FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Carlson, JH Hill, SA AF Carlson, JH Hill, SA TI Identification and characterization of thymidylate synthase from Neisseria gonorrhoeae SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE trimethoprim resistance; thyA; nucleotide salvage ID ESCHERICHIA-COLI; BACILLUS-SUBTILIS; TRANSFORMATION; SEQUENCE; GENES AB Thymidylate synthase converts deoxyuridylate to deoxythymidylate. The thyA gene has been cloned and sequenced from Neisseria gonorrhoeae MS11. This gene has an open reading frame of 795-801 bp and encodes a product which shares 71% identity with its Escherichia coli homolog. Unlike its E. coli counterpart, gonococcal thyA has a large, upstream transcribed region (300+ bp) that lacks a translatable reading frame. Gonococcal thyA is capable of complementing an E. coli thyA null mutant and shares similar levels of sensitivity with trimethoprim. RP Carlson, JH (reprint author), NIAID, ROCKY MT LABS, MICROBIAL STRUCT & FUNCT LAB, DEPT HLTH & HUMAN SERV, NIH, HAMILTON, MT 59840 USA. NR 20 TC 1 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0378-1097 EI 1574-6968 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD JUN 15 PY 1997 VL 151 IS 2 BP 225 EP 230 DI 10.1016/S0378-1097(97)00164-X PG 6 WC Microbiology SC Microbiology GA XJ376 UT WOS:A1997XJ37600018 PM 9228757 ER PT J AU Guru, SC Olufemi, SE Manickam, P Cummings, C Gieser, LM Pike, BL Bittner, ML Jiang, Y Chinault, AC Nowak, NJ Brzozowska, A Crabtree, JS Wang, YP Roe, BA Weisemann, JM Boguski, MS Agarwal, SK Burns, AL Spiegel, AM Marx, SJ Flejter, WL deJong, PJ Collins, FS Chandrasekharappa, SC AF Guru, SC Olufemi, SE Manickam, P Cummings, C Gieser, LM Pike, BL Bittner, ML Jiang, Y Chinault, AC Nowak, NJ Brzozowska, A Crabtree, JS Wang, YP Roe, BA Weisemann, JM Boguski, MS Agarwal, SK Burns, AL Spiegel, AM Marx, SJ Flejter, WL deJong, PJ Collins, FS Chandrasekharappa, SC TI A 2.8-Mb clone contig of the multiple endocrine neoplasia type 1 (MEN1) region at 11q13 SO GENOMICS LA English DT Article ID RADIATION HYBRID MAP; PHYSICAL MAP; HUMAN GENOME; YAC LIBRARY; HUMAN DNA; CHROMOSOME; GENE; LOCUS; CONSTRUCTION; YEAST AB Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder that results ill parathyroid, anterior pituitary, and pancreatic and duodenal endocrine tamers in affected individuals. The MEN1 locus is tightly linked to the marker PYGM on chromosome 11q13, and linkage analysis has placed the MEN1 gene within a 2-Mb interval flanked by D11S1883 and D11S449. As a step toward cloning the MEN1 gene, we have constructed a 2.8-Mb clone contig consisting of YAC and bacterial clones (PAC, BAG, and PI) for the D11S480 to D11S913 region. The bacterial clones alone represent nearly all of the 2.8-Mb contig. The contig was assembled based on a high-density STS-content analysis of 79 genomic clones (YAC, PAC, BAG, and P1) with 118 STSs. The STSs included 22 polymorphic markers and 20 transcripts, with the remainder primarily derived from the end sequences of the genomic clones, An independent cosmid contig for the I-Mb PYGM-SEA region was also generated. Support for correctness of the 2,8-Mb contig map comes from all independent ordering of the clones by fiber-FISH. This sequence-ready contig will be a useful resource for positional cloning of MEN1 and other disease genes Whose loci fall within this region. (C) 1997 Academic Press. C1 NATL HUMAN GENOME RES INST,LGT,NIH,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. ROSWELL PK CANC INST,DEPT HUMAN GENET,BUFFALO,NY 14623. UNIV OKLAHOMA,DEPT CHEM,NORMAN,OK 73019. UNIV OKLAHOMA,DEPT BIOCHEM,NORMAN,OK 73019. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. UNIV UTAH,SCH MED,DEPT HUMAN GENET,SALT LAKE CITY,UT 84132. NIDDK,METAB DIS BRANCH,BETHESDA,MD 20892. NATL HUMAN GENOME RES INST,PHYS MAPPING CORE,GENOME TECHNOL BRANCH,NIH,BETHESDA,MD 20892. NATL HUMAN GENOME RES INST,CANC GENET LAB,NIH,BETHESDA,MD 20892. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 51 TC 38 Z9 38 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 15 PY 1997 VL 42 IS 3 BP 436 EP 445 DI 10.1006/geno.1997.4783 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XG519 UT WOS:A1997XG51900009 PM 9205115 ER PT J AU Lee, JS Scala, S Matsumoto, Y Dickstein, B Robey, R Zhan, ZR Altenberg, G Bates, SE AF Lee, JS Scala, S Matsumoto, Y Dickstein, B Robey, R Zhan, ZR Altenberg, G Bates, SE TI Reduced drug accumulation and multidrug resistance in human breast cancer cells without associated P-glycoprotein or MRP overexpression SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE mitoxantrone; drug resistance; non-Pgp MDR; rhodamine ID POLYMERASE CHAIN-REACTION; SENSITIVE NA+ CHANNEL; MEMBRANE-PROTEIN; CELLULAR ACCUMULATION; MOLECULAR-CLONING; CARCINOMA-CELLS; MESSENGER-RNA; TUMOR SAMPLES; EXPRESSION; MITOXANTRONE AB MCF-7 human breast cancer cells selected in Adriamycin in the presence of verapamil developed a multidrug resistant phenotype, which was characterized by as much as 100,000-fold resistance to mitoxantrone, 667-fold resistance to daunorubicin, and 600-fold resistance to doxorubicin. Immunoblot and PCR analyses demonstrated no increase in MDR-1 for MRP expression in resistant cells, relative to parental cells. This phenotype is similar to one previously described in mitoxantrone-selected cells. The cells, designated MCF-7 AdVp, displayed a slower growth rate without alteration in topoisomerase ll alpha level or activity. increased efflux and reduced accumulation of daunomycin and rhodamine were observed when compared to parental cells. Depletion of ATP resulted in complete abrogation of efflux of both daunomycin and rhodamine. No apparent alterations in subcellular daunorubicin distribution were observed by confocal microscopy. No differences were noted in intracellular pH. Molecular cloning studies using DNA differential display identified increased expression of the alpha subunit of the amiloridc-sensitive sodium channel in resistant cells. Quantitative PCR studies demonstrated an eightfold overexpression of the alpha subunit of the Na+ channel in the resistant subline. This channel may be linked to the mechanism of drug resistance in the AdVp cells. The results presented here support the hypothesis that a novel energy-dependent protein is responsible for the efflux in the AdVp cells. Further identification awaits molecular cloning studies. J. Cell. Biochem. 65:513-526. (C) 1997 Wiley-Liss, Inc. C1 NCI, MED BRANCH, DIV CLIN SCI, BETHESDA, MD 20892 USA. UNIV TEXAS, MED BRANCH, DEPT PHYSIOL & BIOPHYS, GALVESTON, TX 77550 USA. RI Scala, Stefania/K-1380-2016 OI Scala, Stefania/0000-0001-9524-2616 NR 66 TC 81 Z9 86 U1 0 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUN 15 PY 1997 VL 65 IS 4 BP 513 EP 526 DI 10.1002/(SICI)1097-4644(19970615)65:4<513::AID-JCB7>3.0.CO;2-R PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XC663 UT WOS:A1997XC66300007 PM 9178101 ER PT J AU Paulik, MA Hamacher, LL Yarnall, DP Simmons, CJ Maianu, L Pratley, RE Garvey, WT Burns, DK Lenhard, JM AF Paulik, MA Hamacher, LL Yarnall, DP Simmons, CJ Maianu, L Pratley, RE Garvey, WT Burns, DK Lenhard, JM TI Identification of rad's effector-binding domain, intracellular localization, and analysis of expression in Pima Indians SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE insulin resistance; skeletal muscle; NIDDM; GTP-binding protein; thin filaments ID GTPASE-ACTIVATING PROTEIN; RAS FAMILY; MUSCLE; DIFFERENTIATION; CYTOSKELETAL; MECHANISM; P21; RHO AB In order to characterize the endogenous gene product for rad (res-related protein associated with diabetes), we prepared antibodies to synthetic peptides that correspond to amino acids (109-121, 178-195, 254-271) within the protein. These antibodies were used to analyze the expression, structure, and function of rad. Western analysis with these antibodies revealed that rad was a 46 kDa protein which was expressed during myotube formation. Further, immunolocalization studies showed that rad localized to thin filamentous regions in skeletal muscle. Interestingly, when muscle biopsies from diabetic and control Pima Indians were compared, no differences in rad protein or mRNA expression were observed. Similarly, no differences were observed in protein expression in diabetic and control Zucker diabetic fatty (ZDF) rats. Functional analysis of muscle rad revealed that its GTP-binding activity was inhibited by the addition of N-ethylmaliemide, GTP, GTP gamma S, and CDP beta S but not ATP or dithiothreitol. Moreover, cytosol-dependent rad-GTPase activity was stimulated by the peptide corresponding to amino acids 109-121. Antibodies corresponding to this epitope inhibited cytosol-dependent rad-GTPase activity. Taken together, the results indicate that 1) rad is a 46 kDa GTP-binding protein localized to thin filaments in muscle and its expression increases during myoblast fusion, 2) expression of rad in Pima Indians and ZDF rats does not correlate with diabetes, and 3) the amino acids (109-121) may be involved in regulating rad-GTPase activity, perhaps by interacting with a cytosolic factor(s) regulating nucleotide exchange and/or hydrolysis. J. Cell. Biochem. 65:527-541. (C) 1997 Wiley-Liss, Inc. C1 GLAXO WELLCOME INC,DEPT METAB DIS,RES TRIANGLE PK,NC 27709. GLAXO WELLCOME INC,DEPT HUMAN GENET,RES TRIANGLE PK,NC 27709. GLAXO WELLCOME INC,DEPT MOL PHARMACOL,RES TRIANGLE PK,NC 27709. MED UNIV S CAROLINA,DIV ENDOCRINOL,CHARLESTON,SC 29425. VET AFFAIRS MED CTR,CHARLESTON,SC 29403. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. FU NIDDK NIH HHS [DK 38765, DK 47461] NR 33 TC 13 Z9 13 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUN 15 PY 1997 VL 65 IS 4 BP 527 EP 541 DI 10.1002/(SICI)1097-4644(19970615)65:4<527::AID-JCB8>3.0.CO;2-Q PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XC663 UT WOS:A1997XC66300008 PM 9178102 ER PT J AU Dibbern, DA Glazner, GW Gozes, I Brenneman, DE Hill, JM AF Dibbern, DA Glazner, GW Gozes, I Brenneman, DE Hill, JM TI Inhibition of murine embryonic growth by human immunodeficiency virus envelope protein and its prevention by vasoactive intestinal peptide and activity-dependent neurotrophic factor SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE vasoactive intestinal peptide; activity-dependent neurotrophic factor; embryo; human immunodeficiency virus gp120; growth retardation ID CALCIUM-CHANNEL ANTAGONISTS; NECROSIS-FACTOR-ALPHA; HIV-1 INFECTION; GLYCOPROTEIN GP120; COAT PROTEIN; NITRIC-OXIDE; HUMAN BRAIN; PERINATAL TRANSMISSION; VERTICAL TRANSMISSION; CEREBROSPINAL-FLUID AB Intrauterine growth retardation and neurodevelopmental handicaps are common among infants born to HIV-positive mothers and may be due to the actions of virions and/or maternally derived viral products. The viral envelope protein, gp120, is toxic to neurons, induces neuronal dystrophy, and retards behavioral development in neonatal rats. Vasoactive intestinal peptide, a neuropeptide regulator of early post-implantation embryonic growth, and the neuroprotective protein, activity-dependent neurotrophic factor, prevent gp120-induced neurotoxicity. Whole embryo culture of gestational day 9.5 mouse embryos was used to assess the effect of gp120 on growth. Embryos treated with gp120 exhibited a dose-dependent inhibition of growth. gp120-treated embryos (10(-8) M) grew 1.2 somites in the 6-h incubation period, compared with 3.9 somites by control embryos. Embryos treated with gp120 were significantly smaller in cross-sectional area and had significantly less DNA and protein than controls. Growth inhibition induced by gp120 was prevented by cotreatment with vasoactive intestinal peptide or activity-dependent neurotrophic factor. gp120 may play a role in the growth retardation and developmental delays experienced by infants born to HIV-positive mothers. Vasoactive intestinal peptide and related factors may provide a therapeutic strategy in preventing developmental deficits. C1 NICHHD,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT CLIN BIOCHEM,IL-69978 TEL AVIV,ISRAEL. NR 69 TC 24 Z9 25 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 15 PY 1997 VL 99 IS 12 BP 2837 EP 2841 DI 10.1172/JCI119476 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XH277 UT WOS:A1997XH27700007 PM 9185505 ER PT J AU Wang, YH Perfetti, R Greig, NH Holloway, HW DeOre, KA MontroseRafizadeh, C Elahi, D Egan, JM AF Wang, YH Perfetti, R Greig, NH Holloway, HW DeOre, KA MontroseRafizadeh, C Elahi, D Egan, JM TI Glucagon-like peptide-1 can reverse the age-related decline in glucose tolerance in rats SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE insulin; glucose; glucagon; beta cell; aging ID PANCREATIC BETA-CELLS; STIMULATED INSULIN RELEASE; DIABETES-MELLITUS; PROINSULIN BIOSYNTHESIS; RIN-1046-38 CELLS; GENE-EXPRESSION; 7-36 AMIDE; SECRETION; GLUCOKINASE; INCRETIN AB Wistar rats develop glucose intolerance and have a diminished insulin response to glucose with age. The aim of this study was to investigate if these changes were reversible with glucagon-like peptide-1 (GLP-1), a peptide that we have previously shown could increase insulin mRNA and total insulin content in insulinoma cells. We infused 1.5 pmol kg(-1).min(-1) GLP-1 subcutaneously using ALZET microesmotic pumps into 22-mo-old Wistar rats for 48 h. Rat infused with either GLP-1 or saline were then subjected to an intraperitoneal glucose (1 g/kg body weight) tolerance test, 2 h after removing the pump. 15 min after the intraperitoneal glucose, GLP-1-treated animals had lower plasma glucose levels (9.04+/-0.92 mmol/liter, P < 0.01) than saline-treated animals (11.61+/-0.23 mmol/liter). At 30 min the plasma glucose was still lower in the GLP-1-treated animals (8.61+/-0.39 mmol/liter, P < 0.05) than saline-treated animals (10.36+/-0.43 mmol/liter). This decrease in glucose levels was reflected in the higher insulin levels attained in the GLP-1-treated animals (936+/-163 pmol/liter vs. 395+/-51 pmol/liter, GLP-1 vs. saline, respectively, P < 0.01), detected 15 min after glucose injection. GLP-1 treatment also increased pancreatic insulin, GLUT2, and glucokinase mRNA in the old rats. The effects of GLP-1 were abolished by simultaneous infusion of exendin [9-39], a specific antagonist of GLP-1. GLP-1 is therefore able to reverse some of the known defects that arise in the beta cell of the pancreas of Wistar rats, not only by increasing insulin secretion but also by inducing significant changes at the molecular level. C1 NIA,GERONTOL RES CTR,DIABET SECT,LAB CLIN PHYSIOL,NIH,BALTIMORE,MD 21224. NR 37 TC 127 Z9 132 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 15 PY 1997 VL 99 IS 12 BP 2883 EP 2889 DI 10.1172/JCI119482 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XH277 UT WOS:A1997XH27700013 PM 9185511 ER PT J AU Kwon, TK Buchholz, MA Ponsalle, P Chrest, FJ Nordin, AA AF Kwon, TK Buchholz, MA Ponsalle, P Chrest, FJ Nordin, AA TI The regulation of p27(Kip1) expression following the polyclonal activation of murine G(0) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYCLIN-DEPENDENT KINASES; P70 S6 KINASE; LYMPHOCYTES-T; POTENTIAL MEDIATOR; PROTEIN-KINASE; CYCLOSPORINE-A; CDK INHIBITOR; RAPAMYCIN; G1; INTERLEUKIN-2 AB Polyclonal activation of murine G(0) T cells with immobilized anti-CD3 induces entry into the cell cycle as well as the subsequent cytokine-dependent proliferative response, G(0) T cells express high levels of p27(Kip1) protein and specific mRNA, which decline rapidly following activation. The decline in the expression of p27(Kip1) and sequestering of the inhibitor), protein by cdk4 and cdk6 correlated with the increase in cdk2 kinase activity during the G(1) phase, Anti-CD3 activation of G(0) T cells in the presence of cyclosporin A or rapamycin inhibited the down-regulation of p27(Kip1), the cellular levels of the inhibitor remained high, and the cells remained in the G(1) phase, PBu2 activation of G(0) T cells also did not result in the down-regulation of p27(Kip1) and the cells remained in G(1). In each instance IL-2 restored the down-regulation of p27(Kip1), resulting in a significant reduction in the level of the inhibitor, and stimulated the cells to progress through the cell cycle, Jurkat cells transfected with the p27GL-988 plasmid containing +l to -988 nt of the p27(Kip1) promoter region and subsequently exposed to rlL-2 resulted in a significant reduction in the activity of the p27(Kip1) promoter, These findings suggest that in addition to providing the signals required for activated T cells to traverse G(1)/S, IL-2 also influences the promoter function of p27(Kip1), which effectively induces transcriptional downregulation of the gene. C1 NIA,GERONTOL RES CTR,LAB CLIN PHYSIOL,NIH,BALTIMORE,MD 21224. NR 54 TC 55 Z9 56 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1997 VL 158 IS 12 BP 5642 EP 5648 PG 7 WC Immunology SC Immunology GA XE749 UT WOS:A1997XE74900010 PM 9190912 ER PT J AU BenBaruch, A Grimm, M Bengali, K Evans, GA Chertov, O Wang, JM Howard, OMZ Mukaida, N Matsushima, K Oppenheim, JJ AF BenBaruch, A Grimm, M Bengali, K Evans, GA Chertov, O Wang, JM Howard, OMZ Mukaida, N Matsushima, K Oppenheim, JJ TI The differential ability of IL-8 and neutrophil-activating peptide-2 to induce attenuation of chemotaxis is mediated by their divergent capabilities to phosphorylate CXCR2 (IL-8 receptor B) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; GROWTH-STIMULATORY ACTIVITY; NONHEMATOPOIETIC CELLS; SIGNAL-TRANSDUCTION; CARBOXYL-TERMINUS; DESENSITIZATION; BINDING; KINASE; NAP-2; BETA AB IL-8 and neutrophil-activating peptide-2 (NAP-2) are two closely related C-X-C chemokines that differ in their abilities to induce chemotaxis of human polymorphonuclear leukocytes (PMN), Although two IL-8R types are expressed by PMN, only CXCR2 binds NAP-2 and IL-8 with equally high affinity, By using enriched CXCR2-transfected 293 cells, we show that high doses of IL-8 induce attenuation of chemotaxis, while equivalent doses of NAP-2 do not, Phosphorylation analysis shows that IL-8 induces higher levels of phosphorylation of the carboxyl terminus of CXCR2 than does NAP-2, suggesting that the level of phosphorylation contributes to the ability of the chemokines to attenuate the chemotactic response, To directly evaluate this difference, we analyzed the ability of receptors mutated to delete regions that highly express potential phosphorylation sites to be phosphorylated and to mediate chemotactic attenuation, We found that a carboxyl terminus-truncated mutant of CXCR2 was not phosphorylated by high doses of IL-8, as determined by in vivo phosphorylation assays and by analysis of the electrophoretic mobility of the receptors on SDS-PAGE gels, This mutated receptor had a significantly lower ability to attenuate IL-8-induced chemotaxis, indicating that the attenuation of chemotaxis is mediated by chemokine-induced receptor phosphorylation, In conclusion, the data show that the greater ability of IL-8 to induce receptor phosphorylation contributes to its more potent attenuation of chemotaxis as compared with NAP-2, This differential phosphorylation by IL-8 and NAP-2 of CXCR2 provides a basis for the divergent outcome of PMN-induced inflammation in response to these two closely related C-X-C chemokines. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. KANAZAWA UNIV,CANC RES INST,DEPT PHARMACOL,KANAZAWA,ISHIKAWA 920,JAPAN. RI Howard, O M Zack/B-6117-2012; Mukaida, Naofumi/D-7623-2011 OI Howard, O M Zack/0000-0002-0505-7052; Mukaida, Naofumi/0000-0002-4193-1851 NR 41 TC 43 Z9 43 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1997 VL 158 IS 12 BP 5927 EP 5933 PG 7 WC Immunology SC Immunology GA XE749 UT WOS:A1997XE74900044 PM 9190946 ER PT J AU Levine, SJ Wu, T Shelhamer, JH AF Levine, SJ Wu, T Shelhamer, JH TI Extracellular release of the type I intracellular IL-1 receptor antagonist from human airway epithelial cells - Differential effects of IL-4, IL-13, IFN-gamma, and corticosteroids SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BRONCHOALVEOLAR LAVAGE FLUID; INTERLEUKIN-1 RECEPTOR; GENE-EXPRESSION; HUMAN KERATINOCYTES; SYMPTOMATIC ASTHMA; MESSENGER-RNA; BINDING; IL-1-BETA; INTERNALIZATION; IL-1-ALPHA AB Three IL-1R antagonists (IL-1Ra) exist: secreted IL-1Ra and intracellular IL-1Ra (icIL-1Ra) types I and II. We have previously reported that human airway epithelial cells (HAEC) express icIL-1Ra type I, which can be up-regulated by corticosteroids. This study assessed whether cytokines and corticosteroids differentially effect icIL-1Ra type I protein release from HAEC to the extracellular compartment. We report that icIL-1Ra type I mRNA and intracellular protein are up-regulated in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, in response to IL-4, IL-13, IFN-gamma, and dexamethasone. The icIL-1Ra type I protein was detected in concentrated cell culture supernatants from NCI-H292 cells and normal human bronchial epithelial cells. The release of biologically relevant concentrations of active IL-1Ra from normal human bronchial epithelial cells was demonstrated by the ability of a neutralizing anti-IL-1Ra Ab to augment IL-1 beta-mediated IL-8 secretion. IL-4, IL-13, and IFN-gamma induced immunoreactive IL-1Ra release into supernatants from NCI-H292 cells, Dexamethasone inhibited constitutive and cytokine-induced release of immunoreactive IL-1Ra. The release of icIL-1Ra type I protein was not related to cytotoxicity, as measured by lactate dehydrogenase. We propose that icIL-1Ra type I release from HAEC represents a novel mechanism by which IL-1 bioactivity in the airway microenvironment may be modulated, Cytokine-mediated icIL-1Ra type I synthesis may increase both intracellular protein and release to the extracellular space, where cell surface IL-1R can be antagonized, In contrast, corticosteroid-induced increases in icIL-1Ra type I synthesis and inhibition of extracellular protein release promote accumulation of icIL-1Ra type I protein within the intracellular compartment. RP Levine, SJ (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,10 CTR DR,MSC 1662,BETHESDA,MD 20892, USA. NR 42 TC 46 Z9 46 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1997 VL 158 IS 12 BP 5949 EP 5957 PG 9 WC Immunology SC Immunology GA XE749 UT WOS:A1997XE74900047 PM 9190949 ER PT J AU Jones, LS Rizzo, LV Agarwal, RK Tarrant, TK Chan, CC Wiggert, B Caspi, RR AF Jones, LS Rizzo, LV Agarwal, RK Tarrant, TK Chan, CC Wiggert, B Caspi, RR TI IFN-gamma-deficient mice develop experimental autoimmune uveitis in the context of a deviant effector response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; RETINOID-BINDING PROTEIN; INTERFERON-GAMMA; FACTOR-ALPHA; T-CELLS; FUNCTIONAL-PROPERTIES; LYMPHOKINE PRODUCTION; ANTIGEN PRESENTATION; ENDOTHELIAL-CELLS; EXPRESSION AB Experimental autoimmune uveitis (EAU) is a T cell-mediated disease that targets the neural retina and serves as a model of human uveitis, Uveitogenic effector T cells have a Th1-like phenotype (high IFN-gamma, low IL-4), and genetic susceptibility to EAU is associated with an elevated Th1 response, Here we investigate whether the ability to produce IFN-gamma is necessary for the development of EAU by immunizing IFN-gamma-deficient (GKO) mice with the uveitogenic protein interphotoreceptor retinoid binding protein (IRBP) and characterize the associated immunologic responses, GKO mice developed EAU comparable in severity and incidence to that of their wild-type littermates, However, the cytokine profile in their uveitic eyes as well as the cytokines produced by primed lymph node cells ire response to IRBP showed a distinct profile: undiminished TNF-alpha and elevated IL-5, IL-6 IL-10, and lymphotoxin (but not IL-4) responses,The inflammatory infiltrate in GKO eyes contained an excess of granulocytes and IL-5- and IL-6-producing cells, but uveitic GKO mice did not up-regulate inducible nitric oxide synthase, GKOs had enhanced lymphocyte proliferation and delayed-type hypersensitivity responses to IRBP, Histology of the delayed-type hypersensitivity lesion in GKO had superimposed elements of an allergic-like response, Anti-IRBP Ab isotypes of GKO mice showed a reduction of IgG2a, but no enhancement of IgG1. Comparison of responses in +/+ and +/- wild-type mice revealed some limited evidence of a gene-dose effect, We conclude that IFN-gamma is not required for priming of pathogenic T cells or for effecting the retinal damage and photoreceptor loss typical of EAU, However, what appears to be a grossly similar disease is caused in the GKO by a deviant type of effector response. C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NEI,RETINAL CELL & MOL BIOL LAB,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. RI Rizzo, Luiz Vicente/B-4458-2009 NR 41 TC 145 Z9 150 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1997 VL 158 IS 12 BP 5997 EP 6005 PG 9 WC Immunology SC Immunology GA XE749 UT WOS:A1997XE74900052 PM 9190954 ER PT J AU Maurer, JA Wray, S AF Maurer, JA Wray, S TI Neuronal dopamine subpopulations maintained in hypothalamic slice explant cultures exhibit distinct tyrosine hydroxylase mRNA turnover rates SO JOURNAL OF NEUROSCIENCE LA English DT Article DE gene expression; mRNA stability; organotypic; arcuate nucleus; DRB; actinomycin D ID VASOPRESSIN MESSENGER-RNA; MEDIAL ZONA INCERTA; ADRENAL CHROMAFFIN CELLS; PROTEIN-KINASE-C; SUPRACHIASMATIC NUCLEUS; GENE-EXPRESSION; IMMUNOREACTIVE NEURONS; ARCUATE NUCLEI; CYCLIC-AMP; TRANSCRIPTION AB Changes in mRNA stability have been shown to regulate critical intracellular processes, In this investigation, we studied tyrosine hydroxylase (TH) mRNA turnover in functionally and anatomically distinct dopaminergic (DA) populations of the rat hypothalamus. To this end, long-term slice explant cultures from postnatal, preoptic area/hypothalami, containing three anatomically discrete DA populations, were generated and maintained under defined conditions. The organotypic cultures were treated with the transcription inhibitors 5,6-dichloro-1-D-ribofuranosylbenzimidazole or actinomycin D and processed for in situ hybridization histochemistry. Relative TH mRNA content per cell was quantitated. Single-cell analysis showed marked differences in basal TH mRNA turnover rates between DA neuronal populations. Anterior and midhypothalamic DA neurons exhibited half-time turnovers of 9-12 and 11-23 hr, respectively. In contrast, in the caudal hypothalamus, DA neurons of the arcuate nucleus had a significantly lower baseline level and more rapid turnover (6-7 hr) of TH mRNA, This investigation shows that basal turnover of a phenotypic mRNA, TH mRNA in DA neurons, is not an intrinsic property of the phenotypic marker. Furthermore, we found that destabilization of TH mRNA in the caudal hypothalamus corresponds to the known rhythmic output displayed by arcuate DA cells and, as such, may be critical for normal function of this population, We propose that intrinsic differences in the post-transcriptional regulation of TH permits neuronal subpopulations, which subserve different physiological functions, an additional mechanism to control DA biosynthesis in response to their unique needs. C1 NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. OI wray, susan/0000-0001-7670-3915 NR 52 TC 20 Z9 20 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 15 PY 1997 VL 17 IS 12 BP 4552 EP 4561 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XG318 UT WOS:A1997XG31800006 PM 9169516 ER PT J AU Liesi, P Wright, JM Krauthamer, V AF Liesi, P Wright, JM Krauthamer, V TI BAPTA-AM and ethanol protect cerebellar granule neurons from the destructive effect of the weaver gene SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE BAPTA-AM; calcium; cerebellum; ethanol; granule neurons; rescue; weaver ID BRAIN MICROSOMES; MOUSE CEREBELLUM; CALCIUM; CHANNEL; CELLS; DEATH; MICE AB The mechanisms by which the weaver gene (Reeves et al., 1989; Patil et al., 1995) inhibits neurite extension and/or induces death of the granule neurons in homozygous weaver mouse cerebellum are not presently understood, Here we show that BAPTA-AM and ethanol, which either reduce cytosolic levels of free calcium or prevent calcium entry, promote neurite outgrowth of the weaver neurons similar to the L-type calcium channel blocker verapamil (Liesi and Wright, 1996), Importantly, BAPTA-AM, ethanol, and verapamil not only restore neurite outgrowth of the weaver neurons but adjust their depolarized resting membrane potentials to the levels of normal neurons, These results indicate that calcium-dependent mechanisms mediate the action of the weaver gene and that the weaver neurons can be normalized by blocking this calcium effect, We further report that BAPTA-AM and verapamil also have a neuroprotective effect on normal neurons exposed to high concentrations of ethanol. We suggest that verapamil should be evaluated as a drug for treatment of alcohol-induced brain damage and neurodegenerative disorders. (C) 1997 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT PHYSIOL, BALTIMORE, MD USA. US FDA, CTR DEVICES & RADIOL HLTH, ROCKVILLE, MD 20857 USA. RP Liesi, P (reprint author), NIAAA, NIH, MOL & CELLULAR NEUROBIOL LAB, 12501 WASHINGTON AVE, ROCKVILLE, MD 20852 USA. NR 19 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 15 PY 1997 VL 48 IS 6 BP 571 EP 579 DI 10.1002/(SICI)1097-4547(19970615)48:6<571::AID-JNR10>3.0.CO;2-Y PG 9 WC Neurosciences SC Neurosciences & Neurology GA XH195 UT WOS:A1997XH19500010 PM 9210527 ER PT J AU Gelfand, MS Koonin, EV AF Gelfand, MS Koonin, EV TI Avoidance of palindromic words in bacterial and archaeal genomes: A close connection with restriction enzymes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HAEMOPHILUS-INFLUENZAE RD; NUCLEOTIDE-SEQUENCES; DNA-SEQUENCES; MODIFICATION SYSTEMS; OVER-REPRESENTATION; ESCHERICHIA-COLI; LINGUISTICS; EVOLUTION; SELECTION; DIVERSITY AB Short palindromic sequences (4, 5 and 6 bp palindromes) are avoided at a statistically significant level in the genomes of several bacteria, including the completely sequenced Haemophilus influenzae and Synechocystis sp, genomes and in the complete genome of the archaeon Methanococcus jannaschii. In contrast, there is only moderate avoidance of palindromes in the small genome of the bacterium Mycoplasma genitalium and no detectable avoidance in the genomes of chloroplasts and mitochondria. The sites for type II restriction-modification enzymes detected in the given species tend to be among the most avoided palindromes in a particular genome, indicating a direct connection between the avoidance of short oligonucleotide words and restriction-modification systems with the respective specificity. Palindromes corresponding to sites for restriction enzymes from other species are also avoided, albeit less significantly suggesting that in the course of evolution bacterial DNA has been exposed to a wide spectrum of restriction enzymes, probably as the result of lateral transfer mediated by mobile genetic elements, such as plasmids and prophages. Palindromic words appear to accumulate in DNA once it becomes isolated from restriction-modification systems, as demonstrated by the case of organellar genomes. By combining these observations with protein sequence analysis, we show that the most avoided 4-palindrome and the most avoided 6-palindrome in the archaeon M.jannaschii are likely to be recognition sites for two novel restriction-modification systems. C1 NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894. RP Gelfand, MS (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO,MOSCOW REGION,RUSSIA. RI Gelfand, Mikhail/F-3425-2012 NR 32 TC 89 Z9 93 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 15 PY 1997 VL 25 IS 12 BP 2430 EP 2439 DI 10.1093/nar/25.12.2430 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XF705 UT WOS:A1997XF70500026 PM 9171096 ER PT J AU Barlow, C Schroeder, M LekstromHimes, J Kylefjord, H Deng, CX WynshawBoris, A Spiegelman, BM Xanthopoulos, KG AF Barlow, C Schroeder, M LekstromHimes, J Kylefjord, H Deng, CX WynshawBoris, A Spiegelman, BM Xanthopoulos, KG TI Targeted expression of Cre recombinase to adipose tissue of transgenic mice directs adipose-specific excision of loxP-flanked gene segments SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SITE-SPECIFIC RECOMBINATION; DNA RECOMBINATION; BACTERIOPHAGE-P1 AB Functional analysis of mammalian genes relies, in part, on targeted mutations generated by homologous recombination in mice. We have developed a strategy for adipose-specific inactivation of loxP-floxed gene segments. Transgenic mice have been established that express Cre recombinase under the control of the adipose-specific aP2 enhancer/promoter. Crossing of the aP2/Cre mice with any loxP-floxed gene will facilitate its functional analysis in adipose tissue. C1 NATL HUMAN GENOME RES INST,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL SCI & MOL PHARMACOL,BOSTON,MA 02115. RP Barlow, C (reprint author), NIH,LAB GENET DIS RES,BLDG 10,BETHESDA,MD 20892, USA. RI deng, chuxia/N-6713-2016 NR 14 TC 42 Z9 44 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 15 PY 1997 VL 25 IS 12 BP 2543 EP 2545 DI 10.1093/nar/25.12.2543 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XF705 UT WOS:A1997XF70500045 PM 9171115 ER PT J AU Merryman, P Cullinane, A Horne, M AF Merryman, P Cullinane, A Horne, M TI Comparison of two ELISAs for platelet factor 4 SO THROMBOSIS RESEARCH LA English DT Letter DE platelet factor 4; ELISA; immunoassay C1 NIH,DEPT CLIN PATHOL,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NR 2 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD JUN 15 PY 1997 VL 86 IS 6 BP 525 EP 526 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XH022 UT WOS:A1997XH02200010 PM 9219332 ER PT J AU Epinat, JC Whiteside, ST Rice, NR Israel, A AF Epinat, JC Whiteside, ST Rice, NR Israel, A TI Reconstitution of the NF-kappa B system in Saccharomyces cerevisiae for isolation of effectors by phenotype modulation SO YEAST LA English DT Article DE NF-kappa B; genetic complimentation ID DNA-BINDING SUBUNIT; CANDIDATE PROTOONCOGENE BCL-3; SIGNAL-TRANSDUCTION PATHWAY; MAP KINASE; PROTO-ONCOGENE; V-REL; RETICULOENDOTHELIOSIS VIRUS; TRANSCRIPTION FACTORS; ACTIVATION DOMAINS; SHUTTLE VECTORS AB NF-kappa B is a ubiquitous transcription factor that contributes to the induction of many genes playing a central role in immune and inflammatory responses. The NF-kappa B proteins are subject to multiple regulatory influences including post-translational modifications such as phosphorylation and proteolytic processing. A very important component of this regulation is the control of their subcellular localization: cytoplasmic retention of NF-kappa B is achieved through interaction with I kappa B molecules. In response to extracellular signals, these molecules undergo degradation, NF-kappa B translocates to the nucleus and activates its target genes. To investigate novel proteins involved in this dynamic response, we have reconstituted the NF-kappa B/I kappa B system in the yeast Saccharomyces cerevisiae. We have successively introduced p65, the main transcriptional activator of the NF-kappa B family, which leads to the activation of two reporter genes control-ed by kappa B sites, and the I kappa B alpha inhibitory protein, which abolishes this activation. By transforming such a yeast strain with a cDNA library we have performed a genetic screen for cDNAs encoding proteins capable of either dissociating the p65/I kappa B alpha complex or directly transactivating the expression of the reporter genes. The efficiency of our screen was demonstrated by the isolation of a cDNA encoding the p105 precursor of the p50 subunit of NF-kappa B. We also used this system to test stimuli known to activate signalling pathways in yeast, in order to investigate whether the related mammalian cascades might be involved in NF-kappa B activation. We showed that yeast endogenous kinase cascades activated by pheromone, hypo- or hyperosmotic shock cannot modulate NF-kappa B activity in our system, and that the p38 human MAP kinase does not act directly on the p65/I kappa B alpha complex. (C) 1997 by John Wiley & Sons, Ltd. C1 INST PASTEUR,CNRS,UMR 0321,UNITE BIOL MOL EXPRESS GEN,F-75724 PARIS 15,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,LAB MOL VIROL & CARINOGENESIS,FREDERICK,MD 21702. FU PHS HHS [N01-C0-46000] NR 71 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-503X J9 YEAST JI Yeast PD JUN 15 PY 1997 VL 13 IS 7 BP 599 EP 612 DI 10.1002/(SICI)1097-0061(19970615)13:7<599::AID-YEA109>3.0.CO;2-H PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA XE435 UT WOS:A1997XE43500001 PM 9200810 ER PT J AU Rapola, JM Virtamo, J Ripatti, S Huttunen, JK Albanes, D Taylor, PR Heinonen, OP AF Rapola, JM Virtamo, J Ripatti, S Huttunen, JK Albanes, D Taylor, PR Heinonen, OP TI Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction SO LANCET LA English DT Article ID VITAMIN-E CONSUMPTION; HEART-DISEASE; ATHEROSCLEROTIC PLAQUE; RISK; MORTALITY; ANGINA; LASER AB Background Epidemiological data suggest that the intake of antioxidants such as alpha-tocopherol (vitamin E) and beta-carotene has an inverse correlation with the incidence of coronary heart disease. The results from clinical of antioxidant supplementation in people with coronary heart disease are inconclusive. Methods We studied the frequency of major coronary events in 1862 men enrolled in the Alpha-tocopherol Beta-carotene Cancer Prevention Study (smokers aged between 50 and 69 years) who had a previous myocardial infarction. In this randomised, double-blind, placebo-controlled study, men had received dietary supplements of alpha-tocopherol (50 mg/day), beta-carotene (20 mg/day), both, or placebo. The median follow-up was 5.3 years. The endpoint of this substudy was the first major coronary event after randomisation. Analyses were by intention to treat. Findings 424 major coronary events (non-fatal myocardial infarction and fatal coronary heart disease) occurred during follow-up. There were no significant differences in the number of major coronary events between any supplementation group and the placebo group (alpha-tocopherol 94/466; beta-carotene 113/461; alpha-tocopherol and beta-carotene 123/497; placebo 94/438 [log-rank test, p=0.25]). There were significantly more deaths from fatal coronary heart disease in the beta-carotene (74/461, multivariate-adjusted relative risk 1.75 [95% CI 1.16-2.64], p=0.007) and combined alpha-tocopherol and beta-carotene groups (67/497, relative risk 1.58 [1.05-2.40], p=0.03) than in the placebo group (39/438), but there was no significant increase in the alpha-tocopherol supplementation group (54/466, relative risk 1.33 [0.86-2.05], p=0.20). Interpretation The proportion of major coronary events in men with a previous myocardial infarction who smoke was not decreased with either alpha-tocopherol or beta-carotene supplements. In fact, the risk of fatal coronary heart disease increased in the groups that received either beta-carotene or the combination of alpha-tocopherol and beta-carotene; there was a non-significant trend of increased deaths in the alpha-tocopherol group. We do not recommend the use of alpha-tocopherol or beta-carotene supplements in this group of patients. C1 NCI,BETHESDA,MD 20892. UNIV HELSINKI,DEPT PUBL HLTH,HELSINKI,FINLAND. RP Rapola, JM (reprint author), NATL PUBL HLTH INST,MANNERHEIMINTIE 166,FIN-00300 HELSINKI,FINLAND. RI Albanes, Demetrius/B-9749-2015; Ripatti, Samuli/H-9446-2014 OI Ripatti, Samuli/0000-0002-0504-1202 FU NCI NIH HHS [N01-CN-45165] NR 29 TC 409 Z9 419 U1 0 U2 17 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 14 PY 1997 VL 349 IS 9067 BP 1715 EP 1720 DI 10.1016/S0140-6736(97)01234-8 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XE065 UT WOS:A1997XE06500007 PM 9193380 ER PT J AU Rhee, SG Bae, YS AF Rhee, SG Bae, YS TI Regulation of phosphoinositide-specific phospholipase C isozymes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID SMOOTH-MUSCLE CELLS; G-PROTEINS; C-GAMMA-1; RECEPTOR; PHOSPHORYLATION; ACTIVATION; SUBUNIT; SIGNAL; CYCLE; G(Q) RP Rhee, SG (reprint author), NHLBI,LAB CELL SIGNALING,NIH,BLDG 3,RM 122,3 CTR DR,MSC 0320,BETHESDA,MD 20892, USA. NR 50 TC 740 Z9 756 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 1997 VL 272 IS 24 BP 15045 EP 15048 DI 10.1074/jbc.272.24.15045 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE034 UT WOS:A1997XE03400002 PM 9182519 ER PT J AU DellAngelica, EC Ooi, CE Bonifacino, JS AF DellAngelica, EC Ooi, CE Bonifacino, JS TI beta 3A-adaptin, a subunit of the adaptor-like complex AP-3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLATHRIN-COATED VESICLES; PLASMA-MEMBRANE; PROTEIN COMPLEX; ALPHA-ADAPTIN; BINDING; RECEPTOR; PITS; SIGNALS; DOMAIN; PHOSPHORYLATION AB Recent studies have described a widely expressed adaptor-like complex, named AP-3, which is likely involved in protein sorting in exocytic/endocytic pathways. The AP-3 complex is composed of four distinct subunits. Here, we report the identification of one of the subunits of this complex, which we call beta 3A-adaptin. The predicted amino acid sequence of beta 3A-adaptin reveals that the protein is closely related to the neuron-specific protein beta-NAP (61% overall identity) and more distantly related to the beta 1- and beta 2-adaptin subunits of the clathrin-associated adaptor complexes AP-1 and AP-2, respectively. Sequence comparisons also suggest that: beta 3A-adaptin has a domain organization similar to beta-NAP and to beta 1- and beta 2-adaptins, beta 3A-adaptin is expressed in all tissues and cells examined. Go-purification and co-precipitation analysesdemonstrate that beta 3A-adaptin corresponds to the similar to 140-kDa subunit of the ubiquitous AP-3 complex, the other subunits being delta-adaptin, p47A (now called mu 3A) and sigma 3 (A or 8). beta 3A-adaptin is phosphorylated on serine residues in vivo while the other subunits of the complex are not detectably phosphorylated, beta 3A-adaptin is not present in significant amounts in clathrin-coated vesicles, The characteristics of beta 3A-adaptin reported here lend support to the idea that AP-3 is a structural and functional homolog of the clathrin-associated adaptors AP-1 and AP-2. C1 NICHHD, CBMB, NIH, BETHESDA, MD 20892 USA. NR 52 TC 108 Z9 109 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 1997 VL 272 IS 24 BP 15078 EP 15084 DI 10.1074/jbc.272.24.15078 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE034 UT WOS:A1997XE03400009 PM 9182526 ER PT J AU Hatakeyama, S Jensen, JP Weissman, AM AF Hatakeyama, S Jensen, JP Weissman, AM TI Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-END RULE; CELL ANTIGEN RECEPTOR; IN-VIVO; NUCLEAR-LOCALIZATION; ACTIVATING ENZYME; ESCHERICHIA-COLI; CARRIER PROTEIN; ZETA-CHAIN; KAPPA-B; DEGRADATION AB In most instances, the transfer of ubiquitin to target proteins is catalyzed by the action of ubiquitin protein ligases (E3s), Full-length cDNAs encoding murine E6-associated protein (mE6-AP) as well as Nedd-4, a protein that is homologous to E6-AP in its C terminus, were cloned. Nedd-4 and mouse E6-AP are both enzymatically active E3s and function with members of the UbcH5 family of E2s, Mouse E6-AP, like its human counterpart, ubiquitinates p53 in the presence of human papilloma virus E6 protein, while Nedd-4 does not, Consistent with its role in p53 ubiquitination, mE6-AP was found both in the nucleus and cytosol, while Nedd-4 was found only in the cytosol, Binding studies implicate a 150-amino acid region that is 40% identical between mE6-AP and Nedd-4 as a binding site for the C terminal portion of an E2 enzyme (UbcH5B), Nedd-4 was determined to have a second nonoverlapping E2 binding site that recognizes the first 67 amino acids of UbcH5B but not the more C-terminal portion of this E2. These findings provide the first demonstration of physical interactions between mammalian E2s and E3s and establish that these interactions occur independently of ubiquitin and an intact E3 catalytic domain, Furthermore, the presence of two E2 binding sites within Nedd-4 suggests models for ubiquitination involving multiple E2 enzymes associated with E3s. C1 NCI,LAB IMMUNE CELL BIOL,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Hatakeyama, Shigetsugu/C-8333-2012 OI Hatakeyama, Shigetsugu/0000-0002-2150-9979 NR 54 TC 76 Z9 79 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 1997 VL 272 IS 24 BP 15085 EP 15092 DI 10.1074/jbc.272.24.15085 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE034 UT WOS:A1997XE03400010 PM 9182527 ER PT J AU Bessen, RA Raymond, GJ Caughey, B AF Bessen, RA Raymond, GJ Caughey, B TI In situ formation of protease-resistant prion protein in transmissible spongiform encephalopathy-infected brain slices SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CREUTZFELDT-JAKOB DISEASE; FATAL FAMILIAL INSOMNIA; AMYLOID PLAQUES; MOUSE SCRAPIE; PRP; FIBRILS; CONVERSION; HAMSTERS; STRAIN; MICE AB The transmissible spongiform encephalopathies (TSEs) comprise a group of fatal neurodegenerative diseases that are characterized by the conversion of the normal host cellular prion protein (PrPc), to the abnormal protease-resistant prion protein isoform (PrP-res). It has been proposed, though not proven, that the infectious TSE agent consists solely of PrP-res and that PrP-res-induced conformational conversion of PrPc to additional PrP res represents agent replication. In this study we demonstrate in situ conversion of protease-sensitive PrPc to PrP-res in TSE-infected brain slices. One step in this process is the binding of soluble PrPc to endogenous PrP-res deposits. The newly formed PrP-res associated with the slices in a pattern that correlated with the pre-existing brain distribution of PrP-res. Punctate in situ PrP conversion was observed in brain regions containing PrP-res amyloid plaques, and a more dispersed conversion product was detected in areas containing diffuse PrP-res deposits. These studies provide direct evidence that PrP-res formation involves the incorporation of soluble PrPc into both nonfibrillar and fibrillar PrP-res deposits in TSE-infected Ir,rain. Our findings suggest that the in situ PrP conversion reaction leads to additional polymerization of endogenous PrP-res aggregates and is analogous to the process of PrP-res fibril and subfibril growth in vivo. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,NIH,HAMILTON,MT 59840. NR 50 TC 36 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 1997 VL 272 IS 24 BP 15227 EP 15231 DI 10.1074/jbc.272.24.15227 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE034 UT WOS:A1997XE03400029 PM 9182546 ER PT J AU Komissarova, N Kashlev, M AF Komissarova, N Kashlev, M TI RNA polymerase switches between inactivated and activated states by translocating back and forth along the DNA and the RNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACILITATED TRANSCRIPT CLEAVAGE; ESCHERICHIA-COLI; TERNARY COMPLEXES; ELONGATION COMPLEXES; STRUCTURAL-ANALYSIS; CHAIN ELONGATION; TERMINATION; MECHANISM AB Important regulatory events in both prokaryotic and eukaryotic transcription are currently explained in terms of an inchworming model of elongation, In this model, RNA extension is carried out by a mobile catalytic center that, at certain DNA sites, advances within stationary RNA polymerase. This idea emerged from the observation that footprints of individual elongation complexes, halted in vitro at consecutive DNA positions, can remain fixed on the template for several contiguous nucleotide additions. Here, we examine in detail the structural transitions that occur immediately after the enzyme stops at sites where discontinuous advancement of RNA polymerase is observed, We demonstrate that halting at such special sites does not ''freeze'' RNA polymerase at one location but induces it to leave its initial position and to slide backward along the DNA and the RNA without degrading the transcript. The resulting loss of contact between the RNA S'-hydroxyl and the enzyme's catalytic center leads to temporary loss of the catalytic activity, This process is equilibrated with enzyme return to the original location, so that]RNA polymerase is envisaged as an oscillating object switching between catalytically active and inactive states. The retreated isoform constitutes a principal intermediate in factor-induced endonucleolytic RNA cleavage. These oscillations of RNA polymerase can explain its apparent discontinuous advancement, which had been interpreted as indicating flexibility within the enzyme. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. PUBL HLTH RES INST CITY NEW YORK INC,NEW YORK,NY 10016. FU NIGMS NIH HHS [GM49242] NR 32 TC 172 Z9 178 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 1997 VL 272 IS 24 BP 15329 EP 15338 DI 10.1074/jbc.272.24.15329 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE034 UT WOS:A1997XE03400044 PM 9182561 ER PT J AU Kirken, RA Malabarba, MG Xu, J DaSilva, L Erwin, RA Liu, XW Hennighausen, L Rui, H Farrar, WL AF Kirken, RA Malabarba, MG Xu, J DaSilva, L Erwin, RA Liu, XW Hennighausen, L Rui, H Farrar, WL TI Two discrete regions of interleukin-2 (IL2) receptor beta independently mediate IL2 activation of a PD98059/Rapamycin/Wortmannin-insensitive Stat5a/b serine kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-CHAIN; FUNCTIONAL COMPONENT; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; TERMINAL REGION; TYROSINE; ASSOCIATION; EXPRESSION; IL-2 AB Many cytokines, hormones, and growth factors activate Janus kinases to tyrosine phosphorylate select members of the Stat transcription factors, For full transcriptional activation, Stat1 and Stat3 also require phosphorylation of a conserved serine residue within a mitogen-activated protein kinase phosphorylation consensus site. On the other hand, two recently identified and highly homologous Stat5a and Stat5b proteins lack this putative mitogen-activated protein kinase phosphorylation site, The present study set out to establish whether Stat5a and Stat5b are under the control of an interleukin-2 (IL2)-activated Stat5 serine kinase, We now report that IL2 stimulated marked phosphorylation of serine and tyrosine residues of both Stat5a and Stat5b in human T lymphocytes and in several IL2-responsive lymphocytic cell lines, No Stat5a/b phosphothreonine was detected. Phosphoamino acid analysis also revealed that Stat5a/b phosphotyrosine levels were maximized within 1-5 min of IL2 stimulation, whereas serine phosphorylation kinetics were slower, Interestingly, IL2-induced serine phosphorylation of Stat5a differed quantitatively and temporally from that of Stat5b with Stat5a serine phosphorylation leveling off after 10 min and the more pronounced Stat5b response continuing to rise for at least 60 min of IL2 stimulation, Furthermore, we identified two discrete domains of IL2 receptor beta (IL2R beta) that could independently restore the ability of a truncated IL2R beta mutant to mediate Stat5a/b phosphorylation and DNA binding to the gamma-activated site of the beta-casein gene promoter, These observations demonstrated that there is no strict requirement for one particular IL2R beta region for Stat5 phosphorylation. Finally, we established that the IL2-activated Stat5a/b serine kinase is insensitive to several selective inhibitors of known IL2-stimulated kinases including MEK1/MEK2 (PD98059), mTOR (rapamycin), and phosphatidylinositol 3 kinase (wortmannin) as determined by phosphoamino acid and DNA binding analysis, thus suggesting that a yet-to-be-identified serine kinase mediates Stat5a/b activation. C1 SCI APPLICAT INT CORP,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. NIDDK,NIH,BIOCHEM & METAB LAB,BETHESDA,MD 20892. RP Kirken, RA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,LAB MOL IMMUNOREGULAT,FREDERICK,MD 21702, USA. RI Malabarba, Maria Grazia/L-4805-2015 OI Malabarba, Maria Grazia/0000-0002-9457-2047 NR 48 TC 58 Z9 58 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 1997 VL 272 IS 24 BP 15459 EP 15465 DI 10.1074/jbc.272.24.15459 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE034 UT WOS:A1997XE03400061 PM 9182578 ER PT J AU Grossmann, M Szkudlinski, MW Wong, R Dias, JA Ji, TH Weintraub, BD AF Grossmann, M Szkudlinski, MW Wong, R Dias, JA Ji, TH Weintraub, BD TI Substitution of the seat-belt region of the thyroid-stimulating hormone (TSH) beta-subunit with the corresponding regions of choriogonadotropin or follitropin confers luteotropic but not follitropic activity to chimeric TSH SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; SITE-DIRECTED MUTAGENESIS; RECEPTOR-BINDING REGION; GLYCOPROTEIN HORMONES; BIOLOGICAL-ACTIVITY; ALPHA-SUBUNIT; SIGNAL-TRANSDUCTION; HUMAN THYROTROPIN; LUTROPIN; EXPRESSION AB The region between the 10th and 12th cysteine (Cys(88)-Cys(105) in human thyroid-stimulating hormone beta-subunit (hTSH beta)) of the glycoprotein hormone beta-subunits corresponds to the disulfide-linked seat-belt region. It wraps around the common alpha-subunit and has been implicated in regulating specificity between human choriogonado-tropin (hCG) and human follicle-stimulating hormone (hFSH), but determinants of hTSH specificity are unknown, To characterize the role of this region for hTSH, we constructed hTSH chimeras in which the entire seatbelt region Cys(88)-Cys(105) or individual intercysteine segments Cys(88)-Cys(95) and Cys(95)-Cys(105) were replaced with the corresponding sequences of hCG and hFSH or alanine cassettes. Alanine cassette mutagenesis of hTSH showed that the Cys(95)-Cys(105) segment of the seat-belt was more important for TSI-I receptor binding and signal transduction than the Cys(88)-Cys(95) determinant loop region. Replacing the entire seat-belt of hTSH beta with the hCG sequence conferred full hCG receptor binding and activation to the hTSH chimera, whereas TSI-I receptor binding and activation were abolished. Conversely, introduction of the hTSH beta seat-belt sequence into hCG beta generated an hCG chimera that bound to and activated the TSH receptor but not the CG/lutropin (LH) receptor. In contrast, an hTSH chimera bearing hFSH seat-belt residues did not possess any follitropic activity, and its thyrotropic activity was only slightly reduced. This may in part be due to the fact that the net charge of the seat-belt is similar in hTSH and hFSH but different from hCG. However, exchanging other regions of charge heterogeneity between hTSH beta and hFSH beta did not confer follitropic activity to hTSH. Thus, exchanging the seatbelt region between hTSH and hCG; switches hormonal specificity in a mutually exclusive fashion, In contrast, the seat-belt appears not to discriminate between the TSH and the FSH receptors, indicating for the first time that domains outside the seat-belt region contribute to glycoprotein hormone specificity. C1 UNIV MARYLAND,SCH MED,DEPT MED,MOL ENDOCRINOL LAB,BALTIMORE,MD 21201. NIDDK,MOL & CELLULAR ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,ALBANY,NY 12201. UNIV WYOMING,DEPT MOL BIOL,LARAMIE,WY 82071. RP Grossmann, M (reprint author), CTR MED BIOTECHNOL,INST HUMAN VIROL,MOL ENDOCRINOL LAB,725 W LOMBARD ST,N457,BALTIMORE,MD 21201, USA. NR 36 TC 61 Z9 62 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 1997 VL 272 IS 24 BP 15532 EP 15540 DI 10.1074/jbc.272.24.15532 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE034 UT WOS:A1997XE03400072 PM 9182589 ER PT J AU Vaughan, RA Huff, RA Uhl, GR Kuhar, MJ AF Vaughan, RA Huff, RA Uhl, GR Kuhar, MJ TI Protein kinase C-mediated phosphorylation and functional regulation of dopamine transporters in striatal synaptosomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COCAINE; RECEPTORS; CLONING; EXPRESSION; ACTIVATION; CELLS; MODULATION; PROGRESS; BRAIN; CDNA AB Dopamine transporters (DATs) are members of a family of Na+- and Cl--dependent neurotransmitter transporters responsible for the rapid clearance of dopamine from synaptic clefts, The predicted primary sequence of DAT contains numerous consensus phosphorylation sites, In this report we demonstrate that DATs undergo endogenous phosphorylation in striatal synaptosomes that is regulated by activators of protein kinase C. Rat striatal synaptosomes were metabolically labeled with [P-32]orthophosphate, and solubilized homogenates were subjected to immunoprecipitation with am antiserum specific for DAT, Basal phosphorylation occurred in the absence of exogenous treatments, and the phosphorylation level was rapidly increased when synaptosomes were treated with the phosphatase inhibitors okadaic acid or calyculin, Treatment of synaptosomes with the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) also increased the level of phosphate incorporation. This occurred within 10 min and was dose-dependent between 0.1 and 1 mu M PMA, DAT phosphorylation was also significantly increased by two other protein kinase C activators, (-)-indolactam V and 1-oleoyl-2-acetyl sn glycerol. The inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate at 10 mu M was without effect, and PMA-induced phosphorylation was blocked by treatment of synaptosomes with the protein kinase C inhibitors staurosporine and bisindoylmaleimide. These results indicate that DATs undergo rapid in vivo phosphorylation in response to protein kinase C activation and that a robust mechanism exists in synaptosomes for DAT dephosphorylation, Dopamine transport activity in synaptosomes was reduced by all treatments that promoted DAT phosphorylation, with comparable dose, time, and inhibitor characteristics. The change in transport activity was produced by a reduction in V-max with no significant effect on the K-m for dopamine, These results suggest that synaptosomal dopamine transport activity is regulated by phosphorylation of DAT and present a potential mechanism for local neuronal control of synaptic neurotransmitter levels and consequent downstream neural activity. C1 EMORY UNIV,YERKES REG PRIMATE RES CTR,DIV NEUROSCI,ATLANTA,GA 30322. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. RP Vaughan, RA (reprint author), NIDA,IRP,MOL NEUROBIOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. FU NCRR NIH HHS [RR00165] NR 38 TC 178 Z9 179 U1 3 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 1997 VL 272 IS 24 BP 15541 EP 15546 DI 10.1074/jbc.272.24.15541 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE034 UT WOS:A1997XE03400073 PM 9182590 ER PT J AU Olivero, OA Chang, PK LopezLarraza, DM SeminoMora, MC Poirier, MC AF Olivero, OA Chang, PK LopezLarraza, DM SeminoMora, MC Poirier, MC TI Preferential formation and decreased removal of cisplatin-DNA adducts in Chinese hamster ovary cell mitochondrial DNA as compared to nuclear DNA SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article ID COLLOIDAL GOLD; CROSS-LINK; REPAIR; BINDING; BENZOPYRENE; DAMAGE AB Levels of DNA adducts in Chinese hamster ovary (CHO) cells exposed to cis-diamminedichloroplatinum(II) (cisplatin) for 24 h, have been shown to be 4- to 6-fold higher in mitochondrial (mt) DNA as compared to nuclear (n) DNA (Olivero et al., Mutation Res., 346 (1995) 221). The aim of the present study was to understand if the preferential cisplatin binding in mtDNA is partially caused by lack of adduct removal in the mitochondria. Chinese hamster ovary cells were exposed for 6 h to 50 mu M cisplatin, followed by incubation for 24 and 48 h in cisplatin-free medium. At the 30-h time point (6 h with cisplatin, 24 h without cisplatin), half of the cells from each plate were harvested and the remainder were cultured and harvested at 54 h (6 h with cisplatin, 48 h without cisplatin). The 30- and 54-h time points are called 'T-30' and 'T-54', respectively. Cisplatin-DNA adducts were measured in DNA from nuclear and mitochondrial fractions by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA), a sensitive competitive microtiter-based immunoassay utilizing antiserum elicited against cisplatin-modified DNA. An initial higher level of cisplatin-DNA adducts was observed in mtDNA when compared to nDNA, at T-30. In addition, a lack of removal of adducts in mtDNA was demonstrated in cells at T-54. Dilution of DNA adducts by DNA replication was documented in pulse-chase experiments that employed [H-3]thymidine incorporation. Adduct removal by repair-related mechanisms was considered to comprise the difference between total DNA adduct removal and adduct removal related to DNA replication. The final results demonstrated that both, higher initial binding and lack of removal of cisplatin-DNA adducts appear to contribute to the preferential cisplatin-mtDNA binding observed in CHO cells. C1 NATL INST DEAFNESS & COMMUN DISORDERS,MOL ONCOL LAB,BETHESDA,MD. RP Olivero, OA (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,RM 3B12,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 28 TC 39 Z9 42 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUN 13 PY 1997 VL 391 IS 1-2 BP 79 EP 86 DI 10.1016/S0165-1218(97)00037-2 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XG054 UT WOS:A1997XG05400008 PM 9219551 ER PT J AU Hampel, H Schoen, D Schwarz, MJ Kotter, HU Schneider, C Sunderland, T Dukoff, R Levy, J Padberg, F Stubner, S Buch, K Muller, N Moller, HJ AF Hampel, H Schoen, D Schwarz, MJ Kotter, HU Schneider, C Sunderland, T Dukoff, R Levy, J Padberg, F Stubner, S Buch, K Muller, N Moller, HJ TI Interleukin-6 is not altered in cerebrospinal fluid of first-degree relatives and patients with Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE interleukin-6; Alzheimer's disease; family history; healthy controls; cerebrospinal fluid; ELISA ID IL-6 RECEPTOR; CELLS; ALPHA-2-MACROGLOBULIN; RELEASE; INVITRO; CORTEX; STATE AB We investigated interleukin-6 (IL-6) levels in cerebrospinal fluid (CSF) of 25 patients with clinically diagnosed sporadic Alzheimer's disease (AD) and 19 healthy control subjects (HC). For comparison 19 clinically healthy subjects with at least one first-degree relative with clinical or autopsy confirmed AD (CF/AD) were examined. CSF levels of IL-6 did not show statistically significant differences between AD patients, CF/AD and HC subjects. There was no correlation between age, gender, age of onset, degree of cognitive impairment, blood-brain barrier dysfunction and IL-6 values. We could not demonstrate altered CSF concentrations of IL-6 that may indicate an inflammatory response or capability to support neuronal survival in the central nervous system (CNS) of first-degree relatives and patients with AD. We suggest that combined measurement of all parameters of the IL-6-receptor complex could yield more insight in a probably altered IL-6 function. (C) 1997 Elsevier Science Ireland Ltd. C1 NIMH,NIH,GERIATR PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Hampel, H (reprint author), UNIV MUNICH,SCH MED,DEPT PSYCHIAT,GERIATR PSYCHIAT BRANCH,NUSSBAUMSTR 7,D-80663 MUNICH,GERMANY. NR 22 TC 42 Z9 43 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 13 PY 1997 VL 228 IS 3 BP 143 EP 146 DI 10.1016/S0304-3940(97)00379-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA XJ901 UT WOS:A1997XJ90100001 PM 9218628 ER PT J AU Dencoff, JE Rosenberg, GA Harry, GJ AF Dencoff, JE Rosenberg, GA Harry, GJ TI Trimethyltin induces gelatinase B and urokinase in rat brain SO NEUROSCIENCE LETTERS LA English DT Article DE brain; gelatinase; matrix metalloproteinase; rat; trimethyltin; urokinase plasminogen activator ID NECROSIS-FACTOR-ALPHA; TUMOR-CELLS; EXPRESSION; HIPPOCAMPUS; PROTEINS; INJURY; GENES; IV AB The neurotoxicant trimethyltin (TMT) increases mRNA levels for cytokines, tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-6. Cytokines induce matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA). MMPs and uPA disrupt extracellular matrix. Since matrix damage may play a role in the neuropathological changes seen with TMT toxicity, we determined the effect of TMT on proteolytic enzyme production. Adult rats were injected with 8.0 mg TMT/kg. At different times after TMT injection, tissue samples from frontal lobe and hippocampus were assayed for MMPs and uPA, using gelatin-substrate and casein/plasminogen-substrate zymography. Gelatinase B (92 kDa type IV collagenase) production increased significantly in frontal lobe tissue at 24, 48 and 96 h, and in hippocampus at 48 h compared to saline-injected controls. Gelatinase A (72 kDa type IV collagenase) was significantly decreased at 12 and 24 h in frontal lobe compared to controls. Urokinase-type PA was significantly increased in hippocampus at 12 and 96 h, and in frontal lobe at 96 h compared to controls. Gelatinase B and uPA are up-regulated by TMT in frontal lobe and hippocampus, suggesting that they may contribute to the neuropathology of TMT. (C) 1997 Elsevier Science Ireland Ltd. C1 UNIV NEW MEXICO,SCH MED,DEPT NEUROL,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,SCH MED,DEPT PHYSIOL,ALBUQUERQUE,NM 87131. NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. FU NINDS NIH HHS [2 RO1 NS21169-10] NR 16 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 13 PY 1997 VL 228 IS 3 BP 147 EP 150 DI 10.1016/S0304-3940(97)00380-7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA XJ901 UT WOS:A1997XJ90100002 PM 9218629 ER PT J AU Krauzlis, RJ Basso, MA Wurtz, RH AF Krauzlis, RJ Basso, MA Wurtz, RH TI Shared motor error for multiple eye movements SO SCIENCE LA English DT Article ID SUPERIOR COLLICULUS; FIXATION; LESIONS; SYSTEM; MONKEY; AREA AB Most natural actions are accomplished with a seamless combination of individual movements, Such coordination poses a problem: How does the motor system orchestrate multiple movements to produce a single goal-directed action? The results from current experiments suggest one possible solution. Oculomotor neurons in the superior colliculus of a primate responded to mismatches between eye and target positions, even when the animal made two different types of eye movements. This neuronal activity therefore does not appear to convey a command for a specific type of eye movement but instead encodes an error signal that could be used by multiple movements, The use of shared inputs is one possible strategy for ensuring that different movements share a common goal. C1 NEI,SENSORIMOTOR RES LAB,NIH,BETHESDA,MD 20892. NR 14 TC 125 Z9 126 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 13 PY 1997 VL 276 IS 5319 BP 1693 EP 1695 DI 10.1126/science.276.5319.1693 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD947 UT WOS:A1997XD94700041 PM 9180078 ER PT J AU Hoffman, SL Bancroft, WH Gottlieb, M James, SL Burroughs, ECB Stephenson, JR Morgan, MJ AF Hoffman, SL Bancroft, WH Gottlieb, M James, SL Burroughs, ECB Stephenson, JR Morgan, MJ TI Funding for malaria genome sequencing SO NATURE LA English DT Letter C1 USA,MED RES & MAT COMMAND,MIL INFECT DIS RES PROGRAM,FREDERICK,MD 21703. NIAID,NIH,PARASITOL & INT PROGRAMS BRANCH,BETHESDA,MD 20892. WELLCOME FUND,MORRISVILLE,NC 27560. WELLCOME TRUST RES LABS,LONDON NW1 2BE,ENGLAND. RP Hoffman, SL (reprint author), USN,MED RES INST,MALARIA PROGRAM,BETHESDA,MD 20889, USA. NR 0 TC 28 Z9 28 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 12 PY 1997 VL 387 IS 6634 BP 647 EP 647 DI 10.1038/42571 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD869 UT WOS:A1997XD86900018 PM 9192878 ER PT J AU Englund, JA Baker, CJ Raskino, C McKinney, RE Petrie, B Fowler, MG Pearson, D Gershon, A McSherry, GD Abrams, EJ Schliozberg, J Sullivan, JL AF Englund, JA Baker, CJ Raskino, C McKinney, RE Petrie, B Fowler, MG Pearson, D Gershon, A McSherry, GD Abrams, EJ Schliozberg, J Sullivan, JL TI Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLINICAL-TRIALS; GROWTH AB Background Zidovudine has been the drug of choice for the initial treatment of symptomatic children infected with the human immunodeficiency virus (HIV). This trial was designed to assess the efficacy and safety of treatment with zidovudine alone as compared with either didanosine alone or combination therapy with zidovudine plus didanosine. Methods In this multicenter, double-blind study, symptomatic HIV-infected children 3 months through 18 years of age were stratified according to age (<30 months or greater than or equal to 30 months) and randomly assigned to receive zidovudine, didanosine, or zidovudine plus didanosine. The primary end point was length of time to death or to progression of HIV disease. Results Of the 831 children who could be evaluated, 92 percent had never received antiretroviral therapy and 90 percent had acquired HIV perinatally. An interim analysis (median follow-up, 23 months) showed a significantly higher risk of HIV-disease progression or death in patients receiving zidovudine alone than in those receiving combination therapy (relative risk, 0.61; 95 percent confidence interval, 0.42 to 0.88; P=0.007). The study arm with zidovudine alone was stopped and unblinded; the other two treatment arms were continued. At the end of the study, didanosine alone had an efficacy similar to that of zidovudine plus didanosine (median follow-up, 32 months) (relative risk of disease progression or death, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.91). A significantly lower risk of anemia or neutropenia was seen in patients receiving didanosine alone (P=0.036). Conclusions In symptomatic HIV-infected children, treatment with either didanosine alone or zidovudine plus didanosine was more effective than treatment with zidovudine alone. The efficacy of didanosine alone was similar to that of the combination therapy and was associated with less hematologic toxicity. (C) 1997, Massachusetts Medical Society. C1 BAYLOR COLL MED, DEPT PEDIAT, HOUSTON, TX 77030 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT BIOSTAT, BOSTON, MA 02115 USA. DUKE UNIV, SCH MED, DEPT PEDIAT, DURHAM, NC USA. FRONTIER SCI & TECHNOL RES FDN INC, AMHERST, NY USA. NIAID, BETHESDA, MD 20892 USA. UNIV TEXAS, HLTH SCI CTR, DEPT PSYCHIAT & BEHAV SCI, HOUSTON, TX 77225 USA. COLUMBIA UNIV, DEPT PEDIAT, NEW YORK, NY 10027 USA. CHILDRENS HOSP NEW JERSEY, DEPT PEDIAT, NEWARK, NJ USA. HARLEM HOSP MED CTR, DEPT PEDIAT, NEW YORK, NY USA. ALBERT EINSTEIN COLL MED, DEPT PEDIAT, NEW YORK, NY USA. UNIV MASSACHUSETTS, DEPT PEDIAT, AMHERST, MA 01003 USA. RP Englund, JA (reprint author), BAYLOR COLL MED, DEPT MICROBIOL & IMMUNOL, HOUSTON, TX 77030 USA. RI Koranyi, Katalin/E-3421-2011; OI moye, john/0000-0001-9976-8586 NR 21 TC 109 Z9 114 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 12 PY 1997 VL 336 IS 24 BP 1704 EP 1712 DI 10.1056/NEJM199706123362403 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA XD543 UT WOS:A1997XD54300003 PM 9182213 ER PT J AU Whitesell, L Sutphin, P An, WG Schulte, T Blagosklonny, MV Neckers, L AF Whitesell, L Sutphin, P An, WG Schulte, T Blagosklonny, MV Neckers, L TI Geldanamycin-stimulated destabilization of mutated p53 is mediated by the proteasome in vivo SO ONCOGENE LA English DT Article DE ubiquitin; lactacystin; benzoquinone ansamycins; proteasome ID HUMAN PAPILLOMAVIRUS TYPE-16; WILD-TYPE; MULTICATALYTIC PROTEINASE; ACTIVATING MUTATIONS; PROTEOLYTIC SYSTEM; TRANSFORMED-CELLS; E6 ONCOPROTEIN; MUTANT P53; DEGRADATION; COMPLEX AB Mutation of the tumor suppressor gene p53 is the most common genetic abnormality detected in human cancers, Wild type p53 is a short-lived protein with very low basal intracellular levels, Most mutated forms of the protein, however, display markedly increased intracellular levels as an essential feature of their positive transforming activity, In this report, we have used selective inhibitors of the 20S proteasome to demonstrate that processing of p53 by ubiquitination and proteasome-mediated degradation is impaired by commonly occurring mutations of the protein, We found that this impairment of p53 turnover can be reversed by treatment of tumor cells with the benzoquinone ansamycin, geldanamycin, leading to a marked reduction in intracellular p53 levels. Finally, using cells which over-express a mutant p53 protein, we were able to demonstrate that restoration of proteasome-mediated degradation by geldanamycin is accompanied by p53 polyubiquitination, Although much remains to be learned about the mechanisms involved, our data demonstrate that selective de-stabilization of mutant transforming proteins such as p53 can be achieved pharmacologically with agents such as geldanamycin which modify the function of molecular chaperone proteins within tumor cells. C1 UNIV ARIZONA,DEPT PEDIAT,STEELE MEM CHILDRENS RES CTR,TUCSON,AZ 85724. NCI,CLIN PHARMACOL BRANCH,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [R29 CA-69537-01] NR 36 TC 104 Z9 106 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 12 PY 1997 VL 14 IS 23 BP 2809 EP 2816 DI 10.1038/sj.onc.1201120 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XD643 UT WOS:A1997XD64300009 PM 9190897 ER PT J AU Marhin, WW Chen, SJ Facchini, LM Fornace, AJ Penn, LZ AF Marhin, WW Chen, SJ Facchini, LM Fornace, AJ Penn, LZ TI Myc represses the growth arrest gene gadd45 SO ONCOGENE LA English DT Article DE gadd45; Myc; cell cycle; p53; growth arrest ID HUMAN C-MYC; ENHANCER-BINDING-PROTEIN; DNA-DAMAGING AGENTS; CELL-CYCLE ARREST; LARGE T-ANTIGEN; TRANSCRIPTIONAL ACTIVATION; ORNITHINE DECARBOXYLASE; MAMMALIAN-CELLS; IN-VIVO; EXPRESSION AB The c-Myc protein strongly stimulates cellular proliferation, inducing cells to exit G0/G1 and enter the cell cycle. At a molecular level, Myc prevents growth arrest and drives cell cycle progression through the transcriptional regulation of Myc-target genes. Expression of the growth arrest and DNA damage inducible gene 45 (gadd45) is elevated in response to DNA damaging agents, such as ionizing radiation via a p53-dependent mechanism, upon nutrient deprivation, or during differentiation. Gadd35 holds a vital role in growth arrest as ectopic expression confers a strong block to proliferation. Exposure of quiescent cells to mitogen stimulates a rapid increase in c-Myc expression which is followed by the subsequent reduction in gadd45 expression. The kinetics of these two regulatory events suggest that Myc suppresses the expression of gadd45, contributing to G0/G1 phase exit of the cell cycle. Indeed, ectopic Myc expression in primary and immortalized fibroblasts results in the suppression of gadd45 mRNA levels, by a mechanism which is independent of cell cycle progression. Using an inducible MycER(TM) system, rapid suppression of gadd45 mRNA is first evident approximately 0.5 h following Myc activation. The reduction in gadd45 mRNA. expression occurs at the transcriptional level and is mediated by a p53-independent pathway. Moreover, Myc suppression and p53 induction of gadd45 following exposure to ionizing radiation are noncompetitive co-regulatory events. Myc suppression of gadd45 defines a novel pathway through which Myc promotes cell cycle entry and prevents growth arrest of transformed cells. C1 UNIV TORONTO,DEPT MOL & MED GENET,TORONTO,ON M5G 2M9,CANADA. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO,ON M5G 2M9,CANADA. ONTARIO CANC INST,TORONTO,ON M5G 2M9,CANADA. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 83 TC 128 Z9 129 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 12 PY 1997 VL 14 IS 23 BP 2825 EP 2834 DI 10.1038/sj.onc.1201138 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XD643 UT WOS:A1997XD64300011 PM 9190899 ER PT J AU Friis, S McLaughlin, JK Mellemkjaer, L Kjoller, KH Blot, WJ Boice, JD Fraumeni, JF Olsen, JH AF Friis, S McLaughlin, JK Mellemkjaer, L Kjoller, KH Blot, WJ Boice, JD Fraumeni, JF Olsen, JH TI Breast implants and cancer risk in Denmark SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GENETICALLY SUSCEPTIBLE STRAINS; SYSTEMIC-SCLEROSIS; SILICONE GEL; MICE; PLASMACYTOMAS; INDUCTION; LYMPHOMA AB Although millions of women worldwide have received breast implants for cosmetic or medical reasons, possible late effects (in particular cancer) have not been well studied. To provide quantitative information on cancer occurrence among women undergoing breast implant surgery, 1,135 women treated for cosmetic reasons in Denmark were evaluated. Patients were identified using the nationwide Hospital Discharge Registry with linkage to the nationwide Danish Cancer Registry to determine subsequent cancer incidence. The average age of the women at implant surgery was 31 years, and the average follow-up was 8.4 years, up to a maximum of 17 years. Overall, 27 cancers developed after implant surgery compared with 24.7 expected based on incidence rates from the general population (standardized incidence ratio [SIR] = 1.1; 95% Cl: 0.7-1.6). Eight breast cancers were observed vs. 7.8 expected (SIR = 1.0; 95% Cl: 0.4-2.0). No evidence was found to link breast implants with increased cancer risk in the decade after surgery. While the results are encouraging, longer follow-up into later life will be necessary to assess fully any possible adverse effects. (C) 1997 Wiley-Liss, Inc. C1 DANISH CANC SOC,DIV CANC EPIDEMIOL,DK-2100 COPENHAGEN,DENMARK. INT EPIDEMIOL INST,ROCKVILLE,MD. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD. NR 25 TC 43 Z9 43 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 11 PY 1997 VL 71 IS 6 BP 956 EP 958 DI 10.1002/(SICI)1097-0215(19970611)71:6<956::AID-IJC8>3.0.CO;2-X PG 3 WC Oncology SC Oncology GA XC729 UT WOS:A1997XC72900008 PM 9185696 ER PT J AU Costa, PT Somerfield, MR Williams, TF AF Costa, PT Somerfield, MR Williams, TF TI Underrecognition of dementia by caregivers cuts across cultures SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 AMER SOC CLIN ONCOL,ALEXANDRIA,VA. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. RP Costa, PT (reprint author), NIA,BALTIMORE,MD 21224, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 11 PY 1997 VL 277 IS 22 BP 1758 EP 1758 DI 10.1001/jama.277.22.1758 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XC499 UT WOS:A1997XC49900016 PM 9178782 ER PT J AU Ross, GW Petrovitch, H Masaki, K Curb, JD Abbott, R White, L AF Ross, GW Petrovitch, H Masaki, K Curb, JD Abbott, R White, L TI Underrecognition of dementia by caregivers cuts across cultures - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 UNIV VIRGINIA,CHARLOTTESVILLE,VA. NIA,BETHESDA,MD 20892. RP Ross, GW (reprint author), UNIV HAWAII,HONOLULU,HI 96822, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 11 PY 1997 VL 277 IS 22 BP 1758 EP 1759 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XC499 UT WOS:A1997XC49900017 ER PT J AU Quyyumi, AA Mulcahy, D AF Quyyumi, AA Mulcahy, D TI Can ambulatory monitoring identify high-risk patients with stable coronary artery disease? Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID ISCHEMIA RP Quyyumi, AA (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 11 PY 1997 VL 277 IS 22 BP 1760 EP 1761 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XC499 UT WOS:A1997XC49900021 ER PT J AU Soderstrom, CA Smith, GS Dischinger, PC McDuff, DR Hebel, JR Gorelick, DA Kerns, TJ Ho, SM Read, KM AF Soderstrom, CA Smith, GS Dischinger, PC McDuff, DR Hebel, JR Gorelick, DA Kerns, TJ Ho, SM Read, KM TI Psychoactive substance use disorders among seriously injured trauma center patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Association-for-the-Advancement-of-Automotive-Medicine CY OCT 07-09, 1996 CL VANCOUVER, CANADA SP Assoc Adv Automot Med ID HARMFUL ALCOHOL-CONSUMPTION; UNITED-STATES; COLLABORATIVE PROJECT; CAGE QUESTIONNAIRE; SCREENING-TEST; FOLLOW-UP; ABUSE; DEPENDENCE; PREVALENCE; DISEASE AB Objective.-To assess the prevalence of psychoactive substance use disorders (PSUDs) among a large, unselected group of seriously injured trauma center patients, using a standardized diagnostic interview and criteria. Design.-Prevalence study. Setting.-A level I regional trauma center. Patients. Trauma center patients fulfilling the following criteria were eligible subjects: aged 18 years or older, admission from injury scene, length of stay of 2 days or longer, and intact cognition. Outcome Measures. The PSUDs were diagnosed using the Structured Clinical Interview (SCID) for the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) and were categorized as abuse or dependence and past or current (within past 6 months). The SCID results were analyzed with respect to demographic factors, injury type, and blood alcohol concentration and urine toxicology results, using chi(2) and logistic regression techniques. Results.-Of the 1220 patients approached for study, 1118 (91.6%) consented. More than half (54.2%) had a diagnosis of a PSUD in their lifetime. Approximately 90% of alcohol and other drug use diagnoses were for dependence and more than 62% were current. Overall, 24.1% of patients were currently alcohol dependent (men, 27.7%; women, 14.7%; P<.001), and 17.7% were currently dependent on other drugs (men, 20.2%; women, 11.2%; P<.001). Current alcohol dependence rates were not associated with race; rates of dependence on other drugs were higher among nonwhites and victims classified with intentional injuries. While 54.3% of blood alcohol-positive patients were currently alcohol dependent and 38.7% of patients with positive urine screening test results for drugs other than alcohol and nicotine were currently drug dependent, 11.7% of blood alcohol-negative and 3.9% of drug-negative patients, respectively, had current diagnoses of dependence on psychoactive substances. Conclusions. A high percentage of seriously injured trauma center patients are at risk of having current PSUDs. Patients with positive toxicology screening test results and/or positive screening questionnaire responses should be referred for formal evaluation and treatment. C1 JOHNS HOPKINS UNIV,CTR INJURY RES & POLICY,BALTIMORE,MD. UNIV MARYLAND,SCH MED,NATL STUDY CTR TRAUMA & EMERGENCY MED SYST,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL,BALTIMORE,MD 21201. NIDA,DIV INTRAMURAL RES,BALTIMORE,MD. RP Soderstrom, CA (reprint author), UNIV MARYLAND,MED SYST,CTR SHOCK TRAUMA,22 S GREENE ST,BALTIMORE,MD 21201, USA. OI Smith, Gordon/0000-0002-2911-3071 FU NIAAA NIH HHS [R01 AA09050] NR 50 TC 147 Z9 149 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 11 PY 1997 VL 277 IS 22 BP 1769 EP 1774 DI 10.1001/jama.277.22.1769 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XC499 UT WOS:A1997XC49900029 PM 9178789 ER PT J AU Davidson, F Smith, R Hoey, J Lundberg, G Glass, R Horton, R VanDerWeyden, M Utiger, R Nylenna, M Colaianni, LA Clever, LH Woolf, P AF Davidson, F Smith, R Hoey, J Lundberg, G Glass, R Horton, R VanDerWeyden, M Utiger, R Nylenna, M Colaianni, LA Clever, LH Woolf, P TI Policies for posting biomedical journal information on the Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 BMJ,LONDON,ENGLAND. CANADIAN MED ASSOC JOURNAL,OTTAWA,ON,CANADA. LANCET,LONDON,ENGLAND. MED JOURNAL AUSTRALIA,SYDNEY,NSW,AUSTRALIA. NEW ENGLAND JOURNAL MED,WALTHAM,MA 02154. NATL LIB MED,BETHESDA,MD 20894. PRINCETON UNIV,PRINCETON,NJ 08544. RP Davidson, F (reprint author), ANNALS INTERNAL MED,PHILADELPHIA,PA 19106, USA. NR 1 TC 15 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 11 PY 1997 VL 277 IS 22 BP 1808 EP 1808 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XC499 UT WOS:A1997XC49900036 ER PT J AU Buckheit, RW Hollingshead, M Sinson, S FliakasBoltz, V Pallansch, LA Roberson, J Decker, W Elder, C Borgel, S Bonomi, C Shores, R Siford, T Malspeis, L Bader, JP AF Buckheit, RW Hollingshead, M Sinson, S FliakasBoltz, V Pallansch, LA Roberson, J Decker, W Elder, C Borgel, S Bonomi, C Shores, R Siford, T Malspeis, L Bader, JP TI Efficacy, pharmacokinetics, and in vivo antiviral activity of UC781, a highly potent, orally bioavailable nonnucleoside reverse transcriptase inhibitor of HIV type 1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY; OXATHIIN CARBOXANILIDE; TIBO DERIVATIVES; BINDING-SITE; RESISTANCE; REPLICATION; NEVIRAPINE; DRUG; INVITRO; ENZYME AB A series of compounds related to oxathiin carboxanilide has been identified as nonnucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1, and structure-activity relationships have been described (Buckheit RW, et al.: Antinicrob Agents Chemother 1995;39:2718-2727). Three new analogs (UC040, UC82, and UC781) inhibited laboratory and clinical isolates of HIV-1, including isolates representative of the various clades of HIV-1 found worldwide, in both established and fresh human cells, Virus isolates with the amino acid changes L100I, K103N, V106I, and Y181C in the reverse transcriptase were partially resistant to these compounds, However, UC781 inhibited these virus isolates at low nontoxic concentrations, presenting a broad in vitro therapeutic index, As with other NNRTIs, each of the compounds synergistically interacted with AZT to inhibit HIV-1 replication, UC781 possesses a favorable pharmacokinetic profile in mice with a high level of oral bioavailability, Plasma concentrations reached maximum levels within 2 to 4 br of oral administration and remained in excess of those required for in vitro anti-HIV activity for at least 24 hr after a single oral dose, When evaluated in a murine hollow fiber implant model of HIV infection, UC781 dosed orally or parenterally was able to suppress HIV replication completely in this model system, providing evidence of the in vivo efficacy of the compound. C1 NCI,BIOL TESTING BRANCH,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,FREDERICK,MD 21701. NCI,LAB PHARMACEUT CHEM,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,IN VIVO MODEL DEV PROGRAM,FREDERICK,MD 21702. RP Buckheit, RW (reprint author), SO RES INST,FREDERICK RES CTR,VIROL RES GRP,431 AVIAT WAY,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CM-37818] NR 32 TC 24 Z9 24 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN 10 PY 1997 VL 13 IS 9 BP 789 EP 796 DI 10.1089/aid.1997.13.789 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XC324 UT WOS:A1997XC32400008 PM 9171223 ER PT J AU Zhu, PP Nosworthy, N Ginsburg, A Miyata, M Seok, YJ Peterkofsky, A AF Zhu, PP Nosworthy, N Ginsburg, A Miyata, M Seok, YJ Peterkofsky, A TI Expression, purification, and characterization of enzyme IIA(glc) of the phosphoenolpyruvate:sugar phosphotransferase system of Mycoplasma capricolum SO BIOCHEMISTRY LA English DT Article ID GRAM-POSITIVE BACTERIA; PHOSPHOCARRIER PROTEIN; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; CARBON METABOLISM; HPR; PHOSPHORYLATION; SITE; ASSOCIATION; CLONING AB The gene encoding enzyme IIA(glc) (EIIA) of the phosphoenolpyruvate:sugar phosphotransferase system of Mycoplasma capricolum was cloned into a regulated expression vector. The purified protein product of the overexpressed gene was characterized as an active phosphoacceptor from HPr with a higher pI than previously described EIIAs. M. capricolum EIIA was unreactive with antibodies directed against the corresponding proteins from either Gram-positive or Gram-negative bacteria. Enzyme IIA(glc) behaved as a homogeneous, monomeric species of 16 700 M-r in analytical ultracentrifugation. The circular dichroism far-UV spectrum of EIIA reflects a low alpha-helical content and predominantly beta-sheet structural content: temperature-induced changes in ellipticity at 205 nm showed that the protein undergoes reversible, two-state thermal unfolding with T-m = 70.0 +/- 0.3 degrees C and a van't Hoff Delta H of 90 kcal/mol. Enzyme I (64 600 M-r) from M. capricolum exhibited a monomer-dimer-tetramer association at 4 and 20 degrees C with dimerization constants of log K-A = 5.6 and 5.1 [M-1], respectively, in sedimentation equilibrium experiments. A new vector, capable of introducing an N-terminal His tag on a protein, was developed in order to generate highly purified heat-stable protein (HPr). No significant interaction of EIIA with HPr was detected by gel-filtration chromatography, intrinsic tryptophanyl residue fluorescence changes, titration calorimetry, biomolecular interaction, or sedimentation equilibrium studies. While Escherichia coli EIIA inhibits Gram-negative glycerol kinase activity, the M. capricolum EIIA has no effect on the homologous glycerol kinase. The probable regulator of sugar transport systems, HPr(Ser) kinase, was demonstrated in extracts of M. capricolum and Mycoplasma genitalium. Gene mapping studies demonstrated that, in contrast to the clustered arrangement of genes encoding HPr and enzyme I in E. coli, these genes are located diametrically opposite in the M. capricolum chromosome. C1 NHLBI,BIOCHEM GENET & BIOCHEM LAB,NIH,BETHESDA,MD 20892. OSAKA CITY UNIV,FAC SCI,DEPT BIOL,OSAKA 558,JAPAN. OI MIYATA, Makoto/0000-0002-7478-7390 NR 37 TC 17 Z9 19 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 10 PY 1997 VL 36 IS 23 BP 6947 EP 6953 DI 10.1021/bi963090m PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XD805 UT WOS:A1997XD80500011 PM 9188690 ER PT J AU Jones, TLZ Degtyarev, MY Backlund, PS AF Jones, TLZ Degtyarev, MY Backlund, PS TI The stoichiometry of G alpha(s) palmitoylation in its basal and activated states SO BIOCHEMISTRY LA English DT Article ID PROTEIN-ALPHA-SUBUNIT; MEMBRANE ATTACHMENT; LIPID MODIFICATIONS; PLASMA-MEMBRANE; FATTY ACYLATION; COS CELLS; GS-ALPHA; MYRISTOYLATION; BINDING; LOCALIZATION AB Palmitoylation is the dynamic modification of proteins by the addition of palmitate to cysteine residues. The alpha subunits of heterotrimeric G proteins undergo palmitoylation on their amino terminus, and activation of alpha(s) accelerates its palmitate turnover. In previous studies, palmitoylation was assessed by incorporation or turnover of [H-3]palmitate. These studies did not determine the fraction of alpha s( )that is palmitoylated because the specific activity of [H-3]palmitoyl-CoA within cells is indeterminate. We developed an HPLC method to determine the fraction of alpha(s) that was palmitoylated in the basal and activated states. COS and S49 cells were radiolabeled with [S-35]methionine, and alpha(s) was immunoprecipitated from the particulate fraction. The immunoprecipitated proteins were separated by reverse phase HPLC into two peaks that were determined to contain the modified and unmodified forms of alpha(s). Approximately 77% of the endogenous alpha(s) in COS cells and 70% in S49 lymphoma cells were palmitoylated. The fraction of alpha(s) that was modified did not change after treatment with isoproterenol, a beta-adrenergic receptor agonist that causes turnover of palmitate on alpha(s). These results suggest that receptor activation of alpha(s) caused a rapid turnover of palmitate to maintain most of alpha(s) in its palmitoylated form. C1 NIMH,LAB GEN & COMPARAT BIOCHEM,NIH,BETHESDA,MD 20892. RP Jones, TLZ (reprint author), NIDDK,METAB DIS BRANCH,NIH,BLDG 10,ROOM 8C101,BETHESDA,MD 20892, USA. NR 39 TC 34 Z9 34 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 10 PY 1997 VL 36 IS 23 BP 7185 EP 7191 DI 10.1021/bi9628376 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XD805 UT WOS:A1997XD80500040 PM 9188719 ER PT J AU Paik, SY Banerjea, A Chen, CJ Ye, ZP Harmison, GG Schubert, M AF Paik, SY Banerjea, A Chen, CJ Ye, ZP Harmison, GG Schubert, M TI Defective HIV-1 provirus encoding a multitarget-ribozyme inhibits accumulation of spliced and unspliced HIV-1 mRNAs, reduces infectivity of viral progeny, and protects the cells from pathogenesis SO HUMAN GENE THERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MESSENGER-RNA; GENE-EXPRESSION; ANTI-TAT; TYPE-1; CD4; PARTICLES; REPLICATION; RELEASE; DEGRADATION AB A HeLa T4 cell line containing a defective human immunodeficiency virus type 1 (HIV-1) DNA (HD4) was isolated. After transactivation with Tat, the HD4 DNA was transcribed into a single 3.7-kb mRNA that encodes a chimeric CD4/Env protein and a multitarget-ribozyme directed against multiple sites within the gp120 coding region of HIV-1 RNA (Chen et al., 1992). Early steps in HIV infection such as entry, reverse transcription, and proviral DNA formation were not affected in HD4 cells, and HD4 was efficiently transactivated after either HIV-1 or HIV-2 infections. HIV-2, which lacks all of the HIV-1-specific ribozyme target sites, replicated to high levels in HD4 cells whereas HIV-1 replication was selectively inhibited. Despite a reduced accumulation of all HIV-1 transcripts, transactivation of HD4 was efficient. Surprisingly, the most abundant, multiply spliced mRNAs were reduced even though they lack all of the ribozyme target sites. These results strongly suggest that the ribozyme co-localizes with unspliced HIV-1 pre-mRNA and/or genomic HIV-1 RNA in the nucleus. Cleavage of these precursor RNAs explains the reduction of all spliced and unspliced HIV-1 RNAs. Cleavage of genomic RNA probably contributed to the three-fold reduction in the infectivity of viral progeny. Thus, the HD4 ribozyme RNA functioned as a ribozyme in the nucleus and as a mRNA for a chimeric CD4/Env protein in the cytoplasm. Its unusual large size for a ribozyme (3.7 kb) indicates that, in the future, other antiviral proteins, like negative transdominant mutant HIV-1 proteins, may also be encoded to increase its antiviral potential in a gene therapy approach. C1 NINCDS,LMMN,MOL & VIRAL GENET SECT,NIH,BETHESDA,MD 20892. NR 43 TC 26 Z9 28 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUN 10 PY 1997 VL 8 IS 9 BP 1115 EP 1124 DI 10.1089/hum.1997.8.9-1115 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XE655 UT WOS:A1997XE65500010 PM 9189769 ER PT J AU Fiscella, M Zhang, HL Fan, SJ Sakaguchi, K Shen, SF Mercer, WE VandeWoude, GF OConnor, PM Appella, E AF Fiscella, M Zhang, HL Fan, SJ Sakaguchi, K Shen, SF Mercer, WE VandeWoude, GF OConnor, PM Appella, E TI Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL-CYCLE; G(1) ARREST; HUMAN P53; APOPTOSIS; INDUCTION; P21; INHIBITOR; BAX; PHOSPHORYLATION; TRANSCRIPTION AB Exposure of mammalian cells to ionizing radiation (IR) induces a complex array of cellular responses including cell cycle arrest and/or apoptosis. IR-induced GI arrest has been shown to depend on the presence of the tumor suppressor p53, which acts as a transcriptional activator of several genes, p53 also plays a role in the induction of apoptosis in response to DNA damage, and this pathway can be activated by bath transcription-dependent and -independent mechanisms, Here we report the identification of a novel transcript whose expression is induced in response to IR in a p53-dependent manner, and that shows homology to the type 2C protein phosphatases. We have named this novel gent, wip1. In vitro, recombinant Wip1 displayed characteristics of a type 2C phosphatase, including Mg2+ dependence and relative insensitivity to okadaic acid. Studies performed in several cell lines revealed that wip1 accumulation following IR correlates with the presence of wild-type p53, The accumulation of wip1 mRNA following IR was rapid and transient, and the protein was localized to the nucleus, Similar to waf1, ectopic expression of wip1 in human cells suppressed colony formation, These results suggest that Wip1 might contribute to growth inhibitory pathways activated in response to DNA damage in a p53-dependent manner. C1 NCI,CELL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. ADV BIOSCI LABS,BASIC RES PROGRAM,MOL ONCOL SECT,MOL VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,KIMMEL CANC INST,PHILADELPHIA,PA 19107. NR 38 TC 319 Z9 336 U1 4 U2 21 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 1997 VL 94 IS 12 BP 6048 EP 6053 DI 10.1073/pnas.94.12.6048 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400015 PM 9177166 ER PT J AU Critchfield, JW Coligan, JE Folks, TM Butera, ST AF Critchfield, JW Coligan, JE Folks, TM Butera, ST TI Casein kinase II is a selective target of HIV-1 transcriptional inhibitors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VESICULAR STOMATITIS-VIRUS; VPU-PROTEIN; P-PROTEIN; PHOSPHORYLATION SITES; PHOSPHOPROTEIN-P; IDENTIFICATION; TAT; ACTIVATION; DOMAIN; CELLS AB The identification of cellular factors that are required to complete various steps of the HIV-1 life cycle may lead to the development of new therapeutics. One key step, transcription from the integrated provirus, is inhibited by members of two distinct classes of compounds, the flavonoids and the benzothiophenes, via an unknown mechanism, possibly involving a cellular factor, A marked specificity toward inhibiting HIV-1 transcription is evidenced by the ability of drug-treated cells to retain their proliferative and differentiation capabilities, In addition, the compounds do not impede the activation and function of the transcriptional factor NF-kappa B. Here we report on the identification of several cellular proteins that mediate the HIV-1 transcriptional inhibitory property of the flavonoid chrysin, Chemical and immunologic analyses identified these cellular proteins as the individual subunits of casein kinase II (CKII), Though structurally unrelated to chrysin, an HIV-1 inhibitory benzothiophene also bound selectively to CKII, Both chrysin and the benzothiophenes inhibited human recombinant CKII enzymatic activity and showed competitive kinetics with respect to ATP, analogous to the classic CKII inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), Moreover, DRB potently inhibited HIV-1 expression in chronically infected cells, CKII may regulate HIV-1 transcription by phosphorylating cellular proteins involved in HIV-1 transactivation that contain multiple CKII phosphorylation consensus sequences. C1 CTR DIS CONTROL & PREVENT, TB LAB RES, ATLANTA, GA 30333 USA. NIAID, MOL STRUCT LAB, NATL INST HLTH, ROCKVILLE, MD 20852 USA. RP CTR DIS CONTROL & PREVENT, RETROVIRUS DIS BRANCH, ATLANTA, GA 30333 USA. NR 46 TC 112 Z9 118 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 JUN 10 PY 1997 VL 94 IS 12 BP 6110 EP 6115 DI 10.1073/pnas.94.12.6110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400027 PM 9177178 ER PT J AU Liu, SY Stadtman, TC AF Liu, SY Stadtman, TC TI Heparin-binding properties of selenium-containing thioredoxin reductase from HeLa cells and human lung adenocarcinoma cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE heparin affinity; selenocysteine; NADPH-linked reductase; flavoprotein ID PURIFICATION; LIVER; CLONING; SYSTEM AB Mammalian selenocysteine-containing thioredoxin reductase (TR) isolated from HeLa cells and from human lung adenocarcinoma cells was separated into two major enzyme species by heparin-agarose affinity chromatography, The low-affinity enzyme forms that were not retained on heparin agarose showed strong crossreactivity in immunoblot assays with anti-rat liver TR polyclonal antibodies, whereas the high-affinity enzyme forms that mere retained by the heparin column were not detected, Both low and high heparin-affinity enzyme forms contained FAD, were indistinguishable on SDS/PAGE analysis, and exhibited similar catalytic activities in the NADPH-dependent DTNB [5,5'-dithiobis(2-nitrobenzoate)] assay. The C-terminal amino acid sequences of Se-75-labeled tryptic peptides from lung adenocarcinoma low- and high heparin-affinity enzyme forms mere identical to the predicted C-terminal sequence of human placental TR. These two determined peptide sequences were -Ser-Gly-Ala-Ser-Ile-Leu-Gln-Ala-Gly-Cys-Secys-(Gly). Occurrence of the Se-carboxymethyl derivative of radioactive selenocysteine in the position corresponding to TGA in the gene confirmed that UGA is translated as selenocysteine, The presence of cysteine followed by a reactive selenocysteine residue in this C-terminal region of the protein may explain some of the unusual properties of the mammalian TRs. RP Liu, SY (reprint author), NHLBI,BIOCHEM LAB,NATL INST HLTH,BLDG 3,ROOM 108,BETHESDA,MD 20892, USA. NR 15 TC 30 Z9 31 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 1997 VL 94 IS 12 BP 6138 EP 6141 DI 10.1073/pnas.94.12.6138 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400032 PM 9177183 ER PT J AU Wolynes, PG AF Wolynes, PG TI Folding funnels and energy landscapes of larger proteins within the capillarity approximation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SPIN-GLASSES; TEMPERATURE; DYNAMICS; LIQUIDS; MODEL AB The characterization of protein-folding kinetics with increasing chain length under various thermodynamic conditions is addressed using the capillarity picture in which distinct spatial regions of the protein are imagined to be folded or trapped and separated by interfaces. The quantitative capillarity theory is based on the nucleation theory of first-order transitions and the droplet analysis of glasses and random magnets. The concepts of folding funnels and rugged energy landscapes are shown to be applicable in the large size limit just as for smaller proteins, An ideal asymptotic free-energy profile as a function of a reaction coordinate measuring progress down the funnel is shown to be quite broad. This renders traditional transition state theory generally inapplicable but allows a diffusive picture with a transition-state region to be used, The analysis unifies several scaling arguments proposed earlier, The importance of fluctuational fine structure both to the free-energy profile and to the glassy dynamics is highlighted. The fluctuation effects lead to a very broad trapping-time distribution. Considerations necessary for understanding the crossover between the mean field and capillarity pictures of the energy landscapes are discussed, A variety of mechanisms that mag roughen the interfaces and may lead to a complex structure of the transition-state ensemble are proposed. C1 NATL INST HLTH,FOGARTY INT CTR,BETHESDA,MD 20892. RP Wolynes, PG (reprint author), UNIV ILLINOIS,SCH CHEM SCI,URBANA,IL 61801, USA. FU NIGMS NIH HHS [R01 GM044557, R01 GM44557] NR 42 TC 189 Z9 192 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 1997 VL 94 IS 12 BP 6170 EP 6175 DI 10.1073/pnas.94.12.6170 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400038 PM 9177189 ER PT J AU Zappacosta, F Borrego, F Brooks, AG Parker, KC Coligan, JE AF Zappacosta, F Borrego, F Brooks, AG Parker, KC Coligan, JE TI Peptides isolated from HLA-Cw*0304 confer different degrees of protection from natural killer cell-mediated lysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MHC CLASS-I; VIRUS-INFECTED CELLS; COMPLEX CLASS-I; HLA-C; NK CELLS; T-CELLS; MOLECULES; RECOGNITION; CLONES; RECEPTORS AB HLA class I molecules bind peptides derived from proteins degraded in the cytoplasm and display them for surveillance by the immune system, The recognition of HLA class I molecules by natural killer (NK) cells generally inhibits the lytic process, To investigate the role of peptides in the interaction between HLA class I molecules and NK receptors, we first had to identify representative endogenous peptides, Individual peptides bound to HLA-Cw*0304 were isolated and sequenced by tandem mass spectrometry, These peptides ranged in length from 8 to 11 residues and shared an alanine at position 2 and a C-terminal leucine. The murine transporters associated with antigen processing (TAP)-deficient cell line RMA-S was transfected with HLA-Cw*0304 to test whether HLA molecules loaded with a single peptide could deliver the inhibitory signal to NK cells expressing p58.2, which is a killer cell inhibitory receptor known to interact with HLA molecules bearing the HLA-Cw3 public epitope, We found that, in the absence of exogenous peptides, the HLA-Cw*0304 transfectants were killed at levels comparable to untransfected RMA-S cells whereas protection from lysis required both HLA-Cw*0304 heavy chain expression and an exogenously added HLA Cw*0304-binding peptide. Importantly, not only were HLA-Cw*0304-binding peptides required for protection, but the ability of individual peptides to provide protection differed widely, These studies indicate that the ability to distinguish between subsets of peptides may be a general feature of HLA class I recognition by NK cells. C1 NIAID,MOL STRUCT LAB,NIH,ROCKVILLE,MD 20852. OI Parker, Kenneth/0000-0002-6282-2478 NR 45 TC 77 Z9 78 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 1997 VL 94 IS 12 BP 6313 EP 6318 DI 10.1073/pnas.94.12.6313 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400063 PM 9177214 ER PT J AU Yamanaka, R Kim, GD Radomska, HS LekstromHimes, J Smith, LT Antonson, P Tenen, DG Xanthopoulos, KG AF Yamanaka, R Kim, GD Radomska, HS LekstromHimes, J Smith, LT Antonson, P Tenen, DG Xanthopoulos, KG TI CCAAT/enhancer binding protein epsilon is preferentially up-regulated during granulocytic differentiation and its functional versatility is determined by alternative use of promoters and differential splicing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C/EBP FAMILY MEMBERS; NF-KAPPA-B; MESSENGER-RNA; TRANSCRIPTIONAL ACTIVATORS; DNA-BINDING; GENE; EXPRESSION; CELLS; NF-IL6; REGION AB CCAAT/enhancer binding protein (C/EBP) epsilon is a recently cloned member of the C/EBP family of transcription factors and is expressed exclusively in cells of hematopoietic origin, The human C/EBP epsilon gene is transcribed by two alternative promoters, P alpha and P beta. A combination of differential splicing and alternative use of promoters generates four mRNA isoforms, of 2.6 kb and 1.3-1.5 kb in size, These transcripts can encode three proteins of calculated molecular mass 32.2 kDa, 27.8 kDa, and 14.3 kDa, Accordingly, Western blots with antibodies specific for the DNA-binding domain, that is common to all forms, identify multiple proteins, C/EBP epsilon mRNA was greatly induced during in vitro granulocytic differentiation of human primary CD34(+) cells, Retinoic acid treatment of HL60 promyelocytic leukemia cells for 24 hr induced C/EBP epsilon mRNA levels by 4-fold, while prolonged treatment gradually reduced mRNA expression to pretreatment levels. Transient transfection experiments with expression vectors for two of the isoforms demonstrated that the 32.2-kDa protein is an activator of transcription of granulocyte colony-stimulating factor receptor promoter, while the 14.3-kDa protein is not. Thus, C/EBP epsilon is regulated in a complex fashion and may play a role in the regulation of genes involved in myeloid differentiation. C1 NATL HUMAN GENOME RES INST,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD 20892. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,HEMATOL ONCOL DIV,,BOSTON,MA 02215. ROYAL CANC HOSP,INST CANC RES,HADDOW LABS,SUTTON SM2 5NG,SURREY,ENGLAND. FU NCI NIH HHS [CA41456, R01 CA041456]; NIDDK NIH HHS [DK48660, R01 DK048660] NR 39 TC 134 Z9 135 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 1997 VL 94 IS 12 BP 6462 EP 6467 DI 10.1073/pnas.94.12.6462 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400089 PM 9177240 ER PT J AU Furey, ML Pietrini, P Haxby, JV Alexander, GE Lee, HC VanMeter, J Grady, CL Shetty, U Rapoport, SI Schapiro, MB Freo, U AF Furey, ML Pietrini, P Haxby, JV Alexander, GE Lee, HC VanMeter, J Grady, CL Shetty, U Rapoport, SI Schapiro, MB Freo, U TI Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE physostigmine; acetylcholine; positron emission tomography; prefrontal cortex ID ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; CHANDELIER CELLS; PHYSOSTIGMINE; ATTENTION; MONKEYS; YOUNG; BRAIN; RCBF; RAT AB Modulation of the cholinergic neurotransmitter system results in changes in memory performance, including working memory (WM), in animals and in patients with Alzheimer disease, To identify associated changes in the functional brain response, we studied performance measures and regional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task, Eight. control subjects received an infusion of saline throughout the study and 13 experimental subjects received a saline infusion for the first 2 scans followed by a continuous infusion of physostigmine, an acetylcholinesterase inhibitor, for the subsequent 8 scans, rCBF was measured using (H2O)-O-15 and PET in a sequence of 10 PET scans that alternated between rest and task scans. During task scans, subjects performed the WM task for faces, Physostigmine both improved WM efficiency, as indicated by faster reaction times, and reduced WM task-related activity in anterior and posterior regions of right midfrontal gyrus, a region shown previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCBF correlated, These results suggest that enhancement of cholinergic function can improve processing efficiency and thus reduce the effort required to perform a WM task, and that activation of right prefrontal cortex is associated with task effort. C1 NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. BAYCREST CTR GERIATR CARE,ROTMAN RES INST,TORONTO,ON M6A 2EI,CANADA. RP Furey, ML (reprint author), NIA,NEUROSCI LAB,NIH,BLDG 10,ROOM 6C414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Furey, Maura/H-5273-2013 NR 36 TC 116 Z9 116 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 1997 VL 94 IS 12 BP 6512 EP 6516 DI 10.1073/pnas.94.12.6512 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400098 PM 9177249 ER PT J AU Cooke, PS Buchanan, DL Young, P Setiawan, T Brody, J Korach, KS Taylor, J Lubahn, DB Cunha, GR AF Cooke, PS Buchanan, DL Young, P Setiawan, T Brody, J Korach, KS Taylor, J Lubahn, DB Cunha, GR TI Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID KERATINOCYTE GROWTH-FACTOR; MAMMARY EPITHELIUM; GENITAL-TRACT; FEMALE MOUSE; IN-VIVO; CELLS; EXPRESSION; PROLIFERATION; UTERUS; MICE AB Estradiol-17 beta (E-2) acts through the estrogen receptor (ER) to regulate uterine growth and functional differentiation. To determine whether E-2 elicits epithelial mitogenesis through epithelial ER versus indirectly via ER-positive stromal cells, uteri from adult ER-deficient ER knockout (ko) mice and neonatal ER-positive wild-type (wt) BALB/c mice were used to produce the following tissue recombinants containing ER in epithelium (E) and/or stroma (S), or lacking ER altogether: wt-S + wt-E, wt-S + ko-E, ko-S + ko-E, and ko-S + wt-E. Tissue recombinants were grown for 4 weeks as subrenal capsule grafts in intact female nude mice, then the hosts were treated with either E-2 or oil a week after ovariectomy, Epithelial labeling index and ER expression were determined by [H-3] thymidine autoradiography and immunohistochemistry, respectively, In tissue recombinants containing wt S (wt-S + wt-E, wt-S + ko-E), E-2 induced a similar large increase in epithelial labeling index compared with oil-treated controls in both types of tissue recombinants despite the absence of epithelial ER in wt-S + ko-E tissue recombinants, This proliferative effect was blocked by an ER antagonist, indicating it was mediated through ER, In contrast, in tissue recombinants prepared with ko-S (ko-S + ko-E and ko-S + wt-E), epithelial labeling index was low and not stimulated by E-2 despite epithelial ER expression in ko-S + wt-E grafts, In conclusion, these data demonstrate that epithelial ER is neither necessary nor sufficient for E-2-induced uterine epithelial proliferation, Instead, E-2 induction of epithelial proliferation appears to be a paracrine event mediated by ER-positive stroma, These data in the uterus and similar studies in the prostate suggest that epithelial mitogenesis in both estrogen and androgen target organs are stromally mediated events. C1 UNIV CALIF SAN FRANCISCO,DEPT ANAT,SAN FRANCISCO,CA 94143. UNIV ILLINOIS,DEPT VET BIOSCI,URBANA,IL 61801. UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO 65211. UNIV MISSOURI,DEPT CHILD HLTH,COLUMBIA,MO 65211. NIEHS,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27907. OI Korach, Kenneth/0000-0002-7765-418X FU NCI NIH HHS [CA 05388]; NIA NIH HHS [AG 13784]; NICHD NIH HHS [HD 29376] NR 41 TC 382 Z9 392 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 1997 VL 94 IS 12 BP 6535 EP 6540 DI 10.1073/pnas.94.12.6535 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400102 PM 9177253 ER PT J AU Kost, RG Straus, SE AF Kost, RG Straus, SE TI Postherpetic neuralgia - Predicting and preventing risk SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID ATTENUATED VARICELLA VACCINE; HERPES-ZOSTER; IMMUNE-RESPONSE; PAIN RP Kost, RG (reprint author), NIAID, CLIN INVEST LAB,NIH,BLDG 10,ROOM 11N228, 10 CTR DR, BETHESDA, MD 20892 USA. NR 22 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 9 PY 1997 VL 157 IS 11 BP 1166 EP 1167 DI 10.1001/archinte.157.11.1166 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XC812 UT WOS:A1997XC81200002 PM 9183226 ER PT J AU Song, HJ Rossi, A Ceci, R Kim, IG Anzano, MA Jang, SI DeLaurenzi, V Steinert, PM AF Song, HJ Rossi, A Ceci, R Kim, IG Anzano, MA Jang, SI DeLaurenzi, V Steinert, PM TI The genes encoding geranylgeranyl transferase alpha-subunit and transglutaminase 1 are very closely linked but not functionally related in terminally differentiating keratinocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RECESSIVE LAMELLAR ICHTHYOSIS; HUMAN EPIDERMAL-KERATINOCYTES; PROTEIN-KINASE-C; TRANSCRIPTIONAL REGULATION; RETINOIC ACID; EXPRESSION; CALCIUM; MUTATIONS AB We report here the entire exon/intron structure of the gene encoding the alpha-subunit of human Rab geranylgeranyl transferase (RABGGTA) gene, which is positioned in a tandem head-to-tail arrangement with the transglutaminase 1 (TGM1) gene, and its polyadenylation signal sequence is located just 2.3 kbp upstream of the capsite of TGM1. Even though TGM1 and RABGGTA have different functions, their close localization raised the question as to whether they are functionally related in the epidermis. To address this question, we have studied the expression of the two genes by RT-PCR in normal human epidermal keratinocytes cultured under various differentiation conditions. While the expression of the TGM1 gene is markedly affected by the calcium concentration of the medium, all trans retinoic acid, vitamin D-3, and TPA treatment, the expression of the RABGGTA gene was unaffected by these reagents. Taken together, even though these two genes are unusually closely linked, they are not functionally related in the terminal differentiation program of epidermal keratinocytes. (C) 1997 Academic Press. C1 UNIV ROMA TOR VERGATA,DEPT EXPT MED,ROME,ITALY. SEOUL NATL UNIV,DEPT BIOCHEM & MOL BIOL,SEOUL,SOUTH KOREA. IRCCS,IDI,BIOCHEM LAB,ROME,ITALY. RP Song, HJ (reprint author), NIAMSD,SKIN BIOL LAB,BETHESDA,MD 20892, USA. FU Telethon [E.0413] NR 24 TC 5 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 9 PY 1997 VL 235 IS 1 BP 10 EP 14 DI 10.1006/bbrc.1997.6717 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XE346 UT WOS:A1997XE34600003 PM 9196026 ER PT J AU Mitton, KP Tumminia, SJ Arora, J Zelenka, P Epstein, DL Russell, P AF Mitton, KP Tumminia, SJ Arora, J Zelenka, P Epstein, DL Russell, P TI Transient loss of alpha B-crystallin: An early cellular response to mechanical stretch SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HEAT-SHOCK PROTEINS; UBIQUITIN-CARRIER PROTEIN; LENS EPITHELIAL-CELLS; DEGRADATION; EXPRESSION; SYSTEM; ACTIN; GENE; PHOSPHORYLATION; CYTOSKELETON AB Human trabecular meshwork (HTM) is distended and stretched with increases in intraocular pressure. During this stretching, there is a rearrangement of actin filaments. The HTM cells express alpha B-crystallin, a small heat shock protein that may have a role in the stabilization and regulation of the cytoskeleton in mammalian cells. The levels of alpha B-crystallin were examined in trabecular meshwork cells after mechanical stretch. Human TM primary cell cultures, plated onto silicone sheets, were subjected to a single 10% linear stretch and samples were prepared at various times after stretch for immunoblotting or Northern blotting Immunoblots of total protein extracts with antibody specific for alpha B-crystallin detected a 26% decrease of cellular alpha B-crystallin levels within 2 minutes. After 1 hour alpha B-crystallin levels had decreased 90% compared to control cells. The levels of alpha B-crystallin began to recover in cells stretched for 2 hours and returned to initial levels by 24 hours. Northern blots probed with alpha B-crystallin exon III cDNA detected a transcript of 0.65 kb in human TM cells and the levels of the alpha B mRNA remained constant during alpha B-crystallin protein decrease. Later, levels of the 0.65 kb transcript of alpha B-crystallin increased during the cellular recovery. These results suggest that decreased levels of alpha B-crystallin after mechanical stretch were probably not due to transcriptional changes but rather to increased degradation of alpha B-crystallin protein. An increase in mRNA levels may play a role in the recovery of alpha B-crystallin during reorganization of the cytoskeleton and attachment to the substratum. These data raise the possibility of a specific proteolysis of alpha B-crystallin protein in cells after a physiological challenge. (C) 1997 Academic Press. C1 NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT OPHTHALMOL,DURHAM,NC 27706. RP Mitton, KP (reprint author), NEI,LAB MECHANISMS OCULAR DIS,NIH,BETHESDA,MD 20892, USA. FU NEI NIH HHS [EY01894] NR 40 TC 48 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 9 PY 1997 VL 235 IS 1 BP 69 EP 73 DI 10.1006/bbrc.1997.6737 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XE346 UT WOS:A1997XE34600014 PM 9196037 ER PT J AU Shane, BS Lockhart, AMC Winston, GW Tindall, KR AF Shane, BS Lockhart, AMC Winston, GW Tindall, KR TI Mutant frequency of lacI in transgenic mice following benzo[a]pyrene treatment and partial hepatectomy SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE in vivo mutagenesis; transgenic mouse; benzo[a]pyrene; partial hepatectomy ID MOUSE MUTATION ASSAY; IN-VIVO; CARCINOGEN PAIR; DIOL-EPOXIDES; MUTAGENICITY; DNA; 2,4-DIAMINOTOLUENE; 2,6-DIAMINOTOLUENE; INDUCTION; EXPOSURE AB The Big Blue(R) transgenic mouse provides an in vivo mutation system that permits the study of pharmacodynamic parameters on mutant frequency (MF) following xenobiotic exposure. We have studied the effects of cellular proliferation on the frequency of mutations in the loci transgene by evaluating the MF in the liver of male C57B1/6 Big Blue(R) mice following treatment with benzo[a]pyrene (B[a]P) and a partial hepatectomy. Mice received either 40 mg/kg of B[a]P in corn oil or corn oil alone by i.p. injection on three consecutive days, followed by a partial hepatectomy on the fourth day. Three days later (i.e., 7 days following the initial B[a]P injection), the animals were sacrificed and the MF in the liver was compared to the MF observed in the liver of the same mouse at the time of hepatectomy. Induction of cytochrome P-450 1A (CYP1A) following B[a]P treatment was evident by Western blot analysis. The MF in untreated control animals was not significantly different at hepatectomy (4.7 +/- 0.8 x 10(-5)) and 3 days later, at sacrifice (3.0 +/- 0.4 x 10(-5)). Neither was the MF observed in the B[a]P-treated mice at the time of sacrifice (12.0 +/- 2.1 x 10(-5)) significantly different from the MF observed at the time of hepatectomy (10.6 +/- 5.3 x 10(-5)). However, B[a]P-treatment resulted in a 4.0-fold increase in MF at sacrifice which was significantly different (p < 0.05), when compared to the untreated controls. The B[a]P-treated mice at hepatectomy showed a modest 2.2-fold increase in MF which was not statistically significantly different from the untreated controls. In addition, both control and B[a]P-treated tissues gave sectored mutant plaques. The sectored plaque frequency (SPF) was significantly elevated (p < 0.05) in the B[a]P-treated mice at hepatectomy (4.2 +/- 1.0 x 10(-5)) and sacrifice (7.3 +/- 2.4 x 10(-5)) as compared to the respective frequency in the control mice at hepatectomy (1.9 +/- 0.7 x 10(-5)) and sacrifice (1.4 +/- 0.2 x 10(-5)). One explanation for this data is the persistence of the B[a]P adducts in the mouse genomic DNA that was packaged into the lambda phage, and ultimately fixed as mutations in Escherichia coli. C1 ANALYT SCI INC,RES TRIANGLE PK,NC 27709. LOUISIANA STATE UNIV,DEPT BIOCHEM,BATON ROUGE,LA 70803. NIEHS,RES TRIANGLE PK,NC 27709. RP Shane, BS (reprint author), LOUISIANA STATE UNIV,INST ENVIRONM STUDIES,42 ATKINSON HALL,BATON ROUGE,LA 70803, USA. NR 36 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUN 9 PY 1997 VL 377 IS 1 BP 1 EP 11 DI 10.1016/S0027-5107(97)00004-3 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XG852 UT WOS:A1997XG85200002 PM 9219573 ER PT J AU Kuo, TM Lowell, CA Smith, PT AF Kuo, TM Lowell, CA Smith, PT TI Changes in soluble carbohydrates and enzymic activities in maturing soybean seed tissues SO PLANT SCIENCE LA English DT Article DE soybean seeds; embryo; seed coat; galactinol synthase; raffinose saccharides; invertase; sucrose synthase ID DESICCATION TOLERANCE; GALACTINOL SYNTHASE; INVERTASE ACTIVITY; SUCROSE; METABOLISM; SUGARS; ACCUMULATION; PURIFICATION; PATHWAY; LEAVES AB Enzyme activities were compared with the accumulation of soluble carbohydrates in seed coats, cotyledons and embryonic axes of field-grown soybean (Glycine max L. Merr. cv. Williams 82) seeds during seed maturation to examine the function of each seed tissue in non-structural carbohydrate metabolism. The vascularized seed coat was comparatively high in monosaccharides (glucose and fructose) which corresponded to greater acid invertase activity per gram dry weight than cotyledons and axes. The embryo (cotyledon + embryonic axis) was high in oligosaccharide content, and contained greater mean activity levels of sucrose synthase, alkaline invertase, galactinol synthase and a-galactosidase than the seed coat. There was little difference in the sucrose-phosphate synthase activity among these three tissues. The accumulation of raffinose saccharides (raffinose and stachyose) increased rapidly in the embryo during seed maturation. Activities of alkaline invertase, sucrose synthase, galactinol synthase, a-galactosidase, fructose-1,6-bisphosphate aldolase, malate dehydrogenase, and glucose-6-phosphate dehydrogenase were highest in embryonic axes. Initial maturation of soybean seeds may be distinguished developmentally by the yellowing of embryonic axes at 40-45 days after flowering. This change was found to coincide with increases in sucrose synthase and galactinol synthase activities, and with the initiation of a rapid accumulation of raffinose saccharides in the embryonic axis. (C) 1997 Elsevier Science Ireland Ltd. C1 CENT STATE UNIV,DEPT BIOL,WILBERFORCE,OH 45384. NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RP Kuo, TM (reprint author), USDA ARS,NATL CTR AGR UTILIZAT RES,OIL CHEM RES UNIT,1815 N UNIV ST,PEORIA,IL 61604, USA. NR 35 TC 32 Z9 33 U1 0 U2 14 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-9452 J9 PLANT SCI JI Plant Sci. PD JUN 9 PY 1997 VL 125 IS 1 BP 1 EP 11 PG 11 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA XC790 UT WOS:A1997XC79000001 ER PT J AU vonGegerfelt, A Felber, BK AF vonGegerfelt, A Felber, BK TI Replacement of posttranscriptional regulation in SIVmac239 generated a Rev-independent infectious virus able to propagate in rhesus peripheral blood mononuclear cells SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SIMIAN RETROVIRUS TYPE-1; ATTENUATED SIV; NEF GENE; EXPRESSION; ELEMENT; PROTEIN; SEQUENCE; LIVE; AIDS AB Lentiviruses control virion production via posttranscriptional regulation mediated by the viral Rev protein. In this study, we demonstrate that the Rev regulation of SIVmac239 can be replaced by the presence of the cis-acting transport element (CTE) of the type D simian retroviruses 1 (SRV-1). To avoid the possibility of generating revertants, the Rev-independent SIV clones have both rev and the Rev responsive element (RRE) destroyed by multiple point mutations that do not affect the overlapping tat and env open reading frames. Virus stocks generated from these Rev-independent SIV molecular clones can infect and can be propagated in rhesus peripheral blood mononuclear cells (PBMCs). Therefore, the Rev/RRE system of SIVmac239 can be replaced by the SRV-1 CTE as previously shown for HIV-1. In both rhesus and human primary cells, the replicative capacity of the Rev-independent SIV is 10- to 20-fold lower than that of the wild-type virus. Rhesus PBMC-derived virus stocks of the Rev-independent SIV have lower infectivity. Interestingly, in CEM x 174 cells, no difference in replicative capacity between wild-type and Rev-independent SIV has been observed. The Rev-independent SIV has a stable genotype after several passages in primary cells. The availability of such Rev-independent viruses will allow the study of the role of Rev in pathogenesis and the potential generation of attenuated SIV strains. (C) 1997 Academic Press. