTLs) have helped geneticists uncover disease-associated genes. Genetic dissection of complex multigenic diseases such as cancer is being accomplished in part by mapping QTLs in experimental crosses of mice [1]. With the recent construction of dense genetic linkage maps for the mouse, mapping of quantitative trait loci has become practical [2]. Over 6000 polymorphic simple sequence length repeat markers (microsatellite markers) have been napped in the mouse genome [3], and new, analytical approaches to linkage analysis have made QTL mapping a powerful technique for identifying cancer genes [4-7]. In this overview we discuss the design of OIL mapping studies and some of the findings from studies on the mapping of murine lung tumor susceptibility loci. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Devereux, TR (reprint author), NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NR 32 TC 8 Z9 8 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD JUL-AUG PY 1998 VL 24 IS 4 BP 407 EP 417 PG 11 WC Respiratory System SC Respiratory System GA ZW988 UT WOS:000074469100005 PM 9659574 ER PT J AU Lin, L Festing, MFW Devereux, TR Crist, KA Christiansen, SC Wang, Y Yang, A Svenson, K Paigen, B Malkinson, AM You, M AF Lin, L Festing, MFW Devereux, TR Crist, KA Christiansen, SC Wang, Y Yang, A Svenson, K Paigen, B Malkinson, AM You, M TI Additional evidence that the K-ras protooncogene is a candidate for the major mouse pulmonary adenoma susceptibility (Pas-1) gene SO EXPERIMENTAL LUNG RESEARCH LA English DT Article; Proceedings Paper CT 2nd International Mouse Lung Tumorigenesis Symposium CY JUN 18-20, 1997 CL COLUMBUS, OHIO DE mouse lung; genetic susceptibility; recombinant inbred mice; K-ras; Pas-1 ID LUNG-TUMOR SUSCEPTIBILITY; LINKAGE MAP; MICE; ACTIVATION; ONCOGENES; STRAINS; LOCUS; CANCER; CELL; DNA AB A locus for mouse pulmonary adenoma susceptibility, Pas-1, has been mapped on distal chromosome 6, where the X-ras gene is located. Allele-specific activation and expression of the K-ras allele from the susceptible parent has been observed in lung tumors from F1 hybrid mice. We report here genetic mapping of lung tumor susceptibility genes in urethane-treated A x B and B x A recombinant inbred (RI) mice using microsatellite markers to seek further evidence for the K-ras gene as candidate for Pas-1. The K-ras genotype differs between the A/J and C57BL/6J Progenitors of the RI strains, and distal chromosome 6 contained a major lung tumor susceptibility determinant in the RI mice. Additional evidence that Pas-1 is K-ras involved linkage analysis of (A/JOLaHsd x BALB/ cOLaHsd) F2 intercross mice whose parents shared the same K-ras genotype. In contrast to the results with the B x B and B x A RI strains, no distal chromosome 6 site was significantly associated with tumor development in these F2 mice. In addition to this major locus, linkage analysis of the RI mire revealed additional quantitative trait loci for susceptibility on chromosomes 10, 17, and 19. These loci may serve as modifiers of Pas-1. The relationship between the K-ras genotype and the frequency of X-ras mutations in urethane-induced lung tumors from the RI mice was also explored. All 18 tumor NAs from RI mice with high susceptibility contained an AT --> TA transversion at the second base of K-ras codon 61. This was also true for DNAs from 27 of 27 (100%) tumors in mice with high intermediate susceptibility. In RI strains with a low intermediate susceptibility, the DNA from 39 of 47 (83%) tumors contained an AT --> TA transversion at condon 61, and only 13 of 21 (62%) tumors had this mutation in the most resistant group. This reflects a positive correlation between the frequency of K-ras mutations in lung tumors of A x B or B x A RI strains and their susceptibility to lung carcinogenesis. Since K-ras appears to be Pas-1, these results suggest that some RI mice that have the resistant K-ras or Pas-1 allele undergo tumor development by a K-ras-independent route. C1 Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. Med Coll Ohio, Dept Surg, Toledo, OH 43614 USA. Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England. NIEHS, Res Triangle Pk, NC 27709 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Univ Colorado, Denver, CO 80202 USA. RP You, M (reprint author), Med Coll Ohio, Dept Pathol, 3000 Arlington Ave, Toledo, OH 43614 USA. FU NCI NIH HHS [CA58554]; NIEHS NIH HHS [ES02370] NR 45 TC 51 Z9 52 U1 0 U2 1 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD JUL-AUG PY 1998 VL 24 IS 4 BP 481 EP 497 PG 17 WC Respiratory System SC Respiratory System GA ZW988 UT WOS:000074469100010 PM 9659579 ER PT J AU Sabourin, CLK Wang, QS Ralston, SL Evans, J Coate, J Herzog, CR Jones, SL Weghorst, CM Kelloff, GJ Lubet, RA You, M Stoner, GD AF Sabourin, CLK Wang, QS Ralston, SL Evans, J Coate, J Herzog, CR Jones, SL Weghorst, CM Kelloff, GJ Lubet, RA You, M Stoner, GD TI Expression of cell cycle proteins in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced mouse lung tumors SO EXPERIMENTAL LUNG RESEARCH LA English DT Article; Proceedings Paper CT 2nd International Mouse Lung Tumorigenesis Symposium CY JUN 18-20, 1997 CL COLUMBUS, OHIO DE cdk4; cyclin D1; lung; mouse; p16(INK4a); Rb; tumor ID RETINOBLASTOMA SUSCEPTIBILITY GENE; POLYMERASE CHAIN-REACTION; NONSMALL CELL; D1 OVEREXPRESSION; RAS PROTOONCOGENE; RB PROTEIN; CDK4 GENE; SKIN CARCINOGENESIS; HOMOZYGOUS DELETION; SUPPRESSOR GENE AB Cyclin D1 dysregulation and differential inactivation of p16(INK4a) and Rb have been observed in human lung cancer. In chemically induced mouse lung tumors, the p16(INK4a) gene is a target of inactivation, and Rb is reduced at the mRNA level (Northern blot) although similar at the protein level (Western blot) when compared to normal lung tissues. The expression of Cyclin D1, cdk4, p16(INK4a), and Rb protein was examined by immunohistochemistry in 4-( methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced mouse lung tumors. Immunohistochemical staining revealed exclusive nuclear staining of both cyclin D1 and cdk4 that was light to moderate in normal mouse lung tissues, but intense in lung adenomas and adenocarcinomas. Western blot analysis confirmed the increased expression of cyclin D1 and cdk4 in lung tumors compared to normal lung. Immunohistochemical analyses of lung tumors showed focal areas which lacked p16(INK4a) staining. Expression of p16(INK4a), as determined by RT-PCR, was variable in lung turners. Mutations in p16(INK4a) were not found by SSCP analysis. Immunohistochemical analyses of normal lung tissues showed intense staining for Rb protein in alveolar epithelial cells and in other lung cell types; however, in the lung tumors the staining intensity was reduced and the distribution was altered. Expression of Rb was detected in normal lung tissues but was barely detectable by Northern blot hybridization in lung tumors. Western blot analysis indicated the presence of both hypophosphorylated and hyperphosphorylated Rb protein in lung tumors and in normal lung tissues. These results suggest that alterations in the cell cycle proteins, cyclin D1, cdk4, p16(INK4a), and Rb, may play a role in the acquisition of autonomous growth by adenomas. Furthermore, they demonstrate the importance of immunohistochemical studies to examine expression in tissues that contain multiple cell types, such as the lung, and in tumors that by nature are heterogeneous. C1 Ohio State Univ, Sch Publ Hlth, Div Environm Hlth Sci, Columbus, OH 43210 USA. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. RP Sabourin, CLK (reprint author), Ohio State Univ, Sch Publ Hlth, Div Environm Hlth Sci, CHRI Room 1148,300 W 10th Ave, Columbus, OH 43210 USA. FU NCI NIH HHS [CA58544, CA28950] NR 80 TC 19 Z9 19 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD JUL-AUG PY 1998 VL 24 IS 4 BP 499 EP 521 PG 23 WC Respiratory System SC Respiratory System GA ZW988 UT WOS:000074469100011 PM 9659580 ER PT J AU Jakowlew, SB Moody, TW You, L Mariano, JM AF Jakowlew, SB Moody, TW You, L Mariano, JM TI Transforming growth factor-beta expression in mouse lung carcinogenesis SO EXPERIMENTAL LUNG RESEARCH LA English DT Article; Proceedings Paper CT 2nd International Mouse Lung Tumorigenesis Symposium CY JUN 18-20, 1997 CL COLUMBUS, OHIO DE A/J mouse; chemical carcinogenesis; gene expression; tumor progression ID ACCOMPANIES VIRAL TRANSFORMATION; CARCINOMA CELL-LINES; II RECEPTOR GENE; TGF-BETA; MESSENGER-RNAS; MICROSATELLITE INSTABILITY; CANCER CELLS; FACTOR-ALPHA; INHIBITION; PROTEIN AB Transforming growth factor-beta (TGF-beta) is a multifunctional growth modulator that inhibits the proliferation of many epithelial cells while stimulating the proliferation of most fibroblasts. To examine the role of TGF-beta in mouse lung chemically induced tumorigenesis, Expression of the TGF-beta 1, -beta 2, and -beta 3 proteins was examined in,A/J mice treated with the carcinogen urethane to induce lung adenomas using immunohistochemical staining analysis. Immunostaining for the TGF-beta ligands was detected in the epithelium of the bronchioles of untreated A/J mire with immunostaining being more intense for TGF-beta 1 than for TGF-beta 2 and TGF-beta 3; immunostaining for each TGF-beta ligand was also detected in the bronchiolar epithelium of urethane-treated A/J mice at levels similar to untreated mice. Immunostaining for the TGF-beta ligands was also detected in adenomas by 2 months; staining for TGF-beta 1, -beta 2, and -beta 3 in adenomas was detected at levels comparable with bronchioles. Following treatment with urethane for 8 months, immunostaining for TGF-beta s 1, 2, and 3 in bronchioles persisted at levels comparable to that in normal bronchioles and also Persisted in adenomas, with staining for the TGF-beta ligands being very prominent on the edge of the tumor. Expression of TGF-beta 1 mRNA was examined in urethane-treated mouse lung tissue using Northern blot hybridization; here, expression of TGF-beta 1 mRNA increased 2-fold in 3-month urethane-treated lung tissue and an additional 2.5-fold by 8 months following urethane administration. Expression of TGF-beta 1 mRNA was also examined in nontumorigenic and tumorigenic mouse lung cells; in these cells, expression of TGF-beta 1 mRNA was higher in the tumorigenic cells than in the nontumorigenic cell line. These data shout that there is an increase in expression of TGF-beta 1 during tumorigenesis and suggest that TGF-beta may play an important role in mouse lung carcinogenesis induced by urethane. C1 NCI, Med Branch, Dept Cell & Canc Biol, Rockville, MD 20850 USA. RP Jakowlew, SB (reprint author), NCI, Med Branch, Dept Cell & Canc Biol, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 45 TC 12 Z9 12 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD JUL-AUG PY 1998 VL 24 IS 4 BP 579 EP 593 PG 15 WC Respiratory System SC Respiratory System GA ZW988 UT WOS:000074469100015 PM 9659584 ER PT J AU Moody, TW Leyton, J Martinez, A Hong, S Malkinson, A Mulshine, JL AF Moody, TW Leyton, J Martinez, A Hong, S Malkinson, A Mulshine, JL TI Lipoxygenase inhibitors prevent lung carcinogenesis and inhibit non-small cell lung cancer growth SO EXPERIMENTAL LUNG RESEARCH LA English DT Article; Proceedings Paper CT 2nd International Mouse Lung Tumorigenesis Symposium CY JUN 18-20, 1997 CL COLUMBUS, OHIO DE A/J mice; apoptosis; lipoxygenase inhibitors; lung carcinogenesis; non-small cell lung cancer ID BIOSYNTHESIS; BOMBESIN; LINES; 5-LIPOXYGENASE; CARCINOMAS; PEPTIDES; INVITRO; TUMORS AB The effects of lipoxygenase inhibitors were investigated using human lung cancer cell lines and A/J mice. By RT-PCR, 5-, 12-, and 15-lipoxygenase mRNA was detected in NSCLC cells. NDGA inhibited 5-LO activity in adenocarcinoma cell line NCI-H1264. Using an MTT assay, NDGA, MK591 and AA861 inhibited the growth of NSCLC cell lines tested with IC50 values of 3, 2, and 7 mu M, respectively. Using a clonogenic assay, 10 mu M NDGA significantly reduced NSCLC colony number. NDGA significantly slowed NSCLC xenograft growth in nude mice. When the tumors were excised and analyzed, nude mice treated with NDGA had significantly more apoptotic figures than did untreated tumors. A/J mice treated with urethane developed adenomas after 4 months and NDGA administration significantly reduced lung adenoma number. These data indicate that lipoxygenase inhibitors inhibit lung cancer growth and prevent lung carcinogenesis. C1 NCI, Cell & Canc Biol Dept, Med Branch, Rockville, MD 20850 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO USA. RP Moody, TW (reprint author), NCI, Cell & Canc Biol Dept, Med Branch, Bldg KWC,Room 300,9610 Med Ctr Dr, Rockville, MD 20850 USA. EM moodyt@bprb.nci.nih.gov RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 28 TC 76 Z9 79 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD JUL-AUG PY 1998 VL 24 IS 4 BP 617 EP 628 PG 12 WC Respiratory System SC Respiratory System GA ZW988 UT WOS:000074469100018 PM 9659587 ER PT J AU Tang, FI Chiu, TH Wang, Y AF Tang, FI Chiu, TH Wang, Y TI Electrochemical studies of the effects of Substance P on dopamine terminals in the rat striatum SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Substance P; neurokinin; Parkinson's disease; voltammetry; dopamine ID VENTRAL MESENCEPHALIC GRAFTS; PARKINSONS-DISEASE PATIENTS; RECEPTOR IMMUNOREACTIVITY; EXTRACELLULAR DOPAMINE; SELECTIVE AGONISTS; NUCLEUS-ACCUMBENS; BASAL GANGLIA; RELEASE; NEURONS; NIGRA AB The purpose of this study was to investigate the regulation of dopamine (DA) release and clearance by Substance P (SP) in striatum. In vivo high speed chronoamperometric recording techniques, with Nafioncoated carbon-fiber electrodes, were used to evaluate extracellular DA concentrations in urethane-anesthetized Sprague-Dawley rats. SP was locally applied to striatum. Our data indicate that SP can induce DA release in striatum. However, only about half of the striatal sites respond to SP. Readministration of SP to the same site elicited a smaller DA release. These data suggest that SP-evoked release shows tachyphyllaxis and is heterogeneous in the striatum. Lesioning of DA neurons with 6-OHDA into the medial forebrain bundle abolished DA release induced by SP. It has been shown that SP interacts with three different tachykinin receptors. We found that application of the Neurokinin-1 (NK1) agonist [Sar(9), Met (O-2)(11)]SP, but not the NK3 agonist senktide, induced DA release, suggesting that SP-induced DA release may be mediated through NK1 receptors. We further examined SP effects on DA clearance in striatum. We found that pretreatment with SP significantly attenuated extracellular levels of DA after exogeneous application of DA, suggesting that DA clearance is augmented by SP. Taken together, our data demonstrate that substance P facilitates dopamine release and clearance in the striatum. (C) 1998 Academic Press. C1 Natl Def Med Ctr, Dept Pharmacol, Taipei, Taiwan. Natl Yang Ming Univ, Taipei 112, Taiwan. RP Wang, Y (reprint author), NIDA, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 53 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 1998 VL 152 IS 1 BP 41 EP 49 DI 10.1006/exnr.1998.6834 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 106KC UT WOS:000075127600005 PM 9682011 ER PT J AU Lira, R Mendez, S Carrera, L Jaffe, C Neva, F Sacks, D AF Lira, R Mendez, S Carrera, L Jaffe, C Neva, F Sacks, D TI Leishmania tropica: The identification and purification of metacyclic promastigotes and use in establishing mouse and hamster models of cutaneous and visceral disease SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Leishmania tropica; animal models; metacyclic promastigotes; lipophosphoglycan; cutaneous leishmaniasis (CL); visceral leishmaniasis (VL); viscerotropic leishmaniasis (VTL); lipophosphoglycan (LPC) ID OPERATION DESERT-STORM; MEXICANA-AMAZONENSIS; LIPOPHOSPHOGLYCAN; INFECTION; KENYA; MICE; SUSCEPTIBILITY; VECTOR; STAGE; DONOVANI AB The identification and purification of metacyclic promastigotes and use in establishing mouse and hamster models of cutaneous and visceral disease. Experimental Parasitology 89, 331-342. Few experimental studies on Leishmania tropica have been undertaken despite the importance of this parasite as the cause of cutaneous leishmaniasis, and now visceral disease, in the Old World. In part, this is due to the absence of convenient animals models, especially mice, for L. tropica infections. An anti-lipophosphoglycan (LPG) monoclonal antibody XCIV 1H2-A8 (T11), specific for L. tropica, was found to distinguish between culture-derived procyclic and metacyclic promastigotes. The antibody was used to negatively select for nonagglutinated metacyclic forms in stationary cultures, and the exceptional virulence of the purified metacyclics was verified by their infectivity for mouse macrophages in vitro and by their ability to produce cutaneous lesions in footpads of BALB/c mice. The lesions produced by three cutaneous isolates of L, tropica were nonulcerative and nonprogressive. Nonetheless, the lesions failed to heal, and high numbers of parasites could be recovered from footpads and draining lymph nodes up to 9 months after infection. Infections using L. tropica metacyclics purified from cutaneous, visceral and viscerotropic (Desert Storm) isolates of L. tropica were compared in both mouse and hamster models. Differences in disease progression were found that may reflect the parasite tissue tropism and virulence displayed by these strains in their human hosts. These findings suggest a role for parasite-related determinants in the clinical spectrum of disease. (C) 1998 Academic Press. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Complutense Madrid, Fac Vet, Dept Patol Anim 1, E-28040 Madrid, Spain. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Parasitol, IL-91010 Jerusalem, Israel. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,900 Rockville Pk, Bethesda, MD 20892 USA. EM dsacks@nih.gov NR 38 TC 27 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JUL PY 1998 VL 89 IS 3 BP 331 EP 342 DI 10.1006/expr.1998.4283 PG 12 WC Parasitology SC Parasitology GA ZZ500 UT WOS:000074735600007 PM 9676711 ER PT J AU Heyes, MP Saito, K Lackner, A Wiley, CA Achim, CL Markey, SP AF Heyes, MP Saito, K Lackner, A Wiley, CA Achim, CL Markey, SP TI Sources of the neurotoxin quinolinic acid in the brain of HIV-1-infected patients and retrovirus-infected macaques SO FASEB JOURNAL LA English DT Article DE macrophages; astrocytes; indoleamine-2,3-dioxygenase; kynurenine-3-hydroxylase; kynureninase; kynurenine aminotransferase; L-tryptophan; L-kynurenine; kynurenic acid; retrovirus; blood-brain barrier; cytokines; nonhuman primates ID HUMAN-IMMUNODEFICIENCY-VIRUS; KYNURENINE PATHWAY METABOLITES; COMPLEX PARTIAL SEIZURES; CENTRAL-NERVOUS-SYSTEM; CONVERT L-TRYPTOPHAN; CEREBROSPINAL-FLUID; NEUROLOGICAL DISEASE; IMMUNE ACTIVATION; NEUROACTIVE KYNURENINES; CEREBRAL-ISCHEMIA AB This: study investigated the sources of quinolinic acid, a neurotoxic tryptophan-kynurenine pathway metabolite, in the brain and blood of HIV-infected patients and retrovirus-infected macaques.In brain, quinolinic acid concentrations in HIV-infected patients were elevated by >300-fold to concentrations that exceeded cerebrospinal fluid (CSF) by 8.9-fold. There were no significant correlations between elevated serum quinolinic acid levels with those in CSF and brain parenchyma. Because nonretrovirus-induced encephalitis confounds the interpretation of human postmortem data, rhesus macaques infected with retrovirus were used to examine the mechanisms of increased quinolinic acid accumulations and determine the relationships of quinolinic acid to encephalitits and systemic responses. The largest kynurenine pathway responses in brain were associated with encephalitis and were independent of systemic responses. CSF quinolinic acid levels were also elevated in all infected macaques, but particularly those with retrovirus-induced encephalitis. In contrast to the brain changes, there was no difference in any systemic measure between macaques with encephalitis: vs. those without. Direct measures of the amount of quinolinic acid in brain derived from blood in a macaque with encephalitis showed that almost all quinolinic acid (>98%) was synthesized locally within the brain. These results demonstrate a role for induction of indoleamine-2,3-dioxygenase in accelerating the local formation of quinolinic acid within the brain tissue, particularly in areas of encephalitis, rather than entry of quinolinic acid into the brain from the meninges or blood. Strategies to reduce QUIN production, targeted at intracerebral sites, are potential approaches to therapy.-Heyes, M. P., Saito, K., Lackner, A., Wiley, C. A., Achim, C. L., Markey, S. P. Sources of the neurotoxin quinolinic acid in the brain of HIV-l-infected patients and retrovirus-infected macaques. C1 NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Presbyterian Univ Hosp, Div Neuropathol, Pittsburgh, PA 15213 USA. RP Heyes, MP (reprint author), NIMH, Lab Neurotoxicol, Bldg 10,Room 3D40,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NCRR NIH HHS [RR00168, RR00169]; NINDS NIH HHS [NS30769] NR 71 TC 105 Z9 109 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 1998 VL 12 IS 10 BP 881 EP 896 PG 16 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZY035 UT WOS:000074580100013 PM 9657528 ER PT J AU Anasti, JN AF Anasti, JN TI Premature ovarian failure: an update SO FERTILITY AND STERILITY LA English DT Article DE premature ovarian failure; ovarian dysfunction; ovarian physiology ID FOLLICLE-STIMULATING-HORMONE; HUMAN GRANULOSA-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; AUTOIMMUNE OOPHORITIS; HYPERGONADOTROPIC AMENORRHEA; ESTROGEN REPLACEMENT; OVULATION INDUCTION; ANTIGEN EXPRESSION; CLINICAL-FEATURES; RECEPTOR-BINDING AB Objective: To present an overview of potential etiologies, clinical manifestations, and treatment modalities of premature ovarian failure (POF). Design: A search of past and current articles on basic ovarian physiology and POF with use of MEDLINE. Additional information was obtained from an active study section on POF at the National Institutes of Health. Specific sections of this manuscript summarize the strengths and weaknesses of the possible pathophysiologic processes and management options of POF as they appear in the literature. Result(s): POF is not an uncommon disorder. Although the etiology remains elusive in most cases, several rare specific causes have been discovered. Although POF was once thought to be permanent, a substantial number of patients experience spontaneous remissions. Because of the association with other autoimmune diseases, close follow-up is recommended in patients with POF. Hormone replacement therapy remains the cornerstone of treatment, and the best chance of achieving a pregnancy is through oocyte donation. Conclusion(s): An understanding of basic ovarian embryology and physiology will allow clinicians to apply current treatments and develop new innovative therapies for their patients with POF. (Fertil Steril(R) 1998;70:1-15. (C)1998 by American Society for Reproductive Medicine.). C1 St Lukes Hosp, Dept Obstet & Gynecol, Bethlehem, PA 18015 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Anasti, JN (reprint author), St Lukes Hosp, Dept Obstet & Gynecol, 801 Ostrum St, Bethlehem, PA 18015 USA. NR 100 TC 158 Z9 176 U1 0 U2 8 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 1998 VL 70 IS 1 BP 1 EP 15 DI 10.1016/S0015-0282(98)00099-5 PG 15 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ZX102 UT WOS:000074479600001 PM 9660412 ER PT J AU Afeworki, M Miller, NR Devasahayam, N Cook, J Mitchell, JB Subramanian, S Krishna, MC AF Afeworki, M Miller, NR Devasahayam, N Cook, J Mitchell, JB Subramanian, S Krishna, MC TI Preparation and EPR studies of lithium phthalocyanine radical as an oxymetric probe SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE lithium phthalocyanine; oxymetry; FT EPR; RF EPR; free radical ID ELECTRON-SPIN-RESONANCE; PARAMAGNETIC-RESONANCE; OXYGEN CONCENTRATIONS; IN-VIVO; OXIMETRY; TISSUES; TUMORS; CELLS AB The electron paramagnetic resonance (EPR) spectrum of the paramagnetic center in solid lithium phthalocyanine, LiPc, exhibits a pO(2) (partial pressure of oxygen)-dependent line width. The compound is insoluble in water and is not easily biodegradable and, therefore, is a useful spin probe for quantitative in vivo oxymetry. Because EPR spectrometry is potentially a useful technique to quantitatively obtain in vivo tissue pO(2), such probes can be used to obtain physiological information. In this paper, a simple experimental procedure for the preparation of LiPc using potentiostatic electrochemical methods is described. The setup was relatively inexpensive and easy to implement. A constant potential ranging from 0.05 to 0.75 V versus Ag+/AgCl(s) was used for obtaining LiPc. The EPR spectral studies were carried out using spectrometers operating at X-band and at radiofrequency (RF) at different pO(2) values to characterize the spectral response of these crystals. The results indicate that, depending on the electrolysis conditions, the products contain mixtures of crystals exhibiting pO(2)-sensitive and pO(2)-insensitive line widths, Electrolysis conditions are reported whereby the pO(2)-sensitive LiPc crystals were the predominant product. The influence of the working surface of the electrode and the electrolysis time on the yield were also evaluated. The crystals of LiPc were also studied using a time-domain RF EPR spectrometer. In time-domain EPR, the signals that survive beyond the spectrometer dead time are mainly the narrow lines corresponding to the pO(2)-sensitive crystals, whereas the signals arising from the pO(2)-insensitive component of LiPc were found not to survive beyond the spectrometer dead time. This signal survival makes the time-domain EPR method more sensitive for pO(2) measurements using LiPc because the line width becomes very narrow at very low pO(2) and, concomitantly, the relaxation time T-2 longer, with no modulation or power saturation artifacts that are encountered as in the continuous wave (cw) mode. Further, minimal contributions from object motion in the spectral data obtained using time-domain methods make it an advantage for in vivo applications. Published by Elsevier Science Inc. C1 NCI, Radiat Biol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Div Clin Sci, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. NR 24 TC 35 Z9 35 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUL 1 PY 1998 VL 25 IS 1 BP 72 EP 78 DI 10.1016/S0891-5849(98)00039-2 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA ZV455 UT WOS:000074306300010 PM 9655524 ER PT J AU Hoffman, BJ Hansson, SR Mezey, E Palkovits, M AF Hoffman, BJ Hansson, SR Mezey, E Palkovits, M TI Localization and dynamic regulation of biogenic amine transporters in the mammalian central nervous system SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review DE serotonin; dopamine; norepinephrine; epinephrine; histamine; vesicular monoamine transporter; hypothalamus; immobilization stress; in situ hybridization histochemistry; axotomy ID VESICULAR MONOAMINE TRANSPORTER; HUMAN SEROTONIN TRANSPORTER; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; MURINE HEMATOPOIETIC PROGENITORS; PITUITARY-ADRENOCORTICAL SYSTEM; MESSENGER-RNA EXPRESSION; ADULT-RAT HYPOTHALAMUS; EARLY GENE-EXPRESSION; IMMEDIATE-EARLY GENES; DOPAMINE TRANSPORTER AB The monoamines, serotonin, dopamine, norepinephrine, epinephrine and histamine, play a critical role in the function of the hypothalamic-pituitary-adrenal axis and in the integration of information in sensory, limbic, and motor systems. The primary mechanism for termination of monoaminergic neurotransmission is through reuptake of released neurotransmitter by Na+, Cl-dependent plasma membrane transporters. A second family of transporters packages monoamines into synaptic and secretory vesicles by exchange of protons. Identification of those cells which express these two families of neurotransmitter transporters is an initial step in understanding what adaptive strategies cells expressing monoamine transporters use to establish the appropriate level of transport activity and thus attain the appropriate efficiency of monoamine storage and clearance. The most recent advances in this field have yielded several surprises about their function, cellular and subcellular localization, and regulation, suggesting that these molecules are not static and most likely are the most important determinants of extracellular levels of monoamines. Here, information on the localization of mRNAs for these transporters in rodent and human brain is summarized along with immunohistochemical information at the light and electron microscopic levels. Regulation of transporters at the mRNA level by manipulation in rodents and differences in transporter site densities by tomographic techniques as an index of regulation in human disease and addictive states are also reviewed. These studies have highlighted the presence of monoamine neurotransmitter transporters in neurons but not in glia in situ. The norepinephrine transporter is present in all cells which are both tyrosine hydroxylase (TH)- and dopamine p-hydroxylase-positive but not in those cells which are TH- and phenyl N-methyltransferase-positive, suggesting that epinephrine cells may have their own, unique transporter. In most dopaminergic cells, dopamine transporter mRNA completely overlaps with TH mRNA-positive neurons. However, there are areas in which there is a lack of one to one correspondence. The serotonin transporter (5-HTT) mRNA is found in all raphe nuclei and in the hypothalamic dorsomedial nucleus where the 5-HTT mRNA is dramatically reduced following immobilization stress. The vesicular monoamine transporter 2 (VMAT2) is present in all monoaminergic neurons including epinephrine- and histamine-synthesizing cells. Immunohistochemistry demonstrates that the plasma membrane transporters are present along axons, soma, and dendrites. Subcellular localization of DAT by electron microscopy suggests that these transporters are not at the synaptic density but are confined to perisynaptic areas, implying that dopamine diffuses away from the synapse and that contribution of diffusion to dopamine signalling may vary between brain regions. Interestingly, the presence of VMAT2 in vesicles underlying dendrites, axons, and soma suggests that monoamines may be released at these cellular domains. An understanding of the regulation of transporter function may have important therapeutic consequences for neuroendocrine function in stress and psychiatric disorders. C1 NIMH, Lab Cellular & Mol Regulat, Unit Mol Pharmacol, Bethesda, MD 20892 USA. NIMH, Genet Sect, Bethesda, MD 20892 USA. NINDS, Basic Neurosci Program, Bethesda, MD 20892 USA. RP Hoffman, BJ (reprint author), NIMH, Lab Cellular & Mol Regulat, Unit Mol Pharmacol, Bldg 36,Room 3A-17,36 CONVENT Dr MSC 4090, Bethesda, MD 20892 USA. EM beth@codon.nih.gov RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 211 TC 157 Z9 163 U1 1 U2 16 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD JUL PY 1998 VL 19 IS 3 BP 187 EP 231 DI 10.1006/frne.1998.0168 PG 45 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 102AX UT WOS:000074902000002 PM 9665836 ER PT J AU Cawley, HM Meltzer, SJ De Benedetti, VMG Hollstein, MC Muehlbauer, KR Liang, L Bennett, WP Souza, RF Greenwald, BD Cottrell, J Salabes, A Bartsch, H Trivers, GE AF Cawley, HM Meltzer, SJ De Benedetti, VMG Hollstein, MC Muehlbauer, KR Liang, L Bennett, WP Souza, RF Greenwald, BD Cottrell, J Salabes, A Bartsch, H Trivers, GE TI Anti-p53 antibodies in patients with Barrett's esophagus or esophageal carcinoma can predate cancer diagnosis SO GASTROENTEROLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; HIGH-RISK POPULATIONS; P53 MUTATIONS; LUNG-CANCER; IMMUNE-RESPONSE; BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; PRECURSOR LESIONS; SERUM ANTIBODIES; ALLELIC LOSSES AB Background & Aims: We previously discovered anti-p53 antibodies predating a cancer diagnosis in subjects at increased risk for liver, lung, breast, and prostate cancer. Recently, we reported a significant correlation (P < 0.017) between p53 antibodies and p53 mutations in patients with late-stage esophageal carcinoma. Because others have reported p53 mutations and overexpression of p53 protein in Barrett's esophagus, we studied p53 antibodies in plasma of 88 serially endoscoped patients: 36 with Barrett's metaplasia, 23 with esophageal squamous cell carcinoma, 10 with esophageal adenocarcinoma, and 19 with esophagitis or normal esophagus. Methods: We used enzyme immunoassay, immunoblotting, and immunoprecipitation assays for p53 antibodies; polymerase chain reaction, denaturant gradient gel electrophoresis, and sequencing for p53 mutations; and immunohistochemistry for p53 protein. Results: p53 antibodies were detected in 4 patients with Barrett's esophagus, including 1 with dysplasia that later progressed to adenocarcinoma, and in 10 cancer patients (P 0.002) (8 squamous and 2 adenocarcinoma), 2 of whom (1 squamous, 1 adenocarcinoma) had antibodies before cancer was diagnosed. Other patient groups were too small for informative statistical analysis. Six antibody-positive cancer patients had p53 mutations, whereas 2 patients with cancer and 1 with Barrett's esophagus with antibodies had p53 protein overexpressed in esophageal tissues. Conclusions: Patients with Barrett's esophagus and esophageal cancer can develop p53 antibodies that may predate the clinical diagnosis of malignancy. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21201 USA. Baltimore Vet Affairs Hosp, Baltimore, MD USA. German Canc Res Ctr, D-6900 Heidelberg, Germany. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. RP Trivers, GE (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2C05, Bethesda, MD 20892 USA. EM triversg@intra.nci.nih.gov FU NCI NIH HHS [CA67497]; NIDDK NIH HHS [DK47717] NR 46 TC 58 Z9 59 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1998 VL 115 IS 1 BP 19 EP 27 DI 10.1016/S0016-5085(98)70360-9 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZW666 UT WOS:000074434500007 PM 9649454 ER PT J AU Mano, H Ohya, K Miyazato, A Yamashita, Y Ogawa, W Inazawa, J Ikeda, U Shimada, K Hatake, K Kasuga, M Ozawa, K Kajigaya, S AF Mano, H Ohya, K Miyazato, A Yamashita, Y Ogawa, W Inazawa, J Ikeda, U Shimada, K Hatake, K Kasuga, M Ozawa, K Kajigaya, S TI Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase SO GENES TO CELLS LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; HEMATOPOIETIC-CELLS; SIGNALING PATHWAY; FACTOR-RECEPTOR; GRB-IR; PROTEIN; GENE; FAMILY; EXPRESSION; CLONING AB Background: Tec is a member of the recently emerging subfamily among nonreceptor protein-tyrosine kinases (PTKs). Although many members of this family have been shown to be involved in a wide range of cytokine-mediated signalling systems, the molecular mechanism by which they exert in vivo effects remains obscure. To gain insights into the downstream pathways of Tec, we here looked for Tee-interacting proteins (TIPs) by using the yeast two-hybrid screening. Results: One of TIPs turned out to be Grb10/GrbIR, which carries one pleckstrin homology domain and one Src homology 2 domain. Grb10/GrbIR was known to bind receptor PTKs in a ligand-dependent fashion, but not to be phosphorylated on tyrosine residues. In a transient expression system in human kidney 293 cells, however, Grb10/GrbLR becomes profoundly tyrosine-phosphorylated by Tee, but not by Syk, Jak2 or insulin receptor. We also reveal that expression of Grb10/GrbIR suppresses the cytokine-driven and Tec-driven activation of the c-fos promoter. Conclusion: Our results indicate a novel role of Grb10/GrbLR as an effector molecule to a subset of nonreceptor PTKs. C1 Jichi Med Sch, Dept Mol Biol, Minamikawachi, Tochigi 3290498, Japan. Jichi Med Sch, Dept Cardiol, Minamikawachi, Tochigi 3290498, Japan. Jichi Med Sch, Dept Hematol, Minamikawachi, Tochigi 3290498, Japan. Kobe Univ, Sch Med, Dept Internal Med 2, Kobe, Hyogo 650, Japan. Kyoto Prefectural Univ Med, Dept Hyg, Kyoto 602, Japan. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 33 TC 35 Z9 38 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1356-9597 J9 GENES CELLS JI Genes Cells PD JUL PY 1998 VL 3 IS 7 BP 431 EP 441 DI 10.1046/j.1365-2443.1998.00201.x PG 11 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 117RZ UT WOS:000075796700003 PM 9753425 ER PT J AU Bruggemann, EP Doan, B Handwerger, K Storz, G AF Bruggemann, EP Doan, B Handwerger, K Storz, G TI Characterization of an unstable allele of the Arabidopsis HY4 locus SO GENETICS LA English DT Article ID BLUE-LIGHT PHOTORECEPTOR; HYPOCOTYL ELONGATION; THALIANA; EXPRESSION; GENE; MUTATIONS; PROTEIN AB The Arabidopsis Hy4 gene encodes the nonessential blue light photoreceptor CRY1. Loss-of-function hy4 mutants have an elongated hypocotyl phenotype after germination under blue light. We previously analyzed 20 independent hy4 alleles produced by fast neutron mutagenesis. These alleles were grouped into two classes based on their genetic behavior and corresponding deletion size: (1) null hy4 alleles that were semidominant over wild type and contained small or moderate-sized deletions at HY4 and (2) null hy4 alleles that were recessive lethal and contained large HY4 deletions. Here ive describe one additional fast neutron hy4 mutant, B144, that did not fall into either of these two classes. Mutant B144 was isolated as a heterozygote with an intermediate hy4 phenotype. One allele from this mutant, hy4-B144(Delta), contains a large deletion at HY4 and is recessive lethal. The other allele from this mutant, HY4-B144*, appears to be intact and functional but is unstable and spontaneously converts to a nonfunctional hy4 allele. In addition, HI Hy4-B144* is lethal in homozygotes and suppresses local recombination. We discuss genetic and epigenetic mechanisms that may account for the unusual behavior of the HY4-B144* allele. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bruggemann, EP (reprint author), Pioneer Hi Bred Int Inc, Res & Prod Dev, 7300 NW 62nd Ave, Johnston, IA 50131 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 22 TC 4 Z9 5 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUL PY 1998 VL 149 IS 3 BP 1575 EP 1585 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA ZZ226 UT WOS:000074708200034 PM 9649544 ER PT J AU Pruitt, KD AF Pruitt, KD TI WebWise: Guide to the Washington University Center for Genetics in Medicine Web site SO GENOME RESEARCH LA English DT Article C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD JUL PY 1998 VL 8 IS 7 BP 686 EP 689 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 107JB UT WOS:000075203500002 PM 9685315 ER PT J AU Leonard, JC Toji, LH Bender, PK Beiswanger, CM Beck, JC AF Leonard, JC Toji, LH Bender, PK Beiswanger, CM Beck, JC TI Regional Mapping Panels for chromosomes 8, 13, 21, and 22 SO GENOMICS LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; 8-21 TRANSLOCATION; PHYSICAL MAP; C-MOS; LOCALIZATION; BREAKPOINT; GENE; INACTIVATION; LEUKEMIA C1 Coriell Inst Med Res, Coriell Cell Repositories, NIGMS Human Mutant Cell Repository, Camden, NJ 08103 USA. RP Beck, JC (reprint author), Coriell Inst Med Res, Coriell Cell Repositories, NIGMS Human Mutant Cell Repository, Camden, NJ 08103 USA. FU NIGMS NIH HHS [N01-GM4-2102] NR 21 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 1 PY 1998 VL 51 IS 1 BP 17 EP 20 DI 10.1006/geno.1998.5375 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 106ZU UT WOS:000075182000002 PM 9693028 ER PT J AU Stone, AL Melton, DJ Lewis, MS AF Stone, AL Melton, DJ Lewis, MS TI Structure-function relations of heparin-mimetic sulfated xylan oligosaccharides: inhibition of Human Immunodeficiency Virus-1 infectivity in vitro SO GLYCOCONJUGATE JOURNAL LA English DT Article DE heparin-mimetic oligosaccharides; anti-HIV-1 capacity of components of sulfated xylan; mass of sulfated oligosaccharides by equilibrium-ultracentrifugation ID FIBROBLAST GROWTH-FACTOR; HIV AGENT INVITRO; PENTOSAN POLYSULFATE; DEXTRAN SULFATE; BINDING-SITES; FACTOR-H; POLYSACCHARIDES; GLYCOSAMINOGLYCANS; MECHANISM; RECEPTOR AB Heparins/heparan sulfates modulate the function of proteins and cell membranes in numerous biological systems including normal and disease processes in humans. Heparin has been used for many years as an anticoagulant, and anticoagulant heparin-mimetics were developed several decades ago by chemical sulfation of non-mammalian polysaccharides, e.g., an antithrombotic sulfated xylan. This pharmaceutical, which comprises a mixture of sulfated oligoxylans, also mimics most other biological actions of natural heparins in vitro, including inhibition of the human immunodeficiency virus, but the molecular basis for these actions has been unclear. Here, numerous Components of the sulfated oligoxylan mixture were isolated and when bioassayed in the case of anti-HIV-1 infectivity revealed that a structural specificity underlines the capacity of sulfated xylan to inhibit HIV-1, rather than a non-specific mechanism. Components were isolated by chromatographic fractionation through Bio-Gel P10 in 0.5M ammonium bicarbonate. This fractionation revealed an elution range associated with apparent molecular weights of similar to 22000 to <1500 relative to standard heparin and heparan sulfates and newly prepared sulfated oligosaccharide standards. Components were characterized by metachromatic absorption spectroscopy, ultracentrifugation, GlcA analysis, and potency against HIV-1 infectivity, both in the tetrazolium cytotoxicity assay and in syncytium-forming assays, in CD4-lymphocytes. Structural specificity was indicated by the differential potencies exhibited by the Components: Highest activity (cytotoxicity) was exhibited by Components in the chromatographic region greater than or equal to similar to 5400 in mass (50% effective (inhibitory) concentration = 0.5-0.7 mu g ml(-1) in the first fractionation series, and 0.1-0.5 mu g m(-1) in a second series). The potency declined sharply below similar to 5400 in mass, but with an exception; a second structure exhibiting relatively high potency eluted among low-mass oligosaccharides which had an average size of similar to a nonomer. Components displayed differential potencies also against the syncytium-forming infectivity of HIV-1. The high potency against syncytium-formation was retained by Components down to a minimum size of about 4500 in mass, smaller than the greater than or equal to similar to 5400 required above. One in ten of the beta 1,4-linked xyloses in the native xylan are substituted with a monomeric alpha 1,2 DGlcA branch. We have speculated that pharmaceutical actions of sulfated xylan might be related to structures involving the alpha-D linked substituents and this was examined using a space-filling model of a sulfated octaxylan and by analyses of Components for GlcA content. Understanding structure/function relations in the heparin-like actions of these agents would be of general significance for the careful examination of their potential clinical usefulness in many human processes modulated by heparins, including AIDS. C1 NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. NCRR, Biomed Engn & Instrumentat Program, NIH, Bethesda, MD 20892 USA. RP Stone, AL (reprint author), NICHHD, Dev & Mol Immun Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 76 TC 14 Z9 22 U1 2 U2 11 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD JUL PY 1998 VL 15 IS 7 BP 697 EP 712 DI 10.1023/A:1006940632184 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 112RY UT WOS:000075509000009 PM 9881776 ER PT J AU Maxwell, GL Risinger, JI Tong, B Shaw, H Barrett, JC Berchuck, A Futreal, PA AF Maxwell, GL Risinger, JI Tong, B Shaw, H Barrett, JC Berchuck, A Futreal, PA TI Mutation of the PTEN tumor suppressor gene is not a feature of ovarian cancers SO GYNECOLOGIC ONCOLOGY LA English DT Article ID ENDOMETRIAL AB Objective. The PTEN tumor suppressor gene on chromosome 10q23 undergoes inactivating mutations in several types of malignancies including glioblastomas and prostate and endometrial carcinomas. The aim of this study was to determine if mutation of the PTEN tumor suppressor gene is a feature of sporadic or BRCA1-associated ovarian carcinomas. Methods. Genomic deoxyribonucleic acid was extracted from 11 ovarian cancer cell lines and 50 frozen ovarian cancers, including 4 cases that developed in women with germline mutations in the BRCA1 breast/ovarian cancer susceptibility gene. The polymerase chain reaction was used to amplify each of the nine exons and intronic splice sites of the PTEN gene. These products were then screened for mutations using single strand conformation polymorphism analysis. Variant bands were further evaluated using automated DNA sequencing. Results. A previously unreported silent polymorphism at codon 240 (TAT to TAG) in exon 7 was noted in one of the primary ovarian carcinomas. Mutations in the PTEN gene were not found in any of the 50 primary ovarian cancers or 11 immortalized ovarian cancer cell lines. Conclusion. Alteration of the PTEN tumor suppressor gene does not appear to be a feature of sporadic or BRCA1-associated ovarian cancers. (C) 1998 Academic Press. C1 Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Maxwell, GL (reprint author), Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Box 3079, Durham, NC 27710 USA. NR 15 TC 35 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 1998 VL 70 IS 1 BP 13 EP 16 DI 10.1006/gyno.1998.5039 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 108XC UT WOS:000075290200003 PM 9698466 ER PT J AU Ondrey, FG AF Ondrey, FG TI Arachidonic acid metabolism: A primer for head and neck surgeons SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Review DE eicosanoids; head and neck cancer; cyclooxygenase, lipoxygenase; prostaglandins; immunity ID SQUAMOUS-CELL CARCINOMA; PROSTAGLANDIN-SYNTHESIS; PROGNOSTIC-SIGNIFICANCE; TUMOR-CELLS; ORAL-CANCER; INHIBITION; GROWTH; BIOSYNTHESIS; EICOSANOIDS; PATHWAYS AB The arachidonic acid metabolites, or eicosanoids, are a large series of lipid-derived mediators capable of producing a multitude of physiologic effects in the local environment. They play important roles in a variety of signaling pathways in endocrinology, immunology, and oncology. A significant body of work in this area has occurred in squamous cell carcinomas of the head and neck over the past 15 years. This review will attempt to familiarize the head and neck surgical oncologist with the basic biochemical steps in the formation of these compounds, newer developments in the field of eicosanoid biochemistry, and related experimental evidence of the roles of these substances in head and neck cancer. (C) 1998 John Wiley & Sons, Inc. C1 Natl Inst Deafness & Other Commun Dis, Tumor Cell Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. RP Ondrey, FG (reprint author), Natl Inst Deafness & Other Commun Dis, Tumor Cell Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. NR 92 TC 16 Z9 16 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD JUL PY 1998 VL 20 IS 4 BP 334 EP 349 DI 10.1002/(SICI)1097-0347(199807)20:4<334::AID-HED9>3.0.CO;2-# PG 16 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA ZJ794 UT WOS:000073253900009 PM 9588707 ER PT J AU Scher, AI Stewart, WF Liberman, J Lipton, RB AF Scher, AI Stewart, WF Liberman, J Lipton, RB TI Prevalence of frequent headache in a population sample SO HEADACHE LA English DT Article DE CTTH chronic tension-type headache; SES socioeconomic status; FH M frequent headache with migrainous features; FH O other frequent headache ID TENSION-TYPE HEADACHE; NEAR-DAILY HEADACHES; MIGRAINE HEADACHE; CLASSIFICATION; EPIDEMIOLOGY; SOCIETY; CRITERIA; RACE AB Purpose.-Patients with daily or near-daily headaches are commonly seen in neurology practices and in headache subspecialty centers, but there is little information on the prevalence of this condition in the general population. We present the first US-based study describing the. prevalence and characteristics of frequent headache in the general population. Methods.-In Baltimore County, Maryland, 13 343 individuals 18 to 65 years of age were selected by random-digit dialing and interviewed by telephone about their headaches. Subjects reporting 180 or more headaches per year were classified as having frequent headache. Three mutually exclusive subtypes of frequent headache were identified: frequent headache with migrainous features, chronic tension-type headache, and unclassified frequent headache. Results.-The overall prevalence of frequent headache was 4.1% (5.0% female, 2.8% male; 1.8:1 female to male ratio). Frequent headache was 33% more common in Caucasians (4.4%) than in African Americans (3.3%). In both males and females, prevalence was highest in the lowest educational category. Among frequent headache sufferers, more than half (52% female, 56% male:) met criteria for chronic tension-type headache, almost one third (33% female, 25% male) met criteria for frequent headache with migrainous features, and the remainder (15% female, 19% male) were unclassified. Overall, 30% of female and 25% of male frequent headache sufferers met International Headache Society (IHS) criteria for migraine (with or without aura). Conclusions;-Frequent headache is common in the general population and is more prevalent in Caucasians and in those with less than a high school education. Chronic tension-type headache is more common than frequent headache with migrainous features, though the latter is more disabling. Although more common in females than males, the female preponderance of frequent headache is less marked than in migraine. The sex ratio varies by frequent headache subtype. C1 Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD USA. Albert Einstein Coll Med, Dept Neurol, New York, NY USA. Albert Einstein Coll Med, Dept Epidemiol, New York, NY USA. Albert Einstein Coll Med, Dept Med Sociol, New York, NY USA. Monash Med Ctr, Headache Unit, New York, NY USA. Innovat Med Res, Towson, MD USA. RP Stewart, WF (reprint author), Sch Hyg & Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. NR 30 TC 385 Z9 389 U1 0 U2 4 PU AMER ASSOC STUDY HEADACHE PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0017-8748 J9 HEADACHE JI Headache PD JUL-AUG PY 1998 VL 38 IS 7 BP 497 EP 506 DI 10.1046/j.1526-4610.1998.3807497.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 211PA UT WOS:000081168300001 PM 15613165 ER PT J AU Lubin, JH AF Lubin, JH TI On the discrepancy between epidemiologic studies in individuals of lung cancer and residential radon and Cohen's ecologic regression SO HEALTH PHYSICS LA English DT Article DE Rn-222; epidemiology; cancer; lungs, human ID UNITED-STATES HOMES; AGGREGATE DATA; DISEASE RISK; EXPOSURE; MINERS AB There is still substantial confusion in the radiation effects community about the inherent limitations of ecologic analysis. As a result, inordinate attention has been given to the discrepant results of Cohen, in which a negative estimate is observed for the regression of county mortality rates for lung cancer on estimated county radon levels. This paper demonstrates that Cohen's ecologic analysis cannot produce valid inference on the exposure-response relationship for individuals unless lung cancer risk factors (smoking, age, occupation, etc.) for individuals are statistically uncorrelated with indoor radon level within counties or unless risk effects for radon and other factors are additive. Both of these assumptions are contradicted in the literature. Thus, contrary to common assumption, when a linear no-threshold model is the true model for radon risk for individuals, higher average radon concentration for a county does not necessarily imply a higher lung cancer rate for the county. In addition, valid inference from county-level ecologic analysis and the elimination of the ecologic bias cannot be achieved with the addition of county-wide summary variables (including "stratification" variables) to the regression equation. Using hypothetical data for smoking and radon and assuming a true positive association for radon and lung cancer for individuals, the analysis demonstrates that a negative county-level ecologic regression can be induced when correlation coefficients for smoking and radon within county are in the range -0.05 to 0.05. Since adverse effects for radon at low exposures are supported by analysis of miner data (all data and data restricted only to low cumulative exposures), a meta-analysis of indoor radon studies, and molecular and cellular studies, and since ecologic regressions are burdened by severe limitations, the negative results from Cohen's analysis are most likely due to bias and should be rejected. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 20 TC 52 Z9 56 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUL PY 1998 VL 75 IS 1 BP 4 EP 10 DI 10.1097/00004032-199807000-00001 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA ZU966 UT WOS:000074254400002 PM 9645660 ER PT J AU Lubin, JH AF Lubin, JH TI Rejoinder: Cohen's response to "On the discrepancy between epidemiologic studies in individuals of lung cancer and residential radon and Cohen's ecologic regression" SO HEALTH PHYSICS LA English DT Article ID INDOOR RADON C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 8 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUL PY 1998 VL 75 IS 1 BP 29 EP 30 DI 10.1097/00004032-199807000-00005 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA ZU966 UT WOS:000074254400006 ER PT J AU Dayan, D Kozlovsky, A Tal, K Kariv, N Shemesh, M Nyska, A AF Dayan, D Kozlovsky, A Tal, K Kariv, N Shemesh, M Nyska, A TI Castration prevents calcium channel blocker-induced gingival hyperplasia in beagle dogs SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article DE castration; calcium channel-blocker; gingival hyperplasia ID SALIVARY TESTOSTERONE MEASUREMENTS; CELL-DEATH; OXODIPINE; ANDROGEN; RATS; METABOLISM; ESTROGEN AB 1 The purpose of this study was to investigate testosterone's role on the calcium channel antagonist oxodipine-inducing gingival hyperplasia in a dog model. 2 Two experiments were conducted using castrated and intact male dogs. Oxodipine was administered orally for 90 days, at a dose of 24 mg/kg/day. In the first experiment, the occurrence of gingival hyperplasia was evaluated. In the second, the gingival index (GI) and gingival hyperplasia index (GHI) were recorded and correlated with serum levels of testosterone. 3 A significant positive correlation between GI, GHI and plasma testosterone was noted, Castrated dogs were injected with testosterone, 4 months after the start of oxodipine treatment, while in the non-castrated dogs, administration of oxodipine was stopped. Castration correlated with lack of GH, while testosterone injection to the same dogs was associated with an increase of GI and GHI. 4 Since it is known that testosterone receptors are present in the gingiva, ii is proposed that oxodipine-induced gingival hyperplasia could be mediated by the calcium channel blocker on plasma testosterone levels. C1 Tel Aviv Univ, Maurice & Gabriela Goldschleger Sch Dent Med, Dept Oral Pathol & Oral Med, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Maurice & Gabriela Goldschleger Sch Dent Med, Dept Periodontol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. Hebrew Univ Jerusalem, Beit Dagan & Koret Sch Vet Med, Kimron Vet Inst, Dept Hormone Res, Jerusalem, Israel. NIEHS, Res Triangle Pk, NC 27709 USA. RP Dayan, D (reprint author), Tel Aviv Univ, Maurice & Gabriela Goldschleger Sch Dent Med, Dept Oral Pathol & Oral Med, IL-69978 Tel Aviv, Israel. NR 33 TC 7 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD JUL PY 1998 VL 17 IS 7 BP 396 EP 402 DI 10.1191/096032798678908945 PG 7 WC Toxicology SC Toxicology GA 113ZF UT WOS:000075584100006 PM 9726536 ER PT J AU Danel, C Erzurum, SC Prayssac, P Eissa, NT Crystal, RG Herve, P Baudet, B Mazmanian, M Lemarchand, P AF Danel, C Erzurum, SC Prayssac, P Eissa, NT Crystal, RG Herve, P Baudet, B Mazmanian, M Lemarchand, P TI Gene therapy for oxidant injury-related diseases: Adenovirus-mediated transfer of superoxide dismutase and catalase cDNAs protects against hyperoxia but not against ischemia-reperfusion lung injury SO HUMAN GENE THERAPY LA English DT Article ID PULMONARY OXYGEN-TOXICITY; TRANSGENIC MICE; ENDOTHELIAL-CELLS; RATS; RADICALS; LETHAL; HEART AB Hyperoxia and ischemia-reperfusion cause profound lung cellular damage mediated, in part, by generation of oxygen radicals. We hypothesized that gene therapy can be used to overcome oxidant injury by augmenting intracellular antioxidant enzymes, Adult rats were injected intratracheally with an adenovirus (Ad) vector encoding human superoxide dismutase (CuZn-SOD) or catalase cDNA, a mixture of both Ad vectors, or a control Ad vector containing no exogenous gene. Expression of human catalase and CuZn-SOD was demonstrated 3 days later in distal lung epithelial cells and alveolar macrophages, using ELISA and immunochemistry, After exposure to 100% O-2 for 62 hr, survival was greater in rats injected with the catalase and/or SOD Ad vectors than in control rats. Ischemia-reperfusion injury was evaluated in the isolated perfused lung model. Overexpression of SOD worsened ischemia-reperfusion injury. Interestingly, concomitant overexpression of catalase prevented this adverse effect, but did not protect against ischemia-reperfusion injury. We conclude that Ad-mediated transfer to lungs of both catalase and SOD cDNAs protects from pulmonary O-2 toxicity. Absence of protection against ischemia-reperfusion using intratracheal Ad injections may be related to the lack of endothelial protection, despite epithelial expression of catalase and SOD. C1 Fac Med Necker Enfants Malades, INSERM U25, F-75730 Paris 15, France. Univ Paris 05, Hop Laennec, Paris, France. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Hop Marie Lannelongue, Chirurg Expt Lab, F-92350 Le Plessis Robinson, France. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Cornell Univ, Coll Med, New York, NY USA. INSERM U25, F-75730 Paris 15, France. RP Lemarchand, P (reprint author), Fac Med Necker Enfants Malades, INSERM U25, 156 Rue Vaugirard, F-75730 Paris 15, France. FU NHLBI NIH HHS [HL03117] NR 42 TC 74 Z9 79 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL 1 PY 1998 VL 9 IS 10 BP 1487 EP 1496 DI 10.1089/hum.1998.9.10-1487 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZZ212 UT WOS:000074706800012 PM 9681420 ER PT J AU Schaffer, AA AF Schaffer, AA TI Coping with complexity: lessons from the mathematical sciences SO HUMAN GENETICS LA English DT Article ID RETINITIS-PIGMENTOSA; LINKAGE ANALYSIS; YEAST GENOME; DNA; ALIGNMENT; MUTATIONS; GENES; CONSTRUCTION; INHERITANCE; ALGORITHM AB I suggest five research paradigms fundamental in the mathematical sciences that seem relevant to the hunt for explanations of genetic susceptibility to complex diseases. I discuss a few ways in which these paradigms are, or are not, currently being followed in complex disease genetics. This essay is intended to provoke discussion and not to resolve any problems. It represents a written version of remarks that I made as "Discussant" at a session at the 1997 National Institutes of Health Research Festival. C1 Natl Human Genome Res Inst, NIH, Baltimore, MD 21224 USA. RP Schaffer, AA (reprint author), Natl Human Genome Res Inst, NIH, Suite 2000,333 Cassell Dr, Baltimore, MD 21224 USA. EM schaffer@helix.nih.gov RI Schaffer, Alejandro/F-2902-2012 NR 51 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 1998 VL 103 IS 1 BP 5 EP 10 DI 10.1007/s004390050775 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 110VT UT WOS:000075402400002 PM 9737769 ER PT J AU Vincent, JB Kalsi, G Klempan, T Tatuch, Y Sherrington, RP Breschel, T McInnis, MG Brynjolfsson, J Petursson, H Gurling, HMD Gottesman, II Torrey, EF Petronis, A Kennedy, JL AF Vincent, JB Kalsi, G Klempan, T Tatuch, Y Sherrington, RP Breschel, T McInnis, MG Brynjolfsson, J Petursson, H Gurling, HMD Gottesman, II Torrey, EF Petronis, A Kennedy, JL TI No evidence of expansion of CAG or GAA repeats in schizophrenia families and monozygotic twins SO HUMAN GENETICS LA English DT Article ID EXPANDED TRINUCLEOTIDE REPEATS; MACHADO-JOSEPH DISEASE; FRAGILE-X MUTATIONS; SOMATIC MOSAICISM; HUMAN GENOME; BIPOLAR DISORDER; CAG/CTG REPEATS; TRIPLET REPEAT; ANTICIPATION; GENES AB Many diseases caused by trinucleotide expansion exhibit increased severity and decreased age of onset (genetic anticipation) in successive generations, Apparent evidence of genetic anticipation in schizophrenia has led to a search for trinucleotide repeat expansions. We have used several techniques, including Southern blot hybridization, repeat expansion detection (RED) and locus-specific PCR to search for expanded CAG/CTG repeats in 12 families from the United Kingdom and 11 from Iceland that are multiplex for schizophrenia and demonstrate anticipation. The unstable DNA theory could also explain discordance of phenotype for schizophrenia in pairs of monozygotic twins, where the affected twin has a greater number of repeats than the unaffected twin. We used these techniques to look for evidence of different CAG/CTG repeat size in 27 pairs of monozygotic twins who are either concordant or discordant for schizophrenia. We have found no evidence of an increase in CAG/CTG repeat size for affected members in the families, or for the affected twins in the MZ twin sample. Southern hybridization and RED analysis were also performed for the twin and family samples to look for evidence of expansion of GAA/TTC repeats. However, no evidence of expansion was found in either sample. Whilst these results suggest that these repeats are not involved in the etiology of schizophrenia, the techniques used for detecting repeat expansions have limits to their sensitivity. The involvement of other trinucleotide repeats or other expandable repeat sequences cannot be ruled out. C1 Clarke Inst Psychiat, Neurogenet Sect, Toronto, ON M5T 1R8, Canada. UCL, Sch Med, Dept Psychiat & Behav Sci, Mol Psychiat Lab, London WC1E 6BT, England. Sequana Therapeut, La Jolla, CA 92037 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Iceland, Dept Psychiat, Reykjavik, Iceland. Univ Virginia, Dept Psychol, Charlottesville, VA 22903 USA. NIMH, Ctr Neurosci, St Elizabeths Hosp, Washington, DC 20032 USA. RP Kennedy, JL (reprint author), Clarke Inst Psychiat, Neurogenet Sect, R-31,250 Coll St, Toronto, ON M5T 1R8, Canada. EM kennedyj@cs.clarke-inst.on.ca RI G, I/D-8042-2011; McInnis, Melvin/F-6963-2012; Gurling, Hugh/A-5029-2010 OI McInnis, Melvin/0000-0002-0375-6247; NR 39 TC 25 Z9 26 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 1998 VL 103 IS 1 BP 41 EP 47 DI 10.1007/s004390050780 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 110VT UT WOS:000075402400007 PM 9737774 ER PT J AU Lavedan, C Leroy, E Dehejia, A Buchholtz, S Dutra, A Nussbaum, RL Polymeropoulos, MH AF Lavedan, C Leroy, E Dehejia, A Buchholtz, S Dutra, A Nussbaum, RL Polymeropoulos, MH TI Identification, localization and characterization of the human gamma-synuclein gene SO HUMAN GENETICS LA English DT Article ID OVARIAN-CANCER; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; BREAST; PROTEIN; BRAIN; ASSIGNMENT; COMPLEXITY; MUTATIONS; BRCA1 AB We have identified and characterized a new member of the human synuclein gene family, gamma-synuclein (SNCG). This gene is composed of five exons, which en code a 127 amino acid protein that is highly homologous to alpha-synuclein, which is mutated in some Parkinson's disease families, and to beta-synuclein. The gamma-synuclein gene is localized to chromosome 10q23 and is principally expressed In the brain, particularly in the substantia nigra. We have determined its genomic sequence: and established conditions for sequence analysis of each of the exons. The gamma-synuclein gene, also known as BCSG1, was recently found to be overexpressed in advanced infiltrating carcinoma of the breast, Our survey of the EST database Indicated that it might also be overexpressed in an ovarian tumor. C1 Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bayview Med Ctr, Baltimore, MD 21224 USA. Natl Human Genome Res Inst, Lab Gene Transfer, NIH, Bethesda, MD 20892 USA. RP Polymeropoulos, MH (reprint author), Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, 49 Convent Dr,49-4A66, Bethesda, MD 20892 USA. NR 26 TC 128 Z9 140 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 1998 VL 103 IS 1 BP 106 EP 112 DI 10.1007/s004390050792 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 110VT UT WOS:000075402400019 PM 9737786 ER PT J AU Van Hauwe, P Everett, LA Coucke, P Scott, DA Kraft, ML Ris-Stalpers, C Bolder, C Otten, B de Vijlder, JJM Dietrich, NL Ramesh, A Srisailapathy, SCR Parving, A Cremers, CWRJ Willems, PJ Smith, RJH Green, ED Van Camp, G AF Van Hauwe, P Everett, LA Coucke, P Scott, DA Kraft, ML Ris-Stalpers, C Bolder, C Otten, B de Vijlder, JJM Dietrich, NL Ramesh, A Srisailapathy, SCR Parving, A Cremers, CWRJ Willems, PJ Smith, RJH Green, ED Van Camp, G TI Two frequent missense mutations in Pendred syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID CONGENITAL CHLORIDE DIARRHEA; RNA SPLICE JUNCTIONS; REGION; GENES; MAPS AB Pendred syndrome is an autosomal recessive disorder characterized by early childhood deafness and goiter. A century after its recognition as a syndrome by Vaughan Pendred, the disease gene (PDS) was mapped to chromosome 7q22-q31.1 and, recently found to encode a putative sulfate transporter. We performed mutation analysis of the PDS gene in patients from 14 Pendred families originating from seven countries and identified all mutations. The mutations include three single base deletions, one splice site mutation and 10 missense mutations. One missense mutation (L236P) was found in a homozygous state in two consanguineous families and in a heterozygous state in five additional non-consanguineous families. Another missense mutation (T416P) was found in a homozygous state in one family and in a heterozygous state in four families. Pendred patients in three non-consanguineous families were shown to be compound heterozygotes for L236P and T416P. In total, one or both of these mutations were found in nine of the 14 families analyzed. The identification of two frequent PDS mutations will facilitate the molecular diagnosis of Pendred syndrome. C1 Univ Instelling Antwerp, Dept Med Genet, B-2610 Wilrijk, Antwerp, Belgium. NIH, Natl Human Genome Res Inst, Genome Technol Branch, Bethesda, MD USA. Univ Iowa, Dept Otolaryngol, Iowa City, IA USA. Univ Amsterdam, Acad Med Ctr, Dept Pediat Epidemiol, NL-1105 AZ Amsterdam, Netherlands. Univ Nijmegen Hosp, Dept Otolaryngol, NL-6500 HB Nijmegen, Netherlands. Bispebjerg Hosp, Dept Audiol, DK-2400 Copenhagen NV, Denmark. Univ Madras, Dept Genet, Madras, Tamil Nadu, India. RP Van Camp, G (reprint author), Univ Instelling Antwerp, Dept Med Genet, Univ Plein 1, B-2610 Wilrijk, Antwerp, Belgium. RI Van Camp, Guy/F-3386-2013; Cremers, C.W.R.J./L-4254-2015; Otten, B.J./L-4562-2015 OI Van Camp, Guy/0000-0001-5105-9000; FU NIDCD NIH HHS [R01DC02842] NR 18 TC 115 Z9 119 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL PY 1998 VL 7 IS 7 BP 1099 EP 1104 DI 10.1093/hmg/7.7.1099 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA ZX952 UT WOS:000074571900005 PM 9618166 ER PT J AU Weirich, G Sandherr, M Fellbaum, C Richter, T Schmidt, L Kinjerski, T Dietzfelbinger, H Rastetter, J Hofler, H AF Weirich, G Sandherr, M Fellbaum, C Richter, T Schmidt, L Kinjerski, T Dietzfelbinger, H Rastetter, J Hofler, H TI Molecular evidence of bone marrow involvement in advanced case of T gamma delta lymphoma with secondary myelofibrosis SO HUMAN PATHOLOGY LA English DT Article DE T gamma delta lymphoma; myelofibrosis; decalcified fixed bone marrow tissue; PCR; clonality ID CELL LYMPHOMA; MALIGNANT HISTIOCYTOSIS; RECEPTOR; LOCALIZATION; EXPRESSION; ENTITY AB We describe the case of a middle-aged man with long indolent course of generalized T gamma delta lymphoma. The onset of secondary myelofibrosis made cytological monitoring of the bone marrow infiltrates impossible. As during progression of the disease splenectomy revealed typical histological features of a high-grade hepatosplenic T gamma delta lymphoma, the low-grade bone infiltrate was considered a secondary lymphoma. The use of the polymerase chain reaction helped to detect a constant and identical monoclonal rearrangement pattern of the T-cell receptor gamma-chain gene in both bone marrow and splenic T-cell infiltrates. The notion of a secondary spread of malignant T-cells to the bone marrow was thereby confirmed despite striking cytological differences between bone marrow and splenic infiltrates. This is the first report of a diagnostic DNA-based molecular approach using fixed decalcified bone marrow. This method may provide a major tool when dealing with myelofibrosis, which normally hampers sampling of cytological specimens. Copyright (C) 1998 by W.B. Saunders Company. C1 NCI, Frederick Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Tech Univ Munich, Sch Med, Inst Pathol, Dept Hematooncol, D-8000 Munich, Germany. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Res & Dev Ctr, Frederick, MD 21701 USA. RP Weirich, G (reprint author), NCI, Frederick Res & Dev Ctr, Immunobiol Lab, Bldg 560,Rm 12-71, Frederick, MD 21702 USA. NR 20 TC 13 Z9 13 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 1998 VL 29 IS 7 BP 761 EP 765 DI 10.1016/S0046-8177(98)90289-1 PG 5 WC Pathology SC Pathology GA ZZ577 UT WOS:000074744100017 PM 9670837 ER PT J AU Dakak, N Husain, S Mulcahy, D Andrews, NP Panza, JA Waclawiw, M Schenke, W Quyyumi, AA AF Dakak, N Husain, S Mulcahy, D Andrews, NP Panza, JA Waclawiw, M Schenke, W Quyyumi, AA TI Contribution of nitric oxide to reactive hyperemia - Impact of endothelial dysfunction SO HYPERTENSION LA English DT Article DE hyperemia; nitric oxide; endothelium; atherosclerosis ID DEPENDENT VASCULAR RELAXATION; SKELETAL-MUSCLE ARTERIOLES; L-ARGININE; BLOOD-FLOW; CORONARY-ARTERIES; HYPERCHOLESTEROLEMIC PATIENTS; ESSENTIAL-HYPERTENSION; HUMAN FOREARM; HEART-FAILURE; RISK-FACTORS AB Our objectives were to (1) test the hypothesis that nitric oxide (NO) contributes to peak reactive hyperemia (RH) in the human peripheral vasculature, (2) examine the impact of atherosclerosis and its risk factors on RH, and (3) investigate whether L-arginine will improve RH in patients with endothelial dysfunction. The endothelium contributes to shear stress-mediated vasomotion by releasing a variety of dilating factors, including NO, but the contribution of NO to peak RH in patients with and without endothelial dysfunction is unknown. Endothelium-dependent and endothelium-independent function was assessed with intrafemoral arterial acetylcholine (ACh) and sodium nitroprusside. RH was produced by occlusion of blood flow to the leg for 3 minutes. The study was repeated after N-G-monomethyl-L-arginine (L-NMMA) in 44 subjects and L-arginine in 9 patients with atherosclerosis. There were 15 normal control subjects without risk factors for atherosclerosis and 29 patients with risk factors or angiographic atherosclerosis. Microvascular vasodilation in response to ACh, but not to sodium nitroprusside, was lower in the patients with risk factors or atherosclerosis compared with normal control subjects, P=0.048, and the inhibition of ACh-induced microvascular dilation by L-NMMA was also greater in normal control subjects (P=0.045). Similarly, RH, including the peak response, was inhibited by L-NMMA in normal control subjects (P=0.0011) but not in patients with risk factors or atherosclerosis, suggesting that the contribution of NO to both ACh-induced dilation and RH was diminished in patients with risk factors or atherosclerosis. L-Arginine did not affect vasodilation in response to ACh, sodium nitroprusside, or RH. We concluded that (1) NO contributes to all phases of RH in the normal human peripheral vasculature, (2) patients with atherosclerosis or its risks have abnormal NO bioactivity in response to pharmacological and physiological stimulation, and (3) L-arginine does not improve RH in atherosclerosis. Reduced physiological vasodilation in atherosclerosis may contribute to or exacerbate hypertension and ischemia. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Quyyumi, AA (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7b15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. EM quyyumia@gwgate.nhlbi.nih.gov NR 60 TC 97 Z9 100 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 1998 VL 32 IS 1 BP 9 EP 15 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102YA UT WOS:000074952800003 PM 9674631 ER PT J AU Nelms, K Snow, AL Hu-Li, J Paul, WE AF Nelms, K Snow, AL Hu-Li, J Paul, WE TI FRIP, a hematopoietic cell-specific rasGAP-interacting protein phosphorylated in response to cytokine stimulation SO IMMUNITY LA English DT Article ID IRS-1 PTB DOMAIN; INSULIN-RECEPTOR; IL-4 RECEPTOR; TYROSINE KINASES; SIGNAL-TRANSDUCTION; SHC PHOSPHORYLATION; STRUCTURAL BASIS; GROWTH-FACTOR; BINDING; ACTIVATION AB The human IL-4 receptor contains a sequence (the I4R motif) centered on Y497 that, when phosphorylated, interacts with phosphotyrosine-binding (PTB) domain proteins. Here, we describe a PTB domain protein, FRIP, that is phosphorylated in response to cytokine stimulation. FRIP is related to the rasGAP-associated protein p62(dok) and is bound by the N-terminal SH2 domain of rasGAP. The frip gene maps to the hairless (hr) locus on mouse chromosome 14. hr/hr mice exhibit lymphadenopathy, and their lymph node T cells proliferate more vigorously to anti-CDS with IL-4 or IL-2 stimulation than +/hr T cells. FRIP expression is significantly reduced in T cells from hr/hr mice. FRIP may negatively regulate proliferation by acting as an adapter molecule between rasGAP and receptor complexes. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wepaul@helix.nih.gov OI Snow, Andrew/0000-0002-8728-6691 NR 64 TC 95 Z9 96 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 1998 VL 9 IS 1 BP 13 EP 24 DI 10.1016/S1074-7613(00)80584-1 PG 12 WC Immunology SC Immunology GA 105HL UT WOS:000075066600002 PM 9697832 ER PT J AU Coughlin, CM Salhany, KE Gee, MS LaTemple, DC Kotenko, S Ma, XJ Gri, G Wysocka, M Kim, JE Liu, L Liao, F Farber, JM Pestka, S Trinchieri, G Lee, WMF AF Coughlin, CM Salhany, KE Gee, MS LaTemple, DC Kotenko, S Ma, XJ Gri, G Wysocka, M Kim, JE Liu, L Liao, F Farber, JM Pestka, S Trinchieri, G Lee, WMF TI Tumor cell responses to IFN gamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis SO IMMUNITY LA English DT Article ID INTERFERON-INDUCIBLE PROTEIN-10; ANGIOGENESIS IN-VIVO; MESSENGER-RNA; INTERLEUKIN-12; ANTITUMOR; RECEPTOR; IDENTIFICATION; INHIBITION; EXPRESSION; LYMPHOCYTES AB Expression of a dominant negative mutant IFN gamma R1 in murine SCK and K1735 tumor cells rendered them relatively unresponsive to IFN gamma in vitro and more tumorigenic and less responsive to IL-12 therapy in vivo. IL-12 induced histologic evidence of ischemic damage only in IFN gamma-responsive tumors, and in vivo Matrigel vascularization assays revealed that while IFN gamma-responsive and -unresponsive tumor cells induced angiogenesis equally well, IL-12 and its downstream mediator IFN gamma only inhibited angiogenesis induced by the responsive cells. IL-12 induced angiogenesis inhibitory activity in the responsive cells, which may be attributable to production of the chemokine IP-10. Thus, IL-12 and IFN gamma inhibit tumor growth by inducing tumor cells to generate antiangiogenic activity. C1 Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Biomed Grad Program, Philadelphia, PA 19104 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. Wistar Inst, Philadelphia, PA 19104 USA. PharMingen, San Diego, CA 92121 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Lee, WMF (reprint author), Univ Penn, Dept Med, Philadelphia, PA 19104 USA. FU NCI NIH HHS [T32 CA09140] NR 37 TC 238 Z9 242 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 1998 VL 9 IS 1 BP 25 EP 34 DI 10.1016/S1074-7613(00)80585-3 PG 10 WC Immunology SC Immunology GA 105HL UT WOS:000075066600003 PM 9697833 ER PT J AU Schiaffella, E Fuschiotti, P Bensinger, SJ Mage, RG AF Schiaffella, E Fuschiotti, P Bensinger, SJ Mage, RG TI High RAD51 mRNA levels in young rabbit appendix. A role in B-cell gene conversion? SO IMMUNOGENETICS LA English DT Article DE RAD51; rabbit appendix; gene conversion; B-cell development; B-cell class switching ID ESCHERICHIA-COLI RECA; SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS RECOMBINATION; NUCLEAR FOCI; PROTEIN; EXPRESSION; MOUSE; DIVERSIFICATION; LYMPHOCYTES; SEQUENCES AB The rabbit has a limited number of V-H genes that rearrange. As in the chicken, the 3'-most V(H)1 gene is rearranged in most B lymphocytes. This laboratory reported that by 6 weeks after birth, diversification of rearranged VH genes occurs, at least in part, by gene conversion-like events in the appendix, suggesting that this organ is a homologue of the avian bursa of Fabricius. Rad51 contributes to the repair of double-strand breaks in DNA during somatic and meiotic recombination. The gene was first identified in lower eukaryotes, and later in vertebrates including chicken, as encoding an Escherichia coli RecA-like protein. We report the cloning and sequencing of RAD51 from the rabbit. Because the chicken bursa was shown to express high levels of R4D51 message, we investigated the expression of RAD51 in the rabbit appendix and other tissues. Using a quantitative polymerase chain reaction mimic assay and conventional northern analyses, we found high RAD51 expression in young rabbit appendix comparable Is levels in testis where there is an abundance of meiotic recombination. RAD51 levels were three times higher in appendix B lymphocytes compared with T lymphocytes and were lower in adult appendix, as well as in spleen and Peyer's patches of young rabbits. We measured the levels of message in several appendix cell sub-populations obtained by fluorescence-activated cell sorting and found that sub-populations of B lymphocytes corresponding to different stages of B-cell development as well as B cells undergoing isotype switch did not have significantly different mRNA levels. C1 NIAID, Mol Immunogenet Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Mage, RG (reprint author), NIAID, Mol Immunogenet Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 36 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JUL PY 1998 VL 48 IS 2 BP 108 EP 115 DI 10.1007/s002510050410 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA ZZ607 UT WOS:000074747100003 PM 9634474 ER PT J AU Roberson, KM Yancey, DR Padilla-Nash, H Edwards, DW Nash, W Jacobs, S Padilla, GM Larchian, WA Robertson, CM AF Roberson, KM Yancey, DR Padilla-Nash, H Edwards, DW Nash, W Jacobs, S Padilla, GM Larchian, WA Robertson, CM TI Isolation and characterization of a novel human bladder cancer cell line: BK10 SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE bladder; cancer cells; characterization; cytogenetics ID SERUM-FREE MEDIUM; RETINOBLASTOMA GENE; TISSUE-CULTURE; URINARY-BLADDER; UROTHELIAL CELLS; CARCINOMA; GROWTH; EXPRESSION; TUMORS; ULTRASTRUCTURE AB Molecular studies of bladder carcinomas have aided in determining causative generic events and the prognosis of cancers endowed with certain abnormalities. In vitro bladder cancer characterization of key cytogenetic alterations is useful for study of molecular changes that may promote oncogenic events. In our laboratory, a novel human bladder cancer cell line, BK10, has been established in vitro and passaged for more than 20 mo. This new bladder cancer cell line (BK10) was derived from bladder tissue containing grade III-IV/IV transitional cell carcinoma. Bladder cancer tissue was obtained at the time of radical cystoprostatectomy extirpation. Cell cultures derived from this surgical sample exhibited an epithelial morphology and expressed epithelial cytokeratins. Immunostains of BK10 were negative for prostate specific antigen (PSA), fibronectin, smooth muscle actin alpha, and desmin. Karyotypic analysis revealed an aneuploid chromosomal content <4n> with many numerical and structural abnormalities previously linked to bladder oncogenesis. Translocations occurred in chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, 15, 16, 17, 19, 20, 21, 22, X and Y. G-banding analysis revealed rearrangements involving chromosomes 9q and 17p, and the location of the abl1 oncogene and the p53 gene, respectively. The availability of this bladder cancer cell line will provide a useful tool for the further study of bladder carcinoma oncogenesis and gene therapy. C1 Duke Univ, Med Ctr, Div Urol, Dept Surg, Durham, NC 27710 USA. NIH, Natl Human Genome Res Inst, Diagnost Dev Branch, Bethesda, MD 20892 USA. H&W Cytogenet Serv Inc, Lovettsville, VA 20180 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, Div Urol, New York, NY 10021 USA. RP Robertson, CM (reprint author), Duke Univ, Med Ctr, Div Urol, Dept Surg, Box 3062, Durham, NC 27710 USA. NR 47 TC 3 Z9 3 U1 1 U2 2 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD JUL-AUG PY 1998 VL 34 IS 7 BP 537 EP 544 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 108QV UT WOS:000075277700009 ER PT J AU Gupta, RK Taylor, DN Bryla, DA Robbins, JB Szu, SSC AF Gupta, RK Taylor, DN Bryla, DA Robbins, JB Szu, SSC TI Phase 1 evaluation of Vibrio cholerae O1, serotype Inaba, polysaccharide-cholera toxin conjugates in adult volunteers SO INFECTION AND IMMUNITY LA English DT Article ID FIELD TRIAL; ANTIBODY; BANGLADESH; VACCINES; OGAWA; LIPOPOLYSACCHARIDE; PROTECTION; MAGNITUDE; ANTIGENS AB Conjugate vaccines were prepared by binding hydrazine-treated lipopolysaccharide (DeALPS) from Vibrio cholerae O1, serotype Inaba, to cholera toxin (CT) variants CT-1 and CT-2. Volunteers (n = 75) were injected with either 25 mu g of DeALPS, alone or as a conjugate, or the licensed cellular vaccine containing 4 x 10(9) organisms each of serotypes Inaba and Ogawa per mi. No serious adverse reactions were observed. DeALPS alone did not elicit serum LPS or vibriocidal antibodies in mice and only low levels of immunoglobulin M (IgM) anti-LPS in the volunteers. Recipients of the cellular vaccine had the highest IgM anti-LPS levels, but the difference was not statistically significant from that elicited by the conjugates. The conjugates elicited the highest levels of IgG anti-LPS (DeALPS-CT-2 > DeALPS-CT-1 > cellular vaccine). Both conjugates and the cellular vaccine elicited vibriocidal antibodies: after 8 months, recipients of cellular vaccine had the highest geometric mean titer (1,249), followed by DeALPS-CT-2 (588) and DeALPS-CT-1 (330). The correlation coefficient between IgG anti-LPS and 2-mercaptoethanol (2-ME)-resistant vibriocidal antibodies was 0.81 (P = 0.0004). Convalescent sera from cholera patients had a mean vibriocidal titer of 2,525 that was removed by treatment with 2-ME. The vibriocidal activities of sera from all vaccine groups and from the patients were absorbed (>75%) by LPS but not by either CT-1 or CT-2. Conjugate-induced IgG vibriocidal antibodies persisted longer than those elicited by the whole cell vaccine. Both conjugates, but not the cellular vaccine, elicited IgG anti-CT. C1 NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Washington, DC 20307 USA. RP Szu, SSC (reprint author), NICHHD, Dev & Mol Immun Lab, NIH, Bldg 6,Room 424,8800 Rockville Pike, Bethesda, MD 20892 USA. EM scszu@Helix.nih.gov NR 34 TC 45 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1998 VL 66 IS 7 BP 3095 EP 3099 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZW149 UT WOS:000074379900010 PM 9632571 ER PT J AU Klein, MB Hayes, SF Goodman, JL AF Klein, MB Hayes, SF Goodman, JL TI Monocytic differentiation inhibits infection and granulocytic differentiation potentiates infection by the agent of human granulocytic ehrlichiosis SO INFECTION AND IMMUNITY LA English DT Article ID PROMYELOCYTIC LEUKEMIA-CELLS; BONE-MARROW-CELLS; 1,25-DIHYDROXYVITAMIN D-3; HL-60; CULTURE; LINE AB Human granulocytic ehrlichiosis (HGE) is an emerging tick-borne infection with a specific tropism for granulocytes. We previously isolated and cultivated the HGE agent in the promyelocytic leukemia cell line HL-60 and have also demonstrated the susceptibility of both granulocytic and monocytic human marrow progenitors. Circulating monocytes have not been observed to be infected, suggesting that cell susceptibility may be differentiation specific, To evaluate this hypothesis, HL-60 cells were differentiated towards granulocytes with dimethyl sulfoxide or all-trans retinoic acid) or toward monocytes-macrophages (with 12 0-tetradecanoylphorbol-13-acetate [TPA], gamma interferon, or 1,25-dihydroxyvitamin D-3) and then challenged with HGE. HGE binding, internalization, and proliferation were compared in differentiated and untreated control HL-60 cells by immunofluorescence, electron microscopy, and Giemsa staining. Granulocytic differentiation resulted in a doubling of HGE binding and enhanced infection consistent with the agent's clinical tropism for neutrophils, Granulocytic cells were unable to kill internalized ehrlichiae even after activation induced by N-formyl-Met-Leu-Phe alone or together with tumor necrosis factor alpha, In contrast, monocyte-macrophage differentiation with TPA resulted in complete resistance to infection through at least two distinct mechanisms: (i) reduction in binding and uptake and (ii) killing of any internalized organisms. Diminished binding in TPA-treated cells correlated with their reduced expression of sialyl Lewis x (CD15s), a putative cellular receptor component for HGE, The degree of monocytic differentiation and activation induced (i.e., TPA > gamma interferon >vitamin D-3) correlated with resistance to HGE. Thus, HL-60 cells exhibit a striking differentiation-specific susceptibility to HGE. Differentiation-induced changes in bacterial adhesion and killing capacity underlie the tropism of HGE for granulocytic HL-60 cells and, conversely, the resistance of activated macrophages to infection. C1 Univ Minnesota, Dept Med, Div Infect Dis, Minneapolis, MN 55455 USA. NIH, Rocky Mt Lab, Hamilton, MT USA. RP Goodman, JL (reprint author), Univ Minnesota, Dept Med, Div Infect Dis, Box 250 UMHC,420 Delaware St SE, Minneapolis, MN 55455 USA. EM jesse@lenti.umn.edu FU NIAID NIH HHS [1R01AI40952-01]; PHS HHS [A107421] NR 25 TC 10 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1998 VL 66 IS 7 BP 3410 EP 3415 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZW149 UT WOS:000074379900052 PM 9632613 ER PT J AU Singh, Y Ivins, BE Leppla, SH AF Singh, Y Ivins, BE Leppla, SH TI Study of immunization against anthrax with the purified recombinant protective antigen of Bacillus anthracis SO INFECTION AND IMMUNITY LA English DT Article ID TOXIN; PLASMID; STRAINS AB Protective antigen (PA) of anthrax toxin is the major component of human anthrax vaccine. Currently available human vaccines in the United States and Europe consist of alum-precipitated supernatant material from cultures of toxigenic, nonencapsulated strains of Bacillus anthracis. Immunization with these vaccines requires several boosters and occasionally causes local pain and edema. We previously described the biological activity of a nontoxic mutant of PA expressed in Bacillus subtilis. In the present study, we evaluated the efficacy of the purified mutant PA protein alone or in combination with the lethal factor and edema factor components of anthrax toxin to protect against anthrax. Both mutant and native PA preparations elicited high anti-PA titers in Hartley guinea pigs. Mutant PA alone and in combination with lethal factor and edema factor completely protected the guinea pigs from B. anthracis spore challenge. The results suggest that the mutant PA protein may be used to develop an effective recombinant vaccine against anthrax. C1 Ctr Biochem Technol, Delhi 110007, India. USA, Med Res Inst Infect Dis, Bacteriol Div, Ft Detrick, MD 21702 USA. NIDR, Oral Infect & Immunity Branch, NIH, Bethesda, MD 20892 USA. RP Singh, Y (reprint author), Ctr Biochem Technol, Mall Rd,Near Jubilee Hall, Delhi 110007, India. NR 20 TC 40 Z9 43 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1998 VL 66 IS 7 BP 3447 EP 3448 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZW149 UT WOS:000074379900060 PM 9632621 ER PT J AU Matousek, MP Nedrud, JG Cieplak, W Harding, CV AF Matousek, MP Nedrud, JG Cieplak, W Harding, CV TI Inhibition of class II major histocompatibility complex antigen processing by Escherichia coli heat-labile enterotoxin requires an enzymatically active a subunit SO INFECTION AND IMMUNITY LA English DT Article ID ADP-RIBOSYLTRANSFERASE ACTIVITY; TOXIN-B SUBUNIT; CHOLERA-TOXIN; A-SUBUNIT; VIBRIO-CHOLERAE; ADJUVANT; SITE; MICE; MUTAGENESIS; CELLS AB Escherichia coli heat-labile enterotoxin (LT) and cholera toxin (CT) were found to inhibit intracellular antigen processing. Processing was not inhibited by mutant LT with attenuated ADP-ribosyltransferase activity, CT B or LT B subunit, which enhanced presentation of preexisting cell surface peptide-class II major histocompatibility complex complexes. Inhibition of antigen processing correlated with A subunit ADP-ribosyltransferase activity. C1 Case Western Reserve Univ, Inst Pathol, Dept Pathol, Cleveland, OH 44106 USA. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Harding, CV (reprint author), Case Western Reserve Univ, Inst Pathol, Dept Pathol, 2085 Adelbert Rd, Cleveland, OH 44106 USA. EM cvh3@po.cwru.edu FU NCI NIH HHS [CA70149]; NIAID NIH HHS [R01 AI034343, T32 AI007427, R01 AI035726, AI34343, AI35726] NR 35 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1998 VL 66 IS 7 BP 3480 EP 3484 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZW149 UT WOS:000074379900068 PM 9632629 ER PT J AU Abu-Saad, I Abu-Saad, K Lewando-Hundt, G Forman, MR Belmaker, I Berendes, HW Chang, D AF Abu-Saad, I Abu-Saad, K Lewando-Hundt, G Forman, MR Belmaker, I Berendes, HW Chang, D TI Bedouin Arab mothers' aspirations for their children's education in the context of radical social change SO INTERNATIONAL JOURNAL OF EDUCATIONAL DEVELOPMENT LA English DT Article ID NEGEV; UNDERNUTRITION; ISRAEL AB This study examines the aspirations of Bedouin Arab mothers toward their children's educational attainment and future occupations. The study was conducted in 1991-92 among the Bedouin community in Israel which is in the process of being transferred from spontaneous tribal settlements to government planned towns. The study was based on interviews with 309 mothers, 90% of whom had no formal education themselves. The data revealed that 62% of the mothers lived in government planned towns, and 38% lived in spontaneous tribal settlements. Ninety eight percent of mothers would like to see their sons finish high school and 81% would like to see their daughters finish high school (though about 20% of these acknowledged the existence of family or financial barriers to realizing their aspirations). There were no significant differences between the aspirations of mothers who lived in the planned towns and those who lived in spontaneous settlements for their sons' and daughters' high school and higher education, or their future occupations. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Ben Gurion Univ Negev, Dept Educ, IL-84105 Beer Sheva, Israel. London Sch Hyg & Trop Med, London WC1, England. NCI, Bethesda, MD 20892 USA. NICHD, Bethesda, MD USA. Westat Inc, Rockville, MD USA. RP Abu-Saad, I (reprint author), Ben Gurion Univ Negev, Dept Educ, POB 653, IL-84105 Beer Sheva, Israel. NR 45 TC 6 Z9 6 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0738-0593 J9 INT J EDUC DEV JI Int. J. Educ. Dev. PD JUL PY 1998 VL 18 IS 4 BP 347 EP 359 DI 10.1016/S0738-0593(98)00019-4 PG 13 WC Education & Educational Research SC Education & Educational Research GA 137UE UT WOS:000076934100007 ER PT J AU Heselmeyer, K Hellstrom, AC Blegen, H Schrock, E Silfversward, C Shah, K Auer, G Ried, T AF Heselmeyer, K Hellstrom, AC Blegen, H Schrock, E Silfversward, C Shah, K Auer, G Ried, T TI Primary carcinoma of the Fallopian tube: Comparative genomic hybridization reveals high genetic instability and a specific, recurring pattern of chromosomal aberrations SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE fallopian tube; cancer; chromosome aberrations; comparative genomic hybridization (CGH); p53; DNA ploidy; proliferation; human papillomavirus (HPV) ID MOLECULAR CYTOGENETIC ANALYSIS; DNA COPY NUMBER; HUMAN PAPILLOMAVIRUS; P53 OVEREXPRESSION; OVARIAN-CANCER; SOLID TUMORS; AMPLIFICATION; LOSSES; GAINS; ADENOCARCINOMA AB Primary fallopian tube carcinoma (PFTC) is a rare and highly aggressive tumor. Twelve cases of PFTC (stages IA to IV) were analyzed by comparative genomic hybridization. The most consistent DNA gain was mapped to chromosome arm 3q in 11 of 12 cases. In six cases, the gain of 3q was present as a high level copy number increase (amplification) with a consensus region mapped to 3q26.2-qter. In the 12 cases, other frequent gains were located on chromosome arms 1q (in 11 cases), 2q (in 10), 7q (in 9), 8q (in 9), 5p (in 8), 6p (in 7), 12p (in 7), and 14q (in 6). Frequent copy number losses occurred on chromosome arms 16q (in 8 cases), 22q (in 7), 6q (in 6), 8p (in 6), 18q (in 6), Xq (in 6), 1p (in 5), and 17p (in 5). All chromosomes were involved in chromosomal aberrations and the average number of copy alterations per case was 19.7. None of the 12 carcinomas revealed the presence of human papillomavirus (HPV) genomes. All of the cases exhibited crude aneuploidy. Strong p53 immunoreactivity could be observed in 10 of 12 cases while p21/WAF1 expression was low or undetectable. These results indicate that PFTC is a genomically highly unstable cancer, an observation that is in agreement with the poor prognosis associated with this tumor. A high frequency of 3q-gains has also been observed in HPV-related carcinomas of the uterine cervix. However, none of the PFTC was HPV-related, suggesting that the 3q-gain is independent from HPV DNA. C1 NIH, Natl Human Genome Res Inst, Genome Technol Branch, Bethesda, MD 20892 USA. Karolinska Hosp & Inst, Radiumhemmet, Dept Gynaecol Oncol, Stockholm, Sweden. Karolinska Hosp & Inst, Dept Tumor Pathol, Stockholm, Sweden. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. RP Heselmeyer, K (reprint author), NIH, Natl Human Genome Res Inst, Genome Technol Branch, 49 Convent Dr,Bldg 49,Room 4C36, Bethesda, MD 20892 USA. NR 50 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 1998 VL 17 IS 3 BP 245 EP 254 DI 10.1097/00004347-199807000-00009 PG 10 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA ZW677 UT WOS:000074435600009 PM 9656121 ER PT J AU Vargas, MP Merino, MJ AF Vargas, MP Merino, MJ TI Lymphoepitheliomalike carcinoma: An unusual variant of endometrial cancer - A report of two cases SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Epstein Barr virus; lymphoepithelioma; lymphoepitheliomalike endometrial carcinoma ID EPSTEIN-BARR-VIRUS; POLYMERASE CHAIN-REACTION; UTERINE CERVIX; UNDIFFERENTIATED CARCINOMA; NASOPHARYNGEAL CARCINOMA; HODGKINS-DISEASE; DNA; ASSOCIATION; BIOPSIES; GENOMES AB Two undifferentiated cat-cinemas of the endometrium with a prominent inflammatory reaction that were morphologically similar to nasopharyngeal cancers occurred in two patients who had postmenopausal bleeding. Tumor cells in both patients were large with indistinct cytoplasmic borders, vesicular nuclei, and prominent nucleoli, were arranged in sheets; in groups, or singly, and surrounded by an intense inflammatory component of lymphocyte, plasma cells, and karyorrhectic debris. Tumor cells were keratin (AE1/EA3) and epithelial membrane antigen (EMA) positive and leukocyte common antigen (LCA) negative. All three methods used for the detection of Epstein Barr virus (EBV) infection were negative. The first patient (International Federation of Gynecology and Obstetrics [FIGO] stage IVB) received chemotherapy and is alive and free of disease 9 months after diagnosis. The second patient (FIGO stage IIIC)received radiation therapy and chemotherapy 6 months after evidence of extensive retroperitoneal disease and died of disease 1 year after diagnosis. Tumors with these histologic features have been designated as lymphoepitheliomalike carcinomas (LELC) when they occur outside the nasopharynx. LELC can occur in the endometrium and, in this location. may not be associated with EBV infection. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Harbor UCLA Med Ctr, Torrance, CA USA. RP Merino, MJ (reprint author), NCI, Pathol Lab, 9000 Rockville Pike,Bldg 10,Room 2N212, Bethesda, MD 20892 USA. NR 26 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 1998 VL 17 IS 3 BP 272 EP 276 DI 10.1097/00004347-199807000-00013 PG 5 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA ZW677 UT WOS:000074435600013 PM 9656125 ER PT J AU Ratnasinghe, D Phang, JM Yeh, GC AF Ratnasinghe, D Phang, JM Yeh, GC TI Differential expression and activity of phosphatases and protein kinases in adriamycin sensitive and resistant human breast cancer MCF-7 cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE multidrug resistance; P-glycoprotein; drug efflux; phosphorylation; protein kinases; protein phosphatases ID DEPENDENT TRANSPORT-SYSTEMS; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; PHORBOL ESTERS; TUMOR-CELLS; PHOSPHORYLATION; BINDING; DOXORUBICIN; MODULATION; COLCHICINE AB Multidrug resistance is one of the major obstacles in cancer chemotherapy. In tumor cells, overexpression of the transmembrane P-glycoprotein 170 (P-gp) is associated with the multidrug resistance phenotype and serves as a drug efflux pump. The activation of P-gp has been suggested to occur at the post-translational level. Protein kinase C mediated phosphorylation may be associated with the drug effux mechanism but the overall phosphorylation pathway has not been completely defined. We report the novel finding of an increase in phosphatase 1B (a tyrosine phosphatase) and a decrease in PP1 and PP2A (serine/threonine phosphatases) expression and activity in our series of early (R65) and late (R500) stage adriamycin resistant MCF-7 cells. In addition, we show a decrease in protein kinase A (PKA) activity and an increase in protein kinase C (PKC) in our drug resistant cells. Analyses of PKC isoforms ct through E revealed that PKC beta was not expressed and that all other isoforms increased with increasing resistance, except PKC gamma which was detected only in R65 cells. Our findings suggest that in drug resistant cells, there is a pattern consistant with the maintenance of serine and threonine residues in a phosphorylated state. C1 NCI, Cellular Def & Carcinogenesis Sect, LNMR, FCRDC, Frederick, MD 21702 USA. RP Yeh, GC (reprint author), NCI, Cellular Def & Carcinogenesis Sect, LNMR, FCRDC, Bldg 560,Rm 12-91, Frederick, MD 21702 USA. NR 20 TC 25 Z9 29 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUL PY 1998 VL 13 IS 1 BP 79 EP 84 PG 6 WC Oncology SC Oncology GA ZU583 UT WOS:000074212600012 PM 9625806 ER PT J AU Lin, L Gillies, SD Lan, Y Izotova, L Wu, W Schlom, J Pestka, S AF Lin, L Gillies, SD Lan, Y Izotova, L Wu, W Schlom, J Pestka, S TI Construction of phosphorylatable chimeric monoclonal antibody CC49 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE monoclonal antibody; chimeric antibody; cAMP-dependent protein kinase recognition site; cAMP-dependent protein kinase; protein kinase; tumor associated antigens; cancer therapy; cancer diagnosis ID TUMOR-ASSOCIATED ANTIGENS; COLORECTAL-CANCER; INTERFERON-ALPHA; COLON CANCER; B72.3; EXPRESSION; CARCINOMA; CELLS; SPECTRUM; LESIONS AB Phosphorylation sites were introduced into chimeric monoclonal antibody CC49 (MAb-chCC49) by inserting synthetic fragments encoding two and six phosphorylation sites into an expression vector, pdHL7. The phosphorylation sites were created by using the predicted consensus sequences for phosphorylation by the cAMP-dependent protein kinase to the carboxyl terminus of the heavy chain constant region of the MAb-chCC49. The resultant modified antibodies (MAb-chCC49K1 and MAb-chCC49-6P) were expressed in NSO cells and purified. The MAb-chCC49K1 protein contains two phosphorylation sites per heavy chain whereas the MAb-chCC49-6P protein contains six sites per heavy chain. Both MAb-chCC49K1 and MAb-chCC49-6P proteins can be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase with [gamma-P-32]ATP to high specific activity. The P-32-labeled MAb-chCC49K1 and MAb-chCC49-6P proteins bind to cells expressing TAG-72 antigens. The introduction of phosphorylation sites into a monoclonal antibody provides a reagent for the diagnosis and treatment of cancer. The use of multiple phosphorylation sites provides antibodies with very high specific radioactivity and demonstrates that cassettes of phosphorylation sites can be introduced into proteins without altering their functional activity. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. Lexigen Pharmaceut Corp, Lexington, MA 02173 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pestka, S (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, 675 Hoes Lane, Piscataway, NJ 08854 USA. FU NCI NIH HHS [R01 CA52363, R01 CA46465] NR 29 TC 10 Z9 10 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUL PY 1998 VL 13 IS 1 BP 115 EP 120 PG 6 WC Oncology SC Oncology GA ZU583 UT WOS:000074212600018 PM 9625812 ER PT J AU Tumminia, SJ Mitton, KP Arora, J Zelenka, P Epstein, DL Russell, P AF Tumminia, SJ Mitton, KP Arora, J Zelenka, P Epstein, DL Russell, P TI Mechanical stretch alters thc actin cytoskeletal network and signal transduction in human trabecular meshwork cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ACTIVATED PROTEIN-KINASE; C-FOS; TYROSINE PHOSPHORYLATION; SENSITIVE METHOD; GENE-EXPRESSION; CHAIN-REACTION; MESSENGER-RNA; PAXILLIN; STRESS; POLYMERASE AB PURPOSE. Human trabecular meshwork (HTM) cells were mechanically stretched in vitro as a potential model for the distension of this tissue that can occur in vivo in response to increased pressure gradients. Cell morphology and certain components of the signal transduction pathways, including the mitogen-activated protein kinase (MAPK) and c-Jun N-terminal protein kinase (JNK) pathways, were evaluated for stretch-induced alterations. METHODS. Primary HTM cells grown in tissue culture were subjected to a mechanical stretch lasting from 10 seconds to 4 days. The actin cytoskeletal network was visualized by phalloidin staining. Proteins phosphorylated on their tyrosine residues were isolated using an immunoaffinity system and were analyzed by gel electrophoresis and immunostaining. Mitogen-activated protein kinase activity was evaluated using an in-gel assay system, and the mRNA levels of c-fos and c-jun were determined by quantitation of competitive reverse transcription-polymerase chain reaction. In addition, the amount of c-Fos protein was estimated by chemiluminescent immunoblot analysis. RESULTS. On stretching, the HTM cells elongated but regained their normal morphologic characteristics within 24 hours. Unstretched HTM cells displayed a diffuse F-actin microfilament network, whereas stretched cells exhibited complex geodesic patterns. Ten seconds after stretching began, the level of tyrosine phosphorylation on the six major phosphoproteins significantly decreased between 80% and 100%, whereas the level of paxillin tyrosine phosphorylation significantly increased 39% Stretching caused MAPK activity and the amount of mRNA and protein of the immediate-early gene c-fos to decrease more than 60% within 2 minutes, but within 15 to 30 minutes they increased above or equivalent to normal levels. The level of c-jun mRNA was unchanged by stretching. CONCLUSIONS. In response to a mechanical stretch, major cytoskeletal alterations occur in HTM cells, which involve changes in the levels of tyrosine phosphorylation. Mechanotransduction (signal transduction by mechanical stimulation) through the MAPK signaling pathway was Significantly depressed immediately after stretching; however, the JNK pathway appeared to be unaffected. The data suggest that HTM cells adapt to mechanical stress by altering the cytoskeletal network and signaling cascades. C1 NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. RP Tumminia, SJ (reprint author), NEI, Lab Mechanisms Ocular Dis, NIH, Bldg 6,Room 228,6 Ctr Dr MSC 2735, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY01894] NR 50 TC 97 Z9 103 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 1998 VL 39 IS 8 BP 1361 EP 1371 PG 11 WC Ophthalmology SC Ophthalmology GA ZW671 UT WOS:000074435000009 PM 9660484 ER PT J AU Janssen, RS Satten, GA Stramer, SL Rawal, BD O'Brien, TR Weiblen, BJ Hecht, FM Jack, N Cleghorn, FR Kahn, JO Chesney, MA Busch, MP AF Janssen, RS Satten, GA Stramer, SL Rawal, BD O'Brien, TR Weiblen, BJ Hecht, FM Jack, N Cleghorn, FR Kahn, JO Chesney, MA Busch, MP TI New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FRANCISCO MENS HEALTH; HOMOSEXUAL BISEXUAL MEN; EARLY DIAGNOSTIC-TESTS; AIDS EPIDEMIC; TYPE-1 SEROCONVERSION; ANTIBODY-RESPONSE; INCIDENCE RATES; UNITED-STATES; PLASMA AB Context.-Differentiating individuals with early human immunodeficiency virus 1 (HIV-1) infection from those infected for longer periods is difficult but important for estimating HIV incidence and for purposes of clinical care and prevention. Objective.-To develop and validate a serologic testing algorithm in which HIV-1-positive persons with reactive test results on a sensitive HIV-1 enzyme immunoassay (EIA) but nonreactive results on a less sensitive (LS) EIA are identified as having early infection. Design.-Diagnostic test and testing strategy development, validation, and application. Specimens were tested with both a sensitive HIV-1 EIA (3A11 assay) and a less sensitive modification of the same EIA (3A11-LS assay). Settings and Participants.-For assay development: 104 persons seroconverting to HIV-1 comprising 38 plasma donors, 18 patients of a sexually transmitted disease clinic in Trinidad, and 48 participants in the San Francisco Men's Health Study (SFMHS); 268 men without the acquired immunodeficiency syndrome (AIDS) in the SFMHS who had been infected for at least 2.5 years; and 207 persons with clinical AIDS; for testing strategy validation: 488 men in the SFMHS from 1985 through 1990 and 1 275 449 repeat blood donors at 3 American Red Cross blood centers from 1993 through 1995; and for HIV-1 incidence estimates: 2 717 910 first-time blood donors. We retrospectively identified persons eligible for a study of early infection. Main Outcome Measure.-Ability to identify early HIV infection. Results.-Estimated mean time to being 3A11 reactive/3A11-LS nonreactive was 129 days (95% confidence interval [CI], 109-149 days). Our testing strategy accurately diagnosed 95% of persons with early infection; however, 0.4% (1/268) of men with established infection and 2% (5/207) of persons with late-stage AIDS were misdiagnosed as having early HIV-1 infection. Average yearly incidence estimates in SFMHS subjects were 1.5% per year vs observed average incidence of 1.4 per 100 person-years. Incidence in repeat blood donors using the sensitive/less sensitive assay testing strategy was 2.95 per 100 000 per year (95% CI, 1.14-6.53/ 100 000) vs observed incidence of 2.60 per 100 000 person-years (95% CI, 1.49-4.21/100 000). Overall incidence in first-time blood donors was 7.18 per 100 000 per year (95% CI, 4.51-11.20/100 000) and did not change statistically significantly between 1993 and 1996. Use of the sensitive/less sensitive testing strategy alone would have identified all 17 persons with antibodies to HIV-1 eligible for a study of early HIV-1 infection and would have increased enrollment. Conclusions.-The sensitive/less sensitive testing strategy provides accurate diagnosis of early HIV-1 infection, provides accurate estimates of HIV-1 incidence, can facilitate clinical studies of early HIV-1 infection, and provides information on HIV-1 infection duration for care planning. C1 Ctr Dis Control & Prevent, Natl Ctr HIV STD & TB Prevent, Off Commun, Atlanta, GA 30333 USA. Amer Red Cross, Natl Reference Lab Infect Dis, Rockville, MD USA. Blood Ctr Pacific, Irwin Ctr, San Francisco, CA USA. NCI, Viral Epidemiol Branch, Rockville, MD USA. Boston Biomed Inc, W Bridgewater, MA USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, AIDS Program, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Aids Prevent Studies, San Francisco, CA 94143 USA. Med Res Ctr, Port Spain, Trinid & Tobago. Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. RP Janssen, RS (reprint author), Ctr Dis Control & Prevent, Natl Ctr HIV STD & TB Prevent, Off Commun, Mailstop E-06,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 56 TC 513 Z9 530 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 1 PY 1998 VL 280 IS 1 BP 42 EP 48 DI 10.1001/jama.280.1.42 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZW145 UT WOS:000074379400022 PM 9660362 ER PT J AU Schrager, LK D'Souza, MP AF Schrager, LK D'Souza, MP TI Cellular and anatomical reservoirs of HIV-1 in patients receiving potent antiretroviral combination therapy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD8(+) T-CELLS; IN-VIVO; CEREBROSPINAL-FLUID; LYMPHOID-TISSUE; NERVOUS-SYSTEM; TYPE-1 RNA; LIFE-SPAN; INFECTION; LYMPHOCYTES AB The eradication of human immunodeficiency virus 1 (HIV-1) from infected persons is the ultimate goal of HIV therapeutic interventions. Great strides have been made in developing potent antiretroviral regimens that greatly suppress HIV-1 replication. Despite these therapeutic advances, major obstacles remain to eradicating HIV-1. Reservoirs of HIV-1 have been identified that represent major impediments to eradication. Conceptually, there are 2 types of Sanctuaries for HIV-1, cellular and anatomical. Cellular sanctuaries may include latent CD4(+) T cells containing integrated HIV-1 provirus; macrophages, which may express HIV-1 for prolonged periods; and follicular dendritic cells, which may hold infectious HIV-1 on their surfaces for indeterminate lengths of time. The key anatomical reservoir for HIV-1 appears to be the central nervous system. An understanding of the nature of HIV within these reservoirs is critical to devising strategies to hasten viral eradication. C1 NIAID, Div Aids, Epidemiol Branch, Bethesda, MD 20892 USA. NIAID, Div Aids, Pathogenesis & Basic Res Branch, Bethesda, MD 20892 USA. RP Schrager, LK (reprint author), NIAID, Div Aids, Epidemiol Branch, Solar Bldg 2C10, Bethesda, MD 20892 USA. EM LS14M@nih.gov NR 64 TC 223 Z9 225 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 1 PY 1998 VL 280 IS 1 BP 67 EP 71 DI 10.1001/jama.280.1.67 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA ZW145 UT WOS:000074379400026 PM 9660366 ER PT J AU Cohen, OJ Fauci, AS AF Cohen, OJ Fauci, AS TI HIV/AIDS in 1998 - Gaining the upper hand? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), 31 Ctr Dr,MSC 2520,Bldg 31,Room 7A03, Bethesda, MD 20892 USA. NR 31 TC 17 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 1 PY 1998 VL 280 IS 1 BP 87 EP 88 DI 10.1001/jama.280.1.87 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZW145 UT WOS:000074379400029 PM 9660369 ER PT J AU Klausner, RD AF Klausner, RD TI 'Breast cancer prevention trial' SO JAPANESE JOURNAL OF CLINICAL ONCOLOGY LA English DT News Item C1 NCI, Bethesda, MD 20892 USA. RP Klausner, RD (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0368-2811 J9 JPN J CLIN ONCOL JI Jpn. J. Clin. Oncol. PD JUL PY 1998 VL 28 IS 7 BP 459 EP 460 DI 10.1093/jjco/28.7.459 PG 2 WC Oncology SC Oncology GA 116TE UT WOS:000075740000014 PM 9739790 ER PT J AU Wiesler, DG Wen, H Wolff, SD Balaban, RS AF Wiesler, DG Wen, H Wolff, SD Balaban, RS TI Reduction of field of view in MRI using a surface-spoiling local gradient insert SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE field of view reduction; rapid imaging; gradient design; volume localization; surface spoiling; cardiac MRI ID INVIVO SPECTROSCOPY; MAGNETIC-RESONANCE; MULTIPLE DETECTORS; NMR; LOCALIZATION; ACQUISITION AB Herein is presented a method for suppressing the magnetic resonance signal to a controlled depth by applying a spatially heterogeneous spoiler field between the slice-select and readout pulses. Eliminating the signal from near-surface regions allows one to shrink the field of view without introducing aliasing artifacts, thereby decreasing imaging time over a smaller defined volume. A unique planar magnetic gradient coil was constructed to generate the spoiler field. Phantom and human subject studies showed that the signal can be suppressed to controlled distances of up to 90 mm from the coil, with modest requirements on power supplies, pulse sequences, and materials, and with no increase in imaging time. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Wiesler, DG (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Room B1D-161,MSC-1061,10 Ctr Dr, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010 OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997 NR 23 TC 10 Z9 10 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD JUL-AUG PY 1998 VL 8 IS 4 BP 981 EP 988 DI 10.1002/jmri.1880080429 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 193NU UT WOS:000080143600028 PM 9702901 ER PT J AU Beer, B Denner, J Brown, CR Norley, S zur Megede, J Coulibaly, C Plesker, R Holzammer, S Baier, M Hirsch, VM Kurth, R AF Beer, B Denner, J Brown, CR Norley, S zur Megede, J Coulibaly, C Plesker, R Holzammer, S Baier, M Hirsch, VM Kurth, R TI Simian immunodeficiency virus of African green monkeys is apathogenic in the newborn natural host SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE SIVagm; neonates; CD4(+) and CD8(+) lymphocytes; virus load; AIDS; pathogenesis; African green monkeys ID PERIPHERAL-BLOOD; NONHUMAN-PRIMATES; HIGHLY DIVERGENT; TYPE-1 INFECTION; ATTENUATED SIV; FLOW-CYTOMETRY; ANTIBODIES; CELLS; AIDS; PATHOGENICITY AB Several studies have demonstrated that newborn animals are more susceptible to disease development following infection with retroviruses than adults. Adult African green monkeys (AGMs) infected with SIVagm do not develop AIDS-like disease and the objective of the study was to determine whether experimental infection of newborn AGMs with SIVagm would result in pathogenesis. Neonatal AGMs were found to have a higher percentage of circulating CD4(+) lymphocytes than adults (62% versus 14%) and therefore a higher potential pool of target cells for SIVagm infection. However, no differences in the in vitro replication kinetics of SIVagm in peripheral blood mononuclear cells of adult or neonatal AGMs could be observed. In vivo, the neonatal AGMs became viremic at the earliest two months after inoculation whereas the adult AGMs had evidence of virus replication already 2 to 6 weeks after infection. None of the animals developed AIDS-like symptoms upon infection. In the heterologous cynomolgus macaque host, a newborn infected with SIVagm developed early high virus loads and died two months after birth with AIDS-like histopathologic features. It would therefore appear that in contrast to the situation with many other retroviruses, newborn AGMs are no more permissive to SIVagm than are adults. C1 Paul Ehrlich Inst, D-63225 Langen, Germany. NIAID, Mol Microbiol Lab, NIH, Twinbrook Facil 2, Rockville, MD USA. RP Norley, S (reprint author), Paul Ehrlich Inst, Paul Ehrlich str 51-59, D-63225 Langen, Germany. NR 45 TC 47 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUL 1 PY 1998 VL 18 IS 3 BP 210 EP 220 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZX211 UT WOS:000074490500003 PM 9665497 ER PT J AU Diaz, C Hanson, C Cooper, ER Read, JS Watson, J Mendez, HA Pitt, J Rich, K Smeriglio, V Lew, JF AF Diaz, C Hanson, C Cooper, ER Read, JS Watson, J Mendez, HA Pitt, J Rich, K Smeriglio, V Lew, JF CA Women Infants transmission Study TI Disease progression in a cohort of infants with vertically acquired HIV infection observed from birth: The women and infants transmission study (WITS) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE predictors; disease progression; infants; vertically acquired HIV; pediatric HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 INFECTION; NATURAL-HISTORY; CLINICAL-TRIALS; CHILDREN; SURVIVAL; MOTHERS; CULTURE AB Background: The Women and Infants Transmission Study is an ongoing prospective cohort study of HIV-infected pregnant women and their infants. We used the 1994 U.S. Centers for Disease Control and Prevention (CDC) classification system for HIV infection in children to describe HIV disease progression in 128 HIV-infected children, and examined maternal and infant characteristics associated with disease course. Methods: The Kaplan-Meier method was used to calculate probabilities of entry into CDC clinical classes A, B, and C (mild, moderate, and severe HIV disease); CDC immunologic stages 2 and 3; and death. Relative risks of progression for selected predictor events were estimated using the Cox proportional hazards model. Results: With a median 24 months of follow-up, the median ages at entry into clinical classes A, B and C were 5, 11, and 48 months, respectively. Increased risk of progression to class C was seen in infants who had: onset of class B events (p < .001); progression to immunologic stage 2 (p < .001) or 3 (p < .001); early culture positivity tin first 48 hours, p < .01; in first 7 days, p = .03); and early appearance (within the first 3 months of life) of lymphadenopathy, hepatomegaly, or splenomegaly (p < .001). Conclusions: Reaching specific clinical or immunologic stages were strong predictors of progression to AIDS or death. Early onset of clinical signs (onset of lymphadenopathy, hepatomegaly, or splenomegaly less than or equal to 3 months of age), and early culture positivity (within the first 48 hours or within the first week of life); defined the infant with highest risk of disease progression. C1 Univ Puerto Rico, Sch Med, Dept Pediat, San Juan, PR 00936 USA. Baylor Coll Med, Houston, TX 77030 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. New England Res Inst, Watertown, MA 02172 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Univ Illinois, Chicago, IL USA. NIDA, Rockville, MD USA. NIAID, Div Aids, Bethesda, MD 20892 USA. RP Diaz, C (reprint author), Univ Puerto Rico, Childrens Hosp, Women & Infants Transmiss Study, Canc Bldg,Off 296,POB 365067, San Juan, PR 00936 USA. EM diaz_clemente@fsstrf.org FU NIAID NIH HHS [UO1-AI-34841, UO1-AI-34856, UO1-AI-34840] NR 34 TC 33 Z9 34 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUL 1 PY 1998 VL 18 IS 3 BP 221 EP 228 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZX211 UT WOS:000074490500004 PM 9665498 ER PT J AU Melbye, M Begtrup, K Rosenberg, PS Biggar, RJ Goedert, JJ Knudsen, K Andersen, PK AF Melbye, M Begtrup, K Rosenberg, PS Biggar, RJ Goedert, JJ Knudsen, K Andersen, PK TI Differences in susceptibility to AIDS development: A cohort study of Danish and American homosexual-bisexual men, 1981 to 1995 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE incubation period; HIV; AIDS; homosexual men; cohort study ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 INFECTION; TIME; PROGRESSION; SEROCONVERSION; INCUBATION; ANTIBODY; COUNT AB We estimated the annual hazard rate for progression to AIDS as defined by the 1987 case definition in HIV-infected members of a cohort of Danish and American homosexual-bisexual men who were observed from 1981 to 1995. Furthermore, we extrapolated the hazard to 25 years based on imputed future time to AIDS. Of 201 HIV-positive subjects, 112 developed AIDS before the end of follow-up. The hazard increased rapidly during the first years following infection, attained a peak of about 15% per year at year 7, and was moderately lower during years 8 through 10. In subsequent analysis, we imputed future time to AIDS in 89 subjects who had not progressed by the end of follow-up by extrapolation from subject-specific CD4 trend lines. A CD4 count of less than or equal to 100 cells/mu l was the best surrogate for clinical AIDS. Under this model, the imputed AIDS hazard stabilized at around 8% per year after 10 years. We projected that 13% (95% confidence interval [CI], 8%-19%) of the infected men may remain free from AIDS 25 years after seroconversion. Our direct data suggest that incubation times reflect a mixture of a population that is susceptible to disease progression and has short incubation periods with a group that is relatively resistant. Based on an extrapolation model, >10% of HIV-infected persons may survive for up to 25 years without developing AIDS. C1 Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, DK-2300 Copenhagen S, Denmark. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Univ Copenhagen, Dept Biostat, Copenhagen, Denmark. RP Melbye, M (reprint author), Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, Artillerivej 5, DK-2300 Copenhagen S, Denmark. NR 24 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUL 1 PY 1998 VL 18 IS 3 BP 270 EP 276 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZX211 UT WOS:000074490500011 PM 9665505 ER PT J AU Gadkari, DA Quinn, TC Gangakhedkar, RR Mehendale, SM Divekar, AD Risbud, AR Chan-Tack, K Shepherd, M Gaydos, C Bollinger, RC AF Gadkari, DA Quinn, TC Gangakhedkar, RR Mehendale, SM Divekar, AD Risbud, AR Chan-Tack, K Shepherd, M Gaydos, C Bollinger, RC TI HIV-1 DNA shedding in genital ulcers and its associated risk factors in Pune, India SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE genital ulcer disease (GUD); HIV-1 shedding; India; polymerase chain reaction (PCR); sexually transmitted diseases (STD) ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 SEROCONVERSION; INFECTION; SECRETIONS; DISEASE; MEN AB HIV infection status was determined in 302 consecutive patients with genital ulcer disease (GUD) presenting to two sexually transmitted disease (STD) clinics in Pune, India. Of the 71 (24%) individuals with HIV infection, 67 (94%) were HIV antibody-positive, and 4 (6%) were HIV antibody-negative but p24 antigenpositive at the time of presentation. HIV-1 DNA was detected in 24 (34%) specimens. The genital ulcers of all four acutely infected p24-antigenemic subjects were HIV-1 DNA-positive by polymerase chain reaction (PCR) assay, compared with 20 of 67 (30%) seropositive patients (p = .01). Presence of chancroid, GUD symptoms for >10 days, and concurrent diagnosis of cervicitis or urethritis were significantly associated risk factors for HIV-1 DNA shedding in ulcers, Early GUD diagnosis and aggressive treatment of HIV-infected patients may significantly reduce secondary transmission of HIV to other sex partners. C1 Natl AIDS Res Inst, Pune 411026, Maharashtra, India. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Gadkari, DA (reprint author), Natl AIDS Res Inst, G-73 MIDC, Pune 411026, Maharashtra, India. RI Gaydos, Charlotte/E-9937-2010 FU FIC NIH HHS [D43 TW0000]; NCRR NIH HHS [5MO1RR00722]; NIAID NIH HHS [AI 33879-02] NR 17 TC 46 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUL 1 PY 1998 VL 18 IS 3 BP 277 EP 281 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZX211 UT WOS:000074490500012 PM 9665506 ER PT J AU Brown, KM McMahon, RP Biro, FM Crawford, P Schreiber, GB Similo, SL Waclawiw, M Striegel-Moore, R AF Brown, KM McMahon, RP Biro, FM Crawford, P Schreiber, GB Similo, SL Waclawiw, M Striegel-Moore, R TI Changes in self-esteem in black and white girls between the ages of 9 and 14 years - The NHLBI growth and health study SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article; Proceedings Paper CT Society-for-Adolescent-Medicine Scientific Meeting CY MAR 20-24, 1996 CL ARLINGTON, VIRGINIA SP Soc Adolescent Med DE self-esteem; blacks; physical appearance; social acceptance; body mass index; racial differences; adolescents; females; sexual maturation ID ADOLESCENT GIRLS; SEX; DEPRESSION; IMAGE AB Purpose: We examined changes in self-esteem and feelings of competence with physical appearance and social acceptance over approximately 5 years in 1166 white and 1213 black girls, aged 9 and 10 years at baseline. Methods: Maturation stage and body mass index (BMI) were assessed annually. Biennially girls completed Harter's Self-Perception Profile for Children. Changes were analyzed in the context of race, sexual maturation, BMI, and household income. Longitudinal regression models were used to compare trends with age in global self-worth, physical appearance, and social acceptance. Results: Mean global self-worth showed little change over ages 9-14 years in blacks (p = 0.09) but decreased in whites (p < 0.001). Mean physical appearance scores for both races declined between ages 9 and 14 years (blacks, p < 0.001; whites, p < 0.001). Mean social acceptance scores increased for both races between ages 9 and 14 years (blacks, p < 0.001; whites, p < 0.001). For all three scores, these changes differed between blacks and whites (all three p values, less than or equal to 0.002). Adjustment for maturation stage, BMI, and household income did not alter the significance or direction of racial differences in the changes with age in global self-worth and physical appearance scores. Self-worth, physical appearance, and social acceptance scores decreased with increasing BMI. Decreases in physical appearance and social acceptance scores with increasing BMI were smaller in blacks than in whites (p < 0.05). After adjustment for maturation stage and household income, racial differences in social acceptance scores depended on BMI (p < 0.05) but not on age (p = 0.08). Conclusions: This article reports the first data on self-esteem scores by age for a large population of black girls aged 9 and 14 years and concludes that self-esteem does not follow the same developmental pattern in black as in white girls. A reason for black girls' higher and more stable self-worth and their greater satisfaction with their physical appearance compared to white girls may be racial differences in attitudes toward physical appearance and obesity. (C) Society for Adolescent Medicine, 1998. C1 Maryland Med Res Inst, Baltimore, MD 21210 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. WESTAT Corp, Rockville, MD 20850 USA. NHLBI, Bethesda, MD 20892 USA. Wesleyan Univ, Middletown, CT USA. RP Brown, KM (reprint author), Maryland Med Res Inst, 600 Wyndhurst Ave, Baltimore, MD 21210 USA. RI McMahon, Robert/C-5462-2009 FU NHLBI NIH HHS [N01-HC-55024, N01-HC-55025, N01-HC-55023] NR 32 TC 72 Z9 72 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD JUL PY 1998 VL 23 IS 1 BP 7 EP 19 DI 10.1016/S1054-139X(97)00238-3 PG 13 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA ZV463 UT WOS:000074307100003 PM 9648018 ER PT J AU McDyer, JF Wu, CY Seder, RA AF McDyer, JF Wu, CY Seder, RA TI The regulation of IL-12: Its role in infectious, autoimmune, and allergic diseases SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTERLEUKIN-12 PRODUCTION; INTERFERON-GAMMA; T-CELLS; IFN-GAMMA; AIRWAY HYPERRESPONSIVENESS; TOXOPLASMA-GONDII; IMMUNE-RESPONSE; HUMAN MONOCYTES; TNF-ALPHA C1 NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 34 Z9 35 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 1998 VL 102 IS 1 BP 11 EP 15 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 102DX UT WOS:000074909500002 PM 9679841 ER PT J AU Zoeteweij, JP Blauvelt, A AF Zoeteweij, JP Blauvelt, A TI HIV-dendritic cell interactions promote efficient viral infection of T cells SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Review DE dendritic cells; Langerhans cells; T cells; HIV; coreceptors; CXCR4; CCR5 ID EPIDERMAL LANGERHANS CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNE ACTIVATION; RECEPTOR; ANTIGEN; REPLICATION; INDIVIDUALS; BLOOD; PROGRESSION; LYMPHOCYTES AB Dendritic cells (DC) are bone marrow-derived leukocytes that act as powerful stimulators of primary and secondary immune responses. Langerhans cells (LC), which are immature DC in epidermis and genital mucosa, are generally believed to be the initial cells infected with HIV following mucosal exposure to virus. Interestingly, freshly isolated LC express the HIV coreceptor CCR5, but not CXCR4, on their cell surfaces. This expression pattern would theoretically allow only macrophage-tropic [and not T cell (TC)-tropic] HIV to be transmitted across intact mucosal epithelium. In vitro, it is known that HIV infects LC (and other DC) in a CD4- and HIV coreceptor-dependent manner. In addition? HIV can be captured by prominent stellate processes on the surface of LC/DC. HIV-infected DC, as well as DC that have captured HIV, efficiently transmit virus to TC during antigen-specific TC activation. Thus, DC may be involved in HIV plasma viremia increases observed following antigenic exposure, e.g. immunizations, in chronically HIV-infected individuals by (1) activating latently infected TC or (2) activating and transmitting virus to new target TC. In summary, DC most likely play a major role in primary HIV infection by allowing virus to breach mucosal surfaces, and can act during both initial and chronic phases of HIV disease by facilitating infection and depletion of TC. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Blauvelt, A (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. NR 62 TC 29 Z9 31 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD JUL-AUG PY 1998 VL 5 IS 4 BP 253 EP 259 DI 10.1007/BF02255856 PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 105JH UT WOS:000075069600002 PM 9691217 ER PT J AU Markley, JL Bax, A Arata, Y Hilbers, CW Kaptein, R Sykes, BD Wright, PE Wuthrich, K AF Markley, JL Bax, A Arata, Y Hilbers, CW Kaptein, R Sykes, BD Wright, PE Wuthrich, K TI Recommendations for the presentation of NMR structures of proteins and nucleic acids - IUPAC-IUBMB-IUPAB Inter-Union Task Group on the Standardization of Data Bases of Protein and Nucleic Acid Structures Determined by NMR Spectroscopy SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article ID COUPLING-CONSTANTS; MAGNETIC-RESONANCE; 3-DIMENSIONAL STRUCTURES; FILE; CRYSTALLOGRAPHY; CONFORMATION; CONSTRAINTS; PROGRAMS; QUALITY; C-13 AB The recommendations presented here are designed to support easier communication of NMR data and NMR structures of proteins and nucleic acids through unified nomenclature and reporting standards. Much of this document pertains to the reporting of data in journal articles; however, in the interest of the future development of structural biology, it is desirable that the bulk of the reported information be stored in computer-accessible form and be freely accessible to the scientific community in standardized formats for data exchange. These recommendations stem from an IUPAC-IUBMB-IUPAB inter-union venture with the direct involvement of ICSU and CODATA. The Task Group has reviewed previous formal recommendations and has extended them in the light of more recent developments in the field of biomolecular NMR spectroscopy. Drafts of the recommendations presented here have been examined critically by more than 50 specialists in the field and have gone through two rounds of extensive modification to incorporate suggestions and criticisms. C1 Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Water Res Inst, Tsukuba, Ibaraki, Japan. Catholic Univ Nijmegen, Biophys Chem Lab, NL-6525 ED Nijmegen, Netherlands. Univ Utrecht, Dept Chem, NL-3584 CH Utrecht, Netherlands. Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. ETH Honggerberg, Inst Mol & Biophys, CH-8093 Zurich, Switzerland. RP Wuthrich, K (reprint author), Univ Wisconsin, Dept Biochem, 420 Henry Mall, Madison, WI 53706 USA. NR 64 TC 231 Z9 233 U1 1 U2 19 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JUL PY 1998 VL 12 IS 1 BP 1 EP 23 DI 10.1023/A:1008290618449 PG 23 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 111ZZ UT WOS:000075470000001 PM 9729785 ER PT J AU Svensson, J Ohlsson, C Jansson, JO Murphy, G Wyss, D Krupa, D Cerchio, K Polvino, W Gertz, B Baylink, D Mohan, S Bengtsson, BA AF Svensson, J Ohlsson, C Jansson, JO Murphy, G Wyss, D Krupa, D Cerchio, K Polvino, W Gertz, B Baylink, D Mohan, S Bengtsson, BA TI Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 2nd International Meeting of the Growth-Hormone-Research-Society CY NOV, 1996 CL LONDON, ENGLAND SP Growth Hormone Res Soc ID OSTEOBLAST-LIKE CELLS; FACTOR BINDING-PROTEIN; FACTOR-I; MINERAL DENSITY; GH DEFICIENCY; BODY-COMPOSITION; SUBSTITUTION THERAPY; BIOLOGICAL-FLUIDS; CORTICAL BONE; ELDERLY WOMEN AB The effect of 2 months of treatment with the oral growth hormone (GH) secretagogue MK-677 on markers of bone metabolism was determined in healthy obese male subjects. This was a randomized, double-blind, parallel, placebo-controlled study. Twenty-four healthy obese males, 19-49 years of age, with body mass index > 30 kg/m(2) were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. MK-677 increased markers of bone formation; a 23% increase in the carboxy-terminal propeptide of type I procollagen levels and a 28% increase in procollagen III, peptide levels were seen with as little as 2 weeks of MK-677 treatment (p < 0.01 and p = 0.001 vs. placebo, respectively) while a 15% increase in serum levels of osteocalcin was not detected until 8 weeks of treatment (p < 0.01 vs, placebo). Markers of bone resorption were induced within 2 weeks of treatment with MK-677; serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen were increased 26% at 8 weeks (p = 0.001 vs. placebo), and urine hydroxyproline/creatinine and calcium/creatinine ratios at. 8 weeks were increased by 23% (p < 0.05 vs. placebo) and 46% (p < 0.05 vs placebo), respectively, MK-677 increased serum insulin-like growth factor binding protein-5 (IGFBP-5) by 43-44% after 2-8 weeks of treatment (p < 0.01 vs. placebo). Serum IGFBP-4 was increased by 25% after 2 weeks of treatment (p < 0.001 vs, placebo) but no significant change from baseline was observed after 8 weeks of treatment, Plasma interleukin-6 was not significantly changed by active treatment. In conclusion, short-term treatment of healthy obese male volunteers with the GH secretagogue MK-677 increases markers of both bone resorption and formation. Large increases in serum levels of IGF-I and IGFBP-5 and a transient increase in serum IGFBP-4 were found. Future long-term studies are needed to investigate if prolonged treatment with MK-677 increases bone mass. C1 Sahlgrens Univ Hosp, Res Ctr Endocrinol & Metab, S-41345 Gothenburg, Sweden. NIDDK, Diabet Branch, Bethesda, MD USA. Merck Res Labs, Rahway, NJ USA. Loma Linda Univ, Jerry L Pettis Mem Vet Adm Med Ctr, Dept Med, Loma Linda, CA 92350 USA. Loma Linda Univ, Jerry L Pettis Mem Vet Adm Med Ctr, Dept Biochem, Loma Linda, CA 92350 USA. Loma Linda Univ, Jerry L Pettis Mem Vet Adm Med Ctr, Dept Physiol, Loma Linda, CA 92350 USA. RP Svensson, J (reprint author), Sahlgrens Univ Hosp, Res Ctr Endocrinol & Metab, S-41345 Gothenburg, Sweden. NR 64 TC 29 Z9 29 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 1998 VL 13 IS 7 BP 1158 EP 1166 DI 10.1359/jbmr.1998.13.7.1158 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX361 UT WOS:000074507800012 PM 9661080 ER PT J AU Fleischmajer, R Utani, A MacDonald, ED Perlish, JS Pan, TC Chu, ML Nomizu, M Ninomiya, Y Yamada, Y AF Fleischmajer, R Utani, A MacDonald, ED Perlish, JS Pan, TC Chu, ML Nomizu, M Ninomiya, Y Yamada, Y TI Initiation of skin basement membrane formation at the epidermo-dermal interface involves assembly of laminins through binding to cell membrane receptors SO JOURNAL OF CELL SCIENCE LA English DT Article DE basement membrane; laminin; integrin ID DIFFERENTIAL EXPRESSION; BASAL LAMINA; IV COLLAGEN; ALPHA-2-BETA-1 INTEGRINS; KERATINOCYTE ADHESION; EXTRACELLULAR-MATRIX; ELECTRON-MICROSCOPY; ALPHA-3 BETA-1; INVITRO MODEL; IN-VITRO AB To study the mechanism of basement membrane formation, we determined by immunochemistry temporal and spatial expression of laminin-5 (Ln-5), laminin-1 (Ln-1) and their integrin receptors during early skin morphogenesis. A 3-dimensional skin culture was used that allows the study of the sequential molecular events of basement membrane formation at the epidermodermal interface. During early anchorage of keratinocytes to the extracellular matrix there is expression of Ln-5, BP-230 antigen and alpha 3, beta 1 integrin subunits. During epidermal stratification and prior to the formation of the lamina densa there is assembly of Ln-5, Ln-1, collagen IV and nidogen accompanied by keratinocyte basal clustering of alpha 2, alpha 3, alpha 6, beta 1, and beta 4 integrin subunits, The assembly pattern of Ln-1 and Ln-5 can be disturbed with functional antibodies against the pi (AIIB2) and alpha 6 (GoH3) integrin subunits, Ln-1 assembly can also be disturbed with antibodies against its E-8 domain and by competitive inhibition with a synthetic peptide (AG-73) derived from its G-4 domain. Quantitative RT-PCR showed that the dermis contributes about 80% of the laminin gamma 1 chain mRNA while 20% is produced by the epidermis which emphasizes its dual tissue origin and the major contribution of the mesenchyma in laminin production. The laminin gamma 2 chain mRNA, present in Ln-5, was mostly of epidermal origin. This study presents evidence that during the initiation of basement membrane formation, laminins bind to keratinocyte plasma membrane receptors and thus may serve as nucleation sites for further polymerization of these compounds by a self-assembly process. C1 CUNY Mt Sinai Sch Med, Dept Dermatol, New York, NY 10029 USA. National Institute Dental Research, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Dermatol, Philadelphia, PA 19107 USA. Okayama Univ, Sch Med, Dept Biochem & Mol Biol, Okayama 700, Japan. RP Fleischmajer, R (reprint author), CUNY Mt Sinai Sch Med, Dept Dermatol, New York, NY 10029 USA. NR 66 TC 75 Z9 77 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUL PY 1998 VL 111 BP 1929 EP 1940 PN 14 PG 12 WC Cell Biology SC Cell Biology GA 109NB UT WOS:000075327700003 PM 9645941 ER PT J AU Marvin, NJ Dahlstrand, J Lendahl, U McKay, RDG AF Marvin, NJ Dahlstrand, J Lendahl, U McKay, RDG TI A rod end deletion in the intermediate filament protein nestin alters its subcellular localization in neuroepithelial cells of transgenic mice SO JOURNAL OF CELL SCIENCE LA English DT Article DE intermediate filament; cytoskeleton; neural tube; radial; glial cell; CNS precursor cell ID FIBRILLARY ACIDIC PROTEIN; CENTRAL-NERVOUS-SYSTEM; CONSENSUS SEQUENCE MOTIF; ASSEMBLY INVITRO; KERATIN CDNAS; VIMENTIN-FREE; STEM-CELLS; EXPRESSION; DESMIN; ASTROCYTES AB Neuroepithelial and radial glial cells span between the ventricular and the pial surfaces of the neural tube and express two intermediate filaments (IFs), nestin and vimentin, which form a filamentous network throughout the length of the cells. In this report we study the polymerization characteristics of nestin and examine how mutations affect the assembly and localization of the nestin protein in cultured cells and in the developing CNS of transgenic mice. A wild-type rat nestin gene transfected into the IF-free SW13 cell line failed to assemble into a filamentous network but was incorporated into the existing IF network of a subclone expressing vimentin, demonstrating that nestin requires vimentin for proper assembly. In transgenic mice, rat nestin formed a network indistinguishable from that formed by endogenous nestin and vimentin, but a mutant form lacking five amino acids at the carboxy terminus of the rod domain was largely restricted to the pial endfeet, Since nestin mRNA is localized to the pial endfoot region we propose that both transgenes are translated there, but that the wild-type protein is preferentially incorporated into the IF network. These observations provide evidence for hierarchical assembly and a complex organization of the IF network along the ventricular-pial axis in the early CNS. C1 National Institute Neurological Diseases & Stroke, Mol Biol Lab, Bas Neurosci Program, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. RP Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM martha@bcmp.med.harvard.edu NR 76 TC 27 Z9 27 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD JUL PY 1998 VL 111 BP 1951 EP 1961 PN 14 PG 11 WC Cell Biology SC Cell Biology GA 109NB UT WOS:000075327700005 ER PT J AU Takahashi, I Nuckolls, GH Takahashi, K Tanaka, O Semba, I Dashner, R Shum, L Slavkin, HC AF Takahashi, I Nuckolls, GH Takahashi, K Tanaka, O Semba, I Dashner, R Shum, L Slavkin, HC TI Compressive force promotes Sox9, type II collagen and aggrecan and inhibits IL-1 beta expression resulting in chondrogenesis in mouse embryonic limb bud mesenchymal cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE biomechanical force; chondrocyte; type II collagen; aggrecan; sox9; IL-l beta; competitive PCR; mouse embryo; 3-dimensional collagen gel culture ID MANDIBULAR CONDYLAR CARTILAGE; N-CADHERIN EXPRESSION; SECONDARY CHONDROGENESIS; EXTRACELLULAR-MATRIX; HUMAN CHONDROCYTES; GENE-EXPRESSION; GROWING-RAT; GROWTH; CHICK; MORPHOGENESIS AB The initial modeling and subsequent development of the skeleton is controlled by complex gene-environment interactions. Biomechanical forces may be one of the major epigenetic factors that determine the form and differentiation of skeletal tissues. In order to test the hypothesis that static compressive forces are transduced into molecular signals during early chondrogenesis, we have developed a unique three-dimensional collagen gel cell culture system which is permissive for the proliferation and differentiation of chondrocytes, Mouse embryonic day 10 (E10) limb buds were microdissected and dissociated into cells which were then cultured within a collagen gel matrix and maintained for up to 10 days. Static compressive forces were exerted onto these cultures, The time course for expression pattern and level for cartilage specific markers, type II collagen and aggrecan, and regulators of chondrogenesis, Sox9 and IL-1 beta, were analyzed and compared with non-compressed control cultures, Under compressive conditions, histological evaluation showed an apparent acceleration in the rate and extent of chondrogenesis, Quantitatively, there was a significant 2- to 3-fold increase in type II collagen and aggrecan expression beginning at day 5 of culture and the difference was maintained through 10 days of cultures, Compressive force also causes an elevated level of Sox9, a transcriptional activator of type II collagen, In contrast, the expression and accumulation of IL-1 beta, a transcriptional repressor of type II collagen was down-regulated. We conclude that static compressive forces promote chondrogenesis in embryonic limb bud mesenchyme, and propose that the signal transduction from a biomechanical stimuli can be mediated by a combination of positive and negative effecters of cartilage specific extracellular matrix macromolecules. C1 NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD USA. RP Slavkin, HC (reprint author), NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD USA. EM slavkinh@nidr.nih.gov FU NIAMS NIH HHS [Z01-AR41114-02-BCTB] NR 61 TC 127 Z9 130 U1 2 U2 11 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUL PY 1998 VL 111 BP 2067 EP 2076 PN 14 PG 10 WC Cell Biology SC Cell Biology GA 109NB UT WOS:000075327700015 PM 9645953 ER PT J AU Kitano, S Bohr, VA Reed, TD Haggerty, CM May, A Roth, GS AF Kitano, S Bohr, VA Reed, TD Haggerty, CM May, A Roth, GS TI Effect of aging on EGF-stimulated replication of specific genes in rat hepatocytes SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID DNA-POLYMERASE-ALPHA; MITOCHONDRIAL-DNA; CELLS; DELTA AB EGF-stimulated replication of specific genes was examined in primary hepatocyte cultures from mature (6 months) and senescent (24 months) rats. Basal and EGF-stimulated [H-3]thymidine incorporation and DNA polymerase a activities, as well as total cellular DNA, were also assessed. The genes examined were dihydrofolate reductase (DHFR) and c-myc, as well as total mitochondrial DNA (mt DNA). Although [H-3]thymidine incorporation, DNA polymerase alpha activity, total cellular DNA, DHFR, and c-myc gene specific DNA replication stimulated by EGF are reduced with age, mt DNA replication is not affected by either EGF or age. Chromosomal DNA replication is mediated mainly by DNA polymerase alpha while mt DNA replication is mediated by its own DNA polymerase gamma. Thus, the age-related decline in stimulated DNA replication appears to be associated mainly with the DNA polymerase alpha activation pathway. (C) 1998 Wiley-Liss, Inc. C1 NIA, Mol Physiol & Genet Sect, Cellular & Mol Biol Lab, Gerontol Res Ctr,Johns Hopkins Bayview Med Ctr, Baltimore, MD 21224 USA. NIA, Mol Genet Lab, Gerontol Res Ctr, Johns Hopkins Bayview Med Ctr, Baltimore, MD 21224 USA. RP Roth, GS (reprint author), NIA, Mol Physiol & Genet Sect, Cellular & Mol Biol Lab, Gerontol Res Ctr,Johns Hopkins Bayview Med Ctr, Baltimore, MD 21224 USA. NR 28 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 1998 VL 176 IS 1 BP 32 EP 39 DI 10.1002/(SICI)1097-4652(199807)176:1<32::AID-JCP4>3.0.CO;2-9 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ZP476 UT WOS:000073757300004 PM 9618142 ER PT J AU Nambiar, MP Murugesan, R Wu, HC AF Nambiar, MP Murugesan, R Wu, HC TI Inhibition of the cytotoxicity of protein toxins by a novel plant metabolite, mansonone-D SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID DIPHTHERIA-TOXIN; BREFELDIN-A; GOLGI-APPARATUS; PSEUDOMONAS TOXIN; ENDOPLASMIC-RETICULUM; SECRETORY PROTEINS; RICIN; CELLS; TRANSPORT; BINDING AB We have studied the effect of several structurally related mansonones on the cytotoxicity of plant and bacterial toxins in Vero and BER-40, a brefeldin A-resistant mutant of Vero cells. Mansonone-D (MD), a sesquiterpenoid ortho-naphthoquinone, inhibited the cytotoxicity of ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in Vero cells to different extents. The inhibition of ricin cytotoxicity was dose dependent and reversed upon removal of the drug. Protection of ricin cytotoxicity was also observed in the presence of cycloheximide, indicating that de novo protein synthesis is not required for the protective effect. Although MD inhibited the degradation and excretion of ricin, the binding and internalization of ricin was not affected. In contrast, MD strongly reduced the specific binding of diphtheria toxin in Vero cells. Fluorescence microscopic studies show that MD treatment dramatically alters the morphology of the Golgi apparatus in Vero cells. The kinetic studies reveal that the protection of ricin cytotoxicity is the consequence of decreased toxin translocation to the cytosol in MD-treated cells. The reactive ortho-quinone moiety of MD is important for the protective effect as thespesone, a para-naphthoquinone with a heterocyclic ring structure identical to that of MD, did not inhibit the cytotoxicity of toxins. Thespone, a dehydromansonone-D, lacking two hydrogens from the heterocyclic dihydrofuran ring of MD, inhibited the cytotoxicity of ricin, but was albeit less potent than MD. Neither mansonone-E nor mansonone-H with reactive ortho-quinone moiety, but with a different heterocyclic structure, had any effect on the cytotoxicity of ricin indicating that the protective effect of MD is specifically related to the overall structure of the metabolite. (C) 1998 Wiley-Liss, Inc. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Nambiar, MP (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4B04,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM gopi@helix.nih.gov FU NIGMS NIH HHS [GM28810] NR 40 TC 1 Z9 2 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 1998 VL 176 IS 1 BP 40 EP 49 DI 10.1002/(SICI)1097-4652(199807)176:1<40::AID-JCP5>3.0.CO;2-8 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ZP476 UT WOS:000073757300005 PM 9618143 ER PT J AU Sudarshan, C Yaswen, L Kulkarni, A Raghow, R AF Sudarshan, C Yaswen, L Kulkarni, A Raghow, R TI Phenotypic consequences of transforming growth factor beta 1 gene ablation in murine embryonic fibroblasts: Autocrine control of cell proliferation and extracellular matrix biosynthesis SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID CARCINOMA FET CELLS; TGF-BETA; MESSENGER-RNAS; I COLLAGEN; EXPRESSION; TGF-BETA-1; GROWTH-FACTOR-BETA-1; FIBRONECTIN; RECEPTORS; PROTEIN AB The profound effects of transforming growth factor 1 beta (TGF-beta 1) on the immune system, cardiogenesis, in yolk sac hematopoeisis and in differentiation of endothelium have been demonstrated by detailed analyses of TGF-beta 1 knockout mice during embryogenesis. We have systematically examined the autocrine and paracrine roles of TGF-beta 1 in cell proliferation and in its ability to modulate the gene expression of selected components of extracellular matrix (ECM) using embryonic fibroblasts from TGF-beta 1 null mice (TGF-beta 1(-/-)). The rates of cell proliferation of embryonic fibroblasts from normal mice (TGF-beta 1(+/+)) and TGF-beta 1 null mice were compared by cell counting, by H-3 thymidine incorporation, and by measuring the fraction of cells in the G1, S, and G2/M phases of the cell cycle by fluorescent activated cell sorting (FACS). Concurrently, the expression of pro-alpha 1(l) collagen, fibronectin, and plasminogen activator inhibitor-1 (PAI-1) was also quantified by hybridization of total mRNA from TGF-beta 1(+/+) and TGF-beta 1(-/-) embryonic fibroblasts. We report that TGF-beta 1(-/-) cells proliferated at about twice the rate of TGF-beta 1(+/+) cells. Further, TGF-beta 1 null fibroblasts accumulated and synthesized lower constitutive levels of pro-alpha 1(l) collagen, fibronectin, and PAI-1 mRNA. The quantitative differences in the rates of cell proliferation and ECM gene expression between TGF-beta 1(+/+) and TGF-beta 1(-/-) cells could be eliminated by treatment of TGF-beta 1(+/+) cells with a neutralizing antibody of TGF-beta 1. Thus, our results are consistent with the hypothesis that TGF-beta 1 acts as a negative autocrine regulator of growth and a positive autocrine regulator of ECM biosynthesis in embryonic fibroblasts. (C) 1998 Wiley-Liss, Inc. C1 Dept Vet Affairs Med Ctr, Res Serv 151, Memphis, TN 38104 USA. Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Biochem, Memphis, TN 38163 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NIDR, Gene Targeting Res & Core Facil, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Pharmacol, Memphis, TN 38163 USA. RP Raghow, R (reprint author), Dept Vet Affairs Med Ctr, Res Serv 151, 1030 Jefferson Ave, Memphis, TN 38104 USA. EM rraghow@utmem1.utmem.edu FU NIAMS NIH HHS [AR39166] NR 38 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 1998 VL 176 IS 1 BP 67 EP 75 DI 10.1002/(SICI)1097-4652(199807)176:1<67::AID-JCP8>3.0.CO;2-6 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ZP476 UT WOS:000073757300008 PM 9618146 ER PT J AU Wortsman, J McConnachie, P Tahara, K Kohn, LD AF Wortsman, J McConnachie, P Tahara, K Kohn, LD TI Thyrotropin receptor epitopes recognized by Graves' autoantibodies developing under immunosuppressive therapy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; AUTOIMMUNE THYROID-DISEASE; I GENE-EXPRESSION; STIMULATING ANTIBODIES; EXTRACELLULAR DOMAIN; ANTITHYROID DRUGS; TSH RECEPTOR; METHIMAZOLE; MICE; CELLS AB Abnormal modulation of the immune system is a prerequisite for the expression of Graves' disease. Thus, when hyperthyroidism developed in a renal transplant recipient under long term immunosuppression with cyclosporine A and prednisone, we carefully evaluated the basis for her hyperthyroidism and her state of immunosuppression. Immunosuppression was confirmed by finding markedly deficient lymphocyte responses to common mitogens. Lymphocyte phenotype frequencies were those previously found in Graves', i.e. elevated frequencies of CD3/DR, CD5/26, and CD3/25 lymphocytes. There was also reversal of the CD4/CD8 ratio due to increased CD8 frequency; this is not a typical finding in autoimmune hyperthyroidism, but has been seen in the intrathyroidal lymphocyte populations of some Graves' patients and is associated with other forms of autoimmunity. The patient's serum contained a broad spectrum of TSH receptor autoantibodies (TSHRAbs) characteristic of Graves' disease. To determine whether these were an unusual population of autoantibodies, we determined their functional epitopes before and for nearly 1 yr after radioiodine therapy. Stimulating TSHRAbs that increase cAMP levels were human receptor (TSHR) specific and consistently recognized functional epitopes located on TSHR residues 90-165. Stimulating TSHRAbs that increased arachidonate release and inositol phosphate levels recognized residues 25-90, as did TSH binding inhibitory Igs present in the patient. These data demonstrate that Graves' disease with a wide array of TSHRAbs can develop in a patient despite adequate immunosuppression. More importantly, they show that the cAMP-stimulating TSHRAb associated with disease expression in this patient had a homogeneous subtype dependent on TSHR residues 90-165. As persistence of this type of TSHRAb over time has been associated with resistance to methimazole therapy in Graves' patients, we speculate that the development and persistence of TSHRAb with this homogeneous epitope may be linked to resistance to immunosuppressive therapy. C1 NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. So Illinois Univ, Sch Med, Dept Med, Springfield, IL 62701 USA. So Illinois Univ, Sch Med, Dept Immunol Microbiol, Springfield, IL 62701 USA. Chiba Univ, Sch Med, Dept Internal Med 2, Chiba 260, Japan. RP Wortsman, J (reprint author), NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bldg 10,Room 9C101B,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM lenk@bdg10.niddk.nih.gov NR 47 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1998 VL 83 IS 7 BP 2302 EP 2308 DI 10.1210/jc.83.7.2302 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX855 UT WOS:000074562200013 PM 9661599 ER PT J AU Klein, KO Baron, J Barnes, KM Pescovitz, OH Cutler, GB AF Klein, KO Baron, J Barnes, KM Pescovitz, OH Cutler, GB TI Use of an ultrasensitive recombinant cell bioassay to determine estrogen levels in girls with precocious puberty treated with a luteinizing hormone-releasing hormone agonist SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LONG-ACTING ANALOG; TERM TREATMENT; MATURATION; GROWTH; POTENT AB Although treatment of girls with precocious puberty should ideally restore estradiol levels to the normal prepubertal range, treatment effectiveness has usually been monitored by gonadotropin levels because estradiol RIAs have lacked sufficient sensitivity to monitor treatment effectiveness. We hypothesized that a recently developed ultrasensitive recombinant cell bioassay for estradiol would have sufficient sensitivity to demonstrate a dose-dependent suppression of estradiol during LH-releasing hormone agonist treatment and to determine whether currently used doses are able to suppress estradiol levels to the normal prepubertal range. Twenty girls with central precocious puberty were assigned randomly to receive deslorelin for 9 months at a dose of 1, 2, or 4 mu g/ kg day. A significant dose-response relationship was observed, with mean +/- so estradiol levels of 16.7 +/- 6.1, 7.9 +/- 1.6, and 6.5 +/- 0.7 pmol/L at the doses of 1, 2, and 4 mu g/kg day, respectively (P < 0.01). The highest dose suppressed estradiol levels to just above the 95% confidence limits for normal prepubertal girls (<0.07-6.3 pmol/L). We conclude that the ultrasensitive bioassay for estradiol has sufficient sensitivity for monitoring the response to LH-releasing hormone agonist treatment of central precocious puberty. Additionally, the observation that the deslorelin dose of 4 mu g/kg day did not fully restore estradiol levels to the normal prepubertal range suggests that some girls with precocious puberty may require higher doses to receive the maximal benefit of treatment. We suggest that restoration of estradiol levels to the normal prepubertal range should be the ultimate biochemical measure of efficacy, as estradiol is the key hormone that accelerates growth rate, bone maturation rate, and breast development in girls with precocious puberty. C1 Alfred I DuPont Hosp Children, Dept Clin Sci, Wilmington, DE 19899 USA. NICHHD, NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Klein, KO (reprint author), Alfred I DuPont Hosp Children, Dept Clin Sci, POB 269,1600 Rockland Rd, Wilmington, DE 19899 USA. NR 8 TC 32 Z9 33 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1998 VL 83 IS 7 BP 2387 EP 2389 DI 10.1210/jc.83.7.2387 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX855 UT WOS:000074562200029 PM 9661615 ER PT J AU Ryan, AS Egan, JM Habener, JF Elahi, D AF Ryan, AS Egan, JM Habener, JF Elahi, D TI Insulinotropic hormone glucagon-like peptide-1-(7-37) appears not to augment insulin-mediated glucose uptake in young men during euglycemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RAT SKELETAL-MUSCLE; PEPTIDE-I; DIABETES-MELLITUS; HEALTHY-SUBJECTS; TURNOVER RATES; GLP-1; AMIDE; GLP-1(7-36)AMIDE; POLYPEPTIDE; DEGRADATION AB Glucagon-like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that augments insulin secretion in response to meals and lowers blood glucose levels in both type 1 and type 2 diabetic subjects. It has been proposed that a substantial component of the glucose-lowering effects of GLP-1 occurs via insulin-independent mechanisms. However, the interpretations of the studies have been controversial. This study was conducted to examine whether glucagon-like peptide (GLP-1) has an insulin-like effect during euglycemia. Nine young lean men (age, 25 +/- 1.4 yr; body mass index, 24.0 +/- 0.7 kg/m(2)) volunteered to participate in two euglycemic clamp studies (n = 18 clamps) for 120 min. The initial clamp was performed with a primed continuous infusion of GLP-1 at a final rate of 1.5 pmol/kg.min from 0-60 min. At 60 min, the GLP-1 infusion was terminated, and euglycemia was maintained from 60-120 min. After the GLP-1 study, each individual's plasma insulin level was measured. A second study was performed that was identical to the first, with the infusion of regular insulin in place of GLP-1. Insulin infusion rates were designed in each individual to simulate plasma insulin levels produced during the GLP-1 infusion. The rate of disappearance of glucose was calculated for each subject. Basal plasma insulin levels were similar between studies and averaged 49 +/- 5 pmol/L. Basal GLP-1 levels were also similar (6.0 +/- 1.0 pmol/L). In response to the GLP-1 infusion, although basal plasma glucose levels were clamped, significant increases in insulin occurred in all subjects (P < 0.001). With the nearly identical plasma insulin levels during the two studies (30-60 min levels: GLP-1 study, 151 +/- 48; insulin study, 146 +/- 31 pmol/L), the rate of disappearance of glucose progressively increased in response to both GLP-1 and insulin infusions, but was not significantly different between the studies. The design of the study necessitated conducting