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. NR 23 TC 18 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 9 PY 1997 VL 232 IS 2 BP 291 EP 299 PG 9 WC Virology SC Virology GA XE376 UT WOS:A1997XE37600006 PM 9191842 ER PT J AU Wolff, L AF Wolff, L TI Contribution of oncogenes and tumor suppressor genes to myeloid leukemia SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID ACUTE PROMYELOCYTIC LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; NUCLEAR-PORE COMPLEX; NON-T-CELL; 11Q23 CHROMOSOMAL TRANSLOCATIONS; CHRONIC MYELOMONOCYTIC LEUKEMIA; INDUCED PROMONOCYTIC LEUKEMIA; PUTATIVE TRANSCRIPTION FACTOR; MOUSE MYELOBLASTIC LEUKEMIAS RP Wolff, L (reprint author), NCI,CELLULAR ONCOL LAB,BLDG 37,ROOM 2B04,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 352 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD JUN 7 PY 1997 VL 1332 IS 3 BP F67 EP F104 DI 10.1016/S0304-419X(97)00006-1 PG 38 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA XF400 UT WOS:A1997XF40000002 PM 9196020 ER PT J AU Boyd, DR Sharma, ND Agarwal, R Resnick, SM Schocken, MJ Gibson, DT Sayer, JM Yagi, H Jerina, DM AF Boyd, DR Sharma, ND Agarwal, R Resnick, SM Schocken, MJ Gibson, DT Sayer, JM Yagi, H Jerina, DM TI Bacterial dioxygenase-catalysed dihydroxylation and chemical resolution routes to enantiopure cis-dihydrodiols of chrysene SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; REGION DIOL EPOXIDES; RAT-LIVER ENZYMES; ABSOLUTE-CONFIGURATION; ENANTIOMERIC EXCESS; PSEUDOMONAS-PUTIDA; PHENANTHRENE; METABOLISM; OXIDATION; CIS-1,2-DIHYDRODIOL AB Biotransformation of the environmental pollutant chrysene 1 by resting cells of a mutant strain (B8/36) of the soil bacterium Sphingomonas yanoikuyae produces (+)-cis-3,4-dihydroxy-3,4-dihydrochrysene 4 which has been assigned (3S,4R) absolute configuration by stereochemical correlation with (-)(3S,4R)cis-3,4-dihydroxy-1,2,3,4-tetrahydrochrysene 6. Both cis-3,4-diol 6 and cis-1,2-dihydroxy-1,2,3,4-tetrahydrochrysene 12 are obtained in enantiopure form after chromatographic separation of the individual bis(2-methoxy-2-phenyl-2-trifluoromethylacetyl)(bis-MTPA) diastereoisomers of compound 6 and the MTPA diastereoisomers of bromohydrin 19, respectively, followed by hydrolysis. A new general synthetic route to cis-dihydrodiols, from the corresponding cis-tetrahydrodiol cyclic carbonates, is used to obtain both racemic and enantiopure forms of the bay-region diol 4, and the non-bay region diol 5. H-1 NMR and CD spectra of the cis- and trans-dihydrodiols of chrysene are described. C1 UNIV IOWA,DEPT MICROBIOL,IOWA CITY,IA 52242. UNIV IOWA,CTR BIOCATALYSIS & BIOPROC,IOWA CITY,IA 52242. SPRINGBORN LABS INC,WAREHAM,MA 02571. NIDDK,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. RP Boyd, DR (reprint author), QUEENS UNIV BELFAST,SCH CHEM,BELFAST BT9 5AG,ANTRIM,NORTH IRELAND. NR 30 TC 21 Z9 22 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0300-922X J9 J CHEM SOC PERK T 1 JI J. Chem. Soc.-Perkin Trans. 1 PD JUN 7 PY 1997 IS 11 BP 1715 EP 1723 DI 10.1039/a606686k PG 9 WC Chemistry, Organic SC Chemistry GA XF314 UT WOS:A1997XF31400019 ER PT J AU Yamasaki, Y Matsuo, Y Zagorski, J Matsuura, N Onodera, H Itoyama, Y Kogure, K AF Yamasaki, Y Matsuo, Y Zagorski, J Matsuura, N Onodera, H Itoyama, Y Kogure, K TI New therapeutic possibility of blocking cytokine-induced neutrophil chemoattractant on transient ischemic brain damage in rats SO BRAIN RESEARCH LA English DT Article DE cytokine-induced neutrophil chemoattractant; focal cerebral ischemia; ischemic neuronal damage; neutrophil; rat ID CEREBRAL-ARTERY OCCLUSION; EPITHELIOID CELL-LINE; POLYMORPHONUCLEAR LEUKOCYTES; INFLAMMATORY CYTOKINES; SELECTIVE DEPLETION; MONOCLONAL-ANTIBODY; INTERLEUKIN-8 GENE; REPERFUSION; INJURY; EXPRESSION AB Earlier we indicated that neutrophilic invasion into cerebral parenchyma is an important step in rat cerebral ischemia-reperfusion injury and the production of chemotactic factors, cytokine-induced neutrophil chemoattractant (CINC) precede the neutrophilic invasion. The aim of the present study was to evaluate the role of CINC production and the therapeutic possibility of blocking CINC activity in the transient ischemic brain damage in rats. Focal transient ischemia was produced by intraluminal occlusion of the right middle cerebral artery for 60 min. An enzyme immunoassay was used to measure the brain concentration of CINC and myeloperoxidase activity in ischemic areas was measured as a marker of neutrophilic accumulation. An immunohistochemical staining technique was used to detect the immunopositive cells for anti-CINC antibody. Further, application of anti-CINC antibody or anti-neutrophil antibody to rats was used to evaluate the role of CINC production. In ischemic areas, CINC production was detected and peaked 12 h after reperfusion, which followed 60 min of ischemia. Intraperitoneal injection of anti-neutrophil antibody 24 h before and immediately after reperfusion significantly reduced the brain water content and partially reduced the CINC production in ischemic areas. Further, immunohistochemical staining showed that anti-CINC antibody was found on the endothelial surface of venules and on parts of neutrophils that had invaded the ischemic area 6 to 24 h after reperfusion. Also, treatment with anti-CINC antibody reduced ischemic edema formation 24 h after reperfusion and the size of infarction areas 7 days after reperfusion. It thus appears that CINC, mainly produced by endothelium activated by factors released from neutrophils, plays an important role in ischemic brain damage. Furthermore, the blocking of CINC activity with antibody suggests an immune-therapeutic approach to the treatment of stroke patients, C1 SHIONOGI PHARMACEUT CO LTD,DEV RES CTR,OSAKA 561,JAPAN. NIDR,NIH,IMMUNOL LAB,BETHESDA,MD 20892. TOHOKU UNIV,SCH MED,DEPT NEUROL,SENDAI,MIYAGI 980,JAPAN. KANTO NEUROSURG HOSP,INST NEUROPATHOL,KUMAGAYA,SAITAMA 366,JAPAN. RP Yamasaki, Y (reprint author), TAIHO PHARMACEUT CO LTD,HANNO RES CTR,1-27 MISUGIDAI,HANNO,SAITAMA 357,JAPAN. NR 50 TC 84 Z9 88 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 JUN 6 PY 1997 VL 759 IS 1 BP 103 EP 111 DI 10.1016/S0006-8993(97)00251-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA XG026 UT WOS:A1997XG02600013 PM 9219868 ER PT J AU Jurutka, PW Hsieh, JC Remus, LS Whitfield, GK Thompson, PD Haussler, CA Blanco, JCG Ozato, K Haussler, MR AF Jurutka, PW Hsieh, JC Remus, LS Whitfield, GK Thompson, PD Haussler, CA Blanco, JCG Ozato, K Haussler, MR TI Mutations in the 1,25-dihydroxyvitamin D-3 receptor identifying C-terminal amino acids required for transcriptional activation that are functionally dissociated from hormone binding, heterodimeric DNA binding, and interaction with basal transcription factor IIB, in vitro SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VITAMIN-D-RECEPTOR; D-RESPONSIVE ELEMENT; HUMAN ESTROGEN-RECEPTOR; RAT OSTEOCALCIN GENE; RETINOID-X-RECEPTOR; PROTEIN-KINASE-C; THYROID-HORMONE; FACTOR TFIIB; TRANSACTIVATION DOMAIN; CRYSTAL-STRUCTURE AB To investigate a potential ligand-dependent transcriptional activation domain (AF-2) in the C-terminal region of the human vitamin D receptor (hVDR), two conserved residues, Leu-417 and Glu-420, were replaced with alanines by site-directed mutagenesis (L417A and E420A). Transcriptional activation in response to 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) was virtually eliminated when either point mutant was transfected into several mammalian cell lines. Furthermore, both mutants exhibited a dominant negative phenotype when expressed in COS-7 cells. Scatchard analysis at 4 degrees C and a ligand-dependent DNA binding assay at 25 degrees C revealed essentially normal 1,25-(OH)(2)D-3 binding for the mutant hVDRs, which were also equivalent to native receptor in associating with the rat osteocalcin vitamin D responsive element as a presumed heterodimer with retinoid X receptor. Glutathione S-transferase-human transcription factor IIB (TFIIB) fusion protein linked to Sepharose equally coprecipitated the wild-type hVDR and the AF-2 mutants. These data implicate amino acids Leu-417 and Glu-420, residing in a putative alpha-helical region at the extreme C terminus of hVDR, as critical in the mechanism of 1,25-(OH)(2)D-3-stimulated transcription, likely mediating an interaction with a coactivator(s) or a component of the basal transcriptional machinery distinct from TFIIB. C1 UNIV ARIZONA,COLL MED,DEPT BIOCHEM,TUCSON,AZ 85724. NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. OI Jurutka, Peter/0000-0002-4950-9161 FU NIAMS NIH HHS [AR-15781]; NIDDK NIH HHS [DK-33351, DK-49604] NR 60 TC 63 Z9 66 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 1997 VL 272 IS 23 BP 14592 EP 14599 DI 10.1074/jbc.272.23.14592 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XC327 UT WOS:A1997XC32700015 PM 9169418 ER PT J AU Clark, JA AF Clark, JA TI Analysis of the transmembrane topology and membrane assembly of the GAT-1 gamma-aminobutyric acid transporter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN P-GLYCOPROTEIN; HUMAN NOREPINEPHRINE TRANSPORTER; NEUROTRANSMITTER TRANSPORTERS; ENDOPLASMIC-RETICULUM; GLYCINE TRANSPORTER; EXPRESSION CLONING; GLUTAMATE-RECEPTOR; SPANNING REGIONS; N-GLYCOSYLATION; SIGNAL SEQUENCE AB The transmembrane topology of the Na+- and Cl--dependent gamma-aminobutyric acid transporter GAT-1 has been studied using protein chimeras in Xenopus oocytes. A series of COOH-terminal truncations was generated to which a prolactin epitope was fused. Following expression of transporter-prolactin chimeras in Xenopus oocytes, the transmembrane orientation of each chimera was determined by testing for protease sensitivity in an oocyte membrane preparation. Data from protease protection assays with GAT-1-prolactin chimeras has shown that residues in the loops connecting hydrophobic domain (HD)3 and HD4 and HD7 and HD8 are accessible to protease in the cytoplasm and suggest the presence of pore loop structures which extend into the membrane from the extracellular face. Such pore loop structures may be involved in the formation of the substrate binding pocket. Studies presented herein confirm that the NH, and COOH termini are cytosolic and hydrophobic domains span the membrane in a manner con sistent with the predicted hydropathy model for Na+- and Cl- dependent transporters. These data also provide insight into GAT-1 transmembrane assembly and suggest that a complex series of topogenic sequences directs this process. A potential pause-transfer sequence has been identified and may be responsible for the translocational pausing observed in this study. RP Clark, JA (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 43 TC 29 Z9 31 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 1997 VL 272 IS 23 BP 14695 EP 14704 DI 10.1074/jbc.272.23.14695 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XC327 UT WOS:A1997XC32700030 PM 9169433 ER PT J AU Tarasova, NI Stauber, RH Choi, JK Hudson, EA Czerwinski, G Miller, JL Pavlakis, GN Michejda, CJ Wank, SA AF Tarasova, NI Stauber, RH Choi, JK Hudson, EA Czerwinski, G Miller, JL Pavlakis, GN Michejda, CJ Wank, SA TI Visualization of G protein-coupled receptor trafficking with the aid of the green fluorescent protein - Endocytosis and recycling of cholecystokinin receptor type A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PANCREATIC ACINAR-CELLS; TEMPERATURE-DEPENDENCE; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; INTERNALIZATION; BINDING; LIGAND; CCK; COLOCALIZATION; LOCALIZATION AB A chimeric protein consisting of the cholecystokinin receptor type A (CCKAR) and the green fluorescent protein (GFP) was used for studying receptor localization, internalization, and recycling in live cells in real time in four different cell lines. Fusion of the C terminus of the CCKAR to the N terminus of the GFP did not alter receptor ligand binding affinity, signal transduction, or the pattern of receptor surface expression and receptor-mediated cholecystokinin (CCK) internalization. The use of a new GFP mutant with increased fluorescence allowed the continuous observation of CCKAR-GFP in stably expressing cell lines. Newly obtained biologically active fluorescent derivatives of CCK were used for simultaneous observation of receptor and ligand trafficking in CHO, NIH/3T3, and HeLa cells stably expressing the fluorescent CCKAR and in transiently transfected COS-1 cells. Receptor internalization was predominantly ligand dependent in HeLa, COS-1, and CHO cells, but was mostly constitutive in NIH/3T3 cells, suggesting the existence of cell-specific regulation of receptor internalization. The CCKAR antagonists, L-364,718 and CCK 27-32 amide potently inhibited spontaneous internalization of the receptor. The average sorting time of CCK and the receptor in the endosomes was about 25 min. The receptor recycled back to the cell membrane with an average time of 60 min. While the ligands sorted to lysosomes, no receptor molecules could be detected there, and no receptor degradation was observed during recycling. These results demonstrate the usefulness of GFP tagging for real time imaging of G protein-coupled receptor trafficking in living cells and suggest that this technique may be successfully applied to the study of the regulation and trafficking mechanisms of other receptors. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. NIDDK,DIGEST DIS BRANCH,CHEM BIOL BRANCH,NIH,BETHESDA,MD 20892. OI Stauber, Roland/0000-0002-1341-4523 NR 43 TC 155 Z9 156 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 1997 VL 272 IS 23 BP 14817 EP 14824 DI 10.1074/jbc.272.23.14817 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XC327 UT WOS:A1997XC32700047 PM 9169450 ER PT J AU Nagaich, AK Zhurkin, VB Sakamoto, H Gorin, AA Clore, GM Gronenborn, AM Appella, E Harrington, RE AF Nagaich, AK Zhurkin, VB Sakamoto, H Gorin, AA Clore, GM Gronenborn, AM Appella, E Harrington, RE TI Architectural accommodation in the complex of four p53 DNA binding domain peptides with the p21/waf1/cip1 DNA response element SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; MUTANT P53; CURVED DNA; WILD-TYPE; SEQUENCE; PROTEIN; SUPPRESSOR; RESOLUTION; ACTIVATION; CURVATURE AB High resolution chemical footprinting and cross-linking experiments have provided a basis for elucidating the overall architecture of the complex between the core DNA binding domain of p53 (p53DBD, amino acids 98-309) and the p21/waf1/cip1 DNA response element implicated in the G(1)/S phase cell cycle checkpoint. These studies complement both a crystal structure and earlier biophysical studies and provide the first direct experimental evidence that four subunits of p53DBD bind to the response element in a regular staggered array having pseudodyad symmetry, The invariant guanosines in the highly conserved C(A/T)\(T/A)G parts of the consensus half-sites are critical to the p53DBD-DNA binding. Molecular modeling of the complex using the observed peptide-DNA contacts shows that when four subunits of p53DBD bind the response element, the DNA has to bend similar to 50 degrees to relieve steric clashes among different subunits, consistent with recent DNA cyclization studies. The overall lateral arrangement of the four p53 subunits with respect to the DNA loop comprises a novel nucleoprotein assembly that has not been reported previously in other complexes. We suggest that this kind of nucleoprotein superstructure may be important for p53 binding to response elements packed in chromatin and for subsequent transactivation of p53-mediated genes. C1 UNIV NEVADA,SCH MED,DEPT BIOCHEM 330,RENO,NV 89557. RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08855. NCI,LAB EXPT & COMPUTAT BIOL,NIH,BETHESDA,MD 20892. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NIDDK,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008; Sakamoto, Hiroshi/A-3181-2011; Gorin, Andrey/B-1545-2014 OI Clore, G. Marius/0000-0003-3809-1027; FU NCI NIH HHS [CA70274]; NHGRI NIH HHS [HG00656] NR 64 TC 59 Z9 59 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 1997 VL 272 IS 23 BP 14830 EP 14841 DI 10.1074/jbc.272.23.14830 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XC327 UT WOS:A1997XC32700049 PM 9169452 ER PT J AU Nagaich, AK Appella, E Harrington, RE AF Nagaich, AK Appella, E Harrington, RE TI DNA bending is essential for the site-specific recognition of DNA response elements by the DNA binding domain of the tumor suppressor protein p53 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WILD-TYPE; TRANSCRIPTION INITIATION; GEL-ELECTROPHORESIS; CRYSTAL-STRUCTURE; MUTANT P53; SEQUENCE; COMPLEXES; GENE; BIREFRINGENCE; REPLICATION AB We have used circular permutation assays to determine the extent and location of the DNA bend induced by the DNA binding domain of human wild type p53 (p53DBD) upon binding to several naturally occurring DNA response elements. We have found that p53DBD binding induces axial bending in all of the response elements investigated. In particular, response elements having a d(CATG) sequence at the junction of two consensus pentamers in each half-site favor highly bent complexes (bending angle is similar to 50 degrees), whereas response elements having d(CTTG) bases at this position are less bent (bending angles from similar to 37 to similar to 25 degrees). Quantitative electrophoretic mobility shift assays of different complexes show a direct correlation between the DNA bending angle and the binding affinity of the p53DBD with the response elements, i.e. the greater the stability of the complex, the more the DNA is bent by p53DBD binding. The study provides evidence that the energetics of DNA bending, as determined by the presence or absence of flexible sites in the response elements, may contribute significantly to the overall binding affinity of the p53DBD for different sequences. The results therefore suggest that both the structure and the stability of the p53-DNA complex may vary with different response elements. This variability may be correlated with variability in p53 function. C1 UNIV NEVADA,DEPT BIOCHEM 330,RENO,NV 89557. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA70274] NR 64 TC 76 Z9 77 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 1997 VL 272 IS 23 BP 14842 EP 14849 DI 10.1074/jbc.272.23.14842 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XC327 UT WOS:A1997XC32700050 PM 9169453 ER PT J AU Honkakoski, P Negishi, M AF Honkakoski, P Negishi, M TI Characterization of a phenobarbital-responsive enhancer module in mouse P450 Cyp2b10 gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTIONAL REGULATION; GLYCOPROTEIN GENE; RAT-LIVER; INVITRO TRANSCRIPTION; TRANSGENIC MICE; CYTOCHROME-P-450; EXPRESSION; ELEMENTS; INDUCTION; PROMOTER AB Induction of drug- and carcinogen-metabolizing cytochrome P450s by xenobiotic chemicals is a common cellular defense mechanism, usually leading to increased detoxification of xenobiotics but sometimes, paradoxically, to formation of more toxic and carcinogenic metabolites. Phenobarbital (PB) is an archetypal representative for chemicals including industrial solvents, pesticides, plant products, and clinically used drugs that induce several genes within CYP subfamilies 2B, 2A, 2C, and 3A in rodents and humans, Although the transcription of these CYP genes is activated by PB, the associated molecular mechanisms have not yet been elucidated. Here we have analyzed, in detail, enhancer activity of a far upstream region of mouse Cyp2b10 gene and report a 132-base pair PB-responsive enhancer module (PBREM) with a 33-base pair core element containing binding sites for nuclear factor I- and nuclear receptor-like factors. Mutations of these binding sites abolish the ability of PBREM to respond to inducers in mouse primary hepatocyte. C1 NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,NIH,RES TRIANGLE PK,NC 27709. OI Honkakoski, Paavo/0000-0002-4332-3577 NR 46 TC 120 Z9 128 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 1997 VL 272 IS 23 BP 14943 EP 14949 DI 10.1074/jbc.272.23.14943 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XC327 UT WOS:A1997XC32700063 PM 9169466 ER PT J AU Rosson, D OBrien, TG Kampherstein, JA Szallasi, Z Bogi, K Blumberg, PM Mullin, JM AF Rosson, D OBrien, TG Kampherstein, JA Szallasi, Z Bogi, K Blumberg, PM Mullin, JM TI Protein kinase C-alpha activity modulates transepithelial permeability and cell junctions in the LLC-PK1 epithelial cell line SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TIGHT JUNCTIONS; PHOSPHORYLATION; ACTIVATION; PROMOTERS; FAMILY; DELTA AB Modulation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA) disrupts the cell-cell junctions of the epithelial cell line LLC-PK1. To examine the role of specific PKC isoforms in this process we have created modified LLC-PK1 subclones that express wild-type and dominant negative versions of PKC-alpha under control of the tetracycline-responsive expression system. Overexpression of wild-type PKC-alpha rendered the cells more sensitive to the effects of TPA on transepithelial permeability as measured by loss of transepithelial resistance across the cell sheet. Conversely, expression of a dominant negative PKC-alpha rendered the cells more resistant to the effects of TPA as measured both by loss of transepithelial resistance as well as cell scattering. The properties of both subclones could be modulated by the addition of tetracycline, which suppressed the effect of the exogenous genes. These results indicate that the alpha isoform of PKC is at least one of the isoforms that regulate tight junctions and other cell-cell junctions of LLC-PK1 epithelia. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892. RP Rosson, D (reprint author), LANKENAU MED RES CTR,100 LANCASTER AVE,WYNNEWOOD,PA 19096, USA. FU NCI NIH HHS [CA36353, CA48121] NR 25 TC 70 Z9 70 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 1997 VL 272 IS 23 BP 14950 EP 14953 DI 10.1074/jbc.272.23.14950 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XC327 UT WOS:A1997XC32700064 PM 9169467 ER PT J AU Guerrini, R Calo, G Rizzi, A Bianchi, C Lazarus, LH Salvadori, S Temussi, PA Regoli, D AF Guerrini, R Calo, G Rizzi, A Bianchi, C Lazarus, LH Salvadori, S Temussi, PA Regoli, D TI Address and message sequences for the nociceptin receptor: A structure-activity study of nociceptin-(1-13)-peptide amide SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID OPIOID RECEPTOR; PEPTIDES; AGONIST; ANTAGONISTS; DERMORPHIN; MORPHINE; SKIN AB Nociceptin (NC) and some of its fragments as well as nociceptin-(1-13)-peptide amide [NC(1-13)-NH2] and a series of its analogues were prepared and tested in the mouse vas deferens in an attempt to identify the sequences involved in the activation (message) and in the binding (address) of nociceptin to its receptor. The NC receptor that inhibits the electrically evoked twitches of the mouse vas deferens was demonstrated to be distinct from the delta opioid receptor, since naloxone and Dmt-Tic-OH (a selective delta opioid receptor antagonist) block the delta opioid receptor but have no effect on the nociceptin receptor. Results from structure-activity experiments suggest that (a) the entire sequence of NC may not be required for full biological activities, since NC(1-13)-NH2 is as active as NC; (b) fragments of NC have however to be amidated as in NC(1-13)-NH2 in order to be protected from degradation by proteases; (c) cationic residues (as Args(8,12), Lys(9,13)) appear to play a functional role, since their replacement with Ala in the sequence of NC(1-13)-NH2 leads to inactivity; (d) the N-terminal tetrapeptide Phe-Gly-Gly-Phe is essential for activity: its full length and flexibility appear to be required for NC receptor activation and/or occupation; (e) Phe(4) and not Phe(1) appears to be the residue involved in receptor activation, since the replacement of Phe(1) with Leu has no effect, while that of Phe(4) leads to inactivity. Results summarized in this paper indicate that the structural requirements of NC for occupation and activation of its receptor are different from that of opioids, particularly delta agonists. C1 UNIV FERRARA,DIPARTIMENTO SCI FARMACEUT,I-44100 FERRARA,ITALY. UNIV FERRARA,CTR BIOTECHNOL,I-44100 FERRARA,ITALY. UNIV FERRARA,INST PHARMACOL,I-44100 FERRARA,ITALY. NIEHS,RES TRIANGLE PK,NC 27709. UNIV NAPLES FEDERICO II,DEPT CHEM,I-80134 NAPLES,ITALY. OI Guerrini, Remo/0000-0002-7619-0918; SALVADORI, Severo/0000-0002-8224-2358 NR 31 TC 180 Z9 182 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 6 PY 1997 VL 40 IS 12 BP 1789 EP 1793 DI 10.1021/jm970011b PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XC901 UT WOS:A1997XC90100006 PM 9191955 ER PT J AU Li, J Gutell, RR Damberger, SH Wirtz, RA Kissinger, JC Rogers, MJ Sattabongkot, J McCutchan, TF AF Li, J Gutell, RR Damberger, SH Wirtz, RA Kissinger, JC Rogers, MJ Sattabongkot, J McCutchan, TF TI Regulation and trafficking of three distinct 18 S ribosomal RNAs during development of the malaria parasite SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE small subunit (SSU) rRNA; ribosome; development; malaria; translational control ID PLASMODIUM-FALCIPARUM; GENES; 16S; IDENTIFICATION; QUANTITATION; MUTATIONS AB The human malaria parasite Plasmodium vivax has been shown to regulate the transcription of two distinct 18 RNAs during development. Here we show a third and distinctive type of ribosome that is present shortly after zygote formation, a transcriptional pattern of ribosome types that relates closely to the developmental state of the parasite and a phenomenon that separates ribosomal types at a critical phase of maturation. The A-type ribosome is predominantly found in infected erythrocytes of the vertebrate and the mosquito blood meal. Transcripts from the A gene are replaced by transcripts from another locus, the O gene, shortly after fertilization and increase in number as the parasite develops on the mosquito midgut. Transcripts from another locus, the S gene, begins as the oocyst form of the parasite matures. RNA transcripts from the S gene are preferentially included in sporozoites that bud off from the oocyst and migrate to the salivary gland while the O gene transcripts are left within the oocyst. Although all three genes are typically eukaryotic in structure, the O gene transcript, described here, varies from the other two in core regions of the rRNA that are involved in mRNA decoding and translational termination. We now can correlate developmental progression of the parasite with changes in regions of rRNA sequence that are broadly conserved, where sequence alterations have been related to function in other systems and whose effects can be studied outside of Plasm odium. This should allow assessment of the role of translational control in parasite development. (C) 1997 Academic Press Limited. C1 NIAID,GROWTH & DEV SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. UNIV COLORADO,DEPT MCD BIOL,BOULDER,CO 80309. UNIV COLORADO,DEPT CHEM & BIOCHEM,BOULDER,CO 80309. CTR DIS CONTROL & PREVENT,DIV PARASIT DIS,ENTOMOL BRANCH,ATLANTA,GA 30341. USA,MED COMPONENT,DEPT ENTOMOL,BANGKOK,THAILAND. RI Kissinger, Jessica/E-9610-2010 OI Kissinger, Jessica/0000-0002-6413-1101 FU NIGMS NIH HHS [R01 GM048207, GM48207] NR 33 TC 65 Z9 70 U1 1 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 6 PY 1997 VL 269 IS 2 BP 203 EP 213 DI 10.1006/jmbi.1997.1038 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XC851 UT WOS:A1997XC85100004 PM 9191065 ER PT J AU Covell, DG Wallqvist, A AF Covell, DG Wallqvist, A TI Analysis of protein-protein interactions and the effects of amino acid mutations on their energetics. The importance of water molecules in the binding epitope SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE binding energy; mutations; D1.3-HEL; D1.3-E5.2; barnase-barstar; bound water ID MOLAR HEAT-CAPACITY; FREE-ENERGY; SOLVATION THERMODYNAMICS; BIO-POLYMERS; ASSOCIATION; RECOGNITION; BARSTAR; ANTIBODIES; STABILITY; INHIBITOR AB A modelling analysis has been conducted to assess the determinants of binding strength and specificity for three crystal complexes; the anti-hen egg white lysozyme antibody D1.3 complexed with hen egg white lysozyme (HEL), the D1.3 antibody complexed with the anti-lysozyme antibody E5.2, and barnase complexed with barstar. The strengths of individual binding components within these interfaces are evaluated using a model of binding free energy that is based on pairwise surface preferences. Ln all cases the energetics of binding are dominated by a relatively small number of interfacial residues that define the binding epitope. A precise geometric arrangement of these residues was not found; they were either localized to one region, or distributed throughout the binding interface. Surprisingly, interfacial crystal water molecules were calculated to contribute around 25% of the total calculated binding strength. Theoretical alanine mutations were completed by atomic deletions of the wild-type complexes. Strong correlations were observed between the calculated changes in binding free energy (Delta Delta G(calculated)) and the experimental values (Delta Delta G(observed)) for all but three of the 30 single residue mutations in the D1.3-HEL, D1.3-E5.2 and barnase-barstar systems and for all of the double mutations in the barnase-barstar system. This analysis finds that the observed differences in binding strength are consistent with a model that accounts for the changes in binding energy from the direct contacts between each member of the complex and indirect changes due to released crystallographic water molecules that are near the mutation site. The observed energy changes for double mutations in the barnase-barstar system is fully accounted for by considering water molecules bound jointly by each member of the complex. (C) 1997 Academic Press Limited. RP Covell, DG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702, USA. NR 48 TC 68 Z9 69 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 6 PY 1997 VL 269 IS 2 BP 281 EP 297 DI 10.1006/jmbi.1997.1028 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XC851 UT WOS:A1997XC85100010 PM 9191071 ER PT J AU Park, T Brown, MB AF Park, T Brown, MB TI Log-linear models for a binary response with nonignorable nonresponse SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE missing data; contingency table; constrained maximum likelihood; smoothing ID MAXIMUM-LIKELIHOOD ESTIMATION; MISSING CATEGORICAL-DATA; CONTINGENCY-TABLES; CLASSIFIED DATA; VARIABLES; SUBJECT; EXAMPLE AB We focus on the analysis of contingency tables that contain both completely and partially cross-classified data where one of the variables is a binary response variable subject to nonignorable non-response and the other variables are always observed. Log-linear models can be used to adjust for nonresponse in an augmented table where one index corresponds to whether or not the subject is a respondent. The maximum likelihood estimators (MLEs) of the expected cell frequencies in the augmented table can be obtained iteratively using the EM algorithm. ML estimation may yield boundary estimators for the expected frequencies of the nonrespondents' cells. As a result, the odds ratio which represents the nonresponse mechanism is estimated either as 0 or infinity and the estimate of the corresponding log-linear model parameter is infinite. Since such an extreme estimate is not anticipated, it is desirable to use a constraint which limits the range of the odds ratio. We propose a constrained maximum likelihood estimator which maximizes the likelihood function subject to a constraint on the odds ratio. Through a simulation study, the proposed estimators of the expected cell frequencies of the nonrespondents are shown to have smaller mean square errors than those of the MLEs. This estimation procedure is illustrated using polling data in Baker and Laird (1988). In addition, we provide some recommendations on how to choose constraints for practical applications. C1 HANKUK UNIV FOREIGN STUDIES,DEPT STAT,YONGIN GUN 440791,KYUNGKI DO,SOUTH KOREA. NATL INST CHILD HLTH,BIOMETRY BRANCH,BETHESDA,MD 20892. UNIV MICHIGAN,SCH PUBL HLTH,DEPT BIOSTAT,ANN ARBOR,MI 48109. NR 30 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD JUN 5 PY 1997 VL 24 IS 4 BP 417 EP 432 DI 10.1016/S0167-9473(96)00074-6 PG 16 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA XE923 UT WOS:A1997XE92300005 ER PT J AU Wagner, S Castel, M Gainer, H Yarom, Y AF Wagner, S Castel, M Gainer, H Yarom, Y TI GABA in the mammalian suprachiasmatic nucleus and its role in diurnal rhythmicity SO NATURE LA English DT Article ID NEURONS; CLOCK; ACID; NEUROTRANSMISSION; HYPOTHALAMUS; MECHANISMS; RESPONSES; RECEPTORS; HAMSTER AB Mammals manifest circadian behaviour timed by an endogenous clock in the hypothalamic suprachiasmatic nucleus (SCN)(1). Considerable progress has been made in identifying the molecular basis of the circadian clock(2,3), but the mechanisms by which it is translated into cyclic firing activity, high during the day and low at night, are still poorly understood. GABA (gamma-aminobutyric acid), a common inhibitory neurotransmitter in the central nervous system, is particularly densely distributed within the SCN, where it is located in the majority of neuronal somata(4,5) and synaptic terminals(6,7). Using an in vitro brain-slice technique, we have now studied the effect of bath-applied GABA on adult SCN neurons at various times of the day. We find that GABA acts as an inhibitory neurotransmitter at night, decreasing the firing frequency; but during the day GABA acts as an excitatory neurotransmitter, increasing the firing frequency. We show that this dual effect, which is mediated by GABA(A) receptors, may be attributed to an oscillation in intracellular chloride concentration. A likely explanation is that the amplitude of the oscillation in firing rate, displayed by individual neurons, is amplified by the dual effect of GABA in the SCN's GABAergic network. C1 HEBREW UNIV JERUSALEM,INST LIFE SCI,DEPT CELL & ANIM BIOL,IL-91904 JERUSALEM,ISRAEL. NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. RP Wagner, S (reprint author), HEBREW UNIV JERUSALEM,INST LIFE SCI,DEPT NEUROBIOL,IL-91904 JERUSALEM,ISRAEL. OI Wagner, Shlomo/0000-0002-7618-0752 NR 28 TC 210 Z9 211 U1 0 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 5 PY 1997 VL 387 IS 6633 BP 598 EP 603 DI 10.1038/42468 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XC522 UT WOS:A1997XC52200055 PM 9177347 ER PT J AU Mathers, PH Grinberg, A Mahon, KA Jamrich, M AF Mathers, PH Grinberg, A Mahon, KA Jamrich, M TI The Rx homeobox gene is essential for vertebrate eye development SO NATURE LA English DT Article ID XENOPUS-LAEVIS; NERVOUS-SYSTEM; EYELESS GENE; EXPRESSION; DROSOPHILA; ANIRIDIA; RETINA; MOUSE; HEAD AB Development of the vertebrate eye requires a series of steps including specification of the anterior neural plate, evagination of the optic vesicles from the ventral forebrain, and the cellular differentiation of the lens and retina. Homeobox-containing genes, especially the transcription regulator Pax6, play a critical role in vertebrate and invertebrate eye formation. Mutations in Pax6 function result in eye malformations known as Aniridia in humans and Small eye syndrome in mice(1-3). The Drosophila homologue of Pax6, eyeless, is also necessary for correct invertebrate eye development, and its misexpression leads to formation of ectopic eyes in Drosophila(4,5). Here we show that a conserved vertebrate homeobox gene, Rx, is essential for normal eye development, and that its misexpression has profound effects on eye morphology. Xenopus embryos injected with synthetic Rx RNA develop ectopic retinal tissue and display hyperproliferation in the neuroretina. Mouse embryos carrying a null allele of this gene do not form optic cups and so do not develop eyes. The Rx gene family plays an important role in the establishment and/or proliferation of retinal progenitor cells. C1 US FDA,DEV BIOL LAB,ROCKVILLE,MD 20852. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NR 25 TC 465 Z9 476 U1 4 U2 26 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 5 PY 1997 VL 387 IS 6633 BP 603 EP 607 DI 10.1038/42475 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XC522 UT WOS:A1997XC52200056 PM 9177348 ER PT J AU Shin, DY Ishibashi, T Choi, TS Chung, EM Chung, IY Aaronson, SA Bottaro, DP AF Shin, DY Ishibashi, T Choi, TS Chung, EM Chung, IY Aaronson, SA Bottaro, DP TI A novel human ERK phosphatase regulates H-ras and v-raf signal transduction SO ONCOGENE LA English DT Article DE protein tyrosine phosphatase; map kinase phosphatase; protein dephosphorylation ID DUAL-SPECIFICITY PHOSPHATASE; ACTIVATED PROTEIN-KINASE; IMMEDIATE-EARLY GENE; MAP KINASE; TYROSINE-PHOSPHATASE; VACCINIA VIRUS; CLONING SYSTEM; EXPRESSION; GROWTH; DEPHOSPHORYLATES AB A cDNA encoding a novel human extracellularly regulated kinase (ERK) phosphatase, designated B59, was isolated from a B5/589 human mammary epithelial cell cDNA library, The 1104 nucleotide open reading frame encodes 368 amino acids including the highly conserved catalytic site sequence of protein phosphotyrosine phosphatases (PTPs), VXVHCXXGXXR, at amino acid position 276-287, The predicted 70 amino acid stretch surrounding the HC motif shares significant sequence identity with other human dual specificity PTPs (dsPTPs), including the known ERK PTPs CL100, PAC1, B23, as well as the dsPTPs VH-1 and VHR, B59 protein synthesized in vitro in a rabbit reticulocyte lysate dephosphorylated rat ERK1 and ERK2 proteins whose phosphorylation had been stimulated by v-mos kinase added to the lysate, Ectopic expression of B59 in NIH3T3 fibroblasts inhibited the induction of an oncogene-responsive promoter by the dominant-activating paf mutant, raf-BXB, Moreover, cotransfection of NIH3T3 cells with B59 inhibited morphological transformation by H-ras and v-raf oncogenes. These results suggest that B59 suppresses the transforming activity of H-ras or v-raf oncogenes through ERK dephosphorylation and inactivation. C1 NCI, CELLULAR & MOL BIOL LAB, DIV BASIC SCI, BETHESDA, MD 20892 USA. MT SINAI MED CTR, DERALD H RUTTENBERG CANC CTR, NEW YORK, NY 10029 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 50 TC 37 Z9 38 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JUN 5 PY 1997 VL 14 IS 22 BP 2633 EP 2639 DI 10.1038/sj.onc.1201106 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XB978 UT WOS:A1997XB97800002 PM 9178761 ER PT J AU Kurtz, A Wang, HL Darwiche, N Harris, V Wellstein, A AF Kurtz, A Wang, HL Darwiche, N Harris, V Wellstein, A TI Expression of a binding protein for FGF is associated with epithelial development and skin carcinogenesis SO ONCOGENE LA English DT Article DE FGF-binding protein; gene; skin; carcinogenesis; development; expression ID FIBROBLAST GROWTH-FACTOR; SUBENDOTHELIAL EXTRACELLULAR-MATRIX; CELL-GROWTH; MALIGNANT CONVERSION; TARGETED EXPRESSION; WOUND REPAIR; TUMOR-GROWTH; ONCOGENE; DIFFERENTIATION; ANGIOGENESIS AB Fibroblast growth factors (FGF)-1 and -2 are found in most embryonic and adult normal and tumor tissues, where they are immobilized in the extracellular matrix (EM), Mobilization of these FGFs is part of a tightly controlled process resulting in the activation of high-affinity receptors, Recently, we have shown that a novel human FGF-binding protein (FGF-BP) mediates the release of immobilized FGF-2 from the EM. Here we isolated genomic and cDNA clones of the mouse FGF-BP homologue and studied its expression during embryonic development and skin carcinogenesis, The murine gene contains two exons that generate a 1.2 kb mRNA and predicts an 18 kDa secreted protein that is 63% identical to its human homologue, FGF-BP mRNA expression during embryogenesis is restricted to skin, intestine and lung. In the developing skin, FGF-BP expression starts at embryonic day 9, reaches peak levels perinatally and is downregulated during postnatal development. Develepment regulation in the intestine is similar, but in lungs and ovaries high expression was also observed in the adult, FGF-BP mRNA expression in the adult skin is dramatically increased during early stages of carcinogen-induced transformation in vivo and by rasactivation in vitro, Finally, mouse FGF-BP binds to FGF-2 and can function as a modulator of FGF in FGF-responsive cells, Our results suggest a potential function of FGF-BP during development and tumorigenesis. C1 GEORGETOWN UNIV,DEPT PHARMACOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,DEPT NEUROSURG,WASHINGTON,DC 20007. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892. RP Kurtz, A (reprint author), GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,3970 RESERVOIR RD,WASHINGTON,DC 20007, USA. OI Darwiche, Nadine/0000-0002-1862-5426; Wellstein, Anton/0000-0002-0570-4950 FU NCI NIH HHS [CA-58185] NR 41 TC 48 Z9 53 U1 1 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 5 PY 1997 VL 14 IS 22 BP 2671 EP 2681 DI 10.1038/sj.onc.1201117 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XB978 UT WOS:A1997XB97800006 PM 9178765 ER PT J AU Davidson, E AF Davidson, E TI The paradox of technology: Learning to share control with the patient SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Davidson, E (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 4 PY 1997 VL 277 IS 21 BP 1680 EP 1681 DI 10.1001/jama.277.21.1680 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XB088 UT WOS:A1997XB08800021 PM 9169889 ER PT J AU Hildesheim, A AF Hildesheim, A TI Human papillomavirus variants: Implications for natural history studies and vaccine development efforts SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP Hildesheim, A (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,SUITE 443,BETHESDA,MD 20892, USA. NR 12 TC 14 Z9 14 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 4 PY 1997 VL 89 IS 11 BP 752 EP 753 DI 10.1093/jnci/89.11.752 PG 2 WC Oncology SC Oncology GA XC094 UT WOS:A1997XC09400004 PM 9182967 ER PT J AU Rabkin, CS AF Rabkin, CS TI HIV-associated malignancies SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP Rabkin, CS (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 4 PY 1997 VL 89 IS 11 BP 755 EP 755 PG 1 WC Oncology SC Oncology GA XC094 UT WOS:A1997XC09400006 ER PT J AU Costantino, JP Kuller, LH Ives, DG Fisher, B Dignam, J AF Costantino, JP Kuller, LH Ives, DG Fisher, B Dignam, J TI Coronary heart disease mortality and adjuvant tamoxifen therapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NEGATIVE BREAST-CANCER; POSTMENOPAUSAL WOMEN; SERUM-LIPOPROTEINS; RANDOMIZED TRIAL; PLASMA-LIPIDS; MORBIDITY; RISK AB Background and Purpose: Data from randomized clinical trials in Scotland and Sweden testing the efficacy of tamoxifen therapy in patients with breast cancer have suggested that the drug may also reduce the risk of coronary heart disease, In view of these findings, we examined mortality from coronary heart disease among patients with early stage breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project B-14 trial of tamoxifen therapy. Methods: Deaths occurring among women who were randomly assigned to 5 years of either tamoxifen or placebo in the first phase of the B-14 trial were reviewed to determine the cause, Three categories of heart disease-related death were defined: 1) death from a definite fatal myocardial infarction, 2) death from definite fatal coronary heart disease/possible myocardial infarction, and 3) death from possible fatal coronary heart disease. Comparisons of the findings by treatment group were made on the basis of average annual hazard (i.e., death) rates and the corresponding relative hazard of death, Results: The average annual death rate from coronary heart disease was lower for patients who received tamoxifen than for patients who received placebo, but the difference was not statistically significant, There were eight definite heart-related deaths (i.e., definite fatal myocardial infarction or definite fatal coronary heart disease/possible myocardial infarction) among the patients who received tamoxifen, yielding an average annual rate of 0.62 per 1000 patients. There were 12 definite heart-related deaths among the patients who received placebo, yielding an average annual rate of 0.94 per 1000. The corresponding relative hazard of death from definite fatal heart disease (tamoxifen versus placebo) was 0.66 (95% confidence interval = 0.27-1.61). Eleven deaths in the tamoxifen group and 10 deaths in the placebo group were classified as possible cases of fatal coronary heart disease. When these cases and the definite cases were considered together, the average annual death rate for the patients who received tamoxifen was 1.48 per 1000, and the rate for the patients who received placebo was 1.73 per 1000. The corresponding relative hazard of death was 0.85 (95% confidence interval = 0.46-1.58). Conclusions: The findings from the B-14 trial are consistent with the findings from the Scottish and the Swedish trials, suggesting that tamoxifen treatment reduces coronary heart disease among patients with breast cancer. Continued follow-up of the patients in these trials and in ongoing prevention trials is needed to accumulate enough data so that reliable conclusions can be drawn about the benefits of tamoxifen in preventing heart disease. C1 NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA. UNIV PITTSBURGH,DEPT EPIDEMIOL,PITTSBURGH,PA 15261. UNIV PITTSBURGH,DEPT SURG,PITTSBURGH,PA 15261. RP Costantino, JP (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT BIOSTAT,RM 316,PARRAN HALL,130 DESOTO ST,PITTSBURGH,PA 15261, USA. FU NCI NIH HHS [U10CA39086, U10CA12027, U10CA37377] NR 23 TC 95 Z9 95 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 4 PY 1997 VL 89 IS 11 BP 776 EP 782 PG 7 WC Oncology SC Oncology GA XC094 UT WOS:A1997XC09400011 PM 9182975 ER PT J AU Stein, U Walther, W Laurencourt, CM Scheffer, GL Scheper, RJ Shoemaker, RH AF Stein, U Walther, W Laurencourt, CM Scheffer, GL Scheper, RJ Shoemaker, RH TI Tumor necrosis factor-alpha and expression of the multidrug resistance-associated genes LRP and MRP SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL-LINES; PROTEIN MRP; MDR1 GENE; DRUG-RESISTANCE; TNF-ALPHA; PLEIOTROPIC PHENOTYPE; PROMOTER REGION; CARCINOMA; OVEREXPRESSION; SEQUENCE AB Background and Purpose: Cancer cells that express P-glycoprotein, multidrug resistance-associated protein (MRP), or lung resistance protein (LRP) have demonstrated resistance to a nide variety of chemotherapeutic drugs. Recently, we reported that human colon carcinoma cells that express all three proteins exhibit reduced P-glycoprotein gene expression and a loss of multidrug resistance after exposure to tumor necrosis factor-alpha, a hormone-like protein produced by cells of the immune system. In this study, we examined the effects of tumor necrosis factor-alpha on MRP and LRP gene expression in the same colon carcinoma cells. Methods: HCT15 and HCT116 colon carcinoma cells were incubated with tumor necrosis factor-alpha at 100 U/mL for 2, 12, 24, 48, or 72 hours; alternatively, cells transfected with an expression vector containing a human tumor necrosis factor-alpha complementary DNA were studied. The effects of tumor necrosis factor-alpha on MRP and LRP messenger RNA expression were evaluated by means of reverse transcription and the polymerase chain reaction; effects on MRP and LRP protein expression were examined by use of specific monoclonal antibodies and flow cytometry. The flow cytometry data were analyzed by use of the two-sided, nonparametric Mann-Whitney rank sum test. Results: Treatment with exogenous tumor necrosis factor-alpha reduced the level of LRP messenger RNA in both cell types in an apparently time-dependent fashion; in HCT15 cells, almost no LRP messenger RNA was detected after 48 hours of treatment. In contrast, the level of MRP messenger RNA was increased in HCT116 cells by such treatment, but the level in HCT15 cells was unchanged. Treatment with exogenous tumor necrosis factor-alpha induced changes in LRP and MRP protein expression in the two cell types that paralleled the changes found for messenger RNA. In transfected cells, the endogenous production of tumor necrosis factor-alpha reduced LRP gene expression (both messenger RNA and protein) and increased MRP gene expression (both messenger RNA and protein), regardless of cell type. Conclusion: In human colon carcinoma cells, tumor necrosis factor-alpha influences MRP and LRP gene expression in opposite ways. The findings for LRP gene expression parallel our earlier findings for P-glycoprotein expression in these cells. Implication: In developing strategies for overcoming multidrug resistance in tumor cells, the possibility that an agent can suppress one or more mechanisms of drug resistance and enhance others should be considered. C1 NCI,LAB DRUG DISCOVERY RES & DEV,DIV CANC TREATMENT DIAG & CTR,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. FREE UNIV AMSTERDAM HOSP,AMSTERDAM,NETHERLANDS. RP Stein, U (reprint author), MAX DELBRUCK CTR MOL MED,ROBERT ROSSLE STR 10,D-13122 BERLIN,GERMANY. NR 51 TC 61 Z9 66 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 4 PY 1997 VL 89 IS 11 BP 807 EP 813 PG 7 WC Oncology SC Oncology GA XC094 UT WOS:A1997XC09400016 PM 9182980 ER PT J AU Weiderpass, E Gridley, G Ekbom, A Nyren, O Hjalgrim, H Adami, HO AF Weiderpass, E Gridley, G Ekbom, A Nyren, O Hjalgrim, H Adami, HO TI Medical history risk factors for non-Hodgkin's lymphoma in older women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,UPPSALA,SWEDEN. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. STATENS SERUM INST,DANISH EPIDEMIOL SCI CTR,DEPT EPIDEMIOL RES,DK-2300 COPENHAGEN,DENMARK. RP Weiderpass, E (reprint author), UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. RI Weiderpass, Elisabete/M-4029-2016 OI Weiderpass, Elisabete/0000-0003-2237-0128 FU NCI NIH HHS [N01CP85636-05] NR 2 TC 9 Z9 9 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 4 PY 1997 VL 89 IS 11 BP 816 EP 817 PG 2 WC Oncology SC Oncology GA XC094 UT WOS:A1997XC09400017 PM 9182981 ER PT J AU Najjar, SM Blakesley, VA Calzi, SL Kato, H LeRoith, D Choice, CV AF Najjar, SM Blakesley, VA Calzi, SL Kato, H LeRoith, D Choice, CV TI Differential phosphorylation of pp120 by insulin and insulin-like growth factor-1 receptors: Role for the C-terminal domain of the beta-subunit SO BIOCHEMISTRY LA English DT Article ID FACTOR-I-RECEPTOR; STIMULATES TYROSINE PHOSPHORYLATION; LIVER ECTO-ATPASE; ENDOGENOUS SUBSTRATE; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3'-KINASE; SIGNAL TRANSDUCTION; CYTOPLASMIC DOMAIN; HEPATOMA-CELLS; AUTOPHOSPHORYLATION AB pp120, a plasma membrane glycoprotein expressed by hepatocytes, is a substrate of the insulin receptor tyrosine kinase, Since insulin-like growth factor-1 (IGF-1) and insulin receptors are structurally homologous, we investigated whether pp120 is also a substrate of the IGF-1 receptor tyrosine kinase. ICF-1 receptor failed to phosphorylate pp120 in response to IGF-1 in stably transfected NIH 3T3 fibroblasts. However, replacement of the C-terminal domain of the beta-subunit of the IGF-1 receptor with the corresponding fragment in the insulin receptor restored ligand-stimulated pp120 phosphorylation, suggesting that this domain plays a regulatory role in pp120 phosphorylation. Since pp120 is the first identified substrate specific for the insulin vis-a vis the IGF-1 receptor tyrosine kinase, the pp120 signaling pathway may constitute a novel mechanism for the distinct cellular effects of insulin and IGF-1, the former being principally involved in metabolism, and the latter in mitogenesis. C1 NIDDKD,NIH,DIABET BRANCH,BETHESDA,MD 20892. RP Najjar, SM (reprint author), MED COLL OHIO,DEPT PHARMACOL & THERAPEUT,HSCI BLDG,ROOM 270,TOLEDO,OH 43614, USA. NR 45 TC 24 Z9 26 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 3 PY 1997 VL 36 IS 22 BP 6827 EP 6834 DI 10.1021/bi962634h PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XC519 UT WOS:A1997XC51900033 PM 9184166 ER PT J AU Das, R Vonderhaar, BK AF Das, R Vonderhaar, BK TI Tamoxifen inhibits prolactin signal transduction in ER - NOG-8 mammary epithelial cells SO CANCER LETTERS LA English DT Article DE tamoxifen; antilactogen; prolactin ID HUMAN-BREAST-CANCER; PROTEIN-KINASE-C; RECEPTOR; ACTIVATION; LINE; GROWTH; TISSUE AB Tamoxifen (TAM), an antiestrogen, also acts as an antilactogen in mammary cells. In the present study we analyze the effect of TAM on the signal transduction pathway for prolactin (Prl). TAM bound specifically to NOG-8, an estrogen receptor-negative mammary cell line. Within 5 min of Prl treatment, raf-l, MEK and MAP kinase were induced 2-3-fold over the control level. TAM completely inhibited this Prl-induced activation of kinases as well as Prl binding and cell growth. These results indicate the potential role of TAM as an antilactogen in Prl responsive systems. Published by Elsevier Science Ireland Ltd. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 27 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 3 PY 1997 VL 116 IS 1 BP 41 EP 46 DI 10.1016/S0304-3835(97)04750-2 PG 6 WC Oncology SC Oncology GA WZ303 UT WOS:A1997WZ30300007 PM 9177456 ER PT J AU Wang, TTY Hursting, SD Perkins, SN Phang, JM AF Wang, TTY Hursting, SD Perkins, SN Phang, JM TI Effects of dehydroepiandrosterone and calorie restriction on the Bcl-2/Bax-mediated apoptotic pathway in p53-deficient mice SO CANCER LETTERS LA English DT Article DE apoptosis; Bax; Bcl-2; DHEA; p53; knockout mice ID PROGRAMMED CELL-DEATH; SPONTANEOUS TUMORIGENESIS; BCL-2 PROTEIN; IN-VIVO; P53; CHEMOPREVENTION; EXPRESSION; MECHANISMS; CANCER; GENE AB Modulation of apoptosis through altered expression of Bcl-2 and/or Bax may be a mechanism by which dehydroepiandrosterone (DHEA) administration and calorie restriction (CR) exert their chemopreventive effects in p53-deficient (p53(-/-)) mice. Using immunohistochemical detection we found that treatment with both DHEA and CR resulted in decreased expression of the PCNA proliferation marker in the thymus. In addition, treatment with DHEA also increased the rate of apoptosis in the thymus, resulting in marked thymic atrophy. Thus, both DHEA and CR appear to shift cell number homeostasis by favoring apoptosis. To further understand the molecular mechanisms by which DHEA and CR exert their effects, we examined two components of the apoptotic pathway, Bcl-2 and Bax. We found that p53(-/-) mice have much higher levels of Bcl-2 mRNA in the thymus than wild-type (p53(+/+)) mice. Treatment of p53(-/-) animals with DHEA resulted in decreased Bcl-2 but not Bax mRNA levels in the thymus. In contrast, CR did not change either Bcl-2 or Bax mRNA expression. The present study provides molecular evidence that DHEA and CR may modulate tumorigenesis through alterations in the apoptotic and/or proliferative pathways. Published by Elsevier Science Ireland Ltd. C1 UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT EPIDEMIOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT CARCINOGENESIS,HOUSTON,TX 77030. RP Wang, TTY (reprint author), NCI,LAB NUTR & MOL REGULAT,FREDERICK CANC RES & DEV CTR,NIH,BLDG 560-12-48,FREDERICK,MD 21702, USA. FU NCI NIH HHS [5P30 CA 16672] NR 22 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 3 PY 1997 VL 116 IS 1 BP 61 EP 69 DI 10.1016/S0304-3835(97)00175-4 PG 9 WC Oncology SC Oncology GA WZ303 UT WOS:A1997WZ30300010 PM 9177459 ER PT J AU Willert, K Brink, M Wodarz, A Varmus, H Nusse, R AF Willert, K Brink, M Wodarz, A Varmus, H Nusse, R TI Casein kinase 2 associates with and phosphorylates dishevelled SO EMBO JOURNAL LA English DT Article DE casein kinase 2; dishevelled; frizzled; Wingless; Wnt ID DROSOPHILA; PROTEIN; WINGLESS; SUBUNITS AB The dishevelled (dsh) gene of Drosophila melanogaster encodes a phosphoprotein whose phosphorylation state is elevated by Wingless stimulation, suggesting that the phosphorylation of Dsh and the kinase(s) responsible for this phosphorylation are integral parts of the Wg signaling pathway, We found that immunoprecipitated Dsh protein from embryos and from cells in tissue culture is associated with a kinase activity that phosphorylates Dsh in vitro, Purification and peptide sequencing of a 38 kDa protein co-purifying with this kinase activity showed it to be identical to Drosophila Casein Kinase 2 (CK2), Tryptic phosphopeptide mapping indicates that identical peptides are phosphorylated by CK2 in vitro and in vivo, suggesting that CK2 is at least one of the kinases that phosphorylates Dsh. Overexpression of Dfz2 a Wingless receptor, also stimulated phosphorylation of Dsh, Dsh-associated kinase activity, and association of CK2 with Dsh, thus suggesting a role for CK2 in the transduction of the Wg signal. C1 STANFORD UNIV, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USA. STANFORD UNIV, SCH MED, DEPT DEV BIOL, STANFORD, CA 94305 USA. UNIV CALIF SAN FRANCISCO, DEPT BIOCHEM & BIOPHYS, SAN FRANCISCO, CA 94143 USA. NCI, NIH, BETHESDA, MD 20892 USA. RI Wodarz, Andreas/D-4642-2013 OI Wodarz, Andreas/0000-0002-0007-6289 NR 28 TC 178 Z9 182 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD JUN 2 PY 1997 VL 16 IS 11 BP 3089 EP 3096 DI 10.1093/emboj/16.11.3089 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XE748 UT WOS:A1997XE74800012 PM 9214626 ER PT J AU Wadman, IA Osada, H Grutz, GG Agulnick, AD Westphal, H Forster, A Rabbitts, TH AF Wadman, IA Osada, H Grutz, GG Agulnick, AD Westphal, H Forster, A Rabbitts, TH TI The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-bindinq complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins SO EMBO JOURNAL LA English DT Article DE haematopoiesis; Ldb1; LIM; Rbtn2; transcription ID HELIX-LOOP-HELIX; T-CELL LEUKEMIA; TRANSCRIPTION FACTOR GATA-1; CYSTEINE-RICH PROTEIN; ENHANCER-BINDING; CYCLIC AMPLIFICATION; DOMAIN PROTEINS; MICE LACKING; GENE; ASSOCIATION AB The LIM-only protein Lmo2, activated by chromosomal translocations in T-cell leukaemias, is normally expressed in haematopoiesis. It interacts with TAL1 and GATA-1 proteins, but the function of the interaction is unexplained, We now show that in erythroid cells Lmo2 forms a novel DNA-binding complex, with GATA-1, TAL1 and E2A, and the recently identified LIM-binding protein Ldb1/NLI. This oligomeric complex binds to a unique, bipartite DNA motif comprising an E-box, CAGGTG, followed similar to 9 bp downstream by a GATA site, In vivo assembly of the DNA-binding complex requires interaction of all five proteins and establishes a transcriptional transactivating complex, These data demonstrate one function for the LIM-binding protein Ldb1 and establish a function for the LIM-only protein Lmo2 as an obligatory component of an oligomeric, DNA-binding complex which may play a role in haematopoiesis. C1 MRC,MOL BIOL LAB,CAMBRIDGE CB2 2QH,ENGLAND. NICHHD,LAB MAMMALIAN GENES & DEV LAB,NIH,BETHESDA,MD 20892. NR 51 TC 614 Z9 627 U1 4 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 2 PY 1997 VL 16 IS 11 BP 3145 EP 3157 DI 10.1093/emboj/16.11.3145 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XE748 UT WOS:A1997XE74800018 PM 9214632 ER PT J AU Wong, JM Shi, YB Wolffe, AP AF Wong, JM Shi, YB Wolffe, AP TI Determinants of chromatin disruption and transcriptional regulation instigated by the thyroid hormone receptor: Hormone-regulated chromatin disruption is not sufficient for transcriptional activation SO EMBO JOURNAL LA English DT Article DE chromatin; disruption; thyroid hormone receptor; transcriptional activation ID YEAST ALPHA-2 REPRESSOR; RETINOIC-ACID RECEPTOR; MMTV PROMOTER; IN-VIVO; V-ERBA; SACCHAROMYCES-CEREVISIAE; POSITIONED NUCLEOSOMES; XENOPUS-LAEVIS; PHO5 PROMOTER; TRANSACTIVATION DOMAIN AB Chromatin disruption and transcriptional activation are both thyroid hormone-dependent processes regulated by the heterodimer of thyroid hormone receptor and 9-cis retinoic acid receptor (TR-RXR). In the absence of hormone, TR-RXR binds to nucleosomal DNA, locally disrupts histone-DNA contacts and generates a DNase I-hypersensitive site, Chromatin-bound unliganded TR-RXR silences transcription of the Xenopus TR beta A gene within a canonical nucleosomal array. On addition of hormone, the receptor directs the extensive further disruption of chromatin structure over several hundred base pairs of DNA and activates transcription. We define a domain of the TR protein necessary for directing this extensive hormone-dependent chromatin disruption Particular TR-RXR heterodimers containing mutations in this domain are able to bind both hormone and their thyroid hormone receptor recognition element (TRE) within chromatin, yet are unable to direct the extensive hormone-dependent disruption of chromatin or to activate transcription, We distinguish the hormone-dependent disruption of chromatin and transcriptional activation as independently regulated events through the mutagenesis of basal promoter elements and by altering the position and number of TREs within the TR beta A promoter, Chromatin disruption alone on a minichromosome is shown to be insufficient for transcriptional activation of the TR beta A gene. C1 NICHHD,MOL BIOL SECT,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. NICHHD,UNIT MOL MORPHOGENESIS,NIH,BETHESDA,MD 20892. NR 85 TC 120 Z9 121 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 2 PY 1997 VL 16 IS 11 BP 3158 EP 3171 DI 10.1093/emboj/16.11.3158 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XE748 UT WOS:A1997XE74800019 PM 9214633 ER PT J AU Gao, JL Wynn, TA Chang, Y Lee, EJ Broxmeyer, HE Cooper, S Tiffany, HL Westphal, H KwonChung, J Murphy, PM AF Gao, JL Wynn, TA Chang, Y Lee, EJ Broxmeyer, HE Cooper, S Tiffany, HL Westphal, H KwonChung, J Murphy, PM TI Impaired host defense, hematopoiesis, guanulomatous inflammation and type 1-type 2 cytokine balance in mice lacking CC chemokine receptor 1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MYELOID PROGENITOR CELLS; COLONY FORMATION INVITRO; FUNCTIONAL EXPRESSION; SCHISTOSOMA-MANSONI; MOLECULAR-CLONING; CHEMOTACTIC CYTOKINES; PLASMODIUM-VIVAX; RNA EXPRESSION; IL-8 RECEPTOR; PROTEIN-1-ALPHA AB CC chemokine receptor 1 (CCR1) is expressed in neutrophils, monocytes, lymphocytes, and eosinophils, and binds the leukocyte chemoattractant and hematopoiesis regulator macrophage inflammatory protein (MIP)-1 alpha, as well as several related CC chemokines. Four other CCR subtypes are known; their leukocyte and chemokine specificities overlap with, but are not identical to, CCR1, suggesting that CCR1 has both redundant and specific biologic roles. To test this, we have developed CCR1-deficient mice (-/-) by targeted gene disruption. Although the distribution of mature leukocytes was normal, steady state and induced trafficking and proliferation of myeloid progenitor cells were disordered in -/- mice. Moreover, mature neutrophils from -/- mice failed to chemotax in vitro and failed to mobilize into peripheral blood in vivo in response to MIP-1 alpha. Consistent with this, -/- mice had accelerated mortality when challenged with Aspergillus fumigatus, a fungus controlled principally by neutrophils. To test the role of CCR1 in granuloma formation, we injected Schistosoma mansoni eggs intravenously, and observed a 40% reduction in the size of lung granulomas in -/- mice compared to +/+ littermates. This was associated with increased interferon-gamma and decreased interleukin-4 production in -/- versus +/+ lung lymph node cells stimulated with egg-specific antigen, suggesting that CCR1 influences the inflammatory response not only through direct effects on leukocyte chemotaxis, but also through effects on the type 1-type 2 cytokine balance. Thus CCR1 has nonredundant functions in hematopoiesis, host defense, and inflammation. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. INDIANA UNIV,SCH MED,DEPT MICROBIOL IMMUNOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. RP Gao, JL (reprint author), NIAID,HOST DEF LAB,NIH,9000 ROCKVILLE PIKE,BLDG 10,RM 11N113,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011 FU NHLBI NIH HHS [R01 HL056416, P01 HL053586, P01 HL53586, R01 HL54037, R01 HL56416] NR 52 TC 303 Z9 310 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 2 PY 1997 VL 185 IS 11 BP 1959 EP 1968 DI 10.1084/jem.185.11.1959 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XD350 UT WOS:A1997XD35000008 PM 9166425 ER PT J AU Marth, T Kelsall, BL AF Marth, T Kelsall, BL TI Regulation of interleukin-12 by complement receptor 3 signaling SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TYROSINE PHOSPHORYLATION; MYELOMONOCYTIC CELLS; MONOCLONAL-ANTIBODY; LEUKOCYTE ADHESION; MAC-1; TYPE-3; CR3; RECRUITMENT; CD11B/CD18; MONOCYTES AB Complement receptor type 3 (CR3, CD11b/CD18) serves as a receptor for a number of endogenous ligands and infectious organisms, and is involved in adhesion and host defense functions. Here, we report that signaling via CR3 plays an important role in regulating production of interleukin-12 (IL-12), a key mediator of cell-mediated immunity (CMI). We demonstrate with a variety of stimuli a dose-dependent, specific downregulation of IL-12 secretion by hub man monocytes in vitro after exposure to antibodies to CR3 (anti-CD11b and anti-CD18), as well as to the natural CR3 ligands, iC3b, and Histoplasma capsulatum. CR3 antibodies also suppressed interferon-gamma (IFN-gamma) production in cultures of human peripheral blood mononuclear cells (PBMC). We determined that one mechanism by which CR3 antibodies may suppress IL-12 production is by the inhibition of IFN-gamma-induced tyrosine phosphorylation. Finally, in a murine model of IL-12-dependent septic shock, we provide evidence that administration of CR3 antibodies leads to suppression of IL-12 and IFN-gamma in vivo. Our studies thus define a novel role for CR3 in regulating CMI functions via IL-12. RP Marth, T (reprint author), NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 36 TC 201 Z9 205 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 2 PY 1997 VL 185 IS 11 BP 1987 EP 1995 DI 10.1084/jem.185.11.1987 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XD350 UT WOS:A1997XD35000011 PM 9166428 ER PT J AU Liao, F Alkhatib, G Peden, KWC Sharma, G Berger, EA Farber, JM AF Liao, F Alkhatib, G Peden, KWC Sharma, G Berger, EA Farber, JM TI STRL33, a novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RECOMBINANT VACCINIA VIRUS; ENVELOPE GLYCOPROTEIN; IDENTIFICATION; SEARCH; ASSAY; GENES; CD4 AB The chemokine receptors CXCR4, CCR2B, CCR3, and CCR5 have recently been shown to serve along with CD4 as coreceptors for HIV-1. The tropisms of HIV-1 strains for subgroups of CD4(+) cells can be explained, at least partly, by the selective use of G protein-coupled receptors (GPCRs). We have identified a novel human gene, STRL33, located on chromosome 3 that encodes a GPCR with sequence similarity to chemokine receptors and to chemokine receptor-like orphan receptors. STRL33 is expressed in lymphoid tissues and activated T cells, and is induced in activated peripheral blood lymphocytes. When transfected into nonhuman NIH 3T3 cells expressing human CD4, the STRL33 cDNA rendered these cells competent to fuse with cells expressing HIV-1 envelope glycoproteins (Envs). Of greatest interest, STRL33, in contrast with CXCR4 or CCR5, was able to function as a cofactor for fusion mediated by Envs from both T cell line-tropic and macrophage-tropic HIV-1 strains. STRL33-transfected Jurkat cell lines also supported enhanced productive infection with HIV-1 compared with control Jurkat cells. Despite the sequence similarities between STRL33 and chemokine receptors, STRL33-transfected cell. lines did not respond to any in a panel of chemokines. Based on the pattern of tissue expression of the STRL33 mRNA, and given the ability of STRL33 to function with Envs of differing tropisms, STRL33 may play a role in the establishment and/or progression of HIV-1 infection. C1 NIAID,NIH,CLIN INVEST LAB,BETHESDA,MD 20892. NIAID,NIH,VIRAL DIS LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,LAB RETROVIRUS RES,BETHESDA,MD 20892. NR 41 TC 305 Z9 307 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 2 PY 1997 VL 185 IS 11 BP 2015 EP 2023 DI 10.1084/jem.185.11.2015 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XD350 UT WOS:A1997XD35000013 PM 9166430 ER PT J AU Sawchuk, DJ WeisGarcia, F Malik, S Besmer, E Bustin, M Nussenzweig, MC Cortes, P AF Sawchuk, DJ WeisGarcia, F Malik, S Besmer, E Bustin, M Nussenzweig, MC Cortes, P TI V(D)J recombination: Modulation of RAG1 and RAG2 cleavage activity on 12/23 substrates by whole cell extract and DNA-bending proteins SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ARCHITECTURAL ELEMENTS; GENE-TRANSCRIPTION; MOUSE THYMOCYTES; HU; MOLECULES; SIGNALS; BREAKS; HMG1; MU AB Antigen receptor gene rearrangement is directed by DNA motifs consisting of a conserved heptamer and nonamer separated by a nonconserved spacer of either 12 or 23 base pairs (12 or 23 recombination signal sequences [RSS]). V(D)J recombination requires that the rearranging DNA segments be flanked by RSSs of different spacer lengths, a phenomenon known as the 12/23 rule. Recent studies have shown that this restriction operates at the level of DNA cleavage, which is mediated by the products of the recombination activating genes RAG1 and RAG2. Here, we show that RAG1 and RAG2 are not sufficient for 12/23 dependent cleavage, whereas RAG1 and RAG2 complemented with whole cell extract faithfully recapitulates the 12/23 rule. In addition, HMG box containing proteins HMG1 and HMG2 enhance RAG1- and RAG2-mediated cleavage of substrates containing 23 RSS but not of substrates containing only 12 RSS. These results suggest the existence of a nucleoprotein complex at the cleavage site, consisting of architectural, catalytic, and regulatory components. C1 ROCKEFELLER UNIV,LAB MOL IMMUNOL,NEW YORK,NY 10021. ROCKEFELLER UNIV,BIOCHEM & MOL BIOL LAB,NEW YORK,NY 10021. ROCKEFELLER UNIV,HOWARD HUGHES MED INST,RES LAB,NEW YORK,NY 10021. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RI Bustin, Michael/G-6155-2015 NR 35 TC 114 Z9 115 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 2 PY 1997 VL 185 IS 11 BP 2025 EP 2032 DI 10.1084/jem.185.11.2025 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XD350 UT WOS:A1997XD35000014 PM 9166431 ER PT J AU Vacchio, MS Ashwell, JD AF Vacchio, MS Ashwell, JD TI Thymus-derived glucocorticoids regulate antigen-specific positive selection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RECEPTOR TRANSGENIC MICE; T-CELL REPERTOIRE; APOPTOSIS; ACTIVATION; THYMOCYTES; COMPLEX; DEATH; LYMPHOCYTES; TOLERANCE; DELETION AB While it is generally believed that the avidity of the T cell antigen receptor (TCR) for self antigen/major histocompatibility complex (MHC) determines a thymocyte's fate, how the cell discriminates between a stimulus that causes positive selection (survival) and one that causes negative selection (death) is unknown. We have previously demonstrated that glucocorticoids are produced in the thymus, and that they antagonize deletion caused by TCR cross-linking. To examine the role of glucocorticoids during MHC-dependent selection, we examined thymocyte development in organ cultures in which corticosteroid biosynthesis was inhibited. Inhibition of glucocorticoid production in thymi from alpha/beta-TCR transgenic mice resulted in the antigen- and MHC-specific loss of thymocytes that normally recognize self antigen/MHC with sufficient avidity to result in positive selection. Furthermore, inhibition of glucocorticoid production caused an increase in apoptosis only in CD(+)CD8(+) thymocytes bearing transgenic TCRs that recognized self antigen/MHC. These results indicate that the balance of TCR and glucocorticoid receptor signaling influences the antigen-specific thymocyte development by allowing cells with low-to-moderate avidity for self antigen/MHC to survive. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,IMMUNOL LAB,BETHESDA,MD 20852. NCI,LAB IMMUNE CELL BIOL,NIH,BETHESDA,MD 20892. NR 27 TC 113 Z9 114 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 2 PY 1997 VL 185 IS 11 BP 2033 EP 2038 DI 10.1084/jem.185.11.2033 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XD350 UT WOS:A1997XD35000015 PM 9166432 ER PT J AU Zukin, SR AF Zukin, SR TI Phencyclidine, excitatory amino acids, psychiatry and drug abuse: Historical perspectives on clinical-laboratory interactions SO ACTA NEUROPSYCHIATRICA LA English DT Article; Proceedings Paper CT Congress on Biological Psychiatry in the 21st Century CY JUN 05-06, 1997 CL MAASTRICHT, NETHERLANDS DE drug abuse; excitatory amino acids; history; phencyclidine; schizophrenia ID SCHIZOPHRENIA; RECEPTOR C1 NIDA,DIV CLIN & SERV RES,NIH,ROCKVILLE,MD 20857. NR 7 TC 0 Z9 0 U1 1 U2 1 PU MISSET UITGEVERIJI BV PI MAARSSEN PA POSTBUS 1110, 3600 BC MAARSSEN, NETHERLANDS SN 0924-2708 J9 ACTA NEUROPSYCHIATR JI Acta Neuropsychiatr. PD JUN PY 1997 VL 9 IS 2 BP 87 EP 88 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XE941 UT WOS:A1997XE94100017 PM 26972135 ER PT J AU Mofenson, LM AF Mofenson, LM TI Interaction between timing of perinatal human immunodeficiency virus infection and the design of preventive and therapeutic interventions SO ACTA PAEDIATRICA LA English DT Article DE natural history; pediatric HIV infection; perinatal HIV transmission; prevention strategies; risk factors for perinatal HIV transmission ID TO-CHILD TRANSMISSION; VERTICAL TRANSMISSION; HIV-1 INFECTION; ZIDOVUDINE TREATMENT; MATERNAL ANTIBODIES; EARLY DIAGNOSIS; INFANT TRANSMISSION; CELL ACTIVITY; VITAMIN-A; TYPE-1 AB In 1994, the hypothesis that transmission of human immunodeficiency virus (HIV) from mother to child could be interrupted became a reality when it was shown that a regimen of zidovudine given to HIV-infected pregnant women and their newborn infants could reduce the risk of perinatal transmission by two-thirds. An understanding of the pathogenesis of transmission is crucial for interpreting these results, for design of future interventions and for understanding the natural history of perinatal HIV infection. This paper will review current information regarding the timing of and risk factors for perinatal HIV transmission, and the relationship between the timing of transmission and design of efforts to interrupt transmission and to slow disease progression in infected infants. RP Mofenson, LM (reprint author), NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,CTR RES MOTHERS & CHILDREN,NIH,ROCKVILLE,MD 20852, USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 86 TC 3 Z9 4 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD JUN PY 1997 VL 86 SU 421 BP 1 EP 9 PG 9 WC Pediatrics SC Pediatrics GA XM859 UT WOS:A1997XM85900001 PM 9240849 ER PT J AU Goedert, JJ AF Goedert, JJ TI Vertical transmission of human immunodeficiency virus type 1: Insights from studies of multiple pregnancies SO ACTA PAEDIATRICA LA English DT Article DE human immunodeficiency virus; molecular sequencing; natural history; ovine lentivirus; perinatal transmission; twins ID ISOGENEIC TWIN LAMBS; INFANT TRANSMISSION; OVINE LENTIVIRUS; CONCORDANCE; INFECTION; SIBLINGS; MOTHERS AB Because twins share an in utero environment and genetic relationships, similarities and differences between them can provide insight into the epidemiology and natural history of infectious agents, especially human immunodeficiency virus type 1 (HIV-1). Three projects were summarized: HIV-1 transmission and AIDS-free survival in The International Registry of HIV-Exposed Twins; cloning and sequencing of HIV-1 proviral sequences in two sets of identical twins; and transmission and natural history of ovine lentivirus (OvLV) in twin lambs. Both HIV-1 and OvLV transmission were increased for first-born twins. With HIV-1, progression to AIDS appeared independent of zygosity. Development of pneumonitis with experimental OvLV infection was highly concordant in monozygotic lambs. Finally, the identical infected twins in one set had intermingling of each infant's HIV-1 quasispecies, whereas in the second set each twin had its own distinct cluster of quasispecies around a maternal sequence. The studies indicate that most transmission occurs during labor or delivery, and they suggest that immunogenetics may not affect susceptibility to different HIV-1 quasispecies but may affect the manifestations of specific opportunistic diseases. C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 12 TC 0 Z9 0 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD JUN PY 1997 VL 86 SU 421 BP 56 EP 59 PG 4 WC Pediatrics SC Pediatrics GA XM859 UT WOS:A1997XM85900011 ER PT J AU Minkoff, H Willoughby, A AF Minkoff, H Willoughby, A TI The future of prenatal HIV testing SO ACTA PAEDIATRICA LA English DT Article DE ethics; HIV; HIV tests; prenatal ID HUMAN-IMMUNODEFICIENCY-VIRUS; PREGNANT-WOMEN; TRANSMISSION; INFECTION; RISK; ZIDOVUDINE; PREVENTION; POPULATION AB The use of zidovudine for the prevention of mother-to-child transmission of human immunodeficiency virus, as well as continuing advances in our understanding of the determinants of that transmission, and of potential new avenues of intervention augur ever more efficient perinatal prevention strategies in the near future. in this paper the evolving role of prenatal testing in an era of ever more successful interventions will be discussed. At least four factors will be critical in determining what that role will be: clinical, legal, ethical and economic. Each of these are parochial, i.e. they will feature in eradication strategies in different ways in different geographical, economic and cultural settings. An understanding of these factors will help to suggest what course testing policy should take and to determine the role clinicians must play if any testing policy is to succeed in contributing to the end of pediatric HIV disease. C1 NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,CTR RES MOTHERS & CHILDREN,NIH,ROCKVILLE,MD. RP Minkoff, H (reprint author), SUNY HLTH SCI CTR,DEPT OBSTET & GYNECOL,445 LENOX RD,BOX 24,BROOKLYN,NY 11203, USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD JUN PY 1997 VL 86 SU 421 BP 72 EP 77 PG 6 WC Pediatrics SC Pediatrics GA XM859 UT WOS:A1997XM85900015 ER PT J AU Mofenson, LM AF Mofenson, LM TI Reducing the risk of perinatal HIV-1 transmission with zidovudine: Results and implications of AIDS Clinical Trials Group protocol 076 SO ACTA PAEDIATRICA LA English DT Article DE ACTG 076; perinatal HIV transmission; prevention; zidovudine ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; CHILD TRANSMISSION; PREGNANT-WOMEN; INFECTION; TYPE-1; NEWBORNS; MACAQUES; THERAPY; IMPACT AB This paper reviews the rationale for the AIDS Clinical Trials Group (ACTG) protocol 076 design, the study results and the implications of these results, including discussion of the US Public Health Service Task Force recommendations on the use of zidovudine to reduce perinatal transmission and for prenatal human immunodeficiency virus (HIV) counseling and testing. RP Mofenson, LM (reprint author), NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,CTR RES MOTHERS & CHILDREN,NIH,ROCKVILLE,MD 20852, USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 43 TC 1 Z9 1 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD JUN PY 1997 VL 86 SU 421 BP 89 EP 96 PG 8 WC Pediatrics SC Pediatrics GA XM859 UT WOS:A1997XM85900018 PM 9240866 ER PT J AU Fowler, MG Mofenson, L AF Fowler, MG Mofenson, L TI Progress in prevention of perinatal HIV-1 SO ACTA PAEDIATRICA LA English DT Article DE HIV-1 prevention; perinatal HIV-1 interventions AB The findings of a recent human immunodeficiency (HIV-1) prevention trial in the USA demonstrated that administration of an antiretriviral drug, zidovudine, to mothers during the prenatal and intrapartum periods, and to their neonates for 6 weeks, resulted in a two-thirds reduction in risk of perinatal transmission from 25.5% to 8.3%. These results were rapidly disseminated both in the USA and internationally. Since the release of these clinical trial results in the spring of 1994, several observational studies have documented a sharp increase in maternal and neonatal zidovudine use, as well as a significant decrease in perinatal HIV-1 transmission, with rates of about 8% being observed in non-clinical trial settings. Internationally, the results have led to the development of a variety of perinatal prevention trials that build on the success of the U.S. perinatal prevention trial but use modified strategies that can feasibly be carried out in developing countries. C1 NICHHD, BETHESDA, MD 20892 USA. RP Fowler, MG (reprint author), NIAID, DIV AIDS, EFFICACY TRIALS BRANCH, BETHESDA, MD 20892 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 11 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0803-5253 EI 1651-2227 J9 ACTA PAEDIATR JI Acta Paediatr. PD JUN PY 1997 VL 86 SU 421 BP 97 EP 103 PG 7 WC Pediatrics SC Pediatrics GA XM859 UT WOS:A1997XM85900019 ER PT J AU Pickworth, WB Henningfield, JE AF Pickworth, WB Henningfield, JE TI Smokable drugs: Pharmacologic basis for consumer appeal SO ADDICTION LA English DT Editorial Material ID CIGARETTE-SMOKING; PHARMACOKINETICS; PHARMACODYNAMICS; DELIVERY; NICOTINE; COCAINE; HUMANS C1 PINNEY ASSOCIATES,BETHESDA,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV MED,BEHAV BIOL RES CTR,BALTIMORE,MD. RP Pickworth, WB (reprint author), NIDA,CLIN PHARMACOL BRANCH,INTRAMURAL RES PROGRAM,BALTIMORE,MD, USA. NR 11 TC 5 Z9 5 U1 0 U2 1 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD JUN PY 1997 VL 92 IS 6 BP 691 EP 692 DI 10.1111/j.1360-0443.1997.tb02934.x PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XE201 UT WOS:A1997XE20100009 ER PT J AU Preston, KL Silverman, K Schuster, CR Cone, EJ AF Preston, KL Silverman, K Schuster, CR Cone, EJ TI Assessment of cocaine use with quantitative urinalysis and estimation of new uses SO ADDICTION LA English DT Article ID REPORTED DRUG-USE; METHADONE-MAINTENANCE; VALIDITY; URINE; DEPENDENCE; EFFICACY; CLIENTS; ABUSE AB Qualitative urinalysis methods of monitoring cocaine use may over-detect frequency of use, possibly decreasing the ability of clinical trials to detect effective treatments. Quantitative urinalysis and newly developed criteria for identifying new cocaine use were evaluated as alternative measures of cocaine use. Urine specimens collected in a cocaine dosing study in nan-treatment-seeking subjects (n=5) and a cocaine treatment trial (n=37) were analyzed for the cocaine metabolite, benzoylecgonine, with qualitative and quantitative methods. Pharmacokinetic criteria ('New Use' rules) were applied to quantitative data to identify occasions of new cocaine use. Results were compared to known cocaine administrations in the laboratory study and to self-reported drug use and qualitative urinalysis for subjects in the clinical trial. New Use criteria correctly identified cocaine administrations in the cocaine dosing study in all but a small number of specimens. In the clinical trial, quantitative urinalysis and estimated New Uses provided more information about patterns and frequency of use than qualitative urinalysis in the different treatment conditions in the clinical trial. Interpretation of quantitative urinalysis with New Use rules appears to be a useful method for monitoring treatment outcome and may be more accurate than traditional qualitative urinalysis in estimating frequency of cocaine use. RP Preston, KL (reprint author), NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,NIH,5500 NATHAN SHOCK DR,BALTIMORE,MD 21224, USA. RI Preston, Kenzie/J-5830-2013; OI Preston, Kenzie/0000-0003-0603-2479; Silverman, Kenneth/0000-0003-2724-1413 NR 14 TC 80 Z9 81 U1 0 U2 3 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD JUN PY 1997 VL 92 IS 6 BP 717 EP 727 DI 10.1111/j.1360-0443.1997.tb02938.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XE201 UT WOS:A1997XE20100013 PM 9246799 ER PT J AU Weinberg, CR Zhou, H AF Weinberg, CR Zhou, H TI Model-based approaches to studying fertility and contraceptive efficacy SO ADVANCES IN CONTRACEPTION LA English DT Article; Proceedings Paper CT Meeting on Natural Family Planning and Reproductive Health Awareness - Expanding Options and Improving Health CY APR 02-05, 1997 CL GEORGETOWN UNIV, WASHINGTON, DC SP Inst Reproduct Hlth, US Agcy Int Dev, Soc Adv Contracept HO GEORGETOWN UNIV ID CONCEPTION; OVULATION AB Statistical methods recently developed to aid in identifying environmental exposures with reproductive toxicity can also be applied to trials of interventions undertaken specifically to impair fertility, i.e. methods of contraception. Although only applicable in a trial that includes a reliable benchmark for identifying the day of ovulation, the proposed measures of contraceptive efficacy derived from such a trial offer certain interpretive advantages over the more traditional approaches of evaluating contraceptives. Extensions of the same models also allow one to evaluate efficacy under any assumed pattern of imperfect use. One can also evaluate methods based on biomarkers for the fertile phase of the cycle, such as hydration of the cervical mucus, that may prove to be enormously helpful to couples who wish to use periodic abstinence as their method. In prospective studies of fertility, couples who occasionally use a barrier method should not be excluded from the study, but can be retained, without biasing the estimates for fertility parameters. RP Weinberg, CR (reprint author), NIEHS,BIOSTAT BRANCH,POB 12233,MD A3-03,RES TRIANGLE PK,NC 27709, USA. NR 9 TC 6 Z9 6 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0267-4874 J9 ADV CONTRACEPT JI Adv. Contracept. PD JUN-SEP PY 1997 VL 13 IS 2-3 BP 97 EP 103 DI 10.1023/A:1006531316675 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA XU361 UT WOS:A1997XU36100004 PM 9288326 ER PT J AU Allen, JP Litten, RZ Fertig, JB Babor, T AF Allen, JP Litten, RZ Fertig, JB Babor, T TI A review of research on the Alcohol Use Disorders Identification Test (AUDIT) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol screening; Alcohol Use Disorders Identification Test; hazardous drinking; alcohol diagnosis ID SCREENING INSTRUMENT; SHORT-MAST; CAGE; QUESTIONNAIRE; CONSUMPTION; VALIDATION; POPULATION; EMERGENCY; VALIDITY; SAMPLE AB Research on the core version of the Alcohol Use Disorders Identification Test (AUDIT) is reviewed. Sensitivities and specificities of the AUDIT for criteria of current hazardous use and, to a slightly lesser extent, lifetime alcohol dependence are high. In general, AUDIT scores are at least moderately related to other self-report alcohol screening tests. Several studies also show them as correlated with biochemical measures of drinking, Results of the AUDIT have also been associated with more distal indicators of problematic drinking, Indices of internal consistency, including Cronbach's alpha and item-total correlations, are generally in the 0.80's. Future directions for research on the AUDIT are suggested. C1 UNIV CONNECTICUT,CTR HLTH,FARMINGTON,CT. RP Allen, JP (reprint author), NIAAA,TREATMENT RES BRANCH,WILLCO GLDG,SUITE 505,6000 EXECUT BLVD MSC 7003,BETHESDA,MD 20852, USA. NR 31 TC 421 Z9 427 U1 3 U2 26 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1997 VL 21 IS 4 BP 613 EP 619 DI 10.1097/00000374-199706000-00008 PG 7 WC Substance Abuse SC Substance Abuse GA XE768 UT WOS:A1997XE76800008 PM 9194913 ER PT J AU Fawzi, WW Forman, MR Levy, A Graubard, BI Naggan, L Berendes, HW AF Fawzi, WW Forman, MR Levy, A Graubard, BI Naggan, L Berendes, HW TI Maternal anthropometry and infant feeding practices in Israel in relation to growth in infancy: The North African infant feeding study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE anthropometry; height; skinfold thickness; breast-feeding; bottle-feeding; infants; weight; length; growth; pregnancy; humans ID 1ST 3 YEARS; BIRTH-WEIGHT; LIFE; POPULATION; COMMUNITY; LACTATION; CHILDREN AB Relations between maternal anthropometric status during pregnancy and infant feeding practices and growth from birth through the first 6 mo of life were examined in a cohort of 351 Israeli mother-infant pairs of North African descent. Maternal weight, height, and triceps skinfold thicknesses were determined at 6 and 9 mo of pregnancy, while infants' weights and lengths were measured at birth and at 1, 2, 3, and 6 mo of age with concurrent collection of age-specific maternal-reported infant feeding data. On the basis of multiple-linear-regression analysis that adjusted for potential covariates, mean maternal weight at the first prenatal visit and at 6 and 9 mo of pregnancy were positively associated with birth length (P for trend in all cases <0.0001) and with linear growth between birth and 1, 3, and 6 mo of age. Maternal skinfold thickness at 9 mo of pregnancy and maternal height were also significantly associated with birth length. Moreover, maternal height, weight, and skinfold thickness at 6 and 9 mo of pregnancy were positively associated with mean birth weight. After adjustment for morbidity in the past month and other covariates, infants breast-fed exclusively had greater attained weight and weight gain in the first 3 mo compared with infants who were bottle-fed exclusively, breast-fed and bottle-fed, or solid-fed exclusively. These findings underscore the need for programs that improve the nutritional status of women before, during, and after pregnancy, and encourage exclusive breast-feeding of infants for at least the first 3 mo of life. C1 NCI,DCPC,CPRP,CPSB,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,CAMBRIDGE,MA 02138. BEN GURION UNIV NEGEV,FAC HLTH SCI,BEER SHEVA,ISRAEL. NICHHD,DIV EPIDEMIOL BIOSTAT & PREVENT RES,BETHESDA,MD 20892. NR 28 TC 8 Z9 9 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 1997 VL 65 IS 6 BP 1731 EP 1737 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XB663 UT WOS:A1997XB66300006 PM 9174468 ER PT J AU Swanson, CA Brown, CC Sinha, R Kulldorff, M Brownson, RC Alavanja, MCR AF Swanson, CA Brown, CC Sinha, R Kulldorff, M Brownson, RC Alavanja, MCR TI Dietary fats and lung cancer risk among women. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 ST LOUIS UNIV,HLTH SCI CTR,SCH PUBL HLTH,ST LOUIS,MO 63108. NCI,NIH,BETHESDA,MD 20892. RI Kulldorff, Martin/H-4282-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 13 EP 13 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600013 ER PT J AU Ung, A Hildesheim, A Chen, CJ Brinton, LA Yang, CS AF Ung, A Hildesheim, A Chen, CJ Brinton, LA Yang, CS TI Familial and sporadic cases of nasopharyngeal carcinoma in Taiwan. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 HHMI,BETHESDA,MD 20814. NCI,NIH,BETHESDA,MD 20892. NATL TAIWAN UNIV,TAIPEI 10764,TAIWAN. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 17 EP 17 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600017 ER PT J AU Baird, DD Umbach, DM Green, A Setchell, KDR Lansdell, L AF Baird, DD Umbach, DM Green, A Setchell, KDR Lansdell, L TI Cholesterol changes with 4-week soy diet in postmenopausal women. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 31 EP 31 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600030 ER PT J AU Sturgeon, SR Potischman, N Brock, J Needham, L Rothman, N Brinton, LA AF Sturgeon, SR Potischman, N Brock, J Needham, L Rothman, N Brinton, LA TI Pesticide residue and risk of endometrial cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 78 EP 78 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600078 ER PT J AU Hartman, T Albanes, D Rautalahti, M Tangrea, J Stolzenberg, R Taylor, PR AF Hartman, T Albanes, D Rautalahti, M Tangrea, J Stolzenberg, R Taylor, PR TI Physical activity and prostate cancer in the alpha-tocopherol beta-carotene cancer prevention trial (ATBC Study). SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 92 EP 92 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600091 ER PT J AU Longnecker, MP Newcomb, PA Mittendorf, R Greenberg, ER Willett, WC AF Longnecker, MP Newcomb, PA Mittendorf, R Greenberg, ER Willett, WC TI Intake of foods and supplements rich in Beta-carotene and vitamin A in relation to risk of breast cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 112 EP 112 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600111 ER PT J AU Fillmore, CM Ziegler, R Hoover, R Wu, A Pike, M West, D Nomura, A AF Fillmore, CM Ziegler, R Hoover, R Wu, A Pike, M West, D Nomura, A TI Height as a determinant of breast cancer risk in a study of Asian-American women. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 186 EP 186 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600186 ER PT J AU Sinha, R Kulldorff, M Chow, WH Hoover, RN Rothman, N AF Sinha, R Kulldorff, M Chow, WH Hoover, RN Rothman, N TI Well done red meat, heterocyclic amines (HCAs), metabolizing enzymes and risk of colorectal adenomas. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. RI Kulldorff, Martin/H-4282-2011; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 269 EP 269 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600268 ER PT J AU Li, L Schatzkin, A Yong, L Mussolino, M Harris, T Madans, J AF Li, L Schatzkin, A Yong, L Mussolino, M Harris, T Madans, J TI Bone mineral density in the NHANES I epidemiologic follow-up study: A potential marker of endogenous estrogen exposure. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 285 EP 285 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600284 ER PT J AU Weed, DL AF Weed, DL TI Underdetermination and incommensurability in epidemiology. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 292 EP 292 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600291 ER PT J AU Troisi, R Weiss, H Daling, JR Coates, R Schoenberg, JB Hoover, RN Brinton, LA AF Troisi, R Weiss, H Daling, JR Coates, R Schoenberg, JB Hoover, RN Brinton, LA TI Maternal breast cancer risk in relation to pregnancy characteristics. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 295 EP 295 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600293 ER PT J AU Kleinerman, R Tarone, R Wong, L Abramson, D Goldman, M Seddon, J Tarbell, N Boice, J Fraumeni, J Li, F AF Kleinerman, R Tarone, R Wong, L Abramson, D Goldman, M Seddon, J Tarbell, N Boice, J Fraumeni, J Li, F TI Cancer after radiotherapy for retinoblastoma: Evidence for a gene-environment interaction? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 304 EP 304 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600303 ER PT J AU Harty, LC Caporaso, NE Hayes, RB Winn, DM BravoOtero, E Blot, WJ Kleinman, DV Brown, LM Armenian, HK Fraumeni, JF Shields, PG AF Harty, LC Caporaso, NE Hayes, RB Winn, DM BravoOtero, E Blot, WJ Kleinman, DV Brown, LM Armenian, HK Fraumeni, JF Shields, PG TI Susceptibility to oral cancer associated with the alcohol dehydrogenase type 3 gene. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20817. NIDR,BETHESDA,MD 20817. UNIV PUERTO RICO,SAN JUAN,PR 00936. JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 305 EP 305 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600304 ER PT J AU Ziegler, R Nomura, A Craft, N Stemmermann, G Chyou, P AF Ziegler, R Nomura, A Craft, N Stemmermann, G Chyou, P TI Individual carotenoids in the etiology of lung and upper aerodigestive tract cancers. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 316 EP 316 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600314 ER PT J AU Thompson, F Ziegler, R Patterson, B Weinstein, S AF Thompson, F Ziegler, R Patterson, B Weinstein, S TI Serum selenium and cervical cancer risk in the United States. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 318 EP 318 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600317 ER PT J AU Siscovick, DS Fried, L Mittelmark, M Rutan, G Bild, D OLeary, DH AF Siscovick, DS Fried, L Mittelmark, M Rutan, G Bild, D OLeary, DH TI Exercise intensity and subclinical cardiovascular disease in the elderly - The cardiovascular health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aged; atherosclerosis; cardiovascular diseases; echocardiography; electrocardiography; exercise; physical fitness; risk factors ID CORONARY HEART-DISEASE; DEPENDENT DIABETES-MELLITUS; TIME PHYSICAL-ACTIVITY; LEISURE-TIME; RISK-FACTORS; VIGOROUS EXERCISE; OVERWEIGHT MEN; POPULATION; WOMEN; LIPOPROTEINS AB The authors assessed the cross-sectional association between intensity of exercise in later life and coronary heart disease risk factors and subclinical disease among 2,274 men and women, 65 years of age and older, who were participants in the Cardiovascular Health Study (CHS) during 1989-1990. Subjects were free of prior clinical cardiovascular disease or impairment of physical function. Exercise intensity was characterized as low, moderate, or high, based on highest intensity exercise reported over the 2 weeks prior to the CHS baseline examination. After adjustment for age, education, and postmenopausal hormone therapy (among women), there was an inverse dose-response relationship of exercise intensity with selected risk factors. By low, moderate, and high exercise intensity, respectively: fasting insulin-men, 15.6 mu U/ml, 14.1 mu U/ml, and 12.6 mu U/ml, p for trend <0.001; women, 14.8 mu U/ml, 13.8 mu U/ml, and 12.0 mu U/ml, p for trend=0.01; serum fibrinogen-men, 316.2 mg/dl, 315.4 mg/dl, and 300.0 mg/dl, p for trend=0.01; women, 327.3 mg/dl, 317.0 mg/dl, and 310.7 mg/dl, p for trend=0.01; lower extremity arterial disease by percent with ankle-arm index <0.9-men, 18.3, 5.5, and 3.7,p for trend=0.01; women, 10.0, 5.7, and 2.8, p for trend=0.02; evidence of myocardial injury by cardiac infarction/injury score (CIIS)-men, 8.0, 6.0, 3.9, p for trend <0.001; women, 4.6, 3.9, and 3.6, p for trend=0.03. Adjustment for smoking, alcohol consumption, and total kilocalories expended in exercise altered the findings only slightly. The authors conclude that intensity of exercise in later life is associated with favorable coronary disease risk factor levels and a reduced prevalence of several markers of subclinical disease. C1 UNIV WASHINGTON,HARBORVIEW MED CTR,CARDIOVASC HLTH RES UNIV,DEPT MED,SEATTLE,WA 98104. UNIV WASHINGTON,HARBORVIEW MED CTR,CARDIOVASC HLTH RES UNIV,DEPT EPIDEMIOL,SEATTLE,WA 98104. JOHNS HOPKINS MED INST,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT EPIDEMIOL,BALTIMORE,MD 21205. UNIV BERGEN,SCH PSYCHOL,DEPT PSYCHOSOCIAL SCI,BERGEN,NORWAY. UNIV TENNESSEE,DEPT MED,MEMPHIS,TN 38104. VET ADM MED CTR,MEMPHIS,TN 38104. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. GEISINGER MED CTR,DEPT RADIOL,DANVILLE,PA 17822. FU NHLBI NIH HHS [N01-HC-87079, N01-HC-87080, N01-HC-87081] NR 23 TC 97 Z9 98 U1 4 U2 7 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 BP 977 EP 986 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA226 UT WOS:A1997XA22600003 PM 9169906 ER PT J AU TrenthamDietz, A Newcomb, PA Storer, BE Longnecker, MP Baron, J Greenberg, ER Willett, WC AF TrenthamDietz, A Newcomb, PA Storer, BE Longnecker, MP Baron, J Greenberg, ER Willett, WC TI Body size and risk of breast cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE body height; body weight; breast neoplasms; weight gain ID POSTMENOPAUSAL WOMEN; MASS INDEX; RELATIVE WEIGHT; SEX-HORMONES; REPRODUCTIVE FACTORS; NORWEGIAN WOMEN; UNITED-STATES; HEIGHT; RELIABILITY; ACCURACY AB The relation between body size and breast cancer remains uncertain, particularly with regard to differences between pre- and postmenopausal women. The authors examined whether height, weight, body mass index, and weight change were associated with breast cancer risk among pre- and postmenopausal women, This population-based case-control study included women aged 20-74 years (n=6,548) who were diagnosed with invasive breast cancer during 1988-1991 in Maine, Massachusetts, New Hampshire, and Wisconsin. Similarly aged control women (n=9,057) were selected at random from driver's license files and Health Care Financing Administration files. Height, weight, and information on other breast cancer risk factors were ascertained by telephone interview, and logistic regression was used to estimate multivariate-adjusted odds ratios and 95% confidence intervals. Among premenopausal women, the adjusted odds ratio for the upper quintile group of height relative to the lowest was 1.36 (95% confidence interval (CI) 1.05-1.76). The heaviest premenopausal women had a lower risk (odds ratio (OR)=0.87, 95% CI 0.70-1.10). Among postmenopausal women, the adjusted odds ratios were higher for the upper quintile categories of both height (OR=1.27, 95% CI 1.11-1.45) and weight (OR=1.57, 95% CI 1.37-1.79). Weight gain since ages 18 and 35 years was associated with increased postmenopausal breast cancer risk, and risk was lower in women who had lost weight, These findings suggest that programs to avoid weight gain merit study as a means to reduce risk of postmenopausal breast cancer. C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NATL INST ENVIRONM HLTH SCI,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT COMMUNITY & FAMILY MED,HANOVER,NH 03756. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT MED,HANOVER,NH 03756. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,NORRIS COTTON CANC CTR,HANOVER,NH 03756. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHANNING LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. RP TrenthamDietz, A (reprint author), UNIV WISCONSIN,CTR COMPREHENS CANC,MED SCI CTR,RM 4760,1300 UNIV AVE,MADISON,WI 53706, USA. OI Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [R01CA47305, R01CA47147] NR 62 TC 124 Z9 127 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 BP 1011 EP 1019 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA226 UT WOS:A1997XA22600007 PM 9169910 ER PT J AU Lin, T Orrison, BM Leahey, AM Suchy, SF Bernard, DJ Lewis, RA Nussbaum, RL AF Lin, T Orrison, BM Leahey, AM Suchy, SF Bernard, DJ Lewis, RA Nussbaum, RL TI Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID INOSITOL POLYPHOSPHATE-5-PHOSPHATASE; 5-PHOSPHATASE; TRANSLOCATION AB The oculocerebrorenal syndrome of Lowe (OCRL) is a multisystem disorder characterized by congenital cataracts, mental retardation, and renal Fanconi syndrome. The OCRL1 gene, which, when mutated, is responsible for OCRL, encodes a 105-kD Golgi protein with phosphatidylinositol (4,5)bisphosphate (PtdIn[4,5]P-2) 5-phosphatase activity. We have examined the OCRL1 gene in 12 independent patients with OCRL and have found 11 different mutations. Six were nonsense mutations, and one a deletion of one or two nucleotides that leads to frameshift and premature termination. In one, a 1.2-kb genomic deletion of exon 14 was identified. In four others, missense mutations or the deletion of a single codon were found to involve amino acid residues known to be highly conserved among proteins with PtdIns(4,5)P-2 5-phosphatase activity. All patients had markedly reduced PtdIns(4,5)P-2 5-phosphatase activity in their fibroblasts, whereas the ocrl1 protein was detectable by immunoblotting in some patients with either missense mutations or a codon deletion but was not detectable in those with premature termination mutations. These results confirm and extend our previous observation that the OCRL phenotype results from loss of function of the ocrl1 protein and that mutations are generally heterogeneous. Missense mutations that abolish enzyme activity but not expression of the protein will be useful for studying structure-function. relationships in PtdIns(4,5)P-2 5-phosphatases. C1 NIH,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. CHILDRENS HOSP PHILADELPHIA,DEPT PEDIAT,PHILADELPHIA,PA 19104. BAYLOR COLL MED,DEPT OPHTHALMOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. FU NCI NIH HHS [T32-CA09615]; NICHD NIH HHS [R01-HD23245] NR 19 TC 72 Z9 78 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1997 VL 60 IS 6 BP 1384 EP 1388 DI 10.1086/515471 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XE294 UT WOS:A1997XE29400016 PM 9199559 ER PT J AU Devereux, RB Roman, MJ Paranicas, M OGrady, MJ Wood, EA Howard, BV Welty, TK Lee, ET Fabsitz, RR AF Devereux, RB Roman, MJ Paranicas, M OGrady, MJ Wood, EA Howard, BV Welty, TK Lee, ET Fabsitz, RR TI Relations of Doppler stroke volume and its components to left ventricular stroke volume in normotensive and hypertensive American Indians - The strong heart study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE cardiac output; Doppler echocardiography; stroke distance; stroke volume ID CARDIAC-OUTPUT; M-MODE; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ECHOCARDIOGRAPHY; MASS; HYPERTROPHY; ULTRASOUND; DESIGN AB Doppler echocardiographic measurement of time-velocity integral of blood now across the aortic annulus (''stroke distance'') or of stroke volume (SV) have been proposed as noninvasive measures of cardiac pump performance that could elucidate the hemodynamics of hypertension. To evaluate the performance of these measures of hemodynamic volume load in a population with a wide range of body build and other characteristics, we obtained technically adequate imaging and Doppler echocardiograms in 1,935 of 2,212 (87%) American Indian Strong Heart Study participants, without mitral regurgitation or segmental left ventricular (LV) dysfunction, in Arizona, Oklahoma, and South/North Dakota. The subjects ranged widely in age (48 to 81 years) and body mass index (17.0 to 62.6 kg/m(2)); 65% were women; 1,161 were normotensive and 774 were hypertensive. As a reference standard, LV and stroke volumes were calculated from LV internal dimensions by the Teichholz method. Doppler SVs were moderately related to LV SVs (I = 0.63), but Doppler SV was slightly lower in both normotensive (mean = 69.8 and 72.9 mt, respectively) and hypertensive subjects (71.1 v 73.6 mt). Aortic stroke distance was less closely related than was aortic annular area to LV SV (r = 0.34 v 0.40, P < .001). Aortic annular area (r = 0.44) but not stroke distance (r = 0.04) was moderately correlated with body surface area. Stroke distance was inversely related to annular area (r = -0.29) and in subjects stratified by aortic annular diameter 1.6 to 1.9, 2.0 to 2.1, and 2.3 to 2.9 cm, mean LV SV increased from 67 to 74 to 80 mt, but average stroke distance fell from 22.8 to 21.6 to 20.1 cm. Stroke distance also failed to identify gender differences in LV SV but did identify that due to obesity. Thus Doppler SV closely parallels independently measured LV SV but slightly underestimates SV in both normotensive and hypertensive adults, whereas aortic stroke distance yields misleading comparisons between genders or individuals of different body sizes. (C) 1997 American Journal of Hypertension, Ltd. C1 MEDLANT RES INST, WASHINGTON, DC USA. INDIAN HLTH SERV, ABERDEEN AREA, RAPID CITY, SD USA. UNIV OKLAHOMA, SCH PUBL HLTH SCI, OKLAHOMA CITY, OK USA. NHLBI, DIV EPIDEMIOL & DIS CONTROL, BETHESDA, MD 20892 USA. RP Devereux, RB (reprint author), NEW YORK HOSP, CORNELL MED CTR,DIV CARDIOL,DEPT MED,BOX 222, 525 E 68TH ST, NEW YORK, NY 10021 USA. FU NHLBI NIH HHS [U01-HL41642, U01-HL41652]; PHS HHS [U01-41654] NR 35 TC 75 Z9 78 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUN PY 1997 VL 10 IS 6 BP 619 EP 628 DI 10.1016/S0895-7061(97)00059-9 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XD764 UT WOS:A1997XD76400005 PM 9194507 ER PT J AU Shea, KM Farrow, A Little, R AF Shea, KM Farrow, A Little, R TI An investigation of the effect of paternal occupation group at conception on birth weight and gestational age SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE paternal occupation; birth weight; gestation; exposure; reproduction ID PRETERM DELIVERY; EXPOSURES; CHILDREN; INDUSTRY AB The occupational histories of fathers were collected prospectively as apart of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), and were used to investigate the association of paternal job title with a baby's birth weight and gestational age. The analysis cohort consisted of 4,795 singleton live-born babies whose fathers responded fully to questionnaire items regarding occupational history. Jobs were coded using the British Standard Occupational Codes and classified into nine major occupational groups. A 73-gram difference (95% CI: 0.16, 145.17) was found between the mean birth weight of full-term babies born of professional fathers (3,543 gm) and of fathers working in craft and related occupations (3,470 gm). This difference decreased and lost significance after controlling for sociodemographic variables. No difference was found in the mean birth weight of preterm babies, or in the rate of preterm delivery, when analyzed by paternal occupation at conception. Our results suggest that when important sociodemographic variables atr known, the father's jab title alone may not be a useful predictor of birth weight or preterm delivery. (C) 1997 Wiley-Liss, Inc. C1 UNC HOSP, NIEHS PROGRAM, GEN CLIN RES CTR, CHAPEL HILL, NC USA. ROYAL HOSP SICK CHILDREN, DEPT CHILD HLTH, BRISTOL BS2 8BJ, AVON, ENGLAND. RP Shea, KM (reprint author), NIEHS, EPIDEMIOL BRANCH, MD A3-05, POB 12233, 111 TW ALEXANDER DR, RES TRIANGLE PK, NC 27709 USA. FU NIEHS NIH HHS [N01-ES-35356]; Wellcome Trust NR 19 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 1997 VL 31 IS 6 BP 738 EP 743 DI 10.1002/(SICI)1097-0274(199706)31:6<738::AID-AJIM11>3.0.CO;2-Z PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WW145 UT WOS:A1997WW14500011 PM 9131230 ER PT J AU Cassel, C Blank, L Braunstein, G Burke, W Fryhofer, SA Pinn, V Ricks, P Savard, M Toskes, P AF Cassel, C Blank, L Braunstein, G Burke, W Fryhofer, SA Pinn, V Ricks, P Savard, M Toskes, P TI What internists need to know: Core competencies in women's health SO AMERICAN JOURNAL OF MEDICINE LA English DT Article C1 CEDARS SINAI MED CTR,DEPT MED,LOS ANGELES,CA. UNIV WASHINGTON,SCH MED,WOMENS HLTH CTR,SEATTLE,WA 98195. NIH,OFF WOMENS RES,BETHESDA,MD. JEANES HOSP,MENOPAUSE & OSTEOPOROSIS INST,PHILADELPHIA,PA. UNIV FLORIDA,COLL MED,DIV GASTROENTEROL NUTR & DIGEST DIS,GAINESVILLE,FL 32611. RP Cassel, C (reprint author), MT SINAI SCH MED,DEPT GERIATR & ADULT DEV,NEW YORK,NY 10029, USA. NR 14 TC 31 Z9 31 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 1997 VL 102 IS 6 BP 507 EP 512 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XG446 UT WOS:A1997XG44600001 PM 9217662 ER PT J AU Krall, EA DawsonHughes, B Hannan, MT Wilson, PWF Kiel, DP AF Krall, EA DawsonHughes, B Hannan, MT Wilson, PWF Kiel, DP TI Postmenopausal estrogen replacement and tooth retention SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID BONE-MINERAL DENSITY; SKELETAL BONE; SUBGINGIVAL PLAQUE; ELDERLY WOMEN; OSTEOPOROSIS; THERAPY; OLDER; POPULATION; PREVENTION; FEMALES AB PURPOSE TO determine if estrogen replacement therapy (ERT) is associated with improved tooth retention and lower risk of edentulism (no natural teeth remaining) in a cohort of elderly women. PATIENTS AND METHODS Subjects were 488 women, aged 72 to 95, who participated in the 23rd examination cycle (1994 to 1995) of the Framingham Heart Study, a population-based study begun in 1948. The number of teeth remaining and their location were recorded by a trained observer. History and duration of ERT were obtained from records kept since cycle 10 (1960 to 1963). Third molars were excluded from all analyses. RESULTS Women who ever used ERT were younger than nonusers by 1 year (80 +/- 4 years, n = 184, versus 81 +/- 4 years, n = 304, P = 0.019). Estrogen users had more teeth remaining than nonusers (12.5 +/- 0.8 versus 10.7 +/- 0.8 versus 10.7 +/- 0.6 teeth, P = 0.046, mean +/- SE) after controlling for age, smoking status, and education. Duration of estrogen use was an independent predictor of the number of teeth remaining (P = 0.015) such that each 4.2-year interval of use was associated with an increased mean retention of 1 tooth. Long-term estrogen users (more than 8 years, n = 48) had an average of 3.6 more teeth than women who never used estrogen (14.3 +/- 1.5 versus 10.7 +/- 0.6 teeth, P <0.02). The association with duration of use was present among different types of teeth (incisors, canines, and premolars) but less strong for molars. The odds of being edentulous were reduced by 6% for each 1-year increase in duration of estrogen use (odds ratio = 0.94, P = 0.038, 95% confidence interval = 0.90 to 0.99). CONCLUSIONS These data suggest that ERT protects against tooth loss and reduces the risk of edentulism. The associations of estrogen use and tooth retention are evident for all but the molars. (C) 1997 by Excerpta Medica, Inc. C1 TUFTS UNIV,USDA,JEAN MAYER HUMAN NUTR RES CTR AGING,CALCIUM & BONE METAB LAB,BOSTON,MA 02111. HARVARD UNIV,SCH MED,HEBREW REHABIL CTR AGED,BOSTON,MA. HARVARD UNIV,SCH MED,DIV AGING,BOSTON,MA. NHLBI,BOSTON,MA. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,BOSTON,MA. BOSTON UNIV,GOLDMAN SCH DENT MED,DEPT HLTH POLICY & HLTH SERV RES,BOSTON,MA 02215. OI Hannan, Marian/0000-0002-9586-6928; Kiel, Douglas/0000-0001-8474-0310 NR 30 TC 56 Z9 60 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 1997 VL 102 IS 6 BP 536 EP 542 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA XG446 UT WOS:A1997XG44600007 PM 9217668 ER PT J AU Petrella, JR DeCarli, C Dagli, M Duyn, JH Grandin, CB Frank, JA Hoffman, EA Theodore, WH AF Petrella, JR DeCarli, C Dagli, M Duyn, JH Grandin, CB Frank, JA Hoffman, EA Theodore, WH TI Assessment of whole-brain vasodilatory capacity with acetazolamide challenge at 1.5 T using dynamic contrast imaging with frequency-shifted burst SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the Radiological-Society-of-North-America CY DEC 01-06, 1996 CL CHICAGO, IL SP Radiol Soc N Amer DE blood, volume; brain, magnetic resonance; magnetic resonance, technique ID CEREBRAL BLOOD-FLOW; COMPUTED-TOMOGRAPHY; BOLUS TRACKING; NORMAL VALUES; VOLUME; SUSCEPTIBILITY; RESERVE; MRI AB PURPOSE: To determine whether whole-brain acetazolamide-induced changes in regional cerebral blood volume (rCBV) can be assessed on a conventional gradient 1.5-T MR system using 3-D dynamic susceptibility contrast-enhanced MR imaging, METHODS: A 3-D frequency-shifted (FS) burst technique was used to assess the intravascular first pass of contrast agent, Changes in rCBV were calculated in 40 volunteers before and after acetazolamide (n = 30) or saline (n = 10) injection using customized analysis software on an independent workstation. A single-section gradient-echo technique with better spatial resolution was used in one additional volunteer to examine the effect of partial volume averaging on calculation of absolute rCBV, RESULTS: A statistically significant increase in rCBV (gray matter = 23%, white matter = 32.5%) was noted after acetazolamide compared with saline. Baseline fractional CBVs were 22% +/- 3% for gray matter and 12% +/- 2% for white matter. Partial volume averaging was probably responsible for a systematic but linear overestimation of absolute rCBV. CONCLUSION: Acetazolamide-induced changes in rCBV can be assessed using 3-D dynamic susceptibility contrast-enhanced MR imaging with FS-burst on a conventional gradient 1.5-T MR system. Values obtained with this technique overestimate absolute rCBV but are systematically biased and can be used for intersubject and intrasubject ratio comparisons. C1 NINCDS,NIH,BETHESDA,MD 20892. NIH,IN VIVO NMR RES CTR,BETHESDA,MD 20892. HOSP UNIV PENN,DEPT RADIOL,PHILADELPHIA,PA 19104. RP Petrella, JR (reprint author), NIH,LDRR,OIR,OD,BLDG 10,ROOM B1N256,10 CTR DR,MSC 1074,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009; Duyn, Jozef/F-2483-2010 NR 34 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 1997 VL 18 IS 6 BP 1153 EP 1161 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA XE810 UT WOS:A1997XE81000019 PM 9194443 ER PT J AU Hansen, LA Alexander, N Hogan, ME Sundberg, JP Dlugosz, A Threadgill, DW Magnuson, T Yuspa, SH AF Hansen, LA Alexander, N Hogan, ME Sundberg, JP Dlugosz, A Threadgill, DW Magnuson, T Yuspa, SH TI Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FACTOR-ALPHA; TGF-ALPHA; EGF RECEPTOR; SHEEP SKIN; EXPRESSION; KERATINOCYTES; MOUSE; HYPERPLASIA; PAPILLOMAS; PHENOTYPE AB Mice harboring a targeted disruption of the epidermal growth factor receptor (EGFR) allele exhibit a severely disorganized hair follicle phenotype, fuzzy cent, and systemic disease resulting in death before 3 weeks. This skin phenotype was reproduced in whole skin grafts and in grafts of EGFR null hair follicle buds onto nude mice, providing a model to evaluate the natural evolution of skin lacking the EGFR, Hair follicles in grafts of null skin did not progress from anagen to telogen ann scanning electron micrografts revealed wavy, flattened hair fibers with cuticular abnormalities, Marry of the EGFR null hair follicles in the grafted skirr rr,ere consumed by an inflammatory reaction resulting in complete hair loss in 67% of the grafts by 10 weeks, Localization of follicular differentiation markers including keratin 6, transglutaminase, ann the hair keratins mHa2 and hacl-1 revealed a pattern of premature differentiation within the null hair follicles. In intact EGFR null mice, proliferation in the interfollicular epidermis, but not hair follicles, was greatly decreased in the absence of EGFR. In contrast, grafting of EGFR null skin resulted in a hyperplastic response in the epidermis that did not resolve even after 10 weeks, although the wound-induced hyperplasia in EGFR wild-type grafts had resolved within 3 to 4 weeks. Thus, epithelial expression of the EGFR has complex functions in the skin, It is important in delaying follicular differentiation, may serve to protect the hair follicle from immunological reactions, and modifies both normal and wound-induced epidermal proliferation but seems dispensable for follicular proliferation. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, NIH, BETHESDA, MD 20892 USA. CASE WESTERN RESERVE UNIV, DEPT GENET, CLEVELAND, OH 44106 USA. JACKSON LAB, BAR HARBOR, ME 04609 USA. RI Threadgill, David/N-4425-2013 OI Threadgill, David/0000-0003-3538-1635 NR 47 TC 141 Z9 145 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1997 VL 150 IS 6 BP 1959 EP 1975 PG 17 WC Pathology SC Pathology GA XB700 UT WOS:A1997XB70000010 PM 9176390 ER PT J AU Cassano, GB Michelini, S Shear, MK Coli, E Maser, JD Frank, E AF Cassano, GB Michelini, S Shear, MK Coli, E Maser, JD Frank, E TI The panic agoraphobic spectrum: A descriptive approach to the assessment and treatment of subtle symptoms SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID SEPARATION ANXIETY; DIAGNOSTIC INTERVIEW; SOCIAL PHOBIA; LIFE EVENTS; DISORDER; ATTACKS; PERSONALITY; HYPOCHONDRIASIS; SCHIZOPHRENIA; QUESTIONNAIRE AB Objective: Psychiatric classification is still a topic of considerable discussion and debate in spite of major advances in the past two decades. The debate involves categorical versus dimensional approaches, cutoff numbers of symptoms to define a case, degree of impairment, objective diagnostic criteria versus more theoretically based criteria, episodic versus trait-like symptoms, and the role of atypical and subclinical symptoms. All of these issues have been raised for the anxiety disorders and depression. This article presents the conceptualization of a relatively novel and testable approach to the diagnosis and classification of panic and agoraphobia, the panic-agoraphobic spectrum, and pilot data on a new questionnaire to assess it. Method: Pilot testing of the Panic-Agoraphobic Spectrum Questionnaire was undertaken with 100 inpatients who had lifetime diagnoses of panic disorder, unipolar depression, comorbid panic and unipolar depressive disorders, or an eating disorder. The instrument emphasizes impairment related to 144 behaviors and experiences in seven panic-agoraphobic symptom domains. Results: Patients with panic disorder scored highest on the questionnaire, and those with comorbid depression showed even greater severity of illness. The scores of the patients with eating disorders and of the depressed patients differed from those of the other groups but also differed from 0. Conclusions: The spectrum model of panic and agoraphobia is a flexible and comprehensive means of describing this clinical complex. The proposed model, complementary to the categorical approach, presumably expresses a unitary pathophysiology. Its usefulness is discussed in terms of its value for patient-therapist communication, outcome measures, identification of subtle personality traits, and subtyping of patients for research and treatment. C1 UNIV PITTSBURGH, WESTERN PSYCHIAT INST & CLIN, PITTSBURGH, PA 15260 USA. NIMH, ANXIETY & SOMATOFORM DISORDERS PROGRAM, ROCKVILLE, MD 20857 USA. RP Cassano, GB (reprint author), UNIV PISA, SCH MED, INST PSYCHIAT, I-56100 PISA, ITALY. NR 108 TC 91 Z9 94 U1 1 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1997 VL 154 IS 6 SU S BP 27 EP 38 PG 12 WC Psychiatry SC Psychiatry GA XB832 UT WOS:A1997XB83200006 PM 9167542 ER PT J AU Breier, A Malhotra, AK Pinals, DA Weisenfeld, NI Pickar, D AF Breier, A Malhotra, AK Pinals, DA Weisenfeld, NI Pickar, D TI Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CEREBRAL GLUCOSE-UTILIZATION; BLOOD-FLOW; CHRONIC-SCHIZOPHRENIA; BRAIN MEMBRANES; PET IMAGES; RAT-BRAIN; PHENCYCLIDINE; HYPOFRONTALITY; HALLUCINATIONS; METABOLISM AB Objective: Agents that antagonize the N-methyl-D-aspartic acid (NMDA) receptor, such as phencyclidine and ketamine, produce an acute psychotic state in normal individuals that resembles some symptoms of schizophrenia. The aim of this study was to determine which brain regions are involved in NMA receptor-mediated psychosis. Method: Positron emission tomography with [F-18]fluorodeoxyglucose was used to determine cerebral metabolic activity in 17 healthy volunteers while an acute psychotic state was induced simultaneously by the administration of subanesthetic doses of ketamine. Results: Ketamine produced focal increases in metabolic activity in the prefrontal cortex and an acute psychotic state. A change in one psychotic symptom, conceptual disorganization, was significantly related to prefrontal activation. Conclusions: These data suggest that the prefrontal cortex may be involved in mediating NMDA receptor-induced psychosis. RP Breier, A (reprint author), NIMH,EXPT THERAPEUT BRANCH,BLDG 10,RM 4N212,9000 ROCKVILLE PIKE,ROCKVILLE,MD 20892, USA. NR 45 TC 228 Z9 234 U1 0 U2 9 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1997 VL 154 IS 6 BP 805 EP 811 PG 7 WC Psychiatry SC Psychiatry GA XA587 UT WOS:A1997XA58700013 PM 9167508 ER PT J AU Goldberg, TE Gold, JM Coppola, R Weinberger, DR AF Goldberg, TE Gold, JM Coppola, R Weinberger, DR TI Unnatural practices, unspeakable actions: A study of delayed auditory feedback in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: It has been suggested that auditory hallucinations and delusions of control in persons with schizophrenia could involve a disconnection between an ''intention center'' and a ''monitoring center.'' Method: To test this model directly, the authors used a delayed auditory feedback paradigm in which the subject hears his or her own speech delayed electronically by a fraction of a second. In normal subjects this produces dysfluency, which is thought to occur because an expectancy about the perceptual arrival of speech, formed in a monitoring center on the basis of corollary discharge from an intention center, is violated. If, however, a disconnection were present in schizophrenia, such an expectancy would not be formed; hence, less dysfluency should occur. Fifteen patients with chronic schizophrenia (10 of whom experienced auditory hallucinations and/or delusions of control) and 19 normal subjects were studied. Results: Rather than exhibiting less dysfluency than the normal subjects, patients with delusions and/or hallucinations exhibited significantly more dysfluency. Conclusions: These results do not support a cognitive model a disconnection. RP Goldberg, TE (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 9 TC 18 Z9 18 U1 3 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1997 VL 154 IS 6 BP 858 EP 860 PG 3 WC Psychiatry SC Psychiatry GA XA587 UT WOS:A1997XA58700023 PM 9167517 ER PT J AU Greenberg, BD George, MS Martin, JD Benjamin, J Schlaepfer, TE Altemus, M Wassermann, EM Post, RM Murphy, DL AF Greenberg, BD George, MS Martin, JD Benjamin, J Schlaepfer, TE Altemus, M Wassermann, EM Post, RM Murphy, DL TI Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: A preliminary study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: Prefrontal mechanisms are implicated in obsessive-compulsive disorder. The authors investigated whether prefrontal repetitive transcranial magnetic stimulation influenced obsessive-compulsive disorder symptoms. Method: Twelve patients with obsessive-compulsive disorder were given repetitive transcranial magnetic stimulation (80% motor threshold 20 Hz/2 seconds per minute for 20 minutes) to a right lateral prefrontal, a left lateral prefrontal, and a midoccipital (control) site on separate days, randomized. The patients' symptoms and mood were rated for 8 hours afterward. Results: Compulsive urges decreased significantly for 8 hours after right lateral prefrontal repetitive transcranial magnetic stimulation, but there were nonsignificant increases in compulsive urges after repetitive transcranial magnetic stimulation of the midoccipital site. A shorter-lasting (30 minutes), modest, and nonsignificant reduction in compulsive urges occurred after left lateral prefrontal repetitive transcranial magnetic stimulation. Mood improved during and 30 minutes after right lateral prefrontal stimulation. Conclusions: These preliminary results suggest that right prefrontal repetitive transcranial magnetic stimulation might affect prefrontal mechanisms involved in obsessive-compulsive disorder. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NINCDS,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. RP Greenberg, BD (reprint author), NIMH,CLIN SCI LAB,BLDG 10,RM 3D41,10 CTR DR,MSC 1264,BETHESDA,MD 20892, USA. OI Schlaepfer, Thomas/0000-0003-0612-9692 NR 8 TC 176 Z9 185 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1997 VL 154 IS 6 BP 867 EP 869 PG 3 WC Psychiatry SC Psychiatry GA XA587 UT WOS:A1997XA58700026 PM 9167520 ER PT J AU Yoon, JH Gray, T Guzman, K Koo, JS Nettesheim, P AF Yoon, JH Gray, T Guzman, K Koo, JS Nettesheim, P TI Regulation of the secretory phenotype of human airway epithelium by retinoic acid, triiodothyronine, and extracellular matrix SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID HUMAN TRACHEAL EPITHELIUM; GENE-EXPRESSION; MOLECULAR-CLONING; IN-VITRO; CELLS; CDNA; INCREASES; CULTURES AB The purpose of our studies was to identify factors which regulate the composition of airway secretions produced by normal human tracheobronchial epithelial (NHTBE) cells. Individual factors were removed from the culture media of NHTBE cells grown in air-liquid interface (ALI) cultures (which support mucociliary differentiation) and the effects on mucin. lysozyme (LZ), and secretory leukocyte protease inhibitor (SLPI) secretion and gene expression were examined. Deletion of hydrocortisone, epinephrine, transferrin, or gentamycin-amphotericin from the media had no reproducible effects, deletion of insulin was incompatible with culture growth. We identified 3 factors, namely retinoic acid (RA) triiodothyronine (T3) and collagen gel substratum, which had a major impact on the profile of NHTBE secretions. Removal of Ra from the media caused a drastic decrease in mucin secretion and a decrease in expression of the mucin genes MUC2 and MUC5AC. LZ and SLPI secretions were increased in these cultures. Paradoxically LZ mRNA was decreased, while SLPI mRNA levels were increased. Removal of T3 selectively increased mucin secretion, MUC2 gene expression was not affected, but MUC5AC mRNA levels reproducibly increased, suggesting that the expression of these two mucin genes is differentially regulated. LZ and SLPI secretion levels were not significantly affected by deletion of T3 from the culture media: however, LZ mRNA levels were increased in the absence of T3 while SLPI transcript levels were not affected. Omission of the attachment substratum, type I collagen gel, resulted in significant increases in all 3 secretory Products. MUC2 and MUC5AC steady state mRNA levels were not consistently affected. In contrast LZ and SLPI gene expression were reproducibly increased. Our studies show that individual factors in the epithelial environment can regulate expression of specific secretory cell gene products in a highly selective manner. C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. RI Yoon, Joo-Heon/E-5781-2016; OI Yoon, Joo-Heon/0000-0003-2404-7156 NR 34 TC 69 Z9 70 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN PY 1997 VL 16 IS 6 BP 724 EP 731 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA XE820 UT WOS:A1997XE82000012 PM 9191474 ER PT J AU Gorelick, DA Simmons, MS Carriero, N Tashkin, DP AF Gorelick, DA Simmons, MS Carriero, N Tashkin, DP TI Characteristics of smoked drug use among cocaine smokers SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID PROGRESSION; ADULTHOOD; CESSATION; SMOKING AB The authors collected data by structured interview from a convenience sample of 228 physically healthy, largely (82%) treatment-seeking, cocaine smokers with minimal histories of other smoked (other than tobacco and marijuana) or injection drug use. The vast majority of subjects also smoked either marijuana only (17.5%), tobacco only (17%), or both (61%), with onset of such smoking almost always (97%) preceding the initiation of regular cocaine smoking. There were few significant differences in sociodemographic or cocaine use characteristics among the subgroups of subjects smoking either cocaine only or cocaine and marijuana and/or tobacco. More than one-third of marijuana smokers quit (45%) or decreased (38%) their use after starting regular cocaine smoking, whereas only 5% of tobacco smokers did so. These findings suggest that marijuana smoking is more influenced by regular cocaine smoking than is tobacco smoking. RP Gorelick, DA (reprint author), NIDA,DIV INTRAMURAL RES,NIH,POB 5180,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [DA03018, DA04268] NR 17 TC 24 Z9 24 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SUM PY 1997 VL 6 IS 3 BP 237 EP 245 PG 9 WC Substance Abuse SC Substance Abuse GA XN416 UT WOS:A1997XN41600007 PM 9256990 ER PT J AU Likar, R Schafer, M Paulak, F Sittl, R Pipam, W Schalk, H Geissler, D Bernatzky, G AF Likar, R Schafer, M Paulak, F Sittl, R Pipam, W Schalk, H Geissler, D Bernatzky, G TI Intraarticular morphine analgesia in chronic pain patients with osteoarthritis SO ANESTHESIA AND ANALGESIA LA English DT Article ID DORSAL-ROOT GANGLIA; SUBSTANCE-P RELEASE; SPINAL-CORD; KNEE-JOINT; INFLAMMATION; OPIOIDS; QUESTIONNAIRE; MECHANISMS; RECEPTORS; INHIBIT AB Controlled clinical studies have shown that local administration of morphine can significantly relieve acute postoperative pain. This analgesic effect is long-lasting (up to 48 h) and is mediated by peripheral opioid receptors. Experimental evidence shows that analgesic effects of peripheral opioids and the density of opioid receptors on peripheral sensory nerves increase with the duration of painful inflammatory processes. This study examines the analgesic effects of 1 mg of morphine injected into the arthritic knee joints of two groups of chronic pain patients (n = 23) suffering from osteoarthritis. Using a randomized, double-blind cross-over design, patients received either an intraarticular injection of morphine and intravenous saline (Group A, n = 13) or an intraarticular injection of saline and intravenous morphine (Group B, n = 10) during Phase I. Seven days later, patients crossed over to the opposite treatment (Phase II). During Phase I, intraarticular morphine resulted in significantly greater pain relief than intraarticular saline, and this effect was present at rest as well as during movement. The analgesic effect was surprisingly long-lasting and extended into Phase II, a carry-over effect that prevented the analysis of Phase II. No side effects were reported. The treatment of arthritic pain by peripherally acting opioids may be a promising alternative to currently available medications that have serious side effects. C1 LANDESKRANKENANSTALTEN KLAGENFURT,ABT ANASTHESIOL & INTENS MED,KLAGENFURT,AUSTRIA. LANDESKRANKENANSTALTEN KLAGENFURT,INNERE MED ABT,KLAGENFURT,AUSTRIA. JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. NIDA,BEHAV PHARMACOL & GENET SECT,DIV INTRAMURAL RES,NIH,BALTIMORE,MD. UNIV KLIN ERLANGEN,ABT ANASTHESIOL,ERLANGEN,GERMANY. SALZBURG UNIV,NAT WISSENSCH FAK,A-5020 SALZBURG,AUSTRIA. NR 25 TC 93 Z9 100 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 1997 VL 84 IS 6 BP 1313 EP 1317 DI 10.1097/00000539-199706000-00025 PG 5 WC Anesthesiology SC Anesthesiology GA XB414 UT WOS:A1997XB41400025 PM 9174312 ER PT J AU Trawoger, R Kolobow, T Cereda, M Giacomini, M Usuki, J Horiba, K Ferrans, VJ AF Trawoger, R Kolobow, T Cereda, M Giacomini, M Usuki, J Horiba, K Ferrans, VJ TI Clearance of mucus from endotracheal tubes during intratracheal pulmonary ventilation SO ANESTHESIOLOGY LA English DT Article DE anesthetic techniques, endotracheal tube, endotracheal suctioning,; intratracheal pulmonary ventilation, tracheal mucus; trachea, pathology, histology; equipment, design, tracheal tubes ID PRESSURE; CATHETER; DAMAGE AB Background: Intratracheal pulmonary ventilation (ITPV) is a form of tracheal gas insufflation in which all gas emerges in a cephalad direction from the tip of a reverse-thrust catheter positioned within an endotracheal tube. In vitro experiments have shown that this rapid gas flow, with 5 ml/h of normal saline added to the gas flow, continuously removes tracheal secretions from within the endotracheal tube. The authors evaluated its effectiveness to remove mucus in long-term studies in sheep. Methods: Fourteen healthy sheep were tracheally intubated and ventilated for 3 days with ITPV or with volume-controlled ventilation. Measurements were made of the total amount of secretions within the endotracheal tubes (weight gain), the protein content within the endotracheal tubes, and the increase in resistance to constant air flow. The structure of the airways was examined grossly and histologically. Three additional sheep were ventilated for 24 h with ITPV, and Evans Blue dye was added to the saline to assess the distribution of the infused saline. Results: There was significantly less mucus in endotracheal tubes of sheep ventilated with ITPV than with conventional ventilation, as shown by minimal weight gain (0.70 +/- 0.14 g vs. 2.44 +/- 0.81 g; P < 0.001), lower protein content (14.09 +/- 10.79 mg us. 294.99 +/- 153.06 mg; P < 0.001), and lower resistance to constant air flow (6.15 +/- 0.54 cm H2O.l(-1).s(-1) vs. 15.34 +/- 5.28 cm H(2)0.l(-1).s(-1); P < 0.001). Results of gross and histological examinations of the tracheas of animals in both groups were similar, and the tracheas were well preserved. More than 95% of the instilled saline was recovered during ITPV. Only traces of Evans Blue dye were found near the tip of the endotracheal tubes. Conclusions: Intratracheal pulmonary ventilation makes it possible to keep the endotracheal tubes of sheep ventilated for 3 days free of mucus without suctioning. C1 NHLBI,SECT PULM & CARDIAC ASSIST DEVICES,PULM CRIT CARE MED BRANCH,BETHESDA,MD 20892. NHLBI,PATHOL SECT,BETHESDA,MD 20892. NR 19 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 1997 VL 86 IS 6 BP 1367 EP 1374 DI 10.1097/00000542-199706000-00019 PG 8 WC Anesthesiology SC Anesthesiology GA XE806 UT WOS:A1997XE80600019 PM 9197307 ER PT J AU Senderowicz, AM Vitetta, E Headlee, D Ghetie, V Uhr, JW Figg, WD Lush, RM StetlerStevenson, M Kershaw, G Kingma, DW Jaffe, ES Sausville, EA AF Senderowicz, AM Vitetta, E Headlee, D Ghetie, V Uhr, JW Figg, WD Lush, RM StetlerStevenson, M Kershaw, G Kingma, DW Jaffe, ES Sausville, EA TI Complete sustained response of a refractory, post-transplantation, large B-cell lymphoma to an anti-CD22 immunotoxin SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID EPSTEIN-BARR-VIRUS; LYMPHOPROLIFERATIVE DISORDERS; ORGAN-TRANSPLANTATION; BONE-MARROW; PHASE-I; DISEASE; CLASSIFICATION; SITES C1 NCI,DEV THERAPEUT PROGRAM,NIH,ROCKVILLE,MD 20852. NCI,MED BRANCH,DIV CLIN SCI,NIH,ROCKVILLE,MD 20852. NCI,DIV CLIN SCI,PATHOL LAB,NIH,ROCKVILLE,MD 20852. UNIV TEXAS,SW MED CTR,CTR CANC IMMUNOBIOL,DALLAS,TX 75235. UNIV MASSACHUSETTS,MED CTR,DIV RENAL MED,WORCESTER,MA 01655. RI Figg Sr, William/M-2411-2016 FU NCI NIH HHS [CA28149, CA41081] NR 15 TC 46 Z9 47 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 1 PY 1997 VL 126 IS 11 BP 882 EP 885 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XA911 UT WOS:A1997XA91100005 PM 9163289 ER PT J AU Demirci, M Grill, S McShane, L Hallett, M AF Demirci, M Grill, S McShane, L Hallett, M TI A mismatch between kinesthetic and visual perception in Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID COROLLARY DISCHARGES; INTENTION TREMOR; MOVEMENT; BRADYKINESIA; RIGIDITY; LOOP; CUES AB Kinesthesia may be defective in patients with Parkinson's disease (PD), and this defect conceivably has a role in parkinsonian hypokinetic symptoms. In the present study, PD patients used kinesthetic perception to estimate the amplitude of passive angular displacements of the index finger about the metacarpophalangeal joint and to scale them as a percentage of a reference stimulus. The reference stimulus was either a standard kinesthetic stimulus preceding each test stimulus (task K) or a visual representation of the standard kinesthetic stimulus (task V). In task V, the PD patients' underestimation of the amplitudes of finger perturbations was significantly greater than that of normal subjects, but not for task K. PD patients' underestimation was also greater in task V than in task K; the difference between the underestimations was significantly greater than for normal subjects. These results suggest that, when kinesthesia is used to match a visual target, distances are perceived to be shorter by the PD patients. Assuming that visual perception is normal, kinesthesia is ''reduced' in PD patients. This reduced kinesthesia, when combined with the well-known reduced motor output and probably reduced corollary discharges, implies that the sensorimotor apparatus is ''set'' smaller in PD patients than in normal subjects. C1 NINCDS,NIH,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,MATH STAT SECT,BIOMETRY & FIELD STUDIES BRANCH,NIH,BETHESDA,MD 20892. RI Demirci, Mehmet/D-7081-2012 OI Demirci, Mehmet/0000-0002-7316-3877 NR 25 TC 128 Z9 129 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1997 VL 41 IS 6 BP 781 EP 788 DI 10.1002/ana.410410614 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XD559 UT WOS:A1997XD55900011 PM 9189039 ER PT J AU Capello, E Voskuhl, RR McFarland, HF Raine, CS AF Capello, E Voskuhl, RR McFarland, HF Raine, CS TI Multiple sclerosis: Re-expression of a developmental gene in chronic lesions correlates with remyelination SO ANNALS OF NEUROLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; CANDIDATE AUTOANTIGEN; HLA RESTRICTION; CDNA CLONING; SPINAL-CORD; EPITOPE; TRANSCRIPTS; EXON-2 AB Central nervous system tissue from multiple sclerosis and non-multiple sclerosis subjects was studied for the expression of exon 2 myelin basic protein gene products at the protein and message levels by immunocytochemistry and in situ hybridization, respectively. The exon 2-encoded protein sequence is normally expressed during development (myelination) within the 21 . 5- and 20 . 2-kd isoforms of myelin basic protein and is downregulated in the adult central nervous system where the 18 . 5- and 17 . 2-kd isoforms predominate, the latter devoid of exon 2 owing to alternative splicing. Exon 2 myelin basic protein gene products were readily demonstrable in multiple sclerosis samples, the highest levels correlating with remyelination in chronic lesions while normal adult central nervous system and non-multiple sclerosis material showed very low levels and fetal human central nervous system tissue (a positive control) showed high levels. Wk conclude that recapitulation of ontogenetic events during myelin repair accounts for the increased expression of the exon 2-encoded protein sequence in the adult central nervous system during multiple sclerosis, an event that might underly the previously observed T-cell activation to this protein sequence during relapses. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PATHOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10461. UNIV CALIF LOS ANGELES,REED NEUROL RES CTR,DEPT NEUROL,LOS ANGELES,CA 90024. NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. FU NINDS NIH HHS [NS 07098, NS 08952, NS 11920] NR 35 TC 52 Z9 55 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1997 VL 41 IS 6 BP 797 EP 805 DI 10.1002/ana.410410616 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XD559 UT WOS:A1997XD55900013 PM 9189041 ER PT J AU Bartholomew, C Cleghorn, F Jack, N Edwards, J Blattner, W AF Bartholomew, C Cleghorn, F Jack, N Edwards, J Blattner, W TI Human T-cell lymphotropic virus type I-associated facial nerve palsy in Trinidad and Tobago SO ANNALS OF NEUROLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; HTLV-I; BELLS-PALSY; ANTIBODIES; PARALYSIS; DISEASE AB To assess the association of the human T-cell lymphotropic virus type I (HTLV-I) and idiopathic facial nerve palsy of the lower motor neuron type, we studied 78 patients consecutively admitted to the Port of Spain General Hospital in Trinidad, the West Indies, with a confirmed diagnosis of idiopathic facial nerve palsy. Patients were compared with two control groups: a population-based group of persons 20 years and older and a hospital-based group of patients 15 to 84 years old admitted to the medical wards, Sixty-two patients were Trinidadians of African origin and 16 were Trinidadians of East Indian origin. None of the East Indian patients was HTLV-I antibody positive. Three Afro-Trinidadians were infected with human immunodeficiency virus type 1 and 1 was coinfected with this virus and HTLV-I. Of the remaining 58 Afro-Trinidadians, 12 (20.7%) were HTLV-I positive only. This rate was statistically higher than the HTLV-I seroprevalence in the Afro-Trinidadian general population (3.5%) and the hospital control group (5.6%). After age standardization, the HTLV-I prevalence for patients with facial nerve palsy remained significantly elevated, HTLV-I antibody assays should be performed on all patients with idiopathic facial nerve palsy of the lower motor neuron type who live in HTLV-I endemic areas or are migrants from these areas. C1 UNIV W INDIES,DEPT MED,PORT OF SPAIN,TRINID & TOBAGO. NCI,DIV CANC ETIOL,VIRAL EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. RP Bartholomew, C (reprint author), NCI,MED RES CTR,UWI,CAREC,7 QUEENS PK E,PORT OF SPAIN,TRINID & TOBAGO. NR 16 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1997 VL 41 IS 6 BP 806 EP 809 DI 10.1002/ana.410410617 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XD559 UT WOS:A1997XD55900014 PM 9189042 ER PT J AU Noviello, E Allievi, E Russo, P Parodi, S AF Noviello, E Allievi, E Russo, P Parodi, S TI Effects of Dex-Verapamil on Doxorubicin cytotoxicity in P388 murine leukemia cells SO ANTI-CANCER DRUG DESIGN LA English DT Article DE dex-verapamil; doxorubicin; reversing agent ID MEDIATED MULTIDRUG RESISTANCE; P-GLYCOPROTEIN; CROSS-RESISTANCE; CYTO-TOXICITY; TUMOR-CELLS; ATRIOVENTRICULAR-CONDUCTION; MONOCLONAL-ANTIBODIES; ADRIAMYCIN RESISTANCE; VINCA ALKALOIDS; IN-VIVO AB Resistance-modifying agents (RMAs) such as Verapamil have been proved to be effective in reversing multi-drug resistance (MDR) in many in vitro assays. In this study we have investigated the efficacy of Dex-Verapamil, the R-isomer of Verapamil, as a chemosensitizer in a murine leukemia cell line (P388) and in its resistant counterpart (P388/Dx) expressing a typical MDR phenotype. We have examined in vivo the effect of the co-administration of Dex-Verapamil and Doxorubicin in mice transplanted with P388 or P388/Dx cells. Mice treated with the combination of Doxorubicin plus RMA had a significant increase in survival rate as compared to controls; however, the effect was modest. On the contrary, in vitro Dex-Verapamil can enhance Doxorubicin cytotoxicity in P388/Dx cells with a much greater effect depending on the treatment scheme used, by increasing the intracellular content of drug. Taken together our data indicate that Dex-Verapamil can indeed increase the sensitivity to Doxorubicin in resistant cells, but the limited efficacy shown in vivo demonstrates that this phenomenon is strongly dependent on the treatment scheme used and on the maintenance of constantly elevated serum levels. C1 NATL CANC INST,DEPT EXPT ONCOL,GENOA,ITALY. RP Noviello, E (reprint author), ADV BIOTECHNOL CTR,TRANSGEN UNIT,LARGO ROSANNA BENZI 10,I-16132 GENOA,ITALY. NR 41 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0266-9536 J9 ANTI-CANCER DRUG DES JI Anti-Cancer Drug Des. PD JUN PY 1997 VL 12 IS 4 BP 261 EP 276 PG 16 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA XF447 UT WOS:A1997XF44700003 PM 9199659 ER PT J AU Tanaka, M Srinivas, RV Ueno, T Kavlick, MF Hui, FK Fridland, A Driscoll, JS Mitsuya, H AF Tanaka, M Srinivas, RV Ueno, T Kavlick, MF Hui, FK Fridland, A Driscoll, JS Mitsuya, H TI In vitro induction of human immunodeficiency virus type 1 variants resistant to 2'-beta-fluoro-2',3'-dideoxyadenosine SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; BLOOD MONONUCLEAR-CELLS; HIGH-LEVEL RESISTANCE; POL GENE-MUTATIONS; COMBINATION THERAPY; INVITRO SELECTION; IN-VITRO; ZIDOVUDINE; SENSITIVITY; DIDANOSINE AB 2'-beta-Fluoro-2',3'-dideoxyadenosine (F-ddA) is an acid-stable purine dideoxynucleoside analog active against a wide spectrum of human immunodeficiency virus type 1 (HIV-1) and HIV-2 strains in vitro. F-ddA is presently undergoing a phase I clinical trial at the National Cancer Institute. We induced HIV-1 variants resistant to F-ddA by exposing wild-type HIV-1 (HIV-1(LAI)) to increasing concentrations of F-ddA in vitro. After 18 passages, the virus was fourfold less sensitive to F-ddA than HIV-1(LAI). Sequence analyses of the passage 18 virus revealed changes in three amino acids in the reverse transcriptase (RT)-encoding region of the pol gene: P to S at codon 119 (P119S; present in 3 of 13 and 28 of 28 molecular clones before and after F-ddA exposure, respectively), V179D (0 of 13 and 9 of 28, respectively), and L214F (9 of 13 and 28 of 28, respectively). Drug sensitivity assays using recombinant infectious clones confirmed that P119S was directly responsible for the reduced sensitivity of HIV-1 to F-ddA. Various infectious clones with single or multiple amino acid substitutions conferring viral resistance against nucleoside RT inhibitors, including HIV-1 variants with multidideoxynucleoside resistance, were generally sensitive to F-ddA. The moderate level of resistance of HIV-1 to F-ddA, together with the lack of conferment of significant cross-resistance by the F-ddA-associated amino acid substitutions, warrants further investigation of F-ddA as a potential antiviral agent for use in treatment of HIV-1 infection. C1 NCI, MED BRANCH, EXPT RETROVIROL SECT, DIV CLIN SCI, BETHESDA, MD 20892 USA. NCI, DIV BASIC SCI, MED CHEM LAB, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DEPT INFECT DIS, MEMPHIS, TN 38101 USA. RI Ueno, Takamasa/F-5788-2013 OI Ueno, Takamasa/0000-0003-4852-4236 FU NCI NIH HHS [P30-CA21765]; NIAID NIH HHS [R01-AI27652-13] NR 39 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1997 VL 41 IS 6 BP 1313 EP 1318 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA XB712 UT WOS:A1997XB71200019 PM 9174190 ER PT J AU Takle, GB Thierry, AR Flynn, SM Peng, B White, L Devonish, W Galbraith, RA Goldberg, AR George, ST AF Takle, GB Thierry, AR Flynn, SM Peng, B White, L Devonish, W Galbraith, RA Goldberg, AR George, ST TI Delivery of oligoribonucleotides to human hepatoma cells using cationic lipid particles conjugated to ferric protoporphyrin IX (heme) SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article ID ANTISENSE OLIGONUCLEOTIDES; GENE-EXPRESSION; ADULT MICE; BINDING; LIPOSOMES; DNA; RNA; PROTEIN; RAT; RECEPTOR AB The receptor-ligand interaction between hepatocyte heme receptors and heme was evaluated as a basis for developing a targeted cationic lipid delivery reagent for nucleic acids. Heme (ferric protoporphyrin IX) was conjugated to the aminolipid dioleoyl phosphatidylethanolamine (DOPE) and used to form cationic lipid particles with dioleoyl trimethylammonium propane (DOTAP). These lipids particles (DDH) protect oligoribonucleotides from degradation in human serum and increase oligoribonucleotide uptake into 2.2.15 human heptoma cells (to a level of 50-60 ng oligo/10(4) cells) when compared with the same lipid particles (DD) prepared identically without heme. The DDH heme level that was optimal for oligoribonucleotide delivery was also optimal for maximum expression of plasmid-encoded luciferase. The enhancing effect of heme was evident only at net particle negative charge, Fluorescence microscopy showed that DDH delivered oligoribonucleotides into both the 2.2.15 cell cytoplasm and nucleus. DDH may thus he a potentially useful delivery vehicle for oligonucleotide-based therapeutics and transgenes, appropriate for use in such liver diseases as viral hepatitis, hepatoma, and hypercholesterolemia. C1 NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV VERMONT,COLL MED,BURLINGTON,VT 05401. RP Takle, GB (reprint author), INNOVIR LABS INC,510 E 73RD ST,NEW YORK,NY 10021, USA. RI thierry, alain/F-9492-2014 NR 40 TC 19 Z9 19 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD JUN PY 1997 VL 7 IS 3 BP 177 EP 185 DI 10.1089/oli.1.1997.7.177 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA XG514 UT WOS:A1997XG51400006 PM 9212908 ER PT J AU Torrence, PF Xiao, W Li, GY Cramer, H Player, MR Silverman, RH AF Torrence, PF Xiao, W Li, GY Cramer, H Player, MR Silverman, RH TI Recruiting the 2-5A system for antisense therapeutics SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article; Proceedings Paper CT 1st NIH Symposium on Therapeutic Oligonucleotides CY DEC 06, 1996 CL NIH, BETHESDA, MD SP NIH Interinst Therapeut Oligonucleotide Interest Grp HO NIH ID RNA TARGET; CHIMERAS C1 CLEVELAND CLIN FDN,RES INST,DEPT CANC BIOL,CLEVELAND,OH 44195. RP Torrence, PF (reprint author), NIDDKD,SECT BIOMED CHEM,MED CHEM LAB,NIH,BETHESDA,MD 20892, USA. NR 7 TC 27 Z9 28 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD JUN PY 1997 VL 7 IS 3 BP 203 EP 206 DI 10.1089/oli.1.1997.7.203 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA XG514 UT WOS:A1997XG51400010 PM 9212911 ER PT J AU ChoChung, YS Nesterova, M Kondrashin, A Noguchi, K Srivastava, R Pepe, S AF ChoChung, YS Nesterova, M Kondrashin, A Noguchi, K Srivastava, R Pepe, S TI Antisense protein kinase A: A single-gene-based therapeutic approach SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article; Proceedings Paper CT 1st NIH Symposium on Therapeutic Oligonucleotides CY DEC 06, 1996 CL NIH, BETHESDA, MD SP NIH Interinst Therapeut Oligonucleotide Interest Grp HO NIH ID RI-ALPHA-SUBUNIT; REGULATORY SUBUNIT; GROWTH-INHIBITION; HL-60 LEUKEMIA; CELL-CYCLE; DIFFERENTIATION; OLIGODEOXYNUCLEOTIDE; MALIGNANCY; ANALOGS RP ChoChung, YS (reprint author), NCI,CELLULAR BIOCHEM SECT,TUMOR IMMUNOL & BIOL LAB,NIH,BLDG 10,ROOM 5B05,BETHESDA,MD 20892, USA. NR 20 TC 34 Z9 34 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD JUN PY 1997 VL 7 IS 3 BP 217 EP 223 DI 10.1089/oli.1.1997.7.217 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA XG514 UT WOS:A1997XG51400013 PM 9212914 ER PT J AU Bergan, RC AF Bergan, RC TI Ex vivo bone marrow purging with oligonucleotides SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article; Proceedings Paper CT 1st NIH Symposium on Therapeutic Oligonucleotides CY DEC 06, 1996 CL NIH, BETHESDA, MD SP NIH Interinst Therapeut Oligonucleotide Interest Grp HO NIH ID INTRACELLULAR TRAFFICKING; OLIGODEOXYNUCLEOTIDES; INHIBITION; CELLS; BINDING RP Bergan, RC (reprint author), NCI,DEPT CELL & CANC BIOL,MED BRANCH,NIH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD JUN PY 1997 VL 7 IS 3 BP 251 EP 255 DI 10.1089/oli.1.1997.7.251 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA XG514 UT WOS:A1997XG51400019 PM 9212920 ER PT J AU Ramachandran, U Peterkofsky, B AF Ramachandran, U Peterkofsky, B TI Aberrant O-glycosylation in the collagenous domain of pro alpha 2(I) procollagen subunits synthesized by chemically transformed hamster fibroblasts SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE O-glycosylation; collagen; transformation; protein secretion ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; BREFELDIN-A; MOLECULAR-CLONING; I COLLAGEN; UDP-GALNAC; PROTEINS; SPECIFICITY; GENE; LOCALIZATION; EXPRESSION AB Chemically transformed Syrian hamster embryo fibroblasts (NQT-SHE) do not synthesize the pro alpha 1(I) subunit of type I collagen, but they secrete two forms of the pro alpha 2(I) subunit (N33 and N50) with abnormal posttranslational modifications localized in the alpha 2CB3,5 cyanogen bromide peptide of the collagenous domain (B. Peterkofsky and W. Prather (1992) J. Biol. Chem. 267 5388-5395). Isoelectric focusing and treatment of the modified chains with glycosidases and biotinylated Jacalin lectin identified the modifications as Gal beta 1,3-GalNAc-O-Ser/Thr with or without a terminal sialic acid in an alpha 2,6 linkage. Unhydroxylated N33 alpha-chains also reacted with Jacalin, comfirming that the abnormal modification was O-glycosylation and not hyperhydroxylation of proline or lysine, Cells were treated with benzyl GalNAc, a competitive inhibitor of galactosyl transferase that prevents addition of Gal tee GalNAc-O-Ser/Thr and thus blocks elongation of O-glycosyl chains, Treated cells secreted pro alpha 2(l) chains containing GalNAc-O-Ser/Thr but no galactose or sialic acid, which suggested that Gal addition takes place before sialylation. Treatment of NQT-SHE cells with monensin and brefeldin A inhibited secretion and led to intracellular accumulation of pro alpha 2(I) chains that contained only GalNAc. Therefore, it appears that GalNAc addition to pro alpha 2(I) chains in NQT-SHE cells occurs in the cis-Gogli, while sialic acid and galactose are added in the trans-Golgi network. The pro alpha 2(I) chains produced by NQT-SHE cells most likely are modified because they are in the denatured state, and thus potential O-glycosylation sites become available that would not be exposed in normal triple helical procollagen. (C) 1997 Academic Press. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 44 TC 5 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 1 PY 1997 VL 342 IS 1 BP 29 EP 37 DI 10.1006/abbi.1997.0101 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XA555 UT WOS:A1997XA55500005 PM 9185611 ER PT J AU Iwata, F Patronas, NJ Caruso, RC Podgor, MJ Remaley, NA Kupfer, C KaiserKupfer, MI AF Iwata, F Patronas, NJ Caruso, RC Podgor, MJ Remaley, NA Kupfer, C KaiserKupfer, MI TI Association of visual field, cup-disc ratio, and magnetic resonance imaging of optic chiasm SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID GLAUCOMA AB Objective: To assess the association of visual field, vertical cup-disc (VC/D) ratio, and vertical height of optic chiasm. Design: Case series. Setting: Outpatient eye clinic. Patients: Eighteen patients with low, normal, or elevated intraocular pressure, with or without visual field defects. Intervention: Measurement of visual field, VC/D ratio, and vertical height of optic chiasm. Main Outcome Measures: Association between VC/D ratio and visual field defects compared with association between vertical height of optic chiasm and visual field defects. Results: Visual field defects were graded as 0, 1 to 10, and 11 to 20 (from least to most severe). Group mean VC/D ratios were 0.47 (0), 0.55 (1-10), and 0.69 (11-20) for right eyes and 0.48 (0), 0.57 (1-10), and 0.75 (11-20) for left eyes. The significance level for trend was P = .02 for right eyes and P = .006 for left eyes. Group mean chiasm heights were 3.5 (0), 2.9 (1-10), and 2.2 (11-20) mm for right eyes and 3.5 (0), 2.8 (1-10), and 2.2 (11-20) mm for left eyes. The significance level for trend was P < .001 for right eyes and P = .002 for left eyes. To assess the simultaneous effects of VC/D ratio and chiasm height on the visual field defects groups, we used ordinal logistic regression models. Models with both variables implied that chiasm height was a stronger predictor of visual field defects group than VC/D ratio (for right eyes, P = .04 [VC/D ratio], P = .001 [chiasm height]; for left eyes, P = .11 [VC/D ratio], P = .005 [chiasm height]). Conclusions: When chiasm and VC/D ratio were analyzed in the same model, chiasm height was a stronger predictor of visual field defects. In advanced visual field defects, the optic chiasm is atrophic. C1 NIH,CTR CLIN,BETHESDA,MD 20892. RP Iwata, F (reprint author), NCI,NIH,BETHESDA,MD 20892, USA. NR 17 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 1997 VL 115 IS 6 BP 729 EP 732 PG 4 WC Ophthalmology SC Ophthalmology GA XD994 UT WOS:A1997XD99400006 PM 9194723 ER PT J AU Fletcher, AE Ellwein, LB Selvaraj, S Vijaykumar, V Rahmathullah, R Thulasiraj, RD AF Fletcher, AE Ellwein, LB Selvaraj, S Vijaykumar, V Rahmathullah, R Thulasiraj, RD TI Measurements of vision function and quality of life in patients with cataracts in southern India - Report of instrument development SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OF-LIFE; VISUAL FUNCTION; SURGERY; OUTCOMES; ACUITY AB Objective: To develop and validate vision function (VF) and quality of life (QOL) instruments inpatients with cataracts in the context of large volume surgery in a developing country. Materials and Methods: The instruments were developed using a consensus approach. One hundred patients who were undergoing cataract surgery at Aravind Eye Hospital, Madurai, India, were interviewed preoperatively and 3 and 12 months postoperatively. Standard clinical procedures were followed, including measurement of visual acuity. Between-interviewer reproducibility was measured by repeated administration of the preoperative questionnaire. Within-interviewer reproducibility was measured preoperatively in a separate study of 50 patients. Results: Preoperative scores from the VF and QOL instruments were significantly associated with visual acuity (r = 0.4). Internal reliability (Cronbach alpha) was greater than .9. Both instruments showed large changes after surgery, with effect sizes of 3 or greater for most VF scales (range, 1.8-3.7) and 1 or greater for QOL scales (range, 1.0-2.2). Changes in visual acuity after surgery were correlated with changes in the VF (r = 0.44) and QOL (r = 0.41) scale scores. Between interviewer reproducibility was acceptable (total VF scale, Spearman r = 0.7; total QOL scale, r = 0.74). The kappa values were lower for within-interviewer reproducibility. Conclusions: The study provided strong evidence for the validity, reproducibility, and responsiveness of the instruments, and for the feasibility of using them in the setting of a large volume of cataract surgery in a developing country. C1 NEI,NIH,BETHESDA,MD 20892. ARAVIND EYE HOSP,MADURAI,TAMIL NADU,INDIA. RP Fletcher, AE (reprint author), UNIV LONDON LONDON SCH HYG & TROP MED,DEPT EPIDEMIOL & POPULAT SCI,KEPPEL ST,LONDON WC1E 7HT,ENGLAND. NR 17 TC 79 Z9 91 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 1997 VL 115 IS 6 BP 767 EP 774 PG 8 WC Ophthalmology SC Ophthalmology GA XD994 UT WOS:A1997XD99400013 PM 9194729 ER PT J AU Mojcik, CF Shevach, EM AF Mojcik, CF Shevach, EM TI Adhesion molecules - A rheumatologic perspective SO ARTHRITIS AND RHEUMATISM LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; SYNOVIAL-FLUID LYMPHOCYTES; SOLUBLE E-SELECTIN; VASCULAR ENDOTHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; LEUKOCYTE ADHESION; T-CELLS; MONOCLONAL-ANTIBODY; IN-VIVO; PERIPHERAL-BLOOD C1 NIAID,NIH,BETHESDA,MD 20892. RP Mojcik, CF (reprint author), BAYER PHARMACEUT,400 MORGAN LANE,W HAVEN,CT 06516, USA. NR 164 TC 120 Z9 121 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1997 VL 40 IS 6 BP 991 EP 1004 DI 10.1002/art.1780400602 PG 14 WC Rheumatology SC Rheumatology GA XC376 UT WOS:A1997XC37600001 PM 9182908 ER PT J AU Natkunam, Y ElenitobaJohnson, KS Kingma, DW Kamel, OW AF Natkunam, Y ElenitobaJohnson, KS Kingma, DW Kamel, OW TI Epstein-Barr virus strain type and latent membrane protein 1 gene deletions in lymphomas in patients with rheumatic diseases SO ARTHRITIS AND RHEUMATISM LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NASOPHARYNGEAL CARCINOMA; LYMPHOPROLIFERATIVE DISORDERS; HODGKINS-DISEASE; LMP1 ONCOGENE; CELLS; METHOTREXATE; ARTHRITIS; MEMBRANE-PROTEIN-1; IMMUNOSUPPRESSION AB Objective. Recent studies have shown that immunomodulatory therapy for the treatment of rheumatic diseases can be associated with the development of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders. The present study was undertaken to determine the strain type of EBV in lymphoproliferative disorders that occur in patients with rheumatic disease and to investigate EBV latent membrane protein 1 (LMP-1) gene deletions that occur in these lymphoproliferative disorders. Methods. Ten EBV-associated lymphoid neoplasms in patients with rheumatoid arthritis or dermatomyositis were analysed by polymerase chain reaction to determine EBV strain type and to investigate for the presence of a previously characterized 30-basepair deletion in the LMP-1 gene. Results. The results indicated that lymphoproliferative disorders in these patients can harbor EBV strain type A or B, with a predominance of type A infection (80%). It was also shown that both wild-type and mutated LMP-1 genes can be found in these neoplasms, with the deleted form of the LMP-1 gene occurring in one-third of cases in this series. Conclusion. LMP-1 deletions associated with certain aggressive lymphoid neoplasms are not required for the genesis of lymphoproliferative disorders in patients with rheumatic disease, The relative frequencies of type A and type B EBV strains in these lymphoproliferative disorders show similarities to the frequencies in patients with post-solid organ transplantation immunosuppression-associated lymphoproliferative disorders. C1 STANFORD UNIV,SCH MED,STANFORD,CA. NCI,BETHESDA,MD 20892. NR 30 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1997 VL 40 IS 6 BP 1152 EP 1156 DI 10.1002/art.1780400621 PG 5 WC Rheumatology SC Rheumatology GA XC376 UT WOS:A1997XC37600020 PM 9182927 ER PT J AU Barrett, AJ vanRhee, F AF Barrett, AJ vanRhee, F TI Graft-versus-leukaemia SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Article DE chronic myeloid leukaemia; graft-versus-leukaemia; graft-versus-host disease; leukaemic relapse; adoptive immunotherapy ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; T-CELL DEPLETION; MINOR HISTOCOMPATIBILITY ANTIGENS; MINIMAL RESIDUAL DISEASE; POLYMERASE CHAIN-REACTION; CYTOTOXIC LYMPHOCYTES-T; HOST-DISEASE; ADOPTIVE IMMUNOTHERAPY AB The high relapse rate after T-cell depleted bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML) and the ability of donor lymphocyte transfusions to induce stable remission in patients relapsing after BMT has emphasized the importance of allo-reacting donor T-lymphocytes in the graft-versus-leukaemia (GVL) effect in this disease. The mechanisms underlying the GVL response and its relationship with graft-versus-host disease are becoming better defined. There is accumulating evidence that the CD4(+) T-cell plays a central role in the GVL response. The prominent role of GVL in the cure of CML after BMT may be associated with the fact that CML cells are strongly immunogenic. New transplant strategies are being devised to separate GVL from graft-versus-host reactions. Future developments focus on the identification of leukaemia-specific antigens and the amplification of T-cell responses against them. RP Barrett, AJ (reprint author), NHLBI,BONE MARROW TRANSPLANT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 95 TC 23 Z9 24 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD JUN PY 1997 VL 10 IS 2 BP 337 EP 355 PG 19 WC Hematology SC Hematology GA YB451 UT WOS:A1997YB45100011 PM 9376668 ER PT J AU Bornstein, MH AF Bornstein, MH TI Selective vision SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID COLOR AB The physics of color and the psychology of color naming are not isomorphic. Physically, the spectrum is continuous with regard to wavelength - one point in the spectrum differs from another only by the amount of wavelength difference. Psychologically, hue is categorical - colors change qualitatively from one wavelength region to another. The psychologically, hue is categorical - colors change qualitatively from one wavelength region to another. The psychological characterization of hue that characterizes color vision has been revealed in a series of modern psychophysical studies with human adults and infants and with various infrahuman species, including vertebrates and invertebrates. These biopsychological data supplant an older psycholinguistic and anthropological literature that posited that language and culture alone influence perceptual processes; language and culture may modify color naming beyond basic categorizations. RP Bornstein, MH (reprint author), NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892, USA. NR 9 TC 4 Z9 4 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 1997 VL 20 IS 2 BP 180 EP & PG 0 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA YJ788 UT WOS:A1997YJ78800003 ER PT J AU McDonald, MP Wenk, GL Crawley, JN AF McDonald, MP Wenk, GL Crawley, JN TI Analysis of galanin and the galanin antagonist M40 on delayed non-matching-to-position performance in rats lesioned with the cholinergic immunotoxin (192)IgG-saporin SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID CENTRAL NERVOUS-SYSTEM; MEDIAL SEPTAL AREA; 192 IGG-SAPORIN; BASAL FOREBRAIN; ALZHEIMERS-DISEASE; NUCLEUS BASALIS; VENTRAL HIPPOCAMPUS; SENILE DEMENTIA; WORKING-MEMORY; NGF RECEPTOR AB Galanin is a 29-amino-acid neuropeptide that is overexpressed in Alzheimer's disease (AD) and impairs performance on rodent learning and memory tasks. M40, a peptidergic galanin receptor ligand, blocks galanin-induced impairments on delayed non-matching-to-position (DNMTP). The present experiments used the (192)IgG-saporin lesion model of AD to evaluate the actions of galanin and M40 on DNMTP when cholinergic transmission was reduced. Hippocampal choline acetyltransferase levels were correlated with DNMTP choice accuracy in lesioned rats. Intracerebroventricular (icy) galanin reduced choice accuracy in both the lesioned and sham groups. M40 alone, either icy or intrahippocampal, did not affect-choice accuracy in either group. These results suggest that excess galanin can produce further deficits in DNMTP performance in a lesion model of AD, but blocking endogenous galanin is not sufficient alone to improve performance in lesioned rats. C1 UNIV ARIZONA,DIV NEURAL SYST MEMORY & AGING,TUCSON,AZ 85721. RP McDonald, MP (reprint author), NIMH,SECT BEHAV NEUROPHARMACOL,EXPT THERAPEUT BRANCH,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. FU NIA NIH HHS [R01 AG10546] NR 75 TC 32 Z9 33 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD JUN PY 1997 VL 111 IS 3 BP 552 EP 563 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA XC762 UT WOS:A1997XC76200010 PM 9189270 ER PT J AU Mohr, E Claus, JJ Brouwers, P AF Mohr, E Claus, JJ Brouwers, P TI Basal ganglia disease and visuospatial cognition: Are there disease-specific impairments? SO BEHAVIOURAL NEUROLOGY LA English DT Article DE basal ganglia disease; dementia; Huntington's disease; Parkinson's disease; visuospatial impairment ID HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; MENTAL ROTATION; BLOOD-FLOW; MEMORY; DEMENTIAS; DEFICITS; PROFILE AB Visuospatial deficits in basal ganglia disease may be a non-specific function of the severity of dementia or they could reflect disease-specific impairments. To examine this question, Huntington (HD) patients, demented and non-demented Parkinson (PD) patients and healthy controls were examined with neuropsychological tests emphasising visuospatial abilities. Global intellectual function and general visuospatial cognition were less efficient in the two demented patient groups relative to both controls and non-demented PD patients and they did not differ significantly between non-demented Parkinsonians and controls nor between demented PD and HD patients. However, HD patients but not demented PD patients were impaired on a test of person-centred spatial judgement compared to non-demented subjects while demented PD patients scored significantly lower than HD patients on a test of field independence. Factor analysis yielded a factor reflecting general visuospatial processing capacity which discriminated between demented and non-demented PD patients but not between demented PD and HD patients. A unique factor associated with the manipulation of person-centred space discriminated between demented PD and HD patients. These results suggest general visuospatial processing is impaired as a non-specific function of dementia presence in HD and PD. Abnormalities in circumscribed aspects of visuospatial function, on the other hand, may differentiate between HD and PD, suggesting differential involvement of the basal ganglia in the respective illnesses. C1 ELISABETH BRUYERE HLTH CTR,OTTAWA,ON K1N 5C8,CANADA. UNIV OTTAWA,OTTAWA CIVIC HOSP,DIV NEUROL,OTTAWA,ON K1N 6N5,CANADA. UNIV AMSTERDAM,ACAD MED CTR,DEPT NEUROL,NL-1105 AZ AMSTERDAM,NETHERLANDS. NCI,DIV CLIN SCI,NIH,BETHESDA,MD 20892. NR 36 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PD SUM PY 1997 VL 10 IS 2-3 BP 67 EP 75 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA XZ876 UT WOS:A1997XZ87600004 PM 24486746 ER PT J AU Randazzo, PA AF Randazzo, PA TI Resolution of two ADP-ribosylation factor 1 GTPase-activating proteins from rat liver SO BIOCHEMICAL JOURNAL LA English DT Article ID COP-COATED VESICLES; GOLGI MEMBRANES; REGULATORY COMPONENT; GUANINE-NUCLEOTIDE; ADENYLATE-CYCLASE; BINDING PROTEIN; PHOSPHOLIPASE-D; CHOLERA-TOXIN; BREFELDIN-A; FACTOR ARF AB ADP-ribosylation factor 1 (ARF1) is a 21 kDa GTP-binding protein that regulates multiple steps in membrane traffic. Here, two ARF1 GTPase-activating proteins (GAPs) from rat liver were resolved. The GAPs were antigenically distinct. One reacted with a polyclonal antibody raised against the GAP catalytic peptide previously purified by Makler et al. [Makler, Cukierman, Rotman, Admon and Cassel (1995) J. Biol. Chem. 270, 5232-5237], and here is referred to as GAP1. The other GAP (GAP2) did not react with the antibody. These GAPs differed in phospholipid dependencies. GAP1 was activated 3-7-fold by the acid phospholipids phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidic acid (PA) and phosphatidylserine (PS). In contrast, GAP2 was stimulated 20-40-fold by PIP2. PA and PS had no effect by themselves but PA increased GAP2 activity in the presence of PIP2. The GAPs were otherwise similar in activity. In the presence of phosphoinositides, the K-m of GAP1 for ARF1-GTP was estimated to be 8.1 +/- 1.6 mu M and the dissociation constant for ARF1-guanosine 5',3-O-(thio)triphosphate (GTP[SI) was 7.4 +/- 2.2 mu M. GAP2 was similar with a K-m for ARF1-GTP of 5.4 +/- 1.2 mu M and a dissociation constant for ARF1-GTP[S] of 4.8 +/- 0.3 mu M. Similarly, no differences were found in substrate preferences. Both GAP1 and GAP2 used ARF1 and ARF5 as substrates but not ARF6 or ARF-like protein-2. The potential role of multiple ARF GAPs in the independent regulation of ARF at specific steps in membrane traffic is discussed. RP Randazzo, PA (reprint author), NATL CANC INST, DIV BASIC SCI,BIOL CHEM LAB,BLDG 37,RM 5D-02, 37 CONVENT DR MSC 4255, BETHESDA, MD 20892 USA. NR 44 TC 32 Z9 32 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 1997 VL 324 BP 413 EP 419 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XD377 UT WOS:A1997XD37700009 PM 9182698 ER PT J AU Kim, HT Pennie, WD Sun, Y Colburn, NH AF Kim, HT Pennie, WD Sun, Y Colburn, NH TI Differential functional significance of AP-1 binding sites in the promoter of the gene encoding mouse tissue inhibitor of metalloproteinases-3 SO BIOCHEMICAL JOURNAL LA English DT Article ID HUMAN TIMP-3; MOLECULAR-CLONING; EPIDERMAL-CELLS; MESSENGER-RNA; JB6 CELLS; EXPRESSION; FAMILY; MEMBER; TRANSFORMATION; TRANSCRIPTION AB Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular-matrix-associated protein that suppresses tumorigenicity or invasion in several model systems. We have identified, by in vitro footprinting, six AP-1 (activator protein-1) or AP-1-like binding sites in the mouse TIMP-3 promoter that bind purified c-Jun homodimers. Electrophoretic mobility shift assays revealed that the non-consensus fifth AP-1 binding site (AP-720; nt -720 to -714) had the strongest binding activity for recombinant c-Jun protein, and that the fourth binding site (AP-763; nt -763 to -754) and AP-720 showed strong binding activity for cellular nuclear proteins. Antibody supershift and blocking experiments suggest that AP-720, but not AP-763, binds authentic AP-1 components. Transient transfection reporter assays of deletion constructs showed that the region spanning AP-720 has the highest transcriptional activity, and that sequences 5' to this region (nt -2846 to -747) may contain negative regulatory elements. The deletion construct containing about 500 nt 5' to the transcriptional start, but no AP-1 sites, showed lower but significant activity, suggesting both AP-1-dependent and -independent regulation of the mouse TIMP-3 promoter. Mutational inactivation of AP-720 abolished the activity increment that distinguished the reporter construct containing both AP-720 and sixth AP-1 binding site (AP-617; nt -617 to -611) from that containing only AP-617. In summary, we report here that both AP-1 and non-AP-1 elements contribute to activity, with the non-consensus AP-1 site at -720 showing the greatest functional significance among the AP-1 sites. C1 WARNER LAMBERT PARKE DAVIS, PARKE DAVIS PHARMACEUT RES, DEPT MOL BIOL, ANN ARBOR, MI 48105 USA. RP Kim, HT (reprint author), NCI, GENE REGULAT SECT, LAB BIOCHEM PHYSIOL, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NR 27 TC 19 Z9 19 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 1997 VL 324 BP 547 EP 553 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XD377 UT WOS:A1997XD37700028 PM 9182717 ER PT J AU Herning, RI Guo, XY Better, WE Weinhold, LL Lange, WR Cadet, JL Gorelick, DA AF Herning, RI Guo, XY Better, WE Weinhold, LL Lange, WR Cadet, JL Gorelick, DA TI Neurophysiological signs of cocaine dependence: Increased electroencephalogram beta during withdrawal SO BIOLOGICAL PSYCHIATRY LA English DT Article DE cocaine dependence; electroencephalogram; beta power; cocaine withdrawal ID OLDER ADULTS; EEG; ABUSERS; ABSTINENCE; PERFUSION; TECHNETIUM-99M-HMPAO; USERS; SPECT AB To determine whether a central nervous system marker of cocaine dependence might exist, the resting electroencephalogram (EEG) of 33 drug-free, cocaine-dependent men (DSM-III-R criteria) was compared with two control groups [nondrug group (n=10) and drug group who abused drugs, bur were not cocaine dependent (n=20)]. The EEC was recordedfrom eight sites after about 10 days of monitored abstinence (range 4-15 days) on a closed research ward for the drug-using individuals. The EEG was recorded for the nondrug control group as outpatients. The drug history was determined by the drug history questionnaire and a medical screening interview. The percent of EEG beta activity for the cocaine-dependent subjects was greater than that of both control groups (p <.05) as well as a normative database (HZI. Tarrytown, NYJ. The percent of EEG beta in frontal and central areas of the cocaine-dependent individuals was correlated with the frequency of cocaine use during the last 30 days, High levels of EEG beta may be a neurophysiological withdrawal sign in cocaine-dependent men. (C) 1997 Society of Biological Psychiatry. RP Herning, RI (reprint author), NATL INST DRUG ABUSE,MOL NEUROPSYCHIAT SECT,NEUROSCI BRANCH,DIV INTRAMURAL RES,POB 5180,BALTIMORE,MD 21224, USA. NR 39 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 1997 VL 41 IS 11 BP 1087 EP 1094 DI 10.1016/S0006-3223(96)00258-2 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WY482 UT WOS:A1997WY48200002 PM 9146819 ER PT J AU Lin, DY Feuer, EJ Etzioni, R Wax, Y AF Lin, DY Feuer, EJ Etzioni, R Wax, Y TI Estimating medical costs from incomplete follow-up data SO BIOMETRICS LA English DT Article DE censoring; cost analysis; economic evaluation; health services; medical care; missing data; resource utilization; survival analysis; treatment cost AB Estimation of the average total cost for treating patients with a particular disease is often complicated by the fact that the survival times are censored on some study subjects and their subsequent costs are unknown. The naive sample average of the observed costs from all study subjects or from the uncensored cases only can be severely biased, and the standard survival analysis techniques are not applicable. To minimize the bias induced by censoring, we partition the entire time period of interest into a number of small intervals and estimate the average total cost either by the sum of the Kaplan-Meier estimator for the probability of dying in each interval multiplied by the sample mean of the total costs from the observed deaths in that interval or by the sum of the Kaplan-Meier estimator for the probability of being alive at the start of each interval multiplied by an appropriate estimator for the average cost over the interval conditional on surviving to the start of the interval; The resultant estimators are consistent if censoring occurs solely at the boundaries of the intervals. In addition, the estimators are asymptotically normal with easily estimated variances. Extensive numerical studies show that the asymptotic approximations are adequate for practical use and the biases of the proposed estimators are small even when censoring may occur in the interiors of the intervals. An ovarian cancer study is provided. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. HEBREW UNIV JERUSALEM,DEPT STAT,IL-91905 JERUSALEM,ISRAEL. RP Lin, DY (reprint author), UNIV WASHINGTON,DEPT BIOSTAT,BOX 357232,SEATTLE,WA 98195, USA. FU NCI NIH HHS [N0ICN-05230]; NIAID NIH HHS [R01 AI-291968]; NIGMS NIH HHS [R29 GM-47845] NR 11 TC 252 Z9 255 U1 1 U2 12 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1997 VL 53 IS 2 BP 419 EP 434 DI 10.2307/2533947 PG 16 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA XE965 UT WOS:A1997XE96500003 PM 9192444 ER PT J AU Simon, R Freedman, LS AF Simon, R Freedman, LS TI Bayesian design and analysis of two x two factorial clinical trials SO BIOMETRICS LA English DT Article DE Bayesian analysis; clinical trials; factorial design ID UNITED-STATES PHYSICIANS; RANDOMIZED TRIAL AB The 2 x 2 factorial design has been advocated for improving the efficiency of clinical trials. Most such trials are designed on the assumption that there is no interaction between the levels of the factors and outcome. This assumption is often problematic, however, because interactions are usually possible in clinical trials and the sample sizes often used provide little power in testing for interactions. We consider the use of Bayesian methods for the design and analysis of 2 x 2 factorial clinical trials. This approach avoids the need to dichotomize one's assumptions that interactions either do or do not exist and provides a flexible approach to the design and analysis of such clinical trials. Exact results are developed for balanced factorial designs with normal response. Approximations are then presented for factorial designs based on the logistic model for binary response or the proportional hazards model for time-to-event data. The resulting approximate posterior distributions are normal and hence no extensive computations are required. Suggestions for specification of prior distributions are presented. C1 NCI,BIOMETRY BRANCH,BETHESDA,MD 20852. RP Simon, R (reprint author), NCI,BIOMETR RES BRANCH,BETHESDA,MD 20852, USA. NR 13 TC 16 Z9 17 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1997 VL 53 IS 2 BP 456 EP 464 DI 10.2307/2533949 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA XE965 UT WOS:A1997XE96500005 PM 9192445 ER PT J AU Xu, JL Prorok, PC AF Xu, JL Prorok, PC TI Nonparametric estimation of solid cancer size at metastasis and probability of presenting with metastasis at detection SO BIOMETRICS LA English DT Article DE distribution; lung cancer; metastases; nonparametric estimation; size-dependent probability AB Two probabilistic characterizations of the relationship between the size of primary cancers and the occurrence of metastases are considered. The first is the distribution of tumor size at the point of metastatic transition, while the second is the probability that detectable metastases are present when cancer comes to medical attention. We show that the general model for this problem developed by Kimmel and Flehinger (1991, Biometrics 47, 987-1004) is unidentifiable. That is, the quantities to be estimated cannot be uniquely determined by the available information. An identifiable model that includes one limiting model of Kimmel and Flehinger (1991) as a special case is developed by using odds ratios. Under the new model, both quantities of interest are estimated by using a nonparametric maximum likelihood approach. The results are applied to two lung cancer data sets. C1 NCI,BIOMETRY BRANCH,EPN,BETHESDA,MD 20892. RP Xu, JL (reprint author), UNIV HOUSTON,DEPT MATH,HOUSTON,TX 77204, USA. NR 10 TC 7 Z9 7 U1 0 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1997 VL 53 IS 2 BP 579 EP 591 DI 10.2307/2533959 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA XE965 UT WOS:A1997XE96500015 PM 9192453 ER PT J AU McShane, LM Albert, PS Palmatier, MA AF McShane, LM Albert, PS Palmatier, MA TI A latent process regression model for spatially correlated count data SO BIOMETRICS LA English DT Article DE count data; generalised estimating equations; latent process regression; spatial correlation ID LONGITUDINAL DATA-ANALYSIS; STATISTICAL-ANALYSIS; BINARY REGRESSION; TIME-SERIES AB This paper proposes a regression model for spatially correlated count data that generalizes the work of Zeger (1988, Biometrika 75, 621-629) developed in a time-series setting. In this approach, spatial correlation is introduced through a latent process, and the marginal mean function may contain spatial trends and covariates. Generalized estimating equations are used to estimate and perform marginal inference on the spatial trend and covariate effects. The feasibility of this approach is demonstrated using an example of the distribution of neuronal cell counts in a laboratory culture dish. C1 NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,OFF BIOSTAT RES,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06520. NR 19 TC 17 Z9 17 U1 1 U2 4 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1997 VL 53 IS 2 BP 698 EP 706 DI 10.2307/2533969 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA XE965 UT WOS:A1997XE96500025 PM 9192458 ER PT J AU Xie, TD Chen, YD Marszalek, P Tsong, TY AF Xie, TD Chen, YD Marszalek, P Tsong, TY TI Fluctuation-driven directional flow in biochemical cycle: Further study of electric activation of Na,K pumps SO BIOPHYSICAL JOURNAL LA English DT Article ID FREE-ENERGY; NOISE; FIELD; (NA,K)-ATPASE; TRANSDUCTION; ENHANCEMENT; TRANSPORT AB Directional flow of information and energies is characteristic of many types of biochemical reactions, for instance, ion transport, energy coupling during ATP synthesis, and muscle contraction. Can a fluctuating force field, or a noise, induce such a directional flux? Previous work has shown that Na,K-ATPase of human erythrocyte can absorb free energy from an externally applied random-telegraph-noise (RTN) electric field to pump Rb+ up its concentration gradient, However, the RTN field used in these experiments was constant in amplitude and would not mimic fluctuating electric fields of a cell membrane. Here we show that electric fields which fluctuate both in life time and in amplitude, and thus, better mimicking the transmembrane electric fields of a cell, can also induce Rb+ pumping by Na,K-ATPase. A Gaussian-RTN-electric field, or a field with amplitude fluctuating according to the Gaussian distribution, with varied standard deviation (sigma), induced active pumping of Rb+ in human erythrocyte, which was completely inhibited by ouabain. Increased values for sigma led to a nonmonotonic reduction in pumping efficiency. A general formula for calculating the ion transport in a biochemical cycle induced by fluctuating electric field has been derived and applied to a simple four-state electroconformational coupling (ECC) model. It was found that the calculated efficiency in the energy coupling decreased with increasing sigma value, and this effect was relatively small and monotonic, whereas experimental data were more complex: monotonic under certain sets of conditions but nonmonotonic under different sets. The agreement in general features but disagreement in some fine features suggest that there are other properties of the electric activation process for Na,K-ATPase that cannot be adequately described by the simple ECC model, and further refinement of the ECC model is required. C1 HONG KONG UNIV SCI & TECHNOL,DEPT BIOCHEM,KOWLOON,HONG KONG. UNIV MINNESOTA,COLL BIOL SCI,DEPT BIOCHEM,ST PAUL,MN 55108. NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. HONG KONG UNIV SCI & TECHNOL,DEPT BIOCHEM,KOWLOON,HONG KONG. NR 20 TC 45 Z9 46 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1997 VL 72 IS 6 BP 2496 EP 2502 PG 7 WC Biophysics SC Biophysics GA XA636 UT WOS:A1997XA63600011 PM 9168026 ER PT J AU Hartung, K Froehlich, JP Fendler, K AF Hartung, K Froehlich, JP Fendler, K TI Time-resolved charge translocation by the Ca-ATPase from sarcoplasmic reticulum after an ATP concentration jump SO BIOPHYSICAL JOURNAL LA English DT Article ID CALCIUM ADENOSINE-TRIPHOSPHATASE; BLACK LIPID-MEMBRANES; PUMP CURRENTS; REACTION-MECHANISM; RECONSTITUTED PROTEOLIPOSOMES; SKELETAL-MUSCLE; CA-2+ UPTAKE; VESICLES; PHOSPHORYLATION; DISSOCIATION AB Time-resolved measurements of currents generated by Ca-ATPase from fragmented sarcoplasmic reticulum (SR) are described. SR vesicles spontaneously adsorb to a black lipid membrane acting as a capacitive electrode. Charge translocation by the enzyme is initiated by an ATP concentration jump performed by the light-induced conversion of an inactive precursor (caged ATP) to ATP with a time constant of 2.0 ms at pH 6.2 and 24 degrees C. The shape of the current signal is triphasic, an initial current flow into the vesicle lumen is followed by an outward current and a second slow inward current. The time course of the current signal can be described by five relaxation rate constants, lambda(1) to lambda(5) plus a fixed delay D approximate to 1-3 ms. The electrical signal shows that I)the reaction cycle of the Ca-ATPase contains two electrogenic steps; 2) positive charge is moved toward the luminal side in the first rapid step and toward the cytoplasmic side in the second slow step; 3) at least one electroneutral reaction precedes the electrogenic steps. Relaxation rate constant lambda(3) reflects ATP binding, with lambda(3,max) approximate to 100 s(-1). This step is electroneutral. Comparison with the kinetics of the reaction cycle shows that the first electrogenic step (inward current) occurs before the decay of E2P. Candidates are the formation of phosphoenzyme from E(1)ATP (lambda(2) approximate to 200 s(-1)) and the E1P --> E2P transition (D approximate to 1 ms or lambda(1) approximate to 300 s(-1)). The second electrogenic transition (outward current) follows the formation of E2P (lambda(4) approximate to 3 s(-1)) and is tentatively assigned to H+ countertransport after the dissociation of Ca2+. Quenched flow experiments performed under the conditions of the electrical measurements 1) demonstrate competition by caged ATP for ATP-dependent phosphoenzyme formation and 2) yield a rate constant for phosphoenzyme formation of 200 s(-1). These results indicate that ATP and caged ATP compete for the substrate binding site, as suggested by the ATP dependence of lambda(3) and favor correlation of lambda(2) with phosphoenzyme formation. C1 NIA,NIH,BALTIMORE,MD 21224. RP Hartung, K (reprint author), MAX PLANCK INST BIOPHYS,KENNEDYALLEE 70,D-60596 FRANKFURT,GERMANY. NR 59 TC 15 Z9 15 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1997 VL 72 IS 6 BP 2503 EP 2514 PG 12 WC Biophysics SC Biophysics GA XA636 UT WOS:A1997XA63600012 PM 9168027 ER PT J AU Bhaumik, SR Chary, KVR Govil, G Liu, KL Miles, HT AF Bhaumik, SR Chary, KVR Govil, G Liu, KL Miles, HT TI Homopurine and homopyrimidine strands complementary in parallel orientation form an antiparallel duplex at neutral pH with A-C, G-T, and T-C mismatched base pairs SO BIOPOLYMERS LA English DT Article DE DNA duplex; parallel duplex; antiparallel duplex; mismatch base pairs; A-C base pair; T-C base pair; G-T base pair ID NUCLEAR MAGNETIC-RESONANCE; CARCINOGEN-MODIFIED BASES; RNA DOUBLE HELIX; CRYSTAL-STRUCTURE; DNA DUPLEX; DODECANUCLEOTIDE DUPLEXES; G.A MISMATCH; ACIDIC PH; B-DNA; NMR AB DNA sequences d-TCAGGAAAGAAGGT (a 14-mer) and d-CTCCTTITCTTCC (a 12-mer) are complementary in parallel orientation forming either Donohue (reverse Watson-Crick) base pairing at neutral pH or Hoogsteen base pairing at slightly acidic pH. The structure of the complex formed by dissolving the two strands in equimolar ratio in water has been investigated by nmr. At neutral pH, the system forms an ordered antiparallel duplex with five A : T and four G : C Watson-Crick base pairs and three mismatches, namely G-T, AC, and T-C. The nuclear Overhauser effect cross-peak pattern suggests an overall B-DNA conformation with major structural perturbations near the mismatches. The duplex has a low melting point and dissociates directly into single strands with a broad melting profile. The hydrogen-bonding schemes in the mismatched base pairs have been investigated. It has been shown earlier that in acidic pH, the system prefers a triple-stranded structure with two pyrimidine strands and one purine strand. One of the pyrimidine strands has protonated cytosines, forms Hoogsteen base pairing, and is aligned parallel to the purine strand; the other has nonprotonated cytosines and has base-pairing scheme similar to the one discussed in this paper. The parallel duplex is therefore less stable than either the antiparallel duplex or the triplex, in spite of its perfect complementarity. (C) 1997 John Wiley & Sons, Inc. C1 TATA INST FUNDAMENTAL RES,CHEM PHYS GRP,BOMBAY 400005,MAHARASHTRA,INDIA. NIDDK,NATL INST HLTH,BETHESDA,MD 20892. NR 54 TC 11 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD JUN PY 1997 VL 41 IS 7 BP 773 EP 784 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WV590 UT WOS:A1997WV59000006 PM 9128440 ER PT J AU Hickey, CA Cliver, SP Goldenberg, RL McNeal, SF Hoffman, HJ AF Hickey, CA Cliver, SP Goldenberg, RL McNeal, SF Hoffman, HJ TI Low prenatal weight gain among low-income women: What are the risk factors? SO BIRTH-ISSUES IN PERINATAL CARE LA English DT Article ID INSTITUTE-OF-MEDICINE; LOW-BIRTH-WEIGHT; PRETERM BIRTH; GROWTH-RETARDATION; GESTATIONAL-AGE; WHITE WOMEN; PREGNANCY; BEHAVIORS AB Background: Although a large body of evidence suggests that prenatal weight gain is an important determinant of fetal growth, 23 to 38 percent of nonobese women have low prenatal weight gain. Determination of potential risk factors for low gain is essential to develop targeted intervention programs. This study examined the association of maternal sociodemographic, lifestyle, and reproductive characteristics with the actual occurrence of low gain among 536 black and 270 white low-income, nonobese women. Methods: Sociodemographic, pregnancy wantedness, reproductive, and anthropometric data were obtained by interview during the first prenatal visit. A 72-item questionnaire, administered at 24 to 26 weeks' gestation, assessed residential and household characteristics, housing characteristics, income, transportation, physical activity employment, and institutional support. Variables associated with low gain in bivariate analyses were included in logistic regression analysis to determine the adjusted odds ratios for low gain. Results: Three characteristics were associated with increased adjusted odds ratios for low prenatal weight gain among black women: having a mistimed or unwanted pregnancy caring for more than one preschool child at home, and not using own car for errands. One characteristic, working more than 40 hours per week when employed was associated with low gain among white women. Conclusion: Although these preliminary findings require additional confirmation, they suggest that a variety of sociodemographic and lifestyle features deserve investigations that target the identification and characterization of risk factors for low prenatal weight gain. C1 UNIV ALABAMA,SCH MED,DEPT OBSTET & GYNECOL,CTR OBSTET RES,BIRMINGHAM,AL. UNIV ALABAMA,SCH PUBL HLTH,DEPT HLTH CARE ORG & POLICY,BIRMINGHAM,AL 35294. NIDOCD,NIH,BETHESDA,MD. RP Hickey, CA (reprint author), UNIV ALABAMA,SCH PUBL HLTH,DEPT MATERNAL & CHILD HLTH,112 MORTIMER JORDAN HALL,BIRMINGHAM,AL 35294, USA. FU NICHD NIH HHS [1-HD-4-2811]; PHS HHS [MCJ-9040] NR 28 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0730-7659 J9 BIRTH-ISS PERINAT C JI Birth-Issue Perinat. Care PD JUN PY 1997 VL 24 IS 2 BP 102 EP 108 PG 7 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA XH411 UT WOS:A1997XH41100006 PM 9271976 ER PT J AU Issaragrisil, S Kaufman, DW Anderson, T Chansung, K Thamprasit, T Sirijirachai, J Piankijagum, A Porapakkham, Y Vannasaeng, S Leaverton, PE Shapiro, S Young, NS Sompradeekul, S Vuthivatanakul, T Sriratanasatavorn, C Yamcharoen, C Laewsiri, P Kittimongcolporn, S Tepmongcol, K Wongkongdej, R Vejjapinand, R Kiatvirakul, V Kareng, K Suvatte, V Intaragumthornchai, T Chancharunee, S Prayoonwiwat, V Seksan, P Chuansumrit, A Chinarat, V Angkuravorakul, S Atichartkarn, V Chutipong, S Fucharoen, S Hathirat, P Isarankura, P Jetsrisuparb, A Jootar, S Kiatkachorntada, N Kitkornpan, S Laohavinij, S Laosombat, V Lekhakul, A Mahasandana, C Makornkaewkayoon, V Nitiyanont, P Pootrakul, P Singhapan, K Siritanaratanakul, N Sonakul, D Srichaikul, T Sripaisal, T Sucharitchan, P Sukpanichnand, S Sukpanichnand, SY Supradit, P Suwanwela, N Tanphaichitr, VS Tantechanurak, C Tanyavudh, K Vatanavicharn, S Visudhiphan, S Wanachiwanawin, W Watananukul, P AF Issaragrisil, S Kaufman, DW Anderson, T Chansung, K Thamprasit, T Sirijirachai, J Piankijagum, A Porapakkham, Y Vannasaeng, S Leaverton, PE Shapiro, S Young, NS Sompradeekul, S Vuthivatanakul, T Sriratanasatavorn, C Yamcharoen, C Laewsiri, P Kittimongcolporn, S Tepmongcol, K Wongkongdej, R Vejjapinand, R Kiatvirakul, V Kareng, K Suvatte, V Intaragumthornchai, T Chancharunee, S Prayoonwiwat, V Seksan, P Chuansumrit, A Chinarat, V Angkuravorakul, S Atichartkarn, V Chutipong, S Fucharoen, S Hathirat, P Isarankura, P Jetsrisuparb, A Jootar, S Kiatkachorntada, N Kitkornpan, S Laohavinij, S Laosombat, V Lekhakul, A Mahasandana, C Makornkaewkayoon, V Nitiyanont, P Pootrakul, P Singhapan, K Siritanaratanakul, N Sonakul, D Srichaikul, T Sripaisal, T Sucharitchan, P Sukpanichnand, S Sukpanichnand, SY Supradit, P Suwanwela, N Tanphaichitr, VS Tantechanurak, C Tanyavudh, K Vatanavicharn, S Visudhiphan, S Wanachiwanawin, W Watananukul, P TI Low drug attributability of aplastic anemia in Thailand SO BLOOD LA English DT Article AB From 1989 to 1994, a population-based, case-control study of aplastic anemia was conducted in Thailand, including the regions of Bangkok, Khonkaen in the northeast, and Songkla in the south. An annual incidence in Bangkok of 3.7 cases per million population, about twice as high as in Western countries, has been reported. To evaluate the etiologic role of drugs, 253 subjects were compared with 1,174 hospital controls. With multivariate adjustment for confounding, a significant association was identified for exposure 2 to 6 months before admission to thiazide diuretics (relative risk estimate 7.7; 1.5 to 40). There were crude associations with sulfonamides (relative risk estimate, 7.9; P= 0.004) and mebendazole (6.3; P = 0.03) (there were insufficient data for multivariate adjustment). Excess risks for the three drugs were in the range of 9 to 12 cases per million users. There was no significant association with chloramphenicol, although the multivariate relative-risk estimate was elevated (2.7; 0.7 to 10). Other drugs that have been reported to increase the risk of aplastic anemia, such as nonsteroidal anti-inflammatory drugs and anticonvulsants, were not commonly used. There were no associations with commonly used drugs, including benzodiazepines, antihistamines, oral contraceptives, and herbal preparations. For all associated drugs, the overall etiologic fraction (the proportion of cases attributable to an exposure) was 5%, compared with 25% in Europe and Israel. Drugs are uncommon causes of aplastic anemia in Thailand, and their use does not explain the relatively high incidence of the disease in that country. (C) 1997 by The American Society of Hematology. C1 MAHIDOL UNIV,ASEAN INST HLTH DEV,BANGKOK 10700,THAILAND. KHON KAEN UNIV,FAC MED,DEPT MED,KHON KAEN,THAILAND. PRINCE SONGKLA UNIV,DEPT MED,SONGKHLA,THAILAND. BOSTON UNIV,SCH MED,SCH PUBL HLTH,SLONE EPIDEMIOL UNIT,BROOKLINE,MA 02146. UNIV S FLORIDA,DEPT BIOSTAT & EPIDEMIOL,TAMPA,FL. NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RP Issaragrisil, S (reprint author), SIRIRAJ HOSP,DEPT MED,DIV HEMATOL,FAC MED,BANGKOK 10700,THAILAND. OI Issaragrisil, Surapol/0000-0002-8924-0646 FU NHLBI NIH HHS [HL 35068] NR 34 TC 32 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1997 VL 89 IS 11 BP 4034 EP 4039 PG 6 WC Hematology SC Hematology GA XD379 UT WOS:A1997XD37900017 PM 9166842 ER PT J AU Emmons, RVB Doren, S Zujewski, J CottlerFox, M Carter, CS Hines, K OShaughnessy, JA Leitman, SF Greenblatt, JJ Cowan, K Dunbar, CE AF Emmons, RVB Doren, S Zujewski, J CottlerFox, M Carter, CS Hines, K OShaughnessy, JA Leitman, SF Greenblatt, JJ Cowan, K Dunbar, CE TI Retroviral gene transduction of adult peripheral blood or marrow-derived CD34(+) cells for six hours without growth factors or on autologous stroma does not improve marking efficiency assessed in vivo SO BLOOD LA English DT Article ID HUMAN HEMATOPOIETIC-CELLS; BONE-MARROW; MULTIPLE-MYELOMA; STEM-CELLS; CANCER-PATIENTS; BREAST-CANCER; TRANSPLANTATION; ENGRAFTMENT; VECTORS; CHEMOTHERAPY AB Our previous work in patients undergoing autologous transplant for multiple myeloma (MM) or breast cancer (BC) has shown that retroviral transduction of adult CD34(+) cells for 72 hours in the presence of interleukin-3 (IL-3), IL-6, and stem cell factor (SCF) resulted in .01% to 1% long-term marking of peripheral blood and marrow cells (Blood 85:3948, 1995). In this study we compare these previous studies to transduction with no added growth factors, previously shown to result in higher levels of marking in children (Lancet 342:1134, 1993) or transduction in the presence of an autologous stromal layer. Peripheral blood (PB) mononuclear cells were collected via apheresis after high-dose cyclophosphamide and granulocyte colony-stimulating factor. Bone marrow (BM) was also harvested in all patients. One third of both BM and PB collections were enriched for CD34(+) cells and transduced with one of two marking vectors containing the neomycin-resistance gene to distinguish cells originating from BM and PB posttransplantation. Cells from 3 MM and 2 BC patients were transduced without growth factors for 6 hours and cells from 2 MM and 2 BC patients were transduced in the presence of autologous marrow stroma. Immediately posttransduction, the percentage of Neo-resistant PB and BM progenitors (colony-forming units) were: 0% to 19% in the g-hour no growth factor group and 0% to 36% in the autologous stroma group. After conditioning therapy, both transduced and untransduced PB and BM fractions were infused into the patients. Semi-quantitative nested DNA polymerase chain reaction was performed on total, mononuclear, and granulocyte fractions of PB and BM at 1, 3, 6, 9, 12, and 18 months. Poor marking has been observed in both groups, with no consistently positive patients. These results compare unfavorably with our prior experience using growth factors during transduction. Further optimization of transduction conditions and vectors needs to be developed to improve transduction efficiency of adult human repopulating hematopoietic cells. C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NCI,MED BRANCH,NIH,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 30 TC 56 Z9 56 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1997 VL 89 IS 11 BP 4040 EP 4046 PG 7 WC Hematology SC Hematology GA XD379 UT WOS:A1997XD37900018 PM 9166843 ER PT J AU Lamb, LS Robbins, NF Abhyankar, S Joyce, M StetlerStevenson, M HensleeDowney, PJ Gee, AP AF Lamb, LS Robbins, NF Abhyankar, S Joyce, M StetlerStevenson, M HensleeDowney, PJ Gee, AP TI Flow cytometric cell sorting combined with molecular chimerism analysis to detect minimal recurrent leukemia: Good news and bad news SO BONE MARROW TRANSPLANTATION LA English DT Article DE allogeneic bone marrow transplantation; flow cytometry; cell sorting; molecular chimerism analysis; minimal residual disease detection ID RESIDUAL DISEASE AB Allogeneic BMT offers the possibility of cure for a variety of hematopoietic malignancies, but disease relapse remains a major cause of treatment failure. This report describes two cases in which flow cytometric cell sorting (FAGS) and molecular chimerism analysis were combined to increase the sensitivity of minimal residual disease (MRD) detection, In the first case this approach was used to demonstrate that a suspicious phenotype was not recurrent leukemia, thus preventing the use of potentially toxic therapy, In the second case the recurrence of a leukemia which was undetectable by conventional analysis was confirmed, The potential benefits of combining these MRD detection methods are discussed. C1 UNIV S CAROLINA,SCH MED,DIV TRANSPLANTAT MED,COLUMBIA,SC. UNIV S CAROLINA,SCH MED,MOL GENET PROGRAM,CTR CANC TREATMENT & RES,COLUMBIA,SC. NEMOURS CHILDRENS CLIN,DIV PEDIAT HEMATOL & ONCOL,JACKSONVILLE,FL. NCI,PATHOL LAB,HEMATOPATHOL SERV,BETHESDA,MD 20892. RP Lamb, LS (reprint author), RICHLAND MEM HOSP,CTR CANC TREATMENT & RES,DIV TRANSPLANTAT MED,7 MED PK,COLUMBIA,SC 29203, USA. NR 8 TC 12 Z9 13 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 1997 VL 19 IS 11 BP 1157 EP 1161 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA XD803 UT WOS:A1997XD80300017 PM 9193762 ER PT J AU Powe, DG Brough, JL Carter, GI Bailey, EM StetlerStevenson, WG Turner, DR Hewitt, RE AF Powe, DG Brough, JL Carter, GI Bailey, EM StetlerStevenson, WG Turner, DR Hewitt, RE TI TIMP-3 mRNA expression is regionally increased in moderately and poorly differentiated colorectal adenocarcinoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE colorectum; tissue inhibitor of metalloproteinases-3; in situ hybridization; Northern blotting analysis ID HUMAN-TISSUE INHIBITOR; TUMOR INVASION; MESSENGER-RNA; INSITU HYBRIDIZATION; IV COLLAGENASES; METALLOPROTEINASES; FAMILY; GENE; LOCALIZATION; METASTASIS AB In this study, we report on the distribution of tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) mRNA expression in human normal colorectal mucosa, adenomas and adenocarcinomas. Northern blot analysis showed five TIMP-3 mRNA transcripts to be present in normal mucosal epithelium and in moderately and poorly differentiated carcinoma. Adenomas and well-differentiated carcinomas were not examined in this part of the investigation. In situ hybridization studies showed no detectable TIMP-3 mRNA in normal and adenomatous tissue. In contrast, TIMP-3 mRNA is localized to stromal fibroblast-like cells in colorectal carcinomas, with an increased incidence in moderately and poorly differentiated groups compared with well-differentiated carcinomas. Expression in both the moderately and the poorly differentiated tumour groups was strongest at the tumour invasive edge; none of the poorly differentiated carcinomas showed mRNA expression in regions ahead of the invasive edge, compared with 3 of 12 of the moderate group. To our knowledge, this is the first detailed report on the regional localization of TIMP-3 mRNA in colorectal tumours. We suggest that the lack of TIMP-3 mRNA expression in host stromal tissues ahead of poorly differentiated carcinomas may contribute to their increased invasiveness. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RP Powe, DG (reprint author), QUEENS MED CTR,DEPT HISTOPATHOL,NOTTINGHAM NG7 2UH,ENGLAND. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 27 TC 34 Z9 34 U1 0 U2 2 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 JUN PY 1997 VL 75 IS 11 BP 1678 EP 1683 DI 10.1038/bjc.1997.285 PG 6 WC Oncology SC Oncology GA XC744 UT WOS:A1997XC74400018 PM 9184186 ER PT J AU Kuznetsov, SA Friedenstein, AJ Robey, PG AF Kuznetsov, SA Friedenstein, AJ Robey, PG TI Factors required for bone marrow stromal fibroblast colony formation in vitro SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE marrow stromal fibroblasts; colony formation; growth factors; neutralizing antibodies ID GROWTH FACTOR-BETA; CELLS CFU-F; FORMING CELLS; HEMATOPOIETIC MICROENVIRONMENT; DIFFERENTIATION; INVITRO; PROLIFERATION; STIMULATION; ORIGIN AB Marrow stromal fibroblasts (MSFs) are essential for the formation of the haemopoietic microenvironment and bone; however, regulation of MSF proliferation is poorly understood. MSF colony formation was studied in primary mouse and human marrow cell cultures. After a brief exposure to serum, MSF colony formation occurred in the absence of both serum and non-adherent marrow cells, if medium conditioned by marrow cells was present (serum-free conditioned medium, SF-CM). In mouse and human cultures stimulated to proliferate by SF-CM, neutralizing antibodies against PDGF, TGF-beta, bFGF and EGF specifically suppressed MSF colony formation. The degree of suppression was species-dependent, with the most profound inhibition achieved in mouse cultures by anti-PDGF anti-bFGF and anti-EGF and in human cultures by anti-PDGF and anti-TGF-beta. Serum-free medium not conditioned by marrow cells (SFM) did not support MSF colony formation. In mouse cultures in SFM, human recombinant bFGF and bovine natural bFGF were able to partially substitute for the stimulating effect of SF-CM. Other growth factors, including TGF-beta(1), TGF-beta(2), PDGF, EGF, IL-6, IGF-I and IGF-II, showed no activity when tested alone. In human cultures in SFM, none of the growth factors, alone or in combination, stimulated MSF colony formation. Mouse and human MSFs grown in SF-CM formed bone and a haemopoietic microenvironment when transplanted into immunodeficient mice in vivo, and therefore were functionally equivalent to MSFs generated in the presence of serum. These data indicate that stimulation of the initial proliferation of an MSF precursor cell is complex, and requires participation of at least four growth factors: PDGF, bFGF, TGF-beta and EGF. In addition, mouse and human MSF precursor cells have different requirements for each of the growth factors. C1 RUSSIAN ACAD MED SCI,NF GAMALEYA INST EPIDEMIOL & MICROBIOL,MOSCOW,RUSSIA. RP Kuznetsov, SA (reprint author), NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BLDG 30,ROOM 106,30 CONVENT DR MSC 4320,BETHESDA,MD 20892, USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 27 TC 195 Z9 212 U1 3 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1997 VL 97 IS 3 BP 561 EP 570 DI 10.1046/j.1365-2141.1997.902904.x PG 10 WC Hematology SC Hematology GA XC934 UT WOS:A1997XC93400011 PM 9207401 ER PT J AU DAvanzo, B Ron, E LaVecchia, C Franceschi, S Negri, E Ziegler, R AF DAvanzo, B Ron, E LaVecchia, C Franceschi, S Negri, E Ziegler, R TI Selected micronutrient intake and thyroid carcinoma risk SO CANCER LA English DT Article DE thyroid carcinoma; histologic type; micronutrients; case-control study ID CANCER; CAROTENOIDS AB BACKGROUND. Protection from thyroid carcinoma due to certain dietary factors was suggested by several studies, but the findings were relatively inconsistent. The role of micronutrients has not yet been systematically analyzed. To investigate the relationship between micronutrient intake and thyroid carcinoma risk, the authors used data from a case-control study conducted in northern Italy between 1986 and 1992. METHODS. The study included 399 incident, histologically confirmed thyroid carcinoma cases and 617 controls admitted to the hospital for acute, nonneoplastic, nonhormone-related diseases. RESULTS. Retinol intake showed a direct association with thyroid carcinoma risk, with odds ratios (ORs) of 1.39 (95% confidence interval [CI], 0.9-2.0) in the third quartile of consumption and 1.52 (95% CI, 1.0-2.3) in the highest quartile, whereas beta-carotene had an inverse relationship, with ORs of 0.63 (95% CI, 0.4-0.9) in the third quartile of consumption and 0.58 (95% CI, 0.4-0.9) in the highest quartile compared with the lowest quartile. Some protection was observed for measures of vitamin C intake (with an OR of 0.72) and vitamin E (with an OR of 0.67) for the highest quartile of consumption, although the estimates were not statistically significant, and were reduced after adjustment for beta-carotene intake. No clear pattern in risk appeared for vitamin D, folate, calcium, thiamin, or riboflavin. The inverse relationship between beta-carotene and thyroid carcinoma was observed in both papillary and follicular carcinomas. CONCLUSIONS. In this study, a significant inverse association between beta-carotene and thyroid carcinoma was observed, and some protection against thyroid carcinoma from vitamins C and E is as also suggested. (C) 1997 American Cancer Society. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,DIV EPIDEMIOL & GENET,ROCKVILLE,MD. UNIV MILAN,IST NAZL TUMORI,IST STAT MED & BIOMETRIA,MILAN,ITALY. CTR RIFERIMENTO ONCOL,I-33081 AVIANO,PN,ITALY. RP DAvanzo, B (reprint author), IST RIC FARMACOL MARIO NEGRI,VIA ERITREA 62,I-20157 MILAN,ITALY. RI Negri, Eva/B-7244-2013; OI Negri, Eva/0000-0001-9712-8526; La Vecchia, Carlo/0000-0003-1441-897X NR 22 TC 14 Z9 14 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1997 VL 79 IS 11 BP 2186 EP 2192 PG 7 WC Oncology SC Oncology GA XA433 UT WOS:A1997XA43300017 PM 9179066 ER PT J AU Rimer, BK AF Rimer, BK TI The National Cancer Advisory Board - 25 years later SO CANCER LA English DT Letter C1 DUKE UNIV,MED CTR,DURHAM,NC. RP Rimer, BK (reprint author), NCI,NATL CANC ADVISORY BOARD,NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1997 VL 79 IS 11 BP 2269 EP 2271 DI 10.1002/(SICI)1097-0142(19970701)79:11<2269::AID-CNCR32>3.0.CO;2-R PG 3 WC Oncology SC Oncology GA XA433 UT WOS:A1997XA43300032 PM 9179079 ER PT J AU Grem, JL Yee, LK Venzon, DJ Takimoto, CH Allegra, CJ AF Grem, JL Yee, LK Venzon, DJ Takimoto, CH Allegra, CJ TI Inter- and intraindividual variation in dihydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE circadian pharmacology; dihydropyrimidine dehydrogenase; fluorouracil ID METASTATIC COLORECTAL-CANCER; CIRCADIAN-RHYTHM; FLUOROPYRIMIDINE CHEMOTHERAPY; CONTINUOUS INFUSION; POSSIBLE RELEVANCE; DNA-SYNTHESIS; FOLINIC ACID; 5-FLUOROURACIL; FLUOROURACIL; BOLUS AB Purpose: The activity of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in fluorouracil catabolism, has been reported to vary according to time of day. We wished to determine whether peak and trough DPD activities occurred at uniform times in six subjects, whether individual patterns fit a discernible profile, and whether such patterns were consistent and reproducible over time. Methods: Mononuclear cells were isolated from peripheral blood at 3-h intervals over a 24-h period on three different dates over a B-month period. DPD activity was determined by incubating cellular lysates with [H-3]FUra and measuring [H-3]dihydrofluorouracil formation over time. Results: When the data were averaged by study date for each subject, the median value for the average DPD activity (11.0 pmol/min per 10(6) cells) was significantly different from both the median peak (21.1 pmol/min per 10(6) cells, P = 0.004) and median trough activities (4.0 pmol/min per 10(6) cells, P = 0.002). Within the six subjects, the average DPD activity for the three study dates differed by a median of 2.4-foId (range 1.2- to 4.8-fold). The time at which peak and trough DPD activities occurred varied between subjects: 8 of the 17 peaks (47%) occurred between 10:00 p.m. and 6:00 a.m., 6 (35%) occurred between 8:00 a.m. and 3:00 p.m., and 3 (18%) occurred between 5:00 p.m. and 8:15 p.m. Thus, the time of day when the peak occurred was essentially randomly distributed over the 24-h period of observation (P = 0.68). Ten (59%) of the trough DPD activities occurred between 7:00 a.m. and 3:00 p.m. The median interval between the peak and trough was 6.5 h. The data were also expressed as percent of the mean for each individual's 24-h sampling period, and reordered as time from peak rather than as the actual time of day. When the combined data for all cycles was considered, the trough occurred 6-9 h after the peak, and the DPD levels subsequent to the peak did not display merely random variation (P = 0.0055). Conclusions: DPD activity levels and the times at which peak and trough DPD activities occurred varied both between and within subjects. If fluctuations in DPD activity influence the tolerability of fixed-rate infusions of FUra, these data suggest that a single variable-rate infusion regimen may not be suitable for all patients nor for a given individual treated over several months. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP Grem, JL (reprint author), NCI,NAVY MED ONCOL BRANCH,DIV CLIN SCI,NATL NAVAL MED CTR,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. RI Venzon, David/B-3078-2008 NR 33 TC 43 Z9 46 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1997 VL 40 IS 2 BP 117 EP 125 DI 10.1007/s002800050635 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA XB021 UT WOS:A1997XB02100003 PM 9182832 ER PT J AU Nomura, AMY Ziegler, RG Stemmermann, GN Chyou, PH Craft, NE AF Nomura, AMY Ziegler, RG Stemmermann, GN Chyou, PH Craft, NE TI Serum micronutrients and upper aerodigestive tract cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PHARYNGEAL CANCER; ESOPHAGEAL CANCER; ATTRIBUTABLE RISK; LARYNGEAL-CANCER; DIET; MEN; ALCOHOL; CAROTENOIDS; VEGETABLES; SHANGHAI AB Numerous dietary studies have found that vegetables and fruits protect against upper aerodigestive tract cancer, To evaluate the role of beta-carotene and other specific carotenoids, a nested case-control study using prediagnostic serum was conducted among 6832 American men of Japanese ancestry examined from 1971 to 1975, During a surveillance period of 20 years, the study identified 28 esophageal, 23 laryngeal, and 16 oral-pharyngeal cancer cases in this cohort, The 69 cases were matched to 138 controls, A liquid chromatography technique, designed to optimize recovery and separation of the individual carotenoids, was used to measure serum levels of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, retinol, retinyl palmitate, and alpha-, delta-, and gamma-tocopherol. With adjustment for cigarette smoking and alcohol intake, we found that alpha-carotene, beta-carotene, beta-cryptoxanthin, total carotenoids and gamma-tocopherol levels were significantly lower in the 69 upper aerodigestive tract cancer patients than in their controls, Trends in risk by tertile of serum level were significant for these five micronutrients, These significant trends persisted in cases diagnosed 10 or more years after phlebotomy for the three individual carotenoids and total carotenoid measurements, The odds ratios for the highest tertile were 0.19 (95% confidence interval, 0.05-0.75) for alpha-carotene, 0.10 (0.02-0.46) for beta-carotene, 0.25 (0.06-1.04) for beta-cryptoxanthin, and 0.22 (0.05-0.88) for total carotenoids. When the cases were separated into esophageal, laryngeal, and oral-pharyngeal cancer, both alpha-carotene and beta-carotene were consistently and strongly associated with reduced risk at each site, The findings suggest that alpha-carotene and other carotenoids, as well as beta-carotene, may be involved in the etiology of upper aerodigestive tract cancer. C1 NCI,DIV CANC EPIDEMIOL & GENET,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV CINCINNATI,MED CTR,DEPT PATHOL,CINCINNATI,OH 45267. MARSHFIELD MED RES FDN,DEPT EPIDEMIOL & BIOSTAT,MARSHFIELD,WI 54449. CRAFT TECHNOL,WILSON,NC 27893. RP Nomura, AMY (reprint author), KUAKINI MED CTR,JAPAN HAWAII CANC STUDY,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NCI NIH HHS [CA-33644, Y01-CP9-0513] NR 30 TC 54 Z9 56 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1997 VL 6 IS 6 BP 407 EP 412 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XD252 UT WOS:A1997XD25200003 PM 9184773 ER PT J AU Falk, RT Dorgan, JF Kahle, L Potischman, N Longcope, C AF Falk, RT Dorgan, JF Kahle, L Potischman, N Longcope, C TI Assay reproducibility of hormone measurements in postmenopausal women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BINDING GLOBULIN; RELIABILITY; ESTRADIOL; SERUM AB As part of a breast cancer case-control study of serum hormones conducted in Columbia, MO, we included several replicate quality control samples to monitor the consistency of laboratory assays, Sera were obtained from three postmenopausal women; from each woman, three samples were placed randomly in each of nine batches with the laboratory unaware of which sample corresponded to whom, Laboratory assays for estrone (E-1), estradiol (E-2), testosterone, androstenedione (Adione), E1SO4, dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), and percentages of free and albumin-bound E-2 were done at a single academic facility, ANOVA results showed that hormone values varied considerably from one batch to the next, The overall coefficients of variation (CVs) estimated for E-2, percentage of unbound E-2, and percentage of albumin-bound E-2 were higher than 15%, but of these, only percentage of unbound E-2 had both inter- and intraassay CVs greater than 10%, Intraclass correlations (ICC) for FSH, SHBG, and DHEAS were high, suggesting that these assays are suitable for population-based studies attempting to link hormone levels to disease risk, The ICC estimated for E1SO4 was quite low due to aberrant values reported in a single batch, For the remaining hormones, the ICCs were fair (ranging from 47% for albumin-bound E-2 to 67% for Adione), and studies using these assays would require a substantial increase in the sample size to detect small case-control differences. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20904. UNIV MASSACHUSETTS,DEPT OBSTET & GYNECOL,WORCESTER,MA 01655. RP Falk, RT (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,6130 EXECUT BLVD,RM 443,BETHESDA,MD 20892, USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 11 TC 17 Z9 17 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1997 VL 6 IS 6 BP 429 EP 432 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XD252 UT WOS:A1997XD25200006 PM 9184776 ER PT J AU Dimond, E Peters, J Jenkins, J AF Dimond, E Peters, J Jenkins, J TI The genetic basis of cancer SO CANCER NURSING LA English DT Article ID ONCOGENES C1 NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD 20889. RP Dimond, E (reprint author), NCI,USN,NATL NAVAL MED CTR,NIH,8901 WISCONSIN AVE,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. NR 23 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD JUN PY 1997 VL 20 IS 3 BP 213 EP 226 DI 10.1097/00002820-199706000-00007 PG 14 WC Oncology; Nursing SC Oncology; Nursing GA XE572 UT WOS:A1997XE57200007 PM 9190096 ER PT J AU Factor, VM Kao, CY SantoniRugiu, E Woitach, JT Jensen, MR Thorgeirsson, SS AF Factor, VM Kao, CY SantoniRugiu, E Woitach, JT Jensen, MR Thorgeirsson, SS TI Constitutive expression of mature transforming growth factor beta 1 in the liver accelerates hepatocarcinogenesis in transgenic mice SO CANCER RESEARCH LA English DT Article ID TGF-BETA; EPITHELIAL-CELLS; C-MYC; GROWTH-FACTOR-BETA-1; RESISTANCE; ONCOGENE; RECEPTOR; CARCINOGENESIS; FACTOR-BETA-1; MOUSE AB Transforming growth factor beta-1 (TGF-beta 1) is a potent inhibitor of hepatocyte growth both in vivo and in vitro. In this study, we analyzed the effects of TGF-beta 1 on both naturally occurring and diethylnitrosamine-induced hepatocarcinogenesis using single transgenic TGF-beta 1 and double transgenic c-myc/TGF-beta 1 mice in which the expression of both transgenes was targeted to the liver. Hepatocellular tumors developed spontaneously in 59% (10 of 17) of the TGF-beta 1 mice by 16-18 months of age, Coexpression of TGF-beta 1 and c-myc transgenes in the liver accelerated hepatic tumor growth in both the presence and absence of carcinogenic treatment, Moreover, diethylnitrosamine-initiated tumors in the c-myc/TGF-beta 1 mice showed a high rate of malignant conversion associated with a reduced expression or lack of TGF-beta receptor type II, The results suggest that overexpression of TGF-beta 1 may contribute to liver carcinogenesis and that loss of TGF-beta receptor type II transduced inhibitory growth signals and up-regulation of c-myc are critical steps in Liver tumor progression. C1 NCI,EXPT CARCINOGENESIS LAB,DIV BASIC SCI,BETHESDA,MD 20892. RI Jensen, Michael/E-9677-2011 NR 34 TC 88 Z9 92 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1997 VL 57 IS 11 BP 2089 EP 2095 PG 7 WC Oncology SC Oncology GA XB759 UT WOS:A1997XB75900004 PM 9187100 ER PT J AU Hendricks, DT Taylor, R Reed, M Birrer, MJ AF Hendricks, DT Taylor, R Reed, M Birrer, MJ TI FHIT gene expression in human ovarian, endometrial, and cervical cancer cell lines SO CANCER RESEARCH LA English DT Article AB (1)The fragile histidine triad (FHIT) gene, located at 3p14.2, has been shown to be altered in numerous epithelial cancers, Because previous studies have shown a loss of heterozygosity and cytogenetic abnormalities at the 3p region in ovarian, endometrial, and cervical carcinomas, we examined the status of the FHIT gene in 14 ovarian, 8 cervical, and 4 endometrial human cancer cell lines, RNA was isolated and subjected to reverse transcription-PCR to amplify the FHIT gene transcript, Sixty-three % (5 of 8) of cervical cell lines, 14% (2 of 14) of ovarian cell lines, and none (0 of 4) of the endometrial cell lines displayed aberrantly migrating FHIT transcripts. DNA sequencing demonstrated that the aberrantly migrating bands primarily lacked exons 5, 6, and 7 (with other exon losses also observed), resulting in shorter mRNA transcripts, Southern blot analysis of DNA from five of the cervical carcinomas demonstrated alterations in four of them, three of which had exhibited no normally sized FHIT transcripts, The results suggest that the expression of the FHIT gene may be altered, in cervical tumor tissue, potentially implicating this gene in cervical tumorigenesis, whereas the involvement of this gene appears to be less important in the development of ovarian and endometrial cancer. C1 WALTER REED ARMY MED CTR,DEPT OBSTET & GYNECOL GYNECOL ONCOL,WASHINGTON,DC 20307. RP Hendricks, DT (reprint author), NCI,MED BRANCH,DIV CLIN SCI,NIH,ROCKVILLE,MD 20850, USA. NR 15 TC 63 Z9 66 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1997 VL 57 IS 11 BP 2112 EP 2115 PG 4 WC Oncology SC Oncology GA XB759 UT WOS:A1997XB75900009 PM 9187105 ER PT J AU Balsara, BR Sonoda, G duManoir, S Siegfried, JM Gabrielson, E Testa, JR AF Balsara, BR Sonoda, G duManoir, S Siegfried, JM Gabrielson, E Testa, JR TI Comparative genomic hybridization analysis detects frequent, often high-level, overrepresentation of DNA sequences at 3q, 5p, 7p, and 8q in human non-small cell lung carcinomas SO CANCER RESEARCH LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; OVEREXPRESSION; AMPLIFICATION; GENE; LINE AB Comparative genomic hybridization analysis was used to identify chromosomal imbalances in 20 non-small cell lung carcinoma (NSCLC) biopsies and cell lines. The chromosome arms most often overrepresented were 3q (85%), 5p (70%), 7p, (65%), and 8q (65%), which were observed at high copy numbers in many cases. Other common overrepresented sites were Iq, 2p, and 20p. DNA sequence amplification was often observed, with the most frequent site being 3q26 (six cases). Other recurrent sites of amplification included 8q24, 3q13, 3q28-qter, 7q11.2, 8p11-12, 12p12, and 19q13.1-13.2. The most frequent underrepresented segment was 3p21 (50%); other recurrent sites of autosomal loss included 8p21-pter, 15q11.2-13, 5q11.2-15, 9p, 13q12-14, 17p, and 18q21-qter. These regions of copy number decreases are also common sites of allelic loss, further implicating these sites as locations of tumor suppressor genes. Although some of the overrepresented segments harbor known or suspected oncogenes/growth-regulatory genes, we have identified 3q and 5p as new sites that are very frequently overrepresented in NSCLC. These findings could represent entry points for the identification of novel amplified DNA sequences that may contribute to the development or progression of NSCLC. C1 FOX CHASE CANC CTR,DEPT MED ONCOL,PHILADELPHIA,PA 19111. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT PHARMACOL,PITTSBURGH,PA 15261. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21231. FU NCI NIH HHS [CA-06927, CA-50674, CA-58184] NR 26 TC 134 Z9 139 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1997 VL 57 IS 11 BP 2116 EP 2120 PG 5 WC Oncology SC Oncology GA XB759 UT WOS:A1997XB75900010 PM 9187106 ER PT J AU Manzoli, L Billi, AM Rubbini, S Bavelloni, A Faenza, I Gilmour, RS Rhee, SG Cocco, L AF Manzoli, L Billi, AM Rubbini, S Bavelloni, A Faenza, I Gilmour, RS Rhee, SG Cocco, L TI Essential role for nuclear phospholipase C beta(1) in insulin-like growth factor I-induced mitogenesis SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; SWISS 3T3 CELLS; FRIEND-CELLS; DNA-SYNTHESIS; IGF-I; DIFFERENTIATION; CYCLE; ALPHA; POLYPHOSPHOINOSITIDE; DIACYLGLYCEROL AB The nucleus has been shown to be a site for the inositol lipid cycle that can be affected by treatment of quiescent cells with growth factors such as insulin-like growth factor I (IGF-I), Indeed, the exposure of Swiss 3T3 cells to IGF-I results in a rapid and transient increase in nuclear phospholipase C (PLC) beta(1) activity, In addition, several other reports have shown the involvement of PLC beta(1) in nuclear signaling in different cell types, Although the demonstration of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate hydrolysis by nuclear PLC beta(1) established the existence of nuclear PLC signaling, the significance of this autonomous pathway in the nucleus has yet to be thoroughly clarified, By inducing both the inhibition of PLC beta(1) expression by antisense RNA and its overexpression, we show that this nuclear PLC is essential for the onset of DNA synthesis following IGF-I stimulation of quiescent Swiss 3T3 cells. C1 UNIV BOLOGNA,INST HUMAN ANAT,I-40126 BOLOGNA,ITALY. IST ORTOPED RIZZOLI,CNR,CYTOMORPHOL INST,I-40136 BOLOGNA,ITALY. IST ORTOPED RIZZOLI,LAB CELL BIOL & ELECTRON MICROSCOPY,I-40136 BOLOGNA,ITALY. UNIV AUCKLAND,SCH MED,DEPT MOL MED,AUCKLAND,NEW ZEALAND. NHLBI,LAB CELL SIGNALLING,NIH,BETHESDA,MD 20892. NR 24 TC 87 Z9 88 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1997 VL 57 IS 11 BP 2137 EP 2139 PG 3 WC Oncology SC Oncology GA XB759 UT WOS:A1997XB75900014 PM 9187110 ER PT J AU Debelenko, LV Zhuang, ZP EmmertBuck, MR Chandrasekharappa, SC Manickam, P Guru, SC Marx, SJ Skarulis, MC Spiegel, AM Collins, FS Jensen, RT Liotta, LA Lubensky, IA AF Debelenko, LV Zhuang, ZP EmmertBuck, MR Chandrasekharappa, SC Manickam, P Guru, SC Marx, SJ Skarulis, MC Spiegel, AM Collins, FS Jensen, RT Liotta, LA Lubensky, IA TI Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic endocrine tumors SO CANCER RESEARCH LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISM; PARATHYROID TUMORS; SMALL REGION; HETEROZYGOSITY; LOCUS; GENE; LOCALIZATION; INSULINOMA; MARKERS; MAP AB Endocrine tumors (ETs) of pancreas and duodenum occur sporadically and as a part of multiple endocrine neoplasia type 1 (MEN1). The MEN1 tumor suppressor gene has been localized to chromosome 11q13 by linkage analysis but has not yet isolated, Previous allelic deletion studies in enteropancreatic ETs suggested MEN1 gene involvement in tumorigenesis of familial pancreatic ETs (nongastrinomas) and sporadic gastrinomas. However, only a few MEN1-associated duodenal gastrinomas and sporadic pancreatic nongastrinomas have been investigated. We used tissue microdissection to analyze 95 archival pancreatic and duodenal ETs and metastases from 50 patients for loss of heterozygosity (LOH) on 11q13 with 10 polymorphic markers spanning the area of the putative MEN1 gene. Chromosome 11q13 LOH was detected in 23 of 27 (85%) MEN1-associated pancreatic ETs (nongastrinomas), 14 of 34 (41%) MEN1-associated gastrinomas, 3 of 16 (19%) sporadic insulinomas, and 8 of 18 (44%) sporadic gastrinomas. Analysis of LOH on 11q13 showed different deletion patterns in ETs from different MEN1 patients and in multiple tumors from individual MEN1 patients, The present results suggest that the MEN1 gene plays a role in all four tumor types, The lower rate of 1lq13 LOH in MEN1-associated and sporadic gastrinomas and sporadic insulinomas as compared to MEN1 nongastrinomas may reflect alternative genetic pathways for the development of these tumors or mechanisms of the MEN1 gene inactivation that do not involve large deletions, The isolation of the MEN1 gene is necessary to further define its role in pathogenesis of pancreatic and duodenal ETs. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NATL CTR HUMAN GENOME RES,NIH,BETHESDA,MD 20892. NIDDKD,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. NR 36 TC 132 Z9 137 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1997 VL 57 IS 11 BP 2238 EP 2243 PG 6 WC Oncology SC Oncology GA XB759 UT WOS:A1997XB75900031 PM 9187127 ER PT J AU Strickland, J Sun, Y Dong, ZG Colburn, NH AF Strickland, J Sun, Y Dong, ZG Colburn, NH TI Grafting assay distinguishes promotion sensitive from promotion resistant JB6 cells SO CARCINOGENESIS LA English DT Article ID MOUSE EPIDERMAL-CELLS; NASOPHARYNGEAL CARCINOMA; INDUCED TRANSFORMATION; MALIGNANT PROGRESSION; HUMAN KERATINOCYTES; V-FOS; SKIN; DIFFERENTIATION; CONVERSION; EXPRESSION AB The JB6 mouse epidermal cell system has been used extensively as an in vitro transformation model for the study of tumor promotion. The standard JB6 cell assay for promotion of transformation is carried out in soft agar or other anchorage independent conditions. The present study was directed to the development of an in vivo model to distinguish the promotion resistant (P-) and promotion sensitive (P+) progression phenotypes. Results indicate that the grafting assay distinguishes P- and P+ cells in vivo with P+ but not P- cells forming tumors within 7-9 weeks. Expression of dominant negative mutant jun TAM67 blocks both anchorage independent transformation response and graft bed tumor formation by P+ cells, suggesting that the requirement for AP-1 activation in transformation now applies in vivo, Expression of mutated p53 produced a gain of P+ phenotype in P- cells in vitro, but not in vivo. Histochemical and Northern blot analysis for expression of various keratinocyte markers revealed no evidence for expression, suggesting a loss of keratinocyte markers following establishment in culture, In summary, the skin-grafting assay described in this study appears to be a valid in vivo assay for distinguishing the preneoplastic progression phenotypes represented by JB6 P- and P+ cells. C1 NCI,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 25 TC 8 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1997 VL 18 IS 6 BP 1135 EP 1138 DI 10.1093/carcin/18.6.1135 PG 4 WC Oncology SC Oncology GA XF495 UT WOS:A1997XF49500002 PM 9214594 ER PT J AU London, SJ Daly, AK Leathart, JBS Navidi, WC Carpenter, CC Idle, JR AF London, SJ Daly, AK Leathart, JBS Navidi, WC Carpenter, CC Idle, JR TI Genetic polymorphism of CYP2D6 and lung cancer risk in African-Americans and Caucasians in Los Angeles county SO CARCINOGENESIS LA English DT Article ID DEBRISOQUINE METABOLIC PHENOTYPE; OXIDATION PHENOTYPE; SUSCEPTIBILITY; ASSOCIATION; GENOTYPE; IDENTIFICATION; HYDROXYLATION; AMPLIFICATION; EXPOSURE; ALLELE AB The well described genetic polymorphism of the CYP2Dd gene influences response to a wide variety of therapeutic agents metabolized by the CYP2D6 enzyme product, CYP2D6 also appears to play a role, along with other cytochrome P350 enzymes, in the metabolic activation of the tobacco specific nitrosamine, NNK, as well as metabolism of nicotine to cotinine, While impaired activity of CYP2D6 was strongly protective against lung cancer in some studies, primarily based on phenotyping? the Literature is conflicting, The molecular basis of CYP2D6 deficiency is now well understood, enabling the use of genotyping to classify individuals, We therefore examined whether lung cancer risk is reduced by the presence of four CYP2D6 alleles associated with impaired activity due to an inactivating mutation-CYP2D6*4, CYP2D6*3, CYP2D6*5 and CYP2D6*16-among 341 incident cases of lung cancer and 710 population controls of Caucasian or African-American ethnicity in Los Angeles County, California, We did not confirm a strong association between the presence of these inactivating alleles and lung cancer risk [odds ratio (OR) = 0.90, 95% confidence interval (CI) 0.60-1.35 for Caucasians], although there was a small decreased risk among the African-Americans (OR = 0.66, 95% CI 0.38-1.14), Among smokers, when the data are stratified according to lifetime smoking history, there is a suggestion of an association limited to Caucasian smokers of <35 pack-years, the median for all smokers in these data (OR 0.49, 95% CI 0.23-1.04), However, among African-American smokers, who smoke less than Caucasians, the association did not differ between smoking categories, We also examined the possible role of additional copies of the CYP2Dd gene, which lead to enhanced CYP2D6 activity, in increasing lung cancer risk, Among controls the prevalence of having more than two copies of the CYP2Dd gene and no inactivating alleles was 4.3% for Caucasians and 4.9% for African-Americans. Relative to subjects with an inactivating allele, those with an additional copy of the CYP2D6 gene and no inactivating alleles may be at increased risk of lung cancer, particularly for adenocarcinoma (OR = 3.61, 95% CI 1.08-11.7 for African-Americans and OR = 2.20, 95% CI 0.69-6.0 for Caucasians), Our data suggest that the CYP2Dd genetic polymorphism is not the strong risk factor for lung cancer suggested by some studies of phenotype, but may play a minor role. C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV NEWCASTLE UPON TYNE,SCH MED,DEPT PHARMACOL SCI,NEWCASTLE TYNE NE2 4HH,TYNE & WEAR,ENGLAND. RP London, SJ (reprint author), UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033, USA. RI Daly, Ann/H-3144-2011; OI Daly, Ann/0000-0002-7321-0629; Idle, Jeff/0000-0002-6143-1520; London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [N01-CN-25403] NR 48 TC 64 Z9 65 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1997 VL 18 IS 6 BP 1203 EP 1214 DI 10.1093/carcin/18.6.1203 PG 12 WC Oncology SC Oncology GA XF495 UT WOS:A1997XF49500012 PM 9214604 ER PT J AU Bello, D Webber, MM Kleinman, HK Wartinger, DD Rhim, JS AF Bello, D Webber, MM Kleinman, HK Wartinger, DD Rhim, JS TI Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18 SO CARCINOGENESIS LA English DT Article ID POLYMERASE CHAIN-REACTION; URINARY-BLADDER; TUMOR-CELLS; P53 PROTEIN; CANCER; RAS; CARCINOMA; GENE; PROGRESSION; EXPRESSION AB Prostate cancer and benign tumors of the prostate are the two most common neoplastic diseases in men in the United States, however, research on their causes and treatment has been slow because of the difficulty in obtaining fresh samples of human tissue and a lack of well characterized cell lines which exhibit growth and differentiation characteristics of normal prostatic epithelium. Non-neoplastic adult human prostatic epithelial cells from a white male donor were immortalized with human papillomavirus 18 which resulted in the establishment of the RWPE-1 cell line, Cells from the RWPE-1 cell line were further transformed by v-Ki-ras to establish the RWPE-2 cell line, The objectives of this study were to: (1) establish the prostatic epithelial origin and androgen responsiveness of RWPE-1 and RWPE-2 cell lines; (2) examine their response to growth factors; and (3) establish the malignant characteristics of the RWPE-2 cell line, Immunoperoxidase staining showed that both RWPE-1 and RWPE-2 cells express cytokeratins 8 and 18, which are characteristic of luminal prostatic epithelial cells, but they also coexpress basal cell cytokeratins, These cell lines show growth stimulation and prostate specific antigen (PSA) and androgen receptor (AR) expression in response to the synthetic androgen mibolerone, which establishes their prostatic epithelial origin, Both cell lines also show a dose-dependent growth stimulation by EGF and bFGF and growth inhibition when exposed to TGF-P, however, the transformed RWPE-2 cells are less responsive, RWPE-1 cells neither grow in agar nor form tumors when injected into nude mice with or without Matrigel, However, RWPE-2 cells form colonies in agar and tumors in nude mice, In the in vitro invasion assay, RWPE-1 cells are not invasive whereas RWPE-2 cells are invasive, Nuclear expression of p53 and Rb proteins was heterogeneous but detectable by immunostaining in both cell lines, The RWPE-1 cells, which show many normal cell characteristics, and the malignant RWPE-2 cells, provide useful cell culture models for studies on prostate growth regulation and carcinogenesis. C1 MICHIGAN STATE UNIV,DEPT MED,E LANSING,MI 48824. MICHIGAN STATE UNIV,DEPT ZOOL,E LANSING,MI 48824. NIDR,CELL BIOL SECT,NIH,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT OSTEOPATH MED,E LANSING,MI 48824. NCI,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21701. NR 32 TC 224 Z9 228 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1997 VL 18 IS 6 BP 1215 EP 1223 DI 10.1093/carcin/18.6.1215 PG 9 WC Oncology SC Oncology GA XF495 UT WOS:A1997XF49500013 PM 9214605 ER PT J AU Webber, MM Bello, D Kleinman, HK Hoffman, MP AF Webber, MM Bello, D Kleinman, HK Hoffman, MP TI Acinar differentiation by non-malignant immortalized human prostatic epithelial cells and its loss by malignant cells SO CARCINOGENESIS LA English DT Article ID BASEMENT-MEMBRANE; ALPHA-6 SUBUNIT; EXPRESSION; LAMININ; INTEGRIN; BINDING; PHENOTYPE; CARCINOMA; MOLECULES; POLARITY AB Invasive prostatic carcinomas and prostatic intraepithelial neoplasia (PIN) are characterized by a loss of normal cell organization, cell polarity, and cell:cell and cell:basement membrane adhesion, The objective of this study was to establish in vitro three-dimensional (3-D) cell models which can be used to investigate mechanisms involved in acinar morphogenesis and differentiation in normal prostatic epithelium and their abnormalities in cancer cells, The process of acinar morphogenesis, including structural and functional differentiation, was investigated by culture on basement membrane gels (Matrigel). The human papillomavirus 18 immortalized, non-tumorigenic cell line RWPE-1, the v-Ki-ras transformed, tumorigenic RWPE-2 cell line derived from RWPE-1 cells (see previous paper pp, 1221-1229) and the human prostatic carcinoma cell line DU-145 were used, When cultured on Matrigel, RWPE-2 cells remain as single cells or form small aggregates and DU-145 cells form large amorphous cell aggregates without any organization or lumen, In contrast, RWPE-1 cells form acini of polarized epithelium with a distinct lumen, show a distinct laminin basement membrane, and express alpha 6 beta 1 integrins at their basal end, Exposure to conditioned medium from NIH 3T3 cultures accelerates glandular morphogenesis. Parallel cultures maintained as monolayers on plastic remain as monolayers. In the presence of the synthetic androgen mibolerone, acinar cells express prostate specific antigen (PSA) as determined by immunostaining, We conclude that normal prostate cells can undergo acinar morphogenesis while tumorigenic cells have lost this ability, The 3-D cultures provide physiologically relevant in vitro models for elucidating regulation of growth, morphogenesis and differentiation in the normal human prostate, for defining heterotypic interactions in benign prostatic hyperplasia and for establishing the basis for the loss of normal cell organization in early neoplastic lesions such as PIN as well as during tumor progression in prostate cancer. C1 MICHIGAN STATE UNIV,DEPT ZOOL,E LANSING,MI 48824. NIDR,CELL BIOL SECT,NIH,BETHESDA,MD 20892. RP Webber, MM (reprint author), MICHIGAN STATE UNIV,DEPT MED,S-350 PLANT BIOL BLDG,E LANSING,MI 48824, USA. NR 29 TC 94 Z9 95 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1997 VL 18 IS 6 BP 1225 EP 1231 DI 10.1093/carcin/18.6.1225 PG 7 WC Oncology SC Oncology GA XF495 UT WOS:A1997XF49500014 PM 9214606 ER PT J AU Blomeke, B Bennett, WP Harris, CC Shields, PG AF Blomeke, B Bennett, WP Harris, CC Shields, PG TI Serum, plasma and paraffin-embedded tissues as sources of DNA for studying cancer susceptibility genes SO CARCINOGENESIS LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; ARYLAMINE N-ACETYLTRANSFERASE; POLYMERASE CHAIN-REACTION; FRAGMENT-LENGTH-POLYMORPHISMS; SQUAMOUS-CELL CARCINOMA; GSTM1 NULL GENOTYPE; CHRONIC HEPATITIS-C; LUNG-CANCER; CLASS-MU; CYTOCHROME-P450IA1 GENE AB The ability to isolate DNA from archived human serum, plasma and paraffin-embedded human tissues enhances opportunities to study breast, lung and other cancer risk factors, We report herein a simple and fast protocol for the extraction of genomic DNA from these sources, Using a phenol-based extraction method, the recovery for DNA is quantitative and reproducible, DNA yields in serum (250 mu l) were between 162 and 1060 ng (It = 18 subjects), in plasma (250 mu l) were between 165 and 375 ng (it = 5 subjects) and in embedded tissues (5-mu m thick sections for ethanol fixed, and between 5- and 20-mu m sections for formaldehyde fixation) were between 1 mu g and 11.7 mu g (it = 32 subjects), The extraction method was combined with newly designed PCR-based assays for cancer susceptibility marker genes such as CYP1A1 (exon 7), CYP2E1 (Dra1, Rsa1), GSTM1 and NAT2 [NAT2*5A ((CT)-T-481), NAT2*6A (G(590)A), NAT2*7A (G(857)A)I] Genotyping results from the serum and paraffin-embedded tissues compared favorably to results from archived freshly frozen tissues, where concordance was 98% for serum, 100% for ethanol-fixed embedded tissues, and 97% for formaldehyde-fixed and paraffin-embedded tissues, This facile method will allow for the use of archived tissue samples of prospective cohort and other studies where intact DNA was not previously available. C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RI Shields, Peter/I-1644-2012 NR 56 TC 33 Z9 34 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1997 VL 18 IS 6 BP 1271 EP 1275 DI 10.1093/carcin/18.6.1271 PG 5 WC Oncology SC Oncology GA XF495 UT WOS:A1997XF49500021 PM 9214613 ER PT J AU Fawcett, TW Xu, QB Holbrook, NJ AF Fawcett, TW Xu, QB Holbrook, NJ TI Potentiation of heat stress-induced hsp70 expression in vivo by aspirin SO CELL STRESS & CHAPERONES LA English DT Article ID SHOCK FACTOR; ANTIINFLAMMATORY DRUGS; MOLECULAR CHAPERONES; CELLS; ACTIVATION; PROTEINS; GENE; THERMOTOLERANCE; DEPRIVATION; MODULATION AB Studies in cultured cells have demonstrated that non-steroidal anti-inflammatory agents can potentiate heat-induced hsp70 expression through activation of HSF1 to a DNA binding state. We investigated the influence of aspirin an hsp70 expression in intact rats subjected to heat stress. Rats were injected intraperitoneally either with aspirin (100 mg/kg) or vehicle alone, 60 min prior to their placement at 37 degrees C or room temperature for 30 min. hsp70 mRNA expression was analyzed in lung, liver and kidney isolated from animals assigned to one of four different treatment paradigms; untreated controls, heat, aspirin, and aspirin-plus-heat. Comparison of hsp70 expression in the treatment groups revealed that in all tissues examined, aspirin-plus-heat treatment resulted in 3-4 fold higher levels of hsp70 mRNA relative to those seen with heat treatment alone. Little or no hsp70 mRNA expression was detected in the unheated groups, regardless of aspirin treatment. In keeping with the mRNA expression, Hsp70 protein levels were also elevated in aspirin-plus-heat treated animals. Aspirin treatment did not alter hsp70 protein expression in the absence of heat. In contrast to in vitro observations, aspirin treatment in vivo did not alter HSF1 DNA binding properties. Core body temperature measurements revealed that aspirin pretreatment enhanced the rise in body temperature seen in response to heat treatment. This increased hyperthermic response to heat stress probably accounts for the potentiation of hsp70 expression observed in aspirin-plus-heat treated rats. Given the widespread use of aspirin in humans within a dose range comparable to that used here, our findings are likely to have important physiological consequences. C1 NIA,SECT GENE EXPRESS & AGING,BALTIMORE,MD 21224. AUSTRIAN ACAD SCI,INST BIOMED AGING RES,A-6020 INNSBRUCK,AUSTRIA. NR 23 TC 38 Z9 38 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD JUN PY 1997 VL 2 IS 2 BP 104 EP 109 DI 10.1379/1466-1268(1997)002<0104:POHSIH>2.3.CO;2 PG 6 WC Cell Biology SC Cell Biology GA XG200 UT WOS:A1997XG20000005 PM 9250401 ER PT J AU Takeuchi, Y Satoh, A Suzuki, T Kameda, A Dohrin, M Satoh, T Koizumi, T Kirk, KL AF Takeuchi, Y Satoh, A Suzuki, T Kameda, A Dohrin, M Satoh, T Koizumi, T Kirk, KL TI Enantioselective fluorination of organic molecules .1. Synthetic studies of the agents for electrophilic, enantioselective fluorination of carbanions SO CHEMICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE fluorinating agent; electrophilic fluorination; enantioselective fluorination; FClO3; N-fluorosulfonamide derivative ID RESOLUTION; DERIVATIVES; ENANTIOMERS; ACID AB In order to develop novel methods for electrophilic and enantioselective fluorination of active methine compounds, preliminary experiments were carried out, The N-tosyl derivative 5 obtained from D-phenylglycine was fluorinated with FCIO3 or diluted F-2 gas to give the N-fluoro-N-tosyl derivative 6. N-Tosyl- or N-mesyl-(S)-alpha-phenethylamine 7 or 8 was subjected to FCIO3 fluorination to produce the corresponding N-fluoro derivative, 10 or 11, respectively, Enantioselective fluorination of some methine compounds was attempted employing the above N-fluoro agents. Best result was obtained when 2-benzyl-1-tetralone/KHMDS was treated with 10 to produce the fluorinated tetralone 17 in 53% yield with enantiomeric excess (ee) of 48%. C1 NIDDK, BIOORGAN CHEM LAB, NIH, BETHESDA, MD 20892 USA. RP Takeuchi, Y (reprint author), TOYAMA MED & PHARMACEUT UNIV, FAC PHARMACEUT SCI, DEPT CHEM PHARMACOL, SUGITANI 2630, TOYAMA 93001, JAPAN. NR 19 TC 38 Z9 38 U1 0 U2 3 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0009-2363 J9 CHEM PHARM BULL JI Chem. Pharm. Bull. PD JUN PY 1997 VL 45 IS 6 BP 1085 EP 1088 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA XG640 UT WOS:A1997XG64000019 PM 9214712 ER PT J AU Sime, PJ Sarnstrand, B Xing, Z Graham, F Fisher, L Gauldie, J AF Sime, PJ Sarnstrand, B Xing, Z Graham, F Fisher, L Gauldie, J TI Adenovirus-mediated gene transfer of the proteoglycan biglycan induces fibroblastic responses in the lung SO CHEST LA English DT Article; Proceedings Paper CT Thomas L Petty Aspen Lung Conference 39th Annual Meeting - Genes and Gene Therapy CY JUN 05-08, 1996 CL ASPEN, CO C1 NIDR,NIH,BETHESDA,MD 20892. RP Sime, PJ (reprint author), MCMASTER UNIV,DEPT PATHOL,HAMILTON,ON,CANADA. NR 0 TC 16 Z9 16 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1997 VL 111 IS 6 SU S BP S137 EP S137 DI 10.1378/chest.111.6_Supplement.137S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XD732 UT WOS:A1997XD73200033 PM 9184564 ER PT J AU Westergaard, GC Champoux, M Suomi, SJ AF Westergaard, GC Champoux, M Suomi, SJ TI Hand preference in infant rhesus macaques (Macaca mulatta) SO CHILD DEVELOPMENT LA English DT Article ID HANDEDNESS; MONKEYS AB In this research we examined hand preference in infant rhesus macaques (Macaca mulatta). The subjects were 20 Macaca mulatta, each aged between 4 and 11 months. We assessed hand preference using both a unimanual reaching task and a bimanual coordination task. In the unimanual reaching task, we presented subjects with raisins and noted which hand the animals used to retrieve the food. In the bimanual coordination task, we presented the same subjects with plastic tubes filled with raisin paste and noted which hand the animals used to hold the tubes and which hand the animals used to remove the food. We noted a population-level bias toward use of the left hand for both tasks. These results suggest early right hemisphere advantage for reaching and bimanual coordination in Macaca mulatta, although we acknowledge that this issue needs to be examined more directly through neuroimaging procedures such as Positron Emission Tomography (PET) or functional Magnetic Resonance imaging (fMRI). We speculate that early right hemisphere advantage contributes to differential patterns of hand preference development for unimanual and bimanual action, and Mat the development of hand preference for bimanual coordination is related to the emergence of hemispheric specialization for processing species-specific vocalizations. RP Westergaard, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,ANIM CTR,NIH,POB 529,POOLESVILLE,MD 20837, USA. NR 26 TC 42 Z9 42 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD JUN PY 1997 VL 68 IS 3 BP 387 EP 393 PG 7 WC Psychology, Educational; Psychology, Developmental SC Psychology GA XM998 UT WOS:A1997XM99800001 PM 9249955 ER PT J AU Behrens, F Claussen, U Iyer, LM Green, ED Horsthemke, B Wiliamson, R Huxley, G Coutelle, C AF Behrens, F Claussen, U Iyer, LM Green, ED Horsthemke, B Wiliamson, R Huxley, G Coutelle, C TI Isolation of DNA from the centromere of human chromosome 7 by microdissection SO CHROMOSOME RESEARCH LA English DT Article DE centromere of human chromosome 7; chromosomal microdissection; microdissection library; physical mapping; STS analysis ID YEAST ARTIFICIAL CHROMOSOMES; SEQUENCE-TAGGED SITES; ALPHA-SATELLITE DNA; GENERATION; HUMAN-CHROMOSOME-7; CONSTRUCTION; MICROCLONES; LIBRARY; CLONES; PROBES AB Centromeres remain the least characterized regions of human chromosomes because they have a very high content of repetitive DNA. Here, we describe a microdissection library from the centromeric region of human chromosome 7 and its use for generating sequence tagged sites (STSs). The library contains about 1500 clones with an average insert size of 150 bp and only about 15% of the clones harbour repetitive human DNA. Seven clones hybridizing to alphoid DNA were found to correspond to a fragment of the D7Z2 alphoid array on chromosome 7, thus confirming the origin of the library. A number of clones not containing known repetitive DNA were used to generate STSs that identified yeast artificial chromosomes (YACs) and in turn allowed the STSs to be placed on the physical map. One STS is located between the two Genethon genetic markers closest to the centromere on the q side. Another STS was located 3-4cM away in 7q11.2, while a third identified YACs containing both low-copy and alphoid sequences that are not yet mapped but are clearly centromeric. The library therefore comprises a collection of sequences from the centromeric region of chromosome 7 that can be used to generate STSs and to map the entire centromeric region. C1 KLINIKUM UNIV JENA,INST HUMAN GENET & ANTHROPOL,D-07743 JENA,GERMANY. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV ESSEN GESAMTHSCH KLINIKUM,INST HUMAN GENET,D-45122 ESSEN,GERMANY. RP Behrens, F (reprint author), UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT BIOCHEM & MOL GENET,SCH MED,LONDON W2 1PG,ENGLAND. NR 18 TC 3 Z9 3 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD JUN PY 1997 VL 5 IS 4 BP 215 EP 220 DI 10.1023/A:1018459300978 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA XM379 UT WOS:A1997XM37900001 PM 9244447 ER PT J AU Shirkey, BL Slavin, S Vistica, BP Podgor, MJ Gery, I AF Shirkey, BL Slavin, S Vistica, BP Podgor, MJ Gery, I TI Immunomodulatory effects of linomide in animals immunized with immunopathogenic retinal antigens: dissociation between different immune functions SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE linomide; immunomodulation; autoimmune disease; uveitis ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; BINDING PROTEIN; S-ANTIGEN; T-CELLS; RAT; LS-2616; ENCEPHALOMYELITIS; CYCLOSPORINE; MICE; INHIBITION AB Linomide (LS-2616, quinoline-3-carboxamide) has been reported to exert a diverse range of effects on the immune system. On one hand, this drug was found to stimulate the immune system and to enhance activities such as DTH or allograft rejection. On the other hand, linomide was shown to inhibit the induction of experimental autoimmune encephalomyelitis and myasthenia gravis, as well as the development of diabetes in non-obese diabetic (NOD) mice. Here we report the effects of linomide in animals immunized with uveitogenic retinal antigens. Treatment with linomide completely inhibited the development of experimental autoimmune uveoretinitis (EAU) in mice immunized with interphotoreceptor retinoid-binding protein and markedly suppressed EAU in rats immunized with S-antigen (S-Ag). In addition, linomide-treated rats exhibited reduced antibody production and lymphocyte proliferative response to S-Ag. In contrast to these suppressive activities, linomide treatment did not affect the development of adoptively transferred EAU in rats and moderately enhanced the DTH reactions to S-Ag in immunized rats in which EAU and other immune responses to this antigen were suppressed. C1 NEI,NIH,IMMUNOL LAB,BETHESDA,MD 20892. NEI,DIV BIOMETRY & EPIDEMIOL,NIH,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. HADASSAH UNIV HOSP,DEPT BONE MARROW TRANSPLANT,IL-91120 JERUSALEM,ISRAEL. HADASSAH UNIV HOSP,CANC IMMUNOBIOL RES LAB,IL-91120 JERUSALEM,ISRAEL. NR 34 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUN PY 1997 VL 108 IS 3 BP 539 EP 544 DI 10.1046/j.1365-2249.1997.3681268.x PG 6 WC Immunology SC Immunology GA XB122 UT WOS:A1997XB12200026 PM 9182904 ER PT J AU Sharfe, N Dadi, HK OShea, JJ Roifman, CM AF Sharfe, N Dadi, HK OShea, JJ Roifman, CM TI Jak3 activation in human lymphocyte precursor cells SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE thymocytes; IL-7; immunodeficiency; pre-B; Jak3 ID RECEPTOR-GAMMA-CHAIN; SEVERE COMBINED IMMUNODEFICIENCY; PROTEIN-TYROSINE KINASES; MICE LACKING JAK3; IL-2 RECEPTOR; INTERLEUKIN-7 RECEPTOR; MURINE INTERLEUKIN-7; V(D)J REARRANGEMENT; JANUS KINASE; FAMILY AB Although expression of the Jak3 tyrosine kinase in T lymphocytes has been thought to be restricted to mature, activated cells, mutations of Jak3 can lead to the development of a human severe combined immunodeficiency (SCID) characterized by an absence of peripheral T lymphocytes. We therefore examined in detail the expression of Jak3 throughout human T cell differentiation and show that Jak3 is in fact present throughout the entire developmental process, with high levels expressed in thymocytes. Jak3 is highly expressed in double negative (CD4(-)CD8(-)) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. IL-7 is known to stimulate thymocyte proliferation and initiate re-arrangement of the T cell receptor (TCR) beta gene, suggesting that the failure of mutated Jak3 proteins to transduce this signal may be responsible for failures in T cell development. While Jak3 SCID patients possess mature peripheral B cells, we demonstrate that the Jak3 tyrosine kinase is also expressed in human pre-B cells and can be activated by the pre-B cell growth factor IL-7. C1 HOSP SICK CHILDREN,DIV IMMUNOL & ALLERGY,TORONTO,ON M5G 1X8,CANADA. UNIV TORONTO,DEPT PEDIAT,DIV IMMUNOL & ALLERGY,TORONTO,ON,CANADA. NIAMS,NIH,BETHESDA,MD. NR 35 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUN PY 1997 VL 108 IS 3 BP 552 EP 556 DI 10.1046/j.1365-2249.1997.4001304.x PG 5 WC Immunology SC Immunology GA XB122 UT WOS:A1997XB12200028 PM 9182906 ER PT J AU Kremer, R Goltzman, D Amizuka, N Webber, MM Rhim, JS AF Kremer, R Goltzman, D Amizuka, N Webber, MM Rhim, JS TI ras activation of human prostate epithelial cells induces overexpression of parathyroid hormone-related peptide SO CLINICAL CANCER RESEARCH LA English DT Article ID V-KI-RAS; GENE-MUTATIONS; CARCINOMA; ONCOGENE; CANCER; TRANSFORMATION; PROTEIN; EXPRESSION AB Immortalized adult and fetal prostate cell lines grown in serum-free conditions produce low levels of parathyroid hormone-related peptide (PTHRP) in the presence of growth factors as assessed by mRNA analysis, PTHRP immunoreactivity, and immunohistochemistry. Subsequent infection of these cells with Kirsten murine sarcoma virus containing an activated Ki-ms oncogene induces at least a 10-20-fold increase in PTHRP expression and production of both adult and fetal immortalized cell lines in the presence of the same growth factors. These results provide the first evidence of direct activation of PTHRP by the ras oncogene in human prostate cells and suggest its potential usefulness as a tumor marker in prostate malignancies. C1 MCGILL UNIV,DEPT MED,MONTREAL,PQ H3A 1A1,CANADA. MICHIGAN STATE UNIV,DEPT MED,E LANSING,MI 48824. MICHIGAN STATE UNIV,DEPT ZOOL,E LANSING,MI 48824. NCI,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. NR 23 TC 14 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1997 VL 3 IS 6 BP 855 EP 859 PG 5 WC Oncology SC Oncology GA XC514 UT WOS:A1997XC51400004 PM 9815759 ER PT J AU Suzuki, M Sugimoto, Y Tsukahara, S Okochi, E Gottesman, MM Tsuruo, T AF Suzuki, M Sugimoto, Y Tsukahara, S Okochi, E Gottesman, MM Tsuruo, T TI Retroviral coexpression of two different types of drug resistance genes to protect normal cells from combination chemotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID HEMATOPOIETIC STEM-CELLS; HUMAN MDR1 GENE; MULTIDRUG-RESISTANCE; BONE-MARROW; COMPLEMENTARY-DNA; TRANSGENIC MICE; P-GLYCOPROTEIN; EFFICIENT EXPRESSION; MEDIATED TRANSFER; INDUCED TOXICITY AB Drug resistance genes can protect normal hematopoietic cells from the toxicity of anticancer agents. Because chemotherapeutic agents are often used in combination in current clinical protocols, coexpression of two different drug resistance genes should be useful in protecting normal bone marrow cells from the hematotoxicities caused by combination chemotherapy, In this study, we have combined the human multidrug resistance gene (MDR1) and human O-6-methylguanine DNA methyltransferase (MGMT) gene as drug resistance genes, For the coexpression of two drug resistance genes, we have constructed two bicistronic retrovirus vectors, One vector is Ha-MDR-IRES-MGMT, in which translation of the MDR1 cDNA is cap-dependent and MGMT translation is dependent on an internal ribosome entry site (IRES). The other is Ha-MGMT-IRES-MDR, which has cap-dependent MGMT translation and IRES-dependent MDR1 translation, MGMT negative HeLa derivative (MR) cells transduced with these retroviruses showed resistance to vincristine (from MDR1) and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroe (ACNU; from MGMT). Cells transduced with Ha-MDR-IRES-MGMT showed higher resistance to vincristine and lower resistance to ACNU than those transduced with Ha-MGMT-IRES-MDR. In any case, the resistance levels of cells transduced with either vector were high enough to select transduced cells with vincristine or ACNU, The expression levels of P-glycoprotein or MGMT in the transduced cells determined by FAGS and Western blot analysis correlated well with the extent of resistance to vincristine and ACNU, respectively, All of the MGMT-transduced cells expressed higher amounts of MGMT than the MGMT-expressing parental cell line HeLa S3, Murine bone marrow cells transduced with Ha-MDR-IRES-MGMT and selected with vincristine also showed simultaneous resistance to vincristine and ACNU. These results suggest that bicistronic retroviral vectors allow the functional coexpression of two different types of drug resistance genes. This strategy could be applicable to any combination of drug resistance genes. C1 UNIV TOKYO,INST MOL & CELLULAR BIOSCI,BUNKYO KU,TOKYO 113,JAPAN. JAPANESE FDN CANC RES,CTR CANC CHEMOTHERAPY,TOKYO 170,JAPAN. HOECHST JAPAN LTD,KAWAGOE,SAITAMA 350,JAPAN. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 38 TC 19 Z9 22 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1997 VL 3 IS 6 BP 947 EP 954 PG 8 WC Oncology SC Oncology GA XC514 UT WOS:A1997XC51400015 PM 9815770 ER PT J AU Sampson, M Cecco, SA Ruddel, M Rehak, NN Elin, RJ AF Sampson, M Cecco, SA Ruddel, M Rehak, NN Elin, RJ TI Comparison of blood glutathione peroxidase with selected analytes in normal volunteers. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 35 EP 35 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300035 ER PT J AU Spaid, KA Chesler, R Costello, R Csako, G AF Spaid, KA Chesler, R Costello, R Csako, G TI Comparison of five electrophoretic methods for the detection of paraproteins in serum, urine and cerebrospinal fluid (CSF). SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 226 EP 226 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300225 ER PT J AU Cecco, SA Rehak, NN Niemela, JE Elin, RE AF Cecco, SA Rehak, NN Niemela, JE Elin, RE TI The effect of smoking on the concentration of serum ionized magnesium. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 267 EP 267 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300266 ER PT J AU Chan, YW Rehak, NN AF Chan, YW Rehak, NN TI Analytical performance of One Touch II Hospital Blood Glucose Meter. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 268 EP 268 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300267 ER PT J AU Niemela, JE Snader, BM Elin, RJ AF Niemela, JE Snader, BM Elin, RJ TI Relationship of ionized calcium and magnesium concentrations in resting platelets from apparently healthy subjects. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 269 EP 269 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300268 ER PT J AU Niemela, JE Cecco, SA Rehak, NN Elin, RJ AF Niemela, JE Cecco, SA Rehak, NN Elin, RJ TI Analyzer-dependent correlation of results for serum ionized magnesium concentration and white blood cell counts in apparently healthy smoking and nonsmoking subjects. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 272 EP 272 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300271 ER PT J AU Remaley, AT Farsi, BD Hoeg, JM Brewer, HB AF Remaley, AT Farsi, BD Hoeg, JM Brewer, HB TI Differential cholesterol efflux from plasma membrane domains of epithelial cells. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 712 EP 712 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300711 ER PT J AU Niemela, JE Csako, G Bui, MN Elin, RJ AF Niemela, JE Csako, G Bui, MN Elin, RJ TI Gender-specific correlation of platelet ionized magnesium and serum low density lipoprotein cholesterol concentrations in apparently healthy subjects. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT INTERNAL MED,WASHINGTON,DC 20007. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 733 EP 733 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300732 ER PT J AU Csako, G Bui, MN Niemela, JE Rackley, CE Elin, RJ AF Csako, G Bui, MN Niemela, JE Rackley, CE Elin, RJ TI Gender-specific correlation of high density lipoprotein-cholesterol with anti-oxidized low density lipoprotein autoantibodies in healthy adult subjects. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,CPD,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 742 EP 742 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300741 ER PT J AU Rohlfs, EM Yang, Q Skrzynia, C Graham, ML Liu, ET Silverman, LM AF Rohlfs, EM Yang, Q Skrzynia, C Graham, ML Liu, ET Silverman, LM TI Analysis of BRCA1 in high-risk breast and ovarian cancer families. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 UNIV N CAROLINA,LINEBERGER CANC CTR,CHAPEL HILL,NC. NCI,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 775 EP 775 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300774 ER PT J AU Hruszkewycz, AM Delgado, RM Yang, A Walther, MM Hristova, EN Wu, Y AF Hruszkewycz, AM Delgado, RM Yang, A Walther, MM Hristova, EN Wu, Y TI Telomerase activity testing for bladder cancer detection using a non-isotopic telomeric repeat amplification protocol (TRAP). SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 782 EP 782 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300781 ER PT J AU Wu, Y Delgado, RM Hruszkewycz, AM AF Wu, Y Delgado, RM Hruszkewycz, AM TI Quantification of cellular DNA by fluorescence staining. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,CTR CLIN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 786 EP 786 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300785 ER PT J AU Fitzgerald, RL Herold, DA Yergey, AL AF Fitzgerald, RL Herold, DA Yergey, AL TI Trade-offs in mass spectrometry SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 NICHHD,BETHESDA,MD 20892. VET ADM MED CTR,LAB SERV,SAN DIEGO,CA 92161. UNIV CALIF SAN DIEGO,DEPT PATHOL,SAN DIEGO,CA 92161. NR 2 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 IS 6 BP 915 EP 915 PN 1 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XC898 UT WOS:A1997XC89800002 PM 9191539 ER PT J AU Maity, R Caspi, RR Nair, S Rizzo, LV Nelson, LM AF Maity, R Caspi, RR Nair, S Rizzo, LV Nelson, LM TI Murine postthymectomy autoimmune oophoritis develops in association with a persistent neonatal-like Th2 response SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID PREMATURE OVARIAN FAILURE; CD4+ T-CELLS; THYMECTOMIZED MICE; IMMUNE-RESPONSES; CELLULAR EVENTS; IFN-GAMMA; IL-12; REQUIREMENT; DISEASES; ANTIBODIES AB Autoimmune oophoritis develops in some patients despite evidence of impaired cellular immunity. Here, using the murine postthymectomy model of autoimmune oophoritis, we investigate the hypothesis that neonatal thymectomy induces autoimmune oophoritis by disrupting the normal postnatal balance of T helper cell regulation. Stimulated CD4(+) splenic lymphocytes from adult mice sham-operated as neonates produced the expected T helper type 1 (Th1) predominant response normally seen in adult mice (low levels of interleukin-4 and high levels of interferon gamma). In contrast, cells from adult mice thymectomized as neonates produced an inappropriate neonatal-like Th2-predominant response (high levels of interleukin-4 and low levels of interferon-gamma). Manipulations that restored the postnatal shift to an adult Th1-dominant pattern ameliorated the autoimmune oophoritis. Thus, neonatal thymectomy abrogates the postnatal shift to a Th1-dominant pattern, and the resulting persistent neonatal-like Th2-dominant response is tightly associated with the development of postthymectomy autoimmune oophoritis. These results (i) suggest that the postnatal shift to the normal adult Th1/Th2 balance is established by a thymus-dependent process and (ii) raise the possibility that specific genetic defects, as yet to be determined, might mimic the effect of neonatal thymectomy in this model, impair the development of normal Th1/Th2 balance, and be a cause autoimmunity. These results hold implications for the pathogenesis and possibly for the therapy of autoimmune polyglandular failure in humans. (C) 1997 Academic Press. C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RP Maity, R (reprint author), NICHHD,SECT WOMENS HLTH,NIH,BETHESDA,MD 20892, USA. RI Rizzo, Luiz Vicente/B-4458-2009 NR 49 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD JUN PY 1997 VL 83 IS 3 BP 230 EP 236 DI 10.1006/clin.1997.4338 PG 7 WC Immunology; Pathology SC Immunology; Pathology GA XB138 UT WOS:A1997XB13800005 PM 9175911 ER PT J AU Quinn, TC AF Quinn, TC TI Editorial response: Diversity of Campylobacter species and its impact on patients infected with human immunodeficiency virus SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HOMOSEXUAL MEN; QUINOLONE RESISTANCE; UNITED-STATES; JEJUNI; ENTERITIS; ORGANISMS; HIV; FLUOROQUINOLONES; GASTROENTERITIS; HYOINTESTINALIS C1 NIAID,NIH,BETHESDA,MD 20892. NR 36 TC 8 Z9 8 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1997 VL 24 IS 6 BP 1114 EP 1117 DI 10.1086/513645 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XE366 UT WOS:A1997XE36600012 PM 9195066 ER PT J AU OBrien, PC Geller, NL AF OBrien, PC Geller, NL TI Interpreting tests for efficacy in clinical trials with multiple endpoints SO CONTROLLED CLINICAL TRIALS LA English DT Article C1 NHLBI,OFF BIOSTAT RES,BETHESDA,MD. RP OBrien, PC (reprint author), MAYO CLIN & MAYO FDN,BIOSTAT SECT,200 1ST ST SW,ROCHESTER,MN 55905, USA. NR 5 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD JUN PY 1997 VL 18 IS 3 BP 222 EP 227 DI 10.1016/S0197-2456(97)00049-4 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XF534 UT WOS:A1997XF53400003 PM 9204222 ER PT J AU Horne, MK AF Horne, MK TI Recombinant tissue plasminogen activator restores perfusion in meningococcal purpura fulminans SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE tissue plasminogen activator; disseminated intravascular coagulation; meningococcal purpura fulminans; thrombosis ID ACUTE MYOCARDIAL-INFARCTION; THROMBOLYTIC THERAPY; INHIBITOR-1 RP Horne, MK (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 1997 VL 25 IS 6 BP 909 EP 909 DI 10.1097/00003246-199706000-00005 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA XF524 UT WOS:A1997XF52400005 PM 9201041 ER PT J AU Mitton, KP Dzialoszynski, T Sanford, SE Trevithick, JR AF Mitton, KP Dzialoszynski, T Sanford, SE Trevithick, JR TI Cysteine and ascorbate loss in the diabetic rat lens prior to hydration changes SO CURRENT EYE RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 06, 1994 CL SARASOTA, FL SP Assoc Res Vis & Ophthalmol DE ascorbate; cataract; cysteine; dehydroascorbate; diabetes mellitus; rat ID MODELING CORTICAL CATARACTOGENESIS; GAMMA-CRYSTALLIN LEAKAGE; VITAMIN-E; DEHYDROASCORBIC ACID; ELECTROCHEMICAL DETECTION; MYOINOSITOL TRANSPORT; LIQUID-CHROMATOGRAPHY; GLUTATHIONE SYNTHESIS; EPITHELIAL-CELLS; STREPTOZOTOCIN AB Purpose. Glutathione (GSH) loss precedes vacuole formation in the diabetic rat lens, but the cause of this loss is not known. Cysteine availability is a rate limiting factor to glutathione biosynthesis in rat and human lenses but its concentration is not known; therefore free cysteine was measured prior to lens hydration in the diabetic rat lens. GSH can regenerate ascorbate from dehydroascorbate within the lens and potentially modulate the ascorbate pool; therefore ascorbate loss is also a possibility that has not been examined previously. Methods. Diabetes was induced in Wistar rats to provide a slowly progressing model of cortical cataract. Age-matched control rats were injected with buffer vehicle only. Lens condition was monitored by binocular slit-lamp microscope after pupil dilation. Lens cysteine and glutathione were measured in the same lens, while ascorbate and total ascorbate (ascorbate + dehydroascorbate) of the contralateral lens were quantified by high performance liquid chromatography electrochemical detection. The 1- and 2-week periods of diabetes were chosen as they both preceded lens hydration changes and Na+/K+ changes, to avoid leakage due to ruptured cell membranes. Results. Lens weights were not significantly different compared to controls at either the 1- or 2-week periods, and lenses were completely free of initial vacuole formation. Lens GSH concentration was diminished by 72% compared with controls after 1 week of diabetes and 74% after 2 weeks of diabetes. Lens free cysteine was decreased by 62% and 78% compared with controls after 1 and 2 weeks of diabetes, respectively. Total lens ascorbate concentration was decreased by 34% after 1 week of diabetes and 48% after 2 weeks of diabetes. Dehydroascorbate levels represented less than 10% of the total lens ascorbate pool in all experimental groups. GSH and ascorbate concentration were correlated after 1 week of diabetes (p < 0.005) and after 2 weeks of diabetes (p < 0.001). GSH and cysteine concentration were also correlated after 1 week of diabetes (p < 0.001) and after 2 weeks of diabetes (p < 0.001). Conclusions. Decreased free cysteine, in the diabetic rat lens, precedes hydration changes and vacuole formation, contributing to decreased glutathione content. While cysteine was not abundant in the lens, its concentration is greater than previously supposed. The lens ascorbate pool was also diminished prior to lens hydration. C1 UNIV WESTERN ONTARIO, DEPT BIOCHEM, FAC MED, CATARACT & ANTIOXIDANT RES LAB, LONDON, ON N6A 5C1, CANADA. NEI, LAB MECHANISMS OCULAR DIS, BETHESDA, MD 20892 USA. BOEHRINGER INGELHEIM CANADA LTD, BURLINGTON, ON, CANADA. FAC KINESIOL, EXERCISE BIOCHEM LAB, BURLINGTON, ON, CANADA. NR 35 TC 19 Z9 20 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0271-3683 EI 1460-2202 J9 CURR EYE RES JI Curr. Eye Res. PD JUN PY 1997 VL 16 IS 6 BP 564 EP 571 DI 10.1076/ceyr.16.6.564.5078 PG 8 WC Ophthalmology SC Ophthalmology GA XD185 UT WOS:A1997XD18500007 PM 9192165 ER PT J AU Makalowski, W Wolfsberg, TG AF Makalowski, W Wolfsberg, TG TI Genetics of disease SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Editorial Material RP Makalowski, W (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BLDG 38A,ROOM 8N-805,BETHESDA,MD 20894, USA. RI Makalowski, Wojciech/I-2843-2016 NR 0 TC 3 Z9 3 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD JUN PY 1997 VL 7 IS 3 BP 327 EP 327 DI 10.1016/S0959-437X(97)80144-X PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA XJ021 UT WOS:A1997XJ02100001 PM 9273046 ER PT J AU Long, EO Wagtmann, N AF Long, EO Wagtmann, N TI Natural killer cell receptors SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID MHC CLASS-I; HLA-C MOLECULES; T-LYMPHOCYTES; NK CLONES; RECOGNITION; LYSIS; SPECIFICITY; EXPRESSION; PROTECTION AB The specificity in the recognition of hematopoietic target cells by natural killer cells is primarily provided by inhibitory receptors and several such receptors have been identified in the past year. Surprisingly, the recognition of MHC class I molecules by inhibitory receptors on human natural killer cells involves two different types of receptors, one with Ig domains (killer cell inhibitory receptor), and another with C-type lectin domains (CD94-NKG2). Mouse natural killer cells recognize MHC class I molecules through the C-type lectin Ly49 receptors but also express a receptor, of unknown ligand specificity, that is related to the killer cell inhibitory receptor. RP Long, EO (reprint author), NIAID,IMMUNOGENET LAB,NIH,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 69 TC 71 Z9 73 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1997 VL 9 IS 3 BP 344 EP 350 DI 10.1016/S0952-7915(97)80080-5 PG 7 WC Immunology SC Immunology GA XF675 UT WOS:A1997XF67500008 PM 9203417 ER PT J AU Schwartz, RH AF Schwartz, RH TI T cell clonal energy SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID PROTEIN-TYROSINE PHOSPHORYLATION; INTERLEUKIN-2 PROMOTER; C-JUN; NUCLEAR FACTOR; LYMPHOCYTES-T; IN-VIVO; ACTIVATION; IL-2; STIMULATION; BINDING AB Recent experiments have elucidated two molecular mechanisms that may account for the failure of anergic T cell clones to initiate IL-2 gene transcription following TCR stimulation. First, a block has been identified in the ERK and JNK mitogen-activated protein kinase pathways; the block results from a failure to activate p21(ras). It leads to reduced induction of c-Fos and JunB proteins and to a failure to form and phosphorylate the activator protein (AP)-1 heterodimers required for IL-2 gene transcriptional activation. Second, repressor molecules (Nil-2-a and a molecule related to AP-1) have been characterized that dominantly inhibit IL-2 gene transcription. RP Schwartz, RH (reprint author), NIH,CELLULAR & MOL IMMUNOL LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 44 TC 204 Z9 204 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1997 VL 9 IS 3 BP 351 EP 357 DI 10.1016/S0952-7915(97)80081-7 PG 7 WC Immunology SC Immunology GA XF675 UT WOS:A1997XF67500009 PM 9203408 ER PT J AU Shores, EW Love, PE AF Shores, EW Love, PE TI TCR zeta chain in T cell development and selection SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID RECEPTOR SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; NEGATIVE SELECTION; POSITIVE SELECTION; MICE LACKING; BETA-CHAIN; CD4(+)CD8(+) THYMOCYTES; DEFICIENT MICE; ALPHA-BETA; IMMATURE THYMOCYTES AB Current data suggest that an important function of the multimeric structure of the TCR is to enable the assembly of structurally and functionally different forms of the TCR, the pre-TCR and alpha beta TCR complexes, at different stages in development. Four distinct TCR subunits (the CD3 gamma, delta, and epsilon chains and the zeta chain) contain signal transducing motifs; however, the zeta chain is notable for containing three of these elements. These motifs, especially those within the zeta chain, function to amplify signals generated by the TCR, and this property is especially critical during thymocyte selection. The results of several recent experiments argue that positive and negative selection of thymocytes may involve activation of distinct downstream signaling pathways. The outcome of thymocyte selection can also be influenced, however, by quantitative effects such as changes in ligand concentration or direct alteration of the TCR signaling potential. Recent studies pertaining to the kinetics of TCR-ligand interactions may provide insight into how signaling through the TCR can be regulated either quantitatively or qualitatively. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. RP Shores, EW (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892, USA. NR 96 TC 40 Z9 41 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1997 VL 9 IS 3 BP 380 EP 389 DI 10.1016/S0952-7915(97)80085-4 PG 10 WC Immunology SC Immunology GA XF675 UT WOS:A1997XF67500013 PM 9203416 ER PT J AU Margulies, DH AF Margulies, DH TI Interactions of TCRs with MHC-peptide complexes: A quantitative basis for mechanistic models SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL RECEPTOR; ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; ACTIVATION; AFFINITY; KINETICS; PROTEIN; ANTAGONISTS; RESPONSES AB The activation of T lymphocytes is initiated by the binding of MHC-peptide complexes on antigen-presenting cells to MHC-restricted, peptide specific TCRs. Significant progress has recently been made in understanding the structure of the TCR and in the direct quantitative examination of the primary binding interactions between MHC-peptide complexes and the TCR. Attempts to develop quantitative models for the differential activation of T cells by MHC-peptide ligands that differ subtly in their structure have largely been based on either the affinity of the MHC-peptide complexes for the TCR in question or on the dissociation kinetics of the MHC-peptide complex from the T cell. RP Margulies, DH (reprint author), NIAID,MOL BIOL SECT,IMMUNOL LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 55 TC 46 Z9 49 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1997 VL 9 IS 3 BP 390 EP 395 DI 10.1016/S0952-7915(97)80086-6 PG 6 WC Immunology SC Immunology GA XF675 UT WOS:A1997XF67500014 PM 9203420 ER PT J AU Burke, TR Yao, ZJ Smyth, MS Ye, B AF Burke, TR Yao, ZJ Smyth, MS Ye, B TI Phosphotyrosyl-based motifs in the structure-based design of protein-tyrosine kinase-dependent signal transduction inhibitors SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID SOLID-PHASE SYNTHESIS; SRC HOMOLOGY-2 DOMAIN; PROSTATIC ACID-PHOSPHATASE; CELL ANTIGEN RECEPTOR; HIGH-AFFINITY BINDING; TERMINAL SH2 DOMAIN; IRS-1 PTB DOMAIN; CRYSTAL-STRUCTURE; O-PHOSPHOTYROSINE; INSULIN-RECEPTOR AB Transmission of extracellular signals from the cell membrane to the nucleus depends on modification of phosphorylation states of intracellular proteins. Tyrosine, serine and threonine residues are the principal amino acid targets of these phosphorylation events, with tyrosyl residues being particularly important for pathways mediated by growth factors and cytokines. Aberrations in phosphotyrosyl (pTyr)-dependent signalling can contribute to a variety of diseases, including cancers, and for this reason selective modulation of pTyr-dependent signalling may afford new therapeutic approaches. The design of such therapeutics is facilitated by the functional compartmentalization of pTyr dependent signalling into three broad categories: (1) the generation of pTyr residues by protein-tyrosine kinases (PTK); (2) pTyr-dependent protein-protein associations mediated by binding modules such as Src homology 2 (SH2) and phosphotyrosine binding (PTB) domains and (3) the dephosphorylation of pTyr residues by protein-tyrosine phosphatases (PTPs). The pTyr residue itself, which is a unifying component of this signalling triad, potentially affords a starting point for the design of antagonists. In the PTK, SH2/PTB and PTP domain signalling environments, the pTyr residue plays unique roles by participating in interactions characteristic to each. Therefore, depending on which aspects of the L-4'-phosphotyrosyl structure are emphasized, and the manner in which they are utilized, inhibitors can be potentially directed against distinct legs of the signalling triad. This review will provide examples of this, by examining several series of compounds that have been prepared as inhibitors of either PTKs, SH2/PTB domains or PTPs. Also described will be how the pTyr structure can serve as a thematic Rosetta stone for the development of signal transduction inhibitors. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 176 TC 44 Z9 44 U1 0 U2 1 PU BENTHAM SCIENCE PUBL BV PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD JUN PY 1997 VL 3 IS 3 BP 291 EP 304 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XU769 UT WOS:A1997XU76900003 ER PT J AU Seamer, LC Bagwell, CB Barden, L Redelman, D Salzman, GC Wood, JCS Murphy, RF AF Seamer, LC Bagwell, CB Barden, L Redelman, D Salzman, GC Wood, JCS Murphy, RF TI Proposed new data file standard for flow cytometry, version FCS 3.0 SO CYTOMETRY LA English DT Article DE FCS 3.0; Data File Standard; flow cytometry AB In 1984, the first flow cytometry data file format was proposed as Flow Cytometry Standard 1.0 (FCS1.0). FCS 1.0 provided a uniform file format allowing data acquired on one computer to be correctly read and interpreted on other computers running a variety of operating systems. That standard was modified in 1990 and adopted by the Society of Analytical Cytology as FCS 2.0. Here, we report on an update of the FCS 2.0 standard which we propose to designate FCS 3.0. We have retained the basic four segment structure of earlier versions (HEADER, TEXT, DATA and ANALYSIS) in order to maintain analysis software compatibility, where possible. The changes described in this proposal include a method to collect fries larger than 100 megabytes (not possible in earlier versions of the standard), the Inclusion of international characters in the TEXT portions of the file, a method of verifying data integrity using a 16-bit cyclic redundancy check, and increased keyword ord support far cluster analysis and time acquisition. This report summarizes the work of the ISAC Data File Standards Committee. The complete and detailed FCS 3.0 standard is available through the ISAC office [Sherwood Group, 60 Revere Drive, Ste 500, Northbrook, IL 60062, phone: (847) 480-9080 ext. 231, fax: (847) 480-9282, E-mail: isac@sherwood-group.com] or through the internet at the ISAC WWW site, http://nucleus.immunol.washingtsn.edu/ISAC.html. (C) 1997 Wiley-Liss, Inc. C1 LOS ALAMOS NATL LAB,LOS ALAMOS,NM. VER SOFTWARE HOUSE,TOPSHAM,ME. NIH,BETHESDA,MD 20892. SIERRA CYTOMETRY,RENO,NV. COULTER CORP,HIALEAH,FL. CARNEGIE MELLON UNIV,PITTSBURGH,PA 15213. RP Seamer, LC (reprint author), UNIV NEW MEXICO,CANC RES & TREATMENT CTR,915 CAMINO SALUD NE,ALBUQUERQUE,NM 87131, USA. NR 5 TC 44 Z9 46 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0196-4763 J9 CYTOMETRY JI Cytometry PD JUN 1 PY 1997 VL 28 IS 2 BP 118 EP 122 DI 10.1002/(SICI)1097-0320(19970601)28:2<118::AID-CYTO3>3.0.CO;2-B PG 5 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XC495 UT WOS:A1997XC49500003 PM 9181300 ER PT J AU Reeder, JE Cox, C Wheeless, LL Flint, A Liebert, M Grossman, HB AF Reeder, JE Cox, C Wheeless, LL Flint, A Liebert, M Grossman, HB TI Variability of DNA analysis by image cytometry SO CYTOMETRY LA English DT Article DE DNA cytometry; bladder neoplasm; image analysis ID BLADDER-CANCER AB Two laboratories equipped with CAS 200 (Becton Dickinson Image Cytometry Systems, San Jose, CA) instruments participated in this study of variability of DNA analysis of bladder tumor specimens. Formalin fixed paraffin embedded specimens were disaggregated and centrifuged onto microscope slides from ten bladder tumor specimens and two specimens of normal urothelium. Sources of variability considered were Specimen, Slide, Run, Laboratory, and Error. Slides were systematically scanned and 200 cells measured followed by the operator selecting 100 nuclei with abnormal morphology. DNA. index (DI) and hyperdiploid fraction (HDF) were calculated from the DNA frequency distributions. For systematic sampling, 92% of the variability was due to Specimen indicating that differences in HDF values between specimens reflect biological differences. With selective sampling, only 67% of the variability in HDF is due to Specimen differences. Other factors, Laboratory, Error, and Laboratory x Specimen interaction each accounted for approximately 10% of the variability. Similarly variability of DI with selective sampling was also higher, and less specimen dependent than systematic sampling. It is important that sampling schemes and selection criteria be carefully documented in order to control variability. Enriched Cor selective) sampling for abnormal cells has the potential to increase sensitivity but specimen classification based on these measurements must depend on determination of the frequency of such cells in the total population. (C) 1997 Wiley-Liss, Inc. C1 UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. NCI,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. UNIV LAVAL,QUEBEC CITY,PQ,CANADA. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. UNIV OKLAHOMA,MED CTR,OKLAHOMA CITY,OK. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RP Reeder, JE (reprint author), UNIV ROCHESTER,DEPT PATHOL,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. OI Reeder, Jay/0000-0002-7125-6893 FU NCI NIH HHS [CA33148, CA56989] NR 4 TC 8 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0196-4763 J9 CYTOMETRY JI Cytometry PD JUN 1 PY 1997 VL 28 IS 2 BP 176 EP 180 DI 10.1002/(SICI)1097-0320(19970601)28:2<176::AID-CYTO12>3.0.CO;2-N PG 5 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XC495 UT WOS:A1997XC49500012 PM 9181309 ER PT J AU Krause, M Park, M Zhang, JM Yuan, J Harfe, B Xu, SQ Greenwald, I Cole, M Paterson, B Fire, A AF Krause, M Park, M Zhang, JM Yuan, J Harfe, B Xu, SQ Greenwald, I Cole, M Paterson, B Fire, A TI A C-elegans E Daughterless bHLH protein marks neuronal but not striated muscle development SO DEVELOPMENT LA English DT Article DE Caenorhabditis elegans; bHLH; myogenesis; neurogenesis; Daughterless; CeE/DA ID DROSOPHILA SEX DETERMINATION; LOOP-HELIX PROTEIN; NEMATODE CAENORHABDITIS-ELEGANS; DETERMINATION GENE DAUGHTERLESS; MYOD HOMOLOG HLH-1; DNA-BINDING; ACHAETE-SCUTE; GERM-LINE; SEQUENCE; E2A AB The E proteins of mammals, and the related Daughterless (DA) protein of Drosophila, are ubiquitously expressed helix-loop-helix (HLH) transcription factors that play a role in many developmental processes. We report here the characterization of a related C. elegans protein, CeE/DA, which has a dynamic and restricted distribution during development. CeE/DA is present embryonically in neuronal precursors, some of which are marked by promoter activity of a newly described Achaete-scute-like gene hlh-3. In contrast, we have been unable to detect CeE/DA in CeMyoD-positive striated muscle cells. In vitro gel mobility shift analysis detects dimerization of CeE/DA with HLH-3 while efficient interaction of CeE/DA with CeMyoD is not seen. These studies suggest multiple roles for CeE/DA in C. elegans development and provide evidence that both common and alternative strategies have evolved for the use of related HLH proteins in controlling cell fates in different species. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. PRINCETON UNIV,DEPT MOL BIOL,PRINCETON,NJ 08544. CARNEGIE INST WASHINGTON,DEPT EMBRYOL,BALTIMORE,MD 21210. JOHNS HOPKINS UNIV,BIOL GRAD PROGRAM,BALTIMORE,MD 21210. COLUMBIA UNIV,HOWARD HUGHES MED INST,DEPT BIOCHEM & MOL BIOPHYS,NEW YORK,NY 10032. RP Krause, M (reprint author), NIDDK,MOL BIOL LAB,NIH,BETHESDA,MD 20892, USA. OI Krause, Michael/0000-0001-6127-3940 FU NCI NIH HHS [CA55248]; NIGMS NIH HHS [GM15052, GM37602, R01 GM037706] NR 62 TC 78 Z9 80 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1997 VL 124 IS 11 BP 2179 EP 2189 PG 11 WC Developmental Biology SC Developmental Biology GA XH383 UT WOS:A1997XH38300007 PM 9187144 ER PT J AU Opdecamp, K Nakayama, A Nguyen, MTT Hodgkinson, CA Pavan, WJ Arnheiter, H AF Opdecamp, K Nakayama, A Nguyen, MTT Hodgkinson, CA Pavan, WJ Arnheiter, H TI Melanocyte development in vivo and in neural crest cell cultures: Crucial dependence on the Mitf basic-helix-loop-helix-zipper transcription SO DEVELOPMENT LA English DT Article DE DOPAchrome tautomerase; tyrosinase-related protein 2; Trp2; Kit; mast cell growth factor; Steel factor; stem cell factor; endothelin B receptor; endothelin 3 ID ENDOTHELIN-B RECEPTOR; STEEL FACTOR; W-LOCUS; GENE; MICROPHTHALMIA; MUTATIONS; MOUSE; MICE; SURVIVAL; EXPRESSION AB The more than 20 different Mitf mutations in the mouse are all associated with deficiencies in neural crest-derived melanocytes that range from minor functional disturbances with some alleles to complete absence of mature melanocytes with others. In the trunk region of wild-type embryos, Mitf-expressing cells that coexpressed the melanoblast marker Dct and the tyrosine kinase receptor Kit were found in the dorsolateral neural crest migration pathway In contrast, in embryos homozygous for an Mitf allele encoding a non-functional Mitf protein, Mitf-expressing cells were extremely rare, no Dct expression was ever found, and the number of Kit-expressing cells was much reduced. Wild-type neural crest cell cultures rapidly gave rise to cells that expressed Mitf and coexpressed Kit and Dct. With time in culture, Kit expression was increased, and pigmented, dendritic cells developed. Addition of the Kit ligand Mgf or endothelin 3 or a combination of these factors all rapidly increased the number of Dct-positive cells. Cultures from Mitf mutant embryos initially displayed Mitf-positive cells similar in numbers and Kit-expression as did wild-type cultures. However, Kit expression did not increase with time in culture and the mutant cells never responded to Mgf or endothelin 3, did not express Dct, and never showed pigment. In fact, even Mitf expression was rapidly lost. The results suggest that Mitf first plays a role in promoting the transition of precursor cells to melanoblasts and subsequently, by influencing Kit expression, melanoblast survival. C1 NIH,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NINCDS,LAB DEV NEUROGENET,NIH,BETHESDA,MD 20892. NR 40 TC 200 Z9 201 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 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1997 VL 124 IS 12 BP 2377 EP 2386 PG 10 WC Developmental Biology SC Developmental Biology GA XH384 UT WOS:A1997XH38400010 PM 9199364 ER PT J AU Pan, DA Lillioja, S Kriketos, AD Milner, MR Baur, LA Bogardus, C Jenkins, AB Storlien, LH AF Pan, DA Lillioja, S Kriketos, AD Milner, MR Baur, LA Bogardus, C Jenkins, AB Storlien, LH TI Skeletal muscle triglyceride levels are inversely related to insulin action SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; GLUCOSE-UPTAKE; GLYCOGEN-SYNTHESIS; PIMA-INDIANS; HIGH-FAT; RESISTANCE; METABOLISM; EXERCISE; RATS; DISPOSAL AB In animal studies, increased amounts of triglyceride associated with skeletal muscle (mTG) correlate with reduced skeletal muscle and whole body insulin action. The aim of this study was to test this relationship in humans. Subjects were 38 nondiabetic male Pima Indians (mean age 28 +/- 1 years). Insulin sensitivity at physiological (M) and supraphysiological (MZ) insulin levels was assessed by the euglycemic clamp. Lipid and carbohydrate oxidation were determined by indirect calorimetry before and during insulin administration. mTG was determined in vastus lateralis muscles obtained by percutaneous biopsy. Percentage of body fat (mean 29 +/- 1%, range 14-44%) was measured by underwater weighing. In simple regressions, negative relationships were found between mTG (mean 5.4 +/- 0.3 pmol/g, range 1.3-1.9 mu mol/g) and log(10)M (r = -0.53, P less than or equal to 0.001), MZ (r = -0.44, P = 0.006), and nonoxidative glucose disposal (r = -0.48 and -0.47 at physiological and supraphysiological insulin levels, respectively, both P = 0.005) but not glucose or lipid oxidation. mTG was not related to any measure of adiposity. In multiple regressions, measures of insulin resistance (log(10)M, MZ, log(10)[fasting insulin]) were significantly related to mTG independent of all measures of obesity (percentage of body fat, BMI, waist-to-thigh ratio). In turn, all measures of obesity were related to the insulin resistance measures independent of mTG. The obesity measures and mTG accounted for similar proportions of the variance in insulin resistance in these relationships. The results suggest that in this human population, as in animal models, skeletal muscle insulin sensitivity is strongly influenced by local supplies of triglycerides, as well as by remote depots and circulating lipids. The mechanism(s) underlying the relationship between mTG and insulin action on skeletal muscle glycogen synthesis may be central to an understanding of insulin resistance. C1 UNIV WOLLONGONG, DEPT BIOMED SCI, WOLLONGONG, NSW 2522, AUSTRALIA. ROYAL PRINCE ALFRED HOSP, DEPT ENDOCRINOL, CAMPERDOWN, NSW 2050, AUSTRALIA. NIDDKD, NUTR SECT, PHOENIX, AZ USA. RI Lillioja, Stephen/A-8185-2012; Jenkins, Arthur/D-4533-2012; OI Lillioja, Stephen/0000-0001-5333-5240 NR 49 TC 756 Z9 787 U1 6 U2 39 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1997 VL 46 IS 6 BP 983 EP 988 DI 10.2337/diabetes.46.6.983 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XA240 UT WOS:A1997XA24000009 PM 9166669 ER PT J AU Perseghin, G Ghosh, S Gerow, K Shulman, GI AF Perseghin, G Ghosh, S Gerow, K Shulman, GI TI Metabolic defects in lean nondiabetic offspring of NIDDM parents - A cross-sectional study SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; NUCLEAR-MAGNETIC-RESONANCE; NONESTERIFIED FATTY-ACIDS; MUSCLE GLUCOSE-TRANSPORT; INVIVO INSULIN ACTION; PIMA-INDIANS; INCREASED RISK; MAJOR-GENE; 1ST-DEGREE RELATIVES; SEGREGATION ANALYSIS AB First-degree relatives of NIDDM patients have an similar to 40% lifetime risk of developing diabetes, and insulin resistance is the best predictor. However, insulin resistance is altered by many other factors, including age, diet, exercise, and medications. To investigate the metabolic and endocrine alterations associated with insulin resistance when all the above confounding factors are excluded, we examined the first phase of insulin secretion and insulin sensitivity in 49 white normoglycemic (4.99 +/- 0.51 vs. 4.95 +/- 0.41 mmol/l) nonexercising lean (BMI, 24 +/- 3 vs. 23 +/- 2 kg/m(2); 105 +/- 3 vs. 104 +/- 3% of ideal body weight) offspring of NIDDM patients. These subjects were compared with 29 matched healthy control subjects by means of an intravenous glucose bolus (0.3 g/kg body wt), immediately followed by a euglycemic-hyperinsulinemic (similar to 420 pmol/l) clamp, along with lipid and amino acid profiles. The offspring showed fasting hyperinsulinemia (40.6 +/- 15.8 vs. 30.9 +/- 13.6 pmol/l; P = 0.005) and higher free fatty acid (FFA) levels (582 +/- 189 vs. 470 +/- 140 pmol/l; P = 0.007), whereas triglycerides, total cholesterol, and HDL and LDL cholesterol levels were comparable with those of control subjects. Alanine (320 +/- 70 vs. 361 +/- 73 pmol/l; P = 0.017), serine (P = 0.05), and glutamine and glycine (P = 0.02) were lower in the offspring than in the control subjects, whereas branched-chain amino acids (343 +/- 54 vs. 357 +/- 54 mu mol/l; P = 0.28) were not different. Insulin sensitivity was lower (4.86 +/- 1.65 vs. 6.17 +/- 1.56 mg . kg(-1) . min(-1); P = 0.001), and an inverse correlation with fasting FFAs in the offspring (adjusted R-2 = 0.21, P = 0.0005), but not in control subjects (adjusted R-2 = 0.03, P = 0.368), was found. Because insulin sensitivity in the offspring appeared to be a mixture of three distributions, they were subdivided into three subgroups: very low, low, and normal insulin sensitivity (20, 47, and 33%, respectively). The same alterations in amino acid and FFA metabolism were observed in the very low and low subgroups but not in the normal subgroup. The first phase of insulin secretion appeared to compensate significantly for insulin resistance in the low subgroup versus the normal subgroup and controls, but was inappropriately low in the subgroup with very low insulin sensitivity considering its degree of insulin resistance. In conclusion, lean insulin-resistant offspring of NIDDM parents showed 1) trimodal distribution of insulin sensitivity, 2) high fasting plasma FFA concentrations, 3) an inverse correlation between insulin sensitivity and FFA concentration, 4) low plasma gluconeogenic amino acid concentrations, and 5) defective insulin secretion when related to insulin sensitivity in the subgroup of very resistant offspring. These results suggest that, in this white population, insulin sensitivity may be determined by a single major gene and that alterations in FFA metabolism may play a role in the pathogenesis of NIDDM. C1 YALE UNIV, SCH MED, DEPT INTERNAL MED, NEW HAVEN, CT 06520 USA. NIH, NATL CTR HUMAN GENOME RES, LAB GENE TRANSFER, BETHESDA, MD 20892 USA. OI PERSEGHIN, Gianluca/0000-0002-3024-0457 FU NCRR NIH HHS [M01 RR-00125]; NIDDK NIH HHS [R01 DK040936, R01 DK-49230, P30 DK-45735] NR 62 TC 229 Z9 236 U1 2 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUN PY 1997 VL 46 IS 6 BP 1001 EP 1009 DI 10.2337/diabetes.46.6.1001 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XA240 UT WOS:A1997XA24000012 PM 9166672 ER PT J AU Bennett, PH AF Bennett, PH TI Primary prevention of NIDDM: A practical reality SO DIABETES-METABOLISM REVIEWS LA English DT Article ID DEPENDENT DIABETES-MELLITUS; IMPAIRED GLUCOSE-TOLERANCE; INSULIN-RESISTANCE; PIMA-INDIANS; PHYSICAL-ACTIVITY; WEIGHT-LOSS; IMPROVEMENT; DIET; DETERMINANTS; OBESITY C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,NIH,PHOENIX,AZ. NR 23 TC 9 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0742-4221 J9 DIABETES METAB REV JI Diabetes-Metab. Rev. PD JUN PY 1997 VL 13 IS 2 BP 105 EP 111 DI 10.1002/(SICI)1099-0895(199706)13:2<105::AID-DMR182>3.0.CO;2-P PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XH420 UT WOS:A1997XH42000006 PM 9222122 ER PT J AU Knowler, WC Hanson, RL AF Knowler, WC Hanson, RL TI Genomic scan for genetic markers linked to diabetes in Pima Indians. SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIH,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 22 EP 22 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300023 ER PT J AU Valencia, ME Esparza, J Ravussin, E Bennett, PH Fox, C Schulz, L AF Valencia, ME Esparza, J Ravussin, E Bennett, PH Fox, C Schulz, L TI Non insulin dependent diabetes mellitus and obesity in Mexican Pima Indians. SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDK,NIH,PHOENIX,AZ. CTR INVEST ALIMENTAC & DESARROLLO,SONORA,MEXICO. UNIV WISCONSIN,MILWAUKEE,WI 53201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 53 EP 53 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300053 ER PT J AU Notkins, AL Lu, J Xie, H Zhang, B Li, Q Lan, MS AF Notkins, AL Lu, J Xie, H Zhang, B Li, Q Lan, MS TI Comparison of protein tyrosine phosphatases: Expression, processing and antigenic determinants SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 77 EP 77 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300077 ER PT J AU Jun, HS Han, HS Yoon, CS Kim, A Bae, HY Utsugi, T Kim, SJ Yoon, JW AF Jun, HS Han, HS Yoon, CS Kim, A Bae, HY Utsugi, T Kim, SJ Yoon, JW TI Role of TGF beta secreted from a CD4(+) suppressor T cell clone in the prevention of IDDM. SO DIABETOLOGIA LA English DT Meeting Abstract C1 UNIV CALGARY,CALGARY,AB,CANADA. AJOU UNIV,SUWON 441749,SOUTH KOREA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 123 EP 123 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300122 ER PT J AU Eastman, RC Cowie, CC Harmon, J AF Eastman, RC Cowie, CC Harmon, J TI Potential cost-effectiveness of primary prevention of insulin-dependent diabetes mellitus. SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 146 EP 146 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300147 ER PT J AU Smith, U Wang, LM Lonnroth, P Wesslau, C Pierce, JH Rondinone, CM AF Smith, U Wang, LM Lonnroth, P Wesslau, C Pierce, JH Rondinone, CM TI IRS-2 is the main docking protein for PI 3-kinase in adipocytes from NIDDM patients. SO DIABETOLOGIA LA English DT Meeting Abstract C1 SAHLGRENS UNIV HOSP,DEPT INTERNAL MED,LUNDBERG LAB DIABET RES,S-41345 GOTHENBURG,SWEDEN. NCI,DEPT CELL & MOL BIOL,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 147 EP 147 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300146 ER PT J AU Seissler, J Morgenthaler, NG Steinbrenner, H KhooMorgenthaler, UY Lan, MS Notkins, AL Scherbaum, WA AF Seissler, J Morgenthaler, NG Steinbrenner, H KhooMorgenthaler, UY Lan, MS Notkins, AL Scherbaum, WA TI Diagnostic sensitivity of autoantibodies to tyrosine phosphatase-like proteins IA-2 and IA-2 beta in IDDM and NIDDM SO DIABETOLOGIA LA English DT Meeting Abstract C1 UNIV LEIPZIG,DEPT INTERNAL MED 3,D-7010 LEIPZIG,GERMANY. NIH,ORAL MED LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 284 EP 284 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300282 ER PT J AU Ellis, TM Schatz, D Lan, MS Ottendorfer, E Wasserfall, C Notkins, AL Maclaren, NK Atkinson, MA AF Ellis, TM Schatz, D Lan, MS Ottendorfer, E Wasserfall, C Notkins, AL Maclaren, NK Atkinson, MA TI Relationship between humoral and cellular immunity to IA-2 in insulin dependent diabetes SO DIABETOLOGIA LA English DT Meeting Abstract C1 UNIV FLORIDA,GAINESVILLE,FL. NIH,BETHESDA,MD 20892. RI wasserfall, clive/J-9078-2012 OI wasserfall, clive/0000-0002-3522-8932 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 323 EP 323 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300320 ER PT J AU Egan, JM DeOre, K Greig, N Holloway, H Wang, Y Perfetti, R AF Egan, JM DeOre, K Greig, N Holloway, H Wang, Y Perfetti, R TI Glucagon-like peptide-1 restores acute phase insulin release to aged rats SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIA,DIABET SECT,GRC,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 505 EP 505 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300501 ER PT J AU Pratley, RE Thompson, DB Prochazka, M Baier, L Mott, D Ravussin, E Sakul, H Foroud, T Ehm, MG Burns, DK Garvey, WT Knowler, W Bennett, PH Bogardus, C AF Pratley, RE Thompson, DB Prochazka, M Baier, L Mott, D Ravussin, E Sakul, H Foroud, T Ehm, MG Burns, DK Garvey, WT Knowler, W Bennett, PH Bogardus, C TI Genome scan for linkage to pre-diabetic traits in Pima Indians SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIH,PHOENIX,AZ. SEQUANA,LA JOLLA,CA. INDIANA UNIV,INDIANAPOLIS,IN 46204. GLAXO,RES TRIANGLE PK,NC. MUSC,CHARLESTON,SC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 615 EP 615 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300610 ER PT J AU Ghosh, S Hauser, ER Magnuson, VL Ally, DS Valle, T Watanabe, RM Nylund, SJ Kohtamaki, K Bergman, RN Tuomilehto, J Collins, FS Boehnke, M AF Ghosh, S Hauser, ER Magnuson, VL Ally, DS Valle, T Watanabe, RM Nylund, SJ Kohtamaki, K Bergman, RN Tuomilehto, J Collins, FS Boehnke, M TI Multipoint linkage analysis of NIDDM in 534 Finnish families in the fusion study. SO DIABETOLOGIA LA English DT Meeting Abstract C1 NCHGR,BETHESDA,MD. UNIV MICHIGAN,ANN ARBOR,MI 48109. NATL PUBL HLTH INST,HELSINKI,FINLAND. USC,SCH MED,LOS ANGELES,CA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 617 EP 617 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300611 ER PT J AU Xia, X Bogardus, C Prochazka, M AF Xia, X Bogardus, C Prochazka, M TI Analysis of type-1 protein phosphatase glycogen-targeting subunit mRNA in skeletal muscle of Pima Indians SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDK,CDNS,NIH,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 621 EP 621 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300615 ER PT J AU Baier, LJ Wiedrich, C Hanson, R Bogardus, C AF Baier, LJ Wiedrich, C Hanson, R Bogardus, C TI Analysis of a Met->Ile substitution in the regulatory subunit of PI3-K in Pima Indians SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIH,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 623 EP 623 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300618 ER PT J AU Baier, LJ Dobberfuhl, A Thuillez, P Bogardus, C AF Baier, LJ Dobberfuhl, A Thuillez, P Bogardus, C TI Association of a variant of the vitamin D binding protein with plasma glucose levels in non-diabetic Pima Indians SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIH,PHOENIX,AZ. RI Dobberfuhl, Angela/C-9450-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 627 EP 627 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300622 ER PT J AU Knowler, WC Sartor, G Melander, A Schersten, B AF Knowler, WC Sartor, G Melander, A Schersten, B TI Glucose tolerance and mortality, including a substudy of tolbutamide treatment SO DIABETOLOGIA LA English DT Article DE impaired glucose tolerance; mortality; tolbutamide; ischaemic heart disease; clinical trial ID CORONARY HEART-DISEASE; DIABETES-MELLITUS; MEN; DEATH; WHITEHALL; GLYCEMIA AB Mortality according to glucose tolerance was studied to determine the prognosis of impaired glucose tolerance. Among 2500 persons tested in a community screening programme in 1962-1965 and followed-up for mortality to the end of 1987, age-sex-adjusted mortality rates were 37.9 +/- 1.9, 53.6 +/- 4.2, and 70.1 +/- 3.6 deaths per 1000 person-years (+/- SE) in those with normal glucose tolerance, impaired glucose tolerance, and diabetes by World Health Organization criteria at baseline. Age-sex-adjusted mortality rates due to ischaemic heart disease were 14.3 +/- 1.1, 16.3 +/- 2.4, and 25.8 +/- 2.0 deaths per 1000 person-years, respectively. Using criteria predating those of the World Health Organization 147 men with abnormal glucose tolerance were entered into a randomized clinical trial in which 49 were treated with tolbutamide for approximately 10 years. Those treated had lower mortality rates from all causes (mortality rate ratio = 0.66, 95 % confidence interval = 0.39, 1.10) and from ischaemic heart disease (mortality rate ratio = 0.42, 95 % confidence interval = 0.16, 1.12) than those not receiving tolbutamide. Thus mortality rates are increased in persons with impaired glucose tolerance and diabetes, and the small clinical trial suggests that tolbutamide may be beneficial in men with abnormal glucose tolerance. C1 LUND UNIV,DEPT COMMUNITY HLTH SCI,LUND,SWEDEN. CENT HOSP HALMSTAD,DEPT INTERNAL MED,HALMSTAD,SWEDEN. MALMO UNIV HOSP,MED RES CTR,NEPI FDN,MALMO,SWEDEN. RP Knowler, WC (reprint author), NIDDK,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. NR 20 TC 39 Z9 40 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 IS 6 BP 680 EP 686 DI 10.1007/s001250050734 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XF835 UT WOS:A1997XF83500010 PM 9222648 ER PT J AU Thompson, DB Norman, RA Ravussin, E Knowler, WC Bennett, P Bogardus, C AF Thompson, DB Norman, RA Ravussin, E Knowler, WC Bennett, P Bogardus, C TI Association of the Gln223Arg polymorphism in the leptin receptor gene with plasma leptin levels, insulin secretion and NIDDM in Pima Indians. SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDK,NIH,PHOENIX,AZ. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 693 EP 693 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300686 ER PT J AU Norman, RA Tataranni, PA Bogardus, C Ravussin, E AF Norman, RA Tataranni, PA Bogardus, C Ravussin, E TI Autosomal genome-scan for genetic linkages to energy metabolism in Pima Indians SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 701 EP 701 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300694 ER PT J AU Norman, RA Thompson, DB Bogardus, C Ravussin, E AF Norman, RA Thompson, DB Bogardus, C Ravussin, E TI Autosomal genome-wide scan for obesity susceptibility genes in Pima Indians SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 703 EP 703 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300697 ER PT J AU Salbe, AD Fontvieille, AM Pettitt, DJ Ravussin, E AF Salbe, AD Fontvieille, AM Pettitt, DJ Ravussin, E TI Maternal diabetes status does not influence energy expenditure nor physical activity in 5-y old children SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDK,NIH,CDNS,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 766 EP 766 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300759 ER PT J AU Valle, T Langefeld, CD Hauser, ER Watanabe, RM Ghosh, S Kohtamaki, K Forsen, T Tuomilehto, J Buchanan, TA Eriksson, JG AF Valle, T Langefeld, CD Hauser, ER Watanabe, RM Ghosh, S Kohtamaki, K Forsen, T Tuomilehto, J Buchanan, TA Eriksson, JG TI Association between birth weight and adult metabolic profile in the offspring of NIDDM subjects SO DIABETOLOGIA LA English DT Meeting Abstract C1 NATL PUBL HLTH INST,HELSINKI,FINLAND. UNIV MICHIGAN,ANN ARBOR,MI 48109. NCHGR,BETHESDA,MD. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90089. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 842 EP 842 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300835 ER PT J AU Snitker, S Hellmer, J Boschmann, M Odeleye, OE Monroe, MB Ravussin, E AF Snitker, S Hellmer, J Boschmann, M Odeleye, OE Monroe, MB Ravussin, E TI In situ lipolytic response to physiologic stressors and isoproterenol in Pima Indians and Caucasians. SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDK,CDNS,NIH,PHOENIX,AZ. ROCKEFELLER UNIV,NEW YORK,NY 10021. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 958 EP 958 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300952 ER PT J AU Tataranni, PA Mingrone, G Cizza, G Greco, AV Castagneto, M Gasbarrini, G AF Tataranni, PA Mingrone, G Cizza, G Greco, AV Castagneto, M Gasbarrini, G TI Hypoleptinemia in post-obese women: A possible cause for relapse of body weight. SO DIABETOLOGIA LA English DT Meeting Abstract C1 NICHHD,DEB,NIH,BETHESDA,MD. NIDDK,CDNS,NIH,PHOENIX,AZ. CATHOLIC UNIV,ROME,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 1038 EP 1038 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12301031 ER PT J AU Salbe, AD Nicolson, M Ravussin, E AF Salbe, AD Nicolson, M Ravussin, E TI Total energy expenditure and physical activity level correlate with fasting plasma leptin in children. SO DIABETOLOGIA LA English DT Meeting Abstract C1 AMGEN INC,THOUSAND OAKS,CA 91320. NIDDK,NIH,CDNS,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 1044 EP 1044 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12301036 ER PT J AU Tataranni, PA Nicolson, M Snitker, S Pratley, RE Ravussin, E AF Tataranni, PA Nicolson, M Snitker, S Pratley, RE Ravussin, E TI Twenty-four-hour respiratory quotient is negatively related to plasma leptin concentration in Pima males. SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDK,CDNS,NIH,PHOENIX,AZ. AMGEN INC,THOUSAND OAKS,CA 91320. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 1046 EP 1046 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12301039 ER PT J AU Bhathena, SJ Michaelis, OE Hansen, CT AF Bhathena, SJ Michaelis, OE Hansen, CT TI The effect of dietary carbohydrates and lipid lowering agent, probucol, on opioid peptide receptors in SHR/N-cp rat - a genetic model of obesity SO DIABETOLOGIA LA English DT Meeting Abstract C1 ARS,BELTSVILLE,MD. NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 1506 EP 1506 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12301498 ER PT J AU Correa, MLC Wajchenberg, BL LeRoith, D GiannellaNeto, D AF Correa, MLC Wajchenberg, BL LeRoith, D GiannellaNeto, D TI Effect of glycated fibronectin on proliferation and IGFBP4 secretion by cultured human aortic smooth muscle cells (SMC). SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDK,DIABET BRANCH,NIH,BETHESDA,MD. UNIV FED SAO PAULO,SCH MED,DIV ENDOCRINOL,SAO PAULO,BRAZIL. UNIV FED SAO PAULO,SCH MED,FDN HEMOCTR,SAO PAULO,BRAZIL. RI Correa-Giannella, Maria Lucia/D-2003-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 1699 EP 1699 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12301689 ER PT J AU Robison, WG Jacot, JL Glover, JP Basso, MD Hohman, TC AF Robison, WG Jacot, JL Glover, JP Basso, MD Hohman, TC TI Diabetic-like retinopathy: Early and late intervention therapies in the galactose-fed rat model. SO DIABETOLOGIA LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. WYETH AYERST LABS,PRINCETON,NJ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1997 VL 40 SU 1 BP 1930 EP 1930 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12301920 ER PT J AU Miele, L CordellaMiele, E Xing, MZ Frizzell, R Mukherjee, AB AF Miele, L CordellaMiele, E Xing, MZ Frizzell, R Mukherjee, AB TI Cystic fibrosis gene mutation (Delta F-508) is associated with an intrinsic abnormality in Ca2+-induced arachidonic acid release by epithelial cells SO DNA AND CELL BIOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; UNSATURATED FATTY-ACIDS; CHLORIDE CHANNELS; ENDOTHELIAL-CELLS; AIRWAY EPITHELIA; MUSCLE-CELLS; REGULATED CL; PHOSPHOLIPASE-A2; ACTIVATION; CFTR AB The mechanism(s) of chronic airway inflammation in cystic fibrosis (CF) remains poorly understood, We studied Ca2+-induced release of arachidonic acid (AA), a precursor of proinflamatory lipid mediators, in epithelial cell lines with the Delta F-508 mutation in CF transmembrane conductance regulator (CFTR) gene and in those lacking this mutation or cells in which this mutation was corrected by a functional CFTR gene transfer, We found that: (i) the mutant cells manifested an abnormally high Ca2+-induced AA release as compared to controls, (ii) AA release appeared to be catalyzed by a phospholipase A(2) (PLA(2)) but not by phospholipase C followed by diacylglycerol lipase, and (iii) either correction of the CFTR-mutation or inhibition of PLA(2) activity rectified this AA release abnormality, Taken together, our results suggest that CFTR mutation is associated with an intrinsic abnormality in AA release by epithelial cells carrying the Delta F-508 mutation and suggest that the mechanism of chronic airway inflammation in CF, at least in part, involves this abnormality, These results also partly explain the effectiveness of high-dose ibuprofen therapy in arresting the progression of destructive lung disease in CF. Furthermore, they raise the possibility that correction of abnormal AA release by inhibiting PLA(2) activity may improve the therapeutic benefits of ibuprofen. C1 NICHHD,HERITABLE DISORDERS BRANCH,SECT DEV GENET,NIH,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH MED,BYRON E HELMS DEPT CELL BIOL & PHYSIOL,PITTSBURGH,PA 15261. NR 58 TC 40 Z9 40 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUN PY 1997 VL 16 IS 6 BP 749 EP 759 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA XJ160 UT WOS:A1997XJ16000008 PM 9212168 ER PT J AU Celerin, M Gilpin, AA Dossantos, G Laudenbach, DE Clarke, MW Beushausen, S AF Celerin, M Gilpin, AA Dossantos, G Laudenbach, DE Clarke, MW Beushausen, S TI Kinesin light chain in a eubacterium SO DNA AND CELL BIOLOGY LA English DT Article ID BOVINE BRAIN KINESIN; DIVISION PROTEIN FTSZ; ESCHERICHIA-COLI; PEST HYPOTHESIS; BINDING-PROTEIN; MOTOR PROTEINS; HEAVY-CHAIN; IDENTIFICATION; SEQUENCES; GENE AB A eubacterial homolog of a kinesin light chain gene has been isolated and characterized from the cyanobacterium Plectonema boryanum. Although the eubacterial and eukaryotic kinesin light chains are highly similar in amino acid sequence, the eubacterial sequence differs in several distinguishing structural features, including the absence of a putative PEST domain and the presence of additional highly conserved imperfect tandem repeats. Two soluble kinesin light chain antigens have been identified from whole-cell lysates by immunoblot analysis, Attempts to identify a canonical kinesin heavy-chain gene or protein were unsuccessful, suggesting that a kinesin heavy chain may be absent or unnecessary for kinesin light-chain function in this eubacterium. Our findings establish that certain basal elements of eukaryotic cellular transport appear to be resident in eubacteria. We discuss the possibility that the eukaryotic kinesin light chain was acquired by lateral gene transfer. C1 UNIV WESTERN ONTARIO,DEPT PLANT SCI,LONDON,ON N6A 5B7,CANADA. UNIV WESTERN ONTARIO,LONDON,ON N6A 5C1,CANADA. NINCDS,LAB NEUROL,NIH,BETHESDA,MD 20892. NR 47 TC 4 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUN PY 1997 VL 16 IS 6 BP 787 EP 795 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA XJ160 UT WOS:A1997XJ16000012 PM 9212172 ER PT J AU Nims, RW Prough, RA Jones, CR Stockus, DL Dragnev, KH Thomas, PE Lubet, RA AF Nims, RW Prough, RA Jones, CR Stockus, DL Dragnev, KH Thomas, PE Lubet, RA TI In vivo induction and in vitro inhibition of hepatic cytochrome P450 activity by the benzodiazepine anticonvulsants clonazepam and diazepam SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID RAT-LIVER; N-NITROSODIETHYLAMINE; PLEIOTROPIC RESPONSE; EPOXIDE HYDROLASE; MESSENGER-RNAS; CYP2B INDUCTION; F344/NCR RAT; MOUSE-LIVER; DEALKYLATION; HEPATOCYTES AB The ability of the benzodiazepines, as a chemical class, to cause the induction and/or inhibition of cytochromes P450 has not been well characterized, In the present study, the induction of the cytochrome P450 2B subfamily (CYP2B) in vivo and the inhibition of CYP2B activity in vitro by selected benzodiazepines was examined in hepatic tissues derived from male F344/NCr rats, Initial studies of the in vivo induction or in vitro inhibition of benzyloxyresorufin O-dealkylation activity revealed that both clonazepam and diazepam were relatively effective in vivo inducers of CYP2B when administered in the diet at 500 ppm for 5 days and also were fairly potent inhibitors of the activity of these hemoproteins in vitro, Oxazepam, in contrast, was ineffective as an inducer or an inhibitor of this activity, Further studies were performed to characterize the subfamily selectivity of the P450 induction and inhibition displayed by clonazepam. Specifically, microsomes from rats treated with clonazepam (1000 or 1800 ppm in the diet for 5 days) were found to be highly induced with respect to catalytic activities mediated by CYP2B, including benzyloxyresorufin and pentoxyresorufin O-dealkylation or testosterone 16 beta-hydroxylation, bur other CYP proteins were minimally induced, In addition to inducing the CYP2B subfamily, clonazepam also induced the RNA encoding other drug metabolizing enzymes (e.g., epoxide hydrolase and the glutathione S-transferase alpha-subfamily) that are typically induced by phenobarbital-type inducers. Finally, clonazepam proved to be a potent noncompetitive or ''mixed-type'' competitive inhibitor of catalytic activities mediated by CYP2B, but not by other CYP proteins (e.g. CYP2A, CYP3A) in microsomes derived from phenobarbital-pretreated rats. C1 NCI,CHEM SECT,COMPARAT CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,BETHESDA,MD 20892. UNIV LOUISVILLE,SCH MED,DEPT BIOCHEM & MOL BIOL,LOUISVILLE,KY 40292. RUTGERS STATE UNIV,COLL PHARM,DEPT BIOL CHEM,PISCATAWAY,NJ 08855. FU NIEHS NIH HHS [ES05022]; NIGMS NIH HHS [R01 GM 44982] NR 48 TC 25 Z9 25 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUN PY 1997 VL 25 IS 6 BP 750 EP 756 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XD831 UT WOS:A1997XD83100013 PM 9193878 ER PT J AU Samii, A Canos, M Ikoma, K Wassermann, EM Hallet, M AF Samii, A Canos, M Ikoma, K Wassermann, EM Hallet, M TI Absence of facilitation or depression of motor evoked potentials after contralateral homologous muscle activation SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE contralateral; exercise; facilitation; depression; motor evoked potentials; transcranial magnetic stimulation; motor cortex ID MAGNETIC STIMULATION; RESPONSES; HIPPOCAMPUS; FATIGUE; CORTEX; EMG AB We have previously described post-exercise facilitation and post-exercise depression of motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS). To determine the presence of post-exercise facilitation after exercise of a contralateral muscle, MEPs were recorded from the resting right extensor carpi radialis (ECR) muscle while the left ECR muscle was activated, then immediately after brief left ECR activation, and, finally, immediately after brief right ECR activation. We repeated the experiment using the first dorsal interosseous (FDI) muscle. To determine the presence of post-exercise depression after exercise of a contralateral muscle, MEPs were recorded from the right ECR after prolonged exercise of the left ECR, followed by right ECR recording after its fatigue. The mean MEP amplitudes from the right ECR and the right FDI after brief activation were 187% and 266% of their pre-exercise values, respectively. There were no significant changes in MEPs recorded from the right ECR or FDI muscles during or immediately after brief activation of their left counterparts. The mean amplitude of MEPs recorded from the right ECR after it fatigued was approximately half the pre-exercise value, but there was no significant change in MEPs recorded from the right ECR after prolonged exercise of the left ECR. Therefore, neither post-exercise facilitation nor post-exercise depression occurred after contralateral homologous muscle exercise. (C) 1997 Elsevier Science Ireland Ltd. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. NR 15 TC 33 Z9 33 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD JUN PY 1997 VL 105 IS 3 BP 241 EP 245 DI 10.1016/S0924-980X(97)00014-3 PG 5 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA XF637 UT WOS:A1997XF63700009 PM 9216493 ER PT J AU Chen, N Chrambach, A AF Chen, N Chrambach, A TI The resolution between two native proteins and between their sodium dodecyl sulfate-complexes in agarose and polyacrylamide gel electrophoresis SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT Australian-Electrophoresis-Society Annual Conference, at Chromatography 96 - Separation Sciences CY JUL 09-11, 1996 CL ROSEHILL, AUSTRALIA SP Austr Electrophoresis Soc DE agarose; resolution; polyacrylamide gel electrophoresis ID FERGUSON PLOTS; DNA FRAGMENTS AB Commercial gal electrophoresis apparatus with intermittent fluorescence scanning of the migration path (HPGE-1000 apparatus, LabIntelligence) makes it possible to measure band width and migration distance as a function of the duration of electrophoresis. As a result, resolution can be evaluated quantitatively and therefore different gel media can be compared objectively. The resolution of fluorescein carboxylate labeled conalbumin (molecular mass 86 kDa) and soybean trypsin inhibitor (22.7 KDa) in gel electrophoresis was found to increase as a function of the gel type in the order SeaKem GTG-, SeaKem Gold-agarose, 2% N,N'-methylenebisacrylamide cross-linked polyacrylamide, MetaPhor-XR-, and SeaPrep-agarose. The advantage In resolving capacity of SeaPrep agarose over the polyacrylamide gel was by a factor of up to five. The resolving capacity of the agaroses was in indirect relation to the degree of electroendosmosis. In all media, resolution increased with migration distance (time). The same proteins when reacted with sodium dodecyl sulfate (SDS) resolve (i) better al up to 6% SeaPrep agarose concentration than in polyacrylamide, as in the gel electrophoresis of the native proteins; (ii) less effectively, by contrast, at SeaPrep agarose concentrations > 6%: than in polyacrylamide gel; and (iii) significantly better in 4-6% SeaPrep agarose than in 4-6% SeaKem GTG agarose. Since Ferguson plot analysis in both agarose and polyacrylamide gels shows that the two SDS-proteins are larger than the native proteins with which they are complexed, the superiority of polyacrylamide gels above 7% appears to be correlated with the fact that its mean pore radius, estimated for both media using identical assumptions and identical rigid spherical standards - proteins, is approximately seven times larger than that of SeaPrep agarose in the concentration range of 3-8%, and that therefore the molecular ''fit'' in polyacrylamide is closer than that in SeaPrep agarose of the concentration range used. The dependence of resolution on the ratio of particle radius to mean pore radius (''fit'') is also suggested by the fact that the two SDS-proteins resolve in a biphasic dependence on gel concentration in both agarose and polyacrylamide, with a maximum at 6% agarose and 10% polyacrylamide. C1 NICHHD,MACROMOL ANAL SECT,LAB CELLULAR & MOL BIOPHYS,NIH,BETHESDA,MD 20892. NR 24 TC 11 Z9 11 U1 4 U2 13 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 1997 VL 18 IS 7 BP 1126 EP 1132 DI 10.1002/elps.1150180717 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XK713 UT WOS:A1997XK71300016 PM 9237567 ER PT J AU Issaq, HJ Chan, KC Muschik, GM AF Issaq, HJ Chan, KC Muschik, GM TI The effect of column length, applied voltage, gel type, and concentration on the capillary electrophoresis separation of DNA fragments and polymerase chain reaction products SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT Australian-Electrophoresis-Society Annual Conference, at Chromatography 96 - Separation Sciences CY JUL 09-11, 1996 CL ROSEHILL, AUSTRALIA SP Austr Electrophoresis Soc DE DNA fragments; polymerase chain reaction products; short capillaries; capillary electrophoresis parameters ID ZONE ELECTROPHORESIS; OLIGONUCLEOTIDES; GRADIENTS; MOLECULES; PROTEINS AB This work examines the effect of different parameters on migration time, resolution, and speed of analysis of DNA fragments and PCR products. These parameters include column length, applied voltage, gel type and concentration, and buffer ionic strength. Our results indicate that 1 cm capillary at an applied voltage of 185 V/cm, filled with commercial gel, was adequate for the separation of small DNA fragments in under 1 min. Resolution of large fragments is directly proportional to column length at the same field strength. Also, resolution of large fragments is higher (better) at lower field strength at constant column length. Analysis is fastest (high throughput) using a short capillary and moderate field strength (200 v/cm). CE using a single short capillary (2-7 cm) is comparable to slab gel in throughput, but more economical. The Sigma DNA buffer and hydroxyethyl cellulose liquid gel gave equivalent results in terms of resolution and reproducibility. The Sigma DNA replaceable gel gave reproducible results when used as received or diluted at 60%. In our hands hydroxyethyl cellulose gave more reproducible results than polyacrylamide gel. RP Issaq, HJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,POB B,FREDERICK,MD 21702, USA. NR 23 TC 23 Z9 24 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 1997 VL 18 IS 7 BP 1153 EP 1158 DI 10.1002/elps.1150180722 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XK713 UT WOS:A1997XK71300021 PM 9237572 ER PT J AU Post, RM Kimbrell, TA McCann, U Dunn, RT George, MS Weiss, SRB AF Post, RM Kimbrell, TA McCann, U Dunn, RT George, MS Weiss, SRB TI Is a seizure necessary for the antidepressant effects of the electroconvulsive therapy: Implications from repeated transcranial magnetic stimulation (rTMS) SO ENCEPHALE-REVUE DE PSYCHIATRIE CLINIQUE BIOLOGIQUE ET THERAPEUTIQUE LA French DT Article; Proceedings Paper CT 6th Lilly Symposium of the Central Nervous System CY NOV 22-23, 1996 CL PARIS, FRANCE DE antidepressant effect; cerebellar tonsil; clonic convulsion; transcranial magnetic stimulation ID THYROTROPIN-RELEASING-HORMONE; AMYGDALA-KINDLED SEIZURES; DEPRESSED-PATIENTS; AFFECTIVE-ILLNESS; MESSENGER-RNA; ANTICONVULSANT; TRH; EXPRESSION; MECHANISM; BRAIN AB Sismotherapy (ST) brings about numerous neurobiological changes, particularly changes in neuromediators and their receptors, second messengers, neuropeptides and neurotropic factors, a number of which are hypothesized to play a role in the pathophysiology or therapeutics of affective disorders (M. Fink). What is not yet known is which of these mechanisms is crucial for the psychotropic and anticonvulsant effects of ST. However, if is clear that She effects of ST tend to be relatively acute, and do not attack the deep-seated abnormalities that are the underlying causes of reccurrences of affective disorders. This is corroborated by the fact that in animals, most of file effects of ECS on catecholamines and their receptors (and on receptors for benzodiazepines or neuropeptides such as TRH) tend to be relatively transient, and in most cases have been found to represent compensatory adaptations to the induced motor convulsions. However, recent preclinical data using attenuation, and clinical findings using reiterated transcranial magnetic stimulation (rTMS), suggest that if may not be necessary to provoke a clonic convulsion in order to achieve the beneficial psychotropic and anticonvulsant effects of ST. In rodents receiving stimulation to the cerebellar tonsil, seven daily subacute low-frequency sessions (stimulation at 1 Hz for 15 minutes) produced clear improvement in clonic convulsions and in post-discharge thresholds, together with durable inhibition of convulsions when stimulation was resumed (Weiss et al., 1995). Stimulation at 1 Hz for 15 minutes was more effective than stimulation at 10 or 20 Hz in attenuating convulsions. Although reiterated ECS also induced an anti-triggering * effect, this dissipated rapidly over five days (Postet al., 1984). If is of great interest that recent publications have shown that rTMS at 10 or 20 Hz to the left frontal cortex, administered to patients suffering from refractory depression (George ei al., 1995) or to patients (hospitalised or not) with milder degrees of depression (Pasquale-Leon et al., 1996), had a moderate or marked antidepressant effect. In these studies, rTMS showed few unwanted effects (other than mild pain in some patients, due to contraction of the temporal muscles); if did not induce motor convulsions, and did not, as such, appear to be associated with the memory lass described in subjective accounts or in preliminary neuropsychological tests (Little and Kimbrell et al., 1996). The optimal frequencies, durations and positions for rTMS to maximise its antidepressant effect still remain to be determined. However, the first controlled and open studies have fended to show that (because of the capacity of rapid magnetic fluxes to produce sub-convulsant electrical discharges that are relatively localised in the brain), rTMS may be found to be a clinically useful antidepressant model. This would suggest the possibility that some of the neurochemical changes induced by the clonic convulsions of ECS could be directly induced by stimulation at the very edge of the threshold (but still below it); this would open up the hope that one day these endogenous neurochemical processes could be identified and exploited in an optimal way for therapeutic purposes. C1 NIMH, BIOL PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. NR 43 TC 2 Z9 2 U1 0 U2 0 PU DOIN EDITEURS PI PARIS PA 47 RUE SAINT-ANDRE-DES-ARTS, F-75006 PARIS, FRANCE SN 0013-7006 J9 ENCEPHALE JI Enceph.-Rev. Psychiatr. Clin. Biol. Ther. PD JUN PY 1997 VL 23 SI 3 BP 27 EP 35 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XK590 UT WOS:A1997XK59000006 PM 9333558 ER PT J AU Scrimgeour, AG Blakesley, VA Stannard, BS LeRoth, D AF Scrimgeour, AG Blakesley, VA Stannard, BS LeRoth, D TI Mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways are not sufficient for insulin-like growth factor I-induced mitogenesis and tumorigenesis SO ENDOCRINOLOGY LA English DT Article ID TYROSINE PHOSPHORYLATION; RECEPTOR SUBSTRATE; CELLS; TRANSFORMATION; INVITRO; ASSOCIATION; MUTATION; RAF-1; PROLIFERATION; FIBROBLASTS AB Insulin-like growth factor-I (IGF-I) and insulin are known to activate a signaling cascade involving ras-->kappa raf-1-->mitogen-activated protein (MAP) kinase kinase (MEK) --> p42/p44 MAP kinase (Erk-1 and -2). Recent reports suggest that activation of this ras/MAP kinase pathway is involved in mitogenesis and c-ibs transcription but is not required for insulin action on metabolic processes such as glycogen synthesis, lipogenesis, and GLUT-4-mediated glucose transport. Previously we and others have demonstrated that substitution of both tyrosines at positions 1250 and 1251 in the carboxy-terminal region of the human IGF-I receptor has relatively small effects on receptor and endogenous substrate phosphorylation but completely abrogated the ability of these cells to form tumors in nude mice or proliferate in response to IGF-I in culture. Replacement of the tyrosine at position 1316 also did not affect the kinase activity of the receptor with respect to autophosphorylation or phosphorylation of endogenous substrates but did reduce the ability of the receptor to mediate mitogenic or tumorigenic signals. To further characterize the role of these tyrosines in IGF-I receptor Function, are have used three distinct approaches to examine the ras/MAP kinase pathway in IGF-I-induced mitogenesis and tumorigenesis in NIH-3T3 cells overexpressing wild-type and mutated IGF-I receptors: I) tyrosine phosphorylation of the MAP kinases Erk-1 and -2; 2), mobility shifts indicative of MAP kinase phospholylation; and 3) in vitro MAP kinase activation. We have also examined IGF-I-induced phosphatidylinositol (PI) 3-kinase activation in the same cell lines. By each method we show that the IGF-I-induced MAP kinase phosphorylation/activation and PI 3-kinase activation, are not different between cells overexpressing wild-type IGF-I receptors and cells carrying IGF-I receptors having tyrosine motifs replaced at positions 1250 and 1251, We conclude that mitogenic and tumorigenic signals involving tyrosine residues in the C-terminal domain of the IGF-I-receptor include pathways other than the MAP kinase and PI 3-kinase pathways. C1 NIDDK, DIABET BRANCH, SECT MOL & CELLULAR PHYSIOL, NIH, BETHESDA, MD 20892 USA. RI Scrimgeour, Angus/D-6794-2013 NR 45 TC 44 Z9 44 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 JUN PY 1997 VL 138 IS 6 BP 2552 EP 2558 DI 10.1210/en.138.6.2552 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XA025 UT WOS:A1997XA02500047 PM 9165048 ER PT J AU Hunyady, B Hipkin, RW Schonbrunn, A Mezey, E AF Hunyady, B Hipkin, RW Schonbrunn, A Mezey, E TI Immunohistochemical localization of somatostatin receptor SST2A in the rat pancreas SO ENDOCRINOLOGY LA English DT Article ID ELECTRON-MICROSCOPIC AUTORADIOGRAPHY; PERFUSED HUMAN PANCREAS; RELEASE; POLYPEPTIDE; SECRETION; GLUCAGON; BINDING; CELLS; INSULIN; ANALOGS AB Somatostatin (SRIF) acts on specific membrane: receptors to inhibit exocrine and endocrine pancreatic functions. Five SRIF receptor genes have been cloned, producing six receptor proteins (sst-s). We used a recently developed antibody to localize the sst2A splice variant in the rat pancreas. Western blots identified the sst2A. receptor as an 90 kDa glycosylated protein in pancreatic tissue. In tyramide-amplified immunostainings all acinar cells, and the glucagon and pancreatic polypeptide immunoreactive cells (A and PPI respectively) were intensely labeled for sst2A, while no signal was detected in SRIF producing (D) cells. A very few insulin immunoreactive (B) cells were also labeled for sst2A, but the signal in these cells was lower than in exocrine, A or PP cells. Absorption of the sst2A antibody with the receptor peptide abolished specific staining in both immunoblots and tissue sections (negative control). These studies are the first to localize any SRIF receptor subtype in the rat pancreas. The specific localization of sst2A receptor in acinar, A and PP cells if confirmed in humans, would suggest that subtype specific analogs will be useful for the therapeutic relation of exocrine and/or endocrine pancreatic secretion. C1 NINCDS,BASIC NEUROSCI PROGRAM,NIH,BETHESDA,MD 20892. NIMH,BETHESDA,MD 20892. MED UNIV PECS,DEPT MED 1,H-7643 PECS,HUNGARY. UNIV TEXAS,SCH MED,DEPT INTEGRAT BIOL & PHARMACOL,HOUSTON,TX 77225. NR 29 TC 64 Z9 65 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1997 VL 138 IS 6 BP 2632 EP 2635 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XA025 UT WOS:A1997XA02500058 PM 9202253 ER PT J AU Brinton, LA AF Brinton, LA TI Hormone replacement therapy and risk for breast cancer SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID MAMMOGRAPHIC PARENCHYMAL PATTERNS; ESTROGEN-PROGESTIN REPLACEMENT; EXPANDED CASE-CONTROL; MENOPAUSAL ESTROGENS; POSTMENOPAUSAL WOMEN; EXOGENOUS ESTROGEN; UNITED-STATES; ORAL-CONTRACEPTIVES; SEX-HORMONES; BODY-MASS AB A number of methodologic difficulties have prevented clear interpretation of the effects of menopausal estrogens on breast cancer risk. Some studies show that the risk may be elevated among either long-term users or recent users, but results are not entirely consistent. Further complicating this interpretation is the recent trend toward prescribing estrogens in conjunction with a progestin. Dissimilar to endometrial cancer, it does not appear that this regimen eliminates any risk associated with estrogens alone, but whether combined therapy actually has an adverse effect on breast tissue has yet to be resolved. Also requiring further investigation is whether certain subject characteristics alter the effects of hormones, including a family or personal history of breast cancer. RP Brinton, LA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 79 TC 11 Z9 11 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD JUN PY 1997 VL 26 IS 2 BP 361 EP & DI 10.1016/S0889-8529(05)70252-8 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XD842 UT WOS:A1997XD84200008 PM 9193889 ER PT J AU Barrett, JC Vainio, H Peakall, D Goldstein, BD AF Barrett, JC Vainio, H Peakall, D Goldstein, BD TI 12th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals: Susceptibility to environmental hazards SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE susceptibility; biomarkers; exposure assessment; ethics; ecosystems; human health; genes; environment; biological monitoring; methods ID SISTER-CHROMATID EXCHANGE; TUMOR-SUPPRESSOR GENE; GRADIENT GEL-ELECTROPHORESIS; CULTURED HUMAN-LYMPHOCYTES; POLYMERASE CHAIN-REACTION; IN-SITU HYBRIDIZATION; ATOMIC-BOMB SURVIVORS; LUNG-CANCER PATIENTS; S-TRANSFERASE-THETA; GLYCOPHORIN-A LOCUS AB The 12th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) considered the topic of methodologies for determining human and ecosystem susceptibility to environmental hazards. The report prepared at the meeting describes measurement of susceptibility through the use of biological markers of exposure, biological markers of effect, and biomarkers directly indicative of susceptibility of humans or of ecosystems. The utility and validity of these biological markers for the study of susceptibility are evaluated, as are opportunities for developing newer approaches for the study of humans or of ecosystems. For the first time a SGOMSEC workshop also formally considered the issue of ethics in relation to methodology, an issue of particular concern for studies of susceptibility. C1 ENVIRONM & OCCUPAT HLTH SCI INST, PISCATAWAY, NJ 08855 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. FINNISH INST OCCUPAT HLTH, HELSINKI, FINLAND. UNIV LONDON KINGS COLL, MONITORING & RES ASSESSMENT CTR, LONDON WC2R 2LS, ENGLAND. NR 261 TC 30 Z9 33 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1997 VL 105 SU 4 BP 699 EP 737 DI 10.2307/3433276 PG 39 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XN297 UT WOS:A1997XN29700002 PM 9255554 ER PT J AU Poirier, MC AF Poirier, MC TI DNA adducts as exposure biomarkers and indicators of cancer risk SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Mechanisms and Prevention of Environmentally Caused Cancers CY 1995 CL SANTA FE, NM SP Lovelace Inst, US DOE, Bioserv Biotechnol, Johnson & Johnson Inc, Int Life Sci Inst, Dako Corp, VWR, SW Sci Res Inc DE human; environment; carcinogen; DNA binding; dosimetry ID P-32 POSTLABELING ASSAY; WHITE BLOOD-CELLS; COKE-OVEN WORKERS; DIOL-EPOXIDE-DNA; POLYCYCLIC AROMATIC-HYDROCARBONS; REPUBLIC-OF-CHINA; URINARY 8-HYDROXY-2'-DEOXYGUANOSINE; MONOCLONAL-ANTIBODIES; PERIPHERAL LEUKOCYTES; MOLECULAR DOSIMETRY AB Quantitation of DNA adducts in human tissues has been achieved with highly sensitive techniques based on adduct radiolabeling, antisera specific for DNA adducts or modified DNA, and/or adduct structural characterization using chemical instrumentation. Combinations of these approaches now promise to elucidate specific adduct structures and provide detection limits in the range of 1 adduct/10(9) nucleotides. Documentation of human exposure and biologically effective dose (i.e., chemical bound to DNA) has been achieved for a wide variety of chemical carcinogens, including polycyclic aromatic hydrocarbons (PAHs), aromatic amines, heterocyclic amines, aflatoxins, nitrosamines, cancer chemotherapeutic agents, styrene, and malondialdehyde. Due to difficulties in exposure documentation, dosimetry has not been precise with most environmental and occupational exposures, even though increases in human blood cell DNA adduct levels may correlate approximately with dose. Perhaps more significant are observations that lowering exposure results in decreasing DNA adduct levels. DNA adduct dosimetry for environmental agents has been achieved with dietary contaminants. For example, blood cell polycyclic aromatic hydrocarbon-DNA adduct levels were shown to correlate with frequency of charbroiled meat consumption in California firefighters. In addition, in China urinary excretion of the aflatoxin B-1-N-7-guanine (AFB(1)-N-7-G) adduct was shown to increase linearly with the aflatoxin content of ingested food. Assessment of DNA adduct formation as an indicator of human cancer risk requires a prospective nested case-control study design. This has been achieved in one investigation of hepatocellular carcinoma and urinary aflatoxin adducts using subjects followed by a Shanghai liver cancer registry. Individuals who excreted the AFB(1)-N-7-G adduct had a 9.1-fold adjusted increased relative risk of hepatocellular carcinoma compared to individuals with no adducts. Future advances in this field will be dependent on chemical characterization of specific DNA adducts formed in human tissues, more precise molecular dosimetry, efforts to correlate DNA adducts with cancer risk, and elucidation of opportunities to reduce human DNA adduct levels. RP Poirier, MC (reprint author), NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BLDG 37,ROOM 3B25,MSC-4255, 37 CONVENT DR, BETHESDA, MD 20892 USA. NR 97 TC 63 Z9 64 U1 2 U2 11 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1997 VL 105 SU 4 BP 907 EP 912 DI 10.2307/3433302 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XN297 UT WOS:A1997XN29700028 PM 9255579 ER PT J AU Mulshine, JL Scott, F Zhou, J Avis, I Vos, M Treston, AM AF Mulshine, JL Scott, F Zhou, J Avis, I Vos, M Treston, AM TI Recent molecular advances in the approach to early lung cancer detection and intervention SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Mechanisms and Prevention of Environmentally Caused Cancers CY 1995 CL SANTA FE, NM SP Lovelace Inst, US DOE, Bioserv Biotechnol, Johnson & Johnson Inc, Int Life Sci Inst, Dako Corp, VWR, SW Sci Res Inc DE lung cancer; molecular diagnostics; early detection; carcinogenesis; apoptosis ID PREVENTION; ACID; BIOAVAILABILITY; GROWTH AB Lung cancer is a major contributor to overall cancer mortality. Detecting lung cancer while it is still a localized process is a long-cherished goal for improving the outcome of this disease. Recent developments suggest that we are approaching this capability. We next have to think about how to implement a change in our approach to lung cancer management to derive the benefit of better detection capability. This is an area in which our growing understanding of lung cancer biology is providing clues on improving the inhibition of cancer progression. RP Mulshine, JL (reprint author), NCI,BIOMARKERS & PREVENT RES BRANCH,DIV CLIN SCI,KWC 300,9610 MED CTR DR,ROCKVILLE,MD 20850, USA. NR 26 TC 4 Z9 4 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 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1997 VL 105 SU 4 BP 935 EP 939 DI 10.2307/3433307 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XN297 UT WOS:A1997XN29700033 PM 9255584 ER PT J AU Stoner, GD Morse, MA Kelloff, GJ AF Stoner, GD Morse, MA Kelloff, GJ TI Perspectives in cancer chemoprevention SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Mechanisms and Prevention of Environmentally Caused Cancers CY 1995 CL SANTA FE, NM SP Lovelace Inst, US DOE, Bioserv Biotechnol, Johnson & Johnson Inc, Int Life Sci Inst, Dako Corp, VWR, SW Sci Res Inc DE cancer; chemoprevention; mechanisms; anti-initiation; antipromotion; antiprogression ID INDUCED ESOPHAGEAL TUMORIGENESIS; GLUTATHIONE S-TRANSFERASE; GROWTH-FACTOR-BETA; NONSTEROIDAL ANTIINFLAMMATORY DRUG; ORNITHINE DECARBOXYLASE INHIBITOR; DIETARY PHENETHYL ISOTHIOCYANATE; GAP JUNCTIONAL COMMUNICATION; RAT MAMMARY CARCINOGENESIS; DOSE-RELATED INHIBITION; MYELOID-LEUKEMIA CELLS AB Cancer chemoprevention can be defined as prevention of cancer by the administration of one or more chemical entities, either as individual drugs or as naturally occurring constituents of the diet. Based largely on the time period that chemopreventive agents exhibit activity in animal models of carcinogenesis, they can be classified as inhibitors of carcinogen formation, blocking agents, and suppressing agents. The majority of compounds that inhibit the formation of carcinogens prevent the formation of nitrosamines from secondary amines and nitrite in an acidic environment. Blocking agents are inhibitors of tumor initiation, while suppressing agents are inhibitors of tumor promotion/progression. Many well-characterized chemopreventive agents act at one or more steps in both tumor initiation and promotion/progression. The objective of this paper is to provide a general discussion of the mechanisms through which chemopreventive agents inhibit carcinogenesis. Examples of agents that act through these mechanisms are given; however. a complete listing of effective chemopreventive agents is not possible within the context of this paper. At the conclusion is a brief discussion of future prospects in cancer chemoprevention and obstacles to overcome. C1 NCI,NIH,BETHESDA,MD 20892. RP Stoner, GD (reprint author), OHIO STATE UNIV,ARTHUR JAMES CANC HOSP & RES INST,ROOM 1148,300 W 10TH AVE,COLUMBUS,OH 43210, USA. FU NCI NIH HHS [CA28950, CA46535] NR 164 TC 61 Z9 64 U1 1 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 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1997 VL 105 SU 4 BP 945 EP 954 DI 10.2307/3433309 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XN297 UT WOS:A1997XN29700035 PM 9255586 ER PT J AU Trickett, EJ Oliveri, ME AF Trickett, EJ Oliveri, ME TI Ethnography and sociocultural processes: Introductory comments SO ETHOS LA English DT Editorial Material C1 Univ Maryland, College Pk, MD 20742 USA. NIMH, Behav Cognit & Social Sci Res Branch, Rockville, MD 20857 USA. RP Trickett, EJ (reprint author), Univ Maryland, College Pk, MD 20742 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER ANTHROPOLOGICAL ASSOC PI ARLINGTON PA 4350 NORTH FAIRFAX DRIVE SUITE 640, ARLINGTON, VA 22203 USA SN 0091-2131 J9 ETHOS JI Ethos PD JUN PY 1997 VL 25 IS 2 BP 146 EP 151 DI 10.1525/eth.1997.25.2.146 PG 6 WC Anthropology; Psychology, Multidisciplinary SC Anthropology; Psychology GA YV881 UT WOS:000071873200002 ER PT J AU Wiltrout, RH Park, JW Taub, D Brunda, MJ Strieter, R Wigginton, JM AF Wiltrout, RH Park, JW Taub, D Brunda, MJ Strieter, R Wigginton, JM TI The role of T cells, induction of antineovascular chemokines, and apoptotic factors in the antitumor activity of IL-12/pulse IL-2. SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI,EXPT IMMUNOL LAB,FREDERICK,MD 21701. SAIC,CIS,FREDERICK,MD. NCI,PEDIAT ONCOL BRANCH,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. UNIV MICHIGAN,ANN ARBOR,MI 48109. NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUN PY 1997 VL 33 SU 5 BP 14 EP 14 PG 1 WC Oncology SC Oncology GA XG122 UT WOS:A1997XG12200015 ER PT J AU Caspar, CB Hsu, FJ Davis, TA Czerwinski, D Kwak, LW Liles, TM Syrengelas, A Taidi, B Levy, R AF Caspar, CB Hsu, FJ Davis, TA Czerwinski, D Kwak, LW Liles, TM Syrengelas, A Taidi, B Levy, R TI Idiotype vaccination for patients with Non-Hodgkin's Lymphoma SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 STANFORD UNIV,STANFORD,CA 94305. YALE UNIV,NEW HAVEN,CT 06520. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUN PY 1997 VL 33 SU 5 BP 30 EP 30 PG 1 WC Oncology SC Oncology GA XG122 UT WOS:A1997XG12200030 ER PT J AU Mackall, CL Hakim, FT Fleisher, TA Brown, MR Dimitrov, DS Gress, RE AF Mackall, CL Hakim, FT Fleisher, TA Brown, MR Dimitrov, DS Gress, RE TI T cell regeneration after chemotherapy: Implications for immunotherapy in the setting of minimal residual disease SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUN PY 1997 VL 33 SU 5 BP 33 EP 33 PG 1 WC Oncology SC Oncology GA XG122 UT WOS:A1997XG12200035 ER PT J AU Pluda, JM AF Pluda, JM TI Tumor-associated angiogenesis: Pathogenesis and clinical implications SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI,INVEST DRUG BRANCH,CANC THERAPY EVALUAT PROGRAM,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUN PY 1997 VL 33 SU 5 BP 105 EP 105 PG 1 WC Oncology SC Oncology GA XG122 UT WOS:A1997XG12200107 ER PT J AU Sgadari, C Angiolillo, A Farber, J TeruyaFeldstein, J Burd, P Tosato, G AF Sgadari, C Angiolillo, A Farber, J TeruyaFeldstein, J Burd, P Tosato, G TI The chemokines IP-10 and MIG identified as mediators of tumor necrosis in vivo SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 US FDA,CTR BIOL,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUN PY 1997 VL 33 SU 5 BP 107 EP 107 PG 1 WC Oncology SC Oncology GA XG122 UT WOS:A1997XG12200108 ER PT J AU Zwiebel, JA Su, N Freeman, S Ojeifo, JO AF Zwiebel, JA Su, N Freeman, S Ojeifo, JO TI Angiogenesis-directed incorporation of genetically-modified endothelial cells as systemic anti-tumor therapy. SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI,INVEST DRUG BRANCH,BETHESDA,MD 20892. NANJING RAILWAY MED COLL,NANJING,PEOPLES R CHINA. TULANE UNIV MED CTR HOSP & CLIN,NEW ORLEANS,LA. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUN PY 1997 VL 33 SU 5 BP 124 EP 124 PG 1 WC Oncology SC Oncology GA XG122 UT WOS:A1997XG12200125 ER PT J AU Costa, A Hubbard, SM AF Costa, A Hubbard, SM TI Evidence based medicine, a new challenge SO EUROPEAN JOURNAL OF CANCER LA English DT Editorial Material C1 NCI,INT CANC INFORMAT CTR,BETHESDA,MD 20892. RP Costa, A (reprint author), EUROPEAN INST ONCOL,VIA RIPAMONTI 435,I-20141 MILAN,ITALY. NR 6 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUN PY 1997 VL 33 IS 7 BP 987 EP 988 DI 10.1016/S0959-8049(97)00109-3 PG 2 WC Oncology SC Oncology GA XJ250 UT WOS:A1997XJ25000006 PM 9376201 ER PT J AU Tracy, TS Marra, C Wrighton, SA Gonzalez, FJ Korzekwa, KR AF Tracy, TS Marra, C Wrighton, SA Gonzalez, FJ Korzekwa, KR TI Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation SO EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 20-22, 1996 CL ORLANDO, FL SP Amer Soc Clin Pharm & Therapeut DE naproxen; cytochrome P450; human liver microsomes; vaccinia virus; cDNA expression ID HUMAN-LIVER; IDENTIFICATION; HYDROXYLATION; TOLBUTAMIDE; OXIDATION AB Objective: A series of studies was undertaken to determine the cytochrome P450 isoform(s) involved in naproxen demethylation and whether this included the same isoforms reported to be involved in the metabolism of other NSAIDs. Methods: (S)-Naproxen was incubated with human liver microsomes in the presence of a NADPH-generating system and the formation of desmethylnaproxen was measured by high-performance liquid chromatography (HPLC). To further clarify the specific isoforms involved, experiments were conducted with preparations expressing only a single P450 isoform (vaccinia virus-expressed cells and microsomes derived from a lymphoblastoid cell line, each transfected with specific P450 cDNAs) as well as inhibition studies using human liver microsomes and putative specific P450 inhibitors. Results: In human liver microsomes (n = 7), desmethylnaproxen formation was observed with a mean k(M) of 92 (21) mu mol.l(-1), V-max of 538 pmol.min(-1).mg(-1) protein and C-int2 (reflective of a second binding site) of 0.36 mu l.min(-1) mg(-1) protein. This C-int2 term was added since Eadie-Scatchard analysis suggested the involvement of more than one enzyme. Studies using putative specific P450 inhibitors demonstrated inhibition of this reaction by sulfaphenazole, (apparent Ki=1.6 mu mol.l(-1)), warfarin (apparent Ki=27 mu mol.l(-1)), piroxicam (apparent Ki=23 mu mol.l(-1)) and tolbutamide (apparent Ki = 128 mu mol.l(-1)). No effect was observed when alpha-naphthoflavone and troleandomycin were employed as inhibitors, but reaction with furafylline produced, on average, a maximum inhibition of 23%. At a naproxen concentration of 150 mu mol.l(-1) formation of desmethylnaproxen was observed in cells expressing P450 1A2, 2C8, 2C9 and its allelic variant 2C9R144C. To further characterize these reactions, saturation kinetics experiments were conducted for the P450s 1A2, 2C8 and 2C9. The k(M) and V-max for P450 1A2 were 189.5 mu mol.l(-1) and 7.3 pmol.min(-1).pmol(-1) P450, respectively. Likewise, estimates of k(M) and V-max for P450 2C9 were 340.5 mu mol.l(-1) and 41.4 pmol.min(-1).pmol(-1) P450, respectively. Reliable estimates of k(M) and V-max could not be made for P450 2C8 due to the nonsaturable nature of the process over the concentration range studied. Conclusion: Multiple cytochrome P450 isoforms (P450 1A2, 2C8 and 2C9) appear to be involved in naproxen demethylation, although 2C9 appears to be the predominant form. C1 ELI LILLY & CO,DEPT DRUG DESPOSIT,INDIANAPOLIS,IN 46285. NCI,NIH,BETHESDA,MD 20892. UNIV PITTSBURGH,CTR CLIN PHARMACOL,PITTSBURGH,PA. RP Tracy, TS (reprint author), W VIRGINIA UNIV,SCH PHARM,DEPT BASIC PHARMACEUT SCI,HSN PO BOX 9530,MORGANTOWN,WV 26506, USA. FU NIDDK NIH HHS [N01-DK-6-2274] NR 24 TC 49 Z9 52 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6970 J9 EUR J CLIN PHARMACOL JI Eur. J. Clin. Pharmacol. PD JUN PY 1997 VL 52 IS 4 BP 293 EP 298 DI 10.1007/s002280050293 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XJ061 UT WOS:A1997XJ06100009 PM 9248768 ER PT J AU Utsunomiya, I Tani, K Gong, WH Oppenheim, JJ Wang, JM AF Utsunomiya, I Tani, K Gong, WH Oppenheim, JJ Wang, JM TI Differential expression of binding sites for chemokine RANTES on human T lymphocytes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE RANTES; CC chemokine; receptor; T cell ID INFLAMMATORY PROTEIN 1-ALPHA; CHEMOTACTIC CYTOKINES; FUNCTIONAL EXPRESSION; HUMAN-MONOCYTES; CC-CHEMOKINES; CELL ADHESION; RECEPTOR; INTERLEUKIN-8; MIP-1-BETA; IDENTIFICATION AB The C-C chemokine RANTES, a T lymphocyte chemoattractant, is considered an important mediator of inflammation, allergy, and host defense against HIV-1 infection. In this study, we investigated the modulation of binding of RANTES to T lymphocytes. Human peripheral blood CD3(+) T cells, when freshly isolated from buffy-coat blood, expressed a considerable number of high-affinity binding sites for RANTES. These cells also showed significant chemotactic migration in response to RANTES in vitro. After 6-15 h incubation at 37 degrees C, the binding of RANTES, but not of macrophage inflammatory protein-1 alpha (MIP-1 alpha) or of monocyte chemotactic protein-3 (MCP-3), consistently increased. Scatchard analyses indicated that the number of binding sites for RANTES increased about threefold by 15 h without any change in the affinity. The increase in RANTES binding was no longer detected by 24 h. This increase in the specific binding was mainly attributable to CD4(+) T cells and was not associated with increased chemotactic activity of these cells in response to RANTES. Incubation with anti-CD3 antibody for 15 h markedly reduced the binding capability of T cells for RANTES and was associated with decreased chemotactic activity. On the other hand, when T cells were incubated with interleukin-2 (IL-2) for 1 week, the specific binding for all three C-C chemokines, RANTES, MIP-1 alpha, and MCP-3 was markedly increased in comparison to cells cultured in the absence of IL-2. These results suggest that the expression of binding sites on T cells for RANTES is differentially modulated, indicating the existence of novel receptors for RANTES that do not bind MIP-1 alpha. C1 NCI,FREDERICK CANC RES & DEV CTR,IRSP,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. NR 29 TC 12 Z9 12 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1997 VL 27 IS 6 BP 1406 EP 1412 DI 10.1002/eji.1830270617 PG 7 WC Immunology SC Immunology GA XD601 UT WOS:A1997XD60100016 PM 9209492 ER PT J AU Roscoe, DM Pai, LH Pastan, I AF Roscoe, DM Pai, LH Pastan, I TI Identification of epitopes on a mutant form of Pseudomonas exotoxin using serum from humans treated with Pseudomonas exotoxin containing immunotoxins SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE epitope; antigenicity; B cell; immunotoxin; Pseudomonas ID AERUGINOSA EXOTOXIN; MONOCLONAL-ANTIBODY; ANTIGENIC STRUCTURE; SYNTHETIC PEPTIDES; DOMAIN-III; PROTEIN; RESIDUES; CANCER; TOXIN; SITE AB PE38 is a 38-kDa derivative of the 66-kDa Pseudomonas exotoxin (PE) in which the cell binding domain of PE (domain Ia, amino acids 1-252) and a portion of domain Ib (amino acids 365-380) are deleted. The immunotoxins LMB-1 and LMB-7 contain PE38 and kill cancer cells by exploiting the cytotoxic action of PE38. The major human B cell epitopes of PE38 were mapped by measuring the reactivity of 45 serum samples from patients treated with the PE38-containing immunotoxins LMB-1 or LMB-7 to two panels of overlapping synthetic peptides representing the sequence of PE38. One panel of peptides is ten amino acids long and overlap by seven amino acids, and the second panel of peptides is twenty amino acids long and overlap by ten. Five major epitopes were identified: amino acids 274-283, 470-492, 531-540, 555-564, and the C-terminal amino acids 596-609. Two minor epitopes were identified as well: amino acids 501-510 and 582-589. These epitopes are predominantly located on the surface of the protein. The amino acids believed to be critical for binding are highly solvent-accessible residues. The results of the human antibody response to peptides are compared to the pattern of reactivity previously identified with serum samples obtained from monkeys administered LMB-1 and LMB-7. The epitopes between monkey and human are almost identical, demonstrating similarity in the response of antibody repertoires between the two species and providing further support that these are the immunodominant epitopes. This information is critical for genetically engineering less immunogenic immunotoxins and provides a foundation for the development of a vaccine against pseudomonal infections which plague immunocompromised individuals and individuals with cystic fibrosis. C1 NCI,MOL BIOL LAB,NIH,DCBDC,BETHESDA,MD 20892. NR 32 TC 22 Z9 24 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1997 VL 27 IS 6 BP 1459 EP 1468 DI 10.1002/eji.1830270624 PG 10 WC Immunology SC Immunology GA XD601 UT WOS:A1997XD60100023 PM 9209499 ER PT J AU Akukwe, C AF Akukwe, C TI Perinatal and infant mortality: A worldwide issue - Commentary SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE infant and perinatal death; policy implications; public health issues; worldwide AB The editorial on perinatal and infant mortality: a worldwide issue, Eur J Public Hlth 1996;6:157-8, appropriately links reductions in perinatal and infant mortality with improvements in socioeconomic status in developing and developed countries. However, in summary discussions of the worldwide trends of infant deaths, certain critical issues that also influence the rates of perinatal and infant mortality deserve mentioning, even if briefly. These critical issues include race/ethnic status, the pre-conception health status of the mother, the past obstetrics history, the very important effect of low birth weight and preterm delivery, the effect of maternal education and the relationship between maternal mortality/morbidity and infant survival. I briefly review the relationship between infant deaths and these critical issues. Discussing these critical issues in summary articles may help advance policy and programme debate on how to reduce the rate of infant deaths worldwide effectively. C1 NIH,DIST COLUMBIA INITIAT REDUCE INFANT MORTAL,DIST COLUMBIA COMMISS PUBL HLTH,WASHINGTON,DC. NR 8 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 1101-1262 J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD JUN PY 1997 VL 7 IS 2 BP 223 EP 225 DI 10.1093/eurpub/7.2.223 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XM060 UT WOS:A1997XM06000021 ER PT J AU Ronchetti, R Indinnimeo, L Bonci, E Corrias, A Evans, D HindiAlexander, M Midulla, F Pulejo, R Villa, MP Armenio, L Spadaveechia, L Baldini, G Bonfanti, R Barbato, A Zanconato, S Battistini, A Grzincich, PL Boner, A Castellani, C Rossi, G Novembre, E Azzari, C Macri, F LaRosa, M Ranno, C DelGiudice, MM Decimo, F Bernardi, F Castello, D Robusto, C Pulcjo, R LaGrutta, S AF Ronchetti, R Indinnimeo, L Bonci, E Corrias, A Evans, D HindiAlexander, M Midulla, F Pulejo, R Villa, MP Armenio, L Spadaveechia, L Baldini, G Bonfanti, R Barbato, A Zanconato, S Battistini, A Grzincich, PL Boner, A Castellani, C Rossi, G Novembre, E Azzari, C Macri, F LaRosa, M Ranno, C DelGiudice, MM Decimo, F Bernardi, F Castello, D Robusto, C Pulcjo, R LaGrutta, S TI Asthma self-management programmes in a population of Italian children: A multicentric study SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE asthma education; asthma in children; asthma self-management; emergency room utilization ID HEALTH-EDUCATION; CHILDHOOD ASTHMA; CARE; PARENTS; IMPACT AB This study was designed to answer three main questions: 1) Does asthma self-management education reduce asthma morbidity? 2) Are the two programmes ''Living With Asthma'' and ''Open Airways'' equally effective in doing so? 3) Is a shortened version of these programmes (4 weeks) as effective as the longer original programme (8 weeks)? Twelve Italian centres of paediatric bronchopneumology selected 312 children with asthma, who were stratified by disease severity, gender and age, and then randomly assigned to an Experimental group which received an educational programme or to a Comparison group, which did not Of the 312 children selected, 209 (114 Experimental and 95 Comparison) completed the educational protocol and a 1 year follow-up. Data recorded during the last 2 months of follow-up, 10 months after the educational intervention, showed that the Experimental group required significantly fewer emergency treatments: this reduction was more evident in the more severe asthma cases, In the Experimental, but not in the Comparison group, patients with more severe asthma consumed more medications than patients with milder asthma ''Open Airways'' yielded, in some cases, better results than ''Living with Asthma'': but a type 2 error is possible. The standard and the shortened programmes proved equally effective. In conclusion, following education, regardless of receiving a short or long: educational programme, asthma patients use emergency care services less and use medications more appropriately in comparison with standard care without education, This suggests that short educational programmes can be highly cost-effective in children with asthma. C1 UNIV CAGLIARI, DEPT PEDIAT, CAGLIARI, ITALY. COLUMBIA UNIV, NEW YORK, NY 10027 USA. NIH, BETHESDA, MD 20892 USA. CASA DEL SOLE HOSP, PALERMO, ITALY. UNIV HOSP, DEPT PEDIAT, BARI, ITALY. UNIV HOSP, DEPT PEDIAT, PISA, ITALY. UNIV HOSP, DEPT PEDIAT, PADUA, ITALY. UNIV HOSP, DEPT PEDIAT, PARMA, ITALY. UNIV HOSP, DEPT PEDIAT, VERONA, ITALY. UNIV HOSP, DEPT PEDIAT, CAGLIARI, ITALY. UNIV HOSP, DEPT PEDIAT, FLORENCE, ITALY. UNIV HOSP, DEPT PEDIAT, ROME, ITALY. UNIV HOSP, DEPT PEDIAT, CATANIA, ITALY. UNIV HOSP, DEPT PEDIAT, NAPLES, ITALY. OSPED INF REGINA MARGHERITA, TURIN, ITALY. OSPED CASA SOLE, PALERMO, ITALY. RP Ronchetti, R (reprint author), UNIV ROMA LA SAPIENZA, CATTEDRA CLIN PEDIAT 4, DEPT PEDIAT, VIALE REGINA ELENA 324, I-00161 ROME, ITALY. OI Bonci, Enea/0000-0003-3325-1124 NR 21 TC 52 Z9 55 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD JUN PY 1997 VL 10 IS 6 BP 1248 EP 1253 DI 10.1183/09031936.97.10061248 PG 6 WC Respiratory System SC Respiratory System GA XE320 UT WOS:A1997XE32000010 PM 9192924 ER PT J AU Lundberg, C MartinezSerrano, A Cattaneo, E McKay, RDG Bjorklund, A AF Lundberg, C MartinezSerrano, A Cattaneo, E McKay, RDG Bjorklund, A TI Survival, integration, and differentiation of neural stem cell lines after transplantation to the adult rat striatum SO EXPERIMENTAL NEUROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; PRECURSOR CELLS; MAMMALIAN BRAIN; GROWTH-FACTOR; CNS; FOREBRAIN; NEURONS; TEMPERATURE; RESPONSES; MIGRATION AB The in vivo properties of four different neural stem cell lines, generated from embryonic striatum or hippocampus by immortalization with the temperature-sensitive (s) A58/U19 allele of the SV40 Large T-antigen, have been studied with respect to their ability to survive, differentiate, and integrate after transplantation to the adult rat striatum. The cells were labeled with [H-3]thymidine prior to grafting, and combined autoradiography and immunohistochemistry was used to characterize their phenotypic differentiation within the adult brain environment. The results show that all four types of cells survived well, up to at least 1.5-6 months postgrafting, without any signs of tissue perturbation or tumor formation. The cells underwent, on average, 2-3 cell divisions during the first 5 days after implantation and exhibited extensive migration over a distance of 1-1.5 mm from the injection site to become morphologically integrated with the surrounding host striatum. The cell number and tissue distribution attained by 2 weeks remained stable for up to 6 months postgrafting with the exception of one cell line, which showed a 40% loss of cells between 2 and 6 weeks. Twice the number of [H-3]thymidine-labeled cells were recovered when the cells were grafted into a 1-week-old excitotoxic striatal lesion, probably due to an increased proliferation of the cells in response to the neuron-depleting depleting lesion. The immortalized cells behaved as multipotent neural progenitors. The vast majority of the cells developed a glial-like morphology, 6-14% being clearly GFAP-positive; however, a small but consistent proportion of them (1-3%) expressed MAP-2 and exhibited neuron-like morphology. In mature transplants about 75-80% of the grafted cells were located in the striatal grey matter, and 10-15% in white matter, some of which are proposed to have differentiated into oligodendrocytes. Remaining 5-10% occurred around small blood vessels (resembling pericytes) and in the subventricular zone underneath the ependyma of the lateral ventricle. It is concluded that the ts cell lines are highly suitable for intracerebral transplantation and that they allow the creation of a regionally confined cellular chimeras where the graft-derived glial cells become stably integrated with the resident glial cell matrix. (C) 1997 Academic Press. C1 NINCDS,LBM,NIH,BETHESDA,MD. UNIV MILAN,INST PHARMACOL SCI,I-20133 MILAN,ITALY. RP Lundberg, C (reprint author), LUND UNIV,WALLENBERG NEUROSCI CTR,DEPT PHYSIOL & NEUROSCI,SOLVEGATAN 17,S-22362 LUND,SWEDEN. RI Martinez-Serrano, Alberto/J-8146-2014; OI CATTANEO, ELENA/0000-0002-0755-4917 FU NINDS NIH HHS [NS 06701] NR 49 TC 167 Z9 184 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 1997 VL 145 IS 2 BP 342 EP 360 DI 10.1006/exnr.1997.6503 PG 19 WC Neurosciences SC Neurosciences & Neurology GA XJ537 UT WOS:A1997XJ53700004 PM 9217071 ER PT J AU Su, Y Shi, YF Shi, YB AF Su, Y Shi, YF Shi, YB TI Cyclosporin A but not FK506 inhibits thyroid hormone-induced apoptosis in tadpole intestinal epithelium SO FASEB JOURNAL LA English DT Article DE metamorphosis; immunosuppressant; cell death ID PROGRAMMED CELL-DEATH; GENE-EXPRESSION; AMPHIBIAN METAMORPHOSIS; MOLECULAR-BIOLOGY; CONNECTIVE-TISSUE; XENOPUS-LAEVIS; LARVAL; THYMOCYTES; RECEPTOR; INVITRO AB Amphibian metamorphosis and mammalian T cell development represent two of the best known systems where developmental programmed cell death through apoptosis takes place. Two immunosuppressants, cyclosporin A (CsA) and FK506, have been demonstrated to inhibit activation-induced cell death in immature T cells and T cell hybridomas. In this study, we have established an in vitro system in which isolated primary tadpole intestinal epithelial cells undergo typical apoptosis upon treatment with thyroid hormone (T-3), the causative agent of metamorphosis. It is surprising that this T-3-induced apoptosis was found to be inhibited only by CsA but not by FK506, whereas both immunosuppressants block activation-induced apoptosis in T cells. Since T-3 exerts its effect primarily by regulating gene transcription through direct binding to nuclear thyroid hormone receptors, our results strongly suggest that except for their similarity in the T cell receptor-mediated signal transduction process, CsA, but not FK506, also blocks another yet-unidentified step during the induction of apoptosis. The identification of this novel function of CsA may provide an important clue toward the understanding of the mechanism of apoptosis and helps in designing better clinical applications of the immunosuppressants. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. AMER RED CROSS,HOLLAND LAB,DEPT IMMUNOL,ROCKVILLE,MD 20855. NR 41 TC 26 Z9 27 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 1997 VL 11 IS 7 BP 559 EP 565 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA XH342 UT WOS:A1997XH34200007 PM 9212079 ER PT J AU Beveridge, TJ Pouwels, PH Sara, M Kotiranta, A Lounatmaa, K Kari, K Kerosuo, E Haapasalo, M Egelseer, EM Schocher, I Sleytr, UB Morelli, L Callegari, ML Nomellini, JF Bingle, WH Smit, J Leibovitz, E Lemaire, M Miras, I Salamitou, S Beguin, P Ohayon, H Gounon, P Matuschek, M Sahm, K Bahl, H GrogonoThomas, R Dworkin, J Blaser, MJ Woodland, RM Newell, DG Kessel, M Koval, SF AF Beveridge, TJ Pouwels, PH Sara, M Kotiranta, A Lounatmaa, K Kari, K Kerosuo, E Haapasalo, M Egelseer, EM Schocher, I Sleytr, UB Morelli, L Callegari, ML Nomellini, JF Bingle, WH Smit, J Leibovitz, E Lemaire, M Miras, I Salamitou, S Beguin, P Ohayon, H Gounon, P Matuschek, M Sahm, K Bahl, H GrogonoThomas, R Dworkin, J Blaser, MJ Woodland, RM Newell, DG Kessel, M Koval, SF TI Functions of S-layers SO FEMS MICROBIOLOGY REVIEWS LA English DT Article; Proceedings Paper CT 4th International S-Layer Workshop - Structure, Biochemistry, Molecular Biology and Applications of Microbial S-Layers CY SEP, 1996 CL ROTHENBURG, GERMANY DE gram stain; cell wall; s-layer; archaea; protozoa; bacterivory; crystalline outer membrane protein; porin; Campylobacter fetus; ovine abortion; virulence factor; glycosyl hydrolase; cellulosome; cell wall anchoring; Caulobacter crescentus; secretion; adhesion; amylase; Bacillus stearothermophilus; lactobacillus; bacillus; phagocytosis; polymorphonuclear leukocyte; bacteria ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; PARACRYSTALLINE SURFACE-LAYER; LACTOBACILLUS-HELVETICUS ATCC-12046; FRESH-WATER CAULOBACTERS; THERMOANAEROBACTERIUM-THERMOSULFURIGENES EM1; BACILLUS-STEAROTHERMOPHILUS STRAINS; EUBACTERIUM THERMOTOGA-MARITIMA; CAMPYLOBACTER-FETUS INFECTIONS; MOLECULAR-WEIGHT AMYLASE; INTEGRATING PROTEIN CIPA AB Although S-layers are being increasingly identified on Bacteria and Archaea, it is enigmatic that in most cases S-layer function continues to elude us. In a few instances, S-layers have been shown to be virulence factors on pathogens (e.g. Campylobacter fetus ssp. fetus and Aeromonas salmonicida), protective against Bdellovibrio, a depository for surface-exposed enzymes (e.g. Bacillus stearothermophilus), shape-determining agents (e.g. Thermoproteus tenax) and nucleation factors for fine-grain mineral development (e.g. Synechococcus GL 24). Yet, for the vast majority of S-layered bacteria, the natural function of these crystalline arrays continues to be evasive. The following review up-dates the functional basis of S-layers and describes such diverse topics as the effect of S-layers on the Gram stain, bacteriophage adsorption in lactobacilli, phagocytosis by human polymorphonuclear leukocytes, the adhesion of a high-molecular-mass amylase, outer membrane porosity, and the secretion of extracellular enzymes of Thermoanaerobacterium. In addition, the functional aspect of calcium on the Caulobacter S-layer is explained. C1 TNO, MED BIOL LAB, NL-2288 GJ RIJSWIJK, NETHERLANDS. AGR UNIV VIENNA, ZENTRUM ULTRASTRUKTURFORSCH, A-1188 VIENNA, AUSTRIA. AGR UNIV VIENNA, LUDWIG BOLZMANN INST MOL NANOTECHNOL, A-1188 VIENNA, AUSTRIA. UNIV HELSINKI, INST DENT, FIN-0014 HELSINKI, FINLAND. UNIV HELSINKI, INST BIOTECHNOL, BIOCTR 1, FIN-00014 HELSINKI, FINLAND. UNIV OSLO, FAC DENT, OSLO, NORWAY. UNIV CATTOLICA SACRO CUORE, IST MICROBIOL, I-29100 PIACENZO, ITALY. UNIV BRITISH COLUMBIA, DEPT IMMUNOL & MICROBIOL, VANCOUVER, BC V6T 1Z3, CANADA. INST PASTEUR, UNITE PHYSIOL CELLULAIRE, F-75724 PARIS 15, FRANCE. INST PASTEUR, URA 1300 CNRS, DEPT BIOTECHNOL, F-75724 PARIS 15, FRANCE. INST PASTEUR, STN CENT MICROSCOPIE ELECT, F-75724 PARIS 15, FRANCE. UNIV GOTTINGEN, INST MIKROBIOL, D-37077 GOTTINGEN, GERMANY. UNIV ROSTOCK, FACHBEREICH BIOL, D-18051 ROSTOCK, GERMANY. UNIV LONDON ROYAL VET COLL, DEPT FARM ANIM & EQUINE MED & SURG, BOLTONS PK EN6 1NB, HERTS, ENGLAND. VANDERBILT UNIV, SCH MED, DIV INFECT DIS, NASHVILLE, TN 37232 USA. CENT VET LAB, SURREY KT15 3NB, ENGLAND. NIAMS, STRUCT BIOL RES LAB, NIH, BETHESDA, MD USA. HEBREW UNIV JERUSALEM, HADASSAH MED SCH, DEPT MEMBRANE & ULTRASTRUCT RES, IL-91010 JERUSALEM, ISRAEL. UNIV WESTERN ONTARIO, DEPT IMMUNOL & MICROBIOL, LONDON, ON N6A 5C1, CANADA. RP Beveridge, TJ (reprint author), UNIV GUELPH, COLL BIOL SCI, DEPT MICROBIOL, GUELPH, ON N1G 2W1, CANADA. NR 206 TC 96 Z9 103 U1 0 U2 22 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0168-6445 J9 FEMS MICROBIOL REV JI Fems Microbiol. Rev. PD JUN PY 1997 VL 20 IS 1-2 BP 99 EP 149 DI 10.1016/S0168-6445(97)00043-0 PG 51 WC Microbiology SC Microbiology GA XT173 UT WOS:A1997XT17300007 PM 9276929 ER PT J AU Casanova, M Bell, DA Heck, HD AF Casanova, M Bell, DA Heck, HD TI Dichloromethane metabolism to formaldehyde and reaction of formaldehyde with nucleic acids in hepatocytes of rodents and humans with and without glutathione S-transferase T1 and M1 genes SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID RAT NASAL-MUCOSA; METHYLENE-CHLORIDE; COVALENT BINDING; SALMONELLA-TYPHIMURIUM; C-14 FORMALDEHYDE; H-3 FORMALDEHYDE; RISK ASSESSMENT; DNA STRUCTURE; B6C3F1 MICE; IN-VIVO AB Metabolism of dichloromethane (DCM) to formaldehyde (HCHO) via a glutathione S-transferase (GST) pathway is thought to be required, for its carcinogenic effects in B6C3F(1) mice, In humans, this reaction is catalyzed primarily by the protein product of the gene GSTT1, a member of the Theta class of GST, and perhaps to a small extent by the protein product of the gene GSTM1. Humans are polymorphic with respect to both genes. Since HCHO may bind to both DNA and RNA forming DNA-protein crosslinks (DPX) and RNA-formaldehyde adducts (RFA), respectively, these products were determined in isolated hepatocytes from B6C3F(1) mice, F344 rats, Syrian golden hamsters, and humans to compare species with respect to the production of HCHO from DCM and its reaction with nucleic acids, Only mouse hepatocytes formed detectable amounts of DPX, the quantities of which corresponded well with quantities of DPX formed in the livers of mice exposed to DCM in vivo [Casanova, M., Conolly, R. B., and Heck, H. d'A. (1996). Fundam. Appl. Toxicol, 31, 103-116], Hepatocytes from all rodent species and from humans with functional GSTT1 and GSTM1 genes formed RFA, No RFA were detected in human cells lacking these genes, Yields of RFA in hepatocytes of mice were 4-fold higher than in those of rats, 7-fold higher than in those of humans, and 14-fold higher than in those of hamsters. The RFA:DPX ratio in mouse hepatocytes incubated with DCM was approximately 9.0 +/- 1.4, but it was 1.1 +/- 0.3 when HCHO was added directly to the medium, indicating that HCHO generated internally from DCM is not equivalent to that added externally to cells and that it may occupy separate pools. DPX were not detected in human hepatocytes even at concentrations equivalent to an in vivo exposure of 10,000 ppm; however, the possibility that very small amounts of DPX were produced from DCM cannot be excluded, since HCHO was formed in human cells, Maximal amounts of DPXliver that might be formed in humans were predicted from the amounts in mite and the relative amounts of RFA in hepatocytes of both species. With predicted DPXliver as the dosimeter, the unit risk, the upper 95% confidence limit on the cancer risk, and the margin of exposure were calculated at several concentrations using the linearized multistage and benchmark dose methods. Since the actual delivered dose is smaller than that predicted, the results suggest that DCM poses at most a very low risk of liver cancer to humans. (C) 1997 Society of Toxicology. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Casanova, M (reprint author), CHEM IND INST TOXICOL,POB 12137,RES TRIANGLE PK,NC 27709, USA. NR 61 TC 30 Z9 32 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUN PY 1997 VL 37 IS 2 BP 168 EP 180 DI 10.1006/faat.1997.2313 PG 13 WC Toxicology SC Toxicology GA XL407 UT WOS:A1997XL40700010 PM 9242590 ER PT J AU Holden, JP Orsini, JA Siegel, KL Kepple, TM Gerber, LH Stanhope, SJ AF Holden, JP Orsini, JA Siegel, KL Kepple, TM Gerber, LH Stanhope, SJ TI Surface movement errors in shank kinematics and knee kinetics during gait SO GAIT & POSTURE LA English DT Article DE biomechanics; gait; walking; kinematics; kinetics; knee; bone; skin; soft tissue ID WALKING; ANKLE; FOOT AB The movement of surface mounted targets (SMT) on a shell at the mid-shank and of bone mounted targets attached to the distal shank using a Percutaneous Skeletal Tracker (PST) were simultaneously measured during free-speed walking of three adult subjects having different body types. Surface movement errors in shank kinematic estimates were determined by expressing the segmental motion derived from the SMT relative to the PST-based segment coordinate system (SCS) located at the segment center of gravity. The greatest errors were along and around the shank longitudinal axis, with peak magnitudes of 10 mm of translation and 8 degrees of rotation in one subject. Estimates of knee joint center locations differed by less than 11 mm in each SCS direction. Differences in estimates of net knee joint forces and moments were most prominent during stance phase, with magnitudes up to 39 N in the shank mediolateral direction and 9 N.m about the mediolateral axis. The differences in kinetics were primarily related to the effect of segment position and orientation on the expression of joint forces and on the magnitude and expression of joint moments. C1 UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. WARREN G MAGNUSON CLIN CTR,DEPT REHABIL MED,BETHESDA,MD. NIH,BIOMECH LAB,BETHESDA,MD 20892. RP Holden, JP (reprint author), NIAMSD,BETHESDA,MD 20892, USA. RI Siegel, Karen Lohmann/B-5898-2008; OI Siegel, Karen Lohmann/0000-0002-0788-6612 NR 29 TC 92 Z9 95 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD JUN PY 1997 VL 5 IS 3 BP 217 EP 227 DI 10.1016/S0966-6362(96)01088-0 PG 11 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA XF376 UT WOS:A1997XF37600005 ER PT J AU Krempels, K Hunyady, B OCarroll, AM Mezey, E AF Krempels, K Hunyady, B OCarroll, AM Mezey, E TI Distribution of somatostatin receptor messenger RNAs in the rat gastrointestinal tract SO GASTROENTEROLOGY LA English DT Article ID MOLECULAR-CLONING; EXPRESSION; SECRETION; PITUITARY; PANCREAS; SUBTYPE; GROWTH; IDENTIFICATION; AFFINITY; HORMONE AB Background & Aims: The gastrointestinal (Gl) tract is a major source and target of somatostatin (SRIF), Recently, five pharmacologically different SRIF receptors (sst1-5) were cloned. The cellular and tissue distribution of the sst1-5 messenger RNAs (mRNAs) were studied in the rat Gl tract using in situ hybridization histochemistry (ISHH). Methods: Two sets of S-35-Uridine triphosphate (UTP)-labeled antisense and sense riboprobes were prepared for each sst. ISHH was conducted on frozen tissue samples from rat stomach, duodenum, jejunum, ileum, colon, and pancreas, Results: mRNAs of all five sst-s are widely expressed in the rat Gl tract. The distribution pattern for each sst mRNA was identical with both antisense probes, No specific signal was found with any of the sense probes. Each layer of the different parts of the gut expressed mRNAs of multiple sst subtypes, All organs expressed sst3 mRNA very intensely, The lowest levels of mRNA expression for all five subtypes within the GI tract were found in the pancreas, Conclusions: The widespread expression of sst mRNAs suggests a significant: role for SRIF in the regulation of Gl function. C1 NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 37 TC 61 Z9 61 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 1997 VL 112 IS 6 BP 1948 EP 1960 DI 10.1053/gast.1997.v112.pm9178687 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XE188 UT WOS:A1997XE18800026 PM 9178687 ER PT J AU Mouradian, MM Chase, TN AF Mouradian, MM Chase, TN TI Gene therapy for Parkinson's disease: Current knowledge and future perspective SO GENE THERAPY LA English DT Editorial Material RP Mouradian, MM (reprint author), NINCDS,EXPT THERAPEUT BRANCH,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 6 TC 4 Z9 4 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUN PY 1997 VL 4 IS 6 BP 504 EP 506 DI 10.1038/sj.gt.3300449 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XD857 UT WOS:A1997XD85700002 PM 9231065 ER PT J AU Schumann, G Cannon, K Ma, WP Crouch, RJ Boeke, JD AF Schumann, G Cannon, K Ma, WP Crouch, RJ Boeke, JD TI Antiretroviral effect of a gag-RNase HI fusion gene SO GENE THERAPY LA English DT Article DE antiviral gene therapy; murine leukemia virus; RCAS vectors; RNase HI; Serratia nuclease ID HUMAN-IMMUNODEFICIENCY; RETROVIRUS VECTORS; VIRUS; NUCLEASE; EXPRESSION; INSERTION; PROTEINS; VIRIONS; DNA AB We have previously shown that a molecule consisting of a fusion of a Ca2+-dependent nuclease (from Staphylococcus aureus) to a retroviral coat protein specifies a potent antiviral specific for that retrovirus. Genes specifying such fusion proteins can be delivered to virus-susceptible cells, providing an antiviral gene therapy aimed at limiting virus spread. We report here the results of experiments to vary the nuclease moiety of such fusion proteins. We found that one nuclease, Serratia marcescens nuclease, was extremely toxic to host cells and hence not likely to be useful for therapeutic purposes. A second nuclease, Escherichia coli RNase HI was found to be nontoxic and highly effective against a murine leukemia virus when it was fused to the leukemia virus coat protein. The fusion protein was enzymatically active and stably expressed, without apparent toxicity to host cells. Reduction in infectious virus output was as high as 97-99%. These studies provide a model system for the development of gene therapeutic agents aimed at combating retroviral infections in vivo. C1 JOHNS HOPKINS UNIV HOSP,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. NICHHD,GENET MOL LAB,NIH,BETHESDA,MD. FU NIAID NIH HHS [AI352P2] NR 29 TC 12 Z9 16 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUN PY 1997 VL 4 IS 6 BP 593 EP 599 DI 10.1038/sj.gt.3300421 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XD857 UT WOS:A1997XD85700013 PM 9231076 ER PT J AU Hayward, BE Zavanelli, M Furano, AV AF Hayward, BE Zavanelli, M Furano, AV TI Recombination creates novel L1 (LINE-1) elements in Rattus norvegicus SO GENETICS LA English DT Article ID INTERSPERSED REPEATED DNA; EMBRYONAL CARCINOMA-CELLS; MOUSE LINE-1; RIBONUCLEOPROTEIN-PARTICLES; REPETITIVE DNA; NONHOMOLOGOUS RECOMBINATION; RETROTRANSPOSABLE ELEMENT; MURINE RADIATION; FAMILY; SEQUENCES AB Mammalian L1 (long interspersed repeated DNA, LINE-1) retrotransposons consist of a 5' untranslated region (UTR) with regulatory properties, two protein encoding regions (ORF I, ORF II, which encodes a reverse transcriptase) and a 3' UTR. L1 elements have been evolving in mammals for >100 million years and this process continues to generate novel L1 subfamilies in modern species, Here we characterized the youngest known subfamily in Rattus norvegicus, L1(mlvi2), and unexpectedly found that this element has a dual ancestry. While its 3' UTR shares the same lineage as its nearest chronologically antecedent subfamilies, L1(3) and L1(4), its ORF I sequence does not. The L1(mlvi2) ORF I was derived from an ancestral ORF I sequence that was the evolutionary precursor of the L1(3) and L1(4) ORF I. We suggest that an ancestral ORF I sequence was recruited into the modern L1(mlvi2) subfamily by recombination that possibly could have resulted from template strand switching by the reverse transcriptase during L1 replication. This mechanism could also account for some of the structural features of rodent L1 5' UTR and ORF I sequences including one of the more dramatic features of L1 evolution in mammals, namely the repeated acquisition of novel 5' UTRs. C1 NIDDKD,SECT GENOM STRUCT & FUNCT,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 66 TC 35 Z9 37 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 1997 VL 146 IS 2 BP 641 EP 654 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA XD216 UT WOS:A1997XD21600019 PM 9178013 ER PT J AU Hirotsune, S Pack, SD Chong, SS Robbins, CM Pavan, WJ Ledbetter, DH WynshawBoris, A AF Hirotsune, S Pack, SD Chong, SS Robbins, CM Pavan, WJ Ledbetter, DH WynshawBoris, A TI Genomic organization of the murine Miller-Dieker/lissencephaly region: Conservation of linkage with the human region SO GENOME RESEARCH LA English DT Letter ID DIEKER LISSENCEPHALY GENE; SACCHAROMYCES-CEREVISIAE; EXTENDED CHROMATIN; CHROMOSOMES; DNA; DELETION; PROTEINS; SUBUNIT AB Several human syndromes are associated with haploinsufficiency of chromosomal regions secondary to microdeletions. Isolated lissencephaly sequence (ILS), a human developmental disease characterized by a smooth cerebral surface (classical lissencephaly) and microscopic evidence of incomplete neuronal migration, is often associated with small deletions or translocations at chromosome 17p13.3. Miller-Dieker syndrome (MDS) is associated with larger deletions of 17p13.3 and consists of classical lissencephaly with additional phenotypes including facial abnormalities. We have isolated the murine homologs of three genes located inside and outside the MDS region: Lis1, Mnt/Rox, and 14-3-3 epsilon. These genes are all located on mouse chromosome 11B2, as determined by metaphase FISH, and the relative order and approximate gene distance was determined by interphase FISH analysis. The transcriptional orientation and intergenic distance of Lis1 and Mnt/Rox were ascertained by Fragmentation analysis of a mouse yeast artificial chromosome containing both genes. To determine the distance and orientation of 14-3-3 epsilon with respect to Lis1 and Mnt/Rox, we introduced a super-rare cutter site (VDE) that is unique in the mouse genome into 14-3-3 epsilon by gene targeting. Using the introduced VDE site, the orientation of this gene was determined by pulsed field gel electrophoresis and Southern blot analysis. Our results demonstrate that the MDS region is conserved between human and mouse. This conservation of linkage suggests that the mouse can be used to model microdeletions that occur in ILS and MDS. C1 NIH,LAB GENET DIS RES,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. NIH,DIAGNOST DEV BRANCH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. NIH,SEQUENCING CORE FACIL,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. RI Pack, Svetlana/C-2020-2014; Chong, Samuel/D-8098-2015 NR 32 TC 21 Z9 21 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD JUN PY 1997 VL 7 IS 6 BP 625 EP 634 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XF046 UT WOS:A1997XF04600008 PM 9199935 ER PT J AU Zhang, JH Madden, TL AF Zhang, JH Madden, TL TI PowerBLAST: A new network BLAST application for interactive or automated sequence analysis and annotation SO GENOME RESEARCH LA English DT Article ID SEARCH TOOL AB As the rate of DNA sequencing increases, analysis by sequence similarity search will need to become much more efficient in terms of sensitivity, specificity, automation potential, and consistency in annotation. PowerBLAST was developed, in part, to address these problems. PowerBLAST includes a number of options for masking repetitive elements and low complexity subsequences. It also has the capacity to restrict the search to any level of NCBI's taxonomy index, thus supporting ''comparative genomics'' applications. Postprocessing of the BLAST output using the SIM series of algorithms produces optimal, gapped alignments, and multiple alignments when a region of the query sequence matches multiple database sequences. PowerBLAST is capable of processing sequences of any length because it divides long query sequences into overlapping fragments and then merges the results after searching. The results may be viewed graphically, as a textual representation, or as an HTML page with links to GenBank and Entrez. For matching database sequences, annotated features are superimposed on the aligned query sequence in the output, thus greatly increasing the ease of interpretation. Such features may be used for automated annotation of new sequence because PowerBLAST output in ASN.1 form may be ''dragged and dropped'' into NCBI's Sequin program for sequence annotation and submission. PowerBLAST is capable of analyzing and annotating a 100-kb query in 60 min on NCBI's BLAST server. RP Zhang, JH (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. NR 14 TC 202 Z9 213 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD JUN PY 1997 VL 7 IS 6 BP 649 EP 656 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XF046 UT WOS:A1997XF04600011 PM 9199938 ER PT J AU Elkahloun, AG Krizman, DB Wang, ZL Hofmann, TA Roe, B Meltzer, PS AF Elkahloun, AG Krizman, DB Wang, ZL Hofmann, TA Roe, B Meltzer, PS TI Transcript mapping in a 46-kb sequenced region at the core of 12q13.3 amplification in human cancers SO GENOMICS LA English DT Article ID EXON AMPLIFICATION; DNA; MEMBER; GENES AB We used a combination of sequence analysis and exon trapping in an effort to determine the complete transcript map for a cosmid (6E5) derived from 12q13.3, a region of DNA sequence amplification in human cancers. This cosmid, previously known to contain three genes (CDK4, SAS, and OS9), was sequenced, and that information was used for computer-assisted analysis. In addition, 6E5 was subjected to both internal and 3'-terminal exon-trapping protocols, and the results of these studies were used to guide cDNA cloning experiments. These studies demonstrate that this cosmid is derived from a remarkably gene-dense region and add two new transcripts (KIAA0167 and 6E5.2) to the list of sequences that are expressed in tumors bearing amplification of this region. (C) 1997 Academic Press. C1 NATL HUMAN GENOME RES INST,CANC GENET LAB,NIH,BETHESDA,MD 20892. UNIV OKLAHOMA,DEPT CHEM & BIOCHEM,NORMAN,OK 73019. FU NHGRI NIH HHS [HG00313] NR 22 TC 28 Z9 33 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 1 PY 1997 VL 42 IS 2 BP 295 EP 301 DI 10.1006/geno.1997.4727 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XE860 UT WOS:A1997XE86000014 PM 9192850 ER PT J AU Ogawa, Y Kovac, P AF Ogawa, Y Kovac, P TI Synthesis of the dodecasaccharide fragment representing the O-polysaccharide of Vibrio cholerae 0:1, serotype Ogawa, bearing an aglycon offering flexibility for chemical linking to proteins SO GLYCOCONJUGATE JOURNAL LA English DT Article DE Vibrio cholerae O-antigen; dodecasaccharide; neoglycoconjugate; 4-O-benzyl-3-deoxy-L-glycero-tetronic acid ID ANTIGENIC DETERMINANTS; C-13-NMR SPECTRA; BLOCK SYNTHESIS; GLYCOSIDES; PENTASACCHARIDE; THIOGLYCOSIDE; SUGARS AB Two azidohexasaccharide building blocks, of which the glycosyl acceptor was the 5-(methoxycarbonyl)pentyl glycoside, were coupled using the trichloroacetimidate technology. The 12 azido functions present in the dodecasaccharide thus formed were then converted to amino groups using hydrogen sulfide as a reducing reagent, Subsequent N-acylation with 4-O-benzyl-L-glycero-tetronic acid, followed by catalytic debenzylation yielded the desired spacer-equipped, title dodecasaccharide. C1 NIDDK,NIH,BALTIMORE,MD 20892. NR 23 TC 8 Z9 8 U1 0 U2 3 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD JUN PY 1997 VL 14 IS 4 BP 433 EP 438 DI 10.1023/A:1018591132723 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XJ714 UT WOS:A1997XJ71400003 PM 9249140 ER PT J AU Fireman, BH Quesenberry, CP Somkin, CP Jacobsen, AS Baer, D West, D Potosky, AL Brown, ML AF Fireman, BH Quesenberry, CP Somkin, CP Jacobsen, AS Baer, D West, D Potosky, AL Brown, ML TI Cost of care for cancer in a health maintenance organization SO HEALTH CARE FINANCING REVIEW LA English DT Article ID BREAST; STAGE; DIAGNOSIS AB The direct costs of medical care for cancer are examined at Kaiser Permanente (KP) in Northern California. Use data from July 1987 through June 1991 were obtained from KP automated files for all 21,977 KP patients in the Bay Area SEER registry with cancer at one of seven cancer sites. Medical charts were reviewed for a stratified sample of 886 patients. Costs were estimated for initial, continuing, and terminal care, and for all person time within 15 years of diagnosis, by stage at diagnosis. From diagnosis until death or 15 years, long-term costs attributable to cancer were as follows: breast, $35,000; colon, $42,000; rectum, $51,000; lung, $33,000; ovarian, $64,000; prostate, $29,000; and Non-Hodgkin's Lymphoma (NHL), $48,000. The utilization and cost results reported here may be useful in assessing the cost-effectiveness of cancer prevention and control programs, in adjusting capitation rates and budgets, and in estimating the aggregate medical care costs attributable to cancer. C1 NO CALIF CANC CTR,SAN FRANCISCO OAKLAND SEER,UNION CITY,CA. NCI,APPL RES BRANCH,BETHESDA,MD 20892. RP Fireman, BH (reprint author), KAISER PERMANENTE MED CARE PROGRAM,DIV RES,3505 BROADWAY,OAKLAND,CA 94611, USA. FU NCI NIH HHS [N01-CN-05224] NR 20 TC 137 Z9 138 U1 0 U2 2 PU HEALTH CARE FINANCING REVIEW PI BALTIMORE PA 7500 SECURITY BLVD, C-3-11-07, BALTIMORE, MD 21224-1850 SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SUM PY 1997 VL 18 IS 4 BP 51 EP 76 PG 26 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA YJ634 UT WOS:A1997YJ63400005 PM 10175613 ER PT J AU Basile, AS Jones, EA AF Basile, AS Jones, EA TI Ammonia and GABA-ergic neurotransmission: Interrelated factors in the pathogenesis of hepatic encephalopathy SO HEPATOLOGY LA English DT Review ID BENZODIAZEPINE RECEPTOR LIGANDS; GAMMA-AMINOBUTYRIC-ACID; VISUAL EVOKED-POTENTIALS; RABBIT MODEL; PREGNENOLONE-SULFATE; CEREBROSPINAL-FLUID; BINDING-SITES; ANIMAL-MODEL; BRAIN; ANTAGONIST C1 UNIV AMSTERDAM,ACAD MED CTR,DEPT GASTROINTESTINAL & LIVER DIS,NL-1105 AZ AMSTERDAM,NETHERLANDS. RP Basile, AS (reprint author), NIDDK,NEUROSCI LAB,NIH,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. NR 42 TC 76 Z9 81 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 1997 VL 25 IS 6 BP 1303 EP 1305 DI 10.1002/hep.510250636 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XC872 UT WOS:A1997XC87200001 PM 9185743 ER PT J AU Liang, Y Cushman, SM Whitesell, RR Matschinsky, FM AF Liang, Y Cushman, SM Whitesell, RR Matschinsky, FM TI GLUT1 is adequate for glucose uptake in GLUT2-deficient insulin-releasing beta-cells SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE pancreatic islet; glucose uptake; glucose metabolism ID PANCREATIC-ISLETS; GENE-EXPRESSION; TRANSPORTER; LIVER AB GLUT2 may play an important role in pancreatic: beta-cell glucose metabolism. A decrease in glucose uptake due to underexpression of GLUT2 has been considered as the cause of beta-cell dysfunction in diabetes with different pathogenesis. However, this view has been challenged by recent studies, in which the underexpression of GLUT2 was not accompanied by a decrease in glucose uptake. Our present aim is to evaluate the presumed importance of GLUT2 in maintaining the efficiency of beta-cell glucose uptake. We studied the kinetic characteristics of 3-O-methylglucose uptake in two beta-cell lines. one of these is the beta TC3 cell line which expresses GLUT1 and the other is the beta HC9 cell line which expresses both GLUT1 and GLUT2. Under equilibrium exchange conditions, 3-O-methylglucose transport in these two cell lines showed similar values of K-m and V-max. The apparent IC50 of cytochalasin B for inhibiting 3-O-methylglucose transport in beta HC9 cells was nine times as high as in beta TC3 cells, indicating that GLUT1 is the critically important glucose transporter in the beta TC3 cell line and GLUT2 in the beta HC9 cell line. In both cell lines, the rates of glucose uptake we re at least three times as fast as th at of glucose phosphorylation. Our results suggest that GLUT1 is able to compensate for GLUT2 loss as it occurs in beta TC3 and maintains a commensurately high capacity of glucose uptake to sustain glucose metabolism in pancreatic beta-cells. C1 UNIV PENN,SCH MED,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. NIDDK,EXPT DIABET METAB & NUTR SECT,DB,NIH,BETHESDA,MD. VANDERBILT UNIV,SCH MED,DEPT PHYSIOL & MOL BIOPHYS,NASHVILLE,TN 37212. RP Liang, Y (reprint author), UNIV PENN,SCH MED,DIABET RES CTR,ROOM 501,STEMMLER HALL,36TH & HAMILTON WALK,PHILADELPHIA,PA 19104, USA. FU NIDDK NIH HHS [DK-19525, DK-22122] NR 26 TC 3 Z9 3 U1 0 U2 1 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUN PY 1997 VL 29 IS 6 BP 255 EP 260 DI 10.1055/s-2007-979032 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XH664 UT WOS:A1997XH66400001 PM 9230344 ER PT J AU Crawley, JN Paylor, R AF Crawley, JN Paylor, R TI A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice SO HORMONES AND BEHAVIOR LA English DT Article ID INBRED MOUSE STRAINS; RADIAL-MAZE PERFORMANCE; NUCLEUS BASALIS MAGNOCELLULARIS; OPIOID RECEPTOR ANTAGONIST; MOSSY FIBER DISTRIBUTION; VENTRAL TEGMENTAL AREA; MEDIAL SEPTAL AREA; ANXIOLYTIC ACTIVITY; SPATIAL MEMORY; ANIMAL-MODEL AB Behavioral phenotyping of transgenic and knockout mice requires rigorous, formal analyses. Well-characterized paradigms can be chosen from the established behavioral neuroscience literature. This review describes (1) a series of neurological and neuropsychological tests which are effectively used as a first screen for behavioral abnormalities in mutant mice, and (2) a series of specific behavioral paradigms, clustered by category. Included are multiple paradigms for each category, including learning and memory, feeding, analgesia, aggression, anxiety, depression, schizophrenia, and drug abuse models. Examples are given from the experiences of the authors, in applying these experimental designs to transgenic and knockout mice. Extensive references for each behavioral paradigm are provided, to allow new investigators to access the relevant literature on behavioral methodology. RP Crawley, JN (reprint author), NIMH,EXPT THERAPEUT BRANCH,SECT BEHAV NEUROPHARMACOL,BETHESDA,MD 20892, USA. NR 189 TC 379 Z9 384 U1 6 U2 20 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0018-506X J9 HORM BEHAV JI Horm. Behav. PD JUN PY 1997 VL 31 IS 3 BP 197 EP 211 DI 10.1006/hbeh.1997.1382 PG 15 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA XJ368 UT WOS:A1997XJ36800004 PM 9213134 ER PT J AU VanLaer, L VanCamp, G Green, ED Huizing, EH Willems, PJ AF VanLaer, L VanCamp, G Green, ED Huizing, EH Willems, PJ TI Physical mapping of the HOXA1 gene and the hnRPA2B1 gene in a YAC contig from human chromosome 7p14-p15 SO HUMAN GENETICS LA English DT Article ID LOCALIZATION; 7P AB A cluster of homeobox-containing genes (HOXA) and a heterogeneous nuclear ribonucleoprotein (hnRPA2B1) have both previously been assigned to chromosome 7p15 by in situ hybridization. In this report, we constructed a YAC contig from chromosome 7p14-p15, between markers D7S2496 and D7S1838, and determined the position of the HOXA1 gene and the hnRPA2B1 gene in this YAC contig. C1 UNIV ANTWERP,DEPT MED GENET,B-2610 ANTWERP,BELGIUM. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV UTRECHT HOSP,DEPT OTORHINOLARYNGOL,NL-3508 GA UTRECHT,NETHERLANDS. RI Van Camp, Guy/F-3386-2013 OI Van Camp, Guy/0000-0001-5105-9000 NR 16 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 1997 VL 99 IS 6 BP 831 EP 833 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA XB305 UT WOS:A1997XB30500023 PM 9187682 ER PT J AU Pajevic, S Bacharach, SL Carson, RE Weiss, GH AF Pajevic, S Bacharach, SL Carson, RE Weiss, GH TI Effects of time delay in cardiac blood flow measurements by bolus (H2O)-O-15 SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE blood flow; cardiac imaging; Kety model; positron emission tomography ID POSITRON-EMISSION TOMOGRAPHY; COMPUTED-TOMOGRAPHY; QUANTIFICATION; QUANTITATION; INHALATION; STRATEGY; INVIVO; WATER; INPUT; PET AB Myocardial blood flow (rMBF) can be measured using dynamic positron emission tomography (PET) and bolus injection of H-2 O-15. Recent studies indicate that large errors in the estimates of flea ((f) over cap) can be produced by time shifts between the true arterial input function and the measured input function [A(t)]. We have investigated this phenomenon further using A(t) derived from patient data, and using simulated myocardial time activity curves [M(t)]. We found that the judicious choice of scan parameters and region of interest (ROI) placement, these errors can be greatly reduced, In particular, when A(t) is measured from the left ventricular (LV) cavity, the bias in (f) over cap is negligible over a wide range of circumstances, However, when A(t) is not measured from the LV cavity, the bias in dow can be large for short scans (<2 min) or low flow values (f < 0.4 ml/g/min). We show that the bias is primarily due to the spillover term in the model that is most commonly used to compute rMBF and suggest some correction methods. We conclude that it is possible to avoid errors in estimates of flow due to time delay. C1 NIH,DEPT NUCL MED,CTR CLIN,BETHESDA,MD 20982. NIH,PET DEPT,CTR CLIN,BETHESDA,MD 20982. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 17 TC 5 Z9 5 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUN PY 1997 VL 16 IS 3 BP 294 EP 300 DI 10.1109/42.585763 PG 7 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA XC715 UT WOS:A1997XC71500006 PM 9184891 ER PT J AU Johnson, CA Seidel, J Carson, RE Gandler, WR Sofer, A Green, MV DaubeWitherspoon, ME AF Johnson, CA Seidel, J Carson, RE Gandler, WR Sofer, A Green, MV DaubeWitherspoon, ME TI Evaluation of 3D reconstruction algorithms for a small animal PET camera SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1996 Medical Imaging Conference (MIC) / Nuclear Science Symposium (NSS) CY NOV 05-09, 1996 CL ANAHEIM, CA SP Inst Elect & Electr Engineers ID QUANTITATION; SCANNER AB The use of paired, opposing position-sensitive phototube scintillation cameras (SCs) operating in coincidence for small animal imaging with positron emitters is currently under study. Because of the low sensitivity of the system even in 3D mode and the need to produce images with high resolution, it was postulated that a 3D expectation maximization (EM) reconstruction algorithm might be well suited for this application. We investigated six reconstruction algorithms for the 3D SC PET camera: 2D filtered back-projection (FBP), 3D reprojection (3DRP), 2D EM, 3D EM, 2D ordered subset EM (OSEM), and 3D OSEM. Noise was assessed for all slices by the coefficient of variation in a simulated uniform cylinder. Resolution was assessed from a simulation of 15 point sources in the warm background of the uniform cylinder. At comparable noise levels, the resolution achieved with EM and OSEM (0.9-mm to 1.2-mm) is significantly better than that obtained with FBP or 3DRP (1.5-mm to 2.0-mm.) Images of a rat skull labeled with F-18-fluoride suggest that 3D EM and 3D OSEM can improve image quality of a small animal PET camera. C1 NIH,DEPT NUCL MED,CTR CLIN,BETHESDA,MD 20892. NIH,PET DEPT,CTR CLIN,BETHESDA,MD 20892. GEORGE MASON UNIV,FAIRFAX,VA 22030. RP Johnson, CA (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 16 TC 64 Z9 64 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 1997 VL 44 IS 3 BP 1303 EP 1308 DI 10.1109/23.597005 PN 2 PG 6 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA XF300 UT WOS:A1997XF30000035 ER PT J AU Wiest, DL Ashe, JM Howcroft, TK Lee, HM Kemper, DM Negishi, I Singer, DS Singer, A Abe, R AF Wiest, DL Ashe, JM Howcroft, TK Lee, HM Kemper, DM Negishi, I Singer, DS Singer, A Abe, R TI A spontaneously arising mutation in the DLAARN motif of murine ZAP-7O abrogates kinase activity and arrests thymocyte development SO IMMUNITY LA English DT Article ID CELL ANTIGEN RECEPTOR; PROTEIN-TYROSINE KINASE; SEVERE COMBINED IMMUNODEFICIENCY; IMMATURE CD4+CD8+ THYMOCYTES; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODY; ZETA-CHAIN; PHOSPHOLIPASE C-GAMMA-1; NEGATIVE SELECTION; T-CELLS AB Development of immature CD4(+)CD8(+) thymocytes into functionally mature CD4(+) and CD8(+) T cells is driven by selection events that require signals transduced through the T cell antigen receptor (TCR). Transduction of TCR signals in the thymus involves tyrosine phosphorylation of the protein tyrosine kinase ZAP-70 by p56(lck) and results in induction of ZAP-70 enzymatic activity. We have identified a novel, spontaneously arising point mutation within a highly conserved motif (DLAARN) in the kinase domain of murine ZAP-70 that uncouples tyrosine phosphorylation of ZAP-70 from induction of ZAP-70 kinase activity. Mice homozygous for this mutation are devoid of mature T cells because thymocyte development is arrested at the CD4(+)CD8(+) stage of differentiation. The developmental arrest is due to the inability of CD4(+)CD8(+) thymocytes to propagate TCR signals in the absence of ZAP-70 kinase activity despite tyrosine phosphorylation of TCR-associated ZAP-70 molecules. C1 NCI, EXPT IMMUNOL BRANCH, NIH, BETHESDA, MD 20892 USA. USN, MED RES INST, IMMUNE CELL BIOL DEPT, BETHESDA, MD 20889 USA. NIPPON ROCHE RES CTR, KAMAKURA, KANAGAWA 247, JAPAN. SCI UNIV TOKYO, RES INST BIOL SCI, DIV IMMUNOBIOL, TOKYO, CHIBA 278, JAPAN. OI Wiest, David/0000-0002-0792-3188 NR 45 TC 62 Z9 64 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD JUN PY 1997 VL 6 IS 6 BP 663 EP 671 DI 10.1016/S1074-7613(00)80442-2 PG 9 WC Immunology SC Immunology GA XG579 UT WOS:A1997XG57900002 PM 9208839 ER PT J AU Porgador, A Yewdell, JW Deng, YP Bennink, JR Germain, RN AF Porgador, A Yewdell, JW Deng, YP Bennink, JR Germain, RN TI Localization, quantitation, and in situ detection of specific peptide MHC class I complexes using a monoclonal antibody SO IMMUNITY LA English DT Article ID T-CELL RECEPTOR; VIRAL PEPTIDES; ANTIGEN; MOLECULES; AFFINITY; BINDING; RECOGNITION; ACTIVATION; EXPRESSION; RESPONSES AB CD8(+) T lymphocytes recognize antigens as short peptides bound to MHC class I molecules. Available methods cannot determine the number and distribution of these ligands on individual cells or detect antigen-presenting cells in tissues. Here we describe a method for eliciting and identifying monoclonal antibodies specific for a particular peptide-MHC class I combination. One such antibody can identify antigen complexes with a limit of detection approaching that of T cells. We used this antibody to determine the number of peptide-class I complexes generated upon viral infection, to identify antigen-presenting cells in cell mixtures, to determine the site of peptide-MHC class I interaction inside cells, and to visualize cells bearing specific peptide-MHC class I complexes after in vivo infection. Similar antibodies may prove useful for diagnostic or therapeutic purposes in cancer, infectious diseases, and autoimmune disorders. C1 NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 55 TC 505 Z9 511 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 1997 VL 6 IS 6 BP 715 EP 726 DI 10.1016/S1074-7613(00)80447-1 PG 12 WC Immunology SC Immunology GA XG579 UT WOS:A1997XG57900007 PM 9208844 ER PT J AU Mackall, CL Gress, RE AF Mackall, CL Gress, RE TI Pathways of T-cell regeneration in mice and humans: Implications for bone marrow transplantation and immunotherapy SO IMMUNOLOGICAL REVIEWS LA English DT Review ID ATHYMIC NUDE RATS; CD45 ISOFORM EXPRESSION; LYMPHOCYTES-T; INTENSIVE CHEMOTHERAPY; HOMEOSTATIC REGULATION; RHEUMATOID-ARTHRITIS; REPERTOIRE; SUBSETS; SELECTION; GRAFT AB Much of our understanding of the immunobiology of bone marrow transplantation (BMT) has come from studies in young adult mice reconstituted with T-cell-depleted bone marrow after lethal irradiation. Recent evidence indicates, however, that the applicability of conclusions drawn from this model to human BMT may be limited. While mice retain essentially normal thymic function well past sexual maturity, humans show significant age-related declines in thymic function relatively early in life. Therefore, thymic-deficient mice may provide a more accurate model for study of the immunobiology of BMT. T-cell regeneration in thymic-deficient mice occurs primarily via antigen-driven expansion of mature peripheral T cells resulting in limited immune competence due to quantitative deficiencies in T-cell number and severe restriction in the diversity of the regenerated T-cell receptor (TCR) repertoire. Similarly, immune reconstitution in adult humans after BMT is marked by quantitative T-cell deficiencies, especially in the CD4(+) subset, and loss of TCR diversity. Taken together, prevailing evidence suggests that thymic function is suboptimal in most BMT recipients, and that thymic-independent pathways of T-cell regeneration are generally limited in their ability to restore host immune competence. New strategies to enhance thymic function in man after BMT would hold great therapeutic potential. C1 NCI,EXPT IMMUNOL & MED BRANCH,BETHESDA,MD 20892. RP Mackall, CL (reprint author), NCI,PEDIAT ONCOL BRANCH,BLDG 10,RM 13N240,10 CTR DR MSC 1928,BETHESDA,MD 20892, USA. NR 68 TC 176 Z9 178 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 1997 VL 157 BP 61 EP 72 DI 10.1111/j.1600-065X.1997.tb00974.x PG 12 WC Immunology SC Immunology GA XL050 UT WOS:A1997XL05000005 PM 9255622 ER PT J AU Murphy, WJ Longo, DL AF Murphy, WJ Longo, DL TI The potential role of NK cells in the separation of graft-versus-tumor effects from graft-versus-host disease after allogeneic bone marrow transplantation SO IMMUNOLOGICAL REVIEWS LA English DT Review ID NATURAL-KILLER-CELLS; COLONY-STIMULATING FACTOR; ANTI-ASIALO GM1; CHRONIC MYELOGENOUS LEUKEMIA; T-CELLS; GROWTH-HORMONE; RECOMBINANT INTERLEUKIN-2; NEUROENDOCRINE HORMONES; EFFECTS INVIVO; DONOR AB Allogeneic bone marrow transplantation (BMT) is being increasingly used for the treatment of a variety of cancers ranging from leukemias to breast cancer, However, significant obstacles currently limit the efficacy of this treatment procedure. The predominant two are the occurrence of graft-versus-host disease (GVHD) and relapse from the cancer. While regimens exist that prevent the occurrence or severity of GVHD, these same regimens also increase the rate of relapse. Conversely, most attempts to reduce the relapse rate also result in increased GVHD. The use of NK cells as an adoptive immunotherapy after BMT is attractive for several reasons. NK cells exhibit antitumor effects both in vitro and in animal models and may, therefore, promote graft-versus-tumor (GVT) effects to remove minimal residual disease after allogeneic BMT. NK cells have also been shown to promote hematopoietic engraftment and donor cell reconstitution after allogeneic BMT in mice. The effects of NK cells on hematopoiesis are believed to be due to the hematopoietic grow-th factors they can produce after activation. Another advantage in using NK cells is that they can prevent the occurrence of GVHD after allogeneic BMT in mice. This effect is mediated at least in part by the immunosuppressive cytokine, transforming growth factor beta (TGF-beta). BMT studies in mice also indicate that the beneficial effects of NK cells are optimal if they are administered soon after the transplant. Thereafter, NK cells and, more importantly, IL-2, which is used to activate them, are detrimental and can exacerbate the subsequent GVHD. Thus, the use of activated NK cells after allogeneic BMT may provide GVT effects without inducing GVHD. C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. RP Murphy, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,POB B,BLDG 567,FREDERICK,MD 21702, USA. NR 83 TC 54 Z9 56 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 1997 VL 157 BP 167 EP 176 DI 10.1111/j.1600-065X.1997.tb00981.x PG 10 WC Immunology SC Immunology GA XL050 UT WOS:A1997XL05000012 PM 9255629 ER PT J AU Moller, DR Wysocka, M Greenlee, BM Ma, X Wahl, L Trinchieri, G Karp, CL AF Moller, DR Wysocka, M Greenlee, BM Ma, X Wahl, L Trinchieri, G Karp, CL TI Inhibition of human interleukin-12 production by pentoxifylline SO IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BLOOD MONONUCLEAR-CELLS; FACTOR-ALPHA PRODUCTION; STIMULATORY FACTOR; IMMUNE-RESPONSE; LYMPHOCYTES-T; IL-12; PROLIFERATION; ANTIBODIES; EXPRESSION AB Pharmacological control of interleukin-12 (IL-12) production may be a key therapeutic strategy for modulating immunological diseases dominated by type-1 cytokine responses. In this study, we investigated the effects of pentoxifylline on the production of IL-12 by human blood mononuclear cells and primary human monocytes stimulated with heat-killed Staphylococcus aureus Cowan strain I(SAC) or lipopolysaccharide (LPS). Pentoxifylline potently suppressed production of IL-12 in a concentration-dependent manner. In these same experiments, tumour necrosis factor-alpha (TNF-alpha) production was inhibited and IL-IO and prostaglandin E-2 (PGE(2)) production was enhanced by treatment with pentoxifylline. Suppression of IL-12 production by pentoxifylline was found to be independent of several known endogenous inhibitors of IL-12, such as IL-10, transforming growth factor-beta (TGF-beta), IL-4 and PGE(2). RNase protection assays revealed that pentoxifylline inhibited accumulation of both IL-12 p40 and p35 mRNA, suggesting a predominant mRNA locus for pentoxifylline-induced IL-12 inhibition. Low levels of pentoxifylline added to the suppression of IL-12 production by suboptimal inhibiting doses of dexamethasone, suggesting that this drug combination may have therapeutic utility. These results provide a firm rationale for the use of pentoxifylline in clinical trials of immunological disorders characterized by inappropriate type-1 immune responses. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOL MICROBIOL & IMMUNOL,BALTIMORE,MD. UNIV PENN,SCH MED,WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RP Moller, DR (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV PULM & CRIT CARE MED,5501 HOPKINS BAYVIEW CIRCLE,BALTIMORE,MD 21224, USA. FU NHLBI NIH HHS [HL-56065, P01 HL 49545]; NIAID NIH HHS [AI-01223] NR 45 TC 71 Z9 76 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUN PY 1997 VL 91 IS 2 BP 197 EP 203 DI 10.1046/j.1365-2567.1997.00246.x PG 7 WC Immunology SC Immunology GA XD014 UT WOS:A1997XD01400006 PM 9227317 ER PT J AU Candeias, S Peschon, JJ Muegge, K Durum, SK AF Candeias, S Peschon, JJ Muegge, K Durum, SK TI Defective T-cell receptor gamma gene rearrangement in interleukin-7 receptor knockout mice SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 13th European Immunology Meeting CY JUN 22-25, 1997 CL AMSTERDAM, NETHERLANDS DE T-cell receptor; VDJ recombination; interleukin-7 receptor; accessibility ID V(D)J REARRANGEMENT; BETA-GENE; CHAIN; EXPRESSION; THYMOCYTES; ENHANCER; LINEAGE; THYMUS; GROWTH; LOCUS AB T-cell receptor (TCR) genes need to be rearranged by a site specific-VDJ recombinase before they are expressed. This process, initiated in CD44(+)25(+) thymocytes, takes place during the early stages of T-cell differentiation in the thymus. Interleukin-7 receptor a chain knockout (IL-7R(-/-)) mice are severely deficient in B-lymphocytes and alpha beta T-cells and completely lack the gamma delta T-cell lineage. Thymocyte development is arrested at a very early stage (DN CD44(+)CD25(-)). Because this arrest is earlier than in mice with a block in VDJ recombination, we examined the rearrangement status of TCR genes in thymocytes from IL-7R(-/-) mice. The TCR beta locus showed a nearly normal pattern of VDJ rearrangements, consistent with the presence of alpha beta T-cells in these mice. However, TCR gamma locus rearrangement was absent or severely reduced for all the V gamma genes analyzed (V gamma 3, V gamma 4, V gamma 1.1, V gamma 1.2 and V gamma 2). In contrast, the delta locus showed little reduction in rearrangement. The defect in gamma rearrangements in IL-7R(-/-) thymocytes is not simply due to an absence of mature gamma delta T-cells, since TCR delta(-/-) mice, which also have only alpha beta T-cells, had normal levels of gamma and delta rearrangements. These findings indicate that one or both of the two known ligands of IL-7R, IL-7 and thymic stromal lymphopoietin (TSLP) serves as an extrinsic signal to specifically rearrange the TCR gamma locus. (C) 1997 Elsevier Science B.V. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK,MD 21702. IMMUNEX CORP,SEATTLE,WA. NCI,MOL IMMUNOREGULAT LAB,NIH,FREDERICK,MD 21702. NR 36 TC 54 Z9 54 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUN 1 PY 1997 VL 57 IS 1-3 SI SI BP 9 EP 14 DI 10.1016/S0165-2478(97)00062-X PG 6 WC Immunology SC Immunology GA XK606 UT WOS:A1997XK60600003 PM 9232418 ER PT J AU Zewe, M Rybak, SM Dubel, S Coy, JF Welschof, M Newton, DL Little, M AF Zewe, M Rybak, SM Dubel, S Coy, JF Welschof, M Newton, DL Little, M TI Cloning and cytotoxicity of a human pancreatic RNase immunofusion SO IMMUNOTECHNOLOGY LA English DT Article DE cytotoxicity; human pancreatic RNase; immunotoxin; scFv ID EOSINOPHIL-DERIVED NEUROTOXIN; SINGLE-CHAIN FV; ESCHERICHIA-COLI; RIBONUCLEASE; PROTEIN; ANGIOGENIN; ANTIBODY; DNA; IMMUNOTOXINS; EXPRESSION AB Background: Immunotoxins based on plant and bacterial proteins are usually very immunogenic. Human ribonucleases could provide an alternative basis for the construction of less immunogenic reagents. Two members of the human RNase family, angiogenin and eosinophil-derived neurotoxin (EDN), have been fused to a single chain antibody against the transferrin receptor, which is known to be internalised by endocytosis. The fusion proteins proved to be very efficient inhibitors of protein synthesis using various cell lines. It is not yet known whether the side effects of angiogenin and EDN will compromise their potential use as immunotoxins. Objectives: The goal of this work was to construct a human immunotoxin with no harmful side effects. Bovine pancreatic ribonuclease has been shown to be as potent as ricin at abolishing protein synthesis on injection into oocytes. We therefore decided to clone its human analogue, which is fairly ubiquitous and per se non-toxic. An immunofusion of human pancreatic RNase with a single chain antibody against the transferrin receptor was tested for its ability to inhibit protein synthesis in three different human tumor cell lines. Study design: DNA coding for the human pancreatic RNase was cloned partially from a human fetal brain cDNA library and then completed by PCR using a human placental cDNA library as a template. The RNase gene was then fused with a DNA coding for an single chain antibody against the transferrin receptor (CD71). After expressing the fusion protein in E. coli, the gene product was isolated from inclusion bodies and tested for cytotoxicity. Results: This fusion protein inhibited the protein synthesis of three human tumor cell lines derived from a melanoma, a renal carcinoma and a breast carcinoma, with IC50s of 8, 5 and 10 nM, respectively. These values were comparable with those using a similar fusion protein constructed with eosinophil derived neurotoxin (EDN) as the toxic moiety (IC50s of 8, 1.2 and 3 nM, respectively). The slightly lower activities of the human pancreatic RNase-scFv (pancRNase-scFv) with two of the cell lines suggests that fewer molecules are reaching the cytoplasmic compartment, since it was twice as active as EDN-scFv in inhibiting the protein synthesis of a rabbit reticulocyte lysate. Conclusion: These results demonstrate that the human pancreatic RNase, which is expected to have a very low immunogenic potential in humans with no inherent toxicity, may be a potent cytotoxin for tumor cells after antibody targeting. (C) 1997 Elsevier Science B.V. C1 GERMAN CANC RES CTR,DIAGNOST & EXPT THERAPY PROGRAM,RECOMBINANT ANTIBODY GRP,D-69120 HEIDELBERG,GERMANY. NCI,FREDERICK CANC RES FACIL,DIV BASIC SCI,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. GERMAN CANC RES CTR,DEPT MOL GENOME ANAL,D-69120 HEIDELBERG,GERMANY. UNIV HEIDELBERG,INST IMMUNOL,DEPT TRANSPLANTAT IMMUNOL,D-6900 HEIDELBERG,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. OI Dubel, Stefan/0000-0001-8811-7390 NR 34 TC 46 Z9 47 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1380-2933 J9 IMMUNOTECHNOLOGY JI Immunotechnology PD JUN PY 1997 VL 3 IS 2 BP 127 EP 136 DI 10.1016/S1380-2933(97)00070-5 PG 10 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA XK773 UT WOS:A1997XK77300004 PM 9237097 ER PT J AU Su, H Feilzer, K Caldwell, HD Morrison, RP AF Su, H Feilzer, K Caldwell, HD Morrison, RP TI Chlamydia trachomatis genital tract infection of antibody-deficient gene knockout mice SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; FEMALE GUINEA-PIGS; T-CELLS; MONOCLONAL-ANTIBODIES; PROTECTIVE IMMUNITY; MURINE MODEL; NEUTRALIZATION; EPITOPES; MOUSE; RESOLUTION AB The importance of antibody-mediated immunity in primary and secondary Chlamydia trachomatis genital tract infections was examined by using a definitive model of B-cell deficiency, the mu MT/mu MT gene knockout mouse, Vaginally infected B-cell-deficient mu MT/mu MT mice developed a self-limiting primary infection that was indistinguishable from infection of control C57BL/6 mice, Sera and vaginal secretions from infected mice were analyzed for anti-Chlamydia antibodies, C57BL/6 mice produced high-titered serum anti-Chlamydia immunoglobulin G2a (IgG2a), IgG2b, and IgA antibodies, and vaginal washes contained predominately anti-Chlamydia IgA, Serum and vaginal washes from infected B-cell-deficient mice were negative for anti-Chlamydia antibody, T-cell proliferation and delayed-type hypersensitivity assays were used as measures of Chlamydia-specific cell-mediated immunity and were found to be comparable for C57BL/6 and B-cell-deficient mice, Seventy days following primary infection, mice were rechallenged to assess acquired immunity, B-cell-deficient mice which lack anti-Chlamydia antibodies were more susceptible to reinfection than immunocompetent C57BL/6 mice, However, acquired immune resistance was evident in both strains of mice and characterized by decreased shedding of chlamydiae and an infection of shorter duration, Thus, this study demonstrates that cell-mediated immune responses alone were capable of resolving chlamydial infection; however, in the absence of specific antibody, mice were more susceptible to reinfection, Therefore, these data suggest that both humoral and cell-mediated immune responses were important mediators of immune protection in this model, though cell-mediated immune responses appear to play a more dominant role. C1 UNIV ALABAMA,DEPT MED,DIV INFECT DIS,BIRMINGHAM,AL 35294. NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,IMMUNOL SECT,HAMILTON,MT 59840. FU NIAID NIH HHS [AI-38991, R01 AI038991] NR 42 TC 132 Z9 137 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1997 VL 65 IS 6 BP 1993 EP 1999 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XB562 UT WOS:A1997XB56200001 PM 9169723 ER PT J AU Kossaczka, Z Bystricky, S Bryla, DA Shiloach, J Robbins, JB Szu, SC AF Kossaczka, Z Bystricky, S Bryla, DA Shiloach, J Robbins, JB Szu, SC TI Synthesis and immunological properties of Vi and Di-O-acetyl pectin protein conjugates with adipic acid dihydrazide as the linker SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; CAPSULAR POLYSACCHARIDE; SALMONELLA-TYPHI; IMMUNOGENICITY; VACCINES; FEVER; MICE; ANTIBODY; CARRIER; OLIGOSACCHARIDES AB The Vi capsular polysaccharide of Salmonella typhi, a licensed vaccine for typhoid fever in individuals greater than or equal to 5 Sears old, induces low and short-lived antibodies in children, and reinjection does not elicit booster responses at any age, Its immunogenicity was improved by binding Vi to proteins by using N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) as a linker, Similar findings were observed with the structurally related, di-O-acetyl derivative of pectin [poly-alpha(1-->4)-D-GalpA] designated OAcP. Protein conjugates of Vi and OAcP were synthesized by carbodiimide-mediated synthesis with adipic acid dihydrazide (ADI-I) as the linker, Hydrazide groups were introduced into proteins (bovine serum albumin or recombinant Pseudomonas aeruginosa exoprotein A) by treatment with ADH and 1-ethyl-3(3-dimethylaminopropyl carbodiimide (EDC), The resultant adipic acid hydrazide derivatives (AH-proteins), containing 2.3 to 3.4% AH, had antigenic and physicochemical properties similar to those of the native proteins, The AN-proteins were bound to Vi and OAcP by treatment with EDC, The immunogenicity of Vi or OAcP, alone or as protein conjugates, was evaluated in young outbred mice and guinea pigs by subcutaneous injection of 2.5 and 5.0 mu g, respectively, of polysaccharide, and antibodies were measured by enzyme-linked immunosorbent assay, All conjugates were significantly more immunogenic than Vi or OAcP alone and induced booster responses with 5- to 25-foId increases of antibodies, Vi conjugates were significantly more immunogenic than their OAcP analogs, A carboxymethyl derivative of yeast beta-glucan enhanced the anti-Vi response elicited by an OAcP conjugate but had no effect on the immunogenicity of Vi or of OAcP alone, Vi and OAcP conjugates synthesized by this scheme will be evaluated clinically. C1 SLOVAK ACAD SCI,INST CHEM,BRATISLAVA 84238,SLOVAKIA. NIDDKD,BIOTECHNOL UNIT,NIH,BETHESDA,MD 20892. RP Kossaczka, Z (reprint author), NICHHD,DEV & MOL IMMUN LAB,BETHESDA,MD 20892, USA. NR 41 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1997 VL 65 IS 6 BP 2088 EP 2093 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XB562 UT WOS:A1997XB56200014 PM 9169736 ER PT J AU Bos, MP Grunert, F Belland, RJ AF Bos, MP Grunert, F Belland, RJ TI Differential recognition of members of the carcinoembryonic antigen family by Opa variants of Neisseria gonorrhoeae SO INFECTION AND IMMUNITY LA English DT Article ID EPITHELIAL-CELLS; GENE FAMILY; OPACITY PROTEINS; GONOCOCCUS INFECTION; BILIARY GLYCOPROTEIN; ADHESION MOLECULE; HUMAN-NEUTROPHILS; ESCHERICHIA-COLI; EXPRESSION; LEUKOCYTES AB Opacity (Opa) protein variation in Neisseria gonorrhoeae is implicated in the pathogenesis of gonorrhea, possibly by mediating adherence and entry of the bacteria into human tissues, One particular Opa protein mediates adherence to epithelial cells through cell surface proteoglycans, Recently, two other eukaryotic cell receptors for Opa proteins have been reported, These receptors are members of a subgroup of the carcinoembryonic (CEA) gene family that express CD66 antigens, CEA family members vary in their distribution in human tissues, In order to understand whether interactions between Opa and CEA-like molecules play any role in pathogenesis, we must investigate which CEA family members are able to serve as Opa receptors and which Opa proteins recognize CEA-like molecules, We therefore studied HeLa cells that were stably transfected with five different members of the CEA family, i.e., CEA, CEA gene family member la (CGM1a), CGM6, nonspecific cross-reacting antigen (NCA), and biliary glycoprotein a (BGPa), We infected these transfectants with all possible 11 Opa variants of gonococcal strain MS11 and determined the numbers of bacteria that were bound and internalized. To account for proteoglycan-mediated adherence, infection assays were also performed in the presence of heparin, Our results show that of the 11 Opa variants of MS11, the same 4 recognized CGM1a and NCA, CGM6, however, was not recognized by any Opa variant of MS11, CEA was recognized by at least 9 of 11 Opa variants, and the BGP transfectants specifically bound and internalized 10 of 11 Opa variants and also bound Opa-negative gonococci, Immunofluorescence experiments showed that clustering of CEA-like molecules occurred upon infection of HeLa transfectants with those Opa variants that interacted specifically with the CEA family member. Together these data show that CEA family members are differentially recognized by gonococcal Opa variants, suggesting that this phenomenon may contribute to cell tropism displayed by gonococci. C1 UNIV FREIBURG,INST IMMUNOBIOL,D-7800 FREIBURG,GERMANY. RP Bos, MP (reprint author), NIAID,ROCKY MT LABS,LAB MICROBIAL STRUCT & FUNCT,NIH,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 38 TC 107 Z9 108 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1997 VL 65 IS 6 BP 2353 EP 2361 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XB562 UT WOS:A1997XB56200052 PM 9169774 ER PT J AU Robbins, PA Rota, PA Shapiro, SZ AF Robbins, PA Rota, PA Shapiro, SZ TI A broad cytotoxic T lymphocyte response to influenza type B virus presented by multiple HLA molecules SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytotoxic T lymphocyte; HLA-B8; HLA-DR1; influenza B virus; peptides ID HISTOCOMPATIBILITY ANTIGEN; MONOCLONAL-ANTIBODIES; NUCLEOPROTEIN GENE; IMMUNE-RESPONSE; HEMAGGLUTININ; SEQUENCE; INFECTION; EPITOPES; PEPTIDES; PERFORIN AB The HLA restriction and epitope specificity of cytotoxic T lymphocytes (CTL) involved in recovery from influenza type B infection have not been extensively characterized. Here lymphocytes obtained from a healthy individual contained virus-specific CTL restricted by class I HLA molecules, HLA-A1, A2, B7 and B8, and the class II HLA molecules, HLA-DR1 and DR3. Four conserved viral epitopes were predicted from allele-specific motifs for peptides interacting with HLA-B8 and HLA-DR1. Bulk CTL recognized three 9mer HLA-B8-restricted peptides from nucleoprotein, residues 30-38, 263-271 and 413-421, and a 13mer HLA-DR1-restricted peptide from hemagglutinin, residues 308-320. The epitopes presented by HLA-A1, HLA-B7 and HLA-DR3 remain undefined. Peptide-specific CTL lines recognized influenza type B virus-infected cells indicating the peptides are representative of naturally processed epitopes. A hemagglutinin peptide-specific CD4 CTL clone expressed similar to 200 molecules of perforin mRNA/cell, suggestive of a functional perforin pathway for target cell lysis. The results indicate a broad CTL response composed of both CD8 CTL and CD4 CTL recognizing viral epitopes presented by multiple HLA molecules. C1 CTR DIS CONTROL,NATL CTR INFECT DIS,ATLANTA,GA 30333. RP Robbins, PA (reprint author), NIH,CTR BIOL EVALUAT & RES,BLDG 10,BETHESDA,MD 20892, USA. NR 57 TC 14 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 1997 VL 9 IS 6 BP 815 EP 823 DI 10.1093/intimm/9.6.815 PG 9 WC Immunology SC Immunology GA XE891 UT WOS:A1997XE89100002 PM 9199964 ER PT J AU Kolobow, T Cereda, M Sparacino, ME Trawoger, R AF Kolobow, T Cereda, M Sparacino, ME Trawoger, R TI Acute respiratory failure, mechanical ventilation, and ECMO/ECCO2R: quo vadis? SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS LA English DT Editorial Material ID INTRATRACHEAL PULMONARY VENTILATION; LUNG INJURY; PRESSURE; ECMO RP Kolobow, T (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,NIH,10 MED CTR DR,MSC 1590,BLDG 10,ROOM 5D-17,BETHESDA,MD 20892, USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0391-3988 J9 INT J ARTIF ORGANS JI Int. J. Artif. Organs PD JUN PY 1997 VL 20 IS 6 BP 301 EP 303 PG 3 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA XN697 UT WOS:A1997XN69700001 PM 9259204 ER PT J AU Pennypacker, KR Xiao, Y Xu, RH Harry, GJ AF Pennypacker, KR Xiao, Y Xu, RH Harry, GJ TI Lead-induced developmental changes in AP-1 DNA binding in rat brain SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE neurotoxicity; Jun; transcription factor ID FIBRILLARY ACIDIC PROTEIN; KINASE-C; MONOCYTIC DIFFERENTIATION; GROWTH CONES; EXPRESSION; GAP-43; GENE; TRANSCRIPTION; HIPPOCAMPUS; EXPOSURE AB Exposure to lead during ontogeny is detrimental to the growth and development of the brain. Morphological abnormalities occur in the developing brain, which are manifested as mental retardation and other neurological disorders. Despite extensive research. the biochemical mechanism for neurological effects of lead has not been established but appears to be al the level of the genome since aberrant expression of developmentally-important genes has been reported. Basal levels of activator protein 1 (AP-1) transcription factor DNA binding are elevated in the rat brain during the early postnatal period. The AP-1 DNA binding complex is composed of a Jun:cAMP responsive element binding protein dimer, which appears to modulate expression of developmentally-important genes that contain AP-1 binding sites in their promoter. Brain regions from perinatally lead-exposed rats were examined on postnatal days 3, 9 and 15 for DNA binding activity to the AP-1 DNA sequence. AP-1 DNA binding activities were significantly increased on postnatal day 3 in hippocampus and cortex from lead-treated rats with no other area (frontal lobe or brainstem) or timepoint showing significant changes. Since no increases were detected in the level of Jun protein which is a component of the AP-1 binding complex, post-translational modification may be involved in enhancing DNA binding activity. By altering levels of AP-1 DNA binding to the promoter regions, lead exposure may be changing the levels of mRNA synthesis of developmentally important genes. (C) 1997 ISDN. C1 NIEHS,LAB ENVIRONM NEUROSCI,RES TRIANGLE PK,NC 27713. RP Pennypacker, KR (reprint author), UNIV S FLORIDA,DEPT PHARMACOL,12901 BRUCE B DOWNS BLVD,MDC 9,TAMPA,FL 33612, USA. RI Pennypacker, Keith/I-5092-2012 NR 41 TC 18 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD JUN PY 1997 VL 15 IS 3 BP 321 EP 328 DI 10.1016/S0736-5748(97)00006-3 PG 8 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA XN374 UT WOS:A1997XN37400006 PM 9253656 ER PT J AU Sturgeon, SR Brinton, LA Berman, ML Mortel, R Twiggs, LB Barrett, RJ Wilbanks, GD Lurain, JR AF Sturgeon, SR Brinton, LA Berman, ML Mortel, R Twiggs, LB Barrett, RJ Wilbanks, GD Lurain, JR TI Intrauterine device use and endometrial cancer risk SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE intrauterine device (IUD); endometrial cancer; contraception; epidemiology AB Background. Because intrauterine devices (IUD) invoke acute and chronic inflammatory responses in the endometrium, it is possible that prolonged insertion of an IUD could induce endometrial cancer, Methods. We examined the relation between use of an IUD and endometrial cancer risk using data from a multicentre case-control study involving 405 endometrial cancer cases and 297 population controls. Results. A total of 20 (4.9%) cases and 34 (11.4%) controls reported any use of an IUD. After adjustment for potential confounders, IUD use was not associated with an increased risk of endometrial cancer (RR = 0.56 for ever use; 95% CI : 0.3-1.0), Little reduction in risk was observed among women who last used an IUD within 10 years of the index date (RR = 0.84; 95% CI:0.3-2.4) but risk was decreased among women who used an IUD in the more distant past (RR = 0.45; 95% CI :0.2-1.0). Risk did not vary consistently with number of years of IUD use or with years since first use. Risk was not increased among women who used inert devices (RR = 0.46; 95% CI :0.3-3.6) or those who used devices containing copper (RR = 1.08; 95% CI :0.1-3.6). Conclusion. These data are reassuring in that they do not provide any evidence of an increased risk of endometrial cancer among women who have used IUD. C1 UNIV CALIF IRVINE,DEPT OBSTET & GYNECOL,MED CTR,ORANGE,CA 92668. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT OBSTET & GYNECOL,HERSHEY,PA 17033. UNIV MINNESOTA,HLTH SCI CTR,DEPT OBSTET & GYNECOL,MINNEAPOLIS,MN 55455. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT OBSTET & GYNECOL,WINSTON SALEM,NC 27103. RUSH MED COLL,DEPT OBSTET & GYNECOL,CHICAGO,IL 60612. NORTHWESTERN UNIV,SCH MED,DEPT OBSTET & GYNECOL,CHICAGO,IL 60611. RP Sturgeon, SR (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,6130 EXECUT BLVD,EPN443,BETHESDA,MD 20852, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 14 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 1997 VL 26 IS 3 BP 496 EP 500 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XG979 UT WOS:A1997XG97900005 PM 9222773 ER PT J AU Kaufman, DW Issaragrisil, S Anderson, T Chansung, K Thamprasit, T Sirijirachai, J Piankijagum, A Porapakkham, Y Vannasaeng, S Leaverton, PE Shapiro, S Young, NS AF Kaufman, DW Issaragrisil, S Anderson, T Chansung, K Thamprasit, T Sirijirachai, J Piankijagum, A Porapakkham, Y Vannasaeng, S Leaverton, PE Shapiro, S Young, NS TI Use of household pesticides and the risk of aplastic anaemia in Thailand SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aplastic anaemia; pesticides; risk; Thailand ID ORGANOCHLORINE PESTICIDE; BLOOD DYSCRASIAS; ANEMIA; EXPOSURE; LEUKEMIA; CANCER; ASSOCIATION; HEPTACHLOR; CHLORDANE; MORTALITY AB Background. Aplastic anaemia is a severe blood dyscrasia that is more common in Thailand than in Western countries. Its aetiology remains poorly understood. Methods. A case-control study was conducted in Bangkok and two rural regions of Thailand. The effect of household pesticides was evaluated among 253 incident cases of aplastic anaemia and 1174 hospital controls. Results. A total of 54% of the cases and 61% of the controls were exposed 1-6 months previously. For most individual household pesticides and for groups classified according to chemical type (organophosphates, pyrethrins, and organochlorines), the relative risk (RR) estimates approximated 1.0; upper 95% confidence limits were below 2.0 for many comparisons. A significant association was observed for exposure to combination products containing dichlorvos and propoxur, with an overall RR estimate of 1.7 (95% confidence interval [CI] : 1.1-2.6); the estimate for regular use was 1.6 (95% CI : 0.9-2.9). Conclusions. The absence of a higher risk for the regular use of dichlorvos/propoxur reduces the credibility of the apparent association, which could well have been an artefact of multiple comparisons. We conclude that most household pesticides used in Thailand do not appear to increase the risk of aplastic anaemia. C1 BOSTON UNIV,SCH MED,SCH PUBL HLTH,SLONE EPIDEMIOL UNIT,BROOKLINE,MA 02146. MAHIDOL UNIV,ASEAN INST HLTH DEV,BANGKOK 10700,THAILAND. KHON KAEN UNIV,FAC MED,DEPT MED,KHON KAEN 40002,THAILAND. PRINCE SONGKLA UNIV,DEPT MED,SONGKHLA,THAILAND. UNIV S FLORIDA,DEPT EPIDEMIOL & BIOSTAT,TAMPA,FL. NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RP Kaufman, DW (reprint author), SIRIRAJ HOSP,DEPT MED,DIV HEMATOL,BANGKOK 10700,THAILAND. OI Issaragrisil, Surapol/0000-0002-8924-0646 FU NHLBI NIH HHS [HL 35068] NR 42 TC 8 Z9 10 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 1997 VL 26 IS 3 BP 643 EP 650 DI 10.1093/ije/26.3.643 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XG979 UT WOS:A1997XG97900023 PM 9222791 ER PT J AU Westergaard, GC Suomi, SJ AF Westergaard, GC Suomi, SJ TI Modification of clay forms by tufted capuchins (Cebus apella) SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE Cebus; Homo; evolution; Paleolithic art; tool-use ID PAN AB We examined modification of clay forms by tufted capuchins (Cebus apella) by presenting groups of subjects with clay, paint, stones, leaves, and sticks. In Experiment 1, 7 of 10 subjects reshaped portable forms with their hands and with stones, and decorated them with leaves and paint. In Experiment 2, 9 subjects marked clay slabs manually and with stick and stone tools. The manipulative propensities of Cebus can help us to understand psychological processes that underlie artistic expression in Homo and Pan. C1 NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. NR 17 TC 3 Z9 3 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD JUN PY 1997 VL 18 IS 3 BP 455 EP 467 DI 10.1023/A:1026394618857 PG 13 WC Zoology SC Zoology GA XG090 UT WOS:A1997XG09000010 ER PT J AU BeleckyAdams, T Tomarev, S Li, HS Ploder, L McInnes, RR Sundin, O Adler, R AF BeleckyAdams, T Tomarev, S Li, HS Ploder, L McInnes, RR Sundin, O Adler, R TI Pax-6, Prox 1, and Chx10 homeobox gene expression correlates with phenotypic fate of retinal precursor cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE cell differentiation; cell lineage; homeobox genes; photoreceptors; retina development; transcription factors ID CENTRAL-NERVOUS-SYSTEM; DROSOPHILA VISUAL-SYSTEM; GANGLION-CELLS; TRANSCRIPTION FACTORS; PROSPERO GENE; DIFFERENTIATION; NEURONS; MITOSIS; NEURORETINA; VERTEBRATE AB Purpose. To study the expression patterns of the homeobox genes Pax-6, Prox 1, and Chx10 during chick retinal development in vivo and in vitro. Methods. Sections of paraformaldehyde-fixed, paraffin-embedded eyes were obtained at a range of developmental stages. In situ hybridization was carried out on tissue sections using digoxigenin-labelled sense and antisense RNA probes that recognize chicken Pax-6 and Prox 1 (whose sequences were already available), and chicken Chx10 (which was cloned and sequenced as part of this study). Selected developmental stages were also studied by immunocytochemistry With antibodies against Pax-6 and Prox 1, and by Northern blot analysis using (32)p-labelled probes. Results. Until embryonic day (ED) 5, in situ hybridization shows widespread, diffuse distribution of all three genes. Between ED 6 and ED 8, however, they acquire distinct, topographically specific patterns of expression. The Prox 1 signal is predominantly expressed in the prospective horizontal cell layer of the neuroepithelium, decreases vitreally, and is absent from ganglion cells and the prospective photoreceptor layer. Pax-6 is strongly expressed only in the prospective ganglion-cell and amacrine-cell regions at the same stages, and is not detected in prospective photoreceptors. Chx10 expression becomes concentrated in the future bipolar-cell region of the inner nuclear layer. Similar patterns are maintained by ED 15 through ED 18, after cell differentiation has taken place, Pax-6 and Prox 1 immunoreactive materials showed nuclear localization and a pattern of laminar distribution equivalent to that seen by in situ hybridization. Conclusions. These results suggest that the differentiated fate of retinal precursor cells may be influenced by Pax-6, Prox 1, or Chx10; this hypothesis is now being tested using dissociated chick embryo retinal cell cultures. Invest Ophthalmol Vis Sci. 1997;38:1293-1303. C1 JOHNS HOPKINS UNIV,SCH MED,WILMER EYE INST,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21287. NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892. HOSP SICK CHILDREN,DEPT PEDIAT & GENET,TORONTO,ON M5G 1X8,CANADA. OI Belecky-Adams, Teri/0000-0003-1299-8448 FU NEI NIH HHS [EY01765, EY04859, EY10729] NR 50 TC 184 Z9 189 U1 2 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1997 VL 38 IS 7 BP 1293 EP 1303 PG 11 WC Ophthalmology SC Ophthalmology GA XE101 UT WOS:A1997XE10100006 PM 9191592 ER PT J AU Kaufman, FR Gertner, JM Sleeper, LA Donfield, SM Gomperts, E Kaufman, F Nelson, M Pearson, S Hilgartner, M Gertner, J Goldberg, I Hoots, WK Loveland, K Cantini, M Willoughby, A Donfield, S Maeder, MA Contant, C Kisker, CT Stehbens, J Bale, J Cool, V Sirois, P Sexauer, C Huszti, H Hawk, S Arkin, S Forster, A Swindells, S Richard, S Parmley, R Mangos, J Scott, A Honeck, L Lusher, J Warrier, I BairdCox, K Hershey, MS Eyster, ME Pattishall, E Neagley, S Shapiro, A Hatcher, S Davignon, G Rabwin, P Wicklund, B Spoor, M AF Kaufman, FR Gertner, JM Sleeper, LA Donfield, SM Gomperts, E Kaufman, F Nelson, M Pearson, S Hilgartner, M Gertner, J Goldberg, I Hoots, WK Loveland, K Cantini, M Willoughby, A Donfield, S Maeder, MA Contant, C Kisker, CT Stehbens, J Bale, J Cool, V Sirois, P Sexauer, C Huszti, H Hawk, S Arkin, S Forster, A Swindells, S Richard, S Parmley, R Mangos, J Scott, A Honeck, L Lusher, J Warrier, I BairdCox, K Hershey, MS Eyster, ME Pattishall, E Neagley, S Shapiro, A Hatcher, S Davignon, G Rabwin, P Wicklund, B Spoor, M TI Growth hormone secretion in HIV-positive versus HIV-negative hemophilic males with abnormal growth and pubertal development SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE hemophilia; growth hormone; growth factors; puberty ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLINICAL LONGITUDINAL STANDARDS; IMMUNE-DEFICIENCY-SYNDROME; ENDOCRINE FUNCTION; THYROID-FUNCTION; HEIGHT VELOCITY; INFECTION; CHILDREN; BRAIN; AIDS AB Growth and pubertal development in hemophilic males, age 6-19 years at baseline, were evaluated over a 3.5-year period in 207 HIV-positive and 126 HIV-negative subjects as part of the Hemophilia Growth and Development Study. Methods: Thyroid function, insulin-like growth factor I(IGF-1) levels, bone age, cranial magnetic resonance image normality, CD4(+) counts, and serum testosterone levels of study participants were measured at baseline. An extensive endocrine evaluation was performed in subjects who demonstrated declines in height for age (measurement <5th percentile with two pervious heights >10th percentile), who had not achieved Tanner stage 4 level of pubertal development by age 15 years or who had abnormal growth velocity, which included assessment of peak stimulated growth hormone response after clonidine stimulation, 12-hour growth hormone profiles, and serum beta carotene levels (triggered protocol). Results: For almost the entire group (similar to 99%), thyroid function tests were normal for age. IGF-1 levels were normal for 93% of the cohort. A total of 120 subjects, 89 HIV-positive and 31 HIV-negative, had an abnormality of growth, pubertal development, or both; 34 (11.1%) HIV-positive and 4 (3.6%) HIV-negative subjects had declines in height (p =.001), 20 (23.3%) HIV-positive and 5 (15.8%) HIV-negative subjects had not achieved Tanner stage 4 by 15 years of age (p =.372) and 59 (43.4%) HIV-positive and 23 (25.6) HIV-negative subjects had abnormal growth velocity (p < 0.001). Among subjects with abnormal height or growth velocity, the HIV-positive group had significantly lower mean age-adjusted testosterone levels than did the HIV-negative group (p =.030). Within the HIV-positive group, older subjects with abnormal height or growth velocity had significantly lower mean bone age than subjects of similar age without growth abnormalities (p =.0092). Extensive testing was done in 39 patients (32 HIV-positive, 7 HIV-negative). Half of the HIV-positive subjects had mean 12-hour growth hormone levels <3 ng/ml, 47% had peak stimulated levels <10 ng/ml, 28% had peak spontaneous values <10 ng/ml, and 38% had low levels of IGF-1. In the HIV-positive cohort, there was no difference in the rate of abnormalities of growth hormone secretion between those with CD4(+) counts greater than or equal to or <200 cells/mm(3) and between those subjects that met the 1987 Centers for Disease Control (CDC) surveillance definition of AIDS. In the subset of HIV-positive patients with abnormal peak growth hormone levels after clonidine stimulation, growth hormone response correlated positively with CD4(+) count (r =.657, p =.0056) and beta carotene concentration (R =.596, p =.0192). Conclusions: The results of this longitudinal study suggest that abnormalities of growth and pubertal development, particularly an abnormal growth velocity, are common in HIV-infected hemophilic boys and adolescents. These abnormalities might serve as indicators of the presence of HIV infection in this at-risk population. Since thyroid function tests and IGF-1 levels were normal, the etiology of growth impairment in HIV infection does not appear to be secondary to inadequate caloric intake or acquisition, or severe illness such as that caused by recurrent or persistent infection. Rather, HIV infection appears to lead to diminished growth hormone production or release and decreased androgen secretion, even before the development of AIDS and immunocompromise. These results provide a rationale for trials of treatment with growth hormone or androgens in patients with abnormalities of endocrine function. C1 NEW YORK HOSP, CORNELL MED CTR, DEPT PEDIAT, DIV ENDOCRINOL & METAB, NEW YORK, NY 10021 USA. UNIV TEXAS, SCH MED, DALLAS, TX USA. NICHHD, NIH, BETHESDA, MD USA. NEW ENGLAND RES INST, DATA COORDINATING CTR, WATERTOWN, MA 02172 USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. UNIV IOWA HOSP & CLIN, IOWA CITY, IA 52242 USA. TULANE UNIV, NEW ORLEANS, LA 70118 USA. CHILDRENS HOSP OAKLAHOMA, OKLAHOMA CITY, OK USA. MT SINAI MED CTR, NEW YORK, NY USA. UNIV NEBRASKA, MED CTR, LINCOLN, NE 68583 USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. CHILDRENS HOSP MICHIGAN, DETROIT, MI USA. MILTON S HERSHEY MED CTR, HERSHEY, PA USA. INDIANA UNIV, JAMES WHITCOMB RILEY HOSP CHILDREN, BLOOMINGTON, IN 47405 USA. UNIV CALIF SAN DIEGO, MED CTR, SAN DIEGO, CA 92103 USA. CHILDRENS MERCY HOSP, KANSAS CITY SCH MED, KANSAS CITY, MO USA. RP USC, CHILDRENS HOSP LOS ANGELES 61,SCH MED,DEPT PEDIAT, DIV ENDOCRINOL & METAB, 4650 SUNSET BLVD, LOS ANGELES, CA 90027 USA. NR 41 TC 22 Z9 22 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD JUN 1 PY 1997 VL 15 IS 2 BP 137 EP 144 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XM570 UT WOS:A1997XM57000007 ER PT J AU Petrides, JS Gold, PW Mueller, GP Singh, A Stratakis, C Chrousos, GP Deuster, PA AF Petrides, JS Gold, PW Mueller, GP Singh, A Stratakis, C Chrousos, GP Deuster, PA TI Marked differences in functioning of the hypothalamic-pituitary-adrenal axis between groups of men SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE stress; adrenocorticotropic hormone; cortisol; dexamethasone and hydrocortisone ID CORTICOTROPIN-RELEASING HORMONE; BIOCHEMICAL MANIFESTATIONS; TREADMILL EXERCISE; CHRONIC STRESS; VASOPRESSIN; SECRETION; DEXAMETHASONE; DEPRESSION; RESPONSES; ADRENOCORTICOTROPIN AB To compare profiles of hypothalamic-pituitary-adrenal (HPA) responsiveness, healthy, moderately trained men (n = 15) were classified as high (n = 7) or low responders (n = 8) on the basis of plasma adrenocorticotropic hormone (ACTH) responses to strenuous treadmill exercise 4 h after 4 mg of dexamethasone (Dex). These groups were then evaluated to compare 1)HPA and growth hormone responses to exercise at 90% maximal gen uptake 4 h after placebo, Dex (4 mg), and hydrocortisone (100 mg); 2) pituitary-adrenal responses to infusion of arginine vasopressin (AVP); 3) plasma cortisol after a Dex suppression test (1 mg); and 4)behavioral characteristics. In comparison to low responders, high responders exhibited significantly 1) higher plasma ACTH responses to exercise after placebo and Dex; 2) higher plasma AVP secretion with exercise after placebo and marked Dex- and hydrocortisone-induced enhancement of exercise-induced AVP secretion; 3) lower Dex-induced increases in basal and stimulated growth hormone secretion; 4) higher plasma ACTH responses to infusion of AVP; and 5) a trend (P = 0.09) for higher trait anxiety ratings. Similar suppression of plasma cortisol was noted after 1 mg Dex. We conclude that subgroups of healthy male volunteers exhibit unique profiles of HPA responsiveness. We also believe that glucocorticoid pretreatment combined with strenuous exercise allows functional HPA responsiveness to be distinguished between subgroups of healthy controls and may be useful in the determination of susceptibility disorders characterized by hyper- and hypo-HPA activation. C1 UNIFORMED SERV UNIV HLTH SCI, DEPT MIL & EMERGENCY MED, BETHESDA, MD 20814 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT PHYSIOL, BETHESDA, MD 20814 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20814 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20814 USA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 33 TC 55 Z9 56 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUN PY 1997 VL 82 IS 6 BP 1979 EP 1988 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA XD265 UT WOS:A1997XD26500037 PM 9173967 ER PT J AU Notkins, AL Zhang, BW Matsumoto, Y Lan, MS AF Notkins, AL Zhang, BW Matsumoto, Y Lan, MS TI Comparison of IA-2 with IA-2 beta and with six other members of the protein tyrosine phosphatase family: Recognition of antigenic determinants by IDDM sera SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT 2nd Congress of the Immunology-of-Diabetes-Society CY DEC 08-11, 1996 CL CANBERRA, AUSTRALIA SP Immunol Diabet Soc, Juvenile Diabet Fdn, Juvenile Diabet Fdn Int, Sue Alberti & Dansu Construct, Harwood Acad Publ, Sandoz Australia Pty Ltd, Boehringer Mannheim, Aza Res, Bristol Myers Squibb, Embassy of France Cultural & Sci Serv DE protein tyrosine phosphatase; IA-2; IA-2 beta; insulin-dependent diabetes mellitus; IDDM; autoantibodies ID ISLET-CELL ANTIGEN-512; MOLECULAR-CLONING; SEQUENCES; CDNA; RNA AB To study the expression of protein tyrosine phosphatases (PTPs) in pancreatic islets, a cDNA library from islet cells was constructed and analysed. Twenty one different fYTPs were found to be expressed in islet cells, including three previously unknown PTPs. One of these, IA-2 beta, was cloned, sequenced, and found to be related to IA-2, a major autoantigen in insulin-dependent diabetes mellitus (IDDM). The intracellular and extracellular domains of IA-2 beta were 74 and 27% identical, respectively, to the intracellular and extracellular domains of IA-2. Approximately 70 and 45% of sera from patients with IDDM had autoantibodies that immunoprecipitated recombinant IA-2 and IA-2 beta, respectively. By use of deletion mutants; we were able to show that the autoantibodies reacted with the intracellular, and not the extracellular, domains of IA-2 and IA-2 beta, and that the major antigenic determinants resided within the COOH-terminus of the intracellular domains. Further studies revealed that approximately 97% of the IDDM sera that reacted with IA-2 beta also reacted with IA-2, whereas only 50% of IDDM sera that reacted with IA-2 also reacted with IA-2 beta. In contrast to the reactivity of IDDM sera with the IA-2 and IA-2 beta , IDDM sera did not react with six other members of the PTP family. It is concluded that many members of the PTP family are expressed in pancreatic islets, but thus far only IA-2 and IA-2 beta appear to be recognized as autoantigens by IDDM sera. (C) 1997 Academic Press Limited. RP Notkins, AL (reprint author), NIDR,ORAL INFECT & IMMUN BRANCH,NIH,30 CONVENT DR MSC 4322,BLDG 30,ROOM 121,BETHESDA,MD 20892, USA. NR 22 TC 25 Z9 27 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 1997 VL 10 IS 3 BP 245 EP 250 DI 10.1006/jaut.1997.0132 PG 6 WC Immunology SC Immunology GA XG033 UT WOS:A1997XG03300004 PM 9218750 ER PT J AU Ramiya, VK Lan, MS Wasserfall, CH Notkins, AL Maclaren, NK AF Ramiya, VK Lan, MS Wasserfall, CH Notkins, AL Maclaren, NK TI Immunization therapies in the prevention of diabetes SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT 2nd Congress of the Immunology-of-Diabetes-Society CY DEC 08-11, 1996 CL CANBERRA, AUSTRALIA SP Immunol Diabet Soc, Juvenile Diabet Fdn, Juvenile Diabet Fdn Int, Sue Alberti & Dansu Construct, Harwood Acad Publ, Sandoz Australia Pty Ltd, Boehringer Mannheim, Aza Res, Bristol Myers Squibb, Embassy of France Cultural & Sci Serv DE immunologically-mediated diabetes; immunization therapy; NOD mice; islet autoantigens ID GLUTAMIC-ACID DECARBOXYLASE; INTERFERON-GAMMA; CELL TOLERANCE; ORAL TOLERANCE; ISLET-CELL; NOD MICE; T-CELL; INSULIN; CYCLOPHOSPHAMIDE; AUTOANTIGENS AB Insulin-dependent diabetes (IDD), being an autoimmune disease, offers several opportunities for immunological interventions that may result either in the reduction of disease severity or in delaying diabetes onset. Among the various experimental preventative approaches, parenteral immunization with islet-specific autoantigens appears to be practically simpler and promising. We have previously shown that immunization with insulin, insulin B chain and B chain epitope (p9-23), but not insulin A chain, in incomplete Freund's adjuvant (IFA) and in alum (with B chain) delayed/prevented diabetes onset in NOD mice. Here we demonstrate the protective efficacy of affinity purified GAD(65) in IFA. While both insulin B chain and GAD(65) significantly delayed the onset of diabetes (P=0.001), a recently described tyrosine phosphatase (IA-2) antigen did not (P=0.38). Interestingly, B chain immunization reduced the incidence of cyclophosphamide (CY)-accelerated diabetes by about 50-55%. We also provide further evidence that B chain, upon increased adsorption to alum, could improve on its protective capacity in NOD mice. (C) 1997 Academic Press Limited. C1 NIH,DEPT PATHOL & LAB MED,BETHESDA,MD 20892. NIH,ORAL MED LAB,BETHESDA,MD 20892. RES INST CHILDREN,NEW ORLEANS,LA. RI wasserfall, clive/J-9078-2012 OI wasserfall, clive/0000-0002-3522-8932 FU NICHD NIH HHS [R0-1 HD 19469-06] NR 24 TC 22 Z9 29 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 1997 VL 10 IS 3 BP 287 EP 292 DI 10.1006/jaut.1997.0127 PG 6 WC Immunology SC Immunology GA XG033 UT WOS:A1997XG03300010 PM 9218756 ER PT J AU Swanson, J Dorward, D Lubke, L Kao, D AF Swanson, J Dorward, D Lubke, L Kao, D TI Porin polypeptide contributes to surface charge of gonococci SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; POLYANION BINDING-SITE; NEISSERIA-GONORRHOEAE; MONOCLONAL-ANTIBODIES; ELECTROSTATIC PROPERTIES; ALTERNATIVE PATHWAY; ESCHERICHIA-COLI; HEPARAN-SULFATE; BACTERIAL PORIN; HUMAN SERUM AB Each strain of Neisseria gonorrhoeae elaborates a single porin polypeptide, with the porins expressed by different strains comprising two general classes, Por1A and Por1B. In the outer membrane, each porin molecule folds into 16 membrane-spanning beta-strands joined by top- and bottom-loop domains. Por1A and Por1B have similar membrane-spanning regions, but the eight surface-exposed top loops (I to VIII) differ in length and sequence. To determine whether porins, and especially their top loop domains, contribute to bacterial cell surface charge, strain MS11 gonococci that were identical except for expressing a recombinant Por1A, Por1B, or mosaic Por1A-1B polypeptide were compared by whole-cell electrophoresis. These porin variants displayed different electrophoretic mobilities that correlated with the net numbers of charged amino acids within surface-exposed loops of their respective porin polypeptides. The susceptibilities of porin variants to polyanionic sulfated polymers correlated roughly with gonococcal surface charge; those porin variants,vith diminished surface negativity showed increased sensitivity to the polyanionic sulfated compounds. These observations indicate that porin polypeptides in situ contribute to the surface charge of gonococci, and they suggest that the bacterium's interactions with large sulfated compounds are thereby affected. C1 NIAID, ROCKY MT LABS, ELECTRON MICROSCOPY BRANCH, HAMILTON, MT 59840 USA. RP Swanson, J (reprint author), NIAID, ROCKY MT LABS, MICROBIAL STRUCT & FUNCT LAB, HAMILTON, MT 59840 USA. RI Kao, David/K-3288-2013 OI Kao, David/0000-0002-2832-9348 NR 54 TC 11 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1997 VL 179 IS 11 BP 3541 EP 3548 PG 8 WC Microbiology SC Microbiology GA XB491 UT WOS:A1997XB49100021 PM 9171398 ER PT J AU Radnedge, L Davis, MA Youngren, B Austin, SJ AF Radnedge, L Davis, MA Youngren, B Austin, SJ TI Plasmid maintenance functions of the large virulence plasmid of Shigella flexneri SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SEX FACTOR-F; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; P1 PLASMID; BACTERIAL-GROWTH; BINDING-ACTIVITY; PARTITION SITE; HELICASE-I; CELL-DEATH; REPLICATION AB The large virulence plasmid pMYSH6000 of Shigella flexneri contains a replicon and a plasmid maintenance stability determinant (Stb) on adjacent SalI fragments. The presence of a RepFIIA replicon on the SalI C fragment was confirmed, and the complete sequence of the adjacent SalI O fragment was determined. It shows homology to part of the transfer (tra) operon of the F plasmid. Stb stabilizes a partition-defective P1 miniplasmid in Escherichia coli. A 1.1-kb region containing a homolog of the F trbH gene was sufficient to confer stability. However, the trbH open reading frame could be interrupted without impairing stability. Deletion analysis implicated the involvement of two small open reading frames, STBORF1 and STBORF2, that fully overlap trbH in the opposite direction. These open reading frames are closely related to the vagC and vagD genes of the Salmonella dublin virulence plasmid and to open reading frame pairs in the F trbH region and in the chromosomes of Dichelobacter nodosus and Haemophilus influenzae. Stb appears to promote better-than-random distribution of plasmid copies and is a plasmid incompatibility determinant. The F homolog does not itself confer stability but exerts incompatibility against the activity of the Stb system. Stb is likely to encode either an active partition system or a postsegregational killing system. It shows little similarity to previously studied plasmid stability loci, but the genetic organization of STBORF1 and STBORF2 resembles that of postsegregational killing mechanisms. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,GENE REGULAT & CHROMOSOME BIOL LAB,FREDERICK,MD 21702. NR 33 TC 35 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1997 VL 179 IS 11 BP 3670 EP 3675 PG 6 WC Microbiology SC Microbiology GA XB491 UT WOS:A1997XB49100038 PM 9171415 ER PT J AU Sadato, N Ibanez, V Campbell, G Deiber, MP LeBihan, D Hallett, M AF Sadato, N Ibanez, V Campbell, G Deiber, MP LeBihan, D Hallett, M TI Frequency-dependent changes of regional cerebral blood flow during finger movements: Functional MRI compared to PET SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE functional magnetic resonance imaging; positron emission tomography; primary sensorimotor cortex; regional cerebral blood flow ID POSITRON EMISSION TOMOGRAPHY; AUTOMATED ALGORITHM; HUMAN BRAIN; CORTEX; IMAGES; STIMULATION; (H2O)-O-15 AB To evaluate the effect of the repetition rate of a simple movement on the magnitude of neuronal recruitment in the primary sensorimotor cortex, we used a blood flow-sensitive, echo planar functional magnetic resonance imaging (fMRI) sequence in six normal volunteers. Three of the volunteers also had [O-15]water positron emission tomography (PET) studies using the same paradigm. Previous PET studies had shown an increase in regional CBF (rCBF) with movement frequencies up to 2 Hz and then a plateau of regional cerebral blood flow (rCBF) at faster frequencies. To evaluate the extent of the activation, the correlation coefficient (cc) of the Fourier-transformed time-signal intensity change with the Fourier-transformed reference function was calculated pixel by pixel. The degree of activation was measured as the signal percent change of each region of interest with a cc > 0.5. The left primary sensorimotor cortex was constantly activated at 1, 1.5, 2, and 4 Hz, while there was only inconsistent activation at 0.25 and 0.5 Hz. Percent change in signal intensity linearly increased from 1 to 4 Hz. Area of activation increased up to 2 Hz and showed a tendency to decrease at higher frequencies. Individual analysis of PET data showed activation in the same location as that revealed by fMRI. The combination of progressively increasing signal intensity with an area that increases to 2 Hz and declines at faster frequencies explains the PET finding of plateau of rCBF at the faster frequencies. Functional magnetic resonance imaging shows similar results to PET, but is better able to dissociate area and magnitude of change. C1 NINCDS,NIH,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. NINCDS,NIH,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. HOSP FREDERIC JOLIOT,CEA,DEPT RES IMAGING,PHARMACOL & PHYSIOL SERV,ORSAY,FRANCE. FUKUI MED SCH,BIOMED IMAGING RES CTR,FUKUI 91011,JAPAN. RI Deiber, Marie-Pierre/M-5949-2014 NR 32 TC 130 Z9 132 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 1997 VL 17 IS 6 BP 670 EP 679 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA XL368 UT WOS:A1997XL36800008 PM 9236723 ER PT J AU Stapleton, JM Morgan, MJ Liu, X Yung, BCK Phillips, RL Wong, DF Shaya, EK Dannals, RF London, ED AF Stapleton, JM Morgan, MJ Liu, X Yung, BCK Phillips, RL Wong, DF Shaya, EK Dannals, RF London, ED TI Cerebral glucose utilization is reduced in second test session SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE anxiety; cerebral metabolism; glucose utilization; positron emission tomography ID BLOOD-FLOW; METABOLIC MEASUREMENTS; ANXIETY; REPRODUCIBILITY; VARIABILITY; HUMANS; BRAIN AB Cerebral glucose utilization was higher during the first positron emission tomography (PET) session than during the second session, as assayed using the PET [F-18]-fluorodeoxyglucose method in male human volunteers. This difference was due largely to data from subjects with low trait anxiety, since subjects with high anxiety showed similar metabolism in both PET sessions. High-anxiety subjects showed greater right/left ratios of cerebral metabolism than low-anxiety subjects, particularly during the second PET session. These findings suggest that the level of anxiety may be an important variable to consider in PET studies using multiple sessions. C1 NIDA,INTRAMURAL RES PROGRAM,NIH,BRAIN IMAGING CTR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. NR 31 TC 36 Z9 36 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 1997 VL 17 IS 6 BP 704 EP 712 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA XL368 UT WOS:A1997XL36800012 PM 9236727 ER PT J AU Magiakou, MA Mastorakos, G Zachman, K Chrousos, GP AF Magiakou, MA Mastorakos, G Zachman, K Chrousos, GP TI Blood pressure in children and adolescents with Cushing's syndrome before and after surgical cure SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCOCORTICOID-HYPERTENSION; DISEASE; RATS; DEXAMETHASONE; MICROSURGERY; CONTRIBUTE; SYSTEMS; OBESITY; DOGS AB Approximately half of children and adolescents with Cushing's syndrome develop hypertension. To examine the role of hypercortisolism in the pathogenesis of hypertension in young patients and to establish its reversibility, we studied 31 hypertensive children and adolescents with Cushing's syndrome (systolic, diastolic, and/or mean blood pressure more than 2 SD U for age and sex) from a total of 63 patients before, and for a period of 1 yr after surgical cure. Preoperatively, 93.5%, 42%, and 45% of these patients presented with an increase of the systolic, diastolic, and mean blood pressure, respectively. The systolic blood pressure remained increased in 30.7%, 15.8%, and 5.5% of patients at 3, 6, and 12 months after surgical cure, respectively. The diastolic and mean blood pressure completely normalized by 3 months after surgical cure. A significant, positive correlation was observed between the systolic blood pressure and the duration of the disease, but no correlation was seen with the 24-h urinary free cortisol values and/or the patients' body mass indices. The lack of correlation between 24-h urinary free cortisol values and blood pressure suggests that hypercortisolism influences blood pressure through multiple pathways. The positive correlation between the systolic blood pressure and the duration of the disease points towards the deleterious effects of prolonged hypercortisolism and the significance of early diagnosis and treatment. The fact that the blood pressure normalized within a year from the correction of hypercortisolism suggests that, as a rule, young patients with hypercortisolism do not develop essential hypertension. C1 NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 49 TC 29 Z9 31 U1 2 U2 2 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 JUN PY 1997 VL 82 IS 6 BP 1734 EP 1738 DI 10.1210/jc.82.6.1734 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XC080 UT WOS:A1997XC08000016 PM 9177372 ER PT J AU Ramayya, MS Zhou, J Kino, T Segars, JH Bondy, CA Chrousos, GP AF Ramayya, MS Zhou, J Kino, T Segars, JH Bondy, CA Chrousos, GP TI Steroidogenic factor 1 messenger ribonucleic acid expression in steroidogenic and nonsteroidogenic human tissues: Northern blot and in situ hybridization studies SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NUCLEAR RECEPTOR; FACTOR-I; TRANSCRIPTION FACTOR; GENE; AD4BP; HYDROXYLASES; ACTIVATION; REGULATOR; PROTEIN; ENZYME AB Steroidogenic factor-1 (SF-1), a tissue-specific orphan nuclear receptor, regulates the genes of several steroidogenic enzymes, Mullerian inhibiting substance, and the gonadotrophins. Also, this transcription factor is crucial for hypothalamic, adrenal, and gonadal organogenesis in the mouse. We recently cloned the human SF-1 (hSF-1) complementary DNA (cDNA) and now report the distribution of this factor's messenger RNA (mRNA) in human tissues. Northern blot analyses of peripheral tissues revealed high hSF-1 mRNA expression in the adrenal cortex and the gonads, but no hSF-1 mRNA was detected in the placenta. High hSF-1 mRNA expression also was seen in the spleen. In this tissue, in addition to the main transcript of 3.5-4 kb seen in the adrenal and gonads, two additional transcripts of 4.4 kb and 8 kb were noted. The additional 4.4-kb transcript also was seen in several peripheral tissues and various components of the brain. However, adult liver and heart showed only the 4.4-kb transcript. In the human brain, hSF-1 mRNA expression was widespread, including several components of the limbic system. In situ hybridization studies confirmed the strong expression of hSF-1 mRNA in adrenal cortex, ovary, testis, and the spleen, primarily within reticuloendothelial cells. Thus, in the human, the hSF1 mRNA is present in both steroidogenic and nonsteroidogenic tissues, albeit not in the placenta. In the central nervous system, the expression of hSF-1 mRNA is widespread. It is composed of several different mRNA species distributed in a tissue-specific fashion. These findings suggest that hSF-1 may play a role in reticuloendothelial/immune cell maturation and/or function, as well as nervous system development and/or neurosteroid biosynthesis. C1 NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 31 TC 69 Z9 70 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 JUN PY 1997 VL 82 IS 6 BP 1799 EP 1806 DI 10.1210/jc.82.6.1799 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XC080 UT WOS:A1997XC08000029 PM 9177385 ER PT J AU Ross, JL Feuillan, P Kushner, H Roeltgen, D Cutler, GB AF Ross, JL Feuillan, P Kushner, H Roeltgen, D Cutler, GB TI Absence of growth hormone effects on cognitive function in girls with Turner syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CHILDREN; INTELLIGENCE; ACHIEVEMENT AB Turner syndrome (TS) is a genetic disorder characterized by short stature, gonadal dysgenesis, and a particular neurocognitive profile of normally developed language abilities (particularly verbal IQ) and impaired visual-spatial and/or visual-perceptual abilities. We have followed a large sample of girls with Turner syndrome who were enrolled in a long-term, double-blind, placebo-controlled trial of the effects of growth hormone (GH) treatment on final adult height. This study provides a unique opportunity to prospectively evaluate the effects of GH treatment on neurocognitive function in this population of girls with Turner syndrome. The GH- and placebo-treated Turner syndrome subjects were well matched for age, treatment duration, race, karyotype, and socioeconomic status. Treatment (GH or placebo) durations ranged from 1-7 yr. Whether GH deficiency and/or treatment in childhood and adolescence influences cognitive outcome in short children or GH-children is controversial. The major result of this study was the absence of GH treatment effects on cognitive function in girls with Turner syndrome. Our findings are in agreement with most of the previous studies that found no apparent growth hormone treatment effects on cognitive function in growth-hormone deficient children. We conclude that this study does not support a role for growth hormone in influencing childhood brain development in girls with Turner syndrome. Their characteristic nonverbal neurocognitive deficits were not altered with GH treatment into early adolescence. C1 MED COLL PENN & HAHNEMANN UNIV, PHILADELPHIA, PA USA. WILLIAMSPORT HOSP, WILLIAMSPORT, PA 17701 USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Ross, JL (reprint author), THOMAS JEFFERSON UNIV, DEPT PEDIAT, 1025 WALNUT ST, PHILADELPHIA, PA 19107 USA. FU NINDS NIH HHS [NS29857] NR 15 TC 31 Z9 31 U1 0 U2 3 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 JUN PY 1997 VL 82 IS 6 BP 1814 EP 1817 DI 10.1210/jc.82.6.1814 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XC080 UT WOS:A1997XC08000032 PM 9177388 ER PT J AU Yanovski, JA Yanovski, SZ Gold, PW Chrousos, GP AF Yanovski, JA Yanovski, SZ Gold, PW Chrousos, GP TI Differences in corticotropin-releasing hormone-stimulated adrenocorticotropin and cortisol before and after weight loss SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEXAMETHASONE SUPPRESSION TEST; PITUITARY-ADRENAL AXIS; BODY-FAT DISTRIBUTION; LOW-CALORIE DIETS; OBESE WOMEN; ENERGY-EXPENDITURE; DIFFERENT PATTERNS; THYROID-HORMONES; BETA-ENDORPHIN; PROTEIN AB Little is known about the effects of intentional weight loss on the function of the hypothalamic-pituitary-adrenal (HPA) ards of obese individuals. We studied the HPA axis of 34 healthy obese women (body mass index, 40.2 +/- 7.9 kg/m(2)) before and after a 21.0 +/- 7.9-kg weight loss induced by a 26-week weight loss program that included 12 weeks of a 3350 kJ/day (800 Cal/day) liquid formula diet, 6 weeks of gradual refeeding, and 6 weeks of caloric stabilization at 5020-6280 kJ/day (1200-1500 Cal/day). Obese subjects were evaluated twice: before caloric restriction and during the last 3 weeks of caloric stabilization with a 3-h evening 1 mu g/kg ovine CRH (oCRH) stimulation test. CRH-stimulated ACTH and cortisol values were compared to those of a control group of 12 normal weight women. Before caloric restriction, both ACTH and cortisol responses to oCRH were similar in obese women and normal weight controls. Weight loss did not significantly alter the ACTH response to oCRH; however, the total plasma cortisol response to oCRH decreased significantly with weight loss (area under the curve, 96,320 +/- 21,040 nmol/L.min before weight loss; 82,450 +/- 22,460 nmol/L.min after weight loss; P < 0.001). Cortisol-binding globulin also decreased significantly after weight loss (2,270 +/- 1,050 nmol/L) compared either to values obtained before weight loss (3,590 +/- 1,360 nmol/L; P < 0.001) or to those of normal weight controls (3,910 +/- 1,400 nmol/L; P < 0.001). Assay for plasma free cortisol, either before or 180 min after oCRH treatment, showed no significant changes in cortisol responses resulting from weight loss. As plasma free cortisol was not altered by weight reduction, the decrease in the total cortisol response to oCRH after weight loss appears to be secondary to significant decreases in cortisol-binding globulin. We conclude that when obese women lose large amounts of weight with a 3350 kJ/day, very low energy diet, such weight reduction does not significantly affect the HPA axis. C1 NIH, OFF DIRECTOR, WARREN GRANT MAGNUSON CLIN CTR, BETHESDA, MD 20892 USA. NIDDKD, DIV DIGEST DIS & NUTR, NIH, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262-1862, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Biguzzi, Felipe/E-4724-2015; OI Yanovski, Jack/0000-0001-8542-1637 NR 49 TC 36 Z9 36 U1 1 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 JUN PY 1997 VL 82 IS 6 BP 1874 EP 1878 DI 10.1210/jc.82.6.1874 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XC080 UT WOS:A1997XC08000043 PM 9177399 ER PT J AU Patibandla, SA Dallas, JS Seetharamaiah, GS Tahara, K Kohn, LD Prabhakar, BS AF Patibandla, SA Dallas, JS Seetharamaiah, GS Tahara, K Kohn, LD Prabhakar, BS TI Flow cytometric analyses of antibody binding to Chinese hamster ovary cells expressing human thyrotropin receptor SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN TSH RECEPTOR; IDIOPATHIC MYXEDEMA PATIENTS; EXTRACELLULAR DOMAIN; MEDIATED ACTIVATION; IMMUNOGLOBULINS; AUTOANTIBODIES; REGION; IDENTIFICATION; CHIMERAS; PEPTIDES AB To develop a method that can be used to directly detect binding of antibodies to TSH receptor (TSHr), we employed Chinese hamster ovary (CHO) cells permanently transfected with a human TSHr complementary DNA (CHOR). These cells showed increased cAMP production when treated with either human TSH or thyroid-stimulating antibodies and decreased TSH-mediated cAMP production when treated with stimulation-blocking antibodies. We employed now cytometry and rabbit antibodies against the extracellular domain of the TSHr (ETSHr) to test whether these cells can be used to directly detect and quantitate the binding of anti-TSHr antibodies. Rabbit anti-ETSHr bound specifically to CHOR cells, and the binding could be blocked with purified ETSHr. To test the feasibility of using these cells for epitope mapping, we tested the binding of rabbit antibodies raised against several synthetic TSHr peptides. Rabbit antipeptide 92 (amino acids 12-30) and 91 (amino acids 32-46) showed Little or no binding to the CHOR cells. In contrast, antibodies raised against peptides 93 (amino acids 316-330), 95 (aa 325-345), 3A (aa 357-372), 367 (aa 367-386), and 1B (aa 362-376) showed significant binding to the CHOR cells. The specificity of binding of antipeptide antibodies was demonstrated by a complete inhibition of binding by corresponding peptides. When TSH-binding inhibitory Ig-positive sera from 15 patients with hyperthyroidism were tested, 8 of them showed specific binding to the CHOR cells compared to their relative binding to normal CHO cells; sera from all normal individuals tested did not exhibit specific binding to CHOR cells. These studies shelved the usefulness of CHOR cells and flow cytometry in epitope mapping using sera with known specificities and the potential usefulness of the technique to detect anti-TSHr antibodies in patient sera. C1 UNIV TEXAS, MED BRANCH, DEPT IMMUNOL & MICROBIOL, GALVESTON, TX 77555 USA. UNIV TEXAS, MED BRANCH, DEPT PEDIAT, GALVESTON, TX 77555 USA. NIDDKD, CELL REGULAT SECT, METAB DIS BRANCH, NIH, BETHESDA, MD 20892 USA. FU NIDDK NIH HHS [DK-47417, DK-44972] NR 30 TC 13 Z9 13 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 JUN PY 1997 VL 82 IS 6 BP 1885 EP 1893 DI 10.1210/jc.82.6.1885 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XC080 UT WOS:A1997XC08000045 PM 9177401 ER PT J AU Kim, WB Chung, HK Lee, HK Kohn, LD Tahara, K Cho, BY AF Kim, WB Chung, HK Lee, HK Kohn, LD Tahara, K Cho, BY TI Changes in epitopes for thyroid-stimulating antibodies in Graves' disease sera during treatment of hyperthyroidism: Therapeutic implications SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN THYROTROPIN RECEPTOR; N-TERMINAL REGION; TSH RECEPTOR; IDIOPATHIC MYXEDEMA; RABBIT ANTIBODIES; BLOCKING ANTIBODIES; MEDIATED ACTIVATION; SYNTHETIC PEPTIDES; IMMUNOGLOBULIN-G; IDENTIFICATION AB To determine whether there are changes in epitope recognition by stimulating TSH receptor antibodies (TSHRAbs) during treatment of hyperthyroidism and to evaluate the clinical relevance of such changes, we serially measured the activity of IgG preparations from 39 patients with Graves' disease over an 8-month period. To measure epitope changes of the stimulating TSHRAbs, we used Chinese hamster ovary (CHO) cells transfected with wild-type human TSHR (hTSHR) or TSHR chimeras with residues 90-165 (Mc2) substituted by equivalent residues of the rat LH/CG receptor. When initially examined, 37 of the 39 patients had significant stimulating TSHRAb activity measured with wild-type CHO-hTSHR cells. Serial measurements of stimulating TSHRAb activity in Mc2 chimera-transfected cells divided the 39 patients into three distinct groups. Thus, 10 patients (heterogeneous epitope group) exhibited low but significant activity in Mc2 chimera assays at the start of the study; 10 patients who were initially negative in Mc2 chimera assays remained negative (persistently homogeneous epitope group); and 19 patients who were initially negative in Mc2 chimera assays became transiently or persistently positive during treatment, despite a simultaneous decrease in TSHRAb activity measured with wild-type TSHR (changing epitope group). The functional stimulating TSHRAb epitope thus changed from residues 90-165 to residues outside this region in the last group, which comprises nearly two-thirds of the initially Mc2-negative patients (19 of 29) and one-half of all patients (19 of 39). Patients in the changing epitope group responded more quickly and to lower doses of methimazole than, patients in the persistently homogeneous epitope group, behaving in this respect exactly as the patients in the heterogeneous epitope group. Additionally, although the decrease in stimulating TSHRAb activities during the 8-month treatment period was similar in the two groups, the thyrotropin binding inhibitor immunoglobulin (TBII) activities decreased more rapidly in patients in the persistently homogeneous epitope group than in patients in the changing epitope group (P < 0.05). There were no differences in initial stimulating TSHRAb or TBII activities, degree of hyperthyroidism, goiter size, or prior duration of symptoms between the persistently homogeneous epitope group and changing epitope group. In summation, we show that the epitopes of stimulating TSHRAbs in Graves' disease patients may change during their clinical course or treatment period, and that the change is from antibodies recognizing N-terminal TSHR residues 90-165 to antibodies recognizing other regions of the TSHR. We also show that the development of stimulating TSBRAbs with this heterogeneous epitope or their presence at the initial screening for disease activity seems to be associated with increased responsiveness to antithyroid drug therapy. We suggest, therefore, that Mc2 chimera assays may be useful to predict the response of patients to antithyroid drug therapy. C1 SEOUL NATL UNIV, COLL MED, DEPT INTERNAL MED, SEOUL 151, SOUTH KOREA. NIDDKD, CELL REGULAT SECT, METAB DIS BRANCH, NIH, BETHESDA, MD 20892 USA. CHIBA UNIV, SCH MED, DEPT INTERNAL MED 2, CHIBA 260, JAPAN. OI Kim, Won Bae/0000-0003-4544-1750 NR 34 TC 43 Z9 44 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 JUN PY 1997 VL 82 IS 6 BP 1953 EP 1959 DI 10.1210/jc.82.6.1953 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XC080 UT WOS:A1997XC08000057 PM 9177413 ER PT J AU Long, XL Boluyt, MO Hipolito, MD Lundberg, MS Zheng, JS ONeill, L Cirielli, C Lakatta, EG Crow, MT AF Long, XL Boluyt, MO Hipolito, MD Lundberg, MS Zheng, JS ONeill, L Cirielli, C Lakatta, EG Crow, MT TI p53 and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE p53; apoptosis; cardiomyocytes; hypoxia; ischemia ID THYMOCYTE APOPTOSIS; GROWTH ARREST; MESSENGER-RNA; HEART-FAILURE; CELL LOSS; GENE; DNA; HYPERTROPHY; CARDIOMYOCYTES; ACTIVATION AB Myocyte cell loss is a prominent and important pathogenic feature of cardiac ischemia. We have used cultured neonatal rat cardiac myocytes exposed to prolonged hypoxia as an experimental system to identify critical factors involved in cardiomyocyte death. Exposure of myocytes to hypoxia for 48 h resulted in intranucleosomal cleavage of genomic DNA characteristic of apoptosis and was accompanied by increased p53 transactivating activity and protein accumulation. Expression of p21/WAF-1/CIP-1, a well-characterized target of p53 transactivation, also increased in response to hypoxia. Hypoxia did not cause DNA laddering or cell loss in cardiac fibroblasts. To determine whether the increase in p53 expression in myocytes was sufficient to induce apoptosis, normoxic cultures were infected with a replication-defective adenovirus expressing wild-type human p53 (AdCMV.p53). Infected cells expressed high intracellular levels of p53 protein and exhibited the morphological changes and genomic DNA fragmentation characteristic of apoptosis. In contrast, no genomic DNA fragmentation was observed in myocytes infected with the control virus lacking an insert (AdCMV.null) or in cardiac fibroblasts infected with AdCMV.p53. These results suggest that the intracellular signaling pathways activated by p53 might play a critical role in the regulation of hypoxia-induced apoptosis of cardiomyocytes. C1 NIA,CARDIOVASC SCI LAB,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. IST DERMOPAT IMMACOLATA,LAB PATOL VASC,ROME,ITALY. NR 41 TC 227 Z9 245 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 1 PY 1997 VL 99 IS 11 BP 2635 EP 2643 DI 10.1172/JCI119452 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XD357 UT WOS:A1997XD35700013 PM 9169493 ER PT J AU Crotchfelt, KA Welsh, LE DeBonville, D Rosenstraus, M Quinn, TC AF Crotchfelt, KA Welsh, LE DeBonville, D Rosenstraus, M Quinn, TC TI Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in genitourinary specimens from men and women by a coamplification PCR assay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LIGASE CHAIN-REACTION; URINE; DIAGNOSIS; INFECTIONS; URETHRITIS; CULTURES; SWABS AB A coamplification PCR test for the direct detection of Neisseria gonorrhoeae and Chlamydia trachomatis in urethral and endocervical swabs and urine samples from men and women was compared to standard culture techniques. Processed specimens were amplified in single reaction tubes containing primers for both organisms, and PCR products were detected by a colorimetric microwell plate hybridization assay specific for each pathogen. Of 344 specimens from men, 45 (13.1%) urine specimens were PCR positive for C. trachomatis, 51 (14.8%) urethral swab specimens were PCR positive, and 29 urethral swab specimens (8.4%) were culture positive. After analysis of discrepancies, the resolved sensitivity and specificity of PCR for C. trachomatis were 96.2 and 99.3%, respectively, in urethral swab specimens, compared to 88.2 and 98.6% for urine specimens. Of the 192 specimens from women, 28 (14.6%) urine specimens were PCR positive for C. trachomatis, 32 (16.7%) endocervical specimens were PCR positive, and 19 (9.9%) endocervical specimens were culture positive. After analysis of discrepancies, the resolved sensitivity and specificity of PCR for C. trachomatis for endocervical specimens were both 100% compared to 100 and 99.4%, respectively, for urine specimens from women. In men, 68 (19.8%) urine specimens were PCR positive for N. gonorrhoeae, 73 (21.2%) urethral swabs were PCR positive, and 59 (17.2%) urethral swabs were culture positive. After analysis of discrepancies, the resolved sensitivity and specificity of PCR for N. gonorrhoeae were 97.3 and 97.0%, respectively, for urethral specimens compared to 91.1 and 98.5% for urine specimens. In women, 18 (9.4%) urine specimens were PCR positive for N. gonorrhoeae, 23 (12.0%) were endocervical swab PCR positive, and 15 (7.8%) endocervical specimens were culture positive. After analysis of discrepancies, the resolved sensitivity and specificity of PCR for N. gonorrhoeae were 100 and 99.1%, respectively, for endocervical specimens compared to 90.0 and 95.9% for female urine specimens. These results indicate that a multiplex PCR is highly sensitive for detecting both C. trachomatis and N. gonorrhoeae from a single urine or genital swab, providing a more cost-effective way of screening multiple pathogens. C1 JOHNS HOPKINS UNIV,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,NIH,BETHESDA,MD 20892. ROCHE MOL SYST,BRANCHBURG,NJ. NR 22 TC 79 Z9 82 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1997 VL 35 IS 6 BP 1536 EP 1540 PG 5 WC Microbiology SC Microbiology GA XA755 UT WOS:A1997XA75500046 PM 9163477 ER PT J AU Sutliff, VE Doppman, JL Gibril, F Venzon, DJ Yu, F Serrano, J Jensen, RT AF Sutliff, VE Doppman, JL Gibril, F Venzon, DJ Yu, F Serrano, J Jensen, RT TI Growth of newly diagnosed, untreated metastatic gastrinomas and predictors of growth patterns SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; MULTIPLE ENDOCRINE NEOPLASIA; ISLET-CELL CARCINOMA; PANCREATIC TUMORS; GASTROENTEROPANCREATIC TUMORS; ADRENOCORTICOTROPIC HORMONE; AGGRESSIVE RESECTION; LONG-TERM; MANAGEMENT AB Purpose: The growth pattern of untreated metastatic neuroendocrine tumors is unknown, This uncertainty contributes to the disagreement regarding timing and could effect evaluation of the efficacy of antitumor treatment, The purpose of this study was to determine the growth rate of untreated hepatic metastatic gastrinoma and to identify its predictors, Patients and Methods: Nineteen patients with histologically proven metastatic gastrinoma in the liver with Zollinger-Ellison syndrome were studied, Conventional imaging studies were performed initially and at 4- to 6-month intervals before any treatment, Metastases growth rates were calculated and correlated with laboratory and clinical parameters, as well as tumor extent on initial tumor assessment, Results: Twenty-six percent of patients (five of 19) demonstrated no growth over a mean follow-up time of 29 months, 32% (six of 19) had slow growth (1% to 50% increase in volume per month) over a 19-month period, and 42% (eight of 19) had rapid growth (> 50% volume increase per month) over an 11-month period, In patients with rapid growth, 62% died; 0% of the no-growth or slow-growth group died, No clinical or laboratory parameter correlated with growth rate, except the rate increase in fasting serum gastrin and the presence of bilobar liver or bone metastases, The growth rate was highly predictive of death from tumor, Conclusion: The growth rate of metastatic gastrinoma varies markedly in different patients and 26% demonstrated no growth, The growth rate needs to considered in the determination of when and in whom antitumor therapy is initiated, as well us in the assessment of response to tumoricidal therapies. C1 NIDDK,DDB,NIH,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,NIH,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 68 TC 70 Z9 71 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1997 VL 15 IS 6 BP 2420 EP 2431 PG 12 WC Oncology SC Oncology GA XD977 UT WOS:A1997XD97700031 PM 9196158 ER PT J AU Dalgaard, JZ Moser, MJ Hughey, R Mian, IS AF Dalgaard, JZ Moser, MJ Hughey, R Mian, IS TI Statistical modeling, phylogenetic analysis and structure prediction of a protein splicing domain common to inteins and hedgehog proteins SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE hidden Markov model; intein; hedgehog; endonuclease; klbA domain; protein splicing ID INTRON-ENCODED ENDONUCLEASE; ARCHAEA DNA-POLYMERASE; HIDDEN MARKOV-MODELS; SECONDARY STRUCTURE; INTERVENING SEQUENCES; BRANCHED INTERMEDIATE; ESCHERICHIA-COLI; GENE; ELEMENTS; INFORMATION AB Inteins, introns spliced at the protein level, and the hedgehog family of proteins involved in eucaryotic development both undergo autocatalytic proteolysis. Here, a specific and sensitive hidden Markov model (HMM) of a protein splicing domain shared by inteins and the hedgehog proteins has been trained and employed for further analysis. The HMM characterizes the common features of this domain including the position where a site-specific DNA endonuclease domain is inserted in the majority of the inteins, The HMM was used to identify several new putative inteins, such as that in the Methanococcus jannaschii klbA protein, and to generate a multiple sequence alignment of sequences possessing this domain, Phylogenetic analysis suggests that hedgehog proteins evolved from inteins, Secondary and tertiary structure predictions suggest that the domain has a structure similar to a beta-sandwich, Similarities between the serine protease cleavage mechanism and the protein splicing reaction mechanism are discussed, Examination of the locations of inteins indicates that they are not inserted randomly in an extein, but are often inserted at functionally important positions in the host proteins, A specific and sensitive HMM for a domain present in klbA proteins identified several additional bacterial and archaeal family members, and analysis of the site of insertion of the intein suggests residues that may be functionally important, This domain may play a role in formation of surface-associated protein complexes. C1 UNIV CALIF BERKELEY, LAWRENCE BERKELEY LAB, DIV LIFE SCI, BERKELEY, CA 94720 USA. UNIV CALIF SANTA CRUZ, BASKIN CTR COMP ENGN & INFORMAT SCI, SANTA CRUZ, CA 95064 USA. RP NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM,POB B,BLDG 539, ROOM 154, FREDERICK, MD 21702 USA. NR 78 TC 60 Z9 61 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 EI 1557-8666 J9 J COMPUT BIOL JI J. Comput. Biol. PD SUM PY 1997 VL 4 IS 2 BP 193 EP 214 DI 10.1089/cmb.1997.4.193 PG 22 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA XH952 UT WOS:A1997XH95200009 PM 9228618 ER PT J AU Nicklaus, MC AF Nicklaus, MC TI Conformational energies calculated by the molecular mechanics program CHARMm SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article ID FORCE-FIELD AB Following the publication of a comparison of several molecular mechanics methods [Gundertofte et al., J. Comput. Chem. 17, 429 (1996)], we have expanded the set of force fields tested by examining CHARMm 23.0 with its associated parameter set (version 22.0) relative to the gas-phase data used in the Gundertofte et al. study. CHARMm calculated rotational barriers and conformational energies within the same range of accuracy as the most accurate ones of the other force fields. The average absolute error was 0.64 kcal/mol, and 0.52 kcal/mol when the rotational barriers were excluded. (C) 1997 by John Wiley & Sons, Inc.* RP Nicklaus, MC (reprint author), NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BLDG 37,ROOM 5B29,37 CONVENT DR,BETHESDA,MD 20892, USA. RI Nicklaus, Marc/N-4183-2014 NR 9 TC 4 Z9 4 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD JUN PY 1997 VL 18 IS 8 BP 1056 EP 1060 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA XA680 UT WOS:A1997XA68000009 ER PT J AU Kingman, A Imrey, PB Pihlstrom, BL Zimmerman, SO AF Kingman, A Imrey, PB Pihlstrom, BL Zimmerman, SO TI Chilton, Fertig, Fleiss, and the Task Force on Design and Analysis in Dental and Oral Research SO JOURNAL OF DENTAL RESEARCH LA English DT Article ID GUIDELINES; ACCEPTANCE; PRODUCTS C1 UNIV ILLINOIS,DEPT MED INFORMAT SCI,URBANA,IL. UNIV ILLINOIS,DEPT STAT,URBANA,IL. UNIV MINNESOTA,CLIN DENT RES CTR,MINNEAPOLIS,MN. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT BIOMATH,HOUSTON,TX 77030. RP Kingman, A (reprint author), NIDR,ORAL HLTH PROMOT RISK FACTORS & MOL EPIDEMIOL BRA,NIH,45 CTR DR,MSC 6401,ROOM 4AS-13B,BETHESDA,MD 20892, USA. OI Imrey, Peter/0000-0002-0533-4603 NR 11 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 1997 VL 76 IS 6 BP 1239 EP 1243 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XA878 UT WOS:A1997XA87800002 PM 9168856 ER PT J AU DeCarlo, AA Windsor, LJ Bodden, MK Harber, GJ BirkedalHansen, B BirkedalHansen, H AF DeCarlo, AA Windsor, LJ Bodden, MK Harber, GJ BirkedalHansen, B BirkedalHansen, H TI Activation and novel processing of matrix metalloproteinases by a thiol proteinase from the oral anaerobe Porphyromonas gingivalis SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE metalloproteinases; Porphyromonas gingivalis; cysteine proteinases; amino acid sequencing; Western blotting ID HUMAN FIBROBLAST COLLAGENASE; HUMAN PERIODONTAL-DISEASES; LATENT HUMAN NEUTROPHIL; TRYPSIN-LIKE PROTEASE; BACTEROIDES-GINGIVALIS; TISSUE INHIBITOR; IV COLLAGENASE; ACTIVE-SITE; INTERSTITIAL COLLAGENASES; COLLAGENOLYTIC ACTIVITY AB A critical outcome of periodontal disease is degradation of the collagenous periodontal ligament that connects teeth to bone in the dental arch. Periodontal diseases occur in response to bacterial colonization of the teeth, but their molecular pathogenesis is still speculative. One family of enzymes, known as the matrix metalloproteinases (MMPs), has been implicated in the degradation of the periodontal ligament. MMPs, which are also suspected to play a role in many other physiologic and pathologic remodeling processes, can be secreted by epithelial cells surrounding the teeth and are found in relative abundance in tissues and fluids near periodontally diseased sites. Since most MMPs are secreted as inactive zymogens which may be activated by limited proteolysis, it has been suggested that proteinases expressed by the infecting periodontal pathogens might activate latent host MMPs to initiate or accelerate degradation of the collagenous periodontal ligament. The aim of this work was to examine interactions between purified host MMPs and bacterial proteinase. Ln this article, we demonstrate that a proteinase isolated from the periodontopathogen Porphyromonas gingivalis can activate MMP-1, MMP-3, and MMP-9 and can catalyze the superactivation of MMP-1 by MMP-3. Activation of these Mh?Ps is demonstrated to result from initital hydrolysis within their propeptide. Also, for MMP-1 and MMP-9: the P. gingivalis proteinase cleaves the MMP propeptide following a lysine residue at a previously unreported site which, for both MMPs, is one residue NH2-terminal to the known autocatalytic cleavage site. These data describe a mode of virulence for the periodontopathogen Porphyromonas gingivalis that involves activation of host-degradative enzymes. C1 UNIV ALABAMA,DEPT BIOCHEM & MOL GENET,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT RESTORAT DENT,BIRMINGHAM,AL 35294. NCI,DIV CANC BIOL DIAG & CTR,BETHESDA,MD 20892. NIDR,NIH,BETHESDA,MD 20892. RP DeCarlo, AA (reprint author), UNIV ALABAMA,DEPT PERIODONT,DEPT ORAL BIOL,RM 736,BBRB,845 19TH ST S,BIRMINGHAM,AL 35294, USA. FU NIDCR NIH HHS [DE 06028, DE 07256, DE 08228, K16 DE000279] NR 78 TC 91 Z9 92 U1 0 U2 3 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 1997 VL 76 IS 6 BP 1260 EP 1270 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XA878 UT WOS:A1997XA87800005 PM 9168859 ER PT J AU Tomar, SL Winn, DM Swango, PA Giovino, GA Kleinman, DV AF Tomar, SL Winn, DM Swango, PA Giovino, GA Kleinman, DV TI Oral mucosal smokeless tobacco lesions among adolescents in the United States SO JOURNAL OF DENTAL RESEARCH LA English DT Article; Proceedings Paper CT 74th General Session of the International-Association-for-Dental-Research CY MAR 13-17, 1996 CL SAN FRANCISCO, CA SP Int Assoc Dent Res DE smokeless tobacco; oral leukoplakia; mouth mucosa; adolescents; epidemiology ID FOLLOW-UP; MALIGNANT TRANSFORMATION; NATURAL-HISTORY; LEUKOPLAKIA; CANCER; P53; EXPRESSION; USERS; INDIA AB The presence of oral smokeless tobacco lesions among adolescents may be an early indicator of increased risk for oral cancers. Data from the 1986-1987 National Survey of Oral Health in US School Children were used to examine the cross-sectional relationship between the use of tobacco and alcohol and the presence of white or whitish oral soft-tissue lesions. The sample included 17,027 schoolchildren (aged 12 to 17 years) who provided information on the use of snuff, chewing tobacco, cigarettes, and alcohol and who received oral clinical examinations. Smokeless tobacco lesions were detected in 1.5% of students (projects to about 300,000 nationally), including 2.9% of males and 0.1% of females. These lesions were more prevalent among whites (2.0%) than among African Americans (0.2%) or Hispanics (0.8%). Modeling with multivariate logistic regression revealed that, among white males, current snuff use was the strongest correlate of lesions [odds ratio (OR) = 18.4; 95% confidence interval (CI) = 8.5-39.8], followed by current chewing tobacco use [OR = 2.5; 95% CI = 1.3-5.0]. Lesions were strongly associated with duration, monthly frequency, and daily minutes of use of snuff and chewing tobacco. These data suggest that snuff may be a stronger risk factor than chewing tobacco for smokeless tobacco lesions, but the use of either of these forms of oral tobacco exhibits a dose-response relationship with the occurrence of lesions. We found little evidence that the use of alcohol or cigarettes may increase the risk of smokeless tobacco lesions. Preventing smokeless tobacco lesions and their possible malignant transformation may be best accomplished among adolescents by preventing the use of snuff and chewing tobacco. C1 NIDR,NIH,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,OFF SMOKING & HLTH,ATLANTA,GA 30341. FU NIDCR NIH HHS [N01-DE-62560] NR 51 TC 52 Z9 55 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 1997 VL 76 IS 6 BP 1277 EP 1286 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XA878 UT WOS:A1997XA87800007 PM 9168861 ER PT J AU Huffman, LC AF Huffman, LC TI Emotional development: The organization of emotional life in the early years - Sroufe,LA SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Book Review RP Huffman, LC (reprint author), NIMH,DIV NEUROSCI & BEHAV SCI,BEHAV COGNIT & SOCIAL SCI RES BRANCH,PERSONAL & EMOT PROGRAM,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUN PY 1997 VL 18 IS 3 BP 201 EP 201 DI 10.1097/00004703-199706000-00013 PG 1 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA XG168 UT WOS:A1997XG16800012 ER PT J AU Timenetsky, MDST Gouvea, V Santos, N Carmona, RCC Hoshino, Y AF Timenetsky, MDST Gouvea, V Santos, N Carmona, RCC Hoshino, Y TI A novel human rotavirus serotype with dual G5-G11 specificity SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; NEUTRALIZATION EPITOPES; ANTIGENIC CHARACTERIZATION; PORCINE ROTAVIRUSES; NUCLEIC-ACID; VP7; PROTEIN; SITES; IDENTIFICATION; SPECIMENS AB Rotavirus serotype G5 isolates were recently recovered from children with diarrhoea in Brazil. Like most human strains, they exhibited long electropherotypes and subgroup II and Wa-like VP4 specificity. We report the successful propagation and the molecular and antigenic characterization of one of these isolates (IAL-28). Cross-neutralization of IAL-28 and a single gene reassortant, UK x IAL-28, which contains the gene encoding the IAL-28 VP7 in the UK genomic background, with prototype G1 to G14 rotaviruses demonstrated that IAL-28 has antigenic determinants specific for both G5 and G11 serotypes. Sequence analysis of the gene encoding VP7 suggested that one or two amino acid substitutions at positions 96 and 100 on IAL-28 VP7 were possibly responsible for the additional G11 specificity. G5 rotaviruses are found in horses and predominate in piglets, whereas G11 has been identified exclusively as a swine pathogen. C1 NICHHD,HUMAN GENET BRANCH,NIH,BETHESDA,MD 20892. NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. UNIV FED RIO DE JANEIRO,INST MICROBIOL,BR-21941 RIO JANEIRO,BRAZIL. RI TIMENETSKY, MARIA/I-7593-2013; Carmona, Rita de Cassia/B-9650-2012; OI Santos, Norma/0000-0002-5123-9172 NR 27 TC 39 Z9 41 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUN PY 1997 VL 78 BP 1373 EP 1378 PN 6 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA XD484 UT WOS:A1997XD48400025 ER PT J AU Gurevich, P Nyska, A Czernobilsky, B LifschitzMercer, B Zuckerman, A Zusman, I AF Gurevich, P Nyska, A Czernobilsky, B LifschitzMercer, B Zuckerman, A Zusman, I TI Nucleolar organizer regions in the splenic lymphoid cells in low-birth-weight and full-term fetuses and newborns with pneumonia and sepsis SO JOURNAL OF HISTOTECHNOLOGY LA English DT Article DE AgNOR; fetuses; immune reaction; low-birthweight; newborns; sepsis ID IMAGE-ANALYSIS; HUMAN SPLEEN; PATHOLOGY; PROLIFERATION; PROTEINS; TISSUES; TUMORS AB We studied the role of some morphological parameters and the nucleolar organizer regions (AgNORs) of splenic-follicle lymphoid cells, lymphocytes, and lymphoblasts in susceptibility of low-birth-weight (LBW) and full-term fetuses and newborns to bronchopneumonia and sepsis. The observed quantitative changes were compared with alterations in the synthesis of IgM by the studied cells. Full-term fetuses without antigenic effects exhibited a decrease in the number of AgNORs and in the nuclear area of the lymphocytes as compared with LBW fetuses. This was accompanied by an increase in the number of small lymphocytes and by a decrease in the number of lymphoblasts/10,000 mu m(2). In newborns after the 6th day, the number of AgNORs increased, especially in the presence of infection (bronchopneumonia). These changes were related to the proliferation and transformation of lymphocytes into lymphoblasts. A sharp increase in the number of B and T lymphoblasts was the major sign of immune reaction to infection in fetuses and newborns: the number of IgM+ cells increased from 0.1 to 2.8/10,000 mu cm(2) In fetuses and newborns with sepsis, which is accompanied by inhibition and decompensation of immune reactions, the number of splenic follicles decreased to 1.9/mm(2) as compared to 4.9/mm(2) in fetuses with bronchopneumonia. This was related to a sharp decrease (by at least 15-fold) in the number of lymphocytes in the splenic follicles. The number of AgNORs also decreased significantly. A good correlation was found between quantitative changes in the number of AgNORs and number of lymphoblasts (r = 0.67) and the rate of mitosis of the lymphoid cells in the spleen (r = 0.97). The changes in lymphoid cell AgNOR are connected with these cells' reaction to infectious antigenic effects. The finding shows that the AgNOR changes presented here can be used as a reliable parameter in diagnostic practice for evaluating the inflammatory process in newborns. C1 HEBREW UNIV JERUSALEM,KORET SCH VET MED,LAB TERATOL & EXPT ONCOL,IL-76100 REHOVOT,ISRAEL. NIH,RES TRIANGLE PK,NC. ICHILOV HOSP,SURASKI MED CTR,INST PATHOL,IL-64239 TEL AVIV,ISRAEL. ISRAEL INST BIOL SCI,NESS ZIONA,ISRAEL. NR 26 TC 0 Z9 0 U1 0 U2 1 PU NATL SOC HISTOTECHNOLOGY PI BOWIE PA 4201 NORTHVIEW DR, STE 502, BOWIE, MD 20716-1073 SN 0147-8885 J9 J HISTOTECHNOL JI J. Histotechnol. PD JUN PY 1997 VL 20 IS 2 BP 127 EP 132 PG 6 WC Cell Biology SC Cell Biology GA XA940 UT WOS:A1997XA94000007 ER PT J AU Segal, BM Klinman, DM Shevach, EM AF Segal, BM Klinman, DM Shevach, EM TI Microbial products induce autoimmune disease by an IL-12-dependent pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; T-CELL RECEPTOR; MULTIPLE-SCLEROSIS; HEALTHY-INDIVIDUALS; SUSCEPTIBILITY; SUPERANTIGEN; TOLERANCE; INFECTION; LINES AB The development and exacerbation of autoimmune diseases are associated with antecedent infectious illness. Microbial products such as LPS, bacterial DNA, or oligonucleotides containing an unmethylated cytosine-guanine dinucleotide have cytokine modulating properties. These products converted quiescent myelin basic protein-specific T cells into effector cells capable of transferring experimental allergic encephalomyelitis. The disease-promoting properties of the microbial products were solely dependent on their capacity to induce the production of IL-12. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. OI Segal, Benjamin/0000-0002-0906-6319 NR 34 TC 145 Z9 149 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1997 VL 158 IS 11 BP 5087 EP 5090 PG 4 WC Immunology SC Immunology GA XA063 UT WOS:A1997XA06300006 PM 9164922 ER PT J AU Apasov, SG Koshiba, M Chused, TM Sitkovsky, MV AF Apasov, SG Koshiba, M Chused, TM Sitkovsky, MV TI Effects of extracellular ATP and adenosine on different thymocyte subsets - Possible role of ATP-gated channels and C protein-coupled purinergic receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; IMMATURE THYMOCYTES; DNA FRAGMENTATION; LYMPHOCYTES-T; APOPTOSIS; REQUIREMENTS; ACTIVATION; INHIBITION; SELECTION; RESPONSES AB To explore the possible role of purinergic receptors in thymocyte development and in pathogenesis of adenosine deaminase SCID, we studied effects of extracellular adenosine triphosphate (ATP(ext)) and adenosine on TCR- and steroid hormone-triggered processes in mouse thymocytes. Reverse transcriptase-PCR analysis confirms the mRNA expression of several types of purinergic receptors, while the functioning of ATP receptors in thymocytes is reflected by ATP(ext)-induced intracellular calcium increases and by thymocyte subset-specific sensitivity to the effects of ATP(ext) and adenosine, Only ATP(ext), but not the ATP catabolites, adenosine, dexamethasone, or TCR cross-linking, was efficient in triggering rapid protein synthesis independent lysis of CD4(+)8(-) thymocytes and peripheral CD4(+) T cells, In contrast, extracellular adenosine specifically induced the apoptosis of CD4(+)8(+) thymocytes, ATP(ext) also induced a slower process of DNA fragmentation and protein synthesis-dependent apoptosis in all thymocyte subsets, ATP(ext) had an additive effect with TCR cross-linking in the induction of thymocyte death, but, unexpectedly, the effects of ATP(ext) at high concentration were antagonistic to steroid-induced apoptosis, Described here, the properties of ATP(ext) and adenosine are consistent with their involvement in the regulation of T cell development due to differential expression and signaling through purinergic receptors in different thymocyte subsets, The possible role of purinergic receptor signaling in T cell differentiation and adenosine deaminase SCID is discussed. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 43 TC 65 Z9 66 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1997 VL 158 IS 11 BP 5095 EP 5105 PG 11 WC Immunology SC Immunology GA XA063 UT WOS:A1997XA06300008 PM 9164924 ER PT J AU Chen, HJ Huang, H Paul, WE AF Chen, HJ Huang, H Paul, WE TI NK1.1(+)CD4(+) T cells lose NK1.1 expression upon in vitro activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROMPTLY PRODUCE INTERLEUKIN-4; RECEPTOR-ALPHA/BETA(+) CELLS; GENE FAMILY; THYMOCYTES; MICE; CD4+; MOLECULES; COMPLEX; ANTIGEN; SUBSET AB NK1.1(+)CD4(+) T cells produce IL-4 promptly in vivo upon injection of anti-CD3 and may play a role in initiating Th2 cell-immunity, To characterize their in vitro activation properties, NK1.1(+)CD4(+) T cells were obtained in high purity from spleens of normal C57BL/6 mice, where they represent 2 to 5% of CD4(+) T cells, or from MHC-class II I-Ab gene knockout mice, where they constitute 42% of CD4(+) T cells, Activation of NK1.1(+)CD4(+) T cells from either source with plate-bound anti-CD3 resulted in loss of expression of NK1.1 as determined both by flow cytometric analysis and by reverse transcriptase-PCR analysis, A portion of these cells also lost CD4 expression, Both the CD4(+) and CD4(-) activated cells retained the over-representation of V beta 8 and V alpha 14 chains and expressed the intermediate levels of the TCR-CDS complex that is characteristic of resting NK1.1(+)CD4(+) T cells, The anti-NK1.1 mAb used for cell sorting was not the cause of NK1.1 or CD4 disappearance, since the sorted cells remain both NK1.1(+) and CD4(+) when cultured in the absence of anti-CD3 or in the presence of anti-CD3 and cyclosporin A, Furthermore, NK1.1(+)CD4(+) T cells that were not treated with anti-NK1.1 Ab also lost NK1.1 expression after activation, Populations of activated CD4(+) and CD4(-) cells (derived from NK1.1(+)CD4(+) T cells) produced both IL-4 and IFN-gamma upon restimulation with plate-bound anti-CD3. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 32 TC 95 Z9 96 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1997 VL 158 IS 11 BP 5112 EP 5119 PG 8 WC Immunology SC Immunology GA XA063 UT WOS:A1997XA06300010 PM 9164926 ER PT J AU Lacana, E Ganjei, JK Vito, P DAdamio, L AF Lacana, E Ganjei, JK Vito, P DAdamio, L TI Dissociation of apoptosis and activation of IL-1 beta-converting enzyme Ced-3 proteases by ALG-2 and the truncated Alzheimer's gene ALG-3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL HYBRIDOMAS; POLY(ADP-RIBOSE) POLYMERASE; ICE/CED-3 PROTEASE; DEATH; ICE; CLEAVAGE; DISEASE AB Recent attention has been focused on the members of the IL-1 beta-converting enzyme (ICE)/Ced-3 family of cysteine protease as the key components of programmed cell death, However, the molecular events that lead to protease activation and link it to the final apoptotic processes remain poorly characterized, We have shown recently that ALG-2 is a Ca2+-binding protein required for apoptosis. ALG-2 depletion protects the mouse T cell hybridoma 3DO from programmed cell death induced by several stimuli, such as synthetic glucocorticoids, TCR, and Fas triggering, In this work, we show that in the ALG-2-depleted clones the ICE/Ced-3 proteases are normally activated upon TCR, Fas, and dexamethasone stimulation, as determined by cleavage of the endogenous substrate poly(ADP-ribose) polymerase and of a fluorogenic substrate, ALG-3, a truncated form of the familial Alzheimer's disease gene PS2, confers resistance to TCR- and Fas-induced apoptosis, Of interest, it also reduces protease activity and inhibits poly(ADP-ribose) polymerase cleavage upon Fas triggering, Our results suggest that, during apoptosis, ALG-2 functions downstream of, and that ALG-3 interferes with the sequential activation of members of the ICE family proteases. C1 NIAID,CELLULAR & MOL IMMUNOL LAB,T CELL MOL BIOL UNIT,NIH,BETHESDA,MD 20892. NR 33 TC 50 Z9 50 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1997 VL 158 IS 11 BP 5129 EP 5135 PG 7 WC Immunology SC Immunology GA XA063 UT WOS:A1997XA06300012 PM 9164928 ER PT J AU Correa, MR Ochoa, AC Ghosh, P Mizoguchi, H Harvey, L Longo, DL AF Correa, MR Ochoa, AC Ghosh, P Mizoguchi, H Harvey, L Longo, DL TI Sequential development of structural and functional alterations in T cells from tumor-bearing mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR ZETA-CHAIN; ANTIGEN-RECEPTOR; SIGNAL-TRANSDUCTION; LYMPHOCYTES; EXPRESSION; CARCINOMA; COMPLEX AB The TCR alpha beta or -gamma delta chains bind the peptide ligand, whereas the associated CD3 delta epsilon gamma and TCR zeta subunits couple the TCR to intracellular signal transduction components. Recently, several groups have described marked alterations in signal transduction elements in T cells from cancer patients or in mice bearing tumor for a few weeks (>26 days). The sequence in which these alterations develop is unknown. The aim of this study was to explore the kinetics of the development of alterations in signal transduction molecules (TCR zeta chain, NF kappa B family proteins, and tyrosine kinase p56(lck)) in mice bearing MC38 colon adenocarcinoma. The results demonstrate that alterations in NF kappa B family proteins, specifically the failure of p65 translocation to the nucleus, occur earlier and more frequently than the decrease in zeta-chain. These defects are paralleled by an impaired ability to produce Th1 cytokines (IL-2 and IFN-gamma). These initial changes are followed by the eventual loss of TCR zeta chain and p56(lck) and a marked decrease in cytotoxic function. An increased rate of lysosomal degradation is one of the mechanisms responsible for the loss of zeta-chain. C1 NIA,GERONTOL RES CTR,NATL INST HLTH,BALTIMORE,MD 21224. SAIC,SIGNAL TRANSDUCT LAB,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,EXPT IMMUNOL LAB,DIV BASIC SCI,FREDERICK,MD 21702. NIA,BALTIMORE,MD 21224. BIOMIRA US INC,CRANBURY,NJ 08512. NR 23 TC 61 Z9 62 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1997 VL 158 IS 11 BP 5292 EP 5296 PG 5 WC Immunology SC Immunology GA XA063 UT WOS:A1997XA06300032 PM 9164948 ER PT J AU Nakabayashi, T Letterio, JJ Geiser, AG Kong, LP Ogawa, N Zhao, WG Koike, T Fernandes, G Dang, H Talal, N AF Nakabayashi, T Letterio, JJ Geiser, AG Kong, LP Ogawa, N Zhao, WG Koike, T Fernandes, G Dang, H Talal, N TI Up-regulation of cytokine mRNA, adhesion molecule proteins, and MHC class II proteins in salivary glands of TGF-beta 1 knockout mice - MHC class II is a factor in the pathogenesis of TGF-beta 1 knockout mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; SJOGRENS-SYNDROME; HUMAN-LYMPHOCYTES; INTERFERON-GAMMA; DEFICIENT MICE; TGF-BETA; EXPRESSION; MOUSE; ICAM-1; DEATH AB Mice homozygous for a disrupted TGF-beta 1 allele develop multiple lymphoproliferative disorders similar to those seen in the pseudolymphoma of Sjogren's syndrome. At 2 wk of age, these TGF-beta 1 mutant mice begin to develop wasting syndrome and die at around 4 to 5 wk of age, We studied salivary glands from symptomatic mutant mice >14 days of age, Reverse transcriptase-PCR analysis showed up-regulation of proinflammatory cytokine genes such as IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-10, and IFN-gamma in these mutant mice. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1), and MHC class II as well as CD4-positive T lymphocyte infiltration was detected by immunostaining, To elucidate the role of MHC class II, salivary glands from TGF-beta 1/MHC class II double knockout mice were used to investigate the expression of adhesion molecules and MHC class II, In spite of the existence of basal intercellular adhesion molecule-1 expression on vessels, there was neither MHC class II expression, enhanced vascular cell adhesion molecule-1 expression, nor lymphocytic infiltration in the salivary glands, These results suggest that MHC class II plays a significant role in the pathogenesis of TGF-beta 1 mutant mice, Although the mechanism that initiates multiple inflammatory diseases in these mice remains unclear, the context reported here would provide insight into the immunopathology of Sjogren's syndrome. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN IMMUNOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285. HOKKAIDO UNIV,SCH MED,SAPPORO,HOKKAIDO 060,JAPAN. FU NIDCR NIH HHS [DE 09311, DE 10863] NR 41 TC 34 Z9 34 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1997 VL 158 IS 11 BP 5527 EP 5535 PG 9 WC Immunology SC Immunology GA XA063 UT WOS:A1997XA06300061 PM 9164977 ER PT J AU Simpson, RM Hubbard, BS Zhao, TM Kindt, TJ AF Simpson, RM Hubbard, BS Zhao, TM Kindt, TJ TI Experimental perinatal transmission of human immunodeficiency virus type 1 by passage of infected T cells SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; MOLECULAR CHARACTERIZATION; CHILD TRANSMISSION; SEROPOSITIVE WOMEN; MACACA-NEMESTRINA; HIV-1 INFECTION; HTLV-I; RABBITS; FETUSES; INFANTS AB Pediatric AIDS typically follows transmission of human immunodeficiency virus type 1 (HIV-1) from infected mothers to their offspring. The possibility that infected maternal-origin cells serve as a conveyance for mother-to-child HIV-1 transmission was investigated in a rabbit infection model. Administration of HIV-1-infected human T cells to pregnant rabbits was followed by evaluation of offspring, from newborn to 1.5 years of age. HIV-1 was detected in 11 of 19 vaginally delivered offspring born to mothers given infected cells during gestation. Interstitial pneumonias or lymphoid organ lesions, similar to those seen in human pediatric AIDS, occurred in some offspring. Persistence of inoculum cell (HLA)-specific gene sequences in offspring indicated that vertical transmission can be effected by T cell-associated virus. These results along with features of rabbit biology, including primate-type placentation, short gestation, and delivery of litters, suggest that the rabbit model is advantageous for studies of perinatal HIV-1 transmission. RP Simpson, RM (reprint author), NIAID,IMMUNOGENET LAB,NIH,TWINBROOK FACIL,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 51 TC 6 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1997 VL 175 IS 6 BP 1337 EP 1343 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XC322 UT WOS:A1997XC32200008 PM 9180172 ER PT J AU Lubaki, NM Ray, SC Dhruva, B Quinn, TC Siliciano, RF Bollinger, RC AF Lubaki, NM Ray, SC Dhruva, B Quinn, TC Siliciano, RF Bollinger, RC TI Characterization of a polyclonal cytolytic T lymphocyte response to human immunodeficiency virus in persons without clinical progression SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CELLULAR CYTO-TOXICITY; EPSTEIN-BARR-VIRUS; HIV-1 NEF PROTEIN; DISEASE PROGRESSION; ENVELOPE GLYCOPROTEIN; QUANTITATIVE-ANALYSIS; FINE SPECIFICITY; EFFECTOR-CELLS; TYPE-1 HIV-1; EXPANSION AB A total of 82 human immunodeficiency virus (HIV)-1-specific cytolytic T lymphocyte (CTL) clones were isolated and characterized from 5 HIV-infected subjects, utilizing multiple HLA class I alleles. B62-restricted, HIV-1 gag-specific CTL clones isolated from a single blood sample from 1 subject used four different V beta gene rearrangements. Multiple CTL clones could be isolated from the same time point directed against HIV-1 gag, nef, and env from 1 subject. A prospective analysis resulted in the isolation of CTL clones from 1 subject directed against multiple HIV-1 antigens, including the same highly conserved nef peptide, over a 1-year period, in the absence of detectable circulating viral plasma RNA. These data suggest that in some persons without clinical progression and low levels of circulating HIV-1, the CTL response is polyclonal, is directed against multiple HIV-1 proteins, including highly conserved peptides within these proteins, and is maintained over time. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,NIH,BETHESDA,MD 20892. RI Ray, Stuart/B-7527-2008 OI Ray, Stuart/0000-0002-1051-7260 FU NIAID NIH HHS [AI-27668, AI-28108, AI-32871] NR 52 TC 19 Z9 19 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1997 VL 175 IS 6 BP 1360 EP 1367 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XC322 UT WOS:A1997XC32200011 PM 9180175 ER PT J AU Gellin, BG Greenberg, RN Hart, RH Bertino, JS Stein, DH Deloria, MA ClementsMann, ML AF Gellin, BG Greenberg, RN Hart, RH Bertino, JS Stein, DH Deloria, MA ClementsMann, ML TI Immunogenicity of two doses of yeast recombinant hepatitis B vaccine in healthy older adults SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CARE PERSONNEL; EFFICACY AB To determine the immunogenicity of two doses of yeast recombinant hepatitis B virus (HBV) vaccine containing surface (S) protein, an open-label, multicenter trial was conducted in 199 healthy HBV-seronegative adults greater than or equal to 40 years old. Volunteers were randomly assigned to 1 of 5 groups to receive a total of three 10-mu g doses, at 0, 1, and 6 months, or a total of two doses of 20 mu g and 10 mu g, 20 mu g and 20 mu g, 40 mu g and 10 mu g, or 40 mu g and 20 mu g at 0 and 6 months. The 40-mu/20-mu g regimen elicited the highest rate of seroprotection (96.2%), with a geometric mean titer of antibody against the S protein of 369 mIU/mL, not significantly different from the 536 mIU/mL achieved with three doses, These results suggest that a two-dose regimen can achieve seroprotection similar to that of the three-dose regimen. Whether a shorter interval can be used or a booster dose will be needed later to confer durable immunity are unknown. C1 JOHNS HOPKINS UNIV,CTR IMMUNIZAT RES,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. NIAID,DIV MICROBIOL & INFECT DIS,NIH,BETHESDA,MD 20892. LOMA LINDA UNIV,LOMA LINDA,CA 92350. UNIV KENTUCKY,MED CTR,LEXINGTON,KY. BASSETT HEALTHCARE,COOPERSTOWN,NY. NR 15 TC 18 Z9 19 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1997 VL 175 IS 6 BP 1494 EP 1497 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XC322 UT WOS:A1997XC32200028 PM 9180192 ER PT J AU Spiegel, AM AF Spiegel, AM TI Inborn errors of signal transduction: Mutations in G proteins and G protein-coupled receptors as a cause of disease SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article; Proceedings Paper CT 34th SSIEM Annual Symposium CY SEP 11-13, 1996 CL CARDIFF, WALES SP SSIEM ID LUTEINIZING-HORMONE RECEPTOR; LIMITED PRECOCIOUS PUBERTY; MCCUNE-ALBRIGHT SYNDROME; STIMULATORY G-PROTEIN; ACTIVATING MUTATIONS; ENDOCRINE; GENE AB A vast array of neurotransmitters, polypeptide hormones and other extracellular signalling molecules utilize G protein-coupled pathways for transmembrane signalling. In recent years, mutations in G protein-coupled receptors and in G protein alpha subunits have been identified as the cause of a variety of human diseases. Both loss and gain of function mutations have been described in disorders such as Albright hereditary osteodystrophy, nephrogenic diabetes insipidus, McCune-Albright syndrome, and familial male precocious puberty. Identification of mutations in G protein-coupled receptors and in G proteins in human diseases has provided unique insights into G protein-coupled signal transduction, has important implications for diagnosis and potentially for treatment, and should stimulate the search for additional defects in G protein-coupled signal transduction in other diseases. RP Spiegel, AM (reprint author), NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892, USA. NR 20 TC 32 Z9 32 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD JUN PY 1997 VL 20 IS 2 BP 113 EP 121 DI 10.1023/A:1005393501786 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA XH224 UT WOS:A1997XH22400002 PM 9211183 ER PT J AU Suzuki, I Tada, A Ollmann, MM Barsh, GS Im, S Lamoreux, ML Hearing, VJ Nordlund, JJ AbdelMalek, ZA AF Suzuki, I Tada, A Ollmann, MM Barsh, GS Im, S Lamoreux, ML Hearing, VJ Nordlund, JJ AbdelMalek, ZA TI Agouti signaling protein inhibits melanogenesis and the response of human melanocytes to alpha-melanotropin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE melanocortin-1 receptor; melanogenesis; agouti locus; extension locus ID CULTURED HUMAN MELANOCYTES; STIMULATING-HORMONE-RECEPTOR; TYROSINASE ACTIVITY; HUMAN HOMOLOG; GENE; YELLOW; MICE; PIGMENTATION; PHEOMELANIN; BINDING AB In mouse follicular melanocytes, the switch between eumelanin and pheomelanin synthesis is regulated by the extension locus, which encodes the melanocortin-1 receptor (MC1R) and the agouti locus, which encodes a novel paracrine-signaling molecule that inhibits binding of melanocortins to the MC1R. Human melanocytes express the MC1R and respond to melanotropins with increased proliferation and eumelanogenesis, but a potential role for the human homolog of agouti-signaling protein, ASIP, in human pigmentation has not been investigated, Here we report that ASIP blocked the binding of alpha-melanocyte-stimulating hormone (alpha-MSH) to the MC1R and inhibited the effects of alpha-MSH on human melanocytes. Treatment of human melanocytes with 1 nM-10 nM recombinant mouse or human ASIP blocked the stimulatory effects of alpha-MSH on cAMP accumulation, tyrosinase activity, and cell proliferation, In the absence of exogenous alpha-MSH, ASIP inhibited basal levels of tyrosinase activity and cell proliferation and reduced the level of immunoreactive tprosinase-related protein-1 (TRP-1) without significantly altering the level of immunoreactive tyrosinase. In addition, ASIP blocked the stimulatory effects of forskolin or dibutyryl cAMP, agents that act downstream from the MC1R, on tyrosinase activity and cell proliferation, These results demonstrate that the functional relationship between the agouti and MC1R gene products is similar in mice and humans and suggest a potential physiologic role for ASIP in regulation of human pigmentation. C1 UNIV CINCINNATI,DEPT DERMATOL,CINCINNATI,OH 45267. POLA LABS,YOKOHAMA,KANAGAWA,JAPAN. STANFORD UNIV,HOWARD HUGHES MED INST,STANFORD,CA 94305. TEXAS A&M UNIV,DEPT VET PATHOBIOL,COLLEGE STN,TX. NATL CANC INST,NIH,BETHESDA,MD. FU NEI NIH HHS [EY 10223]; NIEHS NIH HHS [R01 ES06882-01 A1] NR 34 TC 97 Z9 103 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1997 VL 108 IS 6 BP 838 EP 842 DI 10.1111/1523-1747.ep12292572 PG 5 WC Dermatology SC Dermatology GA XB836 UT WOS:A1997XB83600001 PM 9182807 ER PT J AU Kim, LT Yamada, KM AF Kim, LT Yamada, KM TI Evidence that beta(1) integrins in keratinocyte cell-cell junctions are not in the ligand-occupied conformation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE focal adhesions; signal transduction; protein conformation ID TERMINAL DIFFERENTIATION; INTERCELLULAR-ADHESION; EXTRACELLULAR-MATRIX; CYTOPLASMIC DOMAINS; ENDOTHELIAL-CELLS; BETA-1 INTEGRINS; FOCAL ADHESIONS; MAJOR ROLE; SUBUNIT; RECEPTOR AB Integrins are a family of heterodimeric cell surface molecules that function as adhesion receptors in cell-cell and cell-extracellular matrix contact, Integrins of the beta(1) family are found on keratinocytes clustered at sites of cell-cell junctions both in culture and in normal skin, The possibility that these integrins function in cell-cell adhesion has been both supported and refuted in recent conflicting publications, Rather than testing further for the presence or absence of an interaction, we present evidence to show that beta(1) integrins in keratinocyte cell-cell junctions are in the non-ligand-occupied conformation, We transfected keratinocytes with a construct that expresses a chimeric cell surface molecule containing the integrin beta(1) cytoplasmic tail, This chimera is thought to mimic the ligand-occupied receptor and has previously been shown to be actively localized to focal adhesions in fibroblasts. We find that keratinocytes are also able to localize this chimera in focal adhesions but do not localize it to areas of cell-cell junctions, A monoclonal anti-beta(1) antibody that has been previously shown to preferentially recognize ligand-occupied beta(1) receptors was used to stain keratinocytes, This antibody showed staining of focal adhesions, with little or no staining of cell-cell junctions, In contrast, four other anti-beta(1) antibodies showed strong, preferential staining at cell-cell junctions, Double staining confirmed that both the conformation-specific monoclonal antibody and a pan-beta(1) antibody were capable of recognizing the same focal adhesions, Taken together, these data indicate that integrins in cell-cell junctions of keratinocytes are in the non-ligand-occupied conformation, Although we do not directly prove the absence of an integrin-integrin interaction at this site, we show that any such interaction does not induce the ligand-occupied conformation and, therefore, is less likely to play a major role in cytoskeletal re-organization or signal transduction. RP Kim, LT (reprint author), NIDR,DEV BIOL LAB,DIR,BLDG 30,RM 424,30 CONVENT DR MSC 4370,BETHESDA,MD 20892, USA. NR 34 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1997 VL 108 IS 6 BP 876 EP 880 DI 10.1111/1523-1747.ep12292589 PG 5 WC Dermatology SC Dermatology GA XB836 UT WOS:A1997XB83600008 PM 9182814 ER PT J AU Merz, JF Sankar, P Taube, SE Livolsi, V AF Merz, JF Sankar, P Taube, SE Livolsi, V TI Use of human tissues in research: Clarifying clinician and researcher roles and information flows SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article; Proceedings Paper CT Symposium on The Impact of Genetic Technology on Civil Liberties CY APR 19, 1996 CL WILMINGTON, DE SP ACLU, Delaware ID INFORMED CONSENT; GENETIC RESEARCH; SAMPLES; BANKING C1 NCI,DEPT HLTH & HUMAN SERV,ROCKVILLE,MD. LEONARD DAVIS INST HLTH ECON,ROCKVILLE,MD. CTR BIOETH,ROCKVILLE,MD. RP Merz, JF (reprint author), UNIV PENN,CTR BIOETH,DEPT PATHOL & LAB MED,3401 MARKET ST,SUITE 320,PHILADELPHIA,PA 19104, USA. NR 29 TC 31 Z9 31 U1 2 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JUN PY 1997 VL 45 IS 5 BP 252 EP 257 PG 6 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA XL434 UT WOS:A1997XL43400003 PM 9249997 ER PT J AU Abassi, Z Kotob, S Pieruzzi, F Abouassali, M Keiser, KR Fratantoni, JC Alayash, AI AF Abassi, Z Kotob, S Pieruzzi, F Abouassali, M Keiser, KR Fratantoni, JC Alayash, AI TI Effects of polymerization on the hypertensive action of diaspirin cross-linked hemoglobin in rats SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID NITRIC-OXIDE; HEMODYNAMIC-RESPONSE; PULMONARY; DCLHB(TM); KIDNEY AB It is believed that the hypertensive effect of diaspirin crosslinked hemoglobin, a viable blood substitute, can be resolved by polymerization, which reduces the diffusion of this derivative into the interstitial space between nitric oxide-producing endothelium and the target vascular smooth muscle, We studied the systemic and renal responses to infusion of three cell-free human hemoglobins in anesthetized isovolemic rats: unmodified (HbAO), crosslinked (alpha-DBBF), and polymerized crosslinked (poly alpha-DBBF). HbAO produced a significant increase in mean arterial blood pressure (MAP) throughout the 60-minute infusion, alpha-DBBF, on the other hand, produced a more marked and prolonged increase in MAP over 120 minutes. Only a moderate increase in MAP was observed in rats after a 30-minute infusion with poly alpha-DBBF. The extent of renal insufficiency produced by these proteins, as determined by the glomerular filtration rate, was in the following order: HbAO > poly alpha-DBBF > alpha-DBBF. Infusion of poly alpha-DBBF, under hypovolemic but not isovolemic conditions in rats, produced an increase in heart rate, cardiac output, and stroke volume and a decrease in total peripheral resistance after 60 minutes. Chemical polymerization to increase the size of alpha-DBBF does not appear to improve its hemodynamic properties in rats, especially under partial exchange transfusion, a more clinically relevant indication for a hemoglobin-based blood substitute. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,LAB CELLULAR HEMATOL,BETHESDA,MD 20892. NHLBI,NIH,BETHESDA,MD 20892. NR 25 TC 68 Z9 70 U1 2 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD JUN PY 1997 VL 129 IS 6 BP 603 EP 610 DI 10.1016/S0022-2143(97)90194-3 PG 8 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA XC640 UT WOS:A1997XC64000005 PM 9178726 ER PT J AU DeRenzo, EG AF DeRenzo, EG TI Decisionally impaired persons in research: Refining the proposed refinements SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID MACARTHUR TREATMENT COMPETENCE; ADVANCE DIRECTIVES; CONSENT; DEMENTIA; GUIDELINES; INCREASE; PATIENT; ACT RP DeRenzo, EG (reprint author), NIH,DEPT CLIN BIOETH,BLDG 10,BETHESDA,MD 20892, USA. NR 58 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SUM-FAL PY 1997 VL 25 IS 2-3 BP 139 EP 149 DI 10.1111/j.1748-720X.1997.tb01889.x PG 11 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA YE926 UT WOS:A1997YE92600007 PM 11066488 ER PT J AU Bradley, EH Blechner, BB Walker, LC Wetle, TT AF Bradley, EH Blechner, BB Walker, LC Wetle, TT TI Institutional efforts to promote advance care planning in nursing homes: Challenges and opportunities SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID SELF-DETERMINATION ACT; MEDICAL-CARE; DIRECTIVES; IMPLEMENTATION C1 UNIV CONNECTICUT,SCH MED,DEPT COMMUNITY MED & HLTH CARE,FARMINGTON,CT. INST LIVING,BRACELAND CTR MENTAL HLTH & AGING,HARTFORD,CT. NIA,NIH,BETHESDA,MD 20892. RP Bradley, EH (reprint author), YALE UNIV,SCH MED,NEW HAVEN,CT 06520, USA. FU AHRQ HHS [1T32HS00052] NR 27 TC 8 Z9 8 U1 3 U2 6 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SUM-FAL PY 1997 VL 25 IS 2-3 BP 150 EP 159 DI 10.1111/j.1748-720X.1997.tb01890.x PG 10 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA YE926 UT WOS:A1997YE92600008 PM 11066489 ER PT J AU Kang, SM Allen, J Graham, JM Grebe, T Clericuzio, C Patronas, N Ondrey, F Green, E Schaffer, A Abbott, M Biesecker, LG AF Kang, SM Allen, J Graham, JM Grebe, T Clericuzio, C Patronas, N Ondrey, F Green, E Schaffer, A Abbott, M Biesecker, LG TI Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE linkage mapping; polydactyly; hypothalamic hamartoma; epiglottis ID CONGENITAL HYPOTHALAMIC HAMARTOBLASTOMA; HUMAN-CHROMOSOMES; IMPERFORATE ANUS; HYPOPITUITARISM; HUMAN-CHROMOSOME-7; STRATEGIES AB Pallister-Hail syndrome is a human developmental disorder that is inherited in an autosomal dominant pattern. The phenotypic features of the syndrome include hypothalamic hamartoma, polydactyly, imperforate anus, laryngeal clefting, and other anomalies. Here we describe the clinical characterisation of a family with 22 affected members and the genetic mapping of the corresponding locus. Clinical, radiographic, and endoscopic evaluations showed that this disorder is a fully penetrant trait with variable expressivity and low morbidity. By analysing 60 subjects in two families using anonymous STRP markers, we have established linkage to 7p13 by two point analysis with D7S691 resulting in a lod score of 7.0 at theta=0, near the GLI3 locus. Deletions and translocations in GLI3 are associated with the Greig cephalopolysyndactyly syndrome. Although Greig cephalopolysyndactyly syndrome has some phenotypic overlap with Pallister-Hail syndrome, these two disorders are clinically distinct. The colocalisation of loci for these distinct phenotypes led us to analyse GLI3 for mutations in patients with Pallister-Hail syndrome. We have previously shown GLI3 mutations in two other small, moderately affected families with Pallister-Hall syndrome. The linkage data reported here suggest that these larger, mildly affected families may also have mutations in GLI3. C1 NATL HUMAN GENOME RES INST,NATL INST HLTH,BETHESDA,MD 20892. NATL INST HLTH,CTR CLIN,BETHESDA,MD. NATL INST DEAFNESS & COMMUNICAT DISORDERS,NATL INST HLTH,BETHESDA,MD. BETH ISRAEL HOSP,DEPT NEUROL,NEW YORK,NY. CEDARS SINAI MED CTR,AHMANSON DEPT PEDIAT,MED GENET BIRTH DEFECTS CTR,LOS ANGELES,CA 90048. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. UNIV ARIZONA,DEPT PEDIAT,TUCSON,AZ 85721. UNIV NEW MEXICO,DEPT PEDIAT,ALBUQUERQUE,NM 87131. JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT PSYCHIAT,BALTIMORE,MD 21218. RI Schaffer, Alejandro/F-2902-2012 NR 27 TC 33 Z9 36 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JUN PY 1997 VL 34 IS 6 BP 441 EP 446 DI 10.1136/jmg.34.6.441 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA XD481 UT WOS:A1997XD48100001 PM 9192261 ER PT J AU Shastry, BS Hejtmancik, JF Rodriguez, A Rodriguez, F Tamayo, ML AF Shastry, BS Hejtmancik, JF Rodriguez, A Rodriguez, F Tamayo, ML TI Linkage mapping of a large Colombian family segregating for X linked retinoschisis: Refinement of the chromosomal location SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE retinoschisis; X linked; linkage ID JUVENILE RETINOSCHISIS; CARRIER DETECTION; GENE; LOCUS; MICROSATELLITE; XP22.1-P22.2 AB Juvenile X linked retinoschisis (RS) is a bilateral vitreoretinal dystrophy that develops early in life. Previous linkage studies have localised the RS gene to Xp22.1-p22.3 between DXS207 and AFM 291Wf5, which represents a genetic distance of approximately 3.7 cM. In an effort to facilitate the eventual cloning of the RS gene, we have analysed a large Colombian family, using 10 microsatellite markers that have been mapped to the region Xp22.1-p22.3. A total of 93 members, including 19 affected and eight unaffected males, two affected females, and six obligate carrier females were analysed. Close linkage was observed between the disease locus and DXS999 (Zmax=2.27, theta max=0.05), DXS987 (Zmax=2.61, theta max=0.1), DXS443 (Zmax=4.23, theta max=0.1), and DXS274 (Zmax=3.49, theta max=0.05) markers. Recombination with the RS locus was found for all marker loci except DXS197, DXS43, and DXS1195. These results place the RS locus within an interval of approximately 2 cM between the flanking markers DXS1053 and DXS999, approximately 1.7 cM closer than the previously reported boundary. The results also further confirm the lack of genetic heterogeneity of RS. C1 NEI,BETHESDA,MD 20892. FDN OFTALMOL NACL,BOGOTA,COLOMBIA. UNIV JAVERIANA,INST GENET HUMANA,BOGOTA,COLOMBIA. RP Shastry, BS (reprint author), OAKLAND UNIV,EYE RES INST,422 DODGE HALL,ROCHESTER,MI 48309, USA. FU NEI NIH HHS [EY05230] NR 17 TC 4 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JUN PY 1997 VL 34 IS 6 BP 504 EP 506 DI 10.1136/jmg.34.6.504 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA XD481 UT WOS:A1997XD48100013 PM 9192273 ER PT J AU Kashanchi, F Melpolder, JC Epstein, JS Sadaie, MR AF Kashanchi, F Melpolder, JC Epstein, JS Sadaie, MR TI Rapid and sensitive detection of cell-associated HIV-1 in latently infected cell lines and in patient cells using sodium-n-butyrate induction and RT-PCR SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE lymphocytic/monocytoid cells; PBMC; diagnostics ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; PERIPHERAL-BLOOD; INSITU HYBRIDIZATION; VIRAL-RNA; EXPRESSION; TYPE-1; REPLICATION; INDIVIDUALS; LYMPHOCYTES AB To develop a rapid and sensitive means of detecting cell-associated human immunodeficiency virus (HIV), donor cells from HIV seropositive patients were treated with the potent viral activator sodium-n-butyrate (NaB) and subsequently assayed by both in situ RNA hybridization and a reverse transcriptase polymerase chain reaction (RT-PCR). The sensitivity of RT-PCR was estimated to be equivalent to 1 x 10(-16) grams (0.1 fg) or approximately 64 copies of the input standard viral RNA per reaction. The present study takes advantage of the ability of NaB to introduce changes in chromatin structure of latently infected cells, leading to increased HIV gene expression. Human ACH-2 and U1 cell lines were used as representatives of T-lymphocytic and monocytoid cells harboring latent inducible proviruses. HIV gene expression was readily detected when these cells were treated with NaB. Viral gag RNA was detected by both in situ and RT-PCR assays. When peripheral blood mononuclear cells (PBMCs) from acquired immunodeficiency syndrome (AIDS) patients, who were all negative for in situ hybridization and serum/ plasma p24 assays, were used for detection of viral gene expression, four categories with distinct patterns of induction were observed. The first set of patients showed HIV-positive PBMCs by RT-PCR without any added NaB, and suppression by added NaB or PHA. The second set of samples showed induction of viral RNA by NaB alone. The third set could be induced with PHA, but not NaB, and the fourth set required both NaB and PHA for induction of HIV gene expression. Our results suggest that direct treatment of the cells with HIV activators may be useful in increasing sensitivity of the RT-PCR intended to be used for detection of cell-associated viral RNAs. This approach may be used to confirm true status of the HIV infection when p24 results are negative or HIV RNAs in serum/plasma are below the threshold of detection. Moreover, this method may identify the presence of latent proviral genomes possibly reflecting the true rate of cell-associated viral load in vivo and without possible mutations brought about by long-term co-cultivation assays with cells from seronegative donors. (C) 1997 Wiley-Liss, Inc. C1 US FDA,CBER,LAB IMMUNOCHEM,DIV TRANSFUS TRANSMITTED DIS,ROCKVILLE,MD 20852. NCI,MOL VIROL LAB,NIH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT TRANSFUS MED,INFECT DIS SECT,BETHESDA,MD 20892. NR 44 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 1997 VL 52 IS 2 BP 179 EP 189 DI 10.1002/(SICI)1096-9071(199706)52:2<179::AID-JMV11>3.0.CO;2-G PG 11 WC Virology SC Virology GA XB771 UT WOS:A1997XB77100011 PM 9179766 ER PT J AU Curtis, SW Shi, H Teng, C Korach, KS AF Curtis, SW Shi, H Teng, C Korach, KS TI Promoter and species specific differential estrogen-mediated gene transcription in the uterus and cultured cells using structurally altered agonists SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID MOUSE LACTOFERRIN GENE; RECEPTOR STEREOCHEMISTRY; RIBONUCLEIC-ACID; LIGAND-BINDING; ACTIVATION; SEQUENCE; LACTOTRANSFERRIN; EXPRESSION; RESPONSES; CONTAINS AB Certain types of estrogenic compounds have been shown to have tissue-specific actions. In addition, some tissues may exhibit differential gene regulation by agonists and antagonists. Our previous studies using structurally modified estrogenic molecules had indicated differential effects on specific estrogen responses, indicating that the activity of the estrogen receptor protein can be altered depending not only upon the structure of the bound ligand but also the regulated gene itself. The mechanism of differential induction, however, was not determined, and might involve altered binding to the estrogen response element (ERE), altered transcription, or post-transcriptional modification of gene products. Our previous studies indicated that differential induction by modified diethylstilbestrol (DES) agonists could not be accounted for by differences in ligand affinity for the estrogen receptor (ER) or differential binding of the ER to a consensus vitellogenin A2 (vit A2) ERE. To determine if this differential hormonal responsiveness was reflected at the level of transcription, we analyzed mouse uterine mRNA of several estrogen-responsive genes, including glucose-6-phosphate dehydrogenase (G6PD), ornithine decarboxylase (ODC) and lactoferrin, by Northern blot following injection with the modified agonists DES, indenestrol A (IA), indenestrol B (IB) and Z-pseudo DES (ZPD). All compounds induced the G6PD message, although IB and ZPD induced expression only transiently, while DES and IA maintained the message for 24 h. No difference in induction was seen for ODC message, which was induced equally by all the compounds. In contrast, lactoferrin, a highly estrogen-responsive gene, was induced only by DES and IA and not by the other agonists IB or ZPD, showing that the lactoferrin gene was differentially regulated by these compounds. To determine whether this difference was due to altered transcriptional activity, the mouse lactoferrin estrogen-responsive module (mERM) linked to a chloramphenicol acetyl transferase (CAT) reporter gene was tested in transfected cells. Using the mouse estrogen receptor in RL95 cells, DES and IA induced expression of CAT, but IB did not, confirming the differential response seen in vivo. To show whether this difference in transcription occurred because of altered binding to the lactoferrin ERE, which is not a perfect consensus ERE, a gel shift assay was used to examine DNA binding of ER bound to the agonists. All ligands produced equivalent binding to the lactoferrin ERE suggesting that differential regulation was not a result of altered DNA binding. Taken together, these observations indicate that the differential induction of lactoferrin by these compounds occurs via altered activation of the transcriptional components unique to lactoferrin and is likely to involve altered interaction with co-activators. Surprisingly, unlike the mouse ER, the human estrogen receptor activated and induced expression of lactoferrin estrogen-responsive module-CAT with all the compounds. Mouse ER is also known to vary from the human ER in its activity with the triphenylethylene estrogen tamoxifen, which has agonist activity with the mouse ER but mixed antagonist/agonist activity with the human ER. The data show that human and mouse estrogen receptors are activated differently by this group of stilbestrol estrogen ligands when assayed on the lactoferrin response element, which is the first description of this type of gene and species specific difference. Lactoferrin gene regulation by estrogen receptor can be used as a model to study the mechanism of differential gene activation by different estrogen agonists and antagonists using a more physiological situation than commonly used with in vitro gene reporter systems. C1 NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,NIH,RES TRIANGLE PK,NC 27709. NIEHS,REPROD & DEV TOXICOL LAB,GENE REGULAT GRP,NIH,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X NR 30 TC 15 Z9 15 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD JUN PY 1997 VL 18 IS 3 BP 203 EP 211 DI 10.1677/jme.0.0180203 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XE210 UT WOS:A1997XE21000004 PM 9195474 ER PT J AU Torron, J Ljubetic, CI Huang, LJ Kimbro, KS Dyer, C Saavedra, RA AF Torron, J Ljubetic, CI Huang, LJ Kimbro, KS Dyer, C Saavedra, RA TI Two proteins bind to a novel motif in the promoter of the myelin basic protein gene from mouse SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE myelin basic protein gene; regulation of gene expression; DNA-protein interactions ID RESPONSE ELEMENT; NERVOUS-SYSTEM; EXPRESSION; BRAIN; TRANSCRIPTION; IDENTIFICATION; CELLS; SHARK; SITE; MICE AB The box 1 and 2 motif of the myelin basic protein (MBP) promoter is a potential regulatory sequence of the MBP transcription unit. A DNA fragment that contained the sequence of the box 1 and 2 motif from mouse was synthesized, and its protein binding properties were examined by gel-shift assays. The box 1 and 2 probe and nuclear extracts from mouse brain generated a pattern of six major DNA-protein complexes (a, b, c, d, e, and f). The box 1 and 2 probe and nuclear extracts from oligodendrocyte-like glioma cells 1C10 generated a pattern of DNA-protein complexes that exhibited only complexes a, b, e, and f. Complex b generated by extracts from 1C10 cells, however, was very intense compared to any of the other complexes. It was determined that dephosphorylation of the proteins in nuclear extracts from 1C10 cells with acid phosphatase significantly altered their DNA binding properties. Two proteins of minimum A I, similar to 32 and similar to 38 kDa (MBP32 and MBP38) that bind to the box 1 and 2 motif were identified in these nuclear extracts by using a UV crosslinking method. MBP32 and MBP38 are found in cell types and tissues known to express the golli transcription unit of the golli-MBP gene complex and may be involved in the modulation of the MBP unit in those cells. C1 ALLEGHENY UNIV HLTH SCI,DEPT NEUROBIOL & ANAT,PHILADELPHIA,PA 19129. CHILDRENS HOSP,ENDERS PEDIAT RES CTR,DEPT NEUROSURG,BOSTON,MA 02115. NIEHS,NIH,RES TRIANGLE PK,NC 27709. UNIV PENN,CHILDRENS HOSP,DEPT NEUROL,PHILADELPHIA,PA 19104. FU NIAMS NIH HHS [IR29AR41046] NR 33 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JUN PY 1997 VL 8 IS 3 BP 181 EP 191 DI 10.1007/BF02736832 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XV490 UT WOS:A1997XV49000002 PM 9297631 ER PT J AU Cuda, G Fananapazir, L Epstein, ND Sellers, JR AF Cuda, G Fananapazir, L Epstein, ND Sellers, JR TI The in vitro motility activity of beta-cardiac myosin depends on the nature of the beta-myosin heavy chain gene mutation in hypertrophic cardiomyopathy SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; PROTEIN-C GENE; ACTIN-FILAMENTS; PROGNOSTIC IMPLICATIONS; MISSENSE MUTATIONS; SLIDING VELOCITY; MOLECULAR-BASIS; EXPRESSION; INVITRO; MOTOR AB Several mutations in the beta-myosin heavy chain gene cause hypertrophic cardiomyopathy. This study investigates (1) the in vitro velocities of translocation of fluorescently-labelled actin by beta-myosin purified from soleus muscle of 30 hypertrophic cardiomyopathy patients with seven distinct beta-myosin heavy chain gene mutations: Thr124Ile, Tyr162Cys, Gly256Glu, Arg403Gln, Val606Met, Arg870His, and Leu908Val mutations; and (2) motility activity of beta-myosin purified from cardiac and soleus muscle biopsies in the same patients. The velocity of translocation of actin by beta-myosin purified from soleus or cardiac muscle of 22 normal controls was 0.48 +/- 0.09 mu m s(-1). By comparison, the motility activity was reduced in all 30 patients with beta-myosin heavy chain gene mutations (range, 0.112 +/- 0.041 to 0.292 +/- 0.066 mu m s(-1)). Notably, the Tyr162Cys and Arg403Gln mutations demonstrated significantly lower actin sliding velocities: 0.123 +/- 0.044, and 0.112 +/- 0.041 mu m s(-1), respectively beta-myosin purified from soleus muscle from four patients with the Arg(403)Gln mutation had a similar actomyosin motility activity compared to beta-myosin purified from their cardiac biopsies (0.127 +/- 0.045 mu m s(-1) versus 0.119 +/- 0.068 mu m s(-1), respectively). Since these seven mutations lie in several distinct functional domains, it is likely that the mechanisms of their inhibitions of motility are different. C1 NHLBI,MOL CARDIOL LAB,BETHESDA,MD 20892. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. RI Cuda, Giovanni/F-5359-2012 OI Cuda, Giovanni/0000-0001-6313-1866 NR 39 TC 86 Z9 89 U1 0 U2 2 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD JUN PY 1997 VL 18 IS 3 BP 275 EP 283 DI 10.1023/A:1018613907574 PG 9 WC Cell Biology SC Cell Biology GA XA411 UT WOS:A1997XA41100001 PM 9172070 ER PT J AU Wang, ZY Sakai, J Matsudaira, PT Baines, IC Sellers, JR Hammer, JA Korn, ED AF Wang, ZY Sakai, J Matsudaira, PT Baines, IC Sellers, JR Hammer, JA Korn, ED TI Amino acid sequence of the light chain of Acanthamoeba myosin IC SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID CALCIUM-MODULATED PROTEINS; HEAVY-CHAIN; CALMODULIN; LOCALIZATION; EVOLUTION; CASTELLANII; ISOFORMS; DOMAIN AB The amino acid sequence of the light chain of Acanthamoeba myosin IC deduced from the cDNA sequence comprises 149 amino acids with a calculated molecular weight of 16739. All but the 3 N-terminal residues were also determined by amino acid sequencing of the purified protein, which also showed the N-terminus to be blocked. Phylogenetic analysis shows Acanthamoeba myosin IC light chain to be more similar to the calmodulin subfamily of EF-hand calcium-modulated proteins than to the myosin II: essential light chain or regulatory Light chain subfamilies. In pairwise comparisons, the myosin IC light chain sequence is most similar to sequences of calmodulins (similar to 50% identical) and a squid calcium-binding protein (similar to 43% identical); the sequence is similar to 37% identical to the calcium-binding essential light chain of Physarum myosin II and similar to 30% identical to the essential light chain of Acanthamoeba myosin II, and the essential light chain and regulatory light chain of Dictyostelium myosin II. The sequence predicts four helix-loop-helix domains with possible calcium-binding sites in domains I and III, suggesting that calcium may affect the activity of this unconventional myosin. This is the first report of the sequence of an unconventional myosin light chain other than calmodulin. C1 NHLBI, CELL BIOL LAB, BETHESDA, MD 20892 USA. MIT, WHITEHEAD INST BIOMED RES, DEPT BIOL, CAMBRIDGE, MA 02142 USA. NHLBI, MOL CARDIOL LAB, BETHESDA, MD 20892 USA. RI Korn, Edward/F-9929-2012; Matsudaira, Paul/H-1475-2012 OI Matsudaira, Paul/0000-0002-8399-3276 NR 30 TC 24 Z9 24 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 EI 1573-2657 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD JUN PY 1997 VL 18 IS 3 BP 395 EP 398 DI 10.1023/A:1018686428955 PG 4 WC Cell Biology SC Cell Biology GA XA411 UT WOS:A1997XA41100012 PM 9172081 ER PT J AU Cragg, GM Baker, JT Borris, RP Carte, B Cordell, GA Soejarto, DD AF Cragg, GM Baker, JT Borris, RP Carte, B Cordell, GA Soejarto, DD TI Interactions with source countries. Guidelines for members of the American Society of Pharmacognosy SO JOURNAL OF NATURAL PRODUCTS LA English DT Editorial Material AB The formulation of a set of guidelines for members of the American Society of Pharmacognosy to follow in their relationship with genetically rich source countries has been discussed for several years. At the 37th Annual Meeting of the American Society of Pharmacognosy, held in July 1996 at the University of California, Santa Cruz, a resolution and set of guidelines promoting the research and training of source country scientists, the facilitation of technology transfer, and the fair and equitable sharing of results and benefits arising from the utilization and commercialization of source country natural resources were officially endorsed by the membership in attendance. C1 OFF COMMISSIONER ENVIRONM,CANBERRA,ACT 2601,AUSTRALIA. MERCK RES LABS,RAHWAY,NJ 07065. NATL UNIV SINGAPORE,INST MOL & CELL BIOL,CTR NAT PROD RES,SINGAPORE 119260,SINGAPORE. UNIV ILLINOIS,COLL PHARM,DEPT MED CHEM & PHARMACOGNOSY,PROGRAM COLLABORAT RES PHARMACEUT SCI,CHICAGO,IL 60612. ESTEFETA UNIV,COLL PHARM,CTR PHARMACOGNOST RES PANAMANIAN FLORA,PANAMA CITY,PANAMA. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,WASHINGTON,DC 20307. NATL MUSEUM,DEPT BOT,MANILA,PHILIPPINES. RP Cragg, GM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,NAT PROD BRANCH,DIV CANC TREATMENT DIAG & CTR,FREDERICK,MD 21702, USA. NR 2 TC 10 Z9 11 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JUN PY 1997 VL 60 IS 6 BP 654 EP 655 DI 10.1021/np970125q PG 2 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA XG185 UT WOS:A1997XG18500033 ER PT J AU Sheppard, CA Simpson, PB Sharp, AH Nucifora, FC Ross, CA Lange, GD Russell, JT AF Sheppard, CA Simpson, PB Sharp, AH Nucifora, FC Ross, CA Lange, GD Russell, JT TI Comparison of type 2 inositol 1,4,5-trisphosphate receptor distribution and subcellular Ca2+ release sites that support Ca2+ waves in cultured astrocytes SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE inositol 1,4,5-trisphosphate; astrocytes; calcium; endoplasmic reticulum; receptors ID CENTRAL-NERVOUS-SYSTEM; CALCIUM WAVES; ENDOPLASMIC-RETICULUM; IMMUNOHISTOCHEMICAL LOCALIZATION; ACTIVATION; CELLS; PROPAGATION; EXPRESSION; CHANNELS; STORES AB We have examined the mechanisms that underlie Ca2+ wave propagation in cultured cortical astrocytes. Norepinephrine evoked Ca2+ waves in astrocytes that began at discrete initiation loci and propagated throughout the cell by regenerative amplification at a number of cellular sites, as shown by very high Ca2+ release rates at these regions. We have hypothesized previously that domains displaying elevated Ca2+ release kinetics in astrocytes may correspond to sites of high inositol 1,4,5-trisphosphate receptor (InsP(3)R) density. To examine this possibility, we compared the distribution pattern of endoplasmic reticulum (ER) and InsP(3)Rs with Ca2+ release kinetics in subcellular regions during propagation of norepinephrine-evoked waves. 3,3'-Dihexyloxacarbocyanine iodide staining revealed that the ER in astrocytes exists as a meshwork of membranes extending throughout the cells, including fine processes. A specific antibody directed against type 2 InsP(3)Rs (InsP(3)R2) detected a 260-kDa band in western blotting of astrocyte membranes. Immunocytochemistry using this antibody stained the entire ER system in a punctate, variegated manner. When Ca2+ responses and InsP(3)R2 immunofluorescence were compared in the same cell, domains of elevated Ca2+ response kinetics (high amplitude and rapid rate of rise) showed significant positive correlation with high local intensity of InsP(3)R2 staining. It appears, therefore, that specializations in the ER responsible for discrete local Ca2+ release sites that support regenerative wave propagation include increased levels of InsP(3)R2 expression. C1 NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,NIH,BETHESDA,MD 20892. NINCDS,INSTRUMENTAT & COMP SECT,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,NEUROBIOL LAB,DEPT PSYCHIAT & NEUROSCI,BALTIMORE,MD. FU NIMH NIH HHS [MH43040] NR 46 TC 61 Z9 61 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1997 VL 68 IS 6 BP 2317 EP 2327 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WZ288 UT WOS:A1997WZ28800011 PM 9166724 ER PT J AU Lin, WW Wang, CW Chuang, DM AF Lin, WW Wang, CW Chuang, DM TI Effects of depolarization and NMDA antagonists on the survival of cerebellar granule cells: A pivotal role for protein kinase C isoforms SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE protein kinase C isoforms; cerebellar granule cells; apoptosis; NMDA receptor antagonists; depolarization; neuronal development ID METHYL-D-ASPARTATE; GLUTAMATE-RECEPTOR AGONISTS; NITRIC-OXIDE; PC12 CELLS; NEURITE OUTGROWTH; PRIMARY CULTURES; ACTIVATION; NEURONS; EXPRESSION; APOPTOSIS AB Primary cultures of cerebellar granule cells (CGCs) grown in high-K+ (25 mM; K25) medium progressively differentiate in vitro. Differentiation is noticeable after 3-4 days in vitro (DIV) and reach a mature stage after 8 DIV. Longer cultivation of CGCs (>13 DIV) triggers the processes of spontaneous cell death. However, if cultured in normal physiological K+ concentration (5 mM; K5),a significant proportion of the cells dies by the end of the first week in culture. To address the role of protein kinase C (PKC) in the development of CGCs, we measured the kinase activity as well as the protein level of the kinase isoforms. As the K25 CGC culture proceeded, the PKC activity time-dependently increased by 3.2-fold, reaching a steady state at 8 DIV. Western blot analysis using PKC isoform-specific antibodies revealed an increase in levels of PKC alpha, gamma, mu, lambda, and iota from 2 to 8 DIV. A slight increase or decrease at 4 DIV was observed for PKC epsilon and beta II, respectively, whereas no significant change was observed for beta I. The isoforms of delta, theta, eta, and zeta were not detected. Comparing the 14 DIV cultures with the 10 DIV cultures, the immunoreactivities of PKC iota and epsilon were decreased, those of PKC alpha, beta I, beta II, gamma, and lambda were unchanged, whereas that of PKC mu was still increased. In K5 cultures, the immunoreactivity of each PKC isoform at 2-4 DIV was similar to that observed in K25 cells, although no remarkable differentiation features were observed. Coordinated with the appearance of cell death at 8 DIV in low-K+ cultures, levels of PKC alpha, mu, lambda, and iota, but not the others, were markedly decreased. The NMDA receptor antagonists MK-801 and 2-amino-5-phosphopentanoic acid markedly prevented the age-induced apoptosis of CGCs, and the cells survived >18 DIV under these conditions. The cytoprotective effect of MK-801 was concomitant with the increases in levels of PKC gamma, lambda, iota, and mu at 10 and 14 DIV. In addition, the PKC epsilon level was increased at 14 DIV but decreased at early stages, whereas PKC alpha, beta I, and beta II levels were unchanged, as compared with K25 culture alone. Taken together, induction and up-regulation of PKC isoforms may play an important role in the maintenance of CGC survival by depolarization and MK-801. C1 NIMH,MOL NEUROBIOL SECT,NIH,BETHESDA,MD 20892. RP Lin, WW (reprint author), NATL TAIWAN UNIV,COLL MED,DEPT PHARMACOL,TAIPEI 10018,TAIWAN. OI Lin, Wan Wan/0000-0002-3207-734X NR 46 TC 42 Z9 44 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1997 VL 68 IS 6 BP 2577 EP 2586 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WZ288 UT WOS:A1997WZ28800042 PM 9166755 ER PT J AU Pette, M Pette, DF Muraro, PA Martin, R McFarland, HF AF Pette, M Pette, DF Muraro, PA Martin, R McFarland, HF TI In vitro modulation of human, autoreactive MBP-specific CD4+ T-cell clones by cyclosporin A SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; T-lymphocytes; cyclosporin A; in vitro ID TUMOR-NECROSIS-FACTOR; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; BLOOD-BRAIN-BARRIER; MULTIPLE-SCLEROSIS; HEALTHY-INDIVIDUALS; MESSENGER-RNA; GROWTH-FACTOR; FACTOR-ALPHA; INVITRO AB Cyclosporin A (CsA) is a potent immunosuppressant affecting many components of cellular and humoral immunity. Its main action probably results from inhibition of T-lymphocyte activation and interference with secretion of cytokines like IL-2, IL-4, IFN-gamma and TNF-alpha. Correspondingly, CsA has beneficial effects on the course of several autoimmune diseases thought to be mediated by T-lymphocytes, including a mild effect on multiple sclerosis. We exposed CD4(+) cytotoxic T-lymphocytes specific for myelin basic protein, a putative target autoantigen in MS, to CsA in vitro, and determined the drug's effects on proliferation, expression of high affinity IL-2R, secretion of the proinflammatory cytokines IFN-gamma and TNF-alpha as well as on the secretion of the chemokines MIP-1 alpha and MIP-1 beta. In all instances, we observed a partial to complete inhibition. In contrast, the response of activated cells to IL-2 was resistant to CsA. Our observations are in line with results obtained in different experimental systems. The discrepancy between the profound inhibition of T-cells and the modest therapeutic effects on MS is discussed. RP Pette, M (reprint author), NINCDS,NEUROIMMUNOL BRANCH,NIH,10 CTR DR MSC 1400,BETHESDA,MD 20892, USA. NR 48 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUN PY 1997 VL 76 IS 1-2 BP 91 EP 99 DI 10.1016/S0165-5728(97)00035-0 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA XC997 UT WOS:A1997XC99700011 PM 9184637 ER PT J AU Suzuki, K Sango, K Proia, RL Langaman, C AF Suzuki, K Sango, K Proia, RL Langaman, C TI Mice deficient in all forms of lysosomal beta-hexosaminidase show mucopolysaccharidosis-like pathology SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE glycosaminoglycans; GM2-gangliosidosis; hypomyelination; knockout mice; microglia; mucopolysaccharidosis ID GLUCURONIDASE DEFICIENCY; TAY-SACHS; MODEL; VII; MOUSE; DISEASES; LECTIN AB Lysosomal beta-hexosaminidase consists of 2 subunits, alpha and beta. Mutations in the alpha-subunit gene cause Tay-Sachs disease, while mutations in the beta-subunit gene cause Sandhoff disease. Mice generated by targeted disruption of either the alpha- or beta-subunit genes displayed the pathological features of Tay-Sachs disease or Sandhoff disease, respectively. In this report we describe the pathologic features of mice that carry both disrupted genes and that are deficient in all forms of beta-hexosaminidase activity. These mice displayed physical dysmorphia and extensive neuro-visceral storage. Neurons in the CNS and PNS contained pleomorphic inclusions in addition to membranous cytoplasmic bodies characteristic of gangliosidosis. Diffuse hypomyelination was also apparent in the CNS. Vacuolated cytoplasm was a conspicuous feature of chondrocytes, osteocytes and renal tubular epithelium on routine hematoxylin and eosin (H&E) -stained sections. Numerous vacuolated cells were also noted in the connective tissue, cornea, heart valves, arterial walls, Liver, spleen, skin and throughout other visceral organs. These vacuolated cells stained positive with PAS, colloidal iron and alcian blue, indicating an accumulation of glycosaminoglycans. Furthermore, cultured fibroblasts showed a defect in the degradation of glycosaminoglycans, and glycosaminoglycans were excreted in the urine of these mice (1). Thus, morphological and biochemical features in these mice are consistent with those of mucopolysaccharidosis and demonstrate an essential role of beta-hexosaminidase in the degradation of glycosaminoglycans. C1 UNIV N CAROLINA,SCH MED,CTR NEUROSCI,CHAPEL HILL,NC 27599. NIDDKD,BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,SECT BIOCHEM GENET,NIH,BETHESDA,MD 20892. RP Suzuki, K (reprint author), UNIV N CAROLINA,SCH MED,DEPT PATHOL & LAB MED,CB 7525,BRINKHOUS BULLITT BLDG,CHAPEL HILL,NC 27599, USA. RI Proia, Richard/A-7908-2012 FU NICHD NIH HHS [P30-HD 03110]; NINDS NIH HHS [R01-NS 24453] NR 33 TC 29 Z9 30 U1 0 U2 3 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 1997 VL 56 IS 6 BP 693 EP 703 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XD281 UT WOS:A1997XD28100007 PM 9184660 ER PT J AU Petit, L Clark, VP Ingeholm, J Haxby, JV AF Petit, L Clark, VP Ingeholm, J Haxby, JV TI Dissociation of saccade-related and pursuit-related activation in human frontal eye fields as revealed by fMRI SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MOVEMENTS; PET; CORTEX; SYSTEM AB The location of the human frontal eye fields (FEFs) underlying horizontal visually guided saccadic and pursuit eye movements was investigated with the use of functional magnetic resonance imaging in five healthy humans. Execution of both saccadic and pursuit eye movements induced bilateral FEF activation located medially at the junction of the precentral sulcus and the superior frontal sulcus and extending laterally to the precentral gyrus. These findings extend previous functional imaging studies by providing the first functional imaging evidence of a specific activation in the FEF during smooth pursuit eye movements in healthy humans. FEF activation during smooth pursuit performance was smaller than during saccades. This finding, which may reflect the presence of a smaller pursuit-related region area in human FEF than the saccade-related region, is consistent with their relative size observed in the monkey. The mean location of the pursuit-related FEF was more inferior rind. lateral than the location of the saccade-related FEF. These results provide the first evidence that there are different subregions in the human FEF that are involved in the execution of two different types of eye movements, namely saccadic and pursuit eye movements. Moreover, this study provides additional evidence that the human FEF is located in Brodmann's area 6, unlike the monkey FEF which is located in the posterior part of Brodmann's area 8. RP Petit, L (reprint author), NIMH, SECT FUNCT BRAIN IMAGING,LAB BRAIN & COGNIT,NIH, BLDG 10,RM 4C110, 10 CTR DR, BETHESDA, MD 20892 USA. RI GINSPAN, All/B-8714-2008; Clark, Vincent/B-3343-2010; Petit, Laurent/D-6583-2011 OI Clark, Vincent/0000-0002-9151-2102; Petit, Laurent/0000-0003-2499-5367 NR 23 TC 188 Z9 188 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1997 VL 77 IS 6 BP 3386 EP 3390 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XJ177 UT WOS:A1997XJ17700043 PM 9212283 ER PT J AU Li, CY Peoples, RW Weight, FF AF Li, CY Peoples, RW Weight, FF TI Mg2+ inhibition of ATP-activated current in rat nodose ganglion neurons: Evidence that Mg2+ decreases the agonist affinity of the receptor SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MAMMALIAN NEURONS; NMDA RECEPTORS; SYNAPTIC TRANSMISSION; SENSORY NEURONS; CHANNELS; MAGNESIUM; CELLS; MODULATION; KINETICS; GLYCINE AB The effect of Mg2+ on ATP-activated current in rat nodose ganglion neurons was investigated with the use of the whole cell patch-clamp technique. Mg2+ decreased the amplitude of ATP-activated current in a concentration-dependent manner over the concentration range of 0.25-8 mM, with a 50% inhibitory concentration value of 1.5 mM for current activated by 10 mu M ATP. Mg2+ shifted the ATP concentration-response curve to the right in a parallel manner, increasing the 50% effective concentration value for ATP from 9.2 mu M in the absence of added Mg2+ to 25 mu M in the presence of 1 mM Mg2+ Mg2+ increased the deactivation rate of ATP-activated current without changing its activation rate. The observations are consistent with an action of Mg2+ to inhibit ATP-gated ion channel function by decreasing the affinity of the agonist binding site on these receptors. RP Li, CY (reprint author), NIAAA,LAB MOL & CELLULAR NEUROBIOL,NIH,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 32 TC 33 Z9 34 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1997 VL 77 IS 6 BP 3391 EP 3395 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XJ177 UT WOS:A1997XJ17700044 PM 9212284 ER PT J AU Lenz, FA Gracely, RH Zirh, TA Leopold, DA Rowland, LH Dougherty, PM AF Lenz, FA Gracely, RH Zirh, TA Leopold, DA Rowland, LH Dougherty, PM TI Human thalamic nucleus mediating taste and multiple other sensations related to ingestive behavior SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID STIMULATION; MONKEY AB Until now, taste was the only primary sensory modality for which the human central nervous system pathways were unknown. We report sensations evoked by stimulation at microampere current levels in the region of the human thalamic nucleus (ventralis caudalis parvocellularis internis) corresponding to the monkey taste relay nucleus. Stimulation in this region during awake neurosurgical procedures evoked special visceral/somatic (taste/pungent smell), general visceral (fullness of a hollow viscus), as well as painful and nonpainful general somatic sensations. General somatic or visceral sensation was evoked by stimulation at 80% of sites where special visceral/somatic sensation was evoked. These results suggest that primate taste relay mediates multiple sensations in addition to taste. C1 JOHNS HOPKINS UNIV HOSP,DEPT NEUROSCI,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV HOSP,DEPT OTOLARYNGOL,BALTIMORE,MD 21287. NIDR,PAIN & NEUROSENSORY MECHANISMS BRANCH,NIH,BETHESDA,MD 20892. RP Lenz, FA (reprint author), JOHNS HOPKINS UNIV HOSP,DEPT NEUROSURG,MEYER BLDG 7-113,600 N WOLFE ST,BALTIMORE,MD 21287, USA. OI Dougherty, Patrick/0000-0002-2177-2734 FU NINDS NIH HHS [K08 NS-01384, NS-28598, P01 NS-32386] NR 19 TC 20 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1997 VL 77 IS 6 BP 3406 EP 3409 PG 4 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XJ177 UT WOS:A1997XJ17700047 PM 9212287 ER PT J AU Nirenberg, MJ Chan, J Vaughan, RA Uhl, GR Kuhar, MJ Pickel, VM AF Nirenberg, MJ Chan, J Vaughan, RA Uhl, GR Kuhar, MJ Pickel, VM TI Immunogold localization of the dopamine transporter: An ultrastructural study of the rat ventral tegmental area SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; transporter; uptake; ultrastructure; ventral tegmental area; midbrain; mesocorticolimbic; electron microscopy; immunogold; dendritic release; plasma membrane; cocaine; amphetamine; neurotoxicity ID DENDRO-DENDRITIC SYNAPSES; SUBSTANTIA-NIGRA; TYROSINE-HYDROXYLASE; AUTORADIOGRAPHIC LOCALIZATION; ENDOPLASMIC-RETICULUM; REGIONAL DIFFERENCES; NUCLEUS-ACCUMBENS; INVIVO DIALYSIS; UPTAKE SITES; NEURONS AB The dopamine transporter (DAT) plays an important role in the plasmalemmal reuptake of dopamine and, thus, in the termination of normal dopaminergic neurotransmission. DAT is also a major binding site for cocaine and other stimulants, the psychoactive effects of which are associated primarily with the inhibition of dopamine reuptake within mesocorticolimbic dopaminergic neurons. We used electron microscopy with an anti-peptide anti-serum directed against the N-terminal domain of DAT to determine the subcellular localization of this transporter in the rat ventral tegmental area (VTA), the region that contains the cell bodies and dendrites of these dopaminergic neurons. We show that in the VTA, almost 95% of the DAT immunogold-labeled profiles are neuronal perikarya and dendrites, and the remainder are unmyelinated axons. Within perikarya and large proximal dendrites, almost all of the DAT immunogold particles are associated with intracellular membranes, including saccules of Golgi and cytoplasmic tubulovesicles. In contrast, within medium- to small-diameter dendrites and unmyelinated axons, most of the DAT gold particles are located on plasma membranes. In dually labeled tissue, peroxidase reaction product for the catecholamine-synthesizing enzyme tyrosine hydroxylase is present in DAT-immunoreactive profiles. These findings suggest that intermediate and distal dendrites are both the primary sites of dopamine reuptake and the principal targets of cocaine and related psychostimulants within dopaminergic neurons in the VTA. C1 NIDA,NEUROSCI BRANCH,BALTIMORE,MD 21224. NIDA,BRANCH MOL NEUROBIOL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. EMORY UNIV,YERKES REG PRIMATE RES CTR,DIV NEUROSCI,ATLANTA,GA 30322. RP Nirenberg, MJ (reprint author), CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,411 E 69TH ST,ROOM KB-410,NEW YORK,NY 10021, USA. FU NIDA NIH HHS [DA04600]; NIMH NIH HHS [MH40342, MH00078] NR 69 TC 28 Z9 28 U1 2 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 1 PY 1997 VL 17 IS 11 BP 4037 EP 4044 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XA056 UT WOS:A1997XA05600007 PM 9151720 ER PT J AU Liesi, P AF Liesi, P TI Ethanol-exposed central neurons fail to migrate and undergo apoptosis SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE apoptosis; cerebellum; ethanol; laminin; neuronal migration; neurite outgrowth ID MULTIPLE ADHESION MOLECULES; OUTGROWTH-PROMOTING DOMAIN; NEURITE OUTGROWTH; NERVOUS-SYSTEM; CELL-DEATH; PROTEOLYTIC ACTIVITY; RAT CEREBELLUM; C-ELEGANS; ALCOHOL; LAMININ AB Prenatal exposure of human brain to ethanol impairs neuronal migration and differentiation and causes mental retardation, The present results indicate that the adverse effects of ethanol on brain development may be partly due to the ethanol-induced disturbance of neuronal interaction with laminin, a protein involved in neuronal migration and axon guidance, This report shows that physiological concentrations (IC50 = 28 mM) of ethanol inhibit neurite outgrowth and neuronal migration of the rat cerebellar granule neurons on a laminin substratum, The ethanol-treated granule neurons undergo apoptosis, degrade their laminin substratum, and appear to release and bind increased amounts of the B2-chain-derived peptides along their surfaces, A protease inhibitor aprotinin, and the NMDA receptor channel, and voltage-gated calcium channel antagonist MK801 partially protect cerebellar granule neurons from ethanol-induced neurotoxicity, These results imply that ethanol-treated granule neurons resemble the granule neurons of the homozygous weaver mouse cerebellum with respect to their apoptosis, laminin expression, and partial rescue by approtinin and MK-801. Thus, ethanol may influence neuronal survival and neurite outgrowth via molecular pathways similar to those involved in neuronal death in other neurodegenerative processes of the central nervous system. (C) 1997 Wiley-Liss, Inc. RP Liesi, P (reprint author), NIAAA,MOL & CELLULAR NEUROBIOL LAB,NIH,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 56 TC 76 Z9 78 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 1 PY 1997 VL 48 IS 5 BP 439 EP 448 DI 10.1002/(SICI)1097-4547(19970601)48:5<439::AID-JNR5>3.0.CO;2-F PG 10 WC Neurosciences SC Neurosciences & Neurology GA XB697 UT WOS:A1997XB69700005 PM 9185667 ER PT J AU Chiou, GCY AF Chiou, GCY TI Recent advances in ocular pharmacology and therapeutics SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Editorial Material RP Chiou, GCY (reprint author), NEI,LAB OCULAR THERAPEUT,NIH,10 CTR DR,MSC 1850,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD JUN PY 1997 VL 13 IS 3 BP 189 EP 190 DI 10.1089/jop.1997.13.189 PG 2 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA XC985 UT WOS:A1997XC98500001 ER PT J AU Qoronfleh, MW Chowdhury, SK Eshraghi, J Ho, T Brake, PG Banks, T Huang, J Pulvino, T Jones, BN AF Qoronfleh, MW Chowdhury, SK Eshraghi, J Ho, T Brake, PG Banks, T Huang, J Pulvino, T Jones, BN TI Identification of new autolytic sites of recombinant truncated mature human fibroblast stromelysin by mass spectrometry SO JOURNAL OF PEPTIDE RESEARCH LA English DT Article DE autodegradation; mass spectrometry; metalloproteinase; MMP-3; mutein (mutant protein); recombinant stromelysin ID MATRIX METALLOPROTEINASE-3 STROMELYSIN; RHEUMATOID SYNOVIAL FIBROBLASTS; ELECTROSPRAY-IONIZATION; CATALYTIC DOMAIN; ESCHERICHIA-COLI; PURIFICATION; COLLAGENASE; EXPRESSION; METALLOENDOPEPTIDASE; COMPONENTS AB Stromelysin has been proposed to play a major role in the pathologic degradation of diseased cartilage of osteoarthritis and rheumatoid arthritis patients, A truncated, recombinant form of this enzyme, with the sequence Phe(83) to Thr(260) (mSL-t), has been expressed and purified from E. coli to investigate its biochemical and biophysical properties, and to develop inhibitors for arthritis treatment, LC/ESI-MS technique was utilized for the characterization of mSL-t, The mass spectra of mSL-t showed the presence of a number of different protein components in addition to the full-length mSL-t form. We have demonstrated that protein degradation arose from autolysis. Molecular weights determined by LC/ESI-MS of these autolysis products allowed for the identification of new autolytic sites in mSL-t. Furthermore, two strategies were undertaken to prepare mSL-t free of degradation products. These include preparation of a mutant form of the enzyme in which Arg(163) was substituted for Leu(163) and purification of mSL-t using affinity chromatography, The LC/ESI-MS data of the mutant protein confirmed the Leu to Arg mutation. The affinity-purified material showed only one LC peak in the LC/MS chromatograms, and the mass spectrum of the peak identified only the intact protein, demonstrating that the full-length protein has been successfully separated from the autodegradation products and further autolysis of the enzyme has been prevented. (C) Munksgaard 1997. C1 SANOFI WINTHROP INC,DEPT CELLULAR & MOL BIOL,MALVERN,PA. SANOFI WINTHROP INC,DEPT BIOCHEM,MALVERN,PA. SANOFI WINTHROP INC,DEPT ANALYT SCI,MALVERN,PA. RP Qoronfleh, MW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,POB B,BLDG 322,FREDERICK,MD 21702, USA. NR 25 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD JUN PY 1997 VL 49 IS 6 BP 612 EP 619 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XN527 UT WOS:A1997XN52700019 PM 9266490 ER PT J AU Albandar, JM Brown, LJ Genco, RJ Loe, H AF Albandar, JM Brown, LJ Genco, RJ Loe, H TI Clinical classification of periodontitis in adolescents and young adults SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE periodontitis, early-onset; periodontitis, juvenile; periodontal attachment loss; longitudinal studies ID LOCALIZED JUVENILE PERIODONTITIS; EARLY-ONSET PERIODONTITIS; PROGRESSION; DISEASE; PATTERN AB THE AIM OF THIS STUDY was to determine the degree to which clinical classifications based on cross-sectional assessments endure in the course of development of early-onset periodontitis (EOP), and to introduce new criteria which might improve the clinical classification of these diseases. Subjects with EOP and a matched group without EOP were identified within a national probability sample examined during the 1986/87 survey of US schoolchildren. Of these, 265 subjects (mean age 16 years) were re-examined during the 1992/93 school year. The clinical attachment level of teeth was assessed, and the individuals were classified into localized juvenile periodontitis (LJP), generalized juvenile periodontitis (GJP), incidental attachment loss (IAL), and no-periodontitis groups using three classification methods previously described, A fourth method that considered the extent and severity of attachment loss and the number of missing teeth was introduced to classify the individuals at baseline and at follow-up as having localized, generalized, or incidental EOP, and no-periodontitis groups, Furthermore, the individuals were classified using criteria based on the rate and pattern of change in attachment loss during 6 years. The results showed low correlations between the baseline classifications and the classifications at the 6-year follow-up examination, irrespective of the method used. In addition, the cross-sectional classifications were not predictive of the rate of progression of periodontal disease in these subjects. In the generalized disease group, two-thirds of the individuals exhibited moderate/rapid disease progression, while one-third had slow or no progression. In the localized disease group, one-half of the individuals had moderate/rapid disease progression and one-half had slow or no progression. In the incidental disease group one-fourth of the individuals had moderate/rapid disease progression and three-fourths had slow or no progression. We propose that the term early-onset periodontitis be used as a generic term to describe periodontal disease before its normal onset. In addition, we suggest that incidental, localized, and generalized EOP are heterogeneous groups comprising rapidly and slowly progressing forms within each classification. The findings suggest that a classification system in which subsets of the disease that are defined according to a combination of cross-sectional criteria and the disease progression may be useful in studies of EOP, Furthermore, the findings suggest that clinical classifications of EOP be used as generic descriptors until a full understanding of the pathogenesis of this disease is accomplished. C1 SUNY BUFFALO,SCH DENT MED,DEPT ORAL BIOL,BUFFALO,NY 14260. UNIV CONNECTICUT,CTR HLTH,SCH DENT MED,DEPT PERIODONTOL,FARMINGTON,CT. RP Albandar, JM (reprint author), NIDR,NATCHER BLDG,ROOM 4AS-13K,45 CTR DR,BETHESDA,MD 20892, USA. OI Albandar, Jasim M./0000-0001-7801-3811 NR 22 TC 64 Z9 66 U1 1 U2 2 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JUN PY 1997 VL 68 IS 6 BP 545 EP 555 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XG945 UT WOS:A1997XG94500006 PM 9203098 ER PT J AU McCann, UD Yuan, J Hatzidimitriou, G Ricaurte, GA AF McCann, UD Yuan, J Hatzidimitriou, G Ricaurte, GA TI Selective serotonin reuptake inhibitors dissociate fenfluramine's anorectic and neurotoxic effects: Importance of dose, species and drug SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RAT-BRAIN; NERVE-ENDINGS; IN-VIVO; RELEASE; METHYLENEDIOXYMETHAMPHETAMINE; INVIVO; DEXFENFLURAMINE; NORFENFLURAMINE; PHARMACOLOGY; DERIVATIVES AB Fenfluramine, a clinically prescribed appetite suppressant, has been found to damage brain serotonin (5-HT) neurons in every animal species tested to date. Recent findings indicate that fluoxetine, a selective 5-HT reuptake inhibitor (SSRI), can prevent fenfluramine-induced 5-HT neurotoxicity without blocking fenfluramine-induced appetite suppression. The purpose of our studies was several-fold: 1) To determine whether the ability for fluoxetine to dissociate fenfluramine-induced anorexia and neurotoxicity is dose-related; 2) to ascertain whether other SSRIs also prevent fenfluramine-induced neurotoxicity without altering its anorectic effect; 3) to determine whether similar fluoxetine/fenfluramine interactions are seen in another animal species (i.e., mice) and 4) to determine whether decreases in food intake seen after the fluoxetine/fenfluramine combination can be attributed to nonspecific behavioral suppression. Results from our studies indicate that fluoxetine's effects are, indeed, dose-related, because higher doses of fluoxetine are required to protect against the 5-HT neurotoxic effects of higher doses of fenfluramine. Further, our results indicate that fluoxetine's effects generalize to all other SSRIs tested (citalopram, paroxetine and sertraline), as well as to other species (mice). Finally, our results demonstrate that anorexia in animals receiving the fenfluramine/fluoxetine combination is not secondary to nonspecific behavioral suppression, because water intake is increased although food intake is decreased in the same animals. Together, these data suggest that the anorectic and 5-HT neurotoxic effects of fenfluramine may involve different mechanisms, and that by combining fenfluramine with SSRIs, it may be possible to exploit fenfluramine's clinically useful properties (e.g., anorexia) without risking brain 5-HT neural injury. C1 JOHNS HOPKINS MED INST,DEPT NEUROL,BALTIMORE,MD 21205. RP McCann, UD (reprint author), NATL INST MENT HLTH,UNIT ANXIETY DISORDERS,BIOL PSYCHIAT BRANCH,NIH,BLDG 10-3N212,MSC 1272,BETHESDA,MD 20892, USA. FU NIDA NIH HHS [R01 DA06275, K02 DA00206] NR 39 TC 28 Z9 29 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 1997 VL 281 IS 3 BP 1487 EP 1498 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XD972 UT WOS:A1997XD97200056 PM 9190887 ER PT J AU Horton, AM AF Horton, AM TI Comorbidity of drug abuse treatment SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE comorbidity; drug abuse treatment; substance abuse disorders; psychiatric disorder ID PSYCHIATRIC-DISORDERS; COCAINE ABUSERS; OPIATE ADDICTS; UNITED-STATES; DIAGNOSIS; DEPENDENCE; ALCOHOL; SCHIZOPHRENIA; PSYCHOTHERAPY; PREVALENCE AB Research has suggested that comorbidity, the concurrence of substance abuse disorders with other psychiatric disorders, may have prognostic value and important implications for the treatment of substance abuse. Knowledge of the prevalence of comorbid disorder is important because it will enable treatment services to be appropriately configured and designed for clinical drug treatment populations. The form and duration of comorbidity may be influenced by a variety of factors, which include the class of drug being abused, the duration of drug use, the individual sensitivity to drug effects, and whether the drug effects are acute or due to withdrawal or residual conditions. This paper addresses three important scientific questions: (1) What is the prevalence of comorbid disorders in a drug abuser population? (2) What is the stability of psychiatric diagnoses in a drug abuser population? (3) Does the existence of a comorbid disorder influence the outcome of drug abuse treatment? RP NIDA, ETIOL & CLIN NEUROBIOL BRANCH, ROOM 10A-46, 5600 FISHERS LANE, ROCKVILLE, MD 20857 USA. NR 37 TC 3 Z9 3 U1 2 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD JUN PY 1997 VL 19 IS 2 BP 79 EP 90 DI 10.1007/BF02229035 PG 12 WC Psychology, Clinical SC Psychology GA YL136 UT WOS:A1997YL13600003 ER PT J AU GilRivas, V Anglin, MD Annon, JJ AF GilRivas, V Anglin, MD Annon, JJ TI Patterns of drug use and criminal activities among Latino arrestees in California: Treatment and policy implications SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE drug use; Latinos; crime ID ADDICTS; SEEKING AB This study examined the patterns of drug use and criminal activities among Latino arrestees. The findings indicate that while the prevalence of drug use at time of arrest and in the prior 12 months were significantly lower for Latinos compared to Whites and Blacks, drug use still is of concern for this ethnic group. Almost 50% of Latinos reported drug use in the last year and more importantly, they were more likely to report using dangerous drugs such as cocaine, heroin, and PCP than any other ethnic group. These findings are even more alarming considering that, for the most part, Latino drug users were treatment-naive, and that less than half perceived a need for drug treatment Regarding criminal activities, Latinos were less likely to have a history of prior arrests and to have been arrested in the year prior to the interview than any other ethnic group. Interestingly, chose immigrants who have resided in the U.S. for less than I year were significantly more likely to have been charged with drug-related crimes. U.S. born Latinos were more likely to have been arrested for property crimes, while Central American immigrants were more likely than any other Latino group to have been arrested for violent and domestic violence crimes. Treatment and policy implications of these findings are discussed. RP GilRivas, V (reprint author), UNIV CALIF LOS ANGELES,DRUG ABUSE RES CTR,NIDA,HISPANIC INITIAT DRUG ABUSE & AIDS RES & RES DEV,LOS ANGELES,CA 90024, USA. NR 35 TC 1 Z9 1 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD JUN PY 1997 VL 19 IS 2 BP 161 EP 174 DI 10.1007/BF02229041 PG 14 WC Psychology, Clinical SC Psychology GA YL136 UT WOS:A1997YL13600009 ER PT J AU Grisius, MM Bermudez, DK Fox, PC AF Grisius, MM Bermudez, DK Fox, PC TI Salivary and serum interleukin 6 in primary Sjogren's syndrome SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE saliva; salivary glands; Sjogren's syndrome; interleukin 6 ID SYSTEMIC LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; GLAND BIOPSIES; IL-6 AB Objective, To measure interleukin 6 (IL-6) salivary and serum concentrations in primary Sjogren's syndrome (SS), to correlate these data with the clinical presentation in patients, and to determine if salivary lL-6 is reflective of local exocrine involvement or of the underlying autoimmune disorder. Methods. Thirty-one patients with primary SS, 15 with primary biliary cirrhosis (PBC), and 14 healthy controls were studied. Parotid secretion was stimulated with 2% citric acid and collected using a Carlson-Crittenden collector. Concentrations of salivary and serum IL-6 were determined using a high sensitivity ELISA. Serologic autoimmune disease markers and salivary functional and histopathologic disease markers in the patients with SS were correlated with salivary and serum IL-6 levels. Results, Mean serum IL-6 concentrations were elevated in both patient groups (SS = 3.05 pg/ml, PBC = 3.07 pg/ml, healthy subjects = 0.843 pg/ml). Mean stimulated salivary IL-6 concentrations were elevated only in the patients with SS (16.21 pg/ml) compared to the PBC (1.07 pg/ml) and healthy subjects (0.769 pg/ml). No correlation was found between serum and salivary IL-6 concentrations for any group. Positive correlations were found between salivary IL-6 concentrations and serum IgG concentrations and between salivary IL-6 and erythrocyte sedimentation rate, Higher IL-6 concentrations were associated with increased disease activity. Conclusion, Salivary IL-6 concentration is elevated in SS compared to healthy subjects and patients with another systemic autoimmune disease without salivary gland involvement. Elevated salivary IL-6 concentrations in SS are reflective of local exocrine involvement and may serve as a useful monitor of disease activity. C1 NIDR,CLIN INVEST SECT,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. NR 12 TC 64 Z9 65 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 1997 VL 24 IS 6 BP 1089 EP 1091 PG 3 WC Rheumatology SC Rheumatology GA XD791 UT WOS:A1997XD79100012 PM 9195514 ER PT J AU Swedo, SE Allen, AJ Glod, CA Clark, CH Teicher, MH Richter, D Hoffman, C Hamburger, SD Dow, S Brown, C Rosenthal, NE AF Swedo, SE Allen, AJ Glod, CA Clark, CH Teicher, MH Richter, D Hoffman, C Hamburger, SD Dow, S Brown, C Rosenthal, NE TI A controlled trial of light therapy for the treatment of pediatric seasonal affective disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE seasonal affective disorder; light therapy; pediatric disorders ID CHILDREN; ADOLESCENTS; BEHAVIOR; MOOD AB Objective: To evaluate the efficacy of light therapy for the treatment of pediatric seasonal affective disorder (SAD). Method: 28 children (aged 7 to 17 years) at two geographically distinct sites were enrolled in a double-blind, placebo-controlled, crossover trial of bright-light treatment. Subjects initially entered a week-long baseline period during which they wore dark glasses for an hour a day. They were then randomly assigned to receive either active treatment (1 hour of bright-light therapy plus 2 hours of dawn simulation) or placebo (1 hour of clear goggles plus 5 minutes of low-intensity dawn simulation) for 1 week. The treatment phase was followed by a second dark-glasses phase lasting 1 to 2 weeks. After this phase, the children received the alternate treatment. Response was measured using the parent and child versions of the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders version (SIGH-SAD). Results: Data were analyzed as change from baseline. SIGH-SAD-P total depression scores were significantly decreased from baseline during light therapy compared with placebo (one-way analysis of variance, p = .009), and no differences were found between the placebo and control phases. Subscores of atypical and typical depression were also significantly decreased during the active treatment (p = .004 and .028, respectively). A similar trend was noted with the SIGH-SAD-C, but this did not reach significance. At the end of the study, 78% of the parents questioned and 80% of the children questioned rated light therapy as the phase during which the child ''felt best.'' Conclusion: Light therapy appears to be an effective treatment for pediatric SAD. C1 NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. MCLEAN HOSP,DEPT PSYCHIAT,BELMONT,MA 02178. RP Swedo, SE (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BEHAV PEDIAT SECT,10 CTR DR,MSC 1381,BETHESDA,MD 20892, USA. FU NIMH NIH HHS [R01 MH48343] NR 16 TC 40 Z9 41 U1 7 U2 9 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1997 VL 36 IS 6 BP 816 EP 821 DI 10.1097/00004583-199706000-00019 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA XB495 UT WOS:A1997XB49500019 PM 9183137 ER PT J AU Kumanyika, SK Cutler, JA AF Kumanyika, SK Cutler, JA TI Dietary sodium reduction: Is there cause for concern? SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Review DE sodium chloride; low-sodium diets; adverse effects; blood pressure; hypertension; dietary guidelines ID HIGH BLOOD-PRESSURE; MILD HYPERTENSION; SALT RESTRICTION; MODERATE HYPERTENSION; NUTRITIONAL THERAPY; PRIMARY PREVENTION; WEIGHT-REDUCTION; CONTROLLED TRIAL; URINARY SODIUM; HIGH-POTASSIUM AB Current dietary guidance includes a recommendation for moderate reduction of sodium (Na) intake of US adults to less than 2400 mg (approximately 100 mmol) per day. The safety of this recommendation tends to be taken for granted, but questions are raised periodically about possible adverse effects. We evaluated the evidence available to address these concerns. Relevant sources were identified through review of policy documents and a systematic MEDLINE search of articles published between 1984 and mid-October 1995. Reviews and commentaries were selected to encompass the spectrum of arguments for or against possible adverse effects. All identified randomized, human intervention trials of Na reduction with at least 6 months' follow up and urinary Na excretion data were included; selected additional evidence was evaluated as needed to address specific issues. Reports of trials were abstracted to describe relevant design features, study populations, level of Na reduction, and comments or data relevant to adverse effects. We found that some concerns were based on short-term, Na-depletion studies and were, therefore, not relevant to moderate Na reduction in the population-at-large. Other concerns were largely speculative and, from our review, were not supported by the combined evidence from 20 randomized Na reduction trials conducted in varied clinical or community settings and involving diverse populations followed for up to 5 years. Overall, we identified extensive data supporting the safety of public health recommendations for moderate Na reduction and none suggesting cause for concern. C1 PENN STATE UNIV, CTR BIOSTAT & EPIDEMIOL, UNIVERSITY PK, PA 16802 USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, BETHESDA, MD 20892 USA. NR 118 TC 20 Z9 20 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0731-5724 EI 1541-1087 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD JUN PY 1997 VL 16 IS 3 BP 192 EP 203 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XB707 UT WOS:A1997XB70700003 PM 9176824 ER PT J AU Slavkin, HC AF Slavkin, HC TI First encounters: Transmission of infectious oral diseases from mother to child SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 6 TC 7 Z9 7 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUN PY 1997 VL 128 IS 6 BP 773 EP 778 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XD266 UT WOS:A1997XD26600029 PM 9188237 ER PT J AU Katzel, LI BusbyWhitehead, M Hagberg, JM Fleg, JL AF Katzel, LI BusbyWhitehead, M Hagberg, JM Fleg, JL TI Abnormal exercise electrocardiograms in master athletes after three months of deconditioning SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID CORONARY ATHEROSCLEROSIS; SUDDEN-DEATH; OLDER MEN AB OBJECTIVE: To determine the effects of 3 months of voluntary deconditioning on cardiac function in master athletes. DESIGN: A prospective study. SETTING: Research participants at the University of Maryland School of Medicine and Johns Hopkins Bayview Medical Center PARTICIPANTS: Ten older (59 +/- 8 years, mean +/- SD), highly conditioned (maximal aerobic capacity (V) over dotO(2) max 50 +/- 5 mL/kg/min), aerobically trained athletes MEASUREMENTS AND RESULTS: Three months after the cessation of training, three of the 10 athletes had unexpected, new, markedly asymptomatic, ischemic-appearing, exercise-induced ST-segment depression on their maximal exercise tests. After retraining, the ST-segment changes disappeared in two of the subjects, but it persisted, although at a higher work load, in one of the athletes. CONCLUSION: In three master athletes, voluntary cardiopulmonary deconditioning was associated with the development of new, asymptomatic, exercise-induced ST-segment depression on exercise EGG. The mechanisms underlying these new ischemic-appearing ST-segment changes accompanying detraining and their clinical significance are not known and warrant further investigation. C1 UNIV MARYLAND, SCH MED, DEPT MED, DIV GERONTOL, BALTIMORE, MD 21201 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV GERIATR MED & GERONTOL, BALTIMORE, MD 21218 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV CARDIOL, BALTIMORE, MD 21218 USA. JOHNS HOPKINS BAYVIEW MED CTR, BALTIMORE, MD USA. NIA, CARDIOVASC SCI LAB, CTR GERONTOL RES, NIH, BALTIMORE, MD 21224 USA. RP BALTIMORE VET AFFAIRS MED CTR, GERIATR SERV 18, CTR GERIATR RES EDUC & CLIN, 10 N GREENE ST, BALTIMORE, MD 21201 USA. FU NIA NIH HHS [5 KO8-AG00383-02, 5-KO8-AG00497, R01 AG-07660] NR 14 TC 3 Z9 3 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 1997 VL 45 IS 6 BP 744 EP 746 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XD361 UT WOS:A1997XD36100014 PM 9180671 ER PT J AU Proschan, MA Follmann, DA AF Proschan, MA Follmann, DA TI A restricted test of circadian rhythm SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Bayes factor; circle data; directional data; imputation; missing data; von Mises distribution ID TRIAL AB In medical applications there is interest in whether deaths or other events occur randomly throughout the day, as opposed to in a definite circadian pattern. At times, knowledge of the circadian phenomenon will suggest that a single cluster of events should occur during a specific period during the day, such as mid-morning. We propose a test that incorporates such knowledge. The test can be viewed as the likelihood ratio test for a restricted alternative for data from the von Mises (i.e., circular normal) distribution. The test's power is compared to a commonly used test of randomness that ignores when a peak is likely to occur. Methods for dealing with interval censored data are discussed, and an example is given. A Bayesian alternative is also explored. RP Proschan, MA (reprint author), NHLBI,OFF BIOSTAT RES,BLDG 10,BETHESDA,MD 20892, USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 1997 VL 92 IS 438 BP 717 EP 724 PG 8 WC Statistics & Probability SC Mathematics GA XE296 UT WOS:A1997XE29600037 ER PT J AU Ono, A Huang, MJ Freed, EO AF Ono, A Huang, MJ Freed, EO TI Characterization of human immunodeficiency virus type 1 matrix revertants: Effects on virus assembly, Gag processing, and env incorporation into virions SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEAR-LOCALIZATION SIGNAL; ENVELOPE GLYCOPROTEIN; NONDIVIDING CELLS; INFECTED-CELLS; PROTEIN; HIV; PRECURSOR; MEMBRANE; MUTANTS; DOMAINS AB The matrix protein of human immunodeficiency virus type 1 (HIV-1) has been postulated to serve a variety of functions in the virus life cycle. Previously, we introduced a large number of mutations into the HIV-1 matrix and determined the effects on virus replication. These studies identified domains involved in virus assembly and release and envelope glycoprotein incorporation into virions. Here we describe the identification and characterization of viral revertants containing second-site changes in the matrix which compensate for the effects of four of the original mutations on matrix function. Specifically, mutations at matrix residues 4 and 6 severely impaired virus assembly and release; substitutions at residues 4 and 6 reversed the phenotype of the amino acid 4 change while second-site mutations at matrix positions 10, 69, and 97 partially or fully reversed the phenotype of the amino acid 6 substitution. A mutation at matrix residue 62 reversed the effect of a position 34 change which blocks envelope glycoprotein incorporation into virions, and substitutions at residues 27 and 51 reversed the phenotype of a position 86 mutation which redirects virus assembly to the cytoplasm. In addition to determining the effects of the compensatory changes in the context of the original mutations, we also introduced and analyzed the second-site changes alone in the context of the wild-type molecular clone. The data presented here define potential intermolecular and intramolecular interactions which occur in the matrix during the virus life cycle and have implications for our understanding of the relationship between matrix structure and function. C1 NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. NR 39 TC 63 Z9 65 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1997 VL 71 IS 6 BP 4409 EP 4418 PG 10 WC Virology SC Virology GA WZ571 UT WOS:A1997WZ57100028 PM 9151831 ER PT J AU Smith, RH Spano, AJ Kotin, RM AF Smith, RH Spano, AJ Kotin, RM TI The Rep78 gene product of adeno-associated virus (AAV) self-associates to form a hexameric complex in the presence of AAV ori sequences SO JOURNAL OF VIROLOGY LA English DT Article ID REPLICATION IN-VITRO; SITE-SPECIFIC INTEGRATION; SV40 T-ANTIGEN; ADENOASSOCIATED VIRUS; DNA-REPLICATION; BINDING MOTIF; PHENOTYPIC CORRECTION; STRUCTURAL PROTEINS; COVALENT ATTACHMENT; NUCLEOTIDE-SEQUENCE AB The Rep78 and Rep68 proteins of adeno-associated virus (AAV) are replication initiator proteins that bind the viral replicative-form origin of replication, nick the origin in a site- and strand-specific fashion, and mediate vectorial unwinding of the DNA duplex via an ATP dependent helicase activity, thus initiating a strand displacement mechanism of viral DNA replication, Genetic and biochemical studies have identified Rep mutants that demonstrate a trans-dominant negative phenotype in vitro and in vivo, suggesting the possibility that multimerization of Rep is essential for certain replicative functions. In this study, we Slave investigated the ability of the largest of the Rep proteins, Rep78, to self-associate in vitro and in vivo. Self-association of Rep78 in vivo was demonstrated through the use of a mammalian two-hybrid system. Rep-Rep protein interaction was confirmed in vitro through coimmunoprecipitation experiments with a bacterially expressed maltose-binding protein-Rep78 fusion protein in combination with [S-35] methionine-labeled Rep78 synthesized in a coupled in vitro transcription-translation system. Mapping Studies with N- and C-terminal truncation mutant forms of Rep indicate that amino acid sequences required for maximal self-association occur between residues 164 and 484. Site-directed mutagenesis identified two essential motifs within this 321-amino-acid region: (i) a putative or-helix bearing a 3,4-hydrophobic heptad repeat reminiscent of those found in coiled-coil domains and (ii) a previously recognized nucleoside triphosphate-binding motif. Deletion of either of these regions from the full-length polypeptide resulted in severe impairment of Rep-Rep interaction. In addition, gel filtration chromatography and protein cross-linking experiments indicated that Rep78 forms a hexameric complex in the presence of AAV ori sequences. C1 NHLBI,MOL HEMATOL BRANCH,BETHESDA,MD 20892. RI kotin, robert/B-8954-2008 NR 87 TC 36 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1997 VL 71 IS 6 BP 4461 EP 4471 PG 11 WC Virology SC Virology GA WZ571 UT WOS:A1997WZ57100034 PM 9151837 ER PT J AU Huang, MJ Martin, MA AF Huang, MJ Martin, MA TI Incorporation of Pr160(gag-pol) into virus particles requires the presence of both the major homology region and adjacent C-terminal capsid sequences within the gag-pol polyprotein SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; BACULOVIRUS-INFECTED CELLS; TYPE-1 INTEGRASE; PRECURSOR; EXPRESSION; MUTATIONS; PROTEINS; PR160GAG-POL; PROTEASE AB The determinants critical for the incorporation of Pr160(gag-pol) into human immunodeficiency virus type 1 (HIV-1) particles were examined by cotransfecting cells with (i) a plasmid expressing wild-type Gag protein and (ii) a series of chimeric Gag-Pol expression plasmids in which individual murine leukemia virus (MLV) Gag regions and subdomains precisely replaced their HIV-1 counterparts. The presence of the MLV MA and NC Gag regions in the chimeric Gag-Pol precursor had no detectable effect on the incorporation of Gag-Pol into progeny virions. In contrast, the entire HIV-1 CA region was required to achieve wild-type levels of Gag Pol assembly into particles; both the CA major homology region and the adjacent C-terminal CA sequences play dominant roles in this process yet, when assayed in the context of a chimeric Gag-Pol polyprotein, restored the defect affecting Gag-Pol incorporation to approximately half of the wild-type level. C1 NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. NR 43 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1997 VL 71 IS 6 BP 4472 EP 4478 PG 7 WC Virology SC Virology GA WZ571 UT WOS:A1997WZ57100035 PM 9151838 ER PT J AU OSullivan, MG Anderson, DK Goodrich, JA Tulli, H Green, SW Young, NW Brown, KE AF OSullivan, MG Anderson, DK Goodrich, JA Tulli, H Green, SW Young, NW Brown, KE TI Experimental infection of cynomolgus monkeys with simian parvovirus SO JOURNAL OF VIROLOGY LA English DT Article ID B19 PARVOVIRUS; IMMUNODEFICIENCY SYNDROME; ANEMIA; DISEASE; HUMANS; AGENT AB Simian parvovirus is a recently discovered parvovirus that was first isolated from cynomolgus monkeys, It is similar to human B19 parvovirus in terms of virus genome, tropism for erythroid cells, and characteristic pathology in natural infections. Cynomolgus monkeys were infected with simian parvovirus to investigate their potential usefulness as an animal model of human B19 parvovirus. Six adult female cynomolgus monkeys were inoculated with purified simian parvovirus by the intravenous or intranasal route and monitored for evidence of clinical abnormalities; this included the preparation of complete hematological profiles, Viremia and simian parvovirus-specific antibody were determined in infected monkeys by dot blot and Western blot assays, respectively. Bone marrow was examined at necropsy 6, 10, or 15 days postinfection. All of the monkeys developed a smoldering, low-grade viremia that peaked approximately 10 to 12 days after inoculation, Peak viremia coincided with the appearance of specific antibody and was followed by sudden clearance of the virus and complete, but transient, absence of reticulocytes from the peripheral blood, Clinical signs were mild and involved mainly anorexia and slight weight loss, Infection,vas associated with a mild decrease in hemoglobin, hematocrit, and erythrocyte numbers. Bone marrow showed marked destruction of erythroid cells coincident with peak viremia, Our findings indicate that infection of healthy monkeys by simian parvovirus is self-limited and mild, with transient cessation of erythropoiesis. Our study has reproduced Koch's postulates and further shown that simian parvovirus infection of monkeys is almost identical to human B19 parvovirus infection of humans, Accordingly, this animal model may prove valuable in the study of the pathogenesis of B19 virus infection. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. RP OSullivan, MG (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. FU NCRR NIH HHS [RR-08562] NR 33 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1997 VL 71 IS 6 BP 4517 EP 4521 PG 5 WC Virology SC Virology GA WZ571 UT WOS:A1997WZ57100041 PM 9151844 ER PT J AU Secchiero, P Sun, D DeVico, AL Crowley, RW Reitz, MS Zauli, G Lusso, P Gallo, RC AF Secchiero, P Sun, D DeVico, AL Crowley, RW Reitz, MS Zauli, G Lusso, P Gallo, RC TI Role of the extracellular domain of human herpesvirus 7 glycoprotein B in virus binding to cell surface heparan sulfate proteoglycans SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SIMPLEX VIRUS; INITIAL INTERACTION; ADSORPTION; PENETRATION; INHIBITION; RECEPTOR; FUSION; GROWTH; IDENTIFICATION AB In an attempt to identify the human herpesvirus 7 (HHV-7) envelope protein(s) involved in cell surface binding, the extracellular domain of the HHV-7 glycoprotein B (gB) homolog protein was cloned and expressed as a fusion product with the Fc domain of human immunoglobulin G heavy chain gamma 1 (gB-Fc) in an eukaryotic cell system. Indirect immunofluorescence followed by pow cytometric analysis revealed specific binding of gB-Fc to the membrane of SupT1 cells hut not to other CD4(+) T-lymphoblastoid cell lines, such as Jurkat or PM1, clearly indicating that gB-Fc did not bind to the CD4 molecule. This was also suggested by the ability of gB-Fc to bind to CD4-negative fibroblastoid Chinese hamster ovary (CHO) cells. The binding was abrogated by enzymatic removal of cell surface heparan sulfate proteoglycans by heparinase and heparitinase but not by treatment with condroitinase ABC. In addition, binding of the gB-Fc fusion protein to CHO cells was severely impaired in the presence of soluble heparin, as well as when heparan sulfate-deficient mutant CHO cells were used. Consistent with these findings, soluble heparin was found to block HHV-7 infection and syncytium formation in the SupT1 cell line. Although the CD4 antigen is a critical component of the receptor for the T-lymphotropic HHV-7, these findings suggest that heparin-like molecules also play an important role in HHV-7-cell surface interactions required for infection and that gB represents one of the HHV-7 envelope proteins involved in the adsorption of virus-to-cell surface proteoglycans. C1 UNIV FERRARA,INST HUMAN ANAT,I-44100 FERRARA,ITALY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. SAN RAFFAELE SCI INST,DIBIT,I-20132 MILAN,ITALY. RP Secchiero, P (reprint author), UNIV MARYLAND,CTR MED BIOTECHNOL,INST HUMAN VIROL,725 W LOMBARD ST,BALTIMORE,MD 21201, USA. RI secchiero, paola/G-9689-2015; OI secchiero, paola/0000-0003-4101-7987; Zauli, Giorgio/0000-0002-3750-8698 NR 54 TC 64 Z9 69 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1997 VL 71 IS 6 BP 4571 EP 4580 PG 10 WC Virology SC Virology GA WZ571 UT WOS:A1997WZ57100048 PM 9151851 ER PT J AU Weed, DL AF Weed, DL TI Underdetermination and incommensurability in contemporary epidemiology SO KENNEDY INSTITUTE OF ETHICS JOURNAL LA English DT Article ID CERVICAL-CANCER; BREAST-CANCER; SMOKING; ALCOHOL AB In the shadowy world between philosophy of science and ethics lie the paired concepts of underdetermination and incommensurability. Typically scientific evidence underdetermines the hypotheses tested in research studies, providing neither proof nor disproof. As a result, scientists must judge the weight of the evidence, and in doing so, bring scientific and extrascientific values to bear in their approaches to assessing and interpreting the evidence. When different scientists employ very different values, their views are said to be incommensurable. Less prominent differences represent partial incommensurabilities. The definitions and analyses provided by McMullin and by Veatch and Stempsey lay the foundation for the description of partial incommensurabilities in the current practice of assessing and interpreting epidemiologic evidence. This practice is called ''causal inference'' and is undertaken for the purpose of making causal conclusions and public health recommendations from population-based studies of exposures and diseases. Following the work of Bayley and Longino, several suggestions are examined for dealing with the partial incommensurabilities found in the general practice of causal inference in contemporary epidemiology. Two specific examples illustrate these ideas: studies on the relationship between induced abortion and breast cancer and those on the relationship between moderate alcohol consumption and breast cancer. RP Weed, DL (reprint author), NIH,DIV CANC PREVENT & CONTROL,CANC PREVENT FELLOWSHIP PROGRAM,BETHESDA,MD 20892, USA. NR 30 TC 31 Z9 32 U1 1 U2 4 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 SN 1054-6863 J9 KENNEDY INST ETHIC J JI Kennedy Inst. Ethics J. PD JUN PY 1997 VL 7 IS 2 BP 107 EP 127 DI 10.1353/ken.1997.0018 PG 21 WC Ethics; Philosophy; Social Issues SC Social Sciences - Other Topics; Philosophy; Social Issues GA XJ295 UT WOS:A1997XJ29500001 PM 11654985 ER PT J AU Hunsicker, LG Adler, S Caggiula, A England, BK Greene, T Kusek, JW Rogers, NL Teschan, PE AF Hunsicker, LG Adler, S Caggiula, A England, BK Greene, T Kusek, JW Rogers, NL Teschan, PE TI Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study SO KIDNEY INTERNATIONAL LA English DT Article ID LONGITUDINAL DATA; BLOOD-PRESSURE; FAILURE; INSUFFICIENCY; PROTEINURIA; HYPERTENSION AB The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and strict blood pressure control on the decline in glomerular filtration rate (GFR) in 840 patients with diverse renal diseases. We describe a systematic analysis to determine baseline factors that predict the decline in GFR, or which alter the efficacy of the diet or blood pressure interventions. Univariate analysis identified 18 of 41 investigated baseline factors as significant (P < 0.05) predictors of GFR decline. In multivariate analysis, six factors-greater urine protein excretion, diagnosis of polycystic kidney disease (PKD), lower serum transferrin, higher mean arterial pressure, black race, and lower serum HDL cholesterol-independently predicted a faster decline in GFR. Together with the study interventions, these six factors accounted for 34.5% and 33.9% of the variance between patients in GFR slopes in Studies A and B, respectively, with proteinuria and PKD playing the predominant role. The mean rate of GFR decline was not significantly related to baseline GFR, suggesting an approximately linear mean GFR decline as renal disease progresses. The 41 baseline predictors were also assessed for their interactions with the diet and blood pressure interventions. A greater benefit of the low blood pressure intervention was found in patients with higher baseline urine protein. None of the 41 baseline factors were shown to predict a greater or lesser effect of dietary protein restriction. C1 NIDDKD,NIH,BETHESDA,MD 20892. NR 35 TC 441 Z9 458 U1 2 U2 11 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1997 VL 51 IS 6 BP 1908 EP 1919 DI 10.1038/ki.1997.260 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA XD057 UT WOS:A1997XD05700029 PM 9186882 ER PT J AU Leypoldt, JK Cheung, AK Agodoa, LY Daugirdas, JT Greene, T Keshaviah, PR AF Leypoldt, JK Cheung, AK Agodoa, LY Daugirdas, JT Greene, T Keshaviah, PR TI Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the American-Society-of-Nephrology CY NOV 05-08, 1995 CL SAN DIEGO, CA SP Amer Soc Nephrol, NIDDKD, DVA Med Res Funds AB The dialyzer mass transfer-area coefficient (K(o)A) for urea is an important determinant of urea removal during hemodialysis and is considered to be constant for a given dialyzer. We determined urea clearance for 22 different models of commercial hollow fiber dialyzers (N = similar to 5/model, total N = 107) in vitro at 37 degrees C for three countercurrent blood (Q(b)) and dialysate (Q(d)) flow rate combinations. A standard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from urea concentrations in the input and ourput flows on both the blood and dialysate sides. Urea K(o)A values, calculated from the mean of the blood and dialysate side clearances, varied between 520 and 1230 ml/min depending on the dialyzer model, but the effect of blood and dialysate flow rate on urea K(o)A was similar for each. Urea K(o)A did not change (690 +/- 160 vs. 680 +/- 140 ml/min, P = NS) when Q(b) increased from 306 +/- 7 to 459 +/- 10 ml/min at a nominal Q(d) of 500 ml/min. When Q(d) increased from 504 +/- 6 to 819 +/- 8 ml/min at a nominal Q(b) of 450 ml/min, however, urea K(o)A increased (P < 0.001) by 14 +/- 7% (range 3 to 33%, depending on the dialyzer model) to 780 +/- 150 ml/min. These data demonstrate that increasing nominal Q(d) from 500 to 800 ml/min alters the mass transfer characteristics of hollow fiber hemodialyzers and results in a larger increase in urea clearance than predicted assuming a constant K(o)A. C1 NIDDK,NATL INST HLTH,BETHESDA,MD. NR 13 TC 77 Z9 80 U1 1 U2 5 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1997 VL 51 IS 6 BP 2013 EP 2017 DI 10.1038/ki.1997.274 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA XD057 UT WOS:A1997XD05700043 PM 9186896 ER PT J AU Clark, JA Myers, PH Goelz, MF Thigpen, JE Forsythe, DB AF Clark, JA Myers, PH Goelz, MF Thigpen, JE Forsythe, DB TI Pica behavior associated with buprenorphine administration in the rat SO LABORATORY ANIMAL SCIENCE LA English DT Article ID POSTOPERATIVE ANALGESIA; MORPHINE AB Marked gastric distention was observed in rats 20 h after they underwent partial hepatectomy under isoflurane anesthesia and received buprenorphine (0.3 mg/kg of body weight) after surgery. Hardwood bedding comprised the bulk of the gastric contents. A study was undertaken to determine the cause of the pica behavior (consumption of non-nutritive substances) and resultant gastric distention. Ten-week-old male Sprague Dawley rats were randomly assigned to one of six groups. Group-1 rats (n = 11) underwent laparotomy under isoflurane anesthesia, with buprenorphine (0.3 mg/kg) administered after surgery. Group-2 rats (n = 12) underwent laparotomy under isoflurane anesthesia with buprenorphine (0.05 mg/kg) administered after surgery. Group-3 rats (n = 24) underwent laparotomy under isoflurane anesthesia, with saline administered after surgery. Isoflurane was administered at the same rate, concentration, and duration for all groups that underwent laparotomy (groups 1 to 3). Buprenorphine or saline was administered subcutaneously as a single injection when anesthesia was discontinued (groups 1 to 3). Group-4 rats (n = 6) received buprenorphine (0.3 mg/kg) only. Group-5 rats (n = 6) received buprenorphine (0.05 mg/kg only. Group-6 rats (n = 12) received saline only. Rats not undergoing laparotomy (groups 4 to 6) received buprenorphine or saline 18 to 20 h before euthanasia. Rats were housed individually in filter-topped polycarbonate cages containing hardwood bedding. A purified, pelleted diet and water were offered ad libitum. Food and water consumption were measured over the posttreatment period. Eighteen to 20 h after treatment, rats were euthanized, each stomach and its contents were weighed, contents were examined grossly, and wet and dry gastric content weights were recorded. All weights were significantly (P < 0.05) increased in rats receiving buprenorphine administered after surgery (groups 1 and 2), compared with rats of the control group (group 3). Weights of the stomach and contents, wet gastric contents, and dry gastric contents were significantly (P < 0.05) increased in rats receiving 0.3 mg of buprenorphine/kg only (group 4), compared with values for their controls (group 6). Hardwood bedding comprised the bulk of the gastric contents in all groups receiving buprenorphine. Stomachs of rats not receiving buprenorphine contained the purified diet with little or no hardwood bedding. These results indicate that a single injection of buprenorphine at a dosage of 0.05 or 0.3 mg/kg resulted in rats ingesting hardwood bedding, leading to gastric distention. It was concluded that pica behavior associated with administration of buprenorphine should be considered when evaluating experimental data from rats housed on contact bedding. RP Clark, JA (reprint author), NIEHS,COMPARAT MED BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 21 TC 48 Z9 48 U1 0 U2 7 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD JUN PY 1997 VL 47 IS 3 BP 300 EP 303 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA XH887 UT WOS:A1997XH88700011 PM 9241634 ER PT J AU Cereseto, A Berneman, Z Koralnik, I Vaughn, J Franchini, G Klotman, ME AF Cereseto, A Berneman, Z Koralnik, I Vaughn, J Franchini, G Klotman, ME TI Differential expression of alternatively spliced pX mRNAs in HTLV-I-infected cell lines SO LEUKEMIA LA English DT Article DE HTLV-I; alternative splicing; adult T cell leukemia (ATL) ID VIRUS TYPE-I; LEUKEMIA-LYMPHOMA VIRUS; BLOOD MONONUCLEAR-CELLS; P21X MESSENGER-RNA; LYMPHOTROPIC VIRUS; MOLECULAR ANALYSIS; PARTIAL DELETION; TAX GENE; PROTEIN; TRANSFORMATION AB Human T cell leukemia/lymphotropic virus (HTLV) is a complex 9 kb human retrovirus with at least eight alternatively spliced mRNAs expressed from the 3' or pX region of the genome. These mRNAs allow for the expression of novel proteins from the previously recognized pX open reading frames I and II in addition to Tax, Rex and p21(rex) encoded from orf III and IV. These alternatively spliced messages have been using reverse-transcriptase polymerase chain (RT/PCR) amplification in HTLV-I-transformed T cell lines as well as in peripheral blood mononuclear cells (PBMC) from infected patients with and without disease. To gain insight into the role of these alternatively spliced mRNAs in pathogenesis, we developed a semi-quantitative non-PCR-based RNase protection assay to detect and quantitate their presence in HTLV-I-infected cells. Analysis of RNA from HTLV-I-infected cells established from patients with adult T cell leukemia (ATL) as well as tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) and both IL-2-dependent and IL-2-independent HTLV-I-infected cell lines by RNase protection has confirmed the existence of all of the alternatively spliced messages in each cell line analyzed. However, the relative quantity of each message was significantly different among these lines suggesting that splice site utilization is an important viral regulatory pathway. C1 NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. RI klotman, mary/A-1921-2016 NR 31 TC 35 Z9 35 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 1997 VL 11 IS 6 BP 866 EP 870 DI 10.1038/sj.leu.2400665 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA XE175 UT WOS:A1997XE17500017 PM 9177442 ER PT J AU Horska, A Spencer, RGS AF Horska, A Spencer, RGS TI Correctly accounting for radiofrequency spillover in saturation transfer experiments: Application to measurement of the creatine kinase reaction rate in human forearm muscle SO MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE LA English DT Article DE saturation transfer; spillover; chemical exchange; creatine kinase; skeletal muscle ID LATTICE RELAXATION-TIMES; P-31 NMR; SKELETAL-MUSCLE; MAGNETIZATION-TRANSFER; KINETIC MEASUREMENTS; INVIVO; BRAIN; HEART; CONTRACTION; EXCHANGE AB Measurements based on transfer of magnetization have been widely used to calculate reaction rates in systems with slow chemical exchange. In these experiments, correction for direct irradiation of the observed resonance is in general accomplished by replacing the equilibrium magnetization in the Bloch equations by a magnetization obtained in an experiment in which a low power radiofrequency (RF) pulse is placed contralaterally, that is, at an equal distance from the observed resonance as the saturated one but on the opposite side. However, the magnetization observed during contralateral irradiation is affected not only by direct irradiation but also by chemical exchange. We demonstrate here that including this effect leads to a substantial improvement in the accuracy of reaction rate determination in steady-state saturation transfer experiments and, if incomplete saturation is present, also in transient saturation transfer experiments. Ln steady-state saturation transfer experiments performed in vivo at 1.9 T, correct interpretation of the contralateral saturation transfer experiment resulted in a correction of the creatine kinase reaction rate by approximately 11% on average. C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 23 TC 20 Z9 20 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 1352-8661 J9 MAGN RESON MATER PHY JI Magn. Reson. Mat. Phys. Biol. Med. PD JUN PY 1997 VL 5 IS 2 BP 159 EP 163 DI 10.1007/BF02592247 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XN947 UT WOS:A1997XN94700011 PM 9268080 ER PT J AU Anna, CH Devereux, TR AF Anna, CH Devereux, TR TI Sequence and chromosomal mapping of the mouse homolog (Madh4) of the human DPC4/MADH4 gene SO MAMMALIAN GENOME LA English DT Article C1 NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 12 TC 15 Z9 16 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUN PY 1997 VL 8 IS 6 BP 443 EP 444 DI 10.1007/s003359900465 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XB343 UT WOS:A1997XB34300014 PM 9166592 ER PT J AU Chin, HM Lyu, MS Kwon, OJ Kozak, CA AF Chin, HM Lyu, MS Kwon, OJ Kozak, CA TI Genetic mapping of the gene encoding cysteine string protein SO MAMMALIAN GENOME LA English DT Article ID DROSOPHILA; CLONING; LAMININ; SUBUNIT; MUTANTS; CHAIN C1 NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. CATHOLIC UNIV,COLL MED,DEPT BIOCHEM,SEOUL,SOUTH KOREA. RP Chin, HM (reprint author), NINCDS,NEUROCHEM LAB,BLDG 36,ROOM FD-20,36 CONVENT DR,MCS4130,BETHESDA,MD 20892, USA. NR 15 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUN PY 1997 VL 8 IS 6 BP 456 EP 457 DI 10.1007/s003359900640 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XB343 UT WOS:A1997XB34300023 PM 9257949 ER PT J AU Segal, R Dayan, M Globerson, A Habut, B Shearer, GM Mozes, E AF Segal, R Dayan, M Globerson, A Habut, B Shearer, GM Mozes, E TI Effect of aging on cytokine production in normal and experimental systemic lupus erythematosus afflicted mice SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT 1st International Conference on Immunology and Aging CY JUN 16-19, 1996 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Inst Adv Studies Immunol & Aging, NIH, WHO HO NIH, NATCHER CONF CTR DE cytokines; systemic lupus erythematosus; aging ID AGE-RELATED-CHANGES; T-CELL SUBSETS; OLD MICE; LYMPHOKINE PRODUCTION; GENE-EXPRESSION; IMMUNE-SYSTEM; INDUCTION; MANIFESTATIONS; PROLIFERATION; LYMPHOCYTES AB The objective of the this study was to determine the cytokine profile of aging mice and to establish whether changes in cytokine production account for the fact that aging mice develop a milder disease than the young in response to induced experimental systemic lupus erythematosus (SLE). Cytokine secretion was evaluated in groups of BALB/c and C3H.SW mice at different ages between 2 and 24 months. The production of IL-2, IL-4, IL-10, IFN gamma and TNF alpha was determined in supernatants of ConA-stimulated splenocytes and that of IL-1 in the supernatants of LPS-stimulated peritoneal macrophages. A gradual age-related decline was observed in the production of IL-2 and IFN gamma, whereas the levels of IL-4, IL-10, IL-1 and TNF alpha progressively increased with aging, in unimmunized BALB/c and C3H.SW mice. Experimental SLE was induced in 2 and 10 month old C3H.SW mice by immunization with the monoclonal anti-DNA antibody bearing the 16/6 Td. The characteristic cytokine profile following immunization of 2 month old mice was early increased production of TNF alpha and IL-1, followed by a peak of Th1 type cytokines (IL-2, IFN gamma). At a later stage of the disease, a peak of Th2 type cytokines (IL-4, IL-10) was observed that was concomitant with low levels of Th1 cytokines. In contrast, in the 10 month old mice that were immunized with 16/6 Id, only a mild increase in all the above cytokines was observed. We suggest that the lower autoantibody production and moderate clinical manifestations in aging mice with experimental SLE are causally related to the decreased production of pro-inflammatory cytokines at the initial stages of the disease followed by a lower production of both Th1 and Th2 type cytokines. (C) 1997 Elsevier Science Ireland Ltd. C1 SHMUEL HAROFEH GERIAT CTR,BEER YAAGOV,ISRAEL. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD. RP Segal, R (reprint author), WEIZMANN INST SCI,DEPT IMMUNOL,IL-76100 REHOVOT,ISRAEL. NR 32 TC 37 Z9 41 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD JUN PY 1997 VL 96 IS 1-3 BP 47 EP 58 DI 10.1016/S0047-6374(97)01891-5 PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA XF711 UT WOS:A1997XF71100004 PM 9223110 ER PT J AU Adler, WH Baskar, PV Chrest, FJ DorseyCooper, B Winchurch, RA Nagel, JE AF Adler, WH Baskar, PV Chrest, FJ DorseyCooper, B Winchurch, RA Nagel, JE TI HIV infection and aging: Mechanisms to explain the accelerated rate of progression in the older patient SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT 1st International Conference on Immunology and Aging CY JUN 16-19, 1996 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Inst Adv Studies Immunol & Aging, NIH, WHO HO NIH, NATCHER CONF CTR DE human immunodeficiency virus-1; human aging; T-lymphocyte; AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACQUIRED-IMMUNE-DEFICIENCY; INTERLEUKIN-2 RECEPTOR EXPRESSION; SOLUBLE IL-2 RECEPTOR; T-LYMPHOCYTE ACTIVITY; CD8 CELL SUBSETS; DISEASE PROGRESSION; HOMOSEXUAL MEN; TYPE-1 INFECTION; BLOOD-DONORS AB Age is an important predictor of progression in HIV infections. Not only do older individuals' develop AIDS more rapidly than younger persons, they die more quickly after developing an AIDS-defining illness. While the elderly have higher morbidity and mortality rates from viral and bacterial infections, the mechanism(s) responsible for the more rapid progression of HIV infection in older individuals has not been described. Our results demonstrate that the destruction of T cells in both young and old HIV infected patients progresses al the same rate. HIV 1-infected cells from older individuals do not appear more susceptible to immune mediated destruction. The more rapid progression appears due to an inability of older persons to replace functional T cells that are being destroyed. These findings suggest that improved survival in older HIV infected individuals will require more aggressive antiretroviral therapies as well as continued research to identify and preserve immune system elements that control the virus. (C) 1997 Elsevier Science Ireland Ltd. C1 JOHNS HOPKINS SCH MED,DEPT SURG,BALTIMORE,MD. RP Adler, WH (reprint author), NIA,GERONTOL RES CTR,NIH,BOX 21,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 164 TC 39 Z9 40 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD JUN PY 1997 VL 96 IS 1-3 BP 137 EP 155 DI 10.1016/S0047-6374(97)01888-5 PG 19 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA XF711 UT WOS:A1997XF71100011 PM 9223117 ER PT J AU Fuhrer, MJ AF Fuhrer, MJ TI Comments on: Rehabilitation care and outcomes from the patient's perspective SO MEDICAL CARE LA English DT Editorial Material RP Fuhrer, MJ (reprint author), NICHHD,NATL CTR MED REHABIL RES,NIH,BLDG 61E,ROOM 2A03,6100 EXECUT BLVD,MSC 7510,ROCKVILLE,MD 20852, USA. NR 7 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 1997 VL 35 IS 6 SU S BP JS58 EP JS60 DI 10.1097/00005650-199706001-00010 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XD871 UT WOS:A1997XD87100010 ER PT J AU Overwijk, WW Surman, DR Tsung, K Restifo, NP AF Overwijk, WW Surman, DR Tsung, K Restifo, NP TI Identification of a K-b-restricted CTL epitope of beta-galactosidase: Potential use in development of immunization protocols for ''self'' antigens SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; RECOMBINANT VACCINIA VIRUSES; TRANSGENIC MICE; DIRECT EXPRESSION; ESCHERICHIA-COLI; GENE-EXPRESSION; HUMAN-MELANOMA; IN-VIVO; PROMOTER; CELLS AB The use of recombinant and synthetic vaccines in the treatment of cancer has recently been explored using model tumor associated antigens (TAA), many of which do not model the immunological state of affairs in which the TAA is expressed by normal tissues. One potentially useful model Ag is beta-galactosidase (beta-gal). Because the activity of this enzyme is so easily detectable, this gene has been inserted into a large number of recombinant viruses and tumors useful to the cancer vaccinologist. In addition, numerous transgenic mouse colonies that have tissue-specific expression of beta-gal have been developed, enabling the modeling of tolerance to ''self'' Ags. Since most of these mice have an H-2(b) background, we generated cytotoxic T lymphocytes (CTL) capable of recognizing beta-gal-expressing tumor cells of C57BL\6 origin and have determined that their restriction element is the K-b molecule. Using an allele-specific epitope forecast to generate a panel of candidate peptides, we have determined that the K-b-restricted sequence is DAPIYTNV and corresponds to amino acids 96-103 of the intact beta-gal molecule. A recombinant vaccinia virus (rVV- pes beta-gal(96-103)) was constructed that encoded the peptide epitope preceded by an endoplasmic reticulum insertion signal sequence. Tumor cells infected with this rVV were recognized by the original CTL that had been used to identify the epitope. Furthermore, splenocytes of mice immunized with a rVV encoding the full-length beta-gal molecule and restimulated with the DAPIYTNV peptide specifically recognized tumor cells expressing beta-gal. The identification of this immunogenic beta-gal sequence enables the modeling of immunization strategies in animal models of malignant disease in which the target antigen is a ''self'' protein. C1 WASHINGTON UNIV,SCH MED,LAB BIOL THERAPY,ST LOUIS,MO 63110. RP Overwijk, WW (reprint author), NCI,SURG BRANCH,NIH,BLDG 10,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 57 TC 45 Z9 45 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1046-2023 J9 METHODS JI Methods PD JUN PY 1997 VL 12 IS 2 BP 117 EP 123 DI 10.1006/meth.1997.0461 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT380 UT WOS:A1997XT38000002 PM 9184376 ER PT J AU Finlay, BB Falkow, S AF Finlay, BB Falkow, S TI Common themes in microbial pathogenicity revisited SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID ENTEROPATHOGENIC ESCHERICHIA-COLI; OUTER-MEMBRANE PROTEIN; ACTIN-BASED MOTILITY; SALMONELLA-TYPHIMURIUM INVASION; GRAM-NEGATIVE BACTERIA; HUMAN EPITHELIAL-CELLS; FIBRONECTIN-BINDING PROTEIN; GREEN FLUORESCENT PROTEIN; MEDIATES SPECIFIC BINDING; CULTURED-MAMMALIAN-CELLS AB Bacterial pathogens employ a number of genetic strategies to cause infection and occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a large number of host targets. Similarly, there are only a few conserved ways to build the bacterial pilus and nonpilus adhesins used by pathogens to adhere to host substrates. Bacterial entry into host cells (invasion) is a complex mechanism. However; several common invasion themes exist in diverse microorganisms. Similarly, once inside a host cell, pathogens have a limited number of ways to ensure their survival whether remaining within a host vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses is key to the success of a pathogen. Several common themes again are employed, including antigenic variation camouflage by binding host molecules, and enzymatic degradation of host immune components. Most virulence factors are found on the bacterial surface or secreted into their immediate environment, yet virulence factors operate through a relatively small number of microbial secretion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate rime that causes infection. Finally, virulence factors maintained on mobile genetic elements and pathogenicity islands ensure that new strains of pathogens evolve constantly. Comprehension of these common themes in microbial pathogenicity is critical to the understanding and study of bacterial virulence mechanisms and to the development of new ''anti-virulence'' agents, which are so desperately needed to replace antibiotics. C1 UNIV BRITISH COLUMBIA,DEPT BIOCHEM & MOL BIOL,VANCOUVER,BC V6T 1Z3,CANADA. UNIV BRITISH COLUMBIA,DEPT IMMUNOL & MICROBIOL,VANCOUVER,BC V6T 1Z3,CANADA. STANFORD UNIV,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. NIAID,ROCKY MT LAB,HAMILTON,MT 59840. RP Finlay, BB (reprint author), UNIV BRITISH COLUMBIA,BIOTECHNOL LAB,237-6174 UNIV BLVD,VANCOUVER,BC V6T 1Z3,CANADA. NR 372 TC 955 Z9 986 U1 22 U2 183 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD JUN PY 1997 VL 61 IS 2 BP 136 EP & PG 36 WC Microbiology SC Microbiology GA XN207 UT WOS:A1997XN20700002 PM 9184008 ER PT J AU Sherman, ME Schiffman, MH Mango, LJ Kelly, D Acosta, D Cason, Z Elgert, P Zaleski, S Scott, DR Kurman, RJ Stoler, M Lorincz, AT AF Sherman, ME Schiffman, MH Mango, LJ Kelly, D Acosta, D Cason, Z Elgert, P Zaleski, S Scott, DR Kurman, RJ Stoler, M Lorincz, AT TI Evaluation of PAPNET testing as an ancillary tool to clarify the status of the ''atypical'' cervical smear SO MODERN PATHOLOGY LA English DT Article DE ASCUS; Bethesda System; cervix; human papillomavirus; PAPNET; reproducibility; smear ID HUMAN PAPILLOMAVIRUS; UNDETERMINED SIGNIFICANCE; QUALITY ASSURANCE; NEGATIVE SMEARS; SQUAMOUS CELLS; HYBRID CAPTURE; CERVICOGRAPHY; DIAGNOSIS; WOMEN; RISK AB To assess the utility of the PAPNET system (Neuromedical Systems Inc., Suffern, NY) in clarifying the status of cervical smears showing borderline abnormalities, we analyzed the results of five cytotechnologists who reclassified 200 ''atypical'' smears by evaluating PAPNET images only. The interobserver agreement (reliability) of the PAPNET reviewers was computed, and their readings were compared with three standards: the consensus diagnosis of five pathologists who used light microscopy, the detection of cancer-associated human papillomavirus DNA by Southern analysis, and the correlation with diagnoses of biopsy specimens obtained during passive follow-up. The PAPNET reviewers classified 18 to 65% of cases as normal, 25 to 42% as equivocal, and 10 to 55% as abnormal. Unanimous interobserver agreement was achieved in only 24 (13%) cases. Four of the five PAPNET reviewers agreed moderately well with the results of the pathology reference panel. In four of the five PAPNET reviews, classification of cases as abnormal was strongly correlated with the detection of cancer-associated types of human papillomavirus. Consensus PAPNET results of abnormal were predictive of abnormal histologic findings at follow-up. Theoretically, if colposcopy had been performed on all of the women with equivocal or abnormal PAPNET results (based on the consensus of the panel), as much as 95% of biopsy-confirmed lesions could have been detected, but 79% of women would have been referred. Restriction of colposcopy referral to women with definitely abnormal PAPNET readings would have reduced referrals to 31%, but the sensitivity of the triage would have dropped to 51% of biopsy-confirmed lesions. C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. NCI,DIV EPIDEMIOL & GENET,BETHESDA,MD 20892. NEUROMED SYST INC,SUFFERN,NY. JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205. UNIV CALIF LOS ANGELES,DEPT PATHOL,LOS ANGELES,CA 90024. UNIV MISSISSIPPI,MED CTR,DEPT PATHOL,JACKSON,MS 39216. MONTEFIORE MED CTR,DEPT PATHOL,BRONX,NY 10467. UNIV IOWA,DEPT PATHOL,IOWA CITY,IA 52242. KAISER PERMANENTE,DEPT PATHOL,PORTLAND,OR. UNIV VIRGINIA,DEPT PATHOL,CHARLOTTESVILLE,VA 22903. DIGENE CORP,SILVER SPRING,MD. NR 23 TC 13 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUN PY 1997 VL 10 IS 6 BP 564 EP 571 PG 8 WC Pathology SC Pathology GA XE334 UT WOS:A1997XE33400008 PM 9195573 ER PT J AU Brown, K Franzoso, G Baldi, L Carlson, L Mills, L Lin, YC Gerstberger, S Siebenlist, U AF Brown, K Franzoso, G Baldi, L Carlson, L Mills, L Lin, YC Gerstberger, S Siebenlist, U TI The signal response of I kappa B alpha is regulated by transferable N- and C-terminal domains SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CANDIDATE PROTOONCOGENE BCL-3; UBIQUITIN-PROTEASOME PATHWAY; ONCOPROTEIN BCL-3; DNA-BINDING; PHOSPHORYLATION; ACTIVATION; INHIBITOR; SITE; TRANSACTIVATION; DEGRADATION AB I kappa B alpha retains the transcription factor NF-kappa B in the cytoplasm, thus inhibiting its function. Various stimuli inactivate I kappa B alpha by triggering phosphorylation of the N-terminal residues Ser32 and Ser36. Phosphorylation of both serines is demonstrated directly by phosphopeptide mapping utilizing calpain protease, which cuts approximately 60 residues from the N terminus, and by analysis of mutants lacking one or both serine residues. Phosphorylation is followed by rapid proteolysis, and the liberated NF-kappa B translocates to the nucleus, where it activates transcription of its target genes. Transfer of the N-terminal domain of I kappa B alpha to the ankyrin domain of the related oncoprotein Bcl-3 or to the unrelated protein glutathione S-transferase confers Signal-induced phosphorylation on the resulting chimeric proteins. If the C-terminal domain of I kappa B alpha is transferred as well, the resulting chimeras exhibit both signal-induced phosphorylation and rapid proteolysis. Thus, the signal response of I kappa B alpha is controlled by transferable N-terminal and C-terminal domains. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. RI Baldi, Lucia/D-9491-2011 OI Baldi, Lucia/0000-0001-5550-9435 NR 48 TC 38 Z9 38 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1997 VL 17 IS 6 BP 3021 EP 3027 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WZ637 UT WOS:A1997WZ63700006 PM 9154800 ER PT J AU Zhang, F Kirouac, M Zhu, NN Hinnebusch, AG Rolfes, RJ AF Zhang, F Kirouac, M Zhu, NN Hinnebusch, AG Rolfes, RJ TI Evidence that complex formation by Bas1p and Bas2p (Pho2p) unmasks the activation function of Bas1p in an adenine-repressible step of ADE gene transcription SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DNA-BINDING; SHUTTLE VECTORS; HIS4 TRANSCRIPTION; MESSENGER-RNA; HO PROMOTER; YEAST; PROTEIN; SEQUENCES; DOMAIN AB Bas1p and Bas2p (Pho2p) are Myb-related and homeodomain DNA binding proteins, respectively, required for transcription of adenine biosynthetic genes in Saccharomyces cerevisiae. The repression of ADE genes in adenine-replete cells involves down-regulation of the functions of one or both of these activator proteins. A LexA-Bas2p fusion protein was found to activate transcription from a lexAop-lacZ reporter independently of both BAS1 function and the adenine Levels in the medium. In contrast, a LexA-Bas1p fusion activated the lexAop reporter in a BAS2-dependent and adenine-regulated fashion. The DNA binding activity of Bas2p was not needed for its ability to support activation of the lexAop reporter by LexA-Bas1p, indicating that LexA-Bas1p recruits Bas2p to this promoter. The activation functions of both authentic Bas1p and LexA-Bas1p were stimulated under adenine-repressing conditions by overexpression of Bas2p, suggesting that complex formation by these proteins is inhibited in adenine-replete cells. Replacement of Asp-617 with Asn in Bas1p or LexA-Bas1p allowed either protein to activate transcription under repressing conditions in a manner fully dependent on Bas2p, suggesting that this mutation reduces the negative effect of adenine on complex formation by Bas1p and Bas2p. Deletions of N-terminal and C-terminal segments from the Bas1p moiety of LexA-Bas1p allowed high-level activation by the truncated proteins independently of Bas2p and adenine levels in the medium. From these results we propose that complex formation between Bas1p and Bas2p unmasks a latent activation function in Bas1p as a critical adenine-regulated step in transcription of the ADE genes. C1 NICHHD,LAB EUKARYOT GENE REGULAT,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT BIOL,WASHINGTON,DC 20057. NR 52 TC 38 Z9 39 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1997 VL 17 IS 6 BP 3272 EP 3283 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WZ637 UT WOS:A1997WZ63700032 PM 9154826 ER PT J AU Attaie, A Kim, E Wilcox, ER Lalwani, AK AF Attaie, A Kim, E Wilcox, ER Lalwani, AK TI A splice-site mutation affecting the paired box of PAX3 in a three generation family with Waardenburg syndrome type I (WS1) SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE Waardenburg syndrome; deafness; PAX3; paired box; splice-site mutation; transcription factor ID SPLOTCH; GENE; MOUSE AB Waardenburg syndrome, an autosomal dominant disorder characterized by sensorineural hearing loss, pigmentary disturbances and other developmental defects, is the most frequent form of congenital deafness in humans. Mutations in the PAX3 gene, a transcription factor expressed during embryonic development, is associated with WS types I and III. Here we report the identification of a novel acceptor splice site mutation (86-2 A-->G) in the paired domain of the human PAX3 gene causing WS type I in a three generation family. (C) 1997 Academic Press Limited. C1 UNIV CALIF SAN FRANCISCO,DEPT OTOLARYNGOL HEAD & NECK SURG,LAB MOL OTOL,EPSTEIN LABS,SAN FRANCISCO,CA 94143. NATL INST DEAFNESS & OTHER COMMUN DISORDERS,MOL GENET LAB,NIH,BETHESDA,MD 20892. NR 13 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD JUN PY 1997 VL 11 IS 3 BP 233 EP 236 DI 10.1006/mcpr.1997.0101 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA XJ255 UT WOS:A1997XJ25500010 PM 9232624 ER PT J AU Orren, DK Petersen, LN Bohr, VA AF Orren, DK Petersen, LN Bohr, VA TI Persistent DNA damage inhibits S-phase and G(2) progression, and results in apoptosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID DIHYDROFOLATE-REDUCTASE GENE; CELL-CYCLE CHECKPOINTS; HAMSTER OVARY CELLS; PYRIMIDINE DIMERS; CHO CELLS; THYMOCYTE APOPTOSIS; REPLICATION FORKS; MOLECULAR-CLONING; HUMAN FIBROBLASTS; INDUCE APOPTOSIS AB We used genetically related Chinese hamster ovary cell lines proficient or deficient in DNA repair to determine the direct role of UV-induced DNA photoproducts in inhibition of DNA replication and in induction of G(2) arrest and apoptosis. UV irradiation of S-phase-synchronized cells causes delays in completion of the S-phase sometimes followed by an extended G, arrest and apoptosis. The effects of UV irradiation during the S-phase on subsequent cell cycle progression are magnified in repair-deficient cells, indicating that these effects are initiated by persistent DNA damage and not by direct UV activation of signal transduction pathways. Moreover, among the lesions introduced by UV irradiation, persistence of (6-4) photoproducts inhibits DNA synthesis much more than persistence of cyclobutane pyrimidine dimers (which appear to be efficiently bypassed by the DNA replication apparatus). Apoptosis begins approximately 24 h after UV irradiation of S-phase-synchronized cells, occurs to a greater extent in repair-deficient cells, and correlates well with the inability to escape from an extended late S-phase-G(2) arrest. We also find that nucleotide excision repair activity (including its coupling to transcription) is similar in the S-phase to what we have previously measured in G(1) and G(2). C1 NIA,GENET MOL LAB,NIH,BALTIMORE,MD 21224. UNIV COPENHAGEN,INST MOL PATHOL,DK-2100 COPENHAGEN,DENMARK. NR 61 TC 107 Z9 109 U1 0 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUN PY 1997 VL 8 IS 6 BP 1129 EP 1142 PG 14 WC Cell Biology SC Cell Biology GA XG993 UT WOS:A1997XG99300015 PM 9201721 ER PT J AU Haroutunian, V Greig, N Pei, XF Utsuki, T Gluck, R Acevedo, LD Davis, KL Wallace, WC AF Haroutunian, V Greig, N Pei, XF Utsuki, T Gluck, R Acevedo, LD Davis, KL Wallace, WC TI Pharmacological modulation of Alzheimer's beta-amyloid precursor protein levels in the CSF of rats with forebrain cholinergic system lesions SO MOLECULAR BRAIN RESEARCH LA English DT Article DE amyloid beta-protein; amyloid beta-protein, precursor; rat; Alzheimer's disease; cerebrospinal fluid; cerebral cortex; basal nucleus of Meynert; acetylcholine; acetylcholinesterase; acetylcholinesterase inhibitor; butyrylcholinesterase; receptor, muscarinic; DFP; phenserine; in vivo ID INDUCED LEARNING IMPAIRMENT; 14-UNIT T-MAZE; ORAL PHYSOSTIGMINE; SENILE DEMENTIA; NUCLEUS BASALIS; CEREBRAL-CORTEX; AGED RATS; DISEASE; MEMORY; CHOLINESTERASE AB Abnormal deposition and accumulation of Alzheimer's amyloid beta-protein (A beta) and degeneration of forebrain cholinergic neurons are among the principal features of Alzheimer's disease. Studies in rat model systems have shown that forebrain cholinergic deficits are accompanied by induction of cortical beta-amyloid precursor protein (beta-APP) mRNAs and increased levels of secreted beta-APP in the CSF. The studies reported here determined whether the CSF levels of secreted beta-APP could be altered pharmacologically. In different experiments, rats with lesions of the forebrain cholinergic system received injections of vehicle, a muscarinic receptor antagonist scopolamine, or one of two cholinesterase inhibitors - diisopropyl phosphorofluoridate (DFP) or phenserine. Scopolamine was administered to determine whether the levels of beta-APP in the CSF could be increased by anticholinergic agents. The cholinesterase inhibitors were administered to determine whether the forebrain cholinergic system lesion-induced increases in CSF beta-APP could be reduced by cholinergic augmentation. Scopolamine administration led to a significant increase in the CSF levels of secreted beta-APP in sham-lesioned rats. Phenserine, a novel, reversible acetyl-selective cholinesterase inhibitor, significantly decreased the levels of secreted beta-APP in the CSF of forebrain cholinergic system-lesioned rats whereas DFP, a relatively non-specific cholinesterase inhibitor, failed to affect CSF levels of secreted beta-APP. These results suggest that the levels of secreted beta-APP in the CSF can be pharmacologically modulated but that this modulation is dependent upon the status of the forebrain cholinergic system and the pharmacological properties of the drugs used to influence it. C1 BRONX VET ADM MED CTR,NEW YORK,NY. MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY. NIA,NEUROSCI LAB,BETHESDA,MD 20892. NIA,MOL & CELLULAR BIOL PROGRAM,MOL PHYSIOL & GENET SECT,BETHESDA,MD 20892. NR 59 TC 60 Z9 60 U1 0 U2 2 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 JUN PY 1997 VL 46 IS 1-2 BP 161 EP 168 DI 10.1016/S0169-328X(96)00297-5 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XA506 UT WOS:A1997XA50600019 ER PT J AU DeBartolomeis, A Koprivica, V Pickar, D Crawley, JN Abbott, LC AF DeBartolomeis, A Koprivica, V Pickar, D Crawley, JN Abbott, LC TI Opioidergic and dopaminergic gene expression in the caudate-putamen and accumbens of the mutant mouse, tottering (tg/tg) SO MOLECULAR BRAIN RESEARCH LA English DT Article DE enkephalin; dynorphin; D-2 dopamine receptor; mRNA; epilepsy; striatum; hybridization histochemistry, in situ ID MESSENGER-RNA LEVELS; RAT-BRAIN; TYROSINE-HYDROXYLASE; ENKEPHALIN; RECEPTORS; NEURONS; INVOLVEMENT; MORPHINE; SEIZURES; AGONISTS AB Expression of preproenkephalin, dynorphin and D-2 dopamine receptor mRNAs was examined in selected regions of the forebrain of homozygous and heterozygous tottering mice, using in situ hybridization histochemistry. Homozygous tottering mice carry an autosomal recessive mutation causing them to exhibit petit mal-like epilepsy. Preproenkephalin mRNA levels were significantly higher in the lateral caudate and the core of the nucleus accumbens of homozygous tottering mice compared to wild-type controls. No differences were observed in the expression of dynorphin and D-2 receptor mRNA distribution in brain regions examined in the mutant mice as compared to wild-type controls. (C) 1997 Elsevier Science B.V. C1 NIMH,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. UNIV ILLINOIS,COLL VET MED,DEPT VET BIOSCI,URBANA,IL 61801. OI de Bartolomeis, Andrea/0000-0002-3188-5652 NR 27 TC 4 Z9 4 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 JUN PY 1997 VL 46 IS 1-2 BP 321 EP 324 DI 10.1016/S0169-328X(97)00027-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA XA506 UT WOS:A1997XA50600038 ER PT J AU Scully, KM Gleiberman, AS Lindzey, J Lubahn, DB Korach, KS Rosenfeld, MG AF Scully, KM Gleiberman, AS Lindzey, J Lubahn, DB Korach, KS Rosenfeld, MG TI Role of estrogen receptor-alpha in the anterior pituitary gland SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; RAT PROLACTIN GENE; MESSENGER-RIBONUCLEIC-ACID; GROWTH-HORMONE; TRANSCRIPTIONAL ACTIVATION; RESPONSIVE ELEMENT; TRANSGENIC MICE; GNRH RECEPTOR; SUBUNIT GENE; EXPRESSION AB Targeted insertional disruption of the mouse estrogen receptor-alpha (ER alpha) gene has provided a genetic model in which to test hypotheses that estrogens exert important effects in development and homeostatic functions of the anterior pituitary gland, particularly in the lactotroph and gonadotroph cell types. Analysis of ER alpha gene-disrupted mice reveals a marked reduction in PRL mRNA and a decrease in lactotroph cell number, but normal specification of lactotroph cell phenotype. Gonadotropin mRNA levels in ERR alpha gene-disrupted female mice are elevated, consistent with previously described transcriptional suppression of gonadotropin subunit gene expression in response to sustained administration of estrogen in wild type mice. These results provide genetic evidence that ER alpha plays a critical role in PRL and gonadotropin gene transcription and is involved in lactotroph cell growth, but is not required for specification of lactotroph cell phenotype. C1 UNIV CALIF SAN DIEGO, HOWARD HUGHES MED INST, DEPT & SCH MED, LA JOLLA, CA 92093 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. OI Korach, Kenneth/0000-0002-7765-418X NR 55 TC 159 Z9 161 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 1997 VL 11 IS 6 BP 674 EP 681 DI 10.1210/me.11.6.674 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XA528 UT WOS:A1997XA52800005 PM 9171231 ER PT J AU Ooi, GT Cohen, FJ Tseng, LYH Rechler, MM Boisclair, YR AF Ooi, GT Cohen, FJ Tseng, LYH Rechler, MM Boisclair, YR TI Growth hormone stimulates transcription of the gene encoding the acid-labile subunit (ALS) of the circulating insulin-like growth factor-binding protein complex and ALS promoter activity in rat liver SO MOLECULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 10th International Congress of Endocrinology CY JUN 12-15, 1996 CL SAN FRANCISCO, CA ID IGF-I TREATMENT; C-FOS; MESSENGER-RNA; TYROSINE PHOSPHORYLATION; LARON-SYNDROME; RAPID CHANGES; SERUM; RECEPTOR; ACTIVATION; ELEMENTS AB The growth-promoting activity of GH, the principal hormonal determinant of body size, is mediated by insulin-like growth factor I (IGF-I). Most of the IGF-I in plasma circulates in a 150-kDa complex that contains IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit (ALS). The 150-kDa complex serves as a reservoir of IGF-I and determines its bioavailability to the tissues. Formation of the 150-kDa complex depends upon the synthesis of ALS, which is synthesized primarily in liver and is regulated by GH. The present study demonstrates that GH stimulates ALS gene transcription in rat liver and ALS promoter activity in a rat hepatoma cell line. ALS messenger RNA (mRNA) and ALS nuclear transcripts were decreased to similar extents in the livers of GH-deficient hypophysectomized rats. GH increased hepatic ALS mRNA within 3-4 h to about 65% of the levels seen in sham-operated control rats. To confirm that GH stimulated ALS gene transcription, we transiently transfected an ALS promoter-luciferase reporter gene construct into H4-II-E rat hepatoma cells and primary rat hepatocytes. Recombinant human GH (hGH) stimulated promoter activity about 3-fold. In contrast, basal promoter activity was lower, and GH stimulation was absent when the ALS reporter construct was transfected into ON-responsive 3T3-F442A mouse preadipocyte fibroblasts. GH stimulation of ALS promoter activity in H4-II-E cells was mediated by functional GN receptors; nonprimate (rat and bovine) OH gave identical stimulation to hGH, and stimulation by hGH occurred at physiological concentrations. Reverse transcriptase-PCR analysis indicated that ON receptor mRNA was present in H4-II-E cells at approximately 40% of the level seen in rat liver. ON also induced the expression of the endogenous c-fos gene, indicating that the signaling pathway necessary for the activation of gene expression by ON was intact in H4-II-E cells. Thus, H4-II-E cells are a ON-responsive liver cell line that should provide a useful system in which to study the molecular mechanism of transcriptional regulation by ON of ALS and other hepatic genes. C1 CORNELL UNIV,DEPT ANIM SCI,ITHACA,NY 14853. RP Ooi, GT (reprint author), NIDDKD,MOL & CELLULAR ENDOCRINOL BRANCH,GROWTH & DEV SECT,NIH,BLDG 10,ROOM 8D14,10 CTR DR,BETHESDA,MD 20892, USA. NR 61 TC 78 Z9 79 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 1997 VL 11 IS 7 BP 997 EP 1007 DI 10.1210/me.11.7.997 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XB329 UT WOS:A1997XB32900016 PM 9178759 ER PT J AU WynshawBoris, A Ryan, G Deng, CX Chan, DC JacksonGrusby, L Larson, D Dunmore, JH Leder, P AF WynshawBoris, A Ryan, G Deng, CX Chan, DC JacksonGrusby, L Larson, D Dunmore, JH Leder, P TI The role of a single formin isoform in the limb and renal phenotypes of limb deformity SO MOLECULAR MEDICINE LA English DT Article ID APICAL ECTODERMAL RIDGE; MOUSE LIMB; SONIC-HEDGEHOG; GENE; GROWTH; EXPRESSION; KIDNEY; FGF-4; MICE; PROTOONCOGENE AB Background: Mutations of the murine limb deformity (ld) locus are responsible for a pleiotropic phenotype of completely penetrant limb malformations and incompletely penetrant renal agenesis and/or dysgenesis. The ld locus encodes a complex family of mRNA and protein isoforms. Materials and Methods: To examine the role of one of the more prominent of these isoforms, isoform IV, we specifically eliminated it by gene targeting. Results: Unlike other mutant ld mice, homozygous mice bearing this isoform IV disruption display incompletely penetrant renal agenesis, but have perfectly normal limbs. Whole mount in situ hybridization demonstrated that this targeted disruption was specific for isoform IV and did not interfere with the expression of other id isoforms. The isoform IV-disrupted allele of Id does not complement the renal agenesis phenotype of other ld alleles, in a manner consistent with its penetrance, and like the isoform IV-deficient mice, these compound heterozygotes have normal limbs. Sequence analysis of formin isoform IV in other ld mutant alleles did not detect any amino acid changes relative to the strain of origin of the mutant allele. Conclusions: Thus, the disruption of isoform IV is sufficient for the renal agenesis phenotype, but not the limb phenotype of ld mutant mice. Structural mutations in this isoform are only one of several genetic mechanisms leading to the renal phenotype, since amino acid changes in this isoform were not detected. These results demonstrate that this gene is limb deformity, and that variable isoform expression may play a role in generating the pleiotropic ld phenotype. C1 HARVARD UNIV,SCH MED,DEPT GENET,HOWARD HUGHES MED INST,BOSTON,MA. RP WynshawBoris, A (reprint author), NATL HUMAN GEONOME RES INST,LAB GENET DIS RES,NIH,BLDG 49-4A68,BETHESDA,MD 20892, USA. RI deng, chuxia/N-6713-2016 NR 49 TC 27 Z9 27 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 1076-1551 J9 MOL MED JI Mol. Med. PD JUN PY 1997 VL 3 IS 6 BP 372 EP 384 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XJ685 UT WOS:A1997XJ68500004 PM 9234242 ER PT J AU Konkel, ME Garvis, SG Tipton, SL Anderson, DE Cieplak, W AF Konkel, ME Garvis, SG Tipton, SL Anderson, DE Cieplak, W TI Identification and molecular cloning of a gene encoding a fibronectin-binding protein (CadF) from Campylobacter jejuni SO MOLECULAR MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; PEPTIDOGLYCAN-ASSOCIATED LIPOPROTEIN; GUILLAIN-BARRE-SYNDROME; HUMAN EPITHELIAL-CELLS; PSEUDOMONAS-FLUORESCENS; NUCLEOTIDE-SEQUENCE; LEGIONELLA-PNEUMOPHILA; HEMOPHILUS-INFLUENZAE; SURFACE-PROTEINS; ESCHERICHIA-COLI AB Campylobacter jejuni, a Gram-negative bacterium, is a common cause of gastrointestinal disease. By analogy with other enteric pathogens such as Salmonella and Shigella, the ability of C. jejuni to bind to host cells is thought to be essential in the pathogenesis of enteritis. Scanning electron microscopy of infected INT407 cells suggested that C. jejuni bound to a component of the extracellular matrix, Binding assays using immobilized extracellular matrix proteins and soluble fibronectin showed specific and saturable binding of fibronectin to C. jejuni. Ligand immunoblot assays using I-125-labelled fibronectin revealed specific binding to an outer membrane protein with an apparent molecular mass of 37 kDa. A rabbit antiserum, raised against the gel-purified protein, reacted with a 37 kDa protein in all C. jejuni isolates (n=15) as tested by immunoblot analysis. Antibodies present in convalescent serum from C. jejuni-infected individuals also recognized a 37 kDa protein. The gene encoding the immunoreactive 37 kDa protein was cloned and sequenced. Sequencing of overlapping DNA fragments revealed an open reading frame (ORF) that encodes a protein of 326 amino acids with a calculated molecular mass of 36 872 Da. The deduced amino acid sequence of the ORF exhibited 52% similarity and 28% identity to the root adhesin protein from Pseudomonas fluorescens. Isogenic C. jejuni mutants which lack the 37 kDa outer membrane protein, which we have termed CadF, displayed significantly reduced binding to fibronectin. Biotinylated fibronectin bound to a protein with an apparent molecular mass of 37 kDa in the outer membrane protein extracts from wild-type C. jejuni as judged by ligand-binding blots. These results indicate that the binding of C. jejuni to fibronectin is mediated by the 37 kDa outer membrane protein which is conserved among C. jejuni isolates. C1 SACRED HEART MED CTR,DEPT LAB MED,SPOKANE,WA 99220. WASHINGTON STATE UNIV,DEPT MICROBIOL,PULLMAN,WA 99164. RP Konkel, ME (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840, USA. OI garvis, steve/0000-0002-0547-0672 NR 47 TC 178 Z9 182 U1 3 U2 11 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUN PY 1997 VL 24 IS 5 BP 953 EP 963 DI 10.1046/j.1365-2958.1997.4031771.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA XG801 UT WOS:A1997XG80100007 PM 9220003 ER PT J AU Daniels, MP AF Daniels, MP TI Intercellular communication that mediates formation of the neuromuscular junction SO MOLECULAR NEUROBIOLOGY LA English DT Review DE neuromuscular junction; synapse development; acetylcholine receptor; nerve terminal; receptor tyrosine kinases; extracellular matrix; cell adhesion; growth factors; agrin; proteolysis ID ACETYLCHOLINE-RECEPTOR CLUSTERS; CULTURED MUSCLE-CELLS; GENE-RELATED PEPTIDE; FIBROBLAST GROWTH-FACTOR; HEPARAN-SULFATE PROTEOGLYCAN; ORIGINAL SYNAPTIC SITES; TORPEDO ELECTRIC ORGAN; ADULT SKELETAL-MUSCLE; EPSILON-SUBUNIT GENE; AGRIN-LIKE MOLECULES AB Reciprocal signals between the motor axon and myofiber induce structural and functional differentiation in the developing neuromuscular junction (NMJ). Elevation of presynaptic acetylcholine (ACh) release on nerve-muscle contact and the correlated increase in axonal-free calcium are triggered by unidentified membrane molecules. Restriction of axon growth to the developing NMJ and formation of active zones for ACh release in the presynaptic terminal may be induced by molecules in the synaptic basal lamina, such as S-laminin, heparin binding growth factors, and agrin. Acetylcholine receptor (AChR) synthesis by muscle cells may be increased by calcitonin gene-related peptide (CGRP), ascorbic acid, and AChR-inducing activity (ARIA)/heregulin, which is the best-established regulator. Heparin binding growth factors, proteases, adhesion molecules, and agrin all may be involved in the induction of AChR redistribution to form postsynaptic-like aggregates. However, the strongest case has been made for agrin's involvement. ''Knockout'' experiments have implicated agrin as a primary anterograde signal for postsynaptic differentiation and muscle-specific kinase (MuSK), as a putative agrin receptor. It is Likely that both presynaptic and postsynaptic differentiation are induced by multiple molecular signals. Future research should reveal the physiological roles of different molecules, their interactions, and the identity of other molecular participants. RP Daniels, MP (reprint author), NHLBI, LAB BIOCHEM GENET, NIH, BLDG 10, BETHESDA, MD 20892 USA. NR 225 TC 18 Z9 19 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD JUN PY 1997 VL 14 IS 3 BP 143 EP 170 DI 10.1007/BF02740654 PG 28 WC Neurosciences SC Neurosciences & Neurology GA XT887 UT WOS:A1997XT88700002 PM 9294861 ER PT J AU Zeldin, DC Foley, J Goldsworthy, SM Cook, ME Boyle, JE Ma, JX Moomaw, CR Tomer, KB Steenbergen, C Wu, S AF Zeldin, DC Foley, J Goldsworthy, SM Cook, ME Boyle, JE Ma, JX Moomaw, CR Tomer, KB Steenbergen, C Wu, S TI CYP2J subfamily cytochrome P450s in the gastrointestinal tract: Expression, localization, and potential functional significance SO MOLECULAR PHARMACOLOGY LA English DT Article ID ARACHIDONIC-ACID EPOXYGENASE; EPOXYEICOSATRIENOIC ACIDS; EXTRAHEPATIC TISSUES; INTESTINAL-MUCOSA; IMMUNOHISTOCHEMICAL LOCALIZATION; IMMUNOCYTOCHEMICAL LOCALIZATION; ENANTIOFACIAL SELECTIVITY; MONOCLONAL-ANTIBODY; EPOXIDE HYDROLASE; HUMAN-KIDNEY AB Our laboratory recently described a new human cytochrome P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3), both of which were expressed in extrahepatic tissues. Northern analysis of RNA prepared from the human and rat intestine demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed primarily in the small intestine and colon. In contrast, immunoblotting studies using a polyclonal antibody raised against recombinant CYP2J2 showed that CYP2J proteins were expressed throughout the gastrointestinal tract. Immunohistochemical staining of formalin-fixed, paraffin-embedded intestinal sections using anti-CYP2J2 IgG and avidin-biotin-peroxidase detection revealed that CYP2J proteins were present at high levels in nerve cells of autonomic ganglia, epithelial cells, intestinal smooth muscle cells, and vascular endothelium. The distribution of this immunoreactivity was confirmed by in situ hybridization using a CYP2J2-specific antisense RNA probe. Microsomal fractions prepared from human jejunum catalyzed the NADPH-dependent metabolism of arachidonic acid to epoxyeicosatrienoic acids as the principal reaction products. Direct evidence for the in vivo epoxidation of arachidonic acid by intestinal cytochrome P450 was provided by documenting, for the first time, the presence of epoxyeicosatrienoic acids in human jejunum by gas chromatography/mass spectrometry. We conclude that human and rat intestine contain an arachidonic acid epoxygenase belonging to the CYP2J subfamily that is localized to autonomic ganglion cells, epithelial cells, smooth muscle cells, and vascular endothelium. in addition to the known effects on intestinal vascular tone, we speculate that CYP2J products may be involved in the release of intestinal neuropeptides, control of intestinal motility, and/or modulation of intestinal fluid/electrolyte transport. C1 NIEHS, LAB EXPT PATHOL, RES TRIANGLE PK, NC 27709 USA. NIEHS, LAB MOL BIOPHYS, RES TRIANGLE PK, NC 27709 USA. PATHOL ASSOCIATES INT, DURHAM, NC 27713 USA. DUKE UNIV, MED CTR, DEPT PATHOL, DURHAM, NC 27710 USA. RP NIEHS, NIH,PULM PATHOBIOL LAB,111 ALEXANDER DR,BLDG 101, D236, RES TRIANGLE PK, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 FU NHLBI NIH HHS [R01 HL039752]; NIA NIH HHS [P50-AG05128] NR 41 TC 92 Z9 94 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 1997 VL 51 IS 6 BP 931 EP 943 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XD653 UT WOS:A1997XD65300005 PM 9187259 ER PT J AU Scala, S Akhmed, N Rao, US Paull, K Lan, LB Dickstein, B Lee, JS Elgemeie, GH Stein, WD Bates, SE AF Scala, S Akhmed, N Rao, US Paull, K Lan, LB Dickstein, B Lee, JS Elgemeie, GH Stein, WD Bates, SE TI P-glycoprotein substrates and antagonists cluster into two distinct groups SO MOLECULAR PHARMACOLOGY LA English DT Article ID PREDICTED TRANSMEMBRANE DOMAIN; MULTIDRUG-RESISTANT CELLS; FUNCTIONAL CONSEQUENCES; ATPASE ACTIVITY; DRUG-RESISTANCE; MUTATIONS; EXPRESSION; TRANSPORT; LINES; CYTOTOXICITY AB To gather further insight into the interaction between P-glycoprotein (Pgp) and its substrates, 167 compounds were analyzed in multidrug resistant human colon carcinoma cells. These compounds were selected from the National Cancer Institute Drug Screen repository using computer-generated correlations with known Pgp substrates and antagonists. The compounds were prospectively defined as Pgp substrates if cytotoxicity was increased greater than or equal to 4-fold by the addition of cyclosporin A (CsA) and as Pgp antagonists if inhibition of efflux increased rhodamine accumulation by 4-fold. Among the 84 agents that met either criterion, 35 met only the criterion for substrates, 42 met only the criterion for antagonists, and only seven met both criteria. Thus, compounds interacting with Pgp form two distinct groups: one comprising cytotoxic compounds that are transported and have poor or no antagonistic activity and a second comprising compounds with antagonistic activity and no evidence of significant transport. Vinblastine accumulation and kinetic studies performed on a subset of 18 compounds similarly differentiated substrates and antagonists, but inhibition of H-3-azidopine labeling and induction of ATPase activity did not. These data support an emerging concept of Pgp in which multiple regions instead of specific sites are involved in drug transport. C1 NCI,NIH,MED BRANCH,DIV CLIN SCI,ROCKVILLE,MD 20892. NCI,NIH,INFORMAT TECHNOL BRANCH,DIV BASIC SCI,ROCKVILLE,MD 20892. UNIV N CAROLINA,DEPT PHARMACOL,CHAPEL HILL,NC 27515. HEBREW UNIV JERUSALEM,ALEXANDER SILBERMAN INST LIFE SCI,JERUSALEM,ISRAEL. GYEONGSANG NATL UNIV,DEPT INTERNAL MED,KYUNGNAM,SOUTH KOREA. HELWAN UNIV,CAIRO,EGYPT. RI Scala, Stefania/K-1380-2016 OI Scala, Stefania/0000-0001-9524-2616 NR 46 TC 178 Z9 180 U1 2 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 1997 VL 51 IS 6 BP 1024 EP 1033 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XD653 UT WOS:A1997XD65300015 PM 9187269 ER PT J AU Germolec, DR Spalding, J Boorman, GA Wilmer, JL Yoshida, T Simeonova, PP Bruccoleri, A Kayama, F Gaido, K Tennant, R Burleson, F Dong, WM Lang, RW Luster, MI AF Germolec, DR Spalding, J Boorman, GA Wilmer, JL Yoshida, T Simeonova, PP Bruccoleri, A Kayama, F Gaido, K Tennant, R Burleson, F Dong, WM Lang, RW Luster, MI TI Arsenic can mediate skin neoplasia by chronic stimulation of keratinocyte-derived growth factors SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Article DE arsenic carcinogenesis; skin cancer, chemicals; growth factor; cytokine ID ALPHA TRANSGENIC MICE; TUMOR-NECROSIS-FACTOR; MOUSE SKIN; TGF-ALPHA; OVEREXPRESSION; HYPERPLASIA; PAPILLOMAS; INDUCTION; GENE; DIFFERENTIATION AB Although numerous epidemiological studies have shown that inorganic arsenicals are human skin carcinogens, there is currently no accepted mechanism for its action or an established animal model for its study. We observed increased mRNA transcripts and secretion of keratinocyte growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-alpha (TGF-alpha) and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) in primary human epidermal keratinocytes cultured in the presence of low micromolar concentrations of sodium arsenite. Total cell numbers, as well as c-myc expression and incorporation of [H-3]thymidine, both indicators of cell proliferation, were also elevated in keratinocyte cultures treated with sodium arsenite, As an in vivo model, the influence of arsenic on mouse skin tumor development was studied in transgenic TG.AC mice which carry the v-Ha-ras oncogene, and can serve as a genetically initiated model for skin carcinogenesis, Following low-dose application of 12-O-tetradecanoyl phorbol-13-acetate (TPA), a marked increase in the number of skin papillomas occurred in transgenic mice receiving arsenic in the drinking water as compared to control drinking water. Papillomas did not develop in arsenic-treated transgenic mice that had not received TPA or arsenic-treated wild-type FVB/N mice, suggesting that arsenic is neither a tumor initiator or promoter but rather an enhancer, Injection of anti-GM-CSF antibodies following application of TPA in transgenic mice reduced the number of papillomas. Consistent with that observed in human keratinocyte cultures, increases in GM-CSF and TGF-alpha mRNA transcripts were found within the epidermis of arsenic-treated mice when compared to controls within 6 weeks of treatment. These results suggest that arsenic enhances papilloma development via the chronic stimulation of keratinocyte-derived growth factors and represents the first example of a chemical carcinogen that acts in this manner. These studies suggest that in vitro studies with human keratinocyte cultures examined in conjunction with TG.AC transgenic mice can provide a useful model for examining the tumor enhancing properties of environmental chemicals. C1 NIH,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. TOKAI UNIV,DEPT ENVIRONM MED,KANAGAWA,JAPAN. UNIV OCCUPAT & ENVIRONM HLTH MED,KITAKYUSHU,FUKUOKA,JAPAN. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. NIOSH,TOXICOL & MOL BIOL BRANCH,MORGANTOWN,WV 26502. RP Germolec, DR (reprint author), NIH,ENVIRONM IMMUNOL & NEUROBIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 119 Z9 120 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD JUN PY 1997 VL 386 IS 3 BP 209 EP 218 DI 10.1016/S1383-5742(97)00006-9 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XG035 UT WOS:A1997XG03500004 PM 9219559 ER PT J AU Gordenin, DA Kunkel, TA Resnick, MA AF Gordenin, DA Kunkel, TA Resnick, MA TI Repeat expansion - All in a flap? SO NATURE GENETICS LA English DT Editorial Material ID DNA RP Gordenin, DA (reprint author), NIEHS,MOL GENET LAB,111 TW ALEXANDER DR,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 28 TC 164 Z9 168 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1997 VL 16 IS 2 BP 116 EP 118 DI 10.1038/ng0697-116 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA XB543 UT WOS:A1997XB54300004 PM 9171819 ER PT J AU Lubeck, MD Natuk, R Myagkikh, M Kalyan, N Aldrich, K Sinangil, F Alipanah, S Murthy, SCS Chanda, PK Nigida, SM Markham, PD ZollaPazner, S Steimer, K Wade, M Reitz, MS Arthur, LO Mizutani, S Davis, A Hung, PP Gallo, RC Eichberg, J RobertGuroff, M AF Lubeck, MD Natuk, R Myagkikh, M Kalyan, N Aldrich, K Sinangil, F Alipanah, S Murthy, SCS Chanda, PK Nigida, SM Markham, PD ZollaPazner, S Steimer, K Wade, M Reitz, MS Arthur, LO Mizutani, S Davis, A Hung, PP Gallo, RC Eichberg, J RobertGuroff, M TI Long-term protection of chimpanzees against high-dose HIV-1 challenge induced by immunization SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT ADENOVIRUS; GLYCOPROTEIN GP120; IMMUNE-RESPONSE; LYMPHOCYTES-T; INFECTION; ANTIBODY; MACAQUES; GP160; CELLS AB A combination AIDS vaccine approach consisting of priming with adenovirus-HIV-1(MN)gp160 recombinants followed by boosting with HIV-1(SF2)gp120 was evaluated in chimpanzees. Long-lasting protection, requiring only three immunizations, was achieved against a low-dose challenge with the SF2 strain of HIV-1 and a subsequent high-dose SF2 challenge administered 1 year later without an intervening boost. Notably, neutralizing antibody responses against both clinical and laboratory isolates developed in three chimpanzees and persisted until the time of high-dose challenge. The possibility that cytotoxic T-lymphocytes contribute to row-dose protection of a chimpanzee lacking neutralizing antibodies is suggested. Our results validate the live vector priming/subunit booster approach and should stimulate interest in assessing this combination vaccine approach in humans. C1 WYETH AYERST RES,RADNOR,PA 19087. NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. CHIRON CORP,EMERYVILLE,CA 94608. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21702. ADV BIOSCI LABS,KENSINGTON,MD 20895. VET AFFAIRS MED CTR,NEW YORK,NY 10010. FU NIAID NIH HHS [AI 32424, AI 36085] NR 42 TC 132 Z9 133 U1 1 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 1997 VL 3 IS 6 BP 651 EP 658 DI 10.1038/nm0697-651 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XB974 UT WOS:A1997XB97400035 PM 9176492 ER PT J AU Zhou, P Goldstein, S Devadas, K Tewari, D Notkins, AL AF Zhou, P Goldstein, S Devadas, K Tewari, D Notkins, AL TI Human CD4(+) cells transfected with IL-16 cDNA are resistant to HIV-1 infection: Inhibition of mRNA expression SO NATURE MEDICINE LA English DT Article ID LYMPHOCYTE CHEMOATTRACTANT FACTOR; HUMAN LYMPHOKINES; MIGRATION; REPLICATION; MODULATION; RECEPTOR; DOMAINS AB Interleukin-16 (IL-16) is secreted by activated CD8+ T lymphocytes and acts on CDC T lymphocytes, monocytes and eosinophils. Recently, the C-terminal 130-amino acid portion of IL-16 was shown to suppress HIV-1 replication in vitro. To explore the potential of human IL-16 for gene therapy, this portion was transfected into HIV-1-susceptible CD4(+) jurkat cells by means of a mammalian expression vector. The stable transfectants synthesized and secreted IL-16 protein. The expression of IL-16 did not alter growth rate and CD4 expression; however, HIV replication was inhibited by as much as 99%. Furthermore, during the initial phase of the infection, equal amounts of HIV-1 proviral DNA were found in cells transfected with IL-16 and with vector alone. In contrast, the 2-kilobase HIV-1 transcripts were markedly reduced and the 4-kb and 9-kb transcripts were undetectable in the cells transfected with IL-16. These findings indicate that IL-16-mediated inhibition of HIV-1 is not at the level of viral entry or reverse transcription, but at messenger RNA expression. C1 NIAID,IMMUNODEFICIENCY VIRUS SECT,INFECT DIS LAB,NIH,ROCKVILLE,MD 20852. RP Zhou, P (reprint author), NIDR,BRANCH ORAL INFECT & IMMUN,NIH,BETHESDA,MD 20892, USA. NR 31 TC 89 Z9 94 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 1997 VL 3 IS 6 BP 659 EP 664 DI 10.1038/nm0697-659 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XB974 UT WOS:A1997XB97400036 PM 9176493 ER PT J AU Tjandra, N Garrett, DS Gronenborn, AM Bax, A Clore, GM AF Tjandra, N Garrett, DS Gronenborn, AM Bax, A Clore, GM TI Defining long range order in NMR structure determination from the dependence of heteronuclear relaxation times on rotational diffusion anisotropy SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; 3-DIMENSIONAL STRUCTURES; BACKBONE DYNAMICS; PROTEINS; SPECTROSCOPY; MACROMOLECULES AB Structure determination by NMR presently relies on short range restraints between atoms in close spatial proximity, principally in the form of short (< 5 Angstrom) interproton distances. In the case of modular or multidomain proteins and linear nucleic acids, the density of short interproton distance contacts between structural elements far apart in the sequence may be insufficient to define their relative orientations. In this paper we show how the dependence of heteronuclear longitudinal and transverse relaxation times on the rotational diffusion anisotropy of non-spherical molecules can be readily used to directly provide restraints for simulated annealing structure refinement that characterize long range order a priori. The method is demonstrated using the N-terminal domain of Enzyme I, a protein of 259 residues comprising two distinct domains with a diffusion anisotropy (D-parallel to/D-perpendicular to of similar to 2. C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 30 TC 149 Z9 151 U1 0 U2 5 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JUN PY 1997 VL 4 IS 6 BP 443 EP 449 DI 10.1038/nsb0697-443 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XC452 UT WOS:A1997XC45200009 PM 9187651 ER PT J AU Jones, CR Arai, T Rapoport, SI AF Jones, CR Arai, T Rapoport, SI TI Evidence for the involvement of docosahexaenoic acid in cholinergic stimulated signal transduction at the synapse SO NEUROCHEMICAL RESEARCH LA English DT Article DE subcellular fractions; docosahexaenoic acid; palmitic acid; cholinergic; phospholipids; signal transduction; synapse; phospholipase; fatty acid model ID RECEPTOR-MEDIATED ACTIVATION; PLASMA C-14 PALMITATE; ARACHIDONIC-ACID; FATTY-ACIDS; AWAKE RATS; ADULT-RAT; BRAIN; PHOSPHOLIPIDS; METABOLISM; OXYGENATION AB [4,5-H-3]Docosahexaenoic acid ([H-3]DHA) or [9,10-H-3]palmitic acid ([H-3]PAM) was infused intravenously for 5 min to awake, adult male rats before and after treatment with arecoline (15 mg/kg, i.p.), a cholinergic agonist. Animals were killed 15 min post-infusion, the brains were rapidly removed and subcellular fractions were obtained after sucrose density centrifugation. In control animals, [H-3]DHA and [H-3]PAM were incorporated into the synaptosomal fractions, representing 50%-60% of total membrane label. Most remaining membrane label (30%-40%) was in the microsomal fraction. Both fractions contained the synaptic marker synaptophysin. The remaining 10% of radioactivity was in the myelin and mitochondrial fractions. Arecoline significantly increased [H-3]DHA entry into the synaptosomal fractions by 100% and into the microsomal fraction by 50%. In these fractions 60%-65% of the [H-3]DHA was in phospholipid, the rest corresponding to free fatty acid and diacylglycerol. In contrast, arecoline did not change [3H]PAM incorporation into any brain fraction. These results demonstrate that plasma [3H]DHA incorporation is selectively increased into synaptic membrane phospholipids of the rat brain in response to cholinergic activation. The increased incorporation of DHA but not of PAM into synaptic membranes in response to cholinergic stimulation indicates a primary role for DHA in phospholipid mediated signal transduction at the synapse involving activation of phospholipase A(2) and/or C. RP NIA, NEUROSCI LAB,NIH,BLDG 10,ROOM 6C103, 10 CTR DR, MSC 1582, BETHESDA, MD 20892 USA. NR 41 TC 89 Z9 93 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 EI 1573-6903 J9 NEUROCHEM RES JI Neurochem. Res. PD JUN PY 1997 VL 22 IS 6 BP 663 EP 670 DI 10.1023/A:1027341707837 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XC139 UT WOS:A1997XC13900001 PM 9178948 ER PT J AU Kawas, C Resnick, S Morrison, A Brookmeyer, R Corrada, M Zonderman, A Bacal, C Lingle, DD Metter, E AF Kawas, C Resnick, S Morrison, A Brookmeyer, R Corrada, M Zonderman, A Bacal, C Lingle, DD Metter, E TI A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: The Baltimore Longitudinal Study of Aging SO NEUROLOGY LA English DT Article ID CHOLINE-ACETYLTRANSFERASE ACTIVITY; DENDRITIC SPINE DENSITY; SENILE DEMENTIA; BASAL FOREBRAIN; OLDER WOMEN; MENSTRUAL-CYCLE; MEMORY FUNCTION; GROWTH-FACTOR; NEURONS; SKILLS AB Previous reports have suggested that estrogen replacement therapy (ERT) in women may exert a protective effect on their risk of developing Alzheimer's disease (AD). We investigated this relationship in the Baltimore Longitudinal Study of Aging (BLSA), a prospective multidisciplinary study of normal aging conducted by the National Institute on Aging. The sample consisted of 472 post- or perimenopausal women followed for up to 16 years in the BLSA. We documented ERT prospectively at each BLSA visit, and we categorized women who had used oral or transdermal estrogens at anytime as ERT users. We used Cox proportional hazards models with time-dependent covariates to estimate the relative risk of developing AD after ERT as compared with women who had not used estrogen replacement. Approximately 45% of the women in the cohort had used ERT, and we diagnosed 34 incident cases of AD (NINCDS/ADRDA criteria) during follow-up, including nine estrogen users. After adjusting for education, the relative risk for AD in ERT users as compared with nonusers was 0.46 (95% CI, 0.209-0.991), indicating a reduced risk of AD for women who had reported the use of estrogen. Our data did not show an effect for duration of ERT usage. Our finding offers additional support for a protective influence of estrogen in AD. Randomized clinical trials are necessary to confirm this association, which could have significant public health impact. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. NIA,LAB PERSONAL & COGNIT,GERONTOL RES CTR,NIH,BALTIMORE,MD. NIA,LONGITUDINAL STUDIES BRANCH,GERONTOL RES CTR,NIH,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOSTAT,BALTIMORE,MD 21205. OI corrada, maria/0000-0002-8168-8593; Zonderman, Alan B/0000-0002-6523-4778 FU NIA NIH HHS [AG05146, AG08325] NR 50 TC 687 Z9 697 U1 4 U2 21 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1997 VL 48 IS 6 BP 1517 EP 1521 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA XE091 UT WOS:A1997XE09100008 PM 9191758 ER PT J AU Litvan, I Sastry, N Sonies, BC AF Litvan, I Sastry, N Sonies, BC TI Characterizing swallowing abnormalities in progressive supranuclear palsy SO NEUROLOGY LA English DT Article ID PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; AMYOTROPHIC-LATERAL-SCLEROSIS; PARKINSONS-DISEASE; DISORDERS; SPEECH; DYSPHAGIA AB The dysphagia that occurs as an early sign of progressive supranuclear palsy (PSP), and which may predispose patients to aspiration pneumonia, has never been fully characterized. We evaluated 27 patients (mean +/- SEM: age, 64.9 +/- 1 years; symptom duration, 52 +/- 5 months) who met the clinical National Institute of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP) criteria for possible or probable PSP, with a swallowing questionnaire, an oral motor and speech examination, and either a modified barium swallow or ultrasound studies. Twenty-eight age- and sex-matched healthy controls (age, 65.6 +/- 1.5 years) were also evaluated with the questionnaire, oral examination, and the ultrasound study. We used ANOVA statistics to evaluate differences between groups; nonparametric correlations to assess associations between swallowing and motor and cognitive abnormalities; and logistic regression analysis to determine if the items of the questionnaire or oral examination predicted ultrasound or modified barium swallow abnormalities. While PSP patients had at least one complaint on the swallowing questionnaire (mean, 6.6), healthy controls had fewer and less relevant complaints (0.31. Patients with moderate-to-severe cognitive disabilities had significantly more complaints of dysphagia than those with mild or no impairment. PSP patients' oral motor skills and speech were mildly impaired but significantly different from those of controls. In the ultrasound studies, PSP patients had significantly fewer continuous swallows and required a longer duration to complete their swallows than did healthy controls. They also had mild-to-moderate abnormalities in the modified barium swallow study. The swallowing questionnaire, oral motor examination, and speech production examination accurately predicted the abnormalities detected with the swallowing studies. While 75% of patients had abnormal speech, all but one had abnormal swallowing studies, Thus, although dysphagia is associated with dysarthria, the two conditions are not always paired in the same patient. Our results suggest that the swallowing questionnaire and oral motor examination are an easy and cost-effective method to predict the swallowing disturbances in PSP. C1 NIH,CTR CLIN,DEPT REHABIL MED,SPEECH & LANGUAGE PATHOL SECT,BETHESDA,MD 20892. RP Litvan, I (reprint author), NINCDS,NEUROEPIDEMIOL BRANCH,NIH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Litvan, Irene/0000-0002-3485-3445 NR 41 TC 35 Z9 39 U1 1 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1997 VL 48 IS 6 BP 1654 EP 1662 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA XE091 UT WOS:A1997XE09100032 PM 9191782 ER PT J AU Rubio, ME Wenthold, RJ AF Rubio, ME Wenthold, RJ TI Glutamate receptors are selectively targeted to postsynaptic sites in neurons SO NEURON LA English DT Article ID DORSAL COCHLEAR NUCLEUS; DIFFERENTIAL EXPRESSION PATTERNS; CEREBELLAR PURKINJE NEURONS; RAT-BRAIN; HIPPOCAMPAL-NEURONS; MESSENGER-RNAS; ENDOPLASMIC-RETICULUM; CA2+ PERMEABILITY; AMPA RECEPTORS; GUINEA-PIG AB The objective of the present study was to determine if a neuron that expresses multiple glutamate receptors targets the same receptors to all glutamatergic postsynaptic populations, or if the receptors are differentially targeted to specific postsynaptic populations. As a model for this study, we chose the fusiform cell of the dorsal cochlear nucleus. This neuron expresses multiple glutamate receptors and receives two distinct glutamatergic inputs: parallel fibers synapse on apical dendrites, and auditory nerve fibers synapse on basal dendrites. Pre- and postembedding immunocytochemistry were combined with retrograde tracing to identify the receptors expressed on postsynaptic membranes of parallel fiber and auditory nerve synapses. Most receptors were found at both populations of synapses, but the AMPA receptor subunit, GluR4, and the metabotropic receptor, mGluR1 alpha, were found only at the auditory nerve synapse. These results demonstrate that glutamate receptors are targeted to specific postsynaptic populations of glutamatergic synapses. RP Rubio, ME (reprint author), NATL INST DEAFNESS & OTHER COMMUN DISORDERS, NEUROCHEM LAB, NIH, BETHESDA, MD 20892 USA. NR 98 TC 173 Z9 175 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN PY 1997 VL 18 IS 6 BP 939 EP 950 DI 10.1016/S0896-6273(00)80333-5 PG 12 WC Neurosciences SC Neurosciences & Neurology GA XJ102 UT WOS:A1997XJ10200012 PM 9208861 ER PT J AU McLean, CA Masters, CL Vladimirtsev, VA Prokhorova, IA Goldfarb, LG Asher, DM Vladimirtsev, AI Alekseev, VP Gajdusek, DC AF McLean, CA Masters, CL Vladimirtsev, VA Prokhorova, IA Goldfarb, LG Asher, DM Vladimirtsev, AI Alekseev, VP Gajdusek, DC TI Viliuisk encephalomyelitis - review of the spectrum of pathological changes SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE chronic neurological disease; encephalitis; epidemiology; infection; Viliuisk encephalomyelitis AB Viliuisk encephalomyelitis (VE) is an unique neurological disease occurring in the Iakut (Sakha) people of Siberia. Evolution of the disease follows one of three broad clinical forms: subacute, slowly progressive or chronic. Death occurs within 3 to 6 months in subacute cases and within 5 years in the slowly progressive cases. Chronic cases lack a subacute phase but show a slowly progressive dementia associated with bradykinesia, dysarthria and spastic paraparesis that stabilizes late in the disease process. In subacute and slowly progressive cases, focal necrotizing encephalomyelitis is seen at necropsy. Chronic cases show multifocal areas of lysis with a gliotic margin, predominantly within grey matter, lacking associated chronic inflammatory changes seen in the other forms of the disease. Epidemiological studies are consistent with a disease of low-grade communicability, but laboratory studies have so far failed to reveal an infectious organism. The spectrum of neuropathological changes are reviewed in this examination of II cases. Although the aetiology of VE remains obscure, further studies are warranted since it may represent a novel disease process. C1 UNIV MELBOURNE,DEPT PATHOL,PARKVILLE,VIC 3052,AUSTRALIA. ROYAL MELBOURNE HOSP,DEPT ANAT PATHOL,MELBOURNE,VIC,AUSTRALIA. VILINISK ENCEPHALOMYELITIS RES CTR,YAKUTSK,RUSSIA. RUSSIAN ACAD SCI,VA ENGELHARDT MOL BIOL INST,MOSCOW,RUSSIA. NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. NR 19 TC 10 Z9 10 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD JUN PY 1997 VL 23 IS 3 BP 212 EP 217 DI 10.1111/j.1365-2990.1997.tb01204.x PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XG978 UT WOS:A1997XG97800004 PM 9223130 ER PT J AU Knusel, B Gao, H Okazaki, T Yoshida, T Mori, N Hefti, F Kaplan, DR AF Knusel, B Gao, H Okazaki, T Yoshida, T Mori, N Hefti, F Kaplan, DR TI Ligand-induced down-regulation of Trk messenger RNA, protein and tyrosine phosphorylation in rat cortical neurons SO NEUROSCIENCE LA English DT Article DE Trk receptor regulation; NGF; BDNF; trophic factor therapy; truncated TrkB; PLC-gamma 1 ID NERVE GROWTH-FACTOR; AFFINITY NEUROTROPHIN RECEPTOR; FOREBRAIN CHOLINERGIC NEURONS; PC12 CELLS; TRUNCATED RECEPTORS; SIGNAL-TRANSDUCTION; SYMPATHETIC NEURONS; GENE-EXPRESSION; NGF RECEPTORS; BRAIN AB Chronic exposure of brain neurons to nerve growth factor in vitro and in vivo results in increased levels of the nerve growth factor receptor TrkA. In contrast, in the present study, we have found that chronic exposure of rat embryonic cortical neurons to brain-derived neurotrophic factor (BDNF) leads to a pronounced reduction of the levels of protein and messenger RNA for the full-length but not the truncated BDNF receptor TrkB. Similar effects were observed with the other TrkB ligands neurotrophin-3 and neurotrophin-4/5. After pretreatment with BDNF, neurotrophin-3 or neurotrophin-4/5, subsequent tyrosine phosphorylation responses of the remaining Trks to the same factors were greatly reduced. Three days exposure of rat embryonic cortical neurons to BDNF induced an absolute refractory period of several hours, with no subsequent response to the same factor. Similar but less pronounced refractory effects were observed with neurotrophin-3 and neurotrophin-4/5. Our results suggest a negative regulatory effect of BDNF and other TrkB ligands on TrkB receptors. Down-regulation of the TrkB response by its ligands might play a role in the control of BDNF action during early development, when BDNF levels significantly increase. Our findings are also of potential clinical relevance, since the possibility of ligand-induced downregulation of the receptor response needs to be addressed when considering BDNF or other neurotrophins for the therapy of neurodegeneration. (C) 1997 IBRO. C1 UNIV SO CALIF,DEPT SCI BIOL,LOS ANGELES,CA 90089. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,EUKARYOT SIGNAL TRANSDUCT GRP,FREDERICK,MD 21702. RP Knusel, B (reprint author), UNIV SO CALIF,DIV NEUROGERONTOL,ANDRUS GERONTOL CTR,LOS ANGELES,CA 90089, USA. FU NIA NIH HHS [AG09793, AG10480]; NINDS NIH HHS [NS22933] NR 47 TC 96 Z9 96 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JUN PY 1997 VL 78 IS 3 BP 851 EP 862 DI 10.1016/S0306-4522(96)00616-1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA WX540 UT WOS:A1997WX54000019 PM 9153663 ER PT J AU Song, AW Wolff, SD Balaban, RS Jezzard, P AF Song, AW Wolff, SD Balaban, RS Jezzard, P TI The effect of off-resonance radiofrequency pulse saturation on fMRI contrast SO NMR IN BIOMEDICINE LA English DT Article DE fMRI; BOLD; off-resonance saturation ID SENSORY STIMULATION; SIGNAL CHANGES; BRAIN; SUSCEPTIBILITY; IMAGE; BLOOD; ACTIVATION; FIELDS; CORTEX AB This paper describes the use of off-resonance saturation to further manipulate the blood oxygenation level dependent (BOLD) contrast of fMRI, A customized narrow bandwidth radiofrequency pulse, applied with a range of frequency offsets prior to selection of each slice, was designed and incorporated into a gradient echo EPI sequence, This application takes advantage of the resonance frequency and linewidth differences between the oxygenated and deoxygenated state of blood in human brain during task activation and rest, and is capable of creating an enhancement in the contrast of the BOLD effect Because of a possible contribution to the signal change from cerebro-spinal fluid, which has a much narrower linewidth and smaller frequency shift compared with the brain tissue, data were also collected using a nulling inversion praise. The inversion pulse was applied before the off-resonance pulse and data acquisition to eliminate the CSF signal, Functional areas are thus wore localized to the brain tissue. (C) 1997 John Wiley & Sons, Ltd. C1 NIMH, LAB BRAIN & COGNIT, NIH, BETHESDA, MD 20892 USA. NHLBI, CARDIAC ENERGET LAB, NIH, BETHESDA, MD 20892 USA. RI Balaban, Robert/A-7459-2009; OI Balaban, Robert/0000-0003-4086-0948; Jezzard, Peter/0000-0001-7912-2251 NR 13 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD JUN-AUG PY 1997 VL 10 IS 4-5 BP 208 EP 215 DI 10.1002/(SICI)1099-1492(199706/08)10:4/5<208::AID-NBM467>3.0.CO;2-S PG 8 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA YJ807 UT WOS:A1997YJ80700010 PM 9430350 ER PT J AU Varricchio, CG AF Varricchio, CG TI Cancer in adults: A focus on prevention and detection in the nurse practitioner's practice SO NURSE PRACTITIONER FORUM-CURRENT TOPICS AND COMMUNICATIONS LA English DT Article AB This article provides a very general overview of the group of diseases called cancer. The clinical practice of the nurse practitioner emphasizes health maintenance and promotion of a healthy life style. This focus can carry over into the survival phase of the cancer experience. Counseling about risk status and risk reduction are an integral part of the total approach to cancer care. These activities can be integrated into standard care delivered by the nurse practitioner. Copyright (C) 1995 by W.B. Saunders Company. RP Varricchio, CG (reprint author), NCI,DIV CANC PREVENT & CONTROL,900 ROCKVILLE PIKE,EPN 300,BETHESDA,MD 20892, USA. NR 13 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1045-5485 J9 NURS PRACT FORUM JI Nurse Pract. Forum-Curr. Top. Commun. PD JUN PY 1997 VL 8 IS 2 BP 64 EP 69 PG 6 WC Nursing SC Nursing GA XT696 UT WOS:A1997XT69600004 PM 9325897 ER PT J AU Tuomala, RE Kalish, LA Zorilla, C Fox, H Shearer, W Landay, A Vermund, SH Landesman, S Burns, D AF Tuomala, RE Kalish, LA Zorilla, C Fox, H Shearer, W Landay, A Vermund, SH Landesman, S Burns, D TI Changes in total, CD4(+), and CD8(+) lymphocytes during pregnancy and 1 year postpartum in human immunodeficiency virus-infected women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID DECREASED LEVELS; CLINICAL-TRIALS; DRUG-USERS; T SUBSETS; SUBPOPULATIONS; COUNT; AIDS; PREDICTION; INCREASE; CELLS AB Objective: To assess changes in lymphocyte subsets during pregnancy and 1 year postpartum in human immunodeficiency virus (HIV)-infected women. Methods: Changes in CD4(+) and CD8(+) cell counts, CD4 and CD8 percents, CD4/CD8 ratio, and total lymphocyte count and percent were assessed in each of 226 HIV-infected women followed during pregnancy and 1 year postpartum, and for each of 100 nonpregnant HIV-infected woman during 1 year. Trends over time were compared between pregnant women with and without several covariates. Postpartum changes over a 1-year period were compared to a 1-year period in the nonpregnant cohort. Results: There was a mean increase of 2.76 per week in the CD4(+) cell count during pregnancy (P = .04). No other characteristics changed significantly during pregnancy. The mean CD4(+) and CD8(+) cell counts, the CD8 percent, and the total lymphocyte count and percent increased immediately postdelivery. During the first postpartum year, there were statistically significant declines in the absolute CD4(+) and CD8(+) cell counts, the relative CD4 and CD8 percentages, and the total lymphocyte count and percentage. The rate of change for CD4(+) and CD8(+) counts, but not for CD4 percent, was less during 1 year in the nonpregnant cohort than in the first postpartum year, and the CD8 percent increased in the nonpregnant women. A wide variability in trends of all measurements during pregnancy was seen. Conclusion: During pregnancy, CD4 and CD8 percentages remain stable. There are no clinically significant changes during pregnancy or postpartum in any lymphocyte parameter we assessed. Postpartum changes in lymphocytes and lymphocyte subsets most likely represent a return to base-line from the physiologic changes of pregnancy and the immediate postpartum period. (C) 1997 by The American College of Obstetricians and Gynecologists. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. UNIV PUERTO RICO,SCH MED,DEPT OBSTET & GYNECOL,SAN JUAN,PR 00936. COLUMBIA UNIV COLL PHYS & SURG,DEPT OBSTET & GYNECOL,NEW YORK,NY 10032. BAYLOR COLL MED,DEPT PEDIAT IMMUNOL,HOUSTON,TX 77030. RUSH MED COLL,DEPT IMMUNOL,CHICAGO,IL 60612. NIAID,DIV AIDS,NIH,BETHESDA,MD 20892. SUNY HLTH SCI CTR,DIV INFECT DIS,BROOKLYN,NY 11203. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,NIH,BETHESDA,MD 20892. RP Tuomala, RE (reprint author), BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,75 FRANCIS ST,BOSTON,MA 02115, USA. OI Vermund, Sten/0000-0001-7289-8698 FU NIAID NIH HHS [AI-34840, AI-34841, AI-34842] NR 38 TC 26 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 1997 VL 89 IS 6 BP 967 EP 974 DI 10.1016/S0029-7844(97)00129-4 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XA688 UT WOS:A1997XA68800017 PM 9170476 ER PT J AU Cohn, CS Gottlieb, M AF Cohn, CS Gottlieb, M TI The acquisition of purines by trypanosomatids SO PARASITOLOGY TODAY LA English DT Article ID LEISHMANIA-DONOVANI; NUCLEOSIDE TRANSPORTERS; ADENOSINE TRANSPORTER; DIFFERENT STRAINS; BRUCEI-BRUCEI; RESISTANT; PROMASTIGOTES; METABOLISM; TUBERCIDIN; ANALOGS AB Parasites of the family Trypanosomatidae have an absolute requirement for purines, yet lack the intracellular machinery to synthesize their own purine ring de novo. As a result, the enzymes devoted to the transport and metabolism of purines are extremely important to the parasite. Here, Claudia Cahn and Michael Gottlieb emphasize the value of understanding purine salvage for the development of trypanocidal drugs, and discuss the putative transporters devoted to purine uptake. C1 JOHNS HOPKINS UNIV,DEPT MOL MICROBIOL & IMMUNOL,BALTIMORE,MD 21205. NIAID,DIV MICROBIOL & INFECT DIS,PARASITOL & INT PROGRAMS BRANCH,NIH,BETHESDA,MD 20892. NR 23 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD JUN PY 1997 VL 13 IS 6 BP 231 EP 235 DI 10.1016/S0169-4758(97)01059-4 PG 5 WC Parasitology SC Parasitology GA XA393 UT WOS:A1997XA39300011 PM 15275076 ER PT J AU Arikawa, J Tokunaga, M Satoh, E Tanaka, S Land, CE AF Arikawa, J Tokunaga, M Satoh, E Tanaka, S Land, CE TI Morphological characteristics of Epstein-Barr virus-related early gastric carcinoma: A case-control study SO PATHOLOGY INTERNATIONAL LA English DT Article DE atrophy; early gastric cancer; Epstein-Barr virus; Epstein-Barr virus encoded RNA in situ hybridization; Helicobacter pylori infection; intestinal metaplasia; reactive lymphocyte ID LYMPHOEPITHELIOMA-LIKE CARCINOMA; POLYMERASE CHAIN-REACTION; HELICOBACTER-PYLORI; LYMPHOID STROMA; SALIVARY-GLAND; ASSOCIATION; STOMACH; ADENOCARCINOMA; CANCER; DNA AB A strong association between Epstein-Barr virus (EBV) and gastric carcinoma has been demonstrated by the uniform presence of EBV in all carcinoma cells, episomal monoclonality, elevated antibodies, and a unique 'lace pattern' in the mucosa. The present study is concerned with morphological changes of intramucosal carcinoma and submucosal invasion, reactive lymphocytes, and with atrophy and intestinal metaplasia of the surrounding mucosa. Fifty-two EBV-positive early gastric carcinomas were matched by age, sex, and site of tumor with 103 EBV-negative carcinomas, all of which had previously been examined by serial cut-sections of the tumors and surrounding mucosa. Epstein-Barr virus involvement was strongly associated with lace pattern morphology as demonstrated previously, and with lymphocytic infiltration in and around the tumor nests in the mucosa. The infiltrating lymphocytes in the tumor nests were mainly composed of CD8(+) T lymphocytes. Lymphoepithelioma (LE)-like carcinoma, was observed in the submucosal portions of 13 of 31 EBV-positive cases with such invasions, including 12 of 29 with lace pattern morphology in the mucosa,The majority of the surrounding gastric mucosa showed moderate to severe atrophy with marked depletion of parietal cells, complete-type intestinal metaplasia in EBV-positive cases, and Helicobacter pylori (H. pylori) infection for both EBV-positive and EBV-negative cases. It is suggested that EBV infection may occur in the atrophic gastric epithelial cells associated with intestinal metaplasia and H. pylori infection, leading to the development of carcinoma. Such cancers show lace pattern and marked lymphocytic reaction in the mucosa, with some tendency for histological change and lymphocytic reaction during the invasive process without lymph node metastasis. C1 KAGOSHIMA CITY HOSP,DEPT PATHOL,KAGOSHIMA 892,JAPAN. KAGOSHIMA UNIV,SCH MED,DEPT PATHOL 2,KAGOSHIMA 890,JAPAN. KAGOSHIMA CITY MED ASSOC HOSP,KAGOSHIMA,JAPAN. NCI,RADIAT EPIDEMIOL BRANCH,ROCKVILLE,MD. NR 29 TC 28 Z9 30 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD JUN PY 1997 VL 47 IS 6 BP 360 EP 367 DI 10.1111/j.1440-1827.1997.tb04509.x PG 8 WC Pathology SC Pathology GA XG103 UT WOS:A1997XG10300004 PM 9211523 ER PT J AU Spector, SA Blanchard, S Wara, DW Oleske, JM McIntosh, K Hodes, D Dankner, WM Salgo, M McNamara, J AF Spector, SA Blanchard, S Wara, DW Oleske, JM McIntosh, K Hodes, D Dankner, WM Salgo, M McNamara, J TI Comparative trial of two dosages of zalcitabine in zidovudine-experienced children with advanced human immunodeficiency virus disease SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE zalcitabine; human immunodeficiency virus disease ID INFECTION C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. CHILDRENS HOSP,NEWARK,NJ. BOSTON CHILDRENS HOSP,BOSTON,MA. MT SINAI MED CTR,NEW YORK,NY 10029. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. NIAID,DIV AIDS,BETHESDA,MD 20892. RP Spector, SA (reprint author), UNIV CALIF SAN DIEGO,PEDIAT AIDS CLIN TRIALS GRP,CLIN SCI BLDG,9500 GILMAN DR,LA JOLLA,CA 92093, USA. RI Oleske, James/C-1951-2016 OI Oleske, James/0000-0003-2305-5605 NR 12 TC 7 Z9 7 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUN PY 1997 VL 16 IS 6 BP 623 EP 626 DI 10.1097/00006454-199706000-00015 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA XD846 UT WOS:A1997XD84600014 PM 9194115 ER PT J AU Brooks, LJ DiFiore, JM Martin, RJ Baird, TM Brooks, LJ Colton, T Corwin, MJ Crowell, D Ward, SLD Hoppenbrouwers, TT Hufford, DR Hunt, CE Keens, TG Lister, G Martin, RJ Neuman, MR Ramanathan, R Schafer, S Silvestri, JM Tinsley, L WeeseMayer, DE Willinger, M AF Brooks, LJ DiFiore, JM Martin, RJ Baird, TM Brooks, LJ Colton, T Corwin, MJ Crowell, D Ward, SLD Hoppenbrouwers, TT Hufford, DR Hunt, CE Keens, TG Lister, G Martin, RJ Neuman, MR Ramanathan, R Schafer, S Silvestri, JM Tinsley, L WeeseMayer, DE Willinger, M TI Assessment of tidal volume over time in preterm infants using respiratory inductance plethysmography SO PEDIATRIC PULMONOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Thoracic-Society CY MAY 21-25, 1994 CL BOSTON, MA SP Amer Thorac Soc DE apnea; infants; respiratory inductance plethysmography; ventilation; sudden infant death syndrome ID INDUCTIVE PLETHYSMOGRAPHY; APNEA AB Non-invasive techniques for monitoring ventilation in infants are widely used in short-term laboratory studies but have not been evaluated in routine clinical settings. To determine whether respiratory inductance plethysmography (RIP) can provide reproducible measurements of tidal volume (V-T) in premature infants over an extended period of time, we monitored respiration in eight healthy preterm infants over 4.9 +/- 1.0 hours (mean +/- SD). The algebraic sum (Sum) of rib cage (RC) and abdominal (AB) motion signals (obtained by RIP) was calculated and presented over the entire recording period as percent of an initial 5 minute calibration period. V-T was simultaneously measured with a nasal mask pneumotachometer with infants in prone and supine positions during active and quiet sleep. Infants were studied in the morning (AM) and again in the afternoon (PM). Between these studies they were returned to the nursery wearing the RIP in a continuous record mode. For all patients there was a significant linear relationship between V-T (in mL measured by pneumotachometer) and Sum (in % of calibration value, RIP). Neither the slope of the relationship (0.074 +/- 0.03 in AM vs. 0.071 +/- 0.02 in PM), nor its variability as measured by standard error of the estimate (SEE) (2.3 +/- 0.5 in AM vs. 2.5 +/- 0.8 in PM) changed significantly from AM to PM. The relationship between V-T and Sum, as well as the variability of that relationship, was not altered by position, asynchrony of RC and AB, respiratory rate, or percent RC contribution to Sum. We conclude that RIP produces consistent measurements of respiratory effort over 5 hours in healthy preterm infants without need for recalibration and is not affected by routine care. (C) 1997 Wiley-Liss. Inc. C1 CASE WESTERN RESERVE UNIV,RAINBOW BABIES & CHILDRENS HOSP,DEPT PEDIAT,DIV PEDIAT PULMONOL,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,RAINBOW BABIES & CHILDRENS HOSP,DEPT PEDIAT,DIV NEONATOL,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,RAINBOW BABIES & CHILDRENS HOSP,DIV PULM,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,RAINBOW BABIES & CHILDRENS HOSP,SLEEP DISORDERS CTR,CLEVELAND,OH 44106. BOSTON UNIV,SCH PUBL HLTH,BOSTON,MA. BOSTON UNIV,BOSTON CITY HOSP,MED CTR,DEPT PEDIAT,BOSTON,MA 02118. KAPIOLANI MED CTR WOMEN & CHILDREN,DEPT PEDIAT,HONOLULU,HI. CHILDRENS HOSP LOS ANGELES,DIV NEONATOL & PEDIAT PULMONOL,LOS ANGELES,CA 90027. UNIV SO CALIF,LOS ANGELES CTY MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90033. UNIV SO CALIF,MED CTR,WOMENS HOSP,LOS ANGELES,CA 90033. TOLEDO HOSP,DEPT PEDIAT,PEDIAT PULM CTR,TOLEDO,OH. MED COLL OHIO,DEPT PEDIAT,TOLEDO,OH 43699. CHILDRENS HOSP LOS ANGELES,DIV NEONATOL & PULMONOL,LOS ANGELES,CA 90027. YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06510. RAINBOW BABIES & CHILDRENS HOSP,DIV NEONATOL,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,METROHLTH MED CTR,DEPT OBSTET & GYNECOL,CLEVELAND,OH. UNIV SO CALIF,WOMENS HOSP,MED CTR,LOS ANGELES,CA 90033. NICHHD,NIH,BETHESDA,MD. RUSH UNIV,RUSH CHILDRENS HOSP,CTR SIDS RES & DISORDERS RESP CONTROL,CHICAGO,IL 60612. NICHHD,CRMC,PREGNANCY & PERINATOL BRANCH,NIH,ROCKVILLE,MD. FU NICHD NIH HHS [HD-29071] NR 12 TC 23 Z9 23 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD JUN PY 1997 VL 23 IS 6 BP 429 EP 433 DI 10.1002/(SICI)1099-0496(199706)23:6<429::AID-PPUL6>3.0.CO;2-D PG 5 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA XJ283 UT WOS:A1997XJ28300006 PM 9220525 ER PT J AU Kawamura, N Ishikawa, T Ago, Y Yamasaki, Y Fukui, T Tatemichi, M Sei, H Morita, Y Horiguchi, E Rahe, RH AF Kawamura, N Ishikawa, T Ago, Y Yamasaki, Y Fukui, T Tatemichi, M Sei, H Morita, Y Horiguchi, E Rahe, RH TI Sleep characteristics of Japanese working men who score alexithymic on the Toronto Alexithymia Scale SO PERCEPTUAL AND MOTOR SKILLS LA English DT Article ID INSOMNIA; INVENTORY; STRESS AB This study examined the relationship of sleep characteristics including insomnia with scores on alexithymia in a sample of 171 Japanese working men. Levels of nonrestorative sleep and daytime sleepiness reported on a sleep questionnaire were significantly associated with scores on Depression and Confusion on the Profile of Mood States for Japanese men who had a high mean score on the Toronto Alexithymia Scale. C1 PSYCHIAT RES INST TOKYO,SETAGAYA KU,TOKYO 156,JAPAN. NIMH,DEPT PSYCHOSOMAT MED,NATL CTR NEUROL & PSYCHIAT,BETHESDA,MD. SONY CORP,RES INST WISDOM,ATSUGI,KANAGAWA,JAPAN. UNIV TOKUSHIMA,SCH MED,DEPT PHYSIOL,TOKUSHIMA 770,JAPAN. KEIO UNIV,SCH MED,YOKOHAMA,JAPAN. NR 20 TC 0 Z9 0 U1 1 U2 1 PU PERCEPTUAL MOTOR SKILLS PI MISSOULA PA PO BOX 9229, MISSOULA, MT 59807 SN 0031-5125 J9 PERCEPT MOTOR SKILL JI Percept. Mot. Skills PD JUN PY 1997 VL 84 IS 3 BP 859 EP 865 PN 1 PG 7 WC Psychology, Experimental SC Psychology GA XA585 UT WOS:A1997XA58500027 ER PT J AU Chang, TKH Yu, L Goldstein, JA Waxman, DJ AF Chang, TKH Yu, L Goldstein, JA Waxman, DJ TI Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-K-m catalysts of cyclophosphamide and ifosfamide activation SO PHARMACOGENETICS LA English DT Article DE CYP2C; cyclophosphamide; ifosfamide; anticancer drug activation ID HUMAN LIVER-MICROSOMES; BONE-MARROW TRANSPLANTATION; AMINO-ACID; S-MEPHENYTOIN; (S)-MEPHENYTOIN 4'-HYDROXYLASE; CYTOCHROME-P-450 ENZYMES; PHOSPHORAMIDE MUSTARD; MESSENGER-RNA; METABOLISM; PHARMACOKINETICS AB Cyclophosphamide and ifosfamide are alkylating agent prodrugs that require activation by cytochrome P450 (CYP) to manifest their cancer chemotherapeutic activity, The present study investigates the activity of four individual human CYP2C enzymes and their allelic variants in cyclophosphamide and ifosfamide activation as an initial attempt to gain insight into the underlying basis for the large interpatient differences in the clinical pharmacokinetics and metabolism of these anticancer drugs, Recombinant CYP2C8, CYP2C19, two allelic variants of CYP2C18, and six variants of CYP2C9 expressed in a yeast cDNA expression system were each enzymatically active, as judged by the ability of the isolated microsomes to catalyse 7-ethoxycoumarin O-deethylation after reconstitution with purified NADPH-cytochrome P450 reductase and cytochrome b(5). With cyclophosphamide as substrate, CYP2C19 had the lowest apparent K-m, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: K-m CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. CYP2C18 had the highest in vitro intrinsic clearance/catalytic efficiency (apparent V-max/K-m) in cyclophosphamide and ifosfamide activation, followed by 2C19 > 2C9 similar to 2C8. Examination of a panel of CYP2C allelic variants revealed that CYP2C18-Thr(385) had both a higher V-max and a higher apparent K-m toward cyclophosphamide than CYP2C18-Met(385) with no difference in catalytic efficiency, whereas with ifosfamide the Thr(385) allele exhibited a strikingly lower apparent K-m resulting in a six-fold higher catalytic efficiency In the case of CYP2C9, a Ile(359) to Leu mutation associated with poor metabolism of the hypoglycemic drug tolbutamide decreased catalytic efficiency toward cyclophosphamide by increasing the apparent K-m, whereas the same mutation reduced the efficiency of this P450 toward ifosfamide by decreasing the V-max. Substitution of CYP2C9-Gly(417) by Asp resulted in a. two-fold lower catalytic efficiency for cyclophosphamide metabolism but. a three-fold higher efficiency for ifosfamide metabolism. A His(276) to Gly substitution resulted in an increase in both V-max and apparent K-m with no net change in catalytic efficiency for either oxazaphosphorine, Mutations at CYP2C9 residues 144 and 358 had little or no effect, Thus (a) wild type CYP2C19 and CYP2C9 are relatively low K-m catalysts of cyclophosphamide and ifosfamide activation and (b) all four human CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies and with striking differences among naturally occuring allelic variants in the case of CYP2C9 and CYP2C18. C1 BOSTON UNIV,DEPT BIOL,DIV CELL & MOL BIOL,BOSTON,MA 02215. UNIV BRITISH COLUMBIA,FAC PHARMACEUT SCI,VANCOUVER,BC V6T 1Z3,CANADA. NIEHS,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA-49248] NR 66 TC 102 Z9 106 U1 0 U2 3 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD JUN PY 1997 VL 7 IS 3 BP 211 EP 221 DI 10.1097/00008571-199706000-00006 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA XK311 UT WOS:A1997XK31100006 PM 9241661 ER PT J AU Gullsten, H Agundez, JAG Benitez, J Laara, E Ladero, JM DiazRubio, M FernandezSalguero, P Gonzalez, F Rautio, A Pelkonen, O Raunio, H AF Gullsten, H Agundez, JAG Benitez, J Laara, E Ladero, JM DiazRubio, M FernandezSalguero, P Gonzalez, F Rautio, A Pelkonen, O Raunio, H TI CYP2A6 gene polymorphism and risk of liver cancer and cirrhosis SO PHARMACOGENETICS LA English DT Article DE CYP2A6 gene polymorphism; liver cancer; cirrhosis ID CYTOCHROMES P450 2A6; COUMARIN 7-HYDROXYLATION; EXPRESSION; MICROSOMES; CELLS; 2E1 C1 UNIV OULU,DEPT PHARMACOL & TOXICOL,FIN-90220 OULU,FINLAND. UNIV EXTREMADURA,SCH MED,DEPT PHARMACOL,BADAJOZ 06071,SPAIN. UNIV OULU,DEPT MATH SCI STAT,FIN-90570 OULU,FINLAND. SAN CARLOS UNIV HOSP,DEPT GASTROENTEROL,MADRID,SPAIN. NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Diaz-Rubio, Manuel/B-5359-2010; Agundez, Jose/A-5503-2008; OI Agundez, Jose/0000-0001-6895-9160; Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 18 TC 32 Z9 33 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD JUN PY 1997 VL 7 IS 3 BP 247 EP 250 DI 10.1097/00008571-199706000-00010 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA XK311 UT WOS:A1997XK31100010 PM 9241665 ER PT J AU Dybing, E Sanner, T Roelfzema, H Kroese, D Tennant, RW AF Dybing, E Sanner, T Roelfzema, H Kroese, D Tennant, RW TI T25: A simplified carcinogenic potency index: Description of the system and study of correlations between carcinogenic potency and species/site specificity and mutagenicity SO PHARMACOLOGY & TOXICOLOGY LA English DT Article ID NATIONAL-TOXICOLOGY-PROGRAM; ANIMAL BIOASSAYS; CHRONOLOGICAL SUPPLEMENT; RODENT CARCINOGENICITY; TARGET ORGANS; CHEMICALS; DATABASE; PREDICTION; TESTS; RATS AB A simplified carcinogenic potency index, the T25, is proposed as a practical method for the inclusion of potency considerations in carcinogen classification systems. The T25 is the chronic daily dose in mg per kg bodyweight which will give 25% of the animals rumours at a specific tissue site, after correction for spontaneous incidence, within the standard life span of that species. Calculated T25 values of a set of 113 US National Cancer Institute/National Toxicology Program (NC/NTP) carcinogens showed excellent correlation (correlation coefficient 0.96, P<0.0001) with the carcinogenic potency index TD50 of Peto et al. (1984). The mean of T25 values for 51 transspecies, multiple common site NCI/NTP carcinogens were 10-fold lower than those for 62 NCI/NTP single species, single site carcinogens. For these 113 carcinogens, the mean T25 values were approximately 3-fold lower for agents that were also mutagenic in Salmonella compared to the nonmutagenic agents. C1 INST CANC RES,LAB ENVIRONM & OCCUPAT CANC,N-0310 OSLO,NORWAY. MINIST HLTH WELF & SPORT,DIRECTORATE FOOD & PROD SAFETY,RIJSWIJK,NETHERLANDS. NATL INST PUBL HLTH & ENVIRONM PROTECT,DEPT CARCINOGENESIS & MUTAGENESIS,NL-3720 BA BILTHOVEN,NETHERLANDS. NIEHS,RES TRIANGLE PK,NC 27709. RP Dybing, E (reprint author), NATL INST PUBL HLTH,DEPT ENVIRONM MED,POB 4404,N-0403 OSLO,NORWAY. NR 36 TC 42 Z9 44 U1 1 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-9928 J9 PHARMACOL TOXICOL JI Pharmacol. Toxicol. PD JUN PY 1997 VL 80 IS 6 BP 272 EP 279 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XJ615 UT WOS:A1997XJ61500004 PM 9225363 ER PT J AU Porra, JM Masoliver, J Weiss, GH AF Porra, JM Masoliver, J Weiss, GH TI When the telegrapher's equation furnishes a better approximation to the transport equation than the diffusion approximation SO PHYSICAL REVIEW E LA English DT Article AB It has been suggested that a solution to the transport equation which includes anisotropic scattering can be approximated by the solution to a telegrapher's equation [A.J. Ishimaru, Appl. Opt. 28, 2210 (1989)]. We show that in one dimension the telegrapher's equation furnishes an exact solution to the transport equation. In two dimensions, we show that, since the solution can become negative, the telegrapher's equation will not furnish a usable approximation. A comparison between simulated data in three dimensions indicates that the solution to the telegrapher's equation is a good approximation to that of the full transport equation at the times at which the diffusion equation furnishes an equally good approximation. C1 NATL INST HLTH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP Porra, JM (reprint author), UNIV BARCELONA,DEPT FIS FONAMENTAL,DIAGONAL 647,E-08028 BARCELONA,SPAIN. RI Masoliver, Jaume/F-7198-2016 OI Masoliver, Jaume/0000-0002-5810-879X NR 14 TC 33 Z9 33 U1 0 U2 4 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD JUN PY 1997 VL 55 IS 6 BP 7771 EP 7774 DI 10.1103/PhysRevE.55.7771 PN B PG 4 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA XG966 UT WOS:A1997XG96600080 ER PT J AU McDowell, G Gahl, WA AF McDowell, G Gahl, WA TI Inherited disorders of glycoprotein synthesis: Cell biological insights SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review ID ANEMIA TYPE-II; N-ACETYLGLUCOSAMINYLTRANSFERASE-II; ALPHA-MANNOSIDASE-II; MOLECULAR-CLONING; LINKED OLIGOSACCHARIDES; LINKAGE DISEQUILIBRIUM; CHONDROITIN SULFATE; MEMBRANE-PROTEINS; KERATAN SULFATE; DEFICIENT AB Disorders of glycoprotein synthesis have been described only recently, and few have been studied extensively at both the clinical and biochemical level, The identification and characterization of these rare diseases are important, not only for the patients and their families, but because they offer enormous insight into biological processes, For example, the targeting of acid hydrolases to lysosomes by mannose-6-phosphate was discovered as a direct result of the elucidation of the defect in I-cell disease, The notion of carbohydrates as targeting agents continues to have ramifications today, with the success of macrophage-targeted enzyme replacement therapy for Gaucher disease, Likewise, confirmation of the in vivo role of fucose containing glycans and selectins in neutrophil function came from studies using specimens from patients with leucocyte adhesion deficiency type II due to reduced availability of GDP-fucose. Identification of the in vivo ligands of selectins also has implications for anti-inflammatory therapies, Macular corneal dystrophy and spondyloepiphyseal dysplasia tarda offer an opportunity to investigate the number of different sulfotransferases in cells, their substrates, and their tissue expression, The Ehlers-Danlos progeroid variant offers insight into the function and regulation of the proteoglycan decorin, and suggests that several of the enzymes involved in proteoglycan synthesis may function as a multienzyme complex, The common occurrence of hypergonadotropic hypogonadism in patients with galactosemia or carbohydrate-deficient glycoprotein syndrome, due to defective N-linked glycosylation, suggests that ovarian function is particularly dependent on proper glycan synthesis, A host of other concepts await discovery as a fuller contingent of human disorders of glycan synthesis achieves recognition. RP McDowell, G (reprint author), NICHHD,SECT HUMAN BIOCHEM GENET,HERITABLE DISORDERS BRANCH,NIH,10 CTR DR,MSC 1830,BLDG 10,BETHESDA,MD 20892, USA. NR 89 TC 20 Z9 20 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUN PY 1997 VL 215 IS 2 BP 145 EP 157 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WY856 UT WOS:A1997WY85600003 PM 9160042 ER PT J AU Grzesiek, S Bax, A Hu, JS Kaufman, J Palmer, I Stahl, SJ Tjandra, N Wingfield, PT AF Grzesiek, S Bax, A Hu, JS Kaufman, J Palmer, I Stahl, SJ Tjandra, N Wingfield, PT TI Refined solution structure and backbone dynamics of HIV-1 Nef SO PROTEIN SCIENCE LA English DT Article DE heteronuclear NMR; HIV-1; multi-dimensional NMR; Nef; protein dynamics; protein structure ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL-SURFACE CD4; PROTEIN-STRUCTURE DETERMINATION; ISOTOPICALLY ENRICHED PROTEINS; MAGNETIC-RESONANCE RELAXATION; CALCIUM-FREE CALMODULIN; MODEL-FREE APPROACH; DOWN-REGULATION; TYPE-1 NEF; CYTOPLASMIC DOMAIN AB The tendency of HTV-1 Nef to form aggregates in solution, particularly at pH values below 8, together with its large fraction of highly mobile residues seriously complicated determination of its three-dimensional structure, both for heteronuclear solution NMR (Grzesiek et al., 1996a, Nat Struct Biol 3:340-345) and for X-ray crystallography (Lee et al., 1996, Cell 85:931-932). Methods used to determine the Nef structure by NMR at pH 8 and 0.6 mM concentration are presented, together with a detailed description of Nef's secondary and tertiary structure. The described techniques have general applicability for the NMR structure determination of proteins that are aggregating and/or have limited stability at low pH values. Extensive chemical shift assignments are reported for backbone and side chain H-1, C-13, and N-15 resonances of the HIV-1 Nef deletion mutants NEFDelta Z2-39, NEFDelta 2-39,Delta 159-173, and of NEFDelta 2-39,Delta 159-173 complex with the SH3 domain of the Hck tyrosine protein kinase. Besides a type II polyproline helix, Nef's structure consists of three alpha-helices, a 310 helix, and a five-stranded anti-parallel beta-sheet. The analysis of N-15 relaxation parameters of the backbone amide sites reveals that all the secondary structure elements are non-mobile on the picosecond to nanosecond and on the millisecond time scale. A large number of slowly exchanging amide protons provides evidence for the stability of the Nef core even on the time scale of hours. Significant internal motions on the ps to us time scale are detected for residues 60 to 71 and for residues 149 to 180, which form solvent-exposed loops. The residues of the HIV-1 protease cleavage site (W57/L58) do not exhibit large amplitude motions on the sub-nanosecond time scale, and their side chains insert themselves into a hydrophobic crevice formed between the C-terminus of helix 1 and the N-terminus of helix 2. A refined structure has been determined based on additional constraints for side-chain and backbone dihedral angles derived from a large number of three-bond J-couplings and ROE data. C1 NIAMSD,PROT EXPRESS LAB,NIH,BETHESDA,MD 20892. RP Grzesiek, S (reprint author), NIDDKD,PHYS CHEM LAB,NIH,BLDG 5,BETHESDA,MD 20892, USA. NR 90 TC 131 Z9 133 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JUN PY 1997 VL 6 IS 6 BP 1248 EP 1263 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE145 UT WOS:A1997XE14500013 PM 9194185 ER PT J AU Szilak, L Moitra, J Vinson, C AF Szilak, L Moitra, J Vinson, C TI Design of a leucine zipper coiled coil stabilized 1.4 kcal mol(-1) by phosphorylation of a serine in the e position SO PROTEIN SCIENCE LA English DT Article DE alpha-helix; coiled coil; leucine zipper; phosphorylation; PKA; protein stability; serine ID DEPENDENT PROTEIN-KINASE; DIMERIZATION SPECIFICITY; TRANSCRIPTION FACTORS; SALT BRIDGES; DNA-BINDING; POLYMERASE; MECHANISM; PEPTIDE; INVITRO; FAMILY AB Using a dimeric bZIP protein, we have designed a leucine zipper that becomes more stable after a serine in the e position is phosphorylated by protein kinase A (Delta Delta G(P) = -1.4 kcal mol(-1) dimer(-1) or - 0.7 kcal mol(-1) residue(-1)). Mutagenesis studies indicate that three arginines form a network of inter-helical (i,i' + 5; i,i' + 2) and intra-helical (i,i + 4) attractive interactions with the phosphorylated serine. When the arginines are replaced with lysines, the stabilizing effect of serine phosphorylation is reduced (Delta Delta G(P) = - 0.5 kcal mol(-1) dimer(-1)). The hydrophobic interface of the leucine zipper needs a glycine in the d position to obtain an increase in stability after phosphorylation. The phosphorylated protein binds DNA with a 15-fold higher affinity. Using a transient transfection assay, we document a PKA dependent four-fold activation of a reporter gene. Phosphorylation of a threonine in the same e position decreases the stability by Delta Delta G(P) = +1.2 kcal mol(-1) dimer(-1). We present circular dichroism (CD) thermal denaturations of 15 bZIP proteins before and after phosphorylation. These data provide insights into the structural determinants that result in stabilization of a coiled coil by phosphorylation. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. OI Szilak, Laszlo/0000-0003-0334-272X NR 30 TC 35 Z9 37 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JUN PY 1997 VL 6 IS 6 BP 1273 EP 1283 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE145 UT WOS:A1997XE14500015 PM 9194187 ER PT J AU Robin, RW Chester, B Rasmussen, JK Jaranson, JM Goldman, D AF Robin, RW Chester, B Rasmussen, JK Jaranson, JM Goldman, D TI Factors influencing utilization of mental health and substance abuse services by American Indian men and women SO PSYCHIATRIC SERVICES LA English DT Article ID PSYCHIATRIC-DISORDERS; NATIVE-AMERICANS; MINORITY-GROUPS; ALASKA NATIVES; SEXUAL ASSAULT; UNITED-STATES; ALCOHOL; CARE; PREVALENCE; POPULATION AB Objective: This study investigated the effects of gender, number of lifetime psychiatric diagnoses, and childhood victimization on utilization of mental health and substance abuse treatment services in a Southwestern American Indian tribe. Methods: A total of 582 individuals were recruited based on tribal enrollment and membership in large multigenerational pedigrees. Subjects were interviewed using a modified version of the Schedule for Affective Disorders and Schizophrenia-Lifetime Version, a semistructured psychiatric interview. For this study the definition of childhood victimization was limited to childhood sexual abuse. Results: Fifty-six percent of the subjects had received mental health treatment, substance abuse treatment, or both. Patterns of service utilization differed by gender with the odds of inpatient and substance abuse treatment higher for men than for women. Women were more likely than men to receive mental health treatment. Subjects who had been sexually abused as children were more likely to have three or more psychiatric diagnoses and to have received extensive treatment, compared with subjects who reported no childhood sexual abuse history. Logistic regression demonstrated strong relationships between number of psychiatric diagnoses and the likelihood of treatment among both men and women. Conclusions: Gender, number of psychiatric diagnoses, and childhood sexual abuse are strong predictors of utilization of mental health and substance abuse treatment services. These factors should be considered in designing treatment interventions. C1 NIAAA,LAB NEUROGENET,ROCKVILLE,MD 20852. CTR PREVENT & RESOLUT VIOLENCE,TUCSON,AZ. UNIV ARIZONA,TUCSON,AZ 85721. UNIV MINNESOTA,ST PAUL RAMSEY MED CTR,ST PAUL,MN 55101. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 54 TC 29 Z9 29 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD JUN PY 1997 VL 48 IS 6 BP 826 EP 832 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA XB452 UT WOS:A1997XB45200015 PM 9175194 ER PT J AU Shoaib, MI Baumann, MH Rothman, RB Goldberg, SR Schindler, CW AF Shoaib, MI Baumann, MH Rothman, RB Goldberg, SR Schindler, CW TI Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE drug discrimination; microdialysis; dopamine; serotonin; phentermine; fenfluramine ID DISCRIMINATIVE STIMULUS PROPERTIES; EXTRACELLULAR SEROTONIN; NUCLEUS ACCUMBENS; D-AMPHETAMINE; COCAINE; DRUGS; DOPAMINE; MORPHINE; INCREASE; CAFFEINE AB Clinical case studies suggest that combined administration of the serotonergic agent fenfluramine (FEN) and the weak amphetamine-like anorexic agent phentermine (PHEN) may be useful in the treatment of alcohol and cocaine addictions. The present experiment examined the nature of the interaction between the two agonists using the drug discrimination paradigm. In vivo microdialysis served to examine the neurochemical profile of dopamine and serotonin release in the nucleus accumbens. In conscious rats, acute injections of FEN (1.0-2.0 mg/kg IP) or PHEN (1.0-2.0 mg/kg IP) selectively elevated levels of serotonin and dopamine in the nucleus accumbens, respectively. A mixture (1 mg/kg of each) increased levels of both amines by similar magnitudes to those observed with each individually. Three groups of Sprague-Dawley rats were trained to discriminate (1) FEN (1.0 mg/kg IP) alone, (2) PHEN (1.0 mg/kg IP) alone or a mixture (3) PHEN+FEN (1 mg/kg of each, IP) from saline under a fixed ratio (FR-10) schedule of food reinforcement. Rats acquired the mixture discrimination rapidly, while for the other groups the training dose had to be increased to 2.0 mg/kg to attain stimulus control. The individual components of the mixture at the training dose generalized partially to the mixture, and complete generalisation was observed following 3.0 mg/kg FEN or PHEN. Rats trained to discriminate the individual components showed respective cross-generalisation profiles. Generalisation to cocaine (0.3-10.0 mg/kg IP), amphetamine (0.1-3.0 mg/kg IP) and nicotine (0.1-0.8 mg/kg SC) was greatest in the MIX-trained rats, while partial or no generalisation was observed in rats trained to discriminate the individual compounds. From the present results, it may be concluded that the two drugs given as a mixture do not produce a novel cue. Rather, these aminergics appear to interact additively. Furthermore, the dual stimulation of the amines by the mixture may be the basis for the cueing effects of the FEN+PHEN drug mixture, and its effectiveness in treating drug addictions. C1 NIDA,PRECLIN PHARMACOL LAB,ADDICT RES CTR,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224. NIDA,CLIN PHARMACOL SECT,ADDICT RES CTR,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224. NR 38 TC 38 Z9 37 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUN PY 1997 VL 131 IS 3 BP 296 EP 306 DI 10.1007/s002130050296 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XG109 UT WOS:A1997XG10900012 PM 9203241 ER PT J AU Jensen, RH Reynolds, JC Robbins, J Bigbee, WL Grant, SG Langlois, RG Pineda, JD Lee, TS Barker, C AF Jensen, RH Reynolds, JC Robbins, J Bigbee, WL Grant, SG Langlois, RG Pineda, JD Lee, TS Barker, C TI Glycophorin a as a biological dosimeter for radiation dose to the bone marrow from iodine-131 SO RADIATION RESEARCH LA English DT Article ID CHERNOBYL ACCIDENT; HPRT GENE; A LOCUS; MUTATIONS; UKRAINE; CANCER; ASSAY; DNA AB The frequency of peripheral blood erythrocyte variants exhibiting allelic loss of glycophorin A (N/M antigen) has been used previously as a biological dosimeter to assess somatic mutations in bone marrow cells from external whole-body irradiation. The aim of the present study was to determine whether this marker could be used as a measure of bone marrow genotoxicity induced by I-131 in the treatment of thyroid cancer. Flow cytometry of immunolabeled erythrocytes was performed to enumerate glycophorin A variants before and after eight therapy doses of I-131 administered to five patients with differentiated thyroid carcinoma. Bone marrow radiation exposure from each dose was calculated from the integrated retention of I-131 in the whole body and in the blood, In addition, the accumulated dose to the bone marrow received from earlier I-131 therapy was calculated for each patient. Regression analysis was performed on the frequency of two glycophorin A variant cell types (N/0 and N/N) as a function of accumulated dose to the bone marrow. Frequency of N/0 variant cells showed a significant dose-related increase with a slope of 10.9 x 10(-6) per sievert. This dose effect is about one-half that previously observed after whole-body external irradiation at high dose rate, This decreased response could be explained by the low dose rate of the radiation to the bone marrow from I-131. (C) 1997 by Radiation Research Society. C1 NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NIH,GENET & BIOCHEM BRANCH,ENDOCRINOL SECT,BETHESDA,MD 20892. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT OCCUPAT ENVIRONM HLTH,PITTSBURGH,PA 15238. LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM,LIVERMORE,CA 94550. RP Jensen, RH (reprint author), UNIV CALIF SAN FRANCISCO,SCH MED,DEPT LAB MED,SAN FRANCISCO,CA 94143, USA. RI Grant, Stephen/D-6984-2014 OI Grant, Stephen/0000-0002-9236-0913 FU NCI NIH HHS [N01-CP-50520] NR 24 TC 9 Z9 10 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUN PY 1997 VL 147 IS 6 BP 747 EP 752 DI 10.2307/3579490 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA XC885 UT WOS:A1997XC88500014 PM 9189175 ER PT J AU Sherman, CD Portier, CJ AF Sherman, CD Portier, CJ TI The two-stage model of carcinogenesis: Overcoming the nonidentifiability dilemma SO RISK ANALYSIS LA English DT Article DE nonidentifiable; two-stage model ID FEMALE B6C3F1 MICE; METHYLENE-CHLORIDE; EXPOSURE; TUMORS AB The two-stage mathematical model of carcinogenesis has been shown to be nonidentifiable whenever tumor incidence data alone is used to fit the model (Hanin and Yakovlev, 1996). This lack of identifiability implies that more than one parameter vector satisfies the optimization criteria for parameter estimation, e.g., maximum likelihood estimation. A question of greater concern to persons using the two-stage model of carcinogenesis is under what conditions can identifiable parameters be obtained from the observed experimental data. We outline how to obtain identifiable parameters for the two-stage model. RP Sherman, CD (reprint author), NIEHS,LAB COMPUTAT BIOL & RISK ASSESSMENT,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 8 TC 7 Z9 7 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD JUN PY 1997 VL 17 IS 3 BP 367 EP 374 DI 10.1111/j.1539-6924.1997.tb00875.x PG 8 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA XK800 UT WOS:A1997XK80000011 PM 9232019 ER PT J AU Wasserman, K Corsi, MM Szekely, L Kono, K Maes, HH Kiessling, R AF Wasserman, K Corsi, MM Szekely, L Kono, K Maes, HH Kiessling, R TI Conversion of in vitro cultured human monocytes into effective presenters of an HER2/neu-encoded CTL peptide epitope SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID BLOOD DENDRITIC CELLS; HUMAN-MELANOMA; IN-VITRO; ANTIGEN; IDENTIFICATION; LYMPHOCYTES; TRANSPORT; LINES AB Tumour-derived peptides have been surveyed, in a variety of systems, for their ability to elicit cytokine release from class I restricted T cells, Analogous studies on ovarian carcinoma have employed the antigen-processing defective T2 cell line. Purified dendritic cells (DC) have been reported to act as highly effective APC. A facile method was developed whereby DC-like cells were generated from monocyte precursors, Herein, evidence is presented suggesting DC-like cells are superior to T?I with respect to their ability to present a defined CTL epitope associated with ovarian carcinoma. C1 UNIV MILAN,FAC MED,INST GEN PATHOL,MILAN,ITALY. KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,MTC,STOCKHOLM,SWEDEN. YAMANASHI MED UNIV,DEPT SURG 1,YAMANASHI,JAPAN. KAROLINSKA HOSP,RADIUM HEMMET,DEPT ONCOL,S-10401 STOCKHOLM,SWEDEN. RP Wasserman, K (reprint author), NCI,FREDERICK CANC RES & DEV CTR,EXPT IMMUNOL LAB,DIV BASIC SCI,FREDERICK,MD 21702, USA. RI Szekely, Laszlo/B-1268-2009; OI Corsi Romanelli, Massimiliano Marco/0000-0001-7928-7697 NR 34 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD JUN PY 1997 VL 45 IS 6 BP 678 EP 682 DI 10.1046/j.1365-3083.1997.d01-450.x PG 5 WC Immunology SC Immunology GA XF251 UT WOS:A1997XF25100013 PM 9201308 ER PT J AU Blaese, RM AF Blaese, RM TI Gene therapy for cancer SO SCIENTIFIC AMERICAN LA English DT Article RP Blaese, RM (reprint author), NIH,NATL HUMAN GENOME RES INST,CLIN GENE THERAPY BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 31 Z9 31 U1 0 U2 1 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD JUN PY 1997 VL 276 IS 6 BP 111 EP 115 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ798 UT WOS:A1997WZ79800032 PM 9163943 ER PT J AU Price, TR Manolio, TA Kronmal, RA Kittner, SJ Yue, NC Robbins, J AntonCulver, H OLeary, DH AF Price, TR Manolio, TA Kronmal, RA Kittner, SJ Yue, NC Robbins, J AntonCulver, H OLeary, DH TI Silent brain infarction on magnetic resonance imaging and neurological abnormalities in community-dwelling older adults - The Cardiovascular Health Study SO STROKE LA English DT Article DE cerebral infarction; cognition; elderly; epidemiology; magnetic resonance imaging ID CEREBRAL INFARCTION; ATRIAL-FIBRILLATION; ACUTE STROKE; RISK-FACTORS; DISEASE; PREVALENCE; MIGRAINE; LESIONS; MR AB Background and Purpose Infarctlike lesions are frequently detected in symptomatic and asymptomatic older persons undergoing cerebral MRI, but their significance in older adults has not been examined. We determined the prevalence of MRI infarcts in a population-based sample of men and women aged greater than or equal to 65 years and related these findings to demographic, cognitive, and neurological status. Methods MRI scanning was performed in 3660 Cardiovascular Health Study (CHS) participants after brief neurological examinations and tests of cognitive function. MRIs were read centrally for the presence of an infarct greater than or equal to 3 mm in diameter or smaller infarctlike lesions. Results MRI infarcts were detected in 1131 of 3647 participants with readable infarct information (31%) and in 961 of the subgroup of 3397 participants (28%) without known prior stroke (''silent'' MRI infarcts). Smaller infarctlike lesions were found in 196 of 2516 participants who had no MRI infarcts greater than or equal to 3 mm. MRI infarcts were more common in participants who were older, had prior stroke, impaired cognition, visual field deficits, slowed repetitive finger tapping (all P < .0001), weakness on toe and heel walking, and history of memory loss, coma, or migraine headaches. Multivariate analysis in those without prier stroke showed strong associations of silent MRI infarcts with older age, history of migraines, lower digit symbol scores, and more abnormalities on neurological examination. Conclusions MRI evidence of brain infarction is common in older men and women without a clinical history of stroke. Their strong associations with impaired cognition and neurological deficits suggest that they are neither silent nor innocuous. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV MARYLAND,MED CTR,DEPT NEUROL,BALTIMORE,MD 21201. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. JOHNS HOPKINS UNIV HOSP,DEPT NEURORADIOL,BALTIMORE,MD 21205. UNIV CALIF DAVIS,DEPT MED,SACRAMENTO,CA 95817. UNIV CALIF IRVINE,DIV EPIDEMIOL,IRVINE,CA 92717. TUFTS UNIV,MED CTR,DEPT RADIOL,BOSTON,MA 02111. FU NHLBI NIH HHS [N01-HC-85080, N01-HC-85079, N01-HC-85081] NR 34 TC 186 Z9 196 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 1997 VL 28 IS 6 BP 1158 EP 1164 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA XC724 UT WOS:A1997XC72400011 PM 9183343 ER PT J AU Verkleij, MW Morton, LF Barnes, MJ Gralnick, HR deGroot, PG Sixma, JJ AF Verkleij, MW Morton, LF Barnes, MJ Gralnick, HR deGroot, PG Sixma, JJ TI Simple collagen-like peptides support platelet adhesion under static but not under flow conditions: Interaction via alpha 2 beta 1 with specific collagen sequences is a requirement to withstand shear forces SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 UNIV UTRECHT HOSP,DEPT HEMATOL,UTRECHT,NETHERLANDS. STRANGEWAYS RES LAB,CAMBRIDGE CB1 4RN,ENGLAND. NIH,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1997 SU S BP OC39 EP OC39 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE898 UT WOS:A1997XE89800039 ER PT J AU Chesney, CM Herd, JA Elam, MB Garg, R Davis, KB Kennedy, JW Applegate, WB AF Chesney, CM Herd, JA Elam, MB Garg, R Davis, KB Kennedy, JW Applegate, WB TI Coagulation parameters in peripheral arterial disease (PAD) SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 UNIV TENNESSEE,MEMPHIS,TN. BAPTIST MEM HOSP,MEMPHIS,TN 38146. BAYLOR UNIV,WACO,TX 76798. NHLBI,DECA,BETHESDA,MD. WASHINGTON UNIV,ST LOUIS,MO 63130. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1997 SU S BP PS527 EP PS527 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE898 UT WOS:A1997XE89800526 ER PT J AU Guimaraes, JA Schneider, M Ribeiro, JMC AF Guimaraes, JA Schneider, M Ribeiro, JMC TI Disruption of Xase complex by nitrophorin 2, the salivary anticoagulant of the blood-sucking bug R-prolixus SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 UNIV FED RIO DE JANEIRO,DEPT BIOCHEM MED,RIO JANEIRO,BRAZIL. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1997 SU S BP P2813 EP P2813 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE898 UT WOS:A1997XE89802812 ER PT J AU KleinSoyer, C Azorsa, DO Moog, S Grunert, M Cazenave, JP Lanza, F AF KleinSoyer, C Azorsa, DO Moog, S Grunert, M Cazenave, JP Lanza, F TI Role of CD9 in endothelial cell migration during in vitro wound repair SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 ETSS,INSERM,U311,F-67065 STRASBOURG,FRANCE. NCHGR,CANC GENET LAB,NIH,BETHESDA,MD. RI Lanza, Francois/H-9252-2016 OI Lanza, Francois/0000-0002-5802-4748 NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1997 SU S BP PS565 EP PS565 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE898 UT WOS:A1997XE89800564 ER PT J AU Lozier, JN Yankaskas, JR Ramsey, WJ Chen, L Berschneider, H Morgan, RA AF Lozier, JN Yankaskas, JR Ramsey, WJ Chen, L Berschneider, H Morgan, RA TI Feasibility of gene transfer to gut epithelial cells for gene therapy of hemophilia SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV N CAROLINA,DIV PULM MED,CHAPEL HILL,NC 27515. N CAROLINA STATE UNIV,SCH VET MED,RALEIGH,NC 27606. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1997 SU S BP PS231 EP PS231 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE898 UT WOS:A1997XE89800230 ER PT J AU Tomer, A Harker, LA Kasey, S Eckman, JR AF Tomer, A Harker, LA Kasey, S Eckman, JR TI Reduced predisposition to thrombosis in sickle cell disease (SCD) patients treated with dietary n-3 fatty acids SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 GEORGIA NIH SICKLE CELL CTR,ATLANTA,GA. EMORY UNIV,SCH MED,DIV HEMATOL ONCOL,ATLANTA,GA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1997 SU S BP P1342 EP P1342 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE898 UT WOS:A1997XE89801340 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 surface-dependent factor IXa-catalyzed factor-X activation SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 TEMPLE UNIV,SCH MED,SOL SHERRY THROMBOSIS RES CTR,PHILADELPHIA,PA 19122. NIAID,MED ENTOMOL SECT,NIH,BETHESDA,MD 20892. FED UNIV RIO DE JANEIRO,ICB,DEPT BIOCHEM MED,RIO JANEIRO,BRAZIL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1997 SU S BP P1780 EP P1780 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE898 UT WOS:A1997XE89801779 ER PT J AU Williams, SB Krutzsch, H McKeown, LP Gralnick, HR AF Williams, SB Krutzsch, H McKeown, LP Gralnick, HR TI Glycocalicin derived peptides inhibit von Willebrand factor binding to platelets. SO THROMBOSIS RESEARCH LA English DT Article DE von Willebrand factor; Glycocalicin; platelets; peptides; asialo von Willebrand; factor; von Willebrand factor binding ID VONWILLEBRAND-FACTOR-BINDING; GLYCOPROTEIN-IB; THROMBIN; IDENTIFICATION; DOMAINS; ALPHA; ACID C1 NCI,SERV HEMATOL,DEPT CLIN PATHOL,WARREN G MAGNUSON CLIN CTR,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 8 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD JUN 1 PY 1997 VL 86 IS 5 BP 417 EP 421 DI 10.1016/S0049-3848(97)00087-X PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XF853 UT WOS:A1997XF85300009 PM 9211633 ER PT J AU Ting, YT Cheng, SY AF Ting, YT Cheng, SY TI Hormone-activated phosphorylation of human beta(1) thyroid hormone nuclear receptor SO THYROID LA English DT Article ID CONFORMATIONAL-CHANGES; TRANSCRIPTION AB To understand the role of phosphorylation in the hormone-dependent transcriptional activation of thyroid hormone receptors (TRs), the present study evaluated the effect of the thyroid hormone, 3,3',5-triiodo-L-thyronine (T-3) on the phosphorylation of TR, human subtype beta 1 [h-TR beta(1)]. The extent of phosphorylation was compared in cells cultured in T-3-depleted (Td) or T-3-supplemented medium (Td+T-3). T-3 was found to activate phosphorylation of h-TR beta(1) approximately threefold. Taking into account the T-3-induced fourfold downregulation in the expression of h-TR beta(1) in the same period, the specific T-3-activated phosphorylation was increased approximately twelvefold. Phosphoamino acid analysis indicates that the phosphorylation of serine and threonine in a ratio of similar to 10:1 was increased approximately threefold by T-3. Comparison of the [P-32]-labeled tryptic maps of h-TR beta(1) phosphorylated in cells cultured in Td medium or Td + T-3 medium indicates that the latter had fewer fragments and changes of intensities in several common fragments, indicating that the phosphorylation sites activated by T-3-treatment differed from those of basal phosphorylation. Partial V8 and chymotrypic proteolysis indicates that h-TR beta(1) phosphorylated in cells cultured in Td + T-3 medium was more resistant to proteolysis. These results indicate that Ts-activated phosphorylation altered the protease susceptibility of h-TR beta(1) that could reflect structural changes in h-TR beta(1). These results raise the possibility that T-3-activated phosphorylation may play an important role in transcriptional activation of h-TR beta(1). C1 NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 24 TC 13 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD JUN PY 1997 VL 7 IS 3 BP 463 EP 469 DI 10.1089/thy.1997.7.463 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XL016 UT WOS:A1997XL01600023 PM 9226220 ER PT J AU Parham, FM Kohn, MC Matthews, HB DeRosa, C Portier, CJ AF Parham, FM Kohn, MC Matthews, HB DeRosa, C Portier, CJ TI Using structural information to create physiologically based pharmacokinetic models for all polychlorinated biphenyls .1. Tissue:blood partition coefficients SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID CHLORINATED BIPHENYLS; ORGANIC-CHEMICALS; RAT; EXCRETION; CONGENERS; TRANSPORT; ALGORITHM; ISOMERS AB Physiologically based pharmacokinetic (PBPK) models are useful in describing the distribution, metabolism, and fate of xenobiotics across multiple species. The eventual goal of the present research is to create PBPK models for all 209 polychlorinated biphenyls (PCBs). Keys parameters in any PBPK model are the tissue-to-blood partition coefficients. Tissue:blood partition coefficients relate the compound's concentration in a target tissue to its concentration in blood under equilibrium conditions. Data on the adipose:plasma partition coefficients of 24 PCBs were used in a regression analysis to find an expression for the adipose:plasma partition coefficient as a function of molecular structure. Using stepwise regression, it was found that three simple structural descriptors were sufficient to predict adipose:plasma partition coefficients for all 209 PCB congeners. Data on the distribution of PCBs among blood components were used to derive the adipose:blood partition coefficient from the adipose:plasma partition coefficient. The lipid contents of li, er. muscle, and skin were used to derive the tissue:blood partition coefficient for those tissues from the adipose:blood partition coefficient. These results allow for the calculation of tissue:blood partition coefficients for liver, skin, muscles, and fat for all 209 PCB congeners. (C) 1997 Academic Press. C1 AGCY TOX SUBST & DIS REGISTRY,ATLANTA,GA. RP Parham, FM (reprint author), NIEHS,OAO,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 27 TC 68 Z9 69 U1 5 U2 16 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN PY 1997 VL 144 IS 2 BP 340 EP 347 DI 10.1006/taap.1997.8139 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XF149 UT WOS:A1997XF14900015 PM 9194418 ER PT J AU Alter, HJ AF Alter, HJ TI G-pers creepers, where'd you get those papers? A reassessment of the literature on the hepatitis G virus SO TRANSFUSION LA English DT Editorial Material ID DONORS; BLOOD RP Alter, HJ (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,INFECT DIS SECT,BETHESDA,MD 20892, USA. NR 23 TC 105 Z9 109 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 1997 VL 37 IS 6 BP 569 EP 572 DI 10.1046/j.1537-2995.1997.37697335149.x PG 4 WC Hematology SC Hematology GA XD776 UT WOS:A1997XD77600001 PM 9191815 ER PT J AU Atwater, I Yanez, A Cea, R Navia, A Jeffs, S Arraya, V SzpakGlasman, M Leighton, X Goping, G Bevilacqua, JA Moreno, R Brito, J Arriaza, C Ommaya, A AF Atwater, I Yanez, A Cea, R Navia, A Jeffs, S Arraya, V SzpakGlasman, M Leighton, X Goping, G Bevilacqua, JA Moreno, R Brito, J Arriaza, C Ommaya, A TI Cerebral spinal fluid shunt is an immunologically privileged site for transplantation of xenogeneic islets SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT International Congress of the Transplant-Society CY SEP 29-OCT 02, 1996 CL MIAMI BEACH, FL SP Transplantat Soc ID INSULIN C1 UNIV CHILE,FAC MED,DEPT NEUROL & NEUROSURG,SANTIAGO 7,CHILE. UNIV CHILE,FAC MED,DEPT ANAT,SANTIAGO 7,CHILE. UNIV CHILE,JJ AGUIRRE CLIN HOSP,DEPT MED,ENDOCRINOL SECT,SANTIAGO 7,CHILE. CYBORGAN INC,BETHESDA,MD. RP Atwater, I (reprint author), NIDDK,LAB CELL BIOCHEM & BIOL,NIH,RM 326,BLDG 8,BETHESDA,MD 20892, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1997 VL 29 IS 4 BP 2111 EP 2115 DI 10.1016/S0041-1345(97)00254-6 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XE833 UT WOS:A1997XE83300094 PM 9193549 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Optimizing multiplex and LA-PCR with betaine SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID MINERAL-OIL; SPECIFICITY; INHIBITION AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses the use of additives fcr optimizing the amount and quality of product obtained through multiplex and 'long and accurate' polymerase chain reaction (LA-PCR). For details on how to partake in the newsgroup, see the accompanying box. RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 8 TC 30 Z9 32 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUN PY 1997 VL 22 IS 6 BP 225 EP 226 DI 10.1016/S0968-0004(97)01069-4 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XF083 UT WOS:A1997XF08300009 PM 9204710 ER PT J AU Choyke, PL Glenn, GM Wagner, JP Lubensky, IA Thakore, K Zbar, B Linehan, WM Walther, MM AF Choyke, PL Glenn, GM Wagner, JP Lubensky, IA Thakore, K Zbar, B Linehan, WM Walther, MM TI Epididymal cystadenomas in von Hippel-Lindau disease SO UROLOGY LA English DT Article ID CELL PAPILLARY CYSTADENOMA AB Objectives. Epididymal cystadenomas (ECs) are frequently found in association with von Hippel-Lindau disease (VHL), but little has been reported about their sonographic appearance. We review the sonographic appearance of ECs, the relationship of ECs to other manifestations of VHL, and the specific genetic mutations associated with ECs. Methods. Fifty-six male patients with VHL were examined with scrotal sonography and physical examination as part of a larger screening program for VHL. The head of the epididymis was measured in two planes on sonography and compared with age-matched normal controls. All VHL patients with palpable epididymal abnormalities or enlargement (more than two standard deviations) of the head of the epididymis on ultrasound were considered positive for EC. Results. Thirty of 56 (54%) male patients with VHL demonstrated a unilateral (n = 10; 33%) or bilateral (n = 20; 67%) solid abnormality in the head of the epididymis suggestive of EC. Sonographic appearances ranged from a solid mass with multiple tiny cysts to an almost completely solid mass. The most common appearance was a 15- to 20-mm solid mass with small cystic components. Dilated efferent ductules were seen within the testicle in 7 men, evidently a result of chronic obstruction. There was no association between the clinical subtype of VHL and the presence of ECs (P > 0.10, chi square). Mutations resulting in a truncated gene product were associated with the development of ECs but the association did not reach statistical significance (P = 0.06). Conclusions. ECs are a common manifestation of VHL in men and exhibit a range of appearances on ultrasound. Sonography can be used to identify ECs and determine the extent of cystic dilation of the rete testes. The benign course of ECs and the usual absence of clinical symptoms favor a conservative approach to their management. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NCI,DIV CANC EPIDEMIOL & GENET,NIH,BETHESDA,MD 20892. NCI,UROL ONCOL SECT,SURG BRANCH,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,IMMUNOBIOL SECT,NIH,FREDERICK,MD 21701. NR 16 TC 36 Z9 39 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUN PY 1997 VL 49 IS 6 BP 926 EP 931 DI 10.1016/S0090-4295(97)00074-5 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA XC721 UT WOS:A1997XC72100023 PM 9187702 ER PT J AU Ray, NB Ewalt, LC Lodmell, DL AF Ray, NB Ewalt, LC Lodmell, DL TI Nanogram quantities of plasmid DNA encoding the rabies virus glycoprotein protect mice against lethal rabies virus infection SO VACCINE LA English DT Article; Proceedings Paper CT International Meeting on Nucleic Acid Vaccines for the Prevention of Infectious Diseases CY FEB 05-07, 1996 CL BETHESDA, MD SP European Commiss, US FDA, Nat Inst Allergy & Infect Dis, WHO DE rabies virus; DNA vaccination; cross-neutralization AB Vaccination against virus infections has proven to be an effective strategy in the improvement of human health. In this study, we evaluated two plasmid DNA vaccines expressing the glycoprotein (G) gene of the challenge virus standard (CVS) rabies virus for their ability to elicit neutralizing antibody and protect BALB/cByJ mice against lethal rabies virus challenge. A single inoculation of 10 mu g of plasmid DNA encoding G protected 100% of the intramuscularly (i.m.) vaccinated mice, and O.1 mu g of DNA protected 83% of the intradermally (i.d.) vaccinated mice. All mice that survived had serum anti-rabies virus neutralizing antibody, titers equal to or greater than 1:40 prior to virus challenge. The highest antibody titers were detected in mice that had been inoculated i.m. with 10-100 mu g of DNA in regenerating muscle. The immunostimulant monophosphoryl lipid A enhanced the neutralizing antibody response of i.d.-vaccinated mice. Anti-rabies virus neutralizing antibody elicited by plasmid DNA vaccination cross-neutralized a global spectrum of rabies virus variants. These results indicate that DNA vaccines could be a solution for providing developing countries with an inexpensive vaccine that is simple to prepare, is highly efficacious and has excellent stability. (C) 1997 Elsevier Science Ltd. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 9 TC 55 Z9 57 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD JUN PY 1997 VL 15 IS 8 BP 892 EP 895 DI 10.1016/S0264-410X(96)00281-2 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XJ336 UT WOS:A1997XJ33600030 PM 9234541 ER PT J AU Smith, HA Goldenthal, KL Vogel, FR Rabinovich, R Aguado, T AF Smith, HA Goldenthal, KL Vogel, FR Rabinovich, R Aguado, T TI Workshop on the control and standardization of nucleic acid vaccines - 8 February 1996, Natcher Conference Center, Bethesda, MD SO VACCINE LA English DT Editorial Material C1 NIAID,NIH,BETHESDA,MD 20892. WHO,GLOBAL PROGRAMME VACCINES & IMMUNIZAT,CH-1211 GENEVA 27,SWITZERLAND. RP Smith, HA (reprint author), US FDA,CTR BIOL EVALUAT & RES,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 2 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD JUN PY 1997 VL 15 IS 8 BP 931 EP 933 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XJ336 UT WOS:A1997XJ33600040 PM 9340950 ER PT J AU Jaeger, MMM Araujo, VC Kachar, B Jaeger, RG AF Jaeger, MMM Araujo, VC Kachar, B Jaeger, RG TI Effect of spatial arrangement of the basement membrane on cultured pleomorphic adenoma cells. Study by immunocytochemistry and electron and confocal microscopy SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY LA English DT Article DE salivary gland neoplasms; myoepithelial cell; extracellular matrix; Matrigel ID SALIVARY-GLAND TUMORS; NEOPLASTIC MYOEPITHELIAL CELLS; FIBRILLARY ACIDIC PROTEIN; PAROTID-GLAND; ULTRASTRUCTURAL ORGANIZATION; DIAGNOSTIC-CRITERIA; FILAMENT PROTEINS; EPITHELIAL-CELLS; COLLAGEN GELS; MUSCLE-ACTIN AB In a cell line from human pleomorphic adenoma (AP2 cells) we studied the response of these cells to basement membrane proteins. The culture was characterized as myoepithelial-like by transmission electron microscopy and immunocytochemistry. AP2 cells were grown in contact with a reconstituted basement membrane (Matrigel). Cells grown on Matrigel showed conspicuous phenotypic alterations, depending on how the substrate was applied. Cells grown on the top of Matrigel developed a dendritic phenotype, exhibiting thin, long and intercommunicating cytoplasmic extensions resembling normal myoepithelial cells. Cells grown inside Matrigel formed multi-layered clusters. Light, confocal and transmission electron microscopy showed that these clusters were formed by double-layered epithelioid cells delimiting luminal spaces. The cells facing the lumen were cuboidal, showing microvilli at the apical plasmalemmal and junctional complexes. The spatial arrangement of basement membrane is a key modulator of morphogenetic changes and cytodifferentiation of tumour myoepithelial cell lineage in culture. C1 UNIV SAO PAULO,SCH DENT,DEPT ORAL PATHOL,SAO PAULO,BRAZIL. NIDOCD,LAB CELLULAR BIOL,NIH,BETHESDA,MD. RI Marques, Marcia/F-3780-2012; Araujo, Vera /G-3586-2014; Jaeger, Ruy/G-8230-2011 OI Marques, Marcia/0000-0002-9398-1252; NR 62 TC 22 Z9 23 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. Int. J. Pathol. PD JUN PY 1997 VL 430 IS 6 BP 467 EP 477 DI 10.1007/s004280050057 PG 11 WC Pathology SC Pathology GA XJ572 UT WOS:A1997XJ57200005 PM 9230912 ER PT J AU Nurnberger, JI DePaulo, JR Gershon, ES Reich, T Blehar, MC Edenberg, HJ Foroud, T Miller, M Bowman, E Mayeda, A Rau, NL Smiley, R Conneally, PM McMahon, F Meyers, D Simpson, S McInnis, M Stine, OC DeteraWadleigh, S Goldin, L Guroff, J Maxwell, E Kazuba, D Gejman, PV Badner, J Sanders, A Rice, J Bierut, L Goate, A AF Nurnberger, JI DePaulo, JR Gershon, ES Reich, T Blehar, MC Edenberg, HJ Foroud, T Miller, M Bowman, E Mayeda, A Rau, NL Smiley, R Conneally, PM McMahon, F Meyers, D Simpson, S McInnis, M Stine, OC DeteraWadleigh, S Goldin, L Guroff, J Maxwell, E Kazuba, D Gejman, PV Badner, J Sanders, A Rice, J Bierut, L Goate, A TI Genomic survey of bipolar illness in the NIMH genetics initiative pedigrees: A preliminary report SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE bipolar affective disorder; genetics; linkage; genomic survey; nonparametric analysis ID MANIC-DEPRESSIVE ILLNESS; X-CHROMOSOME MARKERS; AFFECTED RELATIVE PAIRS; POLYMORPHIC DNA MARKER; AFFECTIVE-DISORDER; LINKAGE ANALYSIS; COMPLEX TRAITS; OVARIAN-CANCER; SUSCEPTIBILITY GENE; MEMBER METHOD AB Four sites collaborated with the NIMH to develop a resource for the genetic study of bipolar (BP) illness. Common methods of ascertainment and assessment were developed in 1989. A series of families with a bipolar I (BPI) proband and at least one BPI or schizoaffective, bipolar type (SA/BP) first-degree relative has been studied. We now report initial data from a genomic survey with an average intermarker interval of 10 cM on 540 subjects from 97 families. This is the largest commonly ascertained and assessed linkage sample for bipolar illness reported to date; it includes 232 subjects with BPI, 32 SA/BP, 72 bipolar II (BPII), and 88 unipolar, recurrent (UPR). Nonparametric methods of analysis were employed, with all sites using affected sib pair analysis. The strongest findings thus far appear to be on chromosomes 1, 6, 7, 10, 16, and 22. Support has also been found for some previously reported linkages, including 21q and possibly Xq26. All these areas (as well as others) will be followed up with additional markers and further analyses. No locus tested thus far meets stringent criteria for an initial finding of significant linkage. Am. J. Med. Genet. 74:227-237, 1997. (C) 1997 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NIMH,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. WASHINGTON UNIV,ST LOUIS,MO 63130. RP Nurnberger, JI (reprint author), INDIANA UNIV,SCH MED,INST PSYCHIAT RES,DEPT PSYCHIAT,791 UNION DR,INDIANAPOLIS,IN 46202, USA. RI McMahon, Francis/A-7290-2009; OI Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X; Edenberg, Howard/0000-0003-0344-9690 NR 84 TC 94 Z9 94 U1 3 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 31 PY 1997 VL 74 IS 3 BP 227 EP 237 DI 10.1002/(SICI)1096-8628(19970531)74:3<227::AID-AJMG1>3.0.CO;2-N PG 11 WC Genetics & Heredity SC Genetics & Heredity GA XC331 UT WOS:A1997XC33100001 ER PT J AU Edenberg, HJ Foroud, T Conneally, PM Sorbel, JJ Carr, K Crose, C Willig, C Zhao, JH Miller, M Bowman, E Mayeda, A Rau, NL Smiley, C Rice, JP Goate, A Reich, T Stine, OC McMahon, F DePaulo, JR Meyers, D DeteraWadleigh, SD Goldin, LR Gershon, ES Blehar, MC Nurnberger, JI AF Edenberg, HJ Foroud, T Conneally, PM Sorbel, JJ Carr, K Crose, C Willig, C Zhao, JH Miller, M Bowman, E Mayeda, A Rau, NL Smiley, C Rice, JP Goate, A Reich, T Stine, OC McMahon, F DePaulo, JR Meyers, D DeteraWadleigh, SD Goldin, LR Gershon, ES Blehar, MC Nurnberger, JI TI Initial genomic scan of the NIMH genetics initiative bipolar pedigrees: Chromosomes 3, 5, 15, 16, 17, and 22 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE genetic linkage; sib pair analysis; family study; unipolar recurrent depression; microsatellite markers ID MANIC-DEPRESSIVE ILLNESS; LINKAGE; MARKERS; LOCUS AB As part of the four-center NIMH Genetics Initiative on Bipolar Disorder we carried out a genomic scan of chromosomes 3, 5, 15, 16, 17, and 22. Genotyping was performed on a set of 540 DNAs from 97 families, enriched for affected relative pairs and parents where available. We report here the results of the initial 74 markers that have been typed on this set of DNAs. The average distance between markers (8) was 12.3 cM. Nonparametric analysis of excess allele sharing among affected sibling pairs used the SIBPAL program of the S.A.G.E. package to test three hierarchical models of affected status. D16S2619 gave some evidence of linkage to bipolar disorder, with P = 0.006 for Model II (in which bipolar 1, bipolar 2 and schizoaffective-bipolar type individuals are considered affected). Nearby markers also showed increased allele sharing. A second interesting region was toward the telomere of chromosome 5q, where D5S1456 and nearby markers showed increased allele sharing; for D5S1456, P = 0.05, 0.015 and 0.008 as the models of affected status become more broad. MOD score analysis also supported the possible presence of a susceptibility locus in this region of chromosome 5. A pair of adjacent markers on chromosome 3, D3S2405 and D3S3038, showed a modest increased allele sharing in the broad model. Several isolated markers had excess allele sharing at the P < 0.05 level under a single model. D15S217 showed a MOD score of 2.37 (P < 0.025). Multipoint analysis flagged the region of chromosome 22 around D22S533 as the most interesting. Thus, several regions showed modest evidence for linkage to bipolar disorder in this initial genomic scan of these chromosomes, including broad regions near previous reports of possible linkage. Am. J. Med. Genet. 74:238-246, 1997. (C) 1997 Wiley-Liss, Inc. C1 WASHINGTON UNIV,ST LOUIS,MO. JOHNS HOPKINS UNIV,BALTIMORE,MD. NIMH,BETHESDA,MD 20892. RP Edenberg, HJ (reprint author), INDIANA UNIV,SCH MED,DEPT BIOCHEM & MOL BIOL,635 BARNHILL DR,MS418,INDIANAPOLIS,IN 46202, USA. RI McMahon, Francis/A-7290-2009; OI Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X; Edenberg, Howard/0000-0003-0344-9690 FU NCRR NIH HHS [1 P41 RR03655]; NIMH NIH HHS [U01 MH54794, U01 MH46280] NR 24 TC 147 Z9 147 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 31 PY 1997 VL 74 IS 3 BP 238 EP 246 DI 10.1002/(SICI)1096-8628(19970531)74:3<238::AID-AJMG2>3.0.CO;2-M PG 9 WC Genetics & Heredity SC Genetics & Heredity GA XC331 UT WOS:A1997XC33100002 PM 9184305 ER PT J AU Rice, JP Goate, A Williams, JT Bierut, L Dorr, D Wu, W Shears, S Gopalakrishnan, G Edenberg, HJ Foroud, T Nurnberger, J Gershon, ES DeteraWadleigh, SD Goldin, LR Guroff, JJ McMahon, FJ Simpson, S MacKinnon, D McInnis, M Stine, OC DePaulo, JR Blehar, MC Reich, T AF Rice, JP Goate, A Williams, JT Bierut, L Dorr, D Wu, W Shears, S Gopalakrishnan, G Edenberg, HJ Foroud, T Nurnberger, J Gershon, ES DeteraWadleigh, SD Goldin, LR Guroff, JJ McMahon, FJ Simpson, S MacKinnon, D McInnis, M Stine, OC DePaulo, JR Blehar, MC Reich, T TI Initial genome scan of the NIMH genetics initiative bipolar pedigrees: Chromosomes 1, 6, 8, 10, and 12 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE bipolar disorder; linkage analysis; genome scan; genome screen; affected sib pairs ID DARIERS-DISEASE; SEGREGATION ANALYSIS; AFFECTIVE-DISORDERS; LINKAGE ANALYSIS; SCHIZOPHRENIA; FAMILY; SUSCEPTIBILITY; 6P24-22; REGION; LOCUS AB A report on an initial genome screen on 540 individuals in 97 families was collected as part of the NIMH Genetics Initiative on Bipolar Disorder. Families were ascertained to be informative for genetic linkage and underwent a common ascertainment and assessment protocol at four clinical sites. The sample was genotyped for 65 highly polymorphic markers from chromosomes 1, 6, 8, 10, and 12. The average intermarker interval was 16 cM. Genotypic data was analyzed using affected sib pair, multipoint affected sib pair, and pedigree analysis methods. Multipoint methods gave lod scores of approximately two on chromosomes 1, 6, and 10. The peak lod score on chromosome 6 occurred at the end of the q-arm, at some distance from the 6p24-22 area previously implicated for Schizophrenia. We are currently genotyping additional markers to reduce the intermarker interval around the signals. The interpretation of results from a genome screen of a complex disorder and the problem of achieving a balance between detecting false positive results and the ability to detect genes of modest effect are discussed. Am. J. Med, Genet. 74:247-253, 1997. (C) 1997 Wiley-Liss, Inc. C1 INDIANA UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,INST PSYCHIAT RES,INDIANAPOLIS,IN. NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205. NIMH,NIH,MOOD ANXIETY & PERSONAL DISORDERS RES BRANCH,ROCKVILLE,MD. RP Rice, JP (reprint author), WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,BOX 8134,4940 CHILDRENS PL,ST LOUIS,MO 63110, USA. RI McMahon, Francis/A-7290-2009; OI Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X; Edenberg, Howard/0000-0003-0344-9690 FU NIMH NIH HHS [MH31302, MH37685, MH46280] NR 28 TC 110 Z9 111 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 31 PY 1997 VL 74 IS 3 BP 247 EP 253 DI 10.1002/(SICI)1096-8628(19970531)74:3<247::AID-AJMG3>3.0.CO;2-N PG 7 WC Genetics & Heredity SC Genetics & Heredity GA XC331 UT WOS:A1997XC33100003 PM 9184306 ER PT J AU DeteraWadleigh, SD Badner, JA Yoshikawa, T Sanders, AR Goldin, LR Turner, G Rollins, DY Moses, T Guroff, JJ Kazuba, D Maxwell, ME Edenberg, HJ Foroud, T Lahiri, D Nurnberger, JI Stine, OC McMahon, F Meyers, DA MacKinnon, D Simpson, S McInnis, M DePaulo, JR Rice, J Goate, A Reich, T Blehar, MC Gershon, ES AF DeteraWadleigh, SD Badner, JA Yoshikawa, T Sanders, AR Goldin, LR Turner, G Rollins, DY Moses, T Guroff, JJ Kazuba, D Maxwell, ME Edenberg, HJ Foroud, T Lahiri, D Nurnberger, JI Stine, OC McMahon, F Meyers, DA MacKinnon, D Simpson, S McInnis, M DePaulo, JR Rice, J Goate, A Reich, T Blehar, MC Gershon, ES TI Initial genome scan of the NIMH genetics initiative bipolar pedigrees: Chromosomes 4, 7, 9, 18, 19, 20, and 21q SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE bipolar pedigree; genome scan; bipolar disorder; linkage ID BY-DESCENT METHOD; AFFECTIVE-DISORDER; LINKAGE; ILLNESS; DISEASE; TRAITS; LOCUS; DNA AB An initial genome scan was performed on 540 individuals from 97 families segregating bipolar disorder, collected through the National Institutes of Mental Health Genetics Initiative. We report here affected-sib-pair (ASP) data on 126 marker loci (approximate to 68,000 genotypes) mapping to chromosomes 4, 7, 9, 18, 19, 20, and 21q, under three affection status models. Modest increases in identical-by-descent (IBD) allele sharing were found at the following loci: D4S2397 and D4S391 (P < 0.05) on 4p, D4S1647 (P < 0.05) on 4q, D7S1802 and D7S1869 (low P = 0.01) on 7p, D9S302 (P = 0.004) on 9q, and D20S604 on 20p and D20S173 on 20q (P less than or equal to 0.05). In addition, five markers on 7q displayed increased IBD sharing (P = 0.046-0.002). Additional ASP analyses on chromosomes 18 and 21q marker data were performed using disease phenotype models defined previously. On chromosome 18, only D18S40 on 18p and D18S70 on 18q yielded a slight elevation in allele sharing (P = 0.02), implying that the reported linkages in these regions were not confirmed. On chromosome 21q, a cluster of markers within an approximate to cM interval: D21S1254, D21S65, D21S1440, and D21S1255 exhibited excess allele sharing (P = 0.041-0.008). Multilocus data on overlapping marker quartets, from D21S1265 to D21S1255, which were consistent with increased IBD sharing (P < 0.01, with a low of 0.0009), overlapped a broad interval of excess allele sharing reported previously, increasing support for a susceptibility locus for bipolar disorder on 21q. Am. J. Med. Genet. 74:254-262, 1997. (C) 1997 Wiley-Liss, Inc. C1 INDIANA UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,INDIANAPOLIS,IN. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205. WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. NIMH,MOOD ANXIETY & PERSONAL DISORDERS RES BRANCH,ROCKVILLE,MD 20857. RP DeteraWadleigh, SD (reprint author), NIMH,CLIN NEUROGENET BRANCH,NIH,BLDG 10,ROOM 3N218,BETHESDA,MD 20892, USA. RI McMahon, Francis/A-7290-2009; OI Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X; Edenberg, Howard/0000-0003-0344-9690 NR 32 TC 132 Z9 134 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 31 PY 1997 VL 74 IS 3 BP 254 EP 262 DI 10.1002/(SICI)1096-8628(19970531)74:3<254::AID-AJMG4>3.0.CO;2-Q PG 9 WC Genetics & Heredity SC Genetics & Heredity GA XC331 UT WOS:A1997XC33100004 PM 9184307 ER PT J AU Stine, OC McMahon, FJ Chen, LS Xu, JF Meyers, DA MacKinnon, DF Simpson, S McInnis, MG Rice, JP Goate, A Reich, T Edenberg, HJ Foroud, T Nurnberger, JI DeteraWadleigh, SD Goldin, LR Guroff, J Gershon, ES Blehar, MC DePaulo, JR AF Stine, OC McMahon, FJ Chen, LS Xu, JF Meyers, DA MacKinnon, DF Simpson, S McInnis, MG Rice, JP Goate, A Reich, T Edenberg, HJ Foroud, T Nurnberger, JI DeteraWadleigh, SD Goldin, LR Guroff, J Gershon, ES Blehar, MC DePaulo, JR TI Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees: Chromosomes 2, 11, 13, 14, and X SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE linkage; occlusion mapping; affective disorder ID MANIC-DEPRESSIVE ILLNESS; MAJOR AFFECTIVE-DISORDER; CHRISTMAS DISEASE; FACTOR-IX; LINKAGE; MARKERS; LINEALITY; FAMILY; LOCI AB We report on an initial genome screen of 540 individuals from 97 families collected as part of the NIMH Genetics Initiative Bipolar Group. Among the individuals studied, 232 were diagnosed with bipolar (BP) I, 72 with BPII, 88 with major depressive disorder-recurrent type (UPR), and 32 with schizoaffective disorder, bipolar type (SA/BP). A total of 53 markers on chromosomes 2, 11, 13, 14, and X (average spacing: 11.5 cM) were studied at Johns Hopkins University. Tests for linkage were performed using nonparametric affected sib-pair and whole pedigree methods with three definitions of affected status. Three regions of interest were identified (13q14-32, Xp22, and Xq26-28). On chromosomes 2, 11, and 14, a disease locus with relative risk lambda(i) = 1.5 could be excluded in <10% of the genetic distance studied, while a locus conferring lambda(i) = 3 or greater could be excluded across at least 96%. The autosomal region that could not be excluded even with lambda(i) = 5 was near 13q14-32. In this region, two-point affected sib-pair analyses revealed a pair of consecutive loci with excess sharing (P < 0.05) and a multipoint affected sib-pair LOD score of 1.12. On the X chromosome, nonparametric multipoint affected sib-pair analyses revealed peak total LOD scores of 0.94 on Xp22 and 1.34 on Xq2628. A locus linked to the markers in Xp22 would have lambda(i) = 3.6 in affected brother-brother pairs, while a locus linked to the markers in Xq26-28 would have lambda(i) greater than or equal to 1.9 in affected sister-sister pairs. The results on 13q14-32, Xp22, and Xq26-28 suggest areas of interest for further studies. Am. J. Med. Genet. 74:263-269, 1997. (C) 1997 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21287. WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. NIMH,NIH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. NIMH,MOOD ANXIETY & PERSONAL DISORDERS RES BRANCH,ROCKVILLE,MD 20857. INDIANA UNIV,MED CTR,INST PSYCHIAT RES,DEPT PSYCHIAT,INDIANAPOLIS,IN. INDIANA UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,INDIANAPOLIS,IN. INDIANA UNIV,MED CTR,DEPT MOL MED GENET,INDIANAPOLIS,IN. RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012; OI McInnis, Melvin/0000-0002-0375-6247; Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X; Edenberg, Howard/0000-0003-0344-9690 FU NCRR NIH HHS [1 P41 RR03655] NR 48 TC 89 Z9 89 U1 5 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 31 PY 1997 VL 74 IS 3 BP 263 EP 269 DI 10.1002/(SICI)1096-8628(19970531)74:3<263::AID-AJMG5>3.0.CO;2-R PG 7 WC Genetics & Heredity SC Genetics & Heredity GA XC331 UT WOS:A1997XC33100005 PM 9184308 ER PT J AU Johnson, JE Cleary, J Ahsan, H Friedman, JH Malaspina, D Cloninger, CR Faraone, SV Tsuang, MT Kaufmann, CA AF Johnson, JE Cleary, J Ahsan, H Friedman, JH Malaspina, D Cloninger, CR Faraone, SV Tsuang, MT Kaufmann, CA TI Anticipation in schizophrenia: Biology or bias? SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT World Congress on Psychiatric Genetics CY AUG-SEP -, 1995 CL CARDIFF, WALES DE trinucleotide repeats; genetics; age of onset; disease severity ID ROSCOMMON FAMILY; DISORDERS; RELATIVES; BIPOLAR; DISEASE; REPEATS; ONSET; AGE AB Anticipation is a genetic phenomenon wherein age of disease onset decreases and/ or severity increases in successive generations, Anticipation has been demonstrated for several neuropsychiatric disorders with expanding trinucleotide repeats recently identified as the underlying molecular mechanism, We report here the results of an analysis of anticipation performed with multiplex families segregating schizophrenia. Thirty-three families were identified through the NIMH Genetics Initiative that met the following criteria: had at least two affected members in successive generations and were not bilineal, Affectation diagnoses included schizophrenia, schizoaffective disorder-depressed, and psychosis NOS, Additional analyses included the Cluster A personality disorders. Three indices of age of onset were used, Disease severity was measured by several different indices. Four sampling schemes as suggested by McInnis et al, were tested, as well as additional analysis using pairs ascertained through the parental generation, Anticipation was demonstrated for age of onset, regardless of the index or sampling scheme used (P < 0.05). Anticipation was not supported for disease severity, Analyses that took into account drug use and diminished fecundity did not affect the results, While the data strongly support intergenerational differences in disease onset consistent with anticipation, they must be viewed cautiously given unavoidable biases attending these analyses, Am, J. Med, Genet. 74:275-280, 1997. (C) 1997 Wiley-Liss, Inc. C1 COLUMBIA UNIV COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY 10032. COLUMBIA UNIV,NIMH,GENET INITIAT,NEW YORK,NY 10027. UNIV WASHINGTON,NIMH,GENET INITIAT,SEATTLE,WA 98195. HARVARD UNIV,NIMH,GENET INIAT,CAMBRIDGE,MA 02138. RI Cloninger, Claude/F-5357-2012; OI Cloninger, Claude/0000-0003-3096-4807; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [2K02MH00682, 5T32MH19970] NR 34 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 31 PY 1997 VL 74 IS 3 BP 275 EP 280 DI 10.1002/(SICI)1096-8628(19970531)74:3<275::AID-AJMG7>3.0.CO;2-P PG 6 WC Genetics & Heredity SC Genetics & Heredity GA XC331 UT WOS:A1997XC33100007 PM 9184310 ER PT J AU Molloy, AM Daly, S Mills, JL Kirke, PN Whitehead, AS Ramsbottom, D Conley, MR Weir, DG Scott, JM AF Molloy, AM Daly, S Mills, JL Kirke, PN Whitehead, AS Ramsbottom, D Conley, MR Weir, DG Scott, JM TI Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: Implications for folate intake recommendations SO LANCET LA English DT Article ID CORONARY-ARTERY DISEASE; NEURAL-TUBE DEFECTS; METHYLENETETRAHYDROFOLATE REDUCTASE; RISK FACTOR; VASCULAR-DISEASE; DEFICIENCY AB Background The dietary reference values for folate, as for other nutrients, are targeted to the general and supposedly normal population, not people with special needs, such as those with genetic or metabolic abnormalities or diseases. However, 5-15% of general populations are homozygous for a thermolabile variant of 5,10-methylenetetrahydrofolate reductase (C677T) which causes mild hyperhomocysteinaemia and is positively associated with the development of vascular disease and the risk of neural-tube defects. If tissue-folate status is compromised in large sectors of the population by this or other genetic variants, the present dietary reference Values may need to be changed. Methods We identified the C677T genotype and measured red-cell folate concentrations in two groups of healthy women (pregnant, 242, not pregnant, 318). We then analysed the effect of genotype on red-cell folates, which are a reliable marker for tissue folate stores. Findings In the pregnant group there were 20 TT homozygotes, 114 wild-type CC homozygotes, and 108 CT heterozygotes. In the non-pregnant group, the numbers were 41, 148, and 129. In both pregnant and non-pregnant groups, red-cell folate was significantly lower among TT homozygous than CC homozygous women (mean 252 [95% CI 202-317] vs 347 [321-372] mu g/L, p=0.002 for pregnant women; 284 [250-327] vs 347 [342-372] mu g/L, p=0.01 for non-pregnant women). Plasma folate was also significantly lower in TT homozygous than in CC homozygous women in the pregnant group (p=0.009) but not in the non-pregnant group. Interpretation These results suggest that a substantial minority of people in general populatgions may have increased folate needs. Future studies may show the presence of other common genetic variants that interact with particular nutrients and place doubts on the validity of assuming ''normality'' for nutrient requirements in any general population. C1 UNIV DUBLIN TRINITY COLL,DEPT BIOCHEM,DUBLIN 2,IRELAND. UNIV DUBLIN TRINITY COLL,DEPT CLIN MED,DUBLIN 2,IRELAND. UNIV DUBLIN TRINITY COLL,DEPT GENET,DUBLIN 2,IRELAND. UNIV DUBLIN TRINITY COLL,INST BIOTECHNOL,DUBLIN 2,IRELAND. COOMBE WOMENS HOSP,DUBLIN,IRELAND. HLTH RES BOARD,DUBLIN,IRELAND. NICHHD,BETHESDA,MD 20892. NR 20 TC 243 Z9 245 U1 0 U2 3 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 31 PY 1997 VL 349 IS 9065 BP 1591 EP 1593 DI 10.1016/S0140-6736(96)12049-3 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA XB673 UT WOS:A1997XB67300010 PM 9174561 ER PT J AU Newman, JD Bachevalier, J AF Newman, JD Bachevalier, J TI Neonatal ablations of the amygdala and inferior temporal cortex alter the vocal response to social separation in rhesus macaques SO BRAIN RESEARCH LA English DT Article DE limbic system; vocalization; primate brain; neuroethology; communication; development ID SQUIRREL-MONKEY; VOCALIZATION; PROJECTIONS; STIMULI; LESIONS; AREA AB Rhesus macaques that had received bilateral ablations to either the amygdala or area TE in inferior temporal cortex in the Ist week of life were briefly separated from familiar conspecifics at 10-14.5 months of age in order to assess the vocal response to this mild challenge. Sound spectrograms were subjected to quantitative analysis and compared with calls from normal, age-matched controls subjected to the same testing conditions. Animals with TE damage called at a higher rate than animals in the other two groups. TE subjects also produced more coos than controls. Males with TE lesions produced noisy calls at a higher rate than males of the other two groups. Females did not differ between groups in this measure. Analysis of the detailed acoustic structure of the 'coo' indicated significant differences in a measure of slope of the fundamental frequency (rate of frequency change over time) between amygdalectomized animals and those of the other 2 groups. The amygdalectomized monkeys produced calls with lower slope values, giving the calls a less inflected quality both in sonagrams and to the listener. These findings suggest an important role for the amygdala and inferior temporal cortex in regulating the vocal response to social separation during development. C1 NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD 20837. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NR 39 TC 23 Z9 23 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 MAY 30 PY 1997 VL 758 IS 1-2 BP 180 EP 186 DI 10.1016/S0006-8993(97)00212-6 PG 7 WC Neurosciences SC Neurosciences & Neurology GA XE606 UT WOS:A1997XE60600022 PM 9203547 ER PT J AU Potapova, O Haghighi, A Bost, F Liu, CT Birrer, MJ Gjerset, R Mercola, D AF Potapova, O Haghighi, A Bost, F Liu, CT Birrer, MJ Gjerset, R Mercola, D TI The Jun kinase stress-activated protein kinase pathway functions to regulate DNA repair and inhibition of the pathway sensitizes tumor cells to cisplatin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAYS; C-JUN; HA-RAS; TOPOISOMERASE GENE; POLYMERASE-BETA; PHOSPHORYLATION; DOMAIN; BINDS; TRANSFORMATION; TRANSCRIPTION AB We have studied the role of Jun/stress-activated protein kinase (JNK/SAPK) pathway in DNA repair and cisplatin resistance in T98G glioblastoma cells. JUN/SAPK is activated by DNA damage and phosphorylates serines 63 and 73 in the N-terminal domain of c-Jun, which is known to increase its transactivation properties, We show that treatment of T98G glioblastoma cells with cisplatin but not the transplatin isomer activates JNK/SAPK about 10-fold, T98G cells, which are highly resistent to cisplatin (IC50 = 140 +/- 13 mu M), modified to express a nonphosphorylatable dominant negative c-Jun (termed dnJun) exhibit decreased viability following treatment with cisplatin, but not transplatin, in proportion (r(Pearson) = 0.98) to the level of dnJun expressed leading to a 7-fold decreased IC50. Similar effects are observed in U87 cells, PC-3 cells, and MCF-7 cells, as well as in T98G cells modified to express TAM-67, a known inhibitor of c-Jun function. In contrast, no sensitization effect was observed in cells modified to express wildtype c-Jun, Furthermore, through quantitative polymerase chain reaction-stop assays, we show that dnJun expressing cells were inhibited in repair of cisplatin adducts (p = 0.55), whereas repair is readily detectable (p = 0.003) in parental cells. These observations indicate that the JNK/SAPK pathway is activated by cisplatin-induced DNA damage and that this response is required for DNA repair and viability following cisplatin treatment, Regulation of DNA repair following genotoxic stress may be a normal physiological role of the JNK/SAPK pathway. C1 SIDNEY KIMMEL CANC CTR,SAN DIEGO,CA 92121. UNIV CALIF SAN DIEGO,CTR MOL GENET,LA JOLLA,CA 92093. NIH,DIV BIOMARKERS,ROCKVILLE,MD 20850. NIH,PREVENT RES BRANCH,ROCKVILLE,MD 20850. FU NCI NIH HHS [CA 63783] NR 33 TC 205 Z9 208 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 1997 VL 272 IS 22 BP 14041 EP 14044 DI 10.1074/jbc.272.22.14041 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB492 UT WOS:A1997XB49200012 PM 9162025 ER PT J AU Mao, SY Metzger, H AF Mao, SY Metzger, H TI Characterization of protein-tyrosine phosphatases that dephosphorylate the high affinity IgE receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNOGLOBULIN-E; FC-EPSILON; MAST-CELLS; PHOSPHORYLATION; KINASES; AGGREGATION; P53/56(LYN); EXPRESSION; COMPONENT; MECHANISM AB An early event that follows aggregation of the high affinity receptor for IgE (Fc epsilon RI) is the phosphorylation of protein tyrosines, especially those on the beta- and gamma-subunits of the receptor. Disaggregation of the receptors leads to their rapid dephosphorylation, but even stably aggregated receptors undergo continual rounds of phosphorylation and dephosphorylation. We developed assays to study dephosphorylation of the receptors and other cellular proteins. Whole cell extracts dephosphorylated both subunits of the receptors rapidly and were as active against aggregated as against disaggregated Fc epsilon RI, Upon disaggregation, the in vivo dephosphorylation of the Fc epsilon RI and several other proteins followed first-order kinetics with closely similar rate constants despite substantial differences in the extent of phosphorylation. These results suggest that the level of phosphorylation of Fc epsilon RI is largely controlled by the aggregation-induced action of kinase(s) and not from changes in susceptibility to or activity of the phosphatases. Much of the total phosphatase is lost when the cells are permeabilized, but the rate of dephosphorylation of disaggregated Fc epsilon RI was comparable in intact and permeabilized cells. Thus, much of the activity utilized by the cell to dephosphorylate the Fc epsilon RI is likely to be associated with the plasma membrane. C1 NIAMS,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. NR 45 TC 32 Z9 32 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 1997 VL 272 IS 22 BP 14067 EP 14073 DI 10.1074/jbc.272.22.14067 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB492 UT WOS:A1997XB49200017 PM 9162030 ER PT J AU Kirken, RA Malabarba, MG Xu, J Liu, XW Farrar, WL Hennighausen, L Larner, AC Grimley, PM Rui, H AF Kirken, RA Malabarba, MG Xu, J Liu, XW Farrar, WL Hennighausen, L Larner, AC Grimley, PM Rui, H TI Prolactin stimulates serine/tyrosine phosphorylation and formation of heterocomplexes of multiple Stat5 isoforms in Nb2 lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR; TYROSINE PHOSPHORYLATION; SERINE PHOSPHORYLATION; GENE-EXPRESSION; HUMAN MONOCYTES; RECEPTOR; ACTIVATION; PROTEIN; KINASE; BINDING AB Transcription factors of the Stat gene family are selectively activated by many hormones and cytokines. Stat5 originally was cloned as a prolactin-stimulated DNA-binding protein, but is also activated by non-lactogenic cytokines in many cell types. The recent identification of two distinct Stat5 genes, which encode a 94-kDa Stat5a and a 92-kDa Stat5b as well as several lower molecular weight isoforms, suggests additional complexity and combinatorial possibilities for transcriptional regulation. We now report a biochemical analysis of prolactin activation of Stat proteins in Nb2 lymphocytes, which was associated with: 1) rapid tyrosine phosphorylation of Stat5a, Stat5b, a COOH-terminally truncated 80-kDa Stat5 form, Stat1 alpha, and Stat3; 2) rapid and selective formation of Stat5a/b heterodimers, without involvement of Stat1 alpha or Stat3; 3) marked serine, but not threonine phosphorylation of Stat5a and Stat5b; and 4) the appearance of two qualitatively distinct Stat5 protein complexes, which discriminated between oligonucleotides corresponding to the prolactin response elements of the beta-casein and interferon regulatory factor-1 gene promoters. Collectively, our analyses showed that Stat5a and Stat5b respond similarly to prolactin receptor activation, but also suggested that the two genes have evolved unique properties that may contribute to the specificity of receptors that utilize Stat5 signaling proteins. C1 UNIFORMED SERV UNIV HLTH SCI,SCH MED,DEPT PATHOL,BETHESDA,MD 20814. SCI APPLICAT INT CORP,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20814. RI Malabarba, Maria Grazia/L-4805-2015 OI Malabarba, Maria Grazia/0000-0002-9457-2047 NR 44 TC 70 Z9 70 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 1997 VL 272 IS 22 BP 14098 EP 14103 DI 10.1074/jbc.272.22.14098 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB492 UT WOS:A1997XB49200022 PM 9162035 ER PT J AU Weigert, R Colanzi, A Mironov, A Buccione, R Cericola, C Sciulli, MG Santini, G Flati, S Fusella, A Donaldson, JG DiGirolamo, M Corda, D DeMatteis, MA Luini, A AF Weigert, R Colanzi, A Mironov, A Buccione, R Cericola, C Sciulli, MG Santini, G Flati, S Fusella, A Donaldson, JG DiGirolamo, M Corda, D DeMatteis, MA Luini, A TI Characterization of chemical inhibitors of brefeldin A-activated mono-ADP-ribosylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERIPHERAL MEMBRANE-PROTEIN; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; GOLGI MEMBRANES; RAT-LIVER; ORGANELLE STRUCTURE; GUANINE-NUCLEOTIDE; NITRIC-OXIDE; CELLS; ENDOSOMES; COMPLEX AB Brefeldin A, a toxin inhibitor of vesicular traffic, induces the selective mono-ADP-ribosylation of two cytosolic proteins, glyceraldehyde 3-phosphate dehydrogenase and the novel GTP-binding protein BARS-50, Here, we have used a new quantitative assay for the characterization of this reaction and the development of specific pharmacological inhibitors, Mono-ADP-ribosylation is activated by brefeldin A with an EC50 of 17.0 +/- 3.1 mu g/ml, but not by biologically inactive analogs including a brefeldin A stereoisomer, Brefeldin A acts by increasing the V-max of the reaction, whereas it does not influence the K-m of the enzyme for NAD(+) (154 +/- 13 mu M). The enzyme is an integral membrane protein present in most tissues and is modulated by Zn2+, Cu2+, ATP (but not by other nucleotides), pH, temperature, and ionic strength, To identify inhibitors of the reaction, a large number of drugs previously tested as blockers of bacterial ADP-ribosyltransferases were screened, Two classes of molecules, one belonging to the coumarin group (dicumarol, coumermycin A(1), and novobiocin) and the other to the quinone group (ilimaquinone, benzoquinone, and naphthoquinone), rather potently and specifically inhibited brefeldin A dependent mono-ADP-ribosylation. When tested in living cells, these molecules antagonized the tubular reticular redistribution of the Golgi complex caused by brefeldin A at concentrations similar to those active in the mono-ADP-ribosylation assay in vitro, suggesting a role for mono-ADP-ribosylation in the cellular actions of brefeldin A. C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RP Weigert, R (reprint author), CONSORZIO MARIO NEGRI SUD,IST RIC FARMACOL MARIO NEGRI,DEPT CELL BIOL & ONCOL,VIA NAZL,I-66030 SANTA MARIA IMBAR,CHIETI,ITALY. RI Colanzi, Antonino/D-6821-2012; Luini, Alberto/L-1372-2013; Corda, Daniela/K-6385-2016 OI Luini, Alberto/0000-0002-8729-2549; Corda, Daniela/0000-0002-3614-751X NR 51 TC 30 Z9 31 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 1997 VL 272 IS 22 BP 14200 EP 14207 DI 10.1074/jbc.272.22.14200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB492 UT WOS:A1997XB49200038 PM 9162051 ER PT J AU Smith, CL Htun, H Wolford, RC Hager, GL AF Smith, CL Htun, H Wolford, RC Hager, GL TI Differential activity of progesterone and glucocorticoid receptors on mouse mammary tumor virus templates differing in chromatin structure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONG TERMINAL REPEAT; HORMONE REGULATORY ELEMENT; DNASEI HYPERSENSITIVE SITES; SOMATIC-CELL HYBRIDS; MMTV PROMOTER; RESPONSE ELEMENTS; GENE ACTIVATION; TRANSCRIPTIONAL ENHANCEMENT; MAMMALIAN-CELLS; NUCLEOSOMAL DNA AB In vivo, transcription factors interact with promoters having complex nucleoprotein structures, The transiently expressed progesterone receptor (PR) efficiently activates a transfected mouse mammary tumor virus (MMTV) promoter but is a poor activator of the MMTV promoter when it acquires an ordered chromatin structure as an endogenous, replicating gene, We show that the deficiency in PR activity is not due to insufficient expression of either B or A isoforms or competition between the two types of MMTV templates, Rather, this deficiency reflects an inability to induce the chromatin remodeling event that is required for activation of the replicated MMTV template, To determine whether this characteristic is common to transiently expressed steroid receptors or specific to the PR, we examined the activity of transiently expressed glucocorticoid (GR) receptor, Unlike the PR, the transiently expressed GR is an effective activator of both MMTV templates and efficiently induces the necessary chromatin remodeling event at the replicated template, These results indicate that the GR and PR have unique requirements for activation of promoters with ordered chromatin structure, These differences may provide a mechanism for establishing target gene specificity in vivo for steroid receptors that recognize and bind to identical DNA interactions between soluble factors, and it would not be an sequences. C1 NCI,LAB RECEPTOR BIOL & GENE EXPRESS,NIH,BETHESDA,MD 20892. NR 52 TC 45 Z9 45 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 1997 VL 272 IS 22 BP 14227 EP 14235 DI 10.1074/jbc.272.22.14227 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB492 UT WOS:A1997XB49200042 PM 9162055 ER PT J AU Hu, ZZ Zhuang, L Guan, XY Meng, JP Dufau, ML AF Hu, ZZ Zhuang, L Guan, XY Meng, JP Dufau, ML TI Steroidogenic factor-1 is an essential transcriptional activator for gonad-specific expression of promoter I of the rat prolactin receptor gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR RECEPTOR; BINDING; PROTEINS; CELLS AB The expression of the prolactin receptor is under the control of two putative tissue-specific (PI, gonads; PII, liver) and one common (PIII) promoters (Hu, Z. Z., Zhuang, L., and Dufau, M. L. (1996) J. Biol. Chem, 271, 10242-10246). The three promoter regions were co-localized to the rat chromosomal locus 2q16, in the order 5'-PIII-PI-PII-3'. To investigate the mechanisms of gonad-specific utilization of PI, the promoter domain, regulatory cis-elements, and trans-factors were identified in gonadal cells. The promoter domain localized to the 152-base pair 5' of the transcriptional start site at -549 is highly active in gonadal cells but has minimal. activity in hepatoma cells. It contains a steroidogenic factor 1 (SF-1) element (-668) that binds the SF-1 protein of nuclear extracts from gonadal cells and is essential for promoter activation. A CCAAT box (-623) contributes minimally to basal activity in the absence of the SF-1 element, and two adjacent TATA-like sequences act as inhibitory elements. Thus, PI belongs to a class of TATA-less/non-initiator gene promoters, These findings demonstrate an essential role for SF-1 in transcriptional activation of promoter I of the prolactin receptor gene, which may explain the tissue-specific expression of PI in the gonads but not in the liver and the mammary gland. C1 NICHHD,SECT MOL ENDOCRINOL,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892. NIH,NATL HUMAN GENOME RES INST,CANC GENET LAB,BETHESDA,MD 20892. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 29 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 1997 VL 272 IS 22 BP 14263 EP 14271 DI 10.1074/jbc.272.22.14263 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB492 UT WOS:A1997XB49200047 PM 9162060 ER PT J AU Zhu, SH Romano, PR Wek, RC AF Zhu, SH Romano, PR Wek, RC TI Ribosome targeting of PKR is mediated by two double-stranded RNA-binding domains and facilitates in vivo phosphorylation of eukaryotic initiation factor-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; NF-KAPPA-B; SACCHAROMYCES-CEREVISIAE; INTERFERON ACTION; MALIGNANT TRANSFORMATION; TRANSLATION INITIATION; IN-VIVO; INTERMOLECULAR AUTOPHOSPHORYLATION; TERMINAL REGION; P68 KINASE AB Protein kinase PKR is activated in mammalian cells during viral infection, leading to phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2 alpha) and inhibition of protein synthesis. This antiviral response is thought to be mediated by association of double-stranded RNA (ds-RNA), a by-product of viral replication, with two ds-RNA-binding domains (DRBDs) located in the amino terminus of PKR, Recent studies have observed that expression of mammalian PKR in yeast leads to a slow growth phenotype due to hyperphosphorylation of eIF-2 alpha. In this report, we observed that while DRBD sequences are required for PKR to function in the yeast model system, these sequences are not required for in vitro phosphorylation of eIF-2 alpha. To explain this apparent contradiction, we proposed that these sequences are required to target the kinase to the translation machinery, Using sucrose gradient sedimentation, we found that wild-type PKR was associated with ribosomes, specifically with 40 S particles, Deletions or residue substitutions in the DRBD sequences blocked kinase interaction with ribosomes. These results indicate that in addition to mediating ds-RNA control of PKR, the DRBD sequences facilitate PKR association with ribosomes, Targeting to ribosomes may enhance in vivo phosphorylation of eIF-2 alpha, by providing PKR access to its substrate. C1 INDIANA UNIV, SCH MED, DEPT BIOCHEM & MOL BIOL, INDIANAPOLIS, IN 46202 USA. NICHHD, LAB EUKARYOT GENE EXPRESS, NIH, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [GM49164] NR 69 TC 66 Z9 66 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 1997 VL 272 IS 22 BP 14434 EP 14441 DI 10.1074/jbc.272.22.14434 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB492 UT WOS:A1997XB49200070 PM 9162083 ER PT J AU Brechbiel, MW Beitzel, PM Gansow, OA AF Brechbiel, MW Beitzel, PM Gansow, OA TI Purification of p-nitrobenzyl C-functionalized diethylenetriamine pentaacetic acids for clinical applications using anion-exchange chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE radioligands; preparative chromatography; diethylenetriamine pentaacetic acids; monoclonal antibodies ID MONOCLONAL-ANTIBODIES; CHELATING AGENT; RADIOIMMUNOTHERAPY; DTPA; LIGANDS AB A general process for the purification of large quantities (5-10 g) of p-nitrobenzyl C-functionalized diethylenetriamine pentaacetic acids is reported. The method of choice to achieve purification for clinical applications is anion-exchange chromatography. RP Brechbiel, MW (reprint author), NCI,RADIAT ONCOL BRANCH,RADIOIMMUNE & INORGAN CHEM SECT,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 17 TC 13 Z9 13 U1 0 U2 0 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 MAY 30 PY 1997 VL 771 IS 1-2 BP 63 EP 69 DI 10.1016/S0021-9673(97)00108-8 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XF413 UT WOS:A1997XF41300007 PM 9210313 ER PT J AU Ma, Y Ito, Y AF Ma, Y Ito, Y TI Peptide separation by pH-zone-refining countercurrent chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE pH-zone-refining countercurrent chromatography; peptides ID PREPARATIVE SEPARATION; PURIFICATION; COMPONENTS; ACIDS AB Peptides without protecting groups have been successfully separated by pH-zone-refining countercurrent chromatography (CCC) using an ion-pair reagent, di-(2-ethylhexyl)phosphoric acid (DEHPA), as a modifier in the stationary phase. Preliminary studies indicated that two parameters, i.e., the DEHPA concentration in the stationary phase and hydrophobicity of the solvent system should be adjusted according to the hydrophobicity of the analytes. Hydrophobic and hydrophilic groups of dipeptides were each separated under optimized conditions. The method was successfully applied to gram-quantity separations of bacitracin complex and bovine insulin. C1 NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 23 TC 25 Z9 26 U1 1 U2 12 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 MAY 30 PY 1997 VL 771 IS 1-2 BP 81 EP 88 DI 10.1016/S0021-9673(97)00065-4 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XF413 UT WOS:A1997XF41300009 PM 9210314 ER PT J AU Oh, JD DelDotto, P Chase, TN AF Oh, JD DelDotto, P Chase, TN TI Protein kinase A inhibitor attenuates levodopa-induced motor response alterations in the hemi-parkinsonian rat SO NEUROSCIENCE LETTERS LA English DT Article DE cyclic AMP; dopamine; N-methyl-D-aspartate receptors; Parkinson's disease; rotational behavior; striatum ID NMDA RECEPTOR BLOCKADE; STRIATUM AB Chronically administered levodopa, the standard treatment for Parkinson's disease, is ultimately associated with disabling alterations in motor response. To evaluate the possible contribution of striatal cAMP-dependent protein kinase A (PKA) signaling pathways to these response modifications, the acute effects of a PKA inhibitor, Rp-cAMPS, on motor response changes attending chronic, twice-daily administration of levodopa were measured in 6-hydroxydopamine lesioned hemi-parkinsonian rats. A single intrastriatal injection of Rp-cAMPS (2.5 or 25 mu g) attenuated both the shortened duration and augmented intensity of levodopa-induced turning in a dose dependent manner. Rp-cAMPS completely normalized motor responses to a dopamine D1 agonist (SKF 38392), but had no effect on those to a dopamine D2 agonist (quinpirole). These results suggest that D1 receptor-mediated PKA activation may contribute to the development of the altered motor responses associated with chronic levodopa treatment. (C) 1997 Elsevier Science Ireland Ltd. C1 NINCDS,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. NR 18 TC 50 Z9 51 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 30 PY 1997 VL 228 IS 1 BP 5 EP 8 DI 10.1016/S0304-3940(97)00355-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA XE798 UT WOS:A1997XE79800002 PM 9197274 ER PT J AU LaBuda, MC Svikis, DS Pickens, RW AF LaBuda, MC Svikis, DS Pickens, RW TI Twin closeness and co-twin risk for substance use disorders: Assessing the impact of the equal environment assumption SO PSYCHIATRY RESEARCH LA English DT Article DE twin study; drug dependence; genetics ID POPULATION-BASED TWIN; GENERALIZED ANXIETY DISORDER; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; DRUG-USE; SIMILARITY; WOMEN; ALCOHOLISM; ILLNESS; INHERITANCE AB Various environmental variables are hypothesized to operate differentially within identical and fraternal twin pairs. To the extent that these factors are correlated with behavioral outcomes, such as alcohol or drug abuse, traditional twin studies of concordance may be biased. Self-ratings of within-pair emotional closeness, assessed in 169 same-sex twin pairs ascertained through alcohol and drug treatment centers, were used to determine the impact of the twin relationship on concordance for alcohol dependence (N = 130 twin pairs) and other drug abuse and/or dependence (N = 85 twin pairs). In general, identical twin pairs reported significantly closer relationships than fraternal twin pairs, and female twin pairs reported significantly closer relationships than male twin pairs. The data did not indicate an overall effect of closeness on co-twin risk for alcohol dependence. In contrast, closeness was significantly related to co-twin risk for other drug abuse and/or dependence. However, the MZ/DZ concordance difference for other drug abuse and/or dependence remained significant when the effects of within-pair closeness were controled. Thus, the initial zygosity and sex differences in concordance for substance use disorders cannot be explained solely by differences in twin relationship due to closeness as assessed in this study. (C) 1997 Elsevier Science Ireland Ltd. C1 NATL INST DRUG ABUSE,BALTIMORE,MD 21224. RP LaBuda, MC (reprint author), JOHNS HOPKINS MED INST,DEPT PSYCHIAT & BEHAV SCI,600 N WOLFE ST,BALTIMORE,MD 21287, USA. FU NIAAA NIH HHS [AA-06500, AA00175] NR 40 TC 23 Z9 23 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 30 PY 1997 VL 70 IS 3 BP 155 EP 164 DI 10.1016/S0165-1781(97)03045-X PG 10 WC Psychiatry SC Psychiatry GA XG326 UT WOS:A1997XG32600003 PM 9211577 ER PT J AU Rall, JE AF Rall, JE TI Evaluating biologics SO SCIENCE LA English DT Letter RP Rall, JE (reprint author), NIDDKD,NIH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 30 PY 1997 VL 276 IS 5317 BP 1319 EP 1320 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XB533 UT WOS:A1997XB53300006 PM 9190671 ER PT J AU Zhang, ZJ Kundu, GC Yuan, CJ Ward, JM Lee, EJ DeMayo, F Westphal, H Mukherjee, AB AF Zhang, ZJ Kundu, GC Yuan, CJ Ward, JM Lee, EJ DeMayo, F Westphal, H Mukherjee, AB TI Severe fibronectin-deposit renal glomerular disease in mice lacking uteroglobin SO SCIENCE LA English DT Article ID GENE-EXPRESSION; PROTEIN; RABBIT; BINDING; GLOMERULONEPHRITIS; TRANSGLUTAMINASE; ANTIGENICITY; PROLACTIN; REGION; FAMILY AB Despite myriads of biological activities ascribed to uteroglobin (UG), a steroid-inducible secreted protein, its physiological functions are unknown. Mice in which the uteroglobin gene was disrupted had severe renal disease that was associated with massive glomerular deposition of predominantly multimeric fibronectin (Fn), The molecular mechanism that normally prevents Fn deposition appears to involve high-affinity binding of UG with Fn to form Fn-UG heteromers that counteract Fn self-aggregation,which is required for abnormal tissue deposition, Thus, UG is essential for maintaining normal renal function in mice, which raises the possibility that an analogous pathogenic mechanism may underlie genetic Fn-deposit human glomerular disease. C1 NICHHD,SECT DEV GENET,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NCI,VET & TUMOR PATHOL SECT,OFF LAB ANIM SCI,FREDERICK,MD 21702. NICHHD,LAB MAMMALIAN GENET & DEV,NIH,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. FU NHLBI NIH HHS [HL47620] NR 42 TC 106 Z9 115 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 30 PY 1997 VL 276 IS 5317 BP 1408 EP 1412 DI 10.1126/science.276.5317.1408 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XB533 UT WOS:A1997XB53300047 PM 9162006 ER PT J AU Parrizas, M Blakesley, VA BeitnerJohnson, D LeRoith, D AF Parrizas, M Blakesley, VA BeitnerJohnson, D LeRoith, D TI The proto-oncogene Crk-II enhances apoptosis by a ras-dependent, Raf-1/MAP kinase-independent pathway SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PC12 CELLS; C-CRK; V-CRK; GROWTH; PROTEINS; DIFFERENTIATION; ACTIVATION; PRODUCT; FIBROBLASTS; DOMAINS AB Human embryonic kidney 293 cells and 293 cells overexpressing different amounts of the adaptor protein Crk-II (ranging from 3- to 10-fold higher levels than the parental cell line) were examined for their ability to undergo apoptosis when maintained in control and serum-free (SF) medium. Parental 293 cells undergo apoptosis only when deprived of serum for prolonged periods of time (24-48 h). On the other hand, 293 cells overexpressing different levels of Crk-II present detectable levels of apoptosis as measured by DNA fragmentation when grown in control medium, with a marked increase when they are deprived of serum for 12-48 h. To determine the pathways involved in Crk-II-induced apoptosis, Crk-II overexpressing cells were transiently transfected with a dominant-negative Pas construct (N17-Ras). Compared to cells transfected with control vectors, the cells overexpressing N17-Ras presented lower levels of apoptosis when maintained in SF-medium. On the other hand, transient transfection of a dominant-negative Raf-1 construct (K375W-Raf-1) did not decrease apoptosis; slightly increasing DNA fragmentation levels were seen. Similar results were obtained when the cells were incubated in the presence of a MEK1 inhibitor. The results presented here suggest that overexpression of Crk-II induces apoptosis via a Ras-dependent, Raf-1/MEK1/ERK-independent pathway. (C) 1997 Academic Press. C1 NIDA,DIABET BRANCH,NIH,BETHESDA,MD 20892. UNIV CINCINNATI,DEPT MOL & CELLULAR PHYSIOL,CINCINNATI,OH 45267. NR 29 TC 20 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 29 PY 1997 VL 234 IS 3 BP 616 EP 620 DI 10.1006/bbrc.1997.6641 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XC939 UT WOS:A1997XC93900016 PM 9175762 ER PT J AU Choudhury, BK Li, SSL AF Choudhury, BK Li, SSL TI Identification and characterization of the SMT3 cDNA and gene from nematode Caenorhabditis elegans SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CENP-C; CENTROMERE AB SMT3 gene from nematode, Caenorhabditis elegans, was identified and sequenced. The nematode SMT3 gene codes for a homolog to the yeast SMT3, suppressor of MIF2 mutation in a centromere protein gene. Further, nematode SMT3 cDNA was amplified by polymerase chain reaction from a cDNA library and its nucleotide sequence determined. A comparison of the SMT3 genomic and cDNA sequences established that the protein-encoding sequence is interrupted by two introns of 56 and 50 bp at codon Nos. 22-23 and 56, respectively. The sequence of 91 amino acids deduced from the nematode SMT3 nucleotide sequence exhibited 42 and 47% identity to the yeast and human SMT3 protein sequences, respectively, The evolutionary relationships of SMT3 proteins from human, nematode, Arabidopsis, rice, and yeast were analyzed. (C) 1997 Academic Press. C1 NIEHS,MOL GENET LAB,NIH,RES TRIANGLE PK,NC 27709. NATL SUN YAT SEN UNIV,INST LIFE SCI,KAOHSIUNG 80424,TAIWAN. NR 9 TC 20 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 29 PY 1997 VL 234 IS 3 BP 788 EP 791 DI 10.1006/bbrc.1997.6709 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XC939 UT WOS:A1997XC93900049 PM 9175795 ER PT J AU Cohen, RM Andreason, PJ Doudet, DJ Carson, RE Sunderland, T AF Cohen, RM Andreason, PJ Doudet, DJ Carson, RE Sunderland, T TI Opiate receptor avidity and cerebral blood flow in Alzheimer's disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Alzheimer's disease; opiate receptors; cerebral blood flow; neurodegeneration; 6-deoxy-6-beta-[F-18]fluoronaltrexone; positron emission tomography ID POSITRON EMISSION TOMOGRAPHY; RAT-BRAIN; ANTAGONIST CYCLOFOXY; INACTIVE ENANTIOMERS; OPIOID RECEPTORS; KINETIC-ANALYSIS; F-18 CYCLOFOXY; BINDING; NALOXONE; DEMENTIA AB Positron emission tomography was performed on 12 Alzheimer's patients and 12 age-matched normal controls following the administration of the opiate receptor antagonist 6-deoxy-6-beta-[F-18]fluoronaltrexone (cyclofoxy, CF). Tracer kinetic analysis was used to determine the volume of distribution of CF, a measure of unoccupied mu and kappa receptor density, i.e. opiate receptor avidity in 34 brain regions. Regional cerebral blood flow rates (CBF) were determined on the same day with H-2[O-15]. Global gray CF avidity and global gray CBF were found to be lower in the Alzheimer's patients and correlated (r=0.73, P<0.03). Regional CBF differences were superimposed on global CBF changes in the Alzheimer's patients, with the subcortex relatively spared. Multivariate statistical analyses, however, failed to demonstrate regional specificity for the CF avidity changes. Furthermore, percent changes in regional CF avidity were not correlated with percent changes in regional CBF (r=0.12, P=NS). These findings demonstrate involvement of the opiate system in Alzheimer's disease. Although, neurodegeneration is the likely underlying process responsible for both the changes in CF avidity and CBF in Alzheimer's disease, the differences with respect to the patterns of these losses suggest that the intermediate mechanisms leading from neurodegeneration to loss are distinct. (C) 1997 Elsevier Science B.V. C1 NIH,DEPT NUCL MED,CTR CLIN,BETHESDA,MD 20892. NIMH,SECT GERIATR PSYCHIAT,CLIN SCI LAB,BETHESDA,MD 20892. RP Cohen, RM (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A05,36 CONVENT DR MSC 4030,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 48 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAY 29 PY 1997 VL 148 IS 2 BP 171 EP 180 DI 10.1016/S0022-510X(96)05315-4 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WU866 UT WOS:A1997WU86600006 PM 9129113 ER PT J AU Baskaran, R Wood, LD Whitaker, LL Canman, CE Morgan, SE Xu, Y Barlow, C Baltimore, D WynshawBoris, A Kastan, MB Wang, JYJ AF Baskaran, R Wood, LD Whitaker, LL Canman, CE Morgan, SE Xu, Y Barlow, C Baltimore, D WynshawBoris, A Kastan, MB Wang, JYJ TI Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation SO NATURE LA English DT Article ID CYCLE CHECKPOINT PATHWAY; DNA-DAMAGING AGENTS; CELL-CYCLE; P53; INDUCTION; DOMAIN; GENE; UV AB Ataxia telangiectasia (AT) is a rare human autosomal recessive disorder with pleiotropic phenotypes, including neuronal degeneration, immune dysfunction, premature ageing and increased cancer risk. The gene mutated in AT, ATM, encodes a putative lipid or protein kinase(1,2). Most of the human AT patient phenotypes are recapitulated in Atm-deficient mice(3,4). Cells derived from Atm(-/-) mice, like those from AT patients, exhibit abnormal response to ionizing radiation(3,5,6). One of the known responses to ionizing radiation is the activation of a nuclear tyrosine kinase encoded by the c-abl proto-oncogene(7,8). Ionizing radiation does not activate c-Abl in cells from AT patients or in thymocytes or fibroblasts from the Arm-deficient mice. Ectopic expression of a functional ATM kinase domain corrects this defect, as it phosphorylates the c-Abl tyrosine kinase in vitro at Ser 465, leading to the activation of c-Abl. A mutant c-Abl with Ser 465 changed to Ala 465 is not activated by ionizing radiation or ATM kinase in vivo. These findings identify the c-Abl tyrosine kinase as a downstream target of phosphorylation and activation by the ATM kinase in the cellular response to ionizing radiation. C1 UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,CTR MOL GENET,LA JOLLA,CA 92093. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. MIT,DEPT BIOL,CAMBRIDGE 02139,ENGLAND. NIH,NCHGR,LAB GENET DIS RES,BETHESDA,MD 20892. FU NCI NIH HHS [R37 CA043054] NR 25 TC 426 Z9 430 U1 1 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 29 PY 1997 VL 387 IS 6632 BP 516 EP 519 DI 10.1038/387516a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XB479 UT WOS:A1997XB47900052 PM 9168116 ER PT J AU Stamler, J Applegate, WB Cohen, JD Cutler, JA Whelton, PK AF Stamler, J Applegate, WB Cohen, JD Cutler, JA Whelton, PK TI More on dietary sodium and blood pressure SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 UNIV TENNESSEE,MEMPHIS,TN. ST LOUIS UNIV,ST LOUIS,MO 63103. NHLBI,BETHESDA,MD 20892. TULANE UNIV,SCH PUBL HLTH,NEW ORLEANS,LA 70118. RP Stamler, J (reprint author), NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611, USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 28 PY 1997 VL 277 IS 20 BP 1594 EP 1595 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XA022 UT WOS:A1997XA02200024 PM 9168287 ER PT J AU Weinmann, G AF Weinmann, G TI A national strategy for research in chronic obstructive pulmonary disease - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Weinmann, G (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 28 PY 1997 VL 277 IS 20 BP 1596 EP 1596 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XA022 UT WOS:A1997XA02200027 ER PT J AU Cook, LS Daling, JR Voigt, LF deHart, P Malone, KE Stanford, JL Weiss, NS Brinton, LA Gammon, MD Brogan, D AF Cook, LS Daling, JR Voigt, LF deHart, P Malone, KE Stanford, JL Weiss, NS Brinton, LA Gammon, MD Brogan, D TI Characteristics of women with and without breast augmentation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CONNECTIVE-TISSUE DISEASES; RHEUMATOID-ARTHRITIS; ORAL-CONTRACEPTIVES; UNITED-STATES; IMPLANTS; CANCER; RISK; SYMPTOMS AB Objective.-To compare selected characteristics of women with and without augmentation mammaplasty to identify differences between these 2 groups of women. Design and Study Participants.-White women identified as controls in previously conducted population-based, case-control studies formed the study population for the present cross-sectional analysis (N=3570). Main Outcome Measure.-Interview information on selected characteristics was compared between women who had received augmentation mammaplasty (n=80) and other women (n=3490) using the prevalence odds ratio (pOR) as the measure of association. Results.-Women with breast implants were more likely to drink a greater average number of alcoholic drinks per week (for greater than or equal to 7 drinks vs 0 drinks: pOR=2.9, 95% confidence interval [CI]=1.5-5.5), be younger at first pregnancy (for age <20 years vs age 20-29 years: pOR=1.6, 95% CI=1.0-2.7), be younger at first birth (for age <20 years vs age 20-29 years: pOR=1.9, 95% CI=1.1-3.3), have a history of terminated pregnancies (for greater than or equal to 1 termination vs 0 terminations: pOR=2.0, 95% CI=1.2-3.4), have ever used oral contraceptives (pOR=2.2, 95% CI=1.0-4.7), have ever used hair dyes (pOR=4.5, 95% CI=1.3-15.4), and have had a greater lifetime number of sexual partners (for greater than or equal to 14 partners vs less than or equal to 4 partners: pOR=8.9, 95% CI=3.1-25.5) than other women. A history of smoking, lactation, high blood pressure, or thyroid disorders, as well as the number of pregnancies, full-term births, or miscarriages, differed little between women with and without implants, Women with breast augmentation were much less likely to be heavy than other women (for greater than or equal to 74 kg vs (56 kg: pOR=0.1, 95% CI=0.03-0.3). Conclusion.-The differences we found between women with and without breast implants suggest that consideration and evaluation of confounding factors in future studies will help to clarify some of the long-term health consequences of having breast implants. C1 UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV UTAH,HUNTSMAN CANC INST,DEPT ONCOL SCI,SALT LAKE CITY,UT. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. COLUMBIA UNIV,DIV EPIDEMIOL,NEW YORK,NY. EMORY UNIV,DEPT BIOSTAT,ATLANTA,GA 30322. RP Cook, LS (reprint author), FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,1110 FAIRVIEW AVE N,POB 19024,SEATTLE,WA 98109, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [KO7-CA-01364, R01-CA-41416, R35-CA-39779] NR 34 TC 67 Z9 68 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 28 PY 1997 VL 277 IS 20 BP 1612 EP 1617 DI 10.1001/jama.277.20.1612 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XA022 UT WOS:A1997XA02200031 PM 9168291 ER PT J AU Whelton, PK He, J Cutler, JA Brancati, FL Appel, LJ Follmann, D Klag, MJ AF Whelton, PK He, J Cutler, JA Brancati, FL Appel, LJ Follmann, D Klag, MJ TI Effects of oral potassium on blood pressure - Meta-analysis of randomized controlled clinical trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID MILD ESSENTIAL-HYPERTENSION; PLACEBO-CONTROLLED TRIAL; MODERATE SODIUM RESTRICTION; DIETARY-SODIUM; DOUBLE-BLIND; NORMOTENSIVE WOMEN; SUPPLEMENTATION; MEN; CHLORIDE; RENIN AB Objective.-To assess the effects of supplementation with oral potassium on blood pressure in humans. Design.-Meta-analysis of randomized controlled trials. Data Sources.-English-language articles published before July 1995. Study Selection.-Thirty-three randomized controlled trials (2609 participants) in which potassium supplementation was the only difference between the intervention and control conditions. Data Extraction.-Using a standardized protocol, 2 of us independently abstracted information on sample size, duration, study design, potassium dose, participant characteristics, and treatment results. Results.-By means of a random-effects model, findings from individual trials were pooled, after results for each trial were weighted by the inverse of its variance. An extreme effect of potassium in lowering blood pressure was noted in 1 trial. After exclusion of this trial, potassium supplementation was associated with a significant reduction in mean (95% confidence interval) systolic and diastolic blood pressure of -3.11 mm Hg (-1.91 to -4.31 mm Hg) and -1.97 mm Hg (-0.52 to -3.42 mm Hg), respectively. Effects of treatment appeared to be enhanced in studies in which participants were concurrently exposed to a high intake of sodium. Conclusions.-Our results support the premise that low potassium intake may play an important role in the genesis of high blood pressure. Increased potassium intake should be considered as a recommendation for prevention and treatment of hypertension, especially in those who are unable to reduce their intake of sodium. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,WELCH CTR PREVENT EPIDEMIOL & CLIN RES,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. FU NCRR NIH HHS [5 MO1 RR00722, RR0035]; NHLBI NIH HHS [5 KO8 HL02642] NR 97 TC 480 Z9 499 U1 1 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 28 PY 1997 VL 277 IS 20 BP 1624 EP 1632 DI 10.1001/jama.277.20.1624 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA XA022 UT WOS:A1997XA02200033 PM 9168293 ER PT J AU Cohen, BE Lee, G Jacobson, KA Kim, YC Huang, Z Sorscher, EJ Pollard, HB AF Cohen, BE Lee, G Jacobson, KA Kim, YC Huang, Z Sorscher, EJ Pollard, HB TI 8-cyclopentyl-1,3-dipropylxanthine and other xanthines differentially bind to the wild-type and Delta F508 mutant first nucleotide binding fold (NBF-1) domains of the cystic fibrosis transmembrane conductance regulator SO BIOCHEMISTRY LA English DT Article ID CHLORIDE EFFLUX; ADENOSINE RECEPTORS; PROTEIN; PURIFICATION; ANTAGONISTS; CELLS; GENE AB Cystic fibrosis is an autosomal recessive disorder affecting chloride transport in pancreas, lung, and other tissues, which is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Certain alkyl xanthines such as CPX (8-cyclopentyl-1,3-dipropylxanthine) stimulate Cl- efflux from cells bearing the Delta F508 genotype common to most cases of cystic fibrosis. We have hypothesized that the CFTR molecule itself might be the site for CPX action, perhaps in the region of the first nucleotide binding fold (NBF-1) domain. Therefore, to test this hypothesis directly we have used a rapid membrane filtration assay to measure the kinetics of association and dissociation of [H-3]CPX to both recombinant NBF-1 and recombinant NBF-1 bearing the Delta F508 mutation. We report that [H-3]CPX binds with higher affinity to the Delta F508-NBF-1 of CFTR (K-d = 1.0 nM) than to the wild-type NBF-1 of CFTR (K-d = 17.0 nM). These K-d values were calculated from direct measurements of the association and dissociation rate constants. The rate constants for the dissociation reaction of the wild-type NBF-1 and Delta F508-NBF-1 of CFTR were not different from each other. However, the corresponding rate constants for the association reaction were k(+1) (NBF-1) = 4.7 +/- 0.9 x 10(4) M-1 s(-1) and k(+1) (Delta F508-NBF-1) = 1.6 +/- 0.3 x 10(5) M-1 s(-1), respectively. These K-d values were corroborated by equilibrium-binding experiments, which gave very similar values. We have also measured the relative displacement of various xanthines from both wild-type NBF-1 and Delta F508-NBF-1, in anticipation. that the order of potencies for binding might parallel the action of the different xanthines on CF cells. For wild-type NBF-1, the rank order was DA-CPX > DAX > CPX > caffeine > adenosine much greater than IBMX > 2-thioCPX. For Delta F508-NBF-1, the rank order was DAX > CPX > caffeine > DA-CPX > adenosine much greater than IBMX > 2-thioCPX. These relative potencies show close parallels with previously observed relative potencies of these drugs on CF cells, and thus lend strong support to the hypothesis that the mechanism of action on CF cells may involve direct interaction with the CFTR molecule itself. C1 NIDDK,NIH,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NIDDK,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. UNIV ALABAMA,DEPT PHYSIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIFORMED SERV UNIV HLTH SCI,SCH MED,DEPT ANAT,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,SCH MED,DEPT CELL BIOL,BETHESDA,MD 20814. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031127-01, Z99 DK999999] NR 25 TC 56 Z9 56 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 27 PY 1997 VL 36 IS 21 BP 6455 EP 6461 DI 10.1021/bi970150v PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB321 UT WOS:A1997XB32100023 PM 9174362 ER PT J AU Henry, ER Jones, CM Hofrichter, J Eaton, WA AF Henry, ER Jones, CM Hofrichter, J Eaton, WA TI Can a two-state MWC allosteric model explain hemoglobin kinetics? SO BIOCHEMISTRY LA English DT Article ID PROTEIN CONFORMATIONAL-CHANGES; LIGAND-BINDING; GEMINATE RECOMBINATION; HEME-PROTEINS; INTERSUBUNIT COMMUNICATION; SOLVENT VISCOSITY; LASER PHOTOLYSIS; SINGLE-CRYSTALS; OXYGEN BINDING; DYNAMICS AB We have analysed the nanosecond-millisecond kinetics of ligand binding and conformational changes in hemoglobin. The kinetics were determined from measurements of precise time-resolved optical spectra following nanosecond photodissociation of the heme-carbon monoxide complex. To fit the data, it was necessary to extend the two-state allosteric model of Monod, Wyman, and Changeux (MWC) to include geminate ligand rebinding and nonexponential tertiary relaxation within the R quaternary structure. Considerable simplification of the model is obtained by using a;linear free energy relation for the rates of quaternary transitions, and by incorporating concepts from recent studies on the physics of geminate rebinding and conformational changes in myoglobin. The model, described by 85 coupled differential equations, quantitatively explains a demanding set of complex kinetic data. Moreover, with the same set of kinetic parameters it simultaneously fits the equilibrium data on ligand binding and the distribution of ligation states. The present results, together with those from single-crystal oxygen binding studies, indicate that the two-state MWC allosteric model has survived its most critical tests. RP Henry, ER (reprint author), NIDDKD,PHYS CHEM LAB,NIH,BLDG 5,BETHESDA,MD 20892, USA. RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 74 TC 85 Z9 85 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 27 PY 1997 VL 36 IS 21 BP 6511 EP 6528 DI 10.1021/bi9619177 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB321 UT WOS:A1997XB32100030 PM 9174369 ER EF