the GLP-1 study first, which may have been accompanied by a greater stress than the second study. We, therefore, measured cortisol levels. Basal cortisol land ACTH) levels were not different. However, cortisol levels significantly increased during the GLP-1 infusions, and this was preceded by an increase in ACTH levels. Somatostatin levels were not different either basally or during the clamps. We conclude that in the euglycemic state, an acute infusion of GLP-1 does not have insulinlike effects in lean nondiabetic men. Intravenous administration of GLP-1 activates hypothalamic neuroendocrine neurons. C1 Harvard Univ, Geriatr Res Lab GRJ1215, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. NIA, NIH, Lab Clin Physiol, Gerontol Res Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Div Gerontol, Baltimore, MD 21201 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Elahi, D (reprint author), Harvard Univ, Geriatr Res Lab GRJ1215, Massachusetts Gen Hosp, Sch Med,Dept Med, 55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-02719]; NIA NIH HHS [AG-00599, T32-AG00219] NR 40 TC 68 Z9 68 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1998 VL 83 IS 7 BP 2399 EP 2404 DI 10.1210/jc.83.7.2399 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX855 UT WOS:000074562200032 PM 9661618 ER PT J AU Weil, SJ Vendola, K Zhou, J Adesanya, OO Wang, J Okafor, J Bondy, CA AF Weil, SJ Vendola, K Zhou, J Adesanya, OO Wang, J Okafor, J Bondy, CA TI Androgen receptor gene expression in the primate ovary: Cellular localization, regulation, and functional correlations SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MALE-TRANSSEXUALS; POLYCYSTIC OVARIES; MENSTRUAL-CYCLE; TREATED FEMALE; HUMAN TISSUES; TESTOSTERONE; FOLLICLE; STEROIDOGENESIS; PROLIFERATION; MORPHOLOGY AB Excess androgens are associated with a characteristic polyfollicular ovarian morphology; however, it is not known to what extent this problem is due to direct androgen action on follicular development us. interference with gonadotropin release at the level of the pituitary or hypothalamus. To elucidate potential androgen effects on the ovary, we investigated the cellular localization of androgen receptor (AR) messenger ribonucleic acid (mRNA) in rhesus monkey using in situ hybridization. To investigate the regulation of ovarian AR gene expression, we compared the relative abundance of AR transcripts in monkeys during follicular and luteal phases of the menstrual cycle and in monkeys treated with testosterone. To assess potential functional consequences of AR expression in the primate ovary, we compared AR mRNA levels with indexes of follicular cell proliferation and apoptosis in serial sections from individual follicles. AR mRNA expression was most abundant in granulosa cells of healthy preantral and antral follicles in the primate ovary. Theca interns and stromal cells also expressed AR mRNA, but to a lesser degree than granulosa cells. No significant cycle stage effects were noted in AR mRNA levels; however, larger numbers of animals would be necessary to definitively establish a cycle stage effect. AR mRNA level was significantly increased in granulosa cells and was decreased in theca interna and stromal cells of testosterone-treated monkeys. Importantly, granulosa cell AR mRNA abundance was positively correlated with expression of the proliferation-specific antigen Ki-67 (r = 0.91; P < 0.001) and negatively correlated with granulosa cell apoptosis (r = -0.64; P < 0.001). In summary, these data show that primate ovary AR gene expression is most abundant in granulosa cells of healthy growing follicles, where its expression is up-regulated by testosterone. The positive correlation between granulosa AR gene expression and cell proliferation and negative correlation with programmed cell death suggests that androgens stimulate early primate follicle development. C1 NICHHD, NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Weil, SJ (reprint author), NICHHD, NIH, Dev Endocrinol Branch, Bldg 10,Room 10N262,10 Ctr Dr 1862, Bethesda, MD 20892 USA. NR 25 TC 195 Z9 203 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1998 VL 83 IS 7 BP 2479 EP 2485 DI 10.1210/jc.83.7.2479 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX855 UT WOS:000074562200045 PM 9661631 ER PT J AU Blagosklonny, MV Giannakakou, P Wojtowicz, M Romanova, LY Ain, KB Bates, SE Fojo, T AF Blagosklonny, MV Giannakakou, P Wojtowicz, M Romanova, LY Ain, KB Bates, SE Fojo, T TI Effects of p53-expressing adenovirus on the chemosensitivity and differentiation of anaplastic thyroid cancer cells SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID WILD-TYPE P53; ANTICANCER AGENTS; CARCINOMAS; MUTATIONS; GENE; REEXPRESSION; PROTEIN; GLAND; DRUG AB We investigated the p53 status and the ability of exogenous wildtype (wt) p53 to affect chemosensitivity in three anaplastic thyroid carcinoma cell lines (BHT-101, SW-1736, and KAT-4). All three cell lines had nonfunctional p53. Treatment with mitomycin C or adriamycin did not result in accumulation of p53 or induction of p21(WAF1/CIP1) or Mdm-2 and did not cause Rb dephosphorylation. BHT-101 and KAT-4 cells had mutant p53. SW-1736 cells were functionally mutant because of marked down-regulation of wt p53 messenger ribonucleic acid, representing a novel mechanism of p53 dysfunction. Infection with a p53-expressing adenovirus (Ad-p53) induced high levels of p21 and Mdm-2 proteins. In BHT-101 cells, induction of p21 and Mdm-2 was evident 10 h after infection. In KAT-4 cells, induction of p21 and Mdm-2 was observed 1 day after infection, and continued to increase over the ensuing 24 h. SW-1736 cells demonstrated intermediate kinetics. Sensitivity to the cytotoxic effect of Ad-p53 paralleled the kinetics of p21/Mdm-2 induction. BHT-101 cells were most sensitive to killing by Ad-p53, with an IC,, of less than 2 multiplicity of infection; SW-1736 cells were intermediate in sensitivity; KAT-B cells were resistant. All three cell lines became more sensitive to adriamycin after wt p53 expression, with a 10-fold decrease in IC,, values. The latter observation may make a combination of wt p53 and chemotherapeutic drugs an attractive modality for treating anaplastic thyroid cancer. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Kentucky, Med Ctr, Thyroid Canc Res Lab, Vet Adm Med Ctr, Lexington, KY 40536 USA. RP Fojo, T (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov RI Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; Giannakakou, Paraskevi/0000-0001-7378-262X NR 22 TC 71 Z9 72 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1998 VL 83 IS 7 BP 2516 EP 2522 DI 10.1210/jc.83.7.2516 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX855 UT WOS:000074562200051 PM 9661637 ER PT J AU Oliva, A Kinter, AL Vaccarezza, M Rubbert, A Catanzaro, A Moir, S Monaco, J Ehler, L Mizell, S Jackson, R Li, YX Romano, JW Fauci, AS AF Oliva, A Kinter, AL Vaccarezza, M Rubbert, A Catanzaro, A Moir, S Monaco, J Ehler, L Mizell, S Jackson, R Li, YX Romano, JW Fauci, AS TI Natural killer cells from human immunodeficiency virus (HIV)-infected individuals are an important source of CC-chemokines and suppress HIV-1 entry and replication in vitro SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE NK cells; chemokines; HIV; innate immunity; human ID CD8(+) T-CELLS; INFECTED INDIVIDUALS; NK CELLS; RECEPTORS; AIDS; INTERLEUKIN-2; PROGRESSION; LYMPHOCYTES; INVITRO; RANTES AB Macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES (regulated on activation, normal T cell expressed and secreted), which are the natural ligands of the CC-chemokine receptor CCR5, inhibit replication of MT-2-negative strains of HIV-1 by interfering with the ability of these strains to utilize CCR5 as a coreceptor for entry in CD4(+) cells. The present study investigates the capacity of natural killer (NK) cells isolated from HIV-infected individuals to produce CC-chemokines and to suppress HIV replication in autologous, endogenously infected cells as well as to block entry of MT-2-negative HIV into the CD4(+) T cell line PM-1. NK cells freshly isolated from HIV-infected individuals had a high number of mRNA copies for MIP-1 alpha and RANTES. NK cells produced significant amounts of RANTES, MIP-1 alpha, and MIP-1 beta constitutively, in response to stimulation with IL-2 alone and when they were performing their characteristic lytic activity (K562 killing). After CD16 cross-linking and stimulation with IL-2 or IL-15 NK cells produced CC-chemokines to levels comparable to those produced by anti-CD3-stimulated CD8(+) T cells. Furthermore, CD16 cross-linked NK cells suppressed (49-97%) viral replication in cocultures of autologous CD8/NK-depleted PBMC to a degree similar to that of PHA or anti-CD3-stimulated CD8+ T cells. In 50% of patients tested, NK-mediated HIV suppression could be abrogated by neutralizing antibodies to MIP-1 alpha, MIP-1 beta and RANTES; in contrast, CD8+ T cell-mediated suppression was not significantly overcome upon neutralization of CC-chemokines. Supernatants derived from cultures of CD16 cross-linked NK cells stimulated with IL-2 or IL-15 dramatically inhibited entry of a MT-2-negative strain of HIV, Bat, in the CD4(+)CCR5(+) PM-1 T cell line. These data suggest that activated NK cells may be an important source of CC-chemokines in vivo and may suppress HIV replication by CC-chemokine-mediated mechanisms in addition to classic NK-mediated lytic mechanisms. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Adv BioSci Labs Inc, Kensington, MD 20895 USA. RP Kinter, AL (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,MSC 1576, Bethesda, MD 20892 USA. EM aoliva@atlas.niaid.nih.gov OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 58 TC 184 Z9 189 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 1 PY 1998 VL 102 IS 1 BP 223 EP 231 DI 10.1172/JCI2323 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 103GA UT WOS:000075148500028 PM 9649576 ER PT J AU Pham, DG Madico, GE Quinn, TC Enzler, MJ Smith, TF Gaydos, CA AF Pham, DG Madico, GE Quinn, TC Enzler, MJ Smith, TF Gaydos, CA TI Use of lambda phage DNA as a hybrid internal control in a PCR-enzyme immunoassay to detect Chlamydia pneumoniae SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ACQUIRED PNEUMONIA; STRAIN TWAR; INFECTION; PREVALENCE; DIAGNOSIS; ASSAY AB An inherent problem in the diagnostic PCR assay is the presence of ill-defined inhibitors of amplification which may cause false-negative results. Addition of an amplifiable fragment of foreign DNA in the PCR to serve as a hybrid internal control (HIC) would allow for a simple way to identify specimens containing inhibitors, Two oligonucleotide hybrid primers were synthesized to contain nucleic acid sequences of the Chlamydia pneumoniae 16S rRNA primers in a position flanking two primers that target the sequences of a 650-bp lambda phage DNA segment. By using the hybrid primers, hybrid DNA comprising a large sequence of lambda phage DNA flanked by short pieces of chlamydia DNA was subsequently generated by PCR, cloned into a plasmid vector, and purified. Plasmids containing the hybrid DNA were diluted and used as a HIC by adding them to each C, pneumoniae PCR test. Consequently, C. pneumoniae primers were able to amplify both chlamydia DNA and the HIC DNA, The production of a 689-bp HIC DNA band on an acrylamide gel indicated that the specimen contained no inhibitors and that internal conditions were compatible with PCR, Subsequently, a biotinylated RNA probe for the HIC was transcribed from a nested sequence of the HIC and was used for its hybridization, Detection of the HIC DNA-RNA hybrid was achieved by enzyme immunoassay (EIA), This PCR-EIA system with a HIC was initially tested with 12 previously PCR-positive and 14 previously PCR-negative specimens. Of the 12 PCR-positive specimens, 11 were reconfirmed as positive; 1 had a negative HIC value, indicating inhibition. Of the 14 previously PCR-negative specimens, 13 were confirmed as true negative; 1 had a negative HIC value, indicating inhibition. The assay was then used with 237 nasopharyngeal specimens from patients with pneumonia, Twenty-one of 237 (8.9%) were positive for C, pneumoniae, and 42 (17.7%) were found to inhibit the PCR, Specimens showing inhibitory activity were diluted 1:10 and were retested, Ten specimens were still inhibitory to the PCR and required further DNA purification. No additional positive samples were detected and 3 nasopharyngeal specimens remained inhibitory to PCR, Coamplification of a HIC DNA can help confirm true-negative PCR results by ruling oat the presence of inhibitors of DNA amplification. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, Bethesda, MD 20892 USA. Univ Peruana Cayetano Heredia, Lima, Peru. Mayo Clin, Rochester, MN USA. RP Gaydos, CA (reprint author), Johns Hopkins Univ, Div Infect Dis, Ross Res Bldg,Room 1159,720 Rutland Ave, Baltimore, MD 21205 USA. EM cgaydos@welchlink.welch.jhu.edu RI Gaydos, Charlotte/E-9937-2010 NR 21 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1998 VL 36 IS 7 BP 1919 EP 1922 PG 4 WC Microbiology SC Microbiology GA ZU042 UT WOS:000074155400017 PM 9650936 ER PT J AU Cohen, LG Ziemann, U Chen, R Classen, J Hallett, M Gerloff, C Butefisch, C AF Cohen, LG Ziemann, U Chen, R Classen, J Hallett, M Gerloff, C Butefisch, C TI Studies of neuroplasticity with transcranial magnetic stimulation SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE plasticity; reorganization; motor cortex; learning; stroke; use ID HUMAN MOTOR CORTEX; LONG-TERM DEPRESSION; ADULT OWL MONKEYS; DECREASED POSTEXERCISE FACILITATION; MASSIVE CORTICAL REORGANIZATION; FREQUENCY-DISCRIMINATION TASK; POSITRON EMISSION TOMOGRAPHY; RABBIT FOLLOWING STIMULATION; CROSS-MODAL PLASTICITY; UPPER-LIMB AMPUTATION AB In recent years, there has been increasing interest in studies of brain plasticity. Although still loosely defined, this term describes the ability of the brain to change. Cortical plasticity encompasses a wide Variety of phenomena and mechanisms, including modifications in cortical properties such as strength of internal connections, representational patterns, or neuronal modifications, either morphological or functional (Donoghue et al., 1996). We focus on the description of different ways in which transcranial magnetic stimulation (TMS) can be used to study patterns of reorganization and some of the mechanisms involved in these changes. Correlation between TMS and neuroimaging studies in humans and animal studies addressing similar questions is discussed. It is important to identify in each situation whether plasticity plays a beneficial role or is maladaptive in terms of functional compensation. The understanding of patterns, mechanisms, and functional relevance of cortical plasticity will hopefully lead to the design of effective strategies to enhance plasticity when it is beneficial and to down-regulate it when it is maladaptive. An example of a possible strategy, using TMS, is discussed. C1 NINDS, Human Cort Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Unit, NIH, Bldg 10,Room 5N234-1430, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 214 TC 94 Z9 94 U1 2 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JUL PY 1998 VL 15 IS 4 BP 305 EP 324 DI 10.1097/00004691-199807000-00003 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 176TR UT WOS:000079168300003 PM 9736465 ER PT J AU Cheson, BD Frame, JN Vena, D Quashu, N Sorensen, JM AF Cheson, BD Frame, JN Vena, D Quashu, N Sorensen, JM TI Tumor lysis syndrome: An uncommon complication of fludarabine therapy of chronic lymphocytic leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BURKITTS-LYMPHOMA; PROLYMPHOCYTIC LEUKEMIA; AGENT; MONOPHOSPHATE; PHOSPHATE; 2-CHLORODEOXYADENOSINE; SURVIVAL; TRIAL AB Purpose: To quantify the incidence and severity of tumor lysis syndrome (TLS) as a consequence of fludarabine therapy in patients with advanced chronic lymphocytic leukemia (CLL). Patients and Methods: A retrospective review and questionnaire follow-up of clinical and laboratory data were performed on patients with intermediate or highrisk CLL on the National Cancer institute Group C protocol or special exception mechanisms, or phase II trials of fludarabine, for whom adverse drug reports of TLS were available. Fludarabine was administered at a dose of 20 to 40 mg/m(2) per day for 5 days at monthly intervals. Results: Among the 6,137 patients, TLS was suspected in 26 (0.42%), with clinical and laboratory features consistent with TLS present in 20 (0.33%). Prophylaxis against TLS had been administered to 60% of these patients. Clinical or laboratory features were similar to patients who did not develop TLS. Of the patients with TLS, 90% herd high-risk CLL, 60 months of prior disease duration, with a median pretreatment WBC of 109 x 10(9)/L, two prior regimens, lymphadenapathy in 89%, splenomegaly and/or hepatomegaly in 90%. TLS developed on approximately day 7 and lasted a median of 9.5 days. Dialysis was required in 30% during the TLS episode; 20% of patients died during cycle one of fludarabine therapy with renal failure, and another 20% died of infection or congestive heart failure. Six patients were retreated with fludarabine without recurrent TLS, Conclusion: TLS after fludarabine therapy is extremely uncommon, but may be associated with significant morbidity and mortality. C1 NCI, Div Canc Diag & Treatment, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Div Hematol, Dept Internal Med, Bethesda, MD USA. Natl Naval Med Ctr, Div Med Oncol, Dept Internal Med, Bethesda, MD USA. EMMES Corp, Potomac, MD USA. RP Cheson, BD (reprint author), NCI, Div Canc Diag & Treatment, Canc Therapy Evaluat Program, Execut Plaza N,Room 741, Bethesda, MD 20892 USA. EM chesonb@ctep.nci.nih.gov NR 41 TC 48 Z9 48 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1998 VL 16 IS 7 BP 2313 EP 2320 PG 8 WC Oncology SC Oncology GA ZY199 UT WOS:000074596200005 PM 9667245 ER PT J AU Wilson, WH Little, R Pearson, D Jaffe, ES Steinberg, SM Cheson, BD Humphrey, R Kohler, DR Elwood, P AF Wilson, WH Little, R Pearson, D Jaffe, ES Steinberg, SM Cheson, BD Humphrey, R Kohler, DR Elwood, P TI Phase II and dose-escalation with or without granulocyte colony-stimulating factor study of 9-aminocamptothecin in relapsed and refractory lymphomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TOPOISOMERASE-I; CLINICAL-TRIALS; DNA CLEAVAGE; CPT-11; CAMPTOTHECIN; TOPOTECAN; INFUSION; CHEMOTHERAPY; XENOGRAFTS; INHIBITOR AB Purpose: To assess the efficacy and maximum dose-intensity of a new topoisomerase I (topa I)-targeting agent, 9-aminocamptothecin (9-AC), in patients with relapsed or refractory lymphomas. Patients and Methods: Eligible patients had measurable disease and were considered incurable. 9-AC was infused over 72 hours at an initial dose rate of 40 mu g/m(2)/h every 3 weeks with subsequent intrapatient escalations or reductions in 10-mu g/m(2)/h increments based on toxicity, To assess the impact of granulocyte-colony stimulating factor (G-CSF) on dose-intensity, the first 16 patients received no G-CSF and the subsequent 29 patients received G-CSF on all cycles. Results: Forty-five patients received a total of 142 cycles of 9-AC, The patients' median age was 55 years, 73% had stage IV disease, and histologies included indolent and aggressive non-Hodgkin's lymphoma (NHL) in 33% and 58% of patients, respectively, and Hodgkin's lymphoma in 9%, Patients had received a median of two prior chemotherapy regimens, and 67% of patients had chemotherapy-sensitive disease. Of 40 assessable patients, 10 (25%) achieved a partial response (PR). Chemotherapy-sensitive patients had a 32% response rate compared with 8% in chemotherapy-resistant patients. With a median follow-up duration of 35 months, the median event-free survival (EFS) and overall survival times were 1.5 and 12.5 months, respectively, and the median duration of response wets 5 months (range, 1 to 10). G-CSF significantly reduced the incidence of neutropenia and diarrhea, but did not permit a significant increase in dose-intensity. Conclusion: 9-AC had a reasonable response rate of 25% in heavily pretreated patients. The low response rate in patients with chemotherapy-resistant disease suggests that there is cross-resistance between 9-AC and standard chemotherapy. However, there was no association between 9-AC response and the number of prior regimens. Due to dose-limiting thrombocytopenia, C-CSF support did not increase dose-intensity, although individual patients benefited from the use of G-CSF. (C) 1998 by American Society of Clinical Oncology. C1 NCI, Med Branch, Bethesda, MD 20892 USA. Natl Canc Inst, HIV & AIDS Malignancy Branch, Bethesda, MD USA. Natl Canc Inst, Biostat & Data Management Sect, Bethesda, MD USA. Natl Canc Inst, Div Clin Sci, Bethesda, MD USA. Natl Canc Inst, Div Canc Treatment & Ctr, Canc Therapy Evaluat Program, Bethesda, MD USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD USA. RP Wilson, WH (reprint author), NCI, Med Branch, Bldg 10,Room 12N-226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonw@box-w.nih.gov NR 30 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1998 VL 16 IS 7 BP 2345 EP 2351 PG 7 WC Oncology SC Oncology GA ZY199 UT WOS:000074596200009 PM 9667249 ER PT J AU Avila, NA Shawker, TH Roach, P Bradford, MH Skarulis, MC Eastman, R AF Avila, NA Shawker, TH Roach, P Bradford, MH Skarulis, MC Eastman, R TI Sonography of gallbladder abnormalities in acromegaly patients following octreotide and ursodiol therapy: Incidence and time course SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Article DE gallbladder; ultrasonography; acromegaly; octreotide; ursodiol ID SOMATOSTATIN ANALOG SMS-201-995; LONG-TERM TREATMENT; VOLUME AB Purpose. We studied the effects of octreotide and ursodiol on the gallbladders of patients with acromegaly. Methods. We performed gallbladder sonography in patients with acromegaly at various intervals during treatment. Group I (18 patients) was treated with subcutaneous injections of the somatostatin analogue octreotide. Group II (10 patients) was treated with ursodiol while receiving octreotide therapy. Results. Seventy-eight percent of patients receiving octreotide developed gallbladder abnormalities: sludge in 72% (13/18) and calculi in 39% (7/18). Ursodiol reversed the gallbladder abnormalities in 7 of 10 patients. Conclusions. A majority of patients receiving octreotide develop gallbladder abnormalities. Ursodiol appears to reverse the abnormalities in most cases. (C) 1998 John Wiley & Sons, Inc. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Avila, NA (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bldg 10,Room 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 13 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD JUL-AUG PY 1998 VL 26 IS 6 BP 289 EP 294 DI 10.1002/(SICI)1097-0096(199807/08)26:6<289::AID-JCU2>3.0.CO;2-E PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA ZT516 UT WOS:000074095700002 PM 9641388 ER PT J AU Rickard, TC Grafman, J AF Rickard, TC Grafman, J TI Losing their configural mind: Amnesic patients fail on transverse patterning SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID HIPPOCAMPAL-FORMATION; ASSOCIATION THEORY; IMPLICIT MEMORY; EXPLICIT MEMORY; DAMAGE; RATS; DISSOCIATION; CA1 AB A configural theory of human amnesia is proposed. The theory predicts that amnesic patients will exhibit selective deficits on tasks that normal subjects perform by learning new configurations of stimulus elements. This prediction is supported by results for four amnesic patients who learned a nonconfigural control task but failed to learn the configural transverse patterning task even after extensive practice. Matched normal subjects easily learned both tasks. The theory provides unique and viable accounts of the central results in the human amnesia literature. Relations between the configural approach and other theories are discussed. C1 Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. NIH, Bethesda, MD 20892 USA. RP Rickard, TC (reprint author), Univ Calif San Diego, Dept Psychol, 9500 Gilman Dr, La Jolla, CA 92093 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 50 TC 42 Z9 42 U1 0 U2 2 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUL PY 1998 VL 10 IS 4 BP 509 EP 524 DI 10.1162/089892998562915 PG 16 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 122DD UT WOS:000076055900008 PM 9712680 ER PT J AU Gift, HC Atchison, KA Drury, TF AF Gift, HC Atchison, KA Drury, TF TI Perceptions of the natural dentition in the context of multiple variables SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE oral health perceptions; oral health status; NHANES III; sociodemographic factors; dental visits ID QUALITY-OF-LIFE; ORAL HEALTH; UNITED-STATES; GENERAL HEALTH; SOCIAL-FACTORS; MEDICAL-CARE; ADULTS; DETERMINANTS; RATINGS; IMPACT AB Perceived oral health status has been shown to be associated with a variety of single clinical and self-reported indicators of oral health and oral health-related behaviors. A behavioral model is utilized which hypothesizes that perceived condition of natural teeth is predicted by multiple factors, including individual demographic and enabling characteristics, other health perceptions and orientations, actual levels of diseases and conditions, and self-defined need for treatment. The data are from the clinical examination and adult questionnaire of Phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey, which is based on a stratified multistage probability sample to produce nationally representative data for the civilian, non-institutionalized US population. Multivariate hierarchical regressions were used to assess perceived condition of natural teeth in two groups of dentate adults (those with a dental visit during the past 12 months, and those with a less recent dental visit). Self-defined treatment need made a significant, non-trivial contribution after other variables had been controlled. In both subpopulation models, the perception of general health and epidemiological indicators of oral health status were also significant factors. Socio-economic indicators did not contribute significantly in either regression. Understanding components of overall perceptions of oral health moves us closer to understanding oral health behaviors and oral-health-related quality of life. C1 NIDR, NIH, Bethesda, MD 20892 USA. Brevard Coll, Brevard, NC 28712 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. RP Drury, TF (reprint author), NIDR, NIH, 45 Ctr Dr,Bldg 45,Rm 3AN-44D, Bethesda, MD 20892 USA. NR 51 TC 49 Z9 53 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUL PY 1998 VL 77 IS 7 BP 1529 EP 1538 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZX850 UT WOS:000074561700008 PM 9663438 ER PT J AU Teikari, JM Rautalahti, M Haukka, J Jarvinen, P Hartman, AM Virtamo, J Albanes, D Heinonen, O AF Teikari, JM Rautalahti, M Haukka, J Jarvinen, P Hartman, AM Virtamo, J Albanes, D Heinonen, O TI Incidence of cataract operations in Finnish male smokers unaffected by a tocopherol or beta carotene supplements SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID HOSPITAL DISCHARGE DATA; LENS OPACITIES; CIGARETTE-SMOKING; VITAMIN-E; RISK; VALIDITY; PREVENTION; NUTRITION; DISEASES; INVITRO AB Objective-To examine the effect of alpha tocopherol and beta carotene supplementation on the incidence of age related cataract extraction. Setting-The Alpha-tocopherol Beta-carotene (ATBC) Study was a randomised, double blind, placebo controlled, 2x2 factorial trial conducted in south western Finland. The cataract surgery study population of 28 934 male smokers 50-69 years of age at the start. Intervention-Random assignment to one of four regimens: alpha tocopherol 50 mg per day, beta carotene 20 mg per day, both alpha tocopherol and beta carotene, or placebo. Follow up continued for five to eight years (median 5.7 years) with a total of 159 199 person years. Outcome measure-Cataract extraction, ascertained from the National Hospital Discharge Registry. Results-425 men had cataract surgery because of senile or presenile cataract during the follow up. Of these, 112 men were in the alpha tocopherol alone group, 112 men in the beta carotene alone group, 96 men in the alpha tocopherol and beta carotene group, and 105 men in the placebo group. When supplementation with alpha tocopherol and with beta carotene were introduced to a Cox proportional hazards model with baseline characteristics (age, education, history of diabetes, body mass index, alcohol consumption, number of cigarettes smoked daily smoking duration, visual acuity and total cholesterol), neither a tocopherol (relative risk, RR, 0.91, 95% confidence intervals, CI, 0.74, 1.11) nor beta carotene (RR 0.97, 95% CI 0.79, 1.19) supplementation affected the incidence of cataract surgery. Conclusion-Supplementation with alpha tocopherol or beta carotene does not affect the incidence of cataract extractions among male smokers. C1 Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. Natl Publ Hlth Inst, Helsinki, Finland. NCI, NIH, Bethesda, MD 20892 USA. RP Teikari, JM (reprint author), PL39, Helsinki 00551, Finland. RI Albanes, Demetrius/B-9749-2015; Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N01-CN-45165] NR 29 TC 47 Z9 48 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD JUL PY 1998 VL 52 IS 7 BP 468 EP 472 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZY630 UT WOS:000074642900011 PM 9799882 ER PT J AU Sham, JSK Song, LS Deng, LH Chen, Y Stern, MD Lakatta, EG Cheng, HP AF Sham, JSK Song, LS Deng, LH Chen, Y Stern, MD Lakatta, EG Cheng, HP TI Local Ca2+ release is terminated by inactivation of ryanodine receptors SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 1998 VL 112 IS 1 MA 22 BP 9A EP 10A PG 2 WC Physiology SC Physiology GA ZZ047 UT WOS:000074690300029 ER PT J AU Rios, E Stern, M Gonzalez, A Shirokova, N AF Rios, E Stern, M Gonzalez, A Shirokova, N TI Two-way calculations of Ca2+ release underlying Ca2+ sparks of skeletal muscle SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 Rush Univ, Dept Physiol & Mol Biophys, Chicago, IL 60612 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 1998 VL 112 IS 1 MA 23 BP 10A EP 10A PG 1 WC Physiology SC Physiology GA ZZ047 UT WOS:000074690300030 ER PT J AU Stern, MD Cheng, HP Song, LS Sham, JSK Rios, E AF Stern, MD Cheng, HP Song, LS Sham, JSK Rios, E TI Local control in cardiac excitation-contraction coupling: Insights from stochastic simulation SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. Rush Univ, Dept Mol Physiol & Biophys, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 1998 VL 112 IS 1 MA 28 BP 12A EP 12A PG 1 WC Physiology SC Physiology GA ZZ047 UT WOS:000074690300035 ER PT J AU Keizer, J Smith, G AF Keizer, J Smith, G TI Spark-to-wave transition: Saltatory transmission of Ca2+ waves by Ca2+ sparks SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 Univ Calif Davis, Inst Theoret Dynam & Neurobiol Physiol & Behav, Davis, CA USA. NIDDKD, Math Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 1998 VL 112 IS 1 MA 100 BP 37A EP 37A PG 1 WC Physiology SC Physiology GA ZZ047 UT WOS:000074690300107 ER PT J AU Pivovarova, NB Hongpaisan, J Andrews, SB Friel, DD AF Pivovarova, NB Hongpaisan, J Andrews, SB Friel, DD TI Depolarization-induced elevation of total mitochondrial calcium in sympathetic neurons SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 1998 VL 112 IS 1 MA 107 BP 39A EP 40A PG 2 WC Physiology SC Physiology GA ZZ047 UT WOS:000074690300114 ER PT J AU Dittmer, U Feldmann, G Sauermann, U Spring, M Uberla, K Stahl-Hennig, C Hunsmann, G AF Dittmer, U Feldmann, G Sauermann, U Spring, M Uberla, K Stahl-Hennig, C Hunsmann, G TI Specificity of helper T-cells generated from macaques infected with attenuated simian immunodeficiency virus SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID CELLULAR IMMUNE-RESPONSE; ENVELOPE GLYCOPROTEIN; RHESUS MACAQUES; NEF GENE; B-CELL; SIV; IMMUNIZATION; DELETION; SIV(MAC); PROTEIN AB Deletion of the simian immunodeficiency virus (SIV) nef gene leads to an attenuated virus phenotype in vivo. We have previously shown that these viruses induce a potent cellular immune response in macaques. To extend these studies, we established virus-specific short-term T-cell lines from four rhesus macaques infected with a nef deletion mutant of SIV, These T-cell lines proliferated upon restimulation with whole SIV or SIV gp140 antigen in vitro. The proliferating cells were characterized as CD4(+) helper T-cells (TH) and their antigen recognition was MHC class II DR-restricted. After antigenic stimulation, they transcribed mRNA for various TH1- and TH2-like cytokines, Using these SIV-specific cell lines, a variety of helper T-cell epitopes in the SIV Env protein were determined with overlapping peptides, TH epitopes were identified throughout the whole SIV Env including both constant and variable regions. Although the recognition of TH epitopes was heterogeneous among different animals, five more broadly reactive T-cell epitopes were identified. As expected, recognition was associated with the MHC class II DRB background of the animals. This is the first report on helper T-cell epitopes in SIV-infected monkeys. Such studies should be of considerable significance for AIDS/vaccine research. C1 Deutsches Primatenzentrum Virol & Immunol, D-37077 Gottingen, Germany. Univ Erlangen Nurnberg, Inst Klin & Mol Virol, D-8520 Erlangen, Germany. RP Dittmer, U (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM udittmer@atlas.niaid.nih.gov RI Uberla, Klaus/C-5676-2008 NR 26 TC 4 Z9 4 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUL PY 1998 VL 79 BP 1801 EP 1807 PN 7 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA ZY138 UT WOS:000074590100027 PM 9680145 ER PT J AU Tamura, K Fukuda, Y Ferrans, VJ AF Tamura, K Fukuda, Y Ferrans, VJ TI Elastic fiber abnormalities associated with a leaflet perforation in floppy mitral valve SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID HEART-VALVES; COLLAGEN; ANEURYSM AB The alterations observed in the elastic fibers of the perforated floppy mitral valve of a 68-year-old man are described. The patient had no history of infective endocarditis and no stigmata of Marfan syndrome or Ehlers-Danlos syndrome. Ultrastructurally, the elastic fibers in the area of the perforation showed unique, round-shaped expansion of the amorphous components, which lacked associated microfibrils. These features resembled those of the elastic fibers in animals treated with beta-aminopropionitrile, an inhibitor of lysyl oxidase. Aggregations of microfibrils without amorphous components were also observed. These abnormalities are considered to be related to the pathogenesis of the perforation in this valve. C1 Nippon Med Sch, Dept Pathol, Bunkyo Ku, Tokyo 113, Japan. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Tamura, K (reprint author), Nippon Med Sch, Dept Pathol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 113, Japan. NR 19 TC 3 Z9 3 U1 0 U2 0 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD, ENGLAND HA6 2ET SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD JUL PY 1998 VL 7 IS 4 BP 460 EP 466 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 103JL UT WOS:000075153800020 PM 9697072 ER PT J AU Moreira, JE Dodane, V Reese, TS AF Moreira, JE Dodane, V Reese, TS TI Immunoelectronmicroscopy of soluble and membrane proteins with a sensitive postembedding method SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE freeze-substitution; immunoelectron microscopy; soluble proteins; membrane proteins ID FREEZE-SUBSTITUTION; GLUTAMATE-RECEPTOR; SQUID AXOPLASM; KINESIN; MICROSCOPY; TRANSPORT; MICROTUBULES; ORGANELLES; IMMUNOCYTOCHEMISTRY; LOCALIZATION AB The application of immunoelectronmicroscopy to soluble proteins is limited because soluble proteins can redistribute during fixation. Fixation may also adversely affect the recognition of proteins associated with membranes. We show here how displacements of soluble proteins can be prevented and antigen sensitivity improved by freeze-substitution immunocytochemistry. The usefulness of this method for soluble cytoplasmic proteins is demonstrated for the twitchin protein in Aplysia muscle and the kinesin motor proteins in squid giant axons, in which the sizes of various cytoplasmic pools of kinesins are estimated. The utility for membrane proteins present in small numbers of copies is demonstrated by labeling a glutamate receptor subunit in mouse cerebellar cortex and the ZO-1 protein in tight junctions between MDCK cells. Thus, freeze-substitution immunocytochemistry can show the native distribution of both soluble and membrane proteins labeled with polyclonal antibodies and, at the same time, can reveal structural features comparable to those in chemically fixed or osmium freeze-substituted samples. C1 NINDS, Neurobiol Lab, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, NIH, Bethesda, MD USA. Marine Biol Lab, Woods Hole, MA 02543 USA. RP Univ Sao Paulo, FMRP, Fac Med, Dept Morphol, BR-14049900 Ribeirao Preto, Brazil. NR 30 TC 15 Z9 17 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUL PY 1998 VL 46 IS 7 BP 847 EP 854 PG 8 WC Cell Biology SC Cell Biology GA ZW503 UT WOS:000074417500008 PM 9632744 ER PT J AU Anderson, DE Dhokalia, A Parsons, D Bagrov, AY AF Anderson, DE Dhokalia, A Parsons, D Bagrov, AY TI Sodium sensitivity in young adults with high resting end-tidal CO(2) SO JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; end-tidal CO(2); endogenous digitalis-like factors; hypertension; sodium sensitivity ID BLOOD-PRESSURE RESPONSE; ESSENTIAL-HYPERTENSION; NORMOTENSIVE MEN; SALT SENSITIVITY; PROTON EXCHANGE; EXCRETION; OUABAIN; PLASMA AB Background Previous research with normotensive adults aged over 40 years ('older') found that sensitivity of blood pressure of subjects with high resting end-tidal partial pressures of CO(2) to high sodium intake was greater than normal, Objective To test the hypothesis that the lesser sensitivity of blood pressure of young normotensive adults to high sodium intake is also a function of resting end-tidal partial pressure of CO(2), Design Forty-eight Caucasian men and women (age 28.5 +/- 1.4 years) had a lower than normal dietary intake of sodium chloride for 4 days, and then ingested sodium chloride capsules for 7 days tan additional 190 mmol/day sodium chloride), Resting end-tidal partial pressure of CO(2) and blood pressure, and 24 h ambulatory blood pressure, were measured before and after the high-sodium diet Overnight urine samples were collected before and after the high-sodium diet to determine dietary compliance, and to assess changes in urinary excretion of endogenous digitalis-like factors (a ouabain-like factor, and a marinobufagenin-like factor) that covary with plasma volume. Results Subjects with high end-tidal partial pressures of CO(2) had lower resting heart rates and lower urinary excretion of ouabain-like factor before sodium loading, Sodium loading decreased mean partial pressure of CO(2) (by 0.8 +/- 0.2 mmHg) and increased only ambulatory systolic blood pressure (by 2.1 +/- 0.8 mmHg) for the whole group, However, the changes in resting systolic (r = 0.32, P < 0.025) and diastolic (r = 0.36, P < 0.01) blood pressures and in 24 h systolic (r = 0.28, P< 0.05) blood pressure after sodium loading were ail positive functions of individual resting end-tidal partial pressures of CO(2), Sodium loading increased urinary excretion of marinobufagenin-like factor (by 1.78 +/- 0.88 nmol) and the magnitude of the individual increase was a function of end-tidal partial pressure of CO(2), Conclusions The results indicate that a high resting partial pressure of CO(2) augments the effects of high sodium intake on plasma volume, levels of endogenous digitalis-like factors, and blood pressure in young normotensive humans, I Hypertens 16:1015-1022 (C) 1998 Lippincott-Raven Publishers. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Anderson, DE (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 45 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUL PY 1998 VL 16 IS 7 BP 1015 EP 1022 DI 10.1097/00004872-199816070-00016 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 105VY UT WOS:000075095300016 PM 9794743 ER PT J AU Smithson, G Couse, JF Lubahn, DB Korach, KS Kincade, PW AF Smithson, G Couse, JF Lubahn, DB Korach, KS Kincade, PW TI The role of estrogen receptors and androgen receptors in sex steroid regulation of B lymphopoiesis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; OSTEOBLAST-LIKE CELLS; MOUSE BONE-MARROW; TFM MOUSE; NEGATIVE REGULATORS; TARGETED DISRUPTION; MESSENGER-RNA; STROMAL CELLS; MUTANT MOUSE; WILD-TYPE AB Several observations suggest that sex steroids might participate in steady state regulation of B lymphopoiesis. B cell precursors decline dramatically in bone marrow of pregnant or estrogen-treated mice. Reciprocally, the same cell populations are increased in hypogonadal mice or male castrates. Estrogen treatment of hypogonadal mice reduced precursors to normal. However, questions remain about which hormones and receptors are the most important. Furthermore, these observations need to be reconciled with advances regarding new sex steroid receptors, We have now characterized B lymphopoiesis in androgen receptor-deficient testicular feminization (Tfm) mice, Testicular feminization mice had substantially elevated numbers of B cell precursors in the bone marrow and B cells in the spleen as compared with wild-type mice, The importance of one estrogen receptor (ER alpha) was evaluated in gene-targeted mice, and B cell precursors were found to be within the normal range, Our previous studies indicated that hormone receptors in stromal cells may be important for estrogen-mediated suppression of B lymphopoiesis, We now show that estrogen-mediated inhibition of B cell precursor expansion in culture was blocked by a specific estrogen receptor antagonist (ICI 182,780), Stromal cells derived from ER alpha-targeted bone marrow were fully estrogen responsive. RT-PCR analyses of these stromal cells revealed splice-variant transcripts of ER alpha, as well as message for a recently discovered estrogen-binding receptor, ER beta. Thus, androgens may normally inhibit B lymphopoiesis through the androgen receptor, whereas estrogens might utilize one or more receptors to achieve the same physiologic response. C1 Oklahoma Med Res Fdn, Immunobiol & Canc Program, Oklahoma City, OK 73104 USA. NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, Res Triangle Pk, NC 27709 USA. Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. Univ Missouri, Dept Child Hlth, Columbia, MO 65211 USA. RP Kincade, PW (reprint author), Oklahoma Med Res Fdn, Immunobiol Program, 825 NE 13Th St, Oklahoma City, OK 73104 USA. OI Korach, Kenneth/0000-0002-7765-418X FU NIAID NIH HHS [AI-20069] NR 55 TC 118 Z9 123 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1998 VL 161 IS 1 BP 27 EP 34 PG 8 WC Immunology SC Immunology GA ZV419 UT WOS:000074302700005 PM 9647203 ER PT J AU Tarrant, TK Silver, PB Chan, CC Wiggert, B Caspi, RR AF Tarrant, TK Silver, PB Chan, CC Wiggert, B Caspi, RR TI Endogenous IL-12 is required for induction and expression of experimental autoimmune uveitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; T-CELL CLONES; RETINOID-BINDING PROTEIN; IFN-GAMMA PRODUCTION; INTERFERON-GAMMA; GENETIC SUSCEPTIBILITY; STIMULATORY FACTOR; LEISHMANIA-MAJOR; IMMUNE-RESPONSES; DENDRITIC CELLS AB Experimental autoimmune uveitis (EAU) has been associated with a Th1 response. However, in IFN-gamma-deficient mice, EAU develops in the context of an effector response having Th2-like elements, and administration of IL-12 to mice immunized for EAU induction can be protective. We, therefore, investigated whether endogenous IL-12 is required for development of EAU, IL-12 p40-deficient mice (12KO) were resistant to EAU induced with the uveitogenic retinal Ag interphotoreceptor retinoid binding protein (IRBP), Delayed hypersensitivity to IRBP was marginally reduced, whereas Ag-specific proliferation was enhanced, Primed lymphocytes of wild-type (wt) mice, cultured with IRBP, produced a Th1-like cytokine profile and transferred EAU to syngeneic wt recipients. interestingly, the same cells were inefficient Ire transferring EAU to 12KO recipients, unless IL-12 was included in the culture. Primed cells of the 12KO mice produced a Th2-like cytokine profile and failed to transfer EAU. However, when IL-12 was added to the culture, 12KO cells produced large amounts of IFN-gamma and transferred EAU to naive 12KO recipients. We conclude that resistance to EAU of 12KO mite is not doe to an inherent inability of these mice to develop ocular disease. Despite an apparent similarity in Ag-specific cytokine responses to IFN-gamma-deficient mice, 12KO mice have inhibited generation of uveitogenic effector cells, a situation that can he reversed even after priming, by adding exogenous IL-12 ex vivo. Lastly, the diminished ability of primed wt lymphocytes to induce EAU in 12KO mice indicates a role for endogenous IL-12 in the efferent phase of disease expression that is distinct from its: role during Ag priming. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N22, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov NR 39 TC 80 Z9 91 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1998 VL 161 IS 1 BP 122 EP 127 PG 6 WC Immunology SC Immunology GA ZV419 UT WOS:000074302700017 PM 9647215 ER PT J AU Yu, CR Kirken, RA Malabarba, MG Young, HA Ortaldo, JR AF Yu, CR Kirken, RA Malabarba, MG Young, HA Ortaldo, JR TI Differential regulation of the Janus kinase STAT pathway and biologic function of IL-13 in primary human NK acid T cells: A comparative study with IL-4 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; RECEPTOR-ALPHA CHAIN; HUMAN B-CELLS; SIGNAL-TRANSDUCTION; INTERLEUKIN-4 RECEPTOR; TYROSINE PHOSPHORYLATION; GAMMA-CHAIN; BINDING SUBUNIT; GROWTH-FACTOR; ACTIVATION AB IL-13, a cytokine similar to IL-4, is a regulates of human B cell and monocyte functions, Biologic effects of IL-13 on primary human NK and T cells have not been well defined. We demonstrate that, in primary NK cells, IL-13, but not IL-4, may induce low levels of IFN-gamma secretion. When NK cells were costimulated with IL-13 and IL-2, IL-13 generally resulted in two types of reactivity: IL-13 synergized with IL-2 to stimulate IFN-gamma production off it modestly inhibited IL-2-mediated IFN-gamma production. In both types of donors, the effect of IL-13 on IL-2-induced IFN-gamma production was in marked contrast to the strong inhibition seen with IL-4 in NK cells. Additionally, IL-13 suppresses IL-2-induced NK cytolytic and proliferative activities although less efficiently than IL-2. In T cells, IL-13 inhibits anti-CD3 mAb/IL-2-or PHA-mediated IFN-gamma production and enhances cytolytic potential, Furthermore, we demonstrate that IL-13, like IL-4, induces distinct STAT6-DNA binding complexes and tyrosine phosphosylation of STAT6 and Janus kinase 3 (JAK3) in NK and T cells. We observed that Abs directed against unique domains of STAT6 have differential effects on complexes in T cells but not in NK cells, suggesting different STAT6 isoforms. These findings show that IL-13 and IL-4 have the ability to regulate NK and T cell activation and that IL-13 is a potent regulator of STAT6 and JAK3 in these cen types. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Sci Applicat Int Corp, Expt Immunol Lab, Frederick, MD USA. Sci Applicat Int Corp, Div Basic Sci, Mol Immunoregulat Lab, Frederick, MD USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD USA. RP Ortaldo, JR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-93, Frederick, MD 21702 USA. EM Ortaldo@nciferf.gov RI Malabarba, Maria Grazia/L-4805-2015 OI Malabarba, Maria Grazia/0000-0002-9457-2047 NR 67 TC 52 Z9 53 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1998 VL 161 IS 1 BP 218 EP 227 PG 10 WC Immunology SC Immunology GA ZV419 UT WOS:000074302700029 PM 9647227 ER PT J AU Fan, J Marshall, JC Jimenez, M Shek, PN Zagorski, J Rotstein, OD AF Fan, J Marshall, JC Jimenez, M Shek, PN Zagorski, J Rotstein, OD TI Hemorrhagic shock primes for increased expression of cytokine-induced neutrophil chemoattractant in the lung: Role in pulmonary inflammation following lipopolysaccharide SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; KAPPA-B-ACTIVATION; MULTIPLE ORGAN FAILURE; ANTIOXIDANT TREATMENT; ALVEOLAR MACROPHAGES; N-ACETYLCYSTEINE; ENDOTOXIN; INJURY; INTERLEUKIN-8; RATS AB Recent studies have suggested that hemorrhagic shock followed by resuscitation renders patients more susceptible to lung injury by priming for an exaggerated response to a second stimulus, the so-called "two-hit" hypothesis, We investigated the role of C-X-C chemokines in mediating the augmented lung inflammation in response to LPS following resuscitated shock, in a rodent model, animals exposed to antecedent shock exhibited enhanced lung neutrophil sequestration and transpulmonary albumin flux in response to intratracheal LPS, This effect correlated with an exaggerated expression of cytokine-induced neutrophil chemoattractant (CINC) protein and mRNA, but not macrophage-inflammatory protein 2. Strategies designed to inhibit CMC, both anti-CINC Ab and supplementation with the antioxidant N-acetyl-cysteine, prevented the enhanced neutrophil sequestration, suggesting that CINC played a central role in the enhanced leukocyte accumulation following shock plus I,PS treatment. Shock alone increased lung nuclear factor-kappa B expression and augmented the response to LPS, Prevention of this effect by N-acetyl-cysteine supplementation of the resuscitation fluid implicates a role for oxidant stress in the priming for lung inflammation following shock, Finally, alveolar macrophages recovered from shock-resuscitated animals released more CINC protein in vitro ire response to LPS than macrophages from sham animals, Considered together, these findings show that augmented release of CINC, in part from primed alveolar macrophages, contributes significantly to the enhanced lung leukosequestration and transpulmonary albumin nux in response to LPS following resuscitated shock. C1 Toronto Gen Hosp, Gen Div, Dept Surg, Toronto, ON M5G 2C4, Canada. Univ Toronto, Dept Surg, Toronto, ON, Canada. Def & Civil Inst Environm Med, Toronto, ON M3M 3B9, Canada. NIDR, NIH, Bethesda, MD 20892 USA. RP Rotstein, OD (reprint author), Toronto Gen Hosp, Gen Div, Dept Surg, 200 Elizabeth St,Eaton N 9-232, Toronto, ON M5G 2C4, Canada. EM orotstein@torhosp.toronto.on.ca NR 37 TC 156 Z9 162 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1998 VL 161 IS 1 BP 440 EP 447 PG 8 WC Immunology SC Immunology GA ZV419 UT WOS:000074302700056 PM 9647254 ER PT J AU Kubota, R Kawanishi, T Matsubara, H Manns, A Jacobson, S AF Kubota, R Kawanishi, T Matsubara, H Manns, A Jacobson, S TI Demonstration of human T lymphotropic virus type I (HTLV-I) tax-specific CD8(+) lymphocytes directly in peripheral blood of HTLV-I-associated myelopathy tropical spastic paraparesis patients by intracellular cytokine detection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SPINAL-CORD LESIONS; NECROSIS-FACTOR-ALPHA; CEREBROSPINAL-FLUID; CELL LEUKEMIA; PROVIRAL DNA; NEUROLOGICAL DISEASE; PATHOGENESIS; ANTIBODIES; EXPRESSION; FEATURES AB Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurologic disease caused by HTLV-I infection and has been associated with elevated levels of several proinflammatory cytokines in both serum and cerebrospinal fluid. It is unknown what kind of cells secrete these cytokines and if HTLV-I Ags are associated with this phenomenon. Here, we investigated the expression of cytokines in PBL from eight HAM/TSP patients, nine HTLV-I-infected asymptomatic carriers, and seven healthy controls by flow cytometry combined with intracellular cytokine staining. PBL were cultured with brefeldin A without mitogen and IL-2 for 14 h, Under these conditions, CD8(+) cells produced proinflammatory cytokines including IFN-gamma, TNF-alpha, and IL-2, which were significantly elevated in HAM/TSP patients. The proportion of CD8(+) cells producing IFN-gamma in HAM/TSP patients, asymptomatic carriers, and healthy controls were, on average, 4.9, 0.4, and 0.3%, respectively. IFN-gamma production by these CD8(+) cells was suppressed by anti-HLA-class I Ab. Purified CD8(+) cells from an HLA-A2 HAM/TSP patient produced IFN-gamma by cocultivation with autologous CD4 cells, the main reservoir of HTLV-I in vivo, or allogenic HLA-A2(+) B cells pulsed with a known immunodominant HTLV-I tax peptide. These data suggest that high levels of circulating HTLV-I-specific CD8(+) T lymphocytes have the potential to produce proinflammatory cytokines and may promote inflammatory responses to HTLV-I in HAM/TSP patients. C1 NINDS, Virol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Viral Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NINDS, Virol Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16, Bethesda, MD 20892 USA. EM steve@helix.nih.gov NR 39 TC 76 Z9 78 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1998 VL 161 IS 1 BP 482 EP 488 PG 7 WC Immunology SC Immunology GA ZV419 UT WOS:000074302700061 PM 9647259 ER PT J AU Kawakami, Y Robbins, PF Wang, RF Parkhurst, M Kang, XQ Rosenberg, SA AF Kawakami, Y Robbins, PF Wang, RF Parkhurst, M Kang, XQ Rosenberg, SA TI The use of melanosomal proteins in the immunotherapy of melanoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma antigens; MART-1; gp100; subdominant epitopes; immunotherapy ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; ESTABLISHED PULMONARY METASTASES; PULSED DENDRITIC CELLS; ANTIGEN GP100; IN-VIVO; SYNTHETIC PEPTIDES; MULTIPLE EPITOPES; PERIPHERAL-BLOOD; TYROSINASE GENE AB Clinical observations in the interleukin (IL) 2-based immunotherapies suggest that T cells play a central role in the rejection of melanoma. Using cDNA expression cloning, we have isolated genes encoding melanoma antigens recognized by tumor-infiltrating T lymphocytes. These antigens are categorized as (a) melanocyte specific melanosomal proteins (MART-1/meian A, gp100; tyrosinase, TRP-I, and TRP-2), (b) tumor-specific mutated proteins (beta-catenin), and (c) others (p15). A variety of mechanisms has been identified for the generation of T cell epitopes on tumor cells. Some of the HLA-A2 binding epitopes from the melanosomal antigens appear to be subdominant self-determinants with relatively low major histocompatibility complex binding affinity. The effectiveness of adoptive transfer into patients of cytotoxic T lymphocytes recognizing the melanosomal antigens, the significant correlation between vitiligo development and clinical response in patients receiving IL-2-based immunotherapies, and the sporadic tumor regressions observed in some patients following immunization with the MART-1 or gp100 peptides in incomplete Freund's adjuvant or recombinant viruses expressing the MART-1 antigen suggest that these epitopes may represent tumor rejection antigens. Phase I immunization trials using peptides or recombinant viruses containing genes encoding the melanosomal antigens MART-1 or gp 100, with or without co-administration of cytokines such as IL-2, IL-12, or granulocyte-macrophage colony-stimulating factor, are being conducted in the Sur gery Branch of the National Cancer Institute. These studies may demonstrate the feasibility of using melanosomal proteins for the immunotherapy of patients with melanoma. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Kawakami, Y (reprint author), NCI, Surg Branch, NIH, Bldg 10,Rm 2B42,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 74 TC 70 Z9 73 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1998 VL 21 IS 4 BP 237 EP 246 DI 10.1097/00002371-199807000-00001 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA ZZ676 UT WOS:000074755400001 PM 9672845 ER PT J AU Friedman, HB Saah, AJ Sherman, ME Busseniers, AE Blackwelder, WC Kaslow, RA Ghaffari, AM Daniel, RW Shah, KV AF Friedman, HB Saah, AJ Sherman, ME Busseniers, AE Blackwelder, WC Kaslow, RA Ghaffari, AM Daniel, RW Shah, KV TI Human papillomavirus, anal squamous intraepithelial lesions, and human immunodeficiency virus in a cohort of gay men SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MULTICENTER AIDS COHORT; HOMOSEXUAL MEN; HIV-INFECTION; CYTOLOGIC DIAGNOSIS; CERVICAL-CANCER; NEOPLASIA; RISK; ASSOCIATION; WOMEN; IMMUNOSUPPRESSION AB Cross-sectional associations between human papillomavirus (HPV), anal squamous intraepithelial lesions (SIL), and human immunodeficiency virus (HIV) were studied in a cohort of gay men. HPV DNA was detected by generic and type-specific polymerase chain reaction (PCR) probes and hybrid capture assay (HC), HPV virus load was estimated by HC relative light unit (RLU) ratio. HPV prevalence, number of HPV types detected, and HC RLU ratios were each greater in HIV-positive than HIV-negative participants, Further, among HIV-positive men, HC RLU ratio was inversely associated with CD4 cell count. SIL was more frequent in HIV-positive participants, particularly those with a CD4 cell count <200/mu L and was positively associated with HPV. Men with a high HC RLU ratio were nearly 3 times more likely to have SIL than were those both PCR- and HC-negative. These data support that HIV augments HPV-associated anal disease in this population. C1 NIAID, Div Microbiol & Infect Dis, NIH, Rockville, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Johns Hopkins Hosp, Dept Pathol, Baltimore, MD 21287 USA. RP Friedman, HB (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Div Epidemiol & Biostat, Room A1039,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM hfriedman@usuhs.mil FU NIAID NIH HHS [AI-35042] NR 37 TC 40 Z9 45 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1998 VL 178 IS 1 BP 45 EP 52 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZV943 UT WOS:000074357900007 PM 9652422 ER PT J AU Lederman, MM Connick, E Landay, A Kuritzkes, DR Spritzler, J St Clair, M Kotzin, BL Fox, L Chiozzi, H Leonard, JM Rousseau, F Wade, M Roe, JD Martinez, A Kessler, H AF Lederman, MM Connick, E Landay, A Kuritzkes, DR Spritzler, J St Clair, M Kotzin, BL Fox, L Chiozzi, H Leonard, JM Rousseau, F Wade, M Roe, JD Martinez, A Kessler, H TI Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: Results of AIDS clinical trials group protocol 315 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th Conference on Retroviruses and Opportunistic Infections CY JAN 22-31, 1997 CL WASHINGTON, D.C. ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; LYMPHOCYTE-PROLIFERATION; IMMUNE FUNCTION; HOMOSEXUAL MEN; TAT PROTEIN; T-CELLS; INHIBITION; RECEPTORS AB Human immunodeficiency virus (HIV)-1 infection is associated with progressive cell-mediated immune deficiency and abnormal immune activation. Although highly active antiretroviral therapy regimens can increase circulating CD4 T lymphocyte counts and decrease the risk of opportunistic complications, the effects of these treatments on immune reconstitution are not well understood. In 44 persons with moderately advanced HIV-1 infection, after 12 weeks of treatment with zidovudine, lamivudine, and ritonavir, plasma HIV-1 RNA fell a median of 2.3 logs (P <.0001). Circulating numbers of naive and memory CD4 T lymphocytes (P <.001), naive CD8 T lymphocytes (P < .004), and B lymphocytes (P <.001) increased. Improved lymphocyte proliferation to certain antigens and a tendency to improvement in delayed-type hypersensitivity also were seen. Dysregulated immune activation was partially corrected by this regimen; however, the perturbed expression of T cell receptor V regions in the CD4 and CD8 T lymphocyte populations was not significantly affected, Ongoing studies will ascertain if longer durations of virus suppression will permit more complete immune restoration. C1 Univ Hosp Cleveland, Div Infect Dis, AIDS Clin Trials Unit, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Vet Adm Med Ctr, Denver, CO 80220 USA. Rush Presbyterian St Lukes Med Ctr, Rush Med Coll, Chicago, IL 60612 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Social & Sci Syst Inc, Rockville, MD USA. RP Lederman, MM (reprint author), Univ Hosp Cleveland, Div Infect Dis, AIDS Clin Trials Unit, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM MXL6@po.cwru.edu FU NIAID NIH HHS [AI-25879, AI-25915, AI-32790] NR 47 TC 298 Z9 305 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1998 VL 178 IS 1 BP 70 EP 79 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZV943 UT WOS:000074357900010 PM 9652425 ER PT J AU Niu, MT Bethel, J Holodniy, M Standiford, HC Schnittman, SM AF Niu, MT Bethel, J Holodniy, M Standiford, HC Schnittman, SM CA DATRI 002 Study Grp TI Zidovudine treatment in patients with primary (Acute) human immunodeficiency virus type 1 infection: A randomized, double-blind, placebo-controlled trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XIth International Conference on AIDS CY JUL 07-13, 1996 CL VANCOUVER, CANADA ID PRIMARY HIV-1 INFECTION; T-LYMPHOCYTE ACTIVITY; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSE; ANTIRETROVIRAL THERAPY; CUBIC MILLIMETER; VIRAL DYNAMICS; CELL COUNTS; VIREMIA; PLASMA AB A multicenter, double-blind, placebo-controlled trial randomized 28 patients with primary (acute) human immunodeficiency virus (HIV)-1 infection (PHI) to receive zidovudine, 1000 mg daily, or placebo for 24 weeks. At week 48, compared with placebo patients, zidovudine-treated patients had significantly higher CD4 cell counts (zidovudine, 666 cells/mm(3); placebo, 362; P =.004) and lower peripheral blood mononuclear cell (PBMC) culture titers (zidovudine, 0.58 log infectious units per million cells; placebo, 1.68; P =.02) but no difference in plasma RNA (zidovudine, 3.93 log copies/mL; placebo, 4.00; P =.83). Serious adverse events and minor clinical events were infrequent and comparable in both arms. There were two deaths: 1 patient died of sepsis and renal disease (zidovudine arm), and 1 patient died of sepsis and tension pneumothorax (placebo arm). Six months of high-dose zidovudine initiated during PHI results in higher CD4 cell counts and lower PBMC culture titers but no difference in plasma HIV-1 RNA. Further studies with more potent antiretroviral combination therapies ape warranted. C1 NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. Vet Adm Med Ctr, Inst Human Virol, Baltimore, MD 21218 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. VA Palo Alto Hlth Care Syst, AIDS Res Ctr, Palo Alto, CA USA. RP Niu, MT (reprint author), US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. EM niu@a1.cber.fda.gov FU NIAID NIH HHS [AI-15123] NR 77 TC 29 Z9 29 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1998 VL 178 IS 1 BP 80 EP 91 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZV943 UT WOS:000074357900011 PM 9652426 ER PT J AU Bouloc, A Cavani, A Katz, SI AF Bouloc, A Cavani, A Katz, SI TI Contact hypersensitivity in MHC class II-deficient mice depends on CD8 T lymphocytes primed by immunostimulating Langerhans cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE CD8 lymphocytes; MHC class II deficiency ID DELAYED-TYPE HYPERSENSITIVITY; DENDRITIC CELLS; MONOCLONAL-ANTIBODY; SURFACE EXPRESSION; SENSITIVITY; ANTIGEN; INVIVO; CD4+; INDUCTION; RESPONSES AB Studies to determine if CD4(+) and/or CD8(+) T cells are critical for the initiation and propagation of contact hypersensitivity (CHS) reactions have yielded conflicting results regarding their roles. We studied the induction and expression of CHS to trinitrochlorobenzene (TNCB) using major histocompatibility complex class TI-deficient mice that display normal numbers of CD8(+) T cells but lack CD4(+) T cells. CHS to TNCB, detected as an increase in ear thickness 24 h after epicutaneous challenge, was significantly enhanced in major histocompatibility complex class II-deficient mice compared with wild-type controls. Ear swelling responses in major histocompatibility complex class IT-deficient mice were decreased by treatment with anti-CD8 antibody or by injection of wild-type CD4(+) T cells. To further characterize mechanisms involved in the initiation of CHS responses, phenotypical and functional characteristics of both freshly isolated and cultured Langerhans cells were studied. Like Langerhans cells from wild-type controls, Langerhans cells from major histocompatibility complex class II-deficient mice upregulated B7-1 and B7-2 costimulatory molecules and enhanced major histocompatibility complex class I expression upon short-term culture. Cultured Langerhans cells induced a 3.5-fold increase in the stimulation of autologous hapten-specific CD8(+) T cell proiliferation compared with fresh Langerhans cells, Finally, TNP-coupled Langerhans cells from major histocompatibility complex class ZI-deficient mice primed naive mice to TNCB after transfer. These results demonstrate that hapten-specific CD8(+) T cells are sufficient. for the expression of CHS and that CD8 priming does not require the presence of CD4(+) T cells or major histocompatibility complex class Il antigen. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NCI, Dermatol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 31 TC 55 Z9 57 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1998 VL 111 IS 1 BP 44 EP 49 DI 10.1046/j.1523-1747.1998.00236.x PG 6 WC Dermatology SC Dermatology GA ZW467 UT WOS:000074413900007 PM 9665385 ER PT J AU Ishiko, A Shimizu, H Masunaga, T Yancey, KB Giudice, GJ Zone, JJ Nishikawa, T AF Ishiko, A Shimizu, H Masunaga, T Yancey, KB Giudice, GJ Zone, JJ Nishikawa, T TI 97 kDa linear IgA bullous dermatosis antigen localizes in the lamina lucida between the NC16A and carboxyl terminal domains of the 180 kDa bullous pemphigoid antigen SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE basement membrane zone; cryoultramicrotomy; hemidesmosome; immunoelectron microscopy ID EPIDERMAL BASEMENT-MEMBRANE; AUTOANTIBODIES; IDENTIFICATION; BP180; SERA AB Linear IgA bullous dermatosis is an autoimmune blistering disease characterized by circulating IgA antibasement membrane autoantibodies, A 97 kDa protein (97-LAD), which localizes at the basement membrane zone of normal human skin, is one of the major autoantigens associated with this disease and possesses multiple regions of amino acid identity with the extracellular domain of the 180 kDa bullous pemphigoid antigen, BPAG2. To investigate further the relationship between 97-LAD and BPAG2, immunogold electron microscopy was performed on cryo-ultrathin sections of normal human skin using a series of polyclonal and monoclonal antibodies. Gold particles immunolabeling two newly developed monoclonal antibodies against 97-LAD were localized to the lamina lucida, This immunolabeling pattern was associated with hemidesmosomes and localized at a mean distance of 28 nm beneath the plasma membrane of basal keratinocytes. In contrast, polyclonal antibodies against a fusion protein containing the NC16A domain of BPAG2 immunolabeled the plasma membrane of the hemidesmosomal complex, whereas polyclonal antibodies against the carboxyl terminus mainly immunolabeled the lower lamina lucida with a mean distance of 42 nm beneath the plasma membrane. By double immunolabeling, 97-LAD was localized as if being sandwiched between the NC16A and the carboxyl terminal domains of BPAG2, These results clearly demonstrated the co-localization of 97-LAD and the extracellular portion of BPAG2 in the lamina lucida, and suggested that 97-LAD is closely related to, and/or forms a complex with, the extracellular domain of BPAG2. C1 Keio Univ, Sch Med, Dept Dermatol, Shinju Ku, Tokyo 1608582, Japan. Nippon Kokan KK, Dept Dermatol, Kawasaki, Kanagawa 210, Japan. NCI, Div Clin Sci, Dermatol Branch, NIH, Bethesda, MD USA. Med Coll Wisconsin, Dept Dermatol & Biochem, Milwaukee, WI 53226 USA. Vet Affairs Med Ctr, Med Serv, Dermatol Sect, Salt Lake City, UT USA. Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT USA. RP Ishiko, A (reprint author), Keio Univ, Sch Med, Dept Dermatol, Shinju Ku, 35 Shinanomachi, Tokyo 1608582, Japan. RI Shimizu, Hiroshi/A-5193-2012 NR 20 TC 25 Z9 25 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1998 VL 111 IS 1 BP 93 EP 96 DI 10.1046/j.1523-1747.1998.00231.x PG 4 WC Dermatology SC Dermatology GA ZW467 UT WOS:000074413900015 PM 9665393 ER PT J AU Boni, R Vortmeyer, AO Stern, B Burg, G Hofbauer, G Zhuang, Z AF Boni, R Vortmeyer, AO Stern, B Burg, G Hofbauer, G Zhuang, Z TI Concordance of genetic changes in basal cell carcinoma and associated clusters of squamous cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter C1 Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Boni, R (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. RI Hofbauer, Gunther/B-2671-2010 OI Hofbauer, Gunther/0000-0003-0542-7989 NR 5 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1998 VL 111 IS 1 BP 173 EP 174 DI 10.1046/j.1523-1747.1998.00247.x PG 2 WC Dermatology SC Dermatology GA ZW467 UT WOS:000074413900029 PM 9665407 ER PT J AU Pathare, PM Hamlin, DK Wilbur, DS Brechbiel, MW Bray, LA AF Pathare, PM Hamlin, DK Wilbur, DS Brechbiel, MW Bray, LA TI Synthesis and radiolabeling of a biotin-CHX-B chelate for Bi-213 SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE bismuth-213; biotin derivative; pretargeting; radioimmunotherapy ID PARTICLE-MEDIATED RADIOIMMUNOTHERAPY; MONOCLONAL-ANTIBODY; EMITTING RADIONUCLIDES; AVIDIN; STREPTAVIDIN; SYSTEM AB The synthesis and radiolabeling of a biotin derivative which contains a chelating group (CHX-B) for binding the alpha-emitting radionuclide, Bi-213, is described. The biotin-CHX-B derivative was readily prepared in high yield through a convergent synthesis that coupled N-methylglycylbiotinamide with anilino-CHX-B. Bismuth-213 labeling of the biotin-CHX-B molecule was facile at room temperature, resulting in >95 % radiochemical yield within 10 min reaction time. C1 Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Pacific NW Lab, Richland, WA 99352 USA. RP Pathare, PM (reprint author), Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. NR 24 TC 2 Z9 2 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUL PY 1998 VL 41 IS 7 BP 595 EP 603 DI 10.1002/(SICI)1099-1344(199807)41:7<595::AID-JLCR116>3.0.CO;2-O PG 9 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA ZY753 UT WOS:000074655900003 ER PT J AU Howard, OMZ Korte, T Tarasova, NI Grimm, M Turpin, JA Rice, WG Michejda, CJ Blumenthal, R Oppenheim, JJ AF Howard, OMZ Korte, T Tarasova, NI Grimm, M Turpin, JA Rice, WG Michejda, CJ Blumenthal, R Oppenheim, JJ TI Small molecule inhibitor of HIV-1 cell fusion blocks chemokine receptor-mediated function SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE chemokine inhibitor; anti-HIV-1; chemokine receptor internalization ID HUMAN RANTES; BINDING; INTERLEUKIN-8; INTERVENTION; DISSOCIATION; ANTAGONIST; ENTRY AB The intersection of the HIV and the chemokine fields began with the observation that HIV entry into cells could be blocked by certain chemokines. Subsequent work showed that HIV entry is dependent on the presence of specific chemokine receptors, These observations led us to evaluate a series of compounds, ureido analogs of distamycin previously reported to block HIV entry into cells in vitro, for chemokine antagonist activity, One of the distamycin analogs, 2,2'[4,4'-[[aminocarbonyl]amino]bis[N,4'-di[pyrrole-2-carboxamide-1,1'-dimethyl]]-6,8 napthalenedisulfonic acid] hexasodium salt (NSC 651016), is shown here to inhibit syncytia formation and cell fusion, Mechanistic studies showed that this inhibition was not due to conformational changes in gp120-gp41 induced by target cell CDP and chemokine co-receptor and was therefore not due to interference with binding of HIV-1. Additional mechanistic studies demonstrated that NSC 651016 inhibited chemokine binding to specific chemokine receptors, induced CXCR4 and CCR5 receptor internalization, and inhibited chemokine-induced chemotaxis by macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, RANTES, and stromal-derived factor-1 alpha but not monocyte chemotactic protein-1, Thus, we describe a novel compound that inhibits in vivo replication of HIV-1 by down-regulation of coreceptors, These data lead us to propose that NSC 651016 may have in vivo anti-inflammatory activity. C1 SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Lab Antiviral Drug Mechanisms, SAIC Frederick, Frederick, MD 21701 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21701 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Aspects Drug Design Sect, Frederick, MD 21701 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Div Basic Sci, Frederick, MD 21701 USA. RP Howard, OMZ (reprint author), POB B, Frederick, MD 21702 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 33 TC 45 Z9 48 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 1998 VL 64 IS 1 BP 6 EP 13 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA ZY385 UT WOS:000074616000003 PM 9665268 ER PT J AU Zhang, HJ Hamilton, JH Salem, N Kim, HY AF Zhang, HJ Hamilton, JH Salem, N Kim, HY TI N-3 fatty acid deficiency in the rat pineal gland: effects on phospholipid molecular species composition and endogenous levels of melatonin and lipoxygenase products SO JOURNAL OF LIPID RESEARCH LA English DT Article DE polyunsaturated fatty acids; lipoxygenase; 12-hydroxyeicosatetraenoic acid; arachidonic acid; pineal; melatonin; phospholipids n-3 fatty acid deficiency; electrospray mass spectrometry; gas chromatography mass spectrometry ID IONIZATION MASS-SPECTROMETRY; SOLID-PHASE EXTRACTION; ARACHIDONIC-ACID; N-ACETYLTRANSFERASE; BRAIN; PLASMA; CELLS; METABOLISM; INHIBITION; PIG AB N-3 essential fatty acid deficiency affects a number of biological and physiological processes. In this study, we investigated the effect of n-3 essential fatty acid status on two key pineal biochemical functions, melatonin production and lipoxygenation, using pineal glands from rats given an n-3-adequate or n-3-deficient diet. The pineal total lipid profile and phospholipid molecular species distribution altered by n-3 deficiency were evaluated in parallel. In pineal glands from n-3-deficient rats, an 87% reduction of 22:6n-3 (docosahexaenoic acid) was observed, and this decrease was accompanied by increases in 22:4n-6 (docosatetraenoic acid, 3-fold), 22:5n-6 (docosapentaenoic acid, 12-fold), and 20:4n-6 (arachidonic acid, 48%), The significant decrease of 22:6n-3 containing species in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) was also evident. These decreases in 22:6n-3 containing PL species were compensated by substantial accumulations of 22:4n-6 or 22:5n-6 and slight increases in 20:4n-6 containing PL species in PC and PE, In PS, however, the accumulation of n-6 species was not adequate to compensate for the loss of 22:6n-3 species. N-3 deficiency significantly reduced non-esterified 20:4n-6 and 22:6n-3 levels in pineals (25% and 65%, respectively), Concomitantly, the endogenous 12-HETE level decreased by 35% in deficient pineals. In contrast, n-3 deficiency led to a more than 60% increase in the daytime pineal melatonin level. In conclusion, n-3 fatty acid deficiency not only has profound effects on pineal lipid profiles but also on pineal biochemical activities. These results suggest that n-3 fatty acids may play a critical role in regulating pineal function. C1 NIAAA, Sect Mass Spectrometry, NIH, Rockville, MD 20852 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Kim, HY (reprint author), NIAAA, Sect Mass Spectrometry, NIH, Rockville, MD 20852 USA. NR 47 TC 26 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 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 1998 VL 39 IS 7 BP 1397 EP 1403 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KZ UT WOS:000074816400009 PM 9684742 ER PT J AU Guivel-Scharen, V Sinnwell, T Wolff, SD Balaban, RS AF Guivel-Scharen, V Sinnwell, T Wolff, SD Balaban, RS TI Detection of proton chemical exchange between metabolites and water in biological tissues SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE urea; ammonia; saturation transfer; pH; urine; kidney; MRI; muscle; chemical exchange ID CREATINE-KINASE REACTION; MAGNETIZATION-TRANSFER; RATES; RELAXATION; INVIVO; CONTRAST AB Metabolites in proton chemical exchange with water were detected via the water proton signal using saturation transfer techniques in model systems and biological tissues. The metabolites were selectively saturated and the resulting decrease in the much larger water proton pool was used to monitor the metabolite. This indirect detection scheme can result in a several orders of magnitude increase in sensitivity for metabolites over direct detection methods. A control irradiation scheme was devised to compensate for macromolecular/water magnetization transfer. Using this approach, significant chemical exchange regions at similar to 1 and 2.5 ppm were detected in kidney medulla. Using a difference imaging technique between a control irradiation above (-1.74 ppm) and below (+1.74 ppm) the water resonance, a chemical exchange image of the kidney was calculated. These data revealed a linear gradient of chemical exchange increasing from the cortex to the medulla. Studies on medullary acid extracts and urine revealed that the exchange observed in the kidney was predominantly with low molecular weight metabolites. Urea (1 ppm) was identified as contributing to the kidney/urine chemical exchange; however, other unidentified metabolites may also contribute to this effect. These studies demonstrate that tissue metabolites can be detected and imaged via the water protons using the signal amplification properties of saturation transfer in the presence of water/macromolecule magnetization transfer. (C) 1998 Academic Press. C1 NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD USA. RP Sinnwell, T (reprint author), NHLBI, Cardiac Energet Lab, Bldg 10,Room BID-161, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 17 TC 102 Z9 105 U1 1 U2 17 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JUL PY 1998 VL 133 IS 1 BP 36 EP 45 DI 10.1006/jmre.1998.1440 PG 10 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA ZZ679 UT WOS:000074755700004 PM 9654466 ER PT J AU Clore, GM Gronenborn, AM Bax, A AF Clore, GM Gronenborn, AM Bax, A TI A robust method for determining the magnitude of the fully asymmetric alignment tensor of oriented macromolecules in the absence of structural information SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE dipolar couplings; molecular alignment; liquid crystal; rhombicity; solution NMR structure determination; long-range restraints; powder pattern ID NMR-SPECTRA; HIGH-RESOLUTION; RELAXATION AB It has recently been shown that the degree of alignment of macromolecules in an aqueous dilute liquid crystalline medium of bicelles is sufficient to permit accurate values of residual N-15-H-1, C-13-H-1, and C-13(alpha)-C' dipolar couplings to be obtained on a routine basis, thereby providing potentially unique long-range structural information. To make use of this information in macromolecular structure determination, the magnitude of the axial and rhombic components of the molecular alignment tensor must be determined. This can be achieved by taking advantage of the fact that different, fixed-distance internuclear vector types are differently distributed relative to the alignment tensor. A histogram of the ensemble of normalized residual dipolar couplings for several such vector types approximates a powder pattern from which the magnitude of the axial and rhombic components are readily extracted in the absence of any prior structural information. The applicability of this method is demonstrated using synthetic data derived from four proteins representative of different sizes, topologies, and secondary structures, and experimental data measured on the small protein ubiquitin. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 30 TC 314 Z9 316 U1 1 U2 19 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JUL PY 1998 VL 133 IS 1 BP 216 EP 221 DI 10.1006/jmre.1998.1419 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA ZZ679 UT WOS:000074755700029 PM 9654491 ER PT J AU Ribeiro, JMC Schneider, M Isaias, T Jurberg, J Galvao, C Guimaraes, JA AF Ribeiro, JMC Schneider, M Isaias, T Jurberg, J Galvao, C Guimaraes, JA TI Role of salivary antihemostatic components in blood feeding by triatomine bugs (Heteroptera) SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE triatomine bugs; saliva; feeding; hematophagy; hemostasis platelets ID MOSQUITO AEDES-AEGYPTI; RHODNIUS-PROLIXUS; NITRIC-OXIDE; BLOODSUCKING INSECT; CONTRACTING FACTORS; HEME PROTEIN; ANTICOAGULANT; ENDOTHELIUM; GLANDS; PURIFICATION AB Salivary gland homogenates from 4 genera of triatomine bugs were assayed for anticlotting, apyrase, and vasodilatory activities, and these activities were correlated with the efficiency of each bug species to initiate a blood meal. Antihemostatic activities spanned a large range of values. Apyrase activity in members of the genus Rhodnius was markedly different from that in other genera with respect to their sensitivity to divalent cation activators. Apyrase and vasodilatory activities, but not anticlotting activity, correlated with feeding efficiency of bugs taking a blood meal on a rat. Results are discussed within the context of the evolution of blood-feeding by insects. C1 Univ Arizona, Dept Entomol, Tucson, AZ 85721 USA. RP Ribeiro, JMC (reprint author), NIH, Parasit Dis Lab, Bldg 4,Room 126,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Galvao, C/F-7088-2011; Jurberg, Jose/C-3103-2013; OI Galvao, C/0000-0003-4027-9205; Guimaraes, Jorge A./0000-0001-6354-6789; Ribeiro, Jose/0000-0002-9107-0818 FU NIAID NIH HHS [AI-18694] NR 45 TC 49 Z9 51 U1 0 U2 2 PU ENTOMOL SOC AMER PI LANHAM PA 9301 ANNAPOLIS RD, LANHAM, MD 20706 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD JUL PY 1998 VL 35 IS 4 BP 599 EP 610 PG 12 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 108PE UT WOS:000075274000042 PM 9701952 ER PT J AU Nagao, E Dvorak, JA AF Nagao, E Dvorak, JA TI An integrated approach to the study of living cells by atomic force microscopy SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE atomic force microscopy; in vitro culture system; light microscopy; living cells ID HUMAN PLATELETS; HOST-CELL; MEMBRANE; DYNAMICS; INVASION AB We describe a technique for studying living cells with the atomic force microscope (AFM) in tapping mode using a thermostated, controlled-environment culture system. We also describe the integration of the AFM with bright field, epifluorescence and surface interference microscopy, achieving the highest level of integration for the AFM thus far described. We succeeded in the continuous, longterm imaging of relatively flat but very fragile cytoplasmic regions of COS cells at a lateral resolution of about 70 nm and a vertical resolution of about 3 nm. In addition, we demonstrate the applicability of our technology for continuous force volume imaging of cultured vertebrate cells. The hybrid instrument we describe can be used to collect simultaneously a diverse variety of physical, chemical and morphological data on living vertebrate cells, The integration of light microscopy with AFM and steady-state culture methods for vertebrate cells represents a new approach for studies in cell biology and physiology. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Dvorak, JA (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike,Bldg 4,Rm B2-11, Bethesda, MD 20892 USA. NR 17 TC 48 Z9 49 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD JUL PY 1998 VL 191 BP 8 EP 19 PN 1 PG 12 WC Microscopy SC Microscopy GA 109CN UT WOS:000075303800002 PM 9723187 ER PT J AU Pettit, GR Tan, R Xu, JP Ichihara, Y Williams, MD Boyd, MR AF Pettit, GR Tan, R Xu, JP Ichihara, Y Williams, MD Boyd, MR TI Antineoplastic agents. 398. Isolation and structure elucidation of cephalostatins 18 and 19 SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID NMR-SPECTROSCOPY; ALKALOIDS AB Continued investigation of murine leukemia (P-388) active fractions from the African marine warm Cephalodiscus gilchristi has resulted in the discovery of cephalostatins 18 (1b) and 19 (1c). The structures were determined by interpretation of their highfield (500 MHz) H-1, C-13, and 2D NMR and HRMS. Both of these new methoxy steroidal alkaloids exhibited strong activity against the murine P-388 lymphocytic leukemia cell line (ED50 ca. 10(-3) mu g/mL), a mini panel of human cancer cell lines (GI(50) < 10(-3) mu g/mL), and the U.S. National Cancer Institute's 60 human cancer cell line panel (mean panel GI(50) ca. 10(-9) M). C1 Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem, Tempe, AZ 85287 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, DTP,DCTDC, Frederick, MD 21702 USA. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. FU NCI NIH HHS [CA44344-01-09] NR 22 TC 50 Z9 53 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JUL PY 1998 VL 61 IS 7 BP 955 EP 958 DI 10.1021/np9800405 PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 106XE UT WOS:000075175900021 PM 9677284 ER PT J AU Rall, JE AF Rall, JE TI How the mind works. SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NIH, Bethesda, MD 20892 USA. RP Rall, JE (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 1998 VL 186 IS 7 BP 442 EP 443 DI 10.1097/00005053-199807000-00011 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 101QT UT WOS:000074880200011 ER PT J AU Newman, JD AF Newman, JD TI Social influences on vocal development. SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. RP Newman, JD (reprint author), NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 1998 VL 186 IS 7 BP 444 EP 445 DI 10.1097/00005053-199807000-00013 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 101QT UT WOS:000074880200013 ER PT J AU Chen, FS Vu, ND Wagner, PD AF Chen, FS Vu, ND Wagner, PD TI Pertussis toxin modification of PC12 cells inhibits a protein phosphatase 2A-like phosphatase SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE protein phosphatase 2A; pertussis toxin; G proteins; PC12 cells; calcineurin ID ADRENAL CHROMAFFIN CELLS; GTP-BINDING PROTEIN; CATECHOLAMINE RELEASE; KINASE-C; CA2+-DEPENDENT SECRETION; NOREPINEPHRINE SECRETION; INOSITOL TRISPHOSPHATE; N-ETHYLMALEIMIDE; CYCLOSPORINE-A; ANGIOTENSIN-II AB We have found that modification of rat PC12 cells with pertussis toxin resulted in an similar to 50% inhibition of a protein phosphatase 2A-like phosphatase. Protein phosphatase 2A (PP2A) is a major cellular serine/threonine-specific protein phosphatase. Treatment of extracts from pertussis toxin-modified PC12 cells with either immobilized alkaline phosphatase or Ca2+ reversed this inhibition. Reactivation of the PP2A-like phosphatase in Ca2+ appears to result from the dephosphorylation of a protein by the Ca2+/calmodulin-dependent protein phosphatase calcineurin. The PP2A-like phosphatase in extracts from pertussis toxin-modified PC12 cells eluted from a Mono Q column at a higher ionic strength than did the PP2A-like phosphatase in extracts from control cells. After incubation in Ca2+ the PP2A-like phosphatase in extracts from pertussis toxin-modified cells eluted from a Mono Q column at the same ionic strength as did the PP2A-like phosphatase in extracts from control cells. These results indicate that the effect of pertussis toxin on this PP2A-like activity results from the phosphorylation of either one of the subunits of the PP2A-like phosphatase or a protein that when phosphorylated binds to and inhibits this phosphatase. Pertussis toxin modification did not result in the phosphorylation of the catalytic subunit of PP2A. Because phosphorylation regulates the activities of many enzymes and cell surface receptors, a pertussis toxin-induced decrease in PP2A activity could alter signaling pathways and other cellular processes in which G proteins are not directly involved. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Wagner, PD (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Rm 4C24, Bethesda, MD 20892 USA. NR 48 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 1998 VL 71 IS 1 BP 248 EP 257 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZV232 UT WOS:000074283600027 PM 9648872 ER PT J AU Sawaya, BE Thatikunta, P Denisova, L Brady, J Khalili, K Amini, S AF Sawaya, BE Thatikunta, P Denisova, L Brady, J Khalili, K Amini, S TI Regulation of TNF alpha and TGF beta-1 gene transcription by HIV-1 Tat in CNS cells SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE TNF alpha and TGF beta-1 gene transcription; HIV Tat; CNS cells ID IMMUNODEFICIENCY-VIRUS TYPE-1; NECROSIS-FACTOR-ALPHA; INDEPENDENT TRANSACTIVATION; MUTATIONAL ANALYSIS; TRANSGENIC MICE; BRAIN CULTURES; IN-VITRO; EXPRESSION; PROTEIN; ACTIVATION AB Tat is a transcription transactivator produced by the human immunodeficiency virus type I (HIV-1) at the early phase of infection and plays a critical role in the expression and replication of the viral genome. This 86 amino acid protein, which can be secreted from the infected cells, has the ability to enter uninfected cells and exert its activity upon the responsive genes. Earlier results indicated that in addition to the HIV-1 promoter, Tat has the capacity to induce transcription of a variety of cellular genes. In this study, we demonstrate that exposure of cells from the central nervous system (U-87MG and SK-N-MC) and the lymphoid T cells (Jurkat) to highly purified Tat increases transcriptional activity of the reporter constructs containing the promoters from the transforming growth factor beta-1 (TGF beta-1), the tumor necrosis factor alpha (TNF alpha), and the HIV-1 LTR. In addition, Tat treatment results in increased levels of TGF beta-1 and TNF alpha mRNAs in these cells. Activation of the TGF beta-1 and TNF alpha promoter constructs by Tat in U-87MG and SK-N-MC cells required amino acid residues 2 to 36 which spans the acidic and the cysteine-rich domains of Tat. In both CNS and lymphoid cells, the level of endogenous TGF beta-1 mRNA was increased by mutant Tar protein containing amino acids 1 to 48 but not with a mutant Tat protein with a deletion between residues 2 to 36. TNF alpha mRNA level was increased by mutant Tat spanning residues 1 to 48 in U-87MG cells, but not in SK-N-MC and Jurkat cells. These observations suggest that activation of cellular and viral genes by Tar in various cells may be mediated by different pathways as evidenced by the requirements of the different regions of Tar. Activation of the TGF beta-1 and TNF alpha promoters by wild-type Tar was severely affected by the mutant peptides spanning residues 2 to 36 and 1 to 48 suggesting that both truncated Tat peptides may function as dominant negative mutants over TNF alpha and TGF beta-1 gene transcription. The importance of these findings in Tar-induced regulation of viral and cellular genes in various cell types is discussed. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Allegheny Univ Hlth Sci, Dept Neurol, Ctr Neurovirol & Neurooncol, Philadelphia, PA 19102 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Amini, S (reprint author), Allegheny Univ Hlth Sci, Dept Neurol, Ctr Neurovirol & Neurooncol, Broad & Vine,MS 406, Philadelphia, PA 19102 USA. EM amini@auhs.edu NR 33 TC 53 Z9 54 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL 1 PY 1998 VL 87 IS 1-2 BP 33 EP 42 DI 10.1016/S0165-5728(98)00044-7 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA ZZ803 UT WOS:000074768700005 PM 9670843 ER PT J AU Reinhold, D Hemmer, B Gran, B Born, I Faust, J Neubert, K McFarland, HF Martin, R Ansorge, S AF Reinhold, D Hemmer, B Gran, B Born, I Faust, J Neubert, K McFarland, HF Martin, R Ansorge, S TI Inhibitors of dipeptidyl peptidase IV/CD26 suppress activation of human MBP-specific CD4+T cell clones SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE dipeptidyl peptidase IV; CD26; inhibitors; autoimmunity; T lymphocyte; myelin basic protein; multiple sclerosis ID HUMAN LYMPHOCYTE-T; FUNCTIONAL-ROLE; IMMUNE-SYSTEM; IV SUPPRESS; CD26; PROLIFERATION; ANTIBODIES; ANTIGEN AB The ectoenzyme dipeptidyl peptidase IV (DP IV, EC 3.4.14.5, CD26) has been shown to play a crucial role in T cell activation. Specific inhibitors of DP IV suppress DNA synthesis as well as cytokine production (IL-2, IL-10, IL-12, IFN-gamma) of stimulated human and mouse T cells suggesting a potential application of these effecters in transplantations and autoimmune diseases. In the present study, we have examined the expression of DP IV/CD26 on six myelin basic protein (MBP)(87-99)-specific, CD4 + T cell clones (TCC) derived from patients with multiple sclerosis (MS) as well as the biological effects of the two synthetic DP IV inhibitors Lys[Z(NO2)]-thiazolidide and Lys[Z(NO2)]-pyrrolidide on the function of these cells. All TCC expressed high levels of DP IV/CD26, as shown by flow cytometry and by enzymatic DP IV assay. Enzymatic activity of resting TCC was found to be three to fourfold higher than on resting peripheral blood T cells and close to that of T cells 48 h after PHA stimulation. The DP IV inhibitors suppress DNA synthesis and IFN-gamma, IL-4, and TNF-alpha production of the antigen-stimulated TCC. These data suggest that CD26 plays a role in regulation of activation of autoreactive TCC. Further in-vivo investigations, first in experimental models, will clarify, whether the inhibition of the enzymatic activity of DP TV could be a useful tool for therapeutic interventions in MS or other autoimmune diseases. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Otto Von Guericke Univ, Dept Internal Med, Inst Expt Internal Med, D-39120 Magdeburg, Germany. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Halle Wittenberg, Inst Biochem, Dept Biochem & Biotechnol, Halle, Germany. RP Reinhold, D (reprint author), Otto Von Guericke Univ, Dept Internal Med, Inst Expt Internal Med, Leipziger Str 44, D-39120 Magdeburg, Germany. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 NR 30 TC 42 Z9 43 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL 1 PY 1998 VL 87 IS 1-2 BP 203 EP 209 DI 10.1016/S0165-5728(98)00100-3 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA ZZ803 UT WOS:000074768700026 PM 9670864 ER PT J AU Tedeschi, G Bonavita, S Barton, NW Bertolino, A Frank, JA Patronas, NJ Alger, JR Schiffmann, R AF Tedeschi, G Bonavita, S Barton, NW Bertolino, A Frank, JA Patronas, NJ Alger, JR Schiffmann, R TI Proton magnetic resonance spectroscopic imaging in the clinical evaluation of patients with Niemann-Pick type C disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE proton magnetic resonance spectroscopy; Niemann-Pick; clinical stage ID N-ACETYLASPARTATE; MR SPECTROSCOPY; METABOLIC ALTERATIONS; H-1-NMR SPECTROSCOPY; COMPUTED-TOMOGRAPHY; CHEMICAL PATHOLOGY; MULTIPLE-SCLEROSIS; NMR-SPECTROSCOPY; CANAVANS DISEASE; HUMAN BRAIN AB Objectives-10 patients with Niemann-Pick disease type C (NP-C) were studied by proton magnetic resonance spectroscopic imaging (H-1-MRSI) to assess the biochemical pathology of the brain and to determine whether this method can be useful to clinically evaluate these patients. Methods-H-1-MRSI permits the simultaneous measurement of N-acetyl aspartate (NA), compounds containing choline (Cho), creatine plus phosphocreatine (Cre), and lactate (Lac) signal intensities from four 15 mm slices divided into 0.84 mi single volume elements. Spectroscopic voxels were identified from seven regions of interest. Results-In patients with NP-C, NA/Cre was significantly decreased in the frontal and parietal cortices, centrum semiovale, and caudate nucleus; Cho/Cre was significantly increased in the frontal cortex and centrum semiovale. Significant correlations were found between clinical staging scale scores and H-1-MRSI abnormalities. Conclusion-H-1-MRSI showed diffuse brain involvement in patients with NP-C consistent with the pathological features of the disease. H-1-MRSI is an objective and sensitive tool to neurologically evaluate patients with NP-C. C1 NINDS, Neuroimaging Branch, Bethesda, MD USA. NINDS, Dev & Metab Neurol Branch, Bethesda, MD USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Radiol Sci, Los Angeles, CA 90024 USA. NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RP Tedeschi, G (reprint author), Univ Naples 2, Ist Sci Neurol, Via Pansini 5, I-80131 Naples, Italy. NR 44 TC 33 Z9 35 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUL PY 1998 VL 65 IS 1 BP 72 EP 79 DI 10.1136/jnnp.65.1.72 PG 8 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA ZY632 UT WOS:000074643100013 PM 9667565 ER PT J AU Eifuku, S Wurtz, RH AF Eifuku, S Wurtz, RH TI Response to motion in extrastriate area MST1: Center-surround interactions SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PURSUIT EYE-MOVEMENTS; TEMPORAL VISUAL AREA; OPTIC FLOW STIMULI; MONKEY SUPERIOR COLLICULUS; CLASSICAL RECEPTIVE-FIELD; MACAQUE MONKEY; EXPANSION CONTRACTION; NEURAL RESPONSES; ROTATION CELLS; IMAGE MOTION AB The medial superior temporal area of the macaque monkey extrastriate visual cortex can be divided into a dorsal medial (MSTd) and a lateral ventral (MSTl) region. The functions of the two regions may not be identical: MSTd may process optic flow information that results from the movement of the observer, whereas MSTl may be related more closely to processing visual motion related specifically to the motion of objects. If MSTl were related to such object motion, one would expect to see mechanisms for the segregation of objects from their surround. We investigated one of these mechanisms in MSTl neurons: the effect of stimuli falling in the region surrounding the receptive field center on the response to stimuli falling in the field center. We found the effects of the surround stimulation to be modulatory with little response to the surround stimulus itself but a clear effect on the response to the stimulus falling on the receptive field center. The response to motion in the center in the direction preferred for the neuron usually increased when the surround motion was in the opposite direction to that in the center and decreased when surround motion was in the same direction as that in the center. Fifty-seven percent of the neurons showed a ratio of response for center motion with a surround moving in the opposite direction to that in the center for center motion alone that was >1.The response to motion in the center also increased when the surround stimulus was stationary, and this increase was sometimes larger than that with a moving surround. Nearly 70% of the neurons showed a ratio of response to center motion with a stationary surround to center motion alone that was >1. This is in contrast to the minimal effect of stationary surrounds in middle temporal area neurons. When the stimulus presentation was reversed so that the stimulus in the center was stationary and the surround moved, some MSTl neurons responded when the direction of motion in the surround was in the direction opposite to the preferred direction of motion in the center of the receptive field. Stimulation of the surround thus had a profound effect on the response of MST1 neurons, and this pronounced effect of the surround is consistent with a role in the segmentation of objects using motion. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. NR 65 TC 94 Z9 94 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 1998 VL 80 IS 1 BP 282 EP 296 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZZ636 UT WOS:000074750800028 PM 9658050 ER PT J AU McDonald, MP Willard, LB Wenk, GL Crawley, JN AF McDonald, MP Willard, LB Wenk, GL Crawley, JN TI Coadministration of galanin antagonist M40 with a muscarinic M-1 agonist improves delayed nonmatching to position choice accuracy in rats with cholinergic lesions SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; acetylcholine; muscarinic receptors; galanin; neuropeptide; lesion model; memory ID FAMILIAL ALZHEIMERS-DISEASE; CENTRAL NERVOUS-SYSTEM; BASAL FOREBRAIN; VENTRAL HIPPOCAMPUS; PHOSPHOINOSITIDE TURNOVER; NUCLEUS BASALIS; ACETYLCHOLINE-RELEASE; MISSENSE MUTATIONS; NGF RECEPTOR; TO-SAMPLE AB The neuropeptide galanin is overexpressed in the basal forebrain in Alzheimer's disease (AD). In rats, galanin inhibits evoked hippocampal acetylcholine release and impairs performance on several memory tasks, including delayed nonmatching to position (DNMTP). Galanin(1-13)-Pro(2)-(Ala-Leu)(2)-Ala-NH2 (M40), a peptidergic galanin receptor ligand, has been shown to block galanin-induced impairment on DNMTP in rats. M40 injected alone, however, does not improve DNMTP choice accuracy deficits in rats with selective cholinergic immunotoxic lesions of the basal forebrain. The present experiments used a strategy of combining M40 with an M-1 cholinergic agonist in rats lesioned with the cholinergic immunotoxin (192)IgG-saporin. Coadministration of intraventricular M40 with intraperitoneal 3-(3-S-n-pentyl-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine (TZTP), an M-1 agonist, improved choice accuracy significantly more than a threshold dose of TZTP alone. These results suggest that a galanin antagonist may enhance the efficacy of cholinergic treatments for the cognitive deficits of AD. C1 NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bethesda, MD 20892 USA. Univ Arizona, Div Neural Syst Memory & Aging, Tucson, AZ 85724 USA. RP McDonald, MP (reprint author), NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bldg 10,Room 4D11, Bethesda, MD 20892 USA. EM mikemc@codon.nih.gov NR 60 TC 33 Z9 33 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 1 PY 1998 VL 18 IS 13 BP 5078 EP 5085 PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZV292 UT WOS:000074290000028 PM 9634573 ER PT J AU Araki, T Taniwaki, T Becerra, SP Chader, GJ Schwartz, JP AF Araki, T Taniwaki, T Becerra, SP Chader, GJ Schwartz, JP TI Pigment epithelium-derived factor (PEDF) differentially protects immature but not mature cerebellar granule cells against apoptotic cell death SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE PEDF; serpin; apoptosis; cerebellar granule cells; culture; neurotrophic ID NEUROTROPHIC FACTOR; NEURITE OUTGROWTH; SURVIVAL FACTOR; NEURONS; CULTURE; RAT; NEXIN; DEPOLARIZATION; INHIBITION; INDUCTION AB We have shown previously that pigment epithelium-derived factor (PEDF) acts as a survival factor for cerebellar granule cell neurons in culture, as well as protecting them against glutamate toxicity. In this study we have examined effects of PEDF on apoptotic cell death. We find that the granule cells die of apoptosis throughout the culture period, what we have termed "natural" apoptosis, PEDF prevents this natural apoptosis if added to immature cells, within the first 2 days in vitro (DIV), and the effect is maintained for up to DIV12 However, PEDF has no effect if added to mature cells at DIV5, Similar results are obtained when apoptosis is induced by shifting the cells from a serum- and 25 mM KCl-containing medium to serum-free medium with 5 mM KCl, PEDF most effectively blocks induced apoptosis in immature cells (DIV2) when added 24 hr prior to the change of medium, but still provides some protection when added simultaneously. However, 24 hr pretreatment with PEDF has a minimal effect when apoptosis is induced in mature DIV6 cells; addition at the same time is completely ineffective. Two polypeptide fragments of PEDF, only one of which contains the serine-protease inhibitory site, are equally active, supporting previous results which suggest that the neurotrophic effects of PEDF are not mediated by protease inhibition. We conclude that PEDF protects immature but not mature granule cells against both natural and induced apoptosis. J, Neurosci, Res. 53:7-15, 1998, (C) 1998 Wiley-Liss, Inc.dagger C1 NINDS, Clin Neurosci Branch, Mol Genet Sect, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, JP (reprint author), NINDS, NIH, Bldg 36,Room 4A27, Bethesda, MD 20892 USA. NR 23 TC 98 Z9 101 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL 1 PY 1998 VL 53 IS 1 BP 7 EP 15 DI 10.1002/(SICI)1097-4547(19980701)53:1<7::AID-JNR2>3.3.CO;2-H PG 9 WC Neurosciences SC Neurosciences & Neurology GA ZX114 UT WOS:000074480800002 PM 9670988 ER PT J AU Matsuzawa, M Tokumitsu, S Knoll, W Liesi, P AF Matsuzawa, M Tokumitsu, S Knoll, W Liesi, P TI Molecular gradient along the axon pathway is not required for directional axon growth SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE axon guidance; gamma 1-chain of laminin-1; hippocampal neurons ID NEURITE OUTGROWTH DOMAIN; HIPPOCAMPAL-NEURONS; C-ELEGANS; LAMININ; GUIDANCE; CELL; PROTEIN; UNC-6; BRAIN; CNS AB We show that axon guidance of embryonic hippocampal neurons is promoted by pathways of a decapeptide (RDIAEIIKDI) derived from a neurite outgrowth domain of the gamma 1 chain of laminin-1. This guidance is directly dependent on: (1) a concentration difference of the decapeptide between the peptide pathway and its surrounding areas, and (2) the optimal surface geometry of the decapeptide pathway. These results indicate that axon guidance of central neurons may proceed along a preferred substratum pathway without a concentration gradient of the guiding molecule along this pathway, or without a repulsive molecule next to the axon pathway. J. Neurosci. Res. 53:114-124, 1998. (C) 1998 Wiley-Liss, Inc.dagger C1 Inst Phys & Chem Res, Frontier Res Program, Lab Exot Nanomat, Wako, Saitama 35101, Japan. Max Planck Inst Polymerforsch, Mainz, Germany. NIAAA, Cellular & Mol Neurobiol Lab, Rockville, MD 20852 USA. RP Liesi, P (reprint author), Univ Helsinki, Inst Biomed, Dept Anat, PL,Siltavuorenpenger 20A, FIN-00014 Helsinki, Finland. NR 26 TC 18 Z9 18 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL 1 PY 1998 VL 53 IS 1 BP 114 EP 124 DI 10.1002/(SICI)1097-4547(19980701)53:1<114::AID-JNR12>3.0.CO;2-9 PG 11 WC Neurosciences SC Neurosciences & Neurology GA ZX114 UT WOS:000074480800012 PM 9670998 ER PT J AU Lanza, E Forman, MR Johnson, EJ Muesing, RA Graubard, BI Beecher, GR AF Lanza, E Forman, MR Johnson, EJ Muesing, RA Graubard, BI Beecher, GR TI alpha-tocopherol concentrations in plasma but not in lipoproteins fluctuate during the menstrual cycle in healthy premenopausal women SO JOURNAL OF NUTRITION LA English DT Article DE tocopherol; vitamin E; premenopausal; humans; lipoproteins ID BETA-CAROTENE SUPPLEMENTATION; HIGH-DENSITY-LIPOPROTEINS; VITAMIN-E; GAMMA-TOCOPHEROL; CONTROLLED DIET; SUBCLASSES; ANTIOXIDANTS; CHOLESTEROL; ABSORPTION; SEPARATION AB Because premenopausal women experience cyclic fluctuations of plasma carotenoids and their lipoprotein carriers, it was hypothesized that plasma alpha-tocopherol (A-T) fluctuates by phase of the menstrual cycle. Twelve free-living women, with a confirmed ovulatory cycle, were given a controlled diet for two consecutive menstrual cycles. Blood was drawn during the menses, early follicular, late follicular and luteal phases to simultaneously measure serum hormones, plasma lipoproteins and A-T concentrations, and A-T distribution in the lipoprotein fractions. Plasma A-T concentrations were significantly lower during menses than during the luteal phase by similar to 12% in each controlled diet cycle (P < 0.001). Adjustment for serum cholesterol and triglyceride concentrations did not alter these findings. The distributions of A-T in lipoprotein cholesterol fractions were not significantly different by menstrual phase. From 61 to 62% of A-T was concentrated in the LDL fraction, with another 9-14% in HDL2, 17-22% in HDL3 and the remaining 6-8% in VLDL+ IDL. There were no significant differences in lipoprotein cholesterol fractions by menstrual phase, except for a significant increase (P = 0.03) in HDL2 cholesterol from the early follicular to the late follicular phase. Spearman rank correlations from data during the second controlled diet month showed A-T in HDL2 in the late follicular phase was positively correlated with HDL cholesterol in the early follicular (r = 0.88), late follicular (r = 0.86) and luteal phases (r = 0.86) and with luteal apolipoprotein (ApoA-1) level (r = 0.90), and luteal HDL3 cholesterol (r = 0.83). A-T in HDL3 in the early follicular phase was negatively correlated with HDL2 cholesterol (r = -0.96) and ApoA-1 (r = -0.85), whereas luteal A-T in HDL3 was correlated with luteal HDL3 cholesterol (r = -0.79). Late follicular A-T in VLDL was positively correlated with early follicular HDL3 cholesterol and late follicular HDL3 cholesterol (r = 0.83). Fluctuations of A-T concentrations by phase of the menstrual cycle should be taken into consideration in future research concerning premenopausal women and the risk of chronic disease. C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. George Washington Univ, Med Ctr, Dept Med, Lipid Res Clin Lab, Washington, DC 20037 USA. USDA ARS, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. RP Lanza, E (reprint author), NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NR 34 TC 8 Z9 8 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUL PY 1998 VL 128 IS 7 BP 1150 EP 1155 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZY293 UT WOS:000074605600014 PM 9649599 ER PT J AU Sala, M Dosemeci, M Zahm, SH AF Sala, M Dosemeci, M Zahm, SH TI A death certificate-based study of occupation and mortality from reproductive cancers among women in 24 US states SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID OVARIAN-CANCER; CERVICAL-CANCER; RISK-FACTORS; POLYCHLORINATED-BIPHENYLS; WORKERS; TALC; SHANGHAI; BREAST; RATIO AB We conducted a study of occupation and mortality from reproductive cancers among women, based on death certificates from 24 US states for the period 1984-1993. There were 9,523 cervical cancer deaths, 12,335 endometrial cancer deaths, and 25, 212 ovarian cancer deaths. Usual occupation and industry, which were obtained from death certificates, were coded using the 1980 Bureau of Census classification system. Morality odds ratios (MORs) and 95% confidence intervals (Cls) were calculated using all non-cancer deaths as the referent disease category. In general, jobs involving professional or administrative occupations were related to increased risk of mortality from endometrial and ovarian cancer, while cervical cancer mortality was increased among women employed in manufacturing, service, farm work, and health care technician and aide occupations. Associations with some occupations involving exposure to chemicals and metals, such as the associations between cervical cancer and employment in printing; typesetting, and machine operating occupations, deserve further attention. Similarly, further investigations should be made into the excess of ovarian cancer observed in several occupations in health care, an industry that has numerous hazardous exposures, including radiation, chemotherapeutic drugs, and viruses. The study results reflect, in part, socioeconomic factors and reproductive patterns but may also indicate a possible etiologic role for occupational chemical exposures. C1 Inst Municipal Invest Med, Unit Resp & Environm Res, E-08003 Barcelona, Spain. Natl Canc Inst, Rockville, MD USA. RP Sala, M (reprint author), Inst Municipal Invest Med, Unit Resp & Environm Res, C-o Dr Aiguader 80, E-08003 Barcelona, Spain. RI sala, maria/A-2593-2011; Zahm, Shelia/B-5025-2015; Martinez, Esther/H-2562-2013; Fernandez , Irene/E-5705-2016; OI Sala Serra, Maria/0000-0002-5516-5967 NR 40 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUL PY 1998 VL 40 IS 7 BP 632 EP 639 DI 10.1097/00043764-199807000-00009 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 100AJ UT WOS:000074791500009 PM 9675722 ER PT J AU Liu, MW Max, MB Robinovitz, E Gracely, RH Bennett, GJ AF Liu, MW Max, MB Robinovitz, E Gracely, RH Bennett, GJ TI The human capsaicin model of allodynia and hyperalgesia: Sources of variability and methods for reduction SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE capsaicin; mechanical allodynia; pinprick hyperalgesia; experimental pain model ID MECHANICAL HYPERALGESIA; PINPRICK HYPERALGESIA; PAIN; NOCICEPTORS; SKIN; RAT AB Intradermal and topical application of capsaicin have been used to study mechanisms of mechanical allodynia (MA) and pinprick hyperalgesia (PPH) and th efficacy of drugs in relieving these symptoms. However, it is associated with significant inter- and intra-subject variability. In order to improve the model's sensitivity, we examined several potential sources of variability of capsaicin-evoked MA and PPH in healthy volunteers, including skin temperature fluctuations, method (intradermal vs. topical) and site (volar forearm vs. foot dorsum) of administration. In study I; 12 subjects received in a 6-session, randomized, crossover trial I) 250 mu g of intradermal (ID) CAP to the volar forearm with skin temperature fixed at 36 degrees C (36 ID). 2) 250 mu g LD CAP with varying skin temperature (VT ID) or 3) 250 mu l of 1 % CAP patch placed on the skin at 36 degrees C The resulting MA and PPH areas observed with each method were measured. In study II; a 4-session, randomized crossover trial, 12 subjects were given 100 mu g ID CAP in the, volar forearm or foot dorsum and subsequent areas of MA and PPH recorded. In study I 5/12 subjects had small MA areas (less than or equal to 5 cm(2)) and one subject had small PPH areas in at least 4/6 sessions. The most consistent intra-subject responses were seen with the 36 ID method. Correlation coefficients for the two sessions using the same method of administration were:: MA; 36 ID r = 0.83, VT ID = 0.19 Topical r = 0.81; PPH: 36 ID r = 0.93; VT ID r = 0.38, Topical r = 0.78. In study II 4/12 subjects had little MA for both forearm and foot though all subjects developed PPH However, greater intra-subject consistency (MA:foot: r = 0.84; arm: r 0.49 PPH r = 0.87; r = 0.39 and significantly larger areas of MA (15.8 +/- 4.2 vs 9. 1 +/- 2.5, p < 0.05) were seen with the foot. (PPH:foot: 28.9 +/- 6.7; arm: 21.6 +/- 4.5 NS). Large variability exists among subjects receiving CAP, with some developing minimal MA. However, these subjects may be screened out pier to entry, increasing the sensitivity of the model, which may be further improved by clamping the skin temperature. (C) U.S. Cancer Pain Relief Committee, 1998. C1 NIDR, Neurobiol & Anesthesiol Branch, NIH, Bethesda, MD 20892 USA. NIH, Clin Ctr Nursing, Bethesda, MD 20892 USA. Hosp Univ Penn, Dept Anesthesia, Philadelphia, PA 19104 USA. Allegheny Univ Hlth Sci, Dept Neurol, Philadelphia, PA 19102 USA. RP Max, MB (reprint author), NIDR, Neurobiol & Anesthesiol Branch, NIH, Bldg 10,Room 3C-405,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 67 Z9 67 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 1998 VL 16 IS 1 BP 10 EP 20 DI 10.1016/S0885-3924(98)00026-8 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 105EH UT WOS:000075059400002 PM 9707653 ER PT J AU Ogershok, PR Keller, FG Favara, BE Ritchey, AK AF Ogershok, PR Keller, FG Favara, BE Ritchey, AK TI An unusual histiocytic disorder responding to cyclosporine therapy: A case report SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE histiocytic disorder; cyclosporine ID FACTOR-XIIIA; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; DENDRITIC CELLS; SKIN AB Purpose: To describe the clinical and pathologic presentation and course of a 7-week-old girl with anemia, thrombocytopenia, and organomegaly who was found to have a histiocytic disorder distinct from previously reported cases. Methods: Bone marrow specimens were studied with conventional methods. A liver biopsy specimen was evaluated by routine and immunohistochemical methods and electron microscopy. Results: The patient was found to have a unique histiocytic disorder in which lesional cells displayed an atypical phenotype. Cyclosporine therapy was associated with a prompt, complete, and apparently permanent resolution of disease. Conclusion: This case appears to represent an atypical histiocytic disorder with unique clinical and pathologic features. The disorder resolved after the initiation of cyclosporine therapy. C1 W Virginia Univ, Sch Med, Dept Pediat, Morgantown, WV 26506 USA. NIH, Rocky Mt Labs, Hamilton, MT USA. RP Keller, FG (reprint author), W Virginia Univ, Sch Med, Dept Pediat, POB 9214, Morgantown, WV 26506 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JUL-AUG PY 1998 VL 20 IS 4 BP 338 EP 341 DI 10.1097/00043426-199807000-00012 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 106HJ UT WOS:000075123600012 PM 9703009 ER PT J AU Ruttimann, UE Patel, KM Pollack, MM AF Ruttimann, UE Patel, KM Pollack, MM TI Length of stay and efficiency in pediatric intensive care units SO JOURNAL OF PEDIATRICS LA English DT Article ID MORTALITY; BEDS AB Objective: Assessment of pediatric intensive care unit (PICU) efficiency with a length of stay prediction model and validation of this assessment by an efficiency measure based on daily use of intensive care unit-specific therapies. Design: Inception cohort study of data acquired between 1989 and 1994. Setting: Thirty-two PICUs, 16 selected randomly and 16 volunteering. Subjects: Consecutive admissions of 10,658 patients (466 deaths) who stayed at least 2 hours and up to 12 days in the PICU. Measurements: Length of stay and its prediction from a model with admission day data (PRISM III-24, diagnostic factors, mechanical ventilation). For validation, 11 PICUs recorded each patient's "efficient" days, that is, days when at least one PICU-specific therapy was given. PICU efficiency was computed as either the ratio of the observed efficient days or the days accounted for by the predictor variables to the total care days, and the agreement was assessed by Spearman's rank correlation analysis. Results: The total care days provided by each PICU (n = 32) were well predicted by the length of stay model (r = 0.946). The agreement in 11 validation PICUs between therapy-based efficiency (range 0.30 to 0.67) and predictor-based efficiency (range 0.31 to 0.63) was excellent (rank correlation r = 0.936, p < 0.0001). Conclusion: PICU efficiency comparisons with either method are nearly equivalent. Predictor-based efficiency has the advantage that it can be computed from admission day data only. C1 NIAAA, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Anesthesiol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. George Washington Univ, Sch Med, Washington, DC USA. Childrens Natl Med Ctr, Childrens Res Inst, Ctr Hlth Serv & Clin Res, Washington, DC 20010 USA. RP Ruttimann, UE (reprint author), NIAAA, NIH, Bldg 10-3C102, Bethesda, MD 20892 USA. FU PHS HHS [MCH-110584] NR 16 TC 24 Z9 25 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 1998 VL 133 IS 1 BP 79 EP 85 DI 10.1016/S0022-3476(98)70182-9 PG 7 WC Pediatrics SC Pediatrics GA ZZ431 UT WOS:000074728700016 PM 9672515 ER PT J AU Havemose-Poulsen, A Holmstrup, P Stoltze, K Birkedal-Hansen, H AF Havemose-Poulsen, A Holmstrup, P Stoltze, K Birkedal-Hansen, H TI Dissolution of type I collagen fibrils by gingival fibroblasts isolated from patients of various periodontitis categories SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article ID LOCALIZED JUVENILE PERIODONTITIS; RABBIT SYNOVIAL FIBROBLASTS; CHRONIC ADULT PERIODONTITIS; PHORBOL-MYRISTATE ACETATE; MATRIX METALLOPROTEINASES; CREVICULAR FLUID; TISSUE DESTRUCTION; MESSENGER-RNA; INTERLEUKIN-1; HEALTHY AB The classification of periodontitis in various disease categories, including juvenile periodontitis, rapidly progressive adult periodontitis and slowly progressive adult periodontitits is based mainly on differences in disease progresssion and age group susceptibility. Because dissolution of collagen fibers is an integral part of periodontal attachment loss, we investigated whether the clinical differences among these periodontitis/control groups are reflected in the collagen-degrading activity of gingival fibroblasts isolated from affected tissues. All fibroblast strains isolated from the 4 groups (n=48) displayed cell-associated collagenolytic activity when seeded in contact with a reconstituted film of type I collagen fibrils. Cells from the control group (n=14) dissolved the collagen fibril film twice as fast as those from each of the 3 disease groups (juvenile periodontitis (n=13), rapidly progressive adult periodontitis (n=7), and slowly progressive adult periodontitits (n=14)). Both interleukin-lp and phorbolesler accelerated the rate of dissolution 2-4-fold, but even after cytokine or phorbolester stimulation control cells were still considerably more effective in dissolving the collagen fibrils than cells from the disease groups. The observation made in this study, that dissolution of collagen fibrils by gingival fibroblasts from periodontally diseased individuals is significantly slower than by cells from healthy control subjects, challenges disease paradigms based on a direct relationship between collagenolytic potential and disease activity. C1 Univ Copenhagen, Dept Periodontol, Sch Dent, Fac Hlth Sci, DK-2200 Copenhagen, Denmark. NIDR, NIH, Bethesda, MD 20892 USA. RP Havemose-Poulsen, A (reprint author), Univ Copenhagen, Dept Periodontol, Sch Dent, Fac Hlth Sci, Norre Alle 20, DK-2200 Copenhagen, Denmark. NR 38 TC 16 Z9 17 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD JUL PY 1998 VL 33 IS 5 BP 280 EP 291 DI 10.1111/j.1600-0765.1998.tb02201.x PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 118ZR UT WOS:000075871300006 PM 9777595 ER PT J AU Ruskin, DN Rawji, SS Walters, JR AF Ruskin, DN Rawji, SS Walters, JR TI Effects of full D-1 dopamine receptor agonists on firing rates in the globus pallidus and substantia nigra pars compacta in vivo: Tests for D-1 receptor selectivity and comparisons to the partial agonist SKF 38393 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ADENYLATE-CYCLASE; POSTSYNAPTIC RECEPTORS; SUBTHALAMIC NUCLEUS; RESERPINE TREATMENT; MOLECULAR-CLONING; MESSENGER-RNA; CELL-ACTIVITY; HIGH-POTENCY; NEURONS; D1 AB Many studies have used the D-1 agonist SKF 38393 to characterize D-1 receptor influences on firing rates in basal ganglia nuclei in vivo. However, SKF 38393 is a partial agonist and so may not be ideal for delineating D-1 receptor effects. This study characterizes the effects of four full D-1 agonists, SKF 82958 (chloro-APB), SKF 81297 (6-chloro-PB), dihydrexidine and A-77636, on the firing rates of midbrain dopamine and globus pallidus neurons. Recordings were done in fully anesthetized or paralyzed, locally anesthetized rats, and drugs were given systemically intravenously. Dihydrexidine, SKF 81297 and A-77636 were free of rate effects on midbrain dopamine neurons (up to 10.2 mg/kg) and also did not antagonize the inhibitory effects of quinpirole. In contrast, SKF 82958 strongly inhibited dopamine cells through activation of D-2 autoreceptors (ED50 = 0.70 mg/kg). Of these drugs, SKF 82958 also was the only one to increase pallidal unit firing rates when given alone (at 5.0 but not 1.0 mg/kg); the other compounds appeared to be selective for postsynaptic D-1 receptors. The results suggest that SKF 82958 may be more properly classified as a mixed D-1/D-2 agonist. In addition, all four agonists strongly potentiated the pallidal response to quinpirole, demonstrating a D-1 receptor potentiation of D-2 receptor effects. The results support the role of D-1 receptors in the midbrain and globus pallidus as previously characterized with SKF 38393. The similar actions of partial and full D-1 agonists in these systems support evidence for a D-1 receptor reserve and possibly an effector system other than adenylate cyclase. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ruskin, DN (reprint author), Rm 5C-210,10 Ctr Dr, Bethesda, MD 20892 USA. NR 92 TC 62 Z9 64 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1998 VL 286 IS 1 BP 272 EP 281 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZY832 UT WOS:000074665700035 PM 9655869 ER PT J AU Negus, SS Gatch, MB Mello, NK Zhang, XY Rice, K AF Negus, SS Gatch, MB Mello, NK Zhang, XY Rice, K TI Behavioral effects of the delta-selective opioid agonist SNC80 and related compounds in rhesus monkeys SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DISCRIMINATIVE STIMULUS; RECEPTOR AGONIST; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; MORPHINE-LIKE; BW373U86; PEPTIDES; MICE; SCHEDULE; COCAINE AB The behavioral effects of the nonpeptidic delta opioid agonist SNC80 and a series of related piperazinyl benzamides derived from the parent compound BW373U86 were evaluated in rhesus monkeys. SNC80 (0.1-10 mg/kg) decreased response rates maintained by food-reinforcement in a dose- and time-dependent manner, with maximal effects occuring within 10 min of intramuscular injection. The potency of SNC80 and five other piperazinyl benzamides in this assay of schedule-controlled responding correlated with their affinity at cloned human delta opioid receptors but not with their affinity for cloned human mu receptors. Moreover, the effects of SNC80 were selectively antagonized by the delta-selective antagonist naltrindole (1.0 mg/kg), but not by the mu selective antagonist quadazocine (0.1 mg/kg) or the kappa-selective antagonist norbinaltorphimine (3.2 mg/kg). These findings indicate that SNC80 functions as a systemically active, delta-selective agonist with a rapid onset of action in rhesus monkeys. The antinociceptive effects of SNC80 were examined in a warm-water tail-withdrawal assay of thermal nociception. SNC80 (0.1-10 mg/kg) produced weak but replicable antinociceptive effects that were antagonized by naltrindole (1.0 mg/kg). SNC80 antinociception was also dose-dependently antagonized by BW373U86 (0.56-1.0 mg/kg), which was inactive in this procedure. These findings suggest that SNC80 may have higher efficacy than BW373U86 at delta opioid receptors. Moreover, SNC80 at doses up to 32 mg/kg did not produce convulsions, which suggests that SNC80 may also be safer than BW373U86. The effects of SNC80 were also examined in monkeys trained to discriminate cocaine (0.4 mg/kg i.m.) or self-administer cocaine (0.032 mg/kg/injection,i.v.). In drug discrimination studies, SNC80 (0.1-10 mg/kg) produced a dose-dependent and naltrindole-reversible increase in cocaine-appropriate responding, and complete substitution for cocaine was observed in five of seven monkeys tested. However, SNC80 (1.0-100 mu g/kg/injection) did not maintain responding in monkeys trained to self-administer cocaine. Thus, despite its ability to produce cocaine-like discriminative stimulus effects, SNC80 may have relatively low abuse potential. C1 Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Negus, SS (reprint author), Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIDA NIH HHS [T32-DA07252, R01-DA02519, P50-DA04059] NR 53 TC 87 Z9 89 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1998 VL 286 IS 1 BP 362 EP 375 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZY832 UT WOS:000074665700047 PM 9655881 ER PT J AU Nonaka, S Katsube, N Chuang, DM AF Nonaka, S Katsube, N Chuang, DM TI Lithium protects rat cerebellar granule cells against apoptosis induced by anticonvulsants, phenytoin and carbamazepine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID METHYL-D-ASPARTATE; NERVE GROWTH-FACTOR; PROMOTES SURVIVAL; CEREBRAL-CORTEX; NEURONS; DEATH; ACTIVATION; EXPRESSION; INOSITOL; KINASE AB We have studied the neuroprotective actions of lithium against various insults in cultured cerebellar granule cells of rats. The anticonvulsants, phenytoin and carbamazepine, have been shown to induce apoptosis of cerebellar granule cells at high concentrations. Here we found that cc-presence of LiCl (1-10 mM) dose-dependently protected against phenytoin (20 mu M)- and carbamazepine (100 mu M)-induced neuronal apoptosis as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide metabolism, morphological inspection, chromatin condensation and DNA fragmentation. These neuroprotective effects were not prevented by inclusion of myoinositol nor mimicked by a potent inositol monophosphatase inhibitor, suggestive of a mechanism independent of inositol monophosphatase blockade. Lithium also significantly protected against apoptosis of cerebellar granule cells induced by aging of the cultures. Additionally, lithium suppressed death of cerebellar granule cells exposed to a low concentration of extracellular potassium. In contrast, it had no protective effect on cell death induced by Ca++ ionophores, a Na+ channel opener, a protein kinase inhibitor, a nitric oxide donor or H2O2. Thus, lithium has robust neuroprotective effects against apoptotic cell death induced by multiple insults with limited selectivity. These actions provide a new avenue to study the molecular and cellular mechanisms of this drug. C1 NIMH, Biol Psychiat Branch, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. Ono Pharmaceut Co Ltd, Minase Res Inst, Osaka, Japan. RP Chuang, DM (reprint author), NIMH, Biol Psychiat Branch, Mol Neurobiol Sect, NIH, Bldg 10,Room 3N212,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. NR 45 TC 115 Z9 121 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1998 VL 286 IS 1 BP 539 EP 547 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZY832 UT WOS:000074665700066 PM 9655900 ER PT J AU Gerloff, C Cohen, LG Floeter, MK Chen, R Corwell, B Hallett, M AF Gerloff, C Cohen, LG Floeter, MK Chen, R Corwell, B Hallett, M TI Inhibitory influence of the ipsilateral motor cortex on responses to stimulation of the human cortex and pyramidal tract SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; CORPUS-CALLOSUM; ELECTRICAL-STIMULATION; SILENT PERIOD; INTERHEMISPHERIC PROJECTIONS; SUPPLEMENTARY MOTOR; CORTICAL AREAS; RHESUS MONKEY; NEURONS; ABNORMALITIES AB 1. The ability of the primary motor cortex (M1) to modulate motor responses in ipsilateral hand muscles seems to be important for normal motor control and potentially also for recovery after brain lesions. It is not clear which pathways mediate this ipsilateral modulation. Transcallosal connections have been proposed, but are known to be sparse between cortical hand motor representations in primates. The present study was performed to determine whether descending ipsilateral modulation of motor responses might also be mediated below the cortical level in humans. 2. A paired-pulse protocol was used, in which motor-evoked potentials (MEPs) were produced by cortical transcranial magnetic stimulation (cTMS) or by electrical stimulation of the pyramidal tract at the level of the pyramidal decussation (pdTES), in both preactivated and relaxed hand muscles. Paired stimuli were applied at various interstimulus intervals (ISIs) between 2 and 100 ms. The conditioning stimulus (CS) was always magnetic, and delivered to the M1 ipsilateral to the target hand, prior to the test stimulus (TX). The magnetic TS was delivered to the M1 contralateral to the target hand; the electrical TX was applied through electrodes placed over the mastoid process bilaterally. Further experiments included cortical electrical stimulation and H-reflexes. The MEP amplitudes were averaged separately for each ISI and the control condition (no CX), and expressed as a percentage of the unconditioned response. 3. Conditioning stimulation of the ipsilateral M1 resulted in significant inhibition of magnetically evoked MEPs, and also of MEPs produced by pdTES. Inhibition occurred at ISIs between 6 and 50 ms, and was observed in preactivated and relaxed muscles. Higher CX intensities caused greater inhibition of both cTMS- and pdTES-evoked MEPs. 4. While the conditioning effects on magnetically evoked muscle responses could be explained by a transcallosal mechanism, the effects on pdTEX-evoked MEPs cannot, because they are elicited subcortically and are therefore not susceptible to inhibitory mechanisms transmitted at the cortico-cortical level. 5. In conclusion, the present results provide novel evidence that the inhibitory influence of the human MJ. on ipsilateral hand muscles is to a significant extent mediated below the cortical level, and not only through cortico-cortical transcallosal connections. They point to a concept of inhibitory interaction between the two primary motor cortices that is relayed at multiple levels along the neuroaxis, thus perhaps providing a structurally redundant system which may become important in case of lesions. C1 NINDS, Human Cort Physiol Unit, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Unit, Med Neurol Branch, NIH, Bldg 10,Room 5N234,10 Ctr Dr,MSC-1430, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 40 TC 172 Z9 175 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 1 PY 1998 VL 510 IS 1 BP 249 EP 259 DI 10.1111/j.1469-7793.1998.249bz.x PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 102FC UT WOS:000074912900020 PM 9625881 ER PT J AU Inciardi, JA Needle, RH AF Inciardi, JA Needle, RH TI HIV/AIDS interventions for out-of-treatment drug users SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Editorial Material C1 Univ Delaware, Ctr Drug & Alcohol Studies, Newark, DE 19716 USA. Univ Delaware, Dept Sociol & Criminal Justice, Newark, DE 19716 USA. NIDA, Community Res Branch, Div Epidemiol & Prevent Res, Lexington, KY 40583 USA. RP Inciardi, JA (reprint author), Univ Delaware, Ctr Drug & Alcohol Studies, Newark, DE 19716 USA. NR 7 TC 6 Z9 6 U1 0 U2 0 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD JUL-SEP PY 1998 VL 30 IS 3 BP 225 EP 229 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 128WE UT WOS:000076430700001 PM 9798787 ER PT J AU Deren, S Beardsley, M Coyle, S Singer, M AF Deren, S Beardsley, M Coyle, S Singer, M TI HIV serostatus and risk behaviors in a multisite sample of drug users SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE crack smokers; drug injectors; HIV/AIDS; risk behaviors; serostatus ID SEXUAL-BEHAVIOR; SEROPOSITIVE GAY; HOMOSEXUAL MEN; BISEXUAL MEN; AIDS; INFECTION; REDUCTION AB In developing HIV prevention efforts, it is critical to determine whether interventions are effective in achieving declines in risk behavior among both HIV-positive and HIV-negative individuals. Based on a multisite intervention study of injection drug users (IDUs) and crack smokers, 488 seropositive IDUs and 364 seropositive crack users were compared with randomly selected matched samples of seronegatives (with matching based on recruitment site, gender, age group and ethnicity) at baseline and six-month follow-up to compare changes in risk behaviors by serostatus. Results indicated that overall. risk behaviors declined substantially over time; significant interaction effects indicated that seropositives reported a greater decline in sex risk behaviors than seronegatives. These data support the utility of HIV testing for high-risk drug users, and indicate that interventions have produced reductions in risk behaviors of both seropositives and seronegatives. Further research on the impact of site seroprevalence, and to enhance our understanding of those who continue to engage in risky behaviors, is needed. C1 Natl Dev & Res Inst, Inst AIDS Res, World Trade Ctr, New York, NY 10048 USA. Natl Dev & Res Inst, Ctr Drug Use & HIV Res, New York, NY 10048 USA. NIDA, Clin Epidemiol & Appl Sci Review Branch, Off Extramural Program Review, Bethesda, MD USA. Hispan Hlth Council, Hartford, CT USA. RP Deren, S (reprint author), Natl Dev & Res Inst, Inst AIDS Res, World Trade Ctr, 16th Floor, New York, NY 10048 USA. NR 24 TC 16 Z9 17 U1 2 U2 2 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD JUL-SEP PY 1998 VL 30 IS 3 BP 239 EP 245 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 128WE UT WOS:000076430700003 PM 9798789 ER PT J AU Sloboda, Z Stephens, RC Alemagno, S AF Sloboda, Z Stephens, RC Alemagno, S TI Where do we go from here? SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article ID INJECTION-DRUG USERS; SELF-EFFICACY; RISK BEHAVIORS; AIDS; HIV; INTERVENTIONS; PREVENTION; POPULATIONS; PROJECT; IMPACT C1 NIDA, Community Res Branch, Div Epidemiol & Prevent Res, Rockville, MD 20857 USA. Univ Akron, Dept Sociol, Akron, OH 44325 USA. Cleveland State Univ, Urban Child Res Ctr, Coll Urban Affairs, Cleveland, OH 44115 USA. RP Stephens, RC (reprint author), NIDA, Community Res Branch, Div Epidemiol & Prevent Res, 5600 Fishers Lane 9A53, Rockville, MD 20857 USA. NR 48 TC 1 Z9 1 U1 2 U2 2 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD JUL-SEP PY 1998 VL 30 IS 3 BP 307 EP 314 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 128WE UT WOS:000076430700011 PM 9798797 ER PT J AU Vgontzas, AN Tsigos, C Bixler, EO Stratakis, CA Zachman, K Kales, A Vela-Bueno, A Chrousos, GP AF Vgontzas, AN Tsigos, C Bixler, EO Stratakis, CA Zachman, K Kales, A Vela-Bueno, A Chrousos, GP TI Chronic insomnia and activity of the stress system: A preliminary study SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article; Proceedings Paper CT 77th Annual Meeting of the Endocrine-Society CY JUN 12-17, 1995 CL WASHINGTON, D.C. SP Endocrine Soc, Minist Educ, Sci & Culture Japan, Dtsch ForschGemeinsch DE cortisol; catecholamines; growth hormone; insomnia; polysomnography; stress ID PITUITARY-ADRENAL AXIS; SLEEP-ONSET INSOMNIA; CORTISOL SECRETION; GROWTH; DISORDERS; PATTERNS; DYSREGULATION AB The aim of this study was to assess whether there is an association between chronic insomnia and the activity of the stress system. Fifteen young adult insomniacs (<40 years) were studied. After an adaptation night, each subject was recorded in the sleep laboratory for three consecutive nights. During this period, 24-hour urine specimens were collected for measurements of urinary free cortisol (UFC), catecholamines, and growth hormone (GH). The 24-hour UFC levels were positively correlated with total wake time (p=0.05). In addition, 24-hour urinary levels of catecholamine metabolites, DHPG, and DOPAC were positively correlated with percent stage 1 sleep (p<0.05) and wake time after sleep onset (WTASO) (p<0.05). Norepinephrine tended to correlate positively with percent stage 1 sleep (p = 0.063) and WTASO (p=0.074), and negatively with percent slow-wave sleep (p=0.059). Twenty-four-hour urinary GH excretion was detectable in only three insomniacs, two of whom had low indices of sleep disturbance. We conclude that, in chronic insomnia, the activity of both limbs of the stress system (i.e., the HPA axis and the sympathetic system) relates positively to the degree of objective sleep disturbance. (C) 1998 Elsevier Science Inc. C1 Penn State Univ, Coll Med, Sleep Res & Treatment Ctr, Hershey, PA 17033 USA. Penn State Univ, Dept Psychiat, Hershey, PA 17033 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Vgontzas, AN (reprint author), Penn State Univ, Coll Med, Sleep Res & Treatment Ctr, 500 Univ Dr, Hershey, PA 17033 USA. NR 35 TC 173 Z9 177 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUL PY 1998 VL 45 IS 1 BP 21 EP 31 DI 10.1016/S0022-3999(97)00302-4 PG 11 WC Psychiatry SC Psychiatry GA ZW731 UT WOS:000074442100004 PM 9720852 ER PT J AU Ebert, AD Perez-Canto, A Schaller, G Entezami, M Hopp, HSG Weitzel, HK AF Ebert, AD Perez-Canto, A Schaller, G Entezami, M Hopp, HSG Weitzel, HK TI Stage I primary malignant mixed mullerian tumor of the fallopian tube - Report of a case with five-year survival after minimal surgery without adjuvant treatment SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE fallopian tube neoplasms; mixed tumor, malignant; mixed tumor, mullerian AB BACKGROUND: Sarcomas of the fallopian tube are rarities in gynecologic oncology, consisting of <1% of all genital sarcomas. CASE: A 70-year-old woman with a stage I malignant mixed mullerian tumor (MMMT) (International Federation of Gynecology and Obstetrics classification of fallopian tube carcinomas) did not undergo radical surgery or adjuvant treatment because of the patient's refusal of them. The patient underwent only abdominal hysterectomy with bilateral salpingo-oophorectomy. She was discharged feeling well and without abnormal clinical findings. Sixty months after primary surgery there were no signs of recurrence. CONCLUSION: This case suggests the possibility of a good prognosis in early-stage MMMT, especially if there is no deep infiltration of the fallopian tube muscle layer or lymphatic permeation and if the peritoneal cytology is negative. The important feature of this report is the five-year disease-free survival after nonradical surgery for prognostically favorable MMMT. C1 Free Univ Berlin, Benjamin Franklin Med Ctr, Dept Gynecol & Obstet, Berlin, Germany. Free Univ Berlin, Benjamin Franklin Med Ctr, Dept Pathol, Berlin, Germany. RP Ebert, AD (reprint author), NCI, LTIB, NIH, Bldg 10,Room 5B39,10 Ctr Dr,MSC 1750, Bethesda, MD 20892 USA. NR 7 TC 5 Z9 8 U1 1 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD JUL PY 1998 VL 43 IS 7 BP 598 EP 600 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 103JE UT WOS:000075153300010 PM 9693413 ER PT J AU Kim, Y AF Kim, Y TI Optimal estimation for continuous state branching processes with discrete sampling SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE continuous state branching process; estimating function; semimartingale models ID STOCHASTIC-PROCESSES; LIKELIHOOD AB This paper is concerned with estimation of the drift parameter in a Glass of continuous state branching processes by use of the estimating function theory (Heyde, 1992, J. Statist. Plann. Inference 33, 121-129). The main interests are to develop a method of estimating the parameter in case when only discrete sampling is available. For this purpose, a discretized quasi-score function is introduced and a discretized optimal estimator derived therefrom is obtained. Large-sample properties of the discretized optimal estimator are established. Finally, two examples of continuous state branching processes are given. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIH, Rockville, MD 20852 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUL 1 PY 1998 VL 70 IS 1 BP 77 EP 89 DI 10.1016/S0378-3758(97)00182-1 PG 13 WC Statistics & Probability SC Mathematics GA ZZ325 UT WOS:000074718100007 ER PT J AU Offord, DR Kraemer, HC Kazdin, AE Jensen, PS Harrington, R AF Offord, DR Kraemer, HC Kazdin, AE Jensen, PS Harrington, R TI Lowering the burden of suffering from child psychiatric disorder: Trade-offs among clinical, targeted, and universal interventions SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE childhood psychiatric disorder; epidemiology; intervention ID HEALTH AB To examine the trade-offs among clinical, targeted, and universal interventions aimed at lowering the burden of suffering from child psychiatric disorders. Method: Data from clinical and research studies were organized to show the advantages and disadvantages of the three strategies. Results: Important trade-offs exist among these three approaches. The strategy to reduce the burden of suffering from child psychiatric disorder should consist of a number of concurrent steps. First, effective universal programs should be in place. Targeted programs should follow for those not helped sufficiently by the universal programs. Finally, for those unaffected by the targeted programs, clinical services should be available. Conclusion: An optimal mix of universal, targeted, and clinical programs is needed. The nature of the combination will change as knowledge accumulates, and there will always be trade-offs among these three. C1 Hamilton Hlth Sci Corp, Ctr Studies Children Risk, Hamilton, ON L8N 3Z5, Canada. McMaster Univ, Hamilton, ON, Canada. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. NIMH, Child & Adolescent Disorders Res Branch, Rockville, MD 20857 USA. Univ Manchester, Manchester, Lancs, England. RP Offord, DR (reprint author), Hamilton Hlth Sci Corp, Ctr Studies Children Risk, Patterson Bldg,POB 2000,Stn A, Hamilton, ON L8N 3Z5, Canada. OI Jensen, Peter/0000-0003-2387-0650 NR 25 TC 125 Z9 126 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1998 VL 37 IS 7 BP 686 EP 694 DI 10.1097/00004583-199807000-00007 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA ZW690 UT WOS:000074437300008 PM 9666623 ER PT J AU Brook, JS Brook, DW De la Rosa, M Duque, LF Rodriguez, E Montoya, ID Whiteman, M AF Brook, JS Brook, DW De la Rosa, M Duque, LF Rodriguez, E Montoya, ID Whiteman, M TI Pathways to marijuana use among adolescents: Cultural/ecological, family, peer, and personality influences SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE marijuana; Colombian adolescents; culture/ecology; personality; family; peer ID DRUG-USE; ECONOMIC-STRESS; ATTACHMENT; ABUSE; RISK AB Objective: To examine the linkages, cultural/ecological factors, and major psychosocial risk factors as they relate to drug use in a sample from Colombia, South America. Method: The participants were 1,687 adolescents living in mixed urban-rural communities in Colombia, South America. An individual interview was administered to youths in their homes by Colombian interviewers. The scales used were based on item intercorrelations grouped into the following risk categories: (1) adolescent personality, (2) family traits, (3) peer factors, and (4) cultural/ecological variables. Results: Pearson correlations were computed for each variable and the frequency of marijuana use. Results show that each of the domains was related to adolescent marijuana use, with some notable gender differences. As regards the interrelation of domains, a mediational model was operative. Conclusions: Findings support a family interactional theory. The domains of family, personality, and peer factors had a direct effect on the adolescents' marijuana use. Implications for prevention are also addressed. C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Natl Inst Drug Abuse, Rockville, MD USA. Colombian Hlth Assoc, Bogota, Colombia. Univ Antioquia, Medellin, Colombia. RP Brook, JS (reprint author), CUNY Mt Sinai Sch Med, 1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIDA NIH HHS [DA 10348, DA 00244] NR 32 TC 52 Z9 53 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1998 VL 37 IS 7 BP 759 EP 766 DI 10.1097/00004583-199807000-00016 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA ZW690 UT WOS:000074437300017 PM 9666632 ER PT J AU Shah, PY Sharma, V Worobec, AS Metcalfe, DD Zwick, DC AF Shah, PY Sharma, V Worobec, AS Metcalfe, DD Zwick, DC TI Congenital bullous mastocytosis with myeloproliferative disorder and c-kit mutation SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article C1 Childrens Mercy Hosp, Dermatol Sect, Dept Dermatol, Kansas City, MO 64108 USA. Childrens Mercy Hosp, Dept Pathol, Kansas City, MO 64108 USA. Univ Illinois, Dept Pediat, Chicago, IL USA. Univ Missouri, Sch Med, Dept Pediat, Kansas City, MO 64108 USA. Univ Kansas, Dept Med Dermatol, Sch Med, Kansas City, MO 64108 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Sharma, V (reprint author), Childrens Mercy Hosp, Dermatol Sect, Dept Dermatol, 2401 Gillham Rd, Kansas City, MO 64108 USA. NR 10 TC 25 Z9 26 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 1998 VL 39 IS 1 BP 119 EP 121 DI 10.1016/S0190-9622(98)70413-X PG 3 WC Dermatology SC Dermatology GA ZY387 UT WOS:000074616200017 PM 9674408 ER PT J AU Grayburn, PA Weiss, JL Hack, TC Klodas, E Raichlen, JS Vannan, MA Klein, AL Kitzman, DW Chrysant, SG Cohen, JL Abrahamson, D Foster, E Perez, JE Aurigemma, GP Panza, JA Picard, MH Byrd, BF Segar, DS Jacobson, SA Sahn, DJ DeMaria, AN AF Grayburn, PA Weiss, JL Hack, TC Klodas, E Raichlen, JS Vannan, MA Klein, AL Kitzman, DW Chrysant, SG Cohen, JL Abrahamson, D Foster, E Perez, JE Aurigemma, GP Panza, JA Picard, MH Byrd, BF Segar, DS Jacobson, SA Sahn, DJ DeMaria, AN TI Phase III multicenter trial comparing the efficacy of 2% dodecafluoropentane emulsion (EchoGen) and sonicated 5% human albumin (Albunex) as ultrasound contrast agents in patients with suboptimal echocardiograms SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MYOCARDIAL CONTRAST; MICROBUBBLES AB Objectives. This study was performed to compare the safety and efficacy of intravenous 2% dadecafluoropentane (DDFP) emulsion (EchoGen) with that of active control (sonicated human albumin [Albunex]) for left ventricular (LV) cavity opacification in adult patients with a suboptimal echocardiogram. Background. The development of new fluorocarbon-based echocardiographic contrast agents such as DDFP has allowed opacification of the left ventricle after peripheral venous injection. We hypothesized that DDFP was clinically superior to the Food and Drug Administration-approved active control. Methods. This was a Phase III, multicenter, single blind, active controlled trial. Sequential intravenous injections of active control and DDFP were given 30 min apart to 254 patients with a suboptimal echocardiogram, defined as one in which the endocardial borders mere not visible in at least two segments in either the apical two- or four-chamber views. Studies were interpreted in blinded manner by two readers and the investigators. Results. Full or intermediate LV cavity opacification was more frequently observed after DDFP than after active control (78% vs. 31% for reader A; 69% vs. 34% for reader B; 83% vs. 55% for the investigators, p < 0.0001). LV cavity opacification scores were higher with DDFP (2.0 to 2.5 vs. 1.1 to 1.5, p < 0.0001). Endocardial border delineation was improved by DDFP in 88% of patients versus 45% with active control (p < 0.001). Similar improvement was seen for duration of contrast effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to affect patient management. There was no difference between agents in the number of patients with adverse events attributed to the test agent (9% for DDFP vs. 6% for active control, p = 0.92). Conclusions. This Phase ill multicenter trial demonstrates that DDFP is superior to sonicated human albumin for LV cavity opacification, endocardial border definition, duration of effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to influence patient management. The two agents had similar safety profiles. C1 Univ Texas, SW Med Ctr, Echocardiog Labs, Div Cardiol, Dallas, TX 75216 USA. Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA. Deaconess Nashoba Hosp, Ayer, MA USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Bowman Gray Med Ctr, Winston Salem, NC USA. Oklahoma Cardiovasc & Hypotens Ctr, Oklahoma City, OK USA. Vet Affairs Med Ctr, E Orange, NJ USA. Orange Cty Heart Inst & Res Ctr, Orange, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Washington Univ, Med Ctr, St Louis, MO USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN USA. Indiana Univ, Indianapolis, IN 46204 USA. Res Hlth Inc, Houston, TX USA. Univ Oregon, Hlth Sci Ctr, Portland, OR USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Grayburn, PA (reprint author), Univ Texas, SW Med Ctr, Echocardiog Labs, Div Cardiol, 5323 Harry Hines Blvd, Dallas, TX 75216 USA. EM grayburn@ryburn.swmed.edu OI Picard, Michael/0000-0002-9264-3243 NR 26 TC 76 Z9 77 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1998 VL 32 IS 1 BP 230 EP 236 DI 10.1016/S0735-1097(98)00219-8 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZZ105 UT WOS:000074696200035 PM 9669275 ER PT J AU Shugars, DC Wahl, SM AF Shugars, DC Wahl, SM TI The role of the oral environment in HIV-1 transmission SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LEUKOCYTE PROTEASE INHIBITOR; CELL-FREE SIV; HOUSEHOLD CONTACTS; HTLV-III; SALIVARY INHIBITION; LANGERHANS CELLS; AIDS PATIENTS; IN-VITRO; T-CELLS AB Human immunodeficiency virus type 1, or HIV-1, is infrequently transmitted through the mouth, unlike other mucosal sites. Factors such as low salivary viral titers, low numbers of CD4-positive target cells, anti-HIV antibodies and endogenous salivary antiviral factors work in concert to protect oral tissues from Infection and reduce the risk of viral transmission through salivary secretions. This review summarizes the various factors thought to influence oral transmission of HIV-1, focusing on the mucosal protein secretory leukocyte protease inhibitor, or SLPI. C1 Univ N Carolina, Sch Dent, Dept Dent Ecol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Immunol & Microbiol, Chapel Hill, NC 27599 USA. NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Shugars, DC (reprint author), Univ N Carolina, Sch Dent, Dept Dent Ecol, CB 7450,Brauer Hill, Chapel Hill, NC 27599 USA. FU NIDCR NIH HHS [R01-DE12162] NR 84 TC 62 Z9 64 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUL PY 1998 VL 129 IS 7 BP 851 EP 858 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 100AG UT WOS:000074791300019 PM 9685760 ER PT J AU Slavkin, HC AF Slavkin, HC TI Protecting the mouth against microbial infections SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article C1 NIDR, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), NIDR, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 4 TC 3 Z9 4 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUL PY 1998 VL 129 IS 7 BP 1025 EP 1030 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 100AG UT WOS:000074791300028 PM 9685769 ER PT J AU Dennis, BH Stewart, P Chin-Hua-Wang Champagne, C Windhauser, M Ershow, A Karmally, W Phillips, K Stewart, K Van Heel, N Farhat-Wood, A Kris-Etherton, PM AF Dennis, BH Stewart, P Chin-Hua-Wang Champagne, C Windhauser, M Ershow, A Karmally, W Phillips, K Stewart, K Van Heel, N Farhat-Wood, A Kris-Etherton, PM CA Delta Res Grp TI Diet design for a multicenter controlled feeding trial: The DELTA program SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID FATTY-ACIDS; CHOLESTEROL; WOMEN; LIPOPROTEINS; MEN AB Objective To describe the process and results of diet standardization, diet validation, and monitoring of diet composition, which were key components of protocol 1 of Dietary Effects on Lipoproteins and Thrombogenic Activity (DELTA-1), the initial protocol in a program of multicenter human feeding studies designed to evaluate the effects of mount and type of fat on lipoproteins and hemostasis parameters in various demographic groups. Design DELTA-1 was based on a randomized, blinded, crossover experimental design. Three diets were fed for 8 weeks to 103 healthy men and women aged 22 to 67 years at 4 field centers. Diet A, an average American diet, was designed to provide 37% of energy from fat, 16% of energy from saturated fatty acids (SFAs); diet B (step 1 diet) was designed to provide 30% of energy from fat, 9% of energy from SFA; and diet C (low SFA diet) was designed to provide 26% of energy from fat, 5% of energy from SFA. Key features of diet standardization included central procurement of fat-containing foods, inclusion of standard ingredients, precision weighing of foods-especially sources of fat and cholesterol-and use of standardized written procedures. Setting For menu validation, a set of 12 menus for each diet was prepared in duplicate and chemically assayed. For monitoring of diet composition during the study, an 8-day diet cycle (6 weekday and 2 weekend menus) was sampled by every field center twice during each of 3 feeding periods. Statistical analyses Means (+/-standard error) were calculated and compared with target nutrient specifications. Results DELTA-1 was able to provide a standardized diet that met nutrient specifications across 4 field centers over 24 weeks of participant feeding spanning a total of 8 months. Applications Prestudy chemical validation of menus and continuous sampling and assay of diets throughout the study are essential to standardize experimental diets and to ensure that nutrient target goals are met and maintained throughout a controlled multicenter feeding study. C1 Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC 27514 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. Columbia Univ, Irving Ctr Clin Res, New York, NY USA. Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA. Univ Minnesota, Nutr Coordinating Ctr, Div Epidemiol, Minneapolis, MN USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. RP Dennis, BH (reprint author), Univ N Carolina, Collaborat Studies Coordinating Ctr, 137 E Franklin St, Chapel Hill, NC 27514 USA. OI Phillips, Katherine/0000-0002-4586-8538 FU NHLBI NIH HHS [U01 HL49648, U01 HL49649, U01-HL49644] NR 19 TC 23 Z9 23 U1 0 U2 2 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUL PY 1998 VL 98 IS 7 BP 766 EP 776 DI 10.1016/S0002-8223(98)00173-4 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZY667 UT WOS:000074647100007 PM 9664917 ER PT J AU Penninx, BWJH Guralnik, JM Simonsick, EM Kasper, JD Ferrucci, L Fried, LP AF Penninx, BWJH Guralnik, JM Simonsick, EM Kasper, JD Ferrucci, L Fried, LP TI Emotional vitality among disabled older women: The Women's Health and Aging Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID SOCIAL SUPPORT; DEPRESSIVE SYMPTOMS; SAMPLE; ADULTS; SYMPTOMATOLOGY; ASSOCIATION; DISABILITY; PREVALENCE; SCALE; RACE AB OBJECTIVE: To examine correlates of high overall level of emotional functioning (emotional vitality) in disabled older women. DESIGN: A community-based study: The Women's Health and Aging Study. POPULATION: A total of 1002 moderately to severely disabled women aged 65 and older living in the community. MEASUREMENTS: Emotional vitality was defined as having a high sense of personal mastery, being happy, and having low depressive symptomatology and anxiety. Correlations with demographics, health status, and social context were examined. RESULTS: Despite their physical disabilities, 35% of the 1002 disabled older women were emotionally vital. The percent of emotionally vital women declined with increasing severity of disability. After adjustment for disability status, a significantly increased likelihood for being emotionally vital was found for black race (OR = 1.69) and for having higher income (OR = 1.77), better cognition (OR = 2.36), no vision problems (OR = 1.61), adequate emotional support (OR = 2.54), and many face-to-face contacts (OR = 1.64). Having more than one negative life event reduced the likelihood of emotional vitality (OR = 0.57). CONCLUSION: A substantial proportion of even the most disabled older women can be described as emotionally vital. Findings also suggest that emotional vitality is not solely a function of stable, enduring individual characteristics bur that health status, disability, and sociodemographic context also have an influence on emotional vitality. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Ist Nazl Ric & Cura Gli Anziani, Fraticini, INRCA, Florence, Italy. Johns Hopkins Med Inst, Sch Med, Baltimore, MD 21205 USA. RP Penninx, BWJH (reprint author), NIA, Epidemiol Demog & Biometry Program, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C-309, Bethesda, MD 20892 USA. NR 36 TC 54 Z9 54 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 1998 VL 46 IS 7 BP 807 EP 815 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZZ397 UT WOS:000074725300001 PM 9670865 ER PT J AU Corn, M AF Corn, M TI Funding for nursing vocabularies SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Editorial Material C1 Natl Lib Med, Extramural Programs, Bethesda, MD 20894 USA. RP Corn, M (reprint author), Natl Lib Med, Extramural Programs, Bldg 38A,Room 5N-505,8600 Rockville Pike, Bethesda, MD 20894 USA. EM corn@nes.nlm.nih.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 1998 VL 5 IS 4 BP 391 EP 392 PG 2 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA ZY220 UT WOS:000074598300011 PM 9670136 ER